Progress on the BRD4 of super enhancer regulatory element in hematologic oncology / 国际儿科学杂志

Abnormal transcription of oncogenes driven by super enhancers was found to be critical for maintaining tumor cell identity.The expression of oncogenes can be effectively suppressed by inhibiting the key regulator that super enhancers regulate oncogene transcription.Bromodomain protein 4(BRD4)is a key protein to recognize the super enhancer regulatory elements, which can bind to acetylated histones or non-histones to regulate gene transcription.The abnormal expression of BRD4 is closely related to the malignant development of a variety of hematologic oncology.Targeting BRD4 can effectively control the malignant development of hematologic tumors.In recent years, BRD4-targeted drugs in hematologic oncology have received extensive attention, and they showed good antitumor effects either as a single drug or in combination with other drugs.In this paper, in order to provide a new understanding of the occurrence of leukemia and treatment of hematologic oncology, the biological functions of BRD4 as well as the molecular drugs targeting BRD4 are reviewed.

Cultivation of students' autonomous learning ability in molecular medicine teaching in medical colleges by flipped classroom teaching model / 中华医学教育探索杂志

This paper aims to explore a new way to cultivate college students' autonomous learning ability by taking the flipped classroom teaching of molecular medicine in medical colleges as an example. In view of the specific teaching content and characteristics of molecular medicine, we formulated a mixed teaching plan based on flipped classroom. By setting the teaching objectives and tasks beforehand, students were guided to explore and acquire knowledge independently from the abundant teaching resources library. In order to test the effect of students' autonomous learning and expand the cultivation of students' ability of information collection and processing, inquiry initiation, and communication and cooperation, we launched classroom discussions, communications, questions answering and group collaborative research topic-based reports. Through the reform of teaching assessment system, students' autonomous learning status can be effectively monitored to help ensure the implementation of the flipped classroom.

Treatment Decisions of World Health Organization Grade II and III Ependymomas in Molecular Era

Surgery and radiotherapy are mainstays of treatment for ependymomas (EPNs). Recent molecular subgrouping could be superior to histopathological grading for predicting the prognosis of patients with EPNs. Gross total resection is an effective treatment approach regardless of its locations or pathologic grades. Adjuvant therapeutic strategies could be decided based on molecular subgrouping with risk-stratification. Information of histologic-molecular biology is now providing clues to therapeutic insights.

Treatment Decisions of World Health Organization Grade II and III Ependymomas in Molecular Era

Surgery and radiotherapy are mainstays of treatment for ependymomas (EPNs). Recent molecular subgrouping could be superior to histopathological grading for predicting the prognosis of patients with EPNs. Gross total resection is an effective treatment approach regardless of its locations or pathologic grades. Adjuvant therapeutic strategies could be decided based on molecular subgrouping with risk-stratification. Information of histologic-molecular biology is now providing clues to therapeutic insights.

Molecular Classification of Colorectal Cancers and Clinical Application / 대한소화기학회지

The molecular genetics of colorectal cancers (CRCs) is among the best understood of common human cancers. It is difficult to predict the prognosis and/or to predict chemoresponding in CRC patients. At present, prognosis is based predominantly on the tumor stage and pathological examination of the disease. Molecular classification of CRCs, based on genomics and transcriptomics, proposed that CRCs can be classified into at least three-to-six subtypes, depending on the gene expression pattern, and groups of marker genes representing to each subtype have also been reported. Gene expression-based subtyping is now widely accepted as a relevant source of disease stratification. We reviewed the previous studies on CRC subtyping, international consortium dedicated to large-scale data sharing and analytics recently established four consensus molecular subtypes with distinguishing features. Predictive markers identified in these studies are under investigation and large-scale clinical evaluations of molecular markers are currently in progress.

Personalized medicine and the clinical laboratory / Medicina personalizada e o laboratório clínico

Personalized medicine is the use of biomarkers, most of them molecular markers, for detection of specific genetic traits to guide various approaches for preventing and treating different conditions. The identification of several genes related to heredity, oncology and infectious diseases lead to the detection of genetic polymorphisms that are involved not only in different clinical progression of these diseases but also in variations in treatment response. Currently, it is possible to detect these polymorphisms using several methodologies: detection of single nucleotide polymorphisms using polymerase chain reaction methods; nucleic acid microarray detection; and nucleic acid sequencing with automatized DNA sequencers using Sanger-derived methods and new generation sequencing. Personalized medicine assays are directed towards detecting genetic variations that alter interactions of drugs with targets or the metabolic pathways of drugs (upstream and downstream) and can be utilized for the selection of drug formulations and detect different immunogenicities of the drug. Personalized medicine applications have already been described in different areas of Medicine and allow specific treatment approaches to be applied to each patient and pathology according to the results of these assays. The application of such a protocol demands an increasing interaction between the clinical laboratory and the clinical staff. For its implementation, a coordinated team composed of basic researchers and physicians highly specialized in their areas supported by a highly specialized team of clinical analysts particularly trained in molecular biology assays is necessary.

