诱导型一氧化氮合酶/环氧合酶2在女性压力性尿失禁中的研究进展

诱导型一氧化氮合酶(inducible nitric oxide synthase,i NOS)、环氧合酶2(cyclooxygenase-2,COX-2)及各自的催化产物一氧化氮和前列腺素对维持机体的各种病理生理活动有重要作用,它们参与了免疫炎症反应、缺血、损伤、肿瘤等相关疾病的发生、发展,两者对人类下尿路的生理病理活动起调控作用。女性压力性尿失禁(female stress urinary incontinence,FSUI)是一种严重影响女性身心健康及生活质量的常见疾病。越来越多的研究表明,i NOS/COX-2与FSUI的发病密切相关。文中综述了i NOS/COX-2在FSUI中可能扮演的角色及机制,这不仅为疾病的治疗提供了一个重要靶点,也为新药的开发和研究提供了理论基础和研究思路。

塞来昔布对鼻咽癌放射治疗增敏作用的临床研究

我们从2006年1月～2008年1月在鼻咽癌放射治疗中,应用塞来昔布配合增敏作用,报道如下。1资料与方法1.1一般资料。鼻咽癌初诊患者64例,男44例,女20例,年龄28～68岁。Karnofsky评分70分以上。临床分期采用1992年福州分期标准,血、尿常规、肝肾功能、心电图均正常,近1个月内未进行抗肿瘤药物治疗。

环氧化酶-2和血管内皮生长因子C表达与喉癌淋巴管转移

环氧化酶-2(cyclooxygenase-2,COX-2)是前列腺素合成的关键酶,在头颈鳞状细胞癌(简称鳞癌)等多种恶性肿瘤中表达上调,并与肿瘤发生和发展有关。淋巴管转移是喉鳞癌最常见的转移方式,血管内皮生长因子C(vascular endothelial growth factor C,VEGF-C)

环氧化酶-2和Survivin mRNA在舌癌中的表达及临床意义

1资料与方法 1.1一般资料。收集我科2006～2011年舌癌手术切除标本60例,其中男37例,女23例,年龄40～75岁,所有患者手术前均未经化疗、放疗或者免疫治疗。另收集舌外伤、舌修整正常舌黏膜组织30例,全部标本1份经甲醛溶液固定,用于病理诊断,另1份置液氮中冻存备做逆转录聚合酶链式反应（RT-PCR）。

Effect of Nimesulide on proliferation and apoptosis of human hepatoma SMMC-7721 cells

AIM: Cyclooxygenase-2 (COX-2) has been suggested to be associated with carcinogenesis. We sought to investigate the effect of the selective COX-2 inhibitor, Nimesulide on proliferation and apoptosis of SMMC-7721 human hepatoma cells.METHODS: This study was carried out on the culture of hepatic carcinoma SMMC-7721 cell line. Various concentrations of Nimesulide (0, 200 micromol/L, 300 micromol/L, 400 micromol/L) were added and incubated. Cell proliferation was detected with MTT colorimetric assay, cell apoptosis by electron microscopy, flow cytometry and TUNEL.RESULTS: Nimesulide could significantly inhibit SMMC-7721 cells proliferation dose-dependent and in a dependent manner compared with that of the control group. The duration lowest inhibition rate produced by Nimesulide in SMMC-7721 cells was 19.06%, the highest inhibition rate was 58.49%. After incubation with Nimesulide for 72 h, the most highest apoptosis rate and apoptosis index of SMMC-7721 cells comparing with those of the control were 21.20%+/-1.62% vs 2.24%+/-0.26% and 21.23+/-1.78 vs 2.01+/-0.23 (P【0.05). CONCLUSION:The selective COX-2 inhibitor, Nimesulide can inhibit the proliferation of SMMC-7721 cells and increase apoptosis rate and apoptosis index of SMMC-7721 cells. The apoptosis rate and the apoptosis index are dose-dependent. Under electron microscope SMMC-7721 cells incubated with 300 micromol and 400 micromol Nimesulide show apoptotic characteristics. With the clarification of the mechanism of selective COX-2 inhibitors, These COX-2 selective inhibitors can become the choice of prevention and treatment of cancers.

