Effect of Oxaliplatin-Loaded Poly (d,l-Lactide-co-Glycolic Acid) (PLGA) Nanoparticles Combined with Retinoic Acid and Cholesterol on Apoptosis, Drug Resistance, and Metastasis Factors of Colorectal Cancer
Identifieur interne : 000F66 ( Ncbi/Merge ); précédent : 000F65; suivant : 000F67Effect of Oxaliplatin-Loaded Poly (d,l-Lactide-co-Glycolic Acid) (PLGA) Nanoparticles Combined with Retinoic Acid and Cholesterol on Apoptosis, Drug Resistance, and Metastasis Factors of Colorectal Cancer
Auteurs : Ana Luiza C. De S. L. Oliveira ; Raimundo Fernandes De Araújo Júnior [Brésil] ; Thaís Gomes De Carvalho ; Alan B. Chan ; Timo Schomann ; Filippo Tamburini ; Lioe-Fee De Geus-Oei ; Luis J. CruzSource :
- Pharmaceutics [ 1999-4923 ] ; 2020.
Abstract
Apoptosis signaling pathways, drug resistance, and metastasis are important targets to develop new cancer treatments. We developed cholesterol-coated Poly(
Url:
DOI: 10.3390/pharmaceutics12020193
PubMed: 32102251
PubMed Central: 7076533
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000795
- to stream Pmc, to step Curation: 000795
- to stream Pmc, to step Checkpoint: 000156
Links to Exploration step
PMC:7076533Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Effect of Oxaliplatin-Loaded Poly (<sc>d</sc>,<sc>l</sc>-Lactide-<italic>co</italic>-Glycolic Acid) (PLGA) Nanoparticles Combined with Retinoic Acid and Cholesterol on Apoptosis, Drug Resistance, and Metastasis Factors of Colorectal Cancer</title><author><name sortKey="C De S L Oliveira, Ana Luiza" sort="C De S L Oliveira, Ana Luiza" uniqKey="C De S L Oliveira A" first="Ana Luiza" last="C. De S. L. Oliveira">Ana Luiza C. De S. L. Oliveira</name><affiliation><nlm:aff id="af1-pharmaceutics-12-00193">Postgraduate Program in Health Science, Federal University of Rio Grande do Norte (UFRN), 59078 970 Natal, RN, Brazil;<email>analuiza_oliveira@outlook.com</email> (A.L.C.d.S.L.O.);<email>thaisbida2011@hotmail.com</email> (T.G.d.C.)</nlm:aff></affiliation><affiliation><nlm:aff id="af2-pharmaceutics-12-00193">Translational Nanobiomaterials and Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;<email>t.schomann@lumc.nl</email></nlm:aff></affiliation></author><author><name sortKey="De Araujo Junior, Raimundo Fernandes" sort="De Araujo Junior, Raimundo Fernandes" uniqKey="De Araujo Junior R" first="Raimundo Fernandes" last="De Araújo Júnior">Raimundo Fernandes De Araújo Júnior</name><affiliation><nlm:aff id="af1-pharmaceutics-12-00193">Postgraduate Program in Health Science, Federal University of Rio Grande do Norte (UFRN), 59078 970 Natal, RN, Brazil;<email>analuiza_oliveira@outlook.com</email> (A.L.C.d.S.L.O.);<email>thaisbida2011@hotmail.com</email> (T.G.d.C.)</nlm:aff></affiliation><affiliation><nlm:aff id="af2-pharmaceutics-12-00193">Translational Nanobiomaterials and Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;<email>t.schomann@lumc.nl</email></nlm:aff></affiliation><affiliation wicri:level="2"><nlm:aff id="af3-pharmaceutics-12-00193">Postgraduate Program in Functional and Structural Biology, Department of Morphology, Federal University of Rio Grande do Norte (UFRN), 59078 970 Natal, RN, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Postgraduate Program in Functional and Structural Biology, Department of Morphology, Federal University of Rio Grande do Norte (UFRN), 59078 970 Natal, RN</wicri:regionArea><placeName><region type="state">Rio Grande do Norte</region></placeName></affiliation></author><author><name sortKey="Gomes De Carvalho, Thais" sort="Gomes De Carvalho, Thais" uniqKey="Gomes De Carvalho T" first="Thaís" last="Gomes De Carvalho">Thaís Gomes De Carvalho</name><affiliation><nlm:aff id="af1-pharmaceutics-12-00193">Postgraduate Program in Health Science, Federal University of Rio Grande do Norte (UFRN), 59078 970 Natal, RN, Brazil;<email>analuiza_oliveira@outlook.com</email> (A.L.C.d.S.L.O.);<email>thaisbida2011@hotmail.com</email> (T.G.d.C.)</nlm:aff></affiliation><affiliation><nlm:aff id="af2-pharmaceutics-12-00193">Translational Nanobiomaterials and Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;<email>t.schomann@lumc.nl</email></nlm:aff></affiliation></author><author><name sortKey="B Chan, Alan" sort="B Chan, Alan" uniqKey="B Chan A" first="Alan" last="B. Chan">Alan B. Chan</name><affiliation><nlm:aff id="af4-pharmaceutics-12-00193">Percuros B.V, Zernikedreef 8, 2333 CL Leiden, The Netherlands;<email>alanchan@clara.net</email> (A.B.C.);<email>tambu.91@hotmail.it</email> (F.T.)</nlm:aff></affiliation></author><author><name sortKey="Schomann, Timo" sort="Schomann, Timo" uniqKey="Schomann T" first="Timo" last="Schomann">Timo Schomann</name><affiliation><nlm:aff id="af2-pharmaceutics-12-00193">Translational Nanobiomaterials and Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;<email>t.schomann@lumc.nl</email></nlm:aff></affiliation><affiliation><nlm:aff id="af4-pharmaceutics-12-00193">Percuros B.V, Zernikedreef 8, 2333 CL Leiden, The Netherlands;<email>alanchan@clara.net</email> (A.B.C.);<email>tambu.91@hotmail.it</email> (F.T.)</nlm:aff></affiliation></author><author><name sortKey="Tamburini, Filippo" sort="Tamburini, Filippo" uniqKey="Tamburini F" first="Filippo" last="Tamburini">Filippo Tamburini</name><affiliation><nlm:aff id="af4-pharmaceutics-12-00193">Percuros B.V, Zernikedreef 8, 2333 CL Leiden, The Netherlands;<email>alanchan@clara.net</email> (A.B.C.);<email>tambu.91@hotmail.it</email> (F.T.)</nlm:aff></affiliation></author><author><name sortKey="De Geus Oei, Lioe Fee" sort="De Geus Oei, Lioe Fee" uniqKey="De Geus Oei L" first="Lioe-Fee" last="De Geus-Oei">Lioe-Fee De Geus-Oei</name><affiliation><nlm:aff id="af5-pharmaceutics-12-00193">Nuclear Medicine, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;<email>l.f.de_geus-oei@lumc.nl</email></nlm:aff></affiliation></author><author><name sortKey="J Cruz, Luis" sort="J Cruz, Luis" uniqKey="J Cruz L" first="Luis" last="J. Cruz">Luis J. Cruz</name><affiliation><nlm:aff id="af2-pharmaceutics-12-00193">Translational Nanobiomaterials and Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;<email>t.schomann@lumc.nl</email></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32102251</idno><idno type="pmc">7076533</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076533</idno><idno type="RBID">PMC:7076533</idno><idno type="doi">10.3390/pharmaceutics12020193</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000795</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000795</idno><idno type="wicri:Area/Pmc/Curation">000795</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000795</idno><idno type="wicri:Area/Pmc/Checkpoint">000156</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000156</idno><idno type="wicri:Area/Ncbi/Merge">000F66</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Effect of Oxaliplatin-Loaded Poly (<sc>d</sc>,<sc>l</sc>-Lactide-<italic>co</italic>-Glycolic Acid) (PLGA) Nanoparticles Combined with Retinoic Acid and Cholesterol on Apoptosis, Drug Resistance, and Metastasis Factors of Colorectal Cancer</title><author><name sortKey="C De S L Oliveira, Ana Luiza" sort="C De S L Oliveira, Ana Luiza" uniqKey="C De S L Oliveira A" first="Ana Luiza" last="C. De S. L. Oliveira">Ana Luiza C. De S. L. Oliveira</name><affiliation><nlm:aff id="af1-pharmaceutics-12-00193">Postgraduate Program in Health Science, Federal University of Rio Grande do Norte (UFRN), 59078 970 Natal, RN, Brazil;<email>analuiza_oliveira@outlook.com</email> (A.L.C.d.S.L.O.);<email>thaisbida2011@hotmail.com</email> (T.G.d.C.)</nlm:aff></affiliation><affiliation><nlm:aff id="af2-pharmaceutics-12-00193">Translational Nanobiomaterials and Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;<email>t.schomann@lumc.nl</email></nlm:aff></affiliation></author><author><name sortKey="De Araujo Junior, Raimundo Fernandes" sort="De Araujo Junior, Raimundo Fernandes" uniqKey="De Araujo Junior R" first="Raimundo Fernandes" last="De Araújo Júnior">Raimundo Fernandes De Araújo Júnior</name><affiliation><nlm:aff id="af1-pharmaceutics-12-00193">Postgraduate Program in Health Science, Federal University of Rio Grande do Norte (UFRN), 59078 970 Natal, RN, Brazil;<email>analuiza_oliveira@outlook.com</email> (A.L.C.d.S.L.O.);<email>thaisbida2011@hotmail.com</email> (T.G.d.C.)</nlm:aff></affiliation><affiliation><nlm:aff id="af2-pharmaceutics-12-00193">Translational Nanobiomaterials and Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;<email>t.schomann@lumc.nl</email></nlm:aff></affiliation><affiliation wicri:level="2"><nlm:aff id="af3-pharmaceutics-12-00193">Postgraduate Program in Functional and Structural Biology, Department of Morphology, Federal University of Rio Grande do Norte (UFRN), 59078 970 Natal, RN, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Postgraduate Program in Functional and Structural Biology, Department of Morphology, Federal University of Rio Grande do Norte (UFRN), 59078 970 Natal, RN</wicri:regionArea><placeName><region type="state">Rio Grande do Norte</region></placeName></affiliation></author><author><name sortKey="Gomes De Carvalho, Thais" sort="Gomes De Carvalho, Thais" uniqKey="Gomes De Carvalho T" first="Thaís" last="Gomes De Carvalho">Thaís Gomes De Carvalho</name><affiliation><nlm:aff id="af1-pharmaceutics-12-00193">Postgraduate Program in Health Science, Federal University of Rio Grande do Norte (UFRN), 59078 970 Natal, RN, Brazil;<email>analuiza_oliveira@outlook.com</email> (A.L.C.d.S.L.O.);<email>thaisbida2011@hotmail.com</email> (T.G.d.C.)