A5023611119- Brain Metastases and Treatment
- Glioma Diagnosis and Treatment
- Lung Cancer Research Studies
- Lung Cancer Treatments and Mutations
- Meningioma and schwannoma management
- Cancer Genomics and Diagnostics
- Advanced Breast Cancer Therapies
- Cancer-related cognitive impairment studies
- Advanced Radiotherapy Techniques
- Mitochondrial Function and Pathology
- Chemical Reactions and Isotopes
- Effects of Radiation Exposure
- Circadian rhythm and melatonin
- Advanced biosensing and bioanalysis techniques
- Sirtuins and Resveratrol in Medicine
- HER2/EGFR in Cancer Research
- Sleep and Wakefulness Research
- Redox biology and oxidative stress
- Traumatic Brain Injury and Neurovascular Disturbances
- Radiation Therapy and Dosimetry
- Free Radicals and Antioxidants
- Radiomics and Machine Learning in Medical Imaging
- Caveolin-1 and cellular processes
- Cancer-related gene regulation
- Breast Cancer Treatment Studies
Center for Cancer Research
2012-2025
National Institutes of Health
2012-2023
National Cancer Institute
2013-2023
Molecular Oncology (United States)
2023
Cornell University
2018
Weill Cornell Medicine
2018
National Institutes of Health Clinical Center
2018
Dana-Farber Cancer Institute
2018
National Institute of Neurological Disorders and Stroke
2018
National Cancer Institute
2015
Clonal evolution of osimertinib-resistance mechanisms in EGFR mutant lung adenocarcinoma is poorly understood. Using multi-region whole-exome and RNA sequencing prospectively collected pre- post-osimertinib-resistant tumors, including at rapid autopsies, we identify a likely mechanism driving osimertinib resistance all patients analyzed. The majority acquire two or more either concurrently temporal sequence. Focal copy-number amplifications occur subclonally are spatially temporally...
Cellular senescence and the senescence-associated secretory phenotype (SASP) may contribute to development of radiation therapy–associated side effects in lung blood vessels by promoting chronic inflammation. In brain, inflammation contributes neurologic disease, including Alzheimer's disease. this study, we investigated roles cellular Δ133p53, an inhibitory isoform p53, radiation-induced brain injury. Senescent cell types irradiated human were identified with immunohistochemical labeling...
Abstract Redox-sensitive signaling factors regulate multiple cellular processes, including proliferation, cell cycle, and prosurvival cascades, suggesting their potential as molecular targets for anticancer agents. It is logical to set constraints that a target should meet at least one of the following criteria: (1) inhibition pathways; (2) cycle progression; or (3) enhancement cytotoxic effects Therefore, we hypothesized thioredoxin reductase 1 (TR), component several redox-regulated...
Abstract Purpose: Brain metastases of breast cancer contribute significantly to patient morbidity and mortality. We have tested pazopanib, a recently approved antiangiogenic drug that targets VEGFR1, VEGFR2, VEGFR3, PDGFRβ, PDGFRα, c-kit, for prevention experimental brain mechanism action. Experimental Design: In vitro assays included B-Raf enzymatic assays, Western blots, angiogenesis assays. For in vivo HER2 transfectants the seeking sublines MDA-MB-231 cells (231-BR-HER2) MCF7...
Preclinical data showed that prophylactic, low-dose temozolomide (TMZ) significantly prevented breast cancer brain metastasis. We present results of a phase I trial combining T-DM1 with TMZ for the prevention additional metastases after previous occurrence and local treatment in patients HER2+ cancer.Eligible had were within 12 weeks whole radiation therapy (WBRT), stereotactic radiosurgery, and/or surgery. Standard doses administered intravenously every 21 days (3.6 mg/kg) was given orally...
Abstract Wnt signaling is critical to maintaining cellular homeostasis via regulation of cell division, mitigation stress, and degradation. Aberrations in contribute carcinogenesis metastasis, whereas sirtuins have purported roles carcinogenesis, aging, neurodegeneration. Therefore, the hypothesis that sirtuin 2 (SIRT2) directly interacts with β-catenin whether this interaction alters expression target genes produce an altered phenotype was tested. Coimmunoprecipitation studies, using mouse...
To investigate radiation oncologists' opinions on important considerations to offering re-irradiation (re-RT) as a treatment option for recurrent glioma. A survey was conducted with 13 oncologists involved in the care of central nervous system tumor patients. The comprised 49 questions divided into 2 domains: demographic section (10 questions) and case (5 re-RT cases 5 6 representing one or several dilemmas may be encountered clinic). Respondents were asked rate relevance various factors...
Brain metastases occur in up to 25–55% of patients with metastatic HER2-positive breast cancer. Standard treatment has high rates recurrence or progression, limiting survival and quality life most patients. Temozolomide (TMZ) is known penetrate the blood–brain barrier US FDA approved for glioblastoma. Our group demonstrated that low doses TMZ administered a prophylactic, metronomic fashion can significantly prevent development brain murine models Based on these findings, we initiated...
The ability to physically target radiotherapy using image-guidance is continually improving with photons and particle therapy that include protons heavier ions such as carbon. unit of dose deposited the gray (Gy); however, therapies produce different patterns ionizations, there evidence biological effects radiation depend on size, schedule, type radiation. This National Cancer Institute (NCI)–sponsored workshop addressed potential radiation-induced perturbations in addition physical dose,...
Abstract Caveolin‐1 is the principal structural and functional component of caveolae, a plasmalemmal compartment that has been proposed to sequester lipid protein components participate in transmembrane signal transduction processes. Multiple studies reveal reduction expression level caveolin‐1 mRNA many carcinomas as well transformed cells. The human gene localized suspected tumor suppressor locus (7q31.1). Collectively, these data have taken imply may function capacity. To determine if...
Despite mounting evidence for the use of re-irradiation (re-RT) in recurrent high grade glioma, optimal patient selection criteria re-RT remain unknown. We present a novel scoring system based on radiobiology principles including target independent factors, likelihood control, and anticipated organ at risk (OAR) toxicity to allow proper setting glioma.Thirty one patients with glioma who received (2008-2016) NCI - NIH were included analysis. A overall survival (OS) progression free (PFS) was...
Whole brain radiotherapy (WBRT) produces unwanted sequelae, albeit via unknown mechanisms. A deacetylase expressed in the central nervous system, Sirtuin 2 (SIRT2), has been linked to neurodegeneration. Therefore, we sought challenge notion that a single disease pathway is responsible for radiation-induced injury Sirt2 wild-type (WT) and knockout (KO) mice at proteomic level. We utilized isobaric tag relative absolute quantitation analyze homogenates from WT KO with without WBRT. Selected...
Nguyen, P., Shukla, S., Liu, R., Abbineni, G. and Smart, D. K. Sirt2 Regulates Radiation-Induced Injury. Radiat. Res. 191, 398–412 (2019).Sirtuin 2 (SIRT2) plays a major role in aging, carcinogenesis neurodegeneration. While it has been shown that SIRT2 is mediator of stress-induced cell death, the mechanism remains unclear. In this study, we report mediating radiation-induced death DNA damage using mouse embryonic fibroblasts (MEFs), progenitor cells tissues from wild-type genomic knockout...