Literature Watch
Respiratory syncytial virus prophylaxis in cystic fibrosis: the Canadian registry of palivizumab data (2005-2016).
Respiratory syncytial virus prophylaxis in cystic fibrosis: the Canadian registry of palivizumab data (2005-2016).
Eur J Clin Microbiol Infect Dis. 2018 May 04;:
Authors: Mitchell I, Wong SK, Paes B, Ruff M, Bjornson C, Li A, Lanctôt KL, CARESS investigators
Abstract
Respiratory syncytial virus (RSV) may cause severe illness in cystic fibrosis (CF) children, but recommendations vary on prophylaxis. CARESS is a prospective registry of children who received palivizumab in 32 Canadian sites from 2005 to 2016. Demographic data were collected at enrollment and respiratory illness-related events recorded monthly. We reviewed respiratory illness hospitalization (RIH) and RSV hospitalization (RSVH) in CF children aged < 24 months versus those prophylaxed for standard indications (SI; prematurity, chronic lung disease [CLD] and congenital heart disease [CHD]), and complex medical disorders (CM). Of 23,228 children analyzed, 19,452 (83.8%) were SI, 3349 (14.4%) were CM, and 427 (1.8%) were CF. CF children were more likely to be Caucasian, heavier at birth and enrollment, and less likely to have a sibling or live in crowded conditions. CF children were similar to the other groups in daycare attendance, history of atopy, and exposure to smoking. RIH incidences were 4.3% (premature), 13.8% CLD, 11.5% CHD, 11.7% CM, and 6.8% CF. RSVH incidence in CF children was similar to that in the SI and CM groups: 1.1, 1.5, and 2.0% groups respectively. Cox regression analyses showed that compared to CF children, the HRs for RSVH in SI (HR 2.0 95% CI 0.5-8.3, p = 0.3) and CM (HR 2.4, 95% CI 0.6-9.8, p = 0.2) did not differ. CF children are equally at risk for RSVH relative to those prophylaxed for other indications. Pending robust evidence from prospective trials, palivizumab could perhaps be considered in the interim, for young CF patients born early during the RSV season with evidence of serious lung disease.
PMID: 29728782 [PubMed - as supplied by publisher]
Tissue-specific mosaicism in hereditary hemorrhagic telangiectasia: Implications for genetic testing in families.
Tissue-specific mosaicism in hereditary hemorrhagic telangiectasia: Implications for genetic testing in families.
Am J Med Genet A. 2018 May 07;:
Authors: McDonald J, Wooderchak-Donahue WL, Henderson K, Paul E, Morris A, Bayrak-Toydemir P
Abstract
Mosaicism in hemorrhagic telangiectasia (HHT) has been previously identified when testing blood samples of HHT patients. We report the first detection of mosaicism not involving blood of a family proband, and discuss implications for genetic testing algorithms in HHT families. Sanger sequencing and large deletion/duplication analysis in a patient with HHT identified no pathogenic variant in ENG, ACVRL1, or SMAD4. Exome sequencing was then performed on this proband, as well as her affected adult child. A pathogenic ENG variant was detected in the proband's affected child, but not in DNA extracted from peripheral blood of the affected parent/proband. Additional tissue samples (saliva and hair bulbs) were obtained from the proband. The variant was not detected in saliva, but was detected in the hair bulb sample (at 33%). This is the first report of an HHT patient with mosaicism in whom the disease-causing mutation was not detected in blood. The molecular findings in this family suggest that the possibility of mosaicism not present or detectable in blood should be considered if a proband with HHT tests "negative" for a mutation in known genes. This occurrence is particularly suspect for families in which the proband does not have a clearly affected parent. This mechanism may explain some patients with classic HHT in whom a pathogenic variant has not been identified in one of the known HHT genes.
PMID: 29736967 [PubMed - as supplied by publisher]
KIF16B is a candidate gene for a novel autosomal-recessive intellectual disability syndrome.