</nlm:aff></affiliation><affiliation><nlm:aff id="af2-pharmaceutics-12-00193">Translational Nanobiomaterials and Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;<email>t.schomann@lumc.nl</email></nlm:aff></affiliation></author><author><name sortKey="B Chan, Alan" sort="B Chan, Alan" uniqKey="B Chan A" first="Alan" last="B. Chan">Alan B. Chan</name><affiliation><nlm:aff id="af4-pharmaceutics-12-00193">Percuros B.V, Zernikedreef 8, 2333 CL Leiden, The Netherlands;<email>alanchan@clara.net</email> (A.B.C.);<email>tambu.91@hotmail.it</email> (F.T.)</nlm:aff></affiliation></author><author><name sortKey="Schomann, Timo" sort="Schomann, Timo" uniqKey="Schomann T" first="Timo" last="Schomann">Timo Schomann</name><affiliation><nlm:aff id="af2-pharmaceutics-12-00193">Translational Nanobiomaterials and Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;<email>t.schomann@lumc.nl</email></nlm:aff></affiliation><affiliation><nlm:aff id="af4-pharmaceutics-12-00193">Percuros B.V, Zernikedreef 8, 2333 CL Leiden, The Netherlands;<email>alanchan@clara.net</email> (A.B.C.);<email>tambu.91@hotmail.it</email> (F.T.)</nlm:aff></affiliation></author><author><name sortKey="Tamburini, Filippo" sort="Tamburini, Filippo" uniqKey="Tamburini F" first="Filippo" last="Tamburini">Filippo Tamburini</name><affiliation><nlm:aff id="af4-pharmaceutics-12-00193">Percuros B.V, Zernikedreef 8, 2333 CL Leiden, The Netherlands;<email>alanchan@clara.net</email> (A.B.C.);<email>tambu.91@hotmail.it</email> (F.T.)</nlm:aff></affiliation></author><author><name sortKey="De Geus Oei, Lioe Fee" sort="De Geus Oei, Lioe Fee" uniqKey="De Geus Oei L" first="Lioe-Fee" last="De Geus-Oei">Lioe-Fee De Geus-Oei</name><affiliation><nlm:aff id="af5-pharmaceutics-12-00193">Nuclear Medicine, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;<email>l.f.de_geus-oei@lumc.nl</email></nlm:aff></affiliation></author><author><name sortKey="J Cruz, Luis" sort="J Cruz, Luis" uniqKey="J Cruz L" first="Luis" last="J. Cruz">Luis J. Cruz</name><affiliation><nlm:aff id="af2-pharmaceutics-12-00193">Translational Nanobiomaterials and Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;<email>t.schomann@lumc.nl</email></nlm:aff></affiliation></author></analytic><series><title level="j">Pharmaceutics</title><idno type="eISSN">1999-4923</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Apoptosis signaling pathways, drug resistance, and metastasis are important targets to develop new cancer treatments. We developed cholesterol-coated Poly(<sc>d</sc>,<sc>l</sc>-Lactide-<italic>co</italic>-Glycolic Acid) (PLGA) nanoparticles for effective encapsulation and delivery of retinoic acid and oxaliplatin to analyze their antitumor activity in colorectal cancer. The cell viability and proliferation of tumoral cells lines (CT-26 and SW-480) decreased when compared to control in vitro after treatment with the nanoparticles. In addition, apoptosis of CT-26 cells increased. Importantly, cytoprotection of nontumor cells was detected. Expression of pro-apoptotic proteins was upregulated, while anti-apoptotic proteins were downregulated either in vitro or in vivo. In addition, drug resistance and metastasis factors were downregulated in vivo. Human colorectal tumors that highly expressed BCL-2 and Ki-67 had a greater tendency towards death within 60 months. Our results show that loading oxaliplatin combined with retinoic acid and cholesterol in a nanoparticle formulation enables determination of optimal antitumor activity and subsequent treatment efficacy.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Kacan, T" uniqKey="Kacan T">T. Kacan</name></author><author><name sortKey="Nayir, E" uniqKey="Nayir E">E. Nayir</name></author><author><name sortKey="Altun, A" uniqKey="Altun A">A. Altun</name></author><author><name sortKey="Kilickap, S" uniqKey="Kilickap S">S. Kilickap</name></author><author><name sortKey="Babacan, N A" uniqKey="Babacan N">N.A. Babacan</name></author><author><name sortKey="Ataseven, H" uniqKey="Ataseven H">H. Ataseven</name></author><author><name sortKey="Kaya, T" uniqKey="Kaya T">T. Kaya</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, X" uniqKey="Wang X">X. Wang</name></author><author><name sortKey="Song, Z J" uniqKey="Song Z">Z.-J. Song</name></author><author><name sortKey="He, X" uniqKey="He X">X. He</name></author><author><name sortKey="Zhang, R Q" uniqKey="Zhang R">R.-Q. Zhang</name></author><author><name sortKey="Zhang, C F" uniqKey="Zhang C">C.-F. Zhang</name></author><author><name sortKey="Li, F" uniqKey="Li F">F. Li</name></author><author><name sortKey="Wang, C Z" uniqKey="Wang C">C.-Z. Wang</name></author><author><name sortKey="Yuan, C S" uniqKey="Yuan C">C.-S. Yuan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, F" uniqKey="Zhang F">F. Zhang</name></author><author><name sortKey="Lu, Y X" uniqKey="Lu Y">Y.-X. Lu</name></author><author><name sortKey="Chen, Q" uniqKey="Chen Q">Q. Chen</name></author><author><name sortKey="Zou, H M" uniqKey="Zou H">H.-M. Zou</name></author><author><name sortKey="Zhang, J M" uniqKey="Zhang J">J.-M. Zhang</name></author><author><name sortKey="Hu, Y H" uniqKey="Hu Y">Y.-H. Hu</name></author><author><name sortKey="Li, X M" uniqKey="Li X">X.-M. Li</name></author><author><name sortKey="Zhang, W J" uniqKey="Zhang W">W.-J. Zhang</name></author><author><name sortKey="Zhang, W" uniqKey="Zhang W">W. Zhang</name></author><author><name sortKey="Lin, C" uniqKey="Lin C">C. Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ferlay, J" uniqKey="Ferlay J">J. Ferlay</name></author><author><name sortKey="Soerjomataram, I" uniqKey="Soerjomataram I">I. Soerjomataram</name></author><author><name sortKey="Dikshit, R" uniqKey="Dikshit R">R. Dikshit</name></author><author><name sortKey="Eser, S" uniqKey="Eser S">S. Eser</name></author><author><name sortKey="Mathers, C" uniqKey="Mathers C">C. Mathers</name></author><author><name sortKey="Rebelo, M" uniqKey="Rebelo M">M. Rebelo</name></author><author><name sortKey="Parkin, D M" uniqKey="Parkin D">D.M. Parkin</name></author><author><name sortKey="Forman, D" uniqKey="Forman D">D. Forman</name></author><author><name sortKey="Bray, F" uniqKey="Bray F">F. Bray</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Krakstad, C" uniqKey="Krakstad C">C. Krakstad</name></author><author><name sortKey="Chekenya, M" uniqKey="Chekenya M">M. Chekenya</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ahmed, F F" uniqKey="Ahmed F">F.F. Ahmed</name></author><author><name sortKey="Abd El Hafeez, A A" uniqKey="Abd El Hafeez A">A.A. Abd El-Hafeez</name></author><author><name sortKey="Abbas, S H" uniqKey="Abbas S">S.H. Abbas</name></author><author><name sortKey="Abdelhamid, D" uniqKey="Abdelhamid D">D. Abdelhamid</name></author><author><name sortKey="Abdel Aziz, M" uniqKey="Abdel Aziz M">M. Abdel-Aziz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hu, T" uniqKey="Hu T">T. Hu</name></author><author><name sortKey="Li, Z" uniqKey="Li Z">Z. Li</name></author><author><name sortKey="Gao, C Y" uniqKey="Gao C">C.-Y. Gao</name></author><author><name sortKey="Cho, C H" uniqKey="Cho C">C.H. Cho</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Asweto, C O" uniqKey="Asweto C">C.O. Asweto</name></author><author><name sortKey="Wu, J" uniqKey="Wu J">J. Wu</name></author><author><name sortKey="Alzain, M A" uniqKey="Alzain M">M.A. Alzain</name></author><author><name sortKey="Hu, H" uniqKey="Hu H">H. Hu</name></author><author><name sortKey="Andrea, S" uniqKey="Andrea S">S. Andrea</name></author><author><name sortKey="Feng, L" uniqKey="Feng L">L. Feng</name></author><author><name sortKey="Yang, X" uniqKey="Yang X">X. Yang</name></author><author><name sortKey="Duan, J" uniqKey="Duan J">J. Duan</name></author><author><name sortKey="Sun, Z" uniqKey="Sun Z">Z. Sun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, H" uniqKey="Zhang H">H. Zhang</name></author><author><name sortKey="Song, H" uniqKey="Song H">H. Song</name></author><author><name sortKey="Yuan, R" uniqKey="Yuan R">R. Yuan</name></author><author><name sortKey="Zhang, X" uniqKey="Zhang X">X. Zhang</name></author><author><name sortKey="Yu, H" uniqKey="Yu H">H. Yu</name></author><author><name sortKey="Zhao, Y" uniqKey="Zhao Y">Y. Zhao</name></author><author><name sortKey="Jiang, T" uniqKey="Jiang T">T. Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, P" uniqKey="Zhang P">P. Zhang</name></author><author><name sortKey="Chen, Z" uniqKey="Chen Z">Z. Chen</name></author><author><name sortKey="Ning, K" uniqKey="Ning K">K. Ning</name></author><author><name sortKey="Jin, J" uniqKey="Jin J">J. Jin</name></author><author><name sortKey="Han, X" uniqKey="Han X">X. Han</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Indran, I R" uniqKey="Indran I">I.R. Indran</name></author><author><name sortKey="Tufo, G" uniqKey="Tufo G">G. Tufo</name></author><author><name sortKey="Pervaiz, S" uniqKey="Pervaiz S">S. Pervaiz</name></author><author><name sortKey="Brenner, C" uniqKey="Brenner C">C. Brenner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hong, Z P" uniqKey="Hong Z">Z.-P. Hong</name></author><author><name sortKey="Wang, L G" uniqKey="Wang L">L.-G. Wang</name></author><author><name sortKey="Wang, H J" uniqKey="Wang H">H.-J. Wang</name></author><author><name sortKey="Ye, W F" uniqKey="Ye W">W.-F. Ye</name></author><author><name sortKey="Wang, X Z" uniqKey="Wang X">X.-Z. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kumar, B" uniqKey="Kumar B">B. Kumar</name></author><author><name sortKey="Jajodia, K" uniqKey="Jajodia K">K. Jajodia</name></author><author><name sortKey="Kumar, P" uniqKey="Kumar P">P. Kumar</name></author><author><name sortKey="Gautam, H" uniqKey="Gautam H">H. Gautam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zang, X" uniqKey="Zang X">X. Zang</name></author><author><name sortKey="Zhao, X" uniqKey="Zhao X">X. Zhao</name></author><author><name sortKey="Hu, H" uniqKey="Hu H">H. Hu</name></author><author><name sortKey="Qiao, M" uniqKey="Qiao M">M. Qiao</name></author><author><name sortKey="Deng, Y" uniqKey="Deng Y">Y. Deng</name></author><author><name sortKey="Chen, D" uniqKey="Chen D">D. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Masloub, S M" uniqKey="Masloub S">S.M. Masloub</name></author><author><name sortKey="Elmalahy, M H" uniqKey="Elmalahy M">M.H. Elmalahy</name></author><author><name sortKey="Sabry, D" uniqKey="Sabry D">D. Sabry</name></author><author><name sortKey="Mohamed, W" uniqKey="Mohamed W">W. Mohamed</name></author><author><name sortKey="Hassan, S" uniqKey="Hassan S">S. Hassan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Benita, S" uniqKey="Benita S">S. Benita</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Y Y" uniqKey="Yang Y">Y.-Y. Yang</name></author><author><name sortKey="Chung, T S" uniqKey="Chung T">T.-S. Chung</name></author><author><name sortKey="Ping Ng, N" uniqKey="Ping Ng N">N. Ping Ng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jelvehgari, M" uniqKey="Jelvehgari M">M. Jelvehgari</name></author><author><name sortKey="Montazam, S H" uniqKey="Montazam S">S.H. Montazam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Imbrogno, A" uniqKey="Imbrogno A">A. Imbrogno</name></author><author><name sortKey="Piacentini, E" uniqKey="Piacentini E">E. Piacentini</name></author><author><name sortKey="Drioli, E" uniqKey="Drioli E">E. Drioli</name></author><author><name sortKey="Giorno, L" uniqKey="Giorno L">L. Giorno</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Imbrogno, A" uniqKey="Imbrogno A">A. Imbrogno</name></author><author><name sortKey="Dragosavac, M M" uniqKey="Dragosavac M">M.M. Dragosavac</name></author><author><name sortKey="Piacentini, E" uniqKey="Piacentini E">E. Piacentini</name></author><author><name sortKey="Vladisavljevi, G T" uniqKey="Vladisavljevi G">G.T. Vladisavljević</name></author><author><name sortKey="Holdich, R G" uniqKey="Holdich R">R.G. Holdich</name></author><author><name sortKey="Giorno, L" uniqKey="Giorno L">L. Giorno</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Iqbal, M" uniqKey="Iqbal M">M. Iqbal</name></author><author><name sortKey="Zafar, N" uniqKey="Zafar N">N. Zafar</name></author><author><name sortKey="Fessi, H" uniqKey="Fessi H">H. Fessi</name></author><author><name sortKey="Elaissari, A" uniqKey="Elaissari A">A. Elaissari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Varan, G" uniqKey="Varan G">G. Varan</name></author><author><name sortKey="Oncul, S" uniqKey="Oncul S">S. Öncül</name></author><author><name sortKey="Ercan, A" uniqKey="Ercan A">A. Ercan</name></author><author><name sortKey="Benito, J M" uniqKey="Benito J">J.M. Benito</name></author><author><name sortKey="Ortiz Mellet, C" uniqKey="Ortiz Mellet C">C. Ortiz Mellet</name></author><author><name sortKey="Bilensoy, E" uniqKey="Bilensoy E">E. Bilensoy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, J J" uniqKey="Lee J">J.-J. Lee</name></author><author><name sortKey="Lee, S Y" uniqKey="Lee S">S.Y. Lee</name></author><author><name sortKey="Park, J H" uniqKey="Park J">J.-H. Park</name></author><author><name sortKey="Kim, D D" uniqKey="Kim D">D.-D. Kim</name></author><author><name sortKey="Cho, H J" uniqKey="Cho H">H.-J. Cho</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Akanda, M H" uniqKey="Akanda M">M.H. Akanda</name></author><author><name sortKey="Rai, R" uniqKey="Rai R">R. Rai</name></author><author><name sortKey="Slipper, I J" uniqKey="Slipper I">I.J. Slipper</name></author><author><name sortKey="Chowdhry, B Z" uniqKey="Chowdhry B">B.Z. Chowdhry</name></author><author><name sortKey="Lamprou, D" uniqKey="Lamprou D">D. Lamprou</name></author><author><name sortKey="Getti, G" uniqKey="Getti G">G. Getti</name></author><author><name sortKey="Douroumis, D" uniqKey="Douroumis D">D. Douroumis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nagar, P" uniqKey="Nagar P">P. Nagar</name></author><author><name sortKey="Goyal, P" uniqKey="Goyal P">P. Goyal</name></author><author><name sortKey="Gupta, A" uniqKey="Gupta A">A. Gupta</name></author><author><name sortKey="Sharma, A K" uniqKey="Sharma A">A.K. Sharma</name></author><author><name sortKey="Kumar, P" uniqKey="Kumar P">P. Kumar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, M C" uniqKey="Chen M">M.-C. Chen</name></author><author><name sortKey="Hsu, S L" uniqKey="Hsu S">S.-L. Hsu</name></author><author><name sortKey="Lin, H" uniqKey="Lin H">H. Lin</name></author><author><name sortKey="Yang, T Y" uniqKey="Yang T">T.-Y. Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cruz, L J" uniqKey="Cruz L">L.J. Cruz</name></author><author><name sortKey="Tacken, P J" uniqKey="Tacken P">P.J. Tacken</name></author><author><name sortKey="Rueda, F" uniqKey="Rueda F">F. Rueda</name></author><author><name sortKey="Domingo, J C" uniqKey="Domingo J">J.C. Domingo</name></author><author><name sortKey="Albericio, F" uniqKey="Albericio F">F. Albericio</name></author><author><name sortKey="Figdor, C G" uniqKey="Figdor C">C.G. Figdor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cruz, L J" uniqKey="Cruz L">L.J. Cruz</name></author><author><name sortKey="Tacken, P J" uniqKey="Tacken P">P.J. Tacken</name></author><author><name sortKey="Eich, C" uniqKey="Eich C">C. Eich</name></author><author><name sortKey="Rueda, F" uniqKey="Rueda F">F. Rueda</name></author><author><name sortKey="Torensma, R" uniqKey="Torensma R">R. Torensma</name></author><author><name sortKey="Figdor, C G" uniqKey="Figdor C">C.G. Figdor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Urbaniak, T" uniqKey="Urbaniak T">T. Urbaniak</name></author><author><name sortKey="Musial, W" uniqKey="Musial W">W. Musiał</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tel, J" uniqKey="Tel J">J. Tel</name></author><author><name sortKey="Lambeck, A J A" uniqKey="Lambeck A">A.J.A. Lambeck</name></author><author><name sortKey="Cruz, L J" uniqKey="Cruz L">L.J. Cruz</name></author><author><name sortKey="Tacken, P J" uniqKey="Tacken P">P.J. Tacken</name></author><author><name sortKey="De Vries, I J M" uniqKey="De Vries I">I.J.M. de Vries</name></author><author><name sortKey="Figdor, C G" uniqKey="Figdor C">C.G. Figdor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cruz, L J" uniqKey="Cruz L">L.J. Cruz</name></author><author><name sortKey="Tacken, P J" uniqKey="Tacken P">P.J. Tacken</name></author><author><name sortKey="Fokkink, R" uniqKey="Fokkink R">R. Fokkink</name></author><author><name sortKey="Joosten, B" uniqKey="Joosten B">B. Joosten</name></author><author><name sortKey="Stuart, M C" uniqKey="Stuart M">M.C. Stuart</name></author><author><name sortKey="Albericio, F" uniqKey="Albericio F">F. Albericio</name></author><author><name sortKey="Torensma, R" uniqKey="Torensma R">R. Torensma</name></author><author><name sortKey="Figdor, C G" uniqKey="Figdor C">C.G. Figdor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, W" uniqKey="Zhang W">W. Zhang</name></author><author><name sortKey="Wang, F" uniqKey="Wang F">F. Wang</name></author><author><name sortKey="Hu, X" uniqKey="Hu X">X. Hu</name></author><author><name sortKey="Liang, J" uniqKey="Liang J">J. Liang</name></author><author><name sortKey="Liu, B" uniqKey="Liu B">B. Liu</name></author><author><name sortKey="Guan, Q" uniqKey="Guan Q">Q. Guan</name></author><author><name sortKey="Liu, S" uniqKey="Liu S">S. