The Expression of Apoptosis-Related Genes Bcl-2 and Bax Protein and Apoptosis Positivity in Cervical Carcinoma during Irradiation

To evaluate the apoptosis positivity, the expression of Bcl-2, bax proteinsin 30 patients with squamous cell cervix carcinoma before and after radiotherapy. Methods: By usingimmuno-histochemical and TDT-dUTP nick end labelling techniques, 30 cases of squamous cell cervicalcarcinoma were analyzed. Results: The apoptosis positivity before and after irradiation was 76.7%and 100% respectively, with the difference being significant (P 【 0.05); The positive rates of Bcl-2protein before and after irradiation were 73.3% and 46.7% respectively, with the difference beingsignificant (P 【 0.05); The positive rates of bax protein before and after irradiation were 86% and100% respectively, with the difference being significant (P 【 0.05). Conclusion: bax and Bcl-2protein play an important role in apoptosis induced by fractionated radiation therapy. Apoptosisinduced by irradiation is contributed to upregulation of bax protein or downregulation of Bcl-2protein.

Effect of Bcl-2 Antisense Oligodeoxynucleotides on Human Lung Carcinoma Transplanted Subcutaneously in Nude Mice

Objective： To investigate the inhibitory effects of the Bcl-2 antisense oligodeoxynucleotides （ASODN） on tumor formation and growth of human lung carcinoma transplanted subcutaneously in nude mice. Methods： Human NCI-H460 cells treated with Bcl-2 ASODN or nonesense oligodeoxynucleotide （NSODN） and untreated NCI-H460 cells were respectively implanted subcutaneously into nude mice. When the diameters of tumor were above 0.5 cm after untreated NCI-H460 cells injection, the mice bearing tumor were randomly divided into three groups： saline control group, Bcl-2 ASODN group, NSODN group. ODN was directly injected into the tumor body for 3 weeks. The weight and volume of subcutaneous tumors were measured, and the morphology of tumor cells was observed. Results： The tumorigenic ability of the treated NCI-H460 cells by Bcl-2 ASODN was reduced. The mean time at which tumor can be detected was prolonged up to 12.6 days （P〈0.01）. The maximum tumor growth inhibitory rate was 87.5%. In therapeutic efficacy, growth of tumor was significantly inhibited in Bcl-2 ASODN group as compared with that in NSODN group, saline-treated group （P〈0.01）. The NSODN control was ineffective. In comparison with NSODN-treated, saline-treated mice, those treated with Bcl-2 ASODN showed a significant decrease in median weight of subcutaneous tumors （P〈0.01）. The growth inhibitory rate was 71.0% in ASODN group. Conclusion： Bcl-2 ASODN could inhibit tumor formation and tumor growth in nude mice.

Effect of Bcl-2 and Bax on survival of side population cells from hepatocellular carcinoma cells

AIM： To understand the role and significance of side population （SP） cells from hepatocellular carcinoma （HCC） in hepatocarcinogenesis, development, relapse and metastasis, we simulated the denutrition conditions that cancer cells experience in clinical therapy, observed the different anti-apoptosis ability of SP cells and non-SP cells under such conditions, and established the possible effects of P53, Bcl-2 and Bax on survival of SP cells. METHODS： We used flow cytometry to analyze and sort the SP and non-SP cells in established HCC lines MHCC97 and hHCC. We evaluated cell proliferation by methyl thiazolyl tetrazolium （MTT） assay and investigated the expression of p53, bcl-2 and bax genes during denutrition, by RT-PCR and immunofluorescence staining. RESULTS： The percentage of SP cells in the two established HCC lines was 0.25% and 0.5%, respectively. SP cells had greater anti-apoptosis and proliferation ability than non-SP cells. Expression of Bcl-2 and Bax in SP and non-SP cells differed during denutrition. The former was up-regulated in SP cells, and the latter was up-regulated in non-SP cells. CONCLUSION： It may be that different upstream molecules acted and led to different expression levels of Bcl-2 and Bax in these two cell lines. There was a direct relationship between up-regulation of Bcl-2 and down-regulation of Bax and higher anti-apoptosis ability in SP cells. It may be that the existence and activity of SP cells are partly responsible for some of the clinical phenomena which are seen in HCC, such as relapse or metastasis. Further research on SP cells may have potential applications in the field of anticancer therapy.