KIF16B is a candidate gene for a novel autosomal-recessive intellectual disability syndrome.
Am J Med Genet A. 2018 May 07;:
Authors: Alsahli S, Arold ST, Alfares A, Alhaddad B, Al Balwi M, Kamsteeg EJ, Al-Twaijri W, Alfadhel M
Abstract
Intellectual disability (ID) and global developmental delay are closely related; the latter is reserved for children under the age of 5 years as it is challenging to reliably assess clinical severity in this population. ID is a common condition, with up to 1%-3% of the population being affected and leading to a huge social and economic impact. ID is attributed to genetic abnormalities most of the time; however, the exact role of genetic involvement in ID is yet to be determined. Whole exome sequencing (WES) has gained popularity in the workup for ID, and multiple studies have been published examining the diagnostic yield in identification of the disease-causing variant (16%-55%), with the genetic involvement increasing as intelligence quotient decreases. WES has also accelerated novel disease gene discovery in this field. We identified a novel biallelic variant in the KIF16B gene (NM_024704.4:c.3611T > G) in two brothers that may be the cause of their phenotype.
PMID: 29736960 [PubMed - as supplied by publisher]
Novel splice-site variant of UCHL1 in an Indian family with autosomal recessive spastic paraplegia-79.
Novel splice-site variant of UCHL1 in an Indian family with autosomal recessive spastic paraplegia-79.
J Hum Genet. 2018 May 07;:
Authors: Das Bhowmik A, Patil SJ, Deshpande DV, Bhat V, Dalal A
Abstract
Spastic Paraplegia-79 (SPG79) is an autosomal recessive type of childhood onset complicated by hereditary spastic paraplegia. SPG79 is characterized by spasticity, paraplegia, optic atrophy, cerebellar signs, and other variable clinical features. Recessive, disease causing variants in Ubiquitin C-terminal hydrolase-L1 (UCHL1) gene have been implicated as a cause for SPG79 in two families till now. In this study, we report on a third family of SPG79 with two similarly affected siblings, harboring a novel homozygous splice-site variant in the UCHL1 gene (NM_004181.4: c.459+2T>C). The variant was identified by whole-exome sequencing and validated by Sanger sequencing in the family.
PMID: 29735986 [PubMed - as supplied by publisher]
Monogenic diabetes in adults: what are the new developments?
Monogenic diabetes in adults: what are the new developments?
Curr Opin Genet Dev. 2018 May 04;50:103-110
Authors: Owen KR
Abstract
Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic causes of beta-cell dysfunction and diabetes arising in children and young adults. Making an accurate diagnosis of MODY is important for establishing the correct management. Recent advances in our understanding of human sequence variation, through data collated in resources such as the Exome Aggregation Consortium have refined guidelines for assessment of rare genetic variants. This will allow a more precise aetiological diagnosis in childhood and young adult diabetes. No major new monogenic causes of diabetes outside the neonatal period have been identified in recent years, but the allelic spectrum of disease phenotype associated with known genes continues to expand. Improving uptake of genetic testing by defining who should be tested is an area of active research. A population based study found that 6.5% of children who have negative beta-cell antibodies at diagnosis have rare functional variants in MODY genes. Defining the high risk groups in adults with diabetes is more difficult, but online decision aids will assist clinicians in selecting who to refer for testing.
PMID: 29734081 [PubMed - as supplied by publisher]
Whole-Exome Sequencing to Identify Rare Variants and Gene Networks that Increase Susceptibility to Scleroderma in African Americans.
Whole-Exome Sequencing to Identify Rare Variants and Gene Networks that Increase Susceptibility to Scleroderma in African Americans.