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, L" uniqKey="Liu L">L. Liu</name></author><author><name sortKey="Mayes, P A" uniqKey="Mayes P">P.A. Mayes</name></author><author><name sortKey="Eastman, S" uniqKey="Eastman S">S. Eastman</name></author><author><name sortKey="Shi, H" uniqKey="Shi H">H. Shi</name></author><author><name sortKey="Yadavilli, S" uniqKey="Yadavilli S">S. Yadavilli</name></author><author><name sortKey="Zhang, T" uniqKey="Zhang T">T. Zhang</name></author><author><name sortKey="Yang, J" uniqKey="Yang J">J. Yang</name></author><author><name sortKey="Seestaller Wehr, L" uniqKey="Seestaller Wehr L">L. Seestaller-Wehr</name></author><author><name sortKey="Zhang, S Y" uniqKey="Zhang S">S.-Y. Zhang</name></author><author><name sortKey="Hopson, C" uniqKey="Hopson C">C. Hopson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y. Liu</name></author><author><name sortKey="Zhang, N" uniqKey="Zhang N">N. Zhang</name></author><author><name sortKey="Cao, Q" uniqKey="Cao Q">Q. Cao</name></author><author><name sortKey="Cui, X" uniqKey="Cui X">X. Cui</name></author><author><name sortKey="Zhou, Q" uniqKey="Zhou Q">Q. Zhou</name></author><author><name sortKey="Yang, C" uniqKey="Yang C">C. Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, H" uniqKey="Liu H">H. Liu</name></author><author><name sortKey="Xu, H W" uniqKey="Xu H">H.W. Xu</name></author><author><name sortKey="Zhang, Y Z" uniqKey="Zhang Y">Y.Z. Zhang</name></author><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y. Huang</name></author><author><name sortKey="Han, G Q" uniqKey="Han G">G.Q. Han</name></author><author><name sortKey="Liang, T J" uniqKey="Liang T">T.J. Liang</name></author><author><name sortKey="Wei, L L" uniqKey="Wei L">L.L. Wei</name></author><author><name sortKey="Qin, C Y" uniqKey="Qin C">C.Y. Qin</name></author><author><name sortKey="Qin, C K" uniqKey="Qin C">C.K. Qin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Carvalho, T G" uniqKey="De Carvalho T">T.G. de Carvalho</name></author><author><name sortKey="Garcia, V B" uniqKey="Garcia V">V.B. Garcia</name></author><author><name sortKey="De Araujo, A A" uniqKey="De Araujo A">A.A. de Araújo</name></author><author><name sortKey="Da Silva Gasparotto, L H" uniqKey="Da Silva Gasparotto L">L.H. da Silva Gasparotto</name></author><author><name sortKey="Silva, H" uniqKey="Silva H">H. Silva</name></author><author><name sortKey="Guerra, G C B" uniqKey="Guerra G">G.C.B. Guerra</name></author><author><name sortKey="De Castro Miguel, E" uniqKey="De Castro Miguel E">E. de Castro Miguel</name></author><author><name sortKey="De Carvalho Leitao, R F" uniqKey="De Carvalho Leitao R">R.F. de Carvalho Leitão</name></author><author><name sortKey="Da Silva Costa, D V" uniqKey="Da Silva Costa D">D.V. da Silva Costa</name></author><author><name sortKey="Cruz, L J" uniqKey="Cruz L">L.J. Cruz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Araujo Jr, R F" uniqKey="Araujo Jr R">R.F. Araújo Jr</name></author><author><name sortKey="Lira, G A" uniqKey="Lira G">G.A. Lira</name></author><author><name sortKey="Vilaca, J A" uniqKey="Vilaca J">J.A. Vilaça</name></author><author><name sortKey="Guedes, H G" uniqKey="Guedes H">H.G. Guedes</name></author><author><name sortKey="Leitao, M C A" uniqKey="Leitao M">M.C.A. Leitão</name></author><author><name sortKey="Lucena, H F" uniqKey="Lucena H">H.F. Lucena</name></author><author><name sortKey="Ramos, C C O" uniqKey="Ramos C">C.C.O. Ramos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Um, H D" uniqKey="Um H">H.-D. Um</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, B" uniqKey="Xu B">B. Xu</name></author><author><name sortKey="Zhou, Z G" uniqKey="Zhou Z">Z.G. Zhou</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L. Wang</name></author><author><name sortKey="Yang, L" uniqKey="Yang L">L. Yang</name></author><author><name sortKey="Zhou, B" uniqKey="Zhou B">B. Zhou</name></author><author><name sortKey="Liu, H Y" uniqKey="Liu H">H.Y. Liu</name></author><author><name sortKey="Song, J M" uniqKey="Song J">J.M. Song</name></author><author><name sortKey="Zeng, Y J" uniqKey="Zeng Y">Y.J. Zeng</name></author><author><name sortKey="Wang, R" uniqKey="Wang R">R. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Heijink, D M" uniqKey="Heijink D">D.M. Heijink</name></author><author><name sortKey="Kleibeuker, J H" uniqKey="Kleibeuker J">J.H. Kleibeuker</name></author><author><name sortKey="Jalving, M" uniqKey="Jalving M">M. Jalving</name></author><author><name sortKey="Boersma Van Ekb, W" uniqKey="Boersma Van Ekb W">W. Boersma-van Ekb</name></author><author><name sortKey="Koornstra, J J" uniqKey="Koornstra J">J.J. Koornstra</name></author><author><name sortKey="Wesseling, J" uniqKey="Wesseling J">J. Wesseling</name></author><author><name sortKey="De Jong, S" uniqKey="De Jong S">S. de Jong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Str Ter, J" uniqKey="Str Ter J">J. Sträter</name></author><author><name sortKey="Herter, I" uniqKey="Herter I">I. Herter</name></author><author><name sortKey="Merkel, G" uniqKey="Merkel G">G. Merkel</name></author><author><name sortKey="Hinz, U" uniqKey="Hinz U">U. Hinz</name></author><author><name sortKey="Weitz, J" uniqKey="Weitz J">J. Weitz</name></author><author><name sortKey="Moller, P" uniqKey="Moller P">P. Möller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, H S" uniqKey="Kim H">H.S. Kim</name></author><author><name sortKey="Lee, J W" uniqKey="Lee J">J.W. Lee</name></author><author><name sortKey="Soung, Y H" uniqKey="Soung Y">Y.H. Soung</name></author><author><name sortKey="Park, W S" uniqKey="Park W">W.S. Park</name></author><author><name sortKey="Kim, S Y" uniqKey="Kim S">S.Y. Kim</name></author><author><name sortKey="Lee, J H" uniqKey="Lee J">J.H. Lee</name></author><author><name sortKey="Park, J Y" uniqKey="Park J">J.Y. Park</name></author><author><name sortKey="Cho, Y G" uniqKey="Cho Y">Y.G. Cho</name></author><author><name sortKey="Kim, C J" uniqKey="Kim C">C.J. Kim</name></author><author><name sortKey="Jeong, S W" uniqKey="Jeong S">S.W. Jeong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Graf, R P" uniqKey="Graf R">R.P. Graf</name></author><author><name sortKey="Keller, N" uniqKey="Keller N">N. Keller</name></author><author><name sortKey="Barbero, S" uniqKey="Barbero S">S. Barbero</name></author><author><name sortKey="Stupack, D" uniqKey="Stupack D">D. Stupack</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abbaszadeh Goudarzi, K" uniqKey="Abbaszadeh Goudarzi K">K. Abbaszadeh-Goudarzi</name></author><author><name sortKey="Shokri, F" uniqKey="Shokri F">F. Shokri</name></author><author><name sortKey="Hosseini, M" uniqKey="Hosseini M">M. Hosseini</name></author><author><name sortKey="Jadidi Niaragh, F" uniqKey="Jadidi Niaragh F">F. Jadidi-Niaragh</name></author><author><name sortKey="Ghalamfarsa, G" uniqKey="Ghalamfarsa G">G. Ghalamfarsa</name></author><author><name sortKey="Saboor Yaraghi, A" uniqKey="Saboor Yaraghi A">A. Saboor-Yaraghi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sutar, Y B" uniqKey="Sutar Y">Y.B. Sutar</name></author><author><name sortKey="Telvekar, V N" uniqKey="Telvekar V">V.N. Telvekar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tummala, S" uniqKey="Tummala S">S. Tummala</name></author><author><name sortKey="Kumar, M N" uniqKey="Kumar M">M.N. Kumar</name></author><author><name sortKey="Pindiprolu, S K" uniqKey="Pindiprolu S">S.K. Pindiprolu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alian, O M" uniqKey="Alian O">O.M. Alian</name></author><author><name sortKey="Azmi, A S" uniqKey="Azmi A">A.S. Azmi</name></author><author><name sortKey="Mohammad, R M" uniqKey="Mohammad R">R.M. Mohammad</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zori Comba, A" uniqKey="Zori Comba A">A. Zori Comba</name></author><author><name sortKey="Blajman, C" uniqKey="Blajman C">C. Blajman</name></author><author><name sortKey="Richardet, E" uniqKey="Richardet E">E. Richardet</name></author><author><name sortKey="Bella, S" uniqKey="Bella S">S. Bella</name></author><author><name sortKey="Vilanova, M" uniqKey="Vilanova M">M. Vilanova</name></author><author><name sortKey="C Ppola, F" uniqKey="C Ppola F">F. Cóppola</name></author><author><name sortKey="Van Kooten, M" uniqKey="Van Kooten M">M. Van Kooten</name></author><author><name sortKey="Rodger, J" uniqKey="Rodger J">J. Rodger</name></author><author><name sortKey="Giglio, R" uniqKey="Giglio R">R. Giglio</name></author><author><name sortKey="Balbiani, L" uniqKey="Balbiani L">L. Balbiani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Prado Almeida, E D" uniqKey="Prado Almeida E">E.D. Prado Almeida</name></author><author><name sortKey="Vieira Dipieri, L" uniqKey="Vieira Dipieri L">L. Vieira Dipieri</name></author><author><name sortKey="Rosseti, F C" uniqKey="Rosseti F">F.C. Rosseti</name></author><author><name sortKey="Maldonado Marchetti, J" uniqKey="Maldonado Marchetti J">J. Maldonado Marchetti</name></author><author><name sortKey="Lopes Badra