The aim of the study was to demonstrate the most common genetic alterations and evaluate possible targets involving phosphatidylinositol-3-OH kinase (PIK3)/AKT/mammalian target of rapamycin (mTOR) signaling and DNA damage repair (DDR) pathways for personalized treatment in patients with non-muscle invasive bladder cancer (NMIBC). Alterations of these pathways were observed in 89.5% and 100% of patients, respectively. Among them, BARD1 was more frequently altered in low/intermediate-risk cases, but PARP4 was more frequently affected in intermediate/high-risk patients. The possible target feasibility of BARD1 and PARP4 alterations should be evaluated for personalized treatment using PARP-inhibitors in NMIBC. It is important to detect high tumor mutation burden (TMB) in patients in terms of immunotherapy.
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http://dx.doi.org/10.1080/07357907.2023.2288640 | DOI Listing |
J Clin Microbiol
December 2024
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, USA.
Unlabelled: Tongue swab (TS) sampling combined with quantitative PCR (qPCR) to detect (MTB) DNA is a promising alternative to sputum testing for tuberculosis (TB) diagnosis. In prior studies, the sensitivity of tongue swabbing has usually been lower than sputum. In this study, we evaluated two strategies to improve sensitivity.
View Article and Find Full Text PDFJ Med Chem
January 2025
SANKEN, Osaka University, Mihogaoka, Ibaraki-shi, Osaka 567-0047, Japan.
Histone methylation, a crucial aspect of epigenetics, intricately involves specialized enzymes such as G9a, a histone methyltransferase (HMT) catalyzing the methylation of histone H3 lysine 9 (H3K9) and H3K27. Apart from histone modification, G9a regulates essential cellular processes such as deoxyribonucleic acid (DNA) replication, damage repair, and gene expression via modulating DNA methylation patterns. The dysregulation and overexpression of G9a are intricately linked to cancer initiation, progression, and metastasis, making it a compelling target for anticancer therapy.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu 610065, China.
Determining mutations in the kinase domain of the epidermal growth factor receptor (EGFR) is critical for the effectiveness of EGFR tyrosine kinase inhibitors (TKIs) in lung cancer. Yet, DNA-based sequencing analysis of tumor samples is time-consuming and only provides gene mutation information on EGFR, making it challenging to design effective EGFR-TKI therapeutic strategies. Here, we present a new image-based method involving the rational design of a quenched probe based on EGFR-TKI to identify mutant proteins, which permits specific and "no-wash" real-time imaging of EGFR in living cells only upon covalent targeting of the EGFR kinase.
View Article and Find Full Text PDFAutophagy
January 2025
Institute for Experimental Pediatric Hematology and Oncology, Goethe University Frankfurt, Frankfurt am Main, Germany.
Lysosomes are the major cellular organelles responsible for nutrient recycling and degradation of cellular material. Maintenance of lysosomal integrity is essential for cellular homeostasis and lysosomal membrane permeabilization (LMP) sensitizes toward cell death. Damaged lysosomes are repaired or degraded via lysophagy, during which glycans, exposed on ruptured lysosomal membranes, are recognized by galectins leading to K48- and K63-linked poly-ubiquitination (poly-Ub) of lysosomal proteins followed by recruitment of the macroautophagic/autophagic machinery and degradation.
View Article and Find Full Text PDFJ Cancer
January 2025
Center for Immunology, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, Jiangxi 341000, China.
Absence in melanoma 2 (AIM2) protein functions as a double-stranded DNA sensor and is critical for host defense against intracellular bacterial and viral pathogens. Recent research has highlighted the significance of AIM2 in the pathogenesis of diverse malignancies. Through its recognition of foreign or intracellular dsDNA, AIM2 triggers inflammasome activation, resulting in the release of pro-inflammatory cytokines such as IL-1β, IL-18, and induction of pyroptosis.
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