A rapid and robust UHPLC-DAD method for the quantification of amphotericin B in human plasma.

J Pharm Biomed Anal. 2017 May 10;138:142-145

Authors: Barco S, Zunino A, D'Avolio A, Barbagallo L, Maffia A, Tripodi G, Castagnola E, Cangemi G

Abstract
Amphotericin B is an antifungal drug widely used in Intensive Care Units. Therapeutic drug monitoring (TDM) of amphotericin B is recommended for the assessment of toxicity surveillance and treatment optimization. In this paper we described the development and validation of a new Ultra High Performance Liquid Chromatography coupled to Diode Array Detection (UHPLC-DAD) method for the quantification of Amphotericin B in 200μL human plasma over a wide range of concentrations (0.125-10mg/L). The new method has been validated following international guidelines on bioanalytical method validation and showed high selectivity, high accuracy and precision and high process efficiency. The new UHPLC-DAD method that we describe is robust, rapid, cost effective and suitable for application to the routine TDM analyses.

PMID: 28199895 [PubMed - indexed for MEDLINE]

11 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 2017/06/28

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.

CYP2E1 Gene Polymorphisms Related to the Formation of Coronary Artery Lesions in Kawasaki Disease.

Pediatr Infect Dis J. 2017 Jun 23;:

Authors: Chang LS, Hsu YW, Lu CC, Lo MH, Hsieh KS, Li SC, Chang WC, Kuo HC

Abstract
BACKGROUND: Kawasaki disease (KD) is an acute febrile systemic vasculitis that disturbs coronary arteries. Patients' risks of adverse cardiovascular events and subclinical atherosclerosis have been found to significantly increase with polymorphisms of the human cytochrome P450. This current study aims to research the possible relationship between Cytochrome P450, Family 2, Subfamily E, and Polypeptide 1 (CYP2E1) polymorphisms with KD.
METHODS: We selected six tag single-nucleotide polymorphisms (tSNPs) of the CYP2E1 gene for TaqMan allelic discrimination assay in 340 KD patients and performed analysis on the clinical phenotypes and coronary artery lesions (CAL). CAL associations of tSNPs were adjusted for age and gender in the logistic regression.
RESULTS: The KD patients with a CC genotype of rs915906 demonstrated a greater proportion of CAL formation (p = 0.009). Furthermore, the GG genotype frequencies of rs2070676 showed a significantly greater risk for CAL formation in KD patients (p = 0.007). However, the SNPs of the CYP2E1 gene did not influence CAL formation in the participating KD patients either with or without high-dose acetylsalicylic acid. Using the expression quantitative trait locus (eQTL) analyses, we found that the SNPs associated with CAL formation in KD also affected CYP2E1 expression in certain cell types.
CONCLUSION: This study is the first to find that the risk of CAL formation is related to CYP2E1 gene polymorphisms in KD patients.

PMID: 28650933 [PubMed - as supplied by publisher]

Synthesis and biological evaluation of indole derivatives as α-amylase inhibitor.

Bioorg Chem. 2017 Jun 19;73:121-127

Authors: Imran S, Taha M, Selvaraj M, Ismail NH, Chigurupati S, Mohammad JI

Abstract
A series of twenty indole hydrazone analogs (1-21) were synthesized, characterized by different spectroscopic techniques such as (1)H NMR and EI-MS, and screened for α-amylase inhibitory activity. All analogs showed a variable degree of α-amylase inhibition with IC50 values ranging between 1.66 and 2.65μM. Nine compounds that are 1 (2.23±0.01μM), 8 (2.44±0.12μM), 10 (1.92±0.12μM), 12 (2.49±0.17μM), 13 (1.66±0.09μM), 17 (2.25±0.1μM), 18 (1.87±0.25μM), 20 (1.83±0.63μM), and 19 (1.97±0.02μM) showed potent α-amylase inhibition when compared with the standard acarbose (1.05±0.29μM). Other analogs showed good to moderate α-amylase inhibition. The structure activity relationship is mainly focusing on difference of substituents on phenyl part. Molecular docking studies were carried out to understand the binding interaction of the most active compounds.

