A5103224908- Glioma Diagnosis and Treatment
- Brain Metastases and Treatment
- Advanced Radiotherapy Techniques
- DNA Repair Mechanisms
- Lung Cancer Research Studies
- Advances in Oncology and Radiotherapy
- Cancer-related Molecular Pathways
- Radiation Therapy and Dosimetry
- Endometrial and Cervical Cancer Treatments
- Carcinogens and Genotoxicity Assessment
- Lung Cancer Treatments and Mutations
- Management of metastatic bone disease
- Neuroendocrine Tumor Research Advances
- Telemedicine and Telehealth Implementation
- Telomeres, Telomerase, and Senescence
- Cancer Research and Treatments
- Ovarian cancer diagnosis and treatment
- Cancer Genomics and Diagnostics
- Radiation Dose and Imaging
- Cancer Cells and Metastasis
- Lung Cancer Diagnosis and Treatment
- Advanced Fluorescence Microscopy Techniques
- Virus-based gene therapy research
- Head and Neck Cancer Studies
- Effects of Radiation Exposure
University Hospitals Seidman Cancer Center
2019-2025
Case Western Reserve University
2019-2025
Samsung (India)
2024
UPMC Hillman Cancer Center
2010-2024
Case Comprehensive Cancer Center
2020-2024
Shadyside Hospital
2024
University School
2019-2023
University of California, San Francisco
2005-2023
University Hospitals of Cleveland
2019-2023
University Hospitals Cleveland Medical Center
2023
A mutant promoter's partner in crime Telomerase is an enzyme that maintains the ends of chromosomes. TERT , gene coding for enzyme's catalytic subunit, not expressed healthy somatic cells, but its expression reactivated majority human cancers. The resultant high levels telomerase help cancer cells survive and multiply. Recurrent mutations promoter region are associated with multiple types. Bell et al. show a specific transcription factor called GABP selectively recruited to form promoter,...
Cancer-associated fibroblasts (CAFs) were presumed absent in glioblastoma given the lack of brain fibroblasts. Serial trypsinization specimens yielded cells with CAF morphology and single-cell transcriptomic profiles based on their copy number variations (CNVs) elevated individual cell probability scores derived from expression 9 markers absence 5 non-CAF stromal sharing features CAFs. Cells without CNVs high identified RNA-Seq 12 patient glioblastomas. Pseudotime reconstruction revealed...
Mitochondrial fission and fusion cycles are integrated with cell cycle progression. In this paper, we demonstrate that the inhibition of mitochondrial protein Drp1 causes an unexpected delay in G2/M progression aneuploidy. investigating underlying molecular mechanism, revealed inhibiting triggers replication stress, which is mediated by a hyperfused structure unscheduled expression cyclin E G2 phase. This persistent stress then induces ATM-dependent activation to M transition checkpoint....
Human embryonic stem (ES) cells are highly sensitive to environmental insults including DNA damaging agents, responding with high levels of apoptosis. To understand the response human ES damage, we investigated function ataxia telangiectasia mutated (ATM) damage signaling pathway in gamma-irradiation. Here, demonstrate for first time that ATM kinase is phosphorylated and properly localized sites double-strand breaks within 15 minutes irradiation. Activation resulted phosphorylation its...
Chemotherapy improves overall survival after surgery and radiotherapy for newly diagnosed high-risk IDH-mutant low-grade gliomas (LGGs), but a proportion of patients treated with temozolomide (TMZ) will develop recurrent tumors TMZ-induced hypermutation. We aimed to determine the prevalence hypermutation at recurrence prognostic implications.We sequenced from 82 initially who underwent reoperation correlated status grade subsequent clinical outcomes.Hypermutation was associated high-grade...
Abstract Background Brain metastases (BM) affect clinical management and prognosis but limited resources exist to estimate BM risk in newly diagnosed cancer patients. Additionally, guidelines for brain MRI screening are limited. We aimed develop validate models predict of at diagnosis the most common types that spread brain. Methods Breast cancer, melanoma, kidney colorectal (CRC), small cell lung (SCLC), non-small (NSCLC) data were extracted from National Cancer Database evaluate variables...
