RESUMEN
É apresentada uma revisäo dos principais aspectos concernentes à anatomia patológica, fisiopatologia e diagnóstico dos insulinomas
Asunto(s)
Humanos , Insulinoma/análisis , Brasil , Insulinoma/fisiopatologíaRESUMEN
A protein with pancreastatin-like immunoreactivity has been isolated and purified from liver metastasis of a patient with insulinoma. NH2-terminal residue analysis, in conjunction with the use of antibodies that are specific for the C-terminal amide peptide of porcine pancreastatin, identified this protein as a 186-amino-acid protein corresponding to human chromogranin A-116-301 (the fragment corresponding to the positions from 116 to 301 of human chromogranin A). Digestion of this protein with trypsin yielded a 48-amino-acid peptide with the retention of full pancreastatin activity. Serum from patient with insulinoma contains a peptide specie(s) that comigrates with the 48-amino-acid pancreastatin, suggesting that this peptide might be a physiologically important circulation form of pancreastatin in humans. A sensitive radioimmunoassay was established using antibody developed against a synthetic 29-amino-acid peptide amide of pancreastatin. Immunocytochemical staining revealed that a major population of human pancreatic islet cells were immunoreactive to the antiserum but with varying intensity of staining. Pancreastatin-like immunoreactivity was not observed in exocrine acinar cells.
Asunto(s)
Adenoma de Células de los Islotes Pancreáticos/metabolismo , Cromograninas/análisis , Insulinoma/metabolismo , Proteínas de Neoplasias/aislamiento & purificación , Proteínas del Tejido Nervioso/análisis , Hormonas Pancreáticas/aislamiento & purificación , Secuencia de Aminoácidos , Anticuerpos/análisis , Cromogranina A , Cromograninas/síntesis química , Humanos , Inmunohistoquímica , Insulinoma/análisis , Insulinoma/secundario , Neoplasias Hepáticas/secundario , Datos de Secuencia Molecular , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Hormonas Pancreáticas/análisis , Radioinmunoensayo , TripsinaRESUMEN
The authors have investigated by immunohistochemistry the distribution of factor X-like antigen in normal pancreatic islets and in a series of 46 pancreatic endocrine tumours. It was found that both glucagon-producing (A) cells and pancreatic polypeptide-producing (PP) cells are immunoreactive for the antigen. Benign glucagonomas and PP-omas presented the highest concentrations of immunoreactive material whose intracellular distribution was consistent with localization within cell secretory granules. Some benign insulinomas also presented factor X immunostaining in spite of the absence of the antigen in normal insulin-producing B cells. Although malignant tumours usually exhibited very low or no immunostaining, two of three malignant glucagonomas showed scattered, intensely immunoreactive cells. The factor X-like antigen identified in this study was found to differ from chromogranin A and B. The possible implications of the present findings for coagulative disorders associated with glucagonomas or diabetes are discussed.
Asunto(s)
Adenoma de Células de los Islotes Pancreáticos/análisis , Antígenos/análisis , Factor X/análisis , Insulinoma/análisis , Islotes Pancreáticos/análisis , Neoplasias Pancreáticas/análisis , Humanos , Polipéptido Pancreático/análisisRESUMEN
A peptide was extracted and purified from rat insulinoma tissue which, although similar, was not identical to normal rat C peptides. The purity of the peptide, called rat insulinoma peptide (RIP), was investigated using polyacrylamide gel electrophoresis, isoelectric focusing and high-performance liquid chromatography. It appears to contain two peptides similar to each other but differing in their isoelectric points. The peptides as assessed by fast atom bombardment mass spectrometry have molecular masses in the region of 1982 Da, given a chain length of approx. 22 amino-acid residues. Evidence obtained using an established rat C peptides radioimmunoassay suggests that RIP shares a common C-terminus with rat C peptides. The antiserum produced to RIP was used to develop a radioimmunoassay using a tracer prepared by iodinating purified tyrosylated RIP.
