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Introducción: La aplicación de actividades fijas en el tratamiento del hipertiroidismo con I131 (yoduro de sodio, conocido también como radioyodo), es el método más usado en nuestro país, a pesar de la individualidad morfo-funcional que caracteriza esta afección. Sin embargo, no existe aún, un consenso internacional sobre la dosis más conveniente para cada caso, y por ende, los resultados no siempre son los deseados. Objetivo: Evaluar la aplicabilidad de varios métodos de cálculo de dosis paciente-específica para el tratamiento de hipertiroidismo con yoduro de sodio. Métodos: Se realizó un análisis de los resultados de varios métodos de cálculo de dosis recomendados internacionalmente a partir de la actividad fija prescrita en 10 pacientes, con el empleo de tecnologías y herramientas ya desarrolladas y disponibles en el país. Se evaluó la variabilidad inter-especialista y su impacto en la dosis planificada para el tratamiento. Resultados: El uso de la información incompleta de la biodistribución y farmacocinética del paciente produjo diferencias entre -42 por ciento y 37 por ciento de las dosis para el mismo paciente. El resultado de la comparación del método de cálculo recomendado por la Sociedad Europea de Medicina Nuclear, manejando la masa por gammagrafía-2D / 3D y por ultrasonido, arrojó diferencias no significativas entre sí. La variabilidad inter-especialista de las actividades prescrita mostró diferencias significativas, que arrojan sobre el mismo paciente, discrepancias entre 44Gy y 243Gy de las dosis terapéuticas a recibir, situación que puede comprometer el éxito del tratamiento y producir efectos secundarios no deseados. Conclusiones: Las técnicas dosimétricas paciente-específicas se pueden implementar satisfactoriamente en nuestro país. Las diferencias numéricas encontradas, especialmente la variabilidad inter-especialista, demuestran la no estandarización terapéutica, lo que apoya el uso de la farmacocinética paciente-específica pre terapéutica y la masa por gammagrafía-3D para planificar el tratamiento siempre que sean posible(AU)
Introduction: Despite of its typical morpho-functional individuality, fixed activities remain as the most used method in Cuba for hyperthyroidism treatment with I (sodium iodide, also known as radioiodine). However, there is not yet an international consensus on the most convenient doses for each case, so, the results are not always the desired ones. Objective: To evaluate the applicability of various patient-specific dose calculation methods for the treatment of hyperthyroidism with sodium iodide. Methods: It was carried out an analysis in 10 patients of the results of some methods for dose calculation from the prescribed fixed activity recommended internationally, with the use of technologies and tools already developed and available in the country. The inter-specialist variability and its impact in the planned dose for the treatment were assessed. Results: The use of uncompleted biodistribution and pharmacokinetics information of the patient showed differences between -42 percent and 37 percent in the doses for the same patient. The outcome of the comparison of the calculation method recommended by the European Society of Nuclear Medicine managing the mass by 3D/2D gammagraphy and ultrasound, presented no significant discrepancies among them. The inter-specialist variability of prescribed activity was statistically significant, and it can produce in the same patient differences between 44Gy and 243Gy of the therapeutic doses, which could affect the treatment success and lead to unnecessary side effects. Conclusions: The patient´s personalized calculation methods can be satisfactorily applied in Cuba. The numeric differences found, especially inter-specialist variability, show the lack of therapeutic standardization, which supports the use of pre-therapeutic patient-specific pharmacokinetics and the mass by 3D-gammagraphy to plan the treatment when possible(AU)
Subject(s)
Humans , Male , Female , Adult , Sodium Iodide/therapeutic use , Pharmacokinetics , Hypothyroidism/therapy , Nuclear Medicine/methods , Reference StandardsABSTRACT
Objective To explore the relationship between urinary iodine level and breast cancer,we compare urinary iodine excretion levels in patients with breast cancer,benign breast disease,other female malignant tumors and control subjects in Xiangya Hospital of Central South University.Methods From December 2018 to January 2019,64 patients with newly diagnosed breast cancer in Xiangya Hospital of Central South University were selected as case group,benign breast disease group (n =49),other female malignant tumor group (n =39) and health examination group (n =50) as control group.Urinary iodine was determined by colorimetry.According to the urinary iodine level the patients divided into three groups:iodine excess (＞300 μg/L),medium iodine (100-300 μg/L) and