No abstract

We previously reported hedgehog (Hh) signal activation in the mucus-secreting pit cell of the stomach and in diffuse-type gastric cancer (GC). Epithelial -mesenchymal transition (EMT) is known to be involved in tumour malignancy. However, little is known about whether and how both signallings cooperatively act in diffuse-type GC. By microarray and reverse transcription -PCR, we investigated the expression of those Hh and EMT signalling molecules in pit cells and in diffuse-type GCs. How both signallings act cooperatively in those cells was also investigated by the treatment of an Hh-signal inhibitor and siRNAs of Hh and EMT transcriptional key regulator genes on a mouse primary culture and on human GC cell lines. Pit cells and diffuse-type GCs co-expressed many Hh and EMT signalling genes. Mesenchymal-related genes (WNT5A, CDH2, PDGFRB, EDNRA, ROBO1, ROR2, and MEF2C) were found to be activated by an EMT regulator, SIP1/ZFHX1B/ZEB2, which was a target of a primary transcriptional regulator GLI1 in Hh signal. Furthermore, we identified two cancer-specific Hh targets, ELK1 and MSX2, which have an essential role in GC cell growth. These findings suggest that the gastric pit cell exhibits mesenchymal-like gene expression, and that diffuse-type GC maintains expression through the Hh -EMT pathway. Our proposed extensive Hh -EMT signal pathway has the potential to an understanding of diffusetype GC and to the development of new drugs.

It has been established that the Hedgehog (Hh) and epithelialmesenchymal transition (EMT) signals act on morphogenesis of embryonic and adult tissues. Recently, both signals have been involved in tumor malignancy. However, little is known as to whether Hh and EMT signals act on normal and malignant epithelial cells in the esophagus. By laser microdissection (LMD)-based microarray and reverse transcription polymerase chain reaction in the undifferentiated and differentiated epithelial cells of the esophagus, we compared the expression profiles of Hh and EMT signaling molecules of these cells with those of cancers. Whether and how both signalings act in undifferentiated cells and in cancer cells are investigated by treatment of a Hh-signal inhibitor and/or siRNAs of Hh and EMT transcriptional key regulator genes on a mouse primary culture and on human esophageal squamous cell carcinoma (ESCC) cell lines. Undifferentiated esophageal epithelial cells and most ESCCs coexpressed Hh and EMT signaling genes. Some mesenchymal-related genes were regulated by an EMT regulator SIP1/ZEB2/ZFHX1B, which was a downstream gene of a primary transcriptional transducer GLI1 in Hh signaling. Hh signal block inhibited esophageal keratinocyte differentiation and cancer cell invasion and growth. These findings suggest that the mesenchymal gene expression of undifferentiated cells is maintained or strengthened in cancer cells through Hh signaling. This is a first report showing the presence of crosstalk between Hh and EMT pathways. ' 2009 UICC

Background and study aims  Topical peppermint oil prevents intestinal spasm, but can cause rebound spasm. Lidocaine hydrochloride, a local anesthetic, may work as an antispasmodic by blocking Na + channels. The aim of this study was to investigate the effect of topical lidocaine on the inhibition of colonic spasm during colonoscopy, compared with peppermint oil. Patients and methods  A randomized, controlled double-blind trial was conducted in an academic endoscopy unit. Patients requiring endoscopic resection were randomly allocated to colonoscopy with topical administration of lidocaine (n = 30) or peppermint oil (n = 30). Similar vials containing different solutions were randomly numbered. Allocation was made based on the vial number. The solution used and the vial number were not revealed during the study. Two endoscopists performed all procedures using midazolam, without anticholinergic agents. When a pre-selected lesion was identified, the solution in the assigned vial was dispersed and the bowel observed for 5 minutes. The primary endpoint was the duration of spasm inhibition, and a secondary endpoint was the occurrence of rebound spasm stronger than before dispersion. Results  There were no significant differences in patient demographics. Spasm was inhibited in almost all patients in both groups, with a similar median duration (lidocaine 227 sec vs. peppermint 212.5 sec, P  = 0.508). In contrast, rebound spasm occurred less frequently in the lidocaine group (lidocaine 7 % vs. peppermint 47 %, P  = 0.001). There were no adverse events or symptoms associated with administration of the solutions. Conclusions  The inhibitory effect of lidocaine is not superior to peppermint oil. However, lidocaine significantly decreases the frequency of rebound spasms.

Background and study aims: Sodium phosphate is a key component of bowel preparation regimen for colon capsule endoscopy (CCE), but may cause serious complications. The aim of this study is to evaluate the use of Gastrografin, substituted for sodium phosphate, in CCE bowel preparation. Patients and methods: In total, 29 patients (median age 64 years; 23 females) underwent CCE, covered by the national health insurance system of Japan. All had a history of laparotomy and/or previously incomplete colonoscopy. On the day before examination, patients ingested 1 L of polyethylene glycol + ascorbic acid with 0.5 L of water in the evening, and again the same laxative on the morning of examination. After capsule ingestion, 50 mL of Gastrografin diluted with 0.9 L of magnesium citrate was administered, and then repeated after 1 hour. Results: The capsule excretion rate was 97 % (28/29). The median colon transit time was 2 hours 45 minutes and rapid transit (< 40 minutes) through the colon occurred in one patient (3.4 %). Bowel cleansing level was adequate in 90 % of patients. The polyp (≥ 6 mm) detection rate was 52 %. Diluted Gastrografin was well tolerated by patients. No adverse events occurred. Conclusion: Gastrografin can be an alternative to sodium phosphate in CCE bowel preparation regimen.