New insights into the mechanisms behind mechanical itch

Gentle tactile stimuli, such as insects crawling on the skin, can cause itching sensation called mechanical itch. Recent studies have begun to shed light on the neural mechanisms of mechanical itch. Interestingly, the neural pathway for mechanical itch is apparently different from that for chemical itch triggered by the activation of pruriceptors with various mediators. Mechanical itch dysesthesia is frequently seen in patients with chronic itch. Mechanisms of this dysesthesia are plausibly involved in central sensitization. In this review, we summarize the current knowledge of mechanical itch under normal and pathological conditions.     

Hepatocyte growth factor (HGF) produced by peritoneal fibroblasts may affect mesothelial cell morphology and promote peritoneal dissemination

Mesothelial cell monolayers have been reported to prevent infiltration of cancer cells into the peritoneum. We have previously reported that peritoneal fibrosis induced by gastric cancer cells prior to metastatization may provide a congenial environment for peritoneal metastases. In this study, we investigated the effects of peritoneal fibroblasts on peritoneal mesothelial cell morphology. Human gastric cancer (OCUM-2MD3), peritoneal fibroblast (NF-2P) and mesothelial (MS-1) cell lines were established in our laboratory. Histology of the peritoneum was investigated following intraperitoneal inoculation of serum-free conditioned media (SF-CM) from OCUM-2MD3 cells into nude mice. SF-CM from peritoneal fibroblasts was added to monolayer-cultured mesothelial cells, and their morphology was examined by phase-contrast microscopy. This experiment was conducted in the presence and absence of neutralizing antibodies against various factors. Mesothelial cells exposed to fibroblasts proliferation became hemispherical and separated from each other, while unexposed mesothelium remained as a flat monolayer. Cultured-mesothelial cells rounded up or exhibited a fibroblast-like shape following the addition of peritoneal fibroblast SF-CM. Anti-hepatocyte growth factor (HGF) neutralizing antibody partly inhibited this effect. We suggest that soluble factors, such as HGF, produced by peritoneal fibroblasts affect the morphology of mesothelial cells in monolayers so that the resulting environment may become prone to the peritoneal dissemination of cancer cells. © 1996 Wiley-Liss, Inc.     

Survival outcomes of non-definitive therapy for muscle-invasive bladder cancer

To analyze the risks and survival outcomes of non-definitive therapy (nDT) for muscle-invasive bladder cancer (MIBC), which may provide useful information for future treatment selection, the present study analyzed 124 patients who were diagnosed with MIBC (cT2-4aN1-2M0) and treated at Kurume University Hospital (Kurume, Japan) with definitive therapy (DT; including radical cystectomy and trimodal therapy) or nDT [transurethral resection of bladder tumor (TURBT) monotherapy or TURBT plus chemotherapy]. Differences in survival outcomes between the two groups were estimated using the Kaplan-Meier method and analyzed using the log-rank test. Cox proportional hazards regression models were used for multivariate analysis of each survival outcome. Of the 124 patients, 45% were treated with nDT, and among these, 50% were treated with TURBT monotherapy and 50% were treated with TURBT plus chemotherapy. Of the patients who chose definitive treatment, 69% were treated with radical cystectomy. The median age in the nDT group was 77 years, which was significantly higher than that in the DT group. Additionally, the proportion of patients with poor performance status, high Charlson comorbidity index and high neutrophil-lymphocyte ratio values was significantly higher in the nDT group. nDT was associated with significantly reduced overall survival, cancer-specific survival and progression-free survival rates, and was a poor prognostic factor for all survival outcomes compared with DT. In conclusion, nDT was associated with a high cancer-related mortality risk. The most appropriate treatment method should be discussed with the patients after providing them with sufficient information on the risks and benefits of each treatment method.     

Comparison of Ca2+ channel inhibitory effects of cibenzoline with verapamil on guinea-pig heart

1. Cibenzoline, a class 1 antiarrhythmic drug, was studied on the effects upon the myocardial slow inward Ca2+ current (ICa) and the contractile force, and was compared with verapamil. 2. In voltage-clamp experiments with guinea-pig ventricular myocytes, cibenzoline caused a concentration-related inhibition of ICa (IC50 = 30 microM), whereas verapamil exerts a stronger effect (IC50 = 0.6 microM). 3. Cibenzoline also produced a concentration-related decrease in contractile force of isolated papillary muscle preparation (IC50 = 30 microM), while IC50 of verapamil was 0.8 microM. 4. Although the myocardial Ca2+ channel blocking effect of cibenzoline is about 1/50 compared to verapamil, cibenzoline possesses an inhibitory action on Ca2+ channel as well as on Na+ channel.     

Novel biomarkers for early detection of gastric cancer

Gastric cancer(GC) remains a leading cause of cancer-related death worldwide. Less than half of GC cases are diagnosed at an advanced stage due to its lack of early symptoms. GC is a heterogeneous disease associated with a number of genetic and somatic mutations. Early detection and effective monitoring of tumor progression are essential for reducing GC disease burden and mortality. The current widespread use of semi-invasive endoscopic methods and radiologic approaches has increased the number ...