Fas/APO-1-Mediated Apoptosis of Human Renal Cell Carcinoma

Nonomura, Norio; Miki, Tsuneharu; Yokoyama, Masayoshi; Imazu, Tetsuo; Takada, Tsuyoshi; Takeuchi, Seiji; Kanno, Nobufumi; Nishimura, Kazuo; Kojima, Yasuyuki; Okuyama, Äkïhïko

doi:10.1006/bbrc.1996.1906

Cited by 25 publications

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“…This effect was attributed to the regulation of downstream caspases (Tomita et al, 2003). Cytokines, including IFNs, upregulate Fas in RCC cells (Nonomura et al, 1996), and thus increase the susceptibility to Fas-mediated apoptosis. In RCC cell lines, Bcl-2 reduction has been shown to be associated with increased sensitivity to anti-Fas (Hara et al, 2001).…”

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Absence of Bcl-2 and Fas/CD95/APO-1 predicts the response to immunotherapy in metastatic renal cell carcinoma

et al. 2006

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Immunotherapy is the only available treatment for metastatic renal cell cancer (RCC), but the response rate is only about 20% and the treatment is occasionally associated with severe adverse effects. Thus, the selection of patients with a high susceptibility to immunotherapy is needed; however, there is no promising molecular marker that can predict the response to immunotherapy for RCC. This study was carried out to elucidate the potential role of apoptosis-related molecules Bcl-2 and Fas, as well as apoptotic and proliferating indexes (AI, PI) as predictors of the susceptibility of metastatic RCC to immunotherapy. Immunohistochemical examination of tumour tissues from 40 patients with metastatic RCC undergoing postoperative immunotherapy after radical nephrectomy was performed. Patients with progressive disease (PD) after immunotherapy presented with decreased survival (P ¼ 0.006). Progressive disease correlated with higher PI in the primary lesion (P ¼ 0.0087). All primary tumours of CR or PR patients were negative for Bcl-2, whereas among NC þ PD patients, 40.6% were positive for Bcl-2 (P ¼ 0.0373). Patients in whom the primary tumours were both Bcl-2-and Fas-negative showed significantly better responses to immunotherapy in comparison with the remaining group (P ¼ 0.0022). The Bcl-2 and Fas status of the primary lesion may become useful criteria for the selection of patients with metastatic RCC for immunotherapy.

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confidence: 99%

Absence of Bcl-2 and Fas/CD95/APO-1 predicts the response to immunotherapy in metastatic renal cell carcinoma

et al. 2006

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“…1,2 The expression of Fas has been found in a variety of cells, including activated lymphocytes and natural killer cells. [3][4][5] Fas and Fas ligand also have been detected in malignant neoplasms, including melanoma, 6 colon carcinoma, 7 renal cell carcinoma, 8 astrocytoma, 9 esophageal carcinoma, 10 and breast carcinoma. 11 It has been suggested that up-regulation of Fas ligand may serve as a mechanism for malignant cells to escape immune surveillance by inducing apoptosis of activated lymphocytes and natural killer cells.…”

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confidence: 99%

“…11 It has been suggested that up-regulation of Fas ligand may serve as a mechanism for malignant cells to escape immune surveillance by inducing apoptosis of activated lymphocytes and natural killer cells. [1][2][3][4][5][6][7][8] Prostate carcinoma is the most common noncutaneous malig-nancy and is the second leading cause of cancerrelated mortality in American men. 12 The pathogenesis of prostate carcinoma is understood incompletely.…”

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Fas and Fas ligand expression is elevated in prostatic intraepithelial neoplasia and prostatic adenocarcinoma

Jiang

Ulbright

Zhang

et al. 2002

Cancer

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BACKGROUNDFas is a Type I membrane receptor of the tumor necrosis factor/nerve growth factor family. On binding to Fas ligand, a Type II transmembrane protein, the Fas/Fas ligand complex, induces apoptosis in target cells. Dysregulation of Fas and Fas ligand expression has been found in some malignant neoplasms.METHODSUsing immunohistochemical analysis, the authors studied the expression of Fas and Fas ligand in prostatic adenocarcinoma, high‐grade prostatic intraepithelial neoplasia (PIN), and adjacent benign prostate tissue from 95 radical prostatectomy specimens.RESULTSThe percentage of cells that stained positively with Fas in benign prostate tissue (mean, 2%) was statistically significantly lower compared with that in prostatic intraepithelial neoplasia (mean, 13%; P = 0.0014) and prostatic adenocarcinoma (mean, 31%; P = 0.0001). The staining intensity of Fas was significantly less in benign prostate tissue compared with the staining intensity in PIN and prostatic adenocarcinoma. The percentage of cells that stained positively with Fas ligand in benign prostate tissue (mean, 13%) was statistically significantly lower compared with that in PIN (mean, 47%; P = 0.0001) and in prostatic adenocarcinoma (mean, 53%; P = 0.0001). The staining intensity of Fas ligand was significantly less in benign prostate tissue compared with that in PIN and prostatic adenocarcinoma.CONCLUSIONSData from the current study indicate that Fas/Fas ligand is elevated in prostatic malignancy, suggesting that Fas‐mediated apoptosis may be a potential target for therapeutic intervention. Cancer 2002;95:296–300. © 2002 American Cancer Society.DOI 10.1002/cncr.10674

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“…The cytotoxic effect of anti-CD95 antibody on certain renal cell carcinoma cell lines was augmented by pretreatment of these cells with interferon-γ (Tomita et al, 1996a). On the other hand, immunohistochemical analysis of resected tissues from the patients with RCC revealed stronger expression of CD95 antigen on the surface of cancer cells than that of normal cells (Nonomura et al, 1996). These results suggested that CD95 may be a possible target for novel approaches to treatment of human RCC.…”

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confidence: 95%

Significance of serum-soluble CD95 (Fas/APO-1) on prognosis in renal cell cancer patients

et al. 1999

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Summary Serum-soluble CD95 (sCD95) levels for 72 renal cell cancer patients were significantly higher than those of 17 healthy donors. Twenty-one of 72 patients had elevated (defined as more than mean of healthy donors + 2 s.d.) sCD95. The disease-specific survival rate was significantly lower in the elevated sCD95 group. Serum sCD95 level was shown to be an independent prognostic factor by univariate and multivariate analysis, indicating a possible significant role in determining treatment strategies.

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Fas/APO-1-Mediated Apoptosis of Human Renal Cell Carcinoma

Cited by 25 publications

References 0 publications

Absence of Bcl-2 and Fas/CD95/APO-1 predicts the response to immunotherapy in metastatic renal cell carcinoma

Absence of Bcl-2 and Fas/CD95/APO-1 predicts the response to immunotherapy in metastatic renal cell carcinoma

Fas and Fas ligand expression is elevated in prostatic intraepithelial neoplasia and prostatic adenocarcinoma

Significance of serum-soluble CD95 (Fas/APO-1) on prognosis in renal cell cancer patients

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