Drug Interactions in Dermatology: What the Dermatologist Should Know.

Drug interactions in dermatology: what the dermatologist should know.

Indian J Dermatol. 2013 Jul; 58(4): 249-54
Coondoo A, Chattopadhyay C

A drug interaction is a process by which a drug or any other substance interacts with another drug and affects its activity by increasing or decreasing its effect, causing a side effect or producing a new effect unrelated to the effect of either. Interactions may be of various types-drug-drug interactions, drug-food interactions, drug-medical condition interactions, or drug-herb interactions. Interactions may occur by single or multiple mechanisms. They may occur in vivo or in vitro (pharmaceutical reactions). In vivo interactions may be further subdivided into pharmacodynamic or pharmacokinetic reactions. Topical drug interactions which may be agonistic or antagonistic may occur between two drugs applied topically or between a topical and a systemic drug. Topical drug-food interaction (for example, grape fruit juice and cyclosporine) and drug-disease interactions (for example, topical corticosteroid and aloe vera) may also occur. It is important for the dermatologist to be aware of such interactions to avoid complications of therapy in day-to-day practice. HubMed – drug

Kinase detection with gallium nitride based high electron mobility transistors.

Appl Phys Lett. 2013 Jul 1; 103(1): 13701
Makowski MS, Bryan I, Sitar Z, Arellano C, Xie J, Collazo R, Ivanisevic A

A label-free kinase detection system was fabricated by the adsorption of gold nanoparticles functionalized with kinase inhibitor onto AlGaN/GaN high electron mobility transistors (HEMTs). The HEMTs were operated near threshold voltage due to the greatest sensitivity in this operational region. The Au NP/HEMT biosensor system electrically detected 1?pM SRC kinase in ionic solutions. These results are pertinent to drug development applications associated with kinase sensing. HubMed – drug

Subtype Specific MEK – PI3 Kinase Feedback as a Therapeutic Target in Pancreatic Adenocarcinoma.

Mol Cancer Ther. 2013 Aug 5;
Mirzoeva OK, Collisson EA, Schaefer PM, Hann B, Hom YK, Ko AH, Korn WM

Mutations in the KRAS oncogene are dominant features in pancreatic adenocarcinoma (PDA). Since KRAS itself is considered “undruggable”, targeting pathways downstream of KRAS is being explored as a rational therapeutic strategy. We investigated the consequences of MEK inhibition in a large PDA cell line panel. Inhibition of MEK activated PI3 kinase in an EGFR-dependent fashion and combinations of MEK and EGFR inhibitors synergistically induced apoptosis. This combinatorial effect was observed in the epithelial but not mesenchymal subtype of PDA. RNA expression analysis revealed predictors of susceptibility to the combination, including E-cadherin, HER3, and the miR200-family of micro-RNAs, while expression of the transcription factor ZEB1 was associated with resistance to the drug combination. Knock-down of HER3 in epithelial-type and ZEB1 in mesenchymal-type PDA cell lines resulted in sensitization to the combination of MEK and EGFR inhibitors. Thus, our findings suggest a new, subtype-specific and personalized therapeutic strategy for pancreatic cancer. HubMed – drug

Chemotherapy counteracts metastatic dissemination induced by antiangiogenic treatment in mice.

Mol Cancer Ther. 2013 Aug 5;
Rovida A, Castiglioni V, Decio A, Scarlato V, Scanziani E, Giavazzi R, Cesca M

The development of resistance and progressive disease after treatment with angiogenesis inhibitors is becoming a controversial issue. We investigated the experimental conditions that cause multikinase receptor inhibitors (RTKI) to augment metastasis and whether opportune combinations with chemotherapy could counteract this effect. The renal Renca-luc tumor was transplanted orthotopically in the kidney of Balb/c mice, which were then or not nephrectomized. The Lewis Lung carcinoma (LLC) was transplanted in the tibial muscle of C57/Bl6 mice. Treatment with the RTKI sunitinib started at different stages of tumor progression, mimicking neo-adjuvant or adjuvant settings. Combination studies with paclitaxel, doxorubicin, cisplatin, gemcitabine and topotecan were done on the LLC model, using opportune regimens. In a neo-adjuvant setting sunitinib inhibited Renca-luc tumor growth, prolonging survival despite an increase in lung metastasis; treatment after primary tumor surgery (adjuvant setting) or on established metastasis prolonged survival and decreased metastasis. Sunitinib increased lung metastasis from mice bearing early-stage LLC, but did not affect established metastases (no acceleration) from advanced tumors. Combinations with doxorubicin, topotecan, gemcitabine, but not cisplatin and paclitaxel, counteracted the increase in metastasis from LLC, partly reflecting their antitumor activity. Histology analysis after sunitinib confirmed tumor vascular changes and increased hypoxia. Topotecan at suboptimal daily doses reduced sunitinib-related metastasis, reducing tumor hypoxia. Tyrosin kinase inhibitors, as sunitinib, can have adverse malignant effects mainly in the neo-adjuvant setting. The addition of chemotherapy might influence metastasis, depending on each drug mechanism of action and its regimen of administration. HubMed – drug