In the world,hepatocellular carcinoma(HCC)is among the top 10 most prevalent malignancies.HCC formation has indeed been linked to numerous etiological factors,including alcohol usage,hepatitis viruses and liver cirrho...In the world,hepatocellular carcinoma(HCC)is among the top 10 most prevalent malignancies.HCC formation has indeed been linked to numerous etiological factors,including alcohol usage,hepatitis viruses and liver cirrhosis.Among the most prevalent defects in a wide range of tumours,notably HCC,is the silencing of the p53 tumour suppressor gene.The control of the cell cycle and the preservation of gene function are both critically important functions of p53.In order to pinpoint the core mechanisms of HCC and find more efficient treatments,molecular research employing HCC tissues has been the main focus.Stimulated p53 triggers necessary reactions that achieve cell cycle arrest,genetic stability,DNA repair and the elimination of DNA-damaged cells’responses to biological stressors(like oncogenes or DNA damage).To the contrary hand,the oncogene protein of the murine double minute 2(MDM2)is a significant biological inhibitor of p53.MDM2 causes p53 protein degradation,which in turn adversely controls p53 function.Despite carrying wt-p53,the majority of HCCs show abnormalities in the p53-expressed apoptotic pathway.High p53 in-vivo expression might have two clinical impacts on HCC:(1)Increased levels of exogenous p53 protein cause tumour cells to undergo apoptosis by preventing cell growth through a number of biological pathways;and(2)Exogenous p53 makes HCC susceptible to various anticancer drugs.This review describes the functions and primary mechanisms of p53 in pathological mechanism,chemoresistance and therapeutic mechanisms of HCC.展开更多
DEAR EDITOR,Despite the generally increased cancer risk in large,long-lived organisms,cetaceans,among the largest and longest-living mammals,appear to possess a counteracting mechanism.Nevertheless,the genetic basis u...DEAR EDITOR,Despite the generally increased cancer risk in large,long-lived organisms,cetaceans,among the largest and longest-living mammals,appear to possess a counteracting mechanism.Nevertheless,the genetic basis underlying this mechanism remains poorly understood.The p53 pathway serves as an ideal target for studying the mechanisms behind cancer resistance,as most cancer types have evolved strategies to circumvent its suppressive functions.展开更多
AIM To study the correlationship between the changes of p53, Waf1p21 and the cell proliferation determined by PCNA at different stages of human esophageal carcinogenesis. METHODS Biopsied and resected esophageal ti...AIM To study the correlationship between the changes of p53, Waf1p21 and the cell proliferation determined by PCNA at different stages of human esophageal carcinogenesis. METHODS Biopsied and resected esophageal tissues from a high risk population for esophageal cancer in northern China were used in this study. All the specimens were fixed with 85% alcohol and further processed with routine histology. The avidin biotin peroxidase complex (ABC) method was used for the detection of p53, Waf1p21 and PCNA. RESULTS The strong nuclear staining for p53, Waf1p21 and PCNA was observed in the normal esophageal epithelium and the epithelia with different severities of lesions. As the lesions progressed to dysplasia (DYS) and to esophageal squamons cell carcinoma (SCC), the percentage of Waf1p21 immunoreactivity decreased. The number of Waf1p21 immunostaining positive cells increased slightly from normal to basal cell hyperplasia (BCH), but there was no further increase in DYS and in SCC. The total number of positive cells for Waf1p21 stain appeared to be lower than that of p53 in normal and BCH esophageal epithelia and much lower in DYS and SCC. The Waf1p21 positive immunostaining cells were located at the third and forth cell layers in half of the samples examined, which was 2~4 cell layers higher than that of PCNA and p53 in the same histological categories of normal, BCH and DYS. CLNCLUSION The low levels of Waf1p21 at the stage of DYS may be related to a functional loss of p53. Other mechanisms may also be responsible to the lack of Waf1p21 expression in DYS and SCC.展开更多
AIM To evaluate the relationship between expression of ras, p53, bcl 2 gene products, and hepatocarcinogenesis since endotoxemia produced from lipopolysaccharide admi nistration and/or the hypophagocytic state of ...AIM To evaluate the relationship between expression of ras, p53, bcl 2 gene products, and hepatocarcinogenesis since endotoxemia produced from lipopolysaccharide admi nistration and/or the hypophagocytic state of splenectomy significantly accelerated hepatocarcinogenesis induced by thioacetamide. 〖WTH4〗METHODS〓〖WTXFZ〗The hepatocarcinoma model was induced by oral intake of 0 03% thioacetamide for six months. During the induction of hepatocarcinoma model, rats were additionally treated with splenectomy and/or lipopolysaccharide administration. The techniques of flow cytometry, immunohistochemistry and immunoelectronmicroscopy were applied to quantitative analysis of the expression of oncogene proteins. RESULTS In this model system, overexpression of ras p21 protein mainly occurred on precancerous cell population or in early stage of hepatocyte transformation. And the levels of ras p21 declined when nuclear DNA aneuploid increased. Expression of bcl 2 protein slowly and steadily rose with more hepatocytes staying in S+G2M phases as the hepatocarcinoma became more malignant. P53 was moderately expressed during the hepatocarcinogenesis. There was no statistical correlation between endotoxemia levels and the changes of ras, p53 and bcl 2 gene products. CONCLUSION Over expression of oncogene ras p21 was likely to be a precursor of the premalignant hepatocytes and it might be responsible for the initiation of hepatocarcinogenesis. Bcl 2 protein expression is proportional to the severity of the malignancies. P53 may be a key pathway on the transformation and development of hepatocarcinoma. This study confirmed the hypothesis that there are multiple genes and multiple steps involved in hepatocarcinogenesis. Expressions of oncogene proteins reflected the properties of the premalignant and malignant cells, but not directly related to endotoxemia statistically.[JP]展开更多
Objective: To detect the expression of hMSH2, hMLH1 and p53 in gastric epithelial cells with and without Helicobactcr pylori (H. pylori) infection and investigate the relationship between H. pylori infection and th...Objective: To detect the expression of hMSH2, hMLH1 and p53 in gastric epithelial cells with and without Helicobactcr pylori (H. pylori) infection and investigate the relationship between H. pylori infection and these genes in gastric carcinogenesis. Methods: H. pylori infection was detected by rapid urease tests. Expression of hMSH2, hMLHland p53 in gastric cancer (GC) tissue, its adjacent mucosa, gastritic mucosa and normal mucosa was assessed by immunohistochemistry SP method. Results: Positive expression rate of hMSH2 in GC tissue (62.7%) was higher than those in adjacent mucosa (29.4%), gastritic mucosa (32.4%) and normal mucosa (30.0%) (P〈0.001). Positive rate of hMSH2 in poorly differentiated adenocarcinoma (76.4%) was higher than those in other carcinomas (54.3%, 53.1%) (P〈0.05). Positive expression rate of hMLH1 in GC tissue (64.3%) mucosa (82.4%) and normal mucosa (80.0%) was lower than those in adjacent mucosa (84.4%), gastritic (P〈0.01). Positive rate of hMLH1 in mucoid carcinoma (43.7%) was lower than those in other carcinomas (78.2%, 64.7%) (P〈0.01). Positive expression rate of p53 in GC tissue (51.9%) was higher than those in adjacent mucosa (3.1%), gastritic mucosa (0.0%) and normal mucosa (0.0%) (P〈0.001). Positive rate of p53 in well differentiated adenocarcinoma (32.6%) was lower than those in other carcinomas (58.8%, 68.7%) (P〈0.01). Positive rates of hMSH2 and hMLH1 in GC with H. pylori infection were lower than those without the infection, respectively (P〈0.05). Positive rate of p53 in GC with H. pylori infection (61.4%) was higher than that without the infection (40.6%) (P〈0.05). Conclusion: Gastric carcinogenesis may be associated with abnormal expression of hMSH2, hMLH1 and p53; H. pylori infection affecting expression of these genes may be one of its carcinogenic mechanisms.展开更多
