p53 gene mutation and numb expression in colorectal cancer and its clinical significance / 中华普通外科杂志

Objective:to study the mutation of p53 gene in colorectal cancer, analyze the relationship between p53 gene mutation and numb expression pattern, and explore its clinicopathological significance in colorectal cancer.Methods:p53 gene mutation in 60 colorectal cancer tissues was analyzed by polymerase chain reaction (PCR) and DNA sequencing, and the expression of numb protein was detected by Western blot. The colon cancer cell lines HCT116 (+), HCT116 (-) and flow cytometry were used. The survival curve was drawn by Kaplan Meier method.Results:p53 gene mutation was found in 31 of 60 tissues (52%), and the mutation times of exons (E) 5, 6, 7 and 8 were 5, 6, 12 and 11 respectively. The expression level of numb in p53 mutation group was significantly lower than that in non mutation group ( P=0.009). The prognosis of patients with low expression of numb (39 cases) was worse than that of high expression of numb (21 cases) ( P=0.015). Its expression level is closely related to the degree of differentiation, lymph node metastasis and TNM stage (all P<0.05). After the two cell lines were transferred into numb, the cell cycle appeared G2-M phase arrest and proliferation was inhibited, while dapt had G1-S phase arrest. Conclusion:p53 gene mutation related to the expression of numb in colon cancer, which has significant effect on the prognosis.

Progress of cell phenotypes and molecular subtypes as well as p53 gene abnormalities in the prognosis of diffuse large B-cell lymphoma / 肿瘤研究与临床

Diffuse large B-cell lymphoma (DLBCL) is a group of heterogeneous diseases, and further classification is of great value for prognostic stratification. In recent years, some subtypes with poor prognosis have been recognized, such as "double-hit" lymphoma or "double-expressing" lymphoma. In addition, the new molecular classification provides a new perspective for the accurate diagnosis and prognosis stratification of DLBCL. The mutation and deletion of p53 gene are high risk factors in the traditional sense of DLBCL, while with the application of the next generation sequencing and other technologies, the influence of more accurate gene mutation or deletion on prognosis and its prognostic value in new cell molecular subtypes still need to be further confirmed. This paper reviews the progress of cell phenotypes and molecular subtypes as well as p53 gene abnormalities in the prognosis of DLBCL.

Inhibitory Effect and Target Prediction of Genistein on the Growth of Human Nasopharyngeal Carcinoma CNE 1 Cells / 中国药房

OBJECTIVE：To study the inhibi tory effects of genistein on the growth of human nasopharyngeal carcinoma. CNE 1 cells and predict its potential target. METHODS ：CCK-8 method was used to test the effects of 0（blank control ），12.5，25，50， 100，150 µmol/L genistein on the proliferation of CNE 1 cells after treated for 24，48，72 h. Flow cytometry was carried out to detect the effects of 0（blank control ），15，30，60 µmol/L genistein on the cell cycle and ap optosis of CNE 1 cells after treated for 24 h. Scratch test was used to investigate the effects of 0（blank control ）， 10， 20， 30 µmol/L genistein on themigration ability of CNE 1 cells after treated for 24 h. High （No.18210156） throughput sequencing was conducted to discover the differential genes in CNE 1 cells after treated with 0（blankcontrol），30 µmol/L genistein for 24 h. RT-qPCR assay was adopted to verify the mRNA expression of related differential genes in above trials. RESULTS ： Compared with blank control，12.5，25，50，100，150 µmol/L genistein sho wed significant inhibitory effect on the proliferation of CNE 1 cells（P＜ 0.01），in a concentration- time-effect manner ；15，30 µmol/L genistein could arrest CNE 1 cell cycle at G 0/G1 stage（P＜0.05 or P＜ 0.01）；30，60 µmol/L could arrest CNE 1 cell cycle at G 2/M stage and promoted cell apoptosis （P＜0.05 or P＜0.01）. 10，20，30 µmol/L genistein could significantly inhibit the migration ability of CNE 1 cells（padj＜0.01）. High throughput sequencing revealed a total of 2 271 differentialgenes（P＜0.05），1 154 of which were up-regulated while 1 117 of which were down-regulated ；8 potential target genes ，including p53，p21，STC2，FGF2，CDK6，CYCLIN D ，PI3K，AKT，were screened by cell experiment. After validated by RT-qPCR assay ，mRNA expression of p53，p21，STC2，FGF2，CDK6，CYCLIN D and AKT were significantly down-regulated（P＜0.05），which consistent with the sequencing results. CONCLUSIONS ：Genistein can effectively inhibit the growth of human nasopharyngeal carcinoma CNE 1 cells，the mechanism of which may associated with inhibiting the expression of mutant gene p53，restoring the function of wild-type P 53 protein and inhibiting the activity of PI 3K/Akt pathway.

