Histopathology of mammary tumours in female rats treated with 1-methyl-1-nitrosourea.
ABSTRACT To induce, evaluate and classify advanced stages of mammary gland tumours induced by MNU.
Female Sprague-Dawley rats were injected intraperitoneally with 1-methyl-1-nitrosourea (MNU; 50 mg.kg-1) on the day 33, 40, 47, 54 and 61 of age in the first experiment and on 50th and 113th day in the second experiment. On the 117th day (first experiment) and on the 153rd day of age (second experiment) the rats were sacrificed by decapitation and their mammary glands were evaluated both macroscopically and microscopically for the presence of grossly detectable mammary tumours. Mammary tumours were classified according to Russo et al. (1990).
The final incidence of palpable carcinomas was ranging from 60 % to 76 %. All microscopically evaluated tumours were malignant. Among the total number of lesions classified the percentage of invasive tumours ranged from 35 % to 44 %. No metastases were observed in other organs in MNU treated animals.
SourceAvailable from: Prafull Kumar Singh
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ABSTRACT: Improved diagnostic screening has led to earlier detection of many tumors, but screening may still miss many aggressive tumor types. Proteomic and genomic profiling studies of breast cancer samples have identified tumor markers that may help improve screening for more aggressive, rapidly growing breast cancers. To identify potential blood-based biomarkers for the early detection of breast cancer, we assayed serum samples via matrix-assisted laser desorption ionization-time of flight mass spectrometry from a rat model of mammary carcinogenesis. We found elevated levels of a fragment of the protein dermcidin (DCD) to be associated with early progression of N-methylnitrosourea-induced breast cancer, demonstrating significance at weeks 4 (p = 0.045) and 5 (p = 0.004), a time period during which mammary pathologies rapidly progress from ductal hyperplasia to adenocarcinoma. The highest serum concentrations were observed in rats bearing palpable mammary carcinomas. Increased DCD was also detected with immunoblotting methods in 102 serum samples taken from women just prior to breast cancer diagnosis. To validate these findings in a larger population, we applied a 32-gene in vitro DCD response signature to a dataset of 295 breast tumors and assessed correlation with intrinsic breast cancer subtypes and overall survival. The DCD-derived gene signature was significantly associated with subtype (p < 0.001) and poorer overall survival [HR (95 % CI) = 1.60 (1.01-2.51), p = 0.044]. In conclusion, these results present novel evidence that DCD levels may increase in early carcinogenesis, particularly among more aggressive forms of breast cancer.Breast Cancer Research and Treatment 02/2014; DOI:10.1007/s10549-014-2880-3 · 4.20 Impact Factor
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