Asunto(s)
Adenoma de Células de los Islotes Pancreáticos/análisis , Péptido C , Insulinoma/análisis , Proteínas de Neoplasias/aislamiento & purificación , Neoplasias Pancreáticas/análisis , Animales , Péptido C/análisis , Péptido C/metabolismo , Cromatografía Líquida de Alta Presión , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Insulina/análisis , Focalización Isoeléctrica , Punto Isoeléctrico , Masculino , Peso Molecular , Radioinmunoensayo , Ratas , Ratas EndogámicasRESUMEN
La hipoglicemia prolongada sobre todo en el neonato tiene múltiples consecuencias, entre ellas la lesión del cerebro; por lo tanto, es fundamental el diagnóstico precoz y tratamiento adecuado. En el caso de tumores células de los islotes pancreáticos, el tratamiento definitivo y curativo, en la mayoría de los casos, es quirúrgico. Presentamos un caso tipico de esta entidad: una lactante, con hipoglicemia persistente desde el nacimiento; la determinación de niveles de glicemia e insulinemia fueron compatibles con la afección; además la TAC y el ecosonograma abdominal fueron de ayuda diagnóstica. Le fue practicada pancreatectomía (extirpado 75% del tejido glandular). El reporte histológico fue "hiperplasia de los islotes de Langerhans". La evolución postoperatoria fue tórpida inicialmente hipoglicemia persistente; eviceración en dos oportunidades, que ameritan reintervención; bronconeumonía y secuelas neurológicas. Posteriormente sin medicación complementaria, las cifras de glicemia e insulinemia se estabilizan y egresa
Asunto(s)
Recién Nacido , Lactante , Adenoma de Células de los Islotes Pancreáticos/diagnóstico , Adenoma de Células de los Islotes Pancreáticos/terapia , Hipoglucemia , Insulinoma/análisisRESUMEN
High levels of pancreastatinlike immunoreactivity were detected in the plasma (2.9 pmol/ml, greater than 200-fold the normal level), pancreas (2.9 nmol/g wet wt, greater than 450-fold the normal level), and liver (1.6 nmol/g wet wt) of a patient with pancreatic insulinoma with metastasis to the liver by a sensitive and specific radioimmunoassay for human pancreastatin. Antiserum was produced against the C-terminal fragment of human pancreastatin-(24-52), which was synthesized according to the sequence of human chromogranin A corresponding to that of pancreastatin. With the antiserum, intense immunocytochemical staining was detected in the tumors. Sephadex G-50 gel filtration showed that the tumors and plasma contained two molecular forms of pancreastatinlike immunoreactivity--a molecular form coeluted with synthetic human pancreastatin-52 and a larger molecular form (Mr approximately 12,000-15,000). The smaller form eluted in the same position as synthetic human pancreastatin-52 on reverse-phase high-performance liquid chromatography.
Asunto(s)
Adenoma de Células de los Islotes Pancreáticos/análisis , Insulinoma/análisis , Neoplasias Hepáticas/secundario , Neoplasias Pancreáticas/análisis , Cromatografía Líquida de Alta Presión , Cromogranina A , Femenino , Humanos , Insulinoma/secundario , Hígado/análisis , Neoplasias Hepáticas/análisis , Persona de Mediana Edad , Páncreas/análisis , Hormonas Pancreáticas , Radioinmunoensayo/métodosRESUMEN
Calbindin-D 28K expression in insulin-producing tumoral cells of the RINm5F line was assessed by Western-blot and high pressure liquid chromatography. Western blot analysis demonstrated the presence in RINm5F cell homogenates of a protein recognized by a specific polyclonal antibody against chick calbindin. Proteins with apparent molecular weights (mol wt) of 44, 47, 56, and 85 kD were also recognized by the antiserum in RINm5F cell extract, but not in normal rat islet extract. HPLC heat-resistant protein extract from RINm5F cell homogenates revealed three calbindin positive peaks: a major peak with a retention time (20.5 min) identical to that found in a rat cerebellar extract and two minor peaks with shorter retention times. The calbindin content of RINm5F cells was apparently unaffected after 9 d culture in a medium supplemented with 10% calf serum pretreated with dextran-charcoal to remove 1,25-dihydroxyvitamin D3.