Arthritis Rheumatol. 2018 May 06;:
Authors: Gourh P, Remmers EF, Boyden SE, Alexander T, Morgan ND, Shah AA, Mayes MD, Doumatey A, Bentley AR, Shriner D, Domsic RT, Medsger TA, Steen VD, Ramos PS, Silver RM, Korman B, Varga J, Schiopu E, Khanna D, Hsu V, Gordon JK, Saketkoo LA, Gladue H, Kron B, Criswell LA, Derk CT, Bridges SL, Shanmugam VK, Kolstad KD, Chung L, Jan R, Bernstein EJ, Goldberg A, Trojanowski M, Kafaja S, Maksimowicz-McKinnon KM, Mullikin JC, NISC Comparative Sequencing Program, Adeyemo A, Rotimi C, Boin F, Kastner DL, Wigley FM
Abstract
OBJECTIVE: Whole-exome sequencing (WES) studies in systemic sclerosis (SSc) patients of European American (EA) ancestry have identified variants in the ATP8B4 gene and enrichment of variants in genes in the extracellular matrix (ECM)-related pathway increasing SSc susceptibility. Our goal was to evaluate the association of the ATP8B4 gene and the ECM-related pathway with SSc in a cohort of African Americans (AA).
METHODS: SSc patients of AA ancestry were enrolled from 23 academic centers across the United States under the Genome Research in African American Scleroderma Patients (GRASP) consortium. Unrelated AA individuals without serological evidence of autoimmunity enrolled in the Howard University Family Study were used as unaffected controls. Functional variants in genes reported in the two WES studies in EA SSc were selected for gene association testing using the optimized sequence kernel association test (SKAT-O) and pathway analysis by Ingenuity pathway analysis in 379 patients and 411 controls.
RESULTS: Principal components analysis demonstrated that the patients and controls had similar ancestral backgrounds with about equal proportions of mean European admixture. Using SKAT-O, we examined the association of individual genes that were previously reported in EAs, and none remained significant including ATP8B4 (PUnCorr =0.98). However, we confirm the previously reported association of the ECM-related pathway with enrichment of variants within the COL13A1, COL18A1, COL22A1, COL4A3, COL4A4, COL5A2, PROK1, and SERPINE1 genes (PCorr =1.95×10-4 ).
CONCLUSION: This is the largest genetic study in AAs with SSc to date, corroborating the role of functional variants aggregating in a fibrotic pathway and increasing SSc susceptibility. This article is protected by copyright. All rights reserved.
PMID: 29732714 [PubMed - as supplied by publisher]
Importance of Comprehensive Molecular Profiling for Clinical Outcome in Children With Recurrent Cancer.
Importance of Comprehensive Molecular Profiling for Clinical Outcome in Children With Recurrent Cancer.
Front Pediatr. 2018;6:114
Authors: Østrup O, Nysom K, Scheie D, Schmidt AY, Mathiasen R, Hjalgrim LL, Olsen TE, Skjøth-Rasmussen J, Henriksen BM, Nielsen FC, Wehner PS, Schrøder H, Sehested AM, Rechnitzer C, Rossing M
Abstract
Purpose: Pediatric cancers are often difficult to classify and can be complex to treat. To ensure precise diagnostics and identify relevant treatment targets, we implemented comprehensive molecular profiling of consecutive pediatric patients with cancer relapse. We evaluated the clinical impact of extensive molecular profiling by assessing the frequency of identified biological onco-drivers, altered diagnosis, and/or identification of new relevant targeted therapies. Patients and Methods: Forty-six tumor samples (44 fresh-frozen; two formalin-fixed paraffin embedded), two bone marrow aspirates, three cerebrospinal fluid samples, and one archived DNA were obtained from 48 children (0-17 years; median 9.5) with relapsed or refractory cancer, where the disease was rapidly progressing in spite of their current treatment or they had exhausted all treatment options. The samples were analyzed by whole-exome sequencing (WES), RNA sequencing (RNAseq), transcriptome arrays, and SNP arrays. Final reports were available within 3-4 weeks after patient inclusion and included mutation status, a description of copy number alterations, differentially expressed genes, and gene fusions, as well as suggestions for targeted treatment. Results: Of the 48 patients, 33 had actionable findings. The most efficient method for the identification of actionable findings was WES (39%), followed by SNP array (37%). Of note, gene fusions were identified by RNAseq in 21% of the samples. Eleven findings led to clinical intervention, i.e., oncogenetic counseling, targeted treatment, and treatment based on changed diagnosis. Four patients received compassionate use targeted therapy. Six patients experienced direct benefits in the form of stable disease or response. Conclusion: The application of comprehensive genetic diagnostics in children with recurrent cancers allowed for discovery and implementation of effective targeted therapies and hereby improvement of outcome in some patients.
