A5002237880- Pancreatic and Hepatic Oncology Research
- Cancer Research and Treatments
- Biochemical and Molecular Research
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- Cancer-related Molecular Pathways
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Phagocytosis and Immune Regulation
- Epigenetics and DNA Methylation
- Ferroptosis and cancer prognosis
- Immunotherapy and Immune Responses
- Autoimmune Bullous Skin Diseases
- Animal Virus Infections Studies
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Viral Infections and Immunology Research
- Single-cell and spatial transcriptomics
- Cancer, Lipids, and Metabolism
- SARS-CoV-2 and COVID-19 Research
- FOXO transcription factor regulation
- Blood disorders and treatments
- Tendon Structure and Treatment
- Retinal Development and Disorders
- Schizophrenia research and treatment
UPMC Hillman Cancer Center
2022-2024
Cancer Research Institute
2022-2024
University of Pennsylvania
2016-2024
Brown University
2022-2023
Cancer Research Institute of the Slovak Academy of Sciences
2020
Abramson Cancer Center
2020
Emory University
2018
Abstract Mutations in the KRAS oncogene are found more than 90% of patients with pancreatic ductal adenocarcinoma (PDAC), Gly-to-Asp mutations (KRASG12D) being most common. Here, we tested efficacy a small-molecule KRASG12D inhibitor, MRTX1133, implantable and autochthonous PDAC models an intact immune system. In vitro studies validated specificity potency MRTX1133. vivo, MRTX1133 prompted deep tumor regressions all tested, including complete or near-complete remissions after 14 days....
Acquired resistance to immunotherapy remains a critical yet incompletely understood biological mechanism. Here, using mouse model of pancreatic ductal adenocarcinoma (PDAC) study tumor relapse following immunotherapy-induced responses, we find that is reproducibly associated with an epithelial-to-mesenchymal transition (EMT), EMT-transcription factors ZEB1 and SNAIL functioning as master genetic epigenetic regulators this effect. in not due immunosuppression the immune microenvironment,...
Tumors depend on a blood supply to deliver oxygen and nutrients, making tumor vasculature an attractive anticancer target. However, only fraction of patients with cancer benefit from angiogenesis inhibitors. Whether antiangiogenic therapy would be more effective if targeted individuals specific characteristics is unknown. To better characterize the vascular environment both within between types, we developed standardized metric - endothelial index (EI) estimate density in over 10,000 human...
Oncogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) are driven by complex interactions between the neoplastic component tumor microenvironment, which includes immune, stromal, parenchymal cells. In particular, most PDACs characterized a hypovascular hypoxic environment that alters cell behavior limits efficacy chemotherapy immunotherapy. Characterization spatial features vascular niche could advance our understanding inter- intratumoral heterogeneity in PDAC. this study,...
Abstract Lymph nodes (LNs) are the staging grounds for anti-tumor immunity, therefore their high susceptibility to metastatic colonization is a paradox. Previous studies have suggested that extrinsic tumor-derived factors precondition draining LN enable tumor cell survival by promoting state of immune suppression. Here, we investigate whether properties itself may impede its ability clear metastasizing cells. Using multiple immunocompetent transplant models, show LNs possess intrinsic...
Septo-optic dysplasia (SOD) is a congenital disorder characterized by optic nerve, pituitary and midline brain malformations. The clinical presentation of SOD highly variable with poorly understood etiology. majority cases are sporadic, but in rare instances inherited mutations have been identified small number transcription factors, some which regulate the expression Sonic hedgehog (Shh) during mouse forebrain development. also associated young maternal age, suggesting that environmental...
The U.S. Food and Drug Administration has to date granted approval or emergency use authorization three vaccines against severe acute respiratory syndrome coronavirus 2 disease 2019. In clinical trials real-use observational studies, the Pfizer-BioNTech BNT162b2 messenger RNA 2019 vaccine, as well Moderna mRNA-1273 have demonstrated high efficacy few adverse events.A 20-year-old male college student in good health developed tinnitus hematuria shortly after vaccination progressed swiftly a...
