SQAP sensitized series of chemotherapeutic agents including doxorubicin, carboplatin, bleomycin, camptothecin, etoposide, methyl methanesulfonate, cisplatin, mitomycin C, and Taxol in canine tumor cells and V79 cells. These results suggest that broad inhibition of DNA repair may play a role in SQAP induced radiosensitization and chemosensitization.
This case report supports the clinical utility of pre-emptive DPYD genotyping to guide initial 5-FU dosing in intermediate metabolizers, and it suggests that all patients still require close monitoring and some (particularly carriers of c.2846 A > T) may require an initial dose reduction greater than the recommended 50% to prevent severe toxicity.
In addition, FANCA disruption followed by mitomycin C treatment resulted in a > 10-fold increase in chromosomal radials, a finding that is considered diagnostic for human FA...Targeting of FANCD2 failed to produce any biallelic animals demonstrating the loss of FANCD2 function is embryonic lethal in pigs. These results indicate that a porcine model of FANCA holds promise for the development of strategies to prevent the development of bone marrow failure and malignancies in patients with FA.
1 month ago
Preclinical • Journal
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FANCA (FA Complementation Group A) • FANCD2 (FA Complementation Group D2)
HUVECs were treated with DNA crosslinkers (doxorubicin, mitomycin C), topoisomerase inhibitors (etoposide, camptothecin), and methotrexate (MTX)...ROS scavenger Mito-Q and ATM inhibitor KU55933 were co-administered to evaluate their modulatory effects...Chemotherapeutic agents triggered endothelial senescence via DNA damage and ROS accumulation, with heterogeneity in potency and mechanisms. ROS scavengers may mitigate methotrexate-associated vascular toxicity, and targeting ROS could enhance chemotherapy safety by preserving endothelial function.
The most employed topical agents include mitomycin C (MMC), 5-fluorouracil (5-FU), and interferon alpha-2b (IFNα2b), each with distinct mechanisms of action, efficacy profiles, and toxicity risks. Timely recognition and management of complications are essential to minimize long-term sequelae. Reliance on compounded formulations highlights the need for stable, standardized, and commercially available topical agents specifically designed for ocular use to ensure safety, reproducibility, and global accessibility.
While increasing the Mitomycin C dose to 80 nM further upregulated HLA-DR and CD86 expression, the release of IL-12 was highest a 50 nM concentration of mitomycin C (686.7 ± 125.7 pg/mL compared to 263.8 ± 4.8 pg/mL in controls; p < 0.05). IL-12 levels were not significantly increased even with 30 nM Mitomycin C. Low concentrations of Mitomycin C contributed to an increase in dendritic cellmaturation and an increase in the expression of co-stimulatory molecules (CD80, CD86, CD83, and HLA-DR), along with the secretion of cytokines such as IL-12p70, IL-2, and GM-CSF.
One key regulator of nuclease activity is the scaffold protein SLX4, which plays important roles in repairing DNA damage induced by mitomycin C (MMC) and camptothecin (CPT) as well as in the resolution of stalled replication forks...These findings suggest that SLX4 and its associate nucleases are confined within PML NBs and that the optimal protein level of SLX4 is maintained by the coordinated activities of RNF4 and USP7. Our findings provide insight into how cells effectively control the potentially harmful activities of nucleases in the absence of DNA damage by a spatial regulatory mechanism.