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Kadowaki, Shigenori,Komori, Azusa,Takahari, Daisuke,Ura, Takashi,Ito, Seiji,Tajika, Masahiro,Niwa, Yasumasa,Oze, Isao,Muro, Kei Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.13
Background: Systemic chemotherapy for patients with metastatic gastric cancer (MGC) is generally palliative, although some patients experience long-term survival after treatment. Thus, we identified clinical characteristics that are associated with long-term survival of patients with MGC after palliative chemotherapy. Materials and Methods: We retrospectively reviewed 514 MGC patients who received systemic chemotherapy at our institution from 2001 to 2008. To identify clinical predictors of survival beyond 2 years, multivariate logistic regression analyses were performed, and 5-year survival rates were estimated among MGC patients following chemotherapy. Results: Among 514 patients, 96 (19%) and 16 (3%) survived beyond 2 and 5 years, respectively, and performance status of 0 or 1 (odds ratio [OR]=3.39; p=0.01), previous gastrectomy (OR=1.86; p=0.01), single metastatic site (OR=1.80; p=0.03), and normal alkaline phosphatase levels (OR=2.81; p<0.01) were identified as independent predictors of long-term survival. Of the 16 5-year survivors, six were alive at the end of the study and showed no evidence of disease despite cessation of chemotherapy. Conclusions: The present data demonstrate distinct clinical characteristics that are associated with long-term survival of MGC patients, and indicated that palliative chemotherapy can be curative in highly selected patients.
Perspective of Small-Molecule AdipoR Agonist for Type 2 Diabetes and Short Life in Obesity
Miki Okada-Iwabu,Masato Iwabu,Kohjiro Ueki,Toshimasa Yamauchi,Takashi Kadowaki 대한당뇨병학회 2015 Diabetes and Metabolism Journal Vol.39 No.5
Obesity associated with unhealthy diet and lack of exercise is shown to contribute to the onset and/or aggravation of the metabolic syndrome and diabetes, thus placing affected individuals at increased risk of cardiovascular disease and cancer. Plasma adiponectin levels are decreased in obesity, which causes insulin resistance and diabetes. Therefore, we identified adiponectin receptors (AdipoRs) as the therapeutic target. It was suggested that, similarly to caloric restriction and exercise, activation of the AdipoRs may have the potential not only to improve lifestyle-related diseases but to contribute to prolonged the shortened lifespan on a high caloric unhealthy diet. To this end, we have identified “AdipoRon” as an adiponectin receptor agonist. Indeed, AdipoRon ameliorated diabetes associated with obesity as well as to increase exercise endurance, thus prolonging shortened lifespan of obese mice fed on a high fat diet. Additionally, we have recently determined the crystal structures of the human AdipoRs. The seven-transmembrane helices of AdipoRs are structurally distinct from those of G-protein coupled receptors. It is expected that these findings will contribute not only to the elucidation of the AdipoR-related signal transduction but to the development and optimization of AdipoR-targeted therapeutics for obesity-related diseases such as diabetes.
Narasimhan, Meena L.,Coca, Maria A.,Jin, Jingbo,Yamauchi, Toshimasa,Ito, Yusuke,Kadowaki, Takashi,Kim, Kyeong-Kyu,Pardo, Jose M,Damsz, Barbara,Hasegawa, Paul M.,Yun, Dae-Jin,Bressan, Ray A. Plant molecular biology and biotechnology research 2005 Plant molecular biology and biotechnology research Vol.2005 No.
The antifungal activity of the PR-5 family of plant defense proteins has been suspected to involve specific plasma membrane component(s) of the fungal target. Osmotin is a tobacco PR-5 family protein that induces apoptosis in the yeast Saccharomyces cerevisiae. We show here that the protein encoded by ORE20/PHO36(YOL002c), a seven transmembrane domain receptor-like polypeptide that regulates lipid and phosphate metabolism, is an osmotin binding plasma mrmbrane protein that is required for full sensitivity to osmotin. PHO36 functions upstream of RAS2 in the osmotin-induced apoptotic pathway. The mammalian homolog of PHO36 is a receptor for the hormone adiponectin and regulates cellular lipid and sugar metabolism. OS-motion and adiponectin, the corresponding "receptor" binding proteins, do not share sequence similarity. However, the β barrel domain of both proteins can be overlapped, and osmotin, like adiponectin, activates AMP kinase in C2C12 myocytes via adiponectin receptors.