Asunto(s)
Adenoma de Células de los Islotes Pancreáticos/análisis , Insulinoma/análisis , Neoplasias Pancreáticas/análisis , Proteína G de Unión al Calcio S100/análisis , Animales , Western Blotting , Calbindinas , Línea Celular , Cerebelo/análisis , Cromatografía Líquida de Alta Presión , Peso Molecular , RatasRESUMEN
The nontumoral endocrine pancreas was studied immunocytochemically and ultrastructurally in 12 patients with isolated insulinomas. Changes affecting hormone content and secretion of B-, A-, and D-cells were found in the islets of insulinoma-bearing patients when compared with controls, in terms of a significant decrease of the insulin-immunoreactive tissue areas and an increase in the glucagon- and somatostatin-immunoreactive ones. Conversely, only in two of the patients examined were PP-immunoreactive tissue areas augmented. Diffuse ducto-endocrine proliferation (nesidioblastosis) was also a common feature in the tumor-associated pancreas. Both morphometry and qualitative features revealed that islet cell hyperplasia occurs in the presence of insulinoma. Ultrastructural examination revealed that the functional activity of B-cells is substantially depressed in the insulinoma-bearing patients, whereas it is maintained or even enhanced in the other cell types. The islet content in immunoreactive insulin decreases along with duration of hypoglycemic symptoms. The present findings indicate that, in the presence of an insulinoma, the endocrine pancreas undergoes changes that can be regarded as an adaptive response to the chronic excess of insulin and are possibly responsible for the patients' postoperative clinical course.
Asunto(s)
Adenoma de Células de los Islotes Pancreáticos/análisis , Insulinoma/análisis , Islotes Pancreáticos/patología , Hormonas Pancreáticas/análisis , Neoplasias Pancreáticas/análisis , Adulto , Anciano , División Celular , Citofotometría , Femenino , Glucagón/análisis , Humanos , Técnicas para Inmunoenzimas , Insulina/análisis , Insulinoma/ultraestructura , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Neoplasias Pancreáticas/ultraestructura , Polipéptido Pancreático/análisis , Somatostatina/análisisRESUMEN
Clinical and experimental data support the concept that type I diabetes mellitus results from autoimmune destruction of pancreatic beta cells. Although both proteins and glycolipids are targets of anti-islet cell antibodies, the Ag have not been purified or characterized. Previously, we observed that rat insulinoma (RIN) cell lines varied in their reactivity with both human antibodies and murine mAb A2B5, which binds to polysialo gangliosides. To determine the chemical basis of the varied immunoreactivity, we analyzed the glycosphingolipids of 5 RIN lines. Glycolipids bound by two mAb and by antibodies in the sera of type I diabetics were identified. The more immunoreactive RIN lines contained a much higher content of gangliosides and a higher proportion of complex gangliosides. The major gangliosides were GM3, GD3, and GT3. By high performance TLC immunostaining, we demonstrated that A2B5 and R2D6, an anti-beta cell murine mAb, bound most strongly to ganglioside GT3. The binding of human sera to gangliosides was analyzed by an ELISA assay. Although both normal and diabetic sera contained antibodies to various glycolipids, binding to GT3 was significantly elevated in 31 new-onset type I diabetics (p less than 0.001). The presence of the GT3 trisialosyl epitope on human islet cells was shown by immunofluorescent staining by both R2D6 and A2B5. These findings support previous suggestions that gangliosides play an important role in the immunopathology of type I diabetes, and identify for the first time a specific ganglioside Ag that is the target for autoantibodies in a subset of diabetic patients.
Asunto(s)
Autoanticuerpos/análisis , Diabetes Mellitus Tipo 1/sangre , Gangliósidos/inmunología , Glicoesfingolípidos/inmunología , Lactosilceramidos/inmunología , Adolescente , Adulto , Animales , Anticuerpos Monoclonales/análisis , Sitios de Unión de Anticuerpos , Niño , Preescolar , Células Clonales/análisis , Células Clonales/inmunología , Células Clonales/patología , Diabetes Mellitus Tipo 1/inmunología , Gangliósidos/aislamiento & purificación , Gangliósidos/metabolismo , Humanos , Sueros Inmunes/análisis , Lactante , Insulinoma/análisis , Insulinoma/inmunología , Insulinoma/patología , Islotes Pancreáticos/metabolismo , Lactosilceramidos/aislamiento & purificación , Lactosilceramidos/metabolismo , RatasRESUMEN
Growth hormone receptors from a rat insulinoma cell line, RIN-5AH were solubilized in the non-ionic detergent Triton X-100. A radioreceptor assay based on polyethylene glycol precipitation of the growth hormone: receptor complex showed time-dependent and saturable hormone binding. The affinity in detergent solution for biosynthetic human growth hormone of approx. 6 ng/ml was found similar to that of intact RIN cells. The solubilization and receptor assay conditions described are useful for further characterization and purification of RIN cell growth hormone receptors, which might provide an initial insight into the molecular mechanism of the growth hormone effects on islet beta-cells.
