Antiproliferative Activity of New Benzimidazole Derivatives.

Antiproliferative activity of new benzimidazole derivatives.

Acta Biochim Pol. 2013 Jul 25;
B?aszczak-?wi?tkiewicz K, Olszewska P, Mikiciuk-Olasik E

A series of new benzimidazole derivatives were synthesized and tested in vitro for possible anticancer activity. Their effect of proliferation into selected tumor cell lines at normoxia and hypoxia conditions was determined by WST-1 test. Additionally, apoptosis test (caspase 3/7 assay) was used to check the mode caused by the agents of cell death. Four of the examined compounds (7, 8, 13, 11) showed a very good antiproliferative effect and three of them were specific for hypoxia conditions (8, 14, 11). Compound 8 was the most cytotoxic against human lung adenocarcinoma A549 cells at hypoxic conditions. Hypoxia/ normoxia cytotoxic coefficient of compound 14 (4.75) is close to hypoxia/normoxia cytotoxic coefficient of tirapazamine (5.59) – a reference compound in our experiments and this parameter locates it between mitomycin C and 2-nitroimidazole (misonidazole). Screening test of caspase-dependent apoptosis proved that exposure to A549 cells of compounds 7-8 and 13-14 for 48 h promote apoptotic cell death. These results supplement our earlier study of the activity of new potentialy cytotoxic heterocyclic compounds against selected tumor cells. HubMed – drug

Dynamic QuantiFERON Response in Psoriasis Patients Taking Long-Term Biologic Therapy.

Dermatol Ther (Heidelb). 2013 Jun; 3(1): 73-81
Drago L, Nicola L, Signori V, Palazzi E, Garutti C, Spadino S, Altomare G

The risk of active tuberculosis is increased in psoriasis patients receiving biologic drug therapy. The QuantiFERON-TB Gold In-Tube assay (QFT) is used for latent tuberculosis screening in these patients. This study presents a retrospective analysis on repeated QFT assays, investigating the influence of biologic drugs and isoniazid therapy on the outcome of the assay.Serial QFTs of 58 psoriasis patients, who received biologic drug therapy, were evaluated at baseline and after 12 months of treatment. Patients were retrospectively divided in four groups according to QFT results at baseline and at follow-up: patients having a QFT reversion (from positive to negative results); patients with a conversion (from negative to positive); patients confirming the baseline results, either positive or negative.At the end of the 12-months period, 11.1% of patients with a negative QFT result at baseline presented a conversion, showing low interferon (IFN)-gamma values, whereas 6.9% of positive patients presented a QFT reversion. When the test was repeated after 2-3 months without isoniazid chemoprophylaxis, patients with QFT conversion showed negative results. No patient developed active tuberculosis.In patients undergoing biologic therapy, a positive QFT assay needs to be further confirmed, as false-positive results may occur after long-term therapy. Repeating QFT tests in patients with low IFN-gamma values could reduce the incidence of false-positive latent tuberculosis infection diagnosis, thus preventing unnecessary tuberculosis chemoprophylaxis. In conclusion, a dynamic QFT response is possible in psoriasis patients undergoing biologic therapy. HubMed – drug

Targeted therapy for advanced Basal-cell carcinoma: vismodegib and beyond.

Dermatol Ther (Heidelb). 2013 Jun; 3(1): 17-31
Cowey CL

Basal-cell carcinoma is a commonly occurring skin malignancy that has the potential to progress into locally invasive or resistant disease, as well as spread distantly. Due to advances in the molecular understanding of the disease over the last two decades, it has been discovered that the Hedgehog pathway plays an important role in the pathogenesis of this disease and can be exploited as a treatment target. Several agents that inhibit the Hedgehog pathway have reached clinical studies and one drug, vismodegib, has recently been US Food and Drug Administration (FDA) approved based on clinical activity and tolerability in patients with advanced basal-cell carcinoma. This review will describe the clinical development of vismodegib, as well as the proper application of the drug in clinical practice. Other important clinical questions, such as mechanisms of resistance to vismodegib and the role of other Hedgehog pathway inhibitors currently in development will also be discussed. HubMed – drug

Cost per patient and potential budget implications of denosumab compared with zoledronic acid in adults with bone metastases from solid tumours who are at risk of skeletal-related events: an analysis for Austria, Sweden and Switzerland.

Eur J Hosp Pharm Sci Pract. 2013 Aug; 20(4): 227-231
Lothgren M, Ribnicsek E, Schmidt L, Habacher W, Lundkvist J, Pfeil AM, Biteeva I, Vrouchou P, Bracco A

To assess cost implications per patient, per year, and to predict the potential annual budget impact when patients with bone metastases secondary to solid tumours at risk of skeletal-related events (SREs) transition from zoledronic acid (ZA; 4?mg every 3-4?weeks) to denosumab (120?mg every 4?weeks) in Austria, Sweden and Switzerland.Country specific costs for medication and administration, patient management and SREs (defined as pathologic fracture, radiation to bone, surgery to bone and spinal cord compression) were assessed over a 1-year time horizon. Drug administration and patient management costs were taken from available public sources. SRE costs were based on local unit costs applied to country specific healthcare resources obtained from a multinational retrospective chart review study. Due to lack of real world data for the included countries, SRE rates were derived from phase III clinical trials in patients with advanced cancer and bone metastases. These trials demonstrated that denosumab was superior to ZA in the reduction of SREs.Estimated total annual cost savings for each patient transitioned from ZA to denosumab varied by country and cancer type, ranging from €1583 to €2375 in Austria, from €1980 to €2319 in Sweden (9.1 SEK/€) and from €3408 to €3857 in Switzerland (1.2 CHF/€). Cost savings were mainly driven by the lower SRE related costs and lower administration costs of denosumab compared with ZA.Denosumab offers superior efficacy compared with ZA in patients with solid tumours and bone metastases. Cost savings are predicted in the Austrian, Swedish and Swiss healthcare systems following treatment transition from ZA to denosumab. HubMed – drug