Background-Despite the significant weight losses and dramatic improvements in comorbidities associated with bariatric surgery, a significant minority of patients appear to experience suboptimal weight losses. The reasons for this are not well understood, but often attributed to preoperative psychosocial characteristics and/or eating behaviors as well as poor adherence to the recommended postoperative diet.
Results of this study provide important information on the preoperative psychiatric status and treatment histories of bariatric surgery candidates. Given the increasing population of bariatric surgery patients, evaluation of patients' preoperative psychiatric status may play an important role in maximizing successful postoperative outcomes.
Purpose: WWOX (WW domain containing oxidoreductase) is a tumor suppressor gene that maps to the common fragile site FRA16D. We showed previously that WWOX is frequently altered in human lung and esophageal cancers. The purpose of this study was to delineate more precisely the role of WWOX in pancreatic carcinogenesis.Experimental Design: We analyzed 15 paired pancreatic adenocarcinoma samples and 9 pancreatic cancer cell lines for WWOX alterations. Colony assay and cell cycle analysis were also performed to evaluate the role of the WWOX as a tumor suppressor gene.Results: Loss of heterozygosity at the WWOX locus was observed in 4 primary tumors (27%). Methylation analysis showed that site-specific promoter hypermethylation was detected in 2 cell lines (22%) and treatment with the demethylating agent 5-aza-2-deoxycytidine demonstrated an increase in the expression of WWOX. In addition, 2 primary tumor samples (13%) showed promoter hypermethylation including the position of site-specific methylation. Transcripts missing WWOX exons were detected in 4 cell lines (44%) and in 2 tumor samples (13%). Real-time reverse transcription PCR revealed a significant reduction of WWOX expression in all of the cell lines and in 6 primary tumors (40%). Western blot analysis showed a significant reduction of the WWOX protein in all of the cell lines.Furthermore, transfection with WWOX inhibited colony formation of pancreatic cancer cell lines by triggering apoptosis.Conclusion: These results indicate that the WWOX gene may play an important role in pancreatic tumor development.
Background-Improvements in psychosocial status are an important aspect of successful outcomes after bariatric surgery. Relatively few studies have investigated changes in psychosocial functioning at a number of points in the first few postoperative years.
Background-Prior studies have reached contradictory conclusions concerning whether binge eating disorder (BED) is associated with greater psychopathology in extremely obese patients who seek bariatric surgery. This study used the Structured Clinical Interview for DSM-IV Diagnoses (SCID) to compare rates of Axis I psychopathology in surgery candidates who were determined to have BED or to be currently free of eating disorders. The relationship of BED to other psychosocial functioning and weight loss goals also was examined.
Rapid glycemic improvements following Roux-en-Y gastric bypass (RYGB) are frequently attributed to the enhanced GLP-1 response, but causality remains unclear. To determine the role of GLP-1 in improved glucose tolerance after surgery, we compared glucose and hormonal responses to a liquid meal test in 20 obese participants with type 2 diabetes mellitus who underwent RYGB or nonsurgical intensive lifestyle modification (ILM) (n = 10 per group) before and after equivalent short-term weight reduction. The GLP-1 receptor antagonist exendin(9–39)-amide (Ex-9) was administered, in random order and in double-blinded fashion, with saline during two separate visits after equivalent weight loss. Despite the markedly exaggerated GLP-1 response after RYGB, changes in postprandial glucose and insulin responses did not significantly differ between groups, and glucagon secretion was paradoxically augmented after RYGB. Hepatic insulin sensitivity also increased significantly after RYGB. With Ex-9, glucose tolerance deteriorated similarly from the saline condition in both groups, but postprandial insulin release was markedly attenuated after RYGB compared with ILM. GLP-1 exerts important insulinotropic effects after RYGB and ILM, but the enhanced incretin response plays a limited role in improved glycemia shortly after surgery. Instead, enhanced hepatic metabolism, independent of GLP-1 receptor activation, may be more important for early postsurgical glycemic improvements.
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