RAS oncogenes are chief tumorigenic drivers, and their mutation constitutes a universal predictor of poor outcome and treatment resistance. Despite more than 30 years of intensive research since the identification of the first RAS mutation, most attempts to therapeutically target RAS mutants have failed to reach the clinic. In fact, the first mutant RAS inhibitor, Sotorasib, was only approved by the FDA until 2021.
View Article and Find Full Text PDFCell cycle progression requires control of the abundance of several proteins and RNAs over space and time to properly transit from one phase to the next and to ensure faithful genomic inheritance in daughter cells. The proteasome, the main protein degradation system of the cell, facilitates the establishment of a proteome specific to each phase of the cell cycle. Its activity also strongly influences transcription.
View Article and Find Full Text PDFPurpose: Downregulation of miR-125b-1 is associated with poor prognosis in breast cancer patients. In this work we investigated the effect of histone modifications on the regulation of this gene promoter.
Methods And Results: We evaluated the enrichment of two histone modifications involved in gene repression, H3K9me3 and H3K27me3, on the miR-125b-1 promoter in two breast cancer cell lines, MCF7 (luminal A subtype) and MDA-MB-231 (triple-negative subtype), compared to the non-transformed breast cell line MCF10A.
Background: Prolonged mitotic arrest in response to anti-cancer chemotherapeutics, such as DNA-damaging agents, induces apoptosis, mitotic catastrophe, and senescence. Disruptions in mitotic checkpoints contribute resistance to DNA-damaging agents in cancer. MAD2 has been associated with checkpoint failure and chemotherapy response.
View Article and Find Full Text PDFBackground: Cisplatin cures over 80% of testicular germ cell tumours (TGCTs), and nucleotide-excision repair (NER) modifies the sensitivity to cisplatin. We explored the association between NER proteins and their polymorphisms with cisplatin sensitivity (CPS) and overall survival (OS) of patients with non-seminomatous (ns)-TGCTs.
Methods: The expression of ERCC1 and XPA and the presence of γH2AX were evaluated in cancer cell lines and in fresh ns-TGCTs.
Theodore Boveri, eminent German pathologist, observed aneuploidy in cancer cells more than a century ago and suggested that cancer cells derived from a single progenitor cell that acquires the potential for uncontrolled continuous proliferation. Currently, it is well known that aneuploidy is observed in virtually all cancers. Gain and loss of chromosomal material in neoplastic cells is considered to be a process of diversification that leads to survival of the fittest clones.
View Article and Find Full Text PDFObjectives: To study the minimum inhibitory concentrations (MIC) of the difluorinated quinolone sparfloxacin against 32 clinical isolates of Mycobacterium kansasii from 23 patients, all of whom had clinically significant infections due to M. kansasii, and 11 the acquired immune-deficiency syndrome (AIDS). To study the correlation between the microdilution and macrodilution techniques in M7H9 broth.
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