Clozapine-induced neutropenia occurs in 3-5% of individuals treated with clozapine. Current US guidelines require interruption clozapine when the absolute neutrophil count (ANC) drops below 1000 cells/mm
In this study, we determine the in vivo effects of injecting sub-populations leukocytes into normal rat Achilles tendons via a controlled laboratory study. Allogenic monocytes, granulocytes, or plasma were injected 24 healthy tendons. Treated and contralateral un-treated control then assessed for cellularity, histologic morphology, vascularity after 7 14 days. Significant increases 221% 249% cellularity (P = 0.014) seen on day within with granulocytes as compared to respectively. Also,...
The regulated glycosylation of the proteome has widespread effects on biological processes that cancer cells can exploit. Expression N-acetylglucosaminyltransferase V (encoded by Mgat5 or GnT-V), which catalyzes addition β1,6-linked N-acetylglucosamine to form complex N-glycans, been linked tumor growth and metastasis across types. Using a panel murine pancreatic ductal adenocarcinoma (PDAC) clonal cell lines recapitulate immune heterogeneity PDAC, we found is required for in vivo but not...
<p>Supplementary Figures S1-S7</p>
<p>Supplementary Figures S1-S7</p>
<div>Abstract<p>Oncogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) are driven by complex interactions between the neoplastic component tumor microenvironment, which includes immune, stromal, parenchymal cells. In particular, most PDACs characterized a hypovascular hypoxic environment that alters cell behavior limits efficacy chemotherapy immunotherapy. Characterization spatial features vascular niche could advance our understanding inter- intratumoral...
<div>Abstract<p>Oncogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) are driven by complex interactions between the neoplastic component tumor microenvironment, which includes immune, stromal, parenchymal cells. In particular, most PDACs characterized a hypovascular hypoxic environment that alters cell behavior limits efficacy chemotherapy immunotherapy. Characterization spatial features vascular niche could advance our understanding inter- intratumoral...
Epidermolysis bullosa acquisita (EBA) is a subepidermal bullous disorder mediated by autoantibodies targeting basement membrane zone (BMZ) anchoring fibrils. Clinically, this presents as skin fragility and blister formation following mechanical trauma. Although most EBA cases involve IgG antibodies directed against type VII collagen, rare of immunoglobulin A (IgA)- M (IgM)-mediated disease have been reported. We present case mixed IgM- IgA-mediated associated with IgM-λ paraproteinemia.
Abstract The KRAS oncogene is mutated in greater than 90% of pancreatic ductal adenocarcinoma (PDAC) cases. MRTX1133 a non-covalent inhibitor targeting the most common mutant PDAC, KRASG12D, and has shown robust efficacy various tumor models, including PDAC (Hallin et al., Nature Medicine, 2022; Kemp Cancer Discovery, 2022). However, interplay between immune system not been characterized. Using immunocompetent mouse models we aimed to elucidate whether effects are dependent. Mice were...
<div>Abstract<p>Mutations in the <i>KRAS</i> oncogene are found more than 90% of patients with pancreatic ductal adenocarcinoma (PDAC), Gly-to-Asp mutations (<i>KRAS</i><sup>G12D</sup>) being most common. Here, we tested efficacy a small-molecule KRAS<sup>G12D</sup> inhibitor, MRTX1133, implantable and autochthonous PDAC models an intact immune system. <i>In vitro</i> studies validated specificity potency MRTX1133....
<p>MRTX1133 exerts in vivo effects early treatment</p>
<p>Supplementary Figures and Table with legend arranged in a single presentable package</p>
<div>Abstract<p>Mutations in the <i>KRAS</i> oncogene are found more than 90% of patients with pancreatic ductal adenocarcinoma (PDAC), Gly-to-Asp mutations (<i>KRAS</i><sup>G12D</sup>) being most common. Here, we tested efficacy a small-molecule KRAS<sup>G12D</sup> inhibitor, MRTX1133, implantable and autochthonous PDAC models an intact immune system. <i>In vitro</i> studies validated specificity potency MRTX1133....
<p>KRASG12D inhibition alters the tumor immune microenvironment</p>