Mammary carcinoma and angiogenesis: study of the role of HER2 in relation to tumor angiogenesis process and to the sensitivity to anti-tumoral drugs

Balboni, Tania (2018) Mammary carcinoma and angiogenesis: study of the role of HER2 in relation to tumor angiogenesis process and to the sensitivity to anti-tumoral drugs, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Oncologia, ematologia e patologia, 30 Ciclo.
Documenti full-text disponibili:
[img]
Anteprima
Documento PDF (English) - Richiede un lettore di PDF come Xpdf o Adobe Acrobat Reader
Disponibile con Licenza: Salvo eventuali più ampie autorizzazioni dell'autore, la tesi può essere liberamente consultata e può essere effettuato il salvataggio e la stampa di una copia per fini strettamente personali di studio, di ricerca e di insegnamento, con espresso divieto di qualunque utilizzo direttamente o indirettamente commerciale. Ogni altro diritto sul materiale è riservato.
Download (3MB) | Anteprima

Abstract

Despite the correlation between HER2 expression and tumor angiogenesis, anti-angiogenesis drugs failed to reach sufficient efficacy in patients to be approved for HER2-positive breast cancer. About half of HER2-positive breast cancer presents an alternative splicing isoform called Δ16. Tumors developed on mouse models transgenic for one or both isoforms of HER2 have different aspects, and angiogenesis seems to occur in different ways. In this way, HER2 and Δ16 seem to drive different angiogenic phenotypes. Therefore, the aim of this thesis was to better analyze the role of the two isoforms in determining different patterns of vascularization. The different vascularization has been put in relation to the different effects of anti-angiogenic and anti-HER2 drugs. This study has been performed through histological, functional and molecular analysis of the tumors. The analysis of the vascularization in F1 tumors, in which one isoform or both can be expressed, revealed that the presence of HER2 is crucial for the establishment of the FVBhuHER2-like phenotype. The dominant role of full-length HER2 in tumor angiogenesis has been confirmed in a dynamic in vivo model of modulation of the expression of this isoform. HER2 isoforms have been found to have a crucial role in tumor angiogenesis. The dominant behavior of full-length HER2 affects the regularity of the vascular pattern, determining a vasculature that is less permeable to drugs and therefore less sensitive to anti-angiogenic and targeted agents. A molecular profile with more genes involved in sprouting angiogenesis suggests the need to further study the role of full-length HER2 in tumor vascularization, to find new targets to improve the pharmacological response to therapies.

Abstract
Tipologia del documento
Tesi di dottorato
Autore
Balboni, Tania
Supervisore
Co-supervisore
Dottorato di ricerca
Ciclo
30
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
mammary carcinoma, animal models, angiogenesis, antitumoral drugs
URN:NBN
Data di discussione
9 Maggio 2018
URI

Altri metadati

Statistica sui download

Gestione del documento: Visualizza la tesi

^