Significance of Fas receptor protein expression in epithelial ovarian cancer

Reed, Jennifer; Hakam, Ardeshir; Nicosia, Santo V.; Coppola, Domenico

doi:10.1016/j.humpath.2005.06.015

Cited by 13 publications

(4 citation statements)

References 39 publications

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“…In addition, ovarian tumors that have retained Fas expression are better differentiated and have a better progression-free and disease-specific survival, which support data showing that loss of Fas expression is implied in dedifferentiation and acquisition of a higher malignant potential in several cancers [27][28][29]. Previous studies examining protein expression of Fas, FasL or both in ovarian cancers showed substantial variation which can be explained by small sample sizes, inclusion of tumors classified as benign, borderline and malignant and different use of antibodies and scoring systems [23,[30][31][32]. Moreover, in agreement with a previous study [33] we used cut-off values for definition of positive or negative staining based on dichotomization of staining classes according to their association with prognosis.…”

Section: Discussionsupporting

confidence: 73%

The extrinsic apoptosis pathway and its prognostic impact in ovarian cancer

Duiker

Zee

Graeff

et al. 2010

Gynecologic Oncology

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Section: Discussionsupporting

confidence: 73%

The extrinsic apoptosis pathway and its prognostic impact in ovarian cancer

Duiker

Zee

Graeff

et al. 2010

Gynecologic Oncology

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“…The significance and deregulation of the Fas-mediated apoptotic pathway has been observed in several cancer types including ovarian 32 and prostate 33 cancers, as well as T cell leukemia 34. However, the status of Fas-mediated apoptosis in CCRCC is unknown.…”

Section: Resultsmentioning

confidence: 99%

Suppression of Hypoxia-Inducible Factor 2α Restores p53 Activity via Hdm2 and Reverses Chemoresistance of Renal Carcinoma Cells

et al. 2009

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Abstractp53 mutations are rarely detected in clear cell renal cell carcinoma (CCRCC), but, paradoxically, these tumors remain highly resistant to chemotherapy and death receptor-induced death. Here, we show that the accumulation of hypoxia-inducible factor 2α (HIF2α), a critical oncogenic event in CCRCC following the loss of von Hippel-Lindau (VHL) tumor suppressor protein, leads to Hdm2-mediated suppression of p53. Primary CCRCC specimens exhibiting strong hypoxic signatures show increased levels of activated nuclear phospho-Hdm2(Ser 166 ), which is concomitant with low p53 expression. The abrogation of Hdm2-p53 interaction using the small-molecule Hdm2 inhibitor nutlin-3 or the downregulation of HIF2α via HIF2α-specific short hairpin RNA or wild-type VHL reconstitution restores p53 function and reverses the resistance of CCRCC cells to Fas-mediated and chemotherapy-induced cell death. These findings unveil a mechanistic link between HIF2α and p53 and provide a rationale for combining Hdm2 antagonists with chemotherapy for the treatment of CCRCC. [Cancer Res 2009;69(23):9056-64]

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“…The pro-apoptotic receptor CD95 was detected in 85% of inclusion cysts, 94% of cystadenomas, 35% of borderline tumours and 4% of invasive cancers80. Thus, invasive ovarian cancers are likely to resist the apoptosis that is induced by exposure to CD95 ligand or agonistic anti-CD95 antibodies.…”

Section: Tumour Biologymentioning

confidence: 99%

The biology of ovarian cancer: new opportunities for translation

2009

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Over the past two decades, the 5-year survival for ovarian cancer patients has substantially improved owing to more effective surgery and treatment with empirically optimized combinations of cytotoxic drugs, but the overall cure rate remains approximately 30%. Many investigators think that further empirical trials using combinations of conventional agents are likely to produce only modest incremental improvements in outcome. Given the heterogeneity of this disease, increases in longterm survival might be achieved by translating recent insights at the molecular and cellular levels to personalize individual strategies for treatment and to optimize early detection.• Several factors make ovarian cancer a difficult disease to treat effectively. Although many patients experience symptoms, these often overlap with other ailments, and many patients are diagnosed after the cancer has metastasized. Ovarian cancer is also heterogeneous -multiple genetic and epigenetic changes are evident in patients with ovarian cancer; however, how such changes are selected for during tumorigenesis is not yet clear.• Mutation and loss of TP53 function is one of the most frequent genetic abnormalities in ovarian cancer and is observed in 60-80% of both sporadic and familial cases. Of the 16 candidate tumour suppressor genes identified to date in ovarian cancer, 3 are imprinted genes. Several growth inhibitory genes are also silenced by methylation or imprinting.• Inheritance of DNA repair defects contributes to as many as 10-15% of ovarian cancers. The lifetime risk of developing ovarian cancer in mutation carriers varies with the genetic defect (for BRCA1 30-60%, for BRCA2 15-30% and for hereditary non-polyposis colon cancer 7%).• At least 15 oncogenes have been implicated in ovarian cancers, and DNA copy number abnormalities have also been found in loci that are known to contain noncoding microRNAs. At least seven signalling pathways are activated in >50% of ovarian cancers, and mutations that affect cell proliferation, apoptosis and autophagy are also evident.• Ovarian cancer can be split into two groups on the basis of genetic changes: low-grade tumours with mutations in KRAS, BRAF and PIK3CA, loss of heterozygosity (LOH) on chromosome Xq, microsatellite instability and expression of amphiregulin; and high-grade tumours with aberrations in TP53 and potential aberrations in BRCA1 and BRCA2, as well as LOH on chromosomes 7q and 9p.Correspondence to: Robert C. Bast, Jr 1 rbast@mdanderson.org. Competing interests statementThe authors declare no competing financial interests. NIH Public Access Author ManuscriptNat Rev Cancer. Author manuscript; available in PMC 2010 February 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript• Changes in cell adhesion and motility also contribute to disease development and metastasis. Adhesion of ovarian cancer cells to the mesothelial cells and to the underlying stroma is mediated by CD44, CA125 and b1 intergrin on the surface of ovarian cancer cells that bind to mesotheli...

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Significance of Fas receptor protein expression in epithelial ovarian cancer

Cited by 13 publications

References 39 publications

The extrinsic apoptosis pathway and its prognostic impact in ovarian cancer

The extrinsic apoptosis pathway and its prognostic impact in ovarian cancer

Suppression of Hypoxia-Inducible Factor 2α Restores p53 Activity via Hdm2 and Reverses Chemoresistance of Renal Carcinoma Cells

The biology of ovarian cancer: new opportunities for translation

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