RESUMEN
AIM: The aim of this study was to determine the ability of G17DT to generate anti-gastrin antibodies in jaundiced patients with biliary obstruction due to advanced pancreatic cancer. METHODS: G17DT was administered to 41 patients with advanced pancreatic adenocarcinoma by intramuscular (i.m.) injection at a dose of 250mcg at weeks 0, 1 and 3 of the study. RESULTS: Thirty-five of 41 patients participating in the study were categorized as responders in terms of their gastrin-17 antibody response. There was no correlation between the maximum G17 antibody response and the bilirubin level at either week 0 or week 12. The median survival of patients from the time of the first injection of G17DT was 204 days with 25% of patients surviving for
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Gastrinas/inmunología , Inmunización , Ictericia/inmunología , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Formación de Anticuerpos/efectos de los fármacos , Bilirrubina/sangre , Vacunas contra el Cáncer/efectos adversos , Vacunas contra el Cáncer/sangre , Colestasis/inmunología , Progresión de la Enfermedad , Femenino , Gastrinas/efectos adversos , Gastrinas/sangre , Gastrinas/uso terapéutico , Humanos , Inmunización/efectos adversos , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/inmunología , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Reino UnidoRESUMEN
PURPOSE: G17DT is a gastrin immunogen, raising antibodies that blockade gastrin-stimulated growth. The aim of the study was to characterise antibody response and assess safety and tolerability of G17DT given to patients with gastric cancer. EXPERIMENTAL DESIGN: G17DT was administered to 52 patients with gastric adenocarcinoma at weeks 0, 2 and 6 by intramuscular injection at doses of 10, 100 and 250 microg. Antibody levels were measured by an ELISA assay. A radioligand displacement assay determined the ability of G17DT-immunised patients' sera to inhibit binding of 125IG17 to cholecystokinin (CCK)-2 receptors. RESULTS: By week 12 of the study, 6/12 evaluable stage I-III patients achieved an antibody response in the 10 microg group, 7/11 in the 100 microg group, and 11/12 in the 250 microg group. Stage IV patients dosed at 250 microg achieved a similar response rate to stage I-III patients dosed at 10 or 100 microg. G17DT was well tolerated in 47/52 patients. Two patients suffered significant adverse reactions including injection site pain and abscess. G17DT antibodies displaced iodinated gastrin from CCK-2 receptors, with the level of displacement correlating with antibody titre. CONCLUSIONS: G17DT immunisation is a well-tolerated method of raising functional antibodies to 17 amino acid gastrin forms in patients with gastric carcinomas.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/inmunología , Formación de Anticuerpos/efectos de los fármacos , Vacunas contra el Cáncer/administración & dosificación , Gastrinas , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/inmunología , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Vacunas contra el Cáncer/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Sueros Inmunes/efectos de los fármacos , Sueros Inmunes/inmunología , Inmunización Secundaria , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Receptor de Colecistoquinina B/efectos de los fármacos , Receptor de Colecistoquinina B/inmunología , Estadística como Asunto , Neoplasias Gástricas/patología , Resultado del TratamientoRESUMEN
BACKGROUND: A stepwise progression through premalignant stages has been identified for the intestinal type of gastric carcinoma. As gastrin has been identified as a growth factor for the intestinal type of gastric adenocarcinoma, the aim of this study was to investigate whether gastrin is expressed in premalignant gastric conditions. METHODS: Ninety archival samples of atrophic gastritis, intestinal metaplasia, mild gastric epithelial dysplasia, moderate gastric epithelial dysplasia, severe gastric epithelial dysplasia and intestinal-type gastric adenocarcinoma were obtained. Immunocytochemistry was performed using antibodies directed against gastrin and its post-translational precursors, and the gastrin/cholecystokinin B receptor. Positive staining was identified using the avidin--biotin immunoperoxidase method and quantified using an image analysis system. RESULTS: Gastrin and its receptor were shown to be expressed in specimens of atrophic gastritis, intestinal metaplasia, epithelial dysplasia and the intestinal type of gastric carcinoma. CONCLUSION: Gastrin seems to be an important growth factor in gastric carcinogenesis.
Asunto(s)
Adenocarcinoma/metabolismo , Biomarcadores de Tumor/metabolismo , Gastrinas/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/etiología , Gastrinas/fisiología , Humanos , Inmunohistoquímica , Precursores de Proteínas/metabolismo , Antro Pilórico/metabolismo , Receptor de Colecistoquinina B , Receptores de Colecistoquinina/metabolismo , Neoplasias Gástricas/etiologíaAsunto(s)
Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Servicios de Atención de Salud a Domicilio/estadística & datos numéricos , Alta del Paciente , Recolección de Datos , Investigación sobre Servicios de Salud , Servicios de Atención de Salud a Domicilio/normas , Servicios de Atención de Salud a Domicilio/provisión & distribución , Tiempo de Internación , Evaluación de Programas y Proyectos de Salud , Medicina Estatal , Reino UnidoRESUMEN
The implementation of the NHS and Community Care Act 1990 made local authority social services departments responsible for the organisation and funding of support and care in the community. This development took effect at the same time as a blurring of the boundaries between health and social care. One consequence is that the relevance of equity (a guiding principle of the 1946 National Health Service Act, but relatively lacking from the 1948 National Assistance Act, the foundation of many social services) has come to be more keenly appreciated within personal social services. Equity questions arise in community care over the distribution of public resources between different client groups, income groups, generations, and localities. Moreover, no mechanisms exist to monitor the trends that emerge from different ways that people get access to care. Yet there is a risk that substantial divisive consequences may occur, particularly between generations.