| Galectin-3 targeted therapy with a small molecule inhibitor activates apoptosis and enhances both chemosensitivity and radiosensitivity in papillary thyroid cancer. | |
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MedLine Citation:
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PMID: 19825987 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although most patients with papillary thyroid cancer (PTC) have favorable outcomes, some have advanced PTC that is refractory to external beam radiation and systemic chemotherapy. Galectin-3 (Gal-3) is a beta-galactoside-binding protein with antiapoptotic activity that is consistently overexpressed in PTC. The purpose of this study is to determine if Gal-3 inhibition promotes apoptosis, chemosensitivity, and radiosensitivity in PTC. PTC cell lines (8505-C and TPC-1) and human ex vivo PTC were treated with a highly specific small molecule inhibitor of Gal-3 (Td131_1). Apoptotic activity was determined by flow cytometric analysis as well as caspase-3 and PARP cleavage. The minimum inhibitory concentrations of Td131_1 and doxorubicin were determined, and their combined effects were measured to test for synergistic activity. The effects of Td131_1 on radiosensitivity were determined by a clonogenic assay. Td131_1 promoted apoptosis, improved radiosensitivity, and synergistically enhanced chemosensitivity to doxorubicin in PTC cell lines. In PTC ex vivo, Td131_1 treatment alone induced the cleavage of caspase-3 and PARP. Td131_1 and doxorubicin together activated apoptosis in PTC ex vivo to a greater degree than their combined individual effects. Td131_1 activated apoptosis and had synergistic activity with doxorubicin in PTC. We conclude that Gal-3 targeted therapy is a promising therapeutic strategy for advanced PTC that is refractory to surgery and radioactive iodine therapy. |
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Authors:
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Chi-Iou Lin; Edward E Whang; David B Donner; Xiaofeng Jiang; Brendan D Price; Adelaide M Carothers; Tamara Delaine; Hakon Leffler; Ulf J Nilsson; Vania Nose; Francis D Moore; Daniel T Ruan |
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Publication Detail:
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Type: Journal Article Date: 2009-10-13 |
Journal Detail:
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Title: Molecular cancer research : MCR Volume: 7 ISSN: 1557-3125 ISO Abbreviation: Mol. Cancer Res. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-10-27 Completed Date: 2010-02-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101150042 Medline TA: Mol Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 1655-62 Citation Subset: IM |
Affiliation:
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Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Combined Chemotherapy Protocols / therapeutic use* Apoptosis / drug effects, physiology Carcinoma, Papillary / drug therapy*, metabolism, radiotherapy Caspase 3 / drug effects, metabolism Cell Line, Tumor Dose-Response Relationship, Drug Doxorubicin / therapeutic use Drug Resistance, Neoplasm / drug effects, physiology Drug Synergism Flow Cytometry Galectin 3 / antagonists & inhibitors*, metabolism Humans Molecular Structure Poly(ADP-ribose) Polymerases / drug effects, metabolism Radiation Tolerance / drug effects, physiology Radiation-Sensitizing Agents / chemical synthesis, therapeutic use* Rats Thiogalactosides / chemical synthesis, therapeutic use Thioglycosides / chemical synthesis, therapeutic use* Thyroid Neoplasms / drug therapy*, metabolism, radiotherapy |
| Chemical | |
Reg. No./Substance:
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0/Galectin 3; 0/Radiation-Sensitizing Agents; 0/Td131-1 compound; 0/Thiogalactosides; 0/Thioglycosides; 23214-92-8/Doxorubicin; EC 2.4.2.30/PARP1 protein, human; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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