Inhibition effects of parathyroid hormone on human medullary thyroid carcinoma cells

Objective： The purpose of the study was to investigate the effects of parathyroid hormone and parathyroid hormone receptor monoclonal antibody on in vitro growth and proliferation of human medullary thyroid carcinoma cell lines. Methods： The medullary thyroid carcinoma cell line was cultured in vitro, with parathyroid hormone and parathyroid hormone receptor monoclonal antibody treatment intervention, the growth of the cells was observed under an inverted contrast micro scope, the MTT assay was used to detect the cell growth inhibition rate. Results： Under the inverted contrast microscope, the cells changed significantly, the parathyroid hormone and parathyroid hormone receptor monoclonal antibodies can effectively inhibit the proliferation of medullary thyroid cancer cells in a time and dose dependent. When parathyroid hormone concentra tion reached a concentration of 2.0 IJmol/L, the parathyroid hormone receptor monoclonal antibody reached a concentration of 1.0 μmol/L, the cell growth was most significantly inhibited （P 〈 0.05）. Conclusion： Parathyroid hormone and parathyroid hormone receptor monoclonal antibody were able to inhibit the proliferation of medullary thyroid carcinoma cells and signifi cantly reduce the proliferation index.

IGF-1 mRNA expression of adult rat thyroid cell cultured in vitro

Objective: To investigate the law of age-related changes of insulin-like growth factor-1 (IGF-1) expression of rat thyroid cells cultured in vitro. Methods: Rat thyroid of different age (10, 45, 65, 100, 150 weeks) was isolated and thyrocytes cultured. Total RNA was extracted in different rat age group when thyroid cells had been cultured for two weeks. mRNA IGF-1 expression was measured with reverse-transcription polymerase chain reaction( RT-PCR) in each group and compared. Results: Quantity of total RNA in thyroid cells decreased with ageing when the rat thyroid cells had been cultured for 2 weeks. There is significant difference among groups (P<0.05). Expression of IGF-1 mRNA could be detected in thyroid cells of different age cultured in vitro. Quantity of IGF-1 mRNA expression by RT-PCR analysis increased from 10 to 45 weeks old, and then decreased with ageing. Conclusion: Rat thyroid cells from different age cultured in vitro can express IGF-1 mRNA. Quantity of total RNA in thyroid cells cultured in vitro decreased with aging. IGF-1 mRNA expression was correlated to age (r=0.401, P<0.05).

In the Basis of Hashimoto’s Thyroiditis, to Form Papillary Thyroid Carcinoma, Metastasized and Then to De-Differentiate into Poorly Differentiated Squamous Cell Carcinoma

Thyroid squamous cell carcinoma is very rare. At present, it is limited to case reports. Since the thyroid follicular epithelium is the non-squamous epithelium, how primary squamous cell carcinoma (SCC) of the thyroid occurs is still a controversial issue. Hashimoto’s thyroiditis (HT) is considered to be an independent risk factor for thyroid cancer, under the basis of HT, how tumor cells evolve and develop to papillary thyroid carcinoma (PTC), and particularly to de-differentiate into SCC is elusive. We report a 72-year-old female patient who developed multiple subtypes of PTC on a basis of HT, and finally to de-differentiate into SCC within the local foci of lymph node metastasis. We found that there was a variety of sub-types of PTC in this patient in the background of HT. SCC was found within local lymph node metastasis. Pathomorphology, immunohistochemistry, and molecular pathology have confirmed that the SCC was derived from PTC, and then developed into poorly differentiated SCC and/or anaplastic carcinoma. We also conducted a comprehensive literature review.

