Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Brazilian Journal of Biology |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1519-69842017000400856 |
Resumo: | Abstract 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. |
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Brazilian Journal of Biology |
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Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancertumorgraftbreast cancercalcitriolproliferationAbstract 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.Instituto Internacional de Ecologia2017-11-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1519-69842017000400856Brazilian Journal of Biology v.77 n.4 2017reponame:Brazilian Journal of Biologyinstname:Instituto Internacional de Ecologia (IIE)instacron:IIE10.1590/1519-6984.04016info:eu-repo/semantics/openAccessFonseca-Filho,V. C. N.Katayama,M. L. H.Lyra,E. C.Maria,D. A.Basso,R. A.Nonogaki,S.Guerra,J. M.Maistro,S.Góes,J. C. G. S.Folgueira,M. A. A. K.eng2017-09-29T00:00:00Zoai:scielo:S1519-69842017000400856Revistahttps://www.scielo.br/j/bjb/https://old.scielo.br/oai/scielo-oai.phpbjb@bjb.com.br||bjb@bjb.com.br1678-43751519-6984opendoar:2017-09-29T00:00Brazilian Journal of Biology - Instituto Internacional de Ecologia (IIE)false |
dc.title.none.fl_str_mv |
Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer |
title |
Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer |
spellingShingle |
Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer Fonseca-Filho,V. C. N. tumorgraft breast cancer calcitriol proliferation |
title_short |
Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer |
title_full |
Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer |
title_fullStr |
Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer |
title_full_unstemmed |
Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer |
title_sort |
Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer |
author |
Fonseca-Filho,V. C. N. |
author_facet |
Fonseca-Filho,V. C. N. Katayama,M. L. H. Lyra,E. C. Maria,D. A. Basso,R. A. Nonogaki,S. Guerra,J. M. Maistro,S. Góes,J. C. G. S. Folgueira,M. A. A. K. |
author_role |
author |
author2 |
Katayama,M. L. H. Lyra,E. C. Maria,D. A. Basso,R. A. Nonogaki,S. Guerra,J. M. Maistro,S. Góes,J. C. G. S. Folgueira,M. A. A. K. |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Fonseca-Filho,V. C. N. Katayama,M. L. H. Lyra,E. C. Maria,D. A. Basso,R. A. Nonogaki,S. Guerra,J. M. Maistro,S. Góes,J. C. G. S. Folgueira,M. A. A. K. |
dc.subject.por.fl_str_mv |
tumorgraft breast cancer calcitriol proliferation |
topic |
tumorgraft breast cancer calcitriol proliferation |
description |
Abstract 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. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-11-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1519-69842017000400856 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1519-69842017000400856 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/1519-6984.04016 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Instituto Internacional de Ecologia |
publisher.none.fl_str_mv |
Instituto Internacional de Ecologia |
dc.source.none.fl_str_mv |
Brazilian Journal of Biology v.77 n.4 2017 reponame:Brazilian Journal of Biology instname:Instituto Internacional de Ecologia (IIE) instacron:IIE |
instname_str |
Instituto Internacional de Ecologia (IIE) |
instacron_str |
IIE |
institution |
IIE |
reponame_str |
Brazilian Journal of Biology |
collection |
Brazilian Journal of Biology |
repository.name.fl_str_mv |
Brazilian Journal of Biology - Instituto Internacional de Ecologia (IIE) |
repository.mail.fl_str_mv |
bjb@bjb.com.br||bjb@bjb.com.br |
_version_ |
1752129884161835008 |