Therapeutic potential of stem cells expressing suicide genes that selectively target human breast cancer cells: Evidence that they exert tumoricidal effects via tumor tropism
Identifieur interne : 000C46 ( Pmc/Corpus ); précédent : 000C45; suivant : 000C47Therapeutic potential of stem cells expressing suicide genes that selectively target human breast cancer cells: Evidence that they exert tumoricidal effects via tumor tropism
Auteurs : Bo-Rim Yi ; Kelvin J. Choi ; Seung U. Kim ; Kyung-Chul ChoiSource :
- International Journal of Oncology [ 1019-6439 ] ; 2012.
Abstract
Breast cancer is the most prevalent cancer in women worldwide and is classified into ductal and lobular carcinoma. Breast cancer as well as lobular carcinoma is associated with various risk factors such as gender, age, female hormone exposure, ethnicity, family history and genetic risk factor-associated genes. Genes associated with a high risk of developing breast cancer include
Url:
DOI: 10.3892/ijo.2012.1523
PubMed: 22736197
PubMed Central: 3582792
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Therapeutic potential of stem cells expressing suicide genes that selectively target human breast cancer cells: Evidence that they exert tumoricidal effects via tumor tropism</title><author><name sortKey="Yi, Bo Rim" sort="Yi, Bo Rim" uniqKey="Yi B" first="Bo-Rim" last="Yi">Bo-Rim Yi</name><affiliation><nlm:aff id="af1-ijo-41-03-0798">Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk,<country>Republic of Korea</country>;</nlm:aff></affiliation></author><author><name sortKey="Choi, Kelvin J" sort="Choi, Kelvin J" uniqKey="Choi K" first="Kelvin J." last="Choi">Kelvin J. Choi</name><affiliation><nlm:aff wicri:cut=" and" id="af2-ijo-41-03-0798">Departments of Chemistry</nlm:aff></affiliation></author><author><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name><affiliation><nlm:aff id="af3-ijo-41-03-0798">Medicine, University of British Columbia, Vancouver, British Columbia,<country>Canada</country>;</nlm:aff></affiliation><affiliation><nlm:aff id="af4-ijo-41-03-0798">Medical Research Institute, Chung-Ang University College of Medicine, Seoul,<country>Republic of Korea</country></nlm:aff></affiliation></author><author><name sortKey="Choi, Kyung Chul" sort="Choi, Kyung Chul" uniqKey="Choi K" first="Kyung-Chul" last="Choi">Kyung-Chul Choi</name><affiliation><nlm:aff id="af1-ijo-41-03-0798">Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk,<country>Republic of Korea</country>;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22736197</idno><idno type="pmc">3582792</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3582792</idno><idno type="RBID">PMC:3582792</idno><idno type="doi">10.3892/ijo.2012.1523</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000C46</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000C46</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Therapeutic potential of stem cells expressing suicide genes that selectively target human breast cancer cells: Evidence that they exert tumoricidal effects via tumor tropism</title><author><name sortKey="Yi, Bo Rim" sort="Yi, Bo Rim" uniqKey="Yi B" first="Bo-Rim" last="Yi">Bo-Rim Yi</name><affiliation><nlm:aff id="af1-ijo-41-03-0798">Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk,<country>Republic of Korea</country>;</nlm:aff></affiliation></author><author><name sortKey="Choi, Kelvin J" sort="Choi, Kelvin J" uniqKey="Choi K" first="Kelvin J." last="Choi">Kelvin J. Choi</name><affiliation><nlm:aff wicri:cut=" and" id="af2-ijo-41-03-0798">Departments of Chemistry</nlm:aff></affiliation></author><author><name sortKey="Kim, Seung U" sort="Kim, Seung U" uniqKey="Kim S" first="Seung U." last="Kim">Seung U. Kim</name><affiliation><nlm:aff id="af3-ijo-41-03-0798">Medicine, University of British Columbia, Vancouver, British Columbia,<country>Canada</country>;</nlm:aff></affiliation><affiliation><nlm:aff id="af4-ijo-41-03-0798">Medical Research Institute, Chung-Ang University College of Medicine, Seoul,<country>Republic of Korea</country></nlm:aff></affiliation></author><author><name sortKey="Choi, Kyung Chul" sort="Choi, Kyung Chul" uniqKey="Choi K" first="Kyung-Chul" last="Choi">Kyung-Chul Choi</name><affiliation><nlm:aff id="af1-ijo-41-03-0798">Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk,<country>Republic of Korea</country>;</nlm:aff></affiliation></author></analytic><series><title level="j">International Journal of Oncology</title><idno type="ISSN">1019-6439</idno><idno type="eISSN">1791-2423</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Breast cancer is the most prevalent cancer in women worldwide and is classified into ductal and lobular carcinoma. Breast cancer as well as lobular carcinoma is associated with various risk factors such as gender, age, female hormone exposure, ethnicity, family history and genetic risk factor-associated genes. Genes associated with a high risk of developing breast cancer include <italic>BRCA1</italic>, <italic>BRCA2</italic>, <italic>p53</italic>, <italic>PTEN</italic>, <italic>CHEK2</italic> and <italic>ATM</italic>. Surgery, chemotherapy, radiotherapy and hormone therapy are used to treat breast cancer but these therapies, except for surgery, have many side-effects such as alopecia, anesthesia, diarrhea and arthralgia. Gene-directed enzyme/prodrug therapy (GEPT) or suicide gene therapy, may improve the therapeutic efficacy of conventional cancer radiotherapy and chemotherapy without side-effects. GEPT most often involves the use of a viral vector to deliver a gene not found in mammalian cells and that produces enzymes which can convert a relatively non-toxic prodrug into a toxic agent. Examples of these systems include cytosine deaminase/5-fluorocytosine (CD/5-FC), carboxyl esterase/irinotecan (CE/CPT-11), and thymidine kinase/ganciclovir (TK/GCV). Recently, therapies based on genetically engineered stem cells (GESTECs) using a GEPT system have received a great deal of attention for their clinical and therapeutic potential to treat breast cancer. In this review, we discuss the potential of GESTECs via tumor tropism effects and therapeutic efficacy against several different types of cancer cells. GESTECs represent a useful tool for treating breast cancer without inducing injuries associated with conventional therapeutic modalities.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Jemal, A" uniqKey="Jemal A">A Jemal</name></author><author><name sortKey="Bray, F" uniqKey="Bray F">F Bray</name></author><author><name sortKey="Center, Mm" uniqKey="Center M">MM Center</name></author><author><name sortKey="Ferlay, J" uniqKey="Ferlay J">J Ferlay</name></author><author><name sortKey="Ward, E" uniqKey="Ward E">E Ward</name></author><author><name sortKey="Forman, D" uniqKey="Forman D">D Forman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vincent Salomon, A" uniqKey="Vincent Salomon A">A Vincent-Salomon</name></author><author><name sortKey="Thiery, Jp" uniqKey="Thiery J">JP Thiery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Middleton, Lp" uniqKey="Middleton L">LP Middleton</name></author><author><name sortKey="Tressera, F" uniqKey="Tressera F">F Tressera</name></author><author><name sortKey="Sobel, Me" uniqKey="Sobel M">ME Sobel</name></author><author><name sortKey="Bryant, Br" uniqKey="Bryant B">BR Bryant</name></author><author><name sortKey="Alburquerque, A" uniqKey="Alburquerque A">A Alburquerque</name></author><author><name sortKey="Grases, P" uniqKey="Grases P">P Grases</name></author><author><name sortKey="Merino, Mj" uniqKey="Merino M">MJ Merino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goldstein, Ns" uniqKey="Goldstein N">NS Goldstein</name></author><author><name sortKey="Vicini, Fa" uniqKey="Vicini F">FA Vicini</name></author><author><name sortKey="Kestin, Ll" uniqKey="Kestin L">LL Kestin</name></author><author><name sortKey="Thomas, M" uniqKey="Thomas M">M Thomas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Ci" uniqKey="Li C">CI Li</name></author><author><name sortKey="Anderson, Bo" uniqKey="Anderson B">BO Anderson</name></author><author><name sortKey="Porter, P" uniqKey="Porter P">P Porter</name></author><author><name sortKey="Holt, Sk" uniqKey="Holt S">SK Holt</name></author><author><name sortKey="Daling, Jr" uniqKey="Daling J">JR Daling</name></author><author><name sortKey="Moe, Re" uniqKey="Moe R">RE Moe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lakhani, Sr" uniqKey="Lakhani S">SR Lakhani</name></author><author><name sortKey="Audretsch, W" uniqKey="Audretsch W">W Audretsch</name></author><author><name sortKey="Cleton Jensen, Am" uniqKey="Cleton Jensen A">AM Cleton-Jensen</name></author><author><name sortKey="Cutuli, B" uniqKey="Cutuli B">B Cutuli</name></author><author><name sortKey="Ellis, I" uniqKey="Ellis I">I Ellis</name></author><author><name sortKey="Eusebi, V" uniqKey="Eusebi V">V Eusebi</name></author><author><name sortKey="Greco, M" uniqKey="Greco M">M Greco</name></author><author><name sortKey="Houslton, Rs" uniqKey="Houslton R">RS Houslton</name></author><author><name sortKey="Kuhl, Ck" uniqKey="Kuhl C">CK Kuhl</name></author><author><name sortKey="Kurtz, J" uniqKey="Kurtz J">J Kurtz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cianfrocca, M" uniqKey="Cianfrocca M">M Cianfrocca</name></author><author><name sortKey="Goldstein, Lj" uniqKey="Goldstein L">LJ Goldstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lehman, Cd" uniqKey="Lehman C">CD Lehman</name></author><author><name sortKey="Gatsonis, C" uniqKey="Gatsonis C">C Gatsonis</name></author><author><name sortKey="Kuhl, Ck" uniqKey="Kuhl C">CK Kuhl</name></author><author><name sortKey="Hendrick, Re" uniqKey="Hendrick R">RE Hendrick</name></author><author><name sortKey="Pisano, Ed" uniqKey="Pisano E">ED Pisano</name></author><author><name sortKey="Hanna, L" uniqKey="Hanna L">L Hanna</name></author><author><name sortKey="Peacock, S" uniqKey="Peacock S">S Peacock</name></author><author><name sortKey="Smazal, Sf" uniqKey="Smazal S">SF Smazal</name></author><author><name sortKey="Maki, Dd" uniqKey="Maki D">DD Maki</name></author><author><name sortKey="Julian, Tb" uniqKey="Julian T">TB Julian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Skinner, Ka" uniqKey="Skinner K">KA Skinner</name></author><author><name sortKey="Silverstein, Mj" uniqKey="Silverstein M">MJ Silverstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Singletary, Se" uniqKey="Singletary S">SE Singletary</name></author><author><name sortKey="Connolly, Jl" uniqKey="Connolly J">JL Connolly</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Askoxylakis, V" uniqKey="Askoxylakis V">V Askoxylakis</name></author><author><name sortKey="Thieke, C" uniqKey="Thieke C">C Thieke</name></author><author><name sortKey="Pleger, St" uniqKey="Pleger S">ST Pleger</name></author><author><name sortKey="Most, P" uniqKey="Most P">P Most</name></author><author><name sortKey="Tanner, J" uniqKey="Tanner J">J Tanner</name></author><author><name sortKey="Lindel, K" uniqKey="Lindel K">K Lindel</name></author><author><name sortKey="Katus, Ha" uniqKey="Katus H">HA Katus</name></author><author><name sortKey="Debus, J" uniqKey="Debus J">J Debus</name></author><author><name sortKey="Bischof, M" uniqKey="Bischof M">M Bischof</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lv, H" uniqKey="Lv H">H Lv</name></author><author><name sortKey="Pan, G" uniqKey="Pan G">G Pan</name></author><author><name sortKey="Zheng, G" uniqKey="Zheng G">G Zheng</name></author><author><name sortKey="Wu, X" uniqKey="Wu X">X Wu</name></author><author><name sortKey="Ren, H" uniqKey="Ren H">H Ren</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name></author><author><name sortKey="Wen, J" uniqKey="Wen J">J Wen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vogel, Kj" uniqKey="Vogel K">KJ Vogel</name></author><author><name sortKey="Atchley, Dp" uniqKey="Atchley D">DP Atchley</name></author><author><name sortKey="Erlichman, J" uniqKey="Erlichman J">J Erlichman</name></author><author><name sortKey="Broglio, Kr" uniqKey="Broglio K">KR Broglio</name></author><author><name sortKey="Ready, Kj" uniqKey="Ready K">KJ Ready</name></author><author><name sortKey="Valero, V" uniqKey="Valero V">V Valero</name></author><author><name sortKey="Amos, Ci" uniqKey="Amos C">CI Amos</name></author><author><name sortKey="Hortobagyi, Gn" uniqKey="Hortobagyi G">GN Hortobagyi</name></author><author><name sortKey="Lu, Kh" uniqKey="Lu K">KH Lu</name></author><author><name sortKey="Arun, B" uniqKey="Arun B">B Arun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Olsson, H" uniqKey="Olsson H">H Olsson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Giordano, Sh" uniqKey="Giordano S">SH Giordano</name></author><author><name sortKey="Cohen, Ds" uniqKey="Cohen D">DS Cohen</name></author><author><name sortKey="Buzdar, Au" uniqKey="Buzdar A">AU Buzdar</name></author><author><name sortKey="Perkins, G" uniqKey="Perkins G">G Perkins</name></author><author><name sortKey="Hortobagyi, Gn" uniqKey="Hortobagyi G">GN Hortobagyi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Iredale, R" uniqKey="Iredale R">R Iredale</name></author><author><name sortKey="Brain, K" uniqKey="Brain K">K Brain</name></author><author><name sortKey="Williams, B" uniqKey="Williams B">B Williams</name></author><author><name sortKey="France, E" uniqKey="France E">E France</name></author><author><name sortKey="Gray, J" uniqKey="Gray J">J Gray</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yager, Jd" uniqKey="Yager J">JD Yager</name></author><author><name sortKey="Davidson, Ne" uniqKey="Davidson N">NE Davidson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nass, Sj" uniqKey="Nass S">SJ Nass</name></author><author><name sortKey="Davidson, Ne" uniqKey="Davidson N">NE Davidson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Antonova, L" uniqKey="Antonova L">L Antonova</name></author><author><name sortKey="Aronson, K" uniqKey="Aronson K">K Aronson</name></author><author><name sortKey="Mueller, Cr" uniqKey="Mueller C">CR Mueller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mctiernan, A" uniqKey="Mctiernan A">A McTiernan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Friedenreich, Cm" uniqKey="Friedenreich C">CM Friedenreich</name></author><author><name sortKey="Courneya, Ks" uniqKey="Courneya K">KS Courneya</name></author><author><name sortKey="Bryant, He" uniqKey="Bryant H">HE Bryant</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Macconaill, Le" uniqKey="Macconaill L">LE MacConaill</name></author><author><name sortKey="Campbell, Cd" uniqKey="Campbell C">CD Campbell</name></author><author><name sortKey="Kehoe, Sm" uniqKey="Kehoe S">SM Kehoe</name></author><author><name sortKey="Bass, Aj" uniqKey="Bass A">AJ Bass</name></author><author><name sortKey="Hatton, C" uniqKey="Hatton C">C Hatton</name></author><author><name sortKey="Niu, L" uniqKey="Niu L">L Niu</name></author><author><name sortKey="Davis, M" uniqKey="Davis M">M Davis</name></author><author><name sortKey="Yao, K" uniqKey="Yao K">K Yao</name></author><author><name sortKey="Hanna, M" uniqKey="Hanna M">M Hanna</name></author><author><name sortKey="Mondal, C" uniqKey="Mondal C">C Mondal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Martin, Am" uniqKey="Martin A">AM Martin</name></author><author><name sortKey="Weber, Bl" uniqKey="Weber B">BL Weber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Plak, K" uniqKey="Plak K">K Plak</name></author><author><name sortKey="Czarnecka, Am" uniqKey="Czarnecka A">AM Czarnecka</name></author><author><name sortKey="Krawczyk, T" uniqKey="Krawczyk T">T Krawczyk</name></author><author><name sortKey="Golik, P" uniqKey="Golik P">P Golik</name></author><author><name sortKey="Bartnik, E" uniqKey="Bartnik E">E Bartnik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lynch, Ht" uniqKey="Lynch H">HT Lynch</name></author><author><name sortKey="Silva, E" uniqKey="Silva E">E Silva</name></author><author><name sortKey="Snyder, C" uniqKey="Snyder C">C Snyder</name></author><author><name sortKey="Lynch, Jf" uniqKey="Lynch J">JF Lynch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Singletary, Se" uniqKey="Singletary S">SE Singletary</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kadouri, L" uniqKey="Kadouri L">L Kadouri</name></author><author><name sortKey="Hubert, A" uniqKey="Hubert A">A Hubert</name></author><author><name sortKey="Rotenberg, Y" uniqKey="Rotenberg Y">Y Rotenberg</name></author><author><name sortKey="Hamburger, T" uniqKey="Hamburger T">T Hamburger</name></author><author><name sortKey="Sagi, M" uniqKey="Sagi M">M Sagi</name></author><author><name sortKey="Nechushtan, C" uniqKey="Nechushtan C">C Nechushtan</name></author><author><name sortKey="Abeliovich, D" uniqKey="Abeliovich D">D Abeliovich</name></author><author><name sortKey="Peretz, T" uniqKey="Peretz T">T Peretz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Campeau, Pm" uniqKey="Campeau P">PM Campeau</name></author><author><name sortKey="Foulkes, Wd" uniqKey="Foulkes W">WD Foulkes</name></author><author><name sortKey="Tischkowitz, Md" uniqKey="Tischkowitz M">MD Tischkowitz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="King, Mc" uniqKey="King M">MC King</name></author><author><name sortKey="Marks, Jh" uniqKey="Marks J">JH Marks</name></author><author><name sortKey="Mandell, Jb" uniqKey="Mandell J">JB Mandell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thorslund, T" uniqKey="Thorslund T">T Thorslund</name></author><author><name sortKey="West, Sc" uniqKey="West S">SC West</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Welcsh, Pl" uniqKey="Welcsh P">PL Welcsh</name></author><author><name sortKey="King, Mc" uniqKey="King M">MC King</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Narod, Sa" uniqKey="Narod S">SA Narod</name></author><author><name sortKey="Foulkes, Wd" uniqKey="Foulkes W">WD Foulkes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thorslund, T" uniqKey="Thorslund T">T Thorslund</name></author><author><name sortKey="Esashi, F" uniqKey="Esashi F">F Esashi</name></author><author><name sortKey="West, Sc" uniqKey="West S">SC West</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Verhoog, Lc" uniqKey="Verhoog L">LC Verhoog</name></author><author><name sortKey="Berns, Em" uniqKey="Berns E">EM Berns</name></author><author><name sortKey="Brekelmans, Ct" uniqKey="Brekelmans C">CT Brekelmans</name></author><author><name sortKey="Seynaeve, C" uniqKey="Seynaeve C">C Seynaeve</name></author><author><name sortKey="Meijers Heijboer, Ej" uniqKey="Meijers Heijboer E">EJ Meijers-Heijboer</name></author><author><name sortKey="Klijn, Jg" uniqKey="Klijn J">JG Klijn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Loman, N" uniqKey="Loman N">N Loman</name></author><author><name sortKey="Johannsson, O" uniqKey="Johannsson O">O Johannsson</name></author><author><name sortKey="Bendahl, P" uniqKey="Bendahl P">P Bendahl</name></author><author><name sortKey="Dahl, N" uniqKey="Dahl N">N Dahl</name></author><author><name sortKey="Einbeigi, Z" uniqKey="Einbeigi Z">Z Einbeigi</name></author><author><name sortKey="Gerdes, A" uniqKey="Gerdes A">A Gerdes</name></author><author><name sortKey="Borg, A" uniqKey="Borg A">A Borg</name></author><author><name sortKey="Olsson, H" uniqKey="Olsson H">H Olsson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lim, Ly" uniqKey="Lim L">LY Lim</name></author><author><name sortKey="Vidnovic, N" uniqKey="Vidnovic N">N Vidnovic</name></author><author><name sortKey="Ellisen, Lw" uniqKey="Ellisen L">LW Ellisen</name></author><author><name sortKey="Leong, Co" uniqKey="Leong C">CO Leong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bergamaschi, D" uniqKey="Bergamaschi D">D Bergamaschi</name></author><author><name sortKey="Gasco, M" uniqKey="Gasco M">M Gasco</name></author><author><name sortKey="Hiller, L" uniqKey="Hiller L">L Hiller</name></author><author><name sortKey="Sullivan, A" uniqKey="Sullivan A">A Sullivan</name></author><author><name sortKey="Syed, N" uniqKey="Syed N">N Syed</name></author><author><name sortKey="Trigiante, G" uniqKey="Trigiante G">G Trigiante</name></author><author><name sortKey="Yulug, I" uniqKey="Yulug I">I Yulug</name></author><author><name sortKey="Merlano, M" uniqKey="Merlano M">M Merlano</name></author><author><name sortKey="Numico, G" uniqKey="Numico G">G Numico</name></author><author><name sortKey="Comino, A" uniqKey="Comino A">A Comino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Geisler, S" uniqKey="Geisler S">S Geisler</name></author><author><name sortKey="Lonning, Pe" uniqKey="Lonning P">PE Lonning</name></author><author><name sortKey="Aas, T" uniqKey="Aas T">T Aas</name></author><author><name sortKey="Johnsen, H" uniqKey="Johnsen H">H Johnsen</name></author><author><name sortKey="Fluge, O" uniqKey="Fluge O">O Fluge</name></author><author><name sortKey="Haugen, Df" uniqKey="Haugen D">DF Haugen</name></author><author><name sortKey="Lillehaug, Jr" uniqKey="Lillehaug J">JR Lillehaug</name></author><author><name sortKey="Akslen, La" uniqKey="Akslen L">LA Akslen</name></author><author><name sortKey="Borresen Dale, Al" uniqKey="Borresen Dale A">AL Borresen-Dale</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beroud, C" uniqKey="Beroud C">C Beroud</name></author><author><name sortKey="Soussi, T" uniqKey="Soussi T">T Soussi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vousden, Kh" uniqKey="Vousden K">KH Vousden</name></author><author><name sortKey="Lane, Dp" uniqKey="Lane D">DP Lane</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Olivier, M" uniqKey="Olivier M">M Olivier</name></author><author><name sortKey="Petitjean, A" uniqKey="Petitjean A">A Petitjean</name></author><author><name sortKey="Marcel, V" uniqKey="Marcel V">V Marcel</name></author><author><name sortKey="Petre, A" uniqKey="Petre A">A Petre</name></author><author><name sortKey="Mounawar, M" uniqKey="Mounawar M">M Mounawar</name></author><author><name sortKey="Plymoth, A" uniqKey="Plymoth A">A Plymoth</name></author><author><name sortKey="De Fromentel, Cc" uniqKey="De Fromentel C">CC de Fromentel</name></author><author><name sortKey="Hainaut, P" uniqKey="Hainaut P">P Hainaut</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hohenstein, P" uniqKey="Hohenstein P">P Hohenstein</name></author><author><name sortKey="Giles, Rh" uniqKey="Giles R">RH Giles</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Coutant, C" uniqKey="Coutant C">C Coutant</name></author><author><name sortKey="Rouzier, R" uniqKey="Rouzier R">R Rouzier</name></author><author><name sortKey="Qi, Y" uniqKey="Qi Y">Y Qi</name></author><author><name sortKey="Lehmann Che, J" uniqKey="Lehmann Che J">J Lehmann-Che</name></author><author><name sortKey="Bianchini, G" uniqKey="Bianchini G">G Bianchini</name></author><author><name sortKey="Iwamoto, T" uniqKey="Iwamoto T">T Iwamoto</name></author><author><name sortKey="Hortobagyi, Gn" uniqKey="Hortobagyi G">GN Hortobagyi</name></author><author><name sortKey="Symmans, Wf" uniqKey="Symmans W">WF Symmans</name></author><author><name sortKey="Uzan, S" uniqKey="Uzan S">S Uzan</name></author><author><name sortKey="Andre, F" uniqKey="Andre F">F Andre</name></author><author><name