Bentley, M V" uniqKey="Lopes Badra Bentley M">M.V. Lopes Badra Bentley</name></author><author><name sortKey="De Souza Nunes, R" uniqKey="De Souza Nunes R">R. de Souza Nunes</name></author><author><name sortKey="Sarmento, V H V" uniqKey="Sarmento V">V.H.V. Sarmento</name></author><author><name sortKey="Giroldo Valerio, M E" uniqKey="Giroldo Valerio M">M.E. Giroldo Valério</name></author><author><name sortKey="Rodrigues, J J" uniqKey="Rodrigues J">J.J. Rodrigues</name></author><author><name sortKey="Martins Montalvao, M" uniqKey="Martins Montalvao M">M. Martins Montalvão</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kumar, S" uniqKey="Kumar S">S. Kumar</name></author><author><name sortKey="Sangwan, P" uniqKey="Sangwan P">P. Sangwan</name></author><author><name sortKey="Lather, V" uniqKey="Lather V">V. Lather</name></author><author><name sortKey="Pandita, D" uniqKey="Pandita D">D. Pandita</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rompicharla, S V K" uniqKey="Rompicharla S">S.V.K. Rompicharla</name></author><author><name sortKey="Bhatt, H" uniqKey="Bhatt H">H. Bhatt</name></author><author><name sortKey="Shah, A" uniqKey="Shah A">A. Shah</name></author><author><name sortKey="Komanduri, N" uniqKey="Komanduri N">N. Komanduri</name></author><author><name sortKey="Vijayasarathy, D" uniqKey="Vijayasarathy D">D. Vijayasarathy</name></author><author><name sortKey="Ghosh, B" uniqKey="Ghosh B">B. Ghosh</name></author><author><name sortKey="Biswas, S" uniqKey="Biswas S">S. Biswas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, C S" uniqKey="Lee C">C.S. Lee</name></author><author><name sortKey="Kim, H" uniqKey="Kim H">H. Kim</name></author><author><name sortKey="Yu, J" uniqKey="Yu J">J. Yu</name></author><author><name sortKey="Yu, S H" uniqKey="Yu S">S.H. Yu</name></author><author><name sortKey="Ban, S" uniqKey="Ban S">S. Ban</name></author><author><name sortKey="Oh, S" uniqKey="Oh S">S. Oh</name></author><author><name sortKey="Jeong, D" uniqKey="Jeong D">D. Jeong</name></author><author><name sortKey="Im, J" uniqKey="Im J">J. Im</name></author><author><name sortKey="Baek, M J" uniqKey="Baek M">M.J. Baek</name></author><author><name sortKey="Kim, T H" uniqKey="Kim T">T.H. Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Watabe, H" uniqKey="Watabe H">H. Watabe</name></author><author><name sortKey="Soma, Y" uniqKey="Soma Y">Y. Soma</name></author><author><name sortKey="Ito, M" uniqKey="Ito M">M. Ito</name></author><author><name sortKey="Kawa, Y" uniqKey="Kawa Y">Y. Kawa</name></author><author><name sortKey="Mizoguchi, M" uniqKey="Mizoguchi M">M. Mizoguchi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="C Tsamandas, A" uniqKey="C Tsamandas A">A. C Tsamandas</name></author><author><name sortKey="Kardamakis, D" uniqKey="Kardamakis D">D. Kardamakis</name></author><author><name sortKey="Tsiamalos, P" uniqKey="Tsiamalos P">P. Tsiamalos</name></author><author><name sortKey="Liava, A" uniqKey="Liava A">A. Liava</name></author><author><name sortKey="Tzelepi, V" uniqKey="Tzelepi V">V. Tzelepi</name></author><author><name sortKey="Vassiliou, V" uniqKey="Vassiliou V">V. Vassiliou</name></author><author><name sortKey="Petsas, T" uniqKey="Petsas T">T. Petsas</name></author><author><name sortKey="Vagenas, K" uniqKey="Vagenas K">K. Vagenas</name></author><author><name sortKey="Zolota, V" uniqKey="Zolota V">V. Zolota</name></author><author><name sortKey="Scopa, C" uniqKey="Scopa C">C. Scopa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, L T" uniqKey="Li L">L.T. Li</name></author><author><name sortKey="Jiang, G" uniqKey="Jiang G">G. Jiang</name></author><author><name sortKey="Chen, Q" uniqKey="Chen Q">Q. Chen</name></author><author><name sortKey="Zheng, J N" uniqKey="Zheng J">J.N. Zheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lowe, M H A S" uniqKey="Lowe M">M.H.a.S. Lowe*</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Toussaint, O" uniqKey="Toussaint O">O. Toussaint</name></author><author><name sortKey="Royer, V" uniqKey="Royer V">V. Royer</name></author><author><name sortKey="Salmon, M" uniqKey="Salmon M">M. Salmon</name></author><author><name sortKey="Remacle, J" uniqKey="Remacle J">J. Remacle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vedagiri, H" uniqKey="Vedagiri H">H. Vedagiri</name></author><author><name sortKey="Helga Jenifer, M" uniqKey="Helga Jenifer M">M. Helga Jenifer</name></author><author><name sortKey="Sneha Mirulalini, G" uniqKey="Sneha Mirulalini G">G. Sneha Mirulalini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pollino, S" uniqKey="Pollino S">S. Pollino</name></author><author><name sortKey="Palmerini, E" uniqKey="Palmerini E">E. Palmerini</name></author><author><name sortKey="Dozza, B" uniqKey="Dozza B">B. Dozza</name></author><author><name sortKey="Bientinesi, E" uniqKey="Bientinesi E">E. Bientinesi</name></author><author><name sortKey="Piccinni Leopardi, M" uniqKey="Piccinni Leopardi M">M. Piccinni-Leopardi</name></author><author><name sortKey="Lucarelli, E" uniqKey="Lucarelli E">E. Lucarelli</name></author><author><name sortKey="Righi, A" uniqKey="Righi A">A. Righi</name></author><author><name sortKey="Benassi, M S" uniqKey="Benassi M">M.S. Benassi</name></author><author><name sortKey="Pazzaglia, L" uniqKey="Pazzaglia L">L. Pazzaglia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mandal, P K" uniqKey="Mandal P">P.K. Mandal</name></author><author><name sortKey="Biswas, S" uniqKey="Biswas S">S. Biswas</name></author><author><name sortKey="Mandal, G" uniqKey="Mandal G">G. Mandal</name></author><author><name sortKey="Purohit, S" uniqKey="Purohit S">S. Purohit</name></author><author><name sortKey="Gupta, A" uniqKey="Gupta A">A. Gupta</name></author><author><name sortKey="Majumdar, A" uniqKey="Majumdar A">A. Majumdar</name></author><author><name sortKey="Roy Chowdhury, S" uniqKey="Roy Chowdhury S">S. Roy Chowdhury</name></author><author><name sortKey="Bhattacharyya, A" uniqKey="Bhattacharyya A">A. Bhattacharyya</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wei, Y" uniqKey="Wei Y">Y. Wei</name></author><author><name sortKey="Wang, T" uniqKey="Wang T">T. Wang</name></author><author><name sortKey="Song, H" uniqKey="Song H">H. Song</name></author><author><name sortKey="Tian, L" uniqKey="Tian L">L. Tian</name></author><author><name sortKey="Lyu, G" uniqKey="Lyu G">G. Lyu</name></author><author><name sortKey="Zhao, L" uniqKey="Zhao L">L. Zhao</name></author><author><name sortKey="Xue, Y" uniqKey="Xue Y">Y. Xue</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yan, X" uniqKey="Yan X">X. Yan</name></author><author><name sortKey="Li, P" uniqKey="Li P">P. Li</name></author><author><name sortKey="Zhan, Y" uniqKey="Zhan Y">Y. Zhan</name></author><author><name sortKey="Qi, M" uniqKey="Qi M">M. Qi</name></author><author><name sortKey="Liu, J" uniqKey="Liu J">J. Liu</name></author><author><name sortKey="An, Z" uniqKey="An Z">Z. An</name></author><author><name sortKey="Yang, W" uniqKey="Yang W">W. Yang</name></author><author><name sortKey="Xiao, H" uniqKey="Xiao H">H. Xiao</name></author><author><name sortKey="Wu, H" uniqKey="Wu H">H. Wu</name></author><author><name sortKey="Qi, Y" uniqKey="Qi Y">Y. Qi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lv, T" uniqKey="Lv T">T. Lv</name></author><author><name sortKey="Li, Z" uniqKey="Li Z">Z. Li</name></author><author><name sortKey="Xu, L" uniqKey="Xu L">L. Xu</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author><author><name sortKey="Chen, H" uniqKey="Chen H">H. Chen</name></author><author><name sortKey="Gao, Y" uniqKey="Gao Y">Y. Gao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kapse Mistry, S" uniqKey="Kapse Mistry S">S. Kapse-Mistry</name></author><author><name sortKey="Govender, T" uniqKey="Govender T">T. Govender</name></author><author><name sortKey="Srivastava, R" uniqKey="Srivastava R">R. Srivastava</name></author><author><name sortKey="Yergeri, M" uniqKey="Yergeri M">M. Yergeri</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Pharmaceutics</journal-id><journal-id journal-id-type="iso-abbrev">Pharmaceutics</journal-id><journal-id journal-id-type="publisher-id">pharmaceutics</journal-id><journal-title-group><journal-title>Pharmaceutics</journal-title></journal-title-group><issn pub-type="epub">1999-4923</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32102251</article-id><article-id pub-id-type="pmc">7076533</article-id><article-id pub-id-type="doi">10.3390/pharmaceutics12020193</article-id><article-id pub-id-type="publisher-id">pharmaceutics-12-00193</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Effect of Oxaliplatin-Loaded Poly (<sc>d</sc>,<sc>l</sc>-Lactide-<italic>co</italic>-Glycolic Acid) (PLGA) Nanoparticles Combined with Retinoic Acid and Cholesterol on Apoptosis, Drug Resistance, and Metastasis Factors of Colorectal Cancer</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>C. de S. L. Oliveira</surname><given-names>Ana Luiza</given-names></name><xref