| Objectives：The earliest in the early19th century, thyroid cancer isclinically discovered and reported in the literature. Due to the lower incidenceand mortality of thyroid cancer, its treatment has not been seriously takenclinically for a long period of time[1]. Thyroid cancer is not only a commonendocrine malignancy, accounting for95%of endocrine malignancies, butalso the highest incidence among the head and neck cancer, accornting forabout0.3%(males) to1.0%(females) of malignant tumors of various partsof the body. The mortality of thyroid cancer is relatively low. The cases ofdeath from thyroid cancer are accounting for about0.5%of cases of deathfrom cancer[2].Pathological type of thyroid cancer can be divided into differentiatedthyroid carcinoma (DTC) and anaplastic thyroid cancer (ATC), differentiatedthyroid cancer includes papillary thyroid carcinoma (PTC) and follicularthyroid cancer (FTC). The apillary thyroid carcinoma is accounting for above80percent of total thyroid cancer.According to foreign literature, the incidence of thyroid cancer in the last20years has shown one of the fastest growth among the malignant tumors, theaverage annual growth of incidence rate reaches6.2%. The epidemiologicaldata from China also shows that the incidence of thyroid cancer shows anincreasing trend, especially in papillary thyroid carcinoma. Papillary thyroidcarcinoma is tumer with higher degree of differentiation and slow-growing, asa result, it has a better clinical prognosis.Integrated clinical treatments include surgical removement of tumor withhormone therapy afterwards. If the effective integrated treatment has not beentaken, the recurrence of papillary thyroid cancer will commonly resulted andthe effectiveness of surgical treatment will be impacted. Papillary thyroid carcinoma has some dependence with thyroid stimulating hormone (TSH). Itis so called thyrotropin-dependent cancers.The suppression of preparation of thyroxine toward the thyrotropineliminates the important growth factor of papillary thyroid carcinomatherefore slowing or preventing cancer from regenerating, growing, as a result,interfering the development of thyroid cancer. NTCTCSG studies have shown[29], Thyrotropin suppression therapy significantly improved overall survivalin patients with papillary thyroid carcinoma.Papillary thyroid carcinoma cell membrane expresses the thyrotropinreceptor and reacts to the stimulation of Thyrotropin therefore resulting therecurrence and hyperplasia of thyroid carcinoma. On this basis, a dosageabove physiological doses of thyroxine is given clinically to patients withthyroid carcinoma aiming at feedback inhibiting thyroid-stimulating hormonesecretion, reducing serum levels of thyroid stimulating hormone, therebyreducing the risk of recurrence of papillary thyroid cancer.Therefore, the goal of the long-term levothyroxine replacement therapyin patients with papillary thyroid carcinoma after surgical removement istwofold: First, retainance of of thyroid hormone levels which is essential to thebody’s normal growth and development. Secondly, suppressionof therecurrence of papillary thyroid carcinoma. Intends to achieve these twoobjectives, The dose of levothyroxine to treat papillary thyroid carcinoma aftersurgery is greater than the hypothyroidism replacement dose. Clinical Guidepointed out that the goals of thyroid-stimulating hormone suppression therapyare as follows:①In the absence of specific contraindications, the serum TSHshould be maintained at <0.1mU/L for patients with continued presence oftumor tissue.②For asymptomatic high-risk patients, the serum TSH shouldbe maintained at0.1~0.5mU/L, treatment time lasts5to10years.③Forlow-risk patients with clinically asymptomatic, thyroid-stimulating hormoneshould be maintained at0.3~2.0mU/L, treatment time lasts5to10years.However, the greater than physiological doses of levothyroxine therapypatients will bring a lot of side effects, including causing the occurrence of subclinical hyperthyroidism, ischemic heart disease symptoms, atrialfibrillation, and osteoporosis in postmenopausal women. To reduce the sideeffects of thyroid-stimulating hormone suppression therapy, theimplementation of individualized treatment is of great significance. Personally,in patients with papillary thyroid cancer, especially with abnormal expressionor dysfunction of