Prognostic value of the Epstein–Barr virus and tumor suppressor gene p53 gene in nasopharyngeal squamous cell carcinoma

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

Effect of Modified Si Junzitang Drug Serum on Expression of Apoptosis-related Molecules of Gastric Cancer Cell SGC-7901 / 中国实验方剂学杂志

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.

The challenge for allogeneic hematopoietic stem cell transplantation in acute leukemia/ myelodyplastic syndrom with TP53, TET2 or DNMT3A gene mutations / 天津医药

@#Recently, much gene mutations have been detected in patients with acute leukemia or myelodysplastic syndrome (MDS) using next-generation sequencing (NSG) technology. Some of them are proved to be important prognostic markers. It has been showed that TP53, TET2 or DNMT3A gene mutations are associated with poor prognosis in acute leukemia or MDS patients. The prognosis of these patients is poor with short remission and survival. Allogeneic hematopoietic stem cell transplantation is the only way to cure these patients. However, the outcomes after transplantation are inferior to those in patients without these mutations. The hypomethylating agents or immune targeting therapy might improve their prognosis when combined with the present strategies. Here, the impact of TP53, TET2 and DNMT3A gene mutations on the prognosis after chemotherapy or transplantation is reviewed.

Effect of SIRT1 on cell proliferation and senescence of human pancreaticβ-cells CRL-1837 / 中华内分泌代谢杂志

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.

Selenium dioxide inducing apoptosis of cervical cancer cells by regulating apoptosis-related proteins / 重庆医学

Objective To investigate the inducing effects of selenium dioxide(SeO2 ) on the apoptosis in human cervical carcino-ma cell line Hela and its influence on the expression of apoptosis-related proteins caspase-3 and P53 .Methods Hela cells were trea-ted with different concentrations of SeO2 for 24 h in vitro ;the morphological changes of Hela cells were observed by the optical mi-croscope;the influence of SeO2 on the cell proliferation and vitality was examined by the MTT assay ;the flow cytometry was em-ployed to detect the cell apoptosis rate ;the expressions of caspase-3 and P53 proteins in Hela cells were determined by the Western blot analysis .Results Under the optical microscopy ,SeO2 generated the obvious influence on the cell growth morphology ,a large number of cells became rounded and shrunken ,and lost the normal form ,while the adherence cell number was evidently decreased and the proliferation was slowed down ;the MTT results showed that SeO2 markedly inhibited the cell proliferation and viability in a dose-dependent manner ,in which ,the cell apoptosis rates induced by the 0 ,1 .875 ,3 .750 ,7 .500 ,15 .000 and 30 .000 μmol/L con-centrations of SeO2 were 3 .12% ,30 .56% ,33 .42% ,37 .50% ,45 .43% and 69 .38% respectively ,which revealing the obviously in-creasing trend;the Western blot assay revealed that SeO2 could up-regulate the caspase-3 and P53 levels ,and reached the peak value at the concentration of 7 .500μmol/L .Conclusion SeO2 could induce the cervical cancer cell apoptosis possibly by up-regulating the expressions of caspase-3 and p53 in Hela cells .

Study on gallic acid induced human hepatoma SMMC-7721 cells apoptosis and its mechanism / 中国药理学通报

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.