sortKey="De The, H" uniqKey="De The H">H de The</name></author><author><name sortKey="Pusztai, L" uniqKey="Pusztai L">L Pusztai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yamashita, H" uniqKey="Yamashita H">H Yamashita</name></author><author><name sortKey="Nishio, M" uniqKey="Nishio M">M Nishio</name></author><author><name sortKey="Toyama, T" uniqKey="Toyama T">T Toyama</name></author><author><name sortKey="Sugiura, H" uniqKey="Sugiura H">H Sugiura</name></author><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z Zhang</name></author><author><name sortKey="Kobayashi, S" uniqKey="Kobayashi S">S Kobayashi</name></author><author><name sortKey="Iwase, H" uniqKey="Iwase H">H Iwase</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Feki, A" uniqKey="Feki A">A Feki</name></author><author><name sortKey="Irminger Finger, I" uniqKey="Irminger Finger I">I Irminger-Finger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, J" uniqKey="Yang J">J Yang</name></author><author><name sortKey="Ren, Y" uniqKey="Ren Y">Y Ren</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author><author><name sortKey="Li, B" uniqKey="Li B">B Li</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name></author><author><name sortKey="Zhao, W" uniqKey="Zhao W">W Zhao</name></author><author><name sortKey="Xu, W" uniqKey="Xu W">W Xu</name></author><author><name sortKey="Li, T" uniqKey="Li T">T Li</name></author><author><name sortKey="Dai, F" uniqKey="Dai F">F Dai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wallace, Ja" uniqKey="Wallace J">JA Wallace</name></author><author><name sortKey="Li, F" uniqKey="Li F">F Li</name></author><author><name sortKey="Leone, G" uniqKey="Leone G">G Leone</name></author><author><name sortKey="Ostrowski, Mc" uniqKey="Ostrowski M">MC Ostrowski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tokunaga, E" uniqKey="Tokunaga E">E Tokunaga</name></author><author><name sortKey="Oki, E" uniqKey="Oki E">E Oki</name></author><author><name sortKey="Kimura, Y" uniqKey="Kimura Y">Y Kimura</name></author><author><name sortKey="Yamanaka, T" uniqKey="Yamanaka T">T Yamanaka</name></author><author><name sortKey="Egashira, A" uniqKey="Egashira A">A Egashira</name></author><author><name sortKey="Nishida, K" uniqKey="Nishida K">K Nishida</name></author><author><name sortKey="Koga, T" uniqKey="Koga T">T Koga</name></author><author><name sortKey="Morita, M" uniqKey="Morita M">M Morita</name></author><author><name sortKey="Kakeji, Y" uniqKey="Kakeji Y">Y Kakeji</name></author><author><name sortKey="Maehara, Y" uniqKey="Maehara Y">Y Maehara</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marty, B" uniqKey="Marty B">B Marty</name></author><author><name sortKey="Maire, V" uniqKey="Maire V">V Maire</name></author><author><name sortKey="Gravier, E" uniqKey="Gravier E">E Gravier</name></author><author><name sortKey="Rigaill, G" uniqKey="Rigaill G">G Rigaill</name></author><author><name sortKey="Vincent Salomon, A" uniqKey="Vincent Salomon A">A Vincent-Salomon</name></author><author><name sortKey="Kappler, M" uniqKey="Kappler M">M Kappler</name></author><author><name sortKey="Lebigot, I" uniqKey="Lebigot I">I Lebigot</name></author><author><name sortKey="Djelti, F" uniqKey="Djelti F">F Djelti</name></author><author><name sortKey="Tourdes, A" uniqKey="Tourdes A">A Tourdes</name></author><author><name sortKey="Gestraud, P" uniqKey="Gestraud P">P Gestraud</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shaw, Rj" uniqKey="Shaw R">RJ Shaw</name></author><author><name sortKey="Cantley, Lc" uniqKey="Cantley L">LC Cantley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Degraffenried, La" uniqKey="Degraffenried L">LA DeGraffenried</name></author><author><name sortKey="Fulcher, L" uniqKey="Fulcher L">L Fulcher</name></author><author><name sortKey="Friedrichs, We" uniqKey="Friedrichs W">WE Friedrichs</name></author><author><name sortKey="Grunwald, V" uniqKey="Grunwald V">V Grunwald</name></author><author><name sortKey="Ray, Rb" uniqKey="Ray R">RB Ray</name></author><author><name sortKey="Hidalgo, M" uniqKey="Hidalgo M">M Hidalgo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tate, G" uniqKey="Tate G">G Tate</name></author><author><name sortKey="Suzuki, T" uniqKey="Suzuki T">T Suzuki</name></author><author><name sortKey="Mitsuya, T" uniqKey="Mitsuya T">T Mitsuya</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Petrocelli, T" uniqKey="Petrocelli T">T Petrocelli</name></author><author><name sortKey="Slingerland, Jm" uniqKey="Slingerland J">JM Slingerland</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, Js" uniqKey="Lee J">JS Lee</name></author><author><name sortKey="Kim, Hs" uniqKey="Kim H">HS Kim</name></author><author><name sortKey="Kim, Yb" uniqKey="Kim Y">YB Kim</name></author><author><name sortKey="Lee, Mc" uniqKey="Lee M">MC Lee</name></author><author><name sortKey="Park, Cs" uniqKey="Park C">CS Park</name></author><author><name sortKey="Min, Kw" uniqKey="Min K">KW Min</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Steelman, Ls" uniqKey="Steelman L">LS Steelman</name></author><author><name sortKey="Navolanic, Pm" uniqKey="Navolanic P">PM Navolanic</name></author><author><name sortKey="Sokolosky, Ml" uniqKey="Sokolosky M">ML Sokolosky</name></author><author><name sortKey="Taylor, Jr" uniqKey="Taylor J">JR Taylor</name></author><author><name sortKey="Lehmann, Bd" uniqKey="Lehmann B">BD Lehmann</name></author><author><name sortKey="Chappell, Wh" uniqKey="Chappell W">WH Chappell</name></author><author><name sortKey="Abrams, Sl" uniqKey="Abrams S">SL Abrams</name></author><author><name sortKey="Wong, Ew" uniqKey="Wong E">EW Wong</name></author><author><name sortKey="Stadelman, Km" uniqKey="Stadelman K">KM Stadelman</name></author><author><name sortKey="Terrian, Dm" uniqKey="Terrian D">DM Terrian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tanaka, M" uniqKey="Tanaka M">M Tanaka</name></author><author><name sortKey="Koul, D" uniqKey="Koul D">D Koul</name></author><author><name sortKey="Davies, Ma" uniqKey="Davies M">MA Davies</name></author><author><name sortKey="Liebert, M" uniqKey="Liebert M">M Liebert</name></author><author><name sortKey="Steck, Pa" uniqKey="Steck P">PA Steck</name></author><author><name sortKey="Grossman, Hb" uniqKey="Grossman H">HB Grossman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bates, Rc" uniqKey="Bates R">RC Bates</name></author><author><name sortKey="Edwards, Ns" uniqKey="Edwards N">NS Edwards</name></author><author><name sortKey="Burns, Gf" uniqKey="Burns G">GF Burns</name></author><author><name sortKey="Fisher, De" uniqKey="Fisher D">DE Fisher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nevanlinna, H" uniqKey="Nevanlinna H">H Nevanlinna</name></author><author><name sortKey="Bartek, J" uniqKey="Bartek J">J Bartek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shaag, A" uniqKey="Shaag A">A Shaag</name></author><author><name sortKey="Walsh, T" uniqKey="Walsh T">T Walsh</name></author><author><name sortKey="Renbaum, P" uniqKey="Renbaum P">P Renbaum</name></author><author><name sortKey="Kirchhoff, T" uniqKey="Kirchhoff T">T Kirchhoff</name></author><author><name sortKey="Nafa, K" uniqKey="Nafa K">K Nafa</name></author><author><name sortKey="Shiovitz, S" uniqKey="Shiovitz S">S Shiovitz</name></author><author><name sortKey="Mandell, Jb" uniqKey="Mandell J">JB Mandell</name></author><author><name sortKey="Welcsh, P" uniqKey="Welcsh P">P Welcsh</name></author><author><name sortKey="Lee, Mk" uniqKey="Lee M">MK Lee</name></author><author><name sortKey="Ellis, N" uniqKey="Ellis N">N Ellis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abraham, Rt" uniqKey="Abraham R">RT Abraham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Angele, S" uniqKey="Angele S">S Angele</name></author><author><name sortKey="Romestaing, P" uniqKey="Romestaing P">P Romestaing</name></author><author><name sortKey="Moullan, N" uniqKey="Moullan N">N Moullan</name></author><author><name sortKey="Vuillaume, M" uniqKey="Vuillaume M">M Vuillaume</name></author><author><name sortKey="Chapot, B" uniqKey="Chapot B">B Chapot</name></author><author><name sortKey="Friesen, M" uniqKey="Friesen M">M Friesen</name></author><author><name sortKey="Jongmans, W" uniqKey="Jongmans W">W Jongmans</name></author><author><name sortKey="Cox, Dg" uniqKey="Cox D">DG Cox</name></author><author><name sortKey="Pisani, P" uniqKey="Pisani P">P Pisani</name></author><author><name sortKey="Gerard, Jp" uniqKey="Gerard J">JP Gerard</name></author><author><name sortKey="Hall, J" uniqKey="Hall J">J Hall</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mckinnon, Pj" uniqKey="Mckinnon P">PJ McKinnon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Milne, Rl" uniqKey="Milne R">RL Milne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, Jh" uniqKey="Lee J">JH Lee</name></author><author><name sortKey="Paull, Tt" uniqKey="Paull T">TT Paull</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Kilpivaara, O" uniqKey="Kilpivaara O">O Kilpivaara</name></author><author><name sortKey="Vahteristo, P" uniqKey="Vahteristo P">P Vahteristo</name></author><author><name sortKey="Falck, J" uniqKey="Falck J">J Falck</name></author><author><name sortKey="Syrjakoski, K" uniqKey="Syrjakoski K">K Syrjakoski</name></author><author><name sortKey="Eerola, H" uniqKey="Eerola H">H Eerola</name></author><author><name sortKey="Easton, D" uniqKey="Easton D">D Easton</name></author><author><name sortKey="Bartkova, J" uniqKey="Bartkova J">J Bartkova</name></author><author><name sortKey="Lukas, J" uniqKey="Lukas J">J Lukas</name></author><author><name sortKey="Heikkila, P" uniqKey="Heikkila P">P Heikkila</name></author><author><name sortKey="Aittomaki, K" uniqKey="Aittomaki K">K Aittomaki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kleibl, Z" uniqKey="Kleibl Z">Z Kleibl</name></author><author><name sortKey="Havranek, O" uniqKey="Havranek O">O Havranek</name></author><author><name sortKey="Novotny, J" uniqKey="Novotny J">J Novotny</name></author><author><name sortKey="Kleiblova, P" uniqKey="Kleiblova P">P Kleiblova</name></author><author><name sortKey="Soucek, P" uniqKey="Soucek P">P Soucek</name></author><author><name sortKey="Pohlreich, P" uniqKey="Pohlreich P">P Pohlreich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Le, Gm" uniqKey="Le G">GM Le</name></author><author><name sortKey="O Alley, Cd" uniqKey="O Alley C">CD O’Malley</name></author><author><name sortKey="Glaser, Sl" uniqKey="Glaser S">SL Glaser</name></author><author><name sortKey="Lynch, Cf" uniqKey="Lynch C">CF Lynch</name></author><author><name sortKey="Stanford, Jl" uniqKey="Stanford J">JL Stanford</name></author><author><name sortKey="Keegan, Th" uniqKey="Keegan T">TH Keegan</name></author><author><name sortKey="West, Dw" uniqKey="West D">DW West</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brown, Sl" uniqKey="Brown S">SL Brown</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bese, Ns" uniqKey="Bese N">NS Bese</name></author><author><name sortKey="Kiel, K" uniqKey="Kiel K">K Kiel</name></author><author><name sortKey="El Gueddari Bel, K" uniqKey="El Gueddari Bel K">K El-Gueddari Bel</name></author><author><name sortKey="Campbell, Ob" uniqKey="Campbell O">OB Campbell</name></author><author><name sortKey="Awuah, B" uniqKey="Awuah B">B Awuah</name></author><author><name sortKey="Vikram, B" uniqKey="Vikram B">B Vikram</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Goss, Pe" uniqKey="Goss P">PE Goss</name></author><author><name sortKey="Ingle, Jn" uniqKey="Ingle J">JN Ingle</name></author><author><name sortKey="Martino, S" uniqKey="Martino S">S Martino</name></author><author><name sortKey="Robert, Nj" uniqKey="Robert N">NJ Robert</name></author><author><name sortKey="Muss, Hb" uniqKey="Muss H">HB Muss</name></author><author><name sortKey="Piccart, Mj" uniqKey="Piccart M">MJ Piccart</name></author><author><name sortKey="Castiglione, M" uniqKey="Castiglione M">M Castiglione</name></author><author><name sortKey="Tu, D" uniqKey="Tu D">D Tu</name></author><author><name sortKey="Shepherd, Le" uniqKey="Shepherd L">LE Shepherd</name></author><author><name sortKey="Pritchard, Ki" uniqKey="Pritchard K">KI Pritchard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Crew, Kd" uniqKey="Crew K">KD Crew</name></author><author><name sortKey="Greenlee, H" uniqKey="Greenlee H">H Greenlee</name></author><author><name sortKey="Capodice, J" uniqKey="Capodice J">J Capodice</name></author><author><name sortKey="Raptis, G" uniqKey="Raptis G">G Raptis</name></author><author><name sortKey="Brafman, L" uniqKey="Brafman L">L Brafman</name></author><author><name sortKey="Fuentes, D" uniqKey="Fuentes D">D Fuentes</name></author><author><name sortKey="Sierra, A" uniqKey="Sierra A">A Sierra</name></author><author><name sortKey="Hershman, Dl" uniqKey="Hershman D">DL Hershman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zoli, W" uniqKey="Zoli W">W Zoli</name></author><author><name sortKey="Ulivi, P" uniqKey="Ulivi P">P Ulivi</name></author><author><name sortKey="Tesei, A" uniqKey="Tesei A">A Tesei</name></author><author><name sortKey="Fabbri, F" uniqKey="Fabbri F">F Fabbri</name></author><author><name sortKey="Rosetti, M" uniqKey="Rosetti M">M Rosetti</name></author><author><name sortKey="Maltoni, R" uniqKey="Maltoni R">R Maltoni</name></author><author><name sortKey="Giunchi, Dc" uniqKey="Giunchi D">DC Giunchi</name></author><author><name sortKey="Ricotti, L" uniqKey="Ricotti L">L Ricotti</name></author><author><name sortKey="Brigliadori, G" uniqKey="Brigliadori G">G Brigliadori</name></author><author><name sortKey="Vannini, I" uniqKey="Vannini I">I Vannini</name></author><author><name sortKey="Amadori, D" uniqKey="Amadori D">D Amadori</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcarthur, Hl" uniqKey="Mcarthur H">HL McArthur</name></author><author><name sortKey="Mahoney, Km" uniqKey="Mahoney K">KM Mahoney</name></author><author><name sortKey="Morris, Pg" uniqKey="Morris P">PG Morris</name></author><author><name sortKey="Patil, S" uniqKey="Patil S">S Patil</name></author><author><name sortKey="Jacks, Lm" uniqKey="Jacks L">LM Jacks</name></author><author><name sortKey="Howard, J" uniqKey="Howard J">J Howard</name></author><author><name sortKey="Norton, L" uniqKey="Norton L">L Norton</name></author><author><name sortKey="Hudis, Ca" uniqKey="Hudis C">CA Hudis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Piccart, M" uniqKey="Piccart M">M Piccart</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weiss, Rb" uniqKey="Weiss R">RB Weiss</name></author><author><name sortKey="Woolf, Sh" uniqKey="Woolf S">SH Woolf</name></author><author><name sortKey="Demakos, E" uniqKey="Demakos E">E Demakos</name></author><author><name sortKey="Holland, Jf" uniqKey="Holland J">JF Holland</name></author><author><name sortKey="Berry, Da" uniqKey="Berry D">DA Berry</name></author><author><name sortKey="Falkson, G" uniqKey="Falkson G">G Falkson</name></author><author><name sortKey="Cirrincione, Ct" uniqKey="Cirrincione C">CT Cirrincione</name></author><author><name sortKey="Robbins, A" uniqKey="Robbins A">A Robbins</name></author><author><name sortKey="Bothun, S" uniqKey="Bothun S">S Bothun</name></author><author><name sortKey="Henderson, Ic" uniqKey="Henderson I">IC Henderson</name></author><author><name sortKey="Norton, L" uniqKey="Norton L">L Norton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hedley, D" uniqKey="Hedley D">D Hedley</name></author><author><name sortKey="Ogilvie, L" uniqKey="Ogilvie L">L Ogilvie</name></author><author><name sortKey="Springer, C" uniqKey="Springer C">C Springer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nawa, A" uniqKey="Nawa A">A Nawa</name></author><author><name sortKey="Tanino, T" uniqKey="Tanino T">T Tanino</name></author><author><name sortKey="Luo, C" uniqKey="Luo C">C Luo</name></author><author><name sortKey="Iwaki, M" uniqKey="Iwaki M">M Iwaki</name></author><author><name sortKey="Kajiyama, H" uniqKey="Kajiyama H">H Kajiyama</name></author><author><name sortKey="Shibata, K" uniqKey="Shibata K">K Shibata</name></author><author><name sortKey="Yamamoto, E" uniqKey="Yamamoto E">E Yamamoto</name></author><author><name sortKey="Ino, K" uniqKey="Ino K">K Ino</name></author><author><name sortKey="Nishiyama, Y" uniqKey="Nishiyama Y">Y Nishiyama</name></author><author><name sortKey="Kikkawa, F" uniqKey="Kikkawa F">F Kikkawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Greco, O" uniqKey="Greco O">O Greco</name></author><author><name sortKey="Dachs, Gu" uniqKey="Dachs G">GU Dachs</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mckeown, Sr" uniqKey="Mckeown S">SR McKeown</name></author><author><name sortKey="Ward, C" uniqKey="Ward C">C Ward</name></author><author><name sortKey="Robson, T" uniqKey="Robson T">T Robson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Voeks, D" uniqKey="Voeks D">D Voeks</name></author><author><name sortKey="Martiniello Wilks, R" uniqKey="Martiniello Wilks R">R Martiniello-Wilks</name></author><author><name sortKey="Madden, V" uniqKey="Madden V">V Madden</name></author><author><name sortKey="Smith, K" uniqKey="Smith K">K Smith</name></author><author><name sortKey="Bennetts, E" uniqKey="Bennetts E">E Bennetts</name></author><author><name sortKey="Both, Gw" uniqKey="Both G">GW Both</name></author><author><name sortKey="Russell, Pj" uniqKey="Russell P">PJ Russell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Anderson, Wf" uniqKey="Anderson W">WF Anderson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chung Faye, Ga" uniqKey="Chung Faye G">GA Chung-Faye</name></author><author><name sortKey="Kerr, Dj" uniqKey="Kerr D">DJ Kerr</name></author><author><name sortKey="Young, Ls" uniqKey="Young L">LS Young</name></author><author><name sortKey="Searle, Pf" uniqKey="Searle P">PF Searle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schepelmann, S" uniqKey="Schepelmann S">S Schepelmann</name></author><author><name sortKey="Hallenbeck, P" uniqKey="Hallenbeck P">P Hallenbeck</name></author><author><name sortKey="Ogilvie, Lm" uniqKey="Ogilvie L">LM Ogilvie</name></author><author><name sortKey="Hedley, D" uniqKey="Hedley D">D Hedley</name></author><author><name sortKey="Friedlos, F" uniqKey="Friedlos F">F Friedlos</name></author><author><name sortKey="Martin, J" uniqKey="Martin J">J Martin</name></author><author><name sortKey="Scanlon, I" uniqKey="Scanlon I">I Scanlon</name></author><author><name sortKey="Hay, C" uniqKey="Hay C">C Hay</name></author><author><name sortKey="Hawkins, Lk" uniqKey="Hawkins L">LK Hawkins</name></author><author><name sortKey="Marais, R" uniqKey="Marais R">R Marais</name></author><author><name sortKey="Springer, Cj" uniqKey="Springer C">CJ Springer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chung Faye, Ga" uniqKey="Chung Faye G">GA Chung-Faye</name></author><author><name sortKey="Chen, Mj" uniqKey="Chen M">MJ Chen</name></author><author><name sortKey="Green, Nk" uniqKey="Green N">NK Green</name></author><author><name sortKey="Burton, A" uniqKey="Burton A">A Burton</name></author><author><name sortKey="Anderson, D" uniqKey="Anderson D">D Anderson</name></author><author><name sortKey="Mautner, V" uniqKey="Mautner V">V Mautner</name></author><author><name sortKey="Searle, Pf" uniqKey="Searle P">PF Searle</name></author><author><name sortKey="Kerr, Dj" uniqKey="Kerr D">DJ Kerr</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hernandez Alcoceba, R" uniqKey="Hernandez Alcoceba R">R Hernandez-Alcoceba</name></author><author><name sortKey="Sangro, B" uniqKey="Sangro B">B Sangro</name></author><author><name sortKey="Prieto, J" uniqKey="Prieto J">J Prieto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yi, Br" uniqKey="Yi B">BR Yi</name></author><author><name sortKey="O, Sn" uniqKey="O S">SN O</name></author><author><name sortKey="Kang, Nh" uniqKey="Kang N">NH Kang</name></author><author><name sortKey="Hwang, Ka" uniqKey="Hwang K">KA Hwang</name></author><author><name sortKey="Kim, Su" uniqKey="Kim S">SU Kim</name></author><author><name sortKey="Jeung, Eb" uniqKey="Jeung E">EB Jeung</name></author><author><name sortKey="Kim, Yb" uniqKey="Kim Y">YB Kim</name></author><author><name sortKey="Heo, Gj" uniqKey="Heo G">GJ Heo</name></author><author><name sortKey="Choi, Kc" uniqKey="Choi K">KC Choi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yi, Br" uniqKey="Yi B">BR Yi</name></author><author><name sortKey="Kang, Nh" uniqKey="Kang N">NH Kang</name></author><author><name sortKey="Hwang, Ka" uniqKey="Hwang K">KA Hwang</name></author><author><name sortKey="Kim, Su" uniqKey="Kim S">SU Kim</name></author><author><name sortKey="Jeung, Eb" uniqKey="Jeung E">EB Jeung</name></author><author><name sortKey="Choi, Kc" uniqKey="Choi K">KC Choi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dachs, Gu" uniqKey="Dachs G">GU Dachs</name></author><author><name sortKey="Hunt, Ma" uniqKey="Hunt M">MA Hunt</name></author><author><name sortKey="Syddall, S" uniqKey="Syddall S">S Syddall</name></author><author><name sortKey="Singleton, Dc" uniqKey="Singleton D">DC Singleton</name></author><author><name sortKey="Patterson, Av" uniqKey="Patterson A">AV Patterson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pfeifer, A" uniqKey="Pfeifer A">A Pfeifer</name></author><author><name sortKey="Verma, Im" uniqKey="Verma I">IM Verma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shah, K" uniqKey="Shah K">K Shah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ramnaraine, M" uniqKey="Ramnaraine M">M Ramnaraine</name></author><author><name sortKey="Pan, W" uniqKey="Pan W">W Pan</name></author><author><name sortKey="Goblirsch, M" uniqKey="Goblirsch M">M Goblirsch</name></author><author><name sortKey="Lynch, C" uniqKey="Lynch C">C Lynch</name></author><author><name sortKey="Lewis, V" uniqKey="Lewis V">V Lewis</name></author><author><name sortKey="Orchard, P" uniqKey="Orchard P">P Orchard</name></author><author><name sortKey="Mantyh, P" uniqKey="Mantyh P">P Mantyh</name></author><author><name sortKey="Clohisy, Dr" uniqKey="Clohisy D">DR Clohisy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nyati, Mk" uniqKey="Nyati M">MK Nyati</name></author><author><name sortKey="Symon, Z" uniqKey="Symon Z">Z Symon</name></author><author><name sortKey="Kievit, E" uniqKey="Kievit E">E Kievit</name></author><author><name sortKey="Dornfeld, Kj" uniqKey="Dornfeld K">KJ Dornfeld</name></author><author><name sortKey="Rynkiewicz, Sd" uniqKey="Rynkiewicz S">SD Rynkiewicz</name></author><author><name sortKey="Ross, Bd" uniqKey="Ross B">BD Ross</name></author><author><name sortKey="Rehemtulla, A" uniqKey="Rehemtulla A">A Rehemtulla</name></author><author><name sortKey="Lawrence, Ts" uniqKey="Lawrence T">TS Lawrence</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ireton, Gc" uniqKey="Ireton G">GC Ireton</name></author><author><name sortKey="Black, Me" uniqKey="Black M">ME Black</name></author><author><name sortKey="Stoddard, Bl" uniqKey="Stoddard B">BL Stoddard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ireton, Gc" uniqKey="Ireton G">GC Ireton</name></author><author><name sortKey="Black, Me" uniqKey="Black M">ME Black</name></author><author><name sortKey="Stoddard, Bl" uniqKey="Stoddard