RESUMEN
Pituitary adenomas account for 10-15% of primary intracranial tumors. Growth hormone (GH)-secreting adenomas account for 13% of all pituitary adenomas and cause acromegaly. These tumors can be aggressive, invade surrounding structures and are highly recurrent. The objective of this study was to evaluate E-cadherin, Slug and neural cell adhesion molecule (NCAM) expression in GH-secreting pituitary adenomas and its relationship to tumor invasiveness. A cross-sectional study of patients who underwent hypophysectomy due to GH-secreting pituitary adenoma from April 2007 to December 2014 was carried out. The medical records were reviewed to collect clinical data. Immediately after surgery, tumor samples were frozen in liquid nitrogen and stored in a biofreezer at -80°C for assessment of E-cadherin 1 (CDH1), SLUG (SNAI2), and NCAM (NCAM1) by real-time PCR. The samples were fixed in formalin and embedded in paraffin for immunohistochemical analysis of E-cadherin and NCAM. Thirty-five patients with acromegaly were included in the study. Of these, 65.7% had invasive tumors. Immunohistochemically, E-cadherin was expressed in 96.7% of patients, and NCAM in 80% of patients. There was no statistically significant relationship between tumor grade or invasiveness and immunohistochemical expression of these markers. Regarding gene expression, 50% of cases expressed CDH1, none expressed SNAI2, and 53.3% expressed NCAM1. There was no statistically significant relationship between tumor grade or invasiveness and gene expression of CDH1, SNAI2, and NCAM1. The absence of Slug overexpression and of E-cadherin and NCAM suppression suggests that expression of these markers is not associated with tumor invasiveness in GH-secreting pituitary adenomas.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Acromegalia/patología , Adenoma/patología , Cadherinas/análisis , Moléculas de Adhesión de Célula Nerviosa/análisis , Factores de Transcripción de la Familia Snail/análisis , Acromegalia/genética , Acromegalia/metabolismo , Inmunohistoquímica , Biomarcadores de Tumor/análisis , Adenoma/genética , Adenoma/química , Expresión Génica , Estudios Transversales , Clasificación del TumorRESUMEN
Pituitary adenomas account for 10-15% of primary intracranial tumors. Growth hormone (GH)-secreting adenomas account for 13% of all pituitary adenomas and cause acromegaly. These tumors can be aggressive, invade surrounding structures and are highly recurrent. The objective of this study was to evaluate E-cadherin, Slug and neural cell adhesion molecule (NCAM) expression in GH-secreting pituitary adenomas and its relationship to tumor invasiveness. A cross-sectional study of patients who underwent hypophysectomy due to GH-secreting pituitary adenoma from April 2007 to December 2014 was carried out. The medical records were reviewed to collect clinical data. Immediately after surgery, tumor samples were frozen in liquid nitrogen and stored in a biofreezer at -80°C for assessment of E-cadherin 1 (CDH1), SLUG (SNAI2), and NCAM (NCAM1) by real-time PCR. The samples were fixed in formalin and embedded in paraffin for immunohistochemical analysis of E-cadherin and NCAM. Thirty-five patients with acromegaly were included in the study. Of these, 65.7% had invasive tumors. Immunohistochemically, E-cadherin was expressed in 96.7% of patients, and NCAM in 80% of patients. There was no statistically significant relationship between tumor grade or invasiveness and immunohistochemical expression of these markers. Regarding gene expression, 50% of cases expressed CDH1, none expressed SNAI2, and 53.3% expressed NCAM1. There was no statistically significant relationship between tumor grade or invasiveness and gene expression of CDH1, SNAI2, and NCAM1. The absence of Slug overexpression and of E-cadherin and NCAM suppression suggests that expression of these markers is not associated with tumor invasiveness in GH-secreting pituitary adenomas.
