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Molecular Pharmacology of Dasatinib Provides Unique Insights into the Mechanistic Basis of Success and Failure of Targeted Cancer Therapy.
ACS Pharmacol Transl Sci
January 2025
Department of Cell and Molecular Biology, University of Rhode Island, 120 Flagg Rd, Kingston, Rhode Island 02881, United States.
Despite the enthusiasm for targeted cancer therapies in preclinical studies and the success of a select few drugs, many promising drug candidates fail in clinical trials. The gap between preclinical promise and clinical outcomes underscores the need to investigate factors influencing the success or failure of targeted therapies. Dasatinib, an inhibitor of Abl and Src protein tyrosine kinases, is highly effective toward chronic myeloid leukemia (CML) by targeting BCR-Abl, but it is ineffective against solid tumors when targeting Src kinases.
View Article and Find Full Text PDFAtypical Femur Fracture in a Teenager on Chronic Imatinib Therapy.
Case Rep Oncol Med
January 2025
Orthopaedic Surgery Department, University of Missouri, Columbia, Missouri, USA.
Atypical femoral fractures (AFFs) are rare fractures usually associated with medications that can ultimately alter bone metabolism. Imatinib, a drug prescribed for treatment of chronic myeloid leukemia (CML), has been associated with altered bone homeostasis, however, with unknown clinical significance. Here, we present the case of a 17-year-old female, with a diagnosis of CML undergoing chronic imatinib therapy, who developed an AFF treated successfully with prophylactic fixation with intramedullary nailing.
View Article and Find Full Text PDFIsolated Central Nervous System Infiltrated and Progressed to Acute Myeloid Leukemia from Chronic Myeloid Leukemia with e1a3 BCR-ABL1 Transcript: A Rare Case Report and Literature Review.
Cancer Manag Res
January 2025
Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, People's Republic of China.
The chronic myeloid leukemia (CML) is easily diagnosed by laboratory examination, however, rare BCR-ABL1 mRNA transcripts variants, such as e1a3 present diagnosis and therapeutic challenges. This case report details the diagnosis and management of a CML patient with the e1a3 transcript by FISH and RT-PCR. Following initial diagnosis, the patient was treated with the tyrosine kinase inhibitor (TKI) Flumatinib.
View Article and Find Full Text PDFTranscription factor Yy1 modulates Trem1 to control LPS-triggered neuroinflammation and oxidative stress in mouse astrocytes via the NF-κB pathway.
Gen Physiol Biophys
January 2025
Department of Psychiatry, Hubei Province Huangshi City Mental Hospital, Huangshi, China.
Dysfunction of astrocytes has a crucial role in the pathology of depression. Here, we aimed to define the exact action of the ubiquitous transcription factor (TF) Yin Yang-1 (Yy1) in depression pathogenesis and astrocytic dysfunction. A chronic unpredictable mild stress (CUMS) mouse model was generated.
View Article and Find Full Text PDFIL-33-activated ILC2s induce tertiary lymphoid structures in pancreatic cancer.
Nature
January 2025
Immuno-Oncology Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Tertiary lymphoid structures (TLSs) are de novo ectopic lymphoid aggregates that regulate immunity in chronically inflamed tissues, including tumours. Although TLSs form due to inflammation-triggered activation of the lymphotoxin (LT)-LTβ receptor (LTβR) pathway, the inflammatory signals and cells that induce TLSs remain incompletely identified. Here we show that interleukin-33 (IL-33), the alarmin released by inflamed tissues, induces TLSs.
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