The phosphoinositide 3 kinase AKT mammalian target of rapamycin (PI3K-AKTmTOR) signaling pathway is an important in the aetiology of pancreatic cancer (PC) and is frequently activated in PC. It is then associated with a poorer prognosis. Aberrant activation of this pathway is involved in cell metabolism and survival, cell cycle progression, regulation of apoptosis, protein synthesis, and genomic instability. Several agents have been developed to target the Akt/PI3K pathways, including PI3K inhibitors, (e.g. LY294002, Wortmannin), PI3K/mTOR inhibitors (e.g. BEZ235), or Akt inhibitors (e.g. perifosine, MK2206), which have been tested alone or in combinations with DNA-targeted agents (e.g., gemcitabine and fluorouracil) in pancreatic ductal adenocarcinoma (PDAC). However, due to their unfavorable pharmaceutical activities, toxicity, and crossover inhibition of other lipid and protein kinases, these compounds have not been used in clinical studies. In this review, we focus on the progress in the development of Akt, PI3K and mTOR inhibitors for clinical applications, together with the need for the development of in PDAC and the need for the identification of predictive biomarkers and combination strategies with less toxicity in counteracting the mechanisms of resistance to the therapy.
Cervical cancer is a common gynecological cancer and a leading cause of cancer-related death in women globally. There is a need for the identification of prognostic and predictive biomarker for risk stratification. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is often dysregulated in cervical cancer, indicating that it may be a potential therapeutic target in the treatment of this malignancy, and could perhaps be used as a novel biomarker in the assessment of risk of developing cervical cancer. We aimed to provide an overview of the potential applications of the PI3K/Akt/mTOR pathway as biomarker for risk stratification, in predicting the prognosis of cervical cancer, and for developing new therapeutic approaches in patients with cervical cancer. J. Cell. Biochem. 118: 4163-4169, 2017. © 2017 Wiley Periodicals, Inc.
Background & aims The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes Coronavirus Disease 2019 (COVID-19) has resulted in a worldwide pandemic. SARS-CoV-2 is highly contagious and its severity highly variable. The fatality rate is unpredictable but is amplified by several factors including advancing age, atherosclerotic cardiovascular disease, diabetes mellitus, hypertension and obesity. A large proportion of patients with these conditions are treated with lipid lowering medication and questions regarding the safety of continuing lipid-lowering medication in patients infected with COVID-19 have arisen. Some have suggested they may exacerbate their condition. It is important to consider known interactions with lipid-lowering agents and with specific therapies for COVID-19. This statement aims to collate current evidence surrounding the safety of lipid-lowering medications in patients, who have COVID-19. We offer a consensus view based on current knowledge and we rated the strength and level of evidence for these recommendations. Methods Pubmed, Google scholar and Web of Science were searched extensively for articles using search terms: SARS-CoV-2, COVID-19, coronavirus, Lipids, Statin, Fibrates, Ezetimibe, PCSK9 monoclonal antibodies, nicotinic acid, bile acid sequestrate, nutraceuticals, red yeast rice, Omega-3-Fatty acids, Lomitapide, hypercholesterolaemia, dyslipidaemia and Volanesorsen. Results & Conclusions : There is no evidence currently that lipid lowering therapy is unsafe in patients with COVID-19 infection. Lipid-lowering therapy should not be interrupted because of the pandemic or in patients at increased risk of COVID-19 infection. In patients with confirmed COVID-19, care should be taken to avoid drug interactions, between lipid-lowering medications and drugs that may be used to treat COVID-19, especially in patients with abnormalities in liver function tests.
These findings suggest that supplementation with selenium during pregnancy might be an effective approach for the prevention of postpartum depression.
This consensus statement addresses the current three main modalities of treatment of homozygous familial hypercholesterolaemia (HoFH): pharmacotherapy, lipoprotein (Lp) apheresis and liver transplantation. HoFH may cause very premature atheromatous arterial disease and death, despite treatment with Lp apheresis combined with statin, ezetimibe and bile acid sequestrants. Two new classes of drug, effective in lowering cholesterol in HoFH, are now licensed in the United Kingdom. Lomitapide is restricted to use in HoFH but, may cause fatty liver and is very expensive. PCSK9 inhibitors are quite effective in receptor defective HoFH, are safe and are less expensive. Lower treatment targets for lipid lowering in HoFH, in line with those for the general FH population, have been proposed to improve cardiovascular outcomes. HEART UK presents a strategy combining Lp apheresis with pharmacological treatment to achieve these targets in the United Kingdom (UK). Improved provision of Lp apheresis by use of existing infrastructure for extracorporeal treatments such as renal dialysis is promoted. The clinical management of adults and children with HoFH including advice on pregnancy and contraception are addressed. A premise of the HEART UK strategy is that the risk of early use of drug treatments beyond their licensed age restriction may be balanced against risks of liver transplantation or ineffective treatment in severely affected patients. This may be of interest beyond the UK.
Background: Improving the training of physicians about communication skills and patient health literacy (HL) is a major priority that remains an open question. We aimed to examine the effectiveness of communication skills training for physicians on the hypertension outcomes and the health literacy skills, self-efficacy and medication adherence in patients with uncontrolled blood pressure (BP). Methods: A randomized, controlled trial method was conducted on 240 hypertensive patients and 35 physicians presenting to healthcare clinics in the Mashhad, Iran, from 2013 to 2014. Using stratified blocking with block sizes of 4 and 6, eligible patients with uncontrolled blood pressure were randomly allocated to the intervention and control groups. Physicians in the intervention group received educational training over 3 sessions of Focus-Group Discussion and 2 workshops. The control group received the routine care. The primary outcome was a reduction in systolic and diastolic BP from baseline to 6 months. The secondary outcome was promoting HL skills in hypertensive patients. Data were analyzed using the regression model and bivariate tests. Results: After the physician communication training, there was a significant improvement in physicians-patient communication skills, hypertension outcomes, medication adherence, and self-efficacy among the patients being managed by the physicians receiving training, compared to the control group. Conclusion: The educational intervention leads to better BP control; it may have been sufficient training of physicians change to impact counseling, HL and self-efficacy and adherence. The quality of physician-patient communication is an important modifiable element of medical communication that may influences health outcomes in hypertensive Iranian patients. Trial registration: Iranian Registry of Clinical Trials (IRCT), IRCT20160710028863N24. Registered April 4, 2018 [retrospectively registered].
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