PMID: 29732366 [PubMed]
Whole Exome Sequencing Identified a Novel Heterozygous Mutation in HMBS Gene in a Chinese Patient With Acute Intermittent Porphyria With Rare Type of Mild Anemia.
Whole Exome Sequencing Identified a Novel Heterozygous Mutation in HMBS Gene in a Chinese Patient With Acute Intermittent Porphyria With Rare Type of Mild Anemia.
Front Genet. 2018;9:129
Authors: Zheng Y, Xu J, Liang S, Lin D, Banerjee S
Abstract
Acute intermittent porphyria (AIP) is a rare hereditary metabolic disease with an autosomal dominant mode of inheritance. Germline mutations of HMBS gene causes AIP. Mutation of HMBS gene results into the partial deficiency of the heme biosynthetic enzyme hydroxymethylbilane synthase. AIP is clinically manifested with abdominal pain, vomiting, and neurological complaints. Additionally, an extreme phenotypic heterogeneity has been reported in AIP patients with mutations in HMBS gene. Here, we investigated a Chinese patient with AIP. The proband is a 28-year-old Chinese male manifested with severe stomach ache, constipation, nausea and depression. Proband's father and mother is normal. Proband's blood sample was collected and genomic DNA was extracted. Whole exome sequencing and Sanger sequencing identified a heterozygous novel single nucleotide deletion (c.809delC) in exon 12 of HMBS gene in the proband. This mutation leads to frameshift followed by formation of a truncated (p.Ala270Valfs∗2) HMBS protein with 272 amino acids comparing with the wild type HMBS protein of 361 amino acids. This mutation has not been found in proband's unaffected parents as well as in 100 healthy normal control. According to the variant interpretation guidelines of American College of Medical Genetics and Genomics (ACMG), this variant is classified as "likely pathogenic" variant. Our findings expand the mutational spectra of HMBS gene related AIP which are significant for screening and genetic diagnosis for AIP.
PMID: 29731767 [PubMed]
Molecular Classification of Primary Immunodeficiencies of T Lymphocytes.
Molecular Classification of Primary Immunodeficiencies of T Lymphocytes.
Adv Immunol. 2018;138:99-193
Authors: Comrie WA, Lenardo MJ
Abstract
Proper regulation of the immune system is required for protection against pathogens and preventing autoimmune disorders. Inborn errors of the immune system due to inherited or de novo germline mutations can lead to the loss of protective immunity, aberrant immune homeostasis, and the development of autoimmune disease, or combinations of these. Forward genetic screens involving clinical material from patients with primary immunodeficiencies (PIDs) can vary in severity from life-threatening disease affecting multiple cell types and organs to relatively mild disease with susceptibility to a limited range of pathogens or mild autoimmune conditions. As central mediators of innate and adaptive immune responses, T cells are critical orchestrators and effectors of the immune response. As such, several PIDs result from loss of or altered T cell function. PID-associated functional defects range from complete absence of T cell development to uncontrolled effector cell activation. Furthermore, the gene products of known PID causal genes are involved in diverse molecular pathways ranging from T cell receptor signaling to regulators of protein glycosylation. Identification of the molecular and biochemical cause of PIDs can not only guide the course of treatment for patients, but also inform our understanding of the basic biology behind T cell function. In this chapter, we review PIDs with known genetic causes that intrinsically affect T cell function with particular focus on perturbations of biochemical pathways.
