Document Detail


Targeted imaging of breast tumor progression and therapeutic response in a human uMUC-1 expressing transgenic mouse model.
MedLine Citation:
PMID:  23015160     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The ability to monitor breast cancer initiation and progression on the molecular level would provide an effective tool for early diagnosis and therapy. In the present study, we focused on the underglycosylated MUC-1 tumor antigen (uMUC-1), which is directly linked to tumor progression from pre-malignancy to advanced malignancy in breast cancer and has been identified as the independent predictor of local recurrence and tumor response to chemotherapy. We investigated whether changes in uMUC-1 expression during tumor development and therapeutic intervention could be monitored non-invasively using molecular imaging approach with the uMUC-1-specific contrast agent (MN-EPPT) detectable by magnetic resonance and fluorescence optical imaging. This was done in mice that express human uMUC-1 tumor antigen (MMT mice) and develop spontaneous mammary carcinoma in a stage-wise fashion. After the injection of MN-EPPT there was a significant reduction in average T2 relaxation times of the mammary fat pad between pre-malignancy and cancer. In addition, T2 relaxation times were already altered at pre-malignant state in these mice compared to non-tumor bearing mice. This indicated that targeting uMUC-1 could be useful for detecting pre-malignant transformation in the mammary fat pad. We also probed changes in uMUC-1 expression with MN-EPPT during therapy with doxorubicin (Dox). We observed that tumor delta-T2s were significantly reduced by treatment with Dox indicating lower accumulation of MN-EPPT. This correlated with a lower level of MUC-1 expression in the Dox-treated tumors, as confirmed by immunoblotting. Our study could provide a very sensitive molecular imaging approach for monitoring tumor progression and therapeutic response.
Authors:
Subrata K Ghosh; Masashi Uchida; Byunghee Yoo; Alana W Ross; Sandra J Gendler; Jianlin Gong; Anna Moore; Zdravka Medarova
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-25
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  132     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-02-14     Completed Date:  2013-05-23     Revised Date:  2014-04-15    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1860-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 UICC.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / therapeutic use*
Blotting, Western
Breast Neoplasms / drug therapy,  metabolism,  pathology*
Disease Models, Animal
Disease Progression
Down-Regulation
Doxorubicin / therapeutic use*
Female
Humans
Immunohistochemistry
Mice
Mice, Inbred C57BL
Mice, Transgenic
Molecular Imaging*
Mucin-1 / metabolism*
Grant Support
ID/Acronym/Agency:
1R01CA135650/CA/NCI NIH HHS; R01 CA064389/CA/NCI NIH HHS; R01 CA135650/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/MUC1 protein, human; 0/Mucin-1; 80168379AG/Doxorubicin
Comments/Corrections

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