B">BL Stoddard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Denny, Wa" uniqKey="Denny W">WA Denny</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ireton, Gc" uniqKey="Ireton G">GC Ireton</name></author><author><name sortKey="Mcdermott, G" uniqKey="Mcdermott G">G McDermott</name></author><author><name sortKey="Black, Me" uniqKey="Black M">ME Black</name></author><author><name sortKey="Stoddard, Bl" uniqKey="Stoddard B">BL Stoddard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fuchita, M" uniqKey="Fuchita M">M Fuchita</name></author><author><name sortKey="Ardiani, A" uniqKey="Ardiani A">A Ardiani</name></author><author><name sortKey="Zhao, L" uniqKey="Zhao L">L Zhao</name></author><author><name sortKey="Serve, K" uniqKey="Serve K">K Serve</name></author><author><name sortKey="Stoddard, Bl" uniqKey="Stoddard B">BL Stoddard</name></author><author><name sortKey="Black, Me" uniqKey="Black M">ME Black</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Ky" uniqKey="Kim K">KY Kim</name></author><author><name sortKey="Kim, Su" uniqKey="Kim S">SU Kim</name></author><author><name sortKey="Leung, Pc" uniqKey="Leung P">PC Leung</name></author><author><name sortKey="Jeung, Eb" uniqKey="Jeung E">EB Jeung</name></author><author><name sortKey="Choi, Kc" uniqKey="Choi K">KC Choi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, Jk" uniqKey="Chen J">JK Chen</name></author><author><name sortKey="Hu, Lj" uniqKey="Hu L">LJ Hu</name></author><author><name sortKey="Wang, D" uniqKey="Wang D">D Wang</name></author><author><name sortKey="Lamborn, Kr" uniqKey="Lamborn K">KR Lamborn</name></author><author><name sortKey="Deen, Df" uniqKey="Deen D">DF Deen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miller, Cr" uniqKey="Miller C">CR Miller</name></author><author><name sortKey="Williams, Cr" uniqKey="Williams C">CR Williams</name></author><author><name sortKey="Buchsbaum, Dj" uniqKey="Buchsbaum D">DJ Buchsbaum</name></author><author><name sortKey="Gillespie, Gy" uniqKey="Gillespie G">GY Gillespie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Humerickhouse, R" uniqKey="Humerickhouse R">R Humerickhouse</name></author><author><name sortKey="Lohrbach, K" uniqKey="Lohrbach K">K Lohrbach</name></author><author><name sortKey="Li, L" uniqKey="Li L">L Li</name></author><author><name sortKey="Bosron, Wf" uniqKey="Bosron W">WF Bosron</name></author><author><name sortKey="Dolan, Me" uniqKey="Dolan M">ME Dolan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bencharit, S" uniqKey="Bencharit S">S Bencharit</name></author><author><name sortKey="Morton, Cl" uniqKey="Morton C">CL Morton</name></author><author><name sortKey="Howard Williams, El" uniqKey="Howard Williams E">EL Howard-Williams</name></author><author><name sortKey="Danks, Mk" uniqKey="Danks M">MK Danks</name></author><author><name sortKey="Potter, Pm" uniqKey="Potter P">PM Potter</name></author><author><name sortKey="Redinbo, Mr" uniqKey="Redinbo M">MR Redinbo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bodor, N" uniqKey="Bodor N">N Bodor</name></author><author><name sortKey="Buchwald, P" uniqKey="Buchwald P">P Buchwald</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wadkins, Rm" uniqKey="Wadkins R">RM Wadkins</name></author><author><name sortKey="Morton, Cl" uniqKey="Morton C">CL Morton</name></author><author><name sortKey="Weeks, Jk" uniqKey="Weeks J">JK Weeks</name></author><author><name sortKey="Oliver, L" uniqKey="Oliver L">L Oliver</name></author><author><name sortKey="Wierdl, M" uniqKey="Wierdl M">M Wierdl</name></author><author><name sortKey="Danks, Mk" uniqKey="Danks M">MK Danks</name></author><author><name sortKey="Potter, Pm" uniqKey="Potter P">PM Potter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wierdl, M" uniqKey="Wierdl M">M Wierdl</name></author><author><name sortKey="Morton, Cl" uniqKey="Morton C">CL Morton</name></author><author><name sortKey="Weeks, Jk" uniqKey="Weeks J">JK Weeks</name></author><author><name sortKey="Danks, Mk" uniqKey="Danks M">MK Danks</name></author><author><name sortKey="Harris, Lc" uniqKey="Harris L">LC Harris</name></author><author><name sortKey="Potter, Pm" uniqKey="Potter P">PM Potter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kojima, A" uniqKey="Kojima A">A Kojima</name></author><author><name sortKey="Hackett, Nr" uniqKey="Hackett N">NR Hackett</name></author><author><name sortKey="Ohwada, A" uniqKey="Ohwada A">A Ohwada</name></author><author><name sortKey="Crystal, Rg" uniqKey="Crystal R">RG Crystal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Dillen, Ij" uniqKey="Van Dillen I">IJ van Dillen</name></author><author><name sortKey="Mulder, Nh" uniqKey="Mulder N">NH Mulder</name></author><author><name sortKey="Vaalburg, W" uniqKey="Vaalburg W">W Vaalburg</name></author><author><name sortKey="De Vries, Ef" uniqKey="De Vries E">EF de Vries</name></author><author><name sortKey="Hospers, Ga" uniqKey="Hospers G">GA Hospers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gerolami, R" uniqKey="Gerolami R">R Gerolami</name></author><author><name sortKey="Cardoso, J" uniqKey="Cardoso J">J Cardoso</name></author><author><name sortKey="Lewin, M" uniqKey="Lewin M">M Lewin</name></author><author><name sortKey="Bralet, Mp" uniqKey="Bralet M">MP Bralet</name></author><author><name sortKey="Sa Cunha, A" uniqKey="Sa Cunha A">A Sa Cunha</name></author><author><name sortKey="Clement, O" uniqKey="Clement O">O Clement</name></author><author><name sortKey="Brechot, C" uniqKey="Brechot C">C Brechot</name></author><author><name sortKey="Tran, Pl" uniqKey="Tran P">PL Tran</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fillat, C" uniqKey="Fillat C">C Fillat</name></author><author><name sortKey="Carrio, M" uniqKey="Carrio M">M Carrio</name></author><author><name sortKey="Cascante, A" uniqKey="Cascante A">A Cascante</name></author><author><name sortKey="Sangro, B" uniqKey="Sangro B">B Sangro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, Q" uniqKey="Huang Q">Q Huang</name></author><author><name sortKey="Pu, P" uniqKey="Pu P">P Pu</name></author><author><name sortKey="Xia, Z" uniqKey="Xia Z">Z Xia</name></author><author><name sortKey="You, Y" uniqKey="You Y">Y You</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cowen, Rl" uniqKey="Cowen R">RL Cowen</name></author><author><name sortKey="Williams, Jc" uniqKey="Williams J">JC Williams</name></author><author><name sortKey="Emery, S" uniqKey="Emery S">S Emery</name></author><author><name sortKey="Blakey, D" uniqKey="Blakey D">D Blakey</name></author><author><name sortKey="Darling, Jl" uniqKey="Darling J">JL Darling</name></author><author><name sortKey="Lowenstein, Pr" uniqKey="Lowenstein P">PR Lowenstein</name></author><author><name sortKey="Castro, Mg" uniqKey="Castro M">MG Castro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Muller, Fj" uniqKey="Muller F">FJ Muller</name></author><author><name sortKey="Snyder, Ey" uniqKey="Snyder E">EY Snyder</name></author><author><name sortKey="Loring, Jf" uniqKey="Loring J">JF Loring</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Su" uniqKey="Kim S">SU Kim</name></author><author><name sortKey="Jeung, Eb" uniqKey="Jeung E">EB Jeung</name></author><author><name sortKey="Kim, Yb" uniqKey="Kim Y">YB Kim</name></author><author><name sortKey="Cho, Mh" uniqKey="Cho M">MH Cho</name></author><author><name sortKey="Choi, Kc" uniqKey="Choi K">KC Choi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tang, Y" uniqKey="Tang Y">Y Tang</name></author><author><name sortKey="Shah, K" uniqKey="Shah K">K Shah</name></author><author><name sortKey="Messerli, Sm" uniqKey="Messerli S">SM Messerli</name></author><author><name sortKey="Snyder, E" uniqKey="Snyder E">E Snyder</name></author><author><name sortKey="Breakefield, X" uniqKey="Breakefield X">X Breakefield</name></author><author><name sortKey="Weissleder, R" uniqKey="Weissleder R">R Weissleder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Power, At" uniqKey="Power A">AT Power</name></author><author><name sortKey="Bell, Jc" uniqKey="Bell J">JC Bell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Ky" uniqKey="Kim K">KY Kim</name></author><author><name sortKey="Yi, Br" uniqKey="Yi B">BR Yi</name></author><author><name sortKey="Lee, Hr" uniqKey="Lee H">HR Lee</name></author><author><name sortKey="Kang, Nh" uniqKey="Kang N">NH Kang</name></author><author><name sortKey="Jeung, Eb" uniqKey="Jeung E">EB Jeung</name></author><author><name sortKey="Kim, Su" uniqKey="Kim S">SU Kim</name></author><author><name sortKey="Choi, Kc" uniqKey="Choi K">KC Choi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aboody, Ks" uniqKey="Aboody K">KS Aboody</name></author><author><name sortKey="Najbauer, J" uniqKey="Najbauer J">J Najbauer</name></author><author><name sortKey="Danks, Mk" uniqKey="Danks M">MK Danks</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gutova, M" uniqKey="Gutova M">M Gutova</name></author><author><name sortKey="Najbauer, J" uniqKey="Najbauer J">J Najbauer</name></author><author><name sortKey="Frank, Rt" uniqKey="Frank R">RT Frank</name></author><author><name sortKey="Kendall, Se" uniqKey="Kendall S">SE Kendall</name></author><author><name sortKey="Gevorgyan, A" uniqKey="Gevorgyan A">A Gevorgyan</name></author><author><name sortKey="Metz, Mz" uniqKey="Metz M">MZ Metz</name></author><author><name sortKey="Guevorkian, M" uniqKey="Guevorkian M">M Guevorkian</name></author><author><name sortKey="Edmiston, M" uniqKey="Edmiston M">M Edmiston</name></author><author><name sortKey="Zhao, D" uniqKey="Zhao D">D Zhao</name></author><author><name sortKey="Glackin, Ca" uniqKey="Glackin C">CA Glackin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bithell, A" uniqKey="Bithell A">A Bithell</name></author><author><name sortKey="Williams, Bp" uniqKey="Williams B">BP Williams</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Sk" uniqKey="Kim S">SK Kim</name></author><author><name sortKey="Kim, Su" uniqKey="Kim S">SU Kim</name></author><author><name sortKey="Park, Ih" uniqKey="Park I">IH Park</name></author><author><name sortKey="Bang, Jh" uniqKey="Bang J">JH Bang</name></author><author><name sortKey="Aboody, Ks" uniqKey="Aboody K">KS Aboody</name></author><author><name sortKey="Wang, Kc" uniqKey="Wang K">KC Wang</name></author><author><name sortKey="Cho, Bk" uniqKey="Cho B">BK Cho</name></author><author><name sortKey="Kim, M" uniqKey="Kim M">M Kim</name></author><author><name sortKey="Menon, Lg" uniqKey="Menon L">LG Menon</name></author><author><name sortKey="Black, Pm" uniqKey="Black P">PM Black</name></author><author><name sortKey="Carroll, Rs" uniqKey="Carroll R">RS Carroll</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sohur, Us" uniqKey="Sohur U">US Sohur</name></author><author><name sortKey="Emsley, Jg" uniqKey="Emsley J">JG Emsley</name></author><author><name sortKey="Mitchell, Bd" uniqKey="Mitchell B">BD Mitchell</name></author><author><name sortKey="Macklis, Jd" uniqKey="Macklis J">JD Macklis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Su" uniqKey="Kim S">SU Kim</name></author><author><name sortKey="Park, Ih" uniqKey="Park I">IH Park</name></author><author><name sortKey="Kim, Th" uniqKey="Kim T">TH Kim</name></author><author><name sortKey="Kim, Ks" uniqKey="Kim K">KS Kim</name></author><author><name sortKey="Choi, Hb" uniqKey="Choi H">HB Choi</name></author><author><name sortKey="Hong, Sh" uniqKey="Hong S">SH Hong</name></author><author><name sortKey="Bang, Jh" uniqKey="Bang J">JH Bang</name></author><author><name sortKey="Lee, Ma" uniqKey="Lee M">MA Lee</name></author><author><name sortKey="Joo, Is" uniqKey="Joo I">IS Joo</name></author><author><name sortKey="Lee, Cs" uniqKey="Lee C">CS Lee</name></author><author><name sortKey="Kim, Ys" uniqKey="Kim Y">YS Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Joo, Km" uniqKey="Joo K">KM Joo</name></author><author><name sortKey="Park, Ih" uniqKey="Park I">IH Park</name></author><author><name sortKey="Shin, Jy" uniqKey="Shin J">JY Shin</name></author><author><name sortKey="Jin, J" uniqKey="Jin J">J Jin</name></author><author><name sortKey="Kang, Bg" uniqKey="Kang B">BG Kang</name></author><author><name sortKey="Kim, Mh" uniqKey="Kim M">MH Kim</name></author><author><name sortKey="Lee, Sj" uniqKey="Lee S">SJ Lee</name></author><author><name sortKey="Jo, My" uniqKey="Jo M">MY Jo</name></author><author><name sortKey="Kim, Su" uniqKey="Kim S">SU Kim</name></author><author><name sortKey="Nam, Dh" uniqKey="Nam D">DH Nam</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Int J Oncol</journal-id><journal-id journal-id-type="iso-abbrev">Int. J. Oncol</journal-id><journal-id journal-id-type="publisher-id">IJO</journal-id><journal-title-group><journal-title>International Journal of Oncology</journal-title></journal-title-group><issn pub-type="ppub">1019-6439</issn><issn pub-type="epub">1791-2423</issn><publisher><publisher-name>D.A. Spandidos</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22736197</article-id><article-id pub-id-type="pmc">3582792</article-id><article-id pub-id-type="doi">10.3892/ijo.2012.1523</article-id><article-id pub-id-type="publisher-id">ijo-41-03-0798</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Therapeutic potential of stem cells expressing suicide genes that selectively target human breast cancer cells: Evidence that they exert tumoricidal effects via tumor tropism</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>YI</surname><given-names>BO-RIM</given-names></name><xref ref-type="aff" rid="af1-ijo-41-03-0798"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>CHOI</surname><given-names>KELVIN J.</given-names></name><xref ref-type="aff" rid="af2-ijo-41-03-0798"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>KIM</surname><given-names>SEUNG U.</given-names></name><xref ref-type="aff" rid="af3-ijo-41-03-0798"><sup>3</sup></xref><xref ref-type="aff" rid="af4-ijo-41-03-0798"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>CHOI</surname><given-names>KYUNG-CHUL</given-names></name><xref ref-type="aff" rid="af1-ijo-41-03-0798"><sup>1</sup></xref><xref ref-type="corresp" rid="c1-ijo-41-03-0798"></xref></contrib></contrib-group><aff id="af1-ijo-41-03-0798"><label>1</label>Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk,<country>Republic of Korea</country>;</aff><aff id="af2-ijo-41-03-0798"><label>2</label>Departments of Chemistry and</aff><aff id="af3-ijo-41-03-0798"><label>3</label>Medicine, University of British Columbia, Vancouver, British Columbia,<country>Canada</country>;</aff><aff id="af4-ijo-41-03-0798"><label>4</label>Medical Research Institute, Chung-Ang University College of Medicine, Seoul,<country>Republic of Korea</country></aff><author-notes><corresp id="c1-ijo-41-03-0798">Correspondence to: Professor Kyung-Chul Choi, Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea, E-mail: <email>kchoi@cbu.ac.kr</email></corresp></author-notes><pub-date pub-type="collection"><month>9</month><year>2012</year></pub-date><pub-date pub-type="epub"><day>20</day><month>6</month><year>2012</year></pub-date><pub-date pub-type="pmc-release"><day>20</day><month>6</month><year>2012</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<volume>41</volume><issue>3</issue><fpage>798</fpage><lpage>804</lpage><history><date date-type="received"><day>21</day><month>3</month><year>2012</year></date><date date-type="accepted"><day>30</day><month>5</month><year>2012</year></date></history><permissions><copyright-statement>Copyright © 2012, Spandidos Publications</copyright-statement><copyright-year>2012</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/3.0"><license-p>This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.</license-p></license></permissions><abstract><p>Breast cancer is the most prevalent cancer in women worldwide and is classified into ductal and lobular carcinoma. Breast cancer as well as lobular carcinoma is associated with various risk factors such as gender, age, female hormone exposure, ethnicity, family history and genetic risk factor-associated genes. Genes associated with a high risk of developing breast cancer include <italic>BRCA1</italic>, <italic>BRCA2</italic>, <italic>p53</italic>, <italic>PTEN</italic>, <italic>CHEK2</italic> and <italic>ATM</italic>. Surgery, chemotherapy, radiotherapy and hormone therapy are used to treat breast cancer but these therapies, except for surgery, have many side-effects such as alopecia, anesthesia, diarrhea and arthralgia. Gene-directed enzyme/prodrug therapy (GEPT) or suicide gene therapy, may improve the therapeutic efficacy of conventional cancer radiotherapy and chemotherapy without side-effects. GEPT most often involves the use of a viral vector to deliver a gene not found in mammalian cells and that produces enzymes which can convert a relatively non-toxic prodrug into a toxic agent. Examples of these systems include cytosine deaminase/5-fluorocytosine (CD/5-FC), carboxyl esterase/irinotecan (CE/CPT-11), and thymidine kinase/ganciclovir (TK/GCV). Recently, therapies based on genetically engineered stem cells (GESTECs) using a GEPT system have received a great deal of attention for their clinical and therapeutic potential to treat breast cancer. In this review, we discuss the potential of GESTECs via tumor tropism effects and therapeutic efficacy against several different types of cancer cells. GESTECs represent a useful tool for treating breast cancer without inducing injuries associated with conventional therapeutic modalities.</p></abstract><kwd-group><kwd>gene-direct enzyme/prodrug therapy</kwd><kwd>stem cell therapy</kwd><kwd>cytosine deaminase</kwd><kwd>carboxyl esterase</kwd><kwd>thymidine kinase</kwd><kwd>breast cancer</kwd></kwd-group></article-meta></front><body><sec><title>Contents</title><list list-type="order"><list-item><p>Breast cancer</p></list-item><list-item><p>GEPT using various prodrug/enzymes</p></list-item><list-item><p>Genetically engineered stem cell (GESTEC)-based therapy for treating breast cancer</p></list-item><list-item><p>Conclusions</p></list-item></list></sec><sec><label>1.</label><title>Breast cancer</title><sec><title>Overview</title><p>Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer mortality in women, accounting for 23% of all cancer cases and 14% of all cases of cancer mortality (<xref rid="b1-ijo-41-03-0798" ref-type="bibr">1</xref>). The breasts are composed of fat, glandular, and connective (fibrous) tissues, and contain several lobes which are divided into lobules that end in milk glands. Tiny ducts run from the glands, converge, and end in the nipple. Breast cancer changes the size or shape of the breast and can be separated into two histopathological categories: ductal and lobular carcinoma (<xref rid="b2-ijo-41-03-0798" ref-type="bibr">2</xref>). Additionally, these carcinomas are further divided into <italic>in situ</italic> and invasive carcinomas according to whether the tumor is confined to the glandular component of the organ or whether it has invaded the stroma (<xref rid="b3-ijo-41-03-0798" ref-type="bibr">3</xref>). Ductal carcinoma represents 80% of breast cancer cases and presumably originates from malignant epithelial cells within the ducts or tubes that carry milk to the nipple from the breast (<xref rid="b4-ijo-41-03-0798" ref-type="bibr">4</xref>). Lobular carcinoma is a less common form of breast cancer that commences in the milk-producing lobules of the breast (<xref rid="b5-ijo-41-03-0798" ref-type="bibr">5</xref>). This type of carcinoma is composed of acini filled with a small, round, polygonal or cuboidal cells (<xref rid="b6-ijo-41-03-0798" ref-type="bibr">6</xref>).</p><p>Breast cancer progression includes five stages defined according to tumor size, spread to the lymph nodes, and metastasis (spread to a more distant part of the body) (<xref rid="b7-ijo-41-03-0798" ref-type="bibr">7</xref>). Stage 0 is a pre-cancerous state in which the cancerous cells have not spread outside of the milk-producing lobules or ducts. Lesions in this stage are also referred to as ductal carcinoma <italic>in situ</italic> (DCIS) and lobular carcinoma <italic>in situ</italic> (LCIS) (<xref rid="b8-ijo-41-03-0798" ref-type="bibr">8</xref>). DCIS is generally categorized into the five most common architectural subtypes, including papillary, micropapillary, cribriform solid, and comedo (<xref rid="b9-ijo-41-03-0798" ref-type="bibr">9</xref>). Stages I to III are characterized by lesions within the breast or regional lymph nodes; these stages are based on the size of the tumor and the spread to the lymph nodes (<xref rid="b10-ijo-41-03-0798" ref-type="bibr">10</xref>). Finally, stage IV is metastatic cancer that has spread to other organs of the body (i.e., lungs, bones, liver, or brain) (<xref rid="b11-ijo-41-03-0798" ref-type="bibr">11</xref>). Although breast cancer is the most frequently diagnosed cancer and the leading cause of cancer mortality in women, if detected during the early stages it can be treated successfully by surgery or chemotherapy (<xref rid="b12-ijo-41-03-0798" ref-type="bibr">12</xref>).</p></sec><sec><title>Causes</title><p>Variable risk factors for breast cancer include gender, age, female hormone exposure, ethnicity, obesity, family history of breast cancer, genetic risk factors, and many abnormal conditions of the breast (<xref rid="b13-ijo-41-03-0798" ref-type="bibr">13</xref>,<xref rid="b14-ijo-41-03-0798" ref-type="bibr">14</xref>). Being female is the main risk factor for developing breast cancer since women have significantly more breast cells than men. Nevertheless, men can also develop breast cancer but they account for <1% of all breast cancer cases (<xref rid="b15-ijo-41-03-0798" ref-type="bibr">15</xref>). Clinically, breast cancer in men is similar to that in women and is also affected by hormonal, genetic, and environmental factors (<xref rid="b16-ijo-41-03-0798" ref-type="bibr">16</xref>).</p><p>In women, cells in the breast are exposed to growth-stimulating female hormones including estrogen (E2) and progesterone (P4) (<xref rid="b17-ijo-41-03-0798" ref-type="bibr">17</xref>). E2 stimulates breast cell division which can increase the risk of permanent DNA damage (<xref rid="b18-ijo-41-03-0798" ref-type="bibr">18</xref>). The growth factor transforming growth factor-α (TGF-α) can also affect cell division, and overexpression of this factor is associated with increased cell division in breast cancer (<xref rid="b19-ijo-41-03-0798" ref-type="bibr">19</xref>).</p><p>The risk of developing breast cancer increases with age and doubles every 10 years until menopause (<xref rid="b20-ijo-41-03-0798" ref-type="bibr">20</xref>). Age is the strongest risk factor for breast cancer after gender (<xref rid="b21-ijo-41-03-0798" ref-type="bibr">21</xref>). There are also numerous genetic risk factors for breast cancer. Numerous cases of cancer begin when one or more genes in a cell mutate, thereby producing an abnormal protein or no protein at all (<xref rid="b22-ijo-41-03-0798" ref-type="bibr">22</xref>). Production of an abnormal protein and lack of protein production may cause cells to divide uncontrollably and become cancerous (<xref rid="b23-ijo-41-03-0798" ref-type="bibr">23</xref>). The normal function of genetic risk factor-associated genes is the suppression of tumorigenesis. Genes associated with a high risk of developing breast cancer include <italic>BRCA1</italic>, <italic>BRCA2</italic>, <italic>p53</italic>, <italic>PTEN</italic>, <italic>STK11</italic>, <italic>CHEK2</italic>, and <italic>ATM</italic>(<xref rid="b24-ijo-41-03-0798" ref-type="bibr">24</xref>,<xref rid="b25-ijo-41-03-0798" ref-type="bibr">25</xref>). Finally, various other factors such as medical history, life style, dense breast tissue, alcohol intake, and smoking can promote the development of breast cancer (<xref rid="b26-ijo-41-03-0798" ref-type="bibr">26</xref>).