PMID: 29731008 [PubMed - in process]
Dysregulation of NRXN1 by mutant MIR8485 leads to calcium overload in pre-synapses inducing neurodegeneration in Multiple sclerosis.
Dysregulation of NRXN1 by mutant MIR8485 leads to calcium overload in pre-synapses inducing neurodegeneration in Multiple sclerosis.
Mult Scler Relat Disord. 2018 Apr 09;22:153-156
Authors: Kattimani Y, Veerappa AM
Abstract
OBJECTIVES: To identify Damaging mutations in microRNAs (miRNAs) and 3' untranslated regions (UTRs) of target genes to establish Multiple sclerosis (MS) disease pathway.
METHODS: Female aged 16, with Relapsing Remitting Multiple sclerosis (RRMS) was reported with initial symptoms of blurred vision, severe immobility, upper and lower limb numbness and backache. Whole Exome Sequencing (WES) and disease pathway analysis was performed to identify mutations in miRNAs and UTRs.
RESULTS: We identified Deleterious/Damaging multibase mutations in MIR8485 and NRXN1. miR-8485 was found carrying frameshift homozygous deletion of bases CA, while NRXN1 was found carrying nonframeshift homozygous substitution of bases CT to TC in exon 8 replacing Serine with Leucine.
CONCLUSIONS: Mutations in miR-8485 and NRXN1 was found to alter calcium homeostasis and NRXN1/NLGN1 cell adhesion molecule binding affinities. The miR-8485 mutation leads to overexpression of NRXN1 altering pre-synaptic Ca2+ homeostasis, inducing neurodegeneration.
PMID: 29729524 [PubMed - as supplied by publisher]
Understanding Skeletal Effects of Type 1 Diabetes (R01 Clinical Trial Optional)
Collaborative Activities to Expedite Environmental Health Science Research, Translation, and Community Engagement Across EHS Core Centers (Admin Supp - Clinical Trial Not Allowed)
(exome OR "exome sequencing") AND disease; +12 new citations
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(exome OR "exome sequencing") AND disease
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"systems biology"; +32 new citations
32 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2018/05/07
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.
Application of Atlas of Cancer Signalling Network in preclinical studies.
Application of Atlas of Cancer Signalling Network in preclinical studies.
Brief Bioinform. 2018 May 03;:
Authors: Monraz Gomez LC, Kondratova M, Ravel JM, Barillot E, Zinovyev A, Kuperstein I
Abstract
Cancer initiation and progression are associated with multiple molecular mechanisms. The knowledge of these mechanisms is expanding and should be converted into guidelines for tackling the disease. Here, we discuss the formalization of biological knowledge into a comprehensive resource: the Atlas of Cancer Signalling Network (ACSN) and the Google Maps-based tool NaviCell, which supports map navigation. The application of ACSN for omics data visualization, in the context of signalling maps, is possible via the NaviCell Web Service module and through the NaviCom tool. It allows generation of network-based molecular portraits of cancer using multilevel omics data. We review how these resources and tools are applied for cancer preclinical studies. Structural analysis of the maps together with omics data helps to rationalize the synergistic effects of drugs and allows design of complex disease stage-specific druggable interventions. The use of ACSN modules and maps as signatures of biological functions can help in cancer data analysis and interpretation. In addition, they empowered finding of associations between perturbations in particular molecular mechanisms and the risk to develop a specific type of cancer. These approaches are helpful, among others, to study the interplay between molecular mechanisms of cancer. It opens an opportunity to decipher how gene interactions govern the hallmarks of cancer in specific contexts. We discuss a perspective to develop a flexible methodology and a pipeline to enable systematic omics data analysis in the context of signalling network maps, for stratifying patients and suggesting interventions points and drug repositioning in cancer and other diseases.
PMID: 29726961 [PubMed - as supplied by publisher]
PregOMICS-Leveraging systems biology and bioinformatics for drug repurposing in maternal-child health.
PregOMICS-Leveraging systems biology and bioinformatics for drug repurposing in maternal-child health.
