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Application of valproate and salt-induced redifferentiation combined with <131> iodine thereof in treating poor differentiation/dedifferentiation thyroid cancer

A technology of thyroid cancer and valproic acid, which is applied in the direction of active ingredients of anhydride/acid/halide, drug combination, biochemical equipment and methods, etc. It can solve problems such as inability to apply radioactive iodine therapy, lower iodine intake, and no iodine intake

Inactive Publication Date: 2009-09-09
JIANGSU INST OF NUCLEAR MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, some poorly differentiated and dedifferentiated thyroid cancers have lost the unique functions and characteristics of thyroid cells, such as decreased expression of sodium / iodide symporter (NIS), decreased iodine uptake or even no iodine uptake, Therefore, radioactive iodine therapy cannot be used

Method used

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  • Application of valproate and salt-induced redifferentiation combined with &lt;131&gt; iodine thereof in treating poor differentiation/dedifferentiation thyroid cancer
  • Application of valproate and salt-induced redifferentiation combined with &lt;131&gt; iodine thereof in treating poor differentiation/dedifferentiation thyroid cancer
  • Application of valproate and salt-induced redifferentiation combined with &lt;131&gt; iodine thereof in treating poor differentiation/dedifferentiation thyroid cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Valproic acid inhibits the proliferation of thyroid cancer cells: Take well-grown cultured cells and dilute 1×10 4 Cells / well were seeded in 96-well cell culture plates, with four parallel wells in each group. After the cells adhered to the wall, different concentrations of valproic acid (0.5, 1, 2, 4, 6, 8 and 12 mmol / L) were added, and no drug was added to the control group. After culturing for 48 hours, the culture plate was taken out, the culture medium was carefully discarded, and 200 μL / well of 10% trichloroacetic acid (TCA) was slowly added, and left at 4°C for 1 hour. After the fixation, the fixative was discarded, and washed three times with distilled water to remove TCA. After air drying, add 150 μL / well of 0.4% sulforhodamine B staining solution, and stain at 37°C for 30 minutes. Discard the dye solution, wash with 1% acetic acid 3 times to fully remove unbound sulforhodamine B, after air drying, add 10mmol / LTris solution at 100μL / well to dissolve, oscillat...

Embodiment 2

[0020] Valproic acid induced the increase of NIS mRNA expression in FTC-133 and K1 cells: Cells in the logarithmic growth phase were seeded in 6-well cell culture plates (5×10 5 / well), cultivated overnight, added different final concentrations of VPA (0, 2, 4, 6 and 8mmol / L), continued to cultivate for 48h, and collected the cells. Total cellular RNA was extracted with Tri-Reagent. cDNA was synthesized by reverse transcription, the transcription level of NIS was detected by PCR, and GAPDH was used as internal reference. The reverse transcription reaction system was 25 μL, and the reaction conditions were: 42° C. for 1 h. The PCR system is 20 μL, the reaction conditions of NIS: 94°C pre-denaturation for 5 minutes, 94°C denaturation for 20s, 64°C annealing for 30s, 72°C extension for 60s, a total of 40 cycles, and finally 72°C extension for 7min; GAPDH PCR reaction conditions: 94°C Pre-denaturation for 5 minutes, denaturation at 94°C for 20s, annealing at 60°C for 30s, extens...

Embodiment 3

[0023] Valproic acid induces thyroid cancer cells to increase the uptake of radioactive iodine: take logarithmic growth FTC-133 and K1 cells, add 4mmol / L and 8mmol / L valproic acid for 48h, digest and count, and use serum-free The medium was adjusted to a cell concentration of 2.5×10 6 cells / mL, add 74kBqNa per milliliter of cell suspension 125 I and 10 μM NaI, mix well and incubate in a 37°C water bath for 1 h, take 200 μl of cell suspension from each tube, centrifuge at 5000 rpm for 5 min, discard the supernatant, wash the cells twice with 4°C pre-cooled saline, and measure each cell suspension with a γ-counter Radioactive counts (cpm) of the tube cell pellet. All manipulations were done in quadruple tubes.

[0024] The iodine uptake of FTC-133 cells was significantly increased after being induced by valproic acid, and it was positively correlated with the drug concentration. P0.05; t=0.272, P>0.05) (see image 3 ).

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Abstract

The invention relates to the application of valproate and salt-induced redifferentiation combined with <131> iodine thereof in treating poor differentiation / dedifferentiation thyroid cancer, belonging to the pharmaceutical field, in particular to the pharmaceutical use of the valproate and salt thereof. Sulfonyl rhodamine B (SRB) dyeing analysis is adopted to detect influence of the valproate and the salt thereof on cell proliferation of follicular thyroid cancer cell strain FTC-133 and cell proliferation of papillary thyroid cancer cell strain K1; RT-PCR detects NIS mRNA expression in FTC-133 and K1 cells induced by the valproate and the salt thereof, and variation of iodine uptake of thyroid cancer cells after induced is analyzed; the result shows that the valproate and the salt thereof can obviously inhibit the proliferation of the thyroid cancer cells, and the inhibition rate is also increased along with increase of concentration; the NIS mRNA expression of FTC-133 and the NIS mRNA expression of K1 are both increased after being induced, and radioactive <131> iodine uptake of cancer cells is also increased; the poor differentiation / dedifferentiation thyroid cancer can select radioactive <131> iodine to carry out treatment because of the radioactive <131> iodine uptake increase of the cancer cells.

Description

technical field [0001] Valproic acid and its salts induce redifferentiation in combination with 131 The application of iodine in the treatment of low / dedifferentiated thyroid cancer relates to the field of medicine, in particular to the medical application of valproic acid and its salt. Background technique [0002] Thyroid cancer is currently the most common malignant tumor of the endocrine system in clinical practice, accounting for about 1% of all clinical tumors, and generally has a good prognosis. The main treatment methods for thyroid cancer include surgical resection, radioactive iodine therapy, TSH suppression, etc. Among them, radioactive iodine is widely used abroad, and it is getting more and more attention in China. However, some poorly differentiated and dedifferentiated thyroid cancers have lost the unique functions and characteristics of thyroid cells, such as decreased expression of sodium / iodide symporter (NIS), decreased iodine uptake or even no iodine upt...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/19A61P35/00G01N21/78C12Q1/18C12Q1/68
Inventor 俞惠新包建东林秀峰高芸张莉谭成叶万忠
Owner JIANGSU INST OF NUCLEAR MEDICINE
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