Drug therapy and monitoring for inflammatory bowel disease: a multinational questionnaire investigation in Asia

Background/Aims@#The incidence and prevalence of inflammatory bowel disease (IBD) is rising in Asia recently. The study aimed to obtain a comprehensive understanding of the current status of drug therapy and monitoring for IBD in Asia. @*Methods@#A questionnaire investigation on drug therapy and monitoring for IBD was conducted right before the 6th Annual Meeting of Asian Organization for Crohn’s & Colitis. Questionnaires were provided to Asian physicians to fill out via emails between March and May 2018. @*Results@#In total, responses of 166 physicians from 129 medical centers were included for analysis. Among the surveyed regions, the most average number of IBD specialist gastroenterologists and nurses was 4.8 per center in Taiwan and 2.5 per center in Mainland China, respectively. 5-Aminosalicylic acid/sulfasalazine (99.4%) was the most preferred first-line choice for mild-moderate ulcerative colitis (UC), meanwhile corticosteroid (83.7%) was widely applied for severe UC. The first-line medication for Crohn’s disease (CD) markedly varied as corticosteroid (68.1%) was the most favored in Mainland China, Japan, and South Korea, followed by infliximab (52.4%) and azathioprine (47.0%). Step-up strategy was preferred in mild-moderate UC (96.4%), while 51.8% of the physicians selected top-down treatment for CD. Only 25.9% and 17.5% of the physicians could test blood concentration of infliximab and antibody to infliximab in their hospitals, respectively. @*Conclusions@#The current status of drug therapy and monitoring for IBD in Asia possesses commonalities as well as differences. Asian recommendations, IBD specialist teams and practice of therapeutic drug monitoring are required to improve IBD management in Asia.

CNTNAP3 Copy Number Variation and its Significance in Crohn's Disease / 胃肠病学

DNA copy number variation is an important pathogenic factor of human diseases and might be involved in the pathogenesis and pathological process of inflammatory bowel disease (IBD).Aims: To investigate the copy number variation of CNTNAP3 gene and its significance in Crohn''s disease (CD).Methods: A total of 101 active CD patients admitted from Jul.2009 to Dec.2010 at Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled.Eighty healthy subjects were served as controls.Peripheral blood or intestinal mucosa samples of CD patients were collected, and the copy number variation of CNTNAP3 gene was screened and validated by array-based comparative genomic hybridization (aCGH, n=8) and real-time PCR (n=93);expression of CNTNAP3 encoding protein was determined by ELISA (n=55).Results: A large fragment copy number amplification was revealed by aCGH at chromosome 9p13 region (including CNTNAP3 gene) in untreated CD patients.Real-time PCR confirmed that the copy number of CNTNAP3 gene was amplified in peripheral blood of CD patients, especially steroid-naive patients as compared with the normal controls (208 616.4±126 984.7 and 233 453.3±113 520.8 vs.161 750.2 ±53 940.3, P0.05).Furthermore, the plasma CNTNAP3 level in CD patients with amplified copy number was not correlated with the simplified endoscopic score for CD (P>0.05).Conclusions: Copy number amplification of CNTNAP3 gene might be involved in the pathogenesis of CD in Chinese population.Glucocorticoid treatment and smoking might affect the copy number variation of CNTNAP3 gene.Plasma CNTNAP3 level cannot discriminate CD patients from healthy subjects.Conclusions of this study needs to be further demonstrated and discussed.

Specific anti-gastric cancer effects of a recombinant plasmid expressing nonstructural protein 1 of parvovirus H1

To investigate the responsiveness of gastric tumor cells to the nonstructural protein [NS]1 of parvovirus H1, which has a preferential lytic growth cycle in cancer cells. This study was carried out in Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai, China from 2009 to 2012. An NS1-expressing plasmid was introduced into gastric cell lines or nude mice bearing tumor grafts. Expression was monitored by tracking fluorescence tag and specific transcription. Tumor growth suppression was measured, and cell cycle dyshomeostasis was verified by flow cytometry. Cell cycle regulators' level was measured on both the transcription and protein level. Gastric cancer cells were efficiently suppressed in vitro, or in the xenograft mice model. The NS1 dependent tumor suppression was specific since plasmid-driven NS1 expression in some normal tissues, in particular, the lungs was not accompanied by adverse side effects. The NS1 expression was found to stall gastric cancer cells in the G0/G1 stage with accumulation of cycle regulator p21. The NS1 expression can suppress gastric cancer cell growth both in vitro and in xenograft model, probably through induction of the cell cycle regulator p21. These results support further development of the parvoviral NS1 protein as an anti-cancer effector

Suppression effect of expressing parvovirus H-1 nonstructural protein 1 gene on human gastric cancer cells / 中华消化杂志

Objective To investigate the suppression effect of expressing parvovirus H-1 nonstructural protein 1 (NS1) gene on human gastric cancer cells and the possible mechanisms.Methods A recombinant enhanced green fluorescent protein (eGFP) labeled NS1 of parvovirus H-1 plasmid was constructed.Human gastric cancer cell line SGC7901 was transfected with recombinant plasmid (experiment group) or blank vector (negative control group) and blank control group was treated with equal amount of phosphate buffered saline (blank control group).After transfection,the distribution of fluorescent signal was observed under fluorescent microscope.The expression of NS1 at gene and protein level was measured.Cell growth curve of each group was drawn.The expression of cell senescence-associated β-galactosidase (SA-β-Gal) was tested.The changes of cell cycle were investigated by flowcytometry.Two groups' comparision was performed by t-test.Results After transfection,NS1 was expressed in SGC7901 cells at gene and protein level.Compared with negative control group,the fluorescent signal accumulated in cell nucleus in experiment group.The percentage of SA-β-Gal positive cell in experiment group ((30.5 ± 1.4) ％) was higher than that of negative control group ((4.4± 1.1) ％) and the difference was statistically significant (t =-12.931,P ＜ 0.01).The growth inhibition rate of SGC7901 cells from the first day to the fourth day was 45％,62％,73％ and 77％,respectively.The cell cycle of eGFP-NS1 expressed SGC7901 cells was arrested at G0/G1 phase.Conclusion Parvovirus H-1 NS1 play the role in cell nucleus of gastric cancer cell line SGC7901 and could make cell cycle arrested at G0/G1 phase,which effectively inhibited the proliferation SGC7901 cell.