Expression of Bcl-2 inhibited Fas-mediated apoptosis in human hepatocellular carcinoma BEL-7404 cells

Apoptosis plays an important role in embryonic development, tissue remodeling, immune regulation and tumor regression. Two groups of molecules (Bcl-2 family and "Death factor" family) are involved in regulating apoptosis. In order to know about the effect of Bcl-2 on apoptosis induced by Fas, a typical member of "Death factor" family, the transfection experiments with expression vectors pcDNA3-fl and pcDNA3-bcl-2 were performed in BEL-7404 cells, a human hepatocellular carcinoma cell line which expresses endogenous Fas, but not FasL and Bcl-2. The data showed that the expression of FasL in pcDNA3-fl transfected hepatoma cells obviously induced the apoptosis of the cells. However, the overexpression of Bcl-2 in pcDNA3-bcl-2 transfected 7404/b-16 cells counteracted pcDNA3-fl transient transfection mediated apoptosis. Further study by cotransfection experiments indicated that Bid but not Bax (both were pro-apoptotic proteins of Bcl-2 family) blocked the inhibitory effect of Bcl-2 on Fas-mediated apoptosis. These results suggested that Fas-mediated apoptosis in human hepatoma cells is possibly regulated by Bcl-2 family proteins via mitochondria pathway.

Correlation between expression of gastrin, somatostatin and cell apoptosis regulation gene bcl-2/bax in large intestine carcinoma

AIM: To explore the correlation between expression of somatostatin (SS), gastrin (GAS) and cell apoptosis regulation gene bcl-2/bax in large intestine carcinoma.METHODS: Sixty-two large intestine cancer tissue samples were randomly and retrospectively selected from patients with large intestine carcinoma. Immunohistochemical staining for bcl-2, bax, GAS, SS was performed according to the standard streptavidin-biotin-peroxidase (S-P) method.According to the semi-quantitative integral evaluation, SS and GAS were divided into three groups as follows. Scores1-3 were defined as the low expression group, 4-8 as the intermediate expression group, 9-16 as the high expression group. Bax and bcl-2 protein expressions in different GAS and SS expression groups of large intestine carcinoma were assessed.RESULTS: The positive expression rate of bax had a prominent difference between SS and GAS high, intermediate and low expression groups (P＜0.05, x2ss = 9.246; P＜0.05,x2GAS = 6.981). The positive expression rate of bax in SS high (80.0%, 8/10) and intermediate (76.5%, 13/17)expression groups was higher than that in low expression group (40.0%, 14/35) (P＜0.05, x2high vs low = 5.242; P＜0.05,x2middle vs low = 6.097). The positive expression rate of bax in GAS high expression group (27.3%, 3/8) was lower than that in low expression group (69.4%, 25/36) (P＜0.05,x2 = 4.594). However, bax expression in GAS intermediate expression group (46.7%, 7/15) was lower than that in low expression group, but not statistically significant. The positive expression rate of bcl-2 had a prominent difference between SS and GAS high, intermediate and low expression groups (P＜0.05, x2ss = 7.178; P＜0.05, x2GAS = 13.831). The positive expression rate of bcl-2 in GAS high (90.9%, 10/11)and intermediate (86.7%, 13/15) expression groups was higher than that in low expression group (44.4%, 16/36)(P＜0.05,x2high vs low = 5.600; P＜0.05, x2 middle vs low = 7.695).However, the positive expression rate of bcl-2 in SS high (40.0%, 4/10) and intermediate (47.1%, 8/9) expression groups was lower than that in low expression group (77.1%, 27/35)(P＜0.05, x2 high vs low = 4.710; P＜0.05, x2 middle vs low = 4.706).There was a significant positive correlation between the integral ratio of GAS to SS and the integral of bcl-2 (P＜0.01,r=0.340). However, there was a negative correlation between the integral ratio of GAS to the SS and bax the integral of (P＜0.05, r = -0.299).CONCLUSION: The regulation and control of gastrin,somatostatin in cell apoptosis of large intestine carcinoma may be directly related to the abnormal expression of bcl-2, bax.

