Cyclophosphamide bimodal effects in antineoplasic therapy

Detalhes bibliográficos
Autor(a) principal: Matar, Pablo
Data de Publicação: 2022
Outros Autores: Scharovsky, O. Graciela
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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spelling 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
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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
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv 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)
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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)
repository.mail.fl_str_mv rbc@inca.gov.br
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