Parthenolide Enhances Dacarbazine Activity Against Melanoma Cells.

Parthenolide enhances dacarbazine activity against melanoma cells.

Anticancer Drugs. 2013 Jun 21;
Koprowska K, Hartman ML, Sztiller-Sikorska M, Czyz ME

Dacarbazine induces a clinical response only in 15% of melanoma patients. New treatment strategies may involve combinations of drugs with different modes of action to target the tumor heterogeneity. We aimed to determine whether the combined treatment of heterogeneous melanoma cell populations in vitro with the alkylating agent dacarbazine and the nuclear factor-?B inhibitor parthenolide could be more effective than either drug alone. A panel of melanoma cell lines, including highly heterogeneous populations derived from surgical specimens, was treated with dacarbazine and parthenolide. The effect of drugs on the viable cell number was examined using an acid phosphatase activity assay, and the combination effect was determined by median-effect analysis. Cell death and cell-cycle arrest were assessed by flow cytometry. Gene expression was measured by real-time PCR and changes in the protein levels were evaluated by western blotting. Secretion of vascular endothelial growth factor and interleukin-8 was determined using an enzyme-linked immunosorbent assay. The self-renewing capacity was assessed using a clonogenic assay. Dacarbazine was less effective in heterogeneous melanoma populations than in the A375 cell line. Parthenolide and dacarbazine synergistically reduced the viable cell numbers. Both drugs induced cell-cycle arrest and apoptotic cell death. Importantly, parthenolide abrogated the baseline and dacarbazine-induced vascular endothelial growth factor secretion from melanoma cells in heterogeneous populations, whereas interleukin-8 secretion was not significantly affected by either drug. Parthenolide eradicated melanoma cells with self-renewing capacity also in cultures simultaneously treated with dacarbazine. The combination of parthenolide and dacarbazine might be considered as a new therapeutic modality against metastatic melanoma. HubMed – drug

Metformin Impairs Glucose Consumption and Survival in Calu-1 Cells by Direct Inhibition of Hexokinase-II.

Sci Rep. 2013 Jun 25; 3: 2070
Salani B, Marini C, Rio AD, Ravera S, Massollo M, Orengo AM, Amaro A, Passalacqua M, Maffioli S, Pfeffer U, Cordera R, Maggi D, Sambuceti G

The anti-hyperglycaemic drug metformin has important anticancer properties as shown by the direct inhibition of cancer cells proliferation. Tumor cells avidly use glucose as a source for energy production and cell building blocks. Critical to this phenotype is the production of glucose-6-phosphate (G6P), catalysed by hexokinases (HK) I and II, whose role in glucose retention and metabolism is highly advantageous for cell survival and proliferation. Here we show that metformin impairs the enzymatic function of HKI and II in Calu-1 cells. This inhibition virtually abolishes cell glucose uptake and phosphorylation as documented by the reduced entrapment of (18)F-fluorodeoxyglucose. In-silico models indicate that this action is due to metformin capability to mimic G6P features by steadily binding its pocket in HKII. The impairment of this energy source results in mitochondrial depolarization and subsequent cell death. These results could represent a starting point to open effective strategies in cancer prevention and treatment. HubMed – drug

Prescription of antibiotic drugs for children at the Brazzaville University Hospital Center (Congo).

Med Sante Trop. 2013 Jun 24;
Mabiala Babela JR, Ollandzobo Ikobo LC, Mbika Cardorelle A, Moyen G

Antibiotics are a class of drugs commonly prescribed in pediatric practice, often inappropriately. Objective. To determine the prevalence of antibiotic prescription in hospitalized children, assess the quality of prescribing, and identify factors related to inappropriate prescriptions. Methods. This retrospective study was conducted from July through December 2009 (6 months). It included data about 464 children aged from 1 month-16 years who received antibiotic therapy. Results. Antibiotics were prescribed to 61.5% of the children admitted to the hospital. Their mean age was 18.6 ± 20.2 months, and most (78%) were younger than 2 years. The indications for antibiotics were dominated by acute respiratory infections (46%), diarrhea (16%), and severe sepsis (12%). The prescriptions were written by pediatricians in 179 cases (38.6%), and by residents or interns in the other cases. The beta-lactam antibiotics (79%), aminoglycosides (8%) and sulfonamides (7%) were prescribed most often. The initial antibiotic therapy was changed in 82 cases. The indication for antibiotic therapy was correct in 325 cases and the type chosen appropriate in 229, the dosage correct in 437 cases, and the duration correct in 390. The route of administration was intravenous in 243 cases (40.3%), oral in 194 (41.8%), and intramuscular in 37 (7.9%). The qualification of the prescriber was associated with relevance, choice and dosage. The dosage was correct when the drug was administered parenterally in 248 cases (56.8%); in contrast, it was incorrect in 189 cases (43.7%; p>0.05) of oral administration. The route of administration was related to the choice of antibiotic. Thus, it was appropriate when the route was parenteral in 162 cases (70.7%) and in only 67 cases (29.3%) for the oral route (p <0.001). Conclusion. Errors in antibiotic prescriptions could be improved by standardized treatment guidelines, compliance with international recommendations, a consistent approach to diagnosis, and better laboratory performance. HubMed – drug