Recombinant anti-podoplanin (NZ-1) immunotoxin for the treatment of malignant brain tumors
Identifieur interne : 003229 ( Pmc/Curation ); précédent : 003228; suivant : 003230Recombinant anti-podoplanin (NZ-1) immunotoxin for the treatment of malignant brain tumors
Auteurs : Vidyalakshmi Chandramohan [États-Unis] ; Xuhui Bao [États-Unis, République populaire de Chine] ; Mika Kato Kaneko [Japon] ; Yukinari Kato [Japon] ; Stephen T. Keir [États-Unis] ; Scott E. Szafranski [États-Unis] ; Chien-Tsun Kuan [États-Unis] ; Ira H. Pastan [États-Unis] ; Darell D. Bigner [États-Unis]Source :
- International journal of cancer. Journal international du cancer [ 0020-7136 ] ; 2012.
Abstract
Current study demonstrates the glioma tumor antigen podoplanin to be present at very high levels (>90%) in both glioblastoma (D2159MG, D08-0308MG, and D08-0493MG) and medulloblastoma (D283MED, D425MED, and DAOY) xenografts and cell line. We constructed a novel recombinant single-chain antibody variable region fragment (scFv), NZ-1, specific for podoplanin from the NZ-1 hybridoma. NZ-1-scFv was then fused to
Url:
DOI: 10.1002/ijc.27919
PubMed: 23115013
PubMed Central: 3809846
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :003230
Links to Exploration step
PMC:3809846Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Recombinant anti-podoplanin (NZ-1) immunotoxin for the treatment of malignant brain tumors</title><author><name sortKey="Chandramohan, Vidyalakshmi" sort="Chandramohan, Vidyalakshmi" uniqKey="Chandramohan V" first="Vidyalakshmi" last="Chandramohan">Vidyalakshmi Chandramohan</name><affiliation wicri:level="2"><nlm:aff id="A1">Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham, NC</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Bao, Xuhui" sort="Bao, Xuhui" uniqKey="Bao X" first="Xuhui" last="Bao">Xuhui Bao</name><affiliation wicri:level="2"><nlm:aff id="A1">Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham, NC</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham</wicri:cityArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040</wicri:regionArea></affiliation></author><author><name sortKey="Kaneko, Mika Kato" sort="Kaneko, Mika Kato" uniqKey="Kaneko M" first="Mika Kato" last="Kaneko">Mika Kato Kaneko</name><affiliation wicri:level="1"><nlm:aff id="A3">Molecular Tumor Marker Research Team, The Oncology Research Center, Advanced Molecular Epidemiology Research Institute, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Molecular Tumor Marker Research Team, The Oncology Research Center, Advanced Molecular Epidemiology Research Institute, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585</wicri:regionArea></affiliation></author><author><name sortKey="Kato, Yukinari" sort="Kato, Yukinari" uniqKey="Kato Y" first="Yukinari" last="Kato">Yukinari Kato</name><affiliation wicri:level="1"><nlm:aff id="A3">Molecular Tumor Marker Research Team, The Oncology Research Center, Advanced Molecular Epidemiology Research Institute, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Molecular Tumor Marker Research Team, The Oncology Research Center, Advanced Molecular Epidemiology Research Institute, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585</wicri:regionArea></affiliation></author><author><name sortKey="Keir, Stephen T" sort="Keir, Stephen T" uniqKey="Keir S" first="Stephen T." last="Keir">Stephen T. Keir</name><affiliation wicri:level="2"><nlm:aff id="A1">Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham, NC</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Szafranski, Scott E" sort="Szafranski, Scott E" uniqKey="Szafranski S" first="Scott E." last="Szafranski">Scott E. Szafranski</name><affiliation wicri:level="2"><nlm:aff id="A1">Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham, NC</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Kuan, Chien Tsun" sort="Kuan, Chien Tsun" uniqKey="Kuan C" first="Chien-Tsun" last="Kuan">Chien-Tsun Kuan</name><affiliation wicri:level="2"><nlm:aff id="A1">Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham, NC</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Pastan, Ira H" sort="Pastan, Ira H" uniqKey="Pastan I" first="Ira H." last="Pastan">Ira