A5047550067- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Cancer Research and Treatments
- HER2/EGFR in Cancer Research
- RNA Interference and Gene Delivery
- Cancer therapeutics and mechanisms
- Melanoma and MAPK Pathways
- CAR-T cell therapy research
- Cell death mechanisms and regulation
- Effects of Radiation Exposure
- Cytokine Signaling Pathways and Interactions
- Microtubule and mitosis dynamics
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Bacteriophages and microbial interactions
- Radiopharmaceutical Chemistry and Applications
- HIV Research and Treatment
- Ferroptosis and cancer prognosis
- Radiation Therapy and Dosimetry
- Monoclonal and Polyclonal Antibodies Research
- Herpesvirus Infections and Treatments
Virginia Commonwealth University
2015-2024
Eskişehir Osmangazi University
2024
University of Richmond
2011-2015
VCU Massey Comprehensive Cancer Center
2014-2015
AstraZeneca (United Kingdom)
2013
The University of Texas Southwestern Medical Center
2013
Lawrence Berkeley National Laboratory
2008-2012
Center for Drug Evaluation and Research
2012
Université de Montréal
2012
Centre Hospitalier de l’Université de Montréal
2012
Abstract Ataxia telangiectasia (A-T) mutated (ATM) is critical for cell cycle checkpoints and DNA repair. Thus, specific small molecule inhibitors targeting ATM could perhaps be developed into efficient radiosensitizers. Recently, a inhibitor of the kinase, KU-55933, was shown to radiosensitize human cancer cells. Herein, we report on an improved analogue KU-55933 (KU-60019) with Ki IC50 values half those KU-55933. KU-60019 10-fold more effective than at blocking radiation-induced...
Poor survival rates of patients with tumors arising from or disseminating into the brain are attributed to an inability excise all tumor tissue (if operable), a lack blood-brain barrier (BBB) penetration chemotherapies/targeted agents, and intrinsic radio-/chemo-resistance. Ataxia-telangiectasia mutated (ATM) protein orchestrates cellular DNA damage response (DDR) cytotoxic double-strand breaks induced by ionizing radiation (IR). ATM genetic ablation pharmacological inhibition results in...
Exposure of A431 squamous and MDA-MB-231 mammary carcinoma cells to ionizing radiation has been associated with short transient increases in epidermal growth factor receptor (EGFR) tyrosine phosphorylation activation the mitogen-activated protein kinase (MAPK) c-Jun NH 2 -terminal (JNK) pathways. Irradiation (2 Gy) caused immediate primary activations (0–10 min) EGFR MAPK JNK pathways, which were surprisingly followed by later prolonged secondary (90–240 min). Primary was abolished molecular...
Subtraction hybridization identified melanoma differentiation-associated gene-7 (mda-7) as a gene induced during terminal differentiation in human cells. On the basis of structure, chromosomal localization and cytokine-like properties, mda-7 is classified IL-24. Administration mda-7/IL-24 by means replication-incompetent adenovirus (Ad.mda-7) induces apoptosis selectively diverse cancer cells without inducing harmful effects normal fibroblast or epithelial The present studies investigated...
Abstract Astrocyte elevated gene-1 (AEG-1) was initially identified as an HIV-1- and tumor necrosis factor α (TNF-α)–inducible transcript in primary human fetal astrocytes by a rapid subtraction hybridization approach. Interestingly, AEG-1 expression is subsets of breast cancer, glioblastoma multiforme melanoma cells cooperates with Ha-ras to promote transformation immortalized melanocytes. Activation the transcription nuclear κB (NF-κB), TNF-α downstream signaling component, associated...
Previous studies have argued that enhanced activity of the epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase (MAPK) pathway can promote tumor cell survival in response to cytotoxic insults. In this study, we examined impact MAPK signaling on primary hepatocytes exposed low concentrations deoxycholic acid (DCA, 50 μM). Treatment with DCA caused activation, which was dependent upon ligand independent activation EGFR, downstream through Ras PI 3 kinase. Neither...
The Epidermal growth factor receptor (EGFR) is frequently dysregulated in malignant glioma that leads to increased resistance cancer therapy. Up-regulation of wild type or expression mutants such as EGFR variant III (EGFRvIII), the most common mutation glioma, associated with tumor radioresistance and poor clinical outcome. This thought be result a strong cytoprotective response fueled by signaling via AKT ERK heightened radiation dose range. Several groups including ours have shown this may...
Bailie et al. [In Vitro Cell Dev. Biol. (1992) 28A, 621-624] reported that primary cultures of rat hepatocytes possess low affinity binding sites for nerve growth factor (NGF). NGF treatment with a maximally effective concentration (20 ng/ml, 0.8 nM) caused acute phasic activation Raf-1 and p42(MAPkinase), smaller sustained B-Raf. The transient increase in p42(MAPkinase) activity returned to baseline within approximately 30 min. did not induce expression cyclin dependent kinase (cdk)...
Abstract The accurate joining of DNA double-strand breaks by homologous recombination repair (HRR) is critical to the long-term survival cell. three major mitogen-activated protein (MAP) kinase (MAPK) signaling pathways, extracellular signal-regulated (ERK), p38, and c-Jun-NH2-kinase (JNK), regulate cell growth, survival, apoptosis. To determine role MAPK in HRR, we used a human vivo I-SceI–based system. First, verified that this platform amenable pharmacologic manipulation show ataxia...
Abstract Purpose: Glioblastoma multiforme (GBM) is the most lethal form of brain cancer with a median survival only 12 to 15 months. Current standard treatment consists surgery followed by chemoradiation. The poor patients GBM due aggressive tumor invasiveness, an inability remove all tissue, and innate chemo- radioresistance. Ataxia–telangiectasia mutated (ATM) excellent target for radiosensitizing because its critical role in regulating DNA damage response p53, among other cellular...
Exposure of MCF-7 breast tumor cells or HCT-116 colon carcinoma to clinically relevant concentrations doxorubicin (Adriamycin; Farmitalia Research Laboratories, Milan, Italy) camptothecin results in both autophagy and senescence. To determine whether is required for chemotherapy-induced senescence, reactive oxygen generation induced by Adriamycin was suppressed <i>N</i>-acetyl cysteine glutathione, the induction ataxia telangiectasia mutated, p53, p21 modulated pharmacologically and/or...
Significance In the setting of glioblastoma multiforme (GBM), invasion cells into normal brain and unlikeliness complete surgical removal contributes to GBM lethality recurrence. “Gold standard” treatment includes adjuvant radiotherapy. Unfortunately, surviving radiation demonstrate increased therapeutic resistance. Melanoma differentiation-associated gene 9 (MDA-9/Syntenin) expression is elevated in patient-derived tumors cell lines, which correlates with decreased survival poor response...