Relationship among COX-2 protein expression,PGs levels and biologic behavior in ovarian carcinoma tissues

Recent epidemiological studies shows thatlong-term use of aspirin or other NSAIDs (non-steroidanti-inflammatory drugs, NSAIDs) reduces the risk ofcolon cancer development by 40% — 60%[1,2].Although the exact mechanisms of NSAIDs on cancerprevention have not been clarified, one of them maybe via the inhibition of COX-2 enzyme. In the presentstudy, we investigated the COX-2 protein,prostaglandin (PG)E2, 6-keto-PGF1α and thromboxane(TX)B2 by Western blot analysis and radio-immunoass…     

STUDY ON RELATIONSHIP BETWEEN CHEMOSENSITIVITY OF BREAST CANCER AND EXPRESSION OF p73α AND p53

Objective： To investigate the relationship between the expression of p73α and p53 versus the chemosensitivity in breast cancer cells. Methods： Twelve surgical samples of breast cancer diagnosed by pathology were used. The cancer sample cells were separately cultured in the incubator at 37℃, 5% CO2 in vitro. The relative inhibition rate of cancer cells by 4 kinds of anticancer drugs, which were EPI, MMC, 5-Fu and DDP, were assayed by MTT method. Immunocytochemistry was used to detect the expression of p73α and p53 in the cancer cells. Results： The positive expression of p73α was found in 5/12 （41.67%）, and p53 positive expression rate was 50.0% （6/12）. The relative inhibition rate of MMC, EPI, 5-Fu and DDP were significantly higher in the p73α positive cancer cells than in the p73α negative cancer cells. A positive correlation was found between expression of p73α and chemosensitivity for all the four anticancer drugs. Condusion： The expression of p73α is related with the chemosensitivity of the breast cancer cells, and it may become one of the markers for judging the effect of chemotherapy in clinic.     

P73、ER、PR在食管癌及癌前病变中的表达及临床意义

Objective： To test the expression of mutant p73, p53, ER and PR proteins in the esophageal normal mucosa, hyperplasia, dysplasia and squamous cell carcinoma, and research the clinically pathological significance and the correlation, for the early diagnosis, prognostic measure and therapy in clinic. Methods： With Immunohistochemistry, it was examined to show these tumor markers＇ expression in different epithelial lesions of 40 esophageal squamous cell carcinomas, 14 dysplasias, 14 hyperplasias and 14 normal mucosas. Results： The expression of p73 was 55%, 21%, 0% and 0% in the esophageal carcinoma, dysplasia, hyperplasia and normal mucosa, respectively. The significant difference in expression of p73 （P〈0.001） was observed between the esophageal normal mucosia, hyperplasia, dysplasia and esophageal squamous cell carcinoma with Fisher＇s exact test. Difference in expression of p73 （P〈0.05） was observed between the esophageal squamous cell carcinoma and dysplasia with X^2 test. The expression of p73 showed non-correlation with the patient＇s age, sex, tumor＇s grade, lymph-node metastasis and invasive depth （P〉0.05）; Similarly, the expression of mutant p53 was 67.5%, 35.7%, 7% and 0%, respectively; In like manner, the expression of ER was 55%, 21.4%, 14.2% and 0%, respectively; The expression of PR was 57.5%,14.28%, 0% and 0%, respectively. The significant difference in expression of PR （P〈0.001） was observed with Fisher＇s exact test. Difference in expression of PR （P〈0.05） was observed between the esophageal squamous cell carcinoma and dysplasia with x2 test. The expression of PR （P〈0.05） was correlated with lymph-node metastasis, and showed non-correlation with the patient＇s age, sex, tumor＇s grade, and invasive depth （P〉0.05）. Moreover, over-expression of mutant p53 and p73 showed significant correlation with ER and PR protein＇s positive expression （P〈0.05）. Conclusion： P73 protein may become a new tumor＇s marker to diagnose esophageal squarnous celt carcinoma. Because the expression of p73 protein was closely correlated with ER and PR, they could be simultaneously examined to help to early diagnose, prognosticate and cure esophageal carcinoma.     