Pokemon reduces Bcl-2 expression through NF-κ Bp65:a possible mechanism of hepatocellular carcinoma

Objective:To investigate the relationship among Pokemon,NF-κB p65 and Bcl-2 in hepatoma cells.Methods:HCC cell HepG2,SMMC7721 and human fetal liver cell line L02 cells were used,and expression of Pokemon,NF-κB p65 and Bcl-2 in three cells were detected by realtime PCR and western blot.Then siRNA of Pokemon was applied to inhibit the expression of Pokemon and NF-κB p65 and apoptotic rate was determined by flow cytometric analysis. Results:Expressions of Pokemon,NF-κB p65 and Bcl-2 in human hepatoma cell HepG2, SMMC7721 expression were significantly higher than those in human embryonic stem cells L02. siRNA of Pokemon inhibited the expression of Pokemon,NF-κB p65 and Bcl-2 in liver cancer cells,and significantly increased apoptosis of liver cells.While siRNA of NF-κB n65 inhibited the expression of NF-κB p65 and Bcl-2,but Pokemon expression in hepatoma cells had no significant change.Conclusions:The proto-oncogene Pokemon can inhibit PI4ARF by specific transcription regulation of cell cycle and can induce tumors.In addition,Pokemon can regulate NF-κB p65 through the expression of apoptosis repressor,and promote the development of liver cancer.It suggests signal network in the liver include the regulation of new non-classical NF-κB regulatory pathway.

Bcl-2 expression is a poor predictor for hepatocellular carcinoma prognosis of andropause-age patients

Objective: The expression of B-cell lymphoma 2(Bcl-2) seems to be influenced by the endocrine environment. Numerous reports demonstrate the diverse expression of Bcl-2 family members under sex steroid regulation. With the exception of estrogen-related tumors, androgen-related tumors have shown their characteristics in Bcl-2 expression. In this study, the status of Bcl-2 expression in male hepatocellular carcinoma(HCC) patients was examined to verify the high incidence of HCC in males.Methods: Tumor tissue microarray was used to examine Bcl-2 expression levels in 374 HCC cases including 306 males and 68 females. Kaplan-Meier method, log-rank test, and Cox proportional hazards model were applied to investigate the predictive value of Bcl-2 in HCC patients.Results: Immunohistochemistry analysis showed that male patients with higher Bcl-2 levels had significantly longer median survival time and recurrence time than those with lower levels. However, no significant differences in outcomes were found between different Bcl-2 levels in female patients. When the male patients were stratified into several age points, the level of Bcl-2expression showed poorer predictive efficiency in the 45–49 and 55–60 age groups in andropause-age patients compared with other age groups. Bcl-2 was an independent prognostic factor for both overall survival(P < 0.0001) and recurrence time(P =0.0001) in male patients. After excluding male patients in the 45–60 age group, the predictive efficiency was enhanced(n = 147,OS, P = 0.0002, TTR, P < 0.0001).Conclusions: Bcl-2 expression is an independent predictor of survival and recurrence in male HCC. Bcl-2 levels may also be regulated by androgens or androgen receptors in male HCC patients. Bcl-2 levels change and exhibit poor predictive efficiency when androgen levels vary dramatically(andropause age).

