RGD Reference Report - Diffusion weighted imaging evaluated the early therapy effect of tamoxifen in an MNU-induced mammary cancer rat model. - Rat Genome Database

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Diffusion weighted imaging evaluated the early therapy effect of tamoxifen in an MNU-induced mammary cancer rat model.

Authors: Zhai, G  Grubbs, CJ  Stockard, CR  Umphrey, HR  Beasley, TM  Kim, H 
Citation: Zhai G, etal., PLoS One. 2013 May 21;8(5):e64445. doi: 10.1371/journal.pone.0064445. Print 2013.
RGD ID: 7364946
Pubmed: PMID:23700476   (View Abstract at PubMed)
PMCID: PMC3660312   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0064445   (Journal Full-text)

PURPOSE: To assess the optimal time point of diffusion-weighted imaging (DWI) for early prognosis of breast cancer following tamoxifen therapy using a methylnitrosourea (MNU)-induced ER-positive breast-cancer model. METHODS: Two groups of Sprague-Dawley rats (n = 15 for group 1; n = 10 for group 2) were used. All animals (50 days old) were intravenously injected with MNU (50 mg/kg body weight) to induce ER-positive mammary tumors. When tumors were approximately 2 cm in diameter, DWI was performed on days 0, 3, and 7, and intratumoral apparent diffusion coefficient (ADC) values were measured. Therapy started on day 0 with tamoxifen (10 mg/kg diet) and continued for 4 weeks for group 1, but only 1 week for group 2, while tumor volume was measured by caliper twice weekly. All animals of group 2 were euthanized on day 7 after imaging, and Ki-67, TUNEL, ERalpha, and ERbeta staining were performed on tumor tissue. RESULTS: DW images of MNU-induced mammary tumors were successfully obtained with minimal motion artifact. For group 1, ADC change for 3 days after therapy initiation (ADC3D) was significantly correlated with tumor-volume change until day 11, but the significant correlation between ADC change for 7 days (ADC7D) and the tumor-volume change was observed until day 18. Similarly, for group 2, either ADC7D or ADC3D was significantly correlated with the tumor-volume change, but the higher significance was observed for ADC7D. Furthermore, ADC7D was significantly correlated with apoptotic (TUNEL stained), proliferative (Ki-67 stained), and ERbeta-positive cell densities, but ADC3D was not significantly correlated with any of those. CONCLUSIONS: ADC7D might be a more reliable surrogate imaging biomarker than ADC3D to assess effectiveness of tamoxifen therapy for ER-positive breast cancer, which may enable personalized treatment. The significant correlation between ADC7D and ERbeta-positive cell density suggests that ERbeta may play an important role as a therapeutic indicator of tamoxifen.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ESR2Humanbreast cancer treatmentISOEsr2 (Rattus norvegicus) RGD 
Esr2Ratbreast cancer treatmentIDA  RGD 
Esr2Mousebreast cancer treatmentISOEsr2 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Esr2  (estrogen receptor 2)

Genes (Mus musculus)
Esr2  (estrogen receptor 2 (beta))

Genes (Homo sapiens)
ESR2  (estrogen receptor 2)


Additional Information