Asunto(s)
Acromegalia/patología , Adenoma/patología , Cadherinas/análisis , Moléculas de Adhesión de Célula Nerviosa/análisis , Neoplasias Hipofisarias/patología , Factores de Transcripción de la Familia Snail/análisis , Acromegalia/genética , Acromegalia/metabolismo , Adenoma/química , Adenoma/genética , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/análisis , Antígeno CD56/análisis , Estudios Transversales , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Neoplasias Hipofisarias/química , Neoplasias Hipofisarias/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Estadísticas no Paramétricas , Adulto JovenRESUMEN
INTRODUCTION: Teeth are often included in the radiation field during head and neck radiotherapy, and recent clinical evidence suggests that dental pulp is negatively affected by the direct effects of radiation, leading to impaired sensitivity of the dental pulp. Therefore, this study aimed to investigate the direct effects of radiation on the microvasculature, innervation, and extracellular matrix of the dental pulp of patients who have undergone head and neck radiotherapy. METHODS: Twenty-three samples of dental pulp from patients who finished head and neck radiotherapy were analyzed. Samples were histologically processed and stained with hematoxylin-eosin for morphologic evaluation of the microvasculature, innervation, and extracellular matrix. Subsequently, immunohistochemical analysis of proteins related to vascularization (CD34 and smooth muscle actin), innervation (S-100, NCAM/CD56, and neurofilament), and extracellular matrix (vimentin) of the dental pulp was performed. RESULTS: The morphologic study identified preservation of the microvasculature, nerve bundles, and components of the extracellular matrix in all studied samples. The immunohistochemical analysis confirmed the morphologic findings and showed a normal pattern of expression for the studied proteins in all samples. CONCLUSIONS: Direct effects of radiotherapy are not able to generate morphologic changes in the microvasculature, innervation, and extracellular matrix components of the dental pulp in head and neck cancer patients.
Asunto(s)
Pulpa Dental/efectos de la radiación , Neoplasias de Cabeza y Cuello/radioterapia , Actinas/análisis , Adolescente , Adulto , Antígenos CD34/análisis , Antígeno CD56/análisis , Colorantes , Caries Dental/etiología , Esmalte Dental/efectos de la radiación , Pulpa Dental/irrigación sanguínea , Pulpa Dental/citología , Pulpa Dental/inervación , Dentina/efectos de la radiación , Matriz Extracelular/efectos de la radiación , Femenino , Fibroblastos/efectos de la radiación , Colorantes Fluorescentes , Humanos , Filamentos Intermedios/química , Masculino , Microvasos/efectos de la radiación , Persona de Mediana Edad , Fibras Nerviosas/efectos de la radiación , Moléculas de Adhesión de Célula Nerviosa/análisis , Dosificación Radioterapéutica , Proteínas S100/análisis , Vimentina/análisisRESUMEN
El síndrome de Apnea Obstructiva del Sueño (SAOS), consiste en la aparición repetida de episodios de obstrucción faríngea durante el sueño como consecuencia de un colapso de la vía respiratoria. La respuesta fisiológica a la hipoxia intermitente crónica es la generación de una respuesta inflamatoria local y sistémica. Se han evidenciado cambios importantes a nivel cardiovascular en pacientes con SAOS; sin embargo, se desconocen cuáles marcadores séricos y genéticos pudieran ser de utilidad. En el presente estudio, se presentan 15 marcadores séricos y 3 genéticos (IL-6, IL-1β y TNF-α) en un grupo de cinco pacientes para determinar cuáles pueden ser los marcadores de interés en la aparición y en el desarrollo de esta patología respiratoria. Se proponen como marcadores los niveles séricos: proteína C reactiva, TNFα, IL-6, el receptor soluble de TNF I, sCD62, sCD154, nitrotirosina y anti-oxLDL. Los niveles de IL-1 β, el receptor de TNF soluble II, sCD25, sCD54, nitritos y nitratos no parecieran ser buenos marcadores en SAOS. Los estudios genéticos no fueron concluyentes.
Obstructive sleep apnea syndrome (OSAS) is a repeated sequences of pharynx obstruction during sleep as a consequence of airway collapse. The physiological response to the desaturation is the generation of a local and systemic inflammatory immune response. Important changes at cardiovascular levels in patients with OSAS have been observed; however, it is not know which serum or genetic parameters could be useful. In the present study, we present 15 serum and 3 genetic (IL-6, IL-1β y TNF-α) markers in a group of five patients in order to determine which marker could be useful to study the genesis and progression of this respiratory pathology. The proposed serum markers are C reactive proteín, TNFα, IL-6, soluble de TNF receptor I, sCD62, sCD154, nitrotirosine and anti-oxLDL. The levels of IL-1 β, soluble TNF receptor II, sCD25, sCD54, nitrite y nitrate do not seem to be good markers for OSAS. The genetic studies were not conclusive.
