Radiation-enhanced therapeutic targeting of galectin-1 enriched malignant stroma in triple negative breast cancer
| Autor: | Elden P. Swindell, Heidi L. Weiss, B. Mark Evers, Amar Jyoti, Meenakshi Upreti, Jonathan Feddock, Ryan Chan, Thomas V. O'Halloran, Pallavi Sethi, Sara E. Johnson, Dana Napier |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology Galectin 1 medicine.medical_treatment Triple Negative Breast Neoplasms Arsenicals Metastasis Mice 0302 clinical medicine Arsenic Trioxide Antineoplastic Combined Chemotherapy Protocols tumor tissue analog (TTA) Molecular Targeted Therapy Neoplasm Metastasis Pharmaceutical sciences Cells Cultured Triple-negative breast cancer stromal-targeting Oxides Chemoradiotherapy Middle Aged 3. Good health 030220 oncology & carcinogenesis Female Research Paper Adult medicine.medical_specialty Stromal cell Mice Nude Young Adult 03 medical and health sciences Cell Line Tumor Internal medicine Human Umbilical Vein Endothelial Cells medicine Animals Humans galectin-1 TNBC tumor model Chemotherapy business.industry Cancer Mesenchymal Stem Cells medicine.disease Xenograft Model Antitumor Assays Clinical trial Regimen 030104 developmental biology triple negative breast cancer Immunology Cisplatin business |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.9490 |
| Popis: | // Meenakshi Upreti 1, 3 , Amar Jyoti 1, 3 , Sara E. Johnson 2 , Elden P. Swindell 4 , Dana Napier 3 , Pallavi Sethi 1, 3 , Ryan Chan 1 , Jonathan M. Feddock 5 , Heidi L. Weiss 3 , Thomas V. O’Halloran 4 , B. Mark Evers 3, 6 1 Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, USA 2 Markey Cancer Center, University of Kentucky, Lexington, KY, USA 3 Department of Pathology, University of Kentucky, Lexington,KY, USA 4 Department of Chemistry, Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, USA 5 Department of Radiation Medicine, University of Kentucky Chandler Hospital, Lexington, KY, USA 6 Department of Surgery, University of Kentucky, Lexington, KY, USA Correspondence to: Meenakshi Upreti, email: m.upreti@uky.edu Keywords: galectin-1, triple negative breast cancer, stromal-targeting, TNBC tumor model, tumor tissue analog (TTA) Received: February 18, 2016 Accepted: May 04, 2016 Published: May 19, 2016 ABSTRACT Currently there are no FDA approved targeted therapies for Triple Negative Breast Cancer (TNBC). Ongoing clinical trials for TNBC have focused primarily on targeting the epithelial cancer cells. However, targeted delivery of cytotoxic payloads to the non-transformed tumor associated-endothelium can prove to be an alternate approach that is currently unexplored. The present study is supported by recent findings on elevated expression of stromal galectin-1 in clinical samples of TNBC and our ongoing findings on stromal targeting of radiation induced galectin-1 by the anginex-conjugated arsenic-cisplatin loaded liposomes using a novel murine tumor model. We demonstrate inhibition of tumor growth and metastasis in response to the multimodal nanotherapeutic strategy using a TNBC model with orthotopic tumors originating from 3D tumor tissue analogs (TTA) comprised of tumor cells, endothelial cells and fibroblasts. The ‘rigorous’ combined treatment regimen of radiation and targeted liposomes is also shown to be well tolerated. More importantly, the results presented provide a means to exploit clinically relevant radiation dose for concurrent receptor mediated enhanced delivery of chemotherapy while limiting overall toxicity. The proposed study is significant as it falls in line with developing combinatorial therapeutic approaches for stroma-directed tumor targeting using tumor models that have an appropriate representation of the TNBC microenvironment. |
| Databáze: | OpenAIRE |
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