Prognostic significance of bcl-2 and p53 expression in colorectal carcinoma

Objective: This study was designed to detect the expression of bcl-2 and p53 proteins in colorectal carcinomas and to determine their association with the patient survival and stage of the diseases. Methods: Immunohistochemistry method was used to detect the expression of bcl-2 and p53 proteins in 93 cases of colorectal carcinoma. The stain results were obtained by analyzing the clinic-pathological characteristics of patients. Results: Fifty-seven percent (53/93) of the colorectal carcinomas were bcl-2 protein positive. The positive rate of bcl-2 protein in lymph node involvement cases was lower (15/37) than the cases without node involvement (38/58, P<0.01). The positive rate of p53 protein was 43% (40/93) in colon-rectum carcinomas. No significant correlation was observed between p53 protein expression and clinic-pathological manifestations (P>0.05) but the survival was significantly worse (P=0.0001) in the p53 protein positive cases. Neither bcl-2 nor p53 alone was correlated with stage of the disease. When combined bcl-2/p53 status was analyzed, a group with bcl-2(+) and p53(?) had the best prognosis. This group was significantly associated with earlier Dukes’ stages (P=0.1763). In multivariate Cox regression analysis, lymph node involvement and p53 protein expression were two independent factors correlated with survival time. Conclusion: The expression of bcl-2 and p53 represent biological characteristics of colorectal carcinomas. Assessment of both bcl-2 and p53 status may be valuable in predicting the prognosis of patients.

H pylori (CagA) and Epstein-Barr virus infection in gastric carcinomas:Correlation with p53 mutation and c-Myc,Bcl-2 and Bax expression

AIM: To investigate the interrelationship between H pylori and Epstein-Barr virus (EBV) infection in the gastric carcinogenesis having in focus the p53 mutation and the c-Myc, Bcl-2 and Bax expression. METHODS: seventy-one gastric carcinoma tissues were assessed by polymerase chain reaction (PCR) for H pylori and in situ hybridization for EBV. c-Myc, Bcl-2 and Bax expression were detected by immunohistochemistry and single-stranded conformational polymorphism (SSCP) for p53 mutation. RESULTS: The positivity rates for H pylori and EBV were 94.4% and 8.45%, respectively. The majority of the cases displayed only the H pylori presence. All EBV positive cases were also H pylori positive. None infectious agent was observed in 5.55% of the cases. The intestinal type tumor was more frequent in the co-infected and non-infected groups. The female predominated in the non-infected group showing statistical significance (70.4% vs 29.6%, P=0.039). The Bcl-2 was only detected in the group exclusively infected by H pylori. However, c-Myc and Bax were detected in the three groups but with a low frequency in the co-infected group. Mutation of p53 was present in all groups, with the highest frequencies in the H pylori positive groups. CONCLUSION: The frequency of H pylori infection in gastric carcinomas was high. The presented data indicated that gastric carcinogenesis has different pathways depending of the presence of the two investigated infectious agents, suggesting a possible involvement of H pylori with apoptotic process. The low expression of c-Myc and Bax in the EBV-positive groups suggests that EBV may inhibit the expression of these proteins. Nevertheless, p53 mutation shows to be a relevant alteration, independent of both infectious agents.

The Relationship of Expression of bcl-2, p53, and Proliferating Cell Nuclear Antigen (PCNA) to Cell Proliferation and Apoptosis in Renal Cell Carcinoma

To investigate the relationship of bcl-2, p53, proliferating cell nuclear antigen (PCNA) to cell proliferation, apoptosis and pathological parameters, the patterns of cell growth and turnover in renal cell carcinoma (RCC), formalin-fixed and paraffin-embedded tissue blocks from 34 patients with RCC were examined. Cell proliferation activity was detected by PCNA immunostaining and the proliferation index (PI) was expressed as a percentage of the PCNA-positive cells in the tumor cells. Apoptosis was detected by terminal deoxy- nucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and the apoptotic index (AI) was expressed as a percentage of the TUNEL-positive cells in the tumor cells. Expressions of bcl-2 and p53 were assessed immunohistochemically. Our results showed that the PI ranged from 6.0 % to 24.0 % (median 12.3 %) and the AI from 2.0 % to 8.0 % (median 5.4 %) in RCC. The expression of the bcl-2 protein was demonstrated in 15 cases (44.1 %); the expression of the p53 protein, however, was seen in only 3 case. bcl-2 positivity was not associated with PI or AI or any pathological parameters. There were close associations between PI and tumor grade and stage, and a significant relationship between AI and the tumor grade of RCC. Our study suggests that bcl-2 positivity was not associated with PI or AI or any pathological parameters. There are close associations between PI and AI and tumor grade and stage of RCC. Active cell proliferation may be accompanied by frequent apoptosis in RCC.

