Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds

Harada, S., Hiromori, Y., Nakamura, S. et al. Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds. Sci Rep 5, 8520 (2015). https://doi.org/10.1038/srep08520

A Case of Laparoscopic Ileocecal Resection for Intussusception Secondary to Cecal Cancer

An 83-year-old woman presented with a right lower abdominal mass, lower abdominal pain, and distension. She had no medical or surgical history. Clinical examination revealed a right lower abdominal mass, abdominal distension, and decreased bowel sounds in the lower abdomen. Abdominal computed tomography showed an intussusception involving the ileocecal junction. A Gastrografin enema showed a tumor shadow with an irregular defect caused by the intussusception in the transverse colon. The protruding tumor was also pushed back into the cecum by the enema pressure. Colonoscopy revealed a protruding mass at the leading edge of the intussusception in the ascending colon, and biopsy results of the cecal mass indicated an adenocarcinoma. The patient underwent laparoscopic ileocecal resection of the intussuscepted cecal cancer using reduced port surgery. The resected specimen contained a type 1 tumor measuring 40mm that was histopathologically diagnosed as cecal cancer. The patient remains asymptomatic 8 months after surgery

Changes in physical and chemical properties of archived sediment

http://www.godac.jamstec.go.jp/darwin/cruise/mirai/mr01-k03/

Anaplastic lymphoma kinase overexpression enhances aggressive phenotypic characteristics of endometrial carcinoma

Abstract Background Although anaplastic lymphoma kinase (ALK) is overexpressed in several primary solid tumor types, its role in endometrial carcinoma (Em Ca) remains unclear. Methods We evaluated expression of ALK and its related molecules in clinical samples consisting of 168 Em Ca tissues. We also used Em Ca cell lines to evaluate the functional role of ALK. Results Cytoplasmic ALK immunoreactivity in the absence of chromosomal rearrangement was positively correlated with ALK mRNA expression, and was significantly higher in Grade (G) 3 Em Ca than in G1 or G2 tumors. ALK immunoreactivity was also significantly associated with expression of cancer stem cell (CSC)-related molecules (cytoplasmic CD133, ALDH1, Sox2) and neuroendocrine markers (CD56 and synaptophysin). Although the proliferative index was significantly higher in ALK-positive Em Ca when compared to ALK- negative malignancies, there was no association between ALK expression and other clinicopathological factors in this disease. In Em Ca cell lines, full-length ALK overexpression increased proliferation, decreased susceptibility to apoptosis, enhanced cancer stem cell features, and accelerated cell mobility, whereas these phenotypes were abrogated in ALK-knockdown cells. Finally, patients with tumors harboring either wild-type ALK or high ALK mRNA expression had a poorer prognosis than those with either mutant ALK or low ALK mRNA expression. Conclusion Full-length ALK overexpression occurs in a subset of Em Ca, particularly in G3 tumors, and contributes to the establishment and maintenance of aggressive phenotypic characteristics through modulation of several biological processes

ASP4058, a Novel Agonist for Sphingosine 1-Phosphate Receptors 1 and 5, Ameliorates Rodent Experimental Autoimmune Encephalomyelitis with a Favorable Safety Profile

<div><p>Sphingosine-1-phosphate (S1P) is a biologically active sphingolipid that acts through the members of a family of five G protein-coupled receptors (S1P₁–S1P₅). S1P₁ is a major regulator of lymphocyte trafficking, and fingolimod, whose active metabolite fingolimod phosphate acts as a nonselective S1P receptor agonist, exerts its immunomodulatory effect, at least in part, by regulating the lymphocyte trafficking by inducing down regulation of lymphocyte S1P₁. Here, we detail the pharmacological profile of 5-{5-[3-(trifluoromethyl)-4-{[(2<i>S</i>)-1,1,1-trifluoropropan-2-yl]oxy}phenyl]-1,2,4-oxadiazol-3-yl}-1<i>H</i>-benzimidazole (ASP4058), a novel next-generation S1P receptor agonist selective for S1P₁ and S1P₅. ASP4058 preferentially activates S1P₁ and S1P₅ compared with S1P_{2, 3, 4} in GTPγS binding assays <i>in vitro</i>. Oral administration of ASP4058 reduced the number of peripheral lymphocytes and inhibited the development of experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Further, ASP4058 prevented relapse of disease in a mouse model of relapsing-remitting EAE. Although these immunomodulatory effects were comparable to those of fingolimod, ASP4058 showed a wider safety margin than fingolimod for bradycardia and bronchoconstriction in rodents. These observations suggest that ASP4058 represents a new therapeutic option for treating multiple sclerosis that is safer than nonselective S1P receptor agonists such as fingolimod.</p></div