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1.
Rinsho Ketsueki ; 60(9): 1084-1091, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597831

RESUMO

The blood supply system for transfusions in Japan functions well. However, in cases of sudden hemorrhagic shock, the swift supply of red blood cell (RBC) product might be difficult, particularly when medical care is required in remote regions and in obstetric medicine, where there is always a risk of hemorrhage. Blood pressure maintenance by infusion of volume expanders, such as crystalloids or colloids, may be insufficient to preserve the function of vital organs because they do not contain any oxygen-carrying molecules. If artificial RBCs were at hand, they could be used as a blood substitute until blood products are received from blood banks. This would save patients without degrading their quality of life. In the 1990s, we developed an artificial RBC in the form of a hemoglobin vesicle (Hb-V). Hb-V is a liposomal microparticle that encloses oxygen-carrying human Hb molecules. Different from RBCs, it has no blood type and is stable at room temperature, ensuring a long shelf-life. Its excellent biocompatibility and oxygen-carrying capacity have been proven in a number of animal experiments, and its production technique has also been established. Therefore, translational research is being designed with the aid of the Japan Agency of Medical Research and Development.


Assuntos
Substitutos Sanguíneos , Eritrócitos , Choque Hemorrágico/terapia , Pesquisa Médica Translacional , Animais , Hemoglobinas , Humanos , Japão , Oxigênio
2.
Rinsho Ketsueki ; 60(9): 1341-1350, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597862

RESUMO

It has been eight years since the first immune checkpoint-blocking antibody, ipilimumab, was approved for metastatic malignant melanoma treatment by FDA in 2011. During this period, several other immune checkpoint blockers have been newly developed and approved for certain cancers, including malignant melanoma. However, there have been several concerns with some of these. The overall response rate did not exceed 30% in many cancers; although combination therapy with ipilimumab and nivolumab increased efficacy, immune-related adverse events also increased. This observation facilitated the reverse translational research (rTR) approach, using clinical specimens from treated patients to gradually elucidate the mechanism of resistance and biomarkers to select patients who can potentially benefit from immunotherapy. This has also promoted the development of novel combination therapies. In this review, immunological findings that highlight the resistance mechanisms of cancers against immune checkpoint blockers and the novel attempts to achieve a break-through will be discussed.


Assuntos
Imunoterapia , Ipilimumab/uso terapêutico , Melanoma/terapia , Nivolumabe/uso terapêutico , Neoplasias Cutâneas/terapia , Resistencia a Medicamentos Antineoplásicos , Humanos , Pesquisa Médica Translacional
3.
BMJ ; 367: l5766, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645328

RESUMO

OBJECTIVE: To determine the extent to which late stage development of new drugs relies on support from public funding. DESIGN: Cohort study. SETTING: All new drugs containing one or more new molecular entities approved by the US Food and Drug Administration (FDA) between January 2008 and December 2017 via the new drug application pathway. MAIN OUTCOME MEASURES: Patents or drug development histories documenting late stage research contributions by a public sector research institution or a spin-off company, as well as each drug's regulatory approval pathway and first-in-class designation. RESULTS: Over the 10 year study period, the FDA approved 248 drugs containing one or more new molecular entities. Of these drugs, 48 (19%) had origins in publicly supported research and development and 14 (6%) originated in companies spun off from a publicly supported research program. Drugs in these groups were more likely to receive expedited FDA approval (68% v 47%, P=0.005) or be designated first in class (45% v 26%, P=0.007), indicating therapeutic importance. CONCLUSIONS: A review of the patents associated with new drugs approved over the past decade indicates that publicly supported research had a major role in the late stage development of at least one in four new drugs, either through direct funding of late stage research or through spin-off companies created from public sector research institutions. These findings could have implications for policy makers in determining fair prices and revenue flows for these products.


Assuntos
Ensaios Clínicos como Assunto/economia , Aprovação de Drogas/economia , Setor Público/economia , Pesquisa Médica Translacional/economia , Ensaios Clínicos como Assunto/estatística & dados numéricos , Estudos de Coortes , Aprovação de Drogas/legislação & jurisprudência , Aprovação de Drogas/estatística & dados numéricos , Humanos , Patentes como Assunto/estatística & dados numéricos , Setor Público/estatística & dados numéricos , Pesquisa Médica Translacional/estatística & dados numéricos , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudência , United States Food and Drug Administration/estatística & dados numéricos
5.
Cancer Sci ; 110(11): 3405-3414, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31495054

