AIM: To confirm if p53 mutation could be a routine predictive marker for the prognosis of hepatocellular carcinoma (HCC) patients. METHODS: Two hundreds and forty-four formalin-fixed paraffin-embedded tumor samples of...AIM: To confirm if p53 mutation could be a routine predictive marker for the prognosis of hepatocellular carcinoma (HCC) patients. METHODS: Two hundreds and forty-four formalin-fixed paraffin-embedded tumor samples of the patients with HCC receiving liver resection were detected for nuclear accumulation of p53. The percent of P53 immunoreactive tumor cells was scored as 0 to 3+ in P53 positive region (【10% -, 10-30% +, 31-50% ++, 】50% +++). Proliferating cell nuclear antigen (PCNA) and some clinicopathological characteristics, including patients' sex, preoperative serum AFP level, tumor size, capsule, vascular invasion (both visual and microscopic), and Edmondson grade were also evaluated. RESULTS: In univariate COX harzard regression model analysis, tumor size, capsule status, vascular invasion, and p53 expression were independent factors that were closely related to the overall survival (OS) rates of HCC patients. The survival rates of patients with 3+ for P53 expression were much lower than those with 2+ or + for P53 expression. Only vascular invasion (P【0.05) and capsule (P【0.01) were closely related to the disease-free survival (DFS) of HCC patients. In multivariate analysis, p53 overexpression (RI 0.5456, P【0.01) was the most significant factor associated with the OS rates of patients after HCC resection, while tumor size (RI 0.5209, P【0.01), vascular invasion (RI 0.5271, P【0.01) and capsule (RI-0.8691, P【0.01) were also related to the OS. However, only tumor capsular status was an independent predictive factor (P【0.05) for the DFS. No significant prognostic value was found in PCNA-LI, Edmondson's grade, patients' sex and preoperative serum AFP level. CONCLUSION: Accumulation of p53 expression, as well as tumor size, capsule and vascular invasion, could be valuable markers for predicting the prognosis of HCC patients after resection. The quantitative immunohistochemical scoring for P53 nuclear accumulation might be more valuable for predicting prognosis of patients after HCC resection than the common qualitative analysis.展开更多
AIMS p53 gene is one of the focuses in the study of tu- mour suppressor genes.So far,there is still controversy about the relationship between p53 alterations and clinicolpathological parameters of gastic cancers such...AIMS p53 gene is one of the focuses in the study of tu- mour suppressor genes.So far,there is still controversy about the relationship between p53 alterations and clinicolpathological parameters of gastic cancers such as macroscopic classifica- tion,stage,degree of differentiation,depth of tumour invasion and lymphonod metastasis.Tamura has reported that p53 gene mutations mainly occur in the aneuploid tumours.But in China, nothing is reported in this field of study.Our aim is to analyze the relationship between p53 gene mutations and these param- eters including DNA ploidy in Chinese primary gasrtic cancers. METHODS Mutations of the p53 gene in exon5-8 were examined in 20 cases of primary gasric cancer by PCR-SSCP (Polymerase-chain-reaction-single-strand-conforma- tion-polymorphism)analysis. RESULTS Mutations were detected in 8(40%)cases:2 cases in exon5-6,2 cases in exon7,4 cases in exon8.These mutations were detected from stage 0 to stage Ⅲ No significant association was found between p53 gene mutations and the clinicopathological parameters such as macroscopic classifico- tion,degree of histological differentiation,depth of tumour in- vasion and lymphonod metastasis.In addition,66.7%(6 of 9) of aneuploid tumours had p53 mutations and only 18.2%(2 of 11)of diploid tumours had mutations. CONCLUSIONS These results suggest that p53 gene muta- tions are related to DNA ploidy alterations and that p53 gene is one of the important turnout suppressor genes in human gastric cancer.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 the...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, 30 H. pylori-negative and 30 H. pylori-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 (AI, 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). AI 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, AI (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%) was significantly higher (22.09+/-8018%, P【0.01). In phases of metaplasia, dysplasia and gastric cancer in the H. pylori-positive group, AIs 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