AIM To investigate hepatocarcinogenesis by detecting the effect of HCV NS 3 protein on P53 protein expression in hepatocellular carcinoma (HCC) and pericarcinomatous liver tissue (PCLT). METHODS The expression of ...AIM To investigate hepatocarcinogenesis by detecting the effect of HCV NS 3 protein on P53 protein expression in hepatocellular carcinoma (HCC) and pericarcinomatous liver tissue (PCLT). METHODS The expression of HCV NS 3 and P53 protein was detected with immunohistochemical technique (SP method) in specimens of HCC and PCLT from 47 patients with negative HBV. RESULTS The positive rate of HCV NS 3 protein was lower in HCC (62%) than in PCLT (83%) ( P <0 025). The better differentiaton of cancer cells, the stronger expression of HCV NS 3 protein ( P <0 025). The positive rate of P53 protein in HCC (81%) was higher than in PCLT (47%) ( P <0 025). The worse differentiaton of cancer cells, the stronger expression of P53 protein ( P <0 05). The P53 protein expression was not correlated with the HCV NS 3 protein expression in HCC ( P >0 5), whereas their expression was closely related to PCLT ( P <0 01), and the expression rate of P53 protein in the cases of positive HCV NS 3 protein was higher than that in the cases of negative HCV NS 3 protein. CONCLUSION HCV NS 3 protein may exert its hepatocarcinogenic effect in early stage on host cells by endogenous pathway which may bring about mutation of p53 gene and transformation of hepatocytes.展开更多
Objective:To investigate the effect of vascular endothelial growth factor(VEGF),P53 and telomerase on angiogenesis in gastric carcinoma tissue.Methods:A total of 95 surgical resection samples of gastric cancer tissue ...Objective:To investigate the effect of vascular endothelial growth factor(VEGF),P53 and telomerase on angiogenesis in gastric carcinoma tissue.Methods:A total of 95 surgical resection samples of gastric cancer tissue after pathological diagnosis are collected to observe the VEGF,P53 and telomerase expression using immunohistochemical methods.Relationship between their expression and its influence on angiogenesis in gastric carcinoma tissue were analyzed.Results:Microvascular density(MVD)and the expression of VEGF,P53 and telomerase were positively correlated.Expression of VEGF and P53 protein were related to tumor type and lymph metastasis,and also a correlation was observed between P53 and VEGF.The telomerase expression had no correlation with VEGF,and P53.Conclusions:VEGF angiogenesis has a angiogenesis promoting effect on gastric cancer tissue development and plays an important role in tumor generation and metastasis.Mutant P53 promotes the tumor angiogenesis generation by adjusting VEGF.Telomerase has a certain role in promoting activity of angiogenesis through different way rather than P53.展开更多
BACKGROUND: It is of significance for single nucleotide polymorphisms (SNPs), a difference of rank, which exists widely in biology, genetics and other fields. OBJECTIVE: To detect polymorphism sites in exon-4 of p...BACKGROUND: It is of significance for single nucleotide polymorphisms (SNPs), a difference of rank, which exists widely in biology, genetics and other fields. OBJECTIVE: To detect polymorphism sites in exon-4 of p53 gene, promotor of Fas gene and intron-7 of Fas gene of healthy people in Han nationality in Zhejiang province. DESIGN: Simple random sampling. SETTING: Department of Surgery of the 118 Hospital of Chinese PLA.PARTICIPANTS: A total of 80 healthy people in Han nationality were selected from hospitals in Zhejiang province from August 2005 to January 2006. There were 43 males and 37 females aged from 3 to 78 years with the mean age of 39.5 years, and all subjects were consent. DNA which was used in genetic analysis was selected from peripheral venous blood of all subjects and maintained at -20℃.METHODS: Polymorphism sites in exon-4 of p53 gene, promotor of Fas gene and intron-7 of Fas gene were detected with directly DNA sequencing technique. MAIN OUTCOME MEASURES : Polymorphism sites in exon-4 of p53 gene, promotor of Fas gene and intron-7 of Fas gene of healthy people in Han nationality in Zhejiang province. RESULTS: A total of 80 samples were involved in the final analysis. SNPs sites were found at the 119^th base of exon-4 of p53 gene (the 72^nd codon of p53 gene), the 670^th base of upper start codon in promotor of Fas gene (Fas-670), and the 995^th base of intron-7 of Fas gene, especially SNPs in the 995^th base of intron-7 pf Fas gene, i.e. C→A transversion, was a new site.CONCLUSION : One unknown SNPs site is discovered in intron-7 of Fas gene of people in Han nationality in Zhejiang province. This study also proves that the 72^nd codon exists in p53 gene and the -670 polymorphism site exists in promotor of Fas gene.展开更多
Objective: Polycystic kidney disease(PKD) is the major cause of kidney failure and mortality in humans. It has always been suspected that the development of cystic kidney disease shares features with tumorigenesis, al...Objective: Polycystic kidney disease(PKD) is the major cause of kidney failure and mortality in humans. It has always been suspected that the development of cystic kidney disease shares features with tumorigenesis, although the evidence is unclear.Methods: We crossed p53 mutant mice(p53N236S, p53S) with Werner syndrome mice and analyzed the pathological phenotypes.The RNA-seq, ss GSEA analysis, and real-time PCR were performed to dissect the gene signatures involved in the development of disease phenotypes.Results: We found enlarged kidneys with fluid-filled cysts in offspring mice with a genotype of G3mTerc^(-/-)WRN^(-/-)p53^(S/S)(G3TM).Pathology analysis confirmed the occurrence of PKD, and it was highly correlated with the incidence of tumorigenesis. RNA-seq data revealed the gene signatures involved in PKD development, and demonstrated that PKD and tumorigenesis shared common pathways, including complement pathways, lipid metabolism, mitochondria energy homeostasis and others. Interestingly, this G3TM PKD and the classical PKD1/2 deficient PKD shared common pathways, possibly because the mutant p53S could regulate the expression levels of PKD1/2, Pkhd1, and Hnf1b.Conclusions: We established a dual mouse model for PKD and tumorigenesis derived from abnormal cellular proliferation and telomere dysfunction. The innovative point of our study is to report PKD occurring in conjunction with tumorigenesis. The gene signatures revealed might shed new light on the pathogenesis of PKD, and provide new molecular biomarkers for clinical diagnosis and prognosis.展开更多
In the present experiment,an inhibitor of superoxide dismutase(SOD),diethyldithiocarbamate(DETC),was used to decrease SOD activity for the observation of the relation between SOD activity and carcinogenesis and the ex...In the present experiment,an inhibitor of superoxide dismutase(SOD),diethyldithiocarbamate(DETC),was used to decrease SOD activity for the observation of the relation between SOD activity and carcinogenesis and the expression of P53 protein in vivo.144 Wistar rats were used for the Present study.The results showed that the SOD activity reduction by DETC resulted markedly in the promotion of the carcinogenesis and the expression of P53 protein in the lung tissues,but the increase of SOD activity by the addition of plus SOD inhibited the pathological changes significantly.The frequency of the pathological lesions and Positive P53 expression are 36/42 and 8/42 in the animals without DETC and SOD:16/52 and 4/52 in the animals with SOD and 46/50 and 26/50 in the animals with DETC respectively.The results reported in this Paper suggest that:(1) the decrease of SOD activity enhanced the carcinogenesis induced by chemical carcinogen;(2) P53 gene may be associated with the process of tumorigenesis;and(3) at the same time the abnormal expression of P53 protein may be associated with the transition from premalignant lesions to carcinoma.展开更多