Asunto(s)
Adenoma de Células de los Islotes Pancreáticos/ultraestructura , Insulinoma/ultraestructura , Neoplasias Pancreáticas/ultraestructura , Receptores de Somatotropina/análisis , Animales , Línea Celular , Insulinoma/análisis , Octoxinol , Neoplasias Pancreáticas/análisis , Polietilenglicoles , Ensayo de Unión Radioligante/métodos , Ratas , Células Tumorales Cultivadas/análisis , Células Tumorales Cultivadas/ultraestructuraRESUMEN
Islet amyloid polypeptide (IAPP) is the 37-amino acid peptide subunit of amyloid found in pancreatic islets of type 2 diabetic patients and in insulinomas. Recently, we isolated the human gene encoding IAPP [(1988) FEBS Lett. 239, 227-232]. We now report the nucleotide sequences of a human insulinoma cDNA encoding a complete IAPP precursor, and of the corresponding parts of the IAPP gene. Two exons, which are approx. 5 kb apart in the human genome, encode the 89-amino acid pre-pro-IAPP. At least one additional exon is present further upstream in the IAPP gene. A putative signal sequence at the amino-terminus of the precursor suggests that IAPP is a secreted protein.
Asunto(s)
Amiloide/genética , Exones , Islotes Pancreáticos/análisis , Precursores de Proteínas/genética , Secuencia de Aminoácidos , Secuencia de Bases , Calcitonina/genética , Péptido Relacionado con Gen de Calcitonina , Codón , ADN/genética , Sondas de ADN , Humanos , Insulinoma/análisis , Polipéptido Amiloide de los Islotes Pancreáticos , Datos de Secuencia Molecular , Neuropéptidos/genética , Hibridación de Ácido Nucleico , Neoplasias Pancreáticas/análisis , Señales de Clasificación de Proteína/genética , Homología de Secuencia de Ácido NucleicoRESUMEN
125I-Labelled glucagon-like peptide-1(7-36)amide was cross-linked to a specific binding protein in plasma membranes prepared from RINm5F rat insulinoma-derived cells using disuccinimidyl suberate. Consistent with the presence of a single class of binding site on the surface of intact cells, only a single radiolabelled band at Mr63,000 was identified by SDS-PAGE after solubilization of the ligand-binding protein complex. The band was not observed when 10nM glucagon-like peptide-1(7-36)amide was included in the binding assay, but 1 microM concentrations of glucagon-like peptide-1(1-36)amide, glucagon-like peptide-2 and glucagon did not decrease the intensity of labelling. No change in the mobility of the band was observed under reducing conditions, suggesting that the binding protein in the receptor is not attached to other subunits via disulphide bonds. In control incubations using plasma membranes from pig intestinal epithelial cells, which do not contain specific binding sites for glucagon-like peptide-1(7-36)amide, no cross-linked ligand-binding protein complex was observed.
Asunto(s)
Adenoma de Células de los Islotes Pancreáticos/patología , Reactivos de Enlaces Cruzados , Insulinoma/patología , Receptores de Glucagón , Animales , Línea Celular , Membrana Celular/análisis , Membrana Celular/ultraestructura , Glucagón , Péptido 1 Similar al Glucagón , Receptor del Péptido 1 Similar al Glucagón , Péptidos Similares al Glucagón , Insulinoma/análisis , Insulinoma/ultraestructura , Péptidos/metabolismo , Ratas , Receptores de Superficie Celular/análisis , Receptores de Superficie Celular/metabolismoRESUMEN
We reported a case of sporadic multiple endocrine neoplasia type 1, with multiple insulinoma, parathyroid adenoma, and pituitary tumor. Measurement of hormone contents and immunohistochemical studies of the pancreatic tumors showed that the tumors contained insulin, glucagon, somatostatin, and pancreatic polypeptide. Furthermore, the concentrations of these hormones were different in each tumor. Insulin extracted from the pancreatic tumors analyzed by reversed-phase high performance liquid chromatography revealed no structural abnormalities. On the other hand, in gel filtration evaluation of the extract of the parathyroid adenoma, it was found that the tumor extract contained a macromolecular parathyroid hormone (molecular weight 20,000 to 25,000).