</p></sec><sec><title>BRCA1 and BRCA2</title><p>Mutation of breast cancer type 1 and 2 susceptibility proteins (BRCA1 and BRCA2) cause most hereditary breast or ovarian cancer syndromes. <italic>BRCA</italic> gene-associated mutations might also be caused by Li-Fraumeni-like syndrome (LFS) (<xref rid="b27-ijo-41-03-0798" ref-type="bibr">27</xref>,<xref rid="b28-ijo-41-03-0798" ref-type="bibr">28</xref>). Mutation of these genes confers a 43–84% risk of breast cancer by the age of 50–70 in women (<xref rid="b29-ijo-41-03-0798" ref-type="bibr">29</xref>,<xref rid="b30-ijo-41-03-0798" ref-type="bibr">30</xref>). It is now clear that the normal protein products of BRCA1 and BRCA2 are tumor suppressors (<xref rid="b31-ijo-41-03-0798" ref-type="bibr">31</xref>). <italic>BRCA1</italic> is located on chromosome 17. The BRCA1 protein acts as a hub protein that promotes genomic stability and DNA repair by its involvement in homologous recombination and nucleotide excision repair, DNA damage response and cell cycle check point control, chromatin remodeling, transcriptional regulation, and protein ubiquitylation (<xref rid="b32-ijo-41-03-0798" ref-type="bibr">32</xref>). <italic>BRCA2</italic> is located on chromosome 13. The BRCA2 protein plays an important role in maintaining genomic stability via homologous recombination, both during meiosis and repair of double-strand breaks (<xref rid="b33-ijo-41-03-0798" ref-type="bibr">33</xref>). Both BRCA1 and BRCA2 mutations have been found more often in patients with high grade breast cancer compared to age-matched control patients (<xref rid="b34-ijo-41-03-0798" ref-type="bibr">34</xref>). However, tumors with BRCA1 mutations have high mitotic counts and ones with BRCA2 mutations mostly contain less tubular structures. Furthermore, BRCA2 mutations are associated with a more extensive intraductal component than BRCA1 mutations, and increase the risks for certain childhood tumors (<xref rid="b35-ijo-41-03-0798" ref-type="bibr">35</xref>).</p></sec><sec><title>p53</title><p><italic>p53</italic> is a known tumor suppressor gene encoding a sequence-specific transcriptional regulator which controls cell cycle progression, senescence, differentiation, DNA repair, and apoptosis (<xref rid="b36-ijo-41-03-0798" ref-type="bibr">36</xref>). This gene has a major function in responding to cellular stress factors, such as DNA damage and hypoxia, resulting in a cascade of events that reduces the risk of cancer and prevents tumor development (<xref rid="b37-ijo-41-03-0798" ref-type="bibr">37</xref>). Moreover, <italic>p53</italic> mutations have been observed in all the major histogenetic groups, including cancer of the colon, stomach, breast, ovary, and esophagus, and account for >50% of all cancer cases (<xref rid="b38-ijo-41-03-0798" ref-type="bibr">38</xref>). A point mutation in the <italic>p53</italic> gene has been found between exon 4 and 10 that is located within the DNA binding domain of the p53 protein (<xref rid="b39-ijo-41-03-0798" ref-type="bibr">39</xref>). A somatic mutation in the <italic>p53</italic> gene is the most common genetic change found in 20–35% of breast cancers and is associated with poor prognosis (<xref rid="b40-ijo-41-03-0798" ref-type="bibr">40</xref>,<xref rid="b41-ijo-41-03-0798" ref-type="bibr">41</xref>). A significant number of breast cancer cases is linked with <italic>BRCA1</italic> mutations that may affect p53 function, and activates a p53-dependent response (<xref rid="b42-ijo-41-03-0798" ref-type="bibr">42</xref>). Furthermore, high expression of p53 is more frequently found in estrogen and progesterone receptor-negative breast cancers (<xref rid="b43-ijo-41-03-0798" ref-type="bibr">43</xref>,<xref rid="b44-ijo-41-03-0798" ref-type="bibr">44</xref>) and is also associated with a high proliferation rate, high histological grade, aneuploidy, and decreased survival rates (<xref rid="b45-ijo-41-03-0798" ref-type="bibr">45</xref>).</p></sec><sec><title>PTEN</title><p>Phosphatase and tensin homolog (PTEN) encoded by the <italic>PTEN</italic> gene in humans has been identified as a tumor suppressor in many types of cancer (<xref rid="b46-ijo-41-03-0798" ref-type="bibr">46</xref>). This lipid phosphatase is involved in cell cycle regulation and prevents cells from growing and dividing too rapidly (<xref rid="b47-ijo-41-03-0798" ref-type="bibr">47</xref>). The phosphatidylinositol (<xref rid="b3-ijo-41-03-0798" ref-type="bibr">3</xref>,<xref rid="b4-ijo-41-03-0798" ref-type="bibr">4</xref>,<xref rid="b5-ijo-41-03-0798" ref-type="bibr">5</xref>)-trisphosphate (PIP3) kinase-protein kinase B (PI3K-AKT) pathway is activated in human cancers. Activated PI3K is phosphorylated phosphatidylinositol-4,5-bisphosphate (PIP2) to generate PIP3 (<xref rid="b48-ijo-41-03-0798" ref-type="bibr">48</xref>,<xref rid="b49-ijo-41-03-0798" ref-type="bibr">49</xref>). PIP3 activates Akt and is an important lipid second messenger that has a role in tumorigenesis (<xref rid="b50-ijo-41-03-0798" ref-type="bibr">50</xref>). On the other hand, the PTEN protein, the key agonist of PI3K-AKT signaling, is inactivated in a broad spectrum of human cancers (<xref rid="b51-ijo-41-03-0798" ref-type="bibr">51</xref>). However, somatic PTEN deletions and mutations have been observed in breast, brain, prostate, and kidney cancer cell lines as well as in several primary tumors such as endometrial carcinomas, malignant gliomas, melanomas, and thyroid tumors (<xref rid="b52-ijo-41-03-0798" ref-type="bibr">52</xref>,<xref rid="b53-ijo-41-03-0798" ref-type="bibr">53</xref>). In particular, Cowden syndrome patients have a germ line PTEN mutation, and an increasing amount of data have associated PTEN loss with breast cancer (5–21%) (<xref rid="b54-ijo-41-03-0798" ref-type="bibr">54</xref>). It has also been reported that suppression of PTEN function increases breast cancer chemotherapeutic drug resistance (<xref rid="b55-ijo-41-03-0798" ref-type="bibr">55</xref>,<xref rid="b56-ijo-41-03-0798" ref-type="bibr">56</xref>). Some cell lines with mutated PTEN have an abnormal cell cycle and defective apoptotic responses (<xref rid="b57-ijo-41-03-0798" ref-type="bibr">57</xref>).</p></sec><sec><title>CHEK2 and ATM</title><p>The product of the cell cycle checkpoint kinase 2 (<italic>CHEK2</italic>) gene responds to DNA damage (double-strand breaks) in a dynamic, multistep process and protects genomic integrity (<xref rid="b58-ijo-41-03-0798" ref-type="bibr">58</xref>). CHEK2 is a serine/threonine protein kinase found in humans and yeast. Activation of CHEK2 is regulated through phosphorylation by ataxia telangiectasia mutated (ATM) in both yeast and humans (<xref rid="b59-ijo-41-03-0798" ref-type="bibr">59</xref>). ATM belongs to the PI3K-related protein kinase (PIKK) family and is responsible for the immediate and rapid response to double-strand breaks (<xref rid="b60-ijo-41-03-0798" ref-type="bibr">60</xref>,<xref rid="b61-ijo-41-03-0798" ref-type="bibr">61</xref>). However, mutation of this gene causes the development of ataxia-telangiectasia (AT), a neurodegenerative disease (<xref rid="b62-ijo-41-03-0798" ref-type="bibr">62</xref>). The relationship between AT and breast cancer was first reported 20 years ago with the observation that relatives of AT patients have an increased risk of breast cancer (<xref rid="b63-ijo-41-03-0798" ref-type="bibr">63</xref>).</p><p>Activated CHEK2 phosphorylates critical cell cycle proteins that results in the stabilization of p53 and the inhibition of Cdc25C phosphatase, leading to G1 cell-cycle arrest along with the prevention of entry into mitosis and the activation of DNA repair (<xref rid="b64-ijo-41-03-0798" ref-type="bibr">64</xref>). This kinase also phosphorylates BRCA1, resulting in get back DNA damage (<xref rid="b65-ijo-41-03-0798" ref-type="bibr">65</xref>). Mutations in the <italic>CHEK2</italic> gene, including truncation variant 1100delC, have been reported to increase breast cancer risk by up to two-fold and may vary according to the Li-Fraumeni syndrome as well as breast cancer (<xref rid="b66-ijo-41-03-0798" ref-type="bibr">66</xref>). Susceptibility to cancer due to this gene variation was first described in 1999, and the products of the <italic>CHEK2</italic> and <italic>ATM</italic> genes are now known to be involved in p53 inactivation (<xref rid="b67-ijo-41-03-0798" ref-type="bibr">67</xref>).</p></sec><sec><title>Breast cancer treatments</title><p>Breast cancer is almost always treated with surgery, chemotherapy, radiotherapy, and hormone therapy. Surgical procedures, called mastectomy or lumpectomy, have a role in treating most patients with breast cancer (<xref rid="b68-ijo-41-03-0798" ref-type="bibr">68</xref>). During these procedures, the cancerous lesions are removed from the breast along with some of the surrounding tissue. For this reason, the number of patients who receive breast implants after undergoing a mastectomy has increased (<xref rid="b69-ijo-41-03-0798" ref-type="bibr">69</xref>). After performing surgery to treat breast cancer, radiation is used as an adjuvant treatment depending on the disease stage (<xref rid="b70-ijo-41-03-0798" ref-type="bibr">70</xref>).</p><p>Hormonal therapy, including administration of tamoxifen, raloxifene (a selective estrogen receptor modulator, SERM), and aromatase inhibitors (AIs), increases the survival rate of hormone-sensitive breast cancer patients (<xref rid="b71-ijo-41-03-0798" ref-type="bibr">71</xref>). Treatment of breast cancer patients with AIs is more effective than tamoxifen although patients receiving AIs have a higher prevalence of osteoporosis, bone fractures, and musculoskeletal symptoms, particularly joint pain and stiffness (<xref rid="b72-ijo-41-03-0798" ref-type="bibr">72</xref>).</p><p>Chemotherapy is given to slow or stop the growth of cancer cells. For this, 5-fluorouracil (5-FU), cyclophosphamide, methotrexate, anthracyclines, trastuzumab, and taxanes are primarily used (<xref rid="b73-ijo-41-03-0798" ref-type="bibr">73</xref>). If the breast cancer is positive for human epidermal growth factor receptor 2 (HER-2), it is treated with trastuzumab (herceptin) which targets the <italic>HER-2</italic> oncogene (<xref rid="b74-ijo-41-03-0798" ref-type="bibr">74</xref>). 5-FU has also been the preferred chemotherapeutic agent for treating a majority of solid tumors, including gastric and colon cancers (<xref rid="b75-ijo-41-03-0798" ref-type="bibr">75</xref>). However, serious side-effects such as alopecia, anesthesia, diarrhea, and arthralgia, as well as high dose requirements have limited the use of these chemotherapeutic agents (<xref rid="b76-ijo-41-03-0798" ref-type="bibr">76</xref>).</p></sec></sec><sec><label>2.</label><title>GEPT using various prodrug/enzymes</title><p>Gene-direct enzyme/prodrug therapy (GEPT), or suicide gene therapy, aims to improve the therapeutic efficacy of conventional cancer radio- and chemotherapy without side-effects (<xref rid="b77-ijo-41-03-0798" ref-type="bibr">77</xref>,<xref rid="b78-ijo-41-03-0798" ref-type="bibr">78</xref>). This system is a novel approach with the potential to selectively eradicate tumor cells (<xref rid="b79-ijo-41-03-0798" ref-type="bibr">79</xref>). For this, an exogenous suicide enzyme gene is delivered to tumor cells (<xref rid="b80-ijo-41-03-0798" ref-type="bibr">80</xref>). GEPT systems most often involve the use of a viral vector (adeno-, lenti-, or retroviral vectors) to deliver a gene not normally found in mammalian cells that produces enzymes which, when expressed, can convert a relatively non-toxic prodrug into a toxic agent (<xref rid="b81-ijo-41-03-0798" ref-type="bibr">81</xref>,<xref rid="b82-ijo-41-03-0798" ref-type="bibr">82</xref>).</p><p>GEPT systems involve two separate events: direct cell death and cell death via the bystander effect (<xref rid="b83-ijo-41-03-0798" ref-type="bibr">83</xref>). The viral vectors transfected into the target tumor cells induced cell death (<xref rid="b84-ijo-41-03-0798" ref-type="bibr">84</xref>). Direct cell death is caused by expression of the viral DNA in the targeted tumor cells (<xref rid="b85-ijo-41-03-0798" ref-type="bibr">85</xref>). Next, cell death via the bystander effect is induced by the gene transfer of a viral or bacterial enzyme into targeted tumor cells. The enzymes convert an inactive prodrug into a short-lived toxic metabolite, leading to the death of cells surrounding the targeted tumor cells (<xref rid="b86-ijo-41-03-0798" ref-type="bibr">86</xref>). Prodrugs can be defined as pharmacologically inactive derivatives which require chemical transformation for the release or conversion into the active drug (<xref rid="b87-ijo-41-03-0798" ref-type="bibr">87</xref>). A suicide enzyme converts the administered non-toxic prodrug into an active drug which subsequently kills tumor cells but not normal tissues (<xref rid="b88-ijo-41-03-0798" ref-type="bibr">88</xref>). Several types of suicidal genes have been studied and used for therapeutic purposes (<xref rid="b82-ijo-41-03-0798" ref-type="bibr">82</xref>).</p><p>An advantage of these GEPT systems derives from the local bystander effect through which more wide-spread cell death is achieved without the need to express the gene in all cells (<xref rid="b89-ijo-41-03-0798" ref-type="bibr">89</xref>). This is due to the ability of the toxic metabolite to diffuse freely across cells membranes or via gap junctions (<xref rid="b90-ijo-41-03-0798" ref-type="bibr">90</xref>). Currently, a large number of enzyme/prodrug systems have been developed for GEPT. These include the cytosine deaminase/5-fluorocytosine (CD/5-FC), carboxyl esterase/irinotecan (CE/CPT-11), and thymidine kinase/ganciclovir (TK/GCV) systems (<xref rid="b91-ijo-41-03-0798" ref-type="bibr">91</xref>).</p><sec><title>Cytosine deaminase/5-fluorocytosine (CD/5-FC)</title><p>One of the most widely used suicidal genes is bacterial or yeast CD (from <italic>Escherichia coli</italic> or <italic>Saccharomyces cerevisiae</italic>) (<xref rid="b92-ijo-41-03-0798" ref-type="bibr">92</xref>). Both bacterial and yeast CD have been shown to inhibit tumor growth (<xref rid="b93-ijo-41-03-0798" ref-type="bibr">93</xref>). The enzyme encoded by the <italic>CD</italic> gene catalyzes the conversion of cytosine into uracil; it is an important member of the pyrimidine salvage pathway in prokaryotes and fungi, but is not present in multicellular eukaryotes (mammalian cells) (<xref rid="b94-ijo-41-03-0798" ref-type="bibr">94</xref>,<xref rid="b95-ijo-41-03-0798" ref-type="bibr">95</xref>). 5-FC is a hydrophilic antifungal drug with low toxicity in humans (<xref rid="b96-ijo-41-03-0798" ref-type="bibr">96</xref>). CD catalyzes the conversion of the non-cytotoxic prodrug 5-fluorocytosine (5-FC) into the cytotoxic chemotherapeutic agent 5-FU, resulting in anti-tumor activity (<xref rid="b97-ijo-41-03-0798" ref-type="bibr">97</xref>). CD is currently being explored for use in gene therapy applications against solid tumors due to this activity (<xref rid="b98-ijo-41-03-0798" ref-type="bibr">98</xref>).</p><p>The CD/5-FC system is very effective for treating human cancers as non-toxic 5-FC systemically administered can be converted into the cytotoxic agent 5-FU by the <italic>CD</italic> gene product located in the vicinity of the cancer (<xref rid="b99-ijo-41-03-0798" ref-type="bibr">99</xref>). Deamination of the 5-FC prodrug by CD results in the formation of two toxic metabolites: 5-fluorodeoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FURTP). FdUMP is a potent inhibitor of thymidylate synthetase (TS) which is an enzyme essential for DNA synthesis. This compound impairs DNA synthesis and promotes apoptosis in bacteria and tumor cells (<xref rid="b100-ijo-41-03-0798" ref-type="bibr">100</xref>,<xref rid="b101-ijo-41-03-0798" ref-type="bibr">101</xref>).</p></sec><sec><title>Carboxyl esterase/irinotecan (CE/CPT-11)</title><p>CE enzyme is a serine esterase found in a variety of tissues from numerous mammalian species (<xref rid="b102-ijo-41-03-0798" ref-type="bibr">102</xref>). This enzyme plays a critical role in increasing the solubility and bio-availability of therapeutic agents (<xref rid="b103-ijo-41-03-0798" ref-type="bibr">103</xref>,<xref rid="b104-ijo-41-03-0798" ref-type="bibr">104</xref>). It is cleaved into the bulky piperidino sidechain of 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyl-oxycamptothecin (irinotecan or CPT-11). The anti-cancer agent CPT-11 is a prodrug that is activated by CE to generate the active form 7-ethyl-10-hydroxycamptothecin (SN-38) (<xref rid="b105-ijo-41-03-0798" ref-type="bibr">105</xref>,<xref rid="b106-ijo-41-03-0798" ref-type="bibr">106</xref>). SN-38 is a strong mammalian topoisomerase I inhibitor that is 1,000-fold more potent than CPT-11. This agent induces the accumulation of double-strand DNA breaks in actively dividing cancer cells (<xref rid="b107-ijo-41-03-0798" ref-type="bibr">107</xref>).</p></sec><sec><title>Thymidine kinase/ganciclovir (TK/GCV)</title><p>The most common GEPT uses the herpes simplex type-1 thymidine kinase enzyme (HSV-TK) in conjunction with a variety of guanosine-based prodrugs, compounds originally developed as antiviral agents (<xref rid="b108-ijo-41-03-0798" ref-type="bibr">108</xref>). The HSV-TK enzyme converts to the prodrug into its monophosphate form, GCV, which is then further converted into the toxic triphosphates form, an intermediary metabolite, by cellular enzymes (<xref rid="b109-ijo-41-03-0798" ref-type="bibr">109</xref>,<xref rid="b110-ijo-41-03-0798" ref-type="bibr">110</xref>). These actions cause cell death by inhibiting the incorporation of dGTP into DNA without preventing progression through the S-phase; chain elongation is also inhibited (<xref rid="b111-ijo-41-03-0798" ref-type="bibr">111</xref>).</p></sec></sec><sec><label>3.</label><title>Genetically engineered stem cell (GESTEC)-based therapy for treating breast cancer</title><p>Toxicity of anticancer agents to normal cells is a major limitation of breast cancer therapy (<xref rid="b112-ijo-41-03-0798" ref-type="bibr">112</xref>). Therefore, stem cells have recently received a great deal of attention for their clinical and therapeutic potential to treat breast cancer. Stem cells are capable of continuous self-renewal and differentiation (<xref rid="b113-ijo-41-03-0798" ref-type="bibr">113</xref>,<xref rid="b114-ijo-41-03-0798" ref-type="bibr">114</xref>). A variety of stem cells, such as neural stem cells (NSCs), neural progenitor cells, and mesenchymal stem cells (MSCs) from bone marrow or adipose tissue, have been found to exert tumor-tropism effects (<xref rid="b115-ijo-41-03-0798" ref-type="bibr">115</xref>). This ability makes these cells attractive for use as targeted delivery vectors for antitumor therapies (<xref rid="b87-ijo-41-03-0798" ref-type="bibr">87</xref>,<xref rid="b88-ijo-41-03-0798" ref-type="bibr">88</xref>,<xref rid="b99-ijo-41-03-0798" ref-type="bibr">99</xref>,<xref rid="b116-ijo-41-03-0798" ref-type="bibr">116</xref>–<xref rid="b117-ijo-41-03-0798" ref-type="bibr">117</xref>). The tumor-tropism effects of stem cells are mediated by multiple cell-surface and secreted proteins, and candidate cytokines/receptors including stromal cell-derived factor-1 (SDF-1)/CXCR4, stem cell factor (SCF)/c-Kit, hepatocyte growth factor (HGF)/Met, vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR), monocyte chemoattractant protein-1 (MCP-1)/CCP, and high-mobility group box1 (HMGB1)/RAGE (<xref rid="b87-ijo-41-03-0798" ref-type="bibr">87</xref>,<xref rid="b88-ijo-41-03-0798" ref-type="bibr">88</xref>,<xref rid="b99-ijo-41-03-0798" ref-type="bibr">99</xref>,<xref rid="b117-ijo-41-03-0798" ref-type="bibr">117</xref>,<xref rid="b118-ijo-41-03-0798" ref-type="bibr">118</xref>). In addition, NSCs appear to migrate to cancer cells more efficiently compared to MSCs. Although both NSCs and MSCs have a tumor tropic effect, NSCs (50–100% of total cell number) were proven to display greater tropism towards tumor cells than MSCs (40–75% of total cell number) (<xref rid="b119-ijo-41-03-0798" ref-type="bibr">119</xref>).</p><p>The field of NSC research in recent years has seen major advances and efforts have been made to develop their use in potential stem cell-based transplantation therapies (<xref rid="b120-ijo-41-03-0798" ref-type="bibr">120</xref>). NSCs can be used to generate all major mature neural cell types such as neurons, oligodendrocytes, glial cells and cells of neuronal lineages (<xref rid="b121-ijo-41-03-0798" ref-type="bibr">121</xref>). The fetal brain, characterized by active neurogenesis, is thought to be a promising source of therapeutic NSCs (<xref rid="b122-ijo-41-03-0798" ref-type="bibr">122</xref>). Previous studies have shown that NSCs derived from human fetal telencephalon can be used for GESTEC-based therapy for treating several different cancers as well as brain diseases (<xref rid="b87-ijo-41-03-0798" ref-type="bibr">87</xref>,<xref rid="b88-ijo-41-03-0798" ref-type="bibr">88</xref>,<xref rid="b99-ijo-41-03-0798" ref-type="bibr">99</xref>). As this is based on a GEPT system, it involves the expression of several suicide enzymes (<xref rid="f1-ijo-41-03-0798" ref-type="fig">Fig. 1</xref>). In previous studies, GESTECs were immortalized by using retrovirus v-myc and suicide genes such as <italic>CD</italic>, <italic>CE</italic>, and <italic>TK</italic>. Therapeutic efficacy has been assessed by monitoring tumor-tropism in a brain cancer animal model (<xref rid="b123-ijo-41-03-0798" ref-type="bibr">123</xref>).</p><p>In other studies, NSCs expressing <italic>CD</italic> or <italic>CE</italic> genes in an animal model of breast cancer brain metastasis were found to significantly reduce breast tumor mass in the brain (<xref rid="b124-ijo-41-03-0798" ref-type="bibr">124</xref>). This demonstrated the therapeutic efficacy of GESTECs in the presence of a prodrug (<xref rid="b114-ijo-41-03-0798" ref-type="bibr">114</xref>). Brain metastases originate from cells that do not reside in the brain. This suggests that breast tumor metastases in the brain attract GESTECs as well as the original brain tumor. The therapeutic efficacy of GESTECs for treating several other types of cancer cells (i.e., ovarian, endometrial, and lung cancer cells) as well as brain tumors, including medulloblastomas and gliomas has also been demonstrated <italic>in vitro</italic>. Furthermore, therapies using GESTECs may use as breast cancer treatment <italic>in vitro</italic> and <italic>in vivo</italic>.</p></sec><sec sec-type="other"><label>4.