Research Interests:
Research Interests:
Gomesin (Gm) is a potent antimicrobial peptide isolated from the spider Acanthoscurria gomesiana. The two disulfide bridges Cys2,15 and Cys6,11 facilitate the folding of the molecule in a β‐hairpin structure, conferring on the peptide a... more
Gomesin (Gm) is a potent antimicrobial peptide isolated from the spider Acanthoscurria gomesiana. The two disulfide bridges Cys2,15 and Cys6,11 facilitate the folding of the molecule in a β‐hairpin structure, conferring on the peptide a high stability in human plasma. We report herein biological and structural features of new linear Gm analogues, obtained by combining the removal of both disulfide bridges and the incorporation of a D‐ or L‐proline. Regarding their biological properties, two analogues, namely, [D‐Thr2,6,11,15, Pro9]‐D‐Gm and [Thr2,6,11,15, D‐Pro9]‐Gm, are as potent as Gm against Candida albicans and only fourfold less against Staphylococcus aureus and Escherichia coli. In addition, at 100 μM they are approximately threefold less hemolytic than Gm. The best therapeutic indices were found for [D‐Thr2,6,11,15, Pro9]‐D‐Gm and for [(Des‐pGlu1, ‐Thr2, ‐Arg3), Thr6,11,15, D‐Pro9]‐Gm with a 32‐fold increase of their activity against bacteria, and from 128‐ to 512‐fold agains...
Research Interests: Chemistry, Nuclear Magnetic Resonance, Medicine, Biological Sciences, Humans, and 15 moreMicelles, Circular Dichroism, Escherichia coli, Biopolymers, Drug Design, Candida albicans, Peptide, Antimicrobial Peptide, CHEMICAL SCIENCES, Antimicrobial Cationic Peptides, Amino Acid Sequence, Drug Stability, Hemolysis, Molecular Sequence Data, and In Vitro Techniques
Background The Hedgehog (Hh) signalling pathway is overexpressed in pancreatic ductal adenocarcinoma (PDA). Preclinical studies have shown that Hh inhibitors reduce pancreatic cancer stem cells (pCSC), stroma and Hh signalling. Methods... more
Background The Hedgehog (Hh) signalling pathway is overexpressed in pancreatic ductal adenocarcinoma (PDA). Preclinical studies have shown that Hh inhibitors reduce pancreatic cancer stem cells (pCSC), stroma and Hh signalling. Methods Patients with previously untreated metastatic PDA were treated with gemcitabine and nab-paclitaxel. Vismodegib was added starting on the second cycle. The primary endpoint was progression-free survival (PFS) as compared with historical controls. Tumour biopsies to assess pCSC, stroma and Hh signalling were obtained before treatment and after cycle 1 (gemcitabine and nab-paclitaxel) or after cycle 2 (gemcitabine and nab-paclitaxel plus vismodegib). Results Seventy-one patients were enrolled. Median PFS and overall survival (OS) were 5.42 months (95% confidence interval [CI]: 4.37–6.97) and 9.79 months (95% CI: 7.85–10.97), respectively. Of the 67 patients evaluable for response, 27 (40%) had a response: 26 (38.8%) partial responses and 1 complete respo...
Research Interests:
Pancreatic neuroendocrine tumors are rare tumors of the pancreas originating from the islets of the Langerhans. These tumors comprise 1% to 3% of all newly diagnosed pancreatic cancers every year and have a unique heterogeneity in... more
Pancreatic neuroendocrine tumors are rare tumors of the pancreas originating from the islets of the Langerhans. These tumors comprise 1% to 3% of all newly diagnosed pancreatic cancers every year and have a unique heterogeneity in clinical presentation. Whole-genome sequencing has led to an increased understanding of the molecular biology of these tumors. In this review, we will summarize the current knowledge of the signaling pathways involved in the tumorigenesis of pancreatic neuroendocrine tumors as well as the major studies targeting these pathways at preclinical and clinical levels.