Molecular iodine/doxorubicin neoadjuvant treatment impair invasive capacity and attenuate side effect in canine mammary cancer
Open Access
- 12 March 2018
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Veterinary Research
- Vol. 14 (1), 87
- https://doi.org/10.1186/s12917-018-1411-6
Abstract
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. 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. 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.Keywords
Funding Information
- PAPIIT-UNAM (200813, 201516, 209717)
- CONACyT (235961, 356685)
This publication has 47 references indexed in Scilit:
- The Extrathyronine Actions of Iodine as Antioxidant, Apoptotic, and Differentiation Factor in Various TissuesThyroid®, 2013
- Use of potassium iodide in Dermatology: updates on an old drugAnais Brasileiros de Dermatologia, 2013
- Iodine and doxorubicin, a good combination for mammary cancer treatment: antineoplastic adjuvancy, chemoresistance inhibition, and cardioprotectionMolecular Cancer, 2013
- Prospective trial of metronomic chlorambucil chemotherapy in dogs with naturally occurring cancerVeterinary and Comparative Oncology, 2011
- Assessment of Japanese iodine intake based on seaweed consumption in Japan: A literature-based analysisThyroid Research, 2011
- Peroxisome Proliferator-Activated Receptor-γ Activation Inhibits Tumor Metastasis by Antagonizing Smad3-Mediated Epithelial-Mesenchymal TransitionMolecular Cancer Therapeutics, 2010
- A complex between 6-iodolactone and the peroxisome proliferator-activated receptor type gamma may mediate the antineoplasic effect of iodine in mammary cancerProstaglandins & Other Lipid Mediators, 2009
- New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)European Journal of Cancer, 2009
- Antineoplastic effect of iodine in mammary cancer: participation of 6-iodolactone (6-IL) and peroxisome proliferator-activated receptors (PPAR)Molecular Cancer, 2009
- PPARgamma agonists can be expected to potentiate the efficacy of metronomic chemotherapy through CD36 up-regulationMedical Hypotheses, 2008