Imunoexpressão das proteínas COX-2, p53 e caspase-3 em adenoma colorretal e mucosa não neoplásica / Immunoexpression of the COX-2, p53, and caspase-3 proteins in colorectal adenoma and non-neoplastic mucosa

OBJETIVO: Analisar a imunoexpressão das proteínas COX-2, p53 e caspase-3 em adenomas colorretais e na mucosa não neoplásica. MÉTODOS: Foram submetidos à colonoscopia 72 indivíduos que forneceram 50 amostras de adenomas e 45 de mucosa colorretal não neoplásica. Os tecidos foram obtidos pela técnica de arranjo em matriz (tissue microarray) e submetidos a estudo imunoistoquímico com anticorpos primários p53, COX-2 e caspase-3. A positividade e intensidade da imunorreação foram classificadas. Foram estudadas as seguintes variáveis: localização do adenoma no colo, grau de displasia, tamanho, e escores de positividade e intensidade da imunoexpressão das proteínas p-53, caspase-3 e COX-2. RESULTADOS: Nos adenomas, a imunoexpressão da proteína p53 mutada foi positiva em 30 (60%) e negativa em 20 (40%) amostras. Na mucosa colorretal não neoplásica, a imunoexpressão da proteína p53 mutada foi negativa em 39 (86,6%) amostras e positiva em 6 (13,3%) (p<0,0001). Houve diferença significativa entre o maior tamanho (p=0,006) e o maior grau de displasia dos adenomas (p<0,0001) e a intensidade de imunoexpressão da proteína p53 mutada. A positividade e intensidade da imunoexpressão das proteínas COX-2 (p=0,14) e caspase-3 (p=0,23), nos adenomas e na mucosa colorretal não neoplásica, não apresentaram diferença significante. CONCLUSÃO: A proteína p53 mutada é hiperexpressada nos adenomas em comparação com a mucosa não neoplásica. Nos adenomas, o maior tamanho e o maior grau de displasia foram associados à maior expressão da proteína p53 mutada. A imunoexpressão das proteínas COX-2 e caspase nos adenomas não apresentou correlação com os aspectos anatomopatológicos e não foi diferente em termos de níveis de expressão correspondentes na mucosa não neoplásica.

OBJECTIVE: To analyze the immunoexpression of the COX-2, p53, and caspase-3 proteins in colorectal adenomas and non-neoplastic mucosa. METHODS: 72 individuals were subjected to colonoscopy, which provided 50 samples of adenomas and 45 samples of non-neoplastic colorectal mucosa. The tissue samples were obtained via the tissue microarray technique and subjected to immunohistochemical analysis using primary anti-p53, anti-COX-2, and anti-caspase-3 antibodies. The positivity and intensity of the immunoreaction were classified. The analyzed variables were as follows: site of the adenomas in the colon, degree of dysplasia, size, and score of positivity and intensity of immunoexpression of the p-53, caspase-3, and COX-2 proteins. RESULTS: The immunoexpression of mutated protein p53 was positive in 30 (60%) adenoma samples and negative in 20 (40%) adenoma samples. The immunoexpression of mutated protein p53 was negative in 39 (86.6%) samples and positive in 6 (13.3%) samples of the non-neoplastic colorectal mucosa (p<0.0001). Significant differences were seen between both the largest size (p=0.006) and the highest degree of dysplasia (p<0.0001) of the adenomas and the intensity of immunoexpression of mutated protein p53. The positivity and intensity of immunoexpression of COX-2 (p=0.14) and caspase-3 (p=0.23) showed no significant differences between the adenomas and the non-neoplastic colorectal mucosa. CONCLUSION: Mutated protein p53 was hyperexpressed in the adenomas compared with the non-neoplastic mucosa. Greater size and greater degree of dysplasia in the adenomas were associated with higher expression of mutated protein p53. The immunoexpression of COX-2 and caspase-3 in the adenomas did not exhibit a correlation with the anatomical-pathological features of the tumors and did not differ from the corresponding expression levels in the non-neoplastic mucosa.

