ABSTRACT
Chromogranin A (ChgA) is an antigenic target of pathogenic CD4(+) T cells in a non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D). Vasostatin-1 is a naturally processed fragment of ChgA. We have now identified a novel H2-K(d) -restricted epitope of vasostatin-1, ChgA 36-44, which elicits CD8(+) T cell responses in NOD mice. By using ChgA 36-44/K(d) tetramers we have determined the frequency of vasostatin-1-specific CD8(+) T cells in pancreatic islets and draining lymph nodes of NOD mice. We also demonstrate that vasostatin-1-specific CD4(+) and CD8(+) T cells constitute a significant fraction of islet-infiltrating T cells in diabetic NOD mice. Adoptive transfer of T cells from ChgA 36-44 peptide-primed NOD mice into NOD/severe combined immunodeficiency (SCID) mice led to T1D development. These findings indicate that vasostatin-1-specific CD8(+) T cells contribute to the pathogenesis of type 1 diabetes in NOD mice.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Chromogranin A/isolation & purification , Diabetes Mellitus, Experimental/immunology , Diabetes Mellitus, Type 1/physiopathology , Peptide Fragments/isolation & purification , Adoptive Transfer , Animals , Autoimmunity/immunology , CD4-Positive T-Lymphocytes/chemistry , CD8-Positive T-Lymphocytes/chemistry , Chromogranin A/immunology , Diabetes Mellitus, Experimental/physiopathology , Diabetes Mellitus, Type 1/immunology , Epitopes, T-Lymphocyte , Islets of Langerhans/immunology , Mice , Mice, Inbred NOD , Mice, SCID , Peptide Fragments/immunologyABSTRACT
La incidencia de los tumores neuroendocrinos en la población caucásica oscila entre 2,5 y 5 casos nuevos anuales por cada 100.000 habitantes. Los tumores neuroendocrinos gastroenteropancreáticos difieren considerablemente entre sí, tanto en su composición hormonal, como en los síndromes que producen, así como en su comportamiento biológico. Esta notable complejidad y heterogeneidad clínica, junto con su conocida dificultad para predecir su comportamiento a partir de características patológicas, han quedado reflejadas en las múltiples clasificaciones que se han realizado a lo largo del tiempo. En este artículo se revisan los principales biomarcadores tisulares y clínicos, y se ofrecen recomendaciones para su uso en la práctica médica. El documento obedece a un consenso fruto de la colaboración entre la Sociedad Española de Oncología Médica (SEOM) y la Sociedad Española de Anatomía Patológica (SEAP) (AU)
The annual incidence of neuroendocrine tumours in the Caucasian population ran- ges from 2.5 to 5 new cases per 100,000 inhabitants. Gastroenteropancreatic neuroendocrine tumours vary considerably in their hormonal composition, the syndromes they cause and their biological behaviour. This high complexity and clinical heterogeneity, together with the well- known difficulty of predicting their behaviour from their pathological features, are reflected in the many classifications that have been formulated over the years. This article reviews the main tissue and clinical biomarkers and makes recommendations for their use in medical prac- tice. This document represents a consensus reached jointly by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) (AU)
Subject(s)
Humans , Male , Female , Endocrine Gland Neoplasms/complications , Endocrine Gland Neoplasms/epidemiology , Endocrine Gland Neoplasms/prevention & control , Biomarkers/analysis , Biomarkers/metabolism , Ki-67 Antigen/isolation & purification , Chromogranin A/isolation & purification , Synaptophysin , Neuroendocrine Tumors/epidemiology , Neuroendocrine Tumors/prevention & control , Societies, Medical/organization & administration , Societies, Medical/standards , Societies, Medical/statistics & numerical data , Diagnosis, Differential , Microscopy , Somatostatin , Gastrinoma/pathology , Hydroxyindoleacetic Acid/classification , Hydroxyindoleacetic Acid , Sensitivity and SpecificityABSTRACT
La asociación de tumor carcinoide y carcinoma broncopulmonar en forma de tumores de aparición sincrónica es excepcional y sólo ha sido publicada en diez ocasiones. En el presente trabajo se describen los hallazgos en 2 pacientes con adenocarcinoma pulmonar en los que en el estudio de la pieza quirúrgica se identificó un tumor carcinoide típico. El hallazgo de un segundo nódulo en un paciente con un carcinoma broncopulmonar, situación cada vez más frecuente por la incorporación de técnicas de imagen con mayor sensibilidad, plantea la necesidad de su evaluación patológica para una correcta estadificación. Un problema adicional es la identificación de segundos nódulos en el curso de la intervención quirúrgica, lo que obliga al estudio intraoperatorio. La correcta valoración de los parámetros morfológicos y su comparación con los del tumor principal puede ser determinante en un correcto diagnóstico y evitar la sobrestadificación(AU)