Anti-Helicobacter pylori therapy followed by celecoxib on progression of gastric precancerous lesions

AIM： To evaluate whether celecoxib, a selective cyclooxygenase 2 （COX-2） inhibitor, could reduce the severity of gastric precancerous lesions following Hel/cobacter pylori （H pylorl） eradication. METHODS： H pylori-eradicated patients with gastric precancerous lesions randomly received either celecoxib （n = 30） or placebo （n = 30） for up to 3 mo. COX-2 expression and activity was determined by immunostaining and prostaglandin E2 （PGE2） assay, cell proliferation by Ki-67 immunostaining, apoptosis by TUNEL staining and angiogenesis by microvascular density （MVD） assay using CD31 staining.RESULTS： COX-2 protein expression was significantly increased in gastric precancerous lesions （atrophy, intestinal metaplasia and dysplasia, respectively） compared with chronic gastritis, and was concomitant with an increase in cell proliferation and angiogenesis. A significant improvement in precancerous lesions was observed in patients who received celecoxib compared with those who received placebo （P 〈 0.001）. Of these three changes, 84.6% of sites with dysplasia regressed in patients treated with celecoxib （P = 0.002） compared with 60% in the placebo group, suggesting that celecoxib was effective on the regression of dysplasia. COX-2 protein expression （P 〈 0.001） and COX-2 activity （P 〈 0.001） in the gastric tissues were consistently lower in celecoxib-treated patients compared with the placebo-treated subjects. Moreover, it was also shown that celecoxib suppressed cell proliferation （P 〈 0.01）, induced cell apoptosis （P 〈 0.01） and inhibited angiogenesis with decreased MVD （P 〈 0.001）. However, all of these effects were not seen in placebo-treated subjects. Furthermore, COX-2 inhibition resulted in the up-regulation of PPARy expression, a protective molecule with anti-neoplastic effects. CONCLUSION： H pylori eradication therapy followed by celecoxib treatment improves gastric precancerous lesions by inhibiting COX-2 activity, inducing apoptosis, and suppressing cell proliferation and angiogenesis.

Microvessel density is a prognostic marker of human gastric cancer

AIM: To investigate whether microvessel density (MVD) is related with prognosis in gastric cancer patients, and the expression of cyclooxygenase-2 (COX-2) and vessel endothelial growth factor (VEGF) so as to determine the possible role of COX-2 and VEGF in gastric cancer angiogenesis.METHODS: Forty-seven formalin-fixed paraffin-embedded tissue samples of gastric cancer were evaluated for COX-2, VEGF by immunohitochemical staining. To assess tumor angiogenesis, MVD was determined by immunohitochemical staining of endothelial protein factor Ⅷ-related antigen. The relationship among COX-2 and VEGF expression, MVD, and clinicopathologic parameters was analyzed. RESULTS: Among the 67 samples, high MVD was significantly associated with lymph node metastasis and poor survival. Multivariate survival analysis showed that MVD value and lymph node metastasis were independent prognostic factors. The expression rate of COX-2 and VEGF was significantly higher than that of the adjacent tissues. COX-2 and VEGF expression in gastric cancer was significantly correlated with tumor differentiation and depth of invasion, but not with survival. The mean MVD value of COX-2 or VEGF positive tumors was higher than that of COX-2 or VEGF negative tumors. A significant correlation was found between the expressions of COX-2and VEGF. CONCLUSION: MVD may be one of the important prognostic factors for gastric cancer patients. COX-2 and VEGF may play an important role in tumor progression by stimulating angiogenesis. VEGF might play a main role in the COX-2 angiogenic pathway. The inhibition of angiogenesis or COX-2, VEGF activity may have an important therapeutic benefit in the control of gastric cancer.