Asunto(s)
Adenoma de Células de los Islotes Pancreáticos , Adenoma , Insulinoma , Neoplasia Endocrina Múltiple , Neoplasias Pancreáticas , Neoplasias de las Paratiroides , Neoplasias Hipofisarias , Adenoma/análisis , Adenoma/patología , Adenoma de Células de los Islotes Pancreáticos/análisis , Adenoma de Células de los Islotes Pancreáticos/patología , Adulto , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Femenino , Glucagón/análisis , Humanos , Técnicas para Inmunoenzimas , Inmunohistoquímica , Insulina/análisis , Insulinoma/análisis , Insulinoma/patología , Microscopía Electrónica , Peso Molecular , Neoplasia Endocrina Múltiple/análisis , Neoplasia Endocrina Múltiple/patología , Neoplasias Pancreáticas/análisis , Neoplasias Pancreáticas/patología , Polipéptido Pancreático/análisis , Hormona Paratiroidea/análisis , Neoplasias de las Paratiroides/análisis , Neoplasias de las Paratiroides/patología , Neoplasias Hipofisarias/análisis , Neoplasias Hipofisarias/patología , Somatostatina/análisisRESUMEN
It has been shown, by using the immunogold technique, that C-peptide and insulin are co-localized in the mature granules of human pancreatic beta cells and insulinomas with typical granules. The mean gold bead densities of both C-peptide and insulin were at least twice as high in the normal pancreas when compared with the insulinomas. The mean granule diameter of the insulinoma cells (D = 0.30 +/- 0.12 micron) was smaller than that of human pancreatic cells (D = 0.45 +/- 0.15 micron). The morphometric data indicate that each of the antigens (C-peptide and insulin) is distributed similarly in the halos and the dense cores of the beta granules. Thus, no topological segregation of these two antigens occurs within the beta granules of either normal human pancreas or insulinomas.
Asunto(s)
Adenoma de Células de los Islotes Pancreáticos/análisis , Péptido C/análisis , Insulina/análisis , Insulinoma/análisis , Islotes Pancreáticos/análisis , Neoplasias Pancreáticas/análisis , Gránulos Citoplasmáticos/análisis , Gránulos Citoplasmáticos/ultraestructura , Humanos , Inmunohistoquímica , Insulinoma/ultraestructura , Islotes Pancreáticos/ultraestructura , Neoplasias Pancreáticas/ultraestructuraRESUMEN
Cathepsins B and H are representative cysteine proteinases localized to lysosomes of a variety of mammalian cells. Previous studies indicated the presence of these enzymes also in secretory granules of endocrine cells. Therefore, the human endocrine pancreas and human insulinomas were investigated by light microscopical immunohistochemistry on serial semithin plastic sections immunostained sequentially for cathepsins B or H and pancreatic hormones. Out of the four established endocrine cell types, insulin (B-) and glucagon (A-) cells showed immunoreactivities for these cathepsins. Cathepsin B immunoreactivities showed a dot-like appearance in A- and B-cells and in insulinoma cells. Immunoreactivities for cathepsin H additionally were found in cell parts containing secretory granules of B-cells and insulinoma cells. By single and double immunoelectron microscopy the dot-like immunoreactivities for cathepsin B were identified as immunoreactive lysosomes of A- and B-cells and insulinoma cells. In addition, some of the secretory granules of A- and B-cells showed cathepsin B immunoreactivities. Cathepsin H immunoreactivities showed an other pattern: they were found regularly in the secretory granules of A- and B-cells and insulinoma cells, and in lysosomes of A-cells. These findings suggest that cathepsins B and H in lysosomes of A- and/or B-cells are involved in the degradation of lysosomal constituents. In secretory granules of these cells, these cysteine proteinases may participate in the processing of the corresponding hormones from their precursor proteins.
Asunto(s)
Adenoma de Células de los Islotes Pancreáticos/análisis , Catepsina B/análisis , Catepsinas/análisis , Cisteína Endopeptidasas , Insulinoma/análisis , Islotes Pancreáticos/análisis , Neoplasias Pancreáticas/análisis , Adulto , Catepsina H , Gránulos Citoplasmáticos/análisis , Gránulos Citoplasmáticos/ultraestructura , Femenino , Humanos , Inmunohistoquímica , Insulinoma/ultraestructura , Islotes Pancreáticos/ultraestructura , Lisosomas/análisis , Lisosomas/ultraestructura , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Neoplasias Pancreáticas/ultraestructura , Neoplasias GástricasRESUMEN
We have carried out an immunohistochemical investigation of 15 human insulinomas applying monoclonal antibodies specifically recognizing proinsulin and insulin. Our results demonstrate that the epitopes unique to proinsulin and insulin can be detected with the respective monoclonal antibodies using the protein A-gold technique after routine formaldehyde fixation and paraffin embedding of the tissues. The immunostaining pattern for proinsulin and insulin in the insulinomas was different from the observed in B cells of pancreatic islets present in the adjacent normal pancreas. Furthermore, the pattern of immunostaining was found to vary from tumor to tumor. These findings strongly suggest the possibility of a disturbed proinsulin to insulin conversion in human insulinomas.
