To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on ch...To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on chromosome 9, 16 and 17. Loss-of-heterozygosity (LOH) is observed with high frequency on chromosomal region 17p13 (36/55, 65%), 9p21-p23 (28/55, 51%), 16q21-q23 (27/55, 49%) in tumors. Meanwhile, microsatellite instability is rarely found in these microsatellite loci. Direct sequencing was performed to detect the tentative mutation of tumor suppressor genes in these regions: p53, MTS1/p16, and CDH1/E-cadherin. Within exon 5-9 of p53 gene, 14 out of 55 HCC specimens (24%) have somatic mutations, and nucleotide deletion of this gene is reported in HCC for the first time. Mutation in MTS1/pl6 is found only in one tumor case. We do not find mutations in CDH1/E-cadherin. Furthermore, a statistically significant correlation is present between p53 gene mutation and loss of chromosome region 16q21q23 and 9p21-p23, which indicates that synergism between p53 inactivation and deletion of 16q21-q23 and 9p21-p23 may play a role in the pathogenesis of HCC. Genetic aberration in hepatocellular展开更多
BACKGROUND: Current studies related to the effects of proanthocyanidins on Alzheimer’s disease have focused primarily on the signal transduction pathway of cellular apoptosis.However,the influence of p53 gene express...BACKGROUND: Current studies related to the effects of proanthocyanidins on Alzheimer’s disease have focused primarily on the signal transduction pathway of cellular apoptosis.However,the influence of p53 gene expression on cell cycle regulation,with regard to the protective mechanisms of proanthocyanidins,has not been reported.OBJECTIVE: To observe the effect of proanthocyanidins on cell cycle distribution,cellular apoptosis,and p53 gene expression in β-amyloid peptide (25-35) (Aβ25-35)-induced PC12 cells cultured in serum-free media,and to investigate the molecular neuroprotective mechanisms of proanthocyanidins with regard to cell cycle regulation.DESIGN,TIME AND SETTING: A parallel,controlled,cellular,and molecular study was performed at the Institute of Biochemistry and Molecular Biology,Guangdong Medical College from July 2006 to July 2008.MATERIALS: Proanthocyanidins were provided by Nanjing Xuezi Medical and Chemical Research Center,China;Aβ25-35 was provided by Sigma,USA;PC12 cells were provided by the Institute of Basic Medical Science,Academy of Military Medical Sciences;and rabbit anti-p53 polyclonal antibody was provided by Santa Cruz Biotechnology,USA.METHODS: PC12 cells were cultured in serum-free media for 24 hours.Cells from the model group were treated with 25 μmol/L Aβ25-35 for 24 hours.Cells in the drug protection group were pre-treated with 30 mg/L proanthocyanidins for 1 hour and then treated with 25 μmol/L Aβ25-35 for 24 hours.The control group was not treated.MAIN OUTCOME MEASURES: Flow cytometry was used to detect cell cycle distribution and rate of apoptosis;reverse-transcriptase polymerase chain reaction was used to detect p53 mRNA expression;and Western blot was used to detect p53 protein expression.RESULTS: After treating with 25 μmol/L Aβ25-35 for 24 hours,the rate of apoptosis and the percentage of cells in S phase were significantly increased (P < 0.01),and p53 mRNA and protein expressions were decreased.Pretreatment with proanthocyanidins for 1 hour blocked the increase in apoptosis and the percentage of cells in S phase in Aβ25-35-induced PC12 cells (P < 0.01) and increased p53 mRNA and protein expressions.CONCLUSION: Proanthocyanidins blocked apoptosis and S-phase arrest in Aβ25-35-induced PC12 cells cultured in serum-free media.The protective mechanism could be related to increased p53 mRNA and protein expressions.展开更多
Transcatheter arterial chemoembolization (TACE) has become the standard treatment for unresectable hepatocellular carcinoma (HCC). But this method has some shortages. p53 gene, which was found to be mutant in many hum...Transcatheter arterial chemoembolization (TACE) has become the standard treatment for unresectable hepatocellular carcinoma (HCC). But this method has some shortages. p53 gene, which was found to be mutant in many human tumors, has been proved with broadspectrum anti-tumor effects. We reported a 23-year-old patient with recurrent HCC after irregular hepatectomy. The p53 gene was applied to this patient. We injected percutaneously and infused transcatheterally p53 gene (Gendicine, Shenzhen Sibiono Bentech, China) into his recurrent nodules in liver respectively and 4 d later, the patient received TACE therapy. In the 2 mo follow-up, the patient was in good clinical condition with normal liver function and no recurrence was identified. The case report proposed that recurrent HCC could be successfully treated with p53 gene therapy combining TACE.展开更多
INTRODUCTIONAdenocarcinomas of the cardia are the lesionsarising from the proximal stomach or within 3 cm ofthe gastroesophageal junction.These cancerstended to be advanced at the time of presentation,usually with poo...INTRODUCTIONAdenocarcinomas of the cardia are the lesionsarising from the proximal stomach or within 3 cm ofthe gastroesophageal junction.These cancerstended to be advanced at the time of presentation,usually with poor prognosis.In recent decade,the incidence of adenocarcinoma of gastric eardiaand esophagus are increasing steadily,while therehas been a decrease in the proportion of the cancersarising from the distal stomach.The展开更多
AIM:To evaluate the efficacy and safety of combination therapy with recombinant adenovirus p53 injection (rAdp53) and transcatheter hepatic arterial chemoembolization (TACE) for advanced hepatocellular carcinoma (HCC)...AIM:To evaluate the efficacy and safety of combination therapy with recombinant adenovirus p53 injection (rAdp53) and transcatheter hepatic arterial chemoembolization (TACE) for advanced hepatocellular carcinoma (HCC).METHODS:A total of 82 patients with advanced HCC treated only with TACE served as control group.Another 68 patients with HCC treated with TACE in combination with recombinant adenovirus-p53 injection served as p53 treatment group.Patients were followed up for 12 mo.Safety and therapeutic effects were evaluated according to the improvement in clinical symptoms,leukocyte count,Karnofsky and RECIST criteria.Survival rate was calculated with Kaplan-Meier method.RESULTS:The total effective rate was 58.3% for p53 treatment group,and 26.5% for control group (P < 0.05).The incidence of gastrointestinal symptoms was lower in p53 treatment group than in control group (P < 0.05).The 3-,6-and 12-mo survival rates were significantly higher for p53 treatment group than for control group (P < 0.01).The combination treatment was well tolerated with such adverse events as fever (51.5%,P=0.006) and pain of muscles and joints (13.2%,P=0.003),which were significantly higher than the chemotherapy.Except for these minor adverse effects,no severe vector-related complications were identified.With respect to the efficacy,patients in p53 treatment group had less gastrointerestinal symptoms (P=0.062),better improvement in tumor-related pain (P=0.003),less downgrade of leukocyte counts (P=0.003) and more upgrade of Karnofsky performance score (P=0.029) than those in control group.The total effective rate (CR + PR) for p53 treatment group and control group was 58.3% and 26.5%,respectively,with distributions of different effect in two groups (P=0.042).The survival rates were 89.71%,76.13%,and 43.30% for p53 treatment group,and 68.15%,36.98%,and 24.02% for control group,respectively,3,6 and 12 mo after treatment,suggesting that the survival rates are significantly higher for p53 treatment group than for control group (P=0.0002).CONCLUSION:The rAd-p53 gene therapy in combination with TACE is a safe and effective treatment modality for advanced HCC.展开更多
