20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2017/08/01

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

BDNF Genotype is Associated with Hippocampal Volume in Mild Traumatic Brain Injury.

Genes Brain Behav. 2017 Jul 28;:

Authors: Hayes JP, Reagan A, Logue MW, Hayes SM, Sadeh N, Miller DR, Verfaellie M, Wolf EJ, McGlinchey RE, Milberg WP, Stone A, Schichman SA, Miller MW

Abstract
The negative long-term effects of mild traumatic brain injury (mTBI) have been a growing concern in recent years, with accumulating evidence suggesting that mTBI combined with additional vulnerability factors may induce neurodegenerative-type changes in the brain. However, the factors instantiating risk for neurodegenerative disease following mTBI are unknown. This study examined the link between mTBI and brain derived neurotrophic factor (BDNF) genotype, which has previously been shown to regulate processes involved in neurodegeneration including synaptic plasticity and facilitation of neural survival through its expression. Specifically, we examined nine BDNF single nucleotide polymorphisms (SNPs; rs908867, rs11030094, rs6265, rs10501087, rs1157659, rs1491850, rs11030107, rs7127507, and rs12273363) previously associated with brain atrophy or memory deficits in mTBI. Participants were 165 white, non-Hispanic Iraq and Afghanistan war veterans between the ages of 19 and 58, 110 who had at least one mTBI in their lifetime. Results showed that the BDNF SNP rs1157659 interacted with mTBI to predict hippocampal volume. Further, exploratory analysis of functional resting state data revealed that rs1157659 minor allele homozygotes with a history of mTBI had reduced functional connectivity in the default mode network compared to major allele homozygotes and heterozygotes. Apolipoprotein E (APOE) was not a significant predictor of hippocampal volume or functional connectivity. These results suggest that rs1157659 minor allele homozygotes may be at greater risk for neurodegeneration after exposure to mTBI and provide further evidence for a potential role for BDNF in regulating neural processes following mTBI.

PMID: 28755387 [PubMed - as supplied by publisher]

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer.

Int J Mol Sci. 2017 Jul 21;18(7):

Authors: Senthebane DA, Rowe A, Thomford NE, Shipanga H, Munro D, Mazeedi MAMA, Almazyadi HAM, Kallmeyer K, Dandara C, Pepper MS, Parker MI, Dzobo K

Abstract
Chemoresistance is a leading cause of morbidity and mortality in cancer and it continues to be a challenge in cancer treatment. Chemoresistance is influenced by genetic and epigenetic alterations which affect drug uptake, metabolism and export of drugs at the cellular levels. While most research has focused on tumor cell autonomous mechanisms of chemoresistance, the tumor microenvironment has emerged as a key player in the development of chemoresistance and in malignant progression, thereby influencing the development of novel therapies in clinical oncology. It is not surprising that the study of the tumor microenvironment is now considered to be as important as the study of tumor cells. Recent advances in technological and analytical methods, especially 'omics' technologies, has made it possible to identify specific targets in tumor cells and within the tumor microenvironment to eradicate cancer. Tumors need constant support from previously 'unsupportive' microenvironments. Novel therapeutic strategies that inhibit such microenvironmental support to tumor cells would reduce chemoresistance and tumor relapse. Such strategies can target stromal cells, proteins released by stromal cells and non-cellular components such as the extracellular matrix (ECM) within the tumor microenvironment. Novel in vitro tumor biology models that recapitulate the in vivo tumor microenvironment such as multicellular tumor spheroids, biomimetic scaffolds and tumor organoids are being developed and are increasing our understanding of cancer cell-microenvironment interactions. This review offers an analysis of recent developments on the role of the tumor microenvironment in the development of chemoresistance and the strategies to overcome microenvironment-mediated chemoresistance. We propose a systematic analysis of the relationship between tumor cells and their respective tumor microenvironments and our data show that, to survive, cancer cells interact closely with tumor microenvironment components such as mesenchymal stem cells and the extracellular matrix.