RELATIONSHIP BETWEEN EXPRESSIONS OF P38 PROTEIN IN HUMAN BREAST CARCINOMA AND LYMPH NODES METASTASIS

Objective： To detect the change of p38 protein expression and investigate the relationship of p38 and lymph nodes metastasis in human breast carcinomas. Methods： Sixty breast cancer cases were checked by S-P immunohistochemistry technique and 30 breast cancer cases were examined by Western Blot. Results： Immunohistochemical results showed that p38 protein was observed in breast cancer and normal cytoplasm. P-p38 was positive in nucleus in breast cancer. P38 protein expressed positively in 29 out of 38 patients who had lymph nodes metastasis （positive rate 76.3%） and in 9 out of 22 patients who had no lymph nodes metastasis （positive rate 40.9%）. There was a significant difference between these two groups （P〈0.01）. The positive rate of p-p38 in patients who had lymph nodes metastasis was 68.4%, and the positive rate in patients who had no metastasis was 36.4%, and there was a significant difference between these two groups （P〈0.05）. The result of western blot showed that the protein contents of p38 and p-p38 in patients with metastasis was higher than those in patients without metastasis （P〈0.05）. P38 and p-p38 protein expressions had relation with clinical pathological grades in breast cancer, higher in grade Ⅲ than in grade Ⅰ, Ⅱ （P〈0.05）, while had no relation with patients＇ age and tumor size （P〉0.05）. Conclusion： p38 and p-p38 protein expressions had relationship with lymph nodes metastasis and the levels of p38 and p-p38 protein expression in groups with lymph nodes metastasis were higher than in groups without lymph nodes metastasis. P38 and p-p38 protein expressions had relationship with clinical grades and had no relationship with patients＇ age and tumor size.     

The expressions and significance of α-, β-catenins and cyclin D1 in breast cancers

Objective  To study the relationship between expressions of α-, β-catenins and cyclin D1 and the occurrence, infiltration and metastasis of breast cancer. Methods  High sensitive S-P immunohistochemical method was used to detect the protein expressions of α-, β-catenins and cyclin D1 in the 60 cases of breast cancer tissues. Results  Abnormal immunoreactivities of α-and β-catenins were observed in 37 (61.7%) and 42 (70%) cases of breast cancer tissues, respectively. There were 28 cases (46.7%) who showed cyclin D1 overexpression. The abnormal expression rates of α-and β-catenins in infiltrating lobular carcinoma (ILC) were significantly higher than those in infiltrating ductal carcinoma (IDC) (P < 0.05), but they had no relations to the extent of differentiation and lymphatic metastasis of breast cancer (P > 0.05). The overexpression rate of cyclin D1 was correlated with tumor stage and lymphatic metastasis of breast cancer (P < 0.05), but not with histological type and the extent of differentiation (P > 0.05). Cyclin D1 overexpression was observed in 57.1% (24/42) of these cases that showed abnormal staining of β-catenin, but only observed in 22.2% (4/18) of these cases with normal membranous staining of β-catenin. There was a significantly positive correlation between the abnormal expression of β-catenin and overexpression of cyclin D1 (r _s = 0.321, P < 0.05). Conclusion  The abnormal expression of β-catenin may play an important role in the genesis of breast cancer by triggering cyclin D1 overexpression in breast cancer. The abnormal expressions of α-and β-catenins are not a key factor in malignant cell metastasis in breast cancer, but may also involve in the progress.     

The Immuno-fluorescence Quantity Analysis of α-Tubulin and γ-Tubulin Protein in Precancerous Lesion and Carcinoma of the Breast and Its Significance

