RESUMO
BACKGROUND: Multifocal papillary thyroid carcinoma (MPTC) has been reported in literature in 18-87 % of cases. This paper aims to review controversies in the molecular pathogenesis, prognosis, and management of MPTC. METHODS: A review of English-language literature focusing on MPTC was carried out, and analyzed in an evidence-based perspective. Results were discussed at the 2013 Workshop of the European Society of Endocrine Surgeons devoted to surgery of thyroid carcinoma. RESULTS: Literature reports no prospective randomized studies; thus, a relatively low level of evidence may be achieved. CONCLUSIONS: MPTC could be the result of either true multicentricity or intrathyroidal metastasis from a single malignant focus. Radiation and familial nonmedullary thyroid carcinoma are conditions at risk of MPTC development. The prognostic importance of multifocal tumor growth in PTC remains controversial. Prognosis might be impaired in clinical MPTC but less or none in MPTC <1 cm. MPTC can be diagnosed preoperatively by FNAB and US, with low sensitivity for MPTC <1 cm. Total or near-total thyroidectomy is indicated to reduce the risk of local recurrence. Prophylactic central node dissection should be considered in patients with total tumor diameter >1 cm, or in cases with high number of cancer foci. Completion thyroidectomy might be necessary when MPTC is diagnosed after less than near-total thyroidectomy. Radioactive iodine ablation should be considered in selected patients with MPTC at increased risk of recurrence or metastatic spread.
Assuntos
Adenocarcinoma Papilar/cirurgia , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Adenocarcinoma Papilar/diagnóstico , Adenocarcinoma Papilar/genética , Adenocarcinoma Papilar/patologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Acidente Nuclear de Chernobyl , Terapia Combinada , Análise Mutacional de DNA , Progressão da Doença , Europa (Continente) , Esvaziamento Cervical , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologia , Neoplasias Induzidas por Radiação/diagnóstico , Neoplasias Induzidas por Radiação/genética , Neoplasias Induzidas por Radiação/patologia , Neoplasias Induzidas por Radiação/cirurgia , Prognóstico , Radioterapia Adjuvante , Fatores de Risco , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , TireoidectomiaRESUMO
BACKGROUND: The determination of sensitive chemotherapy drugs for gastric cancer (GC) is one of the greatest challenges of adjuvant therapy. Here we evaluated the chemosensitivity of GC to anticancer drugs and the telomerase reverse transcriptase (hTERT) mRNA expression, and investigated the relationship of them. METHODS: The GC cells which were collected from 68 patients with primary GC were primary cultured. The chemosensitivity of GC cells to anticancer drugs was evaluated successfully using the MTT assay for 60 cases of GC cells, and the hTERT mRNA expression was examined in 60 cases of GC tissues and corresponding normal gastric mucosa and 6 cases of chronic superficial gastritis mucosa by in situ hybridization. RESULTS: Taxol, cisplatin and 5-fluorouracil were in general more effective than adriamycin and mitomycin for GC cells, and the chemosensitivity to anticancer drugs was associated with tumor histological types and a worse tumor grade. Compared to normal gastric mucosa tissues, hTERT mRNA expression was significantly increased in GC (P<0.05), which was related with a worse differentiation and drug-resistance to 5-fluorouracil or adriamycin in GC. CONCLUSIONS: These data demonstrate for the first time that examinations of hTERT mRNA expression as an important factor could be used to select the chemotherapeutic drugs for GC patients. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1793217009875483.
Assuntos
Adenocarcinoma/genética , Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Resistencia a Medicamentos Antineoplásicos/genética , RNA Mensageiro/metabolismo , Neoplasias Gástricas/genética , Telomerase/genética , Adenocarcinoma/enzimologia , Adenocarcinoma/patologia , Adenocarcinoma Mucinoso/enzimologia , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Papilar/enzimologia , Adenocarcinoma Papilar/genética , Adenocarcinoma Papilar/patologia , Carcinoma de Células em Anel de Sinete/enzimologia , Carcinoma de Células em Anel de Sinete/genética , Carcinoma de Células em Anel de Sinete/patologia , Estudos de Casos e Controles , Diferenciação Celular , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Fluoruracila/farmacologia , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Hibridização In Situ , Mitomicina/farmacologia , Gradação de Tumores , Paclitaxel/farmacologia , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia , Células Tumorais CultivadasRESUMO
We describe a patient with MUTYH-associated polyposis diagnosed with colon cancer at 33 years of age, as well as gastric polyps at a later age. She was also diagnosed with papillary thyroid cancer at age 35. MUTYH-associated polyposis is an autosomal recessively inherited disease which has clinical overlap with Familial adenomatous polyposis and its attenuated form, in that it is associated with risk of colon cancer at a young age. Extra-intestinal cancers have also been reported in patients with MUTYH-associated polyposis; however the tumor spectrum is still evolving. National Comprehensive Cancer Network guidelines recommend screening for colon, duodenal and gastric polyps in individuals with MUTYH-associated polyposis. Screening for extra-intestinal cancers i.e. thyroid cancer is presently not part of these recommendations. These will likely continue to evolve as the MUTYH-associated polyposis tumor spectrum is better understood as a result of future case reports and research.