H. Pastan</name><affiliation wicri:level="2"><nlm:aff id="A4">Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Bigner, Darell D" sort="Bigner, Darell D" uniqKey="Bigner D" first="Darell D." last="Bigner">Darell D. Bigner</name><affiliation wicri:level="2"><nlm:aff id="A1">Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham, NC</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23115013</idno><idno type="pmc">3809846</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3809846</idno><idno type="RBID">PMC:3809846</idno><idno type="doi">10.1002/ijc.27919</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">003230</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003230</idno><idno type="wicri:Area/Pmc/Curation">003229</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">003229</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Recombinant anti-podoplanin (NZ-1) immunotoxin for the treatment of malignant brain tumors</title><author><name sortKey="Chandramohan, Vidyalakshmi" sort="Chandramohan, Vidyalakshmi" uniqKey="Chandramohan V" first="Vidyalakshmi" last="Chandramohan">Vidyalakshmi Chandramohan</name><affiliation wicri:level="2"><nlm:aff id="A1">Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham, NC</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Bao, Xuhui" sort="Bao, Xuhui" uniqKey="Bao X" first="Xuhui" last="Bao">Xuhui Bao</name><affiliation wicri:level="2"><nlm:aff id="A1">Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham, NC</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham</wicri:cityArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040</wicri:regionArea></affiliation></author><author><name sortKey="Kaneko, Mika Kato" sort="Kaneko, Mika Kato" uniqKey="Kaneko M" first="Mika Kato" last="Kaneko">Mika Kato Kaneko</name><affiliation wicri:level="1"><nlm:aff id="A3">Molecular Tumor Marker Research Team, The Oncology Research Center, Advanced Molecular Epidemiology Research Institute, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Molecular Tumor Marker Research Team, The Oncology Research Center, Advanced Molecular Epidemiology Research Institute, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585</wicri:regionArea></affiliation></author><author><name sortKey="Kato, Yukinari" sort="Kato, Yukinari" uniqKey="Kato Y" first="Yukinari" last="Kato">Yukinari Kato</name><affiliation wicri:level="1"><nlm:aff id="A3">Molecular Tumor Marker Research Team, The Oncology Research Center, Advanced Molecular Epidemiology Research Institute, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Molecular Tumor Marker Research Team, The Oncology Research Center, Advanced Molecular Epidemiology Research Institute, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585</wicri:regionArea></affiliation></author><author><name sortKey="Keir, Stephen T" sort="Keir, Stephen T" uniqKey="Keir S" first="Stephen T." last="Keir">Stephen T. Keir</name><affiliation wicri:level="2"><nlm:aff id="A1">Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham, NC</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Szafranski, Scott E" sort="Szafranski, Scott E" uniqKey="Szafranski S" first="Scott E." last="Szafranski">Scott E. Szafranski</name><affiliation wicri:level="2"><nlm:aff id="A1">Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham, NC</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Kuan, Chien Tsun" sort="Kuan, Chien Tsun" uniqKey="Kuan C" first="Chien-Tsun" last="Kuan">Chien-Tsun Kuan</name><affiliation wicri:level="2"><nlm:aff id="A1">Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham, NC</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Pastan, Ira H" sort="Pastan, Ira H" uniqKey="Pastan I" first="Ira H." last="Pastan">Ira H. Pastan</name><affiliation wicri:level="2"><nlm:aff id="A4">Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Bigner, Darell D" sort="Bigner, Darell D" uniqKey="Bigner D" first="Darell D." last="Bigner">Darell D. Bigner</name><affiliation wicri:level="2"><nlm:aff id="A1">Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham, NC</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author></analytic><series><title level="j">International