Abstract Mammalian POLQ (pol theta) is a specialized DNA polymerase with an unknown function in vivo. Roles have been proposed chromosome stability, as backup enzyme base excision repair, and somatic hypermutation of immunoglobulin genes. The purified can bypass AP sites thymine glycol. Mice defective are viable reported to elevated spontaneous radiation-induced frequencies micronuclei circulating red blood cells. To examine the potential roles hematopoiesis responses oxidative stress...
Abstract Background Immune checkpoint inhibitors (ICIs) have efficacy in several solid tumors but limited glioblastoma (GBM). This study evaluated the safety of anti-CTLA-4 and anti-PD-1 ICIs alone or combination newly diagnosed GBM after completion standard radiochemotherapy with subsequent intent to test combinatorial this setting. Methods The primary endpoint was dose-limiting toxicity (DLT) for adults unifocal, supratentorial resection chemoradiation. Ipilimumab nivolumab were tested...
Cells derived from ataxia telangiectasia (A-T) patients exhibit defective cell cycle checkpoints because of mutations in the gene encoding ATM (ataxia mutated). After exposure to ionizing radiation (IR), A-T cells sensitivity IR-induced cellular damage that results increased chromosome aberrations and death (radiosensitivity). is a member family kinases become activated response DNA damage. We showed even transient inhibition kinase for 1 hour, initiated 15 minutes after irradiation,...
Biallelic mutations in ataxia-telangiectasia mutated (ATM), which encodes for a protein kinase, cause ataxia telangiectasia (A-T). A-T is pleiotropic disease, with characteristic hypersensitivity to ionizing radiation (IR). patients typically lack both detectable ATM and kinase activity, small molecule inhibitors of activity have been developed as strategies improve radiotherapy the treatment cancers. As predicted, inhibition sufficient radiosensitize cells. However, we recently showed that...
AbstractMutations in the ATM kinase cause neurodegenerative disorder ataxia telangiectasia (A-T) and affected individuals are exquisitely radiation-sensitive cancer-prone. Cells derived from A-T contain chromosome aberrations exhibit profound cellular radiosensitivity. is an apical critical for activation of cell cycle checkpoints induction apoptosis irradiated cells. However, defects these pathways insufficient to account chromosomal instability seen We show here that small molecule KU55933...
During the COVID-19 pandemic, telemedicine became an attractive alternative to in-person appointments. The role of in patients who undergo frequent on-site treatment, such as radiation therapy, is unclear. purpose this study was examine use, physician satisfaction, and barriers continued use oncology.An anonymous, electronic survey distributed oncologists internationally between June October 2020. Respondents described demographic practice characteristics, a 5-point Likert scale assessed...
AbstractmTOR is a critical regulator of protein translation, and plays an important role in controlling cellular replication. Recent studies indicate that nutrient growth factor mediated activation mTOR deregulated human cancer, therefore represents attractive tumor target. However, complex process not yet fully understood. DNA viruses cells often perturb similar pathways to facilitate their In recent study, we used adenovirus as novel tool probe the mechanisms underlying inappropriate...
The effect of deletion the nitric oxide synthase 1 gene (NOS1−/−) on radiosensitivity was determined. In vitro, long-term cultures bone marrow stromal cells derived from NOS1−/− were more radioresistant than C57BL/6NHsd (wild-type), NOS2−/− or NOS3−/− mice. Mice each strain received 20 Gy thoracic irradiation 9.5 total-body (TBI), and mice sensitive to both. To determine etiology radiosensitivity, studies histopathology, lower esophageal contractility, gastrointestinal transit, blood counts,...
ATM is a protein kinase that initiates well-characterized signaling cascade in cells exposed to ionizing radiation (IR). However, the role for coordinating critical interactions and subsequent exchanges within DNA damage response (DDR) complexes unknown. We combined SILAC-based tandem mass spectrometry subcellular fractionation protocol interrogate proteome of irradiated treated with or without inhibitor KU55933. developed an integrative network analysis identify prioritize proteins were...