No abstract

The aim of this study was to compare the efficacy of physical examination (PE), ultrasound (US), and US combined with fine-needle cytology (US-FNAC) in evaluation of node status before sentinel lymph node biopsy (SLNB) for breast cancer patients. We performed a retrospective study of 3,781 breast cancer patients and calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for PE, US, and US-FNAC, respectively. A total of 3,175