Current Issue : January - March Volume : 2020 Issue Number : 1 Articles : 5 Articles
Cadmium (Cd) is a widespread environmental pollutant and carcinogen. Although the\nexact mechanisms of Cd-induced carcinogenesis remain unclear, previous acute/chronic Cd exposure\nstudies have shown that Cd exerts its cytotoxic and carcinogenic effects through multiple mechanisms,\nincluding interference with the DNA repair system. However, the effects of post-chronic Cd exposure\nremain unknown. Here, we establish a unique post-chronic Cd-exposed human lung cell model\n(the â??CR0â? cells) and investigate the effects of post-chronic Cd exposure on the DNA repair system.\nWe found that the CR0 cells retained Cd-resistant property even though it was grown in Cd-free\nculture medium for over a year. The CR0 cells had lasting DNA damage due to reduced DNA\nrepair capacity and an aberrant DNA repair gene expression profile. A total of 12 DNA repair genes\nassociated with post-chronic Cd exposure were identified, and they could be potential biomarkers\nfor identifying post-chronic Cd exposure. Clinical database analysis suggests that some of the DNA\nrepair genes play a role in lung cancer patients with different smoking histories. Generally, CR0 cells\nwere more sensitive to chemotherapeutic (cisplatin, gemcitabine, and vinorelbine tartrate) and DNA\ndamaging (H2O2) agents, which may represent a double-edged sword for cancer prevention and\ntreatment. Overall, we demonstrated for the first time that the effects of post-chronic Cd exposure on\nhuman lung cells are long-lasting and different from that of acute and chronic exposures. Findings\nfrom our study unveiled a new perspective on Cd-induced carcinogenesis--the post-chronic exposure\nof Cd. This study encourages the field of post-exposure research which is crucial but has long\nbeen ignored....
Background: Progression of breast cancer involves both genetic and epigenetic factors. Parkin gene has been\nidentified as a tumor suppressor gene in the pathogenesis of various cancers. Nevertheless, the putative role of\nParkin in breast cancer remains largely unknown. Therefore, we evaluated the regulation of Parkin through both\ngenetic and epigenetic mechanisms in breast carcinoma.\nMethod: A total of 156 breast carcinoma and their normal adjacent tissue samples were included for mutational\nanalysis through SSCP, and sequencing. MS-PCR was employed for methylation study whereas Parkin protein\nexpression was evaluated using immunohistochemistry and western blotting. For the survival analysis, Kaplanâ??Meier\ncurve and Coxâ??s proportional hazard model were used.\nResults: In expression analysis, Parkin protein expression was found to be absent in 68% cases of breast cancer. We\nfound that aberrant promoter methylation of Parkin gene is a frequent incident in breast cancer tumors and cell\nlines. Our MS-PCR result showed that Parkin promoter methylation has a significant role (p = 0.0001) in reducing the\nexpression of Parkin protein. Consistently, expression of Parkin was rectified by treatment with 5-aza-2-\ndeoxycytidine. We also found significant associations of both Parkin negative expression and Parkin promoter\nmethylation with the clinical variables. Furthermore, we found a very low frequency (5.7%) of Parkin mutation with\nno clinical significance. In survival analysis, patients having Parkin methylation and Parkin loss had a worse outcome\ncompared to those harboring none of these events.\nConclusion: Overall, these results suggested that promoter methylation-mediated loss of Parkin expression could\nbe used as a prognostic marker for the survival of breast cancer....