</label><title>Conclusions</title><p>Breast cancer is the leading cause of cancer related mortality among women worldwide. Several gene mutations lead to the development of breast cancer including ductal and lobular breast carcinoma. Chemo-, hormone-, and radiotherapies are used to treat breast cancer but these therapies are associated with many side-effects. For this reason, GEPT systems have been examined as a novel anticancer therapeutic approach with the potential to selectively eradicate tumor cells. Prodrugs used for GEPT are primarily antimetabolites that require cell cycling (S phase) to induce cytotoxicity and are not active against normal cells. These systems may involve the use of NSCs which express suicide genes and have the ability to selectively migrate to tumors. In summary, GESTECs using GEPT systems may be an effective new modality for treating breast cancer as well as brain tumors without inducing injurious effects commonly associated with more conventional anticancer therapies.</p></sec></body><back><ack><p>This study was supported by two National Research Foundation of Korea (NRF) grants funded by the Ministry of Education, Science and Technology (MEST) of the Korean Government (no. 2010-0003093 and 2011-0015385).</p></ack><ref-list><title>References</title><ref id="b1-ijo-41-03-0798"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jemal</surname><given-names>A</given-names></name><name><surname>Bray</surname><given-names>F</given-names></name><name><surname>Center</surname><given-names>MM</given-names></name><name><surname>Ferlay</surname><given-names>J</given-names></name><name><surname>Ward</surname><given-names>E</given-names></name><name><surname>Forman</surname><given-names>D</given-names></name></person-group><article-title>Global cancer statistics</article-title><source>CA Cancer J Clin</source><volume>61</volume><fpage>69</fpage><lpage>90</lpage><year>2011</year><pub-id pub-id-type="pmid">21296855</pub-id></element-citation></ref><ref id="b2-ijo-41-03-0798"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vincent-Salomon</surname><given-names>A</given-names></name><name><surname>Thiery</surname><given-names>JP</given-names></name></person-group><article-title>Host microenvironment in breast cancer development: epithelial-mesenchymal transition in breast cancer development</article-title><source>Breast Cancer Res</source><volume>5</volume><fpage>101</fpage><lpage>106</lpage><year>2003</year><pub-id pub-id-type="pmid">12631389</pub-id></element-citation></ref><ref id="b3-ijo-41-03-0798"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Middleton</surname><given-names>LP</given-names></name><name><surname>Tressera</surname><given-names>F</given-names></name><name><surname>Sobel</surname><given-names>ME</given-names></name><name><surname>Bryant</surname><given-names>BR</given-names></name><name><surname>Alburquerque</surname><given-names>A</given-names></name><name><surname>Grases</surname><given-names>P</given-names></name><name><surname>Merino</surname><given-names>MJ</given-names></name></person-group><article-title>Infiltrating micropapillary carcinoma of the breast</article-title><source>Mod Pathol</source><volume>12</volume><fpage>499</fpage><lpage>504</lpage><year>1999</year><pub-id pub-id-type="pmid">10349988</pub-id></element-citation></ref><ref id="b4-ijo-41-03-0798"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Goldstein</surname><given-names>NS</given-names></name><name><surname>Vicini</surname><given-names>FA</given-names></name><name><surname>Kestin</surname><given-names>LL</given-names></name><name><surname>Thomas</surname><given-names>M</given-names></name></person-group><article-title>Differences in the pathologic features of ductal carcinoma in situ of the breast based on patient age</article-title><source>Cancer</source><volume>88</volume><fpage>2553</fpage><lpage>2560</lpage><year>2000</year><pub-id pub-id-type="pmid">10861433</pub-id></element-citation></ref><ref id="b5-ijo-41-03-0798"><label>5</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>CI</given-names></name><name><surname>Anderson</surname><given-names>BO</given-names></name><name><surname>Porter</surname><given-names>P</given-names></name><name><surname>Holt</surname><given-names>SK</given-names></name><name><surname>Daling</surname><given-names>JR</given-names></name><name><surname>Moe</surname><given-names>RE</given-names></name></person-group><article-title>Changing incidence rate of invasive lobular breast carcinoma among older women</article-title><source>Cancer</source><volume>88</volume><fpage>2561</fpage><lpage>2569</lpage><year>2000</year><pub-id pub-id-type="pmid">10861434</pub-id></element-citation></ref><ref id="b6-ijo-41-03-0798"><label>6</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lakhani</surname><given-names>SR</given-names></name><name><surname>Audretsch</surname><given-names>W</given-names></name><name><surname>Cleton-Jensen</surname><given-names>AM</given-names></name><name><surname>Cutuli</surname><given-names>B</given-names></name><name><surname>Ellis</surname><given-names>I</given-names></name><name><surname>Eusebi</surname><given-names>V</given-names></name><name><surname>Greco</surname><given-names>M</given-names></name><name><surname>Houslton</surname><given-names>RS</given-names></name><name><surname>Kuhl</surname><given-names>CK</given-names></name><name><surname>Kurtz</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>The management of lobular carcinoma in situ (LCIS). Is LCIS the same as ductal carcinoma in situ (DCIS)?</article-title><source>Eur J Cancer</source><volume>42</volume><fpage>2205</fpage><lpage>2211</lpage><year>2006</year><pub-id pub-id-type="pmid">16876991</pub-id></element-citation></ref><ref id="b7-ijo-41-03-0798"><label>7</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cianfrocca</surname><given-names>M</given-names></name><name><surname>Goldstein</surname><given-names>LJ</given-names></name></person-group><article-title>Prognostic and predictive factors in early-stage breast cancer</article-title><source>Oncologist</source><volume>9</volume><fpage>606</fpage><lpage>616</lpage><year>2004</year><pub-id pub-id-type="pmid">15561805</pub-id></element-citation></ref><ref id="b8-ijo-41-03-0798"><label>8</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lehman</surname><given-names>CD</given-names></name><name><surname>Gatsonis</surname><given-names>C</given-names></name><name><surname>Kuhl</surname><given-names>CK</given-names></name><name><surname>Hendrick</surname><given-names>RE</given-names></name><name><surname>Pisano</surname><given-names>ED</given-names></name><name><surname>Hanna</surname><given-names>L</given-names></name><name><surname>Peacock</surname><given-names>S</given-names></name><name><surname>Smazal</surname><given-names>SF</given-names></name><name><surname>Maki</surname><given-names>DD</given-names></name><name><surname>Julian</surname><given-names>TB</given-names></name><etal></etal></person-group><article-title>MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer</article-title><source>N Engl J Med</source><volume>356</volume><fpage>1295</fpage><lpage>1303</lpage><year>2007</year><pub-id pub-id-type="pmid">17392300</pub-id></element-citation></ref><ref id="b9-ijo-41-03-0798"><label>9</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Skinner</surname><given-names>KA</given-names></name><name><surname>Silverstein</surname><given-names>MJ</given-names></name></person-group><article-title>The management of ductal carcinoma in situ of the breast</article-title><source>Endocr Relat Cancer</source><volume>8</volume><fpage>33</fpage><lpage>45</lpage><year>2001</year><pub-id pub-id-type="pmid">11350725</pub-id></element-citation></ref><ref id="b10-ijo-41-03-0798"><label>10</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Singletary</surname><given-names>SE</given-names></name><name><surname>Connolly</surname><given-names>JL</given-names></name></person-group><article-title>Breast cancer staging: working with the sixth edition of the AJCC Cancer Staging Manual</article-title><source>CA Cancer J Clin</source><volume>56</volume><fpage>37</fpage><lpage>50</lpage><year>2006</year><pub-id pub-id-type="pmid">16449185</pub-id></element-citation></ref><ref id="b11-ijo-41-03-0798"><label>11</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Askoxylakis</surname><given-names>V</given-names></name><name><surname>Thieke</surname><given-names>C</given-names></name><name><surname>Pleger</surname><given-names>ST</given-names></name><name><surname>Most</surname><given-names>P</given-names></name><name><surname>Tanner</surname><given-names>J</given-names></name><name><surname>Lindel</surname><given-names>K</given-names></name><name><surname>Katus</surname><given-names>HA</given-names></name><name><surname>Debus</surname><given-names>J</given-names></name><name><surname>Bischof</surname><given-names>M</given-names></name></person-group><article-title>Long-term survival of cancer patients compared to heart failure and stroke: a systematic review</article-title><source>BMC Cancer</source><volume>10</volume><fpage>105</fpage><year>2010</year><pub-id pub-id-type="pmid">20307299</pub-id></element-citation></ref><ref id="b12-ijo-41-03-0798"><label>12</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lv</surname><given-names>H</given-names></name><name><surname>Pan</surname><given-names>G</given-names></name><name><surname>Zheng</surname><given-names>G</given-names></name><name><surname>Wu</surname><given-names>X</given-names></name><name><surname>Ren</surname><given-names>H</given-names></name><name><surname>Liu</surname><given-names>Y</given-names></name><name><surname>Wen</surname><given-names>J</given-names></name></person-group><article-title>Expression and functions of the repressor element 1 (RE-1)-silencing transcription factor (REST) in breast cancer</article-title><source>J Cell Biochem</source><volume>110</volume><fpage>968</fpage><lpage>974</lpage><year>2010</year><pub-id pub-id-type="pmid">20564196</pub-id></element-citation></ref><ref id="b13-ijo-41-03-0798"><label>13</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vogel</surname><given-names>KJ</given-names></name><name><surname>Atchley</surname><given-names>DP</given-names></name><name><surname>Erlichman</surname><given-names>J</given-names></name><name><surname>Broglio</surname><given-names>KR</given-names></name><name><surname>Ready</surname><given-names>KJ</given-names></name><name><surname>Valero</surname><given-names>V</given-names></name><name><surname>Amos</surname><given-names>CI</given-names></name><name><surname>Hortobagyi</surname><given-names>GN</given-names></name><name><surname>Lu</surname><given-names>KH</given-names></name><name><surname>Arun</surname><given-names>B</given-names></name></person-group><article-title>BRCA1 and BRCA2 genetic testing in Hispanic patients: mutation prevalence and evaluation of the BRCAPRO risk assessment model</article-title><source>J Clin Oncol</source><volume>25</volume><fpage>4635</fpage><lpage>4641</lpage><year>2007</year><pub-id pub-id-type="pmid">17925560</pub-id></element-citation></ref><ref id="b14-ijo-41-03-0798"><label>14</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Olsson</surname><given-names>H</given-names></name></person-group><article-title>Tumour biology of a breast cancer at least partly reflects the biology of the tissue/epithelial cell of origin at the time of initiation - a hypothesis</article-title><source>J Steroid Biochem Mol Biol</source><volume>74</volume><fpage>345</fpage><lpage>350</lpage><year>2000</year><pub-id pub-id-type="pmid">11162943</pub-id></element-citation></ref><ref id="b15-ijo-41-03-0798"><label>15</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Giordano</surname><given-names>SH</given-names></name><name><surname>Cohen</surname><given-names>DS</given-names></name><name><surname>Buzdar</surname><given-names>AU</given-names></name><name><surname>Perkins</surname><given-names>G</given-names></name><name><surname>Hortobagyi</surname><given-names>GN</given-names></name></person-group><article-title>Breast carcinoma in men: a population-based study</article-title><source>Cancer</source><volume>101</volume><fpage>51</fpage><lpage>57</lpage><year>2004</year><pub-id pub-id-type="pmid">15221988</pub-id></element-citation></ref><ref id="b16-ijo-41-03-0798"><label>16</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Iredale</surname><given-names>R</given-names></name><name><surname>Brain</surname><given-names>K</given-names></name><name><surname>Williams</surname><given-names>B</given-names></name><name><surname>France</surname><given-names>E</given-names></name><name><surname>Gray</surname><given-names>J</given-names></name></person-group><article-title>The experiences of men with breast cancer in the United Kingdom</article-title><source>Eur J Cancer</source><volume>42</volume><fpage>334</fpage><lpage>341</lpage><year>2006</year><pub-id pub-id-type="pmid">16377181</pub-id></element-citation></ref><ref id="b17-ijo-41-03-0798"><label>17</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yager</surname><given-names>JD</given-names></name><name><surname>Davidson</surname><given-names>NE</given-names></name></person-group><article-title>Estrogen carcinogenesis in breast cancer</article-title><source>N Engl J Med</source><volume>354</volume><fpage>270</fpage><lpage>282</lpage><year>2006</year><pub-id pub-id-type="pmid">16421368</pub-id></element-citation></ref><ref id="b18-ijo-41-03-0798"><label>18</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nass</surname><given-names>SJ</given-names></name><name><surname>Davidson</surname><given-names>NE</given-names></name></person-group><article-title>The biology of breast cancer</article-title><source>Hematol Oncol Clin North Am</source><volume>13</volume><fpage>311</fpage><lpage>332</lpage><year>1999</year><pub-id pub-id-type="pmid">10363133</pub-id></element-citation></ref><ref id="b19-ijo-41-03-0798"><label>19</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Antonova</surname><given-names>L</given-names></name><name><surname>Aronson</surname><given-names>K</given-names></name><name><surname>Mueller</surname><given-names>CR</given-names></name></person-group><article-title>Stress and breast cancer: from epidemiology to molecular biology</article-title><source>Breast Cancer Res</source><volume>13</volume><fpage>208</fpage><year>2010</year><pub-id pub-id-type="pmid">21575279</pub-id></element-citation></ref><ref id="b20-ijo-41-03-0798"><label>20</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McTiernan</surname><given-names>A</given-names></name></person-group><article-title>Behavioral risk factors in breast cancer: can risk be modified?</article-title><source>Oncologist</source><volume>8</volume><fpage>326</fpage><lpage>334</lpage><year>2003</year><pub-id pub-id-type="pmid">12897329</pub-id></element-citation></ref><ref id="b21-ijo-41-03-0798"><label>21</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Friedenreich</surname><given-names>CM</given-names></name><name><surname>Courneya</surname><given-names>KS</given-names></name><name><surname>Bryant</surname><given-names>HE</given-names></name></person-group><article-title>Influence of physical activity in different age and life periods on the risk of breast cancer</article-title><source>Epidemiology</source><volume>12</volume><fpage>604</fpage><lpage>612</lpage><year>2001</year><pub-id pub-id-type="pmid">11679785</pub-id></element-citation></ref><ref id="b22-ijo-41-03-0798"><label>22</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>MacConaill</surname><given-names>LE</given-names></name><name><surname>Campbell</surname><given-names>CD</given-names></name><name><surname>Kehoe</surname><given-names>SM</given-names></name><name><surname>Bass</surname><given-names>AJ</given-names></name><name><surname>Hatton</surname><given-names>C</given-names></name><name><surname>Niu</surname><given-names>L</given-names></name><name><surname>Davis</surname><given-names>M</given-names></name><name><surname>Yao</surname><given-names>K</given-names></name><name><surname>Hanna</surname><given-names>M</given-names></name><name><surname>Mondal</surname><given-names>C</given-names></name><etal></etal></person-group><article-title>Profiling critical cancer gene mutations in clinical tumor samples</article-title><source>PLoS One</source><volume>4</volume><fpage>e7887</fpage><year>2009</year><pub-id pub-id-type="pmid">19924296</pub-id></element-citation></ref><ref id="b23-ijo-41-03-0798"><label>23</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Martin</surname><given-names>AM</given-names></name><name><surname>Weber</surname><given-names>BL</given-names></name></person-group><article-title>Genetic and hormonal risk factors in breast cancer</article-title><source>J Natl Cancer Inst</source><volume>92</volume><fpage>1126</fpage><lpage>1135</lpage><year>2000</year><pub-id pub-id-type="pmid">10904085</pub-id></element-citation></ref><ref id="b24-ijo-41-03-0798"><label>24</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Plak</surname><given-names>K</given-names></name><name><surname>Czarnecka</surname><given-names>AM</given-names></name><name><surname>Krawczyk</surname><given-names>T</given-names></name><name><surname>Golik</surname><given-names>P</given-names></name><name><surname>Bartnik</surname><given-names>E</given-names></name></person-group><article-title>Breast cancer as a mitochondrial disorder (Review)</article-title><source>Oncol Rep</source><volume>21</volume><fpage>845</fpage><lpage>851</lpage><year>2009</year><pub-id pub-id-type="pmid">19287978</pub-id></element-citation></ref><ref id="b25-ijo-41-03-0798"><label>25</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lynch</surname><given-names>HT</given-names></name><name><surname>Silva</surname><given-names>E</given-names></name><name><surname>Snyder</surname><given-names>C</given-names></name><name><surname>Lynch</surname><given-names>JF</given-names></name></person-group><article-title>Hereditary breast cancer: part I. Diagnosing hereditary breast cancer syndromes</article-title><source>Breast J</source><volume>14</volume><fpage>3</fpage><lpage>13</lpage><year>2008</year><pub-id pub-id-type="pmid">18086272</pub-id></element-citation></ref><ref id="b26-ijo-41-03-0798"><label>26</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Singletary</surname><given-names>SE</given-names></name></person-group><article-title>Rating the risk factors for breast cancer</article-title><source>Ann Surg</source><volume>237</volume><fpage>474</fpage><lpage>482</lpage><year>2003</year><pub-id pub-id-type="pmid">12677142</pub-id></element-citation></ref><ref id="b27-ijo-41-03-0798"><label>27</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kadouri</surname><given-names>L</given-names></name><name><surname>Hubert</surname><given-names>A</given-names></name><name><surname>Rotenberg</surname><given-names>Y</given-names></name><name><surname>Hamburger</surname><given-names>T</given-names></name><name><surname>Sagi</surname><given-names>M</given-names></name><name><surname>Nechushtan</surname><given-names>C</given-names></name><name><surname>Abeliovich</surname><given-names>D</given-names></name><name><surname>Peretz</surname><given-names>T</given-names></name></person-group><article-title>Cancer risks in carriers of the BRCA1/2 Ashkenazi founder mutations</article-title><source>J Med Genet</source><volume>44</volume><fpage>467</fpage><lpage>471</lpage><year>2007</year><pub-id pub-id-type="pmid">17307836</pub-id></element-citation></ref><ref id="b28-ijo-41-03-0798"><label>28</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Campeau</surname><given-names>PM</given-names></name><name><surname>Foulkes</surname><given-names>WD</given-names></name><name><surname>Tischkowitz</surname><given-names>MD</given-names></name></person-group><article-title>Hereditary breast cancer: new genetic developments, new therapeutic avenues</article-title><source>Hum Genet</source><volume>124</volume><fpage>31</fpage><lpage>42</lpage><year>2008</year><pub-id pub-id-type="pmid">18575892</pub-id></element-citation></ref><ref id="b29-ijo-41-03-0798"><label>29</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>King</surname><given-names>MC</given-names></name><name><surname>Marks</surname><given-names>JH</given-names></name><name><surname>Mandell</surname><given-names>JB</given-names></name></person-group><article-title>Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2</article-title><source>Science</source><volume>302</volume><fpage>643</fpage><lpage>646</lpage><year>2003</year><pub-id pub-id-type="pmid">14576434</pub-id></element-citation></ref><ref id="b30-ijo-41-03-0798"><label>30</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Thorslund</surname><given-names>T</given-names></name><name><surname>West</surname><given-names>SC</given-names></name></person-group><article-title>BRCA2: a universal recombinase regulator</article-title><source>Oncogene</source><volume>26</volume><fpage>7720</fpage><lpage>7730</lpage><year>2007</year><pub-id pub-id-type="pmid">18066084</pub-id></element-citation></ref><ref id="b31-ijo-41-03-0798"><label>31</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Welcsh</surname><given-names>PL</given-names></name><name><surname>King</surname><given-names>MC</given-names></name></person-group><article-title>BRCA1 and BRCA2 and the genetics of breast and ovarian cancer</article-title><source>Hum Mol Genet</source><volume>10</volume><fpage>705</fpage><lpage>713</lpage><year>2001</year><pub-id pub-id-type="pmid">11257103</pub-id></element-citation></ref><ref id="b32-ijo-41-03-0798"><label>32</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Narod</surname><given-names>SA</given-names></name><name><surname>Foulkes</surname><given-names>WD</given-names></name></person-group><article-title>BRCA1 and BRCA2: 1994 and beyond</article-title><source>Nat Rev Cancer</source><volume>4</volume><fpage>665</fpage><lpage>676</lpage><year>2004</year><pub-id pub-id-type="pmid">15343273</pub-id></element-citation></ref><ref id="b33-ijo-41-03-0798"><label>33</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Thorslund</surname><given-names>T</given-names></name><name><surname>Esashi</surname><given-names>F</given-names></name><name><surname>West</surname><given-names>SC</given-names></name></person-group><article-title>Interactions between human BRCA2 protein and the meiosis-specific recombinase DMC1</article-title><source>EMBO J</source><volume>26</volume><fpage>2915</fpage><lpage>2922</lpage><year>2007</year><pub-id pub-id-type="pmid">17541404</pub-id></element-citation></ref><ref id="b34-ijo-41-03-0798"><label>34</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Verhoog</surname><given-names>LC</given-names></name><name><surname>Berns</surname><given-names>EM</given-names></name><name><surname>Brekelmans</surname><given-names>CT</given-names></name><name><surname>Seynaeve</surname><given-names>C</given-names></name><name><surname>Meijers-Heijboer</surname><given-names>EJ</given-names></name><name><surname>Klijn</surname><given-names>JG</given-names></name></person-group><article-title>Prognostic