A5029235997- Cancer, Hypoxia, and Metabolism
- Lung Cancer Research Studies
- Cancer Genomics and Diagnostics
- Adrenal and Paraganglionic Tumors
- Lung Cancer Treatments and Mutations
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Glioma Diagnosis and Treatment
- DNA Repair Mechanisms
- Nuclear Receptors and Signaling
- Hormonal Regulation and Hypertension
- Genetics and Neurodevelopmental Disorders
- Mitochondrial Function and Pathology
- DNA and Nucleic Acid Chemistry
- Neuroendocrine Tumor Research Advances
- Epigenetics and DNA Methylation
- Cancer therapeutics and mechanisms
- Pluripotent Stem Cells Research
- PARP inhibition in cancer therapy
- RNA Interference and Gene Delivery
- Hair Growth and Disorders
- CRISPR and Genetic Engineering
- Erythropoietin and Anemia Treatment
- Cancer Cells and Metastasis
- ATP Synthase and ATPases Research
National Cancer Institute
2020-2024
Center for Cancer Research
2020-2024
National Institutes of Health
2022-2024
Dow University of Health Sciences
2023
University of Pennsylvania
2006-2018
Indian Agricultural Research Institute
2018
Central University of Rajasthan
2017
Philadelphia University
2011
Abstract Immune checkpoint blockade (ICB) benefits only a small subset of patients with cell lung cancer (SCLC), yet the mechanisms driving benefit are poorly understood. To identify predictors clinical to ICB, we performed immunogenomic profiling tumor samples from relapsed SCLC. Tumors who derive ICB exhibit cytotoxic T-cell infiltration, high expression antigen processing and presentation machinery (APM) genes, low neuroendocrine (NE) differentiation. However, elevated Notch signaling,...
Small-cell lung cancer (SCLC) is an aggressive neuroendocrine cancer. Oncogenic MYC amplifications drive SCLC heterogeneity, but the genetic mechanisms of amplification and phenotypic plasticity, characterized by nonneuroendocrine cell states, are not known. Here, we integrate whole-genome sequencing, long-range optical mapping, single-cell DNA fluorescence in situ hybridization to find extrachromosomal (ecDNA) as a primary source oncogene driver fusions. ecDNAs bring proximity enhancer...
Abstract MicroRNAs (miRNAs) are short non‐coding RNAs that post‐transcriptionally regulate gene expression. Hsa‐miR‐9 has been shown to have opposite functions in different tumour types; however, the underlying mechanism is unclear. Here we show hsa‐miR‐9 down‐regulated metastatic melanomas compared primary melanomas. Overexpression of miR‐9 melanoma cells resulted significantly decreased cell proliferation and migratory capacity with F‐actin polymerization down‐regulation multiple GTPases...
Abstract Mutations in the BRAF serine/threonine kinase gene are frequently found cutaneous melanomas. Activation of hypoxia inducible factor-1α (HIF-1α) response to both hypoxic stress and oncogenic signals has important implications cancer development progression. Here, we report that mutant BRAFV600E increases HIF-1α expression melanoma cells. Our microarray profiling data 35 melanocyte cell lines showed was significantly increased melanomas harboring mutation. Stable suppression or...
Introduction: Parathyroid carcinoma (PC) is an extremely rare entity, with a frequency of 0.005% all malignancies. Most data related to this disease are limited case series and few database studies. We present large study that aims investigate the demographic, clinical, pathological factors, prognosis, survival PC. Methods: Data parathyroid were extracted from Surveillance, Epidemiology, End Results (SEER) diagnosed between 1975 2016. Results: PC had slightly higher incidence in men (52.2%,...
Endogenous replication stress is a major driver of genomic instability. Current assessments are low throughput precluding its comprehensive assessment across tumors. Here we develop and validate transcriptional profile by leveraging established cellular characteristics that portend stress. The repstress gene signature defines subset tumors lineages characterized activated oncogenes, aneuploidy, extrachromosomal DNA amplification, immune evasion, high instability, poor survival, importantly...
Abstract Colorectal cancers (CRCs) are prevalent worldwide, yet current treatments remain inadequate. Using chemical genetic screens, we identify that co-inhibition of topoisomerase I (TOP1) and NEDD8 is synergistically cytotoxic in human CRC cells. Combination the TOP1 inhibitor irinotecan or its bioactive metabolite SN38 with NEDD8-activating enzyme pevonedistat exhibits synergy patient-derived organoids xenografts. Mechanistically, show blocks ubiquitin/proteasome-dependent repair...
Abstract Small‐cell lung cancer (SCLC) is the most lethal type of cancer. Specifically, MYC‐driven non‐neuroendocrine SCLC particularly resistant to standard therapies. Lurbinectedin was recently approved for treatment relapsed SCLC, but combinatorial approaches are needed increase depth and duration responses lurbinectedin. Using high‐throughput screens, we found inhibitors ataxia telangiectasia mutated rad3 related (ATR) as effective agents augmenting lurbinectedin efficacy. First‐in‐class...
Abstract Current treatment options for metastatic adrenocortical carcinoma (ACC) have limited efficacy, despite the common use of mitotane and cytotoxic agents. This study aimed to identify novel therapeutic ACC. An extensive drug screen was conducted compounds with potential activity against ACC cell lines. We further investigated mechanism action identified compound, TAK-243, its synergistic effects current therapeutics, efficacy in models including patient-derived organoids mouse...
Ataxia telangiectasia and Rad3-related (ATR) checkpoint kinase inhibitors are in clinical trials. Here we explored the molecular pharmacology therapeutic combination strategies of oral ATR inhibitor M1774 (Tuvusertib) with DNA-damaging agents (DDA). As single agent, suppressed cancer cell viability at nanomolar concentrations, showing greater activity than ceralasertib berzosertib, but less potency gartisertib elimusertib small lung H146, H82, DMS114 lines. also efficiently blocked...
Melanoma accounts for only a small portion of skin cancer but it is associated with high mortality. serum biomarkers that may aid early diagnosis or guide therapy are needed clinically. However, studies have often been hampered by the interference causes false readouts in immunological tests. Here we show that, after using special buffer to eliminate interference, IL-8 and cathepsin B levels were significantly elevated melanoma patients (p < 0.05). More importantly, combination also...
Previous reports have documented that cholesterol-lowering simvastatin prevented osteolytic metastasis of breast cancer in animal model which cells were placed into blood circulation. Thus, treatment might a preventive effect inhibiting osteoclast activity metastatic bone microenvironment. This study both and MBCD (cholesterol depleting drug) blocked the cancer-induced TRAP MMP activity, expressions various osteoclastogenic genes (TRAP, Cathepsin K, NFATc1) pre-osteoclast RAW264.7 cells,...
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