OBJECTIVE To investigate the changes and values of the expression of α-tubulin and γ-tubulin in atypical ductal hyperplasia （ADH）, ductal carcinoma in situ （DCIS） and invasive ductal carcinoma （IDC） of the breast. The relationship between centrosome abnormalities and breast tumor development was further discussed. METHODS There were three groups including ADH, DCIS and IDC with 30 cases in each group. They were analyzed by immuno-fiuorescence quantity analysis. The expression levels of α-tubulin and γ-tubulin protein in these tissues were detected by flow cytometry immuno-fiuorescence analysis and compared with the results from normal tissues. Immunohistochemistry was also performed in this research. RESULTS The results showed significant differences of the average of the positive （FITC labeled） cells （P=0.000） among the four groups. The level of the IDC group was the highest, while normal breast tissue showed the lowest level. The results suggested that the expression levels of α-tubulin and γ-tubulin both increased as the grade of cellular proliferation and differentiation increased. The expressions showed significant differences among all the groups, except between the ADH and DCIS. There were no significant differences between α-tubulin and γ-tubulin expression in each group （P〈0.05）, as there was agreement in the immuno-fluorescence and immunohistochemical analysis for protein expression. CONCLUSION There is abnormal expression of centrosome tubulin as an early event in the development of breast tumor. Furthermore these aberrations may play a key role during oncogenesis and promote cellular transformation to malignancy. The immuno-fiuorescence quantitive analysis and immunohistochemistry can complement each other.     

Specificity and significance of lectin receptors in breast carcinoma

Eight lectins were used to study 100 cases of breast carcinoma and 56 cases of non-carcinoma breast tissues by lectin affinity histochemical method. The results showed that Bandeiraea Simplicifolia (BSL) and Peanut agglutinin (PNA) had higher positive rates in breast carcinoma than both normal breast and benign lesions (P<0.005). The positive deposit in malignant lesions was mainly located in cytoplasm, while in non-malignant lesions, it was almost lined along the lumen of glands and small ducts (P<0.005). The authors think that expression of PNA-receptor in the cytoplasm might be associated with the mechanism that the tumor could escape from immune attack. Comparison analysis on the normal breast indicated that PNA affinity histochemistry would be useful to the understanding of the metabolism of β-D-galactosyl-N-acetyl-D-galactosamine during the development of normal breast and histological origin of breast carcinoma.     

Significance of β-tubulin Expression in Breast Premalignant Lesions and Carcinomas

OBJECTIVE To explore the expression of β-tubulin in premalignant lesions and carcinomas of the breast,and to observe the relationship of its expression with breast cancer pathological features. METHODS The expression of β-tubulin was detected immunohistochemically in 50 specimens of premalignant lesions of the breast(ADH and Peri-PM with ADH),50 specimens of breast in situ ductal carcinomas(DCIS),and 50 specimens of invasive ductal carcinomas(IDC).Thirty specimens of normal breast tissues served as a control group. RESULTS Immunohistochemical analysis showed that:the differences among the 4 groups(normal breast tissues,breast premalignant lesions,DCIS and IDC,P<0.05)were significant, and there were also statistically significant differences between any 2 groups(P<0.05)except for the β-tubulin positive expression comparing DCIS versus IDC(P>0.05).In addition,β-tubulin was expressed at a higher level in Peri-PM with ADH compared to ADH(P<0.05).Following the degree of breast epithelial hyperplasia involved,and its development into carcinoma,the β-tubulin positive expression displayed an elevating tendency. We also found a significant positive relationship of β-tubulin expression with lymph node metastasis(P<0.05),but no significant correlation with histological grading and nuclear grade. CONCLUSION Centrosome defects may be an early event in the development of breast cancer and they can also promote tumor progression.Studies of aberrations of centrosomal proteins provide a new way to explore the mechanism of breast tumorigenesis.     