Hepatocellular carcinoma (HCC) is one of the 10 most common cancers worldwide. There is no ideal treatment for HCC yet and many researchers are trying to improve the effects of treatment by changing therapeutic strate...Hepatocellular carcinoma (HCC) is one of the 10 most common cancers worldwide. There is no ideal treatment for HCC yet and many researchers are trying to improve the effects of treatment by changing therapeutic strategies. As the majority of human cancers seem to exhibit either abnormal p53 gene or disrupted p53 gene activation pathways, intervention to restore wild-type p53 (wt-p53) activities is an attractive anti-cancer therapy including HCC. Abnormalities of p53 are also considered a predisposition factor for hepatocarcinogenesis. p53 is frequently mutated in HCC. Most HCCs have defects in the p53-mediated apoptotic pathway although they carry wt-p53. High expression of p53 in vivo may exert therapeutic effects on HCC in two aspects: (1) High expression of exogenous p53 protein induces apoptosis of tumor cells by inhibiting proliferation of cells through several biologic pathways and (2) Exogenous p53 renders HCC more sensitive to some chemotherapeutic agents. Several approaches have been designed for the treatment of HCC via the p53 pathway by restoring the tumor suppression function from inactivation, rescuing the mutated p53 gene from instability, or delivering therapeutic exogenous p53. Products with p53 status as the target have been studied extensively in vitro and in vivo . This review elaborates some therapeutic mechanisms and advances in using recombinant human adenovirus p53 and oncolytic virus products for the treatment of HCC.展开更多
p53 gene mutation (exon4, 5, 6, 7, 8 and intron6) in gastric cancer and precancerous lesions and p53 gene (exon4 and ontron6), APC gene deletion in gastric carcinomas were studied by PCR/SSCP and PCR/RFLP- Results sho...p53 gene mutation (exon4, 5, 6, 7, 8 and intron6) in gastric cancer and precancerous lesions and p53 gene (exon4 and ontron6), APC gene deletion in gastric carcinomas were studied by PCR/SSCP and PCR/RFLP- Results showed mutation rate of p53 in metaplasia, dysplasia and gastric carcinoma was 37. 5 % (3/8), 42. 11 % (8/19), 53. 33 (16/30) respectively- There was significant dif-ference among groups of metaplasia, dysplasia, cancer and normal controls. Noexon8 mutation was found in metaplasia and dysplasia, but 4 cases were found to have exon8 mutation in cancer group. It is suggested that exon8 mutation occurs at the late stage of gastric cancer, but exon 5, 6, 7 mutation occur in the course ofprecancerous lesion to cancer. Loss of heterozygosity (LOH) of exon4, intron6,APC was 47,37 % (9/19), 8. 73% (2/23), 16. 67 % (3/18) respectively. LOH of exon4 had something to do with poor differentiation, lymph node metastasis,depth of invasion- LOH of exon4 may be one of prognostic marker of gastric cancer. We are led to conclude that p53 gene mutation is an early event and perhaps work together with ras oncogene in gastric展开更多
Background and objective Once the malignant pleural or peritoneal effusion is developed it is difficult to control.This report presents a new method for controlling the malignant effusions.Methods Forty-eight patients...Background and objective Once the malignant pleural or peritoneal effusion is developed it is difficult to control.This report presents a new method for controlling the malignant effusions.Methods Forty-eight patients,29 males and 19 females with an average age of 61.2 years old,who were satisfied with the study inclusion criteria,were recruited in this study.Twenty-seven and 21 patients had a malignant pleural and peritoneal effusion,respectively.After draining most of fluids,these patients received intra-cavity infusion of rAd-p53 once per week for 4 weeks,at dose of 2×1012 viral particles(VP) diluted into 200 mL of saline solution for pleural effusions,and 4×1012 VP diluted into 500 mL of saline solution for peritoneal effusions.Results Participants were followed up for a median time of 13.6 month.A total of 11 cases,7 with pleural effusions and 4 with peritoneal effusions achieved a complete response(CR),and 20 cases(12 pleural effusions and 8 peritoneal effusions) had a partial response(PR).The overall response rate is 64.6%.Patients' quality of life,assessed by using Karnofsky performance scale(KPS) scores,was improved by an average of 26.4.The one-year of overall survival rate was 54.2% with a median survival time of 12.5 months.There were no serious side effects observed except for self-limited fever found in 79.8% of the cases.Conclusions Intra-cavity infusion of rAd-p53 is an effective and safe treatment for the patients with malignant pleural or peritoneal effusions,especially for those patients who can't tolerate the standard treatments.展开更多
Objective: To investigate the effect of adenovirus- mediated p53 (Adp53) transfer on thermosensitivity of human gastric carcinoma cell lines (BGC823). Methods: Two human gastric carcinoma cell lines with different p53...Objective: To investigate the effect of adenovirus- mediated p53 (Adp53) transfer on thermosensitivity of human gastric carcinoma cell lines (BGC823). Methods: Two human gastric carcinoma cell lines with different p53 status, BGC823-wtp53 cell (abbreviate W) bearing the wilt-type p53 and BGC823-mutp53 cell (abbreviate M) bearing the mutant p53, were cultured with DMEM medium and were infected with Adp53 at a viral multiplicity of infection of 100 (1:100MOI) for 48h before heating. Cell cycle redistribution and apoptosis of two human gastric carcinoma cell lines in 24h at 37℃ after heat treatment at 42℃ for 2h or 43℃ for 0.5h were analyzed by flow cytometry. Relative tumor volume growth curves were used in a nude mouse tumor model of the two cell lines following hyperthermia at 43℃ for 0.5h after 48h intratumoral injection of 1108 pfu of Adp53 to evaluate thermoenhancemet effect in vivo. Results: In vitro study showed that both W and M cells infected with Adp53 and treated with heating had strong arrest in G2 (after heating at 42℃ for 2h, 34.0% of original population for W cells and 25.3% of original population for M cells) and produced obvious apoptotic response. The apoptosis rate showed 230% increased (for W cells) and 110% increase (for M cells) compared with heating only control. In vivo study showed that the growth of tumor of both W cells and M cells was significantly delayed by hyperthemia combining with Adp53 as compared to tumors receiving either treatment alone. Conclusion: This study demonstrated that Adp53 transfer increased cellular apoptosis and thermo- sensitivity in vitro and tumor thermosensitivity in vivo independent of cellular intrinsic p53 status. These results support the combined used of p53 gene therapy with hyperthermia in clinical trials.展开更多
AIM: To investigate the role of the polymorphism of p53 codon 72 in early gastric cancer (EGC) and advanced gastric cancer (AGC) in Korean patients. METHODS: DNA was extracted from blood samples of gastric cancer pati...AIM: To investigate the role of the polymorphism of p53 codon 72 in early gastric cancer (EGC) and advanced gastric cancer (AGC) in Korean patients. METHODS: DNA was extracted from blood samples of gastric cancer patients (n = 291) and controls (n = 216). In the p53 codon 72 genotypes were determined by PCR-RFLP.RESULTS: Patients with gastric cancer had a significantly higher frequency of the homozygous proline (Pro) allele than the control (P = 0.032). Patients with AGC had a significantly higher frequency of the Arg/Arg (arginine) allele (P = 0.038) than EGC and a similar Pro/Pro allele. The signet ring cell type had a higher frequency of the Pro/Pro allele than other types (P = 0.031). The Pro/Pro genotype carries a 3.9-fold increased risk of developing gastric cancer (95% CI, 1.3-15.4, P = 0.039) when compared to Arg/Arg and Arg/Pro genotypes and to develop EGC is a 5.25 fold increased risk (95% CI, 1.8-19.6, P = 0.021). CONCLUSION: The Pro/Pro genotype of the p53 codon 72 polymorphism carries a higher risk for gastric cancer in general and is also associated with a much higher risk for EGC than AGC.展开更多