Objective: To investigate the relationship of ovcrexpression of p53 protein with angiogenesis and prog-nosis in patients with osteosarcoma. Methods: The edpression of p53 protein. vascular endothelial growth factor(VE...Objective: To investigate the relationship of ovcrexpression of p53 protein with angiogenesis and prog-nosis in patients with osteosarcoma. Methods: The edpression of p53 protein. vascular endothelial growth factor(VEGF ) and intratumoral microvessel density (MVD) were determined with immunohistochernistry and morphometry in 80 cases of osteosarcoma. Results: The overexpression of p53 protein was closely correlated with the ex ∈preswon of VEGF and the value of MVD. All the three were important factors affecting the prognosis of osteosarcoma. VEGF was relatively the most important factor to predict the outcome of paticnts with osteosarcoma, Pc3positivity the second and MVD the third. Conclusion: p53 protein exerts regulative effects on VEGF and MVD.p53 overexpression is one of the important angiogenic phenotypes of angiogenesis in osteosarcoma and p53 protein,VEGF and MVD might be valuable prognostic indicators for patients with osteosarcoma.展开更多
To investigate the association between polymorphisms (SNP) in the p53 and murine double minute 2 homolog (MDM2) promoter 309 in cervical carcinogenesis. SNP at p53 codon 72 polymorphisms and MDM2 promoter 309 (T/G) to...To investigate the association between polymorphisms (SNP) in the p53 and murine double minute 2 homolog (MDM2) promoter 309 in cervical carcinogenesis. SNP at p53 codon 72 polymorphisms and MDM2 promoter 309 (T/G) together with human papillomavirus (HPV) types were examined in a total of 187 cervical smear samples using real time PCR. 27 cases with HPV types 16 and/or 18 had significantly higher frequency of the TG + GG genotype and G allele than 56 with other types of high-risk HPV (P = 0.0136). 48 cases with HPV types 52 and/or 58 had significantly higher frequency of the TG + GG genotype and G allele than 56 with other types of high-risk HPV (P = 0.001). Our studies have demonstrated that the frequency of G allele in MDM2 promoter 309 increased from LSIL to HSIL and that there was an increased OR for G allele in HSIL cases with high-risk HPV types including 52 and 58. It is known that geographically different oncogenic HPV types 52 and 58 are more prevalent than 16 and 18 in a Japanese population.展开更多
INTRODUCTIONIn order to study the relationship between oncogeneexpression and HCC generation,we observed theprecancerous hepatic GGT loci,IGF-Ⅱ,p53 andp21 expression during hepatocarcinogenesis of treeshrew induced b...INTRODUCTIONIn order to study the relationship between oncogeneexpression and HCC generation,we observed theprecancerous hepatic GGT loci,IGF-Ⅱ,p53 andp21 expression during hepatocarcinogenesis of treeshrew induced by hepatitis B virus (HBV) and/oraflatoxin B1 (AFB1).展开更多
Colorectal cancer(CRC) is one of the most common malignancies with high prevalence and low 5-year survival.CRC is a heterogeneous disease with a complex,genetic and biochemical background.It is now generally accepted ...Colorectal cancer(CRC) is one of the most common malignancies with high prevalence and low 5-year survival.CRC is a heterogeneous disease with a complex,genetic and biochemical background.It is now generally accepted that a few important intracellular signaling pathways,including Wnt/β-catenin signaling,Ras signaling,and p53 signaling are frequently dysregulated in CRC.Patients with mutant p53 gene are often resistant to current therapies,conferring poor prognosis.Tumor suppressor p53 protein is a transcription factor inducing cell cycle arrest,senescence,and apoptosis under cellular stress.Emerging evidence from laboratories and clinical trials shows that some small molecule inhibitors exert anti-cancer effect via reactivation and restoration of p53 function.In this review,we summarize the p53 function and characterize its mutations in CRC.The involvement of p53 mutations in pathogenesis of CRC and their clinical impacts will be highlighted.Moreover,we also describe the current achievements of using p53 modulators to reactivate this pathway in CRC,which may have great potential as novel anti-cancer therapy.展开更多
AIM: To investigate p53 mutation and p21 expression in hepatocarcinogenesis induced by hepatitis B virus (HBV) and aflatoxin B1 (AFB1) in tree shrews, and to reveal the role of these genes in hepatocarcinogenesis.METH...AIM: To investigate p53 mutation and p21 expression in hepatocarcinogenesis induced by hepatitis B virus (HBV) and aflatoxin B1 (AFB1) in tree shrews, and to reveal the role of these genes in hepatocarcinogenesis.METHODS: Tree shrews were divided into four groups:group A, those infected with HBV and fed with AFB1 (n = 39);group B, those infected with HBV alone (n = 28); group C,those fed with AFB1 alone (n = 29); and group D, normal controls (n = 20). The tree shrews underwent liver biopsies once every 15 wk. Expression of p53 and p21 proteins and genes in the biopsies and tumor tissues of the experimental tree shrews was detected, respectively, by immunohistochemistry,and by Southem blotting and reverse transcription-polymerase chain reaction and sequencing.RESULTS: The incidence of hepatocellular carcinomas (HCC) was higher in group A (66.7%) than that in group B (3.57%) and C (30%). The time of HCC occurrence was also earlier in group A than that in group C (120.0±16.6 wk vs 153.3±5.8 wk, respectively, P<0.01). p53 protein was not detected by immunohistochemistry in all groups before the 75^th wk of the experiment. At the 105^th wk, the positive rates fo p53 were 78.6%, 60% and 71.4% in groups A, B and C, respectively, which were significantly higher than that in group D (10%) (all P<0.05). An abnormal band of p53 gene was observed in groups A and C. The mutation points of p53gene in tree shrews with HCC were at codons 275, 78 and 13. The nucleotide sequence and amino acid sequence of tree shrew's wild-type p53 showed 91.7% and 93.4% homologies with those of human p53,respectively. The immunopositivity for p21 was found before HCC development. The incidence of HCC was significantly higher in tree shrews that were positive for p21 than those negative for p21 (80.0% vs 11.0%, P<0.001).The incidence of HCC in p21 positive animals in group A was significantly higher than those positive for p21 in group C (P<O.05).CONCLUSION: A remarkable synergistic effect on HCC development exists between HBV and AFB1. p53 mutation promotes the development of HCC. HBV and AFB1 may synergistically induce p53 gene mutation, and stimulate ras gene expression, ras gene is activated at the earlier stage during hepatocarcinogenesis, p21 protein may be an early marker, and the alterations of p53 may be a late event in the development of HCC.展开更多
