Expression of RHOC is associated with metastasis of gastric carcinomas.

OBJECTIVES: RHOC, a member of the RAS-related small GTPase protein family, regulates cytoskeletal structures and has the potential to transform cultured cells. It has recently been reported that RHOC contributes to the metastatic phenotype of melanoma cells. The purpose of this study was to clarify its biological relevance to gastric carcinogenesis and metastasis. METHODS: We examined the expression of RHOC by quantitative RT-PCR in 51 cases of gastric carcinoma tissues from prior surgical cases (intestinal type: 24 cases, diffuse type: 27 cases) and in 8 gastric carcinoma cell lines. RESULTS: RHOC expression levels in primary tumors were significantly higher in cases with metastasis than in those without metastasis (p = 0.0202; Mann-Whitney U test). RHOC expression levels in primary tumor and their metastatic tumors were significantly higher than their corresponding nonneoplastic mucosa (p = 0.0357, and 0.0173, respectively; Wilcoxon signed rank test). RHOC mRNA expression was confirmed in the gastric carcinoma cell lines. CONCLUSION: Our findings suggest that elevated expression of the RHOC gene may be involved in the metastasis of gastric carcinomas and may be a good genetic marker for the prediction of a metastatic potential.     

Effect of skin temperature on the ion reabsorption capacity of sweat glands during exercise in humans

The effect of skin temperature on the ion reabsorption capacity of sweat glands during exercise in humans is unknown. In this study, eight healthy subjects performed a 60-min cycling exercise at a constant intensity (60% VO_2max) under moderate (25°C) and cool (15°C) ambient temperatures at a constant relative humidity of 40%. The sweating rate (SR), index of sweat ion concentration (ISIC) by using sweat conductivity, esophageal temperature (Tes), mean skin temperature, and heart rate (HR) were measured continuously under both ambient temperatures. The SR and ISIC were significantly lower at the cool ambient temperature versus the moderate temperature. There were no significant differences in the changes in HR and esophageal temperature between these ambient temperature conditions, while the mean skin temperature was significantly lower at the cool ambient temperature by almost 3°C (P<0.05). The slopes of the relationships between Tes and the SR and ISIC were significantly lower and the thresholds of these relationships were significantly higher at the cool ambient temperature (P<0.05). The ion reabsorption capacity of the sweat glands was significantly lower (P<0.05) in a cool environment (0.21±0.04 vs. 0.52±0.06 mg/cm²/min at 15 and 25°C, respectively) as evaluated using the relationships for SR and ISIC. The results suggest that the ion reabsorption capacity of the sweat glands is influenced by skin temperature during exercise in humans.     

Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer

Cadherin-17 (CDH17), also called liver–intestine cadherin, is a structurally unique member of the cadherin superfamily. Our serial analysis of gene expression demonstrated that CDH17 was one of the most up-regulated genes in advanced gastric carcinomas. CDH17 expression is known to be regulated by Cdx2. In the present study, we examined the expression of CDH17 in primary gastric carcinoma tissues by immunohistochemistry, and analyzed the correlation of CDH17 expression with clinicopathological characteristics and patients prognosis. CDH17 expression was detected in 63/94 (67%) of gastric adenocarcinomas in addition to intestinal metaplasia. The expression of CDH17 tended to be associated with intestinal type carcinoma, and carcinomas with CDH17 expression was significantly more frequent in advanced stage cases (80%) than in early stage (53%). The prognosis of patients with positive CDH17 expression was significantly poorer than that of the negative cases (P=0.0314). However, multivariate analysis revealed that CDH17 was not an independent prognostic factor. Six of seven cases that showed positive expression of Cdx2 simultaneously expressed CDH17 protein. These results suggested that the expression of CDH17 was characteristic of the advanced gastric carcinoma that is associated with poor prognosis.     

Induction of hRAD9 is required for G2/M checkpoint signal transduction in gastric cancer cells.

DNA damage triggers the activation of checkpoints that delay cell cycle progression to allow for DNA repair. Loss of G2 checkpoints provides a growth advantage for tumor cells undergoing aberrant mitosis. However, the precise mechanisms of G2 checkpoints acting in gastric cancer are unknown. Here, we analyzed the G2 checkpoint function in two gastric cancer cells, MKN-28 cells containing a mutant p53 gene and MKN-45 cells which have wild-type p53. Two agents damaging DNA, camptothecin (CPT) or ultraviolet light (UV), were utilized to trigger a G2 phase cell cycle checkpoint response in these tumor cells. Both CPT and UV inhibited the growth of MKN-45 cells, whereas they did not affect the growth of MKN-28 cells. CPT induced cell cycle arrest at the G2/M phase and enhanced the expression of human RAD9 (hRAD9) in MKN-45 cells. In addition, hRAD9 showed perinuclear staining and similar localization with Bcl-2 in MKN-45 cells but not in MKN-28 cells after having applied CPT or UV light. These results suggest that besides p53 activity, the induction of hRAD9 is required for G2/M checkpoint signal transduction in gastric cancer cells.     