Medicina personalizada é o uso de biomarcadores, em sua maioria marcadores moleculares, para a detecção de traços genéticos específicos, a fim de orientar diversas abordagens para a prevenção e o tratamento de diferentes doenças. A identificação de vários genes relacionados a doenças hereditárias, oncológicas e infecciosas permite a detecção de polimorfismos genéticos que estão envolvidos em diferentes evoluções clínicas dessas doenças, bem como com variações na resposta ao tratamento. Atualmente, já é possível detectar esses polimorfismos utilizando diversas metodologias: a detecção de polimorfismos de nucleotídeo único pela reação de polimerização em cadeia; a detecção de microarranjos de ácidos nucleicos; e o sequenciamento de ácidos nucleicos com sequenciadores de DNA automatizados usando métodos derivados de sequenciamento Sanger ou de nova geração. Os ensaios de medicina personalizada são dirigidos para detectar variações genéticas que alteram interações de fármacos com alvos ou vias metabólicas de fármacos (anabólicas e catabólicas), podendo ser utilizados para a seleção de formulações farmacêuticas e para detectar diferentes imunogenicidades da droga. As aplicações de medicina personalizada já foram descritas em várias áreas da Medicina e permitem que abordagens de tratamento específicas sejam aplicadas para cada paciente e para cada doença, de acordo com os resultados dos ensaios utilizados. A aplicação de um protocolo desse tipo exige uma relação intensa entre o laboratório e o corpo clínico. Para sua execução, é necessária uma equipe coordenada, composta por investigadores de pesquisa básica e médicos altamente especializados em suas áreas, apoiada por um time bastante especializado de analistas clínicos treinados em testes de biologia molecular.

Construction of experimental course group in molecular medicine based on improving medical students' comprehensive ability / 中华医学教育探索杂志

In order to adapt to the requirements of modem medical knowledge and skills for higher medical workers,and to cultivate medical students' molecular medicine quality and comprehensive ability,Weifang Medical University broke the boundaries of disciplines and constructed experimental course group in molecular medicine based on the ideas of curriculum group construction.Molecular medical knowledge was integrated into the teaching process of experimental course group,experimental teaching content system was reasonably integrated and optimized,high quality teaching team was set up,multi-level experimental teaching platform was built and student-centered teaching mode was implemented to explore the experimental teaching approach which helped medical students to form systematic molecular medicine knowledge structure and ability structure.

Investigación preclínica por microPET en la UNAM / Pre-clinical research at UNAM using microPET

La tomografía por emisión de positrones (PET) es una técnica de imágenes de medicina nuclear ya establecida en México, fundamental en el diagnóstico y seguimiento clínico de enfermedades oncológicas, neurológicas y cardiológicas. Esta modalidad de imagenología molecular está basada en la administración de cantidades muy pequeñas de fármacos marcados con emisores de positrones y en la subsecuente detección de radiación con el fin de obtener imágenes tomográficas que reflejan la distribución del radiofármaco en el paciente. El desarrollo de nuevos radiofármacos para PET requiere de un método para verificar que éstos siguen las rutas metabólicas de interés, que su vida media biológica es suficiente para la realización de un estudio, que no tienen efectos adversos y que es viable para estudios en pacientes. El desarrollo de equipos de microtomografía por emisión de positrones (microPET), dedicados a estudiar animales de laboratorio, ha permitido realizar estas pruebas antes de su aplicación clínica. Además, el microPET es una herramienta de gran utilidad en la investigación preclínica de diversas enfermedades, en el desarrollo de tratamientos innovadores que permite el seguimiento no invasivo en modelos animales. En la Unidad PET/CT-Ciclotrón de la Facultad de Medicina de la UNAM, se cuenta desde hace unos años con un equipo microPET para investigación. En este trabajo se muestran algunos resultados de los estudios que se realizan con mayor frecuencia con el microPET utilizando los radiofármacos de mayor uso en el medio clínico y se muestra la utilidad que puede tener en diversos proyectos de investigación.

Positron emission tomography (PET) is a nuclear medicine imaging technique well established in Mexico, essential for the clinical diagnosis and follow-up of oncological, neurological and cardiac pathologies. This molecular imaging modality is based on the administration of small amounts of drugs labeled with a positron emitting radionuclides and the subsequent radiation detection to obtain tomographic images which reflect the distribution of the radiopharmaceutical in the patient. The development of new radiopharmaceuticals for PET requires a method to verify that they follow the expected metabolic pathways, that they have a long-enough biological half-life for imaging studies, that they have no side effects and that it is viable for use in patients. The development of positron emission microtomography (microPET) systems to be used in small laboratory animale has allowed researchers to perform these tests on radiopharmaceuticals before being used in the clinic. In addition, microPET is a useful tool in preclinical research of different diseases in the development of innovating non-invasive treatments allowing to follow up animal models. At the PET/CT-Ciclotron Unit, Facultad de Medicina, UNAM, a microPET system has been available in the last few years for research purposes. In this work, examples of frequent imaging studies performed with the microPET and in-the-clinic commonly-used radiopharmaceuticals, as well the use it may have in different research projects are shown here.