Cyclooxygenase 2 polymorphism and colorectal cancer:-765G>C variant modifies risk associated with smoking and body mass index

AIM： To explore whether cyclooxygenase 2 （COX-2） -765G〉C polymorphism is associated with susceptibility of colorectal cancer （CRC） and to evaluate the risk of colorectal cancer in relation to environmental exposures and polymorphism. METHODS： We conducted a case-control study of 137 patients with colorectal cancer and 199 cancerfree controls in northeast China. Multivariate logistic regression analysis was performed to calculate the adjusted odds ratio （OR） and 95% confidence interval （95% CI）. RESULTS： The -765G〉C polymorphism was not independently associated with CRC risk. However, risk associated with the polymorphism differed by smoking and body mass index （BMI）. Smoking and BMI associated risks were stronger among those with -765GG genotype, showing that smokers had a 2.682-fold greater risk of CRC than nonsmokers （51/43 vs 68/126, P = 0.006）. Compared to those with a normal body mass index （BMI 18.5-22.9）, those with overweight （BMI 23-24.9） had a 3.909-fold higher risk of CRC （OR = 3.909, 95% CI = 2.081-7.344; P 〈 0.001）, while those with obesity （BMI 〉 25） had a 2.031- fold higher risk of CRC （OR = 1.107, 95% CI = 1.107-3.726; P = 0.022）. is not associated with an increased risk of CRC, -765GG genotype appears to be related to an increased risk in the presence of smoking and higher BMI.

Selective COX-2 inhibitor,NS-398,suppresses cellular proliferation in human hepatocellular carcinoma cell lines via cell cycle arrest

AIM: To investigate the growth inhibitory mechanism of NS-398, a selective cyclooxygenase-2 (COX-2) inhibitor, in two hepatocellular carcinoma (HCC) cell lines (HepG2 and Huh7). METHODS: HepG2 and Huh7 cells were treated with NS-398. Its effects on cell viability, cell proliferation, cell cycles, and gene expression were respectively evaluated by water-soluble tetrazolium salt (WST-1) assay, 4’-6-diamidino-2-phenylindole (DAPI) staining, flow cytometer analysis, and Western blotting, with dimethyl sulfoxide (DMSO) as positive control. RESULTS: NS-398 showed dose- and time-dependent growth-inhibitory effects on the two cell lines. Proliferating cell nuclear antigen (PCNA) expressions in HepG2 and Huh7 cells, particularly in Huh7 cells were inhibited in a time- and dose-independent manner. NS-398 caused cell cycle arrest in the G1 phase with cell accumulation in the sub-G1 phase in HepG2 and Huh7 cell lines. No evidence of apoptosis was observed in two cell lines. CONCLUSION: NS-398 reduces cell proliferation by inducing cell cycle arrest in HepG2 and Huh7 cell lines, and COX-2 inhibitors may have potent chemoprevention effects on human hepatocellular carcinoma.

Expression of cyclooxygenase-1 and -2 in extra-hepatic cholangiocarcinoma

Objective: To investigate the expression of cyclooxy- genase-1 (COX-1) and cyclooxygenase-2 (COX-2) in extra-hepatic cholangiocarcinoma and the relation- ship between their expression and clinicopathological parameters. Methods: COX-1 and COX-2 were detected in 56 ex- tra-hepatic cholangiocarcinomas, including 31 matched tissues originating from non-tumorous bile ductal tissue adjacent to tumours and 6 normal bile ductal tissues, by immunohistochemistry strept avi- din-biotin complex using isozyme selective antibod- ies. Results: There was no difference in expression of COX-1 between carcinomas (96%, 54/56) and non- cancerous specimens (94%, 29/31, P>0.05) or normal bile ductal tissues (100%, 6/6, P>0.05). The positive rate of COX-2 expression in extra-hepat- ic cholangiocarcinomas (86%, 48/56) was signifi- cantly higher than their matched tissues (39%, 12/ 31, P<0.01) and normal bile ductal tissues (0%, 0/6, P<0.01). Overexpression of COX-2 in extra- hepatic cholangiocarcinoma was related to the metas- tasis of lymph nodes, distant organs or tissues (P< 0.05) as well as the degree of tumour differentiation (P<0.05). Conclusions: The overexpression of COX-2 plays a crucial role in the carcinogenesis and development of extra-hepatic cholangiocarcinoma, indicating that COX-2 may serve as a target for chemoprevention of extra-hepatic cholangiocarcinoma.