Asunto(s)
Humanos , Masculino , Adulto , Femenino , Persona de Mediana Edad , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/sangre , Citocinas/inmunología , Marcadores Genéticos/inmunología , /métodos , Moléculas de Adhesión de Célula Nerviosa/análisis , Proteína C-Reactiva/análisis , Pruebas Inmunológicas/métodos , Síndromes de la Apnea del Sueño/diagnóstico , Síndromes de la Apnea del Sueño/sangreRESUMEN
This work investigates the influence of heat shock proteins (HSPs) on necrosis and subsequent skeletal muscle regeneration induced by crotoxin (CTX), the major component of Crotalus durissus terrificus venom. Mice were treated with radicicol, a HSP inductor, followed by an intramuscular injection of CTX into the gastrocnemius muscle. Treated groups were sacrificed 1, 10 and 21 days after CTX injection. Muscle histological sections were stained with toluidine blue and assayed for acid phosphatase or immunostained with either neuronal cell adhesion molecule (NCAM) or neonatal myosin heavy chain (MHCn). Muscle samples were also submitted to Western blotting analysis. The results show that CTX alone and CTX combined with radicicol induced a similar degree of myofiber necrosis. CTX-injured muscles treated with radicicol had increased cross-sectional areas at 10 and 21 days post-lesion compared with untreated CTX-injured muscles. Additionally, radicicol significantly increased the number of NCAM-positive satellite cells in the gastrocnemius at one day post-CTX injury. CTX-injured muscles treated with radicicol contained more MHCn-positive regenerating myofibers compared with untreated CTX-injured muscles. These results suggest that HSPs contribute to the regeneration of myofibers damaged by CTX. Additionally, further studies should investigate the potential therapeutic effects of radicicol in skeletal muscles affected by Crotalus venom.
Asunto(s)
Antifúngicos/farmacología , Crotoxina/toxicidad , Macrólidos/farmacología , Músculo Esquelético/efectos de los fármacos , Regeneración/efectos de los fármacos , Animales , Citocinas/genética , Proteínas HSP70 de Choque Térmico/biosíntesis , Masculino , Ratones , Ratones Endogámicos C57BL , Músculo Esquelético/fisiología , Moléculas de Adhesión de Célula Nerviosa/análisisRESUMEN
BACKGROUND: The neural cell adhesion molecule (N-CAM) has been implicated in the behaviour of the adenoid cystic carcinoma. In vitro, it was demonstrated that N-CAM inhibits cell invasion. The aim of this study was to search for N-CAM in the most common salivary gland tumour that has a malignant counterpart. METHODS: We investigated the presence of N-CAM in pleomorphic adenoma and its malignant counterpart, the carcinoma ex-pleomorphic adenoma, using the immunohistochemistry technique. RESULTS: Neural cell adhesion molecule was expressed in all cases of pleomorphic adenoma, strongly labelling the luminal cells of the double-layered ductform structures. This expression was weaker in neoplastic myoepithelial cells and progressively diminished at a distance from the luminal cells. In carcinoma, ex-pleomorphic adenoma N-CAM was either totally absent or faintly present at the apical pole of the few luminal cells. CONCLUSIONS: As a result of the peculiar distribution of N-CAM in pleomorphic adenoma, we speculated that N-CAM behaves as a tumour-suppressor molecule, which is expressed in the benign neoplasm and which is down-regulated after malignancy, when the tumour assumes an invasive behaviour.