ref-type="aff" rid="af1-pharmaceutics-12-00193">1</xref><xref ref-type="aff" rid="af2-pharmaceutics-12-00193">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0003-2349-2354</contrib-id><name><surname>de Araújo Júnior</surname><given-names>Raimundo Fernandes</given-names></name><xref ref-type="aff" rid="af1-pharmaceutics-12-00193">1</xref><xref ref-type="aff" rid="af2-pharmaceutics-12-00193">2</xref><xref ref-type="aff" rid="af3-pharmaceutics-12-00193">3</xref><xref rid="c1-pharmaceutics-12-00193" ref-type="corresp">*</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-1317-8890</contrib-id><name><surname>Gomes de Carvalho</surname><given-names>Thaís</given-names></name><xref ref-type="aff" rid="af1-pharmaceutics-12-00193">1</xref><xref ref-type="aff" rid="af2-pharmaceutics-12-00193">2</xref></contrib><contrib contrib-type="author"><name><surname>B. Chan</surname><given-names>Alan</given-names></name><xref ref-type="aff" rid="af4-pharmaceutics-12-00193">4</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-0948-6209</contrib-id><name><surname>Schomann</surname><given-names>Timo</given-names></name><xref ref-type="aff" rid="af2-pharmaceutics-12-00193">2</xref><xref ref-type="aff" rid="af4-pharmaceutics-12-00193">4</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0001-5991-6871</contrib-id><name><surname>Tamburini</surname><given-names>Filippo</given-names></name><xref ref-type="aff" rid="af4-pharmaceutics-12-00193">4</xref></contrib><contrib contrib-type="author"><name><surname>de Geus-Oei</surname><given-names>Lioe-Fee</given-names></name><xref ref-type="aff" rid="af5-pharmaceutics-12-00193">5</xref></contrib><contrib contrib-type="author"><name><surname>J. Cruz</surname><given-names>Luis</given-names></name><xref ref-type="aff" rid="af2-pharmaceutics-12-00193">2</xref><xref rid="c1-pharmaceutics-12-00193" ref-type="corresp">*</xref></contrib></contrib-group><aff id="af1-pharmaceutics-12-00193"><label>1</label>Postgraduate Program in Health Science, Federal University of Rio Grande do Norte (UFRN), 59078 970 Natal, RN, Brazil;<email>analuiza_oliveira@outlook.com</email> (A.L.C.d.S.L.O.);<email>thaisbida2011@hotmail.com</email> (T.G.d.C.)</aff><aff id="af2-pharmaceutics-12-00193"><label>2</label>Translational Nanobiomaterials and Imaging, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands;<email>t.schomann@lumc.nl</email></aff><aff id="af3-pharmaceutics-12-00193"><label>3</label>Postgraduate Program in Functional and Structural Biology, Department of Morphology, Federal University of Rio Grande do Norte (UFRN), 59078 970 Natal, RN, Brazil</aff><aff id="af4-pharmaceutics-12-00193"><label>4</label>Percuros B.V, Zernikedreef 8, 2333 CL Leiden, The Netherlands;<email>alanchan@clara.net</email> (A.B.C.);<email>tambu.91@hotmail.it</email> (F.T.)</aff><aff id="af5-pharmaceutics-12-00193"><label>5</label>Nuclear Medicine, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;<email>l.f.de_geus-oei@lumc.nl</email></aff><author-notes><corresp id="c1-pharmaceutics-12-00193"><label>*</label>Correspondence: <email>araujojr@cb.ufrn.br</email> (R.F.d.A.J.); <email>l.j.cruz_ricondo@lumc.nl</email> (L.J.C.); Tel.: +55-84-3215-3431 or +31-65-562-0247 (R.F.d.A.J.); +31-71-526-5764 (L.J.C.); Fax: +55-84-3215-3431 (R.F.d.A.J.); +31-71-524-8256 (L.J.C.)</corresp></author-notes><pub-date pub-type="epub"><day>23</day><month>2</month><year>2020</year></pub-date><pub-date pub-type="collection"><month>2</month><year>2020</year></pub-date><volume>12</volume><issue>2</issue><elocation-id>193</elocation-id><history><date date-type="received"><day>16</day><month>12</month><year>2019</year></date><date date-type="accepted"><day>21</day><month>1</month><year>2020</year></date></history><permissions><copyright-statement>© 2020 by the authors.</copyright-statement><copyright-year>2020</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p>Apoptosis signaling pathways, drug resistance, and metastasis are important targets to develop new cancer treatments. We developed cholesterol-coated Poly(<sc>d</sc>,<sc>l</sc>-Lactide-<italic>co</italic>-Glycolic Acid) (PLGA) nanoparticles for effective encapsulation and delivery of retinoic acid and oxaliplatin to analyze their antitumor activity in colorectal cancer. The cell viability and proliferation of tumoral cells lines (CT-26 and SW-480) decreased when compared to control in vitro after treatment with the nanoparticles. In addition, apoptosis of CT-26 cells increased. Importantly, cytoprotection of nontumor cells was detected. Expression of pro-apoptotic proteins was upregulated, while anti-apoptotic proteins were downregulated either in vitro or in vivo. In addition, drug resistance and metastasis factors were downregulated in vivo. Human colorectal tumors that highly expressed BCL-2 and Ki-67 had a greater tendency towards death within 60 months. Our results show that loading oxaliplatin combined with retinoic acid and cholesterol in a nanoparticle formulation enables determination of optimal antitumor activity and subsequent treatment efficacy.</p></abstract><kwd-group><kwd>PLGA nanoparticles</kwd><kwd>oxaliplatin</kwd><kwd>colorectal cancer</kwd><kwd>drug resistance</kwd><kwd>apoptosis</kwd></kwd-group></article-meta></front><floats-group><fig id="pharmaceutics-12-00193-f001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Representative AFM images of blank glass, NPs 1 and NPs 2 in alternating contact (AC) mode in air (scale bar = 500 µm) are showed in the left column of the panel. Fluorescence images in the right columns of the panel show the internalization of NPs by CT-26 cells. The nanoparticles (yellow) were detected in all treated groups and time points. Scale bar: 20 µm.</p></caption><graphic xlink:href="pharmaceutics-12-00193-g001"></graphic></fig><fig id="pharmaceutics-12-00193-f002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Cell viability (<bold>A</bold>,<bold>B</bold>), proliferation (<bold>C</bold>), total death for CT-26 for 24 h (<bold>D</bold>), total death for CT-26 for 48 h (E) and total death for 3T3 cells for 48 h (<bold>F</bold>). Mean cell proliferation of CT-26 cells treated with OXA and PLGA NPs for 24 h (<bold>A</bold>) and 48 h (<bold>B</bold>). Ki-67 immunostaining of CT-26 cells treated with OXA (5 μg/mL), NPs 1 (5 μg/mL), and NPs 2 (5 μg/mL) and compared to negative control for 48 h (<bold>C</bold>). The statistic of the treatments for the total death when compared to the negative control is displayed (* <italic>p</italic> < 0.05, ** <italic>p</italic> < 0.01, *** <italic>p</italic> < 0.001, and **** <italic>p</italic> < 0.0001). Comparison between OXA (5 μg/mL) and NPs 1 (5 μg/mL, ♦) as well as between OXA (5 μg/mL) and NPs 2 (5 μg/mL, ♦♦).</p></caption><graphic xlink:href="pharmaceutics-12-00193-g002"></graphic></fig><fig id="pharmaceutics-12-00193-f003" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Cell viability, proliferation, and detection of caspase-3 of SW-480 cells. Mean cell proliferation of SW-480 cells treated with OXA and PLGA NPs for 24 h (<bold>A</bold>) and 48 h (<bold>B</bold>). All treatment groups were compared to the negative control group (**** <italic>p</italic> < 0.0001 and ** <italic>p</italic> < 0.01). Ki-67 immunostaining of SW-480 cells treated with OXA, NPs 1, and NPs 2, and compared to negative control for 48 h (<bold>C</bold>). All treatments were statistically significant (**** <italic>p</italic> < 0.0001). Representative photomicrographs of caspase-3 in SW-480 cells stained with 4,6-diamidino-2-phenylindole (DAPI) (blue) and anti-caspase-3 antibody (red). Contrast index for caspase-3 after 24 h (<bold>D</bold>) and 48 h (<bold>E</bold>) (*** <italic>p</italic> < 0.001). Scale bar: 50 µm.</p></caption><graphic xlink:href="pharmaceutics-12-00193-g003"></graphic></fig><fig id="pharmaceutics-12-00193-f004" orientation="portrait" position="float"><label>Figure 4</label><caption><p>Detection of fas-associated protein with death domain (FADD), BCL-2, and caspase-3 after 24 h of treatment. CT-26 cells stained with DAPI (blue), anti-FADD, anti-BCL-2, and anti-caspase-3 antibodies (red). Contrast index for FADD, * <italic>p</italic> < 0.05, ** <italic>p</italic> < 0.01 (<bold>A</bold>); BCL-2, <italic>p</italic> > 0.05 (<bold>B</bold>); and caspase-3, ** <italic>p</italic> < 0.01, *** <italic>p</italic> < 0.001, **** <italic>p</italic> < 0.0001 (<bold>C</bold>). Scale bar: 50 µm.</p></caption><graphic xlink:href="pharmaceutics-12-00193-g004"></graphic></fig><fig id="pharmaceutics-12-00193-f005" orientation="portrait" position="float"><label>Figure 5</label><caption><p>Detection of FADD, BCL-2, and caspase-3 after 48 h of treatment. CT-26 cells stained with DAPI (blue), anti-FADD, anti-BCL-2, and anti-caspase-3 antibodies (red). Contrast index for FADD, * <italic>p</italic> < 0.05 (<bold>A</bold>); BCL-2, ** <italic>p</italic> < 0.01, *** <italic>p</italic> < 0.001 (<bold>B</bold>); and caspase-3, ** <italic>p</italic> < 0.01 (<bold>C</bold>). Scale bar: 50 µm.