PMID: 28648924 [PubMed - as supplied by publisher]

DNA Methylation Status of PAX1 and ZNF582 in Esophageal Squamous Cell Carcinoma.

Int J Environ Res Public Health. 2017 Feb 22;14(2):

Authors: Huang J, Wang G, Tang J, Zhuang W, Wang LP, Liou YL, Liu YZ, Zhou HH, Zhu YS

Abstract
Hypermethylation of specific gene promoters is an important mechanism of carcinogenesis. A high frequency of promoter methylation of PAX1 and ZNF582 genes has been detected in cervical cancer. In the present study, we investigated the methylation status of PAX1 and ZNF582 genes in esophageal squamous cell carcinoma (ESCC) tissues. Tumor and paracancerous tissues were obtained from 14 ESCC patients. Genomic DNA was extracted from both tumor and paracancerous tissues, and the concentration of DNA were determined. DNA methylation analysis of PAX1 and ZNF582 genes was carried out using quantitative methylation-specific PCR. To assess the diagnostic performance of the two methylated genes for cancer detection, receiver operating characteristic (ROC) curves were generated. Sensitivities and specificities were tested at cut-offs obtained from the ROC curves. The methylation levels of both PAX1 and ZNF582 genes were significantly higher in tumor tissues compared to non-tumor paracancerous tissues. The methylation rates of PAX1 and ZNF582 in ESCC tumor and paracancerous tissues were 100% and 21.4% (p = 0.006), 85.7% and 0% (p < 0.001), respectively. The sensitivities and specificities of PAX1 and ZNF582 methylation for the detection of cancer were 100% and 85.7%, and 78.6% and 100%, respectively. The DNA methylation levels and frequencies of PAX1 and ZNF582 genes were markedly higher in ESCC tumor tissues compared to those in paracancerous tissues. Moreover, the conclusions were verified by using The Cancer Genome Atlas (TCGA) datasets. DNA methylation status of these two genes showed a relatively good sensitivity and specificity for the detection of ESCC tumors. This data suggests that DNA methylation testing holds a great promise for ESCC screening and warrants further prospective population-based studies.

PMID: 28241446 [PubMed - indexed for MEDLINE]

Is still there a role for IL-2 for solid tumors other than melanoma or renal cancer?

Immunotherapy. 2017 Jan;9(1):25-32

Authors: Roviello G, Zanotti L, Correale P, Gobbi A, Wigfield S, Guglielmi A, Pacifico C, Generali D

Abstract
AIM: IL-2 is one of the first immunomodulating cytokines to be tested in the treatment of cancer patients. The effects of this agent in the treatment of solid tumors other than renal cancer and melanoma are poorly understood.
MATERIALS & METHODS: We have carried out a meta-analysis of randomized studies. We fixed the response rate as the primary outcome.
RESULTS: The pooled risk ratio for an objective response with IL-2 plus chemotherapy versus chemotherapy alone was 1.43 (95% CI: 1.12-1.81; p = 0.004), in favor of colorectal cancer.
CONCLUSION: Further investigation in the treatment of patients with colorectal cancer or other solid malignancies with IL-2 is required, alone or in combination with chemotherapy.

PMID: 28000528 [PubMed - indexed for MEDLINE]

CYP3A4*1G and CYP3A5*3 genetic polymorphisms alter the antihypertensive efficacy of amlodipine in patients with hypertension following renal transplantation
.

