Intracellular trafficking represents a key mechanism that regulates cell fate by participating in either prodeath or prosurvival signaling. Soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein α (αSNAP) is a well known component of vesicle trafficking machinery that mediates intermembrane fusion. αSNAP increases cell resistance to cytotoxic stimuli, although mechanisms of its prosurvival function are poorly understood.
View Article and Find Full Text PDFActivating synthetic ligands for peroxisome proliferator-activated receptor gamma (PPARgamma), such as pioglitazone, are commonly used to treat persons with diabetes mellitus with improvement of insulin resistance. Several reports have clearly demonstrated that PPARgamma ligands could inhibit colorectal cancer cell growth and induce apoptosis. Meanwhile, aberrant crypt foci (ACF) have come to be established as a biomarker of the risk of CRC in azoxymethane-treated mice and rats.
View Article and Find Full Text PDFPurpose: Acute gastrointestinal syndrome (AGS) resulting from ionizing radiation causes death within 7 days. Currently, no satisfactory agent exists for mitigation of AGS. A peptide derived from the receptor binding domain of fibroblast growth factor 2 (FGF-P) was synthesized and its mitigation effect on AGS was examined.
View Article and Find Full Text PDFBiochem Biophys Res Commun
October 2009
Current microtubule-targeting agents interfere with the regulated assembly of microtubules from alpha/beta tubulin heterodimers but do not markedly alter tubulin levels. Previously, we showed that the compound T0070907 interferes with microtubule function by reversibly decreasing alpha and beta tubulin protein levels by more than 50% in multiple CRC cell lines. Since tubulin levels are generally relatively stable, and cells lack regulatory networks to respond to decreased tubulin levels by increasing synthesis, our result suggested the possibility of cancer therapies that act directly on tubulin homeostasis.
View Article and Find Full Text PDFThe microtubule-targeting agents (MTAs) are a very successful class of cancer drugs with therapeutic benefits in both hematopoietic and solid tumors. However, resistance to these drugs is a significant problem. Current MTAs bind to microtubules, and/or to their constituent tubulin heterodimers, and affect microtubule polymerization and dynamics.
View Article and Find Full Text PDFThe microtubule-targeting agents are one of the most successful classes of cancer therapeutics. All known antimicrotubule drugs bind to microtubules, or to their constituent tubulin heterodimers, and affect microtubule polymerization and dynamics. Recently, PPAR-gamma inhibitors were shown to reduce tubulin levels without affecting the polymerization of tubulin in vitro.
View Article and Find Full Text PDFThe nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPARgamma) has been identified as an important therapeutic target in murine models of colorectal cancer (CRC). To examine whether PPARgamma inhibition has therapeutic effects in late-stage CRC, the effects of PPARgamma inhibitors on CRC cell survival were examined in CRC cell lines and a murine CRC model. Low doses (0.
View Article and Find Full Text PDFActivation of the nuclear transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) inhibits growth and survival of hepatocellular carcinoma (HCC) cell lines. To further investigate the function of PPARgamma in HCC, PPARgamma expression patterns in primary tumors were examined, and the responses of two HCC cell lines to PPARgamma activation and inhibition were compared. PPARgamma expression was increased in HCC and benign-appearing peritumoral hepatocytes compared with remote benign hepatocytes.
View Article and Find Full Text PDFCrohn's disease is associated with an excessive T helper (TH) type 1 inflammatory immune response. Reducing the influx of disease-associated CD4+ TH1 cells into the inflamed intestine is likely to be beneficial in preventing a disease flare-up and even possibly in reducing the effect of acute disease. Thiazolidenedione (TZD) ligands, which activate peroxisome proliferator-activated receptor-gamma (PPARgamma), have been shown to reduce TH1 inflammation in murine models of colitis, primarily in a preventative fashion.
View Article and Find Full Text PDFThe maturation of T cells is an intricate process involving the interaction of developing thymocytes with discrete microenvironments within the thymus. Numerous studies have indicated that distinct thymic compartments provide signals required for each stage of thymocyte maturation. In this study we performed a comprehensive analysis of the expression patterns of Eph-A receptors and ephrins-A in the thymus using in situ hybridization and reverse transcription-polymerase chain reaction, and show that expression of these molecules is highly compartmentalized.
View Article and Find Full Text PDFGene Expr Patterns
December 2002
The maturation of T cells is an intricate process involving the interaction of developing thymocytes with discrete microenvironments within the thymus. Numerous studies have indicated that distinct thymic compartments provide signals required for each stage of thymocyte maturation. In this study we performed a comprehensive analysis of the expression patterns of Eph-A receptors and ephrins-A in the thymus using in situ hybridization and reverse transcription-polymerase chain reaction, and show that expression of these molecules is highly compartmentalized.
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