</p></caption><graphic xlink:href="pharmaceutics-12-00193-g005"></graphic></fig><fig id="pharmaceutics-12-00193-f006" orientation="portrait" position="float"><label>Figure 6</label><caption><p>Morphology of all the tumors collected from (<bold>A</bold>) control, (<bold>B</bold>) OXA (5 mg/kg), (<bold>C</bold>) NPs 1 (5 mg/kg), and (<bold>D</bold>) NPs 2 (5 mg/kg) mice. Tumor growth curve of the Balb/c xenografts with different treatments (<bold>E</bold>). All treatment groups were compared to the negative control group (**** <italic>p</italic> < 0.0001).</p></caption><graphic xlink:href="pharmaceutics-12-00193-g006"></graphic></fig><fig id="pharmaceutics-12-00193-f007" orientation="portrait" position="float"><label>Figure 7</label><caption><p>Analysis of apoptosis, drug resistance, and metastasis factors. Representative photomicrographs of immunohistochemistry of tumor fragments of mice receiving different treatments (<bold>A</bold>). Immunohistochemistry score by anti-FADD (<bold>B</bold>), anti-BCL-2 (<bold>C</bold>), anti-caspase-3 (<bold>D</bold>), relative messenger ribonucleic acids (mRNA) expression by RT-PCR for FADD and apoptotic protease activating factor 1 (APAF -1) (<bold>E</bold>), multidrug resistance protein 1 (MDR1) and survivin (<bold>F</bold>), and C-X-C chemokine receptor type 4 (CXCR4), and monocyte-derived chemokine (CCL22) (<bold>G</bold>). All treatment groups were compared to the negative control group (**** <italic>p</italic> < 0.0001). Comparison between OXA (5 mg/kg) and NPs 1 (5 mg/kg, ♦ <italic>p</italic> < 0.05) as well as between OXA (5 mg/kg) and NPs 2 (5 mg/kg, ♦♦ <italic>p</italic> < 0.01) was also performed (<italic>p</italic> < 0.0001 for both). Magnification: 40×.</p></caption><graphic xlink:href="pharmaceutics-12-00193-g007"></graphic></fig><fig id="pharmaceutics-12-00193-f008" orientation="portrait" position="float"><label>Figure 8</label><caption><p>Expression of BCL-2 and caspase-8 in primary colorectal tumors. (<bold>A</bold>) Kaplan–Meier survival curve estimated by BCL-2 staining in colorectal cancer (CRC) tumors (log-rank × 2 = 30.75, <italic>p</italic> < 0.0001), (<bold>B</bold>) Kaplan–Meier survival estimated by caspase-8 staining in CRC tumors (log-rank × 2 = 2.61, <italic>p</italic> = 0.10). Immunohistochemical staining for BCL-2 and caspase-8 in colorectal carcinoma. Colorectal adenocarcinoma with a high modified Dukes’ classification (“3” and “4”) showing: (<bold>C</bold>) Strong cytoplasmic staining of BCL-2, and (<bold>E</bold>) weak BCL-2 cytoplasmic staining. Strong cytoplasmic staining of caspase-8 (<bold>D</bold>), and (<bold>F</bold>) weak caspase-8. Magnification: 40×.</p></caption><graphic xlink:href="pharmaceutics-12-00193-g008"></graphic></fig><table-wrap id="pharmaceutics-12-00193-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">pharmaceutics-12-00193-t001_Table 1</object-id><label>Table 1</label><caption><p>Physicochemical properties of Poly(D,L-Lactide-co-Glycolic Acid) (PLGA) nanoparticles (NPs). Determination of retinoic acid (RA) and oxaliplatin (OXA) content, size distribution, and zeta-potential of PLGA NPs. Particles were characterized by Dynamic Light Scattering (DLS) and zeta-potential measurements. Particle size data represent the mean value ± standard deviation (SD) of dynamic light scattering data. Zeta-potential data represent the mean value ± SD of 10 readings. OXA and RA contents of PLGA NPs were determined by particle digestion and measured by reversed-phase high-performance liquid chromatography (RP-HPLC) analysis.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Samples</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Loading Oxaliplatin Efficiency<break></break>(µg/mg NPs)</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Loading Retinoic Acid Efficiency<break></break>(µg/mg NPs)</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Size ± SD<break></break>(nm)</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">PDI<break></break>(Polydispersity Index)</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Zeta Potential ± SD (mV)</th></tr></thead><tbody><tr><td align="center" valign="middle" rowspan="1" colspan="1">NPs 1 (OXA, RA)-CHO</td><td align="center" valign="middle" rowspan="1" colspan="1">44</td><td align="center" valign="middle" rowspan="1" colspan="1">40</td><td align="center" valign="middle" rowspan="1" colspan="1">801.7 ± 165.4</td><td align="center" valign="middle" rowspan="1" colspan="1">0.598</td><td align="center" valign="middle" rowspan="1" colspan="1">−21.4 ± 8.4</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">NPs 2 (OXA)-CHO</td><td align="center" valign="middle" rowspan="1" colspan="1">48</td><td align="center" valign="middle" rowspan="1" colspan="1">--</td><td align="center" valign="middle" rowspan="1" colspan="1">678.3 ± 118.5</td><td align="center" valign="middle" rowspan="1" colspan="1">0.694</td><td align="center" valign="middle" rowspan="1" colspan="1">−25.8 ± 15.9</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">NPs 3 (RA)-CHO</td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1">46</td><td align="center" valign="middle" rowspan="1" colspan="1">539.8 ± 87.6</td><td align="center" valign="middle" rowspan="1" colspan="1">0.438</td><td align="center" valign="middle" rowspan="1" colspan="1">−28.5 ± 16.1</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">NPs 4 (empty)-CHO</td><td align="center" valign="middle" rowspan="1" colspan="1">--</td><td align="center" valign="middle" rowspan="1" colspan="1">--</td><td align="center" valign="middle" rowspan="1" colspan="1">443.1 ± 27.1</td><td align="center" valign="middle" rowspan="1" colspan="1">0.253</td><td align="center" valign="middle" rowspan="1" colspan="1">−23.6 ± 9.13</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">NPs 5 (empty)</td><td align="center" valign="middle" rowspan="1" colspan="1">--</td><td align="center" valign="middle" rowspan="1" colspan="1">--</td><td align="center" valign="middle" rowspan="1" colspan="1">496.7 ± 35.35</td><td align="center" valign="middle" rowspan="1" colspan="1">0.255</td><td align="center" valign="middle" rowspan="1" colspan="1">−28.8 ± 8.6</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">NPs 6 (OXA)</td><td align="center" valign="middle" rowspan="1" colspan="1">55</td><td align="center" valign="middle" rowspan="1" colspan="1">--</td><td align="center" valign="middle" rowspan="1" colspan="1">391.5 ± 60.53</td><td align="center" valign="middle" rowspan="1" colspan="1">0.182</td><td align="center" valign="middle" rowspan="1" colspan="1">−29.6 ± 9.9</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">NPs 7 (OXA, RA)</td><td align="center" valign="middle" rowspan="1" colspan="1">46</td><td align="center" valign="middle" rowspan="1" colspan="1">44</td><td align="center" valign="middle" rowspan="1" colspan="1">505.6 ± 64.30</td><td align="center" valign="middle" rowspan="1" colspan="1">0.199</td><td align="center" valign="middle" rowspan="1" colspan="1">−27.6 ± 42.1</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">NPs 8 (RA)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">--</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">50</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">514.8 ± 106.7</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.136</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">−25.7 ± 10.8</td></tr></tbody></table></table-wrap><table-wrap id="pharmaceutics-12-00193-t002" orientation="portrait" position="float"><object-id pub-id-type="pii">pharmaceutics-12-00193-t002_Table 2</object-id><label>Table 2</label><caption><p>Primer sequences used for PCR.