Document Detail


Volumetric contrast-enhanced ultrasound imaging to assess early response to apoptosis-inducing anti-death receptor 5 antibody therapy in a breast cancer animal model.
MedLine Citation:
PMID:  23091246     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: The objective of this study was to determine whether volumetric contrast-enhanced ultrasound (US) imaging could detect early tumor response to anti-death receptor 5 antibody (TRA-8) therapy alone or in combination with chemotherapy in a preclinical triple-negative breast cancer animal model.
METHODS: Animal experiments had Institutional Animal Care and Use Committee approval. Thirty breast tumor-bearing mice were administered Abraxane (paclitaxel; Celgene Corporation, Summit, NJ), TRA-8, TRA-8 + Abraxane, or saline as a controlon days 0, 3, 7, 10, 14, and 17. Volumetric contrast-enhanced US imaging was performedon days 0, 1, 3, and 7 before dosing. Changes in parametric maps of tumor perfusion were compared with the tumor volume and immunohistologic findings.
RESULTS: Therapeutic efficacy was detected within 7 days after drug administration using parametric volumetric contrast-enhanced US imaging. Decreased tumor perfusion was observed in both the TRA-8-alone- and TRA-8 + Abraxane-dosed animals compared to control tumors (P = .17; P = .001, respectively). The reduction in perfusion observed in the TRA-8 + Abraxane group was matched with a corresponding regression in tumor size over the same period. Survival curves illustrate that the combination of TRA-8 + Abraxane improves drug efficacy compared to the same drugs administered alone. Immunohistologic analysis revealed increased levels of apoptotic activity in the TRA-8-dosed tumors, confirming enhanced antitumor effects.
CONCLUSIONS: Preliminary results are encouraging, and volumetric contrast-enhanced US-based tumor perfusion imaging may prove clinically feasible for detecting and monitoring the early antitumor effects in response to combination TRA-8 + Abraxane therapy.
Authors:
Kenneth Hoyt; Anna Sorace; Reshu Saini
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Publication Detail:
Type:  Controlled Clinical Trial; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine     Volume:  31     ISSN:  1550-9613     ISO Abbreviation:  J Ultrasound Med     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-23     Completed Date:  2013-04-09     Revised Date:  2014-01-14    
Medline Journal Info:
Nlm Unique ID:  8211547     Medline TA:  J Ultrasound Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1759-66     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / immunology,  therapeutic use*
Antineoplastic Agents / immunology,  therapeutic use
Apoptosis / drug effects
Breast Neoplasms / drug therapy*,  immunology,  ultrasonography*
Cell Line, Tumor
Contrast Media
Female
Fluorocarbons / diagnostic use*
Humans
Imaging, Three-Dimensional / methods*
Mice
Mice, Nude
Prognosis
Receptors, TNF-Related Apoptosis-Inducing Ligand / immunology
Reproducibility of Results
Sensitivity and Specificity
Treatment Outcome
Ultrasonography / methods*
Grant Support
ID/Acronym/Agency:
5P50CA089019/CA/NCI NIH HHS; CA13148/CA/NCI NIH HHS; P30 CA013148/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antineoplastic Agents; 0/Contrast Media; 0/Definity; 0/Fluorocarbons; 0/Receptors, TNF-Related Apoptosis-Inducing Ligand; 0/TRA-8 monoclonal antibody
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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