ABSTRACT
La gammagrafía con radiotrazadores que tienen afinidad por los receptores de somatostatina se ha convertido en metodología eficaz para el diagnóstico y estadificación de los tumores neuroendocrinos. Se presenta un caso en el cual el procedimiento radioisotópico muestra su efectividad en la localización del tumor primario.
Somatostatin receptor scintigraphy has become an important tool for diagnosis and evaluation of neuroendocrine tumors. This case report shows about the importance of the radionuclide procedure for the localization of the primary tumor.
Subject(s)
Humans , Female , Middle Aged , Carcinoma, Medullary , Carcinoma, Medullary/metabolism , Organotechnetium Compounds , Thyroid Neoplasms , Thyroid Neoplasms/metabolism , Receptors, Somatostatin/metabolism , Carcinoma, Medullary/pathology , Organotechnetium Compounds/pharmacokinetics , Thyroid Neoplasms/pathology , Octreotide/analogs & derivatives , Octreotide/pharmacokinetics , Octreotide , Radiopharmaceuticals/pharmacokinetics , RadiopharmaceuticalsABSTRACT
Suvivin is a novel member of the inhibitor of apoptosis protein (IAP) family, which is known to be over-expressed in various carcinomas and associated with their biologically aggressive characteristics. The aim of this study was to investigate survivin expression in human medullary thyroid carcinoma (MTC) and a MTC cell line TT, correlate suvivin expression with clinicopathologic features of MTC, and test effects of antisurvivin oligonucleotides (ASODNs) on growth and apoptosis of TT cells. Survivin expression was immunohistochemically determined in formalin-fixed and paraffin-embedded specimens obtained from 10 cases of normal thyroid (NT) and 10 cases of MTC, and in TT cells. In TT cells, we confirmed survivin expression and its down-regulation by ASODNs using RT-PCR and Western blot analyses, and investigated effects of ASODNs on viability and growth by MTT assay and apoptosis by apoptotic analyses including DNA laddering assay, acridine orange/ethidium bromide staining and flow cytometric cell cycle analysis. Immunohistochemical analysis showed high survivin expression in MTC and TT cells, whereas no immunoreactivity was detectable in NT. Statistical analyses revealed no significant correlation of survivin expression with the clinicopathologic features of MTC. In TT cells, survivin expression at both mRNA and protein levels was confirmed and could be down-regulated by ASODNs concomitant with decrease in viability and growth, and increase in apoptosis. Our results suggest that survivin plays an important role in MTC independent of the conventional clinicopathologic factors, and ASODNs is a promising survivin-targeted gene therapy for MTC.
Subject(s)
Male , Humans , Female , Adult , Time Factors , Thyroid Neoplasms/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Oligonucleotides, Antisense/genetics , Neoplasm Proteins/genetics , Microtubule-Associated Proteins/genetics , Gene Expression Regulation, Neoplastic/drug effects , Down-Regulation/drug effects , Dose-Response Relationship, Drug , Cell Survival/drug effects , Cell Proliferation/drug effects , Cell Line, Tumor , Carcinoma, Medullary/metabolism , Apoptosis/drug effectsABSTRACT
Melanin production in medullary thyroid carcinomas is rare. The present case illustrates melanin and other atypical features of medullary carcinoma of the thyroid in a fifty year old female. The diagnosis was suggested on the cytomorphological features seen on fine needle aspiration cytology smears. On histo-pathological examination the tumor was extensively pigmented with frequent mitosis. Amyloid was conspicuously scarce. Confirmation of diagnosis was done by immunohistochemical positivity for calcitonin and HMB-45 on tissue sections. The case is being presented in view of its rarity and distinct immunoreactivity. Review of literature is done and the implications of such dual positivity in the histogenesis and divergent phenotype of this tumor are discussed.
Subject(s)
Antigens, Neoplasm , Calcitonin/metabolism , Carcinoma, Medullary/metabolism , Female , Humans , Immunohistochemistry , Melanins/biosynthesis , Middle Aged , Neoplasm Proteins/metabolism , Thyroid Neoplasms/metabolismABSTRACT
Em doses farmacológicas a Calcitonina (CT) é tida como um hormônio poupador de cálcio (Ca) e protetor da massa óssea. Devido a isto, tem sido utilizada como alternativa terapêutica das osteoporose pós-menopáusica, doença de grande prevalência entre as mulheres. O papel da CT no desenvolvimento desta forma de osteoporose, entretanto, apesar do grande número de trabalhos respeito, ainda permanece controverso na literatura, assim como a existência de um efeito direto dos estrógenos sobre a secreçao e síntese de CT. Nossa proposta foi avaliar a açao do 17B-estradiol (E2) sobre a secreçao basal e estimulada de CT "in-vitro". Para isso utilizamos uma linhagem de células de carcinoma medular de tireóide humano (TT), na qual já havia sido descrita a presença de receptores estrogênicos. Estudamos o efeito de diferentes concentraçoes de E2 (1 e 100nM) sobre a secreçao basal de CT após períodos de incubaçao que variaram de 6 horas a 6 dias, além do efeito sobre a estimulaçao das células com TPA+Forskolina após 6 dias de pré-incubaçao com E2. A incubaçao das células TT com E2 nao resultou em nenhum incremento na secreçao basal ou estimulada de CT em comparaçao aos grupos controles, em nenhum dos períodos de tempo estudados. O efeito observado, ao contrário, foi de inibiçao transitória da secreçao de CT, de forma dose-dependente (80,5 porcento e 59,1 porcento do controle para 1 a 100 nM respectivamente), cujo nadir apresentou-se após 24h de incubaçao, retornando aos níveis dos grupos controles após 72h. Somado a isto, E2 levou a um efeito estimulatório dose-dependente sonre o conteúdo celular protéico, mas sem qualquer efeito sobre a incorporaçao de timidina triciada, indicando induzir a uma hipertrofia ao invés de uma hiperplasia das células TT. Os dados obtidos demonstraram ausência de qualquer efeito estimulatório direto do E2 sobre a secreçao basal ou estimulada de CT, revelando adicionalmente em efeito de inibiçao transitória na secreçao de CT. (Arq Bras Endocrinol Metab 1994; 38/1:23-28).