PMID: 28754000 [PubMed - in process]

The association of SCN1A p.Thr1067Ala polymorphism with epilepsy risk and the response to antiepileptic drugs in Slovenian children and adolescents with epilepsy.

Seizure. 2017 Jul 20;51:9-13

Authors: Bertok S, Dolžan V, Goričar K, Podkrajšek KT, Battelino T, Rener-Primec Z

Abstract
PURPOSE: The voltage-gated sodium channel SCN1A mutations are involved in epileptogenesis and may be associated with different epilepsy phenotypes. The SCN1A channel is also an important antiepileptic drug (AED) target. The aim of this study was to investigate if the SCN1A c.3184A>G/p.Thr1067Ala polymorphism modifies the epilepsy risk or is associated with the responsiveness to AEDs in Slovenian children and adolescents with epilepsy.
METHODS: In total, 216 paediatric patients with epilepsy were consecutively recruited during routine outpatient follow-up visits between January 2011 and December 2014. All patients and 95 healthy controls, all Central European Caucasians, were genotyped for the SCN1A c.3184A>G/p.Thr1067Ala polymorphism. Clinical data on all patients were collected retrospectively. The response to AEDs was classified as seizure remission (a minimum of one year of seizure freedom before inclusion) or no remission. Univariate and multivariate logistic regression was used to determine the association of genotypes with binary outcomes.
RESULTS: 114 patients (52.8%) had achieved remission, while 102 (47.2%) had failed to do so. Carriers of at least one polymorphic SCN1A c.3184A>G/p.Thr1067Ala G allele tended to have a lower epilepsy risk (OR=0.38, 95% CI=0.18-0.79, P=0.010) and were significantly more likely to achieve remission (OR=2.00, 95% CI=1.16-3.46, P=0.013). Girls were less likely to achieve remission (P=0.055). Patients in remission tended to be older at first seizure in comparison to the group failing to achieve remission (OR=1.06, 95% CI=0.99-1.14, P=0.099), but this association did not reach statistical significance.
CONCLUSION: The polymorphic SCN1A c.3184A>G/p.Thr1067Ala G allele was associated with a lower risk of epilepsy and a higher remission rate in Slovenian children and adolescents with epilepsy.

PMID: 28753467 [PubMed - as supplied by publisher]

Virus-directed enzyme prodrug therapy and the assessment of the cytotoxic impact of some benzimidazole derivatives.

Tumour Biol. 2017 Jul;39(7):1010428317713675

Authors: Szewczuk M, Boguszewska K, Żebrowska M, Balcerczak E, Stasiak M, Świątkowska M, Błaszczak-Świątkiewicz K

Abstract
Virus-directed enzyme prodrug therapy is one of the major strategy of increasing cytotoxicity of bioreductive agents. This research intended to examine new selected benzimidazole derivatives as a substrate for nitroreductase, the enzyme involved in nitroreduction which is responsible to the production of cytotoxic metabolites. In this way, the selectivity and strength of cytotoxicity can be raised. The effect of benzimidazoles on virus transfected cells and non-virus transfected cells A549 cell line was established by Annexin V + propidium iodide test, western blot, and polymerase chain reaction analysis of specific pro- and anti-apoptotic proteins in the corresponding gene expression and additionally nitroreductase gene expression. Our results proved the pro-apoptotic properties of all tested compounds in normoxia and hypoxia, especially according to virused A549 cells where the time of exposition was reduced from 48 to 4 h. In this shorten period of time, the strongest activity was shown by N-oxide compounds with nitro-groups. The apoptosis was confirmed by generation of BAX gene and protein and reduction of BCL2 gene and protein.

PMID: 28752801 [PubMed - in process]

Possible adverse effects of immunotherapy in non-small cell lung cancer; treatment and follow-up of three cases.

