Drug and Alcohol Rehabilitation: Rapid Recognition of Drug-Resistance/sensitivity in Leukemic Cells by Fourier Transform Infrared Microspectroscopy and Unsupervised Hierarchical Cluster Analysis.

Rapid recognition of drug-resistance/sensitivity in leukemic cells by Fourier transform infrared microspectroscopy and unsupervised hierarchical cluster analysis.

Filed under: Drug and Alcohol Rehabilitation

Analyst. 2013 Jan 16;
Bellisola G, Cinque G, Vezzalini M, Moratti E, Silvestri G, Redaelli S, Passerini CG, Wehbe K, Sorio C

We tested the ability of Fourier Transform (FT) InfraRed (IR) microspectroscopy (microFTIR) in combination with unsupervised Hierarchical Cluster Analysis (HCA) in identifying drug-resistance/sensitivity in leukemic cells exposed to tyrosine kinase inhibitors (TKIs). Experiments were carried out in a well-established mouse model of human Chronic Myelogenous Leukemia (CML). Mouse-derived pro-B Ba/F3 cells transfected with and stably expressing the human p210(BCR-ABL) drug-sensitive wild-type BCR-ABL or the V299L or T315I p210(BCR-ABL) drug-resistant BCR-ABL mutants were exposed to imatinib-mesylate (IMA) or dasatinib (DAS). MicroFTIR was carried out at the Diamond IR beamline MIRIAM where the mid-IR absorbance spectra of individual Ba/F3 cells were acquired using the high brilliance IR synchrotron radiation (SR) via aperture of 15 × 15 ?m(2) in sizes. A conventional IR source (globar) was used to compare average spectra over 15 cells or more. IR signatures of drug actions were identified by supervised analyses in the spectra of TKI-sensitive cells. Unsupervised HCA applied to selected intervals of wavenumber allowed us to classify the IR patterns of viable (drug-resistant) and apoptotic (drug-sensitive) cells with an accuracy of >95%. The results from microFTIR + HCA analysis were cross-validated with those obtained via immunochemical methods, i.e. immunoblotting and flow cytometry (FC) that resulted directly and significantly correlated. We conclude that this combined microFTIR + HCA method potentially represents a rapid, convenient and robust screening approach to study the impact of drugs in leukemic cells as well as in peripheral blasts from patients in clinical trials with new anti-leukemic drugs.
HubMed – drug


Coronary stent thrombosis: current insights into new drug-eluting stent designs.

Filed under: Drug and Alcohol Rehabilitation

Chonnam Med J. 2012 Dec; 48(3): 141-9
Kim HK, Jeong MH

The advances of interventional cardiology have been achieved by new device development, finding appropriate drug regimes, and understanding of pathomechanism. Drug-eluting stents (DES) implantation with dual anti-platelet therapy reduced revascularization without increasing mortality or myocardial infarction compared with bare-metal stenting. However, late-term stent thrombosis (ST) and restenosis limited its value and raised the safety concern. Main mechanisms of this phenomenon are impaired endothelialization and hypersensitivity reaction with polymer. The second generation DES further improved safety and/or efficacy by using thinner stent strut and biocompatible polymer. Recently, new concept DES with biodegradable polymer, polymer-free and bioabsorbable scaffold are under investigation in the quest to minimize the risk of ST.
HubMed – drug


Superior therapeutic index of calmangafodipir in comparison to mangafodipir as a chemotherapy adjunct.

Filed under: Drug and Alcohol Rehabilitation

Transl Oncol. 2012 Dec; 5(6): 492-502
Karlsson JO, Kurz T, Flechsig S, Näsström J, Andersson RG

Mangafodipir is a magnetic resonance imaging contrast agent with manganese superoxide dismutase (MnSOD) mimetic activity. The MnSOD mimetic activity protects healthy cells against oxidative stress-induced detrimental effects, e.g., myelosuppressive effects of chemotherapy drugs. The contrast property depends on in vivo dissociation of Mn(2+) from mangafodipir-about 80% dissociates after injection. The SOD mimetic activity, however, depends on the intact Mn complex. Complexed Mn(2+) is readily excreted in the urine, whereas dissociated Mn(2+) is excreted slowly via the biliary route. Mn is an essential but also a potentially neurotoxic metal. For more frequent therapeutic use, neurotoxicity due to Mn accumulation in the brain may represent a serious problem. Replacement of 4/5 of Mn(2+) in mangafodipir with Ca(2+) (resulting in calmangafodipir) stabilizes it from releasing Mn(2+) after administration, which roughly doubles renal excretion of Mn. A considerable part of Mn(2+) release from mangafodipir is governed by the presence of a limited amount of plasma zinc (Zn(2+)). Zn(2+) has roughly 10(3) and 10(9) times higher affinity than Mn(2+) and Ca(2+), respectively, for fodipir. Replacement of 80% of Mn(2+) with Ca(2+) is enough for binding a considerable amount of the readily available plasma Zn(2+), resulting in considerably less Mn(2+) release and retention in the brain and other organs. At equivalent Mn(2+) doses, calmangafodipir was significantly more efficacious than mangafodipir to protect BALB/c mice against myelosuppressive effects of the chemotherapy drug oxaliplatin. Calmangafodipir did not interfere negatively with the antitumor activity of oxaliplatin in CT26 tumor-bearing syngenic BALB/c mice, contrary calmangafodipir increased the antitumor activity.
HubMed – drug



Jim’s Story – Sharing the Strength and Hope – Jim shares his recovery story at Duffy’s Napa Valley Drug and Alcohol Rehabilitation Center Looking for hope and help? 888-717-9725 www.duffysrehab.com


More Drug And Alcohol Rehabilitation Information…