A5039052702- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- Autophagy in Disease and Therapy
- Lymphoma Diagnosis and Treatment
- CAR-T cell therapy research
- RNA modifications and cancer
- HER2/EGFR in Cancer Research
- Lung Cancer Treatments and Mutations
- Angiogenesis and VEGF in Cancer
- Glioma Diagnosis and Treatment
- Cancer-related Molecular Pathways
- Advanced Radiotherapy Techniques
- Epigenetics and DNA Methylation
- Radiation Therapy and Dosimetry
- Effects of Radiation Exposure
- PI3K/AKT/mTOR signaling in cancer
- DNA Repair Mechanisms
- HIV-related health complications and treatments
- Viral-associated cancers and disorders
- Cutaneous lymphoproliferative disorders research
- Immunotherapy and Immune Responses
- Cancer Research and Treatments
- CNS Lymphoma Diagnosis and Treatment
- Sarcoma Diagnosis and Treatment
- Head and Neck Cancer Studies
University of Pennsylvania
2016-2025
University of Utah
2022-2025
Huntsman Cancer Institute
2022-2025
Indian Institute of Science Education and Research Kolkata
2024
Hospital of the University of Pennsylvania
2001-2022
Luton and Dunstable University Hospital NHS Foundation Trust
2022
California University of Pennsylvania
2019-2021
Jadavpur University
2020
Philadelphia University
1993-2019
Baylor College of Medicine
2019
Oncogenic transformation and hypoxia both induceglut1 mRNA. We studied the interaction between theras oncogene in up-regulating glut1mRNA levels using Rat1 fibroblasts transformed with H-ras (Rat1-ras). Transformation led to a substantial increase under normoxic conditions additively increasedglut1 mRNA concert hypoxia. Using luciferase reporter construct containing 6 kilobase pairs of theglut1 promoter, we showed that this effect was mediated at transcriptional level. Promoter activity much...
The proto-oncogene c-Myc paradoxically activates both proliferation and apoptosis. In the pathogenic state, c-Myc–induced apoptosis is bypassed via a critical, yet poorly understood escape mechanism that promotes cellular transformation tumorigenesis. accumulation of unfolded proteins in ER initiates stress program termed protein response (UPR) to support cell survival. Analysis spontaneous mouse human lymphomas demonstrated significantly higher levels UPR activation compared with normal...
PurposeRecent studies suggest that ultrahigh-dose-rate, "FLASH," electron radiation therapy (RT) decreases normal tissue damage while maintaining tumor response compared with conventional dose rate RT. Here, we describe a novel RT apparatus delivers FLASH proton (PRT) using double scattered protons computed tomography guidance and provide the first report of RT-mediated radioprotection.Methods MaterialsAbsolute was measured at multiple depths in solid water validated against an absolute...
Abstract In studies of electron and proton radiotherapy, ultrahigh dose rates FLASH radiotherapy appear to produce fewer toxicities than standard while maintaining local tumor control. FLASH-proton (F-PRT) brings the spatial advantages PRT (>40 Gy/second), making it important understand if how F-PRT spares normal tissues providing antitumor efficacy that is equivalent standard-proton (S-PRT). Here we studied damage skin mesenchymal muscle bone found C57BL/6 murine hind leg produced...
Abstract Epidermal growth factor receptor (EGFR) inhibitors can decrease vascular endothelial (VEGF) expression and tumor angiogenesis. In the current study, we investigate molecular pathways by which this occurs using two drugs that have been used in clinic, gefitinib (Iressa) erlotinib (Tarceva). The VEGF SQ20B squamous cell carcinoma cells was opposed adenoviral of Akt these cells. hypoxia-inducible factor-1 (HIF-1) binding site located at approximately −1 kbp promoter not required for...
Radiation therapy is a mainstay in the treatment of glioblastomas, but these tumors are often associated with radioresistance. Activation phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway, which occurs frequently glioblastomas due to inactivation tumor suppressor phosphatase and tensin homologue (PTEN), correlates To directly test link between Akt activation radioresistance, we utilized PTEN-deficient U251 glioblastoma cells engineered inducibly restore PTEN upon exposure doxycycline....
Increased expression of vascular endothelial growth factor (VEGF) contributes to the many tumors by increasing angiogenesis. Although hypoxia is a potent inducer VEGF, we previously showed that epidermal receptor amplification and loss PTEN, both which can increase phosphatidylinositol-3-kinase (PI3K) activity, VEGF expression. Using adenoviral vectors cell line permanently expressing constitutively active myristoylated Akt (myrAkt), show activation Akt, downstream PI3K, increases in vitro...
Abstract The phosphoinositide 3-kinase (PI3K)/Akt pathway is commonly activated in cancer; therefore, we investigated its role hypoxia-inducible factor-1α (HIF-1α) regulation. Inhibition of PI3K U87MG glioblastoma cells, which have PI3K/Akt activity secondary to phosphatase and tensin homologue deleted on chromosome 10 (PTEN) mutation, with LY294002 blunted the induction HIF-1α protein targets vascular endothelial growth factor glut1 mRNA response hypoxia. Introduction wild-type PTEN into...
Abstract Background Gut microbial diversity is associated with improved response to immune checkpoint inhibitors (ICI). Based on the known detrimental impact that antibiotics have microbiome diversity, we hypothesized antibiotic receipt prior ICI would be decreased survival. Methods Patients stage III and IV melanoma treated between 2008 2019 were selected from an institutional database. A window of within 3 months first infusion was prespecified. The primary outcome overall survival (OS),...
We conducted a phase I trial evaluating pembrolizumab+hypofractionated radiotherapy (HFRT) for patients with metastatic cancers.There were two strata (12 each): (i) NSCLC/melanoma progressing on prior anti-PD-1 therapy, (ii) other cancer types; anti-PD-1-naive. Patients received 6 cycles of pembrolizumab, starting 1 week before HFRT. had ≥2 lesions; only one was irradiated (8 Gy × 3 first half; 17 second half in each stratum) and the other(s) followed response.Of 24 patients, 20 (83%)...
Ultra-high dose rate FLASH proton radiotherapy (F-PRT) has been shown to reduce normal tissue toxicity compared standard (S-PRT) in experiments using the entrance portion of depth profile, while therapy uses a spread-out Bragg peak (SOBP) with unknown effects on sparing. To investigate, biological F-PRT an SOBP and region were S-PRT mouse intestine. In this study, 8–10-week-old C57BL/6J mice underwent 15 Gy (absorbed dose) whole abdomen irradiation four groups: (1) F-PRT, (2) S-PRT, (3) (4)...
Abstract The phosphatidylinositol 3-kinase (PI3K)/Akt pathway can increase vascular endothelial growth factor (VEGF) and hypoxia-inducible 1α (HIF-1α) expression. We examined the effect of nelfinavir, an HIV protease inhibitor that inhibits Akt signaling, on VEGF HIF-1α expression angiogenesis, tumor oxygenation, radiosensitization. Nelfinavir decreases under normoxia via transcription Sp1, which regulates proximal core promoter. decreased Sp1 phosphorylation binding to a probe corresponding...
The c-Myc protein is a helix-loop-helix leucine zipper oncogenic transcription factor that participates in the regulation of cell proliferation, differentiation, and apoptosis. biochemical function has been well described, yet identities downstream effectors are just beginning to emerge. We describe identification set c-Myc-responsive genes Rat1a fibroblast through application cDNA representational difference analysis (RDA) cDNAs isolated from nonadherent Rat1a-myc cells. In this system,...