Respir Med Case Rep. 2017;22:101-105

Authors: Zarogoulidis P, Chinelis P, Athanasiadou A, Tsiouda T, Trakada G, Kallianos A, Veletza L, Hatzibougias D, Mihalopoulou E, Goupou E, Kosmidis C, Sardeli C, Huang H, Hohenforst-Schmidt W

Abstract
In the past decade novel agents are on the market for non-small cell lung cancer adenocarcinoma based on pharmacogenomics. The epidermal growth factor receptor mutation, anaplastic lymphoma kinase and programmed death-ligand 1 investigation is necessary in the everyday clinical practice for the oncologic patient. Immunotherapy is nowadays the novel therapy for advanced stage non-small cell lung cancer with two agents nivolumab and pembrolizumab. In the current case series we will present adverse effects from our centers and comment on the treatment and follow-up of the patients.

PMID: 28752057 [PubMed]

Impact of pharmacogenomics upon the therapeutic response to etanercept in psoriasis and psoriatic arthritis.

Expert Opin Drug Saf. 2017 Jul 28;:

Authors: Murdaca G, Negrini S, Magnani O, Penza E, Pellecchio M, Puppo F

Abstract
INTRODUCTION: TNF-α inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases. Etanercept is a decoy receptor" for TNF-α and it is composed of two p75 TNF-α receptors fused to human IgG1. Areas covered: We discuss the potential role of pharmacogenetics in predicting the response to etanercept in patients with Ps and PsA. Expert opinion: Pharmacogenetics represents the new frontier for the discovery of potential genetic markers of biological response to TNF-α inhibitors. Clinical studies showed that TNF-α -308 G/G, +489 GG and the +489 GA, TNF-α -857C (rs1799724), TNFRSF1B 676T (rs1061622), TNFAIP3 G SNP (rs610604), FcγRIIIA-V158F, HLA-C*06, IL-17 A (rs2275913 and rs10484879), IL-17F (rs763780) and IL17RA (rs4819554) SNPs favor the response to etanercept. However, most of these studies are often small and not sufficiently powered to detect an effect and markers tend to be more prognostic than predictive of therapeutic response. Furthermore, studies often examines only the effects of a single SNP, while it would be more useful to analyze more haplotypes in contemporary in the same patients. Appropriately designed clinical trials are needed before a pharmacogenetic approach may be applicable in daily clinical therapeutic practice.

PMID: 28750567 [PubMed - as supplied by publisher]

Gap junction as an intercellular glue: Emerging roles in cancer EMT and metastasis.

Cancer Lett. 2016 Oct 10;381(1):133-7

Authors: Mao XY, Li QQ, Gao YF, Zhou HH, Liu ZQ, Jin WL

Abstract
Metastasis is a common phenomenon in the progression and dissemination of cancer. It is estimated that metastasis accounts for 90% cancer-related mortality. Although the formation of tumor metastasis is relatively well understood, the underlying molecular mechanisms responsible for the emergence of aggressive cancer phenotype are still elusive. Figuring out the mechanisms by which cancer cells evade from the tumor is beneficial for obtaining novel and effectively therapeutic approaches. Primary tumors are composed of various subpopulations of cells with heterogeneous metastatic characteristics and the occurrence of metastatic dissemination is mainly dependent upon the interactions between tumor and the surrounding microenvironment. Tumor microenvironment (TME) such as extracellular matrix, macrophages, fibroblasts, stem cells and endothelial cells can orchestrate events critical to tumor evolution toward metastasis. GJ serves as an important communication between tumor cells and stromal cells. Increased GJs coupling blocks metastatic potential in some cancer animal models such as breast cancer and melanoma. Besides, epithelial-to-mesenchymal transition (EMT) is also a crucial step in the metastatic process and there are signs that GJs contribute to cell adhesion and migration (the pathological feature of EMT) in breast cancer. Therefore, we propose that GJ serves as an intercellular glue to suppress EMT and cancer metastasis.

PMID: 27490999 [PubMed - indexed for MEDLINE]

Bioinformatics Methods and Tools to Advance Clinical Care. Findings from the Yearbook 2015 Section on Bioinformatics and Translational Informatics.

