Molecular iodine/doxorubicin neoadjuvant treatment impair invasive capacity and attenuate side effect in canine mammary cancer
Abstract Background Mammary cancer has a high incidence in canines and is an excellent model of spontaneous carcinogenesis. Molecular iodine (I2) exerts antineoplastic effects on different cancer cells activating re-differentiation pathways. In co-administration with anthracyclines, I2 impairs chemo...
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| Format: | Article |
| Language: | English |
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BMC
2018-03-01
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| Series: | BMC Veterinary Research |
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| Online Access: | http://link.springer.com/article/10.1186/s12917-018-1411-6 |
| _version_ | 1818574537376137216 |
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| author | Xóchitl Zambrano-Estrada Brianda Landaverde-Quiroz Andrés A. Dueñas-Bocanegra Marco A. De Paz-Campos Gerardo Hernández-Alberto Benjamín Solorio-Perusquia Manuel Trejo-Mandujano Laura Pérez-Guerrero Evangelina Delgado-González Brenda Anguiano Carmen Aceves |
| author_facet | Xóchitl Zambrano-Estrada Brianda Landaverde-Quiroz Andrés A. Dueñas-Bocanegra Marco A. De Paz-Campos Gerardo Hernández-Alberto Benjamín Solorio-Perusquia Manuel Trejo-Mandujano Laura Pérez-Guerrero Evangelina Delgado-González Brenda Anguiano Carmen Aceves |
| author_sort | Xóchitl Zambrano-Estrada |
| collection | DOAJ |
| description | Abstract Background Mammary cancer has a high incidence in canines and is an excellent model of spontaneous carcinogenesis. Molecular iodine (I2) exerts antineoplastic effects on different cancer cells activating re-differentiation pathways. In co-administration with anthracyclines, I2 impairs chemoresistance installation and prevents the severity of side effects generated by these antineoplastic drugs. This study is a random and double-blind protocol that analyzes the impact of I2 (10 mg/day) in two administration schemes of Doxorubicin (DOX; 30 mg/m2) in 27 canine patients with cancer of the mammary gland. The standard scheme (sDOX) includes four cycles of DOX administered intravenously for 20 min every 21 days, while the modified scheme (mDOX) consists of more frequent chemotherapy (four cycles every 15 days) with slow infusion (60 min). In both schemes, I2 or placebo (colored water) was supplemented daily throughout the treatment. Results mDOX attenuated the severity of adverse events (VCOG-CTCAE) in comparison with the sDOX group. The overall tumor response rate (RECIST criteria) for all dogs was 18% (interval of reduction 48–125%), and no significant difference was found between groups. I2 supplementation enhances the antineoplastic effect in mDOX, exhibiting a significant decrease in the tumor epithelial fraction, diminished expression of chemoresistance (MDR1 and Survivin) and invasion (uPA) markers and enhanced expression of the differentiation factor known as peroxisome proliferator-activated receptors type gamma (PPARγ). Significant tumor lymphocytic infiltration was also observed in both I2-supplemented groups. The ten-month survival analysis showed that the entire I2 supplementation (before and after surgery) induced 67–73% of disease-free survival, whereas supplementation in the last period (only after surgery) produced 50% in both schemes. Conclusions The mDOX+I2 scheme improves the therapeutic outcome, diminishes the invasive capacity, attenuates the adverse events and increases disease-free survival. These data led us to propose mDOX+I2 as an effective treatment for canine mammary cancer. |
| first_indexed | 2024-12-15T00:27:57Z |
| format | Article |
| id | doaj.art-9b3a829928f04723abf54f8d379d2388 |
| institution | Directory Open Access Journal |
| issn | 1746-6148 |
| language | English |
| last_indexed | 2024-12-15T00:27:57Z |
| publishDate | 2018-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Veterinary Research |