iodine deficiency (＜ 100 μg/L).The relationship between urinary iodine and clinicopathology of breast cancer was analyzed.Results The level of urinary iodine in benign breast nodule group 319.13 (163.98) μg/L ＞ breast cancer group 273.96 (151.30) μg/L ＞ female other malignant tumor group 212.95 (161.71) μg/L ＞ normal control group 199.15 (194.45) μg/L,with significantly differance (H =9.936,P =0.019).Urinary iodine level in the normal control group was significantly lower than that in the benign breast disease group (P =0.013).The patients were further divided into three groups according to the urinary iodine level:iodine excess,iodine medium and iodine deficiency,the number of urine iodine ＜ 100 μg/L in the normal control group was significantly higher than that in the breast cancer group (P =0.021).The level of urinary iodine was negatively correlated with the size of the primary focus of breast cancer (Z =-2.307,P =0.021).The effect of urinary iodine was analyzed by multiple linear regression method.The size of primary focus was included in the regression equation (R2 =0.136,P=0.007),but had nothing to do with lymph node metastasis and the expression status of estrogen receptor (ER),androgen receptor (AR),progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2).Conclusions There is a negative linear correlation between urinary iodine level and the size of primary focus of breast cancer,but it has nothing to do with lymph node metastasis and the expression of ER,AR,PR and HER-2.
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Objective To observe the effect of long-term intake of low iodine diet on thyroid morphological structure and sodium iodine transporter (NIS) in parental and second filial generation rats, and to explore the changes of NIS protein expression in iodine deficiency disease (IDD), so as to further verify and explore the mechanism of IDD. Methods Referring to "Nutritional Composition of Experimental Animals With Feed" (GB 14924.3-2010), the crops widely planted and with high edible rate in the traditional cretinism epidemic area of Xinjiang were used as the main feed components to prepare different levels of iodine (low iodine groups 1 and 2 feed the iodine contents were about 50 and 20 μg/kg). The IDD rat model was established by the three-generation two-nest method, that is, 132 SPF Wistar rats were selected after weaning, half males and half females, randomly divided into 3 groups according to body mass by random number table method: control group (N, 52 rats, 22 females, 30 males, the iodine content was about 300 μg/kg), low iodine groups 1 and 2 (LⅠ, LⅡ, 40 rats, 22 females, 18 males in each group). Twelve rats in each group were sacrificed at the end of 3, 6, 9 months, respectively, half males and half females. The relative weight of thyroid was calculated and the gross structure and microscopic pathology were observed. The expression of NIS protein was determined by Western blotting. At the end of 3 months after feeding, four female rats in each group were selected to mate with male rats in group N in 1 : 1, and the newborn mice were fed the same way for three months and then subcultured again. The rat generation continued to be fed according to the mother group, and 10-12 rats were sacrificed at the end of 3, 6, 9 months, respectively, and the specimens and observation indexes results were collected same as the parental rats. Results The relative weight of the thyroid in parental LⅠand LⅡ groups were higher than those in the N group at 6 and 9 months [female:(19.67 ± 5.60), (23.81 ± 4.08) vs (10.14 ± 1.20);(22.24 ± 2.06), (33.51 ± 3.24) vs (9.80 ± 1.96);male:(13.0 ± 3.70), (13.84 ± 4.08) vs (5.90 ± 1.20);(14.20 ± 2.67), (19.98 ± 2.84) vs (6.06 ± 0.76), P < 0.05], the females were higher than the males at 3, 6, 9 months (P<0.05). The relative weight of the thyroid in second filial generation LⅠand LⅡgroups were higher than that in the N group at 3, 6 and 9 months (P < 0.05). Except the 6 month LⅠ group, the relative weight of thyroid in the other groups was higher than that in the male (P<0.05). In prolonged iodine-deficiency process, LⅠ and LⅡ groups, the color of the thyroid gland for parental and second filial generation rats appeared darkening, hyperemia and swelling. At the same time, microscopic pathology showed that the thyroid gland of different generations showed increased follicles and smaller follicular cavities. Epithelial cell hyperplasia and interstitial fibrosis and interstitial inflammatory cell infiltration at the end of 9 months were observed. At 3, 6, and 9 months after low iodine, the expression of NIS protein in the LⅠ and LⅡ parental and second filial generation rats was higher than that in the N group (P<0.05). Conclusions Long-term low iodine in different levels of feed can cause compensatory thyroid enlargement and hyperplasia in both parental and offspring rats, the expression of NIS protein has continued to rise.
