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Pancreatic cancer cell-intrinsic transglutaminase-2 promotes T cell suppression through microtubule-dependent secretion of immunosuppressive cytokines.
J Immunother Cancer
January 2025
Internal Medicine I, Ulm University Hospital, Ulm, Germany
Background: Pancreatic ductal adenocarcinoma (PDAC) is mostly refractory to immunotherapy due to immunosuppression in the tumor microenvironment and cancer cell-intrinsic T cell tolerance mechanisms. PDAC is described as a "cold" tumor type with poor infiltration by T cells and factors leading to intratumoral T cell suppression have thus received less attention. Here, we identify a cancer cell-intrinsic mechanism that contributes to a T cell-resistant phenotype and describes potential combinatorial therapy.
View Article and Find Full Text PDFTargeting uPAR with an antibody-drug conjugate suppresses tumor growth and reshapes the immune landscape in pancreatic cancer models.
Sci Adv
January 2025
The Finsen Laboratory, Rigshospitalet, DK-2200 Copenhagen, Denmark.
Antibody-drug conjugates (ADCs) hold promise to advance targeted therapy of pancreatic ductal adenocarcinoma (PDAC), where the desmoplastic tumor stroma challenges effective treatment. Here, we explored the urokinase plasminogen activator receptor (uPAR) as a candidate ADC target in PDAC, harnessing its massive tumoral and stromal expression in this stroma-dense tumor. We generated a site-specific ADC offering high-affinity, cross-species reactivity, and efficient internalization of the anti-uPAR monoclonal antibody, FL1, carrying a potent anthracycline derivative (PNU-158692).
View Article and Find Full Text PDFIRE1 is a Promising Therapeutic Target in Pancreatic Cancer.
Am J Physiol Cell Physiol
January 2025
Department of General, Visceral, and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany.
Pancreatic cancer (PC) is one of the most aggressive malignancies, characterized by an increasing incidence and unfavorable prognosis. Despite recent advances, surgical resection combined with chemotherapy remains the only potentially curative therapeutic option. Therefore, it is of paramount importance to identify novel therapeutic targets and develop effective treatment strategies.
View Article and Find Full Text PDFOral Cyclosporine Treatment for Four Pediatric Patients With Toxic Epidermal Necrolysis That Showed No Response to High-dose Corticosteroids in Combination With Intravenous Immunoglobulin: A Case Series.
Curr Ther Res Clin Exp
December 2024
Department of Critical Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.
Background: Immunosuppressive agents like cyclosporine have proven effective in some pediatric cases, although there are limited case reports considering potential risks such as secondary infections.
Objective: This study investigated the safety and efficacy of Cyclosporine A in children who did not respond to high-dose corticosteroids combined with intravenous immunoglobulin (IVIG).
Methods: We reported four pediatric patients diagnosed with toxic epidermal necrolysis (TEN) received treatment at our institution.
Impact of antiviral prophylaxis on EBV viremia and posttransplant lymphoproliferative disorders in solid organ transplant recipients: a systematic review and meta-analysis.
Virol J
January 2025
Department of Pharmacotherapy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Introduction: Organ transplant recipients face a substantial risk of developing posttransplant lymphoproliferative disorders (PTLD). In over 90% of cases with B-cell PTLD following solid organ transplantation, the Epstein-Barr virus (EBV) genome is promptly identified, usually within the initial year. A continuing discussion revolves around the efficacy of antiviral prophylaxis in mitigating the incidence of PTLD in solid organ transplant (SOT) patients.
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