Kampo medicines Rikkunshito and Hangeshashinto prevent cisplatin-induced intestinal mucosal injury in rats

Background/PurposeWe examined the effects and mechanisms of rikkunshito (RKT) and hangeshashinto (HST) on cisplatin-induced mucosal injuries in the rat small bowel.MethodsJuvenile rats were divided into 6 groups: sham control, cisplatin injection without kampo medicines, and cisplatin injection with oral administration of low and high doses of RKT (1000 mg/kg and 2000 mg/kg) and HST (500 mg/kg and 1000 mg/kg). Fecal condition, intestinal morphological changes, enterocyte proliferation, and enterocyte apoptosis were assessed.ResultsDiarrhea and atrophy of ileal villi observed in the cisplatin group were significantly improved in all kampo groups. Injury scores of the jejunum were significantly lower with RKT (2000 mg/kg) and HST (500 and 1000 mg/kg) than with cisplatin, and those of the ileum were significantly lower with HST (500 and 1000 mg/kg) than with cisplatin. Enterocyte proliferation of the jejunum was significantly increased with RKT (2000 mg/kg) and HST (500 mg/kg) compared with cisplatin, and those of the ileum were significantly increased in all kampo groups compared with the cisplatin group. Jejunal and ileal apoptosis following cisplatin administration was significantly inhibited by HST.ConclusionsRKT and HST prevented cisplatin-induced intestinal mucosal injury with increasing proliferation of intestinal epithelial cells. HST also attenuated cisplatin-induced crypt cell apoptosis.     

Pyloric motor abnormality in patients with infantile hypertrophic pyloric stenosis

There are no published data of manometric studies of pyloric motor function in patients with infantile hypertropic pyloric stenosis (IHPS). The present study attempted to examine the characteristics of motor abnormality of the pylorus in five children with IHPS. Using a transducer-built-in manometric catheter cannulated through the pylorus under fluoroscopy, the pressure in the pyloric canal was recorded continuously over 3 h during fasting. Clusters of high-amplitude spastic contractions of over 300 mmHg were recorded at intervals. The frequency was 1–3/min (mean 1.7 cpm) and the duration was 7–15 s. These periodic spastic contractions were suppressed temporarily for 20–30 min after intravenous injection of 0.01 mg/kg atropine. After pyloromyotomy, these spastic contractions decreased remarkably in amplitude, but there were no changes in frequency. It is concluded that the underlying motor abnormality observed in hypertrophied pyloric muscle is clusters of high-amplitude contractions, although more precise measurements of basal pyloric pressure are needed to explore the pathophysiology of IHPS in detail. The effect of pyloromyotomy may be related to the decrease in high-amplitude contractions. Accepted: 26 May 1998     

Glial-derived growth factor signaling pathway in infantile hypertrophic pyloric stenosis

BACKGROUND/PURPOSE: Glial-derived growth factor (GDNF), which is the ligand of RET is reported to be essential for the development of enteric nervous system. A GDNF knockout mouse model has shown that the gastric region is a critical passing site between GDNF-RET-independent neuroblasts (colonizing the esophagus) and GDNF-RET-dependent neuroblasts (colonizing the small and large bowel). The earliest GDNF site of production is the mesenchyme and the outer smooth muscle cell (SMC) layer of the developing bowel. In the mature gastrointestinal tract the presence of GDNF is restricted to enteric glial cells. The aim of this study was to investigate the expression of GDNF and RET in infantile hypertrophic pyloric stenosis (IHPS). METHODS: Full-thickness muscle biopsy specimens were obtained from 8 IHPS patients at pyloromyotomy and from 8 age-matched controls without gastrointestinal disease. Indirect immunohistochemistry was performed using avidin-biotin-peroxidase complex method with anti-GDNF and anti-RET antibodies. Quantitative analysis was performed using sandwich-type enzyme-linked immunosorbent assay (ELISA) for GDNF. RESULTS: GDNF- and RET-positive nerve fibers were absent or markedly reduced in IHPS compared with controls. GDNF was expressed strongly by smooth muscle cells of both muscular layers in IHPS, whereas no GDNF expression was detected in pyloric muscle of controls. The quantity of total GDNF in IHPS was significantly higher than in controls (P < .01). CONCLUSIONS: The lack or markedly decreased number of GDNF-positive nerve fibers in IHPS supports the hypothesis of a selective immaturity of the enteric glia in the muscular layers in IHPS. The strong expression of GDNF in smooth muscle cells in IHPS and the increased levels of GDNF in IHPS suggest a compensatory mechanism by which the smooth muscle cells continue to produce GDNF until maturation of the enteric glial cells occurs.     

Utility of bedside artificial pancreas for postoperative glycemic control in cardiac surgery

Journal of Artificial Organs - Perioperative hyperglycemia, hypoglycemia, and high glycemic variability are independent risk factors for mortality in critically ill patients. After cardiac surgery,...