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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer

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Fonseca-Filho, V. C. N. [1] ; Katayama, M. L. H. [1] ; Lyra, E. C. [2] ; Maria, D. A. [3] ; Basso, R. A. [2] ; Nonogaki, S. [4] ; Guerra, J. M. [4] ; Maistro, S. [1] ; Goes, J. C. G. S. [2] ; Folgueira, M. A. A. K. [1]
Total Authors: 10
[1] Univ Sao Paulo, Fac Med, Hosp Clin, Dept Radiol & Oncol, Inst Canc Estado Sao Paulo, Ctr Invest Translac On, Ave Dr Arnaldo, 251, BR-01246000 Sao Paulo, SP - Brazil
[2] IBCC, Dept Mastol, Ave Alcantara Machado 2576, Parque Mooca, BR-03102002 Sao Paulo, SP - Brazil
[3] Inst Butantan, Serv Bioquim, Div Ciencias Fisiol & Quim, Ave Vital Brasil 1500, BR-05503900 Sao Paulo, SP - Brazil
[4] IAL, Dept Patol, Ave Dr Arnaldo 355, BR-01246000 Sao Paulo, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Brazilian Journal of Biology; v. 77, n. 4, p. 856-867, NOV 2017.
Web of Science Citations: 1

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 mu g/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. (AU)

FAPESP's process: 11/09103-1 - Proliferation and expression of target genes in breast cancer xenografts from post menopausal patients exposed to intratumoral calcitriol
Grantee:Maria Aparecida Azevedo Koike Folgueira
Support type: Regular Research Grants