Анализ полиморфных локусов генов ферментов антиоксидантной защиты в этнических группах республики Башкортостан

Анализ популяционно-генетической структуры популяций русских, татар и башкир, проживающих в Республике Башкортостан, по аллельным вариантам генов GSTM1, GSTT1, GSTP1, CAT, GPX1, NQO

CYP2D6 and CYP2C19 genotyping in psychiatry:bridging the gap between practice and lab

CYP2D6 and CYP2C19 are liver enzymes that play an important role in the breakdown of psychopharmaceuticals. The number of active alleles in the DNA determines how quickly these enzymes work and is translated into a phenotype. This phenotype can vary greatly per person and per ethnicity. There is a relationship between the speed of the enzyme and the occurrence of medication side effects. This study has mapped the prevalence of the different phenotypes worldwide. It has also been investigated whether there are fewer side effects in patients taking antipsychotics if you adjust the dosage of medication to the phenotype

Human variability in influx and efflux transporters in relation to uncertainty factors for chemical risk assessment

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Advancing the Science of Cancer in Latinos

This open access book gives an overview of the sessions, panel discussions, and outcomes of the Advancing the Science of Cancer in Latinos conference, held in February 2018 in San Antonio, Texas, USA, and hosted by the Mays Cancer Center and the Institute for Health Promotion Research at UT Health San Antonio. Latinos – the largest, youngest, and fastest-growing minority group in the United States – are expected to face a 142% rise in cancer cases in coming years. Although there has been substantial advancement in cancer prevention, screening, diagnosis, and treatment over the past few decades, addressing Latino cancer health disparities has not nearly kept pace with progress. The diverse and dynamic group of speakers and panelists brought together at the Advancing the Science of Cancer in Latinos conference provided in-depth insights as well as progress and actionable goals for Latino-focused basic science research, clinical best practices, community interventions, and what can be done by way of prevention, screening, diagnosis, and treatment of cancer in Latinos. These insights have been translated into the chapters included in this compendium; the chapters summarize the presentations and include current knowledge in the specific topic areas, identified gaps, and top priority areas for future cancer research in Latinos. Topics included among the chapters: Colorectal cancer disparities in Latinos: Genes vs. Environment Breast cancer risk and mortality in women of Latin American origin Differential cancer risk in Latinos: The role of diet Overcoming barriers for Latinos on cancer clinical trials Es tiempo: Engaging Latinas in cervical cancer research Emerging policies in U.S. health care Advancing the Science of Cancer in Latinos proves to be an indispensable resource offering key insights into actionable targets for basic science research, suggestions for clinical best practices and community interventions, and novel strategies and advocacy opportunities to reduce health disparities in Latino communities. It will find an engaged audience among researchers, academics, physicians and other healthcare professionals, patient advocates, students, and others with an interest in the broad field of Latino cancer

Farmacogenética de la quimioterapia de los tumores gastrointestinales.

