New Approaches of PARP-1 Inhibitors in Human Lung Cancer Cells and Cancer Stem-Like Cells by Some Selected Anthraquinone-Derived Small Molecules.

New Approaches of PARP-1 Inhibitors in Human Lung Cancer Cells and Cancer Stem-Like Cells by Some Selected Anthraquinone-Derived Small Molecules.

PLoS One. 2013; 8(2): e56284
Lee YR, Yu DS, Liang YC, Huang KF, Chou SJ, Chen TC, Lee CC, Chen CL, Chiou SH, Huang HS

Poly (ADP-ribose) polymerase-1 (PARP-1) and telomerase, as well as DNA damage response pathways are targets for anticancer drug development, and specific inhibitors are currently under clinical investigation. The purpose of this work is to evaluate anticancer activities of anthraquinone-derived tricyclic and tetracyclic small molecules and their structure-activity relationships with PARP-1 inhibition in non-small cell lung cancer (NSCLC) and NSCLC-overexpressing Oct4 and Nanog clone, which show high-expression of PARP-1 and more resistance to anticancer drug. We applied our library selected compounds to NCI’s 60 human cancer cell-lines (NCI-60) in order to generate systematic profiling data. Based on our analysis, it is hypothesized that these drugs might be, directly and indirectly, target components to induce mitochondrial permeability transition and the release of pro-apoptotic factors as potential anti-NSCLC or PARP inhibitor candidates. Altogether, the most active showed its cytotoxicity and dose-dependent PARP inhibitory manner, thus it emerges as a promising structure for anti-cancer therapy with no significant negative influence on normal cells. Our studies present evidence that telomere maintenance should be taken into consideration in efforts not only to overcome drug resistance, but also to optimize the use of telomere-based therapeutics. These findings will be of great value to facilitate structure-based design of selective PARP inhibitors, in general, and telomerase inhibitors, in particular. Together, the data presented here expand our insight into the PARP inhibitors and support the resource-demanding lead optimization of structurally related small molecules for human cancer therapy. HubMed – drug


Intermittent preventive treatment in pregnant women is associated with increased risk of severe malaria in their offspring.

PLoS One. 2013; 8(2): e56183
Harrington WE, Morrison R, Fried M, Duffy PE

In areas of widespread sulfadoxine-pyrimethamine resistance, intermittent treatment in pregnancy (IPTp) fails to prevent placental malaria (PM) and may exacerbate drug resistant infections. Because PM predicts increased susceptibility to parasitemia during infancy, we hypothesized that IPTp would also increase susceptibility to malaria infection and disease in the offspring.In a birth cohort from NE Tanzania, we evaluated the association between maternal IPTp use and risk of parasitemia and severe malaria in the offspring. Using Cox Proportional Hazards Models as well as Generalized Estimating Equations, we evaluated the effects of IPTp on the entire cohort and on subgroups stratified by PM status at delivery.Offspring of PM+ women who received IPTp had a dose-dependent decrease in time to first parasitemia (AHR?=?2.13, p?=?0.04 [95%CI: 1.04, 4.38]). Among all offspring, IPTp was associated with earlier first severe malaria episode (AHR?=?2.32, p?=?0.02 [95%CI: 1.12, 4.78]) as well as increased overall odds of severe malaria (AOR?=?2.31, p?=?0.03 [95%CI: 1.09, 4.88]). Cost-benefit analyses of IPTp regimens should consider the long term effects on offspring in addition to pregnancy outcomes. HubMed – drug


Oncology and the internet: regulatory failure and reform.

J Oncol Pract. 2012 Nov; 8(6): 341-3
Mackey TK, Liang BA

The oncology drug shortage is exacerbated by current policy and governance failures of Internet regulation, now being exploited by illicit online drug sellers targeting vulnerable patients and providers. HubMed – drug