Micro RNA-320 family is downregulated in colorectal adenoma and affects tumor proliferation by targeting CDK6

AIM: To investigate the microR NA(miR NA) expression during histological progression from colorectal normal mucosa through adenoma to carcinoma within a lesion. METHODS: Using microarray, the sequential changes in miR NA expression profiles were compared in colonic lesions from matched samples; histologically, nonneoplastic mucosa, adenoma, and submucosal invasive carcinoma were microdissected from a tissue sample. Cell proliferation assay was performed to observe the effect of miR NA, and its target genes were predicted using bioinformatics approaches and the expression profile of SW480 transfected with the miR NA mimics. mR NA and protein levels of the target gene in colon cancer cell lines with a mimic control or miR NA mimics were measured using qR TPCR and Western blotting. The expression levels of miR NA and target gene in colorectal tissue samples were also measured.RESULTS: Microarray analysis identified that the miR-320 family, including miR-320 a, miR-320 b, miR-320 c, miR-320 d and miR-320 e, were differentially expressed in adenomaand submucosal invasive carcinoma. The mi R-320 family, which inhibits cell proliferation, is frequently downregulated in colorectal adenoma and submucosal invasive carcinoma tissues. Seven genes including CDK6 were identified to be common in the results of gene expression array and bioinformatics analyses performed to find the target gene of the miR-320 family. We confirmed that mR NA and protein levels of CDK6 were significantly suppressed in colon cancer cell lines with miR-320 family mimics. CDK6 expression was found to increase from non-neoplastic mucosa through adenoma to submucosal invasive carcinoma tissues and showed an inverse correlation with miR-320 family expression.CONCLUSION: MiR-320 family affects colorectal tumor proliferation by targeting CDK6, plays important role in its growth, and is considered to be a biomarker for its early detection.

Short and long-term outcomes of endoscopic balloon dilatation for Crohn's disease strictures

AIM:To investigate the short and long-term outcomes of endoscopic balloon dilatation(EBD) for Crohn's disease(CD) strictures.METHODS:Between January 1995 and December 2011,47 EBD procedures were performed in 30 patients(8 females and 22 males) with CD.All patients had strictures through which an endoscope could not pass,and symptoms of these strictures included abdominal pain,abdominal fullness,nausea,and/or vomiting.The 47 strictures included 17 anastomotic and 30 de novo strictures.Endoscopy and dilatation were performed under conscious sedation with intravenous diazepam or flunitrazepam.The dilatations were all performed using through-the-scope balloons with diameters from 8 mm to 20 mm on inflation and lengths of 30-80 mm.Each dilatation session consisted of two to four,3-min multistep inflations of the balloon,repeated at intervals of 1 wk until adequate dilatation(up to 15-20 mm in diameter) was achieved.The follow-up data were collected from medical records and analyzed retrospectively.Primary success was defined as passage of the scope through the stricture after EBD.Longterm outcomes were analyzed focusing on interventionfree survival and surgery-free survival demonstrated by the Kaplan-Meier method.(Intervention-free meant cases in which neither endoscopic balloon re-dilatation nor surgery was needed after the first dilatation during the observation period).The log rank test was used to evaluate the difference in long-term outcomes between anastomotic and de novo stricture cases.RESULTS:Primary success was achieved in 44 of the 47 strictures(93.6%).Balloon dilatations failed in 3 cases(6.4%).In 1 case,EBD was a technical failure because the guide-wire could not be passed through the stricture which showed severe adhesion and was a flexural lesion of the intestine.In 2 cases,unexpected perforations occurred immediately after balloon dilatation.Of the 47 treatments,complications occurred in 5(10.6%).All 5 patients had de novo strictures.One suffered bleeding,two high fever and there were colorectal perforations.One of the patients with a colorectal perforation was treated surgically,the other was managed conservatively.These 2 cases correspond to the two aforementioned EBD failures.Long-term outcomes were evaluated for the 44 successfully-treated strictures after a median follow-up of 26 mo(range,2-172 mo).During the observation period,re-strictures after EBDs occurred in 26 cases(60.5%).Fourteen of these 26 re-stricture cases underwent EBD again,but in two EBD failed and surgery was ultimately performed in both cases.Twelve of the 26 re-stricture cases were initially treated surgically when the re-strictures occurred.Finally,30 of the 47 strictures(63.8%) were successfully managed with EBD,allowing surgery to be avoided.Intervention-free survival evaluated by the Kaplan-Meier method was 75% at 12 mo,58% at 24 mo,and 43% at 36 mo.There was no significant difference between the anastomotic strictures(n = 16) and de novo strictures(n = 28) in the intervention-free survival as evaluated by the log-rank test.Surgery-free survival evaluated by the Kaplan-Meier method was 90% at 12 mo,75% at 24 mo,and 53% at 36 mo.The 16 anastomotic strictures were associated with significantly better surgery-free survivals than the 28 de novo strictures(log-rank test:P < 0.05).CONCLUSION:Anastomotic strictures were associated with better long-term outcomes than de novo strictures,indicating that stricture type might be useful for predicting the long-term outcomes of EBD.