Curcumin induces the expression of NF-κB and Bcl-2/Bax in human renal cell carcinoma cell line ACHN

Objective： To explore the in vitro effects of curcumin on the proliferation and apoptosis of the human renal cell carcinoma cell line ACHN, and to investigate its mechanisms of action. Methods： The human renal cell carcinoma cell line ACHN was treated with different concentrations of curcumin for 24 h. The MTT assay was used to evaluate the cytotoxic effects of curcumin and flow cytometry was utilized to observe and detect the apoptosis of ACHN cells induced by curcumin. The expression levels of Bcl-2, Bax and NF-κBP65 mRNA were evaluated by Reverse Transcription-Polymerase Chain Reaction （RT-PCR）, while the expression of Bcl- 2, Bax, NF-κBP65 and IκB proteins was evaluated by Western blot. Results： The concentrations of curcumin used significantly inhibited the proliferation of ACHN human renal cell carcinoma cells in vitro in a dose and time-dependent manner （Ftime=5.55, P 〈 0.05; Fdose=110.05, P 〈 0.05）. Obvious apoptosis of cells treated with different concentrations of curcumin could be observed by FCM. Compared with the control group, the apoptosis rates of curcumin-treated cells were markedly increased （F=96.35, P 〈 0.05）. Lower dose of curcumin significantly induced the apoptosis of ACHN cells. With intervention of different concentrations of curcumin （0, 10, 20 and 40 μmol/L） for 24 h, the expression levels of Bcl-2 and NF-κBP65 mRNA in ACHN cells were decreased while the expression level of Bax mRNA was increased （P 〈 0.05）, and Bcl-2, and NF-κBP65 protein decreased, while Bax and IκB protein increased compared with those in the untreated group. Conclusion： Curcumin inhibited proliferation and increased apoptosis of the human renal cell carcinoma cell line ACHN. These curcumin effects appear to involve up-regulating IκB, down-regulating NF-κB, and regulating the expression of the apoptosis genes Bcl-2/Bax.

THE EXPRESSION OF BCL-2 AND BAX PROTEINS IN GASTRIC CARCINOMA AND PRECANCEROUS LESIONS

Objective To investigate the variance of expression of bcl-2 and bax genes in the genesis or gastric carcinoma as well as their relationship. Methods Thirty-five cases of early-stage gastric carcinoma and Twenty-four cases ot chronic atrophic gastritis were studied by immunohistochemical method. Results There were no statistical differences of bcl-2 expression levels between gastric carcinoma and atypical hyperplasia or paracancerous intestinal- epithelial metaplasia(IEM) (P>0.05).There were statistical differences of bcl-2 expression between normal epithe- lial tissues (or non-cancerous IEM) and the other three groups(P<0.05), but no statistical difference between the normal epithelial and the non-cancerous IEM group was observed(P>0.05). The expressions or bax protein were found in the normal epithelial and the other groups in varying degrees,but there were no statistical differences be- tween either two of the groups (P>0.05). The bcl-2/bax ratio was higher in early-stage gastric carcinoma,atypical hy- perplasia and paracancerous intestinal-metaplasia than in the non-cancerous intestinal-metaplasia (P<0.05) and nor- mal epithelial tissues(P<0.01). Conclusion The abnormal expression of bcl-2 protein and bax protein,especially the increased bcl-2/bax ratio, probably play an important role in the course of carcinogenesis or gastric carcinoma.