RESUMO

Gastric cancer (GC) remains the fifth most prevalent cancer worldwide and the third leading cause of global cancer mortality. Comprehensive -omic studies have unveiled a heterogeneous GC landscape, with considerable molecular diversity both between and within tumors. Given the complex nature of GC, a long-sought goal includes effective identification of distinct patient subsets with prognostic and/or predictive outcomes to enable tailoring of specific treatments ("precision oncology"). In this review, we highlight various approaches to molecular classification in GC, covering recent genomic, transcriptomic, proteomic and epigenomic features. We pay special attention to the translational significance of classifier systems and examine potential confounding factors which deserve further investigation. In particular, we discuss recent advancements in our knowledge of intra-subtype, intra-patient and intra-tumor heterogeneity, and the pivotal role of the tumor stromal microenvironment.


Assuntos
Medicina de Precisão , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Dissecação , Epigênese Genética , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Oncologia/métodos , Prognóstico , Proteômica , Neoplasias Gástricas/classificação , Transcriptoma , Pesquisa Médica Translacional , Microambiente Tumoral
8.
Zhonghua Zhong Liu Za Zhi ; 41(9): 648-653, 2019 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-31550853

RESUMO

Malignant peripheral nerve sheath tumor (MPNST) is a rare invasive soft tissue sarcoma that originates from peripheral nerve branches and peripheral nerve sheaths. Early radical surgery is an effective treatment for MPNST. Since it is insensitive to radiotherapy and chemotherapy, the disease manifests a rapid progression, poor prognosis and high mortality. In recent years, the translational researches on the driving factors and therapeutic targets of MPNST have been rapidly developed, including the pathways of NF1-Ras, Raf-MEK-ERK, PI3K-AKT-mTOR, Wnt signaling, and abnormal expressions of apoptotic proteins, the general loss of polycomb repressive complex 2 (PRC2), upregulation of the HDAC family, abnormal expressions of receptor tyrosine kinases, expressions of programmed cell death ligand (PD-L1), aurora kinase and various microRNAs.This review summarizes the current translational researches on potential therapeutic targets of MPNST, and the clinical trials which provide helpful information for MPNST targeted therapy.


Assuntos
Terapia de Alvo Molecular/métodos , Neoplasias da Bainha Neural/terapia , Neurofibrossarcoma/terapia , Humanos , Neoplasias da Bainha Neural/patologia , Neurofibrossarcoma/patologia , Fosfatidilinositol 3-Quinases , Transdução de Sinais , Pesquisa Médica Translacional
9.
Int J Nanomedicine ; 14: 5303-5321, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31406461

RESUMO

Metabolic syndrome is a common metabolic disorder which has become a public health challenge worldwide. There has been growing interest in medications including natural products as complementary or alternative choices for common chemical therapeutics regarding their limited side effects and ease of access. Nanosizing these compounds may help to increase their solubility, bioavailability, and promisingly enhance their efficacy. This study, for the first time, provides a comprehensive overview of the application of natural-products-based nanoformulations in the management of metabolic syndrome. Different phytochemicals including curcumin, berberine, Capsicum oleoresin, naringenin, emodin, gymnemic acid, resveratrol, quercetin, scutellarin, stevioside, silybin, baicalin, and others have been nanosized hitherto, and their nanosizing method and effect in treatment and alleviating metabolic syndrome have been reviewed and discussed in this study. It has been discovered that there are several pathways or molecular targets relevant to metabolic disorders which are affected by these compounds. Various natural-based nanoformulations have shown promising effect in treatment of metabolic syndrome, and therefore can be considered as future candidates instead of or in conjunction with pharmaceutical drugs if they pass clinical trials successfully.


Assuntos
Produtos Biológicos/uso terapêutico , Composição de Medicamentos , Síndrome Metabólica/tratamento farmacológico , Nanopartículas/química , Humanos , Síndrome Metabólica/fisiopatologia , Plantas Medicinais/química , Pesquisa Médica Translacional
10.
Cancer Treat Rev ; 79: 101889, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31445415

RESUMO

The overall 5-year survival of gastric cancer (GC) has change only little in the last decades and it remains the fifth leading cause of cancer-related death worldwide. However, in the past few years a more effective combination chemotherapy has raised the bar of curability of about 10% in resectable disease. Morever, a deeper knowledge of GC biology have unveiled biomarkers to help personalize adjunctive treatments in patients candidate to surgery. Despite a plateau in efficacy of fist-line treatment, incremental survival advantages have been recorded in unresectable advanced disease. The growing number of effective drugs in second and later lines along with a more judicious delivery of cytotoxics and early supportive interventions have enabled more patients to proceed beyond first-line. The continuum of care has become a reality in a considerable proportion of patients that offer opportunities to improve outcomes. Finally, the advent of the immune checkpoint inhibitors has brought great expectations in molecularly-defined subset of patients. This Review summarizes the state-of-the art in the management of GC together with novel concepts that have entered clinical development with the potential of change practice in the foreseeable future.


