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Aims and Methods: Retrospectively, this paper compared the differences of the Epstein–Barr virus (EBV)-encoded small RNAs (EBERs), protein expression and gene mutations of tumor suppressor gene p53 (TP53) in keratinized nasopharyngeal squamous cell carcinoma (KNSCC) and nonKNSCC, and the relationships between pathological features and the prognosis of patients were analyzed. Results: The positive rate of EBERs hybridization and TP53 expressions was 76.3% and 52.2%, respectively, while the mutation rate of TP53 gene was 39.6%. Logistic regression analysis showed direct relationships between the subtypes of nasopharyngeal squamous cell carcinoma (NPSCC) and EBERs-positive, or frequent consumption of pickled food. Overall survival rates of patients with positive TP53 expression, the TP53 gene mutations, vascular invasions, organ metastases, lymph node metastasis, and clinical recurrence were significantly lower than those of patients without those symptoms. The poorer prognosis was related to regularly drinking and the advanced age. According to the Cox regression analysis, we found that the main prognostic factors of NPSCC patients were the aging, recurrence, TP53 gene mutations, especially exon 7 or 8 mutations. Conclusions: We concluded that there were the correlations between NPSCC subtypes with EBV infection and frequent intaking of pickled food, while aging, clinical recurrence, and TP53 gene mutations were independent predictors for the poor prognosis of nasopharyngeal carcinoma
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Objective: To explore the effect of modified Si Junzitang (MSJZT) drug serum on the expression of apoptosis-related molecules of gastric cancer cell SGC-7901 and further its anti-tumor mechanism.Method: A total of 40 SD rats were randomly divided into four groups:low-dose,middle-dose,high-dose MSJZT (0.213,0.426,0.853 g·kg-1) groups and normal group (n=10).The treatment groups were administrated through gastric perfusion,and the normal group was given the equivalent volume of normal saline for 10 days.1.5 h after the last treatment,chloral hydrate peritoneal anesthesia was performed,blood was collected from heart,and different doses of serum were separated to prepare drug-containing serum of low-dose,middle-dose,high-dose MSJZT groups,in order to incubate SGC-7901 gastric cancer cell.Early and late apoptosis rates were detected with flow cytometry.Afterwards,the tumor suppressor gene p53,c-nucleoprotein gene (c-Myc),cysteine-aspartic acid protease-3(Caspase-3),B-cell lymphoma-2(Bcl-2) mRNA expressions were confirmed by fluorescence quantitative polymerase chain reaction (Real-time PCR).The protein expressions of p53,c-Myc,Caspase-3,Bcl-2 were detected by immunofluorescence.Result: Compared with the normal group,the high-dose MSJZT group could obviously increase the apoptosis rate to 22.58%(PPPPPPConclusion: MSJZT drug serum could exert an anti-tumor effect by inhibiting the expression of the anti-apoptotic protein Bcl-2,and promoting the expressions of pro-apoptotic-related molecules p53,c-Myc,Caspase-3.
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Histone deacetylase 1 ( sirtuin 1, SIRT1) is an important member of deacetylase family, and plays an important role in the process of malignant tumor and embryonic development. In this article it was found that overexpression of SIRT1 could accelerate the DNA synthesis in human pancreatic beta cell CRL-1837 and inhibit cell senescence. SIRT1 also could bind to p53 as detected by co-immunoprecipitation and could change the phosphorylation level of p53.
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Aim To investigate the proliferative effect and the apoptosis of human hepatoma SMMC-7721 cells induced by gallic acid ( GA ) , and its underlying mechanism. Methods SMMC-7721 cells were cul-tured in vitro. MTT assay was used to observe the pro-liferation of SMMC-7721 cells induced on GA 24 , 48 , 72 h. The morphological and ultra structural changes of the SMMC-7721 cells were observed by inverted micro-scope and transmission electron microscope respective-ly. Annexin V-FITC/PI staining was used to quantify the percentages of apoptosis in the total cell popula-tion. The expression of p53 mRNA was investigated by RT-PCR. Western blot was used to determine the pro-tein expression of p53. Results GA(6. 25~50 μmol ·L-1 ) markedly inhibited the activity of proliferation and induced apoptosis of SMMC-7721 cells after 48 h in a dose-dependent manner. GA significantly induced cell nuclear condensation and fragmentation. RT-PCR and Western blot results showed that GA could improve the expression of p53 mRNA and protein. Conclusion GA can inhibit the proliferation of human hepatoma SMMC-7721 cells and induce cells apoptosis. The mechanism may be associated with improving tumor suppressor gene p53 expression.
