Drug and Alcohol Rehabilitation: Metformin in Cancer: Translational Challenges.
Metformin in cancer: translational challenges.
Filed under: Drug and Alcohol Rehabilitation
J Mol Endocrinol. 2012 Jun; 48(3): R31-43
Dowling RJ, Niraula S, Stambolic V, Goodwin PJ
The anti-diabetic drug metformin is rapidly emerging as a potential anti-cancer agent. Metformin, effective in treating type 2 diabetes and the insulin resistance syndromes, improves insulin resistance by reducing hepatic gluconeogenesis and by enhancing glucose uptake by skeletal muscle. Epidemiological studies have consistently associated metformin use with decreased cancer incidence and cancer-related mortality. Furthermore, numerous preclinical and clinical studies have demonstrated anti-cancer effects of metformin, leading to an explosion of interest in evaluating this agent in human cancer. The effects of metformin on circulating insulin levels indicate a potential efficacy towards cancers associated with hyperinsulinaemia; however, metformin may also directly inhibit tumour growth. In this review, we describe the mechanism of action of metformin and summarise the epidemiological, clinical and preclinical evidence supporting a role for metformin in the treatment of cancer. In addition, the challenges associated with translating preclinical results into therapeutic benefit in the clinical setting will be discussed.
HubMed – drug
Targeted delivery of nanomedicines.
Filed under: Drug and Alcohol Rehabilitation
ISRN Pharmacol. 2012; 2012: 571394
Kumar Khanna V
The role of targeting of the diseased region by a drug is emphasized. The rationale for resorting to nanomaterials as drug carriers is explained. A clear understanding of the biological environment, its degradation in diseased condition, and the interaction of the drug with it in normal condition and during illness lie at the core of successful drug delivery. Passive and active drug targeting approaches are differentiated. Commonly used drug targets, targeting ligands, and nanoscale systems are elaborated. Mechanisms of internalization of nanomedicines and circumventing P-glycoprotein mediated resistance are outlined. The paper presents an overview of the current scenario of targeted transportation of nanomedicines to the affected organ and suggests future research directions.
HubMed – drug
Gastrointestinal stromal tumors: a review of case reports, diagnosis, treatment, and future directions.
Filed under: Drug and Alcohol Rehabilitation
ISRN Gastroenterol. 2012; 2012: 595968
Tan CB, Zhi W, Shahzad G, Mustacchia P
Gastrointestinal stromal tumor (GIST) is a nonepithelial, mesenchymal tumor first described by Mazur and Clark in 1983. Since then, its molecular biology has been studied in great detail. Special interest in the role of tyrosine kinase in its regulation has been the target by different drug research. Mutation in c-kit exons 9, 11, 13, 17 and PDGFRA mutation in exons 12, 14, 18 are responsible for activation of gene signaling system resulting in uncontrolled phosphorylation and tissue growth. However, 5 to 15% of GISTs does not harbor these mutations, which raises additional questions in another alternate signaling pathway mutation yet to be discovered. Diagnosis of GISTs relies heavily on KIT/CD117 immunohistochemical staining, which can detect most GISTs except for a few 3% to 5% that harbors PDGFRA mutation. Newer staining against PKC theta and DOG-1 genes showed promising results but are not readily available. Clinical manifestation of GISTs is broad and highly dependent on tumor size. Surgery still remains the first-line treatment for GISTs. The advancement of molecular biology has revolutionized the availability of newer drugs, Imatinib and Sunitinib. Together with its advancement is the occurrence of Imatinib/Sunitinib drug resistance. With this, newer monoclonal antibody drugs are being developed and are undergoing clinical trials to hopefully improve survival in patients with GISTs.
HubMed – drug
Development and evaluation of a novel pellet-based tablet system for potential colon delivery of budesonide.
Filed under: Drug and Alcohol Rehabilitation
J Drug Deliv. 2012; 2012: 905191
Varshosaz J, Emami J, Tavakoli N, Minaiyan M, Rahmani N, Dorkoosh F
Budesonide, a potent glucocorticoid, is used for the treatment of inflammatory bowel diseases. Current available oral formulations of budesonide have low efficacy against ulcerative colitis because of the premature drug release in the upper part of the gastrointestinal tract. In this paper a pH- and time-controlled colon-targeted pellet-based tablet of budesonide was established. Pellet cores were prepared by extrusion-spheronization method and further coated with xanthan gum (barrier layer), Eudragit NE30D and L30D55 combination (inner layer), and Eudragit FS30 (as enteric layer) sequentially to achieve the required release profile. The coated pellets then compressed into tablets using inert tabletting granules of Cellactose or Pearlitol. Release studies, performed in simulated gastric, intestinal, and colon pH were used in sequence to mimic the gastrointestinal transit. The influence of formulation variables like barrier layer thickness, inner layer composition, and enteric coat thickness on drug release were investigated and the coated pellets that contained 12% weight gain in xanthan gum layer, Eudragit L30D55 and Eudragit NE30D with a ratio of 3?:?7 in inner layer with 30% weight gain and 25% weight gain in Eudragit FS layer were found to protect the drug release in stomach and small intestine and 83.35 ± 2.4 of budesonide was released at 24?h. The drug release from the tablets prepared using 40% Cellactose 80 as tableting excipient was found to be closely similar to that of uncompressed pellets.
HubMed – drug
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