A5057043456- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Cholesterol and Lipid Metabolism
- Prostate Cancer Treatment and Research
- Immune cells in cancer
- Lipoproteins and Cardiovascular Health
- Peptidase Inhibition and Analysis
- Nanoplatforms for cancer theranostics
- Ferroptosis and cancer prognosis
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- ATP Synthase and ATPases Research
- Immune Cell Function and Interaction
- Trace Elements in Health
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer Research and Treatments
- Pregnancy and Medication Impact
- Receptor Mechanisms and Signaling
- Cancer, Stress, Anesthesia, and Immune Response
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Nephrotoxicity and Medicinal Plants
- Garlic and Onion Studies
Indiana University – Purdue University Indianapolis
2024-2025
University of Indianapolis
2025
Indiana University School of Medicine
2025
Moffitt Cancer Center
2015-2023
Mansoura University
2013-2020
Abstract Cancer immunotherapies, such as immune checkpoint blockade or adoptive T-cell transfer, can lead to durable responses in the clinic, but response rates remain low due undefined suppression mechanisms. Solid tumors are characterized by a highly acidic microenvironment that might blunt effectiveness of antitumor immunity. In this study, we directly investigated effects tumor acidity on efficacy immunotherapy. An pH environment blocked activation and limited glycolysis vitro. IFNγ...
Tumours rapidly ferment glucose to lactic acid even in the presence of oxygen, and coupling high glycolysis with poor perfusion leads extracellular acidification. We hypothesise that acidity, independent from lactate, can augment pro-tumour phenotype macrophages.We analysed publicly available data human prostate cancer for linear correlation between macrophage markers genes. used zwitterionic buffers adjust pH series vitro experiments. then utilised subcutaneous transgenic tumour models...
The acidic pH of tumors profoundly inhibits effector functions activated CD8 + T-cells. We hypothesize that this is a physiological process in immune regulation, and it occurs within lymph nodes (LNs), which are likely because low convective flow high glucose metabolism. Here we show by vivo fluorescence MR imaging, LN paracortical zones acidic. These niches absent athymic Nu/Nu lymphodepleted mice, implicating T-cells the acidifying process. T-cell glycolysis inhibited at observed LNs. due...
Abstract Castration-resistant prostate cancer (CRPC) is a lethal stage of disease in which androgen receptor (AR) signaling persistent despite deprivation therapy (ADT). Most studies have focused on investigating cell-autonomous alterations CRPC, while the contributions tumor microenvironment are less well understood. Here we sought to determine role tumor-associated macrophages based upon their progression and therapeutic resistance. In syngeneic model that reflected mutational landscape...
Induction of cell death represents a primary goal most anticancer treatments. Despite the efficacy such approaches, small population "persisters" develop evasion strategies to therapy-induced death. While previous studies have identified mechanisms resistance apoptosis, by which persisters dampen other forms death, as pyroptosis, remain be elucidated. Pyroptosis is form inflammatory that involves formation membrane pores, ion gradient imbalance, water inflow, and rupture. Herein, we...
Abstract Tumor-associated macrophages (TAMs) are well-known as anti-inflammatory immune cells that contribute to various facets of prostate cancer development. An emerging aspect TAMs is their “iron-rich” phenotype. This accumulation iron can cell initiation and tumor progression. In the current study, we aim explore key role in regulating balance within microenvironment (TME). We induced tumorigenesis NP mice using Tamoxifen. The (Nkx3.1CreERT2/+ ; Ptenflox/flox Rosa26-CAG-LSL-EYFP/+ mice)...
Cisplatin is an effective chemotherapeutic agent successfully used in the treatment of a wide range tumors. Nevertheless, nephrotoxicity has restricted its clinical use. Recent studies have strongly suggested that inflammatory mechanisms may play important role pathogenesis cisplatin nephrotoxicity. Celecoxib, selective cyclooxygenase-2 inhibitor as anti-inflammatory, therefore protective effect on cisplatin-induced renal injury.In present study, rats were injected intraperitoneally with...
