New Immunotherapy Strategies in Breast Cancer.

Int J Environ Res Public Health. 2017 Jan 12;14(1):

Authors: Yu LY, Tang J, Zhang CM, Zeng WJ, Yan H, Li MP, Chen XP

Abstract
Breast cancer is the most commonly diagnosed cancer among women. Therapeutic treatments for breast cancer generally include surgery, chemotherapy, radiotherapy, endocrinotherapy and molecular targeted therapy. With the development of molecular biology, immunology and pharmacogenomics, immunotherapy becomes a promising new field in breast cancer therapies. In this review, we discussed recent progress in breast cancer immunotherapy, including cancer vaccines, bispecific antibodies, and immune checkpoint inhibitors. Several additional immunotherapy modalities in early stages of development are also highlighted. It is believed that these new immunotherapeutic strategies will ultimately change the current status of breast cancer therapies.

PMID: 28085094 [PubMed - in process]

Donors FMO3 polymorphisms affect tacrolimus elimination in Chinese liver transplant patients.

Pharmacogenomics. 2017 Jan 13;:

Authors: Ren L, Teng M, Zhang T, Zhang X, Sun B, Qin S, Zhong L, Peng Z, Fan J

Abstract
AIM: Flavin-containing monooxygenase (FMO) variants were potentially involved in tacrolimus metabolism in kidney transplantion. The influences of FMO3 genotypes on tacrolimus elimination in Chinese liver transplant patients remained unclear.
PATIENTS & METHODS: FMO3 SNPs and CYP3A5 rs776746 were analyzed in 110 Chinese patients.
RESULTS: Donor FMO3 rs1800822 allele T and rs909530 allele T were associated with fast tacrolimus elimination. Combination of polymorphisms of donor FMO3 rs1800822 and rs909530 genotype impacted on tacrolimus elimination (p = 0.0221). The number of donor rs1800822 allele T and rs909530 allele T was confirmed to be an independent predictor of the tacrolimus concentration to dose ratios for weeks 2, 3 and 4 in the multivariate analysis.
CONCLUSION: Donor's FMO3 polymorphisms might affect tacrolimus elimination.

PMID: 28084894 [PubMed - as supplied by publisher]

Pharmacogenomics in epilepsy.

Neurosci Lett. 2017 Jan 09;:

Authors: Balestrini S, Sisodiya SM

Abstract
There is high variability in the response to antiepileptic treatment across people with epilepsy. Genetic factors significantly contribute to such variability. Recent advances in the genetics and neurobiology of the epilepsies are establishing the basis for a new era in the treatment of epilepsy, focused on each individual and their specific epilepsy. Variation in response to antiepileptic drug treatment may arise from genetic variation in a range of gene categories, including genes affecting drug pharmacokinetics, and drug pharmacodynamics, but also genes held to actually cause the epilepsy itself. From a purely pharmacogenetic perspective, there are few robust genetic findings with established evidence in epilepsy. Many findings are still controversial with anecdotal or less secure evidence and need further validation, e.g. variation in genes for transporter systems and antiepileptic drug targets. The increasing use of genetic sequencing and the results of large-scale collaborative projects may soon expand the established evidence. Precision medicine treatments represent a growing area of interest, focussing on reversing or circumventing the pathophysiological effects of specific gene mutations. This could lead to a dramatic improvement of the effectiveness and safety of epilepsy treatments, by targeting the biological mechanisms responsible for epilepsy in each specific individual. Whilst much has been written about epilepsy pharmacogenetics, there does now seem to be building momentum that promises to deliver results of use in clinic.

PMID: 28082152 [PubMed - as supplied by publisher]

Engaging Hmong adults in genomic and pharmacogenomic research: Toward reducing health disparities in genomic knowledge using a community-based participatory research approach.