The Role of Bcl-2, CD10 and CD34 Expression in Differentiation between Basal Cell Carcinoma and Trichoepithelioma

Background: Basal cell carcinoma (BCC) and trichoepithelioma (TE) have some similarities clinically and histologically. The aim of this work is to evaluate the role of Bcl-2, CD10 and CD34 in differentiation between BCC and TE. Methods: The immunohistochemical expression of Bcl-2, CD10 and CD34 was evaluated in 20 BCCs and 12 TEs in a retrospective study. The localization of these markers in tumor and stromal cells was determined and comparison between BCC and TE was done. Immunohistochemistry for Bcl-2, CD10 and CD34 was performed on sections obtained from formalin-fixed, paraffin-embedded blocks. Bcl-2, CD10 and CD34 immunoreactivity in the stromal and/or tumor cells was determined as follows: negative (0);1+ (10% - 50% positive cells);and 2+ (>50% positive cells). Results: In BCC (20 cases), the expression of Bcl-2 in stromal cells showed (0) immunoreactivity in 8 cases (40%), (1+) immunoreactivity in 7 cases (35%), and (2+) immunoreactivity in 5 cases (25%). Tumoral cells showed diffuse positivity in 20 out of 20 cases (100%), (1+) immunoreactivity in 5 cases (25%) and (2+) immunoreactivity in 15 cases (75%). On the other hand, the expression of Bcl2 in TE, 4 cases showed positive stromal cells out of 12 (33.33%), (1+) immunoreactivity in 2 cases (16.6%) and (2+) immunoreactivity in 2 cases (16.6%), and 8 cases showed no immunoreactivity. Tumoral cells showed positivity in 12 out of 12 cases (100%), (1+) immunoreactivity in 5 cases (41.6%), (2+) immunoreactivity in 7 cases (58.3%). In BCC cases, the expression of CD10 was noted in stromal cells in 8 out of 20 cases (40%), 5 cases showed positivity in stromal and basaloid cells and 3 cases showed positivity in stromal cells only, and 12 cases showed no immunoreactivity (60%). Tumor cells showed positivity in 11 cases out of 20 (55%), (1+) immunoreactivity in 6 cases (30%), (2+) in 5 cases (25%), and 9 cases showed no immunoreactivity (45%). On the other hand, the expression of CD10 in TE 7 cases showed positive stromal cells out of 12 (58.33%), (1+) immunoreactivity in 5 cases (41.6%) and (2+) in 2 cases (16.6%), and 5 cases showed no immunoreactivity (41.66%). Tumor cells showed positivity in 5 cases out of 12 (41.66%), (1+) immunoreactivity in 4 cases (33.33%) and (2+) in 1 case (8.3%), and 7 cases showed no immunoreactivity (58.33%). In BCC cases, the expression of CD34 was noted in stromal cells in14 cases out of 20 cases (70%), (1+) immunoreactivity in 10 cases (50%) and (2+) in 4 cases (20%), and 6 cases showed no immunoreactivity (30%). On the other hand, the expression of CD34 in TE, 10 cases showed positive stromal cells out of 12 (83.33%), (1+) immunoreactivity in 6 cases (50%) and (2+) in 4 cases (33.33%), and 2 cases showed no immunoreactivity (16.6%). Tumor cells showed no immunoreactivity for CD 34 in both BCC and trichoepithelioma, (100%) negative tumor cells. Significant difference of tumor\stromal cells immunoreactivity for Bcl-2 and CD34 in both BCC and TE but it was insignificant for CD10. Conclusion: We conclude that Bcl-2 CD10, CD34 are useful markers in the differential diagnosis of BCC versus TE.