Am J Reprod Immunol. 2018 May 04;:e12971
Authors: Goldstein JA, Bastarache LA, Denny JC, Pulley JM, Aronoff DM
Abstract
Obstetric diseases remain underserved and understudied. Drug repurposing-utilization of a drug whose use is accepted in one condition for a different condition-could represent a rapid and low-cost way to identify new therapies that are known to be safe. In diseases of pregnancy, the known safety profile is a strong additional incentive. We describe the techniques and steps used in the use of 'omics data for drug repurposing. We illustrate these techniques using case studies of published drug repurposing projects. We provide a set of available databases with low barriers to entry which investigators can use to perform their own projects. The promise of 'omics techniques is unbiased screening, either of all drug targets or of all patients using particular drugs to find which are likely to alter disease risk or progression. However, we caution that reproducibility across the underlying studies, and thus the drugs suggested for repurposing, can be poor. We suggest that improved nosology, for example correlating patient clinical conditions with placental pathology, could yield more robust associations. We conclude that 'omics-driven drug repurposing represents a potential fruitful path to discover new, safe treatments of obstetric diseases.
PMID: 29726581 [PubMed - as supplied by publisher]
The Mu.Ta.Lig. Chemotheca: A Community-Populated Molecular Database for Multi-Target Ligands Identification and Compound-Repurposing.
The Mu.Ta.Lig. Chemotheca: A Community-Populated Molecular Database for Multi-Target Ligands Identification and Compound-Repurposing.
Front Chem. 2018;6:130
Authors: Ortuso F, Bagetta D, Maruca A, Talarico C, Bolognesi ML, Haider N, Borges F, Bryant S, Langer T, Senderowitz H, Alcaro S
Abstract
For every lead compound developed in medicinal chemistry research, numerous other inactive or less active candidates are synthetized/isolated and tested. The majority of these compounds will not be selected for further development due to a sub-optimal pharmacological profile. However, some poorly active or even inactive compounds could live a second life if tested against other targets. Thus, new therapeutic opportunities could emerge and synergistic activities could be identified and exploited for existing compounds by sharing information between researchers who are working on different targets. The Mu.Ta.Lig (Multi-Target Ligand) Chemotheca database aims to offer such opportunities by facilitating information exchange among researchers worldwide. After a preliminary registration, users can (a) virtually upload structures and activity data for their compounds with corresponding, and eventually known activity data, and (b) search for other available compounds uploaded by the users community. Each piece of information about given compounds is owned by the user who initially uploaded it and multiple ownership is possible (this occurs if different users uploaded the same compounds or information pertaining to the same compounds). A web-based graphical user interface has been developed to assist compound uploading, compounds searching and data retrieval. Physico-chemical and ADME properties as well as substructure-based PAINS evaluations are computed on the fly for each uploaded compound. Samples of compounds that match a set of search criteria and additional data on these compounds could be requested directly from their owners with no mediation by the Mu.Ta.Lig Chemotheca team. Guest access provides a simplified search interface to retrieve only basic information such as compound IDs and related 2D or 3D chemical structures. Moreover, some compounds can be hidden to Guest users according to an owner's decision. In contrast, registered users have full access to all of the Chemotheca data including the permission to upload new compounds and/or update experimental/theoretical data (e.g., activities against new targets tested) related to already stored compounds. In order to facilitate scientific collaborations, all available data are connected to the corresponding owner's email address (available for registered users only). The Chemotheca web site is accessible at http://chemotheca.unicz.it.
PMID: 29725591 [PubMed]
Standard Lexicons, Coding Systems and Ontologies for Interoperability and Semantic Computation in Imaging.
Standard Lexicons, Coding Systems and Ontologies for Interoperability and Semantic Computation in Imaging.