Yearb Med Inform. 2015 Aug 13;10(1):170-3

Authors: Soualmia LF, Lecroq T

Abstract
OBJECTIVES: To summarize excellent current research in the field of Bioinformatics and Translational Informatics with application in the health domain and clinical care.
METHOD: We provide a synopsis of the articles selected for the IMIA Yearbook 2015, from which we attempt to derive a synthetic overview of current and future activities in the field. As last year, a first step of selection was performed by querying MEDLINE with a list of MeSH descriptors completed by a list of terms adapted to the section. Each section editor has evaluated separately the set of 1,594 articles and the evaluation results were merged for retaining 15 articles for peer-review.
RESULTS: The selection and evaluation process of this Yearbook's section on Bioinformatics and Translational Informatics yielded four excellent articles regarding data management and genome medicine that are mainly tool-based papers. In the first article, the authors present PPISURV a tool for uncovering the role of specific genes in cancer survival outcome. The second article describes the classifier PredictSNP which combines six performing tools for predicting disease-related mutations. In the third article, by presenting a high-coverage map of the human proteome using high resolution mass spectrometry, the authors highlight the need for using mass spectrometry to complement genome annotation. The fourth article is also related to patient survival and decision support. The authors present datamining methods of large-scale datasets of past transplants. The objective is to identify chances of survival.
CONCLUSIONS: The current research activities still attest the continuous convergence of Bioinformatics and Medical Informatics, with a focus this year on dedicated tools and methods to advance clinical care. Indeed, there is a need for powerful tools for managing and interpreting complex, large-scale genomic and biological datasets, but also a need for user-friendly tools developed for the clinicians in their daily practice. All the recent research and development efforts contribute to the challenge of impacting clinically the obtained results towards a personalized medicine.

PMID: 26293864 [PubMed - indexed for MEDLINE]

Synthesis, α-glucosidase inhibitory activity and in silico study of tris-indole hybrid scaffold with oxadiazole ring: As potential leads for the management of type-II diabetes mellitus.

Bioorg Chem. 2017 Jul 18;74:30-40

Authors: Taha M, Rahim F, Imran S, Ismail NH, Ullah H, Selvaraj M, Javid MT, Salar U, Ali M, Khan KM

Abstract
Discovery of α-glucosidase inhibitors has been actively pursued with the aim to develop therapeutics for the treatment of type-II diabetes mellitus and the other carbohydrate mediated disease. In continuation of our drug discovery research on potential antidiabetic agents, we synthesized novel tris-indole-oxadiazole hybrid analogs (1-21), structurally characterized by various spectroscopic techniques such as (1)H NMR, EI-MS, and (13)C NMR. Elemental analysis was found in agreement with the calculated values. All compounds were evaluated for α-glucosidase inhibiting potential and showed potent inhibitory activity in the range of IC50=2.00±0.01-292.40±3.16μM as compared to standard acarbose (IC50=895.09±2.04µM). The pharmacokinetic predictions of tris-indole series using descriptor properties showed that almost all compounds in this series indicate the drug aptness. Detailed binding mode analyses with docking simulation was also carried out which showed that the inhibitors can be stabilized by the formation of hydrogen bonds with catalytic residues and the establishment of hydrophobic contacts at the opposite side of the active site.

PMID: 28750203 [PubMed - as supplied by publisher]

DPP4 gene variation affects GLP-1 secretion, insulin secretion, and glucose tolerance in humans with high body adiposity.

