A novel microfluidic device capable of maintaining functional thyroid carcinoma specimens ex vivo provides a new drug screening platform
| Autor: | James England, Ramsah Cheah, Andrew Riley, Laszlo Karsai, Gordon A.G. McKenzie, Victoria L. Green, John Greenman |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Sodium-iodide symporter Cancer Research Microfluidics De-differentiation Antineoplastic Agents lcsh:RC254-282 Tissue Culture Techniques Andrology Thyroid carcinoma 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Lab-On-A-Chip Devices Radioiodine therapy Genetics Humans Medicine Thyroid Neoplasms Propidium iodide Thyroid cancer Thyroid gland business.industry Thyroid lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease 030104 developmental biology medicine.anatomical_structure Viability Oncology Terminal deoxynucleotidyl transferase chemistry Drug Resistance Neoplasm 030220 oncology & carcinogenesis Drug Screening Assays Antitumor business Ex vivo Research Article Explant culture |
| Zdroj: | BMC Cancer BMC Cancer, Vol 19, Iss 1, Pp 1-13 (2019) |
| ISSN: | 1471-2407 |
| DOI: | 10.1186/s12885-019-5465-z |
| Popis: | Background Though the management of malignancies has improved vastly in recent years, many treatment options lack the desired efficacy and fail to adequately augment patient morbidity and mortality. It is increasingly clear that patient response to therapy is unique to each individual, necessitating personalised, or ‘precision’ medical care. This demand extends to thyroid cancer; ~ 10% patients fail to respond to radioiodine treatment due to loss of phenotypic differentiation, exposing the patient to unnecessary ionising radiation, as well as delaying treatment with alternative therapies. Methods Human thyroid tissue (n = 23, malignant and benign) was live-sliced (5 mm diameter × 350-500 μm thickness) then analysed or incorporated into a microfluidic culture device for 96 h (37 °C). Successful maintenance of tissue was verified by histological (H&E), flow cytometric propidium iodide or trypan blue uptake, immunohistochemical (Ki67 detection/ BrdU incorporation) and functional analysis (thyroxine [T4] output) in addition to analysis of culture effluent for the cell death markers lactate dehydrogenase (LDH) and dead-cell protease (DCP). Apoptosis was investigated by Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Differentiation was assessed by evaluation of thyroid transcription factor (TTF1) and sodium iodide symporter (NIS) expression (western blotting). Results Maintenance of gross tissue architecture was observed. Analysis of dissociated primary thyroid cells using flow cytometry both prior to and post culture demonstrated no significant change in the proportion of viable cells. LDH and DCP release from on-chip thyroid tissue indicated that after an initial raised level of release, signifying cellular damage, detectable levels dropped markedly. A significant increase in apoptosis (p |
| Databáze: | OpenAIRE |
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