Objective: To study the effect of Shugan Shuru Granule (疏肝舒乳颗粒,SSG) on the p53 gene expression in patients with hyperplastic disease of breast (HDB) to indirectly explore the mechanism of SSG’s effect on HDB on...Objective: To study the effect of Shugan Shuru Granule (疏肝舒乳颗粒,SSG) on the p53 gene expression in patients with hyperplastic disease of breast (HDB) to indirectly explore the mechanism of SSG’s effect on HDB on the molecular pathological level. Methods: Sixty-six patients with HDB were allocated in the treated group and the control group,with the former treated with SSG and the latter not. All patients underwent breast operation and their diseased mammary tissues were cut out, sectioned, and observed under microscopy with HE staining and immunohistochemical staining, with ABC method adopted to estimate the degree of hyperplasia and p53 gene expression. The severity of HDB was classified into normal, mild, moderate and severe grades (marked as 0 to Ⅲ), according to the degree of hyperplasia in the mammary gland. Results: Hyperplasia in the control group mostly belonged to grade Ⅰ-Ⅲ before treatment, showing overgrowth of gland and proliferation of glandular epithelial cells, which were high columnar shaped, more stratified, with papillary or substantive dysplasia. While in the treated group, most belonged to grade 0-Ⅰ after SSG treatment, with proliferated gland and dysplasia recovered to normal or disappeared. The positive rate of p53 gene expression in the treated group was 9.09%, and in the control group 39.39%, comparison between the two groups showing significant difference (P<0.01), the intensity in the former was significantly weaker than that in the latter.Conclusion: SSG could not only inhibit the proliferation of mammary duct epithelia and lobuli, but also inhibit the over-expression of P53. Therefore, it could be regarded as an effective remedy for treatment of HDB and prevention of mammary cancer genesis.展开更多
AIM: To investigate the inhibitory effect of tumor suppressor p33ING1b and its synergy with p53 gene in hepatocellular carcinoma (HCC).METHODS: Recombinant sense and antisense p33ING1b plasmids were transfected into h...AIM: To investigate the inhibitory effect of tumor suppressor p33ING1b and its synergy with p53 gene in hepatocellular carcinoma (HCC).METHODS: Recombinant sense and antisense p33ING1b plasmids were transfected into hepatoma cell line HepG2 with lipofectamine. Apoptosis, G0/G1 arrest, cell growth rate and cloning efficiency in soft agar of HepG2 were analyzed after transfection. In three hepatoma cell lineswith different endogenous p53 gene expressions, the synergistic effect of p33ING1b with p53 was analyzed by flow cytometry and luciferase assay was performed to detect the activation of p53 downstream gene p21WAF1/CIP1. In addition, the expression and mutation rates of p33ING1b in HCC tissues were measured by immunohistochemistry and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP).RESULTS: Overexpression of p33ING1b inhibited cell growth of HepG2, induced more apoptosis and protected cells from growth in soft agar. Combined transfer of p33ING1b and p53 gene promoted hepatoma cell apoptosis, G0/G1 arrest and elevated expression of p21WAF1/CIP1. Immunostaining results showed co-localized P33ING1b with P53 protein in HCC tissues and there was a significant relation between protein expression rates of these two genes (P＜0.01).Among 28 HCC samples, p33ING1b presented a low gene mutation rate (7.1%).CONCLUSION: p33ING1b collaborates with p53 in cell growth inhibition, cell cycle arrest and apoptosis in HCC. Loss or inactivation of p33ING1b normal function may be an important mechanism for the development of HCC retaining wildtype p53.展开更多
AIM: To characterize the tumor suppressor gene p53 mutations in exon 4, esophageal cancer and adjacent noncancerous tissues.METHODS: We performed p53 (exons 4-8) gene mutation analysis on 24 surgically resected human ...AIM: To characterize the tumor suppressor gene p53 mutations in exon 4, esophageal cancer and adjacent noncancerous tissues.METHODS: We performed p53 (exons 4-8) gene mutation analysis on 24 surgically resected human esophageal cancer specimens by PCR, single-strand conformation polymorphism, and DNA sequencing. RESULTS: p53 gene mutations were detected in 9 of 22 (40.9%) esophageal cancer specimens and 10 of 17 (58.8%) adjacent non-cancerous tissues. Eight of sixteen (50.0%) point mutations detected were G-A transitions and 9 of 18 (50.0%) p53 gene mutations occurred in exon 4 in esophageal cancer specimens. Only 1 of 11 mutations detected was G-A transition and 4 of 11 (36.4%) p53 gene mutations occurred in exon 4 in adjacent non-cancerous tissues.CONCLUSION: Mutation of p53 gene in exon 4 may play an important role in development of esophageal cancer. The observation of p53 gene mutation in adjacent noncancerous tissues suggests that p53 gene mutation may be an early event in esophageal carcinogenesis. Some clinical factors, including age, sex, pre-operation therapy and location of tumors, do not influence p53 gene mutation rates.展开更多
AIM:To study the alterations in p53 gene among Indian gastric cancer patients and to correlate them with the various clinicopathological parameters. METHODS:A total of 103 gastric cancer patients were included in this...AIM:To study the alterations in p53 gene among Indian gastric cancer patients and to correlate them with the various clinicopathological parameters. METHODS:A total of 103 gastric cancer patients were included in this study.The p53 alterations were studied by both immunohistochemical method as well as polymerase chain reaction(PCR)-single strand conformation polymorphism(SSCP)analysis.We only studied four(exon 5,6,7,and 8)of the 11 p53 exons.The alterations in p53 were also correlated with respect to various clinicopathological parameters. RESULTS:Among 103 cases,p53 over-expression and alteration were detected in 37(35.92%)and 19(18.44%)cases,respectively.Most of the p53 alterations were found at exon 5(31.54%),followed by exon 6(26.31%),exon 7(21.04%)and exon 8(21.04%).A significant correlation of p53 over- expression was found with p53 alteration(P=0.000). Concordance between p53 alteration(as detected by SSCP)and over-expression[as detected by immunohistochemistry(IHC)]was found in 75%cases. We found that IHC-positive/SSCP-negative cases accounted for 21%of cases and IHC-negative/SSCP- positive cases accounted for remaining 4%cases. CONCLUSION:Our results show that p53 genemutations are significantly correlated with p53 protein overxpression,with 75%concordance in overexpression and alteration in the p53 gene,but 25% disconcordance also cautions against the assumption that p53 over-expression is always associated with a gene mutation.There may be other mechanisms responsible for stabilization and accumulation of p53 protein with no evidence of gene mutation that reflect an accumulation of a non-mutated protein,or a false negative SSCP result.展开更多