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Background: Mutations in p53 gene are found in a majority of human malignancies and usually occur in the exons 5, 6, 7 and 8. Mutated p53 protein is more stable and gets accumulated in the cells that induce the host to develop anti-p53 antibodies in sera of cancer patients. Aim: This study is aimed to observe the frequency and nature of mutations in exons 5-8 of p53 gene and to evaluate its correlation with prevalence of serum p53 antibodies in Indian patients with gallbladder cancer (GBC). Methods: Mutation studies were done in cancer tissues obtained from 62 patients with proven GBC (40 cytologically proven cases and 22 resected gallbladder cancer tissues) by polymerase chain reaction (PCR), restriction fragment length analysis (RFLP) and single strand conformation polymorphism (SSCP). Presence of serum p53 antibodies was determined using highly specific enzyme linked immunosorbent assay (ELISA) kit in 50 patients with GBC and 30 patients of cholelithiasis. Clinicopathologic characteristics of these patients were given attention. Results: Antibodies to p53 protein was present in the serum in 34% (17/50) of GBC patients and in 3.3% (1/30) patients with cholelithiasis (p<0.018). RFLP failed to detect common mutations in the exons 5- 8 of the p53 gene in 62 samples. Using SSCP analysis we could detect frameshift mutation in p53 gene in 2 of 22 (9.1%) GBC cases. Mutated samples were sequenced and found to have insertion of adenine at codon 271 (GAG) in exon 8 region. Conclusion: Our results show that 1/3rd of the north Indian patients with GBC have antibodies to p53 protein. The commonest identifiable alteration in the p53 gene was a frameshift mutation at codon 271.
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0.05). Conclusion The p53 gene mutation has close relation with nasal malignant tumor , and may has no related to the pathogenesis of IP possible.
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Objective To explore the role of HPV16 and p53 protein in the pathogenesis of tumors of nasal cavity and sinus of Chinese people. Methods The expression of HPV16 and p53 in 58 tumor samples of nasal cavity and sinus was detected by immunohistochemistry. Results There was no p53 expression in inverted pipillomas(IP). HPV16 infection rate in IP was 62.5%. The positive rate of p53 protein in the malignant tumors and IP with atypical hyperplasia was 56.0% and 44.4%, respectively, and HPV16 infection rate in the both tissues was 24.0% and 66.7%, respectively. The positive rate of p53 and HPV16 simultaneous expression in IP with atypical hyperplasia were 33.3%, which was higher than that in the malignant tumors and IP without atypical hyperplasia. Conclusion The high-risk HPV16 infection may be primary cause of IP. p53 gene mutation may be close relation with the pathogenesis of nasal cavity and sinus malignant tumors. HPV16 and p53 may have synergic effect in the malignant transformation of nasal cavity and sinus benign tumors.
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Purpose:To investigate the effects of tumor suppressor gene p53 on the activity of telomerase/hTERT in human HCC-9204 cell line.Methods:Lipofection-mediated gene transfection method was used to transfect wild-type p53(wt-p53) gene into HCC 9204 cell which expresses telomerse /hTERT and carries mutant-type p53 gene. The expression of p53 was confirmed by Western blot. Both the telomerase activity and hTERT mRNA expression were detected by PCR-ELISA,TRAP-silver staining,in-situ hybridization and RT-PCR methods. The apoptotic appearance was examined by FCM.Results:Higher telomerase activity and hTERT mRNA level were detected in HCC-9204,and they were markedly inhibited after transfection with wt-p53. Meanwhile,decreasing level of bcl-2 protein and appearance of apoptosis were also shown in the transfected cells.Conclusions:Over expression of the exogenous wt-p53 gene does suppress both telomrease activity and hTERT mRNA expression in HCC cell line. There is a p53-dependent regulatory pathway for activation and expression of telomerase/hTERT in HCC.
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Objective To study the effect of a recombinant adenovirus carrying p53 gene, B7 1 gene and GM CSF (BB 102) on the nude mice transferred with laryngeal carcinoma. Methods Nude mice model bearing laryngocarcinoma was established using human laryngeal squamous carcinoma cell line (Hep 2). Large amounts of recombinant adenovirus (BB 102) were injected into the tumor. Changes in carcinoma treated with recombinant BB 102 adenovirus were observed under light and electron microscopes. Results The difference between experimental and control groups was statistically significant. The morphology of cells infected with BB 102 was analyzed for evidence of apoptosis by transmission electron microscopy. It has been shown that wild type P53 protein can inhibit cell growth and induce apoptosis, while B7 1 and GM CSF have no such effects. Conclusions The results showed that recombinant adenovirus BB 102 has significant efficacy in suppressing tumor cell growth and in inducing their apoptosis, suggesting that BB 102 might be developed into a therapeutic agent in clinical therapy of laryngeal carcinoma