title: Inhibition of placental growth factor in renal cell carcinoma.
abstract: OBJECTIVE
  Placental growth factor (PlGF) is up-regulated in major malignant diseases or following antiangiogenic therapy, although it is present in low levels under normal physiological conditions. TB403, a monoclonal antibody against PlGF, was investigated in clear cell renal cell carcinoma (ccRCC) xenografts since it has been proposed as a potential target in oncology.
  
  
  METHODS
  Human ccRCCs were implanted in athymic nude mice to evaluate the efficacy of TB403 and to excise xenograft tumors for molecular experiments.
  
  
  RESULTS
  TB403 did not significantly inhibit tumor growth in treatment-naïve or sunitinib-resistant ccRCC xenografts. Gene expression profiling resulted in over-expression of the C1orf38 gene, which induced immunoreactivity in macrophages. Angiogenesis PCR arrays showed that VEGFR-1 was not expressed in ccRCC xenografts.
  
  
  CONCLUSIONS
  PlGF blockade did not have a broad antiangiogenic efficacy; however, it might be effective on-target in VEGFR1-expressing tumors. The inhibition of VEGF pathway may induce the activity of tumor-associated-macrophages for angiogenesis escape.
authors.affiliation: Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore Department of Urology, Kitasato University School of Medicine, Kanagawa, Japan hideji56@gmail.com.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Bessho
authors.affiliation: Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Bernice
authors.initials: B
authors.lastname: Wong
authors.affiliation: Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI, U.S.A.
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.affiliation: Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Ee Yan
authors.initials: EY
authors.lastname: Siew
authors.affiliation: Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Dachuan
authors.initials: D
authors.lastname: Huang
authors.affiliation: Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Jing
authors.initials: J
authors.lastname: Tan
authors.affiliation: Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Choon Kiat
authors.initials: CK
authors.lastname: Ong
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore, Singapore.
authors.forename: Soo Yong
authors.initials: SY
authors.lastname: Tan
authors.affiliation: Department of Urology, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Urology, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Iwamura
authors.affiliation: Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors* / Q000097:blood; D011758:Pyrroles / Q000494:pharmacology; D000077210:Sunitinib; D059467:Transcriptome / Q000187:drug effects; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007211:Indoles; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D011758:Pyrroles; D000072483:Placenta Growth Factor; C569915:TB-403; D000077210:Sunitinib
keywords: Placental growth factor (PlGF); antiangiogenic therapy; renal cell carcinoma; sunitinib resistance