Objective:To investigate the relationship between p53 protein overexpression in esophageal and cervical squamous cell cancer and their clinical radiosensitivity. Methods: The immuno-histochemical assays were done for ...Objective:To investigate the relationship between p53 protein overexpression in esophageal and cervical squamous cell cancer and their clinical radiosensitivity. Methods: The immuno-histochemical assays were done for 52 cases with esophageal and cervical squamous cell cancer. The relationship between the assay results and short-term radiotherapy was investigated. Results: p53 overer-pression was 52.38% and 35. 48% respectively, in esophageal cancer and cervical cancer;p53 over-expression in high differentiated squamous cell cancer was knver than these in moderate and poor differentiated cases(P<0. 05). There was no relationship between p53 overexpression and stages(P>0. 05). In the cases of cervical cancer, p53 overexpression had the less short-term effect(P<0. 05 ), and In esophageal cancers, there was no relationship with radiotherapy effect(P>0. 05).Conclusion:This study suggests that p53 gene has the certain relationship with tumor radiosensitivity.展开更多
AIM: To study the relationship between Helicobacter pylori (H. Pylori) and gastric carcinoma and its possible pathogenesis by H. Pylori.METHODS: DNEL technique and immunohistochemical technique were used to study t...AIM: To study the relationship between Helicobacter pylori (H. Pylori) and gastric carcinoma and its possible pathogenesis by H. Pylori.METHODS: DNEL technique and immunohistochemical technique were used to study the state of apoptosis,proliferation and p53 gene expression. A total of 100 gastric mucosal biopsy specimens, including 20 normal mucosa, 30H. Pylori-negative and 30 H. Pylorf-positive gastric precancerous lesions along with 20 gastric carcinomas were studied.RESULTS: There were several apoptotic cells in the superficial epithelium and a few proliferative cells within the neck of gastric glands, and no p53 protein expression in normal mucosa. In gastric carcinoma, there were few apoptotic cells, while there were a large number of proliferative cells, and expression of p53 protein significantly was increased. In the phase of metaplasia, the apoptotic index (Al, 4.36% ± 1.95%), proliferative index (PI, 19.11% ± 6.79%) and positivity of p53 expression (46.7%) in H. Pylori-positive group were higher than those in normal mucosa (P< 0.01). Al in H. Pylori-positive group was higher than that in H. Pylori-negative group (3.81% ±1.76%), PI in H. Pylori-positive group was higher than that in H. Pylori-negative group (12.25% ±5.63%, P<0.01 ). In the phase of dysplasia, Al (2.31% ± 1.10%) in H. Pylori-positive group was lower (3.05% ± 1.29%) than that in H. Pylori-negative group, but PI (33.89% ± 11.65%)wassignificantly higher(22.09± 8018%, P< 0.01). In phases of metaplasia, dysplasia and gastric cancer in the H. Pylori-positive group, Als had an evidently graduall decreasing trend (P < 0.01 ), while Pis had an evidently gradual increasing trend (P< 0.05 or P< 0.01), and there was also a trend of gradual increase in the expression of p53 gene.CONCLUSION: In the course of the formation of gastric carcinoma, proliferation of gastric mucosa can be greatly increased by H. Pylori, and H. Pylori can induce apoptosis in the phase of metaplasia but in the phase of dysplasia H.pylori can inhibit cellular apoptosis. And H. Pylori infection can strengthen the expression of mutated p53 gene.展开更多
Recently,much research has indicated that more and more cancers pose a threat to human life.Cancers are caused by oncogenes.Many human oncogenes have been found and most of them are located on chromosomes.The discover...Recently,much research has indicated that more and more cancers pose a threat to human life.Cancers are caused by oncogenes.Many human oncogenes have been found and most of them are located on chromosomes.The discovery of the oncogene plays a significant role in the treatment of cancer.The p53 tumor suppressor gene has received much attention because it frequently mutates or deletes in tumor cells of most people.Thus,the study of oncogenes is significant.In order to establish the Galois field (GF (7)),the indefinite gene is introduced as D and oncogene is introduced as O,and P.Taking the polynomial coefficients a 0,a 1,a 2 ∈ GF(7) and the bijective function f:GF (7) → {D,A,C,O,G,T,P},where f(0)=D,f(1)=A,f(2)=C,f(3)=O,f(4)=G,f(5)=T,and f(6)=P,the bijective may be written as (a 0 + a 1 x + a 2 x 2).Based on the algebraic structure,we can not only analyse the DNA sequence of oncogenes,but also predict possible new cancers.展开更多
Objective: To determine the feasibility of detecting p53 gene mutations for early diagnosis of lung cancer using the samples from bronchoscopic examination. Methods: Point mutations of the exon 5-8 of p53 gene were de...Objective: To determine the feasibility of detecting p53 gene mutations for early diagnosis of lung cancer using the samples from bronchoscopic examination. Methods: Point mutations of the exon 5-8 of p53 gene were detected in 85 bronchoscopic samples of 35 patients suspected to be lung cancer using silver staining PCR-SSCP. Results: p53 gene mutations were founded in 10 of 35 patients(28.6%). The incidence of p53 gene mutations (14.9%) was obviously higher than the cytological positive incidence(2.9%) in samples of sputum, bronchoalveolar lavage and brush, especially for the sputum(27.7%). In the bronchoscopic biopsy specimens, the incidence of p53 gene mutations (12.5%) was lower than that of pathologic positive result (50.0%). However, in view of all the bronchoscopic samples, there was no statistically difference between cytopathologic positive results (11.8%) and the incidence of p53 gene mutations (14.1%). Although the p53 mutations were most common in the samples from the patients bronchoscopically manifested as neoplasm compared with other manifestations, there was no statistical difference. It is valuable to notice that 3 patients with p53 gene mutation merely presented as bronchial inflammation in bronchoscope. Conclusion: Results indicated that the value of detecting p53 gene mutation for the diagnosis of lung cancer using the bronchoscopic samples was more superior to cytological examination and detection of p53 gene mutations in post-bronchoscopic sputum was easy and effective, may be used as a valuable method for early diagnosis of lung cancer.展开更多
Objective: In most laryngeal cancers, the function ofp53 gene is down regulated. To explore the potential use ofp53 in gene therapy of laryngeal cancer, by introducingwhd-type p53 into laryngeal cancer cell line via a...Objective: In most laryngeal cancers, the function ofp53 gene is down regulated. To explore the potential use ofp53 in gene therapy of laryngeal cancer, by introducingwhd-type p53 into laryngeal cancer cell line via arecombinant adenoviral vecton Ad5CMV-p53 andanalyring its effects on cell and tumor growth. Methods: Ahuman laryngeal cancer cell line Hep-2 was used.Recombinant cytomegalovi rus - promoted adenovirusescontaining human wild-type p53 cDNA was transientlyintroduced into Hep-2 line. The growth suppression of theHep-2 cells and established s.c. squamous carcinoma modelwas examined. The p53 protein expression was detectedusing immunohistochemical analysis. Results: The transduction cfficiencies of Hep-2 cell line were 100% at amultiplicity of 100 or greater. The p53 protein expressionpeaked on day 2 after infection and lasted far 5 days. Invitro growth assays revealed cell death following Ad5CMVp53 infected. In vivo studies, Ad5CMV-p53 inhibited thetumorigenicity of Hep-2 cell, and in nude mice withestablished s.c. squamous carcinoma nodules showed thattumor volumes were significantly reduced in mice thatreceived peritumoral infiltration of Ad5CMV-p53. Conclusion: Adenovirus-mediated antitumor therapy carryingthe p53 gene is an efficient method to inhibit laryngealcancer growth. Transfection of laryngeal cancer cells withthe wild-type p53 gene via Ad5CMV-p53 is a potential novelapproach to the therapy of laryngeal cancer.展开更多
基金supported by the Chinese High-Tech Program(863)Chinese Key Basic Research Project(973)the National Natural Science Foundation of China.Gratitude was extended to Prof.Zhu CHEN for his suggestion and direction of this work.
