Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AIM:To detect the presence of HPV DNA and study the alteration of p53 expression in anal cancers in Chinese.METHODS:HPV DNA was amplified by PCR.The amplified HPV DNA was classified by DBH. HPV antigen and p53 expression were respectively detected by immunohistochemistry.RESULTS:HPV DNA was amplified only in one case of squamous cell carcinoma of the 72 Chinese anal cancers and further classified as HPV type 16. Others were all HPV negative. HPV antigen and p53 expression were also detected in this case. Positive stainings with anti-p53 antibody were seen in 61.2% anal cancers.There were no statistically significant differences between anal squamous cell carcinomas and adenocarcinomas and between anal adenocarcinomas and rectal adenocarcinomas.p53 protein expression was observed in the basal cells of squamous epithelium of condyloma acuminatum and morphologically normal squamous epithelium in 2 cases invaded by anal adenocarcinoma.CONCLUSION:HPV infection was not associated with these cases of anal cancer.p53 alteration was a common event. Positive p53 immunostaining can not be regarded as a marker for differentiating benign from malignant lesions.
 ...
PMID:Anal cancer in Chinese: human papillomavirus infection and altered expression of p53. 1181 3

Ultimately aiming at a more individualized therapeutic approach in epidermoid anal cancer, this study explored the prognostic and predictive impact of a set of tumour markers. From a population-based cohort of 276 patients with epidermoid anal cancer, treated according to prospective protocols, 215 pre-treatment biopsies were investigated using immunohistochemistry. The expression of p53, p21, Cyclin A and CD31 was measured semi-quantitatively. The expression rate was classified as high when immunostaining was seen in > 5% of the tumour cells for p53 and p21, > 20% in Cyclin A and, above median vessel count for CD31. Marker expression was correlated to survival and treatment response. A high Cyclin A expression correlated significantly with improved overall (77% vs 59%, p = 0.005) and tumour-specific (81% vs 64%, p = 0.009) survival at 5 years. Also, the locoregional failure rate was significantly lower in patients with a high Cyclin A expression (12% vs 24%, p < 0.05). In a multivariate Cox analysis Cyclin A was an independent prognostic factor. A low p21 expression correlated with a reduced rate of locoregional failure (14% vs 27%, p < 0.05) but no impact on survival was found. For p53 and CD31 no significant correlations were obtained. Cyclin A may be an indicator of radiosensitivity and a valuable prognostic marker in epidermoid anal cancer.
 ...
PMID:Prognostic significance of Cyclin A in epidermoid anal cancer. 1686 41

Radiotherapy with concurrent chemotherapy is the standard of care for patients with nonmetastatic squamous cell anal cancer. Most patients treated with chemoradiotherapy have an excellent prognosis. However, some heterogeneity exists among anal cancer patients in their outcomes. This article reviews some of the clinical factors, treatment-related factors, and biologic factors that affect outcomes in patients with squamous cell anal cancer. The most important prognostic factors are the T and N stages. Some studies have suggested that women have better prognosis than men. Histologic subtypes and grade do not have a clear prognostic role. Response to treatment and duration of radiotherapy are likely to be important prognostic factors. Some molecular markers such as p53, p21, and cyclin A expression may have prognostic significance, but their role needs to be studied further. A better knowledge of prognostic factors could help us develop individualized therapies for patients and select high-risk patients for more aggressive and innovative treatments. A better understanding of molecular biology is required to characterize the inherent heterogeneity of anal cancer and thereby develop optimal therapies.
 ...
PMID:Prognostic factors for squamous cell cancer of the anal canal. 1925 18

Human anal cancers are associated with high-risk human papillomaviruses (HPV) that cause other anogenital cancers and head and neck cancers. As with other cancers, HPV16 is the most common high-risk HPV in anal cancers. We describe the generation and characterization of a mouse model for human anal cancer. This model makes use of K14E6 and K14E7 transgenic mice in which the HPV16 E6 and E7 genes are directed in their expression to stratified squamous epithelia. HPV16 E6 and E7 possess oncogenic properties including, but not limited to, their capacity to inactivate the cellular tumor suppressors p53 and pRb, respectively. Both E6 and E7 were found to be functionally expressed in the anal epithelia of K14E6/K14E7 transgenic mice. To assess the susceptibility of these mice to anal cancer, mice were treated topically with dimethylbenz[a]anthracene (DMBA), a chemical carcinogen that is known to induce squamous cell carcinomas in other sites. Nearly 50% of DMBA-treated HPV16 E6/E7 transgenic mice showed overt signs of tumors, whereas none of the like-treated nontransgenic mice showed tumors. Histopathologic analyses confirmed that the HPV16 transgenic mice were increased in their susceptibility to anal cancers and precancerous lesions. Biomarker analyses demonstrated that these mouse anal cancers exhibit properties that are similar to those observed in HPV-positive precursors to human anal cancer. This is the first mouse model for investigating the contributions of viral and cellular factors in anal carcinogenesis, and should provide a platform for assessing new therapeutic modalities for treating and/or preventing this type of cancer.
 ...
PMID:A mouse model for human anal cancer. 2094 89

Despite a growing incidence in developed countries and a recent improved understanding of its pathogenesis, anal cancer management has not evolved over the past decades and drug combination used as first-line regimen still largely depends on clinician preferences. Aiming at paving the way for precision medicine, a large cohort of 372 HIV-negative patients diagnosed over a 20-year time period with locally advanced anal carcinoma was collected and carefully characterized at the clinical, demographic, histopathologic, immunologic, and virologic levels. Both the prognostic relevance of each clinicopathological parameter and the efficacy of different concurrent chemoradiation strategies were determined. Overall, the incidence of anal cancer peaked during the sixth decade (mean: 63.4) and females outnumbered males (ratio: 2.51). After completion of treatment, 95 (25.5%) patients experienced progression of persistent disease or local/distant recurrence and 102 (27.4%) died during the follow-up period (median: 53.8 months). Importantly, uni-multivariate analyses indicated that both negative HPV/p16ink4a status and aberrant p53 expression were far better predictors for reduced progression-free survival than traditional risk factors such as tumor size and nodal status. As for overall survival, the significant influences of age at diagnosis, p16ink4a status, cTNM classification as well as both CD3+ and CD4+ T-cell infiltrations within tumor microenvironment were highlighted. Cisplatin-based chemoradiotherapy was superior to both radiotherapy alone and other concurrent chemoradiation therapies in the treatment of HPV-positive tumors. Regarding their HPV-uninfected counterparts, frequent relapses were observed, whatever the treatment regimen administered. Taken together, our findings reveal that current anal cancer management and treatment have reached their limits. A dualistic classification according to HPV/p53 status should be considered with implications for therapy personalization and optimization.
 ...
PMID:Treatment algorithm and prognostic factors for patients with stage I-III carcinoma of the anal canal: a 20-year multicenter study. 3272 25