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The response of phyllodes tumor of the breast to anticancer therapy: An in vitro and ex vivo study.
Urbaniak, Alicja; Jousheghany, Fariba; Yuan, Youzhong; Piña-Oviedo, Sergio; Huczynski, Adam; Delgado, Magdalena; Kieber-Emmons, Thomas; Monzavi-Karbassi, Behjatolah; Chambers, Timothy C.
Afiliação
  • Urbaniak A; Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • Jousheghany F; Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • Yuan Y; Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • Piña-Oviedo S; Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • Huczynski A; Department of Bioorganic Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznan, Poland.
  • Delgado M; Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • Kieber-Emmons T; Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • Monzavi-Karbassi B; Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • Chambers TC; Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Oncol Lett ; 18(5): 5097-5106, 2019 Nov.
Article em En | MEDLINE | ID: mdl-31612021
Phyllodes tumors of the breast (PTB) are uncommon stromal-epithelial neoplasms, with the main recommended treatment being surgical removal. However, even with adequate resection, the risk of recurrence in the malignant form remains as high as 40%, and there is no recognized consensus on the most effective drugs for PTB. In the present study, an ex vivo model of malignant phyllodes and derived primary cell cultures were used to evaluate the effectiveness of a panel of different drugs, including the Bcl-2/Bcl-xL inhibitor ABT-263, salinomycin (SAL), doxorubicin (DOX), paclitaxel (TAX), vincristine (VCR), colchicine (COL) and cisplatin (CIS). ABT-263, SAL and DOX were highly effective towards phyllodes spindle cells when assessed in the ex vivo model, contributing to ~98% tumor cell death. Furthermore, ABT-263 was highly selective for tumor cells in this system, and exhibited little toxic effect on adjacent normal epithelial cells. Furthermore, consistent with findings in the ex vivo model, ABT-263 was significantly less toxic towards MCF 10A non-tumorigenic breast epithelial cells compared with SAL and DOX. A conditional reprogramming strategy was subsequently used, involving Rho kinase inhibition, to successfully generate primary phyllodes tumor cells that could be cultured for several passages. The primary cells were sensitive to DOX with an IC50 of 0.40±0.07 µM in a standard viability assay and the preliminary results were obtained indicating sensitivity to ABT-263 and SAL. The present study demonstrated the feasibility of using explants and primary cells for drug discovery, selectively targeting PTB cells.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2019 Tipo de documento: Article