Assuntos
Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Animais , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Quimioterapia Combinada , Humanos , Medicina de Precisão , Neoplasias Gástricas/etiologia , Pesquisa Médica Translacional , Resultado do Tratamento
11.
Int J Health Policy Manag ; 8(7): 455-458, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31441283

RESUMO

As a group of Health System Impact (HSI) postdoctoral fellows, Sim and colleagues offer their reflections on 'driving change' within the health system and present a framework for understanding the HSI fellow as an embedded researcher. Our commentary offers a different perspective of the fellow's role by highlighting the integrated knowledge translation (IKT) approach we consider to be foundational to the fellowship experience. Further, we provide several recommendations to enhance Sim and colleagues' framework to ensure we capture the full value of the fellowship program to the HSI fellow, health system organization, and academic institution.


Assuntos
Bolsas de Estudo , Pesquisa Médica Translacional , Programas Governamentais , Pessoal de Saúde , Humanos , Pesquisadores
13.
Stud Health Technol Inform ; 264: 1458-1459, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438180

RESUMO

Standardised, automated quality reports were generated at three pilot locations of the decentralized translational research network DKTK with separated local data warehouses (LDW), for assessing syntactic conformity against common data element definitions deposited in a central metadata repository (MDR). Deviations in the LDW were categorised, and locally corrected. Comparisons of reports from two time points confirm a major improvement in data quality in terms of syntactic conformity, an essential prerequisite for network-wide data integration.


Assuntos
Confiabilidade dos Dados , Pesquisa Médica Translacional , Elementos de Dados Comuns , Data Warehousing , Metadados
16.
Cancer Radiother ; 23(5): 439-448, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31358445

RESUMO

Intensity-modulated radiation therapy (IMRT) is presently the recommended technique for the treatment of locally advanced head and neck carcinomas. Proton therapy would allow to reduce the volume of irradiated normal tissue and, thus, to decrease the risk of late dysphagia, xerostomia, dysgeusia and hypothyroidism. An exhaustive research was performed with the search engine PubMed by focusing on the papers about the physical difficulties that slow down use of proton therapy for head and neck carcinomas. Range uncertainties in proton therapy (±3 %) paradoxically limit the use of the steep dose gradient in distality. Calibration uncertainties can be important in the treatment of head and neck cancer in the presence of materials of uncertain stoichiometric composition (such as with metal implants, dental filling, etc.) and complex heterogeneities. Dental management for example may be different with IMRT or proton therapy. Some uncertainties can be somewhat minimized at the time of optimization. Inter- and intrafractional variations and uncertainties in Hounsfield units/stopping power can be integrated in a robust optimization process. Additional changes in patient's anatomy (tumour shrinkage, changes in skin folds in the beam patch, large weight loss or gain) require rescanning. Dosimetric and small clinical studies comparing photon and proton therapy have well shown the interest of proton therapy for head and neck cancers. Intensity-modulated proton therapy is a promising treatment as it can reduce the substantial toxicity burden of patients with head and neck squamous cell carcinoma compared to IMRT. Robust optimization will allow to perform an optimal treatment and to use proton therapy in current clinical practice.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Física Sanitária , Terapia com Prótons , Lesões por Radiação/prevenção & controle , Radioterapia (Especialidade) , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Pesquisa Médica Translacional , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/prevenção & controle , Disgeusia/etiologia , Disgeusia/prevenção & controle , Humanos , Hipotireoidismo/etiologia , Hipotireoidismo/prevenção & controle , Modelos Teóricos , Órgãos em Risco , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia Guiada por Imagem , Radioterapia de Intensidade Modulada/efeitos adversos , Incerteza , Xerostomia/etiologia , Xerostomia/prevenção & controle
19.
AIDS Behav ; 23(Suppl 2): 214-219, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31270641

RESUMO

The need for research-informed programming and policy making is well established. However, there is limited evidence that, when researchers actively promote utilization of research findings, stakeholders use such findings for decision making in low- and middle-income countries (LMIC). A common barrier for research uptake in LMIC is that researchers focus on passive dissemination of final findings as the primary vehicle to affect research uptake. A more active approach to facilitating research utilization (RU) is necessary. Project SOAR, a six-year USAID-funded operations research project, recognized this gap and developed an approach to include the end data users in the research process from inception to final results dissemination. In this commentary, we make recommendations for active facilitation of research uptake using emerging lessons from SOAR's RU process that focuses on ongoing engagement of stakeholders throughout the life of the study.


