Multivalent Cathepsin Inhibitor, VBY-825, Attenuates Breast-Induced Bone Cancer Remodelling and Pain

Persistent Link:
http://hdl.handle.net/10150/297716
Title:
Multivalent Cathepsin Inhibitor, VBY-825, Attenuates Breast-Induced Bone Cancer Remodelling and Pain
Author:
Nikolich-Zugich, Tuana
Issue Date:
2013
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Metastatic bone cancer originates from breast malignancies causing severe pain and bone destruction in patients. Amongst the novel therapies under clinical development for the treatment of bone metastases are cathepsin inhibitors. Cysteine cathepsins (B, C, F, H, K, L, O, L2/V, W, X/Z) are highly expressed in many human cancers and have been associated with poor patient prognosis. In the RIP1-Tag2 transgenic model of pancreatic cancer, mice treated with VBY-825, reversible inhibitor of cathepsins S, B, V, L, K showed a significant reduction in tumor incidence and growth. In this study, we evaluate the efficacy of the cathepsin inhibitor, VBY-825 as treatment for cancer-induced bone pain. Breast cancer cells, 66.1, were injected within the intramedullary space of the femurs of female mice. After seven days of inoculation, the animals were treated with VBY-825 or vehicle (5% dextrose) subcutaneously for seven days. Spontaneous pain behaviors were significantly attenuated in cancer-induced mice treated with VBY-825, compared to vehicle treated animals. Additionally, cancer-induced animals treated with VBY-825 demonstrated both an improvement in bone integrity and reduction of tumor burden. These results indicate that a cathepsin inhibitor targeting multiple cathepsins, such as VBY-825, could be a novel therapeutic for bone metastases.
Type:
text; Electronic Thesis
Degree Name:
B.S.
Degree Level:
bachelors
Degree Program:
Honors College; Physiology
Degree Grantor:
University of Arizona
Advisor:
Vanderah, Todd W.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleMultivalent Cathepsin Inhibitor, VBY-825, Attenuates Breast-Induced Bone Cancer Remodelling and Painen_US
dc.creatorNikolich-Zugich, Tuanaen_US
dc.contributor.authorNikolich-Zugich, Tuanaen_US
dc.date.issued2013-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractMetastatic bone cancer originates from breast malignancies causing severe pain and bone destruction in patients. Amongst the novel therapies under clinical development for the treatment of bone metastases are cathepsin inhibitors. Cysteine cathepsins (B, C, F, H, K, L, O, L2/V, W, X/Z) are highly expressed in many human cancers and have been associated with poor patient prognosis. In the RIP1-Tag2 transgenic model of pancreatic cancer, mice treated with VBY-825, reversible inhibitor of cathepsins S, B, V, L, K showed a significant reduction in tumor incidence and growth. In this study, we evaluate the efficacy of the cathepsin inhibitor, VBY-825 as treatment for cancer-induced bone pain. Breast cancer cells, 66.1, were injected within the intramedullary space of the femurs of female mice. After seven days of inoculation, the animals were treated with VBY-825 or vehicle (5% dextrose) subcutaneously for seven days. Spontaneous pain behaviors were significantly attenuated in cancer-induced mice treated with VBY-825, compared to vehicle treated animals. Additionally, cancer-induced animals treated with VBY-825 demonstrated both an improvement in bone integrity and reduction of tumor burden. These results indicate that a cathepsin inhibitor targeting multiple cathepsins, such as VBY-825, could be a novel therapeutic for bone metastases.en_US
dc.typetexten_US
dc.typeElectronic Thesisen_US
thesis.degree.nameB.S.en_US
thesis.degree.levelbachelorsen_US
thesis.degree.disciplineHonors Collegeen_US
thesis.degree.disciplinePhysiologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorVanderah, Todd W.-
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