Assuntos
Adenocarcinoma Papilar/genética , Polipose Adenomatosa do Colo/genética , DNA Glicosilases/genética , Mutação em Linhagem Germinativa/genética , Neoplasias da Glândula Tireoide/genética , Adenocarcinoma Papilar/patologia , Adenocarcinoma Papilar/cirurgia , Polipose Adenomatosa do Colo/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Prognóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
The expression of growth hormone-releasing hormone (GHRH) and its receptors has been demonstrated in peripheral tissues as well as CNS. Recently, the functional splice variant SV1 of GHRH receptor was identified in various human cancers and cancer cell lines. Although antineoplastic activity of GHRH antagonists has been clearly demonstrated, the mechanism of action is incompletely understood. The objective of this study was the investigation of direct anti-proliferative effect of GHRH antagonist MZ-5-156 on HEC-1A human endometrial cancer cell line and the elucidation of underlying mechanisms. RT-PCR revealed the expression of mRNA for GHRH and SV1 of GHRH receptor in HEC-1A cells. MZ-5-156, at concentrations between 10(-7) and 10(-5) M, had a dose-dependent antiproliferative effect on HEC-1A cells, as determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, (MTS) assay. Hoechst 33342 staining and flow cytometric analysis indicated that MZ-5-156, at 10(-6) M, induced apoptosis in HEC-1A cells after 48 h of treatment. Western blot analysis of apoptosis-related proteins demonstrated that treatment with MZ-5-156 (10(-6) M) for 48 h significantly increased the protein levels of Fas, phospho-p53 (Ser46), p53AIP1 (p53-regulated Apoptosis-Inducing Protein 1), and caspase-8, -9, and -3, and decreased the protein level of Bcl-2. These results demonstrate that MZ-5-156 can directly inhibit the proliferation of human endometrial cancer cells, which express mRNA for GHRH and SV1 of GHRH receptor, presumably through the induction of p53-dependent apoptosis coupled with the up-regulation of Fas, phospho-p53 (Ser46), p53AIP1, and caspase-8, -9, and -3, and the down-regulation of Bcl-2.
Assuntos
Adenocarcinoma Papilar/patologia , Proliferação de Células/efeitos dos fármacos , Neoplasias do Endométrio/patologia , Hormônio Liberador de Hormônio do Crescimento/antagonistas & inibidores , Sermorelina/análogos & derivados , Adenocarcinoma Papilar/genética , Idoso , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Caspases/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Neoplasias do Endométrio/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Genes bcl-2 , Genes p53 , Hormônio Liberador de Hormônio do Crescimento/genética , Humanos , RNA Mensageiro/metabolismo , Receptores de Neuropeptídeos/genética , Receptores de Neuropeptídeos/metabolismo , Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética , Receptores de Hormônios Reguladores de Hormônio Hipofisário/metabolismo , Sermorelina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genéticaRESUMO
Platelet-derived growth factor receptor (PDGFR) can bind to its ligand and consequently possess a kinase activity, and which is associated with the carcinogenesis of different cell types, including astrocytomas, oligodendrogliomas, and glioblastoma. In a cDNA microarray analysis, we observe the over-expressed mRNA of both PDGF-A and PDGF-alpha receptor in thyroid carcinoma cells. And the elevated protein expressions of PDGF-A and PDGF-alpha receptor in thyroid carcinoma cells were also confirmed by a Western blot analysis. The phosphorylation of PDGF-alpha receptor evaluated by an antibody against Tyr 720-phosphate was found in thyroid carcinoma cells. The tyrosine kinase activity of PDGF-alpha receptor was inhibited by tyrphostin AG1295 and showed a dose-dependent inhibition for the proliferation of thyroid carcinoma cells. These findings imply that autocrine activation of PDGF-alpha receptor plays a crucial role in the carcinogenesis of thyroid cells.
Assuntos
Adenocarcinoma Folicular/metabolismo , Adenocarcinoma Papilar/metabolismo , Comunicação Autócrina , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Adenocarcinoma Folicular/genética , Adenocarcinoma Papilar/genética , Western Blotting , Proliferação de Células/efeitos dos fármacos , DNA Complementar , Ativação Enzimática , Perfilação da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Fosforilação , Fator de Crescimento Derivado de Plaquetas/genética , Fator de Crescimento Derivado de Plaquetas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Neoplasias da Glândula Tireoide/genética , Células Tumorais Cultivadas , Tirosina/metabolismo , Tirfostinas/farmacologiaRESUMO
Apurinic/apyrimidinic endonuclease is a key enzyme in the process of base excision repair, required for the repair of spontaneous base damage that arises as a result of oxidative damage to DNA. In mice, this endonuclease is coded by the Apex gene, disruption of which is incompatible with embryonic life. Here we confirm the embryonic lethality of Apex-null mice and report the phenotypic characterization of mice that are heterozygous mutants for the Apex gene (Apex+/-). We show that Apex heterozygous mutant cells and animals are abnormally sensitive to increased oxidative stress. Additionally, such animals manifest elevated levels of oxidative stress markers in serum, and we show that dietary supplementation with antioxidants restores these to normal levels. Apex+/- embryos and pups manifest reduced survival that can also be partially rescued by dietary supplementation with antioxidants. These results are consistent with a proposed role for this enzyme in protection against the deleterious effects of oxidative stress and raise the possibility that humans with heterozygous mutations in the homologous HAP1 gene may be at increased risk for the phenotypic consequences of oxidative stress in cells.