Immune infiltration is typically quantified using cellular density, not accounting for clustering. Tumor-associated macrophages (TAM) activate oncogenic signaling through paracrine interactions with tumor cells, which may be better reflected by local clustering than global density metrics. Using multiplex immunohistochemistry and digital pathologic analysis we myeloid cell markers in 129 regions of interest from 55 samples 35 patients metastatic ccRCC. CD68+ cells were found to clustered...
The present study was designed to explore the possible protective effects of agmatine, a known nitric oxide (NO) synthase inhibitor, against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated renal structural and functional alterations using histopathological biochemical approaches. Furthermore, effect agmatine on hypersensitivity urinary bladder rings acetylcholine (ACh) evaluated. Twenty-four male Wistar albino rats were randomly divided into 3 groups,...
Abstract Deficits in tumor perfusion and elevated glycolysis combine to reduce the pH of microenvironment. In poorly perfused volumes, oxygen nutrient deprivation may also elicit necrotic areas that trigger infiltration immune cells, including tumor-associated macrophages (TAMs). Inside tumors, TAMs are biased towards an M2 phenotype with anti-inflammatory tumor-promoting characteristics, rather than M1 known be essential for host defense cell killing. We aimed test whether low as a common...
Abstract Immune therapies have shown promise in a number of cancers, and clinical trials using the anti-PD-L1/PD-1 checkpoint inhibitor lung cancer been successful for patients. However, some patients either do not respond to treatment or recurrence after an initial response. It is clear which might fall into these categories what mechanisms are responsible failure. To explore different underlying biological resistance, we created spatially explicit mathematical model with modular framework....
Abstract Lymph nodes are an essential component of the adaptive immune response where antigen-presenting cells closely housed with their cognate effector cells. Protection lymph node resident from activated in such close quarters would need to be robust and reversible. Effector functions T-cells profoundly reversibly inhibited by acidic microenvironment. The underlying mechanisms this inhibition unknown, but may relate glycolysis, which is obligatory for expression functions. Here, we...
Cyclosporine-A (CsA) is an immunosuppressive drug which has been used to prevent rejection after organ transplantation and treat certain autoimmune diseases. However, its therapeutic use limited by nephrotoxicity. In this study, the modulator effect of allicin on oxidative nephrotoxicity CsA in rats was investigated. Furthermore, CsA-induced hypersensitivity urinary bladder rings acetylcholine (ACh) estimated. Rats were divided into three groups, control, (15 mg/kg, subcutaneously),...
Tumors rapidly ferment glucose to lactic acid even in the presence of oxygen, and coupling high glycolysis with poor perfusion leads extracellular acidification. Here we demonstrate that acidity, independent from lactate, augments pro-tumor phenotype macrophages. We used zwitterionic buffers show activating macrophages at pH 6.8 vitro enhanced an IL-4-driven as measured by gene expression, cytokine profiling, functional assays. These results were recapitulated vivo wherein neutralizing...
Abstract Tumor-associated macrophages are key immune cells associated with cancer progression. Here we sought to determine the role of in castration-resistant prostate (CRPC) using a syngeneic model that reflected mutational landscape disease. A transcriptomic analysis CRPC tumors following macrophage depletion revealed lower molecular signatures for steroid and bile acid synthesis, indicating potential perturbation cholesterol metabolism. Since is precursor five major classes hormones,...
Metabolic cross-talk between macrophages and tumor cells results in cancer progression therapeutic resistance.
Lactate drives rheumatoid arthritis progression by altering CD4 + T cell metabolism.
<div>Abstract<p>Castration-resistant prostate cancer (CRPC) is a lethal stage of disease in which androgen receptor (AR) signaling persistent despite deprivation therapy (ADT). Most studies have focused on investigating cell-autonomous alterations CRPC, while the contributions tumor microenvironment are less well understood. Here we sought to determine role tumor-associated macrophages based upon their progression and therapeutic resistance. In syngeneic model that reflected...