significance of germline BRCA2 mutations in hereditary breast cancer patients</article-title><source>J Clin Oncol</source><volume>18</volume><fpage>119S</fpage><lpage>124S</lpage><year>2000</year><pub-id pub-id-type="pmid">11060339</pub-id></element-citation></ref><ref id="b35-ijo-41-03-0798"><label>35</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Loman</surname><given-names>N</given-names></name><name><surname>Johannsson</surname><given-names>O</given-names></name><name><surname>Bendahl</surname><given-names>P</given-names></name><name><surname>Dahl</surname><given-names>N</given-names></name><name><surname>Einbeigi</surname><given-names>Z</given-names></name><name><surname>Gerdes</surname><given-names>A</given-names></name><name><surname>Borg</surname><given-names>A</given-names></name><name><surname>Olsson</surname><given-names>H</given-names></name></person-group><article-title>Prognosis and clinical presentation of BRCA2-associated breast cancer</article-title><source>Eur J Cancer</source><volume>36</volume><fpage>1365</fpage><lpage>1373</lpage><year>2000</year><pub-id pub-id-type="pmid">10899649</pub-id></element-citation></ref><ref id="b36-ijo-41-03-0798"><label>36</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lim</surname><given-names>LY</given-names></name><name><surname>Vidnovic</surname><given-names>N</given-names></name><name><surname>Ellisen</surname><given-names>LW</given-names></name><name><surname>Leong</surname><given-names>CO</given-names></name></person-group><article-title>Mutant p53 mediates survival of breast cancer cells</article-title><source>Br J Cancer</source><volume>101</volume><fpage>1606</fpage><lpage>1612</lpage><year>2009</year><pub-id pub-id-type="pmid">19773755</pub-id></element-citation></ref><ref id="b37-ijo-41-03-0798"><label>37</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bergamaschi</surname><given-names>D</given-names></name><name><surname>Gasco</surname><given-names>M</given-names></name><name><surname>Hiller</surname><given-names>L</given-names></name><name><surname>Sullivan</surname><given-names>A</given-names></name><name><surname>Syed</surname><given-names>N</given-names></name><name><surname>Trigiante</surname><given-names>G</given-names></name><name><surname>Yulug</surname><given-names>I</given-names></name><name><surname>Merlano</surname><given-names>M</given-names></name><name><surname>Numico</surname><given-names>G</given-names></name><name><surname>Comino</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis</article-title><source>Cancer Cell</source><volume>3</volume><fpage>387</fpage><lpage>402</lpage><year>2003</year><pub-id pub-id-type="pmid">12726864</pub-id></element-citation></ref><ref id="b38-ijo-41-03-0798"><label>38</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Geisler</surname><given-names>S</given-names></name><name><surname>Lonning</surname><given-names>PE</given-names></name><name><surname>Aas</surname><given-names>T</given-names></name><name><surname>Johnsen</surname><given-names>H</given-names></name><name><surname>Fluge</surname><given-names>O</given-names></name><name><surname>Haugen</surname><given-names>DF</given-names></name><name><surname>Lillehaug</surname><given-names>JR</given-names></name><name><surname>Akslen</surname><given-names>LA</given-names></name><name><surname>Borresen-Dale</surname><given-names>AL</given-names></name></person-group><article-title>Influence of TP53 gene alterations and c-erbB-2 expression on the response to treatment with doxorubicin in locally advanced breast cancer</article-title><source>Cancer Res</source><volume>61</volume><fpage>2505</fpage><lpage>2512</lpage><year>2001</year><pub-id pub-id-type="pmid">11289122</pub-id></element-citation></ref><ref id="b39-ijo-41-03-0798"><label>39</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Beroud</surname><given-names>C</given-names></name><name><surname>Soussi</surname><given-names>T</given-names></name></person-group><article-title>p53 gene mutation: software and database</article-title><source>Nucleic Acids Res</source><volume>26</volume><fpage>200</fpage><lpage>204</lpage><year>1998</year><pub-id pub-id-type="pmid">9399836</pub-id></element-citation></ref><ref id="b40-ijo-41-03-0798"><label>40</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vousden</surname><given-names>KH</given-names></name><name><surname>Lane</surname><given-names>DP</given-names></name></person-group><article-title>p53 in health and disease</article-title><source>Nat Rev Mol Cell Biol</source><volume>8</volume><fpage>275</fpage><lpage>283</lpage><year>2007</year><pub-id pub-id-type="pmid">17380161</pub-id></element-citation></ref><ref id="b41-ijo-41-03-0798"><label>41</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Olivier</surname><given-names>M</given-names></name><name><surname>Petitjean</surname><given-names>A</given-names></name><name><surname>Marcel</surname><given-names>V</given-names></name><name><surname>Petre</surname><given-names>A</given-names></name><name><surname>Mounawar</surname><given-names>M</given-names></name><name><surname>Plymoth</surname><given-names>A</given-names></name><name><surname>de Fromentel</surname><given-names>CC</given-names></name><name><surname>Hainaut</surname><given-names>P</given-names></name></person-group><article-title>Recent advances in p53 research: an interdisciplinary perspective</article-title><source>Cancer Gene Ther</source><volume>16</volume><fpage>1</fpage><lpage>12</lpage><year>2009</year><pub-id pub-id-type="pmid">18802452</pub-id></element-citation></ref><ref id="b42-ijo-41-03-0798"><label>42</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hohenstein</surname><given-names>P</given-names></name><name><surname>Giles</surname><given-names>RH</given-names></name></person-group><article-title>BRCA1: a scaffold for p53 response?</article-title><source>Trends Genet</source><volume>19</volume><fpage>489</fpage><lpage>494</lpage><year>2003</year><pub-id pub-id-type="pmid">12957542</pub-id></element-citation></ref><ref id="b43-ijo-41-03-0798"><label>43</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Coutant</surname><given-names>C</given-names></name><name><surname>Rouzier</surname><given-names>R</given-names></name><name><surname>Qi</surname><given-names>Y</given-names></name><name><surname>Lehmann-Che</surname><given-names>J</given-names></name><name><surname>Bianchini</surname><given-names>G</given-names></name><name><surname>Iwamoto</surname><given-names>T</given-names></name><name><surname>Hortobagyi</surname><given-names>GN</given-names></name><name><surname>Symmans</surname><given-names>WF</given-names></name><name><surname>Uzan</surname><given-names>S</given-names></name><name><surname>Andre</surname><given-names>F</given-names></name><name><surname>de The</surname><given-names>H</given-names></name><name><surname>Pusztai</surname><given-names>L</given-names></name></person-group><article-title>Distinct p53 gene signatures are needed to predict prognosis and response to chemotherapy in ER-positive and ER-negative breast cancers</article-title><source>Clin Cancer Res</source><volume>17</volume><fpage>2591</fpage><lpage>2601</lpage><year>2011</year><pub-id pub-id-type="pmid">21248301</pub-id></element-citation></ref><ref id="b44-ijo-41-03-0798"><label>44</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yamashita</surname><given-names>H</given-names></name><name><surname>Nishio</surname><given-names>M</given-names></name><name><surname>Toyama</surname><given-names>T</given-names></name><name><surname>Sugiura</surname><given-names>H</given-names></name><name><surname>Zhang</surname><given-names>Z</given-names></name><name><surname>Kobayashi</surname><given-names>S</given-names></name><name><surname>Iwase</surname><given-names>H</given-names></name></person-group><article-title>Coexistence of HER2 over-expression and p53 protein accumulation is a strong prognostic molecular marker in breast cancer</article-title><source>Breast Cancer Res</source><volume>6</volume><fpage>R24</fpage><lpage>30</lpage><year>2004</year><pub-id pub-id-type="pmid">14680497</pub-id></element-citation></ref><ref id="b45-ijo-41-03-0798"><label>45</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Feki</surname><given-names>A</given-names></name><name><surname>Irminger-Finger</surname><given-names>I</given-names></name></person-group><article-title>Mutational spectrum of p53 mutations in primary breast and ovarian tumors</article-title><source>Crit Rev Oncol Hematol</source><volume>52</volume><fpage>103</fpage><lpage>116</lpage><year>2004</year><pub-id pub-id-type="pmid">15501075</pub-id></element-citation></ref><ref id="b46-ijo-41-03-0798"><label>46</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yang</surname><given-names>J</given-names></name><name><surname>Ren</surname><given-names>Y</given-names></name><name><surname>Wang</surname><given-names>L</given-names></name><name><surname>Li</surname><given-names>B</given-names></name><name><surname>Chen</surname><given-names>Y</given-names></name><name><surname>Zhao</surname><given-names>W</given-names></name><name><surname>Xu</surname><given-names>W</given-names></name><name><surname>Li</surname><given-names>T</given-names></name><name><surname>Dai</surname><given-names>F</given-names></name></person-group><article-title>PTEN mutation spectrum in breast cancers and breast hyperplasia</article-title><source>J Cancer Res Clin Oncol</source><volume>136</volume><fpage>1303</fpage><lpage>1311</lpage><year>2010</year><pub-id pub-id-type="pmid">20300775</pub-id></element-citation></ref><ref id="b47-ijo-41-03-0798"><label>47</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wallace</surname><given-names>JA</given-names></name><name><surname>Li</surname><given-names>F</given-names></name><name><surname>Leone</surname><given-names>G</given-names></name><name><surname>Ostrowski</surname><given-names>MC</given-names></name></person-group><article-title>Pten in the breast tumor microenvironment: modeling tumor-stroma coevolution</article-title><source>Cancer Res</source><volume>71</volume><fpage>1203</fpage><lpage>1207</lpage><year>2011</year><pub-id pub-id-type="pmid">21303970</pub-id></element-citation></ref><ref id="b48-ijo-41-03-0798"><label>48</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tokunaga</surname><given-names>E</given-names></name><name><surname>Oki</surname><given-names>E</given-names></name><name><surname>Kimura</surname><given-names>Y</given-names></name><name><surname>Yamanaka</surname><given-names>T</given-names></name><name><surname>Egashira</surname><given-names>A</given-names></name><name><surname>Nishida</surname><given-names>K</given-names></name><name><surname>Koga</surname><given-names>T</given-names></name><name><surname>Morita</surname><given-names>M</given-names></name><name><surname>Kakeji</surname><given-names>Y</given-names></name><name><surname>Maehara</surname><given-names>Y</given-names></name></person-group><article-title>Coexistence of the loss of heterozygosity at the PTEN locus and HER2 overexpression enhances the Akt activity thus leading to a negative progesterone receptor expression in breast carcinoma</article-title><source>Breast Cancer Res Treat</source><volume>101</volume><fpage>249</fpage><lpage>257</lpage><year>2007</year><pub-id pub-id-type="pmid">17006756</pub-id></element-citation></ref><ref id="b49-ijo-41-03-0798"><label>49</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Marty</surname><given-names>B</given-names></name><name><surname>Maire</surname><given-names>V</given-names></name><name><surname>Gravier</surname><given-names>E</given-names></name><name><surname>Rigaill</surname><given-names>G</given-names></name><name><surname>Vincent-Salomon</surname><given-names>A</given-names></name><name><surname>Kappler</surname><given-names>M</given-names></name><name><surname>Lebigot</surname><given-names>I</given-names></name><name><surname>Djelti</surname><given-names>F</given-names></name><name><surname>Tourdes</surname><given-names>A</given-names></name><name><surname>Gestraud</surname><given-names>P</given-names></name><etal></etal></person-group><article-title>Frequent PTEN genomic alterations and activated phosphatidylinositol 3-kinase pathway in basal-like breast cancer cells</article-title><source>Breast Cancer Res</source><volume>10</volume><fpage>R101</fpage><year>2008</year><pub-id pub-id-type="pmid">19055754</pub-id></element-citation></ref><ref id="b50-ijo-41-03-0798"><label>50</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shaw</surname><given-names>RJ</given-names></name><name><surname>Cantley</surname><given-names>LC</given-names></name></person-group><article-title>Ras, PI(3)K and mTOR signalling controls tumour cell growth</article-title><source>Nature</source><volume>441</volume><fpage>424</fpage><lpage>430</lpage><year>2006</year><pub-id pub-id-type="pmid">16724053</pub-id></element-citation></ref><ref id="b51-ijo-41-03-0798"><label>51</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>DeGraffenried</surname><given-names>LA</given-names></name><name><surname>Fulcher</surname><given-names>L</given-names></name><name><surname>Friedrichs</surname><given-names>WE</given-names></name><name><surname>Grunwald</surname><given-names>V</given-names></name><name><surname>Ray</surname><given-names>RB</given-names></name><name><surname>Hidalgo</surname><given-names>M</given-names></name></person-group><article-title>Reduced PTEN expression in breast cancer cells confers susceptibility to inhibitors of the PI3 kinase/Akt pathway</article-title><source>Ann Oncol</source><volume>15</volume><fpage>1510</fpage><lpage>1516</lpage><year>2004</year><pub-id pub-id-type="pmid">15367412</pub-id></element-citation></ref><ref id="b52-ijo-41-03-0798"><label>52</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tate</surname><given-names>G</given-names></name><name><surname>Suzuki</surname><given-names>T</given-names></name><name><surname>Mitsuya</surname><given-names>T</given-names></name></person-group><article-title>Mutation of the PTEN gene in a human hepatic angiosarcoma</article-title><source>Cancer Genet Cytogenet</source><volume>178</volume><fpage>160</fpage><lpage>162</lpage><year>2007</year><pub-id pub-id-type="pmid">17954274</pub-id></element-citation></ref><ref id="b53-ijo-41-03-0798"><label>53</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Petrocelli</surname><given-names>T</given-names></name><name><surname>Slingerland</surname><given-names>JM</given-names></name></person-group><article-title>PTEN deficiency: a role in mammary carcinogenesis</article-title><source>Breast Cancer Res</source><volume>3</volume><fpage>356</fpage><lpage>360</lpage><year>2001</year><pub-id pub-id-type="pmid">11737885</pub-id></element-citation></ref><ref id="b54-ijo-41-03-0798"><label>54</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>JS</given-names></name><name><surname>Kim</surname><given-names>HS</given-names></name><name><surname>Kim</surname><given-names>YB</given-names></name><name><surname>Lee</surname><given-names>MC</given-names></name><name><surname>Park</surname><given-names>CS</given-names></name><name><surname>Min</surname><given-names>KW</given-names></name></person-group><article-title>Reduced PTEN expression is associated with poor outcome and angiogenesis in invasive ductal carcinoma of the breast</article-title><source>Appl Immunohistochem Mol Morphol</source><volume>12</volume><fpage>205</fpage><lpage>210</lpage><year>2004</year><pub-id pub-id-type="pmid">15551732</pub-id></element-citation></ref><ref id="b55-ijo-41-03-0798"><label>55</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Steelman</surname><given-names>LS</given-names></name><name><surname>Navolanic</surname><given-names>PM</given-names></name><name><surname>Sokolosky</surname><given-names>ML</given-names></name><name><surname>Taylor</surname><given-names>JR</given-names></name><name><surname>Lehmann</surname><given-names>BD</given-names></name><name><surname>Chappell</surname><given-names>WH</given-names></name><name><surname>Abrams</surname><given-names>SL</given-names></name><name><surname>Wong</surname><given-names>EW</given-names></name><name><surname>Stadelman</surname><given-names>KM</given-names></name><name><surname>Terrian</surname><given-names>DM</given-names></name><etal></etal></person-group><article-title>Suppression of PTEN function increases breast cancer chemotherapeutic drug resistance while conferring sensitivity to mTOR inhibitors</article-title><source>Oncogene</source><volume>27</volume><fpage>4086</fpage><lpage>4095</lpage><year>2008</year><pub-id pub-id-type="pmid">18332865</pub-id></element-citation></ref><ref id="b56-ijo-41-03-0798"><label>56</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tanaka</surname><given-names>M</given-names></name><name><surname>Koul</surname><given-names>D</given-names></name><name><surname>Davies</surname><given-names>MA</given-names></name><name><surname>Liebert</surname><given-names>M</given-names></name><name><surname>Steck</surname><given-names>PA</given-names></name><name><surname>Grossman</surname><given-names>HB</given-names></name></person-group><article-title>MMAC1/PTEN inhibits cell growth and induces chemosensitivity to doxorubicin in human bladder cancer cells</article-title><source>Oncogene</source><volume>19</volume><fpage>5406</fpage><lpage>5412</lpage><year>2000</year><pub-id pub-id-type="pmid">11103942</pub-id></element-citation></ref><ref id="b57-ijo-41-03-0798"><label>57</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bates</surname><given-names>RC</given-names></name><name><surname>Edwards</surname><given-names>NS</given-names></name><name><surname>Burns</surname><given-names>GF</given-names></name><name><surname>Fisher</surname><given-names>DE</given-names></name></person-group><article-title>A CD44 survival pathway triggers chemoresistance via lyn kinase and phosphoinositide 3-kinase/Akt in colon carcinoma cells</article-title><source>Cancer Res</source><volume>61</volume><fpage>5275</fpage><lpage>5283</lpage><year>2001</year><pub-id pub-id-type="pmid">11431370</pub-id></element-citation></ref><ref id="b58-ijo-41-03-0798"><label>58</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nevanlinna</surname><given-names>H</given-names></name><name><surname>Bartek</surname><given-names>J</given-names></name></person-group><article-title>The CHEK2 gene and inherited breast cancer susceptibility</article-title><source>Oncogene</source><volume>25</volume><fpage>5912</fpage><lpage>5919</lpage><year>2006</year><pub-id pub-id-type="pmid">16998506</pub-id></element-citation></ref><ref id="b59-ijo-41-03-0798"><label>59</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shaag</surname><given-names>A</given-names></name><name><surname>Walsh</surname><given-names>T</given-names></name><name><surname>Renbaum</surname><given-names>P</given-names></name><name><surname>Kirchhoff</surname><given-names>T</given-names></name><name><surname>Nafa</surname><given-names>K</given-names></name><name><surname>Shiovitz</surname><given-names>S</given-names></name><name><surname>Mandell</surname><given-names>JB</given-names></name><name><surname>Welcsh</surname><given-names>P</given-names></name><name><surname>Lee</surname><given-names>MK</given-names></name><name><surname>Ellis</surname><given-names>N</given-names></name><etal></etal></person-group><article-title>Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population</article-title><source>Hum Mol Genet</source><volume>14</volume><fpage>555</fpage><lpage>563</lpage><year>2005</year><pub-id pub-id-type="pmid">15649950</pub-id></element-citation></ref><ref id="b60-ijo-41-03-0798"><label>60</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Abraham</surname><given-names>RT</given-names></name></person-group><article-title>PI 3-kinase related kinases: ‘big’ players in stress-induced signaling pathways</article-title><source>DNA Repair</source><volume>3</volume><fpage>883</fpage><lpage>887</lpage><year>2004</year><pub-id pub-id-type="pmid">15279773</pub-id></element-citation></ref><ref id="b61-ijo-41-03-0798"><label>61</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Angele</surname><given-names>S</given-names></name><name><surname>Romestaing</surname><given-names>P</given-names></name><name><surname>Moullan</surname><given-names>N</given-names></name><name><surname>Vuillaume</surname><given-names>M</given-names></name><name><surname>Chapot</surname><given-names>B</given-names></name><name><surname>Friesen</surname><given-names>M</given-names></name><name><surname>Jongmans</surname><given-names>W</given-names></name><name><surname>Cox</surname><given-names>DG</given-names></name><name><surname>Pisani</surname><given-names>P</given-names></name><name><surname>Gerard</surname><given-names>JP</given-names></name><name><surname>Hall</surname><given-names>J</given-names></name></person-group><article-title>ATM haplotypes and cellular response to DNA damage: association with breast cancer risk and clinical radiosensitivity</article-title><source>Cancer Res</source><volume>63</volume><fpage>8717</fpage><lpage>8725</lpage><year>2003</year><pub-id pub-id-type="pmid">14695186</pub-id></element-citation></ref><ref id="b62-ijo-41-03-0798"><label>62</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McKinnon</surname><given-names>PJ</given-names></name></person-group><article-title>ATM and ataxia telangiectasia</article-title><source>EMBO Rep</source><volume>5</volume><fpage>772</fpage><lpage>776</lpage><year>2004</year><pub-id pub-id-type="pmid">15289825</pub-id></element-citation></ref><ref id="b63-ijo-41-03-0798"><label>63</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Milne</surname><given-names>RL</given-names></name></person-group><article-title>Variants in the ATM gene and breast cancer susceptibility</article-title><source>Genome Med</source><volume>1</volume><fpage>12</fpage><year>2009</year><pub-id pub-id-type="pmid">19348699</pub-id></element-citation></ref><ref id="b64-ijo-41-03-0798"><label>64</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>JH</given-names></name><name><surname>Paull</surname><given-names>TT</given-names></name></person-group><article-title>Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex</article-title><source>Science</source><volume>304</volume><fpage>93</fpage><lpage>96</lpage><year>2004</year><pub-id pub-id-type="pmid">15064416</pub-id></element-citation></ref><ref id="b65-ijo-41-03-0798"><label>65</label><element-citation publication-type="journal"><person-group person-group-type="author"><collab>Consortium TCBCC-C</collab></person-group><article-title>CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies</article-title><source>Am J Hum Genet</source><volume>74</volume><fpage>1175</fpage><lpage>1182</lpage><year>2004</year><pub-id pub-id-type="pmid">15122511</pub-id></element-citation></ref><ref