Venugopal C.,McMaster Stem Cell and Cancer Research Institute |
Li N.,McMaster Stem Cell and Cancer Research Institute |
Wang X.,McMaster Stem Cell and Cancer Research Institute |
Manoranjan B.,McMaster Stem Cell and Cancer Research Institute |
And 11 more authors.
Stem Cell Research | Year: 2012
The master regulatory gene Bmi1 modulates key stem cell properties in neural precursor cells (NPCs), and has been implicated in brain tumorigenesis. We previously identified a population of CD133 + brain tumor cells possessing stem cell properties, known as brain tumor initiating cells (BTICs). Here, we characterize the expression and role of Bmi1 in primary minimally cultured human glioblastoma (GBM) patient isolates in CD133 + and CD133 - sorted populations. We find that Bmi1 expression is increased in CD133 - cells, and Bmi1 protein and transcript expression are highest during intermediate stages of differentiation as CD133 + BTICs lose their CD133 expression. Furthermore, in vitro stem cell assays and Bmi1 knockdown show that Bmi1 contributes to self-renewal in CD133 + populations, but regulates proliferation and cell fate determination in CD133 - populations. Finally, we test if our in vitro stem cell assays and Bmi1 expression in BTIC patient isolates are predictive of clinical outcome for GBM patients. Bmi1 expression profiles show a marked elevation in the proneural GBM subtype, and stem cell frequency as assessed by tumor sphere assays correlates with patient outcome. © 2011 Elsevier B.V.
Dutta U.,Jawaharlal Institute of Postgraduate Medical Education & Research |
Moayyedi P.,1200 Main Street West
Best Practice and Research: Clinical Gastroenterology | Year: 2013
Gastro-oesophageal reflux disease develops when the reflux of gastric contents into the oesophagus results in troublesome symptoms and/or complications . Refluxate contains predominantly acid which causes tissue injury at oesophageal and extra-oesophageal sites. It is one of the commonest gastrointestinal diagnosis worlds over. It is associated with chronic symptoms, reduced QOL, significant cost and serious complications. Goals of therapy are to provide symptom relief, heal oesophagitis and prevent long-term complications. Therapeutic measures are directed at reducing the noxiousness of the refluxate; reducing the gastro-oesophageal reflux; enhancing clearance; protecting the mucosa; reducing the mucosal sensitivity and improving healing. Acid suppression with proton pump inhibitors remains the cornerstone of therapy. Recent studies have resulted in better understanding of disease and relative efficacies of various strategies. This has paved way for a better evidence based approach. The therapy however needs to be individualized depending upon the clinical profile, disease severity, the dominant pathophysiological mechanism, cost, availability and individual preferences. © 2013 Elsevier Ltd. All rights reserved.