Las fluoropirimidinas son agentes citotóxicos utilizados en el esquema de primera línea para el tratamiento de las neoplasias de origen gastrointestinal. Aunque su empleo ha significado un incremento en los tiempos de sobrevida para los pacientes con tumores avanzados, aún persiste una elevada incidencia (>20%) de reacciones tóxicas graves, así como fracasos en la respuesta para un número importante de pacientes. La enzima timidilato sintasa (TS) es el blanco farmacológico de las fluoropirimidinas y como tal se ha propuesto como un potencial marcador de pronóstico para la quimioterapia basada en fluoropirimidinas. Objetivo: En el presente trabajo se abordó el problema de validar a TS como biomarcador de respuesta a quimioterapia en tumores de origen gastrointestinal desde un punto de vista farmacogenético. Métodos: Para ello se evaluó la presencia de algunas variantes de línea germinal en las regiones no codificantes del gen TYMS y su asociación con la respuesta clínica y la toxicidad a fluoropirimidinas, asi como su relación con la expresión tisular de la enzima TS. Resultados: Se estableció que los pacientes con cáncer colorrectal (CCR) con el genotipo 2R/2R (rs45445694), tienen un mayor riesgo (OR=10.000, p=0.021) de presentar toxicidad grave. En un análisis prospectivo en pacientes con tumores gastrointestinales que recibieron quimioterapia basada en fluoropirimidinas, se asoció la presencia conjunta del alelo 3R(rs45445694) y del alelo G (rs2853542) con un fracaso en la respuesta al tratamiento (OR=4.684, p=0.004), mientras que la presencia del genotipo 6bp+/6bp+ para la variante en la región 3’UTR del gen (rs151264360) se asoció con una respuesta positiva al tratamiento (OR=4.176, p=0.004). Ninguno de los genotipos analizados se asoció con la expresión (mRNA) de TS en tejido tumoral. Conclusiones: Tomando en conjunto estos resultados se propone que las variantes en regiones no codificantes del gen TYMS son biomarcadores genéticos de respuesta y toxicidad a la quimioterapia en pacientes con tumores gastointestinales. Este es el primer trabajo que aborda la farmacogenética de la quimioterapia de los tumores gastrointestinales en población mexicana y por primera vez se identifica el diplotipo 3RG como marcador independiente de fracaso en la respuesta clínica a las fluoropirimidinas. _________________________________________________________________________ Dr.C. Augusto Rojas Martínez Director de Tesis ABSTRACT: Fluoropyrimidines are a class of cytotoxic drugs used in the treatment of gastrointestinal neoplasms. Even though their use has resulted in longer survivals for patients with avanzed tumors, severe toxicity has also been evident (>20%) as well as a failed outcome for some patients. Fluoropyrimidines targets thymidylate synthase (TS) enzyme. The latter has been proposed as a potential predictive response marker for fluoropyrimidine-based treatment. In the present work it was hypothesized if TS is a potential pharmacogenetic biomarker for fluoropyrimidne-based chemotherapy response in patients with gastrointestinal tumors. In behalf of this, it was evaluated the presence of germ-line variants in the untranslated regions of the TYMS gene and their association with response and toxicity in a group of patients with gastrointestinal tumors treated with fluoropyrimidine-based chemotherapy. It was also evaluated the expressionión of TS in tumor samples from these patients. It was stablished that colorrectal cancer patients witn the 2R/2R genotype (rs45445694) has a higher risk of severe toxicity (OR=10.000, p=0.021). In a prospective analysis of patients with gastrointestinal tumors, we found an association of alleles 3R(rs45445694) and G (rs2853542) with a worse response to chemotherapy (OR=4.684, p=0.004). The presence of the 6bp+/6bp+ genotype in the 3’UTR variant (rs151264360) was associated with a better response to chemotherapy (OR=4.176, p=0.004). None of the genotypes evaluated was associated with the expression (mRNA) of TS in tumor samples. Taking together these results, it is proposed that germ-line variants in the UTR regions of the TYMS gene are genetic biomakers for response and toxicity in fluoropyrimidine-based chemotherapy treatment of patients with avanzed gastrointestinal tumors. This is the first study related to pharmacogenetics of the chemotherapy of gastrointestinal tumors in mexican population and for the first time it is proposed the 3RG diplotype as an independent marker for response failure to fluoropyrimidines

Federal Register

Daily publication of the U.S. Office of the Federal Register contains rules and regulations, proposed legislation and rule changes, and other notices, including "Presidential proclamations and Executive Orders, Federal agency documents having general applicability and legal effect, documents required to be published by act of Congress, and other Federal agency documents of public interest" (p. ii). Table of Contents starts on page iii

EQUITABLE ACCESS TO HUMAN BIOLOGICAL RESOURCES IN DEVELOPING COUNTRIES: Benefit Sharing Without Undue Inducement.

The main research question of this thesis is: How can cross-border access to human genetic resources, such as blood or DNA samples, be governed to achieve equity for developing countries? Access to and benefit sharing for human biological resources is not regulated through an international legal framework such as the Convention on Biological Diversity, which applies only to plants, animals and micro-organisms as well as associated traditional knowledge. This legal vacuum for the governance of human genetic resources can be attributed (in part) to the concern that benefit sharing might provide undue inducements to research participants and their communities. This thesis shows that: (a) Benefit sharing is crucial to avoiding the exploitation of developing countries in genomic research. (b) With functioning research ethics committees, undue inducement is less of a concern in genetic research than in other medical research (e.g. clinical trials). (c) Concerns remain over research involving indigenous populations and some recommendations are provided. In drawing its conclusions, the thesis resolves a highly pressing topic in global bioethics and international law. Originally, it combines bioethical argument with jurisprudence, in particular reference to the law of equity and the legal concepts of duress (coercion), unconscionable dealing, and undue influence

Amyloidosis

Amyloidoses are a heterogeneous group of diverse etiology diseases. They are characterized by an endogenous production of abnormal proteins called amyloid proteins, which are not hydrosoluble, form depots in various organs and tissue of animals and humans and cause dysfunctions. Despite many decades of research, the origin of the pathogenesis and the molecular determinants involved in amyloid diseases has remained elusive. At present, there is not an effective treatment to prevent protein misfolding in these amyloid diseases. The aim of this book is to present an overview of different aspects of amyloidoses from basic mechanisms and diagnosis to latest advancements in treatment