AIM: In hepatocellular carcinoma (HCC) prevalent areas of China, the point mutation of p53 exon7 is highly correlated with Hepatitis B virus(HBV) infection and aflatoxin B intake. While in non-HCC-prevalent areas of C...AIM: In hepatocellular carcinoma (HCC) prevalent areas of China, the point mutation of p53 exon7 is highly correlated with Hepatitis B virus(HBV) infection and aflatoxin B intake. While in non-HCC-prevalent areas of China, these factors are not so important in the etiology of HCC. Therefore, the point mutation of p53 exon7 may also be different than that in HCC-prevalent areas of China. The aim of this study is to investigate the status and carcinogenic role of the point mutation of p53 gene exon7 in hepatocellular carcinoma from Anhui Province, a non-HCC-prevalent area in China. METHODS: PCR PCR-SSCP and PCR-RFLP were applied to analyze the homozygous deletion and point mutation of p53 exon7 in HCC samples from Anhui, which were confirmed by DNA sequencing and Genbank comparison. RESULTS: In the 38 samples of hepatocellular carcinoma, no homozygous deletion of p53 exon7 was detected and point mutations of p53 exon7 were found in 4 cases, which were found to be heterozygous mutation of codon 249 with a mutation rate of 10.53%(4/38). The third base mutation(G-T) of p53 codon 249 was found by DNA sequencing and Genbank comparison. CONCLUSION: The incidence of point mutation of p53 codon 249 is lower in hepatocellular carcinoma and the heterozygous mutation of p53 exon7 found in these patients only indicate that they have genetic susceptibility to HCC. p53 codon 249 is a hotspot of p53 exon7 point mutation, suggesting that the point mutation of p53 exon 7 may not play a major role in the carcinogenesis of HCC in Anhui Province, a non-HCC-prevalent area in China.展开更多
IM To study the p53 gene mutation and its relationship to aflatoxin B1 exposure in hepatocellular carcinoma (HCC).METHODS Restriction fragment length polymorphism analysis method was used in 62 HCC samples, and DNA...IM To study the p53 gene mutation and its relationship to aflatoxin B1 exposure in hepatocellular carcinoma (HCC).METHODS Restriction fragment length polymorphism analysis method was used in 62 HCC samples, and DNA direct sequencing in another 45 HCC samples.RESULTS In HCC and AFB1 high and lowrisk areas, 36/52 (69%) and 2/10 (20%) cases were found losing the HaeⅢ allele respectively, suggesting one of the base G mutation at the p53 gene codon 249. Similar results appeared in DNA direct sequencing, 20/35 (57%) and 1/10 (10%) respectively mutated at the codon 249 third base G to C transversion.CONCLUSION In HCC after AFB1 exposure, mutation of p53 gene is fixed at codon 249 third base and take the form of G to T transversion. This is a definite marker of mutation which is induced by AFB1 mutagen. It is applicable for molecular epidemiologic survey of the sufferers of AFB1 among HCC cases and for discovering more unknown natural AFB1 contaminated areas..展开更多
OBJECTIVE: To explore new methods for the early diagnosis of pancreatic cancer through detection of K-ras and p53 mutations in pancreatic juice and stool. METHODS: 201 patients in PUMC Hospital from 1994 - 2000 and 60...OBJECTIVE: To explore new methods for the early diagnosis of pancreatic cancer through detection of K-ras and p53 mutations in pancreatic juice and stool. METHODS: 201 patients in PUMC Hospital from 1994 - 2000 and 60 control individuals were enrolled in this study. K-ras point mutation was detected by PCR-RFLP while p53 mutation was detected by PCR-SSCP. RESULTS: K-ras mutation was found in pancreatic juice in 87.8% (36/41) of pancreatic cancer patients and 23.5% (4/17) of benign pancreatic disease patients. In 261 stool specimens, amplification found mutations successfully in 235 patients (90%). K-ras mutation was found in stool in 88% (66/75) of pancreatic cancer patients, 51.1% (24/47) of benign pancreatic disease patients and 19.6% (9/46) of normal individuals. p53 mutation was found in pancreatic juice in 47.4% (18/38) of pancreatic cancer patients and 12.5% (2/16) of benign pancreatic disease patients. p53 mutation was found in stool in 37.1% (23/62) and 19.1% (4/21) of chronic pancreatitis patients. CONCLUSION: K-ras mutation in pancreatic juice has higher diagnosis sensitivity and specificity, and therefore may be used as a supplement in the diagnosis of pancreatic cancer. Detection of K-ras mutation combined with p53 mutation in stool can aid in the screening of pancreatic cancer.展开更多
