Cancer stem cells (CSCs) are proposed to initiate cancer and propagate metastasis. Breast CSCs identified by aldehyde dehydrogenase (ALDH) activity are highly tumorigenic in xenograft models. However, in patient breast tumor immunohistological studies, where CSCs are identified by expression of ALDH isoform ALDH1A1, CSC prevalence is not correlative with metastasis, raising some doubt as to the role of CSCs in cancer. We characterized the expression of all 19 ALDH isoforms in patient breast tumor CSCs and breast cancer cell lines by total genome microarray expression analysis, immunofluorescence protein expression studies, and quantitative polymerase chain reaction. These studies revealed that ALDH activity of patient breast tumor CSCs and cell lines correlates best with expression of another isoform, ALDH1A3, not ALDH1A1. We performed shRNA knockdown experiments of the various ALDH isoforms and found that only ALDH1A3 knockdown uniformly reduced ALDH activity of breast cancer cells. Immunohistological studies with fixed patient breast tumor samples revealed that ALDH1A3 expression in patient breast tumors correlates significantly with tumor grade, metastasis, and cancer stage. Our results, therefore, identify ALDH1A3 as a novel CSC marker with potential clinical prognostic applicability, and demonstrate a clear correlation between CSC prevalence and the development of metastatic breast cancer. STEM CELLS 2011;29:32-45 Disclosure of potential conflicts of interest is found at the end of this article.
This recursive partitioning analysis identified 3 prognostic groups in patients undergoing salvage surgery for recurrent OCSCC. The marked differences in survival between these groups should be taken into consideration when counselling and managing treatment for patients with locoregionally recurrent disease.
ObjectivePublished research in obstructive sleep apnea (OSA) appears limited despite OSA being a highly prevalent adult and pediatric disease leading to many adverse outcomes if left untreated. We aimed to quantify the deficit in OSA scientific literature in order to provide a novel way of identifying gaps in knowledge and a need for further research inquiry.MethodsThis was a Bibliometric analysis study. Using Ovid Medline database we analyzed and compared research output (medical and surgical) between adult OSA and similarly prevalent chronic conditions (Type II diabetes (T2DM), coronary artery disease (CAD) and osteoarthritis (OA)) from December 2016 up to fifty years prior. Linear graphs were utilized to trend collected data. Utilizing same strategy, we compared publication trends for pediatric OSA to asthma and gastroesophageal reflux (GER).ResultsAdult OSA publications (n = 9314) were significantly underrepresented when compared to T2DM (n = 66,023), CAD (n = 31,526) and OA (n = 34,123). Linear plots demonstrated that despite increasing number of publications this disparity persisted annually. Surgical literature composed 10.4% (n = 972) of adult OSA publications and reached a plateau in the last ten years. Pediatric OSA (n = 2994) had less research output when compared to asthma (n = 47,442) and GER (n = 6705). However, over past five years pediatric OSA surpassed GER in annual number of publications. Surgical literature represented 23.1% (n = 693) of pediatric OSA publications and continued increasing over past ten years. Study methodologies for both adult and pediatric OSA showed a lack of randomized controlled trials and meta-analyses in comparison to other diseases.ConclusionOur review shows substantial deficit in total, annual and surgical adult OSA published research compared to similarly prevalent diseases. This trend is not entirely observed in pediatric OSA literature.
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