id="b66-ijo-41-03-0798"><label>66</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kilpivaara</surname><given-names>O</given-names></name><name><surname>Vahteristo</surname><given-names>P</given-names></name><name><surname>Falck</surname><given-names>J</given-names></name><name><surname>Syrjakoski</surname><given-names>K</given-names></name><name><surname>Eerola</surname><given-names>H</given-names></name><name><surname>Easton</surname><given-names>D</given-names></name><name><surname>Bartkova</surname><given-names>J</given-names></name><name><surname>Lukas</surname><given-names>J</given-names></name><name><surname>Heikkila</surname><given-names>P</given-names></name><name><surname>Aittomaki</surname><given-names>K</given-names></name><etal></etal></person-group><article-title>CHEK2 variant I157T may be associated with increased breast cancer risk</article-title><source>Int J Cancer</source><volume>111</volume><fpage>543</fpage><lpage>547</lpage><year>2004</year><pub-id pub-id-type="pmid">15239132</pub-id></element-citation></ref><ref id="b67-ijo-41-03-0798"><label>67</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kleibl</surname><given-names>Z</given-names></name><name><surname>Havranek</surname><given-names>O</given-names></name><name><surname>Novotny</surname><given-names>J</given-names></name><name><surname>Kleiblova</surname><given-names>P</given-names></name><name><surname>Soucek</surname><given-names>P</given-names></name><name><surname>Pohlreich</surname><given-names>P</given-names></name></person-group><article-title>Analysis of CHEK2 FHA domain in Czech patients with sporadic breast cancer revealed distinct rare genetic alterations</article-title><source>Breast Cancer Res Treat</source><volume>112</volume><fpage>159</fpage><lpage>164</lpage><year>2008</year><pub-id pub-id-type="pmid">18058223</pub-id></element-citation></ref><ref id="b68-ijo-41-03-0798"><label>68</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Le</surname><given-names>GM</given-names></name><name><surname>O’Malley</surname><given-names>CD</given-names></name><name><surname>Glaser</surname><given-names>SL</given-names></name><name><surname>Lynch</surname><given-names>CF</given-names></name><name><surname>Stanford</surname><given-names>JL</given-names></name><name><surname>Keegan</surname><given-names>TH</given-names></name><name><surname>West</surname><given-names>DW</given-names></name></person-group><article-title>Breast implants following mastectomy in women with early-stage breast cancer: prevalence and impact on survival</article-title><source>Breast Cancer Res</source><volume>7</volume><fpage>R184</fpage><lpage>193</lpage><year>2005</year><pub-id pub-id-type="pmid">15743498</pub-id></element-citation></ref><ref id="b69-ijo-41-03-0798"><label>69</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brown</surname><given-names>SL</given-names></name></person-group><article-title>Epidemiology of silicone-gel breast implants</article-title><source>Epidemiology</source><volume>13</volume><fpage>S34</fpage><lpage>39</lpage><year>2002</year><pub-id pub-id-type="pmid">12071482</pub-id></element-citation></ref><ref id="b70-ijo-41-03-0798"><label>70</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bese</surname><given-names>NS</given-names></name><name><surname>Kiel</surname><given-names>K</given-names></name><name><surname>El-Gueddari Bel</surname><given-names>K</given-names></name><name><surname>Campbell</surname><given-names>OB</given-names></name><name><surname>Awuah</surname><given-names>B</given-names></name><name><surname>Vikram</surname><given-names>B</given-names></name></person-group><article-title>Radiotherapy for breast cancer in countries with limited resources: program implementation and evidence-based recommendations</article-title><source>Breast J</source><volume>12</volume><fpage>S96</fpage><lpage>102</lpage><year>2006</year><pub-id pub-id-type="pmid">16430403</pub-id></element-citation></ref><ref id="b71-ijo-41-03-0798"><label>71</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Goss</surname><given-names>PE</given-names></name><name><surname>Ingle</surname><given-names>JN</given-names></name><name><surname>Martino</surname><given-names>S</given-names></name><name><surname>Robert</surname><given-names>NJ</given-names></name><name><surname>Muss</surname><given-names>HB</given-names></name><name><surname>Piccart</surname><given-names>MJ</given-names></name><name><surname>Castiglione</surname><given-names>M</given-names></name><name><surname>Tu</surname><given-names>D</given-names></name><name><surname>Shepherd</surname><given-names>LE</given-names></name><name><surname>Pritchard</surname><given-names>KI</given-names></name><etal></etal></person-group><article-title>Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17</article-title><source>J Natl Cancer Inst</source><volume>97</volume><fpage>1262</fpage><lpage>1271</lpage><year>2005</year><pub-id pub-id-type="pmid">16145047</pub-id></element-citation></ref><ref id="b72-ijo-41-03-0798"><label>72</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Crew</surname><given-names>KD</given-names></name><name><surname>Greenlee</surname><given-names>H</given-names></name><name><surname>Capodice</surname><given-names>J</given-names></name><name><surname>Raptis</surname><given-names>G</given-names></name><name><surname>Brafman</surname><given-names>L</given-names></name><name><surname>Fuentes</surname><given-names>D</given-names></name><name><surname>Sierra</surname><given-names>A</given-names></name><name><surname>Hershman</surname><given-names>DL</given-names></name></person-group><article-title>Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer</article-title><source>J Clin Oncol</source><volume>25</volume><fpage>3877</fpage><lpage>3883</lpage><year>2007</year><pub-id pub-id-type="pmid">17761973</pub-id></element-citation></ref><ref id="b73-ijo-41-03-0798"><label>73</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zoli</surname><given-names>W</given-names></name><name><surname>Ulivi</surname><given-names>P</given-names></name><name><surname>Tesei</surname><given-names>A</given-names></name><name><surname>Fabbri</surname><given-names>F</given-names></name><name><surname>Rosetti</surname><given-names>M</given-names></name><name><surname>Maltoni</surname><given-names>R</given-names></name><name><surname>Giunchi</surname><given-names>DC</given-names></name><name><surname>Ricotti</surname><given-names>L</given-names></name><name><surname>Brigliadori</surname><given-names>G</given-names></name><name><surname>Vannini</surname><given-names>I</given-names></name><name><surname>Amadori</surname><given-names>D</given-names></name></person-group><article-title>Addition of 5-fluorouracil to doxorubicin-paclitaxel sequence increases caspase-dependent apoptosis in breast cancer cell lines</article-title><source>Breast Cancer Res</source><volume>7</volume><fpage>R681</fpage><lpage>689</lpage><year>2005</year><pub-id pub-id-type="pmid">16168113</pub-id></element-citation></ref><ref id="b74-ijo-41-03-0798"><label>74</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McArthur</surname><given-names>HL</given-names></name><name><surname>Mahoney</surname><given-names>KM</given-names></name><name><surname>Morris</surname><given-names>PG</given-names></name><name><surname>Patil</surname><given-names>S</given-names></name><name><surname>Jacks</surname><given-names>LM</given-names></name><name><surname>Howard</surname><given-names>J</given-names></name><name><surname>Norton</surname><given-names>L</given-names></name><name><surname>Hudis</surname><given-names>CA</given-names></name></person-group><article-title>Adjuvant trastuzumab with chemotherapy is effective in women with small, node-negative, HER2-positive breast cancer</article-title><source>Cancer</source><volume>117</volume><fpage>5461</fpage><lpage>5468</lpage><year>2011</year><pub-id pub-id-type="pmid">21681735</pub-id></element-citation></ref><ref id="b75-ijo-41-03-0798"><label>75</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Piccart</surname><given-names>M</given-names></name></person-group><article-title>The role of taxanes in the adjuvant treatment of early stage breast cancer</article-title><source>Breast Cancer Res Treat</source><volume>79</volume><issue>Suppl 1</issue><fpage>S25</fpage><lpage>34</lpage><year>2003</year><pub-id pub-id-type="pmid">12868803</pub-id></element-citation></ref><ref id="b76-ijo-41-03-0798"><label>76</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Weiss</surname><given-names>RB</given-names></name><name><surname>Woolf</surname><given-names>SH</given-names></name><name><surname>Demakos</surname><given-names>E</given-names></name><name><surname>Holland</surname><given-names>JF</given-names></name><name><surname>Berry</surname><given-names>DA</given-names></name><name><surname>Falkson</surname><given-names>G</given-names></name><name><surname>Cirrincione</surname><given-names>CT</given-names></name><name><surname>Robbins</surname><given-names>A</given-names></name><name><surname>Bothun</surname><given-names>S</given-names></name><name><surname>Henderson</surname><given-names>IC</given-names></name><name><surname>Norton</surname><given-names>L</given-names></name></person-group><article-title>Natural history of more than 20 years of node-positive primary breast carcinoma treated with cyclophosphamide, methotrexate, and fluorouracil-based adjuvant chemotherapy: a study by the Cancer and Leukemia Group B</article-title><source>J Clin Oncol</source><volume>21</volume><fpage>1825</fpage><lpage>1835</lpage><year>2003</year><pub-id pub-id-type="pmid">12721260</pub-id></element-citation></ref><ref id="b77-ijo-41-03-0798"><label>77</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hedley</surname><given-names>D</given-names></name><name><surname>Ogilvie</surname><given-names>L</given-names></name><name><surname>Springer</surname><given-names>C</given-names></name></person-group><article-title>Carboxypeptidase-G2-based gene-directed enzyme-prodrug therapy: a new weapon in the GDEPT armoury</article-title><source>Nat Rev Cancer</source><volume>7</volume><fpage>870</fpage><lpage>879</lpage><year>2007</year><pub-id pub-id-type="pmid">17943135</pub-id></element-citation></ref><ref id="b78-ijo-41-03-0798"><label>78</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nawa</surname><given-names>A</given-names></name><name><surname>Tanino</surname><given-names>T</given-names></name><name><surname>Luo</surname><given-names>C</given-names></name><name><surname>Iwaki</surname><given-names>M</given-names></name><name><surname>Kajiyama</surname><given-names>H</given-names></name><name><surname>Shibata</surname><given-names>K</given-names></name><name><surname>Yamamoto</surname><given-names>E</given-names></name><name><surname>Ino</surname><given-names>K</given-names></name><name><surname>Nishiyama</surname><given-names>Y</given-names></name><name><surname>Kikkawa</surname><given-names>F</given-names></name></person-group><article-title>Gene directed enzyme prodrug therapy for ovarian cancer: could GDEPT become a promising treatment against ovarian cancer?</article-title><source>Anticancer Agents Med Chem</source><volume>8</volume><fpage>232</fpage><lpage>239</lpage><year>2008</year><pub-id pub-id-type="pmid">18288924</pub-id></element-citation></ref><ref id="b79-ijo-41-03-0798"><label>79</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Greco</surname><given-names>O</given-names></name><name><surname>Dachs</surname><given-names>GU</given-names></name></person-group><article-title>Gene directed enzyme/prodrug therapy of cancer: historical appraisal and future prospectives</article-title><source>J Cell Physiol</source><volume>187</volume><fpage>22</fpage><lpage>36</lpage><year>2001</year><pub-id pub-id-type="pmid">11241346</pub-id></element-citation></ref><ref id="b80-ijo-41-03-0798"><label>80</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McKeown</surname><given-names>SR</given-names></name><name><surname>Ward</surname><given-names>C</given-names></name><name><surname>Robson</surname><given-names>T</given-names></name></person-group><article-title>Gene-directed enzyme prodrug therapy: a current assessment</article-title><source>Curr Opin Mol Ther</source><volume>6</volume><fpage>421</fpage><lpage>435</lpage><year>2004</year><pub-id pub-id-type="pmid">15468601</pub-id></element-citation></ref><ref id="b81-ijo-41-03-0798"><label>81</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Voeks</surname><given-names>D</given-names></name><name><surname>Martiniello-Wilks</surname><given-names>R</given-names></name><name><surname>Madden</surname><given-names>V</given-names></name><name><surname>Smith</surname><given-names>K</given-names></name><name><surname>Bennetts</surname><given-names>E</given-names></name><name><surname>Both</surname><given-names>GW</given-names></name><name><surname>Russell</surname><given-names>PJ</given-names></name></person-group><article-title>Gene therapy for prostate cancer delivered by ovine adenovirus and mediated by purine nucleoside phosphorylase and fludarabine in mouse models</article-title><source>Gene Ther</source><volume>9</volume><fpage>759</fpage><lpage>768</lpage><year>2002</year><pub-id pub-id-type="pmid">12040457</pub-id></element-citation></ref><ref id="b82-ijo-41-03-0798"><label>82</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Anderson</surname><given-names>WF</given-names></name></person-group><article-title>Gene therapy scores against cancer</article-title><source>Nat Med</source><volume>6</volume><fpage>862</fpage><lpage>863</lpage><year>2000</year><pub-id pub-id-type="pmid">10932216</pub-id></element-citation></ref><ref id="b83-ijo-41-03-0798"><label>83</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chung-Faye</surname><given-names>GA</given-names></name><name><surname>Kerr</surname><given-names>DJ</given-names></name><name><surname>Young</surname><given-names>LS</given-names></name><name><surname>Searle</surname><given-names>PF</given-names></name></person-group><article-title>Gene therapy strategies for colon cancer</article-title><source>Mol Med Today</source><volume>6</volume><fpage>82</fpage><lpage>87</lpage><year>2000</year><pub-id pub-id-type="pmid">10652481</pub-id></element-citation></ref><ref id="b84-ijo-41-03-0798"><label>84</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schepelmann</surname><given-names>S</given-names></name><name><surname>Hallenbeck</surname><given-names>P</given-names></name><name><surname>Ogilvie</surname><given-names>LM</given-names></name><name><surname>Hedley</surname><given-names>D</given-names></name><name><surname>Friedlos</surname><given-names>F</given-names></name><name><surname>Martin</surname><given-names>J</given-names></name><name><surname>Scanlon</surname><given-names>I</given-names></name><name><surname>Hay</surname><given-names>C</given-names></name><name><surname>Hawkins</surname><given-names>LK</given-names></name><name><surname>Marais</surname><given-names>R</given-names></name><name><surname>Springer</surname><given-names>CJ</given-names></name></person-group><article-title>Systemic gene-directed enzyme prodrug therapy of hepatocellular carcinoma using a targeted adenovirus armed with carboxypeptidase G2</article-title><source>Cancer Res</source><volume>65</volume><fpage>5003</fpage><lpage>5008</lpage><year>2005</year><pub-id pub-id-type="pmid">15958540</pub-id></element-citation></ref><ref id="b85-ijo-41-03-0798"><label>85</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chung-Faye</surname><given-names>GA</given-names></name><name><surname>Chen</surname><given-names>MJ</given-names></name><name><surname>Green</surname><given-names>NK</given-names></name><name><surname>Burton</surname><given-names>A</given-names></name><name><surname>Anderson</surname><given-names>D</given-names></name><name><surname>Mautner</surname><given-names>V</given-names></name><name><surname>Searle</surname><given-names>PF</given-names></name><name><surname>Kerr</surname><given-names>DJ</given-names></name></person-group><article-title>In vivo gene therapy for colon cancer using adenovirus-mediated, transfer of the fusion gene cytosine deaminase and uracil phosphoribosyltransferase</article-title><source>Gene Ther</source><volume>8</volume><fpage>1547</fpage><lpage>1554</lpage><year>2001</year><pub-id pub-id-type="pmid">11704815</pub-id></element-citation></ref><ref id="b86-ijo-41-03-0798"><label>86</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hernandez-Alcoceba</surname><given-names>R</given-names></name><name><surname>Sangro</surname><given-names>B</given-names></name><name><surname>Prieto</surname><given-names>J</given-names></name></person-group><article-title>Gene therapy of liver cancer</article-title><source>World J Gastroenterol</source><volume>12</volume><fpage>6085</fpage><lpage>6097</lpage><year>2006</year><pub-id pub-id-type="pmid">17036377</pub-id></element-citation></ref><ref id="b87-ijo-41-03-0798"><label>87</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yi</surname><given-names>BR</given-names></name><name><surname>O</surname><given-names>SN</given-names></name><name><surname>Kang</surname><given-names>NH</given-names></name><name><surname>Hwang</surname><given-names>KA</given-names></name><name><surname>Kim</surname><given-names>SU</given-names></name><name><surname>Jeung</surname><given-names>EB</given-names></name><name><surname>Kim</surname><given-names>YB</given-names></name><name><surname>Heo</surname><given-names>GJ</given-names></name><name><surname>Choi</surname><given-names>KC</given-names></name></person-group><article-title>Genetically engineered stem cells expressing cytosine deaminase and interferon-β migrate to human lung cancer cells and have potentially therapeutic anti-tumor effects</article-title><source>Int J Oncol</source><volume>39</volume><fpage>833</fpage><lpage>839</lpage><year>2011</year><pub-id pub-id-type="pmid">21769425</pub-id></element-citation></ref><ref id="b88-ijo-41-03-0798"><label>88</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yi</surname><given-names>BR</given-names></name><name><surname>Kang</surname><given-names>NH</given-names></name><name><surname>Hwang</surname><given-names>KA</given-names></name><name><surname>Kim</surname><given-names>SU</given-names></name><name><surname>Jeung</surname><given-names>EB</given-names></name><name><surname>Choi</surname><given-names>KC</given-names></name></person-group><article-title>Antitumor therapeutic effects of cytosine deaminase and interferon-β against endometrial cancer cells using genetically engineered stem cells in vitro</article-title><source>Anticancer Res</source><volume>31</volume><fpage>2853</fpage><lpage>2861</lpage><year>2011</year><pub-id pub-id-type="pmid">21868529</pub-id></element-citation></ref><ref id="b89-ijo-41-03-0798"><label>89</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dachs</surname><given-names>GU</given-names></name><name><surname>Hunt</surname><given-names>MA</given-names></name><name><surname>Syddall</surname><given-names>S</given-names></name><name><surname>Singleton</surname><given-names>DC</given-names></name><name><surname>Patterson</surname><given-names>AV</given-names></name></person-group><article-title>Bystander or no bystander for gene directed enzyme prodrug therapy</article-title><source>Molecules</source><volume>14</volume><fpage>4517</fpage><lpage>4545</lpage><year>2009</year><pub-id pub-id-type="pmid">19924084</pub-id></element-citation></ref><ref id="b90-ijo-41-03-0798"><label>90</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pfeifer</surname><given-names>A</given-names></name><name><surname>Verma</surname><given-names>IM</given-names></name></person-group><article-title>Gene therapy: promises and problems</article-title><source>Annu Rev Genomics Hum Genet</source><volume>2</volume><fpage>177</fpage><lpage>211</lpage><year>2001</year><pub-id pub-id-type="pmid">11701648</pub-id></element-citation></ref><ref id="b91-ijo-41-03-0798"><label>91</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shah</surname><given-names>K</given-names></name></person-group><article-title>Mesenchymal stem cells engineered for cancer therapy</article-title><source>Adv Drug Deliv Rev</source><volume>64</volume><fpage>739</fpage><lpage>748</lpage><year>2012</year><pub-id pub-id-type="pmid">21740940</pub-id></element-citation></ref><ref id="b92-ijo-41-03-0798"><label>92</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ramnaraine</surname><given-names>M</given-names></name><name><surname>Pan</surname><given-names>W</given-names></name><name><surname>Goblirsch</surname><given-names>M</given-names></name><name><surname>Lynch</surname><given-names>C</given-names></name><name><surname>Lewis</surname><given-names>V</given-names></name><name><surname>Orchard</surname><given-names>P</given-names></name><name><surname>Mantyh</surname><given-names>P</given-names></name><name><surname>Clohisy</surname><given-names>DR</given-names></name></person-group><article-title>Direct and bystander killing of sarcomas by novel cytosine deaminase fusion gene</article-title><source>Cancer Res</source><volume>63</volume><fpage>6847</fpage><lpage>6854</lpage><year>2003</year><pub-id pub-id-type="pmid">14583482</pub-id></element-citation></ref><ref id="b93-ijo-41-03-0798"><label>93</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nyati</surname><given-names>MK</given-names></name><name><surname>Symon</surname><given-names>Z</given-names></name><name><surname>Kievit</surname><given-names>E</given-names></name><name><surname>Dornfeld</surname><given-names>KJ</given-names></name><name><surname>Rynkiewicz</surname><given-names>SD</given-names></name><name><surname>Ross</surname><given-names>BD</given-names></name><name><surname>Rehemtulla</surname><given-names>A</given-names></name><name><surname>Lawrence</surname><given-names>TS</given-names></name></person-group><article-title>The potential of 5-fluorocytosine/cytosine deaminase enzyme prodrug gene therapy in an intrahepatic colon cancer model</article-title><source>Gene Ther</source><volume>9</volume><fpage>844</fpage><lpage>849</lpage><year>2002</year><pub-id pub-id-type="pmid">12080378</pub-id></element-citation></ref><ref id="b94-ijo-41-03-0798"><label>94</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ireton</surname><given-names>GC</given-names></name><name><surname>Black</surname><given-names>ME</given-names></name><name><surname>Stoddard</surname><given-names>BL</given-names></name></person-group><article-title>Crystallization and preliminary X-ray analysis of bacterial cytosine deaminase</article-title><source>Acta Crystallogr D Biol Crystallogr</source><volume>57</volume><fpage>1643</fpage><lpage>1645</lpage><year>2001</year><pub-id pub-id-type="pmid">11679731</pub-id></element-citation></ref><ref id="b95-ijo-41-03-0798"><label>95</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ireton</surname><given-names>GC</given-names></name><name><surname>Black</surname><given-names>ME</given-names></name><name><surname>Stoddard</surname><given-names>BL</given-names></name></person-group><article-title>The 1.14 A crystal structure of yeast cytosine deaminase: evolution of nucleotide salvage enzymes and implications for genetic