Publications by authors named "M Rusin"
Article Synopsis
- The FAS ligand (FASLG) activates cell death receptors on lymphocytes, but cancer cells usually resist this apoptosis.
- This study reveals that a combination of actinomycin D (ActD) and nutlin-3a (Nut3a) can overcome this resistance by activating pro-apoptotic genes, resulting in over 99% cancer cell death when paired with FASLG.
- The drug combination works by fully activating the p53 pathway, engaging both intrinsic and extrinsic apoptosis mechanisms, and shows less effect on normal human fibroblasts, suggesting a potential advancement in cancer immunotherapy.
Article Synopsis
- p53, a tumor suppressor protein, activates different genes based on its modifications, which vary according to cellular stress levels.
- The combination of actinomycin D and nutlin-3a enhances the phosphorylation of p53 and significantly increases the expression of a gene coding for an obscure phosphatase with two forms, linked to testis and skeletal muscle.
- New findings show that in cancer cells treated with this drug combination, an alternative promoter induces the expression of a specific isoform, TMDP-L1, whose protein product was confirmed via Western blotting across multiple cancer cell lines.
Article Synopsis
- The p53 tumor suppressor protein regulates cell cycle arrest and apoptosis, with only some of its target genes directly influencing cellular replication and cell death processes.
- p53 target genes can be classified into a core transcriptional program activated across most cell types and another group activated under specific conditions or stressors.
- Interestingly, traditional key p53 targets involved in cell cycle inhibition and apoptosis may not be essential for cancer protection in mouse models, indicating the need to investigate p53's non-classical roles for a deeper understanding of its tumor suppressive functions.
Transcriptomic and proteomic study of cancer cell lines exposed to actinomycin D and nutlin-3a reveals numerous, novel candidates for p53-regulated genes.
Chem Biol Interact
April 2024
Transcriptomic analyses have revealed hundreds of p53-regulated genes; however, these studies used a limited number of cell lines and p53-activating agents. Therefore, we searched for candidate p53-target genes by employing stress factors and cell lines never before used in a high-throughput search for p53-regulated genes. We performed RNA-Seq on A549 cells exposed to camptothecin, actinomycin D, nutlin-3a, as well as a combination of actinomycin D and nutlin-3a (A + N).
View Article and Find Full Text PDFIntroduction: Targeting tumor vasculature is an efficient weapon to fight against cancer; however, activation of alternative pathways to rebuild the disrupted vasculature leads to rapid tumor regrowth. Immunotherapy that exploits host immune cells to elicit and sustain potent antitumor response has emerged as one of the most promising tools for cancer treatment, yet many treatments fail due to developed resistance mechanisms. Therefore, our aim was to examine whether combination of immunotherapy and anti-vascular treatment will succeed in poorly immunogenic, difficult-to-treat melanoma and triple-negative breast tumor models.
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