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BACKGROUND AND OBJECTIVES: Sodium-iodine symporter (NIS) is a marker for the degree of differentiation in thyroid cancer. The genetic factors or microenvironment surrounding tumors can affect transcription of NIS. In this study, we investigated the NIS mRNA expression according to mutational status and coexistent lymphocytic thyroiditis in papillary thyroid cancer (PTC). MATERIALS AND METHODS: The RNA expression levels of NIS in the samples from database of The Caner Genome Atlas (TCGA; n=494) and our institute (n=125) were analyzed. RESULTS: The PTCs with the BRAFV600E mutation and the coexistence of BRAFV600E and TERT promoter mutations showed significantly lower expression of NIS (p < 0.001, respectively), and those with BRAF-like molecular subtype also had reduced expression of NIS (p < 0.001). NIS expression showed a positive correlation with thyroid differentiation score (r=0.593, p < 0.001) and negative correlations with expressions of genes involved in ERK signaling (r=−0.164, p < 0.001) and GLUT-1 gene (r=−0.204, p < 0.001). The PTCs with lymphocytic thyroiditis showed significantly higher NIS expression (p=0.013), regardless of mutational status. CONCLUSION: The NIS expression was reduced by the BRAFV600E mutation and MAPK/ERK pathway activation, but restored by the presence of lymphocytic thyroiditis.
Subject(s)
Genome , Ion Transport , RNA , RNA, Messenger , Thyroid Gland , Thyroid Neoplasms , Thyroiditis, AutoimmuneABSTRACT
ABSTRACT The objective of this study was to identify thyroid hormones and to examine their putative site of synthesis in Achatina fulica snails. For this purpose, radioimmunoassays were performed for T3 and T4 before and after long starvation with or without hemolymph deproteinization. Sodium/iodide symporter activity in vivo was analyzed through 125I administration with and without KClO4 pretreatment. Only T4 was detected, and its concentration decreased due to starvation or deproteinization. However, high-performance liquid chromatography analysis also showed the presence of T2 and T3 apart from T4, but rT3 was not detected in the A. fulica hemolymph. The sodium/iodide symporter activity was greater in cerebral ganglia than digestive gland, but KClO4 treatment did not inhibit iodide uptake in any of the tissues analyzed. Altogether, our data confirm for the first time the presence of thyroid hormones in A. fulica snails and suggest their participation in the metabolism control in this species, although the putative site of hormone biosynthesis remains to be elucidated.
Subject(s)
Animals , Snails/chemistry , Thyroxine/analysis , Thyroxine/metabolism , Biological Transport , Hemolymph , Chromatography, High Pressure Liquid , Sodium Chloride SymportersABSTRACT
The expression and function of NIS are the prerequisites of radioactive iodine ( RAI ) treatment for DTC, which in turn determine the iodine uptake and outcome in DTC patients. Studies for the factors that might influence the function of NIS for the development of redifferentiation therapy should be conducted in conjunction with the individualized course of treatment in DTC patients having poor iodine up?take in their thyroid tumors. This review summarizes the factors that influence the function and expression of NIS in these patients.
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BACKGROUND AND OBJECTIVES: Alpha-lipoic acid (ALA) is a naturally occurring fatty acid with strong antioxidant properties that exerts protective effects against harmful free radical damage. The aim of the present study was to assess the effect of ALA on iodine uptake and expression of sodium iodine symporter (NIS) using FRTL-5 cells. MATERIALS AND METHODS: Cells were treated with ALA for various time and doses, in the presence or absence of thyrotropin (TSH). Cell viability assay, iodine uptake assay and NIS promoter activity assay were performed. RESULTS: ALA increased NIS promoter activity. It showed an additive effect when concomitantly added with TSH. After 48 hours of incubation with ALA in the presence or absence of TSH, there was no difference in iodine uptake according to doses of ALA. After 72 hours of incubation with ALA and TSH, ALA decreased iodine uptake in dose-dependent way. CONCLUSION: ALA induced NIS gene transcription of FRTL-5, but suppressed iodine uptake in the presence of TSH. ALA may suppress iodine uptake through effect for post-translation stage of NIS protein.
