Cyclophosphamide bimodal effects in antineoplasic therapy
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | |
Tipo de documento: | Artigo |
Idioma: | por |
Título da fonte: | Revista Brasileira de Cancerologia (Online) |
Texto Completo: | https://rbc.inca.gov.br/index.php/revista/article/view/2880 |
Resumo: | Cyclophosphamide (Cy), one ofthe chemotherapeutic agents more frequently used in clinical oncology, was originated after the Chemical strueture of mechlorethamine was modified to obtain an anticancer agent with higher selectivity for neoplastic tissues. The systematic use of chemotherapeutic drugs in cancer treatment made apparent that these compounds, given in large doses, usually cause impairment of the host defense mechanisms as a consequence of the inhibition of cellular proliferation. Nevertheless, it was demonstrated in several experimental models, that the administration of a single-low dose of Cy to tumor bearing animais, when the antitumoral immune response has fully developed, produces an immunopotentiation through a selective inhibition of T suppressor lymphocytes. Moreover, the observation of a total inhibition of metastases formation without altering the primary tumor growth, demonstrated an interesting new effect of such therapeutic modality: its preferential action against tumoral cells with metastatic phenotype, probably to a selective immunomodulation on these cellular subpopulations. These findings indicate a bimodal effect of Cy: depending on the dose and schedule of administration, it causes immunodepression or immunopotentiation. The use of biological response modifiers has led to what nowadays is know as the fourth therapeutic modality against cancer. It is proposed that Cy should also be considered within that context. |
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Cyclophosphamide bimodal effects in antineoplasic therapyEfecto bimodal de la ciclofosfamida en la terapia antineoplásicaCyclophosphamideMetastasisBiological Response ModifiersImmunomodulationCiclofosfamidaMetástasesModificadores de la Respuesta BiológicaInmunomodulaciónCyclophosphamide (Cy), one ofthe chemotherapeutic agents more frequently used in clinical oncology, was originated after the Chemical strueture of mechlorethamine was modified to obtain an anticancer agent with higher selectivity for neoplastic tissues. The systematic use of chemotherapeutic drugs in cancer treatment made apparent that these compounds, given in large doses, usually cause impairment of the host defense mechanisms as a consequence of the inhibition of cellular proliferation. Nevertheless, it was demonstrated in several experimental models, that the administration of a single-low dose of Cy to tumor bearing animais, when the antitumoral immune response has fully developed, produces an immunopotentiation through a selective inhibition of T suppressor lymphocytes. Moreover, the observation of a total inhibition of metastases formation without altering the primary tumor growth, demonstrated an interesting new effect of such therapeutic modality: its preferential action against tumoral cells with metastatic phenotype, probably to a selective immunomodulation on these cellular subpopulations. These findings indicate a bimodal effect of Cy: depending on the dose and schedule of administration, it causes immunodepression or immunopotentiation. The use of biological response modifiers has led to what nowadays is know as the fourth therapeutic modality against cancer. It is proposed that Cy should also be considered within that context.La Ciclofosfamida (Cy) es el agente alquilante más utilizado en el tratamento quimioterápico de diversas neoplasias humanas; habitualmente se la administra em combinación con otros citostáticos para lograr una mayor eficacia terapêutica. La mayoría de los protoeolos clínicos la emplean en dosis altas y suministrada en repetidas ocaciones a lo largo del tratamento antineoplásico, con Ias ya conocidas acciones colaterales, entre ellas la inmunodepresión. Sin embargo, en diferentes modelos experimentales en animales portadores de un tumor, la administración de uma dosis única y relativamente baja en un determinado momento de la respuesta inmune antitumoral, produce inmunopotenciación, a través de una inhibieión selectiva sobre los linfocitos T supresores. Posteriormente se demostró un efecto interesante y novedoso de éstas dosis bajas de Cy: su acción preferencial sobre células tumorales com fenotipo metastásico (probablemente debido a una inmunomodulación selectiva sobre dichas subpoblaciones celulares), ya que se observo una inhibieión total en la formación de Ias metástasis sin afectar el desarrollo dei tumor primário. Estos resultados senalan el efecto bimodal de la Cy sobre el sistema inmune dei huésped cuando se la utiliza en el tratamiento antineoplásico em diferentes dosis y esquemas de administración. La utilización de sustancias naturales denominadas “modificadores de la respuesta biológica”, ha derivado en lo que se conoce como cuarta modalidad terapêutica contra el cáncer. Se propone que la Cy sea considerada también dentro de ese contexto.INCA2022-10-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArtigos, Avaliado pelos paresapplication/pdfhttps://rbc.inca.gov.br/index.php/revista/article/view/288010.32635/2176-9745.RBC.1996v42n1.2880Revista Brasileira de Cancerologia; Vol. 42 No. 1 (1996): Jan./Feb./Mar.; 33-42Revista Brasileira de Cancerologia; Vol. 42 Núm. 1 (1996): ene./feb./mar.; 33-42Revista Brasileira de Cancerologia; v. 42 n. 1 (1996): jan./fev./mar.; 33-422176-9745reponame:Revista Brasileira de Cancerologia (Online)instname:Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA)instacron:INCAporhttps://rbc.inca.gov.br/index.php/revista/article/view/2880/1759https://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessMatar, PabloScharovsky, O. Graciela2023-06-19T13:18:58Zoai:rbc.inca.gov.br:article/2880Revistahttps://rbc.inca.gov.br/index.php/revistaPUBhttps://rbc.inca.gov.br/index.php/revista/oairbc@inca.gov.br0034-71162176-9745opendoar:2023-06-19T13:18:58Revista Brasileira de Cancerologia (Online) - Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA)false |
