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Full-Text Articles in Medicine and Health Sciences

Intact Lkb1 Activity Is Required For Survival Of Dormant Ovarian Cancer Spheroids, Teresa M. Peart, Yudith R. Valdes, Rohann J.M. Correa, Elena Fazio, Monique Bertrand, Jacob Mcgee, Michel Prefontaine, Akira Sugimoto, Gabriel E. Dimattia, Trevor G. Shepherd Jun 2015

Intact Lkb1 Activity Is Required For Survival Of Dormant Ovarian Cancer Spheroids, Teresa M. Peart, Yudith R. Valdes, Rohann J.M. Correa, Elena Fazio, Monique Bertrand, Jacob Mcgee, Michel Prefontaine, Akira Sugimoto, Gabriel E. Dimattia, Trevor G. Shepherd

Anatomy and Cell Biology Publications

Metastatic epithelial ovarian cancer (EOC) cells can form multicellular spheroids while in suspension and disperse directly throughout the peritoneum to seed secondary lesions. There is growing evidence that EOC spheroids are key mediators of metastasis, and they use specific intracellular signalling pathways to control cancer cell growth and metabolism for increased survival. Our laboratory discovered that AKT signalling is reduced during spheroid formation leading to cellular quiescence and autophagy, and these may be defining features of tumour cell dormancy. To further define the phenotype of EOC spheroids, we have initiated studies of the Liver kinase B1 (LKB1)-5′-AMP-activated protein kinase (AMPK) …


Induction Of Autophagy Markers Is Associated With Attenuation Of Mir-133a In Diabetic Heart Failure Patients Undergoing Mechanical Unloading., Shyam Sundar Nandi, Michael J. Duryee, Hamid R. Shahshahan, Geoffrey M. Thiele, Daniel R. Anderson, Paras K. Mishra Apr 2015

Induction Of Autophagy Markers Is Associated With Attenuation Of Mir-133a In Diabetic Heart Failure Patients Undergoing Mechanical Unloading., Shyam Sundar Nandi, Michael J. Duryee, Hamid R. Shahshahan, Geoffrey M. Thiele, Daniel R. Anderson, Paras K. Mishra

Journal Articles: Cellular & Integrative Physiology

Autophagy is ubiquitous in all forms of heart failure and cardioprotective miR-133a is attenuated in human heart failure. Previous reports from heart failure patients undergoing left ventricular assist device (LVAD) implantation demonstrated that autophagy is upregulated in the LV of the failing human heart. Studies in the murine model show that diabetes downregulates miR-133a. However, the role of miR-133a in the regulation of autophagy in diabetic hearts is unclear. We tested the hypothesis that diabetes exacerbates cardiac autophagy by inhibiting miR-133a in heart failure patients undergoing LVAD implantation. The miRNA assay was performed on the LV of 15 diabetic (D) …


Amp-Activated Protein Kinase Controls Exercise Training - And Aicar-Induced Increases In Sirt3 And Mnsod, Josef Brandauer, Marianne A. Andersen, Holti Kellezi, Steve Risis, Christian Frozig, Sara G. Vienberg, Jonas T. Treebak Mar 2015

Amp-Activated Protein Kinase Controls Exercise Training - And Aicar-Induced Increases In Sirt3 And Mnsod, Josef Brandauer, Marianne A. Andersen, Holti Kellezi, Steve Risis, Christian Frozig, Sara G. Vienberg, Jonas T. Treebak

Health Sciences Faculty Publications

The mitochondrial protein deacetylase sirtuin (SIRT) 3 may mediate exercise training-induced increases in mitochondrial biogenesis and improvements in reactive oxygen species (ROS) handling. We determined the requirement of AMP-activated protein kinase (AMPK) for exercise training-induced increases in skeletal muscle abundance of SIRT3 and other mitochondrial proteins. Exercise training for 6.5 weeks increased SIRT3 (p < 0.01) and superoxide dismutase 2 (MnSOD; p < 0.05) protein abundance in quadriceps muscle of wild-type (WT; n = 13–15), but not AMPK α2 kinase dead (KD; n = 12–13) mice. We also observed a strong trend for increased MnSOD abundance in exercise-trained skeletal muscle of healthy humans (p = 0.051; n = 6). To further elucidate a role for …