Objective: The objective of this study was to examine the presence of mutant-p53 protein (p53Ag) and antibodies to p53 protein (p53Ab) in a population of workers exposed to vinyl chloride (VC).
Method: We have investigated the presence of two cancer markers in the plasma of 151 subjects exposed to varying concentrations of VC (4-2823 ppm). The investigation took place in two sessions: in 1999, the analysis was limited to p53Ab, and in 2000, the analysis was repeated and extended to include also the mutant-p53Ag. The available information on the subjects in this study includes age, total years of employment in the VC polymerization industry, exposure concentration, results of abdominal ultrasonogram, hepatitis status, smoking and alcohol drinking status, and clinical records. Logistic regression analyses were performed to calculate the association between prevalence of positivity for p53Ab or mutant-p53Ag and cumulative VC exposure concentration after adjustment for confounding factors. t test and chi analyses were performed to test significant differences among groups.
Results: Three (1.9%) of the 151 workers exposed to VC resulted seropositive for the mutant-p53Ag and five (3.3%) for the p53Ab. All seropositive subjects are distributed in the highest exposure classes (>1000 ppm). No seropositivity was found among controls. The stratified relationship between seropositivity and exposure appeared statistically significant (chi = 23.65 for mutant-p53Ag and 30.35 for p53Ab).
Conclusions: revealing its presence in subjects having a history of VC exposure greater than 1000 ppm. On the basis of this study, and the clinical experience of the authors, the presence of a minimum threshold for the carcinogenic effects of VC is hypothesized.
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http://dx.doi.org/10.1097/01.jom.0000183097.72738.a7 | DOI Listing |
Molecules
December 2024
Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.
Enhancer of zeste homolog 2 (EZH2) is a methyltransferase involved in cell cycle regulation, cell differentiation, and cell death and plays a role in modulating the immune response. Although it mainly functions by catalyzing the tri-methylation of H3 histone on K27 (H3K27), to inhibit the transcription of target genes, EZH2 can directly methylate several transcription factors or form complexes with them, regulating their functions. EZH2 expression/activity is often dysregulated in cancer, contributing to carcinogenesis and immune escape, thereby representing an important target in anti-cancer therapy.
View Article and Find Full Text PDFGenes (Basel)
December 2024
Laboratory of Molecular Genetics of Aging & Tumor, Medical School, Kunming University of Science and Technology, Chenggong Campus, 727 South Jingming Road, Kunming 650500, China.
The tumor secretome comprises the totality of protein factors secreted by various cell components within the tumor microenvironment, serving as the primary medium for signal transduction between tumor cells and between tumor cells and stromal cells. The deletion or mutation of the gene leads to alterations in cellular secretion characteristics, contributing to the construction of the tumor microenvironment in a cell non-autonomous manner. This review discusses the critical roles of mutant p53 in regulating the tumor secretome to remodel the tumor microenvironment, drive tumor progression, and influence the plasticity of cancer-associated fibroblasts (CAFs) as well as the dynamics of tumor immunity by focusing on both secreted protein expression and secretion pathways.
View Article and Find Full Text PDFFront Oncol
December 2024
Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States.
Rituximab combined with systemic chemotherapy significantly improves the rate of complete response in B-cell lymphomas. However, acquired rituximab resistance develops in most patients leading to relapse. The mechanisms underlying rituximab resistance are not well-understood.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
About 50% of all cancers carry a mutation in p53 that impairs its tumor suppressor function. The p53 missense mutation p53 (p53 in mice) is a hotspot mutation in various cancer types. Therefore, monoclonal antibodies selectively targeting clinically relevant mutations like p53 could prove immensely value.
View Article and Find Full Text PDFCancer Med
January 2025
Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu, People's Republic of China.
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