journal of cancer. Journal international du cancer</title><idno type="ISSN">0020-7136</idno><idno type="eISSN">1097-0215</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 id="P1">Current study demonstrates the glioma tumor antigen podoplanin to be present at very high levels (>90%) in both glioblastoma (D2159MG, D08-0308MG, and D08-0493MG) and medulloblastoma (D283MED, D425MED, and DAOY) xenografts and cell line. We constructed a novel recombinant single-chain antibody variable region fragment (scFv), NZ-1, specific for podoplanin from the NZ-1 hybridoma. NZ-1-scFv was then fused to <italic>Pseudomonas</italic> exotoxin A, carrying a C-terminal KDEL peptide (NZ-1-PE38KDEL). The immunotoxin was further stabilized by a disulfide (ds) bond between the heavy-chain and light-chain variable regions as the construct NZ-1-(scdsFv)-PE38KDEL. NZ-1-(scdsFv)-PE38KDEL exhibited significant reactivity to glioblastoma and medulloblastoma cells. The affinity of NZ-1-(scdsFv), NZ-1-(scdsFv)-PE38KDEL and NZ-1 antibody, for podoplanin peptide was 2.1×10<sup>−8</sup> M, 8.0×10<sup>−8</sup> M, and 3.9×10<sup>−10</sup> M, respectively. In a protein stability assay, NZ-1-(scdsFv)-PE38KDEL retained 33-98% of its activity while that of NZ-1-PE38KDEL declined to 13% of its initial levels after incubation at 37°C for 3 days. <italic>In vitro</italic> cytotoxicity of the NZ-1-(scdsFv)-PE38KDEL was measured in cells isolated from glioblastoma xenografts, D2159MG, D08-0308MG, D08-0493MG, and in the medulloblastoma D283MED, D425MED, and DOAY xenografts and cell line. The NZ-1-(scdsFv)-PE38KDEL immunotoxin was highly cytotoxic, with an IC<sub>50</sub> in the range of 1.6–29 ng/mL. Significantly, NZ-1-(scdsFv)-PE38KDEL demonstrated tumor-growth delay, averaging 24 days (<italic>P</italic><0.001) and 21 days (<italic>P</italic><0.001) in D2159MG and D283MED <italic>in vivo</italic> tumor models, respectively. Crucially, in the D425MED intracranial tumor model, NZ-1-(scdsFv)-PE38KDEL caused a 41% increase in survival (<italic>P</italic>≤0.001). In preclinical studies, NZ-1-(scdsFv)-PE38KDEL exhibited significant potential as a targeting agent for malignant brain tumors.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0042124</journal-id><journal-id journal-id-type="pubmed-jr-id">4284</journal-id><journal-id journal-id-type="nlm-ta">Int J Cancer</journal-id><journal-id journal-id-type="iso-abbrev">Int. J. Cancer</journal-id><journal-title-group><journal-title>International journal of cancer. Journal international du cancer</journal-title></journal-title-group><issn pub-type="ppub">0020-7136</issn><issn pub-type="epub">1097-0215</issn></journal-meta><article-meta><article-id pub-id-type="pmid">23115013</article-id><article-id pub-id-type="pmc">3809846</article-id><article-id pub-id-type="doi">10.1002/ijc.27919</article-id><article-id pub-id-type="manuscript">NIHMS520128</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Recombinant anti-podoplanin (NZ-1) immunotoxin for the treatment of malignant brain tumors</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Chandramohan</surname><given-names>Vidyalakshmi</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Bao</surname><given-names>Xuhui</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kaneko</surname><given-names>Mika Kato</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Kato</surname><given-names>Yukinari</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Keir</surname><given-names>Stephen T.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Szafranski</surname><given-names>Scott E.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Kuan</surname><given-names>Chien-Tsun</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Pastan</surname><given-names>Ira H.</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Bigner</surname><given-names>Darell D.