- Email: [email protected]
OC.07.5 HCV-ANTIVIRAL THERAPY DELAYS GASTRIC EMPTYING TIME AND MODIFIES CCK AND MOTILIN SERUM LEVELS
S72
Abstracts of the 18th National Congress of Digestive Diseases / Digestive and Liver Disease 44S (2012) S55–S220
OC.07.5 HCV-ANTIVIRAL THERAPY DELAYS GASTRIC EMPTYING TIME AND MODIFIES CCK AND MOTILIN SERUM LEVELS G. De Nucci ∗ , A. Rocco, D. Compare, L. Donnarumma, V. Varriale, O.M. Nardone, M. Sanduzzi Zamparelli, F. Morisco, G. Nardone Department of Clinical and Experimental Medicine, Gastroenterology Unit, University of Naples “Federico II”, Naples, Italy, Naples, Italy Background and aim: Digestive symptoms are common side effects of antiviral therapy in patients with HCV chronic hepatitis (CH). The occurrence of digestive symptoms significantly impairs quality of life and requires reduction or even suspension of the therapy in up to 15% of the cases. Recent advances in pathophisiology of functional dyspepsia indicate that delay of gastric emptying time (GET) likely depending on altered Cholecystokinin (CCK) and Motilin serum levels is implicated in the onset of symptoms. In this study we evaluated digestive symptoms, GET and CCK and motilin fasting and post-prandial serum levels in patients with HCV-related CH before, during and after standard antiviral therapy. Material and methods: Twenty-eight patients (M/F 11/17 male, age range 28-70 yrs) with histologically proven HCV-related CH and absence of digestive diseases were enrolled in the study. Baseline, during the therapy (3th month) and after a month by the end of therapy patients underwent: an oriented questionnaire evaluating digestive symptoms. 13C-octanoate breath test (13C-OBT) was performed to evaluate GET. Fasting and post-prandial CCK and Motilin serum levels were assessed ELISA. Antiviral therapy was performed according to standard protocols. Results: Baseline none of the patients complained of significant digestive symptoms. GET was normal (t/2 <120 min) in all cases but 3/28 (2%). Baseline and post-prandial CCK and Motilin levels were 0.6±0.4 and 1.57±0.5 and 5.9±5.2 and 1.7±0.9, respectively. At three-month therapy, epigastric burning, belching, epigastric pain, post-prandial fullness, early satiety, bloating, nausea and vomiting were reported by 31%, 57%, 7%, 60%, 57%, 53%, 46% and 14%, respectively. GET rate was significantly delayed in all cases (p <0.0001). CCK fasting and post-prandial serum levels significantly increased (p<0.0001) while Motilin decreased in respect to baseline values (p<0.003). Interestingly, there was a direct significant relation between GI symptom score, GET and CCK and Motilin serum level (p<0.05). After 1 month by the end of therapy, all patients were symptom-free and GET as well as CCK and Motilin serum levels returned to baseline values. Conclusions: Digestive symptoms caused by HCV-antiviral therapy depend on the delay of GET as well as deregulation of CCK/Motilin homeostasis.
OC.07.6 ITALIAN MULTICENTER STUDY ON INFLAMMATORY BOWEL DISEASES WITH HBV OR HCV INFECTION UNDERGOING IMMUNOSUPPRESSIVE THERAPY F. Morisco ∗ ,1 , F. Castiglione 1 , A. Rispo 1 , T. Stroffolini 2 , R. Vitale 1 , S. Sansone 1 , M. Guarino 1 , L. Donnarumma 1 , L. Biancone 3 , F. Zorzi 3 , R. D’Incà 4 , S. Camera 1 , A. Caruso 4 , R. Marmo 5 , A. Orlando 6 , S. Renna 6 , G. Riegler 7 , V. Bove 7 , M. Vecchi 8 , G.E. Tontini 8 , N. Caporaso 1 1 Department of Clinical and Experimental Medicine, Gastroenterology Unit, University “Federico II”, Naples, Italy; 2 Department of Infectious and Tropical Diseases, University “La Sapienza”, Rome, Italy; 3 Gastroenterology Unit University “Tor Vergata”, Rome, Italy; 4 Gastroenterology Unit, University of Padova, Padova, Italy; 5 Gastroenterology Unit, Polla Hospital, Salerno, Italy; 6 Ospedale “V. Cervello”, Palermo, Italy; 7 Gastroenterology Unit, Second University of Naples, Naples, Italy; 8 Gastroenterology and Gastrointestinal Endoscopy Unit, Irccs Policlinico San Donato & University of Milan, Milan, Italy
Background and aim: Ulcerative colitis and Crohn’s disease are chronic immune-mediated inflammatory bowel diseases (IBD) of an unknown etiology. Traditional and biological immunosuppressors represent an important therapeutic option for patients affected by steroid-dependent or steroid-refractory IBD, with an overall efficacy of about 50%. Viral hepatitis reactivation has been widely reported in patients undergoing immunosuppressive therapy;