Thyroid follicular renal cell carcinoma excluding thyroid metastases:A case report

BACKGROUND Thyroid follicular renal cell carcinoma is a special type of renal cell carcinoma newly recognized in recent years.It has attracted attention because of its unique histology,immunophenotype,and clinical characteristics.It has a very low incidence,and the number of case reports available for review is limited.Moreover,a thyroid mass with type of tumour is rare.CASE SUMMARY We report a case of a renal mass with a bilateral thyroid mass that was accidentally discovered in a 60-year-old man during physical examination.B-mode ultrasound showed a hypoechoic mass in the middle and lower parenchyma of the right kidney,and computed tomography showed an iso-density shadow tumour in the right kidney.Contrast agents had a significant continuous enhancement effect on the tumour,and the enhancement was not uniform.After partial nephrectomy,pathological analysis was performed to rule out the possibility that the renal tumour was caused by thyroid tumour metastasis.Needle biopsy of the thyroid tumour confirmed that the renal cell carcinoma was not related to the thyroid tumour.The patient was alive at the last postoperative follow-up.CONCLUSION This is the third published case in which thyroid tumour biopsy was performed to confirm that thyroid follicular renal cell carcinoma is not thyroid related.

Lenvatinib-induced multiorgan adverse events in Hurthle cell thyroid cancer: A case report

BACKGROUND The management of metastatic progressive radioiodine-resistant differentiated thyroid cancer remains challenging for clinicians.The availability of tyrosine kinase inhibitors(TKIs),sorafenib and lenvatinib,within the last decade has expanded treatment options;however,these lead to significant adverse effects,which may curtail their use.CASE SUMMARY We report the case of a 47-year-old female with Hurthle cell thyroid cancer who underwent total thyroidectomy followed by radioiodine ablation.During followup,she developed noniodine-avid renal and pulmonary metastases.With respect to her pre-existing diabetes,hypertension,and polycystic kidney disease,the tumor board decided against performing renal metastasectomy because of the risk of future renal decline requiring dialysis.Metastases were treated using sorafenib,which provided stability followed by progression within a year.We switched to lenvatinib,which led to disease regression.However,the patient experienced severe adverse effects,including cardiomyopathy,bicytopenia,renal impairment,and the rarely reported nephrotic syndrome.Renal metastasis is a rare manifestation of Hurthle cell thyroid cancer with only two reported cases in literature.We report the experience of our first case of renal metastasis and its treatment with TKIs.This case serves as a reminder of the adverse drug reactions associated with TKI use.CONCLUSION We advocate close monitoring of patients’hematological and renal profiles as well as their cardiac status using an echocardiogram.

Fine-needle aspiration cytology of an intrathyroidal nodule diagnosed as squamous cell carcinoma: A case report

BACKGROUND Both squamous cell carcinoma(SCC)and papillary thyroid carcinoma(PTC)are common malignant tumors in the neck.However,seldom has SCC of the thyroid been diagnosed.Further,cytological features of SCC and PTC have rarely been reported.The significance of fine-needle aspiration cytology(FNAC)in the diagnosis of neck masses has been established.Herein,we present an exceedingly rare case of an intrathyroidal SCC diagnosed using FNAC,along with its cytological features.CASE SUMMARY A 66-year-old man presented with a left-sided neck mass.Ultrasound examination showed an ill-defined nodule.The appearance was hypoechoic with a few hyperechoic spots.FNAC of the left thyroid nodule was performed.A cellular smear was obtained,and it showed a large number of neoplastic cells with rich cytoplasm and poor cell adhesion.Tumor cell nuclei showed coarse nuclear chromatin and a few enlarged prominent nucleoli.An increased nuclear/cytoplasm ratio was observed.Thus,malignancy was diagnosed without a confirmed tumor type.Percutaneous tumor biopsy was performed to make a definite diagnosis.The tumor cells showed typical squamous cell characteristics.CONCLUSION Head and neck SCC and PTC have different cytologies.Measures are needed to ensure accurate diagnosis using FNAC.

