Efficacy and safety of HMB/Gln/Arg for the prophylaxis of chemoradiation -induced mucositis in head and neck squamous cell carcinoma: Randomized Phase II Clinical Study - Efficacy and safety of HMB/Gln/Arg for the prophylaxis of chemoradiation -induced mucositis in head and neck squamous cell carcinoma: Randomized Phase II Clinical Study

开始日期2018-03-01

申办/合作机构-

JPRN-UMIN000010111 / Completed临床2期IIT

Phase 2a trial of GBS-01 for advanced pancreatic cancer refractory to gemcitabine and fluoropyrimidine chemotherapy. - GBS-01 Phase IIa

开始日期2013-03-11

申办/合作机构

National Cancer Center Hospital East

[+1]

JPRN-UMIN000005787 / CompletedIIT

Phase 1/2 study of GBS-01 in patients with gemcitabine-refractory advanced pancreatic cancer. - GBS-01 Phase I/II

开始日期2011-06-01

申办/合作机构

National Cancer Center Hospital East

100 项与 PP2A x ADIPOR1 相关的临床结果

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100 项与 PP2A x ADIPOR1 相关的转化医学

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0 项与 PP2A x ADIPOR1 相关的专利（医药）

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项与 PP2A x ADIPOR1 相关的文献（医药）

Cell Death & Disease1区 · 生物学

Adiponectin receptor agonist ameliorates cardiac lipotoxicity via enhancing ceramide metabolism in type 2 diabetic mice

1区 · 生物学

ArticleOA

作者: Kim, Eun Nim ; Choi, Bum Soon ; Park, Cheol Whee ; Park, Hun-Jun ; Park, Ji Yong ; Lim, Ji Hee ; Kim, Hye Won ; Kim, Yaeni ; Chung, Sungjin ; Hong, Yu Ah ; Kim, Yong-Soo

AbstractAccumulation of lipids and their metabolites induces lipotoxicity in diabetic cardiomyopathy. Lowering ceramide concentration could reduce the impact of metabolic damage to target organs. Adiponectin improves lipotoxicity through its receptors (AdiopRs), which have sequence homology with ceramidase enzymes. Therefore, cardioprotective role of AdipoR agonism by AdipoRon was investigated. Sixteen-week-old male db/m and db/db mice were fed a diet containing AdipoRon for four weeks. Phenotypic and metabolic profiles with associated cellular signaling pathways involved in lipid metabolism were investigated in the mice heart and human cardiomyocytes to establish treatment effect of AdipoRon. AdipoRon ameliorated insulin resistance, fibrosis, M1-dominant inflammation, and apoptosis in association with reduced accumulations of free fatty acid, triglycerides, and TLR4-related ceramide in the heart. This resulted in overall reduction in the level of oxidative stress which ameliorated cardiac hypertrophy and its function. AdipoRon increased the expression of AdipoR1 and AdipoR2 via pAMPK/FoxO1-induced Akt phosphorylation resulting from a decrease in PP2A level. It also increased acid ceramidase activity which reduced ceramide and increased sphingosine-1 phosphate levels in the heart of db/db mice and cultured human cardiomyocytes. Consistent upregulation of AdipoRs and their downstream regulatory pathways involving pAMPK/PPARα/PGC-1α levels led to lipid metabolism enhancement, thereby improving lipotoxicity-induced peroxisome biogenesis and oxidative stress. AdipoRon might control oxidative stress, inflammation, and apoptosis in the heart through increased AdipoR expression, acid ceramidase activity, and activation of AMPK-PPARα/PGC-1α and related downstream pathways, collectively improving cardiac lipid metabolism, hypertrophy, and functional parameters.