Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P52742 (pT3)
 1,034 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deregulation of apoptosis plays an important role in carcinogenesis, tumor progression, and resistance to chemotherapy. XIAP is considered to be the most potent caspase inhibitor of all known IAP (inhibitor of apoptosis) family members. To explore the relevance of XIAP for progression and prognosis in renal cell carcinomas (RCCs) of the clear-cell type, we analyzed XIAP protein expression in formalin-fixed tissue from 145 clear-cell RCCs by immunohistochemistry. XIAP protein expression was found in 95% of clear-cell RCCs. A significant increase of XIAP expression became evident from well (G1) to poorly (G3) differentiated clear-cell RCCs (P < 0.0001) and from low (pT1) to advanced (pT3) tumor stages (P = 0.0016). Log-rank test showed a significant inverse correlation (P = 0.0174) between XIAP expression and tumor aggressiveness as indicated by patients' survival. Most important, multivariate Cox regression analysis revealed that XIAP expression is an independent prognostic parameter (P = 0.018) in clear-cell RCCs. Our results suggest an important role for XIAP-mediated inhibition of apoptosis during progression of clear-cell RCCs and introduce XIAP expression as a new independent prognostic marker in this tumor type.
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PMID:XIAP expression is an independent prognostic marker in clear-cell renal carcinomas. 1529 70

Dysregulation of apoptosis plays an important role in tumour progression and resistance to chemotherapy. The X-linked inhibitor of apoptosis (XIAP) is considered to be the most potent caspase inhibitor of all known inhibitor of apoptosis-family members. Only recently, an antagonist of XIAP has been identified, termed Smac/DIABLO. To explore the relevance of antiapoptotic XIAP and proapoptotic Smac/DIABLO for tumour progression in renal cell carcinomas (RCCs), we analysed XIAP and Smac/DIABLO mRNA and protein expression in the primary tumour tissue from 66 RCCs of all major histological types by quantitative real-time PCR, Western blot and ELISA. X-linked inhibitor of apoptosis and Smac/DIABLO mRNA expression was found in all RCCs. Importantly, the relative XIAP mRNA expression levels significantly increased from early (pT1) to advanced (pT3) tumour stages (P=0.0002) and also with tumour dedifferentiation (P=0.04). Western blot analysis confirmed the tumour stage-dependent increase of XIAP expression on the protein level. In contrast, mRNA and protein expression levels of Smac/DIABLO did not significantly change between early and advanced tumour stages or between low and high tumour grades. Consequently, the mRNA expression ratio between antiapoptotic XIAP and proapoptotic Smac/DIABLO markedly increased during progression from early (pT1) to advanced (pT3) tumour stages. Moreover, RCCs confined within the organ capsule (pT1 and pT2) exhibited a significantly lower XIAP to Smac/DIABLO expression ratio when compared with RCCs infiltrating beyond the kidney (pT3; P=0.01). Thus, our investigation demonstrates that the delicate balance between XIAP and Smac/DIABLO expression is gradually disturbed during progression of RCCs, resulting in a relative increase of antiapoptotic XIAP over proapoptotic Smac/DIABLO, thereby probably contributing to the marked apoptosis resistance of RCC.
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PMID:Disturbed balance of expression between XIAP and Smac/DIABLO during tumour progression in renal cell carcinomas. 1532 23

Transcriptional downregulation of the putative tumor suppressor gene XIAP-associated Factor 1 (XAF1) by promoter methylation has been shown to relate to tumor progression of gastric and bladder cancer. This study determined the mRNA expression levels and the methylation status of XAF1 by real-time RT-PCR and quantitative methylation specific PCR in tumor tissue obtained from 91 renal cell carcinoma (RCC) patients (median follow-up 50.5 months) following surgical treatment. Expression data was correlated to histopathological variables and outcome. XAF1 expression levels were not related to standard pathological parameters for outcome prediction but results from crude and explorative multivariable-adjusted analyses revealed low XAF1 levels to significantly increase the relative risk (RR) for tumor recurrence (RR 4.6; CI 95%: 1.4-14.6) and tumor-related death (RR 3.6; CI 95%: 1.4-9.7). The association of low XAF1 expression with an abbreviated recurrence-free (p=0.009) and disease-specific survival (p=0.005) was most pronounced in patients with locally advanced (pT3) tumors. XAF1 promoter methylation was rarely detected (10%) but, if present, XAF1 mRNA expression levels correlated inversely to the normalized index of methylation (p=0.01). Our findings suggest that low XAF1 mRNA expression levels relate to an unfavorable clinical course in RCC patients. Promoter methylation may be one, but probably not the essential mechanism for transcriptional downregulation of the XAF1 gene in RCC.
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PMID:Gene expression and promoter methylation of the XIAP-associated Factor 1 in renal cell carcinomas: correlations with pathology and outcome. 1744 73

Inhibitor of apoptosis (IAP) family proteins is involved in mechanisms of resistance to apoptosis in various cancer cells. The aim of this study was to assess the expression of selected IAP proteins such as XIAP, cIAP-1, cIAP-2 and survivin in breast cancer patients and evaluates their relationship with the prognostic and predictive factors and their impact to overall survival (OS) and progression free survival (PFS). The study was conducted with the use of tissue samples prospectively collected from 92 previously untreated female breast cancer patients. The control encompassed 10 fibroadenoma patients. The expression of XIAP, cIAP-1, cIAP-2 and survivin was assessed using flow multicolor cytometry. XIAP expression was present in 99 % of the breast cancer patients (91/92) with the median expression 13.65% (range 1-66.8%). Expression of XIAP in breast cancer was significantly higher compared to the control group (p=0.006). Median expression of cIAP-1, cIAP-2 and survivin in the study group was 25.95% (range 0.8-83.7%), 16.7% (range 1-53.2%) and 4.6% (range 0-43%) respectively. In the rank Spearman test, strong correlations (p<0.001) were seen among the expressions of XIAP, cIAP-2 and survivin, in all combination. Additionally, week correlation between XIAP and cIAP-1 was observed (p=0.02). The median expression of XIAP and survivin was significantly higher in more advanced tumors (stages pT2/pT3 vs. pT1). The median PFS and OS in breast cancer group were 46.15 and 47.1 months respectively. No significant correlations were observed among expressions of IAP family proteins and survival. However, low expression of XIAP in breast cancer showed trend to longer PFS (p=0.08). XIAP, cIAP-1 cIAP-2 and survivin participate in antiapoptotic mechanisms in breast cancer and XIAP and survivin seem to have the most significant prognostic importance. Further studies are needed to establish more complete prognostic and predictive values of IAP family proteins in breast cancer patients.
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PMID:Expression of IAP family proteins and its clinical importance in breast cancer patients. 2599 66