The influence of l -triiodothyronine, l -thyroxine, estradiol-17β, the luteinizing-hormone-releasing hormone, the epidermal growth factor and gastrin on cell proliferation in organ cultures of 35 benign and 13 malignant human thyroid tumors

Nagy, Nathalie; Camby, Isabelle; Decaestecker, Christine; Chaboteaux, Carole; Gras, Thierry; Darro, Francis; Rocmans, Pierre Arthur; Kiss, Róbert; Salmon, Isabelle

doi:10.1007/s004320050287

Cited by 7 publications

(4 citation statements)

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“…These two studies suggest a preneoplastic nature of microfollicular adenomas. We reached the same conclusions by the identification of distinct glycan epitopes in thyroid adenomas, as opposed to thyroid carcinomas (22), and by the analysis of the influence of various growth factors and hormones on the cell proliferation of human thyroid tumors (51). These data, with conspicuously very different experimental designs, clearly suggest the preneoplastic nature of a set of thyroid adenomas that exhibit microfollicular histopathological characteristics.…”

Section: Discussionsupporting

confidence: 56%

Changes in Galectin-7 and Cytokeratin-19 Expression during the Progression of Malignancy in Thyroid Tumors: Diagnostic and Biological Implications

et al. 2002

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Galectin-7 is associated with p53-dependent onset of apoptosis and proliferation control/differentiation in keratinocyte development. It is also upregulated in chemically induced rat mammary carcinogenesis. Because the levels of expression of galectin-7 have never been investigated in thyroid tumors (in contrast to those of galectin-1 and -3 associated with malignancy), we initiated analysis of the expression of galectin-7 in benign and malignant thyroid lesions together with that of cytokeratin-19 (CK19), a marker already demonstrated to be useful in diagnosing this kind of lesion. The immunohistochemical expression levels were quantitatively determined by means of computerassisted microscopy on a series of 84 thyroid lesions including 10 multinodular goiters, 32 adenomas, and 42 carcinomas. Our data clearly indicate a marked down-regulation of galectin-7 expression in a large proportion of adenomas (including the normomacrofollicular, microfollicular, and trabecular variants) if compared with carcinomas. In accordance with results of previous studies, a marked up-regulation of CK19 expression was observed in the thyroid carcinomas, and this contrasted in particular with the low CK19 expression observed in the microfollicular adenomas. Of importance for diagnostic implications, the combination of these two markers enabled our series of microfollicular adenomas (characterized by low galectin-7 and CK19 expression) to be efficiently distinguished from the encapsulated follicular variant of papillary thyroid carcinomas (high galectin-7 and CK19 expression).

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Section: Discussionsupporting

confidence: 56%

Changes in Galectin-7 and Cytokeratin-19 Expression during the Progression of Malignancy in Thyroid Tumors: Diagnostic and Biological Implications

et al. 2002

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“…The microfluidic system described herein uses precision cut tissue slices (PCTS) which maintain the multicellular 3D architecture of the thyroid tissue essential for intercellular communication, which is not well recapitulated in standard in vitro systems. Two previous studies have employed static culture of thyroid tissue explants: Russo et al [16] investigated apoptosis subsequent to 131 I treatment in 1mm 3 tissue fragments, whereas Nagy et al [17] examined the effect of various hormones and cytokines on the proliferation of 2mm 3 thyroid fragments. The results from these studies demonstrated that thyroid tissue cultured ex vivo can respond to external stimuli, however clinical utility was not assessed.…”

Section: Introductionmentioning

confidence: 99%

A novel microfluidic device capable of maintaining functional thyroid carcinoma specimens ex vivo provides a new drug screening platform

et al. 2019

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BackgroundThough 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.MethodsHuman 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).ResultsMaintenance 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 < 0.01) was observed after tissue was perfused with etoposide and JNK inhibitor, but not in control tissue incubated for the same time period. No significant difference in Ki-67 positivity or TTF1/NIS expression was detected between fresh and post-culture thyroid tissue samples, moreover BrdU positive nuclei indicated on-chip cellular proliferation. Cultured thyroid explants were functionally viable as determined by production of T4 throughout the culture period.ConclusionsThe described microfluidic platform can maintain the viability of thyroid tissue slices ex vivo for a minimum of four days, providing a platform for the assessment of thyroid tissue radioiodine sensitivity/adjuvant therapies in real time.

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“…The microfluidic system described herein uses precision cut tissue slices (PCTS) which maintain the multicellular 3D architecture of the thyroid tissue essential for intercellular communication, which is not well recapitulated in standard in vitro systems. Two previous studies have employed static culture of thyroid tissue explants: Russo et al (16) investigated apoptosis subsequent to 131 I treatment in 1mm 3 tissue fragments, whereas Nagy et al (17) examined the effect of various hormones and cytokines on the proliferation of 2mm 3 thyroid fragments. The results from these studies demonstrated that thyroid tissue cultured ex vivo can respond to external stimuli, however clinical utility was not assessed.…”

Section: Introductionmentioning

confidence: 99%

The effect of radioiodine treatment on the diseased thyroid gland

Riley

McKenzie

Green

et al. 2019

International Journal of Radiation Biology

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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 (5mm diameter x 350-500µm thickness) then analysed or incorporated into a microfluidic culture device for 96hr (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<0.01) was observed after tissue was perfused with etoposide and JNK inhibitor, but not in control tissue incubated for the same time period. No significant difference in Ki-67 positivity or TTF1/NIS expression was detected between fresh and post-culture thyroid tissue samples, moreover BrdU positive nuclei indicated onchip cellular proliferation. Cultured thyroid explants were functionally viable as determined by production of T4 throughout the culture period. Conclusions:The described microfluidic platform can maintain the viability of thyroid tissue slices ex vivo for a minimum of four days, providing a platform for the assessment of thyroid tissue radioiodine sensitivity/adjuvant therapies in real time.

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The influence of l -triiodothyronine, l -thyroxine, estradiol-17β, the luteinizing-hormone-releasing hormone, the epidermal growth factor and gastrin on cell proliferation in organ cultures of 35 benign and 13 malignant human thyroid tumors

Cited by 7 publications

References 54 publications

Changes in Galectin-7 and Cytokeratin-19 Expression during the Progression of Malignancy in Thyroid Tumors: Diagnostic and Biological Implications

Changes in Galectin-7 and Cytokeratin-19 Expression during the Progression of Malignancy in Thyroid Tumors: Diagnostic and Biological Implications

A novel microfluidic device capable of maintaining functional thyroid carcinoma specimens ex vivo provides a new drug screening platform

The effect of radioiodine treatment on the diseased thyroid gland

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