however, few data are available on the risk of HBV and HCV reactivation in patients with inflammatory bowel disease (IBD) receiving immunosuppressive drugs. The aim of this multicenter study was to assess the prevalence of HBV and HCV infection in a consecutive series of patients with IBD and to value the effects of immunosuppressive therapy during the course of the infection. Material and methods: Retrospective observational multicenter study, including all consecutive patients with IBD observed in 7 Italian tertiary referral hospitals from January 2000 to December 2008. Results: A total of 5096 IBD patients were consecutively included: 2485 Crohn’s disease (CD) and 2611 Ulcerative Colitis (UC). The 30.5% and 29.7% of the patients were investigated for HBV and HCV infection. A total of 30 HBsAg positive, 17 isolated anti-HBc and 60 anti-HCV positive patients were identified. In all, 20 patients with HBV or HCV infection received immunosuppressive therapy (6 HBsAg+; 4 isolated anti-HBc+ and 10 antiHCV+). One out of 6 patients HBsAg+, one of 4 isolated anti-HBc+ and one of anti-HCV+ experienced reactivation of hepatitis with mild liver disfunction. Conclusions: Screening procedures for HBV and HCV infection at diagnosis have been underused in IBD population. We confirm the role of immunosuppressive therapy in HBV reactivation, but the impact on clinical course seems to be less relevant than previously reported. Finally, our study confirms the light effect of immunosuppressive therapy on HCV infection.
OC.08.1 CD133 ANTIGEN IS ASSOCIATED WITH COLONY FORMATION AND INVASIVENESS ABILTY IN COLORECTAL CANCER CELLS BY MODULATION OF SPECIFIC GENE PROFILES M.A. Puglisi ∗ ,2 , M. Corbi 3 , V. Tesori 2 , W. Lattanzi 4 , M. Barba 4 , A. Boninsegna 3 , F. Michetti 4 , A. Cittadini 3 , G.B. Gasbarrini 1 , A. Sgambato 3 , A. Gasbarrini 2 1 Medical
Research Foundation Onlus, Bologna, Italy; 2 Institute of Internal Medicine and Gastroenterology-Gemelli Hospital, Rome, Italy; 3 Institute of General Pathology-Gemelli Hospital, Rome, Italy; 4 Institute of Anatomy and Cell Biology-Gemelli Hospital, Rome, Italy Background and aim: CD133 antigen is considered a marker of cancer stem cells (CSC) in a number of human cancers, including colon cancer (CC). However, despite constant research efforts, the molecular mechanisms and signaling pathways that regulate the behavior of CD133-expressing cells remain unknown. Aim of this study was to better characterize the role of CD133 in the definition of stemness potential by clarifying the precise contribution of CD133+ tumor-initiating cells in CC pathogenesis. Material and methods: The expression of CD133 was silenced in four colon cancer cell lines (CaCo-2, HT29, LoVo, HCT-116) by transfecting cells with CD133specific small interfering RNA (siRNA). CD133 overexpression was induced in HCT-116 cells by transient transfection with an eukaryotic CD133 expression vector. CD133 expression was then evaluated using qRT-PCR, Western Blot and by flow cytometry. The effect of CD133 modulation on tumor-initiating properties of CC cells was tested by soft-agar assay and matrigel transwell migration assay. Results: Upon the successful silencing of CD133 in CC cell lines, a parallel decrease of expression was observed for selected genes involved in cell proliferation and invasion (e.g. Endothelin-1 and NR4A2). In addition, all CC cell lines displayed a significantly lower capacity to give rise to colonies in soft agar; colonies were smaller in dimensions compared to scramble controls. Moreover, the down-regulation of CD133 was associated with inhibition of the cells’ migration and invasiveness ability. On the other hand, the overexpression of CD133 in HCT-116 cells correlated with major invasiveness of CC cells and higher anchorage-independent growth in soft agar. It is noteworthy that increased expression of CD133 mRNA (average 4.7-fold) was able to induce an increased expression of both Endothelin-1 and NR4A2 mRNA (average 4.6- and 1.7-fold, respectively), thus further supporting the functional relationship amongst the three molecules. Conclusions: We provide for the first time evidence that CD133 is not only a marker for CSC but also a master regulator of specific gene profiles in these cells, being involved in the regulation of clonogenicity and invasiveness properties in the CC cells.
