Effect of miR­449a­mediated Notch signaling pathway on the proliferation, apoptosis and invasion of papillary thyroid carcinoma cells.

The present study aimed to investigate the effect of miR­449a­mediated Notch signaling pathway on the proliferation, apoptosis and invasion of papillary thyroid carcinoma cells. Human papillary thyroid carcinoma cell line TPC­1 was selected, and cells were grouped and transfected: Control group (without any treatment), negative control (NC) group (transfection with NC plasmid), miR­449a mimic group (transfection with miR­449a mimic), miR­449a inhibitor group (transfection with miR­449a inhibitor), DAPT group (addition of γ­secretase inhibitor DAPT to inhibit the Notch signaling pathway), and miR­449a inhibitor + DAPT group (transfection with miR­449a inhibitor and addition of DAPT). The target relationship between miR­449a and Notch1 was detected by dual­luciferase reporter assay. qRT­PCR and western blotting were used to assess the expression of miR­449a, Notch1 and Jagged1 in cells. Cell proliferation was detected using EdU; the cell cycle and apoptosis were detected by flow cytometry; cell invasion ability was detected by Transwell assay. PCNA, MMP­2, MMP­9, Bcl­2 and Bax mRNA and protein expression were assessed by qRT­PCR and western blotting. The results revealed that miR­449a negatively regulated Notch1. Compared with the control group, there was significantly increased miR­449a expression in the miR­449a mimic group, and there was significantly decreased expression of Notch1, Jagged1, PCNA, MMP­2, MMP­9 and Bcl­2, increased Bax, reduced cell proliferation, increased G1­phase cell fraction, decreased S­phase cell fraction, an increased apoptosis rate, and decreased invasion ability in the miR­449a mimic group and DAPT group (all P<0.05). However, the results in the miR­449a inhibitor group were the opposite of those in miR­449a mimic group (all P<0.05). There was no significant difference in cell proliferation, apoptosis and invasion in the NC group and miR­449a inhibitor + DAPT group compared to the control group (all P>0.05). miR­449a overexpression can inhibit Notch signaling pathway, thereby inhibiting the proliferation and invasion of papillary thyroid carcinoma cells and promoting cell apoptosis.

Correlative studies of ultrasonic classification diagnosis and clinicopathological features of thyroid calcification lesions / 中华内分泌外科杂志

Objective To investigate correlative relations between the ultrasonic classification diagnosis and the clinicopathological features of thyroid calcification lesions.Methods The clinical data of 198 cases diagnosed as thyroid calcification lesions by ultrasonic,surgery and pathology were retrospectively analyzed.Spearman method was used to analyze the relationship of TCL ultrasonic diagnosis,clinical pathological traits and the classification of differentiated thyroid carcinoma(DTC).Results Among the 198 TCL cases,ultrasonic diagnosis and pathologic diagnosis were accordant in 178 (90.40％) cases.Among 119(60.10％) cases of thyroid carcinoma (TC),101 cases(84.87％)were papillary carcinoma,11 cases(9.24％)were follicular carcinoma,5 cases(4.20％) were medullary carcinoma and 2 cases(1.68％)were anaplastic carcinoma.Among 79 cases (39.90％) of benign lesions,34 cases(43.04％)were adenoma,27 cases(34.18％)were nodular goiter,and 18 cases(22.78％)were hashimoto's thyroiditis (HT).Calcified classification were as following 74 cases (37.37％)were type Ⅰ a and 4 cases (2.02％) were type Ⅰ b(both were TC);20 cases(10.10％)were type Ⅰ c,among which 19 cases were nodular goiter,and 1 case was TC.Among the 37 cases (23.74％) of type Ⅱ,28 cases were TC,and 19 cases were benign lesions.Among the 20 cases(10.10％) of type Ⅲ,8 cases were TC,and 12 cases were benign lesions.Among 22 cases(11.11％) of type Ⅳ,2 cases were TC,and 20 cases were benign lesions.Among 11 cases(5.56％) of type V patients,2 cases were TC,and 9 cases were benign lesions.The rate of TC with cervical metastasis was 41.18％(49/119).68.91％(82/119) of carcinoma nodules were grade Ⅱ-Ⅲ in color Doppler flow imaging (CDFI),grade 0-Ⅰ were mainly benign nodules,and grade Ⅲ with mussy blood flow in CDFI were HT.Conclusions Type Ⅰ a and Ⅰ b micro calcification is the pathological basis of ultrasonic diagnosis of papillary thyroid carcinoma and follicular carcinoma,which is closely related to DTC.Calcified isolation nodule of type Ⅱ and Ⅲ with level Ⅱ-Ⅲ bleeding is a risk factor for TC.Type Ⅰ c,Ⅲ,Ⅳ and Ⅴcalcification is closely related to benign TCL.CDFI has important value for identifying benign and malignant CLT.