Investigação do gene p53 de frangos expostos às aflatoxinas / Investigation of p53 gene in poultries exposed to aflatoxins

Identificou-se o efeito das aflatoxinas (AFs) sobre o gene p53 de frangos de corte, de linhagem comercial, separados em: grupo experimental, tratado (GT) com ração comercial contendo 2,8ppm de AFs totais durante 21 dias consecutivos, e grupo-controle (GC), sem exposição às AFs. Macroscopicamente, as alterações caracterizaram-se por hepatomegalia e aspecto pálido-amarelado com alguns focos hemorrágicos e, histologicamente, por desarranjo trabecular, pleomorfismo hepatocítico com cariomegalia, degeneração vacuolar intracitoplasmática, necrose com infiltração linfocítica e hiperplasia de ductos biliares. A PCR com os primers GSPT53c-1 com base no gene candidato a p53 (GenBank XM_424937.2) gerou um produto de aproximadamente 350 pares de base. O amplicon sequenciado a partir do DNA dos frangos do GT não apresentou mutação ou deleção, assim como padrão de bandas do PCR-RFLP não foi distinto entre ambos os grupos experimentais e a sequência depositada no banco de genes. Os resultados sugerem que não ocorreu transversão devido à exposição às AFs no fragmento amplificado. Conclui-se que a PCR-RFLP e o sequenciamento do produto da PCR não são ferramentas apropriadas para diagnóstico da exposição de frangos às AFs nas condições experimentais empregadas.

To identify the effects of aflatoxins (AFs), Cobb lineage poultry were separated in an experimental group in which they were treated with commercial ration containing 2.8ppm of total AFs during 21 days (TG) and a control group without AFs exposure (CG). In the liver of poultries exposed to AFs, alterations were microscopically observed, which were characterized by hepatomegaly, a pale yellowish aspect with some hemorrhagic spots, and histologically a trabecullar disarranging pleomorphic hepatocytes with cariomegaly, intracytoplasmatic vacuolar degeneration, necrosis, lymphocytic infiltration and hyperplasia of biliary ducts. The PCR with GSPT53c-1 primers based on p53 candidate gen (GenBank XM_424937.2) generated a product of approximately 350 base pairs. The sequenced amplicon obtained from the DNA of treated poultry did not display any mutation or deletion, and the PCR- RFLP bands patterns were also not distinct in both experimental groups. The results indicated that transversion did not occur in the fragment amplified due to AFs exposure. As a consequence of results obtained with p53 gene (NM_205264.1) we concluded that PCR-RFLP and sequencing of PCR product are not appropriate diagnostic tools for the detection of poultry exposure to AFs, at least in the experimental conditions performed.

The role of p53 in induction of growth arrest DNA damage-inducible gene 45β in human hepatoma cells by oxaliplatin / 中华肝胆外科杂志

Objective To identify the role of p53 in the induction of growth arrest DNA damage-inducible gene 45β (GADD45β) in HCC cells by Oxaliplatin.Methods A Hep3B+p53 clone was established by transfection of the full-length p53 sequence to Hep3B.Following oxaliplatin administration,quantitative real-time PCR was employed to validate the expression changes of GADD45β.pGL3 basic luciferase plasmids including promoter fragments were synthesized in vitro and transfected into cells.The effects on promoter activity,cell growth and the cleavage of Caspase-3 were further focused on.Results Hep3B+p53 expressed p53 protein stably.The transfection of p553 enhanced the induction of GADD45β in Hep3B by Oxaliplatin.The promoter activity of fragments constructed NF-κB and E2F-1 binding sites was induced about 1.5 and 0.8 folds by transfection of p53.The colony formation and DNA syntheses were inhibited apparently in Hep3B+p53 with p53 by Oxaliplatin (30.41％ and 75.60％ by 100 μmol/L Oxaliplatin,respectively).Moreover,p53 transfection triggered cleavage of Caspase-3 more rapidly.Conclusion p53 played a role in the induction of GADD45β in Hep3B by Oxaliplatin.

