A5059897477- T-cell and Retrovirus Studies
- Cutaneous lymphoproliferative disorders research
- Cancer, Hypoxia, and Metabolism
- Lymphoma Diagnosis and Treatment
- Histone Deacetylase Inhibitors Research
- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- Glioma Diagnosis and Treatment
- Tryptophan and brain disorders
- Metabolism, Diabetes, and Cancer
- Chronic Lymphocytic Leukemia Research
- Lung Cancer Treatments and Mutations
- Chronic Myeloid Leukemia Treatments
- Advanced Breast Cancer Therapies
- Cancer-related gene regulation
- Protein Degradation and Inhibitors
- Estrogen and related hormone effects
- Chemokine receptors and signaling
- Amino Acid Enzymes and Metabolism
- Mitochondrial Function and Pathology
- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- Adenosine and Purinergic Signaling
- Lung Cancer Research Studies
- Computational Drug Discovery Methods
Sanofi (United States)
2023-2024
AVEO Oncology (United States)
2024
Gilead Sciences (United States)
2021
Pfizer (United States)
2012-2020
Merck & Co., Inc., Rahway, NJ, USA (United States)
2006-2017
PCR Oncology
2017
Agios Pharmaceuticals (United States)
2009-2013
Pfizer (Italy)
2013
La Jolla Pharmaceutical (United States)
2013
Molecular Oncology (United States)
2010
Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2), are present most gliomas secondary glioblastomas, but rare other neoplasms. IDH1/2 mutations heterozygous, affect a single arginine residue. Recently, IDH1 were identified 8% of acute myelogenous leukemia (AML) patients. A glioma study revealed that cause gain-of-function, resulting the production accumulation 2-hydroxyglutarate (2-HG). Genotyping 145 AML biopsies 11 R132 mutant samples. Liquid chromatography-mass spectrometry...
Abstract Cancers of origin in the gallbladder and bile ducts are rarely curable with current modalities cancer treatment. Our clinical application broad-based mutational profiling for patients diagnosed a gastrointestinal malignancy has led to novel discovery mutations gene encoding isocitrate dehydrogenase 1 (IDH1) tumors from subset cholangiocarcinoma. A total 287 (biliary tract, colorectal, gastroesophageal, liver, pancreatic, small intestine carcinoma) were tested during routine...
2-Hydroxyglutarate, a metabolite overproduced in IDH -mutated gliomas, can be detected noninvasively patients with brain tumors by optimized magnetic resonance spectroscopy.
We have previously identified a 160-kDa protein in human embryonic kidney (HEK) 293 cells that undergoes rapid tyrosine phosphorylation response to insulin (PY160) (Kuhné, M. R., Zhao, Z., and Lienhard, G. E. (1995) Biochem. Biophys. Res. Commun. 211, 190-197). The phosphotyrosine form of PY160 was purified from insulin-treated HEK by anti-phosphotyrosine immunoaffinity chromatography, the sequences peptides determined, its cDNA cloned. encodes 1257-amino acid contains, order N terminus,...
Purpose Vorinostat, a histone deacetylase inhibitor, represents rational therapeutic target in glioblastoma multiforme (GBM). Patients and Methods with recurrent GBM who had received one or fewer chemotherapy regimens for progressive disease were eligible. Vorinostat was administered at dose of 200 mg orally twice day 14 days, followed by 7-day rest period. Results A total 66 patients treated. Grade 3 worse nonhematologic toxicity occurred 26% consisted mainly fatigue (17%), dehydration...
Oncogenic c-ros oncogene1 (ROS1) fusion kinases have been identified in a variety of human cancers and are attractive targets for cancer therapy. The MET/ALK/ROS1 inhibitor crizotinib (Xalkori, PF-02341066) has demonstrated promising clinical activity ROS1 fusion-positive non-small cell lung cancer. However, emerging evidence shown that patients can develop resistance by acquiring secondary point mutations kinase. In this study we characterized the PF-06463922, novel, orally available,...
Macroautophagy is a key stress-response pathway that can suppress or promote tumorigenesis depending on the cellular context. Notably, Kirsten rat sarcoma (KRAS)-driven tumors have been reported to rely macroautophagy for growth and survival, suggesting potential therapeutic approach of using autophagy inhibitors based genetic stratification. In this study, we evaluated whether KRAS mutation status predict efficacy inhibition. By profiling 47 cell lines with pharmacological loss-of-function...
The insulin receptor substrates (IRSs) function in signaling. Four members of the family, IRS-1 through IRS-4, are known. Previously, mice with targeted disruption genes for IRS-1, -2, and -3 have been characterized. To examine physiological role we generated characterized lacking IRS-4. Male IRS-4-null were ∼10% smaller size than wild-type male at 9 wk age beyond, whereas female null normal size. Breeding pairs reproduced less well mice. exhibited slightly lower blood glucose concentration...
The Björnstad syndrome, an autosomal recessive disorder associated with sensorineural hearing loss and pili torti, is caused by mutation of a previously unidentified gene on chromosome 2q34–36.
Optimization of a series R132H IDH1 inhibitors from high throughput screen led to the first potent molecules that show robust tumor 2-HG inhibition in xenograft model. Compound 35 shows good potency U87 cell based assay and ∼90% corresponding mouse model following BID dosing. The magnitude duration correlates with free plasma concentration.
Abstract Vorinostat is a histone deacetylase inhibitor that induces differentiation, growth arrest, and/or apoptosis of malignant cells both in vitro and vivo has shown clinical responses ∼30% patients with advanced mycosis fungoides Sézary syndrome cutaneous T-cell lymphoma (CTCL). The purpose this study was to identify biomarkers predictive vorinostat response CTCL using preclinical model systems assess these samples. signal transducer activator transcription (STAT) signaling pathway...