Preoperative evaluation of P53 and bcl-2 over expression in clinical stage 1 endometrial carcinoma and their correlation with surgico-pathological data and prognosis of patients

Introduction: P53 and bcl-2 over expression was reported to affect the biology and prognosis of patients endometrial carcinoma. Methods: This prospective study included 38 patients with histologically confirmed endometrial carcinoma and staged clinically as stage I. Immunohistochemical staining of the tumor specimens obtained by dilatation and curettage (D&C) with P53 and bcl-2 monoclonal antibodies was done. The surgical, pathological and follow up data of all patients were studied. Results: There were 18 cases (47.4%) with positive P53 over expression. P53 over expression was found to be associated with increasing grade of differentiation, advanced stage, and non endometrioid type (significant), and increased depth of myometrial invasion (non-significant). It was associated with more recurrence rate (22% versus 15%) and shorter mean survival time (33.9 versus 29.2 months). Bcl-2 expression was present in24 cases (63.2%) of the studied group. There was significant decrease in bcl-2expression with poorly differentiated, advanced stage, increased depth of myometrial invasion, and non-endometrioid type. It was not significantly correlated with recurrence rate and mean survival time. Conclusion: P53 over expression in the D&C specimens was associated with adverse surgicopathological criteria, increased mortality rate, and shorter survival time in patients with endometrial carcinoma. A significant decrease in bcl-2 expression was associated with adverse surgicopathological criteria, but it was not significantly correlated with prognosis of the patients.

THE OVEREXPRESSION OF APOPTOSIS-RELATED GENES OF P_53 AND BCL-2 IN CERVICAL CARCINOMA

Objective To investigate the significance of overexpression of p5s and bcl-2 protein in carcinogene- sis of cervix. Methods 10 cases of cervical intraepithelial neoplasis(CIN) and 57 cases of invasive cancer were in- vestigated with immunohistochemistry technique. Results The overexpresion or P53 protein ir CIN and cervical can- cer was significantly higher than that or control, respectively (P<0.01). But there was no significant difference be- tween CIN and cervical cancer(P>0.05). The immunoreactivity of bcl-2 in CIN was much more higher than that of control (P<0.05). The positive rate and immunoreactivity of bcl-2 in cervical carcinoma were both remarkably high- er than those of control (P<0.0l),but there was no significant difference between CIN and cervical carcinoma (P> 0.05). It was also found that there was a remarkably positive correlation between the overexpression of bcl-2 and P53 (P<0.01). Conclusion Because of the loss of wtP53 function,the expression of bcl-2 can not be down-reguated, which is associated with the pathogenesis and development of cervical carcinoma.

The relationship between bcl-2 gene abnormality and nasopharyeal carcinoma

objective To explore the relationship between bcl--2 gene abnormality and nasopharyngeal carcinoma (NPC) Methods: bcl--2/JH fusion gene and bcl-2 protein expression were examined with semi--nested insitu PCR (SNISPCR) and immunohistochemistry technique in 41 NPC. Results: (l) Bcl-2/JH fusion genewere found in 6 cases of 41 NPC (positivity rate, 14. 6% ). (2)Bol-2 protein was expressed in 34 cases of 41NPC, the positivity rate being 82. 9 %. No bcl-2 expression was seen in benign nasopharyngeal lesions. Conclusion: (l) Translocation was not a specific change in lymphoma, but mbr and mcr regions are the two important breakpoint regions in NPC. Bcl-2/JH fusion gene formation may not play an important role in pathogenesis of NPC for its low positive rate. (2) There was no corresponding relationship between formation ofhcf-2/JH fusion gene and aberrant hcf-2 protein expression in NPC.