| spelling | doaj.art-9b3a829928f04723abf54f8d379d23882022-12-21T22:42:07ZengBMCBMC Veterinary Research1746-61482018-03-0114111410.1186/s12917-018-1411-6Molecular iodine/doxorubicin neoadjuvant treatment impair invasive capacity and attenuate side effect in canine mammary cancerXóchitl Zambrano-Estrada0Brianda Landaverde-Quiroz1Andrés A. Dueñas-Bocanegra2Marco A. De Paz-Campos3Gerardo Hernández-Alberto4Benjamín Solorio-Perusquia5Manuel Trejo-Mandujano6Laura Pérez-Guerrero7Evangelina Delgado-González8Brenda Anguiano9Carmen Aceves10Instituto de Neurobiología, Universidad Nacional Autónoma de MéxicoFacultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de MéxicoFacultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de MéxicoFacultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de MéxicoFacultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de MéxicoFacultad de Ciencias Naturales, Universidad Autónoma de QuerétaroFacultad de Ciencias Naturales, Universidad Autónoma de QuerétaroFacultad de Ciencias Naturales, Universidad Autónoma de QuerétaroInstituto de Neurobiología, Universidad Nacional Autónoma de MéxicoInstituto de Neurobiología, Universidad Nacional Autónoma de MéxicoInstituto de Neurobiología, Universidad Nacional Autónoma de MéxicoAbstract Background Mammary cancer has a high incidence in canines and is an excellent model of spontaneous carcinogenesis. Molecular iodine (I2) exerts antineoplastic effects on different cancer cells activating re-differentiation pathways. In co-administration with anthracyclines, I2 impairs chemoresistance installation and prevents the severity of side effects generated by these antineoplastic drugs. This study is a random and double-blind protocol that analyzes the impact of I2 (10 mg/day) in two administration schemes of Doxorubicin (DOX; 30 mg/m2) in 27 canine patients with cancer of the mammary gland. The standard scheme (sDOX) includes four cycles of DOX administered intravenously for 20 min every 21 days, while the modified scheme (mDOX) consists of more frequent chemotherapy (four cycles every 15 days) with slow infusion (60 min). In both schemes, I2 or placebo (colored water) was supplemented daily throughout the treatment. Results mDOX attenuated the severity of adverse events (VCOG-CTCAE) in comparison with the sDOX group. The overall tumor response rate (RECIST criteria) for all dogs was 18% (interval of reduction 48–125%), and no significant difference was found between groups. I2 supplementation enhances the antineoplastic effect in mDOX, exhibiting a significant decrease in the tumor epithelial fraction, diminished expression of chemoresistance (MDR1 and Survivin) and invasion (uPA) markers and enhanced expression of the differentiation factor known as peroxisome proliferator-activated receptors type gamma (PPARγ). Significant tumor lymphocytic infiltration was also observed in both I2-supplemented groups. The ten-month survival analysis showed that the entire I2 supplementation (before and after surgery) induced 67–73% of disease-free survival, whereas supplementation in the last period (only after surgery) produced 50% in both schemes. Conclusions The mDOX+I2 scheme improves the therapeutic outcome, diminishes the invasive capacity, attenuates the adverse events and increases disease-free survival. These data led us to propose mDOX+I2 as an effective treatment for canine mammary cancer.http://link.springer.com/article/10.1186/s12917-018-1411-6Canine mammary cancerMolecular iodineNeoadjuvant chemotherapyDoxorubicinAnimal welfare |
| spellingShingle | Xóchitl Zambrano-Estrada Brianda Landaverde-Quiroz Andrés A. Dueñas-Bocanegra Marco A. De Paz-Campos Gerardo Hernández-Alberto Benjamín Solorio-Perusquia Manuel Trejo-Mandujano Laura Pérez-Guerrero Evangelina Delgado-González Brenda Anguiano Carmen Aceves Molecular iodine/doxorubicin neoadjuvant treatment impair invasive capacity and attenuate side effect in canine mammary cancer BMC Veterinary Research Canine mammary cancer Molecular iodine Neoadjuvant chemotherapy Doxorubicin Animal welfare |
| title | Molecular iodine/doxorubicin neoadjuvant treatment impair invasive capacity and attenuate side effect in canine mammary cancer |
| title_full | Molecular iodine/doxorubicin neoadjuvant treatment impair invasive capacity and attenuate side effect in canine mammary cancer |
| title_fullStr | Molecular iodine/doxorubicin neoadjuvant treatment impair invasive capacity and attenuate side effect in canine mammary cancer |
| title_full_unstemmed | Molecular iodine/doxorubicin neoadjuvant treatment impair invasive capacity and attenuate side effect in canine mammary cancer |
| title_short | Molecular iodine/doxorubicin neoadjuvant treatment impair invasive capacity and attenuate side effect in canine mammary cancer |
| title_sort | molecular iodine doxorubicin neoadjuvant treatment impair invasive capacity and attenuate side effect in canine mammary cancer |
| topic | Canine mammary cancer Molecular iodine Neoadjuvant chemotherapy Doxorubicin Animal welfare |
| url | http://link.springer.com/article/10.1186/s12917-018-1411-6 |
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