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Fujisawa T.,Sumitomo Chemical | Ichise-Shibuya K.,Sumika Technoservice Corporation | Katagi T.,Sumitomo Chemical
Journal of Pesticide Science | Year: 2010

Uptake and transformation of phenol and its five derivatives each labeled with 14C were examined in duckweed (Lemna gibba). A kinetic analysis on uptake and metabolic transformation was conducted using the assumed compartments. Positive correlation was observed between log P and the logarithm value of relative uptake rate constant with respect to phenol, and an even higher correlation was obtained against the physico-chemical index, EffTox, where the undissociated fraction of phenol was incorporated. No significant correlation was observed between any of the electronic parameters of the phenol derivatives and the transformation rate. These analyses showed that the uptake of phenols by duckweed is mainly controlled by the hydrophobic profile of the undissociated form. For the metabolic profile, the glycoside conjugate was detected as a typical major metabolite for all phenols and the glutathione conjugate as a unique metabolite for 4-chlorophenol. © Pesticide Science Society of Japan. Source


Suzuki M.,Sumika Technoservice Corporation | Kanae Y.,D Laboratory | Kagawa Y.,North Laboratory | Ano N.,Marupi Lifetech Co. | And 3 more authors.
Journal of Comparative Pathology | Year: 2011

Twelve cases of feline malignant lymphoma with emperipolesis-like invasion of neoplastic lymphocytes were examined microscopically, immunohistochemically and ultrastructurally. Intracytoplasmic invasion of neoplastic cells varied in severity between the cases, between hepatic lobules and between areas within the lobules. The number of infiltrating neoplastic cells ranged from one to several per hepatocyte. Neoplastic cells exhibited widely varying morphology from case-to-case and cell-to-cell within each case, and contained eosinophilic cytoplasmic granules in four cases. Immunohistochemical examination revealed that neoplastic cells in 11 of the 12 cases expressed one or both T-cell markers (CD3 and TIA-1). Diagnosis of T-cell lymphoma was also confirmed by assessment of clonality by polymerase chain reaction. Ultrastructural analysis revealed that the neoplastic lymphocytes were contained within an invagination of the cell membrane of the hepatocyte, rather than directly infiltrating into the cytoplasm of the cell. There was no evidence that the invasive neoplastic lymphocytes had a cytotoxic effect. © 2010 Elsevier Ltd. Source


Suzuki M.,Small Animal Pathology Service Inc. | Onchi M.,Sumika Technoservice Corporation | Ozaki M.,Sumika Technoservice Corporation
Journal of Toxicologic Pathology | Year: 2013

Feline gastrointestinal eosinophilic sclerosing fibroplasia was diagnosed in an 8-month-old Scottish fold that had a primary gastrointestinal mass involving the stomach, duodenum and mesenteric lymph nodes. Histopathologically, the most characteristic feature of this mass was granulation tissue with eosinophil infiltration and hyperplasia of sclerosing collagen fiber. Immunohistochemically, large spindle-shaped cells were positive for smooth muscle actin and vimentin. This case emphasizes the importance of feline gastrointestinal eosinophilic sclerosing fibroplasia as a differential diagnosis of gastrointestinal neoplastic lesions such as osteosarcoma and mast cell tumor in cats. ©2013 The Japanese Society of Toxicologic Pathology. Source


Harada K.,Sumitomo Chemical | Kubo H.,Sumitomo Chemical | Abe J.,Sumitomo Chemical | Haneta M.,Sumitomo Chemical | And 4 more authors.
Bioorganic and Medicinal Chemistry | Year: 2012

We have previously reported the discovery of a new class of potent inhibitors of 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) derived from benzylidene oxazolidinedione and thiazolidinedione scaffolds. In this study, these analogs were designed, synthesized, and evaluated in a human cell-based assay. The detailed structure-activity relationship (SAR) surrounding this pharmacophore were developed, and consequently a number of compounds from this series demonstrated single-digit nanomolar 17β-HDS3 inhibitory activity in vitro. Subsequent optimization work in pursuit of the improvement of oral bioavailability demonstrated in vivo proof-of-concept by prodrug strategy based on phosphate esters for these 17β-HSD3 inhibitors. When a phosphate ester 16 was administered orally at a high dose of 100 mg/kg, 16 showed approximately two times more potent testosterone (T)-lowering effect against a positive control in the luteinizing hormone-releasing hormone (LH-RH)-induced T production assay. The T-lowering effect continued at ca 10% level of control over 4 h after administration. The nonsteroidal molecules based on this series have the potential to provide unique and effective clinical opportunities for treatment of prostate cancer. © 2012 Elsevier Ltd. All rights reserved. Source

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