J Community Genet. 2017 Jan 10;:

Authors: Culhane-Pera KA, Straka RJ, Moua M, Roman Y, Vue P, Xiaaj K, Lo MX, Lor M

Abstract
Advancing precision medicine relies in part on examining populations that may exhibit unique genetic variants that impact clinical outcomes. Failure to include diverse populations in genomic-based research represents a health disparity. We implemented a community-based participatory research (CBPR) process with the Hmong community in Minnesota, who were refugees from Laos, in order to assess the feasibility of conducting genomic and pharmacogenomic-based research for genetic variants that are relevant to the Hmong community. Our Hmong Genomics Board, consisting of Hmong and non-Hmong professionals, used CBPR principles and built on previous formative research to create and implement culturally and linguistically appropriate informed consent processes for Hmong people at six community venues. The Board chose genetic variants for diabetes risk and warfarin response as relevant to the community. The Institutional Review Board approved aggregate but not individual return of results. Two hundred thirty-seven Hmong participants with mean (range) age of 30.2 (18-81) years and diverse levels of education (22% without and 75% with high-school education) provided saliva for genetic (DNA) analyses. Eighty-five percent of participants agreed to store DNA for future analyses, 82% agreed to share DNA with other researchers, and 78% agreed to be contacted for future studies. Twenty-five elders refused to participate because they wanted individual results. Aggregate results were shared with all participants. This CBPR approach proved highly successful to obtain informed consent and recruit a sample from the Hmong community for a genomic and pharmacogenomic study. Investment in the CBPR process may prove successful to address the gap of genomic information in under-represented communities.

PMID: 28074382 [PubMed - as supplied by publisher]

Characterizing pharmacogenomic-guided medication use with a clinical data repository.

Clin Pharmacol Ther. 2017 Jan 10;:

Authors: Mathias PC, Hendrix N, Wang WJ, Keyloun K, Khelifi M, Tarczy-Hornoch P, Devine B

Abstract
The extent to which pharmacogenomic-guided medication use has been adopted in various health systems is unclear. To assess the uptake of pharmacogenomic-guided medication use, we determined its frequency across our health system, which does not have a structured testing program. Using a multi-site clinical data repository, we identified adult patients' first prescribed medications between January 2011 and December 2013 and investigated the frequency of germline and somatic pharmacogenomic testing, by PharmGKB level of FDA label information. There were 268,262 medication orders for drugs with germline pharmacogenomic testing information in their drug labels. Pharmacogenomic testing was detected for 1.5% (129/8,718) of medication orders with recommended or required testing. Of the 3,817 medication orders associated with somatic pharmacogenomic testing information in their drug labels, 20% (372/1,819) of required tests were detected. The low rates of detectable pharmacogenomic testing suggest that structured testing programs are required to achieve the success of precision medicine. This article is protected by copyright. All rights reserved.

PMID: 28073152 [PubMed - as supplied by publisher]

A review of connectivity map and computational approaches in pharmacogenomics.

Brief Bioinform. 2017 Jan 09;:

Authors: Musa A, Ghoraie LS, Zhang SD, Galzko G, Yli-Harja O, Dehmer M, Haibe-Kains B, Emmert-Streib F

Abstract
Large-scale perturbation databases, such as Connectivity Map (CMap) or Library of Integrated Network-based Cellular Signatures (LINCS), provide enormous opportunities for computational pharmacogenomics and drug design. A reason for this is that in contrast to classical pharmacology focusing at one target at a time, the transcriptomics profiles provided by CMap and LINCS open the door for systems biology approaches on the pathway and network level. In this article, we provide a review of recent developments in computational pharmacogenomics with respect to CMap and LINCS and related applications.

PMID: 28069634 [PubMed - as supplied by publisher]

Norepinephrine Transporter Gene Variants and Remission From Depression With Venlafaxine Treatment in Older Adults.

Am J Psychiatry. 2017 Jan 10;:appiajp201616050617

Authors: Marshe VS, Maciukiewicz M, Rej S, Tiwari AK, Sibille E, Blumberger DM, Karp JF, Lenze EJ, Reynolds CF, Kennedy JL, Mulsant BH, Müller DJ

