Novel Animal Glioma Models that Separately Exhibit Two Different Invasive and Angiogenic Phenotypes of Human Glioblastomas

Inoue, Satoshi; Ichikawa, Tomotsugu; Kurozumi, Kazuhiko; Maruo, Tomoko; Onishi, Manabu; Yoshida, Kôichi; Fujii, Kentaro; Kambara, Hirokazu; Chiocca, E. Antonio; Date, Isao

doi:10.1016/j.wneu.2011.09.005

Cited by 37 publications

(45 citation statements)

References 47 publications

(47 reference statements)

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“…We reported that cilengitide exerts its antitumor effects by inhibiting tumor angiogenesis and invasion or by inducing apoptosis-related pathways [9], [13], [21]. We recently established two novel invasive animal glioma models (J3T-1 and J3T-2) that reflect the invasive phenotype of human malignant gliomas [22]. These models were particularly beneficial to investigate the anti-invasive effects of cilengitide [13].…”

Section: Discussionmentioning

confidence: 99%

Integrin Inhibitor Suppresses Bevacizumab-Induced Glioma Invasion

Ishida

Onishi

Kurozumi

et al. 2014

Translational Oncology

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Glioblastoma is known to secrete high levels of vascular endothelial growth factor (VEGF), and clinical studies with bevacizumab, a monoclonal antibody to VEGF, have demonstrated convincing therapeutic benefits in glioblastoma patients. However, its induction of invasive proliferation has also been reported. We examined the effects of treatment with cilengitide, an integrin inhibitor, on bevacizumab-induced invasive changes in glioma. U87ΔEGFR cells were stereotactically injected into the brain of nude mice or rats. Five days after tumor implantation, cilengitide and bevacizumab were administered intraperitoneally three times a week. At 18 days after tumor implantation, the brains were removed and observed histopathologically. Next, the bevacizumab and cilengitide combination group was compared to the bevacizumab monotherapy group using microarray analysis. Bevacizumab treatment led to increased cell invasion in spite of decreased angiogenesis. When the rats were treated with a combination of bevacizumab and cilengitide, the depth of tumor invasion was significantly less than with only bevacizumab. Pathway analysis demonstrated the inhibition of invasion-associated genes such as the integrin-mediated cell adhesion pathway in the combination group. This study showed that the combination of bevacizumab with cilengitide exerted its anti-invasive effect. The elucidation of this mechanism might contribute to the treatment of bevacizumab-refractory glioma.

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Section: Discussionmentioning

confidence: 99%

Integrin Inhibitor Suppresses Bevacizumab-Induced Glioma Invasion

Ishida

Onishi

Kurozumi

et al. 2014

Translational Oncology

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“…Two cell lines, J3T-1 and J3T-2, were developed from the J3T parental canine glioma cell line, as previously described [3]. J3T-1 and J3T-2 cells were seeded in tissue culture dishes (BD Falcon, Franklin Lakes, NJ) and cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10 % fetal bovine serum (FBS), penicillin (100 U/ml) and streptomycin (0.1 mg/ml) [2][3][4]6].…”

Section: Glioma Cell Linesmentioning

confidence: 99%

“…Therefore, understanding the mechanisms underlying angiogenesis and invasion in glioblastoma is essential for the development of novel, curative therapies. However, glioma angiogenesis and invasion are challenging to study in experimental settings since the majority of animal models fail to mimic the unique angiogenesis and invasiveness of human glioma cells [2,3].…”

Section: Introductionmentioning

confidence: 99%

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Annexin A2 regulates angiogenesis and invasion phenotypes of malignant glioma

et al. 2015

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BACKGROUND: Despite advances in multimodal therapy, patients with malignant glioma have a dismal prognosis. Aberrant angiogenesis and diffuse glioma cell invasion are major obstacles for effective treatment. Therefore, investigation of angiogenesis and invasion is essential for the development of a curative therapy. We established animal models that histologically mimic two invasive and angiogenic phenotypes of glioma, ie, angiogenesis-dependent invasion (J3T-1) and angiogenesis-independent invasion (J3T-2). In our previous study, comparative proteomic analysis showed that annexin A2 was more highly expressed in J3T-1 than in J3T-2. In this study, the function of annexin A2 in

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“…Recently, a novel glioma model has been used to demonstrate, histologically, two distinct patterns of invasion – namely, angiogenesis-dependent invasion with the overexpression of angiogenesis-related genes such as those for VEGF, MMP9, hypoxia-inducible factor 1, and platelet-derived growth factor, and angiogenesis-independent invasion with overexpression of invasion-related genes such as those for integrin alpha-v beta-3, MMP2, nestin, and secreted protein acidic and rich in cysteine 19. In another aspect, SDF-1α, interleukin-6, basic fibroblast growth factor, and circulating progenitor cells are considered other escape biomarkers for antiangiogenic therapy 17.…”

Section: Molecular Mechanism Of Bevacizumab Treatment Failure On Recumentioning

confidence: 99%

Bevacizumab in Japanese patients with malignant glioma: from basic research to clinical trial

Takano¹,

Ishikawa²,

Nakai³

et al. 2014

OTT

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An antiangiogenic approach is especially suitable for the treatment of malignant gliomas. Recently, two large clinical trials in newly diagnosed glioblastoma (the Avastin in Glioblastoma study and Radiation Therapy Oncology Group 0825 study) showed a 3- to 4-month prolongation of progression-free survival (PFS) with bevacizumab, but no significant effect on overall survival (OS). Japan is the first, and so far only, country to approve the use of bevacizumab in newly diagnosed glioblastoma in combination with radiotherapy and temozolomide chemotherapy. The drug is also approved for use as monotherapy for recurrent glioblastoma and certain other types of high-grade glioma after previous therapy. The effectiveness of bevacizumab on Japanese malignant glioma patients was reviewed. The Phase II clinical trial demonstrated that the PFS with bevacizumab alone was 34% at 6 months and 3.3 months at median for 32 patients with recurrent malignant gliomas. In the Avastin in Glioblastoma study, 44 Japanese patients were registered from Japan. PFS and OS for bevacizumab combined with standard temozolomide and radiotherapy were 12.2 months and 29.2 months at median, respectively, for the patients with newly diagnosed glioblastoma. PFS and OS tended to be longer for those treated with bevacizumab than for those not treated with the drug. In addition, biomarkers of bevacizumab effectiveness were investigated in Japanese patients. Vascular endothelial growth factor concentration, matrix metalloproteinase 9 activities in urine, and apparent diffusion coefficient values on magnetic resonance imaging may be biomarkers that predict patient prognosis. Finally, novel experiments for vascular endothelial growth factor antibody action were described; these include the induction of glioma cell apoptosis, an antibody treatment failure model, and a study of the synergistic effect with chemotherapeutic agents.

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Novel Animal Glioma Models that Separately Exhibit Two Different Invasive and Angiogenic Phenotypes of Human Glioblastomas

Cited by 37 publications

References 47 publications

Integrin Inhibitor Suppresses Bevacizumab-Induced Glioma Invasion

Integrin Inhibitor Suppresses Bevacizumab-Induced Glioma Invasion

Annexin A2 regulates angiogenesis and invasion phenotypes of malignant glioma

Bevacizumab in Japanese patients with malignant glioma: from basic research to clinical trial

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