The muscles of IL-6 transgenic mice suffer from atrophy. Experiments were carried out on these transgenic mice to elucidate activation of proteolytic systems in the gastrocnemius muscles and blockage of this activation by treatment with the anti-mouse IL-6 receptor (mIL-6R) antibody. Muscle atrophy observed in 16-wk-old transgenic mice was completely blocked by treatment with the mIL-6R antibody. In association with muscle atrophy, enzymatic activities and mRNA levels of cathepsins (B and L) and mRNA levels of ubiquitins (poly-and mono-ubiquitins) increased, whereas the mRNA level of muscle-specific calpain (calpain 3) decreased. All these changes were completely eliminated by treatment with the mIL-6R antibody. This IL-6 receptor antibody could, therefore, be effective against muscle wasting in sepsis and cancer cachexia, where IL-6 plays an important role.

ID 000000648 (University Hospital Medical Information Network (UMIN) database).

No abstract

Three surgical procedures for U-EGC did not result in differences in weight loss, but PG-EG and PG-JI were better than TG-RY according to some nutritional markers. In U-EGC, where patients are expected to have long survival times, PG-EG and PG-JI should be used rather than TG-RY.

Progression of skeletal muscle atrophy is one of the characteristic features in cancer patients. Interleukin-6 (IL-6) has been reported to be responsible for the loss of lean body mass during cancer cachexia in colon-26 adenocarcinoma (C-26)-bearing mice. This study was carried out to elucidate the intracellular proteolytic pathways operating in skeletal muscle in C-26-bearing mice, and to examine the effect of anti IL-6 receptor antibody on muscle atrophy. On day I 7 after tumor inoculation, trocnemius muscle weight of C-26-bearing mice had the sign' I F = icantly decreased to 69% of that of the pair-fed control mice. This weight loss occurred in association with increases in the mRNA levels of cathepsins B and L, poly-ubiquitin (Ub) and the subunits of proteasomes in the muscles. Furthermore, enzymatic activiky of cathepsin B+L in the muscles also increased to 119% of the control. The administration of antimurine IL-6 receptor antibody to C-26-bearing mice reduced the weight loss of the gastrocnemius muscles to 84% of that of the control mice, whose enzymatic activity of cathepsin B+L and mRNA levels of cathepsin L and poly-Ub were significantly suppressed compared with those of the C-26-bearing mice. Our data indicate that both the lysosomal cathepsin pathway and the ATP-dependent proteolytic pathway might be invoked in the muscle atrophy of C-26-bearing mice. The results also suggest that anti IL-6 receptor antibody could be a potential therapeutic agent against muscle atrophy in cancer cachexia by inhibiting these proteolytic systems.o 1996 Wiley-Liss, Inc.Cachexia is a characteristic syndrome observed in cancer patients; it reduces the response to chemotherapy and diminishes the chance of success for curative surgical treatment. If the progression of muscle wasting seen in malignant neoplastic diseases could be prevented, it would be of clinical importance in terms of improving the prognosis and the quality of life of patients. In cancer cachexia the host suffers from alterations in the metabolism of proteins and amino acids. These changes are characterized by a decrease in protein synthesis and an increase in protein degradation in skeletal muscle (Smith and Tisdale, 1993); the precise mechanism remains unknown, however.Skeletal muscle contains 3 major proteolytic pathways: lysosomal cathepsins, cytosolic Ca?+-dependent proteases (calpain), and the ATP-ubiquitin (Ub)-dependent system. Increases in the mRNA levels of poly-Ub and in the subunits (Llovera et al., 1994). It has thus been concluded that the ATP-Ub-dependent proteolytic pathway is most responsible for the muscle protein degradation seen in the tumor-bearing state. Studies from our laboratory on interleukin-6 (IL-6) transgenic mice revealed that IL-6 is a potent factor that induces muscle atrophy and that it can modulate not only the ATP-Ub-dependent pathway but also the lysosomal cathepsin systems (Tsujinaka et al., 1996).Murine colon-26 adenocarcinoma (C-26) is an undiffcrentiated carcinoma induced by a carcinogen, N-nitroso-Nmethylurethane. ...