Abstract
OBJECTIVE: The primary objective of this study was to investigate five putatively functional variants of the norepinephrine transporter (SLC6A2, NET) and serotonin transporter (SLC6A4, SERT) genes and remission in depressed older adults treated with venlafaxine. A secondary objective was to analyze 17 other variants in serotonergic system genes (HTR1A, HTR2A, HTR1B, HTR2C, TPH1, TPH2) potentially involved in the mechanism of action of venlafaxine.
METHOD: The sample included 350 adults age 60 or older with DSM-IV-defined major depressive disorder and a score of at least 15 on the Montgomery-Åsberg Depression Rating Scale (MADRS). Participants received protocolized treatment with open-label venlafaxine, up to 300 mg/day for approximately 12 weeks, as part of a three-site clinical trial. Each individual was genotyped for 22 polymorphisms in eight genes, which were tested for association with venlafaxine remission (a MADRS score ≤10) and changes in MADRS score during treatment.
RESULTS: After adjusting for multiple comparisons, NET variant rs2242446 (T-182C) was significantly associated with remission (odds ratio=1.66, 95% CI=1.13, 2.42). Individuals with the rs2242446 C/C genotype were more likely to remit (73.1%) than those with either the C/T (51.8%) or the T/T genotype (47.3%). Individuals with the C/C genotype also had a shorter time to remission than those with the C/T or T/T genotypes and had a greater percentage change in MADRS score from baseline to end of treatment (up to week 12).
CONCLUSIONS: NET rs2242446/T-182C may serve as a biomarker to predict the likelihood of remission with venlafaxine in older adults with major depression. These findings may help to optimize antidepressant outcomes in older adults.

PMID: 28068779 [PubMed - as supplied by publisher]

Does Pharmacogenomic Testing Improve Clinical Outcomes for Major Depressive Disorder? A Systematic Review of Clinical Trials and Cost-Effectiveness Studies.

J Clin Psychiatry. 2017 Jan 03;:

Authors: Rosenblat JD, Lee Y, McIntyre RS

Abstract
OBJECTIVE: Pharmacogenomic testing has become scalable and available to the general public. Pharmacogenomics has shown promise for predicting antidepressant response and tolerability in the treatment of major depressive disorder (MDD). In theory, pharmacogenomics can improve clinical outcomes by guiding antidepressant selection and dosing. The current systematic review examines the extant literature to determine the impact of pharmacogenomic testing on clinical outcomes in MDD and assesses its cost-effectiveness.
DATA SOURCES: The MEDLINE/PubMed and Google Scholar databases were systematically searched for relevant articles published prior to October 2015. Search terms included various combinations of the following: major depressive disorder (MDD), depression, mental illness, mood disorder, antidepressant, response, remission, outcome, pharmacogenetic, pharmacogenomics, pharmacodynamics, pharmacokinetic, genetic testing, genome wide association study (GWAS), CYP450, personalized medicine, cost-effectiveness, and pharmacoeconomics.
STUDY SELECTION: Of the 66 records identified from the initial search, relevant clinical studies, written in English, assessing the cost-effectiveness and/or efficacy of pharmacogenomic testing for MDD were included.
DATA EXTRACTION: Each publication was critically examined for relevant data.
RESULTS: Two nonrandomized, open-label, 8-week, prospective studies reported overall greater improvement in depressive symptom severity in the group of MDD subjects receiving psychiatric care guided by results of combinatorial pharmacogenomic testing (GeneSight) when compared to the unguided group. One industry-sponsored, randomized, double-blind, 10-week prospective study reported a trend for improved outcomes for the GeneSight-guided group; however, the trend did not reach statistical significance. Another industry-sponsored, randomized, double-blind, 12-week prospective study reported a 2.5-fold increase in remission rates in the CNSDose-guided group (P < .0001). One naturalistic, unblinded, industry-sponsored study showed clinical improvement when pharmacogenomics testing guided prescribing; however, this study lacked a control group. A single cost-effectiveness study concluded that single gene testing was not cost-effective. Conversely, a separate study reported that combinatorial pharmacogenomic testing is cost-effective.
CONCLUSIONS: A limited number of studies have shown promise for the clinical utility of pharmacogenomic testing; however, cost-effectiveness of pharmacogenomics, as well as demonstration of improved health outcomes, is not yet supported with replicated evidence.

PMID: 28068459 [PubMed - as supplied by publisher]

A Novel Sensitive Method to Measure Catechol-O-Methyltransferase Activity Unravels the Presence of This Activity in Extracellular Vesicles Released by Rat Hepatocytes.