The association of carcinoid tumour and bronchopulmonary carcinoma is very rare, with only 10 cases published to date. We present two cases of pulmonary adenocarcinoma in which a typical carcinoid tumour was an incidental finding on microscopy of the surgical specimen. The improved sensitivity of imaging techniques increases the possibility of detecting the presence of secondary nodules during the work-up for bronchopulmonary carcinoma, indicating further intraoperatory investigation. A correct morphological assessment and comparison with the main tumour could prove to be a key diagnostic factor, avoiding incorrect overstaging(AU)
Subject(s)
Humans , Male , Middle Aged , Adenocarcinoma/pathology , Carcinoid Tumor/complications , Carcinoid Tumor/pathology , Neoplasms, Multiple Primary/pathology , Immunohistochemistry/methods , Immunohistochemistry , Immunohistochemistry/trends , Keratins , /methods , Neoadjuvant Therapy/methods , Neoadjuvant Therapy , Chromogranin A , Chromogranin A/isolation & purificationABSTRACT
In 1997, we identified a novel peptide, catestatin (CST: bovine chromogranin A [CHGA](344-364): RSMRLSFRARGYGFRGPGLQL; human CHGA(352-372): SSMKLSFRARGYGFRGPGPQL), which is a potent inhibitor of nicotinic-cholinergic-stimulated catecholamine secretion. CST shows characteristic inhibitory effects on nicotinic cationic (Na(+), Ca(2+)) signal transduction, which are specific to the neuronal nicotinic receptor. Utilizing systematic polymorphism discovery at the human CHGA locus we discovered three human variants of CST: G(364)S, P(370)L, and R(374)Q that showed differential potencies towards the inhibition of catecholamine secretion. In humans, CHGA is elevated and its processing to CST is diminished in hypertension. Diminished CST is observed not only in hypertensive individuals but also in the early-normotensive offspring of patients with hypertension, suggesting that an early deficiency of CST might play a pathogenic role in the subsequent development of the disease. Consistent with human findings, prevention of endogenous CST expression by targeted ablation (knockout) of the mouse Chga locus (Chga-KO) resulted in severe hypertension that can be "rescued" specifically by replacement of the CST peptide. CST acts directly on the heart to inhibit the inotropic and lusitropic properties of the rodent heart and also acts as a potent vasodilator in rats and humans. While the G(364)S CST variant caused profound changes in human autonomic activity and seemed to reduce the risk of developing hypertension, CST replacement rescued Chga-KO mice from dampened baroreflex sensitivity. In addition, CST has been shown to induce chemotaxis and acts as an antimicrobial as well as an antimalarial peptide. The present review summarizes these multiple actions of CST.
Subject(s)
Chromogranin A/chemistry , Peptide Fragments/physiology , Amino Acid Sequence , Animals , Chemotaxis , Chromogranin A/isolation & purification , Chromogranin A/physiology , Humans , Molecular Sequence Data , Peptide Fragments/chemistry , Peptide Fragments/isolation & purification , Protein Processing, Post-Translational , Sequence Homology, Amino Acid , Signal TransductionABSTRACT
El tumor neuroendocrino de mama es poco frecuente, mástípico de mujeres con edad avanzada y asociado a un componentemucinoso. No se han publicado series acerca de tratamientoadyuvante en este grupo de pacientes, por lo que noexiste unanimidad en cuanto al empleo de quimioterapia o elesquema a utilizar. Se presenta un caso clínico en una mujerjoven con tumor neuroendocrino de mama que fue tratadacon cirugía, quimioterapia y hormonoterapia adyuvantes, y sehace una revisión de la literatura existente(AU)
Neuroendocrine breast tumor is an unusual breast cancerusually related to advanced age and a mucinous tumoral component.There are no series of adjuvant treatment of this kindof tumor, so that there is no a consensus about the best chemotherapyschedule to use in them. We present a case of ayoung woman with neuroendocrine breast cancer who wastreated with surgery, adjuvant chemoterapy and hormonetherapy.A literature review is made(AU)