Abstracts of the 18th National Congress of Digestive Diseases / Digestive and Liver Disease 44S (2012) S55–S220
OC.07.5 HCV-ANTIVIRAL THERAPY DELAYS GASTRIC EMPTYING TIME AND MODIFIES CCK AND MOTILIN SERUM LEVELS G. De Nucci ∗ , A. Rocco, D. Compare, L. Donnarumma, V. Varriale, O.M. Nardone, M. Sanduzzi Zamparelli, F. Morisco, G. Nardone Department of Clinical and Experimental Medicine, Gastroenterology Unit, University of Naples “Federico II”, Naples, Italy, Naples, Italy Background and aim: Digestive symptoms are common side effects of antiviral therapy in patients with HCV chronic hepatitis (CH). The occurrence of digestive symptoms significantly impairs quality of life and requires reduction or even suspension of the therapy in up to 15% of the cases. Recent advances in pathophisiology of functional dyspepsia indicate that delay of gastric emptying time (GET) likely depending on altered Cholecystokinin (CCK) and Motilin serum levels is implicated in the onset of symptoms. In this study we evaluated digestive symptoms, GET and CCK and motilin fasting and post-prandial serum levels in patients with HCV-related CH before, during and after standard antiviral therapy. Material and methods: Twenty-eight patients (M/F 11/17 male, age range 28-70 yrs) with histologically proven HCV-related CH and absence of digestive diseases were enrolled in the study. Baseline, during the therapy (3th month) and after a month by the end of therapy patients underwent: an oriented questionnaire evaluating digestive symptoms. 13C-octanoate breath test (13C-OBT) was performed to evaluate GET. Fasting and post-prandial CCK and Motilin serum levels were assessed ELISA. Antiviral therapy was performed according to standard protocols. Results: Baseline none of the patients complained of significant digestive symptoms. GET was normal (t/2 <120 min) in all cases but 3/28 (2%). Baseline and post-prandial CCK and Motilin levels were 0.6±0.4 and 1.57±0.5 and 5.9±5.2 and 1.7±0.9, respectively. At three-month therapy, epigastric burning, belching, epigastric pain, post-prandial fullness, early satiety, bloating, nausea and vomiting were reported by 31%, 57%, 7%, 60%, 57%, 53%, 46% and 14%, respectively. GET rate was significantly delayed in all cases (p <0.0001). CCK fasting and post-prandial serum levels significantly increased (p<0.0001) while Motilin decreased in respect to baseline values (p<0.003). Interestingly, there was a direct significant relation between GI symptom score, GET and CCK and Motilin serum level (p<0.05). After 1 month by the end of therapy, all patients were symptom-free and GET as well as CCK and Motilin serum levels returned to baseline values. Conclusions: Digestive symptoms caused by HCV-antiviral therapy depend on the delay of GET as well as deregulation of CCK/Motilin homeostasis.
OC.07.6 ITALIAN MULTICENTER STUDY ON INFLAMMATORY BOWEL DISEASES WITH HBV OR HCV INFECTION UNDERGOING IMMUNOSUPPRESSIVE THERAPY F. Morisco ∗ ,1 , F. Castiglione 1 , A. Rispo 1 , T. Stroffolini 2 , R. Vitale 1 , S. Sansone 1 , M. Guarino 1 , L. Donnarumma 1 , L. Biancone 3 , F. Zorzi 3 , R. D’Incà 4 , S. Camera 1 , A. Caruso 4 , R. Marmo 5 , A. Orlando 6 , S. Renna 6 , G. Riegler 7 , V. Bove 7 , M. Vecchi 8 , G.E. Tontini 8 , N. Caporaso 1 1 Department of Clinical and Experimental Medicine, Gastroenterology Unit, University “Federico II”, Naples, Italy; 2 Department of Infectious and Tropical Diseases, University “La Sapienza”, Rome, Italy; 3 Gastroenterology Unit University “Tor Vergata”, Rome, Italy; 4 Gastroenterology Unit, University of Padova, Padova, Italy; 5 Gastroenterology Unit, Polla Hospital, Salerno, Italy; 6 Ospedale “V. Cervello”, Palermo, Italy; 7 Gastroenterology Unit, Second University of Naples, Naples, Italy; 8 Gastroenterology and Gastrointestinal Endoscopy Unit, Irccs Policlinico San Donato & University of Milan, Milan, Italy
Background and aim: Ulcerative colitis and Crohn’s disease are chronic immune-mediated inflammatory bowel diseases (IBD) of an unknown etiology. Traditional and biological immunosuppressors represent an important therapeutic option for patients affected by steroid-dependent or steroid-refractory IBD, with an overall efficacy of about 50%. Viral hepatitis reactivation has been widely reported in patients undergoing immunosuppressive therapy;