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">mRNA</th><th colspan="2" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1">Oligonucleotides Primers</th><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Temperature</th></tr></thead><tbody><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>β</italic>-actin</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5′-AAC-TTT-GGC-ATCGTG-GAA-GG-3′</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5′-GTGGATGCAGGGATGATGTTC-3′</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">60 °C</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">FADD</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5′-AGAAGAAGAACGCCTCGGTG-3′</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5′-GCTCACAGATTCCTGGGCTT-3′</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">56.5 °C</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">APAF-1</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5′-TTCCAGTGGCAAGGACACAG-3′</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5′-CCACTCTCCACAGGGACAAC-3′</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">56.8 °C</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">MDR1</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5′-TCAGCAACAGCAGTCTGGAG-3′</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5′-ACTATGAGCACACCAGCACC-3′</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">55.2 °C</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Survivin</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5′-AGAACAAAATTGCAAAGGAGACA-3′</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5′-GGCATGTCACTCAGGTCCAA-3′</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">55.2 °C</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CXCR4</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5′-ACCTCGGTGTCCTCTTGCTGTCCA-3′</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5′-GCTTGACGTTGGCTCTGGCGATGT-3′</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">56.5 °C</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">CCL22</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5′-GAGACAACAGTGGTCCCAGG-3′</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">5′-CTGGCACTGTCAATCCCTGT-3′</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">56.8 °C</td></tr></tbody></table></table-wrap><table-wrap id="pharmaceutics-12-00193-t003" orientation="portrait" position="float"><object-id pub-id-type="pii">pharmaceutics-12-00193-t003_Table 3</object-id><label>Table 3</label><caption><p>Clinicopathological characteristics of CRC patients in relation to caspase-8 and BCL-2 expression. Distributions of tumor caspase-8 and BCL-2 expression categorizations according to clinical-pathological and Ki-67 expression (percentages in parenthesis). High expression of caspase-8 was associated with higher tumor grade, lymph node metastasis, and proliferation (Ki-67), while high expression of BCL-2 was associated with higher tumor grade and lymph node metastasis. Fisher’s exact = 1, chi-square = 2.</p></caption><table frame="hsides" rules="groups"><thead><tr><th rowspan="2" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" colspan="1">Clinicopathological Characteristics of CRC Patients </th><th colspan="3" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1">Caspase-8 (<italic>n</italic> = 180)</th><th colspan="3" align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1">BCL-2 (<italic>n</italic> = 180)</th></tr><tr><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Weak</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Strong</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>p</italic> Value</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Weak</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Strong</th><th align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><italic>p</italic> Value</th></tr></thead><tbody><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Number of Patients</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">75<break></break>(41.6%)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">105<break></break>(58.3%)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">69<break></break>(38.33%)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">111<break></break>(41.67%)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">-</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Lymph Node Status</bold></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td rowspan="3" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">0.0002 <sup>1</sup></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td rowspan="3" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">0.0002 <sup>1</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Negative</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">15(20%)</td><td align="center" valign="middle" rowspan="1" colspan="1">03(2.86%)</td><td align="center" valign="middle" rowspan="1" colspan="1">39(56.52%)</td><td align="center" valign="middle" rowspan="1" colspan="1">23(20.72%)</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>Positive</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">60(80%)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">102(97.14%)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">30(43.48%)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">88(79.28%)</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Modified Dukes’ Criteria Grade</bold></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td rowspan="3" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">0.0001 <sup>1</sup></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td rowspan="3" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">0.07 <sup>1</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Low (I and II)</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">25(33.3%)</td><td align="center" valign="middle" rowspan="1" colspan="1">07(6.67%)</td><td align="center" valign="middle" rowspan="1" colspan="1">41(59.42%)</td><td align="center" valign="middle" rowspan="1" colspan="1">35(31.53%)</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>High (III and IV)</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">50(66.7%)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"> 98(93.33%)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">28(40.58%)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">76(68.47%)</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>Ki-67</bold></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td rowspan="4" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">0.04 <sup>2</sup></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td align="center" valign="middle" rowspan="1" colspan="1"></td><td rowspan="4" align="center" valign="middle" style="border-bottom:solid thin" colspan="1">0.0001 <sup>2</sup></td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold><10%</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">02(2.7%)</td><td align="center" valign="middle" rowspan="1" colspan="1">02(1.9%)</td><td align="center" valign="middle" rowspan="1" colspan="1">09(13.05%)</td><td align="center" valign="middle" rowspan="1" colspan="1">24(21.62%)</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1"><bold>11–25%</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">18(24%)</td><td align="center" valign="middle" rowspan="1" colspan="1">11(10.48%)</td><td align="center" valign="middle" rowspan="1" colspan="1">11(15.94%)</td><td align="center" valign="middle" rowspan="1" colspan="1">52(46.85%)</td></tr><tr><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1"><bold>>25%</bold></td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">55(73.3%)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">92(87.62%)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">49(71.01%)</td><td align="center" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">35(31.53%)</td></tr></tbody></table></table-wrap></floats-group></pmc><affiliations><list><country><li>Brésil</li></country><region><li>Rio Grande do Norte</li></region></list><tree><noCountry><name sortKey="B Chan, Alan" sort="B Chan, Alan" uniqKey="B Chan A" first="Alan" last="B. Chan">Alan B. Chan</name><name sortKey="C De S L Oliveira, Ana Luiza" sort="C De S L Oliveira, Ana Luiza" uniqKey="C De S L Oliveira A" first="Ana Luiza" last="C. De S. L. Oliveira">Ana Luiza C. De S. L. Oliveira</name><name sortKey="De Geus Oei, Lioe Fee" sort="De Geus Oei, Lioe Fee" uniqKey="De Geus Oei L" first="Lioe-Fee" last="De Geus-Oei">Lioe-Fee De Geus-Oei</name><name sortKey="Gomes De Carvalho, Thais" sort="Gomes De Carvalho, Thais" uniqKey="Gomes De Carvalho T" first="Thaís" last="Gomes De Carvalho">Thaís Gomes De Carvalho</name><name sortKey="J Cruz, Luis" sort="J Cruz, Luis" uniqKey="J Cruz L" first="Luis" last="J. Cruz">Luis J. Cruz</name><name sortKey="Schomann, Timo" sort="Schomann, Timo" uniqKey="Schomann T" first="Timo" last="Schomann">Timo Schomann</name><name sortKey="Tamburini, Filippo" sort="Tamburini, Filippo" uniqKey="Tamburini F" first="Filippo" last="Tamburini">Filippo Tamburini</name></noCountry><country name="Brésil"><region name="Rio Grande do Norte"><name sortKey="De Araujo Junior, Raimundo Fernandes" sort="De Araujo Junior, Raimundo Fernandes" uniqKey="De Araujo Junior R" first="Raimundo Fernandes" last="De Araújo Júnior">Raimundo Fernandes De Araújo Júnior</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Ncbi/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000F66 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd -nk 000F66 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= Ncbi
|étape= Merge
|type= RBID
|clé= PMC:7076533
|texte= Effect of Oxaliplatin-Loaded Poly (d,l-Lactide-co-Glycolic Acid) (PLGA) Nanoparticles Combined with Retinoic Acid and Cholesterol on Apoptosis, Drug Resistance, and Metastasis Factors of Colorectal Cancer
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/RBID.i -Sk "pubmed:32102251" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd \
| NlmPubMed2Wicri -a ChloroquineV1
| This area was generated with Dilib version V0.6.33. |  |