p53和nm23-H1蛋白表达与食管癌浸润转移的关系

Objective To study the relationship between expression of p53 and nm23-H1 and differentiation, invasiveness and metastasis in human esophageal carcinoma, and the correlation between expression of p53 and nm23-H1. Methods Expression of p53 and nm23-H1 in 50 patients with squamous cell carcinoma of esophagus was detected by using immuno-histochemical S-P methods. Results 35 cases (70%) and 32 cases (64%) of esophageal squamous cell carcinoma were positive for nm23-H1 protein and p53 protein, respectively. The expression of nm23-H1 was related to lymphatic metastasis (P<0.025), but not related to tumor differentiation, invasiveness, tumor location, tumor length, patient's gender and age (P>0.05). The lymphatic metastasis location positive group had a very lower expression of nm23-H1 and the negative rate was 70.8%, but the negative group had a higher expression and the positive rate was 65.4%. The expression of p53 was related to tumor differentiation and invasiveness (P<0.05), but not related to lymphatic metastasis, tumor location, tumor length, patient's gender and age(P>0.05). Among the three groups, the high differentiation group had the lowest expression of p53 and the positive rate was 29.2%, but the low differentiation group had the highest positive rate (71.4%). As for tumor invasiveness, the group of outer membrane of esophagus infiltrated had the highest p53 protein positive rate (56%), but in the group, of mucous or submucous layer infiltrated p53 protien was not detectable. The low expression of nm23-H1 and the high expression of p53 were also correlated. The expression of nm23-H1 and p53 were both correlated with TNM stage of esophageal carcinoma (P<0.05). The better esophageal carcinomas differentiated, the lower nm23-H1 expressed and higher p53 expressed. Conclusion Low expression of nm23-H1 and high expression of p53 play an important role in the progression of squamous cell carcinoma of esophagus. Nm23-H1 might beta gene markef in the prophecy of patients' prognosis and benefit tumor treatment clinically.     

Expression of p16, cyclin D<Subscript>1</Subscript> and RB protein in gastric carcinoma and premalignant lesions

Objective: To investigate the expression of p16, cyclin D₁ and Rb protein in gastric carcinoma and premalignant lesions including dysplastic gastric mucosa and intestinal metaplasia gastric mucosa. Methods: Using SP immunohistochemical methods, the expression of p16, cyclin D1 and Rb proteins was detected in 10 specimens of normal gastric mucosa, 15 specimens of dysplastic gastric mucosa, 15 specimens of intestinal metaplasia gastric mucosa, 30 specimens of gastric carcinoma. The clinical characteristics of the 30 patients with gastric carcinoma were analysed to explore the relationship between the parameter detected and biological action of gastric cancer. Results: Expression of p16 protein was detected in 90% of normal gastric mucosa, 86.67% of dysplastic gastric mucosa, 86.67% of intestinal metaplasia gastric mucosa, 36.67% of gastric carcinoma. The positive rate of p16 protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.01). Expression of cyclin D₁ protein was detected in 10% of normal gastric mucosa, 20% of dysplastic gastric mucosa, 20% of intestinal metaplasia gastric mucosa, 53.33% of gastric carcinoma. The positive rate of cyclin D₁, protein expression in gastric carcinoma is significantly higher than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.05). Expression of Rb protein was detected in 90% of normal gastric mucosa, 80% of dysplastic gastric mucosa, 80% of intestinal metaplasia gastric mucosa, 50% of gastric carcinoma. The positive rate of Rb protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa (P<0.05). The expression of p16, cyclin D₁ gene were associated with the degree of differentiation of gastric carcinoma, lymphnodes metastasis and distant metastasis. Conclusion: p16, Cyclin D₁ and Rb gene play important role in gastric carcinoma genesis. The expression of p16, cyclin D₁ and Rb gene have some value to the diagnosis at earlier stage of gastric cancer. Detection of expression of p16, cyclin D₁ gene would be helpful to judge the prognosis of gastric cancer. Biography: MIAO Lin (1966–), male, master of medicine, associate professor, Second Affiliated Hospital, Nanjing Medical University, majors in gastroenterological cancer.     

