Greater than 55% of all lung cancers contain mutations in the p53 tumor suppressor gene, and the frequency of p53 mutations has been directly correlated with the use of tobacco and the smoking of cigarettes. To determine if environmental tobacco smoke (ETS) is associated with changes in p53 expression in human lung cancer in never-smokers, we determined the degree of p53 protein expression in ten lung tumors from never-smokers exposed to ETS. We show that 5 of 8 (62.5%) adenocarcinomas contained significant levels of p53 protein overexpression as detected by immunohistochemical staining. While these findings suggest that ETS is a possible inducer of altered p53 expression in lung adenocarcinoma in non-smokers, larger studies are needed to confirm this relationship.
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http://dx.doi.org/10.3892/or.4.4.825 | DOI Listing |
Hum Pathol
January 2025
Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland.
Colorectal carcinoma brain metastases (n=60) were studied using next-generation sequencing and immunohistochemistry. RAS and BRAF mutations were detected in 58.2% and 7.
View Article and Find Full Text PDFComput Biol Chem
January 2025
D3 Drug Tech Lab Pvt Ltd, Chennai, Tamilnadu, India.
Lung cancer is the leading cause of mortality in both men and women due to genetic and epigenetic modifications. Our study focuses on fabricating phenmiazine ring leads by a functional group-based drug design to inhibit p53 -7A1W and MDM2-7AU9 proteins responsible for cancer cell growth. One hundred molecules are designed and allowed to bind inside the active site of 7A1W and 7AU9 protein using a glide dock platform and subjected to find MMGBSA.
View Article and Find Full Text PDFActa Neuropathol
January 2025
Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
The foremost feature of glioblastoma (GBM), the most frequent malignant brain tumours in adults, is a remarkable degree of intra- and inter-tumour heterogeneity reflecting the coexistence within the tumour bulk of different cell populations displaying distinctive genetic and transcriptomic profiles. GBM with primitive neuronal component (PNC), recently identified by DNA methylation-based classification as a peculiar GBM subtype (GBM-PNC), is a poorly recognized and aggressive GBM variant characterised by nodules containing cells with primitive neuronal differentiation along with conventional GBM areas. In addition, the presence of a PNC component has been also reported in IDH-mutant high-grade gliomas (HGGs), and to a lesser extent to other HGGs, suggesting that regardless from being IDH-mutant or IDH-wildtype, peculiar genetic and/or epigenetic events may contribute to the phenotypic skewing with the emergence of the PNC phenotype.
View Article and Find Full Text PDFCancer Chemother Pharmacol
January 2025
Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Purpose: Relapsed and/or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome continue to have a poor prognosis with limited treatment options despite advancements in rational combination and targeted therapies. Belinostat (an HDAC inhibitor) and Pevonedistat (a NEDD8 inhibitor) have each been independently studied in hematologic malignancies and have tolerable safety profiles with limited single-agent activity. Preclinical studies in AML cell lines and primary AML cells show the combination to be highly synergistic, particularly in high-risk phenotypes such as p53 mutant and FLT-3-ITD positive cells.
View Article and Find Full Text PDFSci Rep
January 2025
Institute of Comparative Molecular Endocrinology, Ulm University, 89081, Ulm, Germany.
Hepatocellular carcinoma (HCC) remains the most prevalent type of primary liver cancer worldwide. p53 is one of the most frequently mutated tumor-suppressor genes in HCC and its deficiency in hepatocytes triggers tumor formation in mice. To investigate iron metabolism during liver carcinogenesis, we employed a model of chronic carbon tetrachloride injections in liver-specific p53-deficient mice to induce liver fibrosis, cirrhosis and subsequent carcinogenesis.
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