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Nuclear factor-kB in thyroid carcinogenesis and progression: a novel therapeutic target for advanced thyroid cancer
Namba, Hiroyuki; Saenko, Vladimir; Yamashita, Shunichi.
  • Namba, Hiroyuki; Nagasaki University. Department of Molecular Medicine. Nagasaki. JP
  • Saenko, Vladimir; Nagasaki University. School of Biomedical Sciences. Department of International Health and Radiation Research. Nagasaki. JP
  • Yamashita, Shunichi; Nagasaki University. Department of Molecular Medicine. Nagasaki. JP
Arq. bras. endocrinol. metab ; 51(5): 843-851, jul. 2007. ilus, graf
Article in English | LILACS | ID: lil-461334
ABSTRACT
Apoptosis is an essential physiological process of elimination of destined cells during the development and differentiation or after damage from external stresses such as ionizing radiation or chemotherapeutic agents. Disruption of apoptosis is proved to cause various diseases including cancer. Among numerous molecules involved in diverse anti- or pro-apoptotic signaling pathways, NF-kappaB is one of the key factors controlling anti-apoptotic responses. Its anti-apoptotic effect is thought to be mediated through not only transcriptional activation of dependent genes but also by crosstalking with the JNK pathway. Oncogenic proteins such as Ret/PTC, Ras and BRAF can induce NF-kappaB activation making it an important change in thyroid cancer. A number of specific or non-specific NF-kappaB inhibitors have been tried to take over the cascade in in vitro and in vivo experiments. These agents can induce massive apoptosis especially in combination with radio- or chemotherapy. Current results suggest that the inhibition of the NF-kappaB may be a promising strategy for advanced thyroid cancer treatment but further investigations are warranted to develop specific and clinically effective NF-kappaB inhibitors in future.
RESUMO
A apoptose é um processo fisiológico essencial destinado a eliminar células durante o desenvolvimento e diferenciação ou após danos decorrentes de estresses externos com a radiação ionizante ou agentes quimioterápicos. Distúrbios na apoptose têm sido demonstrados como causadores de várias doenças, incluindo câncer. Entre as inúmeras moléculas envolvidas nas várias vias de sinalização anti- ou pró-apoptoticas, NF-kapaB é um dos fatores-chave que controlam as respostas anti-apoptóticas. Acredita-se que seu efeito anti-apoptótico seja mediado não apenas pela ativação transcricional de genes dependentes mas também por crosstalking com a via JNK. Proteínas oncogênicas como Ret/PTC, Ras e BRAF podem induzir ativação de NF-kapaB promovendo importante transformação no câncer da tireóide. Uma série de inibidores específicos e não-específicos do NF-kapaB tem sido usada em experimentos in vitro e in vivo procurando inibir a cascata. Esses agentes podem induzir apoptose maciça especialmente em combinação com radio ou quimioterapia. Resultados atuais sugerem que a inibição de NF-kapaB pode ser uma estratégia promissora no tratamento do câncer da tireóide avançado, mas novas investigações são necessárias para desenvolver inibidores específicos e clinicamente efetivos do NF-kapaB.
Subject(s)

Full text: Available Index: LILACS (Americas) Main subject: Thyroid Neoplasms / Carcinoma / NF-kappa B / Apoptosis Limits: Animals / Humans Language: English Journal: Arq. bras. endocrinol. metab Journal subject: Endocrinology / Metabolism Year: 2007 Type: Article Affiliation country: Japan Institution/Affiliation country: Nagasaki University/JP

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Full text: Available Index: LILACS (Americas) Main subject: Thyroid Neoplasms / Carcinoma / NF-kappa B / Apoptosis Limits: Animals / Humans Language: English Journal: Arq. bras. endocrinol. metab Journal subject: Endocrinology / Metabolism Year: 2007 Type: Article Affiliation country: Japan Institution/Affiliation country: Nagasaki University/JP