OBJECTIVE: To investigate the relationship between p53 gene and tumors of adipose tissue at the level of protein and gene. METHODS: Immunohistochemical LSAB, PCR-SSCP and DNA sequencing were used in 82 cases. RESULTS:...OBJECTIVE: To investigate the relationship between p53 gene and tumors of adipose tissue at the level of protein and gene. METHODS: Immunohistochemical LSAB, PCR-SSCP and DNA sequencing were used in 82 cases. RESULTS: p53 protein is expressed only in liposarcomas, in which the positive staining rate was 48.08% (25/52). In different subtypes of liposarcomas, the positive staining rate in well differentiated liposarcomas was 30.00% (9/30), which is much lower than that of the poorly differentiated liposarcomas (P ATC) were detected by DNA sequencing. Another heterozygotic cosense mutation may exist at exon 6 codon 221 of p53 gene (GAG-->GAA). CONCLUSIONS: The data suggest that the p53 protein has a relationship with development, differentiation and malignancy of liposarcoma. Detecting the level of p53 protein expression may be valuable in evaluating the level of differentiation and malignancy of liposarcoma. There appear point mutation on exon 8, 6 of p53 gene.展开更多
Objective： To investigate the mechanism of herb cake-partitioned moxibustion treating ulcerative colitis （UC） from the relationship between expression of p53 and C-myc protein, and morbidity of UC. Methods： Rats m...Objective： To investigate the mechanism of herb cake-partitioned moxibustion treating ulcerative colitis （UC） from the relationship between expression of p53 and C-myc protein, and morbidity of UC. Methods： Rats model of UC was made with immune methods and local stimulation. Forty SD rats were divided into normal, model, herb cake-partitioned, and mild moxibustion group by a random number table, 10 rats in each group. Hanging moxibustion in the mild moxibustion group was applied to Tianshu （ST 25） and Qihai （CV 6） for 10 rain. Two moxa cones of herb cake-partitioned moxibustion were applied to the same acupoints respectively, in the herb cake-partitioned moxibustion group. Expression of p53 and C-myc protein was measured with immuno- histochemistical method in the colonic tissue of rats with UC. Results： Postive area, strength, and the immunohistochemistry index of the expression of p53 and C-myc protein were found more in the model rats than those in the normal rats （P〈0.01）, whereas less in the herb cake-partitioned moxibustion and mild moxibustion groups than those in the model group （P〈0.01）. Conclusion： p53 and C-myc play important roles in the morbidity and development of UC, and herb cake-partitioned moxibustion could regulate the expression of p53 and C-myc protein in the colonic tissue of UC rats.展开更多
The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to ...The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (MVD) have been evaluated and found to be of prognostic significance. Body fluid (particularly blood and urinary) testing for biomarkers is easily accessible and useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum, and its genetic alterations in HCC are other important trends. More attention should be paid to these two areas in future. As the progress of the human genome project advances, so does a clearer understanding of tumor biology, and more and more new prognostic markers with high sensitivity and specificity will be found and used in clinical assays. However, the combination of some items, i.e., the pathological features and some biomarkers mentioned above, seems to be more practical for now.展开更多
Background Gene therapy and epigenetic therapy have gained more attention in cancer treatment. However, the effect of a combined treatment of gene therapy and epigenetic therapy on head and neck squamous cell carcinom...Background Gene therapy and epigenetic therapy have gained more attention in cancer treatment. However, the effect of a combined treatment of gene therapy and epigenetic therapy on head and neck squamous cell carcinoma have not been studied yet. To study the mechanism and clinical application, human laryngeal carcinoma cell （Hep-2） tumor-bearing mice were used. Methods A xenograft tumor model was established by the subcutaneous inoculation of Hep-2 cells in the right armpit of BALB/c nu/nu mice. The mice with well-formed tumor were randomly divided into six groups. Multisite