Front Pharmacol. 2016;7:501

Authors: Casal E, Palomo L, Cabrera D, Falcon-Perez JM

Abstract
There is a clear need for drug treatments to be selected according to the characteristics of an individual patient, in order to improve efficacy and reduce the number and severity of adverse drug reactions. One of the main enzymes to take into account in pharmacogenomics is catechol O-methyltransferase (COMT), which catalyzes the transfer of a methyl group from S-adenosylmethionine to catechols and catecholamines, like the neurotransmitters dopamine, epinephrine, and norepinephrine. Although, most of this enzyme is associated to intracellular vesicles, recently it has also been detected in extracellular vesicles secreted by hepatocytes and in serum circulating vesicles. COMT has implications in many neurological and psychiatric disorders like Parkinson's disease, chronic fatigue, pain response, schizophrenia, and bipolar disorders. Remarkably, genetic variations of COMT affect its activity and are associated to various human disorders from psychiatric diseases to estrogen-induced cancers. Consequently, the establishment of new methods to evaluate COMT activity is an important aspect to investigate the biology of this drug-metabolizing enzyme. Herein, we have developed a sensitive and selective method to determine COMT activity. We first optimized the activity in rat liver incubated with two different substrates; norepinephrine and dopamine. The enzymatically formed products (normetanephrine and 3-methoxytyramine, respectively) were extracted by solid-phase extraction using weak cation exchange cartridges, chromatographically separated, and detected and quantified using a mass spectrometer. The range of quantitation for both products was from 0.005 to 25 μg/mL. This methodology offers acceptable recovery for both enzymatic products (≥75%) and good accuracy and precision (≤15%). The lower limit of quantifications were 0.01 and 0.005 μM for 3-methoxytyramine and normetanephrine, respectively. Importantly, this sensitive assay was able to detect the presence of COMT activity in extracellular vesicles secreted by hepatocytes supporting a potential role of these vesicles in catecholamines and catecholestrogens metabolisms. In addition, the presence of COMT activity in extracellular vesicles opens new possibilities to develop tools to evaluate personalized drug response in a low invasive manner.

PMID: 28066248 [PubMed - in process]

Primer design for SNP genotyping based on allele-specific amplification-Application to organ transplantation pharmacogenomics.

J Pharm Biomed Anal. 2016 Dec 29;136:14-21

Authors: Tortajada-Genaro LA, Puchades R, Maquieira Á

Abstract
Diagnostic methods based on single nucleotide polymorphism (SNP) biomarkers are essential for the real adoption of personalized medicine. Allele specific amplification in a homogeneous format or combined to microarray hybridization are powerful approaches for SNP genotyping. However, primers must be properly selected to minimize cross-reactivity, dimer formation and nonspecific hybridization. This study presents a design workflow diagram for the selection of required oligonucleotides for multiplex assays. Based on thermodynamic restrictions, the oligonucleotide sets are chosen for a specific amplification of wild- and mutant-type templates. Design constraints include the structural stability of primer-template duplexes, template-probe duplexes and self-annealing complexes or hairpins for each targeted gene. The performance of the design algorithm was evaluated for the simultaneous genotyping of three SNPs related to immunosuppressive drugs administered after solid organ transplantation. The assayed polymorphisms were rs1045642 (ABCB1 gene), rs1801133 (MTHFR gene) and rs776746 (CYP3A5 gene). Candidates were confirmed by discriminating homozygote and heterozygote populations using a fluorescence solution method and two colorimetric microarray methods on polycarbonate chips. The analysis of patient samples provided excellent genotyping results compared to those obtained by a reference method. The study demonstrates that the development of the allele-specific methods as pharmacogenetic tools can be simplified.

PMID: 28061365 [PubMed - as supplied by publisher]

Nontraditional Career Opportunities for Pharmacists.

Hosp Pharm. 2016 Dec;51(11):944-949

Authors: Bai S, Hertig JB, Weber RJ

Abstract
The changing landscape of health care mirrors that of health-system pharmacy, with pharmacists' scope of practice and provider status being the most significant changes. This creates new roles and opportunities; many of these roles are considered to be nontraditional in today's practice. This article reviews some new roles for pharmacy leaders that provide different career options and pathways. Nontraditional career opportunities discussed include expanded consulting roles in pricing analytics and drug pricing programs (contracting, 340B programs), pharmacogenomics patient consult services and clinics, specialty drug pharmacies, and compounding pharmacy services. To continue to develop high-performing pharmacy departments, pharmacy directors should recognize these roles and ensure they are clearly defined and managed. With the advent of these nontraditional opportunities, pharmacy departments can further expand their ability to provide advanced patient-centered pharmacy services.

