AppId is over the quota
Scheme of PARP1/SIRT1/Akt/mTOR signalingThe targeting of PARP1 is showing considerable potential for selectively killing tumor cells while sparing normal cells, and offers a scientifically rational clinical application.
In this paper, G. Pinton et al. investigate PARP1 expression in normal mesothelial and malignant mesothelioma tissue samples.
Immunohistochemical analysis revealed low PARP1 staining in peri-tumoral normal mesothelium. In contrast, staining was found to be elevated in mesothelioma with a progressive increase from moderate staining in epithelioid mesotheliomas to the highest staining in the most aggressive sarcomatoid mesotheliomas. In mesothelioma-derived cell lines, increased PARP1 expression correlated with sensitivity to its inhibitor CO-338. As a single agent, CO-338 significantly reduced cell viability and, when combined with cisplatin, was synergistically active. The authors also described a pathway by which PARP inhibition led to activation of a deacetylase enzyme, SIRT1, which could modulate Akt activity. In conclusion, this study demonstrates that PARP1 overexpression defines increased responsiveness to its inhibition and that a substantial fraction of patients could be candidates for therapy with PARP1 inhibitors.
Read the article here.
No comments:
Post a Comment