Expression and significance of NDRG1, p53 and VEGF in esophageal squamous cell carcinoma / 肿瘤研究与临床

ObjectiveTo study the expression and significance of NDRG1(N-myc downstream regulated gene-1), p53 and VEGF in esophageal squamous cell carcinoma (ESCC). MethodsNDRG1, p53 and VEGF protein were detected by immunohistochemistry (IHC, SP method) in 20 cases of normal esophageal squamous epithelium and 78 cases of ESCC.ResultsThe results of IHC shows that in normal esophageal squamous epithelium and esophageal squamous cell carcinoma,the positive rate of NDRG1 was 100.0 ％(20/20) and 55.1％ (43/78) respectively, p53 was 0 (0/20) and 65.4 ％ (51/78) respectively, VEGF was 30.0 ％(6/20)and 67.9 ％(53/78)respectively,all had statistical significance.There was inverse correlationof NDRG1 expression and lymphatic invasion(r =-0.237,P = 0.036).However expression of NDRG1 was no statistical significance with patient' s age,gender,grade,TNM stage,patient' s five year survival.The expression of p53 was inverse correlated with NDRG1,and the expression of VEGF was inverse correlated with NDRG1 (r =-0.331, P = 0.003). ConclusionNDRG1 may be a new tumor suppress gene and play an important role in the development and metastasis of ESCC.

Expression and clinical significance of EZH2 and p53 protein in human prostate cancer / 肿瘤研究与临床

ObjectiveTo explore the expression of EZH2 and p53 protein in primary prostate cancer (Pca) and its clinical significance.Methods High-throughput tissue microarray technique and immunohistochemistry was used to detect the expression of EZH2 and p53 protein in 48 human prostate cancer specimens without a history of chemo-radiation therapy and 15 cases of benign prostate hyperplasic (BPH) tissues. The pathological characteristics and the relationship of the expression of EZH2 and p53 protein in primary prostate cancer was analyzed. ResultsImmunohistochemical results showed that the positive rates of EZH2 and p53 protein in prostate cancer were 87.50 ％ (42/48) and 33.33 ％ (16/48), respectively, which were significantly higher than that in BPH tissues[13.33 ％ (2/15) and 0 (0/15)](x2=26.429, x2=5.058,P ＜0.05). The expression of EZH2 and p53 protein was significantly related to Gleason score, TNM stage (P ＜0.05), but not to age and serum prostate-specific antigen (PSA) level (P ＞0.05). The positive expression in patients with Gleason＞6 was higher than that with Gleason≤6(P ＜0.05).The positive expression in patients with T3-T4 stage was higher than that with T1-T2 stage(P ＜0.05).Spearman rank correlation showed a significantly positive correlation between EZH2 and p53 protein (r=0.294, P ＜0.05). ConclusionEZH2 and p53 protein may participate in the pathogenesis of prostate cancer.The overexpression of EZH2 and p53 protein could become an index for the evaluation of the level of malignancy and progression of prostate cancer.Furthermore,combining detection of EZH2 and p53 protein may provide a new theoretical basis for the treatment of prostate cancer.

Significance of SIRT1 expression in breast cancer / 肿瘤研究与临床

Objective Toinvestigatetheexpressionof SIRT1anditsassociationwith clinicopathologic features in breast carcinoma with type 2 diabetes mellitus.MethodsThe expression of SIRT1 in 30 breast cancer with type 2 diabetes mellitus,65 samples of breast cancer without diabetes mellitus and 18 samples of corresponding normal breast tissues was investigated using immunohistochemistry.ResultsThe positive rate of SIRT1 in breast cancer tissues was significantly higher than that breast cancer with type 2 diabetes mellitus and normal breast tissue (P ＜0.05). In breast cancer with type 2 diabetes mellitus group.The positive rate of SIRT1 was significantly higher than that normal breast tissue(P ＜0.05).The expression of SIRT1 was positively correlated with the number of lymph node(P =0.011),pTNM tumor stage (P =0.028), p53 (P =0.003) and Her-2 (P =0.031) in breast cancer with type 2 diabetes mellitus group. The expression level of SIRT1 in lymph node-positive group was higher than that in lymph node-negative group (P ＜0.05).The expression level of SIRT1 was in lymph node-positive group was higher than that in lymph node-negative group(P ＜0.05).ConclusionSIRTI was up-regulated in breast cancer with type 2 diabetes mellitus,but its expression was lower than that breast cancer without diabetes mellitus,and was associated with the progression of diabetes mellitus. SIRT1 was positively correlated with lymph node, pTNM tumor stage,p53 and Her-2, SIRT1 may be a novel biological parameter to evaluate the malignant degree of breast carcinoma and to predict prognosis of breast cancer.

Alterations of p53 gene in gallbladder cancer patients of North India.

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.