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib></contrib-group><aff id="A1"><label>1</label>Preston Robert Tisch Brain Tumor Center at Duke and Department of Pathology, Duke University Medical Center, Durham, NC</aff><aff id="A2"><label>2</label>Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China</aff><aff id="A3"><label>3</label>Molecular Tumor Marker Research Team, The Oncology Research Center, Advanced Molecular Epidemiology Research Institute, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan</aff><aff id="A4"><label>4</label>Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD</aff><author-notes><corresp id="FN1">Correspondence to: Darell D. Bigner, M.D., Ph.D., Department of Pathology, Duke University Medical Center, Box 3156, 177 MSRB1, Research Drive, Durham, NC 27710, USA, Tel.: 1-919-684-5018, Fax: 1-919-684-6458, <email>bigne001@mc.duke.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>30</day><month>9</month><year>2013</year></pub-date><pub-date pub-type="epub"><day>23</day><month>11</month><year>2012</year></pub-date><pub-date pub-type="ppub"><day>15</day><month>5</month><year>2013</year></pub-date><pub-date pub-type="pmc-release"><day>15</day><month>5</month><year>2014</year></pub-date><volume>132</volume><issue>10</issue><elocation-id>10.1002/ijc.27919</elocation-id><abstract><p id="P1">Current study demonstrates the glioma tumor antigen podoplanin to be present at very high levels (>90%) in both glioblastoma (D2159MG, D08-0308MG, and D08-0493MG) and medulloblastoma (D283MED, D425MED, and DAOY) xenografts and cell line. We constructed a novel recombinant single-chain antibody variable region fragment (scFv), NZ-1, specific for podoplanin from the NZ-1 hybridoma. NZ-1-scFv was then fused to <italic>Pseudomonas</italic> exotoxin A, carrying a C-terminal KDEL peptide (NZ-1-PE38KDEL). The immunotoxin was further stabilized by a disulfide (ds) bond between the heavy-chain and light-chain variable regions as the construct NZ-1-(scdsFv)-PE38KDEL. NZ-1-(scdsFv)-PE38KDEL exhibited significant reactivity to glioblastoma and medulloblastoma cells. The affinity of NZ-1-(scdsFv), NZ-1-(scdsFv)-PE38KDEL and NZ-1 antibody, for podoplanin peptide was 2.1×10<sup>−8</sup> M, 8.0×10<sup>−8</sup> M, and 3.9×10<sup>−10</sup> M, respectively. In a protein stability assay, NZ-1-(scdsFv)-PE38KDEL retained 33-98% of its activity while that of NZ-1-PE38KDEL declined to 13% of its initial levels after incubation at 37°C for 3 days. <italic>In vitro</italic> cytotoxicity of the NZ-1-(scdsFv)-PE38KDEL was measured in cells isolated from glioblastoma xenografts, D2159MG, D08-0308MG, D08-0493MG, and in the medulloblastoma D283MED, D425MED, and DOAY xenografts and cell line. The NZ-1-(scdsFv)-PE38KDEL immunotoxin was highly cytotoxic, with an IC<sub>50</sub> in the range of 1.6–29 ng/mL. Significantly, NZ-1-(scdsFv)-PE38KDEL demonstrated tumor-growth delay, averaging 24 days (<italic>P</italic><0.001) and 21 days (<italic>P</italic><0.001) in D2159MG and D283MED <italic>in vivo</italic> tumor models, respectively. Crucially, in the D425MED intracranial tumor model, NZ-1-(scdsFv)-PE38KDEL caused a 41% increase in survival (<italic>P</italic>≤0.001). In preclinical studies, NZ-1-(scdsFv)-PE38KDEL exhibited significant potential as a targeting agent for malignant brain tumors.</p></abstract><kwd-group><kwd>podoplanin</kwd><kwd>glioblastoma multiforme</kwd><kwd>medulloblastoma</kwd><kwd>recombinant immunotoxin</kwd><kwd>single-chain disulfide Fv</kwd></kwd-group><funding-group><award-group><funding-source country="United States">National Cancer Institute : NCI</funding-source><award-id>R37 CA011898 || CA</award-id></award-group><award-group><funding-source country="United States">National Institute of Neurological Disorders and Stroke : NINDS</funding-source><award-id>P50 NS020023 || NS</award-id></award-group></funding-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/Pmc/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 003229 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 003229 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= LymphedemaV1
|flux= Pmc
|étape= Curation
|type= RBID
|clé= PMC:3809846
|texte= Recombinant anti-podoplanin (NZ-1) immunotoxin for the treatment of malignant brain tumors
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i -Sk "pubmed:23115013" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd \
| NlmPubMed2Wicri -a LymphedemaV1
| This area was generated with Dilib version V0.6.31. |  |