Objective
To describe the characteristics of patients who undergo total artificial heart support and to explore the ethical aspects of its withdrawal.
Patients and Methods
We retrospectively reviewed the medical records of all adult recipients of total artificial heart at our institution from the program’s inception in 2007 to June 30, 2015. Management of other life-sustaining therapies, approach to end-of-life decision making, engagement of ethics and palliative care consultation, and causes of death were analyzed.
Results
Of 47 total artificial heart recipients, 14 patients or their surrogates (30%) requested withdrawal of total artificial heart support. No request was denied by treatment teams. All 14 patients were supported with at least 1 other life-sustaining therapy. Only 1 patient was able to participate in decision making.
Conclusion
It is widely held to be ethically permissible to withdraw a life-sustaining treatment when the treatment no longer meets the patient’s health care–related goals (ie, the burdens outweigh the benefits). Our data suggest that some patients, surrogates, physicians, and other care providers believe that this principle extends to the withdrawal of total artificial heart support.
Introduction: Glucagon-like peptide 1 (GLP1) an incretin has demonstrated to increase insulin secretion in a glucose-dependent manner and is shown to be neuroprotective. GLP1 also promotes angiogenesis. Hypoxia, a common feature in solid tumors including neuroblastoma, promotes tumor progression by upregulation of hypoxia responsive factors. Little is known about alterations of GLP1 expression in neuroblastoma under hypoxic condition. GLP1 is rapidly inactivated by dipeptidyl peptidase IV (DPPIV) mediated enzymatic cleavage. Previously we have shown that DPPIV suppresses neuroblastoma survival and angiogenesis. In this study, we examined whether GLP1, its receptor GLP1R, and DPPIV expressions are altered after exposing neuroblastoma cells to hypoxic conditions of oxygen and nutrient deprivation (OND). We then examined the direct effects of GLP1 on neuroblastoma proliferation and survival, and evaluated if DPPIV modulates GLP1 mediated functions.
Methods: We used Neuro-2a, a mouse neuroblastoma cells as a model. In vitro experiments were performed exposing these cells to conditions mimicking tumor areas that display oxygen and nutrient deprivation, followed by re-oxygenation. Immunofluorescence staining was used to analyze the protein expression of GLP1, GLP-1R, and DPPIV. RT-PCR was used to measure mRNA levels. Effects of DPPIV on GLP1 mediated Neuro-2a cell proliferation and survival was evaluated by MTT and live/dead cell assay. Levels of PI3K/AKT were determined by western blot analysis.
Results: Neuro-2a cells subjected to OND showed about 2 fold increase in the GLP1 protein and mRNA levels at four hours of
re-oxygenation after 4 hours of OND. However, GLP1 protein levels decreased drastically after one day of re-oxygenation, while DPPIV levels were highly upregulated. GLP1R was also downregulated at one day of re-oxygenation. At this time point, cell viability was decreased by 30-40%. Pre-treatment with DPPIV inhibitor rescued the protective effects of GLP1. Furthermore, exogenous GLP1 stimulated cell proliferation and increased Neuro-2a cell viability by 2-3 fold. GLP1dependent action was mediated via increased levels of phosphorylated AKT, a pro-survival signaling molecule. The effects of GLP1 were suppressed in presence of DPPIV.
Conclusion: The results indicate an inverse correlation between DPPIV and GLP1 levels in Neuro-2a cells. Together, these studies indicate that GLP1-DPPIV interaction may play an important role in promoting neuroblastoma cell proliferation and survival.
Citation Format: Umadevi V. Wesley, Nausheen Singh, Robert J. Dempsey. Glucagon like peptide 1 (GLP1) up-regulation in hypoxic and nutrient deprived microenvironment promotes neuroblastoma cell survival. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5108.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.