J Digit Imaging. 2018 May 03;:
Authors: Wang KC
Abstract
Standard clinical terms, codes, and ontologies promote clarity and interoperability. Within radiology, there is a variety of relevant content resources, tools and technologies. These provide the basis for fundamental imaging workflows such as reporting and billing, and also facilitate a range of applications in quality improvement and research. This article reviews the key characteristics of lexicons, coding systems, and ontologies. A number of standards are described, including International Classification of Diseases-10-Clinical Modification (ICD-10-CM), Current Procedural Terminology (CPT), Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT), Logical Observation Identifiers Names and Codes (LOINC), and RadLex. Tools for accessing this material are reviewed, such as the National Center for Biomedical Ontology BioPortal system. Web services are discussed as a mechanism for semantic application development. Several example systems, workflows, and research applications using semantic technology are also surveyed.
PMID: 29725962 [PubMed - as supplied by publisher]
Development and validation of an HPLC-UV method for quantification of elvitegravir and others new antiretrovirals, dolutegravir and rilpivirine, in the plasma of HIV-positive patients.
Development and validation of an HPLC-UV method for quantification of elvitegravir and others new antiretrovirals, dolutegravir and rilpivirine, in the plasma of HIV-positive patients.
Biomed Chromatogr. 2018 May 04;:e4274
Authors: Tempestilli M, Ammassari A, D'Avolio A, Cicalini S, Gallo AL, Fazio S, Antinori A, Pucillo LP
Abstract
Therapeutic drug monitoring may be crucial in selected clinical conditions for the management of HIV infection. In the last years, new antiretrovirals have been introduced and in particular elvitegravir (EVG) is now recommended for first-line and in simplification treatment as well as dolutegravir (DTG) and rilpivirine (RPV). The aim of this study was to develop and validate a High Performance Liquid Chromatography-Ultra Violet (HPLC-UV) method for determining EVG and others newest antiretrovirals DTG and RPV in human plasma. A solid-phase extraction was applied to a 600 μL plasma sample. Chromatographic separation of the three drugs and internal standard were achieved with a gradient of acetonitrile and phosphate buffer on a C-18 reverse-phase analytical column with a 20-minute analytical run time. EVG, DTG were detected at 265nm and RPV at 290nm. Mean intra-day and inter-day precisions were < 10%; the mean accuracy was < 15%. Extraction recovery ranged between 105% and 82% for the drugs analyzed. Calibration curves were optimized according to the expected ranges of drug concentrations in patients; the coefficient of determination was higher than 0.997 for all drugs. This method allows for monitoring EVG, DTG and RPV in the plasma of HIV-positive patients using HPLC-UV.
PMID: 29726595 [PubMed - as supplied by publisher]
Expression levels of the runt-related transcription factor 1 and 3 genes in the development of acute myeloid leukemia.
Expression levels of the runt-related transcription factor 1 and 3 genes in the development of acute myeloid leukemia.
Oncol Lett. 2018 May;15(5):6733-6738
Authors: Krygier A, Szmajda D, Żebrowska M, Jeleń A, Balcerczak E
Abstract
The aim of the present study was to evaluate the mRNA expression level of the runt-related transcription factor 1 (RUNX1) and runt-related transcription factor 3 (RUNX3) genes in patients with acute myeloid leukemia (AML). The etiology of AML is not yet fully known, but certain genetic factors may contribute to its manifestation. The RUNX1 and RUNX3 genes have been demonstrated to serve a role in the transcription process. The group investigated in the present study included 43 patients diagnosed with AML, and the relative RUNX1 and RUNX3 expression levels were determined using reverse transcription-quantitative polymerase chain reaction. The results indicated that RUNX1 and RUNX3 expression was associated with clinicopathological features, including sex and mortality risk. Expression levels of the RUNX1 gene were higher and more variable among females (P=0.044), and mortality was more frequent among patients with a higher RUNX3 expression level (P=0.036). The data obtained from the present study suggested that RUNX3 expression may have potential value as a prognostic factor; furthermore, sex is potentially a factor that may affect the difference in RUNX1 gene expression level among females and males. Further analyses in this field will aid in the identification and elucidation of the molecular basis of leukemia.
PMID: 29725413 [PubMed]
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