injections of rAd-p53 and/or 5-aza-dC were used to treat tumor. Tumor growth was monitored by measuring tumor volume and growth rate. p53 and E-cadherin protein levels in tumor tissues were detected by immunohistochemical staining. The mRNA levels were monitored with FQ-PCR. Results Gene therapy was much more effective than single epigenetic therapy and combined therapy. The gene therapy group has the lowest tumor growth rate and the highest expression levels of p53 and E-cadherin. Conclusions The combined treatment of gene and epigenetic therapy is not suggested for treating head and neck carcinoma, because gene therapy shows an antagonistic effect to epigenetic therapy. However, the mechanisms of action are still unclear.展开更多
基金the Key Project of Medical Development in Shanghaithe National Science Funding for Young Scientists (No.30000075)Fund for Leading Specialty of Shanghai Metropolitan Burean of Public Health
文摘AIM: To confirm if p53 mutation could be a routine predictive marker for the prognosis of hepatocellular carcinoma (HCC) patients. METHODS: Two hundreds and forty-four formalin-fixed paraffin-embedded tumor samples of the patients with HCC receiving liver resection were detected for nuclear accumulation of p53. The percent of P53 immunoreactive tumor cells was scored as 0 to 3+ in P53 positive region (【10% -, 10-30% +, 31-50% ++, 】50% +++). Proliferating cell nuclear antigen (PCNA) and some clinicopathological characteristics, including patients' sex, preoperative serum AFP level, tumor size, capsule, vascular invasion (both visual and microscopic), and Edmondson grade were also evaluated. RESULTS: In univariate COX harzard regression model analysis, tumor size, capsule status, vascular invasion, and p53 expression were independent factors that were closely related to the overall survival (OS) rates of HCC patients. The survival rates of patients with 3+ for P53 expression were much lower than those with 2+ or + for P53 expression. Only vascular invasion (P【0.05) and capsule (P【0.01) were closely related to the disease-free survival (DFS) of HCC patients. In multivariate analysis, p53 overexpression (RI 0.5456, P【0.01) was the most significant factor associated with the OS rates of patients after HCC resection, while tumor size (RI 0.5209, P【0.01), vascular invasion (RI 0.5271, P【0.01) and capsule (RI-0.8691, P【0.01) were also related to the OS. However, only tumor capsular status was an independent predictive factor (P【0.05) for the DFS. No significant prognostic value was found in PCNA-LI, Edmondson's grade, patients' sex and preoperative serum AFP level. CONCLUSION: Accumulation of p53 expression, as well as tumor size, capsule and vascular invasion, could be valuable markers for predicting the prognosis of HCC patients after resection. The quantitative immunohistochemical scoring for P53 nuclear accumulation might be more valuable for predicting prognosis of patients after HCC resection than the common qualitative analysis.
文摘AIMS p53 gene is one of the focuses in the study of tu- mour suppressor genes.So far,there is still controversy about the relationship between p53 alterations and clinicolpathological parameters of gastic cancers such as macroscopic classifica- tion,stage,degree of differentiation,depth of tumour invasion and lymphonod metastasis.Tamura has reported that p53 gene mutations mainly occur in the aneuploid tumours.But in China, nothing is reported in this field of study.Our aim is to analyze the relationship between p53 gene mutations and these param- eters including DNA ploidy in Chinese primary gasrtic cancers. METHODS Mutations of the p53 gene in exon5-8 were examined in 20 cases of primary gasric cancer by PCR-SSCP (Polymerase-chain-reaction-single-strand-conforma- tion-polymorphism)analysis. RESULTS Mutations were detected in 8(40%)cases:2 cases in exon5-6,2 cases in exon7,4 cases in exon8.These mutations were detected from stage 0 to stage Ⅲ No significant association was found between p53 gene mutations and the clinicopathological parameters such as macroscopic classifico- tion,degree of histological differentiation,depth of tumour in- vasion and lymphonod metastasis.In addition,66.7%(6 of 9) of aneuploid tumours had p53 mutations and only 18.2%(2 of 11)of diploid tumours had mutations. CONCLUSIONS These results suggest that p53 gene muta- tions are related to DNA ploidy alterations and that p53 gene is one of the important turnout suppressor genes in human gastric cancer.