Clinical significance of HBME-1,Galectin-3,and CK19 expression and the status of BRAF mutation in papillary thyroid carcinoma

Objective The aim of this study was to explore the clinical significance of the expression of proteins human bone marrow endothelial cell markers(HBME-1), Galectin-3, and cytokeratin19(CK19), as well as the status of v-raf murine sarcoma viral oncogene homolog B1(BRAF) mutation in papillary thyroid carcinoma(PTC). Methods Immunohistochemical staining was performed in 82 specimens each of PTC and papillary benign lesions to detect the expression of HBME-1, Galectin-3, and CK19. Polymerase chain reaction(PCR) and gene sequencing were performed on 60 specimens each of PTC and papillary benign lesions to detect the status of BRAF mutation. Results The positive expression ratios of HBME-1, Galectin-3, and CK19 in PTC were 98.8%, 97.6% and 100% respectively, which were significantly higher than the expressions in papillary benign lesions(P < 0.05). No significant relationship was observed between the expression of these makers and the clinicopathological features of PTC. The sensitivity of co-expression of HBME-1 and CK19 or HBME-1 and Galectin-3 as diagnostic criteria of PTC was 99.9%, with a specificity of 95.4%. BRAF mutation was detected in 40 of 60 PTC(66.7%) specimens. There was a statistical difference in BRAF mutations between PTC and papillary benign lesions(P < 0.05); there were no associations between BRAF mutation and the clinicopathological features of PTC. Conclusion Combined immunohistochemical staining of HBME-1, Galectin-3, and CK19 can further improve the sensitivity and specificity of differential diagnosis of PTC. BRAF mutation is a significant genetic event, which may have diagnostic value for PTC.

Regulation of Interleukin-6 Production by Cultured Human Thyrocytes

Objective To study the modulation of interleukin 6 (IL 6) generation from human thyroid cells. MethodsThyroid tissues were obtained at surgery from patients with Graves disease. IL 6 in the supernatant of cultured thyrocytes was detected with ultra sensitive ELISA. mRNA was extracted respectively from primary human cultured thyroidal cells under stimulated and unstimulated conditions,and semiquantitative reverse transcriptase polymerase chain reaction (RT PCR) technique was used for IL 6 mRNA detection. Results① In the basic conditions,thyroid cells can produce high concentration IL 6. Thyrotropin (TSH,10 3mU/L), tumor necrosis factor α(TNF α,10 -1 U/ml),interleukin 1(IL 1,10 U/ml) and adrenaline(10 -5 mol/L) significantly increased IL 6 levels in the supernatant of cultured thyroid cells,whereas dexamethasone (10 mmol/L) markedly suppressed IL 6 release from thyrocytes. NaI of 10 -4 mol/L exerted no effect on the production of IL 6. ② Compared with the basal results,at a concentration of 10-10 3 mmol/L,dexamethasone could gradually suppress IL 6 gene expression on human thyrocytes,while TNF α could obviously stimulate the production of IL 6 mRNA in the range of 10 -1 -10 2 U/ml. On the level of 10 2 U/ml,IL 1 increased the expression of IL 6,but the same effect could not be shown when IL 1 was 10 -1 or 10 U/ml. Sodium iodine (NaI) could not affect IL 6 gene from the level of 10 -8 to 10 -4 mol/L. ConclusionIL 6 produced by thyrocytes might be regulated by many factors that modulate thyroid functions in vitro as well as in vivo.

Role of natural killer T cells in Graves' disease

Objective To explore the role of natural killer T (NK T) cells in the pathogenesis of Graves’ disease.Methods NK T cell deficient mice and wild BALB/c mice were immunized with cells expressing TSH receptor once every two weeks 6 times. Two weeks after the final immunization, the mice were killed and serum thyroxine levels, anti-TSH receptor antibodies and thyroid pathological changes were examined.Results The mean levels of TT 4 and TRAb in the immunized NK T cell deficient group were slightly elevated but significantly different from those of the non-immunized control group, while comparable to those in the immunized wild group. There were no significant changes of the activity levels of TSAb or TSBAb in the immunized NK T cell deficient mice compared to those in immunized wild control mice. Thyroids from immunized NK T cell deficient mice showed mild hypertrophy of some follicles as compared with non-immunized control mice. This change was comparable to immunized wild control mice.Conclusion NK T cells may not be involved in the pathogenesis of Graves’ disease.