AIM: To explore the relationship between clinicobiological behavior and the expression levels of telomerase activity, apoptosis, p53 gene and bcl-2 gene in gastrointestinal stromal tumors (GISTs). METHODS: The int...AIM: To explore the relationship between clinicobiological behavior and the expression levels of telomerase activity, apoptosis, p53 gene and bcl-2 gene in gastrointestinal stromal tumors (GISTs). METHODS: The intensity of telomerase activity, apoptosis, p53 and bcl-2 expression in GISTs were detected by telomeric repeat amplification protocol, in situ end-labeling technique, and immunohistochemistry, respectively. RESULTS: The positive rates of telomerase activity of malignant GIST, potential malignant GIST and benign GIST were 85% (17/20), 22.8% (2/9) and 0 (0/9), respectively. The apoptosis indices of malignant GIST, potential malignant GIST, and benign GIST were 11.7±5.4, 30.2±5.6 and 45.2 ±7.2, respectively. The intensity of telomerase activity and apoptosis were related to the biological characteristics of GISTs (85% vs 22.8%, 0, 0; P 〈 0.01 or 11.7±5.4 vs 30.2±5.6, 45.2±7.2, 72.1±9.3; P 〈 0.05). The intensity of telomerase activity was negatively correlated with cellular apoptosis (22.9±8.4 vs 9.5±5.7, P 〈 0.01). The intensity of telomerase activity was positively correlated with/753, bcl-2 expression (40.0% vs 78.9%, 40.0% vs 84.2%; P 〈 0.05). CONCLUSION: The detection of telomerase activity, apoptosis and its control genes in GIST will be helpful for the discrimination of the malignant and benign GIST and evaluation of the prognosis.展开更多
BACKGROUND Growth arrest-specific gene 2(GAS2)plays a role in modulating in reversible growth arrest cell cycle,apoptosis,and cell survival.GAS2 protein is universally expressed in most normal tissues,particularly in ...BACKGROUND Growth arrest-specific gene 2(GAS2)plays a role in modulating in reversible growth arrest cell cycle,apoptosis,and cell survival.GAS2 protein is universally expressed in most normal tissues,particularly in the liver,but is depleted in some tumor tissues.However,the functional mechanisms of GAS2 in hepatocellular carcinoma(HCC)are not fully defined.AIM To investigate the function and mechanism of GAS2 in HCC.METHODS GAS2 expression in clinic liver and HCC specimens was analyzed by real-time PCR and western blotting.Cell proliferation was analyzed by counting,MTS,and colony formation assays.Cell cycle analysis was performed by flow cytometry.Cell apoptosis was investigated by Annexin V apoptosis assay and western blotting.RESULTS GAS2 protein expression was lower in HCC than in normal tissues.Overexpression of GAS2 inhibited the proliferation of HCC cells with wide-type p53,while knockdown of GAS2 promoted the proliferation of hepatocytes(P<0.05).Furthermore,GAS2 overexpression impeded the G1-to-S cell cycle transition and arrested more G1 cells,particularly the elevation of sub G1(P<0.01).Apoptosis induced by GAS2 was dependent on p53,which was increased by etoposide addition.The expression of p53 and apoptosis markers was further enhanced when GAS2 was upregulated,but became diminished upon downregulation of GAS2.In the clinic specimen,GAS2 was downregulated in more than 60%of HCCs.The average fold changes of GAS2 expression in tumor tissues were significantly lower than those in paired non-tumor tissues(P<0.05).CONCLUSION GAS2 plays a vital role in HCC cell proliferation and apoptosis,possibly by regulating the cell cycle and p53-dependent apoptosis pathway.展开更多
AIM To investigate the effect of Boschniakiarossica(BR)extract on expression of GST-P,p53 and p21<sup>ras</sup>proteins in early stage of chemicalhepatocarcinogenesis in rats and its anti-inflammatory ac...AIM To investigate the effect of Boschniakiarossica(BR)extract on expression of GST-P,p53 and p21<sup>ras</sup>proteins in early stage of chemicalhepatocarcinogenesis in rats and its anti-inflammatory activities.METHODS The expression of tumor marker-placental form glutathione S-transferase(GST-P),p53 and p21<sup>ras</sup>proteins were investigated byimmunohistochemical techniques and ABCmethod.Anti-inflammatory activities of BR werestudied by xylene and croton oil-induced mouseear edema,carrageenin,histamine and hotscald-induced rat pow edema,adjuvant-inducedrat arthritis and cotton pellet-induced mousegranuloma formation methods.RESULTS The 500 mg/kg of BR-H<sub>2</sub>O extractfractionated from BR-Methanol extract hadinhibitory effect on the formation of DEN-inducedGST-P-positive foci in rat liver(GST-P stainingwas 78% positive in DEN+AAF group vs 20%positive in DEN+AAF+BR group,P【0.05)andthe expression of mutant p53 and p21<sup>ras</sup>proteinwas lower than that of hepatic preneoplasticlesions(33% and 22% positive respectively inDEN+AAF group vs negative in DEN+AAF+BRgroup).Both CH<sub>2</sub>Cl<sub>2</sub> and H<sub>2</sub>O extracts from BRhad anti-inflamatory effect in xylene and crotonoil-induced mouse ear edema(inhibitory rateswere 26%-29% and 35%-59%,respectively). BR-H<sub>2</sub>O extract exhibited inhibitory effect incarrageenin,histamine and hot scald-inducedhind paw edema and adjuvant-induced arthritis inrats and cotton pellet-induced granulomaformation in mice.CONCLUSION BR extract exhibited inhibitory effect on formation of preneoplastic hepatic foci in early stage of rat chemical hepato-carcinogenesis. Both CH<sub>2</sub>CI<sub>2</sub> and H<sub>2</sub>O extracts from BR exerted anti-inflammatory effect in rats and mice.展开更多
AIM: To investigate the possible roles of p53 and C-mycgenes in the primary hepatocellular carcinogenesis and therelationship between the liver hyperplastic nodule(LHN) andhepatocellular carcinoma(HCC).METHODS: The ex...AIM: To investigate the possible roles of p53 and C-mycgenes in the primary hepatocellular carcinogenesis and therelationship between the liver hyperplastic nodule(LHN) andhepatocellular carcinoma(HCC).METHODS: The expression of p53 and C-myc genes wasdetected immunohist-ochemically in 73 and 60 cases of HCCand pericarcinomatous tissues, respectively .RESULTS: The positive expression of p53 in HCC wassignificantly higher than that in pericarcinomatous tissues(P<0.05). In pericarcinomatous tissues, the p53 expressionwas observed only in LHN, but not in liver cirrhosis (LC) andnormal liver tissues. The positive expression rate of C-mycin HCC or LHN was significantly higher than that in LC ornormal liver tissues (P<0.05 and P<0.01), however, nosignificant difference was found between HCC and LHN(P>0.05). The positive expression rate of p53 and C-myc inHCC was correlated with the histological differentiation, thatin the poorly differentiated was significantly higher than thatin well differentiated samples (P<0.05).CONCLUSION: The overexpression of p53 and C-myc genesmight play a role in the carcinogenesis of HCC; And LHNseems a preneoplastic lesion related to hepatocarcinogenesis;No evidence supports that LC contribute directly to thehepatocarcinogenesis.展开更多
AIM: This study investigated the anti-cancer effect ofcombined quercetin and a recombinant adenovirus vectorexpressing the human p53, GM-CSF and B7-1 genes(designated BB-102) on human hepatocellular carcinoma(HCC) cel...AIM: This study investigated the anti-cancer effect ofcombined quercetin and a recombinant adenovirus vectorexpressing the human p53, GM-CSF and B7-1 genes(designated BB-102) on human hepatocellular carcinoma(HCC) cell lines in vitro.METHODS: The sensitivity of HCC cells to anticancer agentswas evaluated by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The viability of cells infectedwith BB-102 was determined by trypan blue exclusion. Theexpression levels of human wild-type p53, GM-CSF and B7-1genes were determined by Western blot, enzyme-linkedimmunosorbent assay (ELISA) and flow cytometric analysis,respectively. The apoptosis of BB-102-infected or quercetin-treated HCC cells was detected by terminal deoxynucleotidyltransferase (TdT) assay or DNA ladder electrophoresis.RESULTS: Quercetin was found to suppress proliferation ofhuman HCC cell lines BEL-7402, HUH-7 and HLE, with peaksuppression at 50 μmol/L quercetin. BB-102 infection wasalso found to significantly suppress proliferation of HCC celllines. The apoptosis of BB-102-infected HCC cells was greaterin HLE and HUH-7 cells than in BEL-7402 cells. Quercetin didnot affect the expression of the three exogenous genes inBB-102-infected HCC cells (P>0.05), but it was found to furtherdecrease proliferation and promote apoptosis of BB-102-infected HCC cells.CONCLUSION: BB-102 and quercetin synergeticallysuppress HCC cell proliferation and induce HCC cell apoptosis,suggesting a possible use as a combined anti-cancer agent.展开更多
