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Folic Acid-Modified Milk Exosomes Delivering c-Kit siRNA Overcome EGFR-TKIs Resistance in Lung Cancer by Suppressing mTOR Signaling and Stemness.
Int J Biol Sci
January 2025
Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China, 610041.
Article Synopsis
- The study addresses a common issue in lung cancer treatment, where patients develop resistance to EGFR-TKIs like gefitinib, leading to worse outcomes.
- The researchers developed a novel therapy using folic acid-modified milk exosomes loaded with c-kit siRNA (FA-mExo-siRNA-c-kit) to counteract this resistance by targeting the c-kit gene, which is linked to stemness traits in cancer cells.
- Results showed that this approach not only reduced c-kit expression and stemness characteristics but also slowed tumor growth and improved survival in experimental models, highlighting its potential as a new treatment strategy for resistant lung cancer.
Discovery of 3-amide-pyrimidine-based derivatives as potential fms-like tyrosine receptor kinase 3 (FLT3) inhibitors for treating acute myelogenous leukemia.
Bioorg Med Chem Lett
December 2024
Department of Medicinal Chemistry and Pharmaceutical Analysis, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi 710032, China. Electronic address:
Article Synopsis
- FLT3-ITD and TKD mutants are key drivers in acute myeloid leukemia (AML), making FLT3 a promising target for new treatments.
- To identify next-generation FLT3 inhibitors, researchers modified G-749 and found that a derivative named MY-10 showed strong and selective inhibition against FLT3-ITD and FLT3-D835Y mutants.
- MY-10 was effective in blocking cell cycle progression, inducing apoptosis, and reducing harmful reactive oxygen species, while not affecting c-KIT kinase, suggesting its potential as a targeted ACML therapy.
Determination of QLNC-3A6 in canine plasma by UHPLC-MS/MS and its application in pharmacokinetic studies.
Vet Q
December 2024
Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Multi-targeted tyrosine kinase inhibitor QLNC-3A6 Di-maleate, a structurally novel small molecule compound, has therapeutic efficacy for the treatment of canine cutaneous mast cell tumor (CMCT) caused by mutations in the c-Kit gene. Since pharmacokinetic (PK) information plays an important role in the development and application of new drugs, etc., a rapid, highly sensitive and selective UHPLC-MS/MS analytical method was developed and validated for the first time in this study for the quantitative detection of QLNC-3A6 in canine plasma.
View Article and Find Full Text PDFEffects of Saccharomyces boulardii on microbiota composition and metabolite levels in the small intestine of constipated mice.
BMC Microbiol
November 2024
Department of Gastroenterology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100039, China.
Saccharomyces boulardii (S. boulardii) is a fungal probiotic used to treat digestive disorders. However, the mechanism(s) by which S.
View Article and Find Full Text PDFThe acetylglucosaminyltransferase GnT-Ⅲ regulates erythroid differentiation through ERK/MAPK signaling.
J Biol Chem
December 2024
Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan. Electronic address:
Differentiation therapy is an alternative strategy used in treating chronic myelogenous leukemia to induce the differentiation of immature or cancerous cells toward mature cells and inhibit tumor cell proliferation. We aimed to explore N-glycans' roles in erythroid differentiation using the sodium butyrate (NaBu)-induced model of K562 cells (WT/NaBu cells). Here, using lectin blot, flow cytometry, real-time PCR, and mass spectrometry analyses, we demonstrated that the mRNA levels of N-acetylglucosaminyltransferase Ⅲ ((encoded by the MGAT3 gene) and its product (bisected N-glycans) were significantly increased during erythroid differentiation.
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