MicroRNA-375-3p inhibitor suppresses angiotensin II-induced cardiomyocyte hypertrophy by promoting lactate dehydrogenase B expression.

Cardiac hypertrophy is a myocardial enlargement due to overload pressure, and the primary cause of heart failure. We investigated the function of miR-375-3p in cardiac hypertrophy and its regulating mechanisms. miR-375-3p was upregulated in hearts of the transverse aortic constriction rat model and angiotensin II (Ang II)-induced primary cardiomyocyte hypertrophy model; the opposite was observed for lactate dehydrogenase B (LDHB) protein expression. miR-375-3p knockdown reduced the surface area of primary cardiomyocytes increased by Ang II treatment and decreased the B-natriuretic peptide (BNP) and ß-myosin heavy chain (ß-MHC) messenger RNA (mRNA) and protein levels. miR-375-3p was also observed to directly target LDHB. LDHB knockdown increased the surface area of Ang II-treated primary cardiomyocytes and increased the BNP and ß-MHC mRNA and protein levels. LDHB knockdown attenuated the effects of miR-375-3p on the surface area of primary cardiomyocytes and BNP and ß-MHC levels. Therefore, miR-375-3p inhibitor suppresses Ang II-induced cardiomyocyte hypertrophy by promoting LDHB expression.

SIZE OF THE LARGEST METASTATIC FOCUS TO THE LYMPH NODE IS ASSOCIATED WITH INCOMPLETE RESPONSE OF PN1 PAPILLARY THYROID CARCINOMA.

Objective: To evaluate the influence of the size of the metastatic focus in lymph nodes (LNs) on therapeutic response among papillary thyroid cancer (PTC) and cervical pathologically proven LN metastases (pN1). Methods: Patients with pN1 PTC who underwent total or near-total thyroidectomy, LN dissection, and postoperative radioactive iodine therapy in a university hospital between 2014 and 2016 were retrospectively reviewed. Furthermore, 554 patients were assigned to three groups according to the size of the metastatic focus in the LNs (≤0.2 cm, 0.2 to 1.0 cm, ≥1.0 cm). Structural incomplete response (SIR) was defined as structural or functional evidence of disease with any thyroglobulin level and/or anti-thyroglobulin antibodies. Results: Among the 554 patients, the proportion of patients with SIR was 2.5% (4/161) in group 1, 13.9% (37/267) in group 2, and 46.8% (59/126) in group 3 (χ2 = 100.073; P<.001). The optimal cutoff value of the size of the largest metastatic focus to the LNs was 0.536 cm to predict SIR with a corresponding sensitivity of 0.82, a specificity of 0.716, and an area under the curve of 0.821 (95% confidence interval [CI], 0.777 to 0.864; P<.001). Size of the largest metastatic focus to the LNs was confirmed to be an independent predictive factor for SIR (odds ratio, 9.650; 95% CI, 4.925 to 18.909; P<.001). Conclusion: In patients with pN1 PTC, there is an association between the size of the largest metastatic focus to the LNs and incomplete response. Abbreviations: AJCC = American Joint Committee on Cancer; ATA = American Thyroid Association; BIR = biochemical incomplete response; CI = confidence interval; ER = excellent response; ETE = extranodal extension; 18F-FDG = 18F-fluorodeoxyglucose; IDR = indeterminate response; LN = lymph node; OR = odds ratio; PET/CT = positron emission tomography/computed tomography; pN1 = pathologically proven LN metastases; PTC = papillary thyroid carcinoma; RAI = radioactive iodine; ROC = receiver operating characteristic; SIR = structural incomplete response; sTg = stimulated thyroglobulin; TgAb = anti-thyroglobulin antibody; TSH = thyroid-stimulating hormone.

Clinical significance of the BRAFV600E mutation in PTC and its effect on radioiodine therapy.

The goal of this study was to explore the relationship of the BRAFV600E mutation with clinicopathologic factors and evaluate the effect of radioactive iodine (RAI) therapy in a large group of intermediate- and high-risk papillary thyroid cancer (PTC) patients with the BRAFV600E mutation and without distant metastases. We collected data for PTC patients who underwent total or near-total thyroidectomy and RAI treatment in our hospital from January 2014-December 2017. There were 1220 PTC patients who met the criteria, and the BRAFV600E mutation was observed in 979 of them (80.2%). Multivariate analysis identified that the BRAFV600E mutation remained independently associated with age at diagnosis, and bilaterality (OR = 1.023, 95% CI = 1.012-1.039, P < 0.001; OR = 1.685, 95% CI = 1.213-2.341, P = 0.002, respectively). In addition, the patients with bilateral PTCs had a higher prevalence of extrathyroid invasion, capsular invasion and fusion of metastatic lymph nodes than the unilateral PTC patients. The response to RAI therapy was evaluated in both the entire series and the patients with a high recurrence risk; no significant difference was discerned between the BRAFV600E mutation and the wild-type groups (P = 0.237 and P = 0.498, respectively). To summarize, our results confirmed that PTC patients with the BRAFV600E mutation exhibit more aggressive characteristics. In addition, the patients with bilateral PTC have a higher incidence of extrathyroid invasion. Moreover, BRAFV600E mutation PTC patients did not show a poorer clinical response after postsurgical RAI therapy, suggesting that RAI therapy may improve the general clinical outcome of these patients.