文摘In the world,hepatocellular carcinoma(HCC)is among the top 10 most prevalent malignancies.HCC formation has indeed been linked to numerous etiological factors,including alcohol usage,hepatitis viruses and liver cirrhosis.Among the most prevalent defects in a wide range of tumours,notably HCC,is the silencing of the p53 tumour suppressor gene.The control of the cell cycle and the preservation of gene function are both critically important functions of p53.In order to pinpoint the core mechanisms of HCC and find more efficient treatments,molecular research employing HCC tissues has been the main focus.Stimulated p53 triggers necessary reactions that achieve cell cycle arrest,genetic stability,DNA repair and the elimination of DNA-damaged cells’responses to biological stressors(like oncogenes or DNA damage).To the contrary hand,the oncogene protein of the murine double minute 2(MDM2)is a significant biological inhibitor of p53.MDM2 causes p53 protein degradation,which in turn adversely controls p53 function.Despite carrying wt-p53,the majority of HCCs show abnormalities in the p53-expressed apoptotic pathway.High p53 in-vivo expression might have two clinical impacts on HCC:(1)Increased levels of exogenous p53 protein cause tumour cells to undergo apoptosis by preventing cell growth through a number of biological pathways;and(2)Exogenous p53 makes HCC susceptible to various anticancer drugs.This review describes the functions and primary mechanisms of p53 in pathological mechanism,chemoresistance and therapeutic mechanisms of HCC.
基金supported by the National Key Program of Research and Development,Ministry of Science and Technology of China (2022YFF1301600)National Natural Science Foundation of China (32070409,32270453 to S.X.X.)+1 种基金Priority Academic Program Development of Jiangsu Higher Education Institutions to G.Y.and S.X.X.Qing Lan Project of Jiangsu Province to S.X.X.
文摘DEAR EDITOR,Despite the generally increased cancer risk in large,long-lived organisms,cetaceans,among the largest and longest-living mammals,appear to possess a counteracting mechanism.Nevertheless,the genetic basis underlying this mechanism remains poorly understood.The p53 pathway serves as an ideal target for studying the mechanisms behind cancer resistance,as most cancer types have evolved strategies to circumvent its suppressive functions.
文摘AIM To study the correlationship between the changes of p53, Waf1p21 and the cell proliferation determined by PCNA at different stages of human esophageal carcinogenesis. METHODS Biopsied and resected esophageal tissues from a high risk population for esophageal cancer in northern China were used in this study. All the specimens were fixed with 85% alcohol and further processed with routine histology. The avidin biotin peroxidase complex (ABC) method was used for the detection of p53, Waf1p21 and PCNA. RESULTS The strong nuclear staining for p53, Waf1p21 and PCNA was observed in the normal esophageal epithelium and the epithelia with different severities of lesions. As the lesions progressed to dysplasia (DYS) and to esophageal squamons cell carcinoma (SCC), the percentage of Waf1p21 immunoreactivity decreased. The number of Waf1p21 immunostaining positive cells increased slightly from normal to basal cell hyperplasia (BCH), but there was no further increase in DYS and in SCC. The total number of positive cells for Waf1p21 stain appeared to be lower than that of p53 in normal and BCH esophageal epithelia and much lower in DYS and SCC. The Waf1p21 positive immunostaining cells were located at the third and forth cell layers in half of the samples examined, which was 2~4 cell layers higher than that of PCNA and p53 in the same histological categories of normal, BCH and DYS. CLNCLUSION The low levels of Waf1p21 at the stage of DYS may be related to a functional loss of p53. Other mechanisms may also be responsible to the lack of Waf1p21 expression in DYS and SCC.
文摘AIM To evaluate the relationship between expression of ras, p53, bcl 2 gene products, and hepatocarcinogenesis since endotoxemia produced from lipopolysaccharide admi nistration and/or the hypophagocytic state of splenectomy significantly accelerated hepatocarcinogenesis induced by thioacetamide. 〖WTH4〗METHODS〓〖WTXFZ〗The hepatocarcinoma model was induced by oral intake of 0 03% thioacetamide for six months. During the induction of hepatocarcinoma model, rats were additionally treated with splenectomy and/or lipopolysaccharide administration. The techniques of flow cytometry, immunohistochemistry and immunoelectronmicroscopy were applied to quantitative analysis of the expression of oncogene proteins. RESULTS In this model system, overexpression of ras p21 protein mainly occurred on precancerous cell population or in early stage of hepatocyte transformation. And the levels of ras p21 declined when nuclear DNA aneuploid increased. Expression of bcl 2 protein slowly and steadily rose with more hepatocytes staying in S+G2M phases as the hepatocarcinoma became more malignant. P53 was moderately expressed during the hepatocarcinogenesis. There was no statistical correlation between endotoxemia levels and the changes of ras, p53 and bcl 2 gene products. CONCLUSION Over expression of oncogene ras p21 was likely to be a precursor of the premalignant hepatocytes and it might be responsible for the initiation of hepatocarcinogenesis. Bcl 2 protein expression is proportional to the severity of the malignancies. P53 may be a key pathway on the transformation and development of hepatocarcinoma. This study confirmed the hypothesis that there are multiple genes and multiple steps involved in hepatocarcinogenesis. Expressions of oncogene proteins reflected the properties of the premalignant and malignant cells, but not directly related to endotoxemia statistically.[JP]
文摘Objective: To detect the expression of hMSH2, hMLH1 and p53 in gastric epithelial cells with and without Helicobactcr pylori (H. pylori) infection and investigate the relationship between H. pylori infection and these genes in gastric carcinogenesis. Methods: H. pylori infection was detected by rapid urease tests. Expression of hMSH2, hMLHland p53 in gastric cancer (GC) tissue, its adjacent mucosa, gastritic mucosa and normal mucosa was assessed by immunohistochemistry SP method. Results: Positive expression rate of hMSH2 in GC tissue (62.7%) was higher than those in adjacent mucosa (29.4%), gastritic mucosa (32.4%) and normal mucosa (30.0%) (P〈0.001). Positive rate of hMSH2 in poorly differentiated adenocarcinoma (76.4%) was higher than those in other carcinomas (54.3%, 53.1%) (P〈0.05). Positive expression rate of hMLH1 in GC tissue (64.3%) mucosa (82.4%) and normal mucosa (80.0%) was lower than those in adjacent mucosa (84.4%), gastritic (P〈0.01). Positive rate of hMLH1 in mucoid carcinoma (43.7%) was lower than those in other carcinomas (78.2%, 64.7%) (P〈0.01). Positive expression rate of p53 in GC tissue (51.9%) was higher than those in adjacent mucosa (3.1%), gastritic mucosa (0.0%) and normal mucosa (0.0%) (P〈0.001). Positive rate of p53 in well differentiated adenocarcinoma (32.6%) was lower than those in other carcinomas (58.8%, 68.7%) (P〈0.01). Positive rates of hMSH2 and hMLH1 in GC with H. pylori infection were lower than those without the infection, respectively (P〈0.05). Positive rate of p53 in GC with H. pylori infection (61.4%) was higher than that without the infection (40.6%) (P〈0.05). Conclusion: Gastric carcinogenesis may be associated with abnormal expression of hMSH2, hMLH1 and p53; H. pylori infection affecting expression of these genes may be one of its carcinogenic mechanisms.