COX-2及P16在非霍奇金淋巴瘤中的表达及临床意义

Objective:To investigate the expression of cyclooxygenase-2(COX-2)and p16 proteins in non-Hodgkin's lym phomas(NHL)and their relationship with the genesis and progress of it.Methods:The expression of COX-2 and p16 protein were studied in the lymph nodes tissue from 60 NHL patients and 10 control patients with non-malignant diseases by flow cytometry.Results:Positive rate of COX-2 protein expression in NHL tissues(63.3%.38/60)was higher than that in normal lymphaden tissues(0,0/10).The difiefence was significant between the two groups(P＜0.01).Expression of COX-2 protein was related with the clinical stage of NHL.In stage Ⅰ+Ⅱ patients,it was significantly lower(35.0%+54.6%)than that in stage Ⅲ+Ⅳ patients(84.6%+87.5%)(P＜0.01).In different sex,age,tumor malignant degree,IPI grade,extranodal involvement and B symptoms groups,the differences of COX-2 expression were not statistically significant (P＞0.05).Positive fate of p16 protein expression(41.7%,25/60)in NHL' was statistically lower than that in normal lymphomas(100%,10/10)(P＜0.01). Expression of p16 protein was related to malignant degree of NHL.The positive rates of p16 protein in low malignant degree tissues(64.7%,11/17)was higher than that in high malignant degree tissues(14.3%,2/14)(P＜0.05).Positive rates of p16 protein of NHL tissues in different sex.age.IPI grade,extranodal involvement,dinical stages and B symptoms were not statistically significant(P＞0.05).The p16 protein expression in COX-2 positive patients was 47.4%(18/38),and in negative patients it was 31.8%(7/22).There was no statistically difference between them(P＞0.05).Correlation analysis revealed there was no correlation between expression of COX-2 and p16 protein.Conclusion:B0th COX-2 and P16 protein may all have relationship with the genesis and progress of NHL.The expression of COX-2 protein in NHL may be a poor prognostic indicator.COX-2 and p16 protein probably have dilferent mechanisms in the genesis and progress of NHL.Their relationship is firstly put forward in this article and needed further studying.     

Signal mechanism of inhibition of bifidobacteria on growth of colon cancer

Bifidobacteria, a physiologically beneficial organism in intestinal tract of human body, are the most in number with the most important function. It can prevent occurrence and evolution of a great variety of tumors in human body. We have proved that the bifidobacteria adolescence could inhibit the growth of colon cancer significantly in vivo and explored its antitumor mechanisms from the angle of cellular apoptosis[1,2]. Nowadays it has been known that in colon cancer there exists a high-level…     

Expression and clinical significance of vascular endothelial growth factor in benign and malignant tissues of breast

Objective:To detect the expression of vascular endothelial growth factor(VEGF)and microvessel density(MVD)count in breast benign affection,breast atypical hyperplasia and breast carcinoma in situ,and to clarify the relationship between VEGF expression,MVD and the clinicopathological features of these diseases. Methods:The expression of VEGF and MVD count in 115 cases breast benign diseases(including 40 breast fibroid tumor,40 breast cystic hyperplasia and 35 intraductal papilloma,19 breast atypical hyperplasias and 32 breast carcinomas in situ were examined by immunohistochemistry staining(SP-method). Results:The positive rate of VEGF in breast benign diseases,breast atypical hyperplasia and breast carcinoma in situ were 21.74%(25/115)、31.58.%(6/19)and 53.13%(17/32)respectively.It was the lowest in breast benign affection group,and was the highest breast carcinoma in situ group.The expression of VEGF increased gradually in the three groups(P＜0.05).The MVD count of the three groups were 14.41±2.59,18.89±4.47 and 21.13±4.12 respectively,It was the lowest in breast benign affection group,and was the highest breast carcinoma in situ group.The MVD count of the three groups increased gradually(P＜0.05).In VEGF positive group,MVD count was 19.41±4.78;In VEGF negative group,MVD count was 14.91±3.15.The MVD count was higher in VEGF positive group than that in VEGF negative group(P＜0.05). Conclusion:The results of this study suggested that VEGF could promote microvessel growth in breast tumors.The occurrence and progression of breast cancer might be related with the expression of VEGF.     

Let-7 family miRNAs regulate estrogen receptor alpha signaling in estrogen receptor positive breast cancer

In order to understand how microRNAs (miRNAs) regulate breast cancer tumorigenesis, a miRNA expression microarray screening was performed using RNA from formalin-fixed paraffin-embedded (FFPE) breast tissues, which included benign (n = 13), ductal carcinoma in situ (DCIS) (n = 16), and invasive ductal carcinoma (IDC) (n = 15). Twenty-five differentially expressed miRNAs (P < 0.01) were identified, of which let-7 family miRNAs were down-regulated in human breast cancer tissues at stages of DCIS and IDC compared to benign stage. We further found that there was an inverse correlation between ER-α expression and several members of let-7 family in the FFPE tissues. Next, we performed bioinformatics analysis and found that let-7 miRNA sequences match sequence in the 3′-UTR of estrogen receptor alpha (ER-α), suggesting ER-α may be a target of let-7, which was further confirmed by a number of experimental assays, including luciferase assay, protein expression, and mRNA expression. Overexpression of let-7 miRNAs in ER-positive breast cancer MCF7 cell line negatively affected ER-α activity. As expected, dampening of the ER-α signaling by let-7 miRNAs inhibited cell proliferation, and subsequently triggered the cell apoptotic process in MCF7 cells. In conclusion, our findings indicate a new regulatory mechanism of let-7 miRNAs in ER-α mediated cellular malignant growth of breast cancer.     

