Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Organotin compounds showed more antineoplastic effect against P388 leukemia in mice than any other class of compounds. However, they have not received as much attention as the platinum compounds. The present compound, Et2SnCl2.L [L = N-(2-pyridylmethylene)-4-toluidine] (OTC), showed an Sn-N bond length of 2.46 A which, because it is bigger than 2.39 A, is expected to achieve better formation of tin-DNA complexes. We previously reported on the synthesis and biological activity of this compound and on its ability to cause a delay in cell proliferation and sister chromatid exchanges in mouse bone marrow cells. In this study, we carried out further investigations on the antiproliferative and antitumor activity of OTC in relation to the cellular glutathione (GSH) level, which plays an important role in the cellular defense mechanism. OTC induced significant delay in the cell cycle in mouse bone marrow cells and, when the GSH level was low, the extent of the delay was reduced. The antitumor activity was determined in accordance with the US National Cancer Institute (NCI) standard protocol for primary screening in Dalton's lymphoma (DL) that was maintained by serial intraperitoneal transplantation. The T/C (treated/control) value was 146% when organotin was treated after transplantation; this improved significantly when buthionine sulfoximine (BSO), a GSH-depleting agent, was added 24 hours before the tin treatment. Our data suggest that the present tin compound has antiproliferative ability and can increase the survival of mice bearing DL. The endogenous GSH level influences the effect of the tin compound.
 ...
PMID:Inhibition of cell proliferation and antitumor activity of a novel organotin compound. 1179 43

Autoimmune regulator (AIRE) gene is a responsible gene for the rare autosomal recessive autoimmune disease: autoimmune-polyendocrinopathy-candidiasis ectodermal dystrophy (APECED). Although it has been reported that AIRE is expressed in the thymic epithelial cells and monocyte-dendritic cell lineage, the regulatory mechanisms of AIRE gene expression have as yet been poorly understood. Here we show that the expression of AIRE gene was induced in granulo-monocyte colony stimulating factor (GM-CSF)-stimulated myelomonocytic leukemia OTC-4 cells. In GM-CSF-stimulated OTC-4 cells, stat5 was not phosphorylated, while mitogen-activated protein kinases (MAPKs), including MAPK kinase (MEK) 1/2 and p38 MAPK, were phosphorylated, indicating activation of MAPK pathway. In addition, the expression of AIRE gene was inhibited by specific p38 MAPK inhibitor (SB203580), whereas the expression was rather enhanced by the MEK1/2 inhibitor (U0126), suggesting that AIRE gene expression is regulated by mitogen-activated protein kinase pathway.
 ...
PMID:Mitogen-activated protein kinase pathway controls autoimmune regulator (AIRE) gene expression in granulo-monocyte colony stimulating factor (GM-CSF)-stimulated myelomonocytic leukemia OTC-4 cells. 1589 21

The objective of the study was to compare executive functioning (EF) profiles across several pediatric medical conditions and explore the influence of age of diagnosis and evaluation. A retrospective, cross-sectional study of 734 children aged 5 to 18 years was conducted across five medical groups (brain tumor, leukemia [ALL], epilepsy [EPI], neurofibromatosis type 1 [NF1], and ornithine transcarbamylase deficiency [OTC-D]), attention deficit hyperactivity disorder (ADHD) controls, and matched healthy controls. We compared groups across the scales of a parent-completed Behavior Rating Inventory of Executive Functioning (BRIEF) using a repeated measures analysis of variance (ANOVA). Separate ANOVAs were conducted to look at age factors. The results showed that the ADHD group differed from all other groups and had the highest level of reported EF problems. The NF1 and OTC-D groups differed significantly from the healthy comparison group for overall EF problems, while the EPI and cancer groups did not. Working memory was the most elevated scale across medical groups, followed by plan/organize. Children with medical disorders were two to four times more likely than healthy controls to have clinically significant problems in several EF domains. There was a main effect for age at diagnosis and age at evaluation. A subset of children with medical disorders were found to have parent-reported EF difficulties, with particular vulnerability noted in working memory and organizational/planning skills. This has relevance for the development of interventions that may be helpful across disorders. Children with particular diagnoses and earlier age of diagnosis and evaluation had greater reported EF problems.
 ...
PMID:Executive functioning profiles from the BRIEF across pediatric medical disorders: Age and diagnosis factors. 2614 38