Hsp90 facilitates the maturation and stability of numerous oncoproteins, including HER2. The aim of this study was to assess the antitumor activity of the Hsp90 inhibitor IPI-504 in trastuzumab-resistant, HER2-overexpressing breast cancer cells. Therapy with trastuzumab, IPI-504, and the combination of trastuzumab and IPI-504 was evaluated in trastuzumab-sensitive and trastuzumab-resistant cell...

Policy iteration (PI) is a recursive process of policy evaluation and improvement to solve an optimal decision-making, e.g., reinforcement learning (RL) or optimal control problem and has served as the fundamental to develop RL methods. Motivated by integral PI (IPI) schemes in optimal control and RL methods in continuous time and space (CTS), this paper proposes on-policy IPI to solve the gene...

This study aimed to investigate the risk of element/heavy metal pollution caused by listvenitization. In this context, heavy listvenite-derived soils in region where listvenitized ultrabasic rocks are present as a result hydrothermal alterations vicinity Alakeçi (Bayramiç Çanakkale/Western Türkiye) was investigated with index, geoaccumulation index and integrated parameters. For purpose, Cu, Zn...

BACKGROUND There are few studies for evaluating plaque characteristics of nonstenotic basilar arteries (BA). Our aim was to determine entire BA plaques with a three-dimensional volumetric isotropic turbo spin-echo acquisition (VISTA) and investigate the differences between the patients with and without isolated pontine infarction (IPI). METHODS Twenty-four consecutive symptomatic patients wit...

Purpose: KIT activity is crucial for gastrointestinal stromal tumors (GIST). Imatinib (IMA) and sunitinib (SUN) are very effective KIT-inhibitors in patients with advanced GIST but have no curative potential. We evaluated the efficacy of the novel HSP90 inhibitor IPI-493 alone, or in combination with IMA or SUN in GIST xenografts with KIT mutations. Experimental Design:Nude mice (n1⁄4 98) were ...

The activity of the receptor tyrosine kinase KIT is crucial for gastrointestinal stromal tumor (GIST) growth and survival. Imatinib and sunitinib are very effective in advanced GIST, but have no curative potential. The observation that heat shock protein 90 (HSP90) inhibition results in KIT degradation prompted us to assess the efficacy of the HSP90 inhibitor retaspimycin hydrochloride (IPI-504...

PURPOSE KIT activity is crucial for gastrointestinal stromal tumors (GIST). Imatinib (IMA) and sunitinib (SUN) are very effective KIT-inhibitors in patients with advanced GIST but have no curative potential. We evaluated the efficacy of the novel HSP90 inhibitor IPI-493 alone, or in combination with IMA or SUN in GIST xenografts with KIT mutations. EXPERIMENTAL DESIGN Nude mice (n = 98) were ...

IPI-504, a water-soluble ansamycin analogue currently being investigated in clinical trials, is a potent inhibitor of the protein chaperone heat shock protein 90 (Hsp90). Inhibition of Hsp90 by IPI-504 triggers the degradation of important oncogenic client proteins. In cells, the free base of IPI-504 hydroquinone exists in a dynamic redox equilibrium with its corresponding quinone (17-AAG); the...

PURPOSE To identify CHST6 mutations in five additional Icelandic cases of macular corneal dystrophy (MCD) type I and in four families with MCD type II from Iceland. METHODS Genomic DNA was extracted from blood leukocytes of patients with MCD, their healthy family members, and from control individuals. CHST6 mutations were determined by PCR-sequencing. Immunophenotypes of MCD were determined b...

Methionine-choline-deficient (MCD) diets cause steatohepatitis in rodents and are used to study the pathophysiology of fatty liver disease in human beings. The most widely used commercial MCD formulas not only lack methionine and choline but also contain excess sucrose and fat. The objective of this study was to determine whether dietary sucrose in the MCD formula plays a role in the pathogenes...