Asunto(s)
Adenocarcinoma/patología , Adenoma Pleomórfico/patología , Moléculas de Adhesión de Célula Nerviosa/análisis , Neoplasias de las Glándulas Salivales/patología , Colorantes , Regulación hacia Abajo , Células Epiteliales/patología , Humanos , Músculo Liso/patología , Conductos Salivales/patología , Proteínas Supresoras de Tumor/análisisRESUMEN
Neurons from the anterior subventricular zone (SVZ) of the cerebral cortex migrate tangentially to become interneurons in the olfactory bulb during development and in adult rodents. This migration was defined as neuronophilic, independent of a radial glial substrate. The cortical SVZ and the rostral migratory stream to the olfactory bulb were shown to be rich in 9-O-acetyl GD3 gangliosides (9-O-acGD3), which have been previously shown to be implicated in gliophilic migration in the rodent cerebral cortex and cerebellum. In the present study, we performed SVZ explant cultures using rats during their first postnatal week to analyze the expression of these gangliosides in chain migration of neuronal precursors. We characterized migrating chains of these neuroblasts through morphological analysis and immunocytochemistry for the neural cell adhesion molecule. By using the Jones monoclonal antibody which binds specifically to 9-O-acGD3 we showed that migrating chains from the SVZ explants express 9-O-acGD3 which is distributed in a punctate manner in individual cells. 9-O-acGD3 is also present in migrating chains that form in the absence of radial glia, typical of the neuronophilic chain migration of the SVZ. Our data indicate that 9-O-acetylated gangliosides may participate in neuronophilic as well as gliophilic migration
Asunto(s)
Animales , Ratas , Movimiento Celular/fisiología , Corteza Cerebral/metabolismo , Gangliósidos/metabolismo , Técnicas In Vitro , Moléculas de Adhesión de Célula Nerviosa/análisis , Neuronas/metabolismo , Corteza Cerebral/citología , Ventrículos Cerebrales/citología , Moléculas de Adhesión de Célula Nerviosa/ultraestructura , Neuroglía/citología , Neuronas/ultraestructuraRESUMEN
Defective innervation of the neuromuscular junctions (NMJ) was recently described in intestinal neuronal dysplasia type B (IND B). The aim of the present study was to correlate the alterations in NMJs to other classically described parameters in dysganglionoses and to determine the relationship between NMJ abnormalities in IND B and clinical symptoms. The rectal biopsies and full-thickness colonic biopsy specimens of 17 patients were studied applying histochemical (acetylcholinesterase [AChE], lactic dehydrogenase [LDH], and succinic dehydrogenase [SDH] reactions) and immunohistochemical (neuronal-cell adhesion molecule [NCAM] and SY antibodies) methods. Thirteen patients had Hirschsprung's disease (HD). IND B was diagnosed in 11 (associated with HD in 8 cases, isolated in 2, and associated with hypoganglionosis in 1). In the aganglionic segment of HD there was very intense AChE activity; in contrast, NCAM- and SY-immunoreactive nerve fibers were markedly decreased. A spectrum of abnormalities was observed in IND B, usually more severe in the most distal segments: giant and immature ganglia in the submucous plexus were observed in all cases; heterotopic myenteric ganglia were frequent (72.7%); hyperganglionosis was observed in 6 (54.5%) and was not related to the patients' age; thick and tortuous NCAM- and SY-immunoreactive nerve fibers, irregularly distributed in the colonic wall, were observed in 81.8% of the cases. No relationship was observed between abnormalities of NCAM- and SY-immunoreactive nerve fibers and AChE activity, ganglion-cell maturity, heterotopy, or the clinical symptoms presented by the patients with IND B. In hypoganglionism, low AChE activity and a slight decrease in NCAM- and SY-immunoreactive nerves were observed. Thick and tortuous, irregularly-distributed intrinsic NCAM- and SY-immunoreactive nerves were observed in every colon layer in IND B. Our results do not support IND B as a NMJ disorder.
Asunto(s)
Sistema Nervioso Entérico/patología , Enfermedad de Hirschsprung/patología , Niño , Preescolar , Colectomía , Colon/inervación , Colon/patología , Femenino , Enfermedad de Hirschsprung/cirugía , Humanos , Lactante , Recién Nacido , Masculino , Fibras Nerviosas/patología , Proteínas del Tejido Nervioso/análisis , Moléculas de Adhesión de Célula Nerviosa/análisis , Unión Neuromuscular/patología , Recto/inervación , Recto/patología , Sinapsis/patologíaRESUMEN
OBJECTIVE: Systemic sclerosis (SSc) is characterized by abnormal deposition of collagen in the skin and by visceral involvement. Muscle weakness is a relatively frequent complication of SSc, although severity varies. We studied muscle pathology in patients with SSc with progressive muscle involvement. METHODS: We performed histochemical and immunohistochemical investigations to detect neural cell adhesion molecule (NCAM). RESULTS: Five of the 6 cases of SSc expressed NCAM in atrophic angulated fibers (some fibers stained heavily with oxidative enzymes). CONCLUSION: Neurogenic involvement in SSc is more frequent than reported.