Extract of buckwheat sprouts scavenges oxidation and inhibits pro-inflammatory mediators in lipopolysaccharide-stimulated macrophages (RAW264.7)

OBJECTIVE： Buckwheat has been considered as a potential source of nutraceutical components on the world market of probiotic foodstuffs. The purpose of this study was to evaluate the effects of tartary buckwheat （Fagopyrum tataricum） sprouts on oxidation and pro-inflammatory mediators. METHODS： The anti-oxidant effects of buckwheat extract （BWE） and rutin were evaluated by using 1,1-diphenyl-2-picrylhydrazyl （DPPH）-and nitric oxide （NO）-scavenging activities, serum peroxidation and chelating assays. Lipopolysaccharide （LPS）-stimulated RAW264.7 cells were used to evaluate anti-inflammatory activities of buckwheat and rutin. NO production in LPS- stimulated RAW264.7 cells was determined by using Griess reagent. The expressions of inducible nitric oxide synthase （iNOS）, cyclooxygenase-2 （COX-2）, nuclear factor-kappa B （NF-κB） p65 subunit in cytosolic and nuclear portions were determined by Western blot analysis. Also, the production of inflammatory cytokines interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） was determined by enzyme-linked immunosorbent assay. RESULTS： Inhibitory concentration 50 values for DPPH- and NO-scavenging activities of BWE were 24.97 and 72.54 μg/mL respectively. BWE inhibited serum oxidation and possessed chelating activity. Furthermore, BWE inhibited IL-6 and TNF-a production in LPS-stimulated RAW264.7 cells. Also, BWE inhibited iNOS and COX-2 expression and NF-KB p65 translocation. CONCLUSION： Buckwheat sprouts possessed strong antioxidant activity and inhibited production of pro-inflammatory mediators in the applied model systems. Thus, buckwheat can be suggested to be beneficial in inflammatory diseases by inhibiting the free radicals and inflammatory mediators.

COX-2 in liver,from regeneration to hepatocarcinogenesis:What we have learned from animal models?

The use of animals lacking genes or expressing genes under the control of cell-specific promoters has signifi cantly increased our knowledge of the genetic and molecular basis of physiopathology,allowing testing of functional hypotheses and validation of biochemical and pharmacologic approaches in order to understand cell function.However,with unexpected frequency,gene knockout animals and,more commonly,animal models of transgenesis give experimental support to even opposite conclusions on gene function.Here we summarize what we learned on the role of cyclooxygenase 2(COX-2) in liver and revise the results obtained in 3 independent models of mice expressing a COX-2 transgene specifi cally in the hepatocyte.Upon challenge with pro-inflammatory stimuli,the animals behave very differently,some transgenic models having a protective effect but others enhancing the injury.In addition,one transgene exerts differential effects on normal liver physiology depending on the transgenic animal model used.

Thymoquinone suppresses migration of Lo Vo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activation

