title: Antitumor effects of bevacizumab in a microenvironment-dependent human adult T-cell leukemia/lymphoma mouse model.
abstract: OBJECTIVE
  The objective of this study was to evaluate the therapeutic potential of bevacizumab with or without systemic chemotherapy for adult T-cell leukemia/lymphoma (ATL) and clarify the significance of angiogenesis for ATL pathogenesis.
  
  
  METHODS
  NOD/Shi-scid, IL-2Rγ(null) (NOG) mice were used as recipients of tumor cells from a patient with ATL, which engraft and proliferate in a microenvironment-dependent manner. The ATL cells could be serially transplanted in NOG mice, but could not be maintained in in vitro cultures.
  
  
  RESULTS
  Injection of bevacizumab alone significantly increased necrosis and decreased vascularization in the tumor tissue. Levels of human soluble interleukin two receptor in the serum (reflecting the ATL tumor burden) of bevacizumab-treated mice were significantly lower than in untreated mice. Although bevacizumab monotherapy showed these clear anti-angiogenesis effects, it did not prolong survival. In contrast, injection of bevacizumab together with cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) led to a significant prolongation of survival of the ATL mice relative to CHOP alone.
  
  
  CONCLUSIONS
  This is the first report to evaluate the efficacy of bevacizumab for ATL in a tumor microenvironment-dependent model. Bevacizumab therapy combined with chemotherapy could be a valuable treatment strategy for that subgroup of ATL probably depending to a large extent on angiogenesis via vascular endothelial growth factor.
authors.affiliation: Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Mori
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishida
authors.forename: Asahi
authors.initials: A
authors.lastname: Ito
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Sato
authors.forename: Ayako
authors.initials: A
authors.lastname: Masaki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Narita
authors.forename: Susumu
authors.initials: S
authors.lastname: Suzuki
authors.forename: Tomiko
authors.initials: T
authors.lastname: Yamada
authors.forename: Hisashi
authors.initials: H
authors.lastname: Takino
authors.forename: Masaki
authors.initials: M
authors.lastname: Ri
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kusumoto
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Komatsu
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Hishizawa
authors.forename: Kazunori
authors.initials: K
authors.lastname: Imada
authors.forename: Akifumi
authors.initials: A
authors.lastname: Takaori-Kondo
authors.forename: Akio
authors.initials: A
authors.lastname: Niimi
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ueda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inagaki
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Iida
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000737:chemistry*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D011239:Prednisolone / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000068258:Bevacizumab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Adult T-cell leukemia-lymphoma; Bevacizumab; tumor microenvironment