PMID: 28057956 [PubMed - in process]

Genomic translational research: Paving the way to individualized cardiac functional analyses and personalized cardiology.

Int J Cardiol. 2016 Dec 21;:

Authors: Pasipoularides A

Abstract
For most of Medicine's past, the best that physicians could do to cope with disease prevention and treatment was based on the expected response of an average patient. Currently, however, a more personalized/precise approach to cardiology and medicine in general is becoming possible, as the cost of sequencing a human genome has declined substantially. As a result, we are witnessing an era of precipitous advances in biomedicine and bourgeoning understanding of the genetic basis of cardiovascular and other diseases, reminiscent of the resurgence of innovations in physico-mathematical sciences and biology-anatomy-cardiology in the Renaissance, a parallel time of radical change and reformation of medical knowledge, education and practice. Now on the horizon is an individualized, diverse patient-centered, approach to medical practice that encompasses the development of new, gene-based diagnostics and preventive medicine tactics, and offers the broadest range of personalized therapies based on pharmacogenetics. Over time, translation of genomic and high-tech approaches unquestionably will transform clinical practice in cardiology and medicine as a whole, with the adoption of new personalized medicine approaches and procedures. Clearly, future prospects far outweigh present accomplishments, which are best viewed as a promising start. It is now essential for pluridisciplinary health care providers to examine the drivers and barriers to the clinical adoption of this emerging revolutionary paradigm, in order to expedite the realization of its potential. So, we are not there yet, but we are definitely on our way.

PMID: 28057368 [PubMed - as supplied by publisher]

Participant-perceived understanding and perspectives on pharmacogenomics: the Mayo Clinic RIGHT protocol (Right Drug, Right Dose, Right Time).

Genet Med. 2017 Jan 05;:

Authors: Olson JE, Rohrer Vitek CR, Bell EJ, McGree ME, Jacobson DJ, St Sauver JL, Caraballo PJ, Griffin JM, Roger VL, Bielinski SJ

Abstract
PURPOSE: To examine predictors of understanding preemptive CYP2D6 pharmacogenomics test results and to identify key features required to improve future educational efforts of preemptive pharmacogenomics testing.
METHODS: One thousand ten participants were surveyed after receiving preemptive CYP2D6 pharmacogenomics test results.
RESULTS: Eighty-six percent (n = 869) of patients responded. Of the responders, 98% were white and 55% were female; 57% had 4 years or more of post-secondary education and an average age of 58.9 ± 5.5 years. Twenty-six percent said that they only somewhat understood their results and 7% reported they did not understand them at all. Only education predicted understanding. The most common suggestion for improvement was the use of layperson's terms when reporting results. In addition, responders suggested that results should be personalized by referring to medications that they were currently using. Of those reporting imperfect drug adherence, most (91%) reported they would be more likely to use medication as prescribed if pharmacogenomic information was used to help select the drug or dose.
CONCLUSION: Despite great efforts to simplify pharmacogenomic results (or because of them), approximately one-third of responders did not understand their results. Future efforts need to provide more examples and tailor results to the individual. Incorporation of pharmacogenomics is likely to improve medication adherence.Genet Med advance online publication 05 January 2017Genetics in Medicine (2017); doi:10.1038/gim.2016.192.

PMID: 28055020 [PubMed - as supplied by publisher]

Psychological and behavioural impact of returning personal results from whole-genome sequencing: the HealthSeq project.