AIM To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration. METHODS Our experiments used high dose thymoquinone (TQ) as an inhibitor to arrest LoVo (a human colon adenocarcinoma cell line) cancer cell growth, which was detected by cell proliferation assay and immunoblotting assay. Low dose TQ did not significantly reduce LoVo cancer cell growth. Cyclooxygenase 2 (COX-2) is an enzyme that is involved in the conversion of arachidonic acid into prostaglandin E2 (PGE2) in humans. PGE2 can promote COX-2 protein expression and tumor cell proliferation and was used as a control. RESULTS Our results showed that 20 mu mol/L TQ significantly reduced human LoVo colon cancer cell proliferation. TQ treatment reduced the levels of p-PI3K, p-Akt, p-GSK3 beta, and beta-catenin and thereby inhibited the downstream COX-2 expression. Results also showed that the reduction in COX-2 expression resulted in a reduction in PGE2 levels and the suppression of EP2 and EP4 activation. Further analysis showed that TG treatment inhibited the nuclear translocation of beta-catenin in LoVo cancer cells. The levels of the cofactors LEF-1 and TCF-4 were also decreased in the nucleus following TQ treatment in a dose-dependent manner. Treatment with low dose TQ inhibited the COX-2 expression at the transcriptional level and the regulation of COX-2 expression efficiently reduced LoVo cell migration. The results were further verified in vivo by confirming the effects of TQ and/or PGE2 using tumor xenografts in nude mice. CONCLUSION TQ inhibits LoVo cancer cell growth and migration, and this result highlights the therapeutic advantage of using TQ in combination therapy against colorectal cancer.

Identification of specific genes and pathways involved in NSAIDs-induced apoptosis of human colon cancer cells

AIM: To study whether indomethacin (IND), a nonselective cyclooxygenase (COX) inhibitor or NS-398 (NS), a COX-2-selective inhibitor, induces apoptosis in human colon cancer cells and which apoptosis-related genes and pathways are involved. METHODS: Human colon cancer Caco-2 cells were treated with either: placebo, IND (0.05-0.5 mmol/L) or NS (0.01-0.2 mmol/L) for 1, 5 and 18 h. We then studied: (1) Cell death by the TUNEL method, (2) mRNA expression of 96 apoptosis-related genes using DNA microarray, (3) expression of selected apoptosis related proteins by Western blotting. RESULTS: Both IND and NS induced apoptosis in 30%-50% of Caco-2 cells in a dose dependent manner. IND (0.1 mmol/L for 1 h) significantly up-regulated pro-apoptotic genes in four families: (1) TNF receptor and ligand, (2) Caspase, (3) Bcl-2 and (4) Caspase recruiting domain. NS treatment up-regulated similar pro-apoptotic genes as IND. In addition, IND also down-regulated anti-apoptotic genes of the IAP family. CONCLUSION: (1) Both non-selective and COX-2-selective NSAIDs induce apoptosis in colon cancer cells in a dose dependent manner. (2) Both NSAIDs induce apoptosis by activating two main apoptotic pathways: the death receptor pathway (involving TNF-R) and the mitochondrial pathway. (3) IND induces apoptosis by up-regulating pro-apoptotic genes and down-regulating anti-apoptotic genes, while NS only up-regulates pro-apoptotic genes. (4) Induction of apoptosis in coloncancer cells by NSAIDs may explain in part, their inhibitory action on colon cancer growth.

Relationship between expression and distribution of cyclooxygenase-2 and bcl-2 in human gastric adenocarcinoma

AIM: To explore expression and distribution features of COX-2 and bcl-2 in human gastric adenocarcinoma tissues and to study its biological significance.METHODS: Totally 36 human gastric carcinoma samples were enrolled in this study (cardiac adenocarcinoma 16 cases, distal gastric adenocarcinoma 20 cases). The expressions of COX-2 and bcl-2 in cancerous tissues and corresponding para-cancerous tissues were investigated by immunohistochemistry using COX-2 polyclonal antibody and bcl-2 monoclonal antibody. The normal gastric mucosa tissues were used as control.RESULTS: The expressions of COX-2 and bcl-2 in gastric carcinoma were significantly higher than that in the paracancerous tissues (77.8% vs 47.2%, P＜0.01, 80.56% vs 58.33%, P＜0.05). The expression of COX-2 in cardiac adenocarcinoma was remarkably higher than that in the distal gastric carcinoma (93.8% vs 65.0%, P＜0.01). The expression of COX-2 was mainly localized in the cytoplasm of tumor cells and partly in the nucleus. There is a transition of the COX-2 cytoplasmic positivity to nucleic in tumor cells with the increase of gastric carcinoma pathological grade. Interstitial macrophages, fibroblasts and vascular endothelial cells also expressed COX-2. The tissues with higher expression of COX-2 also expressed high level of bcl-2 protein.CONCLUSION: Abnormal expression pattern of COX-2within the tissues of human gastric cancer is correlated with tumor location and lymph node metastasis. COX-2may regulate expression of apoptosis suppressor gene (bcl-2) through interaction of tumor cells and stromal cells and play an important role in the generation and development of tumors, which will be of great help in developing new methods for antitumor therapy.