Subject(s)
Animals , Rats , Cell Line , Cell Survival , Iodine , Ion Transport , Sodium , Symporters , Thioctic Acid , Thyroid Gland , ThyrotropinABSTRACT
Thyroid carcinogenesis is accompanied by loss of thyroid-specific functions and refractory to radioiodine and thyroid stimulating hormone (TSH) suppression therapy. Redifferentiating agents have been shown to inhibit tumor growth and improve the response to conventional therapy. Polyphenol phytochemicals (PPs) in fruits and vegetables have been reported to inhibit cancer initiation, promotion, progression and induce redifferentiation in selected types. In this study we examined PPs induce redifferentiation in thyroid cancer cell lines. We investigated the effects of genistein, resveratrol, quercetin, kaempferol, and resorcinol on the F9 embryonal carcinoma cell differentiation model. The thyroid cancer cell lines, TPC-1, FTC-133, NPA, FRO, and ARO, displayed growth inhibition in response to genistein, resveratrol, quercetin. We further demonstrated that genistein decreased the dedifferention marker CD97 in NPA cells and resveratrol decreased CD97 in FTC-133, NPA, FRO cells and quercetin decreased CD97 in all cell lines. We observed increased expression of differentiation marker NIS in FTC-133 cells in response to genistein, and resveratrol but no change in NPA, FRO, ARO cells. Quercetin increased or induced NIS in FTC-133, NPA, FRO cells. These findings suggest that PPs may provide a useful therapeutic intervention in thyroid cancer redifferentiation therapy.
Subject(s)
Humans , Antigens, CD/metabolism , Antineoplastic Agents/pharmacology , Carcinoma, Embryonal/drug therapy , Cell Differentiation/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Flavonoids/pharmacology , Gene Expression Regulation, Neoplastic , Genistein/pharmacology , Kaempferols/pharmacology , Models, Biological , Phenols/pharmacology , Quercetin/pharmacology , Resorcinols/pharmacology , Stilbenes/pharmacology , Symporters/metabolism , Thyroid Neoplasms/drug therapyABSTRACT
PURPOSE: Response to radioiodine therapy for thyroid cancer is related to the loss of sodium-iodine symporter protein caused by dedifferentiation of thyroid cancer cells. So we aimed to study mRNA expression of CD97, dedifferentiation marker, and sodium-iodine symporter after retinoic acid treatment according to retinoids receptor status. METHODS: Thyroid cancer cell lines; ARO, FRO, NPA, TPO, and FTC133 were prepared. 5µM of all trans retinoic acid were administered to each cell lines and then expression of m RNA for retinoids receptors (RARα, RARβ, RARγ, RXRα, RXRβ, RXRγ), CD97, and Sodium-Iodine symporter by RT-PCR. RESULTS: RARs and RXRs were differently expressed in each cell line. After retinoic acid treatment, relative density of retinoic acid receptor mRNA were increased by time dependently in each cell line except TPO cell line. Expression of CD97 also was decreased in every cell lines (P<0.001). Retinoic acid increased expression of sodium-iodine symporter only in FTC133 cell line (P<0.001), and TSH or forskolin did not enhance NIS expression by retinoic acid. RARβ and RXRγ were expressed only in FTC 133cell line before treatment. Induction of sodium-iodine symporter by retinoids disappeared after RARβ specific antagonist LE135 or pan RXR antagonist PA452 administration. CONCLUSION: Retinoic acid reduced expression of CD97 in five thyroid cancer cell lines. However, retinoic acid could restore sodium-iodine symporter expression in only FTC 133 cell line specifically containing RARβ and RXRγ. Restoration of sodium-iodine symporter expression by retinoic acid is related to RARβ and RXRγ expression.