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Suppressive impact of metronomic chemotherapy using UFT and/or cyclophosphamide on mediators of breast cancer dissemination and invasion
- Source :
- UVaDOC: Repositorio Documental de la Universidad de Valladolid, Universidad de Valladolid, PLoS ONE, PLoS ONE, Vol 14, Iss 9, p e0222580 (2019), UVaDOC. Repositorio Documental de la Universidad de Valladolid, instname
- Publication Year :
- 2019
- Publisher :
- PLOS, 2019.
-
Abstract
- Producción Científica<br />Metronomic chemotherapy using the 5-FU prodrug uracil-tegafur (UFT) and cyclophosphamide (CTX) was previously shown to only modestly delay primary tumor growth, but nevertheless markedly suppressed the development of micro-metastasis in an orthotopic breast cancer xenograft model, using the metastatic variant of the MDA-MB-231 cell line, 231/LM2-4. Furthermore, a remarkable prolongation of survival, with no toxicity, was observed in a model of postsurgical advanced metastatic disease. A question that has remained unanswered is the seemingly selective anti-metastatic mechanisms of action responsible for this treatment. We assessed the in vivo effect of metronomic UFT, CTX or their combination, on vascular density, collagen deposition and c-Met (cell mediators or modulators of tumor cell invasion or dissemination) via histochemistry/immunohistochemistry of primary tumor sections. We also assessed the effect of continuous exposure to low and non-toxic doses of active drug metabolites 5-fluorouracil (5-FU), 4-hydroperoxycyclophosphamide (4-HC) or their combination, on 231/LM2-4 cell invasiveness in vitro. In the in vivo studies, a significant reduction in vascular density and p-Met[Y1003] levels was associated with UFT+CTX treatment. All treatments reduced intratumoral collagen deposition. In the in vitro studies, a significant reduction of collagen IV invasion by all treatments was observed. The 3D structures formed by 231/LM2-4 on Matrigel showed a predominantly Mass phenotype under treated conditions and Stellate phenotype in untreated cultures. Taken together, the results suggest the low-dose metronomic chemotherapy regimens tested can suppress several mediators of tumor invasiveness highlighting a new perspective for the anti-metastatic efficacy of metronomic chemotherapy.<br />Canadian Institutes of Health Research (grant 364411)
- Subjects :
- 0301 basic medicine
medicine.medical_treatment
Cell
Cancer Treatment
Mice, SCID
Pathology and Laboratory Medicine
Biochemistry
Mice
0302 clinical medicine
Breast cancer
Breast Tumors
Antineoplastic Combined Chemotherapy Protocols
Medicine and Health Sciences
Staining
Multidisciplinary
Neovascularization, Pathologic
Pharmaceutics
Invasive Tumors
Primary tumor
3. Good health
medicine.anatomical_structure
Oncology
Tegafur-uracilo
030220 oncology & carcinogenesis
Medicine
Female
Fluorouracil
Uracil-tegafur
medicine.drug
Research Article
Clinical Oncology
Cyclophosphamide
Science
Breast Neoplasms
Ciclofosfamida
Research and Analysis Methods
03 medical and health sciences
Cancer Chemotherapy
Necrosis
Signs and Symptoms
Drug Therapy
Cáncer de mama
In vivo
Diagnostic Medicine
Cell Line, Tumor
Breast Cancer
medicine
Animals
Humans
Chemotherapy
Neoplasm Invasiveness
Uracil
Cytoplasmic Staining
Tegafur
Matrigel
business.industry
Biology and Life Sciences
Proteins
Cancers and Neoplasms
medicine.disease
Metronomic Chemotherapy
Xenograft Model Antitumor Assays
Nuclear Staining
030104 developmental biology
Specimen Preparation and Treatment
Cancer research
Quimioterapia
Clinical Medicine
business
Collagens
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- UVaDOC: Repositorio Documental de la Universidad de Valladolid, Universidad de Valladolid, PLoS ONE, PLoS ONE, Vol 14, Iss 9, p e0222580 (2019), UVaDOC. Repositorio Documental de la Universidad de Valladolid, instname
- Accession number :
- edsair.doi.dedup.....9b14acdee354daf738a3bb4b99b348a8