Cyclooxygenase-2 promotes angiogenesis by increasing vascular endothelial growth factor and predicts prognosis in gallbladder carcinoma

AIM: To investigate the relationships between the expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and the degree of vascularization, clinicopathologic feature, survival time of patients with gallbladder carcinomas. METHODS: Sixty-four gallbladder carcinoma specimens were evaluated for COX-2, VEGF expression by immunohi stochemical methods. Microvessel counts (MVC) were determined using CD34. The relationships between COX-2, VEGF expression, CD34-stained MVC, clinicopathologic features and survival time were analyzed. The correlations between COX-2 and VEGF expression, CD34-stained MVC were also investigated. RESULTS: COX-2, VEGF immunoreactivity were observed in 71.9% (46/64) and 54.7% (35/64) specimens, respectively. The average MVC in 64 cases of gallbladder carcinoma was 57±14 per high power vision field. The status of MVC was closely correlated with Nevin staging, tumor differentiation and lymph node metastasis (P<0.01, 0.002, and 0.003, 0.000, respectively). Increased VEGF expression was significantly correlated with tumor differentiation (poorly and moderately>well differentiated, P<0.05, P = 0.016). Clinical stages had no relation with the expression of VEGF (P>0.05, P = 0.612). There was a positive correlation between COX-2 expression and clinical stages. The positive rate of COX-2 was higher in cases of Nevin stages S4-S5 (81.8%) than in those of Nevin stages S1-S3 (50.0%) with a statistical significance (P0.01, P = 0.009). The expression of COX-2 did not vary with differentiation (P>0.05, P= 0.067). Statistically significant differences were also observed according to lymph node metastasis, COX-2 expression and VEGF expression (P<0.01,0.000, and 0.001, respectively). There was no relation between VEGF, COX-2 expression, MVC and the age and sex of patients. MVC and VEGF positive rate in the COX-2 positive gallbladder carcinoma tissue was higher than that in the COX-2 negative tissue (P<0.05, 0.000, and 0.032, respectively). Patients with VEGF, COX-2 positive tumors had a significantly shorter survival time than those with negative tumors (P<0.05,0.004, 0.01, respectively). CONCLUSION: Augmented tumor neovascularization induced by VEGF may be one of the several effects of COX-2 responsible for poor prognosis of human gallbladder carcinoma. COX-2 inhibitor, either in combination therapy with other agents, or for chemoprevention, may be effective via suppression of angiogenesis in this fatal disease.

Non-steroidal anti-inflammatory drugs in prevention of gastric cancer

Non-steroidal anti-inflammatory drugs （NSAIDs） including cydooxygenase 2 （COX-2） selective inhibitors, are potential agents for the chemoprevention of gastric cancer. Epidemiological and experimental studies have shown that NSAID use is associated with a reduced risk of gastric cancer although many questions remain unanswered such as the optimal dose and duration of treatment. The possible mechanisms for the suppressor effect of NSAIDs on carcinogenesis are the ability to induce apoptosis in epithelial cells and regulation of angiogenesis. Both COX-dependent and COX- independent pathways have a role in the biological activity of NSAIDs. Knowledge of how NSAIDs prevent neoplastic growth will greatly aid the design of better chemopreventive drugs and novel treatments for gastric cancer.

