To reach a clinically detectable size, neoplasms must be able to suppress or evade a host immune response. Activated T cells may enter apoptosis in the presence of Fas ligand (FasL) (1), and tissue expression of FasL has been shown to contribute to immune privilege in the eye and testis (2, 3). We have demonstrated that all human lung carcinoma cell lines tested (16 of 16) express a Mr 38,000 protein consistent with FasL by immunoblotting, whereas the majority of resected tumors (23 of 28) show positive staining for FasL by immunohistochemistry. DNA sequencing of reverse transcription-PCR products from lung cancer cells and resected lung tumors confirms the presence of human FasL mRNA in these neoplastic tissues. Furthermore, lung carcinoma cells are capable of killing a Fas-sensitive human T cell line (Jurkat) in coculture experiments; this killing was inhibited by a recombinant form of the soluble portion of the Fas receptor (FasFc). FasL expression by neoplastic cells represents a potential mechanism for peripheral deletion of tumor-reactive T-cell clones.
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JAMA Netw Open
January 2025
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
Importance: Sensitivity to environmental stress and adversity may influence lung cancer risk, highlighting a critical link between psychosocial factors and cancer etiology.
Objective: To evaluate whether genetically estimated sensitivity to environmental stress and adversity is associated with lung cancer risk.
Design, Setting, And Participants: Data were obtained from a genome-wide association study identifying 37 independent genetic variants strongly associated with sensitivity to environmental stress and adversity and a cross-ancestry genome-wide meta-analysis from the International Lung Cancer Consortium.
Clin Physiol Funct Imaging
January 2025
Centre for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Background: Cardiopulmonary exercise testing (CPET) is usually considered the gold standard for assessing maximal oxygen consumption (V̇O), a health and performance marker in patients with chronic obstructive pulmonary disease (COPD). Despite the widespread application of CPET, the absolute and relative test-retest reliability of CPET-derived metrics remains unexamined.
Objective: To examine and compare test-retest reliability of CPET derived metrics in individuals with COPD and healthy matched controls.
Biochem Cell Biol
January 2025
Department of Histology and Embryology, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, China.
Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease with high mortality and limited treatment options. While single-dose bleomycin-induced models are commonly used to investigate the pathogenesis of IPF, they fail to adequately replicate the complex pathological features in human patients, thereby hindering comprehensive investigations. Previous studies utilizing repetitive bleomycin injections have demonstrated a closer resemblance to human IPF pathology; however, the time- and resource-intensive nature of this approach presents significant drawbacks.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
February 2025
Department of Urology and Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Cancer-associated fibroblasts (CAFs) are key stroma cells that play dominant roles in the migration and invasion of several types of cancer through the secretion of inflammatory cytokine IL-17A. This study aims to identify the potential role and regulatory mechanism of CAFs-secreted IL-17A in the migration and invasion of prostate cancer (PC). CAFs and normal fibroblasts (NFs) were obtained from fresh PC and its adjacent normal tissues, respectively.
View Article and Find Full Text PDFJ Med Chem
January 2025
College of Chemistry, Zhengzhou University, Zhengzhou 450001, China.
The P2YR is activated by UDP and UDP glucose and is involved in many human inflammatory diseases. Based on the molecular docking analysis of currently reported P2YR antagonists and the crystallographic overlap study between PPTN and compound , a series of 3-substituted 5-amidobenzoate derivatives were designed, synthesized, and identified as promising P2YR antagonists. The optimal compound (methyl 3-(1-benzo[]imidazol-2-yl)-5-(2-(-tolyl) acetamido)benzoate, IC = 0.
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