dc.title.none.fl_str_mv |
Cyclophosphamide bimodal effects in antineoplasic therapy Efecto bimodal de la ciclofosfamida en la terapia antineoplásica |
title |
Cyclophosphamide bimodal effects in antineoplasic therapy |
spellingShingle |
Cyclophosphamide bimodal effects in antineoplasic therapy Matar, Pablo Cyclophosphamide Metastasis Biological Response Modifiers Immunomodulation Ciclofosfamida Metástases Modificadores de la Respuesta Biológica Inmunomodulación |
title_short |
Cyclophosphamide bimodal effects in antineoplasic therapy |
title_full |
Cyclophosphamide bimodal effects in antineoplasic therapy |
title_fullStr |
Cyclophosphamide bimodal effects in antineoplasic therapy |
title_full_unstemmed |
Cyclophosphamide bimodal effects in antineoplasic therapy |
title_sort |
Cyclophosphamide bimodal effects in antineoplasic therapy |
author |
Matar, Pablo |
author_facet |
Matar, Pablo Scharovsky, O. Graciela |
author_role |
author |
author2 |
Scharovsky, O. Graciela |
author2_role |
author |
dc.contributor.author.fl_str_mv |
Matar, Pablo Scharovsky, O. Graciela |
dc.subject.por.fl_str_mv |
Cyclophosphamide Metastasis Biological Response Modifiers Immunomodulation Ciclofosfamida Metástases Modificadores de la Respuesta Biológica Inmunomodulación |
topic |
Cyclophosphamide Metastasis Biological Response Modifiers Immunomodulation Ciclofosfamida Metástases Modificadores de la Respuesta Biológica Inmunomodulación |
description |
Cyclophosphamide (Cy), one ofthe chemotherapeutic agents more frequently used in clinical oncology, was originated after the Chemical strueture of mechlorethamine was modified to obtain an anticancer agent with higher selectivity for neoplastic tissues. The systematic use of chemotherapeutic drugs in cancer treatment made apparent that these compounds, given in large doses, usually cause impairment of the host defense mechanisms as a consequence of the inhibition of cellular proliferation. Nevertheless, it was demonstrated in several experimental models, that the administration of a single-low dose of Cy to tumor bearing animais, when the antitumoral immune response has fully developed, produces an immunopotentiation through a selective inhibition of T suppressor lymphocytes. Moreover, the observation of a total inhibition of metastases formation without altering the primary tumor growth, demonstrated an interesting new effect of such therapeutic modality: its preferential action against tumoral cells with metastatic phenotype, probably to a selective immunomodulation on these cellular subpopulations. These findings indicate a bimodal effect of Cy: depending on the dose and schedule of administration, it causes immunodepression or immunopotentiation. The use of biological response modifiers has led to what nowadays is know as the fourth therapeutic modality against cancer. It is proposed that Cy should also be considered within that context. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-10-04 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Artigos, Avaliado pelos pares |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://rbc.inca.gov.br/index.php/revista/article/view/2880 10.32635/2176-9745.RBC.1996v42n1.2880 |
url |
https://rbc.inca.gov.br/index.php/revista/article/view/2880 |
identifier_str_mv |
10.32635/2176-9745.RBC.1996v42n1.2880 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.none.fl_str_mv |
https://rbc.inca.gov.br/index.php/revista/article/view/2880/1759 |
dc.rights.driver.fl_str_mv |
https://creativecommons.org/licenses/by/4.0 info:eu-repo/semantics/openAccess |
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https://creativecommons.org/licenses/by/4.0 |
eu_rights_str_mv |
openAccess |
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application/pdf |
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INCA |
publisher.none.fl_str_mv |
INCA |
dc.source.none.fl_str_mv |
Revista Brasileira de Cancerologia; Vol. 42 No. 1 (1996): Jan./Feb./Mar.; 33-42 Revista Brasileira de Cancerologia; Vol. 42 Núm. 1 (1996): ene./feb./mar.; 33-42 Revista Brasileira de Cancerologia; v. 42 n. 1 (1996): jan./fev./mar.; 33-42 2176-9745 reponame:Revista Brasileira de Cancerologia (Online) instname:Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA) instacron:INCA |
instname_str |
Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA) |
instacron_str |
INCA |
institution |
INCA |
reponame_str |
Revista Brasileira de Cancerologia (Online) |
collection |
Revista Brasileira de Cancerologia (Online) |
repository.name.fl_str_mv |
Revista Brasileira de Cancerologia (Online) - Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA) |
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rbc@inca.gov.br |
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