Drug and Alcohol Rehabilitation: Polymer-Drug Conjugates for Intracellar Molecule-Targeted Photoinduced Inactivation of Protein and Growth Inhibition of Cancer Cells.
Polymer-drug conjugates for intracellar molecule-targeted photoinduced inactivation of protein and growth inhibition of cancer cells.
Filed under: Drug and Alcohol Rehabilitation
Sci Rep. 2012; 2: 766
Wang B, Yuan H, Zhu C, Yang Q, Lv F, Liu L, Wang S
For most molecule-targeted anticancer systems, intracellular protein targets are very difficult to be accessed by antibodies, and also most efforts are made to inhibit protein activity temporarily rather than inactivate them permanently. In this work we firstly designed and synthesized multifunctional polymer-drug conjugates (polythiophene-tamoxifen) for intracellular molecule-targeted binding and inactivation of protein (estrogen receptor ?, ER?) for growth inhibition of MCF-7 cancer cells. Small molecule drug was conjugated to polymer side chain for intracellular signal protein targeting, and simultaneously the fluorescent characteristic of polymer for tracing the cellular uptake and localization of polythiophene-drug conjugates by cell imaging. Under light irradiation, the conjugated polymer can sensitize oxygen to produce reactive oxygen species (ROS) that specifically inactivate the targeted protein, and thus inhibit the growth of tumor cells. The conjugates showed selective growth inhibition of ER? positive cancer cells, which exhibits low side effect for our intracellular molecule-targeted therapy system.
HubMed – drug
Flux Analysis of the Trypanosoma brucei Glycolysis Based on a Multiobjective-Criteria Bioinformatic Approach.
Filed under: Drug and Alcohol Rehabilitation
Adv Bioinformatics. 2012; 2012: 159423
Ghozlane A, Bringaud F, Soueidan H, Dutour I, Jourdan F, Thébault P
Trypanosoma brucei is a protozoan parasite of major of interest in discovering new genes for drug targets. This parasite alternates its life cycle between the mammal host(s) (bloodstream form) and the insect vector (procyclic form), with two divergent glucose metabolism amenable to in vitro culture. While the metabolic network of the bloodstream forms has been well characterized, the flux distribution between the different branches of the glucose metabolic network in the procyclic form has not been addressed so far. We present a computational analysis (called Metaboflux) that exploits the metabolic topology of the procyclic form, and allows the incorporation of multipurpose experimental data to increase the biological relevance of the model. The alternatives resulting from the structural complexity of networks are formulated as an optimization problem solved by a metaheuristic where experimental data are modeled in a multiobjective function. Our results show that the current metabolic model is in agreement with experimental data and confirms the observed high metabolic flexibility of glucose metabolism. In addition, Metaboflux offers a rational explanation for the high flexibility in the ratio between final products from glucose metabolism, thsat is, flux redistribution through the malic enzyme steps.
HubMed – drug
Cardiovascular and cerebrovascular outcomes in elderly hypertensive patients treated with either ARB or ACEI.
Filed under: Drug and Alcohol Rehabilitation
J Geriatr Cardiol. 2012 Sep; 9(3): 252-7
Ma C, Cao J, Lu XC, Guo XH, Gao Y, Liu XF, Fan L
Although angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are equally important in the treatment of hypertension, there is less evidence whether they have equal cardiovascular and cerebrovascular protective effects, especially in elder hypertensive patients. This study aims to clarify this unresolved issue.This cross-sectional study included clinical data on 933 aged male patients with hypertension who received either an ARB or ACEI for more than two months between January 2007 and May 2011. The primary outcome was the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary endpoints were unstable angina, new atrial fibrillation, and transient ischemic attack.The median follow-up time was 24 months. Age, drug types, cerebral infarction history, renal dysfunction history were the independent predictors of the primary endpoint. The risk of an occurrence of a primary endpoint event was higher in the ARB group than the ACEI group [P = 0.037, hazard ratios (HR): 2.124, 95% confidence interval (95% CI): 1.048-4.306]. The Kaplan-Meier method also suggests that the rate of primary endpoint occurrence was higher in the ARB group than the ACEI group (P = 0.04). In regard to the secondary endpoints, there were no significant differences between the two treatment arms (P = 0.137, HR: 1.454, 95% CI: 0.888-2.380). Patient age and coronary heart disease history were independent predictors of the secondary endpoint.ACEI were more effective than ARB in reducing cardiovascular and cerebrovascular morbidity and mortality in aged patients with hypertension.
HubMed – drug
Novel Model for Basaloid Triple-negative Breast Cancer: Behavior In Vivo and Response to Therapy.
Filed under: Drug and Alcohol Rehabilitation
Neoplasia. 2012 Oct; 14(10): 926-42
Volk-Draper LD, Rajput S, Hall KL, Wilber A, Ran S
The basaloid triple-negative breast cancer (B-TNBC) is one of the most aggressive, therapy-resistant, and metastatic tumors. Current models do not recapitulate the basaloid phenotype of TNBC, thus limiting the understanding of its biology and designing new treatments. We identified HCC1806 as a line expressing typical B-TNBC markers, engineered a subline with traceable reporters, and determined growth, drug sensitivity, recurrence, and vascular and metastatic patterns of orthotopic xenografts in immunodeficient mice.mRNA and protein analyses showed that HCC1806 expresses basal but not luminal or mesenchymal markers. HCC1806-RR subline stably expressing red fluorescent protein and Renilla luciferase was generated and characterized for sensitivity to chemodrugs, orthotopic growth, vascular properties, recurrence, metastasis, and responsiveness in vivo.The HCC1806 cells were highly sensitive to paclitaxel, but cytotoxicity was accompanied by pro-survival vascular endothelial growth factor-A loop. In vivo, HCC1806-RR tumors display linear growth, induce peritumoral lymphatics, and spontaneously metastasize to lymph nodes (LNs) and lungs. Similarly to human B-TNBC, HCC1806-RR tumors were initially sensitive to taxane therapy but subsequently recur. Bevacizumab significantly suppressed recurrence by 50% and reduced the incidence of LN and pulmonary metastases by, respectively, 50% and 87%.The HCC1806-RR is a new model that expresses bona fide markers of B-TNBC and traceable markers for quantifying metastases. Combination of bevacizumab with nab-paclitaxel significantly improved the outcome, suggesting that this approach can apply to human patients with B-TNBC. This model can be used for defining the metastatic mechanisms of B-TNBC and testing new therapies.
HubMed – drug
Skateboarding Legend Dennis Martinez tells us the meaning of the artwork on his skateboard mean – I caught up recently with skateboarding’s trailblazer Dennis Martinez. Star of the movie DOPE, the 1977 World freestyle Champion and 1978 US Champion, Dennis was on the fast track to fame and fortune, saying “I was still in high school when I paid cash for a new car and paid for a full year on my own apartment.” With this newly acquired fame and money came the lure of drugs, and by the age of 16, Dennis had a cocaine habit that would lead to 16-years on the needle. From the life of a top pro athlete, Dennis took to the streets, using guns to perform armed robberies and to protect his drug stash! Today, Dennis is a volunteer prison chaplain at Calipatria State Prison and a founder of Training Center, a drug and alcohol rehabilitation center in Spring Valley, San Diego, CA!
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