文摘AIM To investigate hepatocarcinogenesis by detecting the effect of HCV NS 3 protein on P53 protein expression in hepatocellular carcinoma (HCC) and pericarcinomatous liver tissue (PCLT). METHODS The expression of HCV NS 3 and P53 protein was detected with immunohistochemical technique (SP method) in specimens of HCC and PCLT from 47 patients with negative HBV. RESULTS The positive rate of HCV NS 3 protein was lower in HCC (62%) than in PCLT (83%) ( P <0 025). The better differentiaton of cancer cells, the stronger expression of HCV NS 3 protein ( P <0 025). The positive rate of P53 protein in HCC (81%) was higher than in PCLT (47%) ( P <0 025). The worse differentiaton of cancer cells, the stronger expression of P53 protein ( P <0 05). The P53 protein expression was not correlated with the HCV NS 3 protein expression in HCC ( P >0 5), whereas their expression was closely related to PCLT ( P <0 01), and the expression rate of P53 protein in the cases of positive HCV NS 3 protein was higher than that in the cases of negative HCV NS 3 protein. CONCLUSION HCV NS 3 protein may exert its hepatocarcinogenic effect in early stage on host cells by endogenous pathway which may bring about mutation of p53 gene and transformation of hepatocytes.
基金supported by Handan City Technology Bureau Scientific Research Project(No 1023108101-8)
文摘Objective:To investigate the effect of vascular endothelial growth factor(VEGF),P53 and telomerase on angiogenesis in gastric carcinoma tissue.Methods:A total of 95 surgical resection samples of gastric cancer tissue after pathological diagnosis are collected to observe the VEGF,P53 and telomerase expression using immunohistochemical methods.Relationship between their expression and its influence on angiogenesis in gastric carcinoma tissue were analyzed.Results:Microvascular density(MVD)and the expression of VEGF,P53 and telomerase were positively correlated.Expression of VEGF and P53 protein were related to tumor type and lymph metastasis,and also a correlation was observed between P53 and VEGF.The telomerase expression had no correlation with VEGF,and P53.Conclusions:VEGF angiogenesis has a angiogenesis promoting effect on gastric cancer tissue development and plays an important role in tumor generation and metastasis.Mutant P53 promotes the tumor angiogenesis generation by adjusting VEGF.Telomerase has a certain role in promoting activity of angiogenesis through different way rather than P53.
文摘BACKGROUND: It is of significance for single nucleotide polymorphisms (SNPs), a difference of rank, which exists widely in biology, genetics and other fields. OBJECTIVE: To detect polymorphism sites in exon-4 of p53 gene, promotor of Fas gene and intron-7 of Fas gene of healthy people in Han nationality in Zhejiang province. DESIGN: Simple random sampling. SETTING: Department of Surgery of the 118 Hospital of Chinese PLA.PARTICIPANTS: A total of 80 healthy people in Han nationality were selected from hospitals in Zhejiang province from August 2005 to January 2006. There were 43 males and 37 females aged from 3 to 78 years with the mean age of 39.5 years, and all subjects were consent. DNA which was used in genetic analysis was selected from peripheral venous blood of all subjects and maintained at -20℃.METHODS: Polymorphism sites in exon-4 of p53 gene, promotor of Fas gene and intron-7 of Fas gene were detected with directly DNA sequencing technique. MAIN OUTCOME MEASURES : Polymorphism sites in exon-4 of p53 gene, promotor of Fas gene and intron-7 of Fas gene of healthy people in Han nationality in Zhejiang province. RESULTS: A total of 80 samples were involved in the final analysis. SNPs sites were found at the 119^th base of exon-4 of p53 gene (the 72^nd codon of p53 gene), the 670^th base of upper start codon in promotor of Fas gene (Fas-670), and the 995^th base of intron-7 of Fas gene, especially SNPs in the 995^th base of intron-7 pf Fas gene, i.e. C→A transversion, was a new site.CONCLUSION : One unknown SNPs site is discovered in intron-7 of Fas gene of people in Han nationality in Zhejiang province. This study also proves that the 72^nd codon exists in p53 gene and the -670 polymorphism site exists in promotor of Fas gene.
基金supported by National Natural Science Foundation of China (NSFC) (Grant No. 30771194 and 31170735)
文摘Objective: Polycystic kidney disease(PKD) is the major cause of kidney failure and mortality in humans. It has always been suspected that the development of cystic kidney disease shares features with tumorigenesis, although the evidence is unclear.Methods: We crossed p53 mutant mice(p53N236S, p53S) with Werner syndrome mice and analyzed the pathological phenotypes.The RNA-seq, ss GSEA analysis, and real-time PCR were performed to dissect the gene signatures involved in the development of disease phenotypes.Results: We found enlarged kidneys with fluid-filled cysts in offspring mice with a genotype of G3mTerc^(-/-)WRN^(-/-)p53^(S/S)(G3TM).Pathology analysis confirmed the occurrence of PKD, and it was highly correlated with the incidence of tumorigenesis. RNA-seq data revealed the gene signatures involved in PKD development, and demonstrated that PKD and tumorigenesis shared common pathways, including complement pathways, lipid metabolism, mitochondria energy homeostasis and others. Interestingly, this G3TM PKD and the classical PKD1/2 deficient PKD shared common pathways, possibly because the mutant p53S could regulate the expression levels of PKD1/2, Pkhd1, and Hnf1b.Conclusions: We established a dual mouse model for PKD and tumorigenesis derived from abnormal cellular proliferation and telomere dysfunction. The innovative point of our study is to report PKD occurring in conjunction with tumorigenesis. The gene signatures revealed might shed new light on the pathogenesis of PKD, and provide new molecular biomarkers for clinical diagnosis and prognosis.
