PURPOSE Leishmaniasis is a major health problem in many tropical and sub-tropical countries and development of a safe and easily-available vaccine has high priority. Although several antigens potentially capable of inducing protective immunity have been studied, in the absence of pharmaceutical industry interest they have remained as fine publications only. Amongst them, Cathepsin L-like cystei...

BACKGROUND A high concentration of cisplatin (CDDP) induces apoptosis in many tumor cell lines. CDDP has been administered by infusion to avoid severe toxicity. Recently, it has been reported that changes in survivin expression or function may lead to tumor sensitization to chemical and physical agents. The aim of this study was to determine whether a dominant-negative mouse survivin mutant cou...

BACKGROUND Gene carriers based on lipids or polymers-rather than on engineered viruses-constitute the latest technique for delivering genes into cells for gene therapy. Cationic liposome-DNA (CL-DNA) complexes have emerged as leading nonviral vectors in worldwide gene therapy clinical trials. To arrive at therapeutic dosages, however, their efficiency requires substantial further improvement. ...

Restenosis after balloon angioplasty is a serious clinical problem arising in cardiology. Restenosis is caused by the induction of uncontrolled proliferation of vascular smooth muscle cells following damage of the endothelial lining of the vessel by balloon dilation. A gene therapy approach may provide the means to control the mechanisms responsible for restenosis. Several viral systems (adenov...

Heterotrimeric G proteins (composed of a , p and y subunits) mediate extracellular signals by coupling membrane bound receptors to intracellular second messenger systems [ 11. Despite the lack of obvious hydrophobic domains [2], G a subunits are associated with the cytoplasmic face of the membrane. This association has been proposed to be mediated by Py association [3], however studies of Goa, ...

MicroRNAs (miRs) are small noncoding RNA sequences that negatively regulate the expression of target genes by posttranscriptional repression. miRs are dysregulated in various diseases, including cancer. let-7a miR, an antioncogenic miR, is downregulated in lung cancers. Our earlier studies demonstrated that let-7a miR inhibits tumor growth in malignant pleural mesothelioma (MPM) and could be a ...

The antidiuretic effects of arginine vasopressin (AVP) on the kidney are mediated by V2 subtype AVP receptors (V2R). To investigate the role of regulation of V2R in water and sodium homeostasis, we have developed a method for small interfering RNA (siRNA)-mediated inhibition of V2R expression in vivo. Three 21-nt siRNA sequences were chosen that specifically targeted the mouse V2R but shared no...

It is well known that the vagina is an excellent route of mucosal drug delivery for local applications. However, an important parameter to consider and which could interfere with the performance of a delivery system is the vaginal mucus and its natural clearance process. This study has a double objective. The first consists on the elaboration of a solid mucoadhesive system which will be retaine...

RNA INTERFERENCE using short, double-stranded RNA (small interfering RNA, or siRNA) was recently introduced for suppressing gene expression in mammalian cells. Although the molecular mechanism of siRNA is not completely understood, it is generally believed that siRNA induces the degradation of target mRNA in a sequence-specific manner, leading to posttranscriptional silencing of gene expression...