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Project description:The activities of the dithiolethione analogs, D3T, OLT, and TBD are pharmacologically well-understood. These compounds act as chemopreventive agents whose ability is to block or diminish early stages of carcinogenesis. In addition, the three compounds are classified as monofunctional Phase II enzyme inducers and activate the same pathway, namely the Keap1-Nrf2 signal pathway. The three dithiolethiones were showed to ameliorate the AFB1-induced toxicity through increasing phase II enzymes including glutathione S-transferase (GST). The parent D3T was observed to be the most potent chemoprotective agent. Oltipraz, a clinically approved drug, has been shown to exhibit less efficacy than its analogs for inhibition of aflatoxin-induced hepatic foci.TBD was suggested to be better than OLT as a chemopreventive agent because of its reduced toxicity profile. Thus based on gene expressions, our goal is to study the closely related structure activities that lie within the three compounds and the activity of OLT versus TBD at the 5 position of their dithiole rings and to determine whether the activity of TBD is closely related to OLT or its parent D3T. Keywords: treatment effects
2008-12-30 | GSE8882 | GEO
Project description:The activities of the dithiolethione analogs, D3T, OLT, and TBD are pharmacologically well-understood. These compounds act as chemopreventive agents whose ability is to block or diminish early stages of carcinogenesis. In addition, the three compounds are classified as monofunctional Phase II enzyme inducers and activate the same pathway, namely the Keap1-Nrf2 signal pathway. The three dithiolethiones were showed to ameliorate the AFB1-induced toxicity through increasing phase II enzymes including glutathione S-transferase (GST). The parent D3T was observed to be the most potent chemoprotective agent. Oltipraz, a clinically approved drug, has been shown to exhibit less efficacy than its analogs for inhibition of aflatoxin-induced hepatic foci.TBD was suggested to be better than OLT as a chemopreventive agent because of its reduced toxicity profile. Thus based on gene expressions, our goal is to study the closely related structure activities that lie within the three compounds and the activity of OLT versus TBD at the 5 position of their dithiole rings and to determine whether the activity of TBD is closely related to OLT or its parent D3T. Experiment Overall Design: Male Fischer F344 rats (80-100g) were obtained from Harlan at 6 wk of age. General procedures for animal care and housing were in accordance with the Guide for the Care and use of Laboratory Animals, National Research Council, 1996. The animals were singly housed in polycarbonate cages in a temperature (22 ± 1°C)- and humidity (30-70%)-controlled room with a 14:10-h light-dark cycle, respectively. Rat AIN 76A chow (Harlan Teklad) and tap water were provided at libitum. Sixteen animals were randomly assigned into four groups (n=16) and treated by gavage with 100?l of either vehicle (saturated sucrose), 3H-1,2-dithiole-3-thione (D3T), (0.3 mmol/kg body wt), 4-methyl-5-pyrazinyl-3H-1,2-dithiole-3-thione (oltipraz-OLT), (0.3 mmol/kg), and 5-tert-butyl-3H-1,2-dithiole-3-thione (TBD) , (0.3mmol/kg body wt), once every other day for 5 days. Animals were killed 24h after the third dose. Liver tissues were harvested and snap frozen. The protocol for this study was approved by the University of Memphis Animal Care Committee and Johns Hopkins University.
2009-01-02 | E-GEOD-8882 | biostudies-arrayexpress
Project description:TBD
| PRJEB20843 | ENA
Project description:Dyskeratosis congenita (DC) is an inherited multi-system disorder, characterized by oral leukoplakia, nail dystrophy, and abnormal skin pigmentation, as well as high rates of bone marrow failure, solid tumors, and other medical problems such as osteopenia. DC and telomere biology disorders (collectively referred to as TBD here) are caused by germline mutations in telomere biology genes leading to very short telomeres and limited proliferative potential of hematopoietic stem cells. We found that skeletal stem cells (SSCs) within the bone marrow stromal cell population (BMSCs, also known as bone marrow-derived mesenchymal stem cells), may contribute to the hematological phenotype. TBD-BMSCs exhibited reduced clonogenicity, reduced telomerase activity, spontaneous differentiation into adipocytes and fibrotic cells, and increased senescence in vitro. Upon in vivo transplantation into mice, TBD-BMSCs failed to form bone or support hematopoiesis, unlike normal BMSCs. TERC reduction (a TBD-associated gene) in normal BMSCs by siTERC-RNA recapitulated the TBD-BMSC phenotype by reducing proliferation and secondary colony forming efficiency, and by accelerating senescence in vitro. Microarray profiles of control and siTERC-BMSCs showed decreased hematopoietic factors at the mRNA level, and decreased secretion of factors at the protein level. These findings are consistent with defects in SSCs/BMSCs contributing to bone marrow failure in TBD.
2014-12-09 | GSE64023 | GEO
Project description: Not available
| S-EPMC6332191 | biostudies-literature