A5016962837- Cancer Genomics and Diagnostics
- Cancer, Hypoxia, and Metabolism
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- Glioma Diagnosis and Treatment
- DNA Repair Mechanisms
- Enzyme Structure and Function
- Amino Acid Enzymes and Metabolism
- Gene expression and cancer classification
- PARP inhibition in cancer therapy
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- Cancer-related molecular mechanisms research
- Ubiquitin and proteasome pathways
- Innovative Microfluidic and Catalytic Techniques Innovation
- Colorectal Cancer Surgical Treatments
- Polyamine Metabolism and Applications
- RNA modifications and cancer
- Health and Medical Research Impacts
- Immune cells in cancer
- scientometrics and bibliometrics research
- Viral-associated cancers and disorders
- Colorectal and Anal Carcinomas
- Cancer therapeutics and mechanisms
Columbia University Irving Medical Center
2022-2024
Cornell University
2008-2022
Memorial Sloan Kettering Cancer Center
2008-2022
Herbert Irving Comprehensive Cancer Center
2022
Cancer Genetics (United States)
2010
Harvard University
2008
Abstract Somatic mutations in cytosolic or mitochondrial isoforms of isocitrate dehydrogenase (IDH1 IDH2, respectively) contribute to oncogenesis via production the metabolite 2-hydroxyglutarate (2HG). Isoform-selective IDH inhibitors suppress 2HG and induce clinical responses patients with IDH1- IDH2-mutant malignancies. Despite promising activity inhibitors, mechanisms that mediate resistance inhibition are poorly understood. Here, we describe four cases identify mutant isoform switching,...
Hec1 (Highly Expressed in Cancer 1) is one of four proteins the outer kinetochore Ndc80 complex involved dynamic interface between centromeres and spindle microtubules. Its overexpression seen a variety human tumors correlates with tumor grade prognosis. We show here that an inducible mouse model results mitotic checkpoint hyperactivation. As previously observed Mad2 gene, hyperactivation leads to aneuploidy vitro sufficient generate vivo harbor significant levels aneuploidy. These...
Polyamines are polycationic alkyl-amines abundant in proliferating stem and cancer cells. How these metabolites influence numerous cellular functions remains unclear. Here we show that polyamine levels decrease during differentiation inhibiting synthesis leads to a differentiated-like cell state. concentrate the nucleus further enriched nucleoli of cells culture
Oncogenic IDH1/2 mutations produce 2-hydroxyglutarate (2HG), resulting in competitive inhibition of DNA and protein demethylation. IDH-mutant cancer cells show an inability to differentiate but whether 2HG accumulation is sufficient perturb differentiation directed by lineage-specifying transcription factors unknown. A MyoD-driven model was used study the role IDH mesenchymal cells. The presence produced oncogenic IDH2 blocks ability MyoD drive into myotubes. 5mC hypermethylation dispensable...
<h3>Importance</h3> Predicting outcomes in patients receiving neoadjuvant therapy for rectal cancer is challenging because of tumor downstaging. Validated clinical calculators that can estimate recurrence-free survival (RFS) and overall (OS) among with who have received multimodal are needed. <h3>Objective</h3> To develop validate providing estimates recurrence better individualized decision-making than the American Joint Committee on Cancer (AJCC) staging system or (NAR) score. <h3>Design,...
Article Tools CASE REPORTS OPTIONS & TOOLS Export Citation Track Add To Favorites Rights Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/PO.21.00560 JCO Precision Oncology no. 6 (2022) e2100560. Published online June 8, 2022. PMID: 35675575 Concurrent Germline BRCA1/2 and Mismatch Repair Mutations in Young-Onset Pancreatic Colorectal Cancer: The Importance of Comprehensive Somatic Characterization to Inform Therapeutic Options Muhammet Ozer , MD1xMuhammet...
Summary Oncogenic mutations in the metabolic enzyme isocitrate dehydrogenase 1 and 2 (IDH1/2) have been found a number of liquid solid tumors. Their pathogenic mechanism action involves production 2-hydroxyglutarate (2HG), an oncometabolite that acts part by inhibiting members family dioxygenases modulate chromatin dynamics. Recent work has suggested mutant IDH (mIDH) 2HG also impact sensitivity to inhibitors poly-ADP ribose polymerases (PARP) but molecular basis for this is unclear. Unlike...
Abstract Somatic mutations in cytosolic or mitochondrial isoforms of isocitrate dehydrogenase (IDH1 IDH2, respectively) contribute to oncogenesis via production the metabolite 2-hydroxyglutarate (2HG). Isoform-selective IDH inhibitors suppress 2HG and induce clinical responses patients with IDH1- IDH2-mutant malignancies. Despite promising activity inhibitors, mechanisms that mediate resistance inhibition are poorly understood. Here, we describe four cases identify mutant isoform switching,...
Abstract Poor differentiation (the divergence of tumor cell morphology from the cellular normal tissue origin) is associated with unfavorable responses to chemotherapy and poor clinical outcomes in solid tumors. Recurrent somatic mutations genes encoding for metabolic enzymes isocitrate dehydrogenase (IDH) 1 2 have recently been identified patients acute myeloid leukemias, chrondrosarcomas, cholangiocarcinomas glioblastomas. Point IDH lead production 2-hydroxyglutarate (2HG). 2HG acts as a...
<p>Figures S1 through S4</p>
<div>Abstract<p>Somatic mutations in cytosolic or mitochondrial isoforms of isocitrate dehydrogenase (<i>IDH1</i> <i>IDH2</i>, respectively) contribute to oncogenesis via production the metabolite 2-hydroxyglutarate (2HG). Isoform-selective IDH inhibitors suppress 2HG and induce clinical responses patients with <i>IDH1</i>- <i>IDH2</i>-mutant malignancies. Despite promising activity inhibitors, mechanisms that mediate resistance...
<p>Next-generation sequencing and droplet digital PCR</p>
<p>Supplemental Methods. DNA constructs, Gel electrophoresis and western blotting, Metabolite extraction analysis</p>
<p>Figures S1 through S4</p>
<p>Next-generation sequencing and droplet digital PCR</p>