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, 30 H. pylori-negative and 30 H. pylori-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 (AI, 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). AI 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, AI (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%) was significantly higher (22.09+/-8018%, P【0.01). In phases of metaplasia, dysplasia and gastric cancer in the H. pylori-positive group, AIs 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the Natural Science Foundation of Anhui Province,No.99044312(WY) and No.9741006(LX)Natural Science Foundation of Anhui Educational Commission,No.JL-97-077(WY).
文摘AIM: In hepatocellular carcinoma (HCC) prevalent areas of China, the point mutation of p53 exon7 is highly correlated with Hepatitis B virus(HBV) infection and aflatoxin B intake. While in non-HCC-prevalent areas of China, these factors are not so important in the etiology of HCC. Therefore, the point mutation of p53 exon7 may also be different than that in HCC-prevalent areas of China. The aim of this study is to investigate the status and carcinogenic role of the point mutation of p53 gene exon7 in hepatocellular carcinoma from Anhui Province, a non-HCC-prevalent area in China. METHODS: PCR PCR-SSCP and PCR-RFLP were applied to analyze the homozygous deletion and point mutation of p53 exon7 in HCC samples from Anhui, which were confirmed by DNA sequencing and Genbank comparison. RESULTS: In the 38 samples of hepatocellular carcinoma, no homozygous deletion of p53 exon7 was detected and point mutations of p53 exon7 were found in 4 cases, which were found to be heterozygous mutation of codon 249 with a mutation rate of 10.53%(4/38). The third base mutation(G-T) of p53 codon 249 was found by DNA sequencing and Genbank comparison. CONCLUSION: The incidence of point mutation of p53 codon 249 is lower in hepatocellular carcinoma and the heterozygous mutation of p53 exon7 found in these patients only indicate that they have genetic susceptibility to HCC. p53 codon 249 is a hotspot of p53 exon7 point mutation, suggesting that the point mutation of p53 exon 7 may not play a major role in the carcinogenesis of HCC in Anhui Province, a non-HCC-prevalent area in China.
文摘IM To study the p53 gene mutation and its relationship to aflatoxin B1 exposure in hepatocellular carcinoma (HCC).METHODS Restriction fragment length polymorphism analysis method was used in 62 HCC samples, and DNA direct sequencing in another 45 HCC samples.RESULTS In HCC and AFB1 high and lowrisk areas, 36/52 (69%) and 2/10 (20%) cases were found losing the HaeⅢ allele respectively, suggesting one of the base G mutation at the p53 gene codon 249. Similar results appeared in DNA direct sequencing, 20/35 (57%) and 1/10 (10%) respectively mutated at the codon 249 third base G to C transversion.CONCLUSION In HCC after AFB1 exposure, mutation of p53 gene is fixed at codon 249 third base and take the form of G to T transversion. This is a definite marker of mutation which is induced by AFB1 mutagen. It is applicable for molecular epidemiologic survey of the sufferers of AFB1 among HCC cases and for discovering more unknown natural AFB1 contaminated areas..
基金ThisstudywassupportedbytheMinistryofHealth (No .970 0 0 0 )
文摘OBJECTIVE: To explore new methods for the early diagnosis of pancreatic cancer through detection of K-ras and p53 mutations in pancreatic juice and stool. METHODS: 201 patients in PUMC Hospital from 1994 - 2000 and 60 control individuals were enrolled in this study. K-ras point mutation was detected by PCR-RFLP while p53 mutation was detected by PCR-SSCP. RESULTS: K-ras mutation was found in pancreatic juice in 87.8% (36/41) of pancreatic cancer patients and 23.5% (4/17) of benign pancreatic disease patients. In 261 stool specimens, amplification found mutations successfully in 235 patients (90%). K-ras mutation was found in stool in 88% (66/75) of pancreatic cancer patients, 51.1% (24/47) of benign pancreatic disease patients and 19.6% (9/46) of normal individuals. p53 mutation was found in pancreatic juice in 47.4% (18/38) of pancreatic cancer patients and 12.5% (2/16) of benign pancreatic disease patients. p53 mutation was found in stool in 37.1% (23/62) and 19.1% (4/21) of chronic pancreatitis patients. CONCLUSION: K-ras mutation in pancreatic juice has higher diagnosis sensitivity and specificity, and therefore may be used as a supplement in the diagnosis of pancreatic cancer. Detection of K-ras mutation combined with p53 mutation in stool can aid in the screening of pancreatic cancer.