文摘In the present experiment,an inhibitor of superoxide dismutase(SOD),diethyldithiocarbamate(DETC),was used to decrease SOD activity for the observation of the relation between SOD activity and carcinogenesis and the expression of P53 protein in vivo.144 Wistar rats were used for the Present study.The results showed that the SOD activity reduction by DETC resulted markedly in the promotion of the carcinogenesis and the expression of P53 protein in the lung tissues,but the increase of SOD activity by the addition of plus SOD inhibited the pathological changes significantly.The frequency of the pathological lesions and Positive P53 expression are 36/42 and 8/42 in the animals without DETC and SOD:16/52 and 4/52 in the animals with SOD and 46/50 and 26/50 in the animals with DETC respectively.The results reported in this Paper suggest that:(1) the decrease of SOD activity enhanced the carcinogenesis induced by chemical carcinogen;(2) P53 gene may be associated with the process of tumorigenesis;and(3) at the same time the abnormal expression of P53 protein may be associated with the transition from premalignant lesions to carcinoma.
文摘Objective: To investigate the relationship of ovcrexpression of p53 protein with angiogenesis and prog-nosis in patients with osteosarcoma. Methods: The edpression of p53 protein. vascular endothelial growth factor(VEGF ) and intratumoral microvessel density (MVD) were determined with immunohistochernistry and morphometry in 80 cases of osteosarcoma. Results: The overexpression of p53 protein was closely correlated with the ex ∈preswon of VEGF and the value of MVD. All the three were important factors affecting the prognosis of osteosarcoma. VEGF was relatively the most important factor to predict the outcome of paticnts with osteosarcoma, Pc3positivity the second and MVD the third. Conclusion: p53 protein exerts regulative effects on VEGF and MVD.p53 overexpression is one of the important angiogenic phenotypes of angiogenesis in osteosarcoma and p53 protein,VEGF and MVD might be valuable prognostic indicators for patients with osteosarcoma.
文摘To investigate the association between polymorphisms (SNP) in the p53 and murine double minute 2 homolog (MDM2) promoter 309 in cervical carcinogenesis. SNP at p53 codon 72 polymorphisms and MDM2 promoter 309 (T/G) together with human papillomavirus (HPV) types were examined in a total of 187 cervical smear samples using real time PCR. 27 cases with HPV types 16 and/or 18 had significantly higher frequency of the TG + GG genotype and G allele than 56 with other types of high-risk HPV (P = 0.0136). 48 cases with HPV types 52 and/or 58 had significantly higher frequency of the TG + GG genotype and G allele than 56 with other types of high-risk HPV (P = 0.001). Our studies have demonstrated that the frequency of G allele in MDM2 promoter 309 increased from LSIL to HSIL and that there was an increased OR for G allele in HSIL cases with high-risk HPV types including 52 and 58. It is known that geographically different oncogenic HPV types 52 and 58 are more prevalent than 16 and 18 in a Japanese population.
基金the National Natural Science Foundation of China,No.39260033.
文摘INTRODUCTIONIn order to study the relationship between oncogeneexpression and HCC generation,we observed theprecancerous hepatic GGT loci,IGF-Ⅱ,p53 andp21 expression during hepatocarcinogenesis of treeshrew induced by hepatitis B virus (HBV) and/oraflatoxin B1 (AFB1).
基金Supported by National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiativeNMRC Clinician-Scientist IRG Grant CNIG11nov38(Zhou J)Chng WJ is also supported by NMRC Clinician Scientist Investigator award
文摘Colorectal cancer(CRC) is one of the most common malignancies with high prevalence and low 5-year survival.CRC is a heterogeneous disease with a complex,genetic and biochemical background.It is now generally accepted that a few important intracellular signaling pathways,including Wnt/β-catenin signaling,Ras signaling,and p53 signaling are frequently dysregulated in CRC.Patients with mutant p53 gene are often resistant to current therapies,conferring poor prognosis.Tumor suppressor p53 protein is a transcription factor inducing cell cycle arrest,senescence,and apoptosis under cellular stress.Emerging evidence from laboratories and clinical trials shows that some small molecule inhibitors exert anti-cancer effect via reactivation and restoration of p53 function.In this review,we summarize the p53 function and characterize its mutations in CRC.The involvement of p53 mutations in pathogenesis of CRC and their clinical impacts will be highlighted.Moreover,we also describe the current achievements of using p53 modulators to reactivate this pathway in CRC,which may have great potential as novel anti-cancer therapy.
基金Supported by the National Natural Science Foundation of China,No.39260033Natural Science Foundation of Guangxi,No.0143058
文摘AIM: To investigate p53 mutation and p21 expression in hepatocarcinogenesis induced by hepatitis B virus (HBV) and aflatoxin B1 (AFB1) in tree shrews, and to reveal the role of these genes in hepatocarcinogenesis.METHODS: Tree shrews were divided into four groups:group A, those infected with HBV and fed with AFB1 (n = 39);group B, those infected with HBV alone (n = 28); group C,those fed with AFB1 alone (n = 29); and group D, normal controls (n = 20). The tree shrews underwent liver biopsies once every 15 wk. Expression of p53 and p21 proteins and genes in the biopsies and tumor tissues of the experimental tree shrews was detected, respectively, by immunohistochemistry,and by Southem blotting and reverse transcription-polymerase chain reaction and sequencing.RESULTS: The incidence of hepatocellular carcinomas (HCC) was higher in group A (66.7%) than that in group B (3.57%) and C (30%). The time of HCC occurrence was also earlier in group A than that in group C (120.0±16.6 wk vs 153.3±5.8 wk, respectively, P<0.01). p53 protein was not detected by immunohistochemistry in all groups before the 75^th wk of the experiment. At the 105^th wk, the positive rates fo p53 were 78.6%, 60% and 71.4% in groups A, B and C, respectively, which were significantly higher than that in group D (10%) (all P<0.05). An abnormal band of p53 gene was observed in groups A and C. The mutation points of p53gene in tree shrews with HCC were at codons 275, 78 and 13. The nucleotide sequence and amino acid sequence of tree shrew's wild-type p53 showed 91.7% and 93.4% homologies with those of human p53,respectively. The immunopositivity for p21 was found before HCC development. The incidence of HCC was significantly higher in tree shrews that were positive for p21 than those negative for p21 (80.0% vs 11.0%, P<0.001).The incidence of HCC in p21 positive animals in group A was significantly higher than those positive for p21 in group C (P<O.05).CONCLUSION: A remarkable synergistic effect on HCC development exists between HBV and AFB1. p53 mutation promotes the development of HCC. HBV and AFB1 may synergistically induce p53 gene mutation, and stimulate ras gene expression, ras gene is activated at the earlier stage during hepatocarcinogenesis, p21 protein may be an early marker, and the alterations of p53 may be a late event in the development of HCC.
文摘AIM: To explore the relationship between clinicobiological behavior and the expression levels of telomerase activity, apoptosis, p53 gene and bcl-2 gene in gastrointestinal stromal tumors (GISTs). METHODS: The intensity of telomerase activity, apoptosis, p53 and bcl-2 expression in GISTs were detected by telomeric repeat amplification protocol, in situ end-labeling technique, and immunohistochemistry, respectively. RESULTS: The positive rates of telomerase activity of malignant GIST, potential malignant GIST and benign GIST were 85% (17/20), 22.8% (2/9) and 0 (0/9), respectively. The apoptosis indices of malignant GIST, potential malignant GIST, and benign GIST were 11.7±5.4, 30.2±5.6 and 45.2 ±7.2, respectively. The intensity of telomerase activity and apoptosis were related to the biological characteristics of GISTs (85% vs 22.8%, 0, 0; P 〈 0.01 or 11.7±5.4 vs 30.2±5.6, 45.2±7.2, 72.1±9.3; P 〈 0.05). The intensity of telomerase activity was negatively correlated with cellular apoptosis (22.9±8.4 vs 9.5±5.7, P 〈 0.01). The intensity of telomerase activity was positively correlated with/753, bcl-2 expression (40.0% vs 78.9%, 40.0% vs 84.2%; P 〈 0.05). CONCLUSION: The detection of telomerase activity, apoptosis and its control genes in GIST will be helpful for the discrimination of the malignant and benign GIST and evaluation of the prognosis.
