Research Progress on Pathogenic Factors of Breast Cancer Combined with Thyroid Cancer / 肿瘤防治研究

Thyroid cancer and breast cancer are two of the most common malignant tumors in women. Concurrent tumors of the thyroid and breast are relatively rare in clinical practice; however, the incidence of such dual malignancies has recently increased. Researches conducted in the past mainly focused on the possible increase in the incidence of contralateral breast cancer, while the increased risk of synchronized thyroid cancer in women with breast cancer has attracted widespread attention recently. The specific mechanism has not been fully understood. This article reviews the pathogenic factors between these two diseases, and evaluates the etiological role of these factors in these double primary cancers, so as to provide a better basis for clinical practice.

Expression of sodium iodide symporter mRNA and its clinical significance in differentiated thyroid carcinoma / 西安交通大学学报(医学版)

Objective To investigate the expression of sodium iodide symporter (NIS ) mRNA in differentiated thyroid Carcinoma (DTC)and further explore its value in clinical diagnosis and therapy of DTC. Methods The expression of NIS mRNA was detected and analyzed in 21 nodular goiter and 45 cases of DTC (including 35 cases of papillary thyroid carcinoma and 10 cases of follicular thyroid carcinoma)by using real-time fluorescent quantitative reverse transcription polymerase chain reaction (real-time RT-PCR).Results Compared with that in nodular goiter,the mRNA expression of NIS in DTC tissue was significantly decreased (P < 0.05 ). Moreover,the mRNA expression of NIS was significantly correlated with lymph node metastasis and AJCC stage, respectively.The expression of NIS mRNA in DTC with lymph node metastasis was significantly decreased compared with that in DTC without lymph node metastasis (P <0.05).In addition,the expression of NIS mRNA in Ⅱ-Ⅳstage DTC was significantly decreased compared with that in Ⅰ - Ⅱ stage DTC (P < 0.05 ).Conclusion Differential expression of NIS can provide evidence for individual 1 3 1 I therapy for DTC.

Effects of fluoride on the expression of functional genes related with the metabolism of thyroid hormone in FRTL cells / 中国兽医学报

To investigate the effects of fluoride on the expression of thyroglobulin (TG),thyroid peroxidase(TPO),odium iodide symporter (NIS) genes in FRTL cells,FRTL cells cultured in vitro were treated in logarithmic phase with sodium fluoride at different concentration of 20.0,10.0,5.0,2.5,1.25 mg/L,respectively.After 72 h,the cells were collected and semi-quantitative RT-PCR for TG mRNA,TPO mRNA and NIS mRNA and β-actin was performed.The results showed that compared with the control cells,the expression levels of TG gene in FRTL cells treated with lower concentration of sodium fluoride increased compensatively,but decreased significantly (P<0.05) with higher concentration(>5.0 mg/L);the RT-PCR products of TPO and NIS in FRTL cells treated with all concentration of sodium fluoride reduced,some of them were significant (P<0.05).It is concluded that fluoride can reduce the expression of TG,TPO,NIS genes in thyroid cells,conseguently cause dysfunction" of thyroid in uptaking and unilizing of iodine,and synthesizing,storing,secreting of thyroid hormones.

Comparison of Na+/I- Symporter Expression Rate in Malignant and Benign Thyroid Diseases: Immunohistochemical Study / 핵의학분자영상

PURPOSE: Previous studies have not showed consistent results for the level of expression of sodium/iodide symporter (NIS) in thyroid diseases, especially malignant tumor. We undertook this study to evaluate the distribution of NIS expression in malignant thyroid diseases and compare with that in benign thyroid disease. MATERIALS AND METHODS: Total patients were 119 cases (Men 15, 48+/-13 yrs). Total number of samples were 205 pieces. In malignant thyroid disease, there were 153 samples: 90 in papillary carcinoma, 4 in follicular carcinoma, 2 in medullary carcinoma and 57 in metastatic lymph node. In benign thyroid disease, there were 52 samples: 36 in goiter/cyst, 11 in thyroiditis and 5 in follicular adenoma. Using immunohistochemical methods, we probed 205 samples with monoclonal anti-NIS Ab. Grading of staining was scored as 0 (negative or absent), 1 (weakly positive), 2 (moderately positive) or 3 (strongly positive). Expression rate (ER) of NIS positivity in individual disease entity was expressed as percentage of total number divided by number in 2 plus 3 grade. RESULTS: ERs of malignant thyroid diseases were 63% in papillary carcinoma, 81% in metastatic lymph node, 71% in follicular carcinoma and 100% in medullary carcinoma. ERs of benign thyroid disease were 53% in goiter/cyst, 64% in thyroiditis and 40% in follicular adenoma. ER of malignant thyroid diseases was higher than benign thyroid diseases (71% vs 54%). Grading of NIS expression in papillary carcinoma or goiter/cyst was heterogeneously distributed in considerable cases. Normal tissue also showed heterogeneous distribution of NIS expression, which was not correlated with that of primary lesion. CONCLUSION: In papillary thyroid carcinoma, distribution of NIS expression was heterogeneous and increased, and not different compared with that of benign thyroid disease.

