RESUMEN
The dynorphin/κ-opioid receptor system has been implicated in the pathogenesis and pathophysiology of several psychiatric disorders. In the present review, we present evidence indicating a key role for this system in modulating neurotransmission in brain circuits that subserve mood, motivation, and cognitive function. We overview the pharmacology, signaling, post-translational, post-transcriptional, transcriptional, epigenetic and cis regulation of the dynorphin/κ-opioid receptor system, and critically review functional neuroanatomical, neurochemical, and pharmacological evidence, suggesting that alterations in this system may contribute to affective disorders, drug addiction, and schizophrenia. We also overview the dynorphin/κ-opioid receptor system in the genetics of psychiatric disorders and discuss implications of the reviewed material for therapeutics development.
Asunto(s)
Dinorfinas/fisiología , Trastornos Mentales/etiología , Receptores Opioides kappa/fisiología , Encéfalo/fisiología , Estimulantes del Sistema Nervioso Central/farmacología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/fisiología , Dinorfinas/genética , Encefalinas/genética , Epigénesis Genética , Regulación de la Expresión Génica , Humanos , Trastornos Mentales/tratamiento farmacológico , Modelos Animales , Precursores de Proteínas/genética , Receptores Opioides kappa/agonistas , Receptores Opioides kappa/genética , Autoestimulación , Transducción de SeñalRESUMEN
PURPOSE: To determine the ethnic/racial distribution of patients entered in national pediatric cancer clinical trials relative to the patient population served. METHODS: The ethnic/racial distribution of 29,134 patients < 20 years of age entered in clinical trials conducted by the Children's Cancer Group (CCG) and Pediatric Oncology Group (POG) between January 1, 1991 and June 30, 1994 were compared with the expected distribution of patients of the same age in the United States. The latter was predicted from the 1989 to 1991 crude incidence data of the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) program applied to the 1990 United States census. RESULTS: Of the patients on CCG and POG trials, 11.6% were reported to be Hispanic, 10.4% were African-American, and 4.7% were other racial groups. The expected values were 9.1%, 10.7% and 4.3%, respectively. Representation of minority patients was equal or greater than expected for 24 of 27 subgroups analyzed. CONCLUSIONS: In the United States, minority children with cancer are proportionately represented on clinical trials of the two national pediatric cancer cooperative groups. They and their families are provided with an equal opportunity to access clinical cancer trials and the potential benefits of cancer research.
Asunto(s)
Ensayos Clínicos como Asunto , Grupos Minoritarios , Estudios Multicéntricos como Asunto , Neoplasias/terapia , Selección de Paciente , Niño , Etnicidad , Humanos , National Institutes of Health (U.S.) , Grupos Raciales , Programa de VERF , Estados UnidosRESUMEN
BACKGROUND: The National Cancer Institute (NCI)-sponsored clinical trials cooperative groups place more than 25 000 American patients in treatment trials every year. Equal access and proportional representation of all races/ethnicities is desired. PURPOSE: Our objectives were to evaluate the inclusion of African-Americans, Hispanics, and non-Hispanic whites in NCI-sponsored treatment trials and to determine if there is proportional racial/ethnic representation. METHODS: During the period of January 1, 1991, through June 30, 1994, 99 495 cancer patients were enrolled in clinical trials and declared themselves as non-Hispanic black, non-Hispanic white, or Hispanic (of any race). In the analysis, participants in NCI treatment trials were subdivided into three age groups: birth to 19 years, 20-49 years, and 50 or more years. The racial/ethnic composition of each of these age groups was compared with the racial/ethnic makeup of the American population with cancer. Estimates of the number of incident cancer cases per year were made for each racial/ethnic group within each age group using data from the Surveillance, Epidemiology, and End Results (SEER) Program and the 1990 Census. The percentage of all cancer patients who were in each racial/ethnic group were compared with the population that entered clinical trials. Comparisons are also made separately for patients with leukemia and breast, colorectal, lung, and prostate cancers. RESULTS: Among patients 0-19 years old, 20-49 years old, and 50 years old or older there is relatively proportional representation of non-Hispanic blacks, Hispanics, and non-Hispanic whites in trials. It is noted that more than 70% of cancer patients aged 0-19 years are estimated to enter cooperative group clinical trials compared with 4.0% of cancer patients aged 20-49 years and 1.5% of patients aged 50 years or older. CONCLUSIONS: Accrual of American cancer patients to NCI-sponsored treatment trials generally parallels the incident burden of disease among non-Hispanic African-Americans, Hispanics, and non-Hispanic whites. IMPLICATIONS: This study shows that the NCI clinical trials are, as a whole, racially/ethnically representative of the American population and suggests that there is equal access to NCI clinical trials.