Aspectos moleculares do câncer tiroideano

Abstract

Proliferation of the normal thyroid cell is regulated by stimulatory and inhibitory growth factors acting through their cognate cell surface receptors and subsequently through intracellular transduction pathways. In the normal adult gland, the balance of signals is such that proliferation is negligible. In the neoplastic cells, growth results from an irreversible disturbance of this equilibrium. Despite the apparent diversity of potential signal molecules that might theoretically be involved, it seems that only a small subset is capable of engendering tumor growth and is, therefore, selected in human thyroid neoplasia. Such proteins are coded for by genes RAS, RET, NTRK1 and TP53. The signal transducer ras is activated by point mutation and constitutes an early genetic alteration in tumors displaying a follicular histology. The genetic mechanisms for activation of growth factor receptor genes RET and NTRK1 are translocations or inversions in the papillary carcinomas and point mutations in the medullary carcinomas. Alterations of TP53 gene are reported in poorly differentiated and in most undifferentiated thyroid carcinomas suggesting that TP53 deregulation can play a significant role in the mechanism of dedifferentiation and progression of the disease. Although incomplete, the molecular model of thyroid carcinogenesis provides relevant tools for a better differential diagnosis and for the development of novel therapeutic

Artigo de revisão: diagnóstico cromosômico em rabdomiossarcoma

“…The success of cytogenetic studies from solid tumors has been limited by the difficulties faced in obtaining an adequate number of metaphase cells and by the poor quality of the spread and banded chromosomes 53,54 . However, lately these limitations of the conventional method have been bypassed using the fluorescence in situ hybridization (FISH) method 55 . The use of this technique on metaphases and interphase nuclei, associated with the classical cytogenetic studies, has played a major role in the detection of specific chromosome rearrangements 56 .…”

Tumorigênese Molecular Tiroideana: Implicações Para a Prática Médica

“…A MEN2 é uma síndrome neoplásica rara caracterizada pela transmissão autossômica dominante com penetrância e expressividade variáveis entre as cerca de 1000 famílias afetadas descritas até hoje (1)(2)(3)(4)(5)(6)(7)(8). Diversas variantes da doença têm sido relatadas, todas apresentando penetrância elevada para MTC (tabela 1).…”

“…Como mencionado, o RET é o receptor dos fatores de crescimento pertencentes à família dos fatores neurotróficos GDNF, semelhantes a TGFβ, que apresentam influências tróficas em diversas populações de neurônios e incluem, além do GDNF, a neurturina (NTN), a persefina (PSP) e a artemina (1,2). A resposta fisiológica a esses agentes requer a interação com um complexo multimérico composto pelo RET e por co-receptores de alta-afinidade para o glicosil-fosfatidil-inositol (GPI).…”