文摘OBJECTIVE: To investigate the relationship between p53 gene and tumors of adipose tissue at the level of protein and gene. METHODS: Immunohistochemical LSAB, PCR-SSCP and DNA sequencing were used in 82 cases. RESULTS: p53 protein is expressed only in liposarcomas, in which the positive staining rate was 48.08% (25/52). In different subtypes of liposarcomas, the positive staining rate in well differentiated liposarcomas was 30.00% (9/30), which is much lower than that of the poorly differentiated liposarcomas (P ATC) were detected by DNA sequencing. Another heterozygotic cosense mutation may exist at exon 6 codon 221 of p53 gene (GAG-->GAA). CONCLUSIONS: The data suggest that the p53 protein has a relationship with development, differentiation and malignancy of liposarcoma. Detecting the level of p53 protein expression may be valuable in evaluating the level of differentiation and malignancy of liposarcoma. There appear point mutation on exon 8, 6 of p53 gene.
文摘Objective： To investigate the mechanism of herb cake-partitioned moxibustion treating ulcerative colitis （UC） from the relationship between expression of p53 and C-myc protein, and morbidity of UC. Methods： Rats model of UC was made with immune methods and local stimulation. Forty SD rats were divided into normal, model, herb cake-partitioned, and mild moxibustion group by a random number table, 10 rats in each group. Hanging moxibustion in the mild moxibustion group was applied to Tianshu （ST 25） and Qihai （CV 6） for 10 rain. Two moxa cones of herb cake-partitioned moxibustion were applied to the same acupoints respectively, in the herb cake-partitioned moxibustion group. Expression of p53 and C-myc protein was measured with immuno- histochemistical method in the colonic tissue of rats with UC. Results： Postive area, strength, and the immunohistochemistry index of the expression of p53 and C-myc protein were found more in the model rats than those in the normal rats （P〈0.01）, whereas less in the herb cake-partitioned moxibustion and mild moxibustion groups than those in the model group （P〈0.01）. Conclusion： p53 and C-myc play important roles in the morbidity and development of UC, and herb cake-partitioned moxibustion could regulate the expression of p53 and C-myc protein in the colonic tissue of UC rats.
文摘The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (MVD) have been evaluated and found to be of prognostic significance. Body fluid (particularly blood and urinary) testing for biomarkers is easily accessible and useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum, and its genetic alterations in HCC are other important trends. More attention should be paid to these two areas in future. As the progress of the human genome project advances, so does a clearer understanding of tumor biology, and more and more new prognostic markers with high sensitivity and specificity will be found and used in clinical assays. However, the combination of some items, i.e., the pathological features and some biomarkers mentioned above, seems to be more practical for now.
文摘Background Gene therapy and epigenetic therapy have gained more attention in cancer treatment. However, the effect of a combined treatment of gene therapy and epigenetic therapy on head and neck squamous cell carcinoma have not been studied yet. To study the mechanism and clinical application, human laryngeal carcinoma cell （Hep-2） tumor-bearing mice were used. Methods A xenograft tumor model was established by the subcutaneous inoculation of Hep-2 cells in the right armpit of BALB/c nu/nu mice. The mice with well-formed tumor were randomly divided into six groups. Multisite injections of rAd-p53 and/or 5-aza-dC were used to treat tumor. Tumor growth was monitored by measuring tumor volume and growth rate. p53 and E-cadherin protein levels in tumor tissues were detected by immunohistochemical staining. The mRNA levels were monitored with FQ-PCR. Results Gene therapy was much more effective than single epigenetic therapy and combined therapy. The gene therapy group has the lowest tumor growth rate and the highest expression levels of p53 and E-cadherin. Conclusions The combined treatment of gene and epigenetic therapy is not suggested for treating head and neck carcinoma, because gene therapy shows an antagonistic effect to epigenetic therapy. However, the mechanisms of action are still unclear.