文摘To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on chromosome 9, 16 and 17. Loss-of-heterozygosity (LOH) is observed with high frequency on chromosomal region 17p13 (36/55, 65%), 9p21-p23 (28/55, 51%), 16q21-q23 (27/55, 49%) in tumors. Meanwhile, microsatellite instability is rarely found in these microsatellite loci. Direct sequencing was performed to detect the tentative mutation of tumor suppressor genes in these regions: p53, MTS1/p16, and CDH1/E-cadherin. Within exon 5-9 of p53 gene, 14 out of 55 HCC specimens (24%) have somatic mutations, and nucleotide deletion of this gene is reported in HCC for the first time. Mutation in MTS1/pl6 is found only in one tumor case. We do not find mutations in CDH1/E-cadherin. Furthermore, a statistically significant correlation is present between p53 gene mutation and loss of chromosome region 16q21q23 and 9p21-p23, which indicates that synergism between p53 inactivation and deletion of 16q21-q23 and 9p21-p23 may play a role in the pathogenesis of HCC. Genetic aberration in hepatocellular
基金Key Discipline Key Projects in Guangdong Province (9808)
文摘BACKGROUND: Current studies related to the effects of proanthocyanidins on Alzheimer’s disease have focused primarily on the signal transduction pathway of cellular apoptosis.However,the influence of p53 gene expression on cell cycle regulation,with regard to the protective mechanisms of proanthocyanidins,has not been reported.OBJECTIVE: To observe the effect of proanthocyanidins on cell cycle distribution,cellular apoptosis,and p53 gene expression in β-amyloid peptide (25-35) (Aβ25-35)-induced PC12 cells cultured in serum-free media,and to investigate the molecular neuroprotective mechanisms of proanthocyanidins with regard to cell cycle regulation.DESIGN,TIME AND SETTING: A parallel,controlled,cellular,and molecular study was performed at the Institute of Biochemistry and Molecular Biology,Guangdong Medical College from July 2006 to July 2008.MATERIALS: Proanthocyanidins were provided by Nanjing Xuezi Medical and Chemical Research Center,China;Aβ25-35 was provided by Sigma,USA;PC12 cells were provided by the Institute of Basic Medical Science,Academy of Military Medical Sciences;and rabbit anti-p53 polyclonal antibody was provided by Santa Cruz Biotechnology,USA.METHODS: PC12 cells were cultured in serum-free media for 24 hours.Cells from the model group were treated with 25 μmol/L Aβ25-35 for 24 hours.Cells in the drug protection group were pre-treated with 30 mg/L proanthocyanidins for 1 hour and then treated with 25 μmol/L Aβ25-35 for 24 hours.The control group was not treated.MAIN OUTCOME MEASURES: Flow cytometry was used to detect cell cycle distribution and rate of apoptosis;reverse-transcriptase polymerase chain reaction was used to detect p53 mRNA expression;and Western blot was used to detect p53 protein expression.RESULTS: After treating with 25 μmol/L Aβ25-35 for 24 hours,the rate of apoptosis and the percentage of cells in S phase were significantly increased (P < 0.01),and p53 mRNA and protein expressions were decreased.Pretreatment with proanthocyanidins for 1 hour blocked the increase in apoptosis and the percentage of cells in S phase in Aβ25-35-induced PC12 cells (P < 0.01) and increased p53 mRNA and protein expressions.CONCLUSION: Proanthocyanidins blocked apoptosis and S-phase arrest in Aβ25-35-induced PC12 cells cultured in serum-free media.The protective mechanism could be related to increased p53 mRNA and protein expressions.
文摘Transcatheter arterial chemoembolization (TACE) has become the standard treatment for unresectable hepatocellular carcinoma (HCC). But this method has some shortages. p53 gene, which was found to be mutant in many human tumors, has been proved with broadspectrum anti-tumor effects. We reported a 23-year-old patient with recurrent HCC after irregular hepatectomy. The p53 gene was applied to this patient. We injected percutaneously and infused transcatheterally p53 gene (Gendicine, Shenzhen Sibiono Bentech, China) into his recurrent nodules in liver respectively and 4 d later, the patient received TACE therapy. In the 2 mo follow-up, the patient was in good clinical condition with normal liver function and no recurrence was identified. The case report proposed that recurrent HCC could be successfully treated with p53 gene therapy combining TACE.
文摘INTRODUCTIONAdenocarcinomas of the cardia are the lesionsarising from the proximal stomach or within 3 cm ofthe gastroesophageal junction.These cancerstended to be advanced at the time of presentation,usually with poor prognosis.In recent decade,the incidence of adenocarcinoma of gastric eardiaand esophagus are increasing steadily,while therehas been a decrease in the proportion of the cancersarising from the distal stomach.The
文摘AIM:To evaluate the efficacy and safety of combination therapy with recombinant adenovirus p53 injection (rAdp53) and transcatheter hepatic arterial chemoembolization (TACE) for advanced hepatocellular carcinoma (HCC).METHODS:A total of 82 patients with advanced HCC treated only with TACE served as control group.Another 68 patients with HCC treated with TACE in combination with recombinant adenovirus-p53 injection served as p53 treatment group.Patients were followed up for 12 mo.Safety and therapeutic effects were evaluated according to the improvement in clinical symptoms,leukocyte count,Karnofsky and RECIST criteria.Survival rate was calculated with Kaplan-Meier method.RESULTS:The total effective rate was 58.3% for p53 treatment group,and 26.5% for control group (P < 0.05).The incidence of gastrointestinal symptoms was lower in p53 treatment group than in control group (P < 0.05).The 3-,6-and 12-mo survival rates were significantly higher for p53 treatment group than for control group (P < 0.01).The combination treatment was well tolerated with such adverse events as fever (51.5%,P=0.006) and pain of muscles and joints (13.2%,P=0.003),which were significantly higher than the chemotherapy.Except for these minor adverse effects,no severe vector-related complications were identified.With respect to the efficacy,patients in p53 treatment group had less gastrointerestinal symptoms (P=0.062),better improvement in tumor-related pain (P=0.003),less downgrade of leukocyte counts (P=0.003) and more upgrade of Karnofsky performance score (P=0.029) than those in control group.The total effective rate (CR + PR) for p53 treatment group and control group was 58.3% and 26.5%,respectively,with distributions of different effect in two groups (P=0.042).The survival rates were 89.71%,76.13%,and 43.30% for p53 treatment group,and 68.15%,36.98%,and 24.02% for control group,respectively,3,6 and 12 mo after treatment,suggesting that the survival rates are significantly higher for p53 treatment group than for control group (P=0.0002).CONCLUSION:The rAd-p53 gene therapy in combination with TACE is a safe and effective treatment modality for advanced HCC.
