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Neoadjuvant Intratumoral MBT(A) Immunotherapy Prevents Distant Metastases and Recurrence in Murine Models.
Cancer Lett
January 2025
Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, USA. Electronic address:
Neoadjuvant immunotherapy represents a pioneering approach in the preoperative treatment of cancer, offering novel avenues for tumor reduction and improved patient outcomes by modulating the immune response. This study investigated neoadjuvant immunotherapy using intratumoral administration of mannan-BAM, Toll-like receptor ligands, and antiCD40 antibody (MBTA therapy) followed by surgery in murine models of mouse tumor tissue (MTT) pheochromocytoma, B16-F10 melanoma, and 4T1 and E0771.lmb mammary carcinomas.
View Article and Find Full Text PDFSpontaneous adverse drug reactions reported in a thirteen-year pharmacovigilance program in a tertiary university hospital.
Front Pharmacol
December 2024
Service of Clinical Pharmacology, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
Objectives: We aimed to assess the characteristics of adverse drug reactions (ADRs) collected in a university hospital.
Methods: A retrospective analysis of ADRs spontaneously reported in the Hospital Pharmacovigilance Program database (RutiRAM) over a 13-year period was conducted. The analysis included a description of ADRs [System Organ Class (SOC)] and their seriousness, the drugs involved [level 1 of the Anatomical Therapeutic Chemical (ATC) Classification System], drug-drug interactions, medication errors, drugs 'under additional monitoring', positive rechallenge, and the 'pharmacovigilance interest' of ADRs.
Co-targeting of the thymic stromal lymphopoietin receptor to decrease immunotherapeutic resistance in CRLF2-rearranged Ph-like and Down syndrome acute lymphoblastic leukemia.
Leukemia
December 2024
Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
CRLF2 rearrangements occur in >50% of Ph-like and Down syndrome (DS)-associated B-acute lymphoblastic leukemia (ALL) and induce constitutive kinase signaling targetable by the JAK1/2 inhibitor ruxolitinib under current clinical investigation. While chimeric antigen receptor T cell (CART) immunotherapies have achieved remarkable remission rates in children with relapsed/refractory B-ALL, ~50% of CD19CART-treated patients relapse again, many with CD19 antigen loss. We previously reported preclinical activity of thymic stromal lymphopoietin receptor-targeted cellular immunotherapy (TSLPRCART) against CRLF2-overexpressing ALL as an alternative approach.
View Article and Find Full Text PDFAdditional expression of T-cell engager in clinically tested oncolytic adeno-immunotherapy redirects tumor-infiltrated, irrelevant T cells against cancer cells to enhance antitumor immunity.
J Immunother Cancer
December 2024
Department of Medicine, Baylor College of Medicine, Houston, TX, USA
Background: Oncolytic adenoviruses (OAds) are the most clinically tested viral vectors for solid tumors. However, most clinically tested "Armed" OAds show limited antitumor effects in patients with various solid tumors even with increased dosages and multiple injections. We developed a binary oncolytic/helper-dependent adenovirus system (CAdVEC), in which tumors are coinfected with an OAd and a non-replicating helper-dependent Ad (HDAd).
View Article and Find Full Text PDFEvolution of Rapid Clonal Dynamics and Non-Cross-Resistance in Response to Alternating Targeted Therapy and Chemotherapy in BRAF-V600E-Mutant Colon Cancer.
JCO Precis Oncol
December 2024
Department of Medicine, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ.
Purpose: Combined BRAF, MEK, and EGFR inhibition can induce clinical responses in BRAF-V600E-mutant colon cancer, but rapid resistance often occurs.
Methods: We use serial monitoring of circulating tumor DNA cell-free plasma DNA (cfDNA) in a patient case study in addition to organoids derived from mouse models of BRAF-V600E-mutant intestinal cancer, which emulated the patient's mutational profile to assess drug treatment efficacy.
Results: We demonstrate dynamic evolution of resistance to combined EGFR/BRAF/MEK inhibition in a pediatric patient with metastatic BRAF-V600E-mutant, mismatch repair-stable colon cancer.
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