Effect of LiCl on Iodine Kinetics in Thyroid Cancer Cell Lines Transduced by Recombinant Adenovirus Containing Sodium Iodide Symporter(NIS) Gene / 대한내분비학회지

BACKGROUND: Lithium is known to increase the retention of iodide in the thyroid gland, or in well differentiated thyroid cancer tissue. The effects of lithium on the function of the sodium iodide symporter (NIS) protein, especially when the lithium is increased in the retention of iodide in NIS-producing cells, the effect of lithium, on the kinetics of undifferentiated thyroid cancer cells transduced by a recombinant adenovirus containing the NIS gene, were checked. METHOD: Human NIS cDNA was inserted into pAxCAwt, a recombinant adenoviral cosmid vector, where the E1 & E2 genes have been deleted, making Rad-hNIS, which was propagated in 293 cells. The iodide uptake was evaluated by the 125I uptake assay in the undifferentiated thyroid cancer cells, ARO, FRO and NPA, following the infection with Rad-hNIS (1 or 10 MOI) in the presence, or absence, of LiCl at optimized concentrations. The iodide efflux was evaluated by the 125I efflux assay, for 1 hour, in the same cells expressing the NIS in the presence, or absence, of LiCl. Similar experiments were performed in the normal thyroid cell line, FRTL-5, cultured in 6H5 media. RESULTS: LiCl, at concentrations over 1.0mM, caused a significant decrease in the cell viability, as evaluated by trypan blue dye exclusion, in a dose dependent manner. When infected with Rad-hNIS, the iodide uptake was not affected by the LiCl in the ARO or NPA cells. However, LiCl(0.1and 1.0mM) increased the iodide uptake by 50 to 100%(vs. control) in the Rad-hNIS transduced FRO cells. In the Rad-hNIS transduced FRO cells, the iodide was released rapidly from the cells, with only 20.7+/-4.8% of the iodide uptake remaining at 1 hour, which was no different in the presence of LiCl (24.5+/-7.9%). The iodide efflux was not affected by the LiCl in the FRTL-5 cells cultured in the presence of TSH. CONCLUSION: These results suggest that the lithium-induced iodide retention in the thyroid gland, or in well differentiated thyroid cancer tissue, is not caused by the effect of the lithium on the NIS function, or the function of proteins or channels, involved in iodide transport via cell membranes. Although the iodide uptake can be markedly increased by the expression of NIS, with the transduction of Rad-hNIS, in undifferentiated thyroid cancer cells, the iodide taken up is rapidly released from the cells. A method for inducing the iodide retention in the cell should be elucidated in order to render the NIS gene therapy effective.

Factors Associated with Expression of Sodium/iodide Symporter (NIS) mRNA in Breast Cancer / 한국유방암학회지

PURPOSE: Cells of mammary gland as well as breast cancer uptake iodide through sodium/iodide symporter (NIS). The pathophysiologic importance of NIS is not evaluated well. The purpose of this study is to find relationships between the expression of NIS and other findings of breast cancer including ER, PR, C-erbB2, topoisomerase IIa, p53, and histologic grade of breast cancer. METHODS: Fresh frozen specimens from 21 female breast cancer patients (mean age 50 13 years) with breast cancer were examined by RT-PCR for NIS mRNA. Immunohistochemical staining for ER, PR, C-erb B2, topoisomerase IIa and p53. Staging and degree of differentiation of cancer cells were also performed to evaluate the biological behavior of breast cancer. RESULTS: NIS mRNA was expressed in 90% of the evaluated breast cancer tissues. The mean semiquantitative value of NIS mRNA in PR positive group was 2.02+/-0.35, which was higher than that of PR negative group (1.11+/-0.18; P=0.001). ER positive group showed higher value of NIS mRNA (2.02+/-0.35) than ER negative group (1.19+/-0.63; P=0.002). In addition, NIS mRNA values was significantly different according to differentiation of cancer cells (well differentiated type, 2.20+/-0.37 vs. less differentiated type, 1.39+/-0.63, P=0.01). However, there was no significant association between NIS mRNA levels and the other biologic characteriscs such as C-erb B2, topoisomerase IIa, and p53. CONCLUSION: The results showed that the expression of NIS in breast cancer may be associated with the presence of PR and ER as well as the degree of differentiation of breast cancer cells.