Molecular medicine: a path towards a personalized medicine / Medicina molecular: um passo em direção à medicina personalizada

Psychiatric disorders are among the most common human illnesses; still, the molecular and cellular mechanisms underlying their complex pathophysiology remain to be fully elucidated. Over the past 10 years, our group has been investigating the molecular abnormalities in major signaling pathways involved in psychiatric disorders. Recent evidences obtained by the Instituto Nacional de Ciência e Tecnologia de Medicina Molecular (National Institute of Science and Technology - Molecular Medicine, INCT-MM) and others using behavioral analysis of animal models provided valuable insights into the underlying molecular alterations responsible for many complex neuropsychiatric disorders, suggesting that "defects" in critical intracellular signaling pathways have an important role in regulating neurodevelopment, as well as in pathophysiology and treatment efficacy. Resources from the INCT have allowed us to start doing research in the field of molecular imaging. Molecular imaging is a research discipline that visualizes, characterizes, and quantifies the biologic processes taking place at cellular and molecular levels in humans and other living systems through the results of image within the reality of the physiological environment. In order to recognize targets, molecular imaging applies specific instruments (e.g., PET) that enable visualization and quantification in space and in real-time of signals from molecular imaging agents. The objective of molecular medicine is to individualize treatment and improve patient care. Thus, molecular imaging is an additional tool to achieve our ultimate goal.

Os transtornos psiquiátricos estão entre as doenças humanas mais comuns. Os mecanismos celulares e moleculares subjacentes à sua complexa fisiopatologia ainda não estão totalmente esclarecidos. Nosso grupo está envolvido na investigação de anormalidades moleculares nas principais vias de sinalização das doenças psiquiátricas nos últimos 10 anos. Evidências recentemente obtidas pelo Instituto Nacional de Ciência e Tecnologia de Medicina Molecular (INCT-MM), utilizando análise comportamental de modelos animais, forneceram informações valiosas sobre as alterações moleculares subjacentes responsáveis por muitos distúrbios neuropsiquiátricos complexos, sugerindo que os "defeitos" nas vias de sinalização intracelular têm um papel importante na regulação do neurodesenvolvimento, bem como na fisiopatologia e eficácia do tratamento. Recursos do INCT nos permitiram iniciar pesquisas na área de imagem molecular. A imagem molecular é uma disciplina de investigação que visualiza, caracteriza e quantifica processos biológicos que ocorrem em níveis celular e molecular em seres humanos, e em outros sistemas vivos, através dos resultados de imagem dentro da realidade do ambiente fisiológico. A fim de reconhecer alvos, a imagem molecular aplica instrumentos específicos (PET, por exemplo) que permitem a visualização e quantificação em espaço e tempo real dos sinais dos agentes de imagem molecular, fornecendo medições de processos a nível molecular e celular. O objetivo da medicina molecular é individualizar o tratamento e melhorar a assistência ao paciente. Desse modo, a imagem molecular consiste em mais uma ferramenta para atingirmos nosso objetivo final.

Molecular Optical Imaging in Neuroscience

Molecular imaging is leading an important role in the era of molecular medicine. Optical imaging, a rising star in the filed of molecular imaging, largely consists of bioluminescent imaging and fluorescent imaging. It has been shown that well-aimed and creatively-built optical-imaging-reporters let researchers explore and answer a lot of biologically important questions in living subjects. Despite relatively short history, molecular optical imaging is rapidly being implemented not only in many clinical areas but also in various research fields from tracking gene expression, protein-protein interaction or migrating cells to molecular diagnosis and treatment.

Optical Imaging in the Field of Molecular Imaging

Molecular imaging is leading an important role in the era of molecular medicine. Optical imaging, a rising star in the filed of molecular imaging, largely consists of fluorescent imaging and bioluminescent imaging. In the fluorescence imaging, an illuminating light excites fluorescent reporters in the living subject, and a charged coupled device (CCD) camera collects an emission light of shifted wavelength. In the bioluminescent imaging, reporter genes code for the luciferase that is responsible for fireflies' glow. After the injection of the substrate iuciferin, animals carrying the luciferase gene are imaged with a supersensitive CCD camera to pick up the small number of photons transmitted through tissues. It has been shown that well aimed and creatively built reporters let researchers explore and answer a lot of biologically important questions in living subjects. Despite its relatively short history, optical imaging is rapidly being implemented in various clinical areas as well as research fields.