thyroid-stimulating hormone receptor, the postoperativeindividualized treatment of thyroid-stimulating hormone suppression is moreimportant. At present, for thyroid cancer, studies on thyroid-stimulatinghormone receptor expression or abnormal function were rarely reported.The binding of thyroid stimulating hormone with its receptors play aphysiological role through the activation of adenylate cyclase (AC)-cyclicadenosine monophosphate (cAMP)-protein kinase pathway. Under normalphysiological conditions, thyroid stimulating hormone binds its receptor, andthereby activates the G protein, so that GDPTransformates into GTP, whichcan activate adenylyl cyclase, cAMP produced a large number of thyrotropinleading to a range of biological effects. Therefore, cAMP levels in aconsistent activity and thyroid stimulating hormone receptor, indirectlyreflects the activity of thyrotropin receptor.In this study, surgical resection specimens from patients with papillarythyroid cancer were celected as the study materials. The thyroid cancer cellswere activated in vitro with TSH and cAMP concentration in papillary thyroidcancer was detected by ELISA detection. Patients with nodular goiter thyroidcells were selected as control group. The thyroid stimulating hormone receptoractivity levels in patients with papillary thyroid cancer were assessed so as toprovide a reference for individualized thyroxine treatment for postoperativepatients with papillary thyroid cancer.Methods: Thyroid tumor tissues were collected from44cases withpapillary thyroid carcinoma admited to Second Clinical Hospital of HebeiMedical University after thyroid surgery from January to June of2013asstudy group. Thyroid tissues from44cases with nodules goiter after surgicaltreatment were selected as control group. For each specimen the diagnosis was confirmed by two pathologists. Intracellular cAMP was measured by ELISAkit. The absorbance (value) was measured with a microplate reader in450nmwavelength to calculate the sample concentration and cAMP concentrationwas compared between study and control group.Results:1Morphology of cultured cells of papillary thyroid carcinoma andnodular goiterPapillary thyroid carcinoma cells began to adhere after cultured for24hours in24-well plates. Most adherent cells were round, oval or spindleduring the first1-2days. after3-4days, the cells were gathered into a sheet ora connected group on an irregular basis. The cells gradually extended to thesurrounding adherent growth in monolayer gradually covered the bottom wellsafter5-7days.At this point, the cells were epithelioid cells, mostly round, oval orspindle-shaped, There are abundant cytoplasm containing particulate matter,the nucleus is located in the cell side, nucleoli were visible.Cultured nodular goiter cells in24-well cell culture plates for24hoursbegan to adhere to the wall. The adherent cells were mostly round or oval cells;the cells connected into pieces after4-5days. Cultured cells graduallycovered bottom of the hole. the shapes were mostly round, oval orspindle-shaped cytoplasmic particulate matter, cell nuclei were visible after7-10days.2The comparison of cAMP concentrations between that in papillarythyroid carcinoma and nodular goiter cells.The standard curve graph were drawed according to the measurementresults. The linear equation Y=0.0036*X-0.0493，R2=0.9665, which showed agood correlation. The standard curve equation is X (cAMP concentration)=277.7778*Y+13.6944. Based on the above equation, the cAMP concentrationis (64.8337±7.8349) pmol/ml in cultured papillary thyroid carcinoma cellsand (72.7295±8.6754) pmol/ml in nodular goiter group. As a result, thecAMP concentrations in papillary thyroid cultured cancer cells is lower than that in nodular goiter group. The difference was of statistical significance (t=4.4804, P=0.0000<0.05).Conclusion:1The cAMP levels in papillary thyroid carcinoma cells are lower thanthose in nodular goiter cells, which presumably infered that the function ofthyroid stimulating hormone receptors is lower than that of nodular goitercells.2Human thyroid cells with primary culture techniques are applied toresearch on functional aspects of thyroid cell, therefore, other study methodscan make up for functional deficiencies which other study can not reached onliving cells. |
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