Asunto(s)
Adenoma de Células de los Islotes Pancreáticos/análisis , Insulina/análisis , Insulinoma/análisis , Neoplasias Pancreáticas/análisis , Proinsulina/análisis , Humanos , InmunohistoquímicaRESUMEN
We investigated a variety of endocrine tumors for the presence of chromogranins A and B and secretogranin II. These antigens were identified by one- and two-dimensional immunoblotting and in some cases by immunohistochemistry. An antigen corresponding in electrophoretic behavior to adrenal chromogranin A was present in all types of tumors, including insulinomas, oat cell carcinomas, and Merkel cell tumors of the skin. Chromogranin B had a much more limited distribution. This antigen could not be detected in parathyroid adenomas, oat cell carcinomas, or Merkel cell tumors, either by immunoblotting and immunohistochemistry. The occurrence of secretogranin II was similar to that of chromogranin B, with the exception of a positive reaction in Merkel cell tumors. In benign pheochromocytomas, all three antigens were found consistently; whereas in two of three malignant pheochromocytomas, chromogranin B was absent. Our study establishes that in most cases chromogranins and secretogranin in tumors are identical to the adrenal antigens, but that these antigens are not always stored together. Chromogranin A is the most widely distributed marker for endocrine tumors.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/análisis , Cromograninas/análisis , Proteínas del Tejido Nervioso/análisis , Proteínas/análisis , Neoplasias Cutáneas/análisis , Carcinoma de Células de Merkel/análisis , Carcinoma de Células Pequeñas/análisis , Cromogranina A , Electroforesis , Humanos , Immunoblotting , Inmunohistoquímica , Insulinoma/análisis , Feocromocitoma/análisis , Extractos de Tejidos/análisisRESUMEN
The well-characterized erythrocyte glucose transporter is also expressed in brain, adipocytes, kidney, muscle, and certain transformed cells, but not in liver, intestine, or the islets of Langerhans. Using as probe a cDNA encoding the rat brain glucose transporter, we isolated from a rat liver cDNA library a clone encoding a protein 55% identical in sequence to the rat brain transporter, and with a superimpossible hydropathy plot. We expressed this protein in an E. coli mutant defective in glucose uptake; the protein was incorporated into the bacterial membrane and functioned as a glucose transporter. This new transporter is expressed in liver, intestine, kidney, and the islets of Langerhans; immunofluorescence analysis showed that it is present in the plasma membrane of the insulin-producing beta cells. Insulinoma cells express, inappropriately, the erythrocyte glucose transporter, and we suggest that this may be related to their inability to secrete insulin in response to elevations in glucose.
Asunto(s)
Clonación Molecular , Escherichia coli/genética , Regulación de la Expresión Génica , Proteínas de Transporte de Monosacáridos/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Química Encefálica , ADN/metabolismo , Inmunohistoquímica , Insulinoma/análisis , Intestinos/análisis , Islotes Pancreáticos/análisis , Riñón/análisis , Hígado/análisis , Datos de Secuencia Molecular , Neoplasias Pancreáticas/análisis , RatasRESUMEN
Somatostatin receptor frequency was evaluated in 12 human exocrine pancreatic carcinomas taken after surgery. The tumors were analyzed by receptor autoradiography on tissue sections and by in vitro binding techniques on tumor homogenates. None of the tested human pancreatic carcinomas was shown to possess specific somatostatin receptors. In comparison, five single tumors taken from rats transplanted with the rat pancreatic adenocarcinoma CA 20948 were found to contain specific high-affinity somatostatin receptors. Also, human endocrine pancreatic tumors, i.e., two insulinomas, did contain somatostatin receptors under identical experimental conditions. These data confirm previous results with other tumors, documenting the absence of somatostatin receptors in highly malignant human carcinomas. They also may represent an explantation at the molecular level for the lack of therapeutic effect of somatostatin analogues such as SMS 201-995 seen in patients with advanced exocrine pancreatic carcinomas.