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Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors

Authors: Mercè Juliachs, August Vidal, Xavier Garcia del Muro, Josep M Piulats, Enric Condom, Oriol Casanovas, Mariona Graupera, Jose R Germà, Alberto Villanueva, Francesc Viñals

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

Cisplatin (CDDP) resistance in testicular germ cell tumors (GCTs) is still a clinical challenge, and one associated with poor prognosis. The purpose of this work was to test pazopanib, an anti-tumoral and anti-angiogenic multikinase inhibitor, and its combination with lapatinib (an anti-ErbB inhibitor) in mouse orthotopic models of human testicular GCTs.

Methods

We used two different models of human testicular GCTs orthotopically grown in nude mice; a CDDP-sensitive choriocarcinoma (TGT38) and a new orthotopic model generated from a metastatic GCT refractory to first-line CDDP chemotherapy (TGT44). Nude mice implanted with these orthotopic tumors were treated with the inhibitors and the effect on tumoral growth and angiogenesis was evaluated.

Results

TGT44 refractory tumor had an immunohistochemical profile similar to the original metastasis, with characteristics of yolk sac tumor. TGT44 did not respond when treated with cisplatin. In contrast, pazopanib had an anti-angiogenic effect and anti-tumor efficacy in this model. Pazopanib in combination with lapatinib in TGT38, an orthotopic model of choriocarcinoma had an additive effect blocking tumor growth.

Conclusions

We present pazopanib as a possible agent for the alternative treatment of CDDP-sensitive and CDDP-refractory GCT patients, alone or in combination with anti-ErbB therapies.
Appendix
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Metadata
Title
Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors
Authors
Mercè Juliachs
August Vidal
Xavier Garcia del Muro
Josep M Piulats
Enric Condom
Oriol Casanovas
Mariona Graupera
Jose R Germà
Alberto Villanueva
Francesc Viñals
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-382

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