Background: miR-182-5p (miR-182) is an oncogenic microRNA (miRNA) found in different tumor types and one of\nthe most up-regulated miRNA in colorectal cancer (CRC). Although this microRNA is expressed in the early steps of\ntumor development, its role in driving tumorigenesis is unclear.\nMethods: The effects of miR-182 silencing on transcriptomic profile were investigated using two CRC cell lines\ncharacterized by different in vivo biological behavior, the MICOL-14h-tert cell line (dormant upon transfer into\nimmunodeficient hosts) and its tumorigenic variant, MICOL-14tum. Apoptosis was studied by annexin/PI staining and\ncleaved Caspase-3/PARP analysis. The effect of miR-182 silencing on the tumorigenic potential was addressed in a\nxenogeneic model of MICOL-14tum transplant.\nResults: Endogenous miR-182 expression was higher in MICOL-14tum than in MICOL-14h-tert cells. Interestingly, miR-\n182 silencing had a strong impact on gene expression profile, and the positive regulation of apoptotic process was\none of the most affected pathways. Accordingly, annexin/PI staining and caspase-3/PARP activation demonstrated\nthat miR-182 treatment significantly increased apoptosis, with a prominent effect in MICOL-14tum cells. Moreover, a\nsignificant modulation of the cell cycle profile was exerted by anti-miR-182 treatment only in MICOL-14tum cells,\nwhere a significant increase in the fraction of cells in G0/G1 phases was observed. Accordingly, a significant growth\nreduction and a less aggressive histological aspect were observed in tumor masses generated by in vivo transfer of\nanti-miR-182-treated MICOL-14tum cells into immunodeficient hosts.\nConclusions: Altogether, these data indicate that increased miR-182 expression may promote cell proliferation,\nsuppress the apoptotic pathway and ultimately confer aggressive traits on CRC cells....
Background: Low-grade glioma is grade I-II glioma. Immunotherapy is a promising way of tumor killing. Research\non immune molecular mechanisms in low-grade gliomas and discovery of new immune checkpoints for low-grade\ngliomas are of great importance.\nMethods: Gene sequencing data and clinical data of low-grade glioma were downloaded from TCGA database.\nPrognosis related lncRNAs were identified by Cox regression and their possible functions were found by gene\nenrichment set analysis.\nResults: A total of 529 low-grade glioma samples and 5 non-tumor brain tissue samples are obtained from the\nTCGA database. Two hundred forty-seven immune-associated lncRNAs are screened. Cox regression showed that 16\nimmune-related lncRNAs are associated with low-grade glioma prognosis, and 7 lncRNAs are independent risk\nfactors. Gene set enrichment analysis suggests that these molecules are enriched in extracellular region, sequencespecific\nDNA binding, neuropeptide signaling pathway, transcriptional misregulation in cancer, cytokine-cytokine\nreceptor interaction, protein digestion and absorption, chemokine signaling pathway, etc.\nConclusion: The identification of immune-related lncRNA may provide new targets for the research of the\nmolecular mechanisms and treatment of low-grade glioma....
Background: The aim of this study was to investigate the potential of cell-free DNA (cfDNA) as a disease biomarker\nin oesophageal squamous cell carcinoma (ESCC) that can be used for treatment response evaluation and early\ndetection of tumour recurrence.\nMethods: Matched tumour tissue, pre- and post-surgery plasma and WBCs obtained from 17 ESCC patients were\nsequenced using a panel of 483 cancer-related genes.\nResults: Somatic mutations were detected in 14 of 17 tumour tissues. Putative harmful mutations were observed in\ngenes involved in well-known cancer-related pathways, including PI3K-Akt/mTOR signalling, Proteoglycans in\ncancer, FoxO signalling, Jak-STAT signalling, Chemokine signalling and Focal adhesion. Forty-six somatic mutations\nwere found in pre-surgery cfDNA in 8 of 12 patients, with mutant allele frequencies (MAF) ranging from 0.24 to\n4.91%. Three of the 8 patients with detectable circulating tumour DNA (ctDNA) had stage IIA disease, whereas the\nothers had stage IIB-IIIB disease. Post-surgery cfDNA somatic mutations were detected in only 2 of 14 patients, with\nmutant allele frequencies of 0.28 and 0.36%. All other somatic mutations were undetectable in post-surgery cfDNA,\neven in samples collected within 3-4 h after surgery.\nConclusion: Our study shows that somatic mutations can be detected in pre-surgery cfDNA in stage IIA to IIIB\npatients, and at a lower frequency in post-surgery cfDNA. This indicates that cfDNA could potentially be used to\nmonitor disease load, even in low disease-stage patients....
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