PLoS One. 2017;12(7):e0181880

Authors: Böhm A, Wagner R, Machicao F, Holst JJ, Gallwitz B, Stefan N, Fritsche A, Häring HU, Staiger H

Abstract
OBJECTIVE: Dipeptidyl-peptidase 4 (DPP-4) cleaves and inactivates the insulinotropic hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide, collectively termed incretins. DPP-4 inhibitors entered clinical practice as approved therapeutics for type-2 diabetes in 2006. However, inter-individual variance in the responsiveness to DPP-4 inhibitors was reported. Thus, we asked whether genetic variation in the DPP4 gene affects incretin levels, insulin secretion, and glucose tolerance in participants of the TÜbingen Family study for type-2 diabetes (TÜF).
RESEARCH DESIGN AND METHODS: Fourteen common (minor allele frequencies ≥0.05) DPP4 tagging single nucleotide polymorphisms (SNPs) were genotyped in 1,976 non-diabetic TÜF participants characterized by oral glucose tolerance tests and bioimpedance measurements. In a subgroup of 168 subjects, plasma incretin levels were determined.
RESULTS: We identified a variant, i.e., SNP rs6741949, in intron 2 of the DPP4 gene that, after correction for multiple comparisons and appropriate adjustment, revealed a significant genotype-body fat interaction effect on glucose-stimulated plasma GLP-1 levels (p = 0.0021). Notably, no genotype-BMI interaction effects were detected (p = 0.8). After stratification for body fat content, the SNP negatively affected glucose-stimulated GLP-1 levels (p = 0.0229), insulin secretion (p = 0.0061), and glucose tolerance (p = 0.0208) in subjects with high body fat content only.
CONCLUSIONS: A common variant, i.e., SNP rs6741949, in the DPP4 gene interacts with body adiposity and negatively affects glucose-stimulated GLP-1 levels, insulin secretion, and glucose tolerance. Whether this SNP underlies the reported inter-individual variance in responsiveness to DPP-4 inhibitors, at least in subjects with high body fat content, remains to be shown.

PMID: 28750074 [PubMed - in process]

Patient Decisions to Receive Secondary Pharmacogenomic Findings and Development of a Multidisciplinary Practice Model to Integrate Results Into Patient Care.

Clin Transl Sci. 2017 Jul 27;:

Authors: Hicks JK, Shealy A, Schreiber A, Coleridge M, Noss R, Natowicz M, Moran R, Moss T, Erwin A, Eng C

Abstract
Whole exome sequencing (WES) has the potential of identifying secondary findings that are predictive of poor pharmacotherapy outcomes. The purpose of this study was to investigate patients' wishes regarding the reporting of secondary pharmacogenomic findings. WES results (n = 106 patients) were retrospectively reviewed to determine the number of patients electing to receive secondary pharmacogenomic results. Phenotypes were assigned based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. The percent of patients with a predicted phenotype associated with a gene-based CPIC dosing recommendation was determined. Ninety-nine patients (93.4%) elected to receive secondary pharmacogenomic findings. For each gene-drug pair analyzed, the number of patients with an actionable phenotype ranged from two (2%) to 43 patients (43.4%). Combining all gene-drug pairs, 84 unique patients (84.8%) had an actionable phenotype. A prospective multidisciplinary practice model was developed for integrating secondary pharmacogenomic findings into clinical practice. Our model highlights a unique collaboration between physician-geneticists, pharmacists, and genetic counselors.

PMID: 28749586 [PubMed - as supplied by publisher]

Clinical applications of pharmacogenomics.

Rev Med Chil. 2017 Apr;145(4):483-500

Authors: Quiñones L, Roco Á, Cayún JP, Escalante P, Miranda C, Varela N, Meneses F, Gallegos B, Zaruma-Torres F, Lares-Asseff I

Abstract
Pharmacogenomics is an emergent field aimed at tailoring pharmacological therapy. Genetic polymorphisms can modify the expression and function of enzymes and proteins involved in drug metabolism, affecting absorption, distribution, biotransformation and excretion as well as the drug-target interaction. Therefore, the presence of allelic variants will classify people as poor, extensive or rapid/ultra rapid metabolizers, modifying drug efficacy and safety. In this work, the state of art in relation to this discipline is presented and the genetic variants of enzymes that are involved in drug pharmacokinetics or pharmacodynamics are described. The effects of these variants on the therapeutic response to drugs used in our country are also discussed.