文摘Hepatocellular carcinoma (HCC) is one of the 10 most common cancers worldwide. There is no ideal treatment for HCC yet and many researchers are trying to improve the effects of treatment by changing therapeutic strategies. As the majority of human cancers seem to exhibit either abnormal p53 gene or disrupted p53 gene activation pathways, intervention to restore wild-type p53 (wt-p53) activities is an attractive anti-cancer therapy including HCC. Abnormalities of p53 are also considered a predisposition factor for hepatocarcinogenesis. p53 is frequently mutated in HCC. Most HCCs have defects in the p53-mediated apoptotic pathway although they carry wt-p53. High expression of p53 in vivo may exert therapeutic effects on HCC in two aspects: (1) High expression of exogenous p53 protein induces apoptosis of tumor cells by inhibiting proliferation of cells through several biologic pathways and (2) Exogenous p53 renders HCC more sensitive to some chemotherapeutic agents. Several approaches have been designed for the treatment of HCC via the p53 pathway by restoring the tumor suppression function from inactivation, rescuing the mutated p53 gene from instability, or delivering therapeutic exogenous p53. Products with p53 status as the target have been studied extensively in vitro and in vivo . This review elaborates some therapeutic mechanisms and advances in using recombinant human adenovirus p53 and oncolytic virus products for the treatment of HCC.
文摘p53 gene mutation (exon4, 5, 6, 7, 8 and intron6) in gastric cancer and precancerous lesions and p53 gene (exon4 and ontron6), APC gene deletion in gastric carcinomas were studied by PCR/SSCP and PCR/RFLP- Results showed mutation rate of p53 in metaplasia, dysplasia and gastric carcinoma was 37. 5 % (3/8), 42. 11 % (8/19), 53. 33 (16/30) respectively- There was significant dif-ference among groups of metaplasia, dysplasia, cancer and normal controls. Noexon8 mutation was found in metaplasia and dysplasia, but 4 cases were found to have exon8 mutation in cancer group. It is suggested that exon8 mutation occurs at the late stage of gastric cancer, but exon 5, 6, 7 mutation occur in the course ofprecancerous lesion to cancer. Loss of heterozygosity (LOH) of exon4, intron6,APC was 47,37 % (9/19), 8. 73% (2/23), 16. 67 % (3/18) respectively. LOH of exon4 had something to do with poor differentiation, lymph node metastasis,depth of invasion- LOH of exon4 may be one of prognostic marker of gastric cancer. We are led to conclude that p53 gene mutation is an early event and perhaps work together with ras oncogene in gastric
文摘Background and objective Once the malignant pleural or peritoneal effusion is developed it is difficult to control.This report presents a new method for controlling the malignant effusions.Methods Forty-eight patients,29 males and 19 females with an average age of 61.2 years old,who were satisfied with the study inclusion criteria,were recruited in this study.Twenty-seven and 21 patients had a malignant pleural and peritoneal effusion,respectively.After draining most of fluids,these patients received intra-cavity infusion of rAd-p53 once per week for 4 weeks,at dose of 2×1012 viral particles(VP) diluted into 200 mL of saline solution for pleural effusions,and 4×1012 VP diluted into 500 mL of saline solution for peritoneal effusions.Results Participants were followed up for a median time of 13.6 month.A total of 11 cases,7 with pleural effusions and 4 with peritoneal effusions achieved a complete response(CR),and 20 cases(12 pleural effusions and 8 peritoneal effusions) had a partial response(PR).The overall response rate is 64.6%.Patients' quality of life,assessed by using Karnofsky performance scale(KPS) scores,was improved by an average of 26.4.The one-year of overall survival rate was 54.2% with a median survival time of 12.5 months.There were no serious side effects observed except for self-limited fever found in 79.8% of the cases.Conclusions Intra-cavity infusion of rAd-p53 is an effective and safe treatment for the patients with malignant pleural or peritoneal effusions,especially for those patients who can't tolerate the standard treatments.
基金This work was supported by the National Natural Foundation of China (No. 39670234 )
文摘Objective: To investigate the effect of adenovirus- mediated p53 (Adp53) transfer on thermosensitivity of human gastric carcinoma cell lines (BGC823). Methods: Two human gastric carcinoma cell lines with different p53 status, BGC823-wtp53 cell (abbreviate W) bearing the wilt-type p53 and BGC823-mutp53 cell (abbreviate M) bearing the mutant p53, were cultured with DMEM medium and were infected with Adp53 at a viral multiplicity of infection of 100 (1:100MOI) for 48h before heating. Cell cycle redistribution and apoptosis of two human gastric carcinoma cell lines in 24h at 37℃ after heat treatment at 42℃ for 2h or 43℃ for 0.5h were analyzed by flow cytometry. Relative tumor volume growth curves were used in a nude mouse tumor model of the two cell lines following hyperthermia at 43℃ for 0.5h after 48h intratumoral injection of 1108 pfu of Adp53 to evaluate thermoenhancemet effect in vivo. Results: In vitro study showed that both W and M cells infected with Adp53 and treated with heating had strong arrest in G2 (after heating at 42℃ for 2h, 34.0% of original population for W cells and 25.3% of original population for M cells) and produced obvious apoptotic response. The apoptosis rate showed 230% increased (for W cells) and 110% increase (for M cells) compared with heating only control. In vivo study showed that the growth of tumor of both W cells and M cells was significantly delayed by hyperthemia combining with Adp53 as compared to tumors receiving either treatment alone. Conclusion: This study demonstrated that Adp53 transfer increased cellular apoptosis and thermo- sensitivity in vitro and tumor thermosensitivity in vivo independent of cellular intrinsic p53 status. These results support the combined used of p53 gene therapy with hyperthermia in clinical trials.