however, few data are available on the risk of HBV and HCV reactivation in patients with inflammatory bowel disease (IBD) receiving immunosuppressive drugs. The aim of this multicenter study was to assess the prevalence of HBV and HCV infection in a consecutive series of patients with IBD and to value the effects of immunosuppressive therapy during the course of the infection. Material and methods: Retrospective observational multicenter study, including all consecutive patients with IBD observed in 7 Italian tertiary referral hospitals from January 2000 to December 2008. Results: A total of 5096 IBD patients were consecutively included: 2485 Crohn’s disease (CD) and 2611 Ulcerative Colitis (UC). The 30.5% and 29.7% of the patients were investigated for HBV and HCV infection. A total of 30 HBsAg positive, 17 isolated anti-HBc and 60 anti-HCV positive patients were identified. In all, 20 patients with HBV or HCV infection received immunosuppressive therapy (6 HBsAg+; 4 isolated anti-HBc+ and 10 antiHCV+). One out of 6 patients HBsAg+, one of 4 isolated anti-HBc+ and one of anti-HCV+ experienced reactivation of hepatitis with mild liver disfunction. Conclusions: Screening procedures for HBV and HCV infection at diagnosis have been underused in IBD population. We confirm the role of immunosuppressive therapy in HBV reactivation, but the impact on clinical course seems to be less relevant than previously reported. Finally, our study confirms the light effect of immunosuppressive therapy on HCV infection.
OC.08.1 CD133 ANTIGEN IS ASSOCIATED WITH COLONY FORMATION AND INVASIVENESS ABILTY IN COLORECTAL CANCER CELLS BY MODULATION OF SPECIFIC GENE PROFILES M.A. Puglisi ∗ ,2 , M. Corbi 3 , V. Tesori 2 , W. Lattanzi 4 , M. Barba 4 , A. Boninsegna 3 , F. Michetti 4 , A. Cittadini 3 , G.B. Gasbarrini 1 , A. Sgambato 3 , A. Gasbarrini 2 1 Medical
Research Foundation Onlus, Bologna, Italy; 2 Institute of Internal Medicine and Gastroenterology-Gemelli Hospital, Rome, Italy; 3 Institute of General Pathology-Gemelli Hospital, Rome, Italy; 4 Institute of Anatomy and Cell Biology-Gemelli Hospital, Rome, Italy Background and aim: CD133 antigen is considered a marker of cancer stem cells (CSC) in a number of human cancers, including colon cancer (CC). However, despite constant research efforts, the molecular mechanisms and signaling pathways that regulate the behavior of CD133-expressing cells remain unknown. Aim of this study was to better characterize the role of CD133 in the definition of stemness potential by clarifying the precise contribution of CD133+ tumor-initiating cells in CC pathogenesis. Material and methods: The expression of CD133 was silenced in four colon cancer cell lines (CaCo-2, HT29, LoVo, HCT-116) by transfecting cells with CD133specific small interfering RNA (siRNA). CD133 overexpression was induced in HCT-116 cells by transient transfection with an eukaryotic CD133 expression vector. CD133 expression was then evaluated using qRT-PCR, Western Blot and by flow cytometry. The effect of CD133 modulation on tumor-initiating properties of CC cells was tested by soft-agar assay and matrigel transwell migration assay. Results: Upon the successful silencing of CD133 in CC cell lines, a parallel decrease of expression was observed for selected genes involved in cell proliferation and invasion (e.g. Endothelin-1 and NR4A2). In addition, all CC cell lines displayed a significantly lower capacity to give rise to colonies in soft agar; colonies were smaller in dimensions compared to scramble controls. Moreover, the down-regulation of CD133 was associated with inhibition of the cells’ migration and invasiveness ability. On the other hand, the overexpression of CD133 in HCT-116 cells correlated with major invasiveness of CC cells and higher anchorage-independent growth in soft agar. It is noteworthy that increased expression of CD133 mRNA (average 4.7-fold) was able to induce an increased expression of both Endothelin-1 and NR4A2 mRNA (average 4.6- and 1.7-fold, respectively), thus further supporting the functional relationship amongst the three molecules. Conclusions: We provide for the first time evidence that CD133 is not only a marker for CSC but also a master regulator of specific gene profiles in these cells, being involved in the regulation of clonogenicity and invasiveness properties in the CC cells.