Expression and clinical significance of HPSE, VEGF-C and D2-40 in thyroid carcinoma / 中国癌症杂志

Background and purpose: Thyroid carcinoma cells spread mainly through lymph node metastasis, and lymphangiogenesis plays an important role during the lymph node metastasis, but it is not very clear to understand the formation mechanism. This study was to investigate the correlative expressions of HPSE, VEGF-C, D2-40 and lymphangiogenesis in thyroid carcinoma. Methods: Immunohistochemistry SP method was used to detect the expressions of HPSE, VEGF-C and D2-40 in 77 patients with thyroid carcinoma including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC),medullary thyroid carcinoma (MTC), 32 of them with lymph node metastasis was enrolled into the study, D2-40 stained the lymphatic vessels, and lymphatic vessel density (LVD) was scanned under the light-microscope, and the correlation among the above indexes in different thyroid carcinoma types were analyzed respectively. Results: The expressions of HPSE, VEGF-C and D2-40 were observed to have a different degree in thyroid carcinoma, and the highest expression of the protein could be seen in the patients with papillary carcinoma (P<0.05),The expression ratios of HPSE,VEGF-C and D2-40 in different carcinoma types were 54.9%, 68.6%, 12.8±5.7 for PTC, 37.5%, 50%, 8.6±1.7 for FTC, 20% and 20%, 4.9±0.8 for MTC, respectively. There were significant different expressions of HPSE, VEGF-C and D2-40 between the patients with lymph node-positive group and node-negative group (P=0.014, P=0.048, respectively). In addition, the expressions of them were positively correlated (P<0.001, r=0.616). Conclusion: HPSE, VEGF-C and D2-40 have a close relationship with lymph node metastasis, HPSE and VEGF-C are related to the lymphangiogenesis.

Sistema Glutation-S-Transferase como fator prognóstico no carcinoma papilífero da tireoide / GST genes expression as prognostic factor in papillary thyroid cancer

OBJETIVO: Analisar se existe relação entre os fatores moleculares dos genes GTS e a mortalidade dos pacientes com câncer de tireoide dado pelo índice AMES de prognóstico clínico. MÉTODOS: Foram coletadas amostras da tireoide de 66 pacientes com carcinoma papilífero (53 mulheres e 13 homens), de modo a permitir extração do material genético das enzimas. Foram constituídos dois grupos, segundo os fatores prognósticos clínicos de alto e baixo risco, de acordo a classificação AMES. Cada grupo foi avaliado pela presença ou não do genótipo nulo para as enzimas estudadas, correlacionando-os com os fatores prognósticos clínicos (AMES). RESULTADOS: Foram analisados os resultados de 17 doentes com alto risco (grupo A) e 49 com baixo (grupo B). Todas combinações de genótipos do GSTT1 e GSTM1 foram encontrados. O genótipo nulo dos dois genes do grupo de alto risco foi encontrado em 5,8 por cento e no de baixo risco em 6,1 por cento. CONCLUSÃO: A presença ou deleção dos genes GST (GSTT1 e GSTM1) não são bom fatores prognósticos no câncer papilífero da tireoide.

PURPOSES: Analyze the relationship between the AMES classification and molecular factors from Glutation-S-Transferase System, specifically the GSTT1 and GSTM1 in patients with well differentiated thyroid cancer. METHODS: Samples of thyroid tissue of 66 patients with papillary thyroid carcinoma were obtained (53 women and 13 men). Patients were divided in two groups (high and low risk) according to the AMES classification. In each group, presence of the null genotype of both GST enzymes system was studied. These results were compared with the AMES classification. Samples were obtained in the operating room immediately after thyroidectomy, placed in cryotubes, immersed in liquid nitrogen and stored in a freezer at -80ºC. DNA of this enzymes was extracted by the fenol-cloroformium method. RESULTS: There were 17 high risk patients and 49 low risk patients. The null genotype of the high risk group was 5.8 percent and in the other group was 6.1 percent. CONCLUSION: There was no relationship between absence of genes GSTT1 and GSTM1 and prognosis of the papillary thyroid carcinoma when compared to the AMES classifications.