基金Supported by Ewha Womans University Mokdong Hospital Clinical Research Grant of 2006
文摘AIM: To investigate the role of the polymorphism of p53 codon 72 in early gastric cancer (EGC) and advanced gastric cancer (AGC) in Korean patients. METHODS: DNA was extracted from blood samples of gastric cancer patients (n = 291) and controls (n = 216). In the p53 codon 72 genotypes were determined by PCR-RFLP.RESULTS: Patients with gastric cancer had a significantly higher frequency of the homozygous proline (Pro) allele than the control (P = 0.032). Patients with AGC had a significantly higher frequency of the Arg/Arg (arginine) allele (P = 0.038) than EGC and a similar Pro/Pro allele. The signet ring cell type had a higher frequency of the Pro/Pro allele than other types (P = 0.031). The Pro/Pro genotype carries a 3.9-fold increased risk of developing gastric cancer (95% CI, 1.3-15.4, P = 0.039) when compared to Arg/Arg and Arg/Pro genotypes and to develop EGC is a 5.25 fold increased risk (95% CI, 1.8-19.6, P = 0.021). CONCLUSION: The Pro/Pro genotype of the p53 codon 72 polymorphism carries a higher risk for gastric cancer in general and is also associated with a much higher risk for EGC than AGC.
文摘Objective: To study the effect of Shugan Shuru Granule (疏肝舒乳颗粒,SSG) on the p53 gene expression in patients with hyperplastic disease of breast (HDB) to indirectly explore the mechanism of SSG’s effect on HDB on the molecular pathological level. Methods: Sixty-six patients with HDB were allocated in the treated group and the control group,with the former treated with SSG and the latter not. All patients underwent breast operation and their diseased mammary tissues were cut out, sectioned, and observed under microscopy with HE staining and immunohistochemical staining, with ABC method adopted to estimate the degree of hyperplasia and p53 gene expression. The severity of HDB was classified into normal, mild, moderate and severe grades (marked as 0 to Ⅲ), according to the degree of hyperplasia in the mammary gland. Results: Hyperplasia in the control group mostly belonged to grade Ⅰ-Ⅲ before treatment, showing overgrowth of gland and proliferation of glandular epithelial cells, which were high columnar shaped, more stratified, with papillary or substantive dysplasia. While in the treated group, most belonged to grade 0-Ⅰ after SSG treatment, with proliferated gland and dysplasia recovered to normal or disappeared. The positive rate of p53 gene expression in the treated group was 9.09%, and in the control group 39.39%, comparison between the two groups showing significant difference (P<0.01), the intensity in the former was significantly weaker than that in the latter.Conclusion: SSG could not only inhibit the proliferation of mammary duct epithelia and lobuli, but also inhibit the over-expression of P53. Therefore, it could be regarded as an effective remedy for treatment of HDB and prevention of mammary cancer genesis.
基金Supported by the National Natural Science Foundation of China (Grants No.30070344 and No.30070839)
文摘AIM: To investigate the inhibitory effect of tumor suppressor p33ING1b and its synergy with p53 gene in hepatocellular carcinoma (HCC).METHODS: Recombinant sense and antisense p33ING1b plasmids were transfected into hepatoma cell line HepG2 with lipofectamine. Apoptosis, G0/G1 arrest, cell growth rate and cloning efficiency in soft agar of HepG2 were analyzed after transfection. In three hepatoma cell lineswith different endogenous p53 gene expressions, the synergistic effect of p33ING1b with p53 was analyzed by flow cytometry and luciferase assay was performed to detect the activation of p53 downstream gene p21WAF1/CIP1. In addition, the expression and mutation rates of p33ING1b in HCC tissues were measured by immunohistochemistry and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP).RESULTS: Overexpression of p33ING1b inhibited cell growth of HepG2, induced more apoptosis and protected cells from growth in soft agar. Combined transfer of p33ING1b and p53 gene promoted hepatoma cell apoptosis, G0/G1 arrest and elevated expression of p21WAF1/CIP1. Immunostaining results showed co-localized P33ING1b with P53 protein in HCC tissues and there was a significant relation between protein expression rates of these two genes (P＜0.01).Among 28 HCC samples, p33ING1b presented a low gene mutation rate (7.1%).CONCLUSION: p33ING1b collaborates with p53 in cell growth inhibition, cell cycle arrest and apoptosis in HCC. Loss or inactivation of p33ING1b normal function may be an important mechanism for the development of HCC retaining wildtype p53.
基金Supported by Ministry of Science and Technology of the People´ s Republic of China grants, No. 2003CA04200 and 2004CB720301 National Natural Science Foundation of China grant,No.10490195 and 30271465 Beijing Municipal Science & Technology Commission grant, No. H030230160130 in part by a grant from Tsinghua University YUYUAN foundation
文摘AIM: To characterize the tumor suppressor gene p53 mutations in exon 4, esophageal cancer and adjacent noncancerous tissues.METHODS: We performed p53 (exons 4-8) gene mutation analysis on 24 surgically resected human esophageal cancer specimens by PCR, single-strand conformation polymorphism, and DNA sequencing. RESULTS: p53 gene mutations were detected in 9 of 22 (40.9%) esophageal cancer specimens and 10 of 17 (58.8%) adjacent non-cancerous tissues. Eight of sixteen (50.0%) point mutations detected were G-A transitions and 9 of 18 (50.0%) p53 gene mutations occurred in exon 4 in esophageal cancer specimens. Only 1 of 11 mutations detected was G-A transition and 4 of 11 (36.4%) p53 gene mutations occurred in exon 4 in adjacent non-cancerous tissues.CONCLUSION: Mutation of p53 gene in exon 4 may play an important role in development of esophageal cancer. The observation of p53 gene mutation in adjacent noncancerous tissues suggests that p53 gene mutation may be an early event in esophageal carcinogenesis. Some clinical factors, including age, sex, pre-operation therapy and location of tumors, do not influence p53 gene mutation rates.
文摘AIM:To study the alterations in p53 gene among Indian gastric cancer patients and to correlate them with the various clinicopathological parameters. METHODS:A total of 103 gastric cancer patients were included in this study.The p53 alterations were studied by both immunohistochemical method as well as polymerase chain reaction(PCR)-single strand conformation polymorphism(SSCP)analysis.We only studied four(exon 5,6,7,and 8)of the 11 p53 exons.The alterations in p53 were also correlated with respect to various clinicopathological parameters. RESULTS:Among 103 cases,p53 over-expression and alteration were detected in 37(35.92%)and 19(18.44%)cases,respectively.Most of the p53 alterations were found at exon 5(31.54%),followed by exon 6(26.31%),exon 7(21.04%)and exon 8(21.04%).A significant correlation of p53 over- expression was found with p53 alteration(P=0.000). Concordance between p53 alteration(as detected by SSCP)and over-expression[as detected by immunohistochemistry(IHC)]was found in 75%cases. We found that IHC-positive/SSCP-negative cases accounted for 21%of cases and IHC-negative/SSCP- positive cases accounted for remaining 4%cases. CONCLUSION:Our results show that p53 genemutations are significantly correlated with p53 protein overxpression,with 75%concordance in overexpression and alteration in the p53 gene,but 25% disconcordance also cautions against the assumption that p53 over-expression is always associated with a gene mutation.There may be other mechanisms responsible for stabilization and accumulation of p53 protein with no evidence of gene mutation that reflect an accumulation of a non-mutated protein,or a false negative SSCP result.
