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 ...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 adenocarcinomas of different grade and stage. The results were compared with microvessel density and clinicopathological 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.展开更多
AIM:To investigate the association of variations in the cyclooxygenase-2(COX2) and uridine diphosphate glucuronosyltransferase 1A6(UGT1A6) genes and non-steroidal anti-inflammatory drugs(NSAIDs) use with risk of colon...AIM:To investigate the association of variations in the cyclooxygenase-2(COX2) and uridine diphosphate glucuronosyltransferase 1A6(UGT1A6) genes and non-steroidal anti-inflammatory drugs(NSAIDs) use with risk of colon cancer.METHODS:NSAIDs,which are known to reduce the risk of colon cancer,act directly on COX2 and reduce its activity.Epidemiological studies have associated variations in the COX2 gene with colon cancer risk,but others were unable to replicate this finding.Similarly,enzymes in the UGT1A6 gene have been demonstrated to modify the therapeutic effect of NSAIDs on colon adenomas.Polymorphisms in the UGT1A6 gene have been statistically shown to interact with NSAID intake to influence risk of developing colon adenomas,but not colon cancer.Here we examined the association of tagging single nucleotide polymorphisms(SNPs) in the COX2 and UGT1A6 genes,and their interaction with NSAID consumption,on risk of colon cancer in a population of 422 colon cancer cases and 481 population controls.RESULTS:No SNP in either gene was individually statistically significantly associated with colon cancer,nor did they statistically significantly change the protective effect of NSAID consumption in our sample.Like others,we were unable to replicate the association of variants in the COX2 gene with colon cancer risk(P > 0.05),and we did not observe that these variants modify the protective effect of NSAIDs(P > 0.05).We were able to confirm the lack of association of variants in UGT1A6 with colon cancer risk,although further studies will have to be conducted to confirm the association of these variants with colon adenomas.CONCLUSION:Our study does not support a role of COX2 and UGT1A6 genetic variations in the development of colon cancer.展开更多
To investigate the relationship between the expression of cyclooxygenase-2 （COX-2） and menstrual cycle, the regulatory effects of 17-β-estradiol （E2） and medroxyprogesterone acetate （MPA） on the expression of C...To investigate the relationship between the expression of cyclooxygenase-2 （COX-2） and menstrual cycle, the regulatory effects of 17-β-estradiol （E2） and medroxyprogesterone acetate （MPA） on the expression of COX-2 in cervical cancer Hela cells were examined. Cervical cancer specimens were obtained from 47 pre-menopausal patients. The phase of menstrual cycle was determined by case history and HE staining of uterine endometrium. COX-2 was immunohistochemically stained by SABC staining and the staining intensity was determined with computerized image analysis system. Hela cells were incubated with alcohol, E2, E2＋MPA, MPA for 12, 24 and 48 h respectively. The expression of COX-2 in Hela cells was detected by Western blotting and reverse transcriptase-polymerase chain reaction （RT-PCR）. Our results showed that the expression of COX-2 was significantly higher during proliferative phase than secretory phase （P〈0.05）, but there was no difference in the positive rate between proliferative phase and secretory phase （P〉0.05）. Incubation with E2 could significantly enhance the expression of COX-2 continually. On the contrary, E2＋MPA and MPA alone could decrease the expression of COX-2 as compared with the control and E2 group （P〈0.05 and P〈0.01 respectively）. It is concluded that the expression of COX-2 in cervical cancer of pre-menopausal patients and Hela cells was regulated by estrogen/progestogen.展开更多
Objective To investigate the expression of cyclooxygenase-2 (Cox-2) and microvessel density (MVD) in benign and malignant pheochromocytomas, and the relationship between Cox-2 and MVD. Methods Specimens and clinical d...Objective To investigate the expression of cyclooxygenase-2 (Cox-2) and microvessel density (MVD) in benign and malignant pheochromocytomas, and the relationship between Cox-2 and MVD. Methods Specimens and clinical data from 38 patients (21 benign and 17 malignant pheochromocytomas) were studied. Slides of normal adrenal glands in nephrectomy specimens from another 20 patients with benign renal tumors were used as control. Immunohistochemical technology was performed to detect the Cox-2 and MVD in all specimens. Results Expression of Cox-2 was observed in 5 of the 21 benign pheochromocytomas (23.8%), and in 14 of the 17 malignant (82.4%). No expression of Cox-2 was observed in control slides. There were significant differences of Cox-2 expression between benign and malignant pheochromocytomas, as well as between malignant pheochromocytomas and control (P<0.05). Expressions of MVD were 36.41±13.00, 21.43±8.05, and 13.36±4.34 in malignant, benign pheochromocytomas, and in control, respectively. Conclusion Cox-2 may contribute to the invasive characteristics of malignant pheochromocytomas and be used as a marker to distinguish malignant from benign pheochromocytomas. Expression of MVD in malignant pheochromocytomas was directly correlated with Cox-2.展开更多
文摘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 adenocarcinomas of different grade and stage. The results were compared with microvessel density and clinicopathological 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.
基金Supported by A Damon Runyon Cancer Research Foundation Clinical Investigator Award,CI-8An R25 training grant from the National Cancer Institute,R25T CA094186+1 种基金The Case Center for Transdisciplinary Research on Energetics and Cancer,1U54 CA-116867-01A National Cancer Institute K22 Award,1K22 CA120545-01
文摘AIM:To investigate the association of variations in the cyclooxygenase-2(COX2) and uridine diphosphate glucuronosyltransferase 1A6(UGT1A6) genes and non-steroidal anti-inflammatory drugs(NSAIDs) use with risk of colon cancer.METHODS:NSAIDs,which are known to reduce the risk of colon cancer,act directly on COX2 and reduce its activity.Epidemiological studies have associated variations in the COX2 gene with colon cancer risk,but others were unable to replicate this finding.Similarly,enzymes in the UGT1A6 gene have been demonstrated to modify the therapeutic effect of NSAIDs on colon adenomas.Polymorphisms in the UGT1A6 gene have been statistically shown to interact with NSAID intake to influence risk of developing colon adenomas,but not colon cancer.Here we examined the association of tagging single nucleotide polymorphisms(SNPs) in the COX2 and UGT1A6 genes,and their interaction with NSAID consumption,on risk of colon cancer in a population of 422 colon cancer cases and 481 population controls.RESULTS:No SNP in either gene was individually statistically significantly associated with colon cancer,nor did they statistically significantly change the protective effect of NSAID consumption in our sample.Like others,we were unable to replicate the association of variants in the COX2 gene with colon cancer risk(P > 0.05),and we did not observe that these variants modify the protective effect of NSAIDs(P > 0.05).We were able to confirm the lack of association of variants in UGT1A6 with colon cancer risk,although further studies will have to be conducted to confirm the association of these variants with colon adenomas.CONCLUSION:Our study does not support a role of COX2 and UGT1A6 genetic variations in the development of colon cancer.
文摘To investigate the relationship between the expression of cyclooxygenase-2 （COX-2） and menstrual cycle, the regulatory effects of 17-β-estradiol （E2） and medroxyprogesterone acetate （MPA） on the expression of COX-2 in cervical cancer Hela cells were examined. Cervical cancer specimens were obtained from 47 pre-menopausal patients. The phase of menstrual cycle was determined by case history and HE staining of uterine endometrium. COX-2 was immunohistochemically stained by SABC staining and the staining intensity was determined with computerized image analysis system. Hela cells were incubated with alcohol, E2, E2＋MPA, MPA for 12, 24 and 48 h respectively. The expression of COX-2 in Hela cells was detected by Western blotting and reverse transcriptase-polymerase chain reaction （RT-PCR）. Our results showed that the expression of COX-2 was significantly higher during proliferative phase than secretory phase （P〈0.05）, but there was no difference in the positive rate between proliferative phase and secretory phase （P〉0.05）. Incubation with E2 could significantly enhance the expression of COX-2 continually. On the contrary, E2＋MPA and MPA alone could decrease the expression of COX-2 as compared with the control and E2 group （P〈0.05 and P〈0.01 respectively）. It is concluded that the expression of COX-2 in cervical cancer of pre-menopausal patients and Hela cells was regulated by estrogen/progestogen.
文摘Objective To investigate the expression of cyclooxygenase-2 (Cox-2) and microvessel density (MVD) in benign and malignant pheochromocytomas, and the relationship between Cox-2 and MVD. Methods Specimens and clinical data from 38 patients (21 benign and 17 malignant pheochromocytomas) were studied. Slides of normal adrenal glands in nephrectomy specimens from another 20 patients with benign renal tumors were used as control. Immunohistochemical technology was performed to detect the Cox-2 and MVD in all specimens. Results Expression of Cox-2 was observed in 5 of the 21 benign pheochromocytomas (23.8%), and in 14 of the 17 malignant (82.4%). No expression of Cox-2 was observed in control slides. There were significant differences of Cox-2 expression between benign and malignant pheochromocytomas, as well as between malignant pheochromocytomas and control (P<0.05). Expressions of MVD were 36.41±13.00, 21.43±8.05, and 13.36±4.34 in malignant, benign pheochromocytomas, and in control, respectively. Conclusion Cox-2 may contribute to the invasive characteristics of malignant pheochromocytomas and be used as a marker to distinguish malignant from benign pheochromocytomas. Expression of MVD in malignant pheochromocytomas was directly correlated with Cox-2.