Eur J Hum Genet. 2017 Jan 04;:

Authors: Sanderson SC, Linderman MD, Suckiel SA, Zinberg R, Wasserstein M, Kasarskis A, Diaz GA, Schadt EE

Abstract
Providing ostensibly healthy individuals with personal results from whole-genome sequencing could lead to improved health and well-being via enhanced disease risk prediction, prevention, and diagnosis, but also poses practical and ethical challenges. Understanding how individuals react psychologically and behaviourally will be key in assessing the potential utility of personal whole-genome sequencing. We conducted an exploratory longitudinal cohort study in which quantitative surveys and in-depth qualitative interviews were conducted before and after personal results were returned to individuals who underwent whole-genome sequencing. The participants were offered a range of interpreted results, including Alzheimer's disease, type 2 diabetes, pharmacogenomics, rare disease-associated variants, and ancestry. They were also offered their raw data. Of the 35 participants at baseline, 29 (82.9%) completed the 6-month follow-up. In the quantitative surveys, test-related distress was low, although it was higher at 1-week than 6-month follow-up (Z=2.68, P=0.007). In the 6-month qualitative interviews, most participants felt happy or relieved about their results. A few were concerned, particularly about rare disease-associated variants and Alzheimer's disease results. Two of the 29 participants had sought clinical follow-up as a direct or indirect consequence of rare disease-associated variants results. Several had mentioned their results to their doctors. Some participants felt having their raw data might be medically useful to them in the future. The majority reported positive reactions to having their genomes sequenced, but there were notable exceptions to this. The impact and value of returning personal results from whole-genome sequencing when implemented on a larger scale remains to be seen.European Journal of Human Genetics advance online publication, 4 January 2017; doi:10.1038/ejhg.2016.178.

PMID: 28051073 [PubMed - as supplied by publisher]

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Pharmacogenomics[Title/Abstract]

These pubmed results were generated on 2017/01/04

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A genome-wide interaction analysis of tricyclic/tetracyclic antidepressants and RR and QT intervals: a pharmacogenomics study from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.

J Med Genet. 2016 Dec 30;:

Authors: Noordam R, Sitlani CM, Avery CL, Stewart JD, Gogarten SM, Wiggins KL, Trompet S, Warren HR, Sun F, Evans DS, Li X, Li J, Smith AV, Bis JC, Brody JA, Busch EL, Caulfield MJ, Chen YI, Cummings SR, Cupples LA, Duan Q, Franco OH, Méndez-Giráldez R, Harris TB, Heckbert SR, van Heemst D, Hofman A, Floyd JS, Kors JA, Launer LJ, Li Y, Li-Gao R, Lange LA, Lin HJ, de Mutsert R, Napier MD, Newton-Cheh C, Poulter N, Reiner AP, Rice KM, Roach J, Rodriguez CJ, Rosendaal FR, Sattar N, Sever P, Seyerle AA, Slagboom PE, Soliman EZ, Sotoodehnia N, Stott DJ, Stürmer T, Taylor KD, Thornton TA, Uitterlinden AG, Wilhelmsen KC, Wilson JG, Gudnason V, Jukema JW, Laurie CC, Liu Y, Mook-Kanamori DO, Munroe PB, Rotter JI, Vasan RS, Psaty BM, Stricker BH, Whitsel EA

Abstract
BACKGROUND: Increased heart rate and a prolonged QT interval are important risk factors for cardiovascular morbidity and mortality, and can be influenced by the use of various medications, including tricyclic/tetracyclic antidepressants (TCAs). We aim to identify genetic loci that modify the association between TCA use and RR and QT intervals.
METHODS AND RESULTS: We conducted race/ethnic-specific genome-wide interaction analyses (with HapMap phase II imputed reference panel imputation) of TCAs and resting RR and QT intervals in cohorts of European (n=45 706; n=1417 TCA users), African (n=10 235; n=296 TCA users) and Hispanic/Latino (n=13 808; n=147 TCA users) ancestry, adjusted for clinical covariates. Among the populations of European ancestry, two genome-wide significant loci were identified for RR interval: rs6737205 in BRE (β=56.3, pinteraction=3.9e(-9)) and rs9830388 in UBE2E2 (β=25.2, pinteraction=1.7e(-8)). In Hispanic/Latino cohorts, rs2291477 in TGFBR3 significantly modified the association between TCAs and QT intervals (β=9.3, pinteraction=2.55e(-8)). In the meta-analyses of the other ethnicities, these loci either were excluded from the meta-analyses (as part of quality control), or their effects did not reach the level of nominal statistical significance (pinteraction>0.05). No new variants were identified in these ethnicities. No additional loci were identified after inverse-variance-weighted meta-analysis of the three ancestries.
CONCLUSIONS: Among Europeans, TCA interactions with variants in BRE and UBE2E2 were identified in relation to RR intervals. Among Hispanic/Latinos, variants in TGFBR3 modified the relation between TCAs and QT intervals. Future studies are required to confirm our results.

