Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The OX-40 receptor (OX-40R) is a cell surface glycoprotein of the tumor necrosis factor receptor family that is expressed primarily on activated CD4 T cells. Engagement of OX-40R by the OX-40 ligand (OX-40L) is known to costimulate the production of cytokines by activated T lymphocytes and to rescue effector T cells from activation-induced cell death. It was previously reported that in vivo ligation of OX-40R by administration of OX-40L:immunoglobulin fusion protein or OX-40R monoclonal antibody (mAb) resulted in a significant prolongation of survival of tumor-bearing mice in four histologically distinct solid tumors. In this study, we demonstrate that the therapeutic efficacy of OX-40R mAb was influenced by the tumor burden, the intrinsic immunogenicity of the tumor as well as by the histological site of tumor growth. Whereas subdermal and intracranial growth of weakly immunogenic MCA 203 and MCA 205 sarcomas and GL261 glioma were susceptible to the mAb treatment, established pulmonary MCA 205 metastases were refractory to the same regimen of treatment. Furthermore, the mAb administration had no impact on the growth of the poorly immunogenic B16/D5 mela noma. Tumor regression mediated by OX-40R mAb was dependent on the participation of both CD4 and CD8 T cells and as a result of tumor rejection, a long-term tumor-specific immunity was established. Analysis of tumor-infiltrating T cells revealed the presence of a far greater number of OX-40R+ T cells of both CD4 and CD8 phenotypes in the intracranial immunogenic GL261 glioma than that in the poorly immunogenic B16/D5 melanoma. These results suggest that ligation of OX-40R on activated T cells in situ in the tumor may provide a necessary costimulatory signal to augment immune responses leading to tumor regression and immunological memory.
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PMID:Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth. 1103 96

In our previous study, PAb, a VEGF polyclonal antibody was found to inhibit murine tumor growth significantly. The main objective of this study was to investigate the efficacy of combination therapy of (PAb) and cisplatin on human ovarian cancer xenograft. Effect of VEGF, PAb, PAb-cisplatin combination, and cisplatin alone on cultured human ovarian teratocarci-noma cell line PA-1 were assessed by measuring cell proliferation, matrigel invasion, MMP-9 expression, and MMP-9 secretion. In vivo, effect of PAb was observed in a xenograft model of ovarian cancer. Antitumor efficacy was monitored by assessment of tumor volume, MVD, serum NO, serum VEGF, and p53 expression. VEGF increased proliferation of PA-1 cell in a dose-dependent manner while addition of PAb inhibited cell proliferation, cell invasion as well as MMP-9 secretion in vitro. Tumor burden in PAb and PAb-cisplatin combination group was reduced by 41% (p < 0.05) and 66% (p < 0.01), respectively. A significant decrease in MVD, serum NO, serum VEGF, and p53 expression was also observed after PAb and PAb-cisplatin combination treatment when compared to normal mouse serum IgG-treated control mice. Thus, it was concluded that VEGF immunoneutralization may enhance cisplatin-in-duced apoptosis in human ovarian cancer and thus may be an effective way to reduce tumor growth in ovarian carcinoma.
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PMID:VEGF antibody plus cisplatin reduces angiogenesis and tumor growth in a xenograft model of ovarian cancer. 2052 44