Everolimus causing severe hypertriglyceridemia and acute pancreatitis.
ABSTRACT Everolimus is an mTOR inhibitor commonly used to treat metastatic pancreatic neuroendocrine tumors (pNETs) and renal cell carcinoma, and for posttransplant immunosuppression. This report presents a case of a 36-year-old man being treated with everolimus for a metastatic pNET who developed severe hypertriglyceridemia and acute pancreatitis. The incidence of hypertriglyceridemia reported in large prospective randomized trials is reviewed and the management of hypertriglyceridemic pancreatitis is discussed. Careful monitoring of triglyceride levels and dose adjustments of everolimus together with lipid-lowering therapy can allow patients to continue this medication. Because there are increasing indications for the use of everolimus, prescribing oncologists must be cognizant of the common and serious side effects.
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ABSTRACT: Macrophage infiltration contributes to the instability of atherosclerotic plaques. In the present study, we investigated whether selective inhibition of PI3K/Akt/mTOR signaling pathway can enhance the stability of atherosclerotic plaques by activation of macrophage autophagy. In vitro study, selective inhibitors or siRNA of PI3K/Akt/mTOR pathways were used to treat the rabbit's peritoneal primary macrophage cells. Inflammation related cytokines secreted by macrophages were measured. Ultrastructure changes of macrophages were examined by transmission electron microscope. mRNA or protein expression levels of autophagy related gene Beclin 1, protein 1 light chain 3 II dots (LC3-II) or Atg5-Atg12 conjugation were assayed by quantitative RT-PCR or Western blot. In vivo study, vulnerable plaque models were established in 40 New Zealand White rabbits and then drugs or siRNA were given for 8 weeks to inhibit the PI3K/Akt/mTOR signaling pathway. Intravascular ultrasound (IVUS) was performed to observe the plaque imaging. The ultrastructure of the abdominal aortic atherosclerosis lesions were analyzed with histopathology. RT-PCR or Western blot methods were used to measure the expression levels of corresponding autophagy related molecules. We found that macrophage autophagy was induced in the presence of Akt inhibitor, mTOR inhibitor and mTOR-siRNA in vitro study, while PI3K inhibitor had the opposite role. In vivo study, we found that macrophage autophagy increased significantly and the rabbits had lower plaque rupture incidence, lower plaque burden and decreased vulnerability index in the inhibitors or siRNA treated groups. We made a conclusion that selective inhibition of the Akt/mTOR signal pathway can reduce macrophages and stabilize the vulnerable atherosclerotic plaques by promoting macrophage autophagy.PLoS ONE 03/2014; 9(3):e90563. DOI:10.1371/journal.pone.0090563 · 3.53 Impact Factor
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ABSTRACT: Cancer survivorship should be defined starting not from completion of treatment, but from the time of diagnosis. Assessing and controlling the cancer patient's cardiovascular risk before, during, and after treatment is crucial to improving their overall outcome. There are many cancer therapies, including but not limited to anthracyclines, radiation, and vascular signaling pathway inhibitors which should be considered nontraditional cardiovascular risk factors with significant morbidity. Monitoring novel populations, such as a younger age group, for ischemic coronary disease or congestive heart failure (CHF) is not intuitive to many clinicians. Symptoms of CHF and coronary artery disease overlap with common side effects of cancer and cancer treatment. Cancer survivors may also have fewer typical symptoms of cardiovascular disease. Increased surveillance and aggressive control of cardiovascular disease is important in cancer patients both while undergoing active treatment and in the long term. Despite the increasing interest in cardio-oncology, data-driven guidelines are lacking due to small study sizes and low event rates over a short period of time. Most practice guidelines have been based on clinical practice and expert opinion. The list of cardiotoxic cancer therapies continues to grow each year. This review is not intended to be a comprehensive review of all cancer therapy toxicity, but will focus on recent literature regarding prevention of CHF and coronary artery disease (CAD) during active cancer therapy as well as current screening guidelines for long-term survivors.Current Atherosclerosis Reports 03/2015; 17(3):484. DOI:10.1007/s11883-014-0484-3 · 3.06 Impact Factor