A5064761055- Phagocytosis and Immune Regulation
- Cancer Immunotherapy and Biomarkers
- Pancreatic and Hepatic Oncology Research
- Immune cells in cancer
- Pomegranate: compositions and health benefits
- Garlic and Onion Studies
- Cancer Cells and Metastasis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Tannin, Tannase and Anticancer Activities
- Nanoplatforms for cancer theranostics
- Sesame and Sesamin Research
- Cancer, Stress, Anesthesia, and Immune Response
- Atherosclerosis and Cardiovascular Diseases
- Pancreatitis Pathology and Treatment
- Cancer Mechanisms and Therapy
- Bioactive Compounds in Plants
- Cell Adhesion Molecules Research
- Cancer Research and Treatments
- Advanced Breast Cancer Therapies
- Inflammatory Biomarkers in Disease Prognosis
- Cynara cardunculus studies
- Cancer Genomics and Diagnostics
- Lung Cancer Research Studies
- Ferroptosis and cancer prognosis
- Protease and Inhibitor Mechanisms
University of Miami
2020-2024
Sylvester Comprehensive Cancer Center
2020-2024
Dr D Y Patil Dental College & Hospital
2023
All India Institute of Medical Sciences
2015-2019
Abstract We have shown that KRAS–TP53 genomic coalteration is associated with immune-excluded microenvironments, chemoresistance, and poor survival in pancreatic ductal adenocarcinoma (PDAC) patients. By treating cooperativity as a model for high-risk biology, we now identify cell-autonomous Cxcl1 key mediator of spatial T-cell restriction via interactions CXCR2+ neutrophilic myeloid-derived suppressor cells human PDAC using imaging mass cytometry. Silencing cell-intrinsic...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by a KRAS-driven inflammatory program and desmoplastic stroma, which contribute to the profoundly chemoresistant phenotype. The tumor stroma contains an abundance of cancer-associated fibroblasts (CAF), engage in extensive paracrine cross-talk with cells perpetuate protumorigenic inflammation. IL1α, pleiotropic, cell–derived cytokine, plays critical role shaping stromal landscape. To provide insights into molecular mechanisms...
Oxidant/antioxidant balance has been suggested as an important factor for initiation and progression of cancer. The objective this study was to determine changes in the levels malondialdehyde (MDA), nitric oxide (NO), total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, antioxidant capacity (TAC), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activities serum samples breast cancer patients (n=30) healthy subjects (n=100). MDA NO were found be increased compared...
Lack of durable response to cytotoxic chemotherapy is a major contributor the dismal outcomes seen in pancreatic ductal adenocarcinoma (PDAC). Extensive tumor desmoplasia and poor vascular supply are two predominant characteristics which hinder delivery chemotherapeutic drugs into PDAC tumors mediate resistance therapy. Previously, we have shown that STAT3 key biomarker therapeutic gemcitabine treatment PDAC, can be overcome by combined inhibition Src EGFR pathways. Although it...
Abstract A hallmark of pancreatic ductal adenocarcinoma (PDAC) is the presence a dense, desmoplastic stroma and consequent altered interactions between cancer cells their surrounding tumor microenvironment (TME) that promote disease progression, metastasis, chemoresistance. We have previously shown IL6 secreted from stellate (PSC) stimulates activation STAT3 signaling in cells, an established mechanism therapeutic resistance PDAC. now identified cell–derived cytokine IL1α as upstream...
Partial/complete pathologic response following neoadjuvant chemotherapy (NAC) in pancreatic cancer (PDAC) patients undergoing pancreatectomy is associated with improved survival. We sought to determine whether neutrophil-to-lymphocyte ratio (NLR) dynamics predict PDAC, and if manipulating NLR impacts chemosensitivity preclinical models uncovers potential mechanistic underpinnings underlying these effects. Pathologic PDAC (n=94) NAC (7/2015-12/2019) was dichotomized as partial/complete or...
Activating KRAS mutations, a defining feature of pancreatic ductal adenocarcinoma (PDAC), promote tumor growth in part through the activation cyclin-dependent kinases (CDK) that induce cell-cycle progression. p16INK4a (p16), encoded by gene CDKN2A, is potent inhibitor CDK4/6 and serves as critical checkpoint cell proliferation. Mutations subsequent loss p16 occur PDAC at rate higher than reported any other type results Rb inactivation unrestricted cellular growth. Therefore, strategies...
Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is projected to become a leading cause of cancer-related mortality, driven by its late-stage diagnosis, aggressive progression, and propensity for metastasis. Currently, no approved therapeutic effectively targets PDAC Emerging evidence implicates extracellular matrix (ECM), cytoskeletal dynamics are key invasion, pertinent contributor Our previous studies identified cAMP-response element binding protein 1 (CREB) as regulator ECM...
Abstract Background: Smoking, a major risk factor for pancreatic cancer, significantly attenuates the survival benefits of standard therapies, contributing to poor clinical outcomes in this malignancy. Previously, we have identified that hyperactivation cyclic AMP response element-binding protein (CREB) as driver immunosuppressive tumor immune microenvironment (TME), which limits therapeutic potential checkpoint blockade (ICB) therapies. The present study explores strategy targeting CREB...
Pancreatic ductal adenocarcinoma (PDAC) is a significant contributor to cancer-related morbidity and mortality, it known for its resistance conventional treatment regimens, including chemotherapy immune checkpoint blockade (ICB)-based therapies. We have previously shown that Urolithin A (Uro A), gut microbial metabolite derived from pomegranates, can target inhibit
Heavy alcohol consumption is the dominant risk factor for chronic pancreatitis (CP); however, treatment and prevention strategies alcoholic (ACP) remains limited. The present study demonstrates that ACP induction in C57BL/6 mice causes significant acinar cell injury, pancreatic stellate (PSC) activation, exocrine function insufficiency, an increased fibroinflammatory response when compared with or CP alone. Although withdrawal of during recovery led to reversion damage, continued established...
<div>Abstract<p>Pancreatic ductal adenocarcinoma (PDAC) is characterized by a KRAS-driven inflammatory program and desmoplastic stroma, which contribute to the profoundly chemoresistant phenotype. The tumor stroma contains an abundance of cancer-associated fibroblasts (CAF), engage in extensive paracrine cross-talk with cells perpetuate protumorigenic inflammation. IL1α, pleiotropic, cell–derived cytokine, plays critical role shaping stromal landscape. To provide insights into...
Pancreatic ductal adenocarcinoma (PDAC) is characterized by intratumoral abundance of neutrophilic/polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) which inhibit T-cell function through JAK2/STAT3-regulated arginase activity. To overcome limitations systemic inhibition PMN-MDSCs in cancer-bearing patients-i.e., neutropenia and compensatory myelopoietic adaptations-we develop a nanoengineering strategy to target cell-specific signaling exclusively without provoking neutropenia....
Heat shock protein 70 (Hsp70), a chaperone, is known to promote cell survival and tumor progression. However, its role in the microenvironment (TME) largely unknown. We specifically evaluated Hsp70 TME by implanting tumors wild-type (WT) controls or Hsp70−/- animals, thus creating with without Hsp70. Loss of led significantly smaller tumors; there were no differences stromal markers, but interestingly, depletion CD8 + T-cells abrogated this suppressive effect, indicating that loss affects...
Background: Gallbladder carcinoma (GBC) exhibits poor prognosis due to its detection at an advanced stage. Upregulation of lysosomal cysteine proteases cathepsin L (CTSL) and B (CTSB) has been implicated in several tumorigenic processes. However, no such information GBC was available. Therefore, the present study planned investigate expression clinical significance these cathepsins GBC. Methods: Activities CTSL CTSB were assayed gallbladder (GB) tissues obtained from patients (n = 43)...
Abstract BACKGROUND AND AIMS In vivo induction of alcoholic chronic pancreatitis (ACP) causes significant acinar damage, increased fibroinflammatory response, and heightened activation cyclic response element binding protein 1 (CREB) when compared with alcohol (A) or (CP) mediated pancreatic damage. However, the study elucidating cooperative interaction between CREB oncogenic Kras G12D/+ ( Kras* ) in promoting cancer progression ACP remains unexplored. METHODS Experimental was established...
Abstract Introduction: The desmoplastic stroma of pancreatic ductal adenocarcinoma (PDAC) perpetuates therapeutic resistance by impairing drug delivery and effector immune cell infiltration activation. We have identified tumor cell-derived interleukin-1α (IL1α) as a critical activator the stroma, comprised cancer-associated fibroblasts (CAF), towards pro-inflammatory phenotype via IL1 receptor, IL1R1, subsequent activation p38 MAPK. Our hypothesis is that disruption CAF-specific IL1α/p38...