PMID: 28039329 [PubMed - as supplied by publisher]

Addressing the Crisis in the Treatment of Osteoporosis: A Path Forward.

J Bone Miner Res. 2016 Dec 29;:

Authors: Khosla S, Cauley JA, Compston J, Kiel DP, Rosen C, Saag KG, Shane E

Abstract
Considerable data and media attention have highlighted a potential "crisis" in the treatment of osteoporosis. Specifically, despite the availability of several effective drugs to prevent fractures, many patients who need pharmacological therapy are either not being prescribed these medications or if prescribed a medication, are simply not taking it. Although there are many reasons for this "gap" in the treatment of osteoporosis, a major factor is physician and patient concerns over the risk of side effects, especially atypical femur fractures (AFFs) related to bisphosphonate (and perhaps other anti-resorptive) drug therapy. In this perspective, we review the current state of under-treatment of patients at increased fracture risk and suggest possible short-, intermediate-, and long-term approaches to address patient concerns, specifically those related to AFF risk. We suggest improved patient and physician education on prodromal symptoms, extended femur scans using DXA to monitor patients on anti-resorptive treatment, better identification of high risk patients perhaps using geometrical parameters from DXA and other risk factors, and more research on pharmacogenomics to identify risk markers. Although not the only impediment to appropriate treatment of osteoporosis, concern over AFFs remains a major issue and one that needs to be resolved for effective dissemination of existing treatments to reduce fracture risk. This article is protected by copyright. All rights reserved.

PMID: 28032660 [PubMed - as supplied by publisher]

Rapid Naked-Eye Discrimination of Cytochrome P450 Genetic Polymorphism through Non-Crosslinking Aggregation of DNA-Functionalized Gold Nanoparticles.

ChemistryOpen. 2016 Dec;5(6):508-512

Authors: Akiyama Y, Wang G, Shiraishi S, Kanayama N, Takarada T, Maeda M

Abstract
Involvement of single-nucleotide polymorphism (SNP) genotyping in healthcare should allow for more effective use of pharmacogenomics. However, user-friendly assays without the requirement of a special instrument still remain unavailable. This study describes naked-eye SNP discrimination in exon 5 of the human cytochrome P450 2C19 monooxygenase gene, CYP2C19*1 (the wild-type allele) and CYP2C19*2 (the variant allele with G681A point mutation). The present assay is composed of allele-specific single-base primer extension and salt-induced aggregation of DNA-modified gold nanoparticles (DNA-AuNPs). Genetic samples extracted from human hair roots are subjected to this assay. The results are verified by direct sequencing. This study should promise the prospective use of DNA-AuNPs in gene diagnosis.

PMID: 28032016 [PubMed]

Pharmacogenetics of cancer therapy: breakthroughs from beyond?

Future Sci OA. 2015 Nov;1(4):FSO80

Authors: Lu DY, Lu TR, Xu B, Ding J

Abstract
'Pharmacogenetics or Pharmacogenomics' (PG) is one of the most practiced cancer therapeutic strategies, tailored for individualized patients. Despite its popularity and rapid advancements in the field, many obstacles for cancer therapy PG still need to be overcome. By borrowing scientific systems from other disciplines such as cancer diagnosis, and therapeutic information from the diversity of tumor origins, categories and stages, cancer therapy PG may hopefully be improved. Furthermore, to quickly acquire genetic and pathologic information and seek therapeutic interventions, possible breakthroughs may come from beyond - changing the cancer therapeutic landscapes. The next generations of PG protocols and hospital routines for searching deadly cancer pathogenic pathways versus drug-targeting predictions are of great clinical significance for the future. Yet, progress of cancer therapy PG is entering into a bottleneck stage owing to simple model of relevant techniques and routines. Promoting or even innovating present PG modular is very necessary. This perspective highlights this issue by introducing new initiatives and ideas.

PMID: 28031929 [PubMed]

Clinical Impact of Pharmacogenomics of Clopidogrel in Stroke.

Circulation. 2017 Jan 03;135(1):34-37

Authors: Simon T, Danchin N

PMID: 28028061 [PubMed - in process]