THE QUANTITATIVE MEASUREMENT OF BCL-2, P53 PROTEIN AND PCNA EXPRESSION IN BREAST CARCINOMA AND THEIR CORRELATION WITH PROGNOSIS

To study quantitative index of bci-2, P53, Nroliferating cell nuclear antigen (PCNA),ER and PR in breast carcinoma and their correiation and their relatiousbip with prognosis, the ex expression of bcl-2, P53 and PCNA were studied by immunohistochemical technique. The measurementof ER and PR used enzyme linked affinuity histochemical methods. The quantitative index was analyzed by image technique. All analyses were hased on 60 breast carcinomas. The results were as follows:the more bcl-2 protein, the lower histological graded the longer survival term and the highersurvival rate (P< 0. 05). The quautitative measurement of bcl-2, P53 and PCNA expression were ofvalue in evaluating the degree of differentiation and prognosis in breast carcinoma. The quantitativeand qualitative measurement or p53 protein expression showed a Ⅰwerful evidence in evaluatingprognosis of bcl-2 were more significant in evaluating poor prognosis of breast carcinoma. A relationship between bcl-2 and ER, PR showed a better value for response to endocrine therapy in breastcarcinoma patients.

口腔鳞癌中Cyclin D1和Bcl-2蛋白表达相关性的研究

目的研究Cyc lin D1和Bc l-2在口腔鳞癌组织和正常口腔粘膜中的表达及意义。方法用免疫组织化学S-P法对62例口腔鳞癌手术切除标本和10例正常口腔粘膜标本中Cyc lin D1和Bc l-2基因蛋白的表达情况进行检测。结果口腔鳞癌组织中Cyc lin D1表达率67.7%(42/62),正常口腔粘膜组织中未见表达,两组间差异有显著性(P<0.05);Bc l-2在正常口腔粘膜组织中也未见表达,在癌组织中Bc l-2蛋白阳性表达率58.1%(36/62),两组间差异也有显著性(P<0.05)。结论Cyc lin D1和Bc l-2两种蛋白在癌组织中存在过表达,口腔鳞癌组织中Cyc lin D1与Bc l-2的表达呈正相关。过表达的Cyc lin D1与Bc l-2可作为评价口腔鳞癌组织分级的参考指标之一。

Survivin、Bcl-2和Bax在肝外胆管异型增生组织和癌组织中的表达及意义

目的探讨Survivin、Bcl-2和Bax在肝外胆管癌发生发展中的作用和临床意义。方法用免疫组化S-P法检测27例肝外胆管癌组织、10例异型增生组织和5例正常组织中Survivin、Bcl-2和Bax的表达。结果Survivin在肝外胆管正常上皮组织、异型增生组织和癌组织中阳性表达率分别为20%,50%和74%,正常组织和癌组织中Survivin表达差异有统计学意义(P=0.037<0.05)。Bcl-2在肝外胆管正常上皮组织、异型增生组织和癌组织中阳性表达率分别为0,10%和37%,表达差异无统计学意义(P=0.092>0.05)。Bax在肝外胆管正常上皮组织、异型增生组织和癌组织中阳性表达率分别为40%,30%和74%,异型增生组织和癌组织中表达差异有统计学意义(P=0.023<0.05)。Survivin与Bcl-2在肝外胆管正常上皮组织、异型增生组织和癌组织的表达有明显相关性(P=0.039<0.05)。Bcl-2和Bax在肝外胆管正常上皮组织、异型增生组织和癌组织的表达有明显相关性(P=0.005<0.05)。Survivin、Bcl-2和Bax的表达与肝外胆管癌组织病理学特征和临床分期无关。结论Survivin、Bcl-2和Bax凋亡相关基因参与了肝外胆管癌的发生发展,凋亡在其发生发展中起重要作用。

Bcl-2与Bax蛋白在肝细胞癌中的研究进展

肝细胞性肝癌（hepatocellular carcinoma,HCC）是临床常见的恶性肿瘤之一,位居全球恶性肿瘤死因的第三位,其发生发展是多因素、多阶段、多基因突变的复杂病变过程。由于HCC早期诊断困难,术后易于复发转移,生存期短,除了传统的手术治疗、放疗和化疗外,靶向治疗、基因治疗也是目前肝癌研究的热点。Bcl-2与Bax（Bcl-2是Bcl-2家族成员中调控细胞凋亡最具代表性的基因,在多种肿瘤中都有表达,