Biomedical subjects

Talat Waseem

Publications and source records attributed to Talat Waseem.

5 recordsLinked to original sources

PubMed2006

RNA interference: a potential revolution in disease therapy.

Gene therapy is the most recent face of modern biotechnology, which has shown promise of disease diagnosis and management at a newer and the most sophisticated level. The reason of enormous interest in gene therapy lies in the fact that most of lethal pathologies including hepatitis B and C, AIDS and carcinogenesis are refractory to contemporary treatments. These techniques, at least in controlled environment, allow turning on and off various genomic sequences. Relevant to this subject, RNA interference (RNAi) is the most recent, highly precise method to silence almost any gene of choice. Currently, RNAi for various disorders is being tried in humans; if this therapeutic strategy works at clinical level as well, it would be possible to design therapies against certain intractable pathologies including hepatitis C and AIDS.

Genetic Engineering↗

PubMed2005

RNA interference demonstrates a novel role for integrin-linked kinase as a determinant of pancreatic adenocarcinoma cell gemcitabine chemoresistance.

Integrin-linked kinase (ILK) facilitates signal transduction between extracellular events and important intracellular survival pathways involving protein kinase B/Akt. We examined the role of ILK in determining pancreatic adenocarcinoma cellular chemoresistance to the nucleoside analogue gemcitabine. Cellular ILK expression was quantified by Western blot analysis. We examined the effects of overexpression of active ILK and of ILK knockdown induced by RNA interference on gemcitabine chemoresistance. We also examined the effects of modulating ILK expression on gemcitabine-induced caspase 3-mediated apoptosis, phosphorylation status of Akt (Ser473) and glycogen synthase kinase. Overexpression of ILK increased cellular gemcitabine chemoresistance, whereas ILK knockdown induced chemosensitization via increased caspase 3-mediated apoptosis. ILK knockdown attenuated Akt Ser473 and glycogen synthase kinase phosphorylation, whereas overexpression of constitutively active myristoylated Akt was sufficient to induce significant recovery in gemcitabine chemoresistance in the presence of ILK knockdown. Levels of ILK expression affect gemcitabine chemoresistance in pancreatic adenocarcinoma cells. This novel finding suggests that therapies directed against ILK and its downstream signaling targets may have the potential to enhance the efficacy of gemcitabine-based chemotherapy.

Adenocarcinoma↗

PubMed2005

Technologic advances in Robotic Surgery.

Medical science has achieved enormous accomplishments during the past couple of decades. These advances encompass the list of techniques involving manipulations of DNA and stem cells to minimally invasive techniques. The recent advances in integration of computer sciences, biomechanics and electronic miniaturization have made it possible to make the surgical techniques less invasive and highly precise. Much progress has been made in integrating robotic technologies with surgical instrumentation, as evident by thousands of successful robot-assisted surgical procedures. Such advances will enable continued progress in surgical instrumentation and, ultimately, surgical care.

Humans↗

PubMed2004

A novel role for carcinoembryonic antigen-related cell adhesion molecule 6 as a determinant of gemcitabine chemoresistance in pancreatic adenocarcinoma cells.

Most patients with pancreatic adenocarcinoma present with surgically incurable disease. Gemcitabine, the principal agent used to treat such patients, has little impact on outcome. Overexpression of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 6, a feature of this malignancy, is associated with resistance to anoikis and increased metastasis. The purpose of this study was to determine the role of CEACAM6 in cellular chemoresistance to gemcitabine. CEACAM6 was stably overexpressed in Capan2 cells, which inherently express very low levels of the protein. Suppression of CEACAM6 expression was achieved in BxPC3 cells, which inherently overexpress CEACAM6, by stable transfection of a CEACAM6 small interfering RNA-generating vector. The effects of modulating CEACAM6 expression on gemcitabine-induced cytotoxicity were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity assay, flow cytometric apoptosis quantification, caspase profiling, and Western analysis of cytoplasmic cytochrome c release. The roles of Akt and c-Src kinases as downstream targets of CEACAM6 signaling were examined. Stable overexpression of CEACAM6 in Capan2 increased gemcitabine chemoresistance, whereas CEACAM6 gene silencing in BxPC3 markedly increased the sensitivity of these cells to gemcitabine. Differential expression of CEACAM6 modulates Akt activity in a c-Src-dependent manner, and CEACAM6 overexpression appears to protect cells from cytochrome c-induced caspase 3 activation and apoptosis.

Adenocarcinoma↗

PubMed2003

Ghrelin promotes pancreatic adenocarcinoma cellular proliferation and invasiveness.

Ghrelin, a newly described potent orexigenic peptide, may have therapeutic potential in patients with cachexia. We assessed whether pancreatic adenocarcinoma, commonly associated with marked cachexia, is a ghrelin-responsive malignancy. Pancreatic adenocarcinoma cells were exposed to ghrelin (0-100 nM). Proliferation was determined by MTT assay. Ghrelin, ghrelin 1a and 1b receptor expression and Akt phosphorylation were assessed. The effects of ghrelin (+/- its antagonist D-Lys-GHRP6, or the PI3-K inhibitor Wortmannin) on cellular motility and invasiveness were quantified by Matrigel Boyden chamber assay. All cell lines expressed ghrelin 1a and 1b receptor transcript and protein, but only PANC1 weakly expressed ghrelin transcript. Ten nanomolar ghrelin increased proliferation, motility, invasiveness, and Akt phosphorylation in all cell lines. Proliferation was affected dose-dependently, being suppressed at higher ghrelin concentrations. D-Lys-GHRP6 suppressed ghrelin-induced proliferation, invasion, and Akt phosphorylation. Wortmannin abolished the effects of ghrelin on motility and invasiveness. Pancreatic adenocarcinoma is a ghrelin-responsive malignancy.

Adenocarcinoma↗