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Brazilian Journal of Biology

versión impresa ISSN 1519-6984versión On-line ISSN 1678-4375

Resumen

FONSECA-FILHO, V. C. N. et al. Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer. Braz. J. Biol. [online]. 2017, vol.77, n.4, pp.856-867.  Epub 04-Mayo-2017. ISSN 1519-6984.  http://dx.doi.org/10.1590/1519-6984.04016.

Calcitriol antiproliferative effects were observed in xenografts of breast cancer cell lines, however they were not yet investigated in tumorgrafts, consisting of freshly collected breast cancer samples xenografted into animals.

Objectives

To establish a tumorgraft model, from freshly collected breast cancer samples, which were directly implanted in nude mice, to study calcitriol effects.

Methods

Breast cancer samples collected from 12 patients were orthotopically implanted into nude mice. Animals were treated with weekly intratumoral injections of calcitriol 3 μg/Kg, which was previously shown to induce peak serum calcitriol levels in the predicted therapeutic range.

Results

Success engraftment rate was 25%. Tumorgrafts were established from aggressive (HER2 positive or histological grade 3) highly proliferative samples and original tumor characteristics were preserved. Calcitriol highly induced its target gene, CYP24A1, indicating that the genomic vitamin D pathway is active in tumorgrafts. However, no differences in the expression of proliferation and apoptosis markers (BrdU incorporation, Ki67, CDKN1A, CDKN1B, BCL2 expression) were observed in these highly proliferative tumor samples.

Conclusions

Tumorgrafts seem a promising model to explore other calcitriol doses and regimens, considering the heterogeneity of the disease and microenvironment interactions.

Palabras clave : tumorgraft; breast cancer; calcitriol; proliferation.

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