PMID: 28748996 [PubMed - in process]

Implementing pharmacogenomics in modern health care: The 2017 scientific meeting of the Human Genome Variation Society.

Hum Mutat. 2017 Jul 27;:

Authors: Lanting P, Oetting WS

PMID: 28748604 [PubMed - as supplied by publisher]

Impact of Genetic Polymorphisms on Phenytoin Pharmacokinetics and Clinical Outcomes in the Middle East and North Africa Region.

Drugs R D. 2017 Jul 26;:

Authors: Dagenais R, Wilby KJ, Elewa H, Ensom MHH

Abstract
BACKGROUND: Genetic polymorphisms are known to influence outcomes with phenytoin yet effects in the Middle East and North Africa region are poorly understood.
OBJECTIVES: The objective of this systematic review was to evaluate the impact of genetic polymorphisms on phenytoin pharmacokinetics and clinical outcomes in populations originating from the Middle East and North Africa region, and to characterize genotypic and allelic frequencies within the region for genetic polymorphisms assessed.
METHODS: MEDLINE (1946-3 May, 2017), EMBASE (1974-3 May, 2017), Pharmacogenomics Knowledge Base, and Public Health Genomics Knowledge Base online databases were searched. Studies were included if genotyping and analyses of phenytoin pharmacokinetics were performed in patients of the Middle East and North Africa region. Study quality was assessed using a National Institutes of Health assessment tool. A secondary search identified studies reporting genotypic and allelic frequencies of assessed genetic polymorphisms within the Middle East and North Africa region.
RESULTS: Five studies met the inclusion criteria. CYP2C9, CYP2C19, and multidrug resistance protein 1 C3435T variants were evaluated. While CYP2C9*2 and *3 variants significantly reduced phenytoin metabolism, the impacts of CYP2C19*2 and *3 variants were unclear. The multidrug resistance protein 1 CC genotype was associated with drug-resistant epilepsy, but reported impacts on phenytoin pharmacokinetics were conflicting. Appreciable variability in minor allele frequencies existed both between and within countries of the Middle East and North Africa region.
CONCLUSIONS: CYP2C9 decrease-of-function alleles altered phenytoin pharmacokinetics in patients originating from the Middle East and North Africa region. The impacts of CYP2C19 and multidrug resistance protein 1 C3435T variants on phenytoin pharmacokinetic and clinical outcomes are unclear and require further investigation. Future research should focus on the clinical outcomes associated with phenytoin therapy. PROSPERO 2017: CRD42017057850.

PMID: 28748348 [PubMed - as supplied by publisher]

Editorial.

Therapie. 2017 Apr;72(2):173-174

Authors: Becquemont L, Picard N, Verstuyft C

PMID: 28238399 [PubMed - indexed for MEDLINE]

17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

pharmacogenomics

These pubmed results were generated on 2017/07/27

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Single Nucleotide Polymorphisms in Genes MACC1, RAD18, MMP7 and SDF-1a As Prognostic Factors in Resectable Colorectal Cancer.

Radiol Oncol. 2017 Jun;51(2):151-159

Authors: Horvat M, Potocnik U, Repnik K, Kavalar R, Zadnik V, Potrc S, Stabuc B

Abstract
BACKGROUND: Colorectal cancer (CRC) represents one of the most common malignancies worldwide. Research has indicated that functional gene changes such as single nucleotide polymorphism (SNP) influence carcinogenesis and metastasis and might have an influence on disease relapse. The aim of our study was to evaluate the role of SNPs in selected genes as prognostic markers in resectable CRC.
PATIENTS AND METHODS: In total, 163 consecutive patients treated surgically for CRC of stages I, II and III at the University Medical Centre in Maribor in 2007 and 2008 were investigated. DNA was isolated from formalin-fixed paraffin-embedded CRC tissue from the Department of Pathology and SNPs in genes SDF-1a, MMP7, RAD18 and MACC1 were genotyped using polymerase chain reaction followed by high resolution melting curve analysis or restriction fragment length polymorphism.
RESULTS: We found worse disease-free survival (DFS) for patients with TT genotype of SNP rs1990172 in gene MACC1 (p = 0.029). Next, we found worse DFS for patients with GG genotype for SNP rs373572 in gene RAD18 (p = 0.020). Higher frequency of genotype GG of MMP7 SNP rs11568818 was found in patients with T3/T4 stage (p = 0.014), N1/N2 stage (p = 0.041) and with lymphovascular invasion (p = 0.018). For MACC1 rs1990172 SNP we found higher frequency of genotype TT in patients with T3/T4 staging (p = 0.024). Higher frequency of genotype GG of RAD18 rs373572 was also found in patients with T1/T2 stage with disease relapse (p = 0.041).
CONCLUSIONS: Our results indicate the role of SNPs as prognostic factors in resectable CRC.