Effects of eb virus encoded LMP1 on differentiation of nasopharyngeal carcinoma cells

Latent membrane protein 1 (LMP1) is encoded by the BNLF1 fragment of Epstein-Barr virus (EBV) and recognized as an important oncoprotein nowadays. It is popularly known that EBV infection is closely associated with the development of nasopharyngeal carcinoma (NPC), and LMP1 would play its crucial role in nasopharyngeal carcino- genesis. LMP1 has a variety of carcinogenic functions. LMP1 can immortalize and malignantly transform normal lymphocytes or epithelial cells with the cooperat…     

食管癌细胞P-糖蛋白与CD44表达相关性研究

Objective： To investigate the relationship between P-glycoprotein （P-gp） and adhesion molecule CD44 expression as well as their clinical significance in esophageal carcinoma. Methods： To examine the expressed level of P-gp and CD44 by flow cytometry （FCM） in the operated samples of 70 cases with esophageal carcinoma and their normal mucosa of esophageal incision, and to evaluate their relationship with clinicopathological factors. Results： Among the 70 cases with esophageal carcinoma, the expression of P-gp in the 27 cases （38.6%） was negative （positive cells 〈25%）; 11 cases （15.7%） were 25%-40% expression of P-gp positive cells; 14 cases （20%） were 41%-60% expression of P-gp positive cells; 18 cases （25.7%） were the high expression （positive cells 〉60%） of P-gp. Of the cases with the tumor sizes being more than 4 cm, the expression of CD44 showed a significant difference （P〈0.05） in 25 cases with P-gp positive, compared with 19 cases with P-gp negative. Of the cases with high-mild differentiated esophageal carcinoma, the expression of CD44 showed a significant difference （P〈0.05） in 22 cases with P-gp positive, compared with 17 cases with P-gp negative. Of the cases with clinical Ⅲ-Ⅳ stage, the expression of CD44 showed a significant difference （P〈0.05） in 26 cases with P-gp positive, compared with 10 cases with P-gp negative. Of the cases with lymph node metastasis, the CD44 expression showed a significant difference （P=0.050） in 27 cases with P-gp positive, compared with 11 cases with P-gp negative. Of the cases of the patients＇ age being more than 56 years, the expression of CD44 showed a significant difference （P〈0.01） in 27 cases with P-gp positive, compared with 12 cases with P-gp negative. When the P-gp and CD44 expression were positive, the clinical Ⅱ stage and Ⅲ-Ⅳ stage in esophageal carcinoma was showed a significant difference （P〈0.05）. Conclusion： When the CD44 and P-gp both have the positive high expression, it will be significantly associated with the esophageal carcinoma progression and metastasis, so both were a positive expression in esophageal carcinoma, it might suggest a poor and unfavorable prognosis result.     

Expression of GPC3 protein and its significance in lung squamous cell carcinoma

The purpose of this study was to investigate GPC3 gene expression in lung squamous cell carcinoma tissue and its correlation with clinical and tumor characteristics. Using RT–PCR, the presence of GPC3 gene expression was detected in cancer tissue and adjacent normal tissue in 66 cases of lung squamous cell carcinoma and positive rates were calculated. Using Western blot, changes in GPC3 protein expression were detected in lung squamous cell carcinoma and adjacent normal tissues. The percentage of tissue samples expressing GPC3 mRNA was significantly higher in lung squamous cell carcinoma than in adjacent normal tissue (P < 0.05). This percentage was also significantly higher for cases with lymph node metastasis than for those without lymph node metastasis (P < 0.05). Further, the percentage of samples expressing GPC3 mRNA was higher with lowering degrees of tumor differentiation (P < 0.05). Rates of GPC3 expression were, however, independent of patient gender, age, and tumor size (P > 0.05). The expression of GPC3 protein in lung squamous cell carcinoma was significantly higher than that in adjacent normal tissues (P < 0.05). The expression in cases with lymph node metastasis was significantly higher than in those without lymph node metastasis (P < 0.05), and GPC3 protein expression increased with lowering degrees of tumor differentiation (P < 0.05). Further investigation is warranted for the association of initiation, development, invasion, and metastasis of disease.     