基金Supported by the National Natural Science Foundation of China,No.81702777Natural Science Foundation of Guangdong Province,No.2015A030310053
文摘BACKGROUND Growth arrest-specific gene 2(GAS2)plays a role in modulating in reversible growth arrest cell cycle,apoptosis,and cell survival.GAS2 protein is universally expressed in most normal tissues,particularly in the liver,but is depleted in some tumor tissues.However,the functional mechanisms of GAS2 in hepatocellular carcinoma(HCC)are not fully defined.AIM To investigate the function and mechanism of GAS2 in HCC.METHODS GAS2 expression in clinic liver and HCC specimens was analyzed by real-time PCR and western blotting.Cell proliferation was analyzed by counting,MTS,and colony formation assays.Cell cycle analysis was performed by flow cytometry.Cell apoptosis was investigated by Annexin V apoptosis assay and western blotting.RESULTS GAS2 protein expression was lower in HCC than in normal tissues.Overexpression of GAS2 inhibited the proliferation of HCC cells with wide-type p53,while knockdown of GAS2 promoted the proliferation of hepatocytes(P<0.05).Furthermore,GAS2 overexpression impeded the G1-to-S cell cycle transition and arrested more G1 cells,particularly the elevation of sub G1(P<0.01).Apoptosis induced by GAS2 was dependent on p53,which was increased by etoposide addition.The expression of p53 and apoptosis markers was further enhanced when GAS2 was upregulated,but became diminished upon downregulation of GAS2.In the clinic specimen,GAS2 was downregulated in more than 60%of HCCs.The average fold changes of GAS2 expression in tumor tissues were significantly lower than those in paired non-tumor tissues(P<0.05).CONCLUSION GAS2 plays a vital role in HCC cell proliferation and apoptosis,possibly by regulating the cell cycle and p53-dependent apoptosis pathway.
基金the National Natural Science Foundation of China,No.39660021
文摘AIM To investigate the effect of Boschniakiarossica(BR)extract on expression of GST-P,p53 and p21<sup>ras</sup>proteins in early stage of chemicalhepatocarcinogenesis in rats and its anti-inflammatory activities.METHODS The expression of tumor marker-placental form glutathione S-transferase(GST-P),p53 and p21<sup>ras</sup>proteins were investigated byimmunohistochemical techniques and ABCmethod.Anti-inflammatory activities of BR werestudied by xylene and croton oil-induced mouseear edema,carrageenin,histamine and hotscald-induced rat pow edema,adjuvant-inducedrat arthritis and cotton pellet-induced mousegranuloma formation methods.RESULTS The 500 mg/kg of BR-H<sub>2</sub>O extractfractionated from BR-Methanol extract hadinhibitory effect on the formation of DEN-inducedGST-P-positive foci in rat liver(GST-P stainingwas 78% positive in DEN+AAF group vs 20%positive in DEN+AAF+BR group,P【0.05)andthe expression of mutant p53 and p21<sup>ras</sup>proteinwas lower than that of hepatic preneoplasticlesions(33% and 22% positive respectively inDEN+AAF group vs negative in DEN+AAF+BRgroup).Both CH<sub>2</sub>Cl<sub>2</sub> and H<sub>2</sub>O extracts from BRhad anti-inflamatory effect in xylene and crotonoil-induced mouse ear edema(inhibitory rateswere 26%-29% and 35%-59%,respectively). BR-H<sub>2</sub>O extract exhibited inhibitory effect incarrageenin,histamine and hot scald-inducedhind paw edema and adjuvant-induced arthritis inrats and cotton pellet-induced granulomaformation in mice.CONCLUSION BR extract exhibited inhibitory effect on formation of preneoplastic hepatic foci in early stage of rat chemical hepato-carcinogenesis. Both CH<sub>2</sub>CI<sub>2</sub> and H<sub>2</sub>O extracts from BR exerted anti-inflammatory effect in rats and mice.
基金the scientific research fundation of Shandong Provincial Education Committee(J94,K26)
文摘AIM: To investigate the possible roles of p53 and C-mycgenes in the primary hepatocellular carcinogenesis and therelationship between the liver hyperplastic nodule(LHN) andhepatocellular carcinoma(HCC).METHODS: The expression of p53 and C-myc genes wasdetected immunohist-ochemically in 73 and 60 cases of HCCand pericarcinomatous tissues, respectively .RESULTS: The positive expression of p53 in HCC wassignificantly higher than that in pericarcinomatous tissues(P<0.05). In pericarcinomatous tissues, the p53 expressionwas observed only in LHN, but not in liver cirrhosis (LC) andnormal liver tissues. The positive expression rate of C-mycin HCC or LHN was significantly higher than that in LC ornormal liver tissues (P<0.05 and P<0.01), however, nosignificant difference was found between HCC and LHN(P>0.05). The positive expression rate of p53 and C-myc inHCC was correlated with the histological differentiation, thatin the poorly differentiated was significantly higher than thatin well differentiated samples (P<0.05).CONCLUSION: The overexpression of p53 and C-myc genesmight play a role in the carcinogenesis of HCC; And LHNseems a preneoplastic lesion related to hepatocarcinogenesis;No evidence supports that LC contribute directly to thehepatocarcinogenesis.
文摘AIM: This study investigated the anti-cancer effect ofcombined quercetin and a recombinant adenovirus vectorexpressing the human p53, GM-CSF and B7-1 genes(designated BB-102) on human hepatocellular carcinoma(HCC) cell lines in vitro.METHODS: The sensitivity of HCC cells to anticancer agentswas evaluated by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The viability of cells infectedwith BB-102 was determined by trypan blue exclusion. Theexpression levels of human wild-type p53, GM-CSF and B7-1genes were determined by Western blot, enzyme-linkedimmunosorbent assay (ELISA) and flow cytometric analysis,respectively. The apoptosis of BB-102-infected or quercetin-treated HCC cells was detected by terminal deoxynucleotidyltransferase (TdT) assay or DNA ladder electrophoresis.RESULTS: Quercetin was found to suppress proliferation ofhuman HCC cell lines BEL-7402, HUH-7 and HLE, with peaksuppression at 50 μmol/L quercetin. BB-102 infection wasalso found to significantly suppress proliferation of HCC celllines. The apoptosis of BB-102-infected HCC cells was greaterin HLE and HUH-7 cells than in BEL-7402 cells. Quercetin didnot affect the expression of the three exogenous genes inBB-102-infected HCC cells (P>0.05), but it was found to furtherdecrease proliferation and promote apoptosis of BB-102-infected HCC cells.CONCLUSION: BB-102 and quercetin synergeticallysuppress HCC cell proliferation and induce HCC cell apoptosis,suggesting a possible use as a combined anti-cancer agent.