文摘Objective:To investigate the relationship between p53 protein overexpression in esophageal and cervical squamous cell cancer and their clinical radiosensitivity. Methods: The immuno-histochemical assays were done for 52 cases with esophageal and cervical squamous cell cancer. The relationship between the assay results and short-term radiotherapy was investigated. Results: p53 overer-pression was 52.38% and 35. 48% respectively, in esophageal cancer and cervical cancer;p53 over-expression in high differentiated squamous cell cancer was knver than these in moderate and poor differentiated cases(P<0. 05). There was no relationship between p53 overexpression and stages(P>0. 05). In the cases of cervical cancer, p53 overexpression had the less short-term effect(P<0. 05 ), and In esophageal cancers, there was no relationship with radiotherapy effect(P>0. 05).Conclusion:This study suggests that p53 gene has the certain relationship with tumor radiosensitivity.
基金Supported by National Ninth Five-Year Study Program for Tacking Key Scientific Problems.No.96-906-01-04
文摘AIM: To study the relationship between Helicobacter pylori (H. Pylori) and gastric carcinoma and its possible pathogenesis by H. Pylori.METHODS: DNEL technique and immunohistochemical technique were used to study the state of apoptosis,proliferation and p53 gene expression. A total of 100 gastric mucosal biopsy specimens, including 20 normal mucosa, 30H. Pylori-negative and 30 H. Pylorf-positive gastric precancerous lesions along with 20 gastric carcinomas were studied.RESULTS: There were several apoptotic cells in the superficial epithelium and a few proliferative cells within the neck of gastric glands, and no p53 protein expression in normal mucosa. In gastric carcinoma, there were few apoptotic cells, while there were a large number of proliferative cells, and expression of p53 protein significantly was increased. In the phase of metaplasia, the apoptotic index (Al, 4.36% ± 1.95%), proliferative index (PI, 19.11% ± 6.79%) and positivity of p53 expression (46.7%) in H. Pylori-positive group were higher than those in normal mucosa (P< 0.01). Al in H. Pylori-positive group was higher than that in H. Pylori-negative group (3.81% ±1.76%), PI in H. Pylori-positive group was higher than that in H. Pylori-negative group (12.25% ±5.63%, P<0.01 ). In the phase of dysplasia, Al (2.31% ± 1.10%) in H. Pylori-positive group was lower (3.05% ± 1.29%) than that in H. Pylori-negative group, but PI (33.89% ± 11.65%)wassignificantly higher(22.09± 8018%, P< 0.01). In phases of metaplasia, dysplasia and gastric cancer in the H. Pylori-positive group, Als had an evidently graduall decreasing trend (P < 0.01 ), while Pis had an evidently gradual increasing trend (P< 0.05 or P< 0.01), and there was also a trend of gradual increase in the expression of p53 gene.CONCLUSION: In the course of the formation of gastric carcinoma, proliferation of gastric mucosa can be greatly increased by H. Pylori, and H. Pylori can induce apoptosis in the phase of metaplasia but in the phase of dysplasia H.pylori can inhibit cellular apoptosis. And H. Pylori infection can strengthen the expression of mutated p53 gene.
基金Project supported in part by the Program for Innovative Research Team of Jiangnan University,China(Grant No.2008CX002)
文摘Recently,much research has indicated that more and more cancers pose a threat to human life.Cancers are caused by oncogenes.Many human oncogenes have been found and most of them are located on chromosomes.The discovery of the oncogene plays a significant role in the treatment of cancer.The p53 tumor suppressor gene has received much attention because it frequently mutates or deletes in tumor cells of most people.Thus,the study of oncogenes is significant.In order to establish the Galois field (GF (7)),the indefinite gene is introduced as D and oncogene is introduced as O,and P.Taking the polynomial coefficients a 0,a 1,a 2 ∈ GF(7) and the bijective function f:GF (7) → {D,A,C,O,G,T,P},where f(0)=D,f(1)=A,f(2)=C,f(3)=O,f(4)=G,f(5)=T,and f(6)=P,the bijective may be written as (a 0 + a 1 x + a 2 x 2).Based on the algebraic structure,we can not only analyse the DNA sequence of oncogenes,but also predict possible new cancers.
基金the Research Foundation of the Ministry of Public Health of PR China !(No. 94-1-316).
文摘Objective: To determine the feasibility of detecting p53 gene mutations for early diagnosis of lung cancer using the samples from bronchoscopic examination. Methods: Point mutations of the exon 5-8 of p53 gene were detected in 85 bronchoscopic samples of 35 patients suspected to be lung cancer using silver staining PCR-SSCP. Results: p53 gene mutations were founded in 10 of 35 patients(28.6%). The incidence of p53 gene mutations (14.9%) was obviously higher than the cytological positive incidence(2.9%) in samples of sputum, bronchoalveolar lavage and brush, especially for the sputum(27.7%). In the bronchoscopic biopsy specimens, the incidence of p53 gene mutations (12.5%) was lower than that of pathologic positive result (50.0%). However, in view of all the bronchoscopic samples, there was no statistically difference between cytopathologic positive results (11.8%) and the incidence of p53 gene mutations (14.1%). Although the p53 mutations were most common in the samples from the patients bronchoscopically manifested as neoplasm compared with other manifestations, there was no statistical difference. It is valuable to notice that 3 patients with p53 gene mutation merely presented as bronchial inflammation in bronchoscope. Conclusion: Results indicated that the value of detecting p53 gene mutation for the diagnosis of lung cancer using the bronchoscopic samples was more superior to cytological examination and detection of p53 gene mutations in post-bronchoscopic sputum was easy and effective, may be used as a valuable method for early diagnosis of lung cancer.
文摘Objective: In most laryngeal cancers, the function ofp53 gene is down regulated. To explore the potential use ofp53 in gene therapy of laryngeal cancer, by introducingwhd-type p53 into laryngeal cancer cell line via arecombinant adenoviral vecton Ad5CMV-p53 andanalyring its effects on cell and tumor growth. Methods: Ahuman laryngeal cancer cell line Hep-2 was used.Recombinant cytomegalovi rus - promoted adenovirusescontaining human wild-type p53 cDNA was transientlyintroduced into Hep-2 line. The growth suppression of theHep-2 cells and established s.c. squamous carcinoma modelwas examined. The p53 protein expression was detectedusing immunohistochemical analysis. Results: The transduction cfficiencies of Hep-2 cell line were 100% at amultiplicity of 100 or greater. The p53 protein expressionpeaked on day 2 after infection and lasted far 5 days. Invitro growth assays revealed cell death following Ad5CMVp53 infected. In vivo studies, Ad5CMV-p53 inhibited thetumorigenicity of Hep-2 cell, and in nude mice withestablished s.c. squamous carcinoma nodules showed thattumor volumes were significantly reduced in mice thatreceived peritumoral infiltration of Ad5CMV-p53. Conclusion: Adenovirus-mediated antitumor therapy carryingthe p53 gene is an efficient method to inhibit laryngealcancer growth. Transfection of laryngeal cancer cells withthe wild-type p53 gene via Ad5CMV-p53 is a potential novelapproach to the therapy of laryngeal cancer.