Expression of Inducible Nitric Oxide Synthase, p53 and Bcl-2 in Gastric Precancerous and Cancerous Lesions： Correlation with Clinical Features

OBJECTIVE To explore the expression of inducible nitric oxide synthase (iNOS), p53 and bcl -2 in gastric precancerous and cancerous lesions and to examine the expression of these proteins in relation to clinical features. METHODS The expressions of iNOS, p53 and bcl-2 proteins in gastric precancerous and cancerous lesions and their correlations with the clinical features were determined using immunohistochemical assays (Power VisionTM two -step method) on 84 gastric carcinomas and 54 gastric atypical hyperplastic tissues. Apoptotic cells were evaluated by terminal deoxynucleotidyl transferase- mediated dUTP-biotin nick-end labeling (TUNEL). RESULTS Expression of iNOS, p53 and bcl-2 was significantly higher in gastric carcinoma (GC) tissues than in gastric atypical hyperplastic tissues. Among the 84 carcinomas, the expression of p53 was observed in 50 (59.52%), bcl-2 in 43 (51.19%), and iNOS in 65 (77.58%). Overex-pression of iNOS and bcl-2 in gastric carcinoma was related to tumor size and iNOS was related to the presence of lymph node metastasis (P< 0.05). The expression of proteins did not correlate with age, sex, stage of disease, or differentiation. Expression of iNOS in gastric carcinoma tissues was positively correlated with bcl-2 expression (X2=8.926, P=0.003), and also with p53 expression (X2= 5.2430, P= 0.022). The mean apoptotic indexes (Al) were 1.29%±0.50 in low-grade atypical hyperplasia (LG), 0.96%±0.36 in high-grade atypical hyperplasia (HG) and 0.70%±0.43 in GC, with the difference being significant between LG, HG and GC (P< 0.05). There was a significant positive correlation between iNOS expression and the Al in GC (t=3.0815, P=0.0028). CONCLUSION iNOS was expressed in the majority of gastric carcinoma tissues and correlated with cellular apoptosis associated with p53 and bcl -2 expression. iNOS overexpression is closely associated with p53 and bcl-2 accumulation status. iNOS may play a synergistic role in the pathogenesis of GC.     

P130Cas和PTEN信号蛋白在胃癌中的表达及相互关系

Objective  To research the contributions of p130Cas and PTEN signal molecules to the carcinogenesis of gastric carcinoma and the relationship between them. Methods  Detecting proteins of p130Cas, PTEN and PTEN mRNA of 76 cases normal gastric mucosa and 112 cases gastric carcinoma by immunohistochemistry EnVision method and molecular hybridization in situ method respectively. Detecting PTEN genetic mutation of 30 cases normal gastric mucosa, 7 cases early gastric cancer and 30 cases progressive gastric cancer by PCR-SSCP. Results  The expression of p130Cas protein of gastric carcinoma increased significantly than that of normal gastric mucosa (P < 0.05). Opposite to above, the expression of PTEN protein of gastric carcinoma group was significantly lower than that of normal gastric mucosa group (P < 0.05). The expression of PTEN mRNA of gastric carcinoma group decreased obviously than normal gastric mucosa group (P < 0.001). Only one case exon 5 and one case exon 8 of PTEN appeared gene mutation of progressive gastric carcinoma group, the difference has no significance compared with normal gastric mucosa group and early gastric cancer group. Conclusion  The signaling molecules p130Cas and PTEN play an important role in the carcinogenesis of gastric carcinoma, and p130Cas plays the part of promoter, oppositely, maybe PTEN can inhibit it. Supported by a grant from Sanitary Science and Technological Development Foundation of Shandong Province (No. 2003HW015).