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Preclinical study and parallel phase II trial evaluating antisense STAT3 oligonucleotide and checkpoint blockade for advanced pancreatic, non-small cell lung cancer and mismatch repair-deficient colorectal cancer.
BMJ Oncol
July 2024
Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Objective: To evaluate signal transducer and activator of transcription 3 (STAT3) inhibition we conducted a co-clinical trial testing danvatirsen, a STAT3 antisense oligonucleotide (ASO) and checkpoint inhibition in conjunction with preclinical experiments.
Methods And Analysis: Orthotopically implanted pancreatic cancer (pancreatic adenocarcinoma (PDAC)) was treated with STAT3 ASO with immune checkpoint inhibition. Tumour infiltrating immune cell populations were characterised via flow cytometry.
Epstein-Barr Virus-Induced 3 Attributes to TLR7-Mediated Splenomegaly.
Immunology
January 2025
Department of Immunology and Molecular Genetics, Kawasaki Medical School, Kurashiki, Japan.
Epstein-Barr virus-induced 3 (EBI3) functions as a component of the heterodimer cytokine IL-27, which regulates innate and acquired immune responses. The expression of EBI3 gene is induced by Toll-like receptors (TLRs). Repeated treatment with imiquimod (IMQ), a TLR7 agonist, induces splenomegaly and cytopaenia due to increased splenic function.
View Article and Find Full Text PDFMany inflammatory stimuli can induce progenitor cells in the bone marrow to produce increased numbers of myeloid cells as part of the process of emergency myelopoiesis. These events are associated with innate training and can have long-term impacts on hematopoietic stem and progenitor cell (HSPC) development but can also compromise their function. While many cytokines support emergency myelopoiesis, less is known about the mechanisms that temper these events.
View Article and Find Full Text PDFRNase T2 deficiency promotes TLR13-dependent replenishment of tissue-protective Kupffer cells.
J Exp Med
March 2025
Division of Innate Immunity, The Institute of Medical Science, The University of Tokyo, Minato-ku, Japan.
Lysosomal stress due to the accumulation of nucleic acids (NAs) activates endosomal TLRs in macrophages. Here, we show that lysosomal RNA stress, caused by the lack of RNase T2, induces macrophage accumulation in multiple organs such as the spleen and liver through TLR13 activation by microbiota-derived ribosomal RNAs. TLR13 triggered emergency myelopoiesis, increasing the number of myeloid progenitors in the bone marrow and spleen.
View Article and Find Full Text PDFTransition to Survivorship Care for Adolescents and Young Adults (AYAs) with Acute Leukemia: Provider Perspectives.
J Adolesc Young Adult Oncol
January 2025
Rutgers Cancer Institute, New Brunswick, New Jersey, USA.
Adolescent and young adult (AYA) survivors of acute lymphoblastic or myeloid leukemia diagnosed between the ages of 15 and 39 years are at risk for adverse late health effects following cancer treatment and require ongoing survivorship care. This study aims to understand the landscape of transitioning AYAs with leukemia from active treatment to survivorship care. A cross-sectional, anonymous online survey was sent out via listserv/email.
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