Anti-Cancer Drug Validation: the Contribution of Tissue Engineered Models

Drug toxicity frequently goes concealed until clinical trials stage, which is the most challenging, dangerous and expensive stage of drug development. Both the cultures of cancer cells in traditional 2D assays and animal studies have limitations that cannot ever be unraveled by improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. Considering the NCI60, a panel of 60 cancer cell lines representative of 9 different cancer types: leukemia, lung, colorectal, central nervous system (CNS), melanoma, ovarian, renal, prostate and breast, we propose to review current “state of art” on the 9 cancer types specifically addressing the 3D tissue models that have been developed and used in drug discovery processes as an alternative to complement their study.     

Fat gain with physical detraining is correlated with increased glucose transport and oxidation in periepididymal white adipose tissue in rats

As it is a common observation that obesity tends to occur after discontinuation of exercise, we investigated how white adipocytes isolated from the periepididymal fat of animals with interrupted physical training transport and oxidize glucose, and whether these adaptations support the weight regain seen after 4 weeks of physical detraining. Male Wistar rats (45 days old, weighing 200 g) were divided into two groups (n=10): group D (detrained), trained for 8 weeks and detrained for 4 weeks; and group S (sedentary). The physical exercise was carried out on a treadmill for 60 min/day, 5 days/week for 8 weeks, at 50-60% of the maximum running capacity. After the training protocol, adipocytes isolated from the periepididymal adipose tissue were submitted to glucose uptake and oxidation tests. Adipocytes from detrained animals increased their glucose uptake capacity by 18.5% compared with those from sedentary animals (P<0.05). The same cells also showed a greater glucose oxidation capacity in response to insulin stimulation (34.55%) compared with those from the S group (P<0.05). We hypothesize that, owing to the more intense glucose entrance into adipose cells from detrained rats, more substrate became available for triacylglycerol synthesis. Furthermore, this increased glucose oxidation rate allowed an increase in energy supply for triacylglycerol synthesis. Thus, physical detraining might play a role as a possible obesogenic factor for increasing glucose uptake and oxidation by adipocytes.     

Pharmacokinetics and dose finding of a potent aromatase inhibitor, aromasin (exemestane), in young males

Suppression of estrogen, via estrogen receptor or aromatase blockade, is being investigated in the treatment of different conditions. Exemestane (Aromasin) is a potent and selective irreversible aromatase inhibitor. To characterize its suppression of estrogen and its pharmacokinetic (PK) properties in males, healthy eugonadal subjects (14-26 yr of age) were recruited. In a cross-over study, 12 were randomly assigned to 25 and 50 mg exemestane daily, orally, for 10 d with a 14-d washout period. Blood was withdrawn before and 24 h after the last dose of each treatment period. A PK study was performed (n = 10) using a 25-mg dose. Exemestane suppressed plasma estradiol comparably with either dose [25 mg, 38% (P 相似文献   

Association Between Maximal Activated Clotting Time and Major Bleeding Complications During Transradial and Transfemoral Percutaneous Coronary Intervention

Objectives

This study sought to determine whether higher maximal activated clotting time (ACT) during transradial (TR) percutaneous coronary intervention (PCI) is associated with greater bleeding risk.

Histoplasmosis mimicking tuberculosis spondylodiscitis in a patient with rheumatoid arthritis

Osteoarticular infection caused by lt i gt Histoplasma capsulatum lt i gt is rare in Rheumatoid Arthritis (RA) making its diagnosis difficult. In the immunocompetent individuals this infection is autolimited or localized, while in immunodepressed patients the infection may be disseminated, and represents the reactivation of latent focuses or exogenous acquisition. Fungemia occurs in 20% of the cases; bones and joints are involved in 15%, being the spine the most common site of infection. We describe a clinical case of a woman with RA and spondylodiscitis caused by Histoplasma capsulatum with an initial diagnosis of vertebral tuberculosis. The complications of the treatment with amphotericin B, such as, vomiting and severe hypokalemia, led to several interruptions in the medication causing the spread of the pathogen into the liver and lungs.