9 research outputs found
Real-world effectiveness and safety of Vedolizumab for the treatment of Inflammatory Bowel Disease:The Scottish Vedolizumab Cohort
Response to Interferon-γ plus pentavalent antimony in Indian visceral leishmaniasis
One hundred fifty-six previously untreated Indian patients with visceral leishmaniasis were treated with pentavalent antimony (Sb) alone for 30 days (group A), Sb plus interferon-γ (IFN-γ) for 30 days (group B), or Sb plus IFN-γ for 15 days (group C). The purpose was to show that IFN-γ would increase the response to 30 days of Sb treatment and that short-course (15 days) combination therapy was as effective as 30 days of Sb alone. Six months after treatment, 36% of group A, 49% of group B, and 42% of group C patients were designated as definitively cured. The success rates for long-term responses to Sb alone (36%) and Sb plus IFN-γ (49%) were unexpectedly low, and responses in groups A, B, and C were not significantly different. These results suggest that the beneficial effects of adjunctive IFN-γ in visceral leishmaniasis may be limited in regions where this disseminated intracellular infection shows high-level resistance to Sb
Design, synthesis, and discovery of novel non-peptide inhibitor of Caspase-3 using ligand based and structure based virtual screening approach
Caspase-3 belonging to a family of cysteine proteases is main executioner of apoptotic cascade pathway. The inhibitors of this protein are useful in the treatment of cardiomyopathy and neurodegenerative diseases. For the discovery of novel Caspase-3 non-peptide inhibitors from Maybridge database, ligand based and structure based virtual screening methods were used. Quantitative 3D pharmacophore models were generated using 25 known inhibitors of Caspase-3 and it was used as initial screen to retrieve the hits from the database. These compounds with high estimated activity were analyzed for drug like properties and docking studies were performed, to study the interaction between new hits and active site. One of the hits (AW01208), with good predictions was selected for synthesis and biological screening. This compound showed an inhibition activity against Caspase-3 in SKNH cell lines
Serofendic acid prevents 6-hydroxydopamine-induced nigral neurodegeneration and drug-induced rotational asymmetry in hemi-parkinsonian rats
Selective Cancer Targeting via Aberrant Behavior of Cancer Cell-associated Glucocorticoid Receptor
Glucocorticoid receptors (GRs) are ubiquitous, nuclear hormone receptors residing in cell types of both cancer and noncancerous origin. It is not known whether cancer cell–associated GR alone can be selectively manipulated for delivery of exogenous genes to its nucleus for eliciting anticancer effect. We find that GR ligand, dexamethasone (Dex) in association with cationic lipoplex (termed as targeted lipoplex) could selectively manipulate GR in cancer cells alone for the delivery of transgenes in the nucleus, a phenomenon that remained unobserved in normal cells. The targeted lipoplex (i) showed GR-targeted transfections in all cancer cells experimented (P < 0.01), (ii) significantly diminished transfection in cancer cells when GR is downregulated (P < 0.01), and (iii) elicited specific nuclear translocation of targeted lipoplex in cancer cells, followed by upregulated transactivation of glucocorticoid response element (GRE)– promoted gene. Using anticancer gene, targeted lipoplex induced significant tumor growth retardation in mice in comparison to different control groups (P < 0.05). Interestingly, cell surface–associated Hsp90 in cancer cells assisted the intracellular uptake of GR-targeted lipoplex. Moreover, selective inhibition of Hsp90 in noncancer cells resulted in cancer cell-like, aberrant, GR activation. The current study discovers a therapeutically important, unique property of cancer cell associated–GR that may be linked to a compromised role of Hsp90