Int J Clin Pharmacol Ther. 2017 Feb;55(2):109-118

Authors: Huang Y, Wen G, Lu Y, Wen J, Ji Y, Xing X, Li Y, Wen J, Yuan H

Abstract
OBJECTIVE: Previous studies have determined that CYP3A and multidrug resistance protein 1 (MDR1) polymorphisms can affect the pharmacokinetics and pharmacodynamics of amlodipine in both healthy subjects and those with early hypertensive renal disease. In the current study, our objective was to analyze the association between the CYP3A4*1G, CYP3A5*3, and MDR1 C3435T gene polymorphisms and the antihypertensive efficacy of amlodipine in hypertensive patients after renal transplantation. <u>Materials:</u> Blood samples were collected from 76 patients on amlodipine therapy (5 mg/d).
METHODS: The CYP3A4*1G, CYP3A5*3, and MDR1 C3435T genetic polymorphisms were detected using both polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and gene sequencing. Subsequently, antihypertensive effects were analyzed according to genotype, and blood pressure values were measured and recorded weekly.
RESULTS: Four weeks of treatment with amlodipine was sufficient to successfully control blood pressure in 79% of patients. The efficacy of amlodipine in patients with the CYP3A5*3*3 genotype was significantly higher than that in patients with other CYP3A5 genotypes (p < 0.05). In addition, the reduction in diastolic blood pressure (DBP) in patients with the CYP3A5*3*3 and CYP3A4*1G*1G genotypes was significantly higher than that in patients with other CYP3A5 and CYP3A4 genotypes, respectively (p < 0.05). Furthermore, we found that linkage disequilibrium exists between the CYP3A4 *1G and CYP3A5*3 alleles and observed that the most significant reduction in DBP occurred in patients with the *1/*1 and *3/*3 genotype.
CONCLUSIONS: Our study demonstrates that amlodipine treatment may effectively control blood pressure (BP) for hypertensive patients following renal transplantation. Additionally, we found that the CYP3A5*3 polymorphism affects the antihypertensive efficacy of amlodipine in Chinese hypertensive patients after renal transplantation.
.

PMID: 27841150 [PubMed - indexed for MEDLINE]

Warfarin dose requirements with different genotypes of CYP2C9 and VKORC1 for patients with atrial fibrillation and valve replacement.

Int J Clin Pharmacol Ther. 2017 Feb;55(2):126-132

Authors: Chen W, Wu L, Liu X, Shen Y, Liang Y, Zhu J, Tan H, Yang Y, Liu Q, Wang M, Liu L, Wang X

Abstract
AIMS: To investigate whether genetic variants of <i>CYP2C9</i> and <i>VKORC1</i> have different effects on the dose of warfarin in 180 Han Chinese patients who were recruited from the Fu Wai Hospital. All were on maintenance treatment with stable daily warfarin doses for a period of at least 3 months.
METHODS: DNA was isolated and genotyped using a Warfarin dosage Prediction Kit for single nucleotide polymorphisms (SNPs) of <i>CYP2C9</i> and <i>VKORC1</i>.
RESULTS: The <i>VKORC1</i> and <i>CYP2C9*3</i> polymorphisms are significantly associated with warfarin maintenance dosages. Patients with AG&GG genotype in <i>VKORC1</i> needed higher doses than those with AA genotypes (4.55 ± 1.27 mg/ day vs. 2.90 ± 0.97 mg/day, p < 0.001). Patients with *1/*3 genotype in <i>CYP2C9</i> need doses lower than those with *1/*1 genotypes (1.73 ± 0.95 mg/day vs. 3.23 ± 1.13 mg/day, p < 0.001). There were no significant differences between the warfarin maintenance dosages in patients with atrial fibrillation (3.09 ± 1.16 mg/day), patients with heart valve replacement (2.95 ± 1.21 mg/day) and those with both atrial fibrillation and heart valve replacement (3.36 ± 1.13 mg/day) (p > 0.05). The mean warfarin daily dose requirements in the genotypes of <i>VKORC1</i> and <i>CYP2C9</i> were not dependent on the medical indication(s) present.
CONCLUSIONS: Genetic variants of <i>CYP2C9, VKORC1</i>, and age are significant determinants of the maintenance dose of warfarin. The medical indications atrial fibrillation, valve replacement, or a combination of both are not determinants of the warfarin dose requirements.

PMID: 27117036 [PubMed - indexed for MEDLINE]

Prevalence and risk factors of Blastocystis infection among underprivileged communities in rural Malaysia.