Effects of Nano Red Elemental Selenium on Expression of bax and p53 Protein in Experimental Liver Injure of Rats / 环境与健康杂志

0.05), the same results were seen in the interferential experiment groups and the positive group. There were no alternating effects between nano red elemental selenium and CCl4. Conclusion In the present paper, nano red elemental selenium does not show an adverse effect on the liver of rats and a protective effect on liver injury induced by CCl4.

Significance of abnormal expression of Rb,p53 and PCNA in patients with bladder carcinoma / 肿瘤研究与临床

Objective To discuss the significance of abnormal expression of Rb,p53 and PCNA in patients with bladder carcinoma and the correlation with the tumor grade,clinical stage and relapse.Meth- ods Immunohistochemical method was used to detect the Rb,p53 and PCNA gene expression in 60 cases with bladder carcinoma.Results The positive rates of p53,PCNA in 60 cases of bladder cancer is both 40.0 %.There were 27(45 %)cases lack of Rb expression.Multiple altered expression was found in 30 cases (50.0 %).The abnormal expression of Rb,p53 and PCNA was closely related to the tumor grade,clinical stage and relapse.Conclusion The detection of multiple gene is more valuable than that of single gene. Multiple altered expression of Rb,p53 and PCNA and their synergistic action might play an important role in the genesis and development of bladder cancer.

In vivo study of the effect of MDM2-p53 feedback loop on the sensitivity to cisplatin in ovarian cancer / 肿瘤研究与临床

Objective To investigate the effect of MDM2-p53 feedback loop on the sensitivity to cis- platin in ovarian cancer xenograft in vivo and explore its mechanism.Methods Human ovarian cancer cell line A2780 with wild type p53 was inoculated subcutaneously into the back of nude mice.When tumor nod- ules could be observed after 7 days of inoculation,the mice were randomly divided into 5 groups with each of 6 mice.Treatment group received an intratumoral injection of a combination of pCMV-MDM2-Lipofectamine and cisplatin.Control groupⅠwas injected with cisplatin,control groupⅡwas injected with pCMV-MDM2- Lipofectamine,control groupⅢwas injected with empty pCMV-Lipofectamine,control groupⅣwas injected with RPMI1640.General conditions and tumor growth rate were observed.The volume and the weight of the tumor were compared among these five groups.The expression of MDM2 and p53 in these tumors were de- tected by immunohistochemistry and Western blot.The changes of cell cycles in these tumors were examined by using flow cytometry assay.Results Tumor volume in treatment group[(0.321?0.086) cm~3]was significant- ly smaller than control groupⅠandⅡ[(1.832?0.165) cm~3 and (3.251?0.179) cm~3,respectively)].The weight of the treatment group [(0.513?0.089) g]was also significantly lower than control groupⅠandⅡ[(1.412?0.134) g,and (2.665?0.153) g,respectively)].There was a significant difference between control groupⅠandⅡ, but no difference between the other three control groups.Obvious MDM2 protein expression and pronounced S-phase arrest were observed in treatment group.However,control groupⅠwas with intact wild type p53,and arrested primarily in G_2/M phase.Conclusion MDM2 overexpression can increase cisplatin cytotoxicity on experimental ovarian cancer through inhibition of p53 expression and the loss of G_1 check point of cell cycle.

Mechanism of change in runx3 in gastric carcinoma and its difference with p53 mutation / 吉林大学学报(医学版)

Objective To observe the mechanism of the change in runx3 in gastric carcinoma its difference and with p53 mutation.Methods A total of 30 cases of gastric carcinoma were taken from clinical operation.PCR-SSCP method was used to detect mutations in exons 2,3,4 of runx3 gene in the gastric carcinoma.The methylation status of runx3 gene was examined by methylation-specific polymerase chain reaction(MS-PCR),PCR-SSCP method was used to detect mutations in exons 5,6,7,8 of p53 gene in the gastric carcinoma.Results Two cases with mutation were found,methylation of runx3 promoter region was confirmed in 87%(26/30) specimens of gastric carcinoma,53.3%(16/30)cases were confirmed with mutation in the p53 gene.The rate of methylation of runx3 was higher than the rate of mutation of p53(P