RY reconstruction was not superior to BI in terms of body weight change or other aspects of nutritional status at 1 year after surgery, although RY more effectively prevented reflux esophagitis and remnant gastritis after distal gastrectomy.

Background Both Billroth I (B-I) and Roux-en-Y (R-Y) reconstructions are commonly performed as standard procedures, but it has yet to be determined which reconstruction is better for patients. A randomized prospective phase II trial with body weight loss at 1 year after surgery as a primary endpoint was performed to address this issue. The current report delivers data on the quality of life and degree of postoperative dysfunction, which were the secondary endpoints of this study.Methods Gastric cancer patients who underwent distal gastrectomy were intraoperatively randomized to B-I or R-Y. Postsurgical QOL was evaluated using the EORTC QLQ-C30 and DAUGS 20. Results Between August 2005 and December 2008, 332 patients were enrolled in a randomized trial comparing B-I versus R-Y. A mail survey questionnaire sent to 327 patients was completed by 268 (86.2%) of them. EORTC QLQ-C30 scores were as follows: global health status was similar in each group (B-I 73.5 ± 18.8, R-Y 73.2 ± 20.2, p = 0.87). Scores of five functional scales were also similar. Only the dyspnea symptom scale showed superior results for R-Y than for B-I (B-I 13.6 ± 17.9, R-Y 8.6 ± 16.3, p = 0.02). With respect to DAUGS 20, the total score did not differ significantly between the R-Y and B-I groups (24.8 vs. 23.6, p = 0.41). Only reflux symptoms were significantly worse for B-I than for R-Y (0.7 ± 0.6 vs. 0.5 ± 0.6, p = 0.01). Conclusions The B-I and R-Y techniques were generally equivalent in terms of postoperative QOL and dysfunction. Both procedures seem acceptable as standard reconstructions after distal gastrectomy with regard to postoperative QOL and dysfunction.

Background Although some small-scale studies have suggested that human epidermal growth factor receptor 2 (HER2)-positive status in gastric cancer is associated with poor outcomes, the prognostic value of HER2 is still controversial. Since intratumoral HER2 heterogeneity is also an important issue, a multicenter large-scale study was conducted to evaluate the prognostic impacts of HER2 expression and intratumoral heterogeneity in gastric cancer. Methods This study included 1,148 gastric cancer patients who underwent gastrectomy in 11 institutions. HER2 expression was centrally evaluated with immunohistochemistry and fluorescence in situ hybridization, and intratumoral HER2 heterogeneity was evaluated for HER2-positive tumors. Overall survival was compared between HER2-positive and HER2-negative patients and between the homogeneous and heterogeneous groups. Results The HER2-positive rate was 15.7 %, and HER2 expression was significantly associated with histological type. HER2 expression scores obtained by immunohistochemistry showed a distinct influence on survival, and HER2-positive patients showed much poorer survival than HER2-negative patients [hazard ratio (HR) 1.59, 95 % confidence interval (CI) 1.24-2.02; P \ 0.001). The subgroup analysis by pathological tumor stage showed a similar trend of poor survival in HER2-positive patients. Both intestinal type and diffuse type showed significant poor survival in HER2-positive patients. Cox multivariate analysis revealed that HER2 expression was an independent prognostic factor (HR 1.96, 95 % CI 1.51-2.55; P \ 0.001). HER2 heterogeneity was observed in 75.4 % of HER2-positive cases, but the prognosis in the heterogeneous group was similar to that in the homogeneous group. Conclusions Our study demonstrated that HER2 overexpression is an independent prognostic factor in patients with any stage of resectable gastric cancer. Intratumoral HER2 heterogeneity did not affect prognosis.