Libertini, Silvana (2008) Anaplastic thyroid carcinoma: novel therapeutic targets and strategies. [Tesi di dottorato] (Unpublished)

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Item Type: Tesi di dottorato
Language: English
Title: Anaplastic thyroid carcinoma: novel therapeutic targets and strategies
Creators:
CreatorsEmail
Libertini, SilvanaUNSPECIFIED
Date: 2008
Date Type: Publication
Number of Pages: 101
Institution: Università degli Studi di Napoli Federico II
Department: Biologia e patologia cellullare e molecolare "L. Califano"
PHD name: Oncologia ed endocrinologia molecolare
PHD cycle: 20
PHD Coordinator:
nameemail
Vecchio, GiancarloUNSPECIFIED
Tutor:
nameemail
Portella, GiuseppeUNSPECIFIED
Date: 2008
Number of Pages: 101
Uncontrolled Keywords: Anaplastic thyroid carcinoma
MIUR S.S.D.: Area 06 - Scienze mediche > MED/05 - Patologia clinica
Date Deposited: 03 Jul 2008
Last Modified: 30 Apr 2014 19:31
URI: http://www.fedoa.unina.it/id/eprint/2630

Abstract

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies, with a mean survival of only 6 months. Therefore, novel therapeutic approaches are desperately required. - dl1520 is a replication competent adenovirus that, due to lack of a functional E1B-55kD gene, can complete its life cycle solely in tumoural cells. We previously demonstrated that dl1520 efficiently kills ATC cells, but high multiplicity of infection (MOI) are required to obtain a significant antineoplastic effect. One of the major limiting factor in the efficient adenoviral transduction is the presence on cell surface of CAR receptor. Inhibition of the Raf/MEK/ERK pathway up-regulates CAR expression in cancer cells, thus improving adenoviral entry and cell killing by adenoviral mutants. To enhance its oncolytic activity, we decided to combine dl1520 with lovastatin, a drug that, blocking mevalonate synthesis, inhibits Raf/MEK/ERK pathway. However, lovastatin does not up-regulate CAR levels but, acting on viral genes expression, enhances viral replication. Indeed, lovastatin enhances in vitro and in vivo dl1520 effects, thus suggesting its potential role as dl1520 adjuvant in ATC therapy. - A common feature of anaplastic thyroid carcinoma is represented by aneuploidy. Aberrant expression of Aurora B occurs in solid tumours and it is associated with chromosome instability and carcinogenesis. Therefore, Aurora B expression has been evaluated in cell lines and samples from human thyroid carcinoma, showing that its expression paralleles the malignant phenotype. To establish a molecular target for ATC, Aurora B expression has been inhibited by RNAi or a specific inhibitor, showing that Aurora B inhibition blocks cell proliferation and cell survival.

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