Haplotype of prostaglandin synthase 2/cyclooxygenase 2 is involved in the susceptibility to inflammatory bowel disease

AIM： Prostaglandin G/H synthase 2 （PTGS2 or COX2） is one of the key factors in the cellular response to inflammation. PTGS2 is expressed in the affected intestinal segments of patients with inflammatory bowel diseases （IBD）. In IBD patients, non-steroidal anti-inflammatory drugs, which have been shown to reduce both the production and activity of PTGS2, may activate IBD and aggravate the symptoms. We aimed at examining genetic variants of PTGS2 that may be risk factors for IBD. METHODS： We genotyped 291 individuals diagnosed with IBD and 367 controls from the Dutch population for the five most frequent polymorphisms of the PTG52 gene. Clinical data were collected on all patients. DNA was extracted via normal laboratory methods. Genotyping was carried out using multiplex PCR followed by the Invader Assay and the 5＇ exonuclease assay （TaqMan）. New polymorphism screening was performed by pre-screening with denaturing high-performance liquid chromatography, followed by fluorescent sequencing. RESULTS： Allele 5209G was weakly associated with Crohn＇s disease （odds ratio [OR] 1.63, 95% confidence interval [CI] 1.03-2.57）, and allele 8473T with ulcerativecolitis （OR 1.50, 95%CI 1.00-2.27）. The haplotype including both alleles showed a strong association with IBD （OR 13.15, 95%CI 3.17-116.15）. This haplotype, while rare （-0.3%） in the general population, is found more frequently in patients （3.5%）. CONCLUSION： Our data suggest that this haplotype of PTGS2 contributes to the susceptibility of IBD.

Expression of inducible nitric oxide synthase and cyclooxygenase-2 in pancreatic adenocarcinoma:Correlation with microvessel density

AIM:Cydooxygenases (COX) are key enzymes for conversion of arachidonic acid to prostaglandins.Nitric oxide synthase (NOS) is the enzyme responsible for formation of nitric oxide. Both have constitutive and inducible isoforms.The inducible isoforms (iNOS and COX-2) are of great interest as regulators of tumor angiogenesis,tumorigenesis and inflammatory processes.This study was to clarify their role in pancreatic adenocarcinomas. METHODS:We investigated the immunohistochemical iNOS and COX-2 expression in 40 pancreatic ductal adenocardnomas of different grade and stage.The results were compared with microvessel density and dinicopathological data. RESULTS:Twenty-one (52.5%) of the cases showed iNOS expression,15 (37.5%) of the cases were positive for COX-2. The immunoreaction was heterogeneously distributed within the tumors.Staining intensity was different between the tumors.No correlation between iNOS and COX-2 expression was seen.There was no relationship with microvessel density. However,iNOS positive tumors developed more often distant metastases and the more malignant tumors showed a higher COX-2 expression.There was no correlation with other clinicopathological data. CONCLUSION:Approximately half of the cases expressed iNOS and COX-2.These two enzymes do not seem to be the key step in angiogenesis or carcinogenesis of pancreatic adenocarcinomas.Due to a low prevalence of COX-2 expression,chemoprevention of pancreatic carcinomas by COX-2 inhibitors can only achieve a limited success.

Protective effects of electroacupuncture on acetylsalicylic acid-induced acute gastritis in rats

AIM: To investigate the protective effects of electroacupuncture (EA) pretreatment on acetylsalicylic acid (ASA)-induced ulceration in rats. METHODS: We randomly divided 72 rats into three groups including control (administered with distilled water), ASA group (administered 100 mg/kg ASA) and EA group (administered EA + 100 mg/kg ASA). Each rat was fasted for 18 to 24 h before experimentation, and lesion scores, gastric acidity, cyclooxygenase (COX)-1 and -2 mRNA levels, and total nitric oxide (NO) concentration were measured. RESULTS: The lesion scores of the EA group were significantly lower than those of the ASA group. Gastric acidity of the ASA and EA groups was reduced compared to the control group. COX-1 and -2 mRNA levels were significantly increased in the EA group as compared to the control and ASA groups, and NO levels were also significantly increased in the EA group as compared to the ASA group. CONCLUSION: These results suggest that EA-mediated protection against ASA-induced ulceration in rats may occur via gastric defense components.