chemotherapy</article-title><source>Structure</source><volume>11</volume><fpage>961</fpage><lpage>972</lpage><year>2003</year><pub-id pub-id-type="pmid">12906827</pub-id></element-citation></ref><ref id="b96-ijo-41-03-0798"><label>96</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Denny</surname><given-names>WA</given-names></name></person-group><article-title>Prodrugs for Gene-Directed Enzyme-Prodrug Therapy (Suicide Gene Therapy)</article-title><source>J Biomed Biotechnol</source><volume>2003</volume><fpage>48</fpage><lpage>70</lpage><year>2003</year><pub-id pub-id-type="pmid">12686722</pub-id></element-citation></ref><ref id="b97-ijo-41-03-0798"><label>97</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ireton</surname><given-names>GC</given-names></name><name><surname>McDermott</surname><given-names>G</given-names></name><name><surname>Black</surname><given-names>ME</given-names></name><name><surname>Stoddard</surname><given-names>BL</given-names></name></person-group><article-title>The structure of Escherichia coli cytosine deaminase</article-title><source>J Mol Biol</source><volume>315</volume><fpage>687</fpage><lpage>697</lpage><year>2002</year><pub-id pub-id-type="pmid">11812140</pub-id></element-citation></ref><ref id="b98-ijo-41-03-0798"><label>98</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fuchita</surname><given-names>M</given-names></name><name><surname>Ardiani</surname><given-names>A</given-names></name><name><surname>Zhao</surname><given-names>L</given-names></name><name><surname>Serve</surname><given-names>K</given-names></name><name><surname>Stoddard</surname><given-names>BL</given-names></name><name><surname>Black</surname><given-names>ME</given-names></name></person-group><article-title>Bacterial cytosine deaminase mutants created by molecular engineering show improved 5-fluorocytosine-mediated cell killing in vitro and in vivo</article-title><source>Cancer Res</source><volume>69</volume><fpage>4791</fpage><lpage>4799</lpage><year>2009</year><pub-id pub-id-type="pmid">19487291</pub-id></element-citation></ref><ref id="b99-ijo-41-03-0798"><label>99</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>KY</given-names></name><name><surname>Kim</surname><given-names>SU</given-names></name><name><surname>Leung</surname><given-names>PC</given-names></name><name><surname>Jeung</surname><given-names>EB</given-names></name><name><surname>Choi</surname><given-names>KC</given-names></name></person-group><article-title>Influence of the prodrugs 5-fluorocytosine and CPT-11 on ovarian cancer cells using genetically engineered stem cells: tumor-tropic potential and inhibition of ovarian cancer cell growth</article-title><source>Cancer Sci</source><volume>101</volume><fpage>955</fpage><lpage>962</lpage><year>2010</year><pub-id pub-id-type="pmid">20704576</pub-id></element-citation></ref><ref id="b100-ijo-41-03-0798"><label>100</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>JK</given-names></name><name><surname>Hu</surname><given-names>LJ</given-names></name><name><surname>Wang</surname><given-names>D</given-names></name><name><surname>Lamborn</surname><given-names>KR</given-names></name><name><surname>Deen</surname><given-names>DF</given-names></name></person-group><article-title>Cytosine deaminase/5-fluorocytosine exposure induces bystander and radiosensitization effects in hypoxic glioblastoma cells in vitro</article-title><source>Int J Radiat Oncol Biol Phys</source><volume>67</volume><fpage>1538</fpage><lpage>1547</lpage><year>2007</year><pub-id pub-id-type="pmid">17394949</pub-id></element-citation></ref><ref id="b101-ijo-41-03-0798"><label>101</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Miller</surname><given-names>CR</given-names></name><name><surname>Williams</surname><given-names>CR</given-names></name><name><surname>Buchsbaum</surname><given-names>DJ</given-names></name><name><surname>Gillespie</surname><given-names>GY</given-names></name></person-group><article-title>Intratumoral 5-fluorouracil produced by cytosine deaminase/5-fluorocytosine gene therapy is effective for experimental human glioblastomas</article-title><source>Cancer Res</source><volume>62</volume><fpage>773</fpage><lpage>780</lpage><year>2002</year><pub-id pub-id-type="pmid">11830532</pub-id></element-citation></ref><ref id="b102-ijo-41-03-0798"><label>102</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Humerickhouse</surname><given-names>R</given-names></name><name><surname>Lohrbach</surname><given-names>K</given-names></name><name><surname>Li</surname><given-names>L</given-names></name><name><surname>Bosron</surname><given-names>WF</given-names></name><name><surname>Dolan</surname><given-names>ME</given-names></name></person-group><article-title>Characterization of CPT-11 hydrolysis by human liver carboxylesterase isoforms hCE-1 and hCE-2</article-title><source>Cancer Res</source><volume>60</volume><fpage>1189</fpage><lpage>1192</lpage><year>2000</year><pub-id pub-id-type="pmid">10728672</pub-id></element-citation></ref><ref id="b103-ijo-41-03-0798"><label>103</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bencharit</surname><given-names>S</given-names></name><name><surname>Morton</surname><given-names>CL</given-names></name><name><surname>Howard-Williams</surname><given-names>EL</given-names></name><name><surname>Danks</surname><given-names>MK</given-names></name><name><surname>Potter</surname><given-names>PM</given-names></name><name><surname>Redinbo</surname><given-names>MR</given-names></name></person-group><article-title>Structural insights into CPT-11 activation by mammalian carboxylesterases</article-title><source>Nat Struct Biol</source><volume>9</volume><fpage>337</fpage><lpage>342</lpage><year>2002</year><pub-id pub-id-type="pmid">11967565</pub-id></element-citation></ref><ref id="b104-ijo-41-03-0798"><label>104</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bodor</surname><given-names>N</given-names></name><name><surname>Buchwald</surname><given-names>P</given-names></name></person-group><article-title>Soft drug design: general principles and recent applications</article-title><source>Med Res Rev</source><volume>20</volume><fpage>58</fpage><lpage>101</lpage><year>2000</year><pub-id pub-id-type="pmid">10608921</pub-id></element-citation></ref><ref id="b105-ijo-41-03-0798"><label>105</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wadkins</surname><given-names>RM</given-names></name><name><surname>Morton</surname><given-names>CL</given-names></name><name><surname>Weeks</surname><given-names>JK</given-names></name><name><surname>Oliver</surname><given-names>L</given-names></name><name><surname>Wierdl</surname><given-names>M</given-names></name><name><surname>Danks</surname><given-names>MK</given-names></name><name><surname>Potter</surname><given-names>PM</given-names></name></person-group><article-title>Structural constraints affect the metabolism of 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11) by carboxylesterases</article-title><source>Mol Pharmacol</source><volume>60</volume><fpage>355</fpage><lpage>362</lpage><year>2001</year><pub-id pub-id-type="pmid">11455023</pub-id></element-citation></ref><ref id="b106-ijo-41-03-0798"><label>106</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wierdl</surname><given-names>M</given-names></name><name><surname>Morton</surname><given-names>CL</given-names></name><name><surname>Weeks</surname><given-names>JK</given-names></name><name><surname>Danks</surname><given-names>MK</given-names></name><name><surname>Harris</surname><given-names>LC</given-names></name><name><surname>Potter</surname><given-names>PM</given-names></name></person-group><article-title>Sensitization of human tumor cells to CPT-11 via adenoviral-mediated delivery of a rabbit liver carboxylesterase</article-title><source>Cancer Res</source><volume>61</volume><fpage>5078</fpage><lpage>5082</lpage><year>2001</year><pub-id pub-id-type="pmid">11431344</pub-id></element-citation></ref><ref id="b107-ijo-41-03-0798"><label>107</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kojima</surname><given-names>A</given-names></name><name><surname>Hackett</surname><given-names>NR</given-names></name><name><surname>Ohwada</surname><given-names>A</given-names></name><name><surname>Crystal</surname><given-names>RG</given-names></name></person-group><article-title>In vivo human carboxylesterase cDNA gene transfer to activate the prodrug CPT-11 for local treatment of solid tumors</article-title><source>J Clin Invest</source><volume>101</volume><fpage>1789</fpage><lpage>1796</lpage><year>1998</year><pub-id pub-id-type="pmid">9541511</pub-id></element-citation></ref><ref id="b108-ijo-41-03-0798"><label>108</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>van Dillen</surname><given-names>IJ</given-names></name><name><surname>Mulder</surname><given-names>NH</given-names></name><name><surname>Vaalburg</surname><given-names>W</given-names></name><name><surname>de Vries</surname><given-names>EF</given-names></name><name><surname>Hospers</surname><given-names>GA</given-names></name></person-group><article-title>Influence of the bystander effect on HSV-tk/GCV gene therapy. A review</article-title><source>Curr Gene Ther</source><volume>2</volume><fpage>307</fpage><lpage>322</lpage><year>2002</year><pub-id pub-id-type="pmid">12189718</pub-id></element-citation></ref><ref id="b109-ijo-41-03-0798"><label>109</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gerolami</surname><given-names>R</given-names></name><name><surname>Cardoso</surname><given-names>J</given-names></name><name><surname>Lewin</surname><given-names>M</given-names></name><name><surname>Bralet</surname><given-names>MP</given-names></name><name><surname>Sa Cunha</surname><given-names>A</given-names></name><name><surname>Clement</surname><given-names>O</given-names></name><name><surname>Brechot</surname><given-names>C</given-names></name><name><surname>Tran</surname><given-names>PL</given-names></name></person-group><article-title>Evaluation of HSV-tk gene therapy in a rat model of chemically induced hepatocellular carcinoma by intratumoral and intrahepatic artery routes</article-title><source>Cancer Res</source><volume>60</volume><fpage>993</fpage><lpage>1001</lpage><year>2000</year><pub-id pub-id-type="pmid">10706115</pub-id></element-citation></ref><ref id="b110-ijo-41-03-0798"><label>110</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fillat</surname><given-names>C</given-names></name><name><surname>Carrio</surname><given-names>M</given-names></name><name><surname>Cascante</surname><given-names>A</given-names></name><name><surname>Sangro</surname><given-names>B</given-names></name></person-group><article-title>Suicide gene therapy mediated by the Herpes Simplex virus thymidine kinase gene/Ganciclovir system: fifteen years of application</article-title><source>Curr Gene Ther</source><volume>3</volume><fpage>13</fpage><lpage>26</lpage><year>2003</year><pub-id pub-id-type="pmid">12553532</pub-id></element-citation></ref><ref id="b111-ijo-41-03-0798"><label>111</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>Q</given-names></name><name><surname>Pu</surname><given-names>P</given-names></name><name><surname>Xia</surname><given-names>Z</given-names></name><name><surname>You</surname><given-names>Y</given-names></name></person-group><article-title>Exogenous wt-p53 enhances the antitumor effect of HSV-TK/GCV on C6 glioma cells</article-title><source>J Neurooncol</source><volume>82</volume><fpage>239</fpage><lpage>248</lpage><year>2007</year><pub-id pub-id-type="pmid">17102907</pub-id></element-citation></ref><ref id="b112-ijo-41-03-0798"><label>112</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cowen</surname><given-names>RL</given-names></name><name><surname>Williams</surname><given-names>JC</given-names></name><name><surname>Emery</surname><given-names>S</given-names></name><name><surname>Blakey</surname><given-names>D</given-names></name><name><surname>Darling</surname><given-names>JL</given-names></name><name><surname>Lowenstein</surname><given-names>PR</given-names></name><name><surname>Castro</surname><given-names>MG</given-names></name></person-group><article-title>Adenovirus vector-mediated delivery of the prodrug-converting enzyme carboxypeptidase G2 in a secreted or GPI-anchored form: High-level expression of this active conditional cytotoxic enzyme at the plasma membrane</article-title><source>Cancer Gene Ther</source><volume>9</volume><fpage>897</fpage><lpage>907</lpage><year>2002</year><pub-id pub-id-type="pmid">12386828</pub-id></element-citation></ref><ref id="b113-ijo-41-03-0798"><label>113</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Muller</surname><given-names>FJ</given-names></name><name><surname>Snyder</surname><given-names>EY</given-names></name><name><surname>Loring</surname><given-names>JF</given-names></name></person-group><article-title>Gene therapy: can neural stem cells deliver?</article-title><source>Nat Rev Neurosci</source><volume>7</volume><fpage>75</fpage><lpage>84</lpage><year>2006</year><pub-id pub-id-type="pmid">16371952</pub-id></element-citation></ref><ref id="b114-ijo-41-03-0798"><label>114</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>SU</given-names></name><name><surname>Jeung</surname><given-names>EB</given-names></name><name><surname>Kim</surname><given-names>YB</given-names></name><name><surname>Cho</surname><given-names>MH</given-names></name><name><surname>Choi</surname><given-names>KC</given-names></name></person-group><article-title>Potential tumor-tropic effect of genetically engineered stem cells expressing suicide enzymes to selectively target invasive cancer in animal models</article-title><source>Anticancer Res</source><volume>31</volume><fpage>1249</fpage><lpage>1258</lpage><year>2011</year><pub-id pub-id-type="pmid">21508372</pub-id></element-citation></ref><ref id="b115-ijo-41-03-0798"><label>115</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tang</surname><given-names>Y</given-names></name><name><surname>Shah</surname><given-names>K</given-names></name><name><surname>Messerli</surname><given-names>SM</given-names></name><name><surname>Snyder</surname><given-names>E</given-names></name><name><surname>Breakefield</surname><given-names>X</given-names></name><name><surname>Weissleder</surname><given-names>R</given-names></name></person-group><article-title>In vivo tracking of neural progenitor cell migration to glioblastomas</article-title><source>Hum Gene Ther</source><volume>14</volume><fpage>1247</fpage><lpage>1254</lpage><year>2003</year><pub-id pub-id-type="pmid">12952596</pub-id></element-citation></ref><ref id="b116-ijo-41-03-0798"><label>116</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Power</surname><given-names>AT</given-names></name><name><surname>Bell</surname><given-names>JC</given-names></name></person-group><article-title>Cell-based delivery of oncolytic viruses: a new strategic alliance for a biological strike against cancer</article-title><source>Mol Ther</source><volume>15</volume><fpage>660</fpage><lpage>665</lpage><year>2007</year><pub-id pub-id-type="pmid">17264852</pub-id></element-citation></ref><ref id="b117-ijo-41-03-0798"><label>117</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>KY</given-names></name><name><surname>Yi</surname><given-names>BR</given-names></name><name><surname>Lee</surname><given-names>HR</given-names></name><name><surname>Kang</surname><given-names>NH</given-names></name><name><surname>Jeung</surname><given-names>EB</given-names></name><name><surname>Kim</surname><given-names>SU</given-names></name><name><surname>Choi</surname><given-names>KC</given-names></name></person-group><article-title>Stem cells with fused gene expression of cytosine deaminase and interferon-β migrate to human gastric cancer cells and result in synergistic growth inhibition for potential therapeutic use</article-title><source>Int J Oncol</source><volume>40</volume><fpage>1097</fpage><lpage>1104</lpage><year>2012</year><pub-id pub-id-type="pmid">22159640</pub-id></element-citation></ref><ref id="b118-ijo-41-03-0798"><label>118</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Aboody</surname><given-names>KS</given-names></name><name><surname>Najbauer</surname><given-names>J</given-names></name><name><surname>Danks</surname><given-names>MK</given-names></name></person-group><article-title>Stem and progenitor cell-mediated tumor selective gene therapy</article-title><source>Gene Ther</source><volume>15</volume><fpage>739</fpage><lpage>752</lpage><year>2008</year><pub-id pub-id-type="pmid">18369324</pub-id></element-citation></ref><ref id="b119-ijo-41-03-0798"><label>119</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gutova</surname><given-names>M</given-names></name><name><surname>Najbauer</surname><given-names>J</given-names></name><name><surname>Frank</surname><given-names>RT</given-names></name><name><surname>Kendall</surname><given-names>SE</given-names></name><name><surname>Gevorgyan</surname><given-names>A</given-names></name><name><surname>Metz</surname><given-names>MZ</given-names></name><name><surname>Guevorkian</surname><given-names>M</given-names></name><name><surname>Edmiston</surname><given-names>M</given-names></name><name><surname>Zhao</surname><given-names>D</given-names></name><name><surname>Glackin</surname><given-names>CA</given-names></name><etal></etal></person-group><article-title>Urokinase plasminogen activator and urokinase plasminogen activator receptor mediate human stem cell tropism to malignant solid tumors</article-title><source>Stem Cells</source><volume>26</volume><fpage>1406</fpage><lpage>1413</lpage><year>2008</year><pub-id pub-id-type="pmid">18403751</pub-id></element-citation></ref><ref id="b120-ijo-41-03-0798"><label>120</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bithell</surname><given-names>A</given-names></name><name><surname>Williams</surname><given-names>BP</given-names></name></person-group><article-title>Neural stem cells and cell replacement therapy: making the right cells</article-title><source>Clin Sci</source><volume>108</volume><fpage>13</fpage><lpage>22</lpage><year>2005</year><pub-id pub-id-type="pmid">15462670</pub-id></element-citation></ref><ref id="b121-ijo-41-03-0798"><label>121</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>SK</given-names></name><name><surname>Kim</surname><given-names>SU</given-names></name><name><surname>Park</surname><given-names>IH</given-names></name><name><surname>Bang</surname><given-names>JH</given-names></name><name><surname>Aboody</surname><given-names>KS</given-names></name><name><surname>Wang</surname><given-names>KC</given-names></name><name><surname>Cho</surname><given-names>BK</given-names></name><name><surname>Kim</surname><given-names>M</given-names></name><name><surname>Menon</surname><given-names>LG</given-names></name><name><surname>Black</surname><given-names>PM</given-names></name><name><surname>Carroll</surname><given-names>RS</given-names></name></person-group><article-title>Human neural stem cells target experimental intracranial medulloblastoma and deliver a therapeutic gene leading to tumor regression</article-title><source>Clin Cancer Res</source><volume>12</volume><fpage>5550</fpage><lpage>5556</lpage><year>2006</year><pub-id pub-id-type="pmid">17000692</pub-id></element-citation></ref><ref id="b122-ijo-41-03-0798"><label>122</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sohur</surname><given-names>US</given-names></name><name><surname>Emsley</surname><given-names>JG</given-names></name><name><surname>Mitchell</surname><given-names>BD</given-names></name><name><surname>Macklis</surname><given-names>JD</given-names></name></person-group><article-title>Adult neurogenesis and cellular brain repair with neural progenitors, precursors and stem cells</article-title><source>Philos Trans R Soc Lond B Biol Sci</source><volume>361</volume><fpage>1477</fpage><lpage>1497</lpage><year>2006</year><pub-id pub-id-type="pmid">16939970</pub-id></element-citation></ref><ref id="b123-ijo-41-03-0798"><label>123</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>SU</given-names></name><name><surname>Park</surname><given-names>IH</given-names></name><name><surname>Kim</surname><given-names>TH</given-names></name><name><surname>Kim</surname><given-names>KS</given-names></name><name><surname>Choi</surname><given-names>HB</given-names></name><name><surname>Hong</surname><given-names>SH</given-names></name><name><surname>Bang</surname><given-names>JH</given-names></name><name><surname>Lee</surname><given-names>MA</given-names></name><name><surname>Joo</surname><given-names>IS</given-names></name><name><surname>Lee</surname><given-names>CS</given-names></name><name><surname>Kim</surname><given-names>YS</given-names></name></person-group><article-title>Brain transplantation of human neural stem cells transduced with tyrosine hydroxylase and GTP cyclohydrolase 1 provides functional improvement in animal models of Parkinson disease</article-title><source>Neuropathology</source><volume>26</volume><fpage>129</fpage><lpage>140</lpage><year>2006</year><pub-id pub-id-type="pmid">16708545</pub-id></element-citation></ref><ref id="b124-ijo-41-03-0798"><label>124</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Joo</surname><given-names>KM</given-names></name><name><surname>Park</surname><given-names>IH</given-names></name><name><surname>Shin</surname><given-names>JY</given-names></name><name><surname>Jin</surname><given-names>J</given-names></name><name><surname>Kang</surname><given-names>BG</given-names></name><name><surname>Kim</surname><given-names>MH</given-names></name><name><surname>Lee</surname><given-names>SJ</given-names></name><name><surname>Jo</surname><given-names>MY</given-names></name><name><surname>Kim</surname><given-names>SU</given-names></name><name><surname>Nam</surname><given-names>DH</given-names></name></person-group><article-title>Human neural stem cells can target and deliver therapeutic genes to breast cancer brain metastases</article-title><source>Mol Ther</source><volume>17</volume><fpage>570</fpage><lpage>575</lpage><year>2009</year><pub-id pub-id-type="pmid">19127251</pub-id></element-citation></ref></ref-list></back><floats-group><fig id="f1-ijo-41-03-0798" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Schematic of genetically engineered stem cell (GESTEC)-based therapy. GESTECs are immortalized by retroviral vectors and contain suicide genes such as ones encoding cytosine deaminase (CD), carboxyl esterase (CE), and thymidine kinase (TK). CD converts the prodrug 5-fluorocytosine (5-FC) into a toxic agent, 5-fluorouracil (5-FU), which inhibits RNA and DNA synthesis. CPT-11 is a prodrug converted by CE into its active form, SN-38, which is a potent mammalian topoisomerase I inhibitor. Finally, the TK gene is found in herpes simplex virus (HSV). The product of this gene converts non-toxic ganciclovir into its toxic active form. These GESTECs exert tumor-tropism effects and may be used to treat several types of tumors.</p></caption><graphic xlink:href="IJO-41-03-0798-g00"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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