Assuntos
Fortalecimento Institucional , Tomada de Decisões , Infecções por HIV , Pesquisa Operacional , Participação dos Interessados , Humanos , Formulação de Políticas , Projetos de Pesquisa , Pesquisadores , Pesquisa Médica Translacional
20.
Rev. Hosp. El Cruce ; (24): 35-49, 18/07/2019.
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1006626

RESUMO

OBJETIVO: Introducir al hospital en la investigación traslacional mediante la secuenciación de nueva generación sobre muestras de pacientes que concurrieron al Servicio de Hematología del Hospital El Cruce Dr. Néstor C. Kirchner -SAMIC- durante el año 2018. Analizar las mutaciones (variantes) encontradas en los pacientes con diagnóstico Síndrome Mielodisplásico (SMD), e identificar factores pronósticos. MATERIAL Y MÉTODOS: Se ha utilizado la tecnología de Secuenciación de Nueva generación, Next Generation Sequencing (NGS) en 11 pacientes, que concurrieron al Servicio de Hematología con patología mieloide, 6 Síndrome Mielodisplásicos (SMD), 3 Leucemias Mielomonocíticas crónicas y dos Leucemias Agudas. La extracción del ADN se realizó en equipo automatizado MagnaPure Compact de Roche, la cuantificación en un Fluorómetro Qubit 3.0 y la secuenciación propiamente dicha en la empresa Biosystems en un secuenciador MySeq de Illumina, su cuantificación y la generación de las librerías se llevaron a cabo en el área de biología molecular del Servicio de Laboratorio del Hospital El Cruce. La extracción RESULTADOS: Se encontraron 774 variantes totales, de las cuales 35 resultaron variantes en regiones codificantes patogénicas. De éstas, 23 fueron por cambio en un solo nucleótido, 7 inserciones con cambio de lectura, 4 deleciones y 1 variante en múltiples nucleótidos. CONCLUSIONES: Los resultados obtenidos en esta primera experiencia cumplieron con las métricas exigidas por el fabricante, ya que los indicadores de calidad de muestra ADN, preparación de biblioteca y parámetros de secuenciación fueron satisfactorios. Se encontraron mutaciones en 10 de 11 pacientes. Por un lado se hallaron afectados los mismos genes que aparecen reportados en la bibliografía y por el otro hay un número importante de variantes aún no reportadas.


OBJECTIVE: Introduce the hospital in translational research through the sequencing of new generation on samples of patients who attended the Hematology Service of El Cruce Hospital Dr. Néstor C. Kirchner -SAMIC- during the year 2018. To analyze the mutations (variants) found in patients diagnosed with Myelodysplastic Syndrome (MDS), and to identify prognostic factors. MATERIAL AND METHODS: The Next Generation Sequencing (NGS) Sequencing technology was used in 11 patients, who attended the Hematology Service with a diagnosis of Myelodysplastic Syndrome (MDS). DNA extraction was performed on Roche's MagnaPure Compact automated equipment, quantification on a Qubit 3.0 Fluorometer and actual sequencing at the Biosystems company on a MySeq sequencer from Illumina, its quantification and generation of the libraries were carried out in the molecular biology area of the Laboratory Service of El Cruce Hospital. The removal RESULTS: We found 801 total variants, of which 35 were variants in pathogenic coding regions. Of these, 23 were by change in a single nucleotide, 7 insertions with change of reading, 4 deletions and 1 variant in multiple nucleotides. CONCLUSIONS: The results obtained in this first experience complied with the metrics required by the manufacturer, since the indicators of DNA sample quality, library preparation and sequencing parameters were satisfactory. Mutations were found in all samples. On the one hand, the same genes that are reported in the literature were affected and on the other there are a significant number of variants not yet reported or that can not be associated with SMD.


Assuntos
Síndromes Mielodisplásicas , Análise de Sequência de DNA , Pesquisa Médica Translacional
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