PMID: 28740450 [PubMed]

A distinct plasma lipid signature associated with poor prognosis in castration-resistant prostate cancer: Authors.

Int J Cancer. 2017 Jul 25;:

Authors: Lin HM, Mahon KL, Weir JM, Mundra PA, Spielman C, Briscoe K, Gurney H, Mallesara G, Marx G, Stockler MR, Consortium P, Parton RG, Hoy AJ, Daly RJ, Meikle PJ, Horvath LG

Abstract
Lipids are known to influence tumour growth, inflammation, and chemoresistance. However, the association of circulating lipids with the clinical outcome of metastatic castration-resistant prostate cancer (CRPC) is unknown. We investigated associations between the plasma lipidome and clinical outcome in CRPC. Lipidomic profiling by liquid chromatography-tandem mass spectrometry was performed on plasma samples from a Phase 1 discovery cohort of 96 CRPC patients. Results were validated in an independent Phase 2 cohort of 63 CRPC patients. Unsupervised analysis of lipidomic profiles (323 lipid species) classified the Phase 1 cohort into two patient subgroups with significant survival differences (HR 2.31, 95% CI 1.44-3.68, P=0.0005). The levels of 46 lipids were individually prognostic, and were predominantly sphingolipids with higher levels associated with poor prognosis. A prognostic three-lipid signature was derived (ceramide d18:1/24:1, sphingomyelin d18:2/16:0, phosphatidylcholine 16:0/16:0), and was also associated with shorter survival in the Phase 2 cohort (HR 4.8, 95% CI 2.06-11.1, P=0.0003). The signature was an independent prognostic factor when modelled with clinicopathological factors or metabolic characteristics. The association of plasma lipids with CRPC prognosis suggests a possible role of these lipids in disease progression. Further research is required to determine if therapeutic modulation of the levels of these lipids by targeting their metabolic pathways may improve patient outcome. This article is protected by copyright. All rights reserved.

PMID: 28741687 [PubMed - as supplied by publisher]

The Pharmacogenomic and Metabolomic Predictors of ACE Inhibitor and Angiotensin II Receptor Blocker Effectiveness and Safety.

Cardiovasc Drugs Ther. 2017 Jul 24;:

Authors: Flaten HK, Monte AA

Abstract
Hypertension (HTN) is the most common chronic disease in the USA. Hypertensive patients frequently require repeat primary care visits to find an effective drug or drug combination to control their disease. Currently, patients are prescribed drugs for HTN based on race, age, and comorbidities and although the current guidelines are reasonable starting points for prescribing, 50% of hypertensive patients still fail to achieve target blood pressures. Despite numerous strategies to improve compliance, drug effectiveness, and optimization of initial drug choice, effectiveness has remained largely unchanged over the past two decades. Therefore, it is important to pursue alternative strategies to more effectively treat patients and to decrease medical costs. Additional precision medicine work is needed to identify factors associated with effectiveness of commonly used antihypertensive medications. The objective of this manuscript is to present a comprehensive review of the pharmacogenomic and metabolomic factors associated with ACEI and ARB effectiveness and safety.

PMID: 28741243 [PubMed - as supplied by publisher]