Asian Pac J Trop Med. 2017 May;10(5):491-497

Authors: Mohammad NA, Al-Mekhlafi HM, Moktar N, Anuar TS

Abstract
OBJECTIVES: To determine the prevalence and risk factors of Blastocystis among underprivileged communities living in rural Malaysia.
METHODS: This cross-sectional study was conducted among 253 participants aged between 1 and 85 years. Stool samples were examined using Wheatley's trichrome stain after in-vitro cultivation in Jones' medium to detect the presence of Blastocystis. Information pertaining to the demography, socioeconomic and environment were collected using pre-validated questionnaires.
RESULTS: The total prevalence of Blastocystis infection was 40.7%. The multiple logistic regression analysis revealed that age ≥15 years (OR = 2.72; 95% CI = 1.47-5.04) and presence of infected family members (OR = 8.56; 95% CI = 4.47-16.38) were the significant risk factors associated with blastocystosis in these communities.
CONCLUSIONS: Blastocystosis is revealed through this study to be still prevalent among Orang Asli communities in rural Malaysia. The two main approaches that should be implemented by the public health authority in battling this infection would be the screening of other family members and giving treatment to the infected individuals. Moreover, it is imperative for health education on good personal and food hygiene practices are provided in order to reduce the morbidity and transmission of Blastocystis infection among the Orang Asli in their communities meaningfully.

PMID: 28647187 [PubMed - in process]

Success of tardive electroconvulsive therapy sessions after loxapine-induced malignant syndrome in the context of very poor metabolisation.

Therapie. 2017 May 29;:

Authors: Descoeur J, Philibert L, Chalard K, Attal J, Petit P, Klouche K, Olivier M

Abstract
We report the success of tardive electroconvulsive therapy in a case of loxapine malignant syndrome with catatonia. Loxapine and its metabolites were measured in biological samples by liquid chromatography coupled to tandem mass spectrometry. Genes were studied by sequencing and quantitative polymerase chain reaction (PCR). Plasmatic drug concentrations showed a supratherapeutic concentration of loxapine with a very low 8-hydroxyloxapine/loxapine ratio (range from 0.32 to 0.66, normal value>2 for 100mg) and a very long elimination half-life of loxapine (half-life>140h, normal value from 1 to 4hours). We tried to explain this kinetics by exploring the main pharmacogenes implicated in the metabolism of loxapine. No genetic abnormality for CYP1A2 was observed. The study of associated treatments showed the potential contribution of valproate. Pharmacokinetics and pharmacogenetics investigations revealed a blockade of the CYP1A2 metabolic pathway without genetic abnormalities, probably due to valproate co-medication. Toxicological monitoring of loxapine and its metabolites helped to explain the persistence of symptoms and to adapt the therapeutic management.

PMID: 28647110 [PubMed - as supplied by publisher]

A systematic review of pharmacogenetic studies on the response to biologics in psoriasis patients.

Br J Dermatol. 2017 Jun 24;:

Authors: van Vugt LJ, van den Reek JMPA, Coenen MJH, de Jong EMGJ

Abstract
Biologics are indicated for treating moderate to severe psoriasis. As the number of biologics registered for psoriasis increases, so does the need for biomarkers to guide personalized therapeutic decisions. Genetic variants might serve as predictors for treatment response, a field of research known as pharmacogenetics. The aim of this systematic review was to assess which genetic variants are associated with the response to biologics in psoriasis patients. A systematic search was performed in EMBASE, MEDLINE, the Cochrane Library and Web of Science. Twenty-six papers were included in this systematic review: 24 original studies and two meta-analyses. Quality was assessed using a predesigned form. Risk of bias was assessed using the Newcastle-Ottawa Scale. The majority of studies reported a candidate gene approach, focusing on polymorphisms in genes related the therapeutical target or to psoriasis susceptibility. Studied populations were small and results were divergent, especially for studies investigating tumour necrosis factor inhibitors. The evidence for the role of HLA-Cw6 in ustekinumab efficacy shows minimal heterogeneity, with a higher response rate among HLA-Cw6 positive patients reported across three out of five studies. However, replication of these findings in larger cohorts is required. Large scale hypothesis-free searches for genetic biomarkers are needed to uncover the complete genetic background of biologics treatment outcome. This article is protected by copyright. All rights reserved.

PMID: 28646581 [PubMed - as supplied by publisher]

A Comprehensive Mouse Transcriptomic BodyMap across 17 Tissues by RNA-seq.

Sci Rep. 2017 Jun 23;7(1):4200

Authors: Li B, Qing T, Zhu J, Wen Z, Yu Y, Fukumura R, Zheng Y, Gondo Y, Shi L

Abstract
The mouse has been widely used as a model organism for studying human diseases and for evaluating drug safety and efficacy. Many diseases and drug effects exhibit tissue specificity that may be reflected by tissue-specific gene-expression profiles. Here we construct a comprehensive mouse transcriptomic BodyMap across 17 tissues of six-weeks old C57BL/6JJcl mice using RNA-seq. We find different expression patterns between protein-coding and non-coding genes. Liver expressed the least complex transcriptomes, that is, the smallest number of genes detected in liver across all 17 tissues, whereas testis and ovary harbor more complex transcriptomes than other tissues. We report a comprehensive list of tissue-specific genes across 17 tissues, along with a list of 4,781 housekeeping genes in mouse. In addition, we propose a list of 27 consistently and highly expressed genes that can be used as reference controls in expression-profiling analysis. Our study provides a unique resource of mouse gene-expression profiles, which is helpful for further biomedical research.

PMID: 28646208 [PubMed - in process]

26 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 2017/06/24

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.

Pharmacokinetic drug evaluation of extended release lorcaserin for the treatment of obesity.

Expert Opin Drug Metab Toxicol. 2017 Jun 21;:

Authors: Hurren K, Dunham MW

Abstract
INTRODUCTION: Lorcaserin is a serotonin 2C receptor antagonist that was FDA approved in 2012. Lorcaserin is recently available as an extended-release (ER) formulation for the treatment of obesity as an adjunct to lifestyle modification. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy, and safety of lorcaserin ER will be reviewed. Expert opinion: Lorcaserin ER 20mg daily provides drug exposure bioequivalent to lorcaserin immediate release (IR) 10mg twice daily. Lorcaserin IR is associated with 3.3% and 3.0% placebo-subtracted weight loss in patients without and with diabetes, respectively. A1C was reduced by 0.9% in patients with diabetes. Common side effects include headache, dry mouth, constipation, dizziness, fatigue, and nausea. Lorcaserin provides potential advantages over other antiobesity medications in regards to tolerability and simplicity of medication initiation, but may not be as effective as other options. Lorcaserin ER offers improved ease of administration and anticipated adherence compared to the IR formulation. The place in therapy for lorcaserin ER and other antiobesity medications will be further clarified by results of pending clinical trials addressing cardiovascular outcomes as well as the role pharmacogenomics and comorbid disease states may play in choosing patient-specific therapy.

PMID: 28636828 [PubMed - as supplied by publisher]

Psychotropic pharmacogenetics - Distraction or destiny?

Aust N Z J Psychiatry. 2017 Jul;51(7):665-667

Authors: Singh AB, Baune BT, Hamilton A, Das P, Outhred T, Morris G, Bassett D, Berk M, Boyce P, Lyndon B, Mulder R, Parker G, Malhi GS

PMID: 28633577 [PubMed - in process]

Vitamin D is not associated with incident dementia or cognitive impairment: an 18-y follow-up study in community-living old men.

Am J Clin Nutr. 2017 Apr;105(4):936-943

Authors: Olsson E, Byberg L, Karlström B, Cederholm T, Melhus H, Sjögren P, Kilander L

Abstract
Background: Vitamin D has been implicated as being important for maintaining cognitive function in old age. Results from longitudinal studies examining the association of vitamin D with incident dementia and cognitive impairment have been inconsistent.Objective: We investigated the relation between vitamin D, assessed in 3 different ways, and the risk of dementia.Design: We measured plasma 25-hydroxyvitamin D [25(OH)D] with the use of high-performance liquid chromatography-mass spectrometry, assessed dietary vitamin D intake with the use of 7-d dietary records, and created a vitamin D-synthesis genetic risk score (GRS) at baseline (1991-1995) in a cohort of 1182 Swedish men (mean age: 71 y). In a maximum of 18 y (median: 12 y) of follow-up, 116 men developed Alzheimer disease, 64 men developed vascular dementia, and 250 men developed all-cause dementia. An additional 80 men declined in cognitive function as assessed with the use of the Mini-Mental State Examination. Adjusted HRs and ORs were calculated with the use of Cox and logistic regressions.Results: The mean ± SD plasma 25(OH)D concentration was 68.7 ± 19.1 nmol/L. Plasma 25(OH)D, dietary vitamin D intake, and vitamin D-synthesis GRS were not associated with any cognitive outcomes (crude and adjusted HRs and ORs were ∼1.0 for all continuous exposures). The adjusted HR for all-cause dementia was 0.88 (95% CI: 0.59, 1.31) in men with plasma 25(OH)D concentrations ≤50 compared with >75 nmol/L. The adjusted HR for all-cause dementia was 0.92 (95% CI: 0.63, 1.32) for the lowest compared with highest tertiles of vitamin D intake. The adjusted HR for the continuous GRS for all-cause dementia was 1.04 (95% CI: 0.91, 1.19).Conclusion: In this cohort study, we show that there is no association between baseline vitamin D status and long-term risk of dementia or cognitive impairment over an 18-y period of time.

PMID: 28202477 [PubMed - indexed for MEDLINE]

The influence of genetic susceptibility and calcium plus vitamin D supplementation on fracture risk.

Am J Clin Nutr. 2017 Apr;105(4):970-979

Authors: Wang Y, Wactawski-Wende J, Sucheston-Campbell LE, Preus L, Hovey KM, Nie J, Jackson RD, Handelman SK, Nassir R, Crandall CJ, Ochs-Balcom HM

Abstract
Background: Fracture is a complex trait, affected by both genetic and environmental factors. A meta-analysis of genome-wide association studies (GWASs) identified multiple bone mineral density (BMD) and fracture-associated loci.Objective: We conducted a study to evaluate whether fracture genetic risk score (Fx-GRS) and bone mineral density genetic risk score (BMD-GRS) modify the association between the intake of calcium with vitamin D (CaD) and fracture risk.Design: Data from 5823 white postmenopausal women from the Women's Health Initiative CaD randomized trial were included. Participants received 1000 mg elemental Ca with 400 IU vitamin D3/d or placebo (median follow-up: 6.5 y). Total fracture was defined as first fracture of any type. We computed the Fx-GRS with 16 fracture- and BMD-associated variants, and the BMD-GRS with 50 BMD-associated variants. We used Cox regression and a case-only approach to test for multiplicative interaction. Additive interaction was assessed with the relative excess risk due to interaction (RERI). We analyzed genetic risk score as a continuous variable and a categorical variable based on quartile (quartile 1, quartiles 2-3, and quartile 4).Results: We observed no interaction between the Fx-GRS and CaD on fracture risk; however, we observed a significant multiplicative interaction between the BMD-GRS and CaD assignment (P-interaction = 0.01). In addition, there was a significant negative additive interaction between placebo assignment and higher BMD-GRS: quartiles 2-3, PRERI = 0.03; quartile 4, PRERI = 0.03. In a stratified analysis, the protective effect of CaD on fracture risk was observed in women in the lowest BMD-GRS quartile (HR: 0.60, 95% CI: 0.44, 0.81) but not in women with a higher BMD-GRS.Conclusions: We observed significant effects of CaD intake on fracture risk only in women with the lowest genetic predisposition to low BMD. Future large-scale studies with functional characterization of GWAS findings are warranted to assess the utility of genetic risk score in analysis of risks and benefits of CaD for bone.

PMID: 28148500 [PubMed - indexed for MEDLINE]

Identifying and annotating human bifunctional RNAs reveals their versatile functions.

Sci China Life Sci. 2016 Oct;59(10):981-992

Authors: Chen G, Yang J, Chen J, Song Y, Cao R, Shi T, Shi L

Abstract
Bifunctional RNAs that possess both protein-coding and noncoding functional properties were less explored and poorly understood. Here we systematically explored the characteristics and functions of such human bifunctional RNAs by integrating tandem mass spectrometry and RNA-seq data. We first constructed a pipeline to identify and annotate bifunctional RNAs, leading to the characterization of 132 high-confidence bifunctional RNAs. Our analyses indicate that bifunctional RNAs may be involved in human embryonic development and can be functional in diverse tissues. Moreover, bifunctional RNAs could interact with multiple miRNAs and RNA-binding proteins to exert their corresponding roles. Bifunctional RNAs may also function as competing endogenous RNAs to regulate the expression of many genes by competing for common targeting miRNAs. Finally, somatic mutations of diverse carcinomas may generate harmful effect on corresponding bifunctional RNAs. Collectively, our study not only provides the pipeline for identifying and annotating bifunctional RNAs but also reveals their important gene-regulatory functions.

PMID: 27650948 [PubMed - indexed for MEDLINE]

PEG-Fmoc-Ibuprofen Conjugate as a Dual Functional Nanomicellar Carrier for Paclitaxel.

Bioconjug Chem. 2016 Sep 21;27(9):2198-205

Authors: Zhao M, Huang Y, Chen Y, Xu J, Li S, Guo X

Abstract
Ibuprofen is a kind of nonsteroidal anti-inflammatory drug (NSAIDs), and it is considered to possess some antitumor effect. In this study, a novel nanomicellar carrier based on PEG-derivatized ibuprofen, PEG2K-Fmoc-Ibuprofen (PEG2K-FIbu), was developed for delivery of anticancer agents such as paclitaxel (PTX). This conjugate readily forms stable mixed micelles with PTX with a relatively high PTX loading capacity of 67%. The release of PTX from PTX-loaded PEG2K-FIbu micelles was significantly slower than that from Taxol formulation. PTX-loaded PEG2K-FIbu micelles and Taxol showed a comparable in vitro cytotoxicity. Importantly, PTX-loaded PEG2K-FIbu micelles demonstrated a much more pronounced in vivo therapeutic efficacy compared with Taxol with respect to both inhibition of tumor growth and animal survival. Our system may represent an attractive dual-functional delivery system to achieve synergistic activity with PTX while minimizing the carrier-associated toxicity.

PMID: 27532881 [PubMed - indexed for MEDLINE]

Pharmacogenetic biomarkers of response in Crohn's disease.

Pharmacogenomics J. 2017 Jun 20;:

Authors: Linares-Pineda TM, Cañadas-Garre M, Sánchez-Pozo A, Calleja-Hernández MÁ

Abstract
Crohn's disease (CD) is a chronic condition, which affects the immune system. It can also affect any part of the digestive tract and be associated with external manifestations. The causes of the disease remain unknown, although it seems to be the result of a combination of factors, such as genetic predisposition, environment, lifestyle and the composition of the microbiota, among others. The treatment protocol begins with a change in eating and smoking habits, and is continued with different lines of treatment, including corticosteroids, immunomodulators and biologic therapy (infliximab and adalimumab), which have shown differences in response among patients, especially with biologic treatment. Several studies have considered the possibility that these differences in response are caused by the genetic variability of patients. Many genes have been investigated as potential predictors of response to biological drugs, such as ADAM17, ATG16L1, EMSY, CASP9, CCNY, CNTN5, FASLG, FCGR, NOD2, PTGER4, IL13, IL1B, IL27, IL11, IL17F, TNF and TNFR genes. In this review, we will gather the information on influence of gene polymorphisms investigated to date on response to biological drugs in CD patients.The Pharmacogenomics Journal advance online publication, 20 June 2017; doi:10.1038/tpj.2017.27.

PMID: 28631723 [PubMed - as supplied by publisher]