Coexpression of inducible nitric oxide synthase and COX-2 in hepatocellular carcinoma and surrounding liver : Possible involvement of COX-2 in the angiogenesis of hepatitis C virus-positive cases
Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) has been reported to be responsible for enhanced tumor growth and angiogenesis in various tumors. However, the relationships between tumor vascularity and COX-2 and iNOS expression have not been evaluated in hepatocell...
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| Veröffentlicht in: | Clinical cancer research 2001-05, Vol.7 (5), p.1325-1332 |
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| creator | ATIQUR RAHMAN, Md DIPOK KUMAR DHAR YAMAGUCHI, Emi MARUYAMA, Seiji SATO, Takashi HAYASHI, Hikota ONO, Takashi YAMANOI, Akira KOHNO, Hitoshi NAGASUE, Naofumi |
| description | Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) has been reported to be responsible for enhanced tumor growth and angiogenesis in various tumors. However, the relationships between tumor vascularity and COX-2 and iNOS expression have not been evaluated in hepatocellular carcinoma (HCC). In this study, we examined the expression of iNOS and COX-2 and microvessel density (MVD) by immunohistochemical staining in 100 tissue sections collected from HCC patients. iNOS expression was significantly higher in hepatitis C virus (HCV)-positive HCCs (P = 0.011). COX-2 expression was significantly correlated with iNOS expression (P = 0.046) and tumor MVD (P = 0.011) in HCV-positive HCCS: iNOS expression was neither correlated with MVD nor had any influence on patient survival; however, combined negative expression of iNOS and COX-2 had a significant impact on patient survival (P = 0.041 and 0.018, log-rank test for overall and recurrence-free survival rate, respectively). The present findings suggest that combined expression of iNOS and COX-2 may play an important role in prognosis of HCV-positive HCC patients and that this could be partially attributable to modulation of angiogenesis by COX-2. |
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However, the relationships between tumor vascularity and COX-2 and iNOS expression have not been evaluated in hepatocellular carcinoma (HCC). In this study, we examined the expression of iNOS and COX-2 and microvessel density (MVD) by immunohistochemical staining in 100 tissue sections collected from HCC patients. iNOS expression was significantly higher in hepatitis C virus (HCV)-positive HCCs (P = 0.011). COX-2 expression was significantly correlated with iNOS expression (P = 0.046) and tumor MVD (P = 0.011) in HCV-positive HCCS: iNOS expression was neither correlated with MVD nor had any influence on patient survival; however, combined negative expression of iNOS and COX-2 had a significant impact on patient survival (P = 0.041 and 0.018, log-rank test for overall and recurrence-free survival rate, respectively). The present findings suggest that combined expression of iNOS and COX-2 may play an important role in prognosis of HCV-positive HCC patients and that this could be partially attributable to modulation of angiogenesis by COX-2.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 11350902</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adult ; Aged ; Antibodies - analysis ; Antigens, CD34 - immunology ; Biological and medical sciences ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - physiopathology ; Carcinoma, Hepatocellular - virology ; Cyclooxygenase 2 ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Hepacivirus - isolation & purification ; Humans ; Isoenzymes - biosynthesis ; Isoenzymes - physiology ; Liver Neoplasms - metabolism ; Liver Neoplasms - physiopathology ; Liver Neoplasms - virology ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; Membrane Proteins ; Middle Aged ; Multivariate Analysis ; Neovascularization, Pathologic - etiology ; Neovascularization, Pathologic - virology ; Nitric Oxide Synthase - biosynthesis ; Nitric Oxide Synthase Type II ; Prostaglandin-Endoperoxide Synthases - biosynthesis ; Prostaglandin-Endoperoxide Synthases - physiology ; Tumors</subject><ispartof>Clinical cancer research, 2001-05, Vol.7 (5), p.1325-1332</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1023987$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11350902$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ATIQUR RAHMAN, Md</creatorcontrib><creatorcontrib>DIPOK KUMAR DHAR</creatorcontrib><creatorcontrib>YAMAGUCHI, Emi</creatorcontrib><creatorcontrib>MARUYAMA, Seiji</creatorcontrib><creatorcontrib>SATO, Takashi</creatorcontrib><creatorcontrib>HAYASHI, Hikota</creatorcontrib><creatorcontrib>ONO, Takashi</creatorcontrib><creatorcontrib>YAMANOI, Akira</creatorcontrib><creatorcontrib>KOHNO, Hitoshi</creatorcontrib><creatorcontrib>NAGASUE, Naofumi</creatorcontrib><title>Coexpression of inducible nitric oxide synthase and COX-2 in hepatocellular carcinoma and surrounding liver : Possible involvement of COX-2 in the angiogenesis of hepatitis C virus-positive cases</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) has been reported to be responsible for enhanced tumor growth and angiogenesis in various tumors. However, the relationships between tumor vascularity and COX-2 and iNOS expression have not been evaluated in hepatocellular carcinoma (HCC). In this study, we examined the expression of iNOS and COX-2 and microvessel density (MVD) by immunohistochemical staining in 100 tissue sections collected from HCC patients. iNOS expression was significantly higher in hepatitis C virus (HCV)-positive HCCs (P = 0.011). COX-2 expression was significantly correlated with iNOS expression (P = 0.046) and tumor MVD (P = 0.011) in HCV-positive HCCS: iNOS expression was neither correlated with MVD nor had any influence on patient survival; however, combined negative expression of iNOS and COX-2 had a significant impact on patient survival (P = 0.041 and 0.018, log-rank test for overall and recurrence-free survival rate, respectively). The present findings suggest that combined expression of iNOS and COX-2 may play an important role in prognosis of HCV-positive HCC patients and that this could be partially attributable to modulation of angiogenesis by COX-2.</description><subject>Adult</subject><subject>Aged</subject><subject>Antibodies - analysis</subject><subject>Antigens, CD34 - immunology</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - physiopathology</subject><subject>Carcinoma, Hepatocellular - virology</subject><subject>Cyclooxygenase 2</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Hepacivirus - isolation & purification</subject><subject>Humans</subject><subject>Isoenzymes - biosynthesis</subject><subject>Isoenzymes - physiology</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - physiopathology</subject><subject>Liver Neoplasms - virology</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Proteins</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Neovascularization, Pathologic - etiology</subject><subject>Neovascularization, Pathologic - virology</subject><subject>Nitric Oxide Synthase - biosynthesis</subject><subject>Nitric Oxide Synthase Type II</subject><subject>Prostaglandin-Endoperoxide Synthases - biosynthesis</subject><subject>Prostaglandin-Endoperoxide Synthases - physiology</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkM9q3DAQh01Iaf60r1B0KLkZJMuS7d6CadNAIDmk0Nuilca7E2zJ0dgmeb68WOVkm5xmhvn4fcwcZadCqSqXhVbHqedVnfNSFifZGdED56IUvPycnQghFW94cZq9tAGexghEGDwLHUPvZovbHpjHKaJl4QkdMHr2094QMOMda2__5kUi2R5GMwULfT_3JjJrokUfBvNK0RxjmL1Dv2M9LhDZD3YXkmgNR7-EfoEB_LRa3xOn_arYYdiBB0Jal68WnNLQsgXjTPkYKM0LJCMBfck-daYn-Hqo59mfXz_v29_5ze3VdXt5k4-F1FOuRV3XDcjKFCCFVa7RXWONKDrnXPpNYbmQTdfprRbCCFVCqQ0ocE3ptNVSnmcXb7ljDI8z0LQZkNbjjYcw06bitVRK6QR-O4DzdgC3GSMOJj5v_r89Ad8PgCFr-i4ab5E-uIQ0dSX_AWtWkCg</recordid><startdate>20010501</startdate><enddate>20010501</enddate><creator>ATIQUR RAHMAN, Md</creator><creator>DIPOK KUMAR DHAR</creator><creator>YAMAGUCHI, Emi</creator><creator>MARUYAMA, Seiji</creator><creator>SATO, Takashi</creator><creator>HAYASHI, Hikota</creator><creator>ONO, Takashi</creator><creator>YAMANOI, Akira</creator><creator>KOHNO, Hitoshi</creator><creator>NAGASUE, Naofumi</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20010501</creationdate><title>Coexpression of inducible nitric oxide synthase and COX-2 in hepatocellular carcinoma and surrounding liver : Possible involvement of COX-2 in the angiogenesis of hepatitis C virus-positive cases</title><author>ATIQUR RAHMAN, Md ; DIPOK KUMAR DHAR ; YAMAGUCHI, Emi ; MARUYAMA, Seiji ; SATO, Takashi ; HAYASHI, Hikota ; ONO, Takashi ; YAMANOI, Akira ; KOHNO, Hitoshi ; NAGASUE, Naofumi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p236t-618889e37a2e31c5d96f9ca12fddd0012c0139ff6b611a154e46ae5ed94d6c633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antibodies - analysis</topic><topic>Antigens, CD34 - immunology</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - physiopathology</topic><topic>Carcinoma, Hepatocellular - virology</topic><topic>Cyclooxygenase 2</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Hepacivirus - isolation & purification</topic><topic>Humans</topic><topic>Isoenzymes - biosynthesis</topic><topic>Isoenzymes - physiology</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - physiopathology</topic><topic>Liver Neoplasms - virology</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Membrane Proteins</topic><topic>Middle Aged</topic><topic>Multivariate Analysis</topic><topic>Neovascularization, Pathologic - etiology</topic><topic>Neovascularization, Pathologic - virology</topic><topic>Nitric Oxide Synthase - biosynthesis</topic><topic>Nitric Oxide Synthase Type II</topic><topic>Prostaglandin-Endoperoxide Synthases - biosynthesis</topic><topic>Prostaglandin-Endoperoxide Synthases - physiology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ATIQUR RAHMAN, Md</creatorcontrib><creatorcontrib>DIPOK KUMAR DHAR</creatorcontrib><creatorcontrib>YAMAGUCHI, Emi</creatorcontrib><creatorcontrib>MARUYAMA, Seiji</creatorcontrib><creatorcontrib>SATO, Takashi</creatorcontrib><creatorcontrib>HAYASHI, Hikota</creatorcontrib><creatorcontrib>ONO, Takashi</creatorcontrib><creatorcontrib>YAMANOI, Akira</creatorcontrib><creatorcontrib>KOHNO, Hitoshi</creatorcontrib><creatorcontrib>NAGASUE, Naofumi</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ATIQUR RAHMAN, Md</au><au>DIPOK KUMAR DHAR</au><au>YAMAGUCHI, Emi</au><au>MARUYAMA, Seiji</au><au>SATO, Takashi</au><au>HAYASHI, Hikota</au><au>ONO, Takashi</au><au>YAMANOI, Akira</au><au>KOHNO, Hitoshi</au><au>NAGASUE, Naofumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Coexpression of inducible nitric oxide synthase and COX-2 in hepatocellular carcinoma and surrounding liver : Possible involvement of COX-2 in the angiogenesis of hepatitis C virus-positive cases</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2001-05-01</date><risdate>2001</risdate><volume>7</volume><issue>5</issue><spage>1325</spage><epage>1332</epage><pages>1325-1332</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) has been reported to be responsible for enhanced tumor growth and angiogenesis in various tumors. However, the relationships between tumor vascularity and COX-2 and iNOS expression have not been evaluated in hepatocellular carcinoma (HCC). In this study, we examined the expression of iNOS and COX-2 and microvessel density (MVD) by immunohistochemical staining in 100 tissue sections collected from HCC patients. iNOS expression was significantly higher in hepatitis C virus (HCV)-positive HCCs (P = 0.011). COX-2 expression was significantly correlated with iNOS expression (P = 0.046) and tumor MVD (P = 0.011) in HCV-positive HCCS: iNOS expression was neither correlated with MVD nor had any influence on patient survival; however, combined negative expression of iNOS and COX-2 had a significant impact on patient survival (P = 0.041 and 0.018, log-rank test for overall and recurrence-free survival rate, respectively). The present findings suggest that combined expression of iNOS and COX-2 may play an important role in prognosis of HCV-positive HCC patients and that this could be partially attributable to modulation of angiogenesis by COX-2.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>11350902</pmid><tpages>8</tpages></addata></record> |
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| ispartof | Clinical cancer research, 2001-05, Vol.7 (5), p.1325-1332 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research; Alma/SFX Local Collection |
| subjects | Adult Aged Antibodies - analysis Antigens, CD34 - immunology Biological and medical sciences Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - physiopathology Carcinoma, Hepatocellular - virology Cyclooxygenase 2 Female Gastroenterology. Liver. Pancreas. Abdomen Hepacivirus - isolation & purification Humans Isoenzymes - biosynthesis Isoenzymes - physiology Liver Neoplasms - metabolism Liver Neoplasms - physiopathology Liver Neoplasms - virology Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences Membrane Proteins Middle Aged Multivariate Analysis Neovascularization, Pathologic - etiology Neovascularization, Pathologic - virology Nitric Oxide Synthase - biosynthesis Nitric Oxide Synthase Type II Prostaglandin-Endoperoxide Synthases - biosynthesis Prostaglandin-Endoperoxide Synthases - physiology Tumors |
| title | Coexpression of inducible nitric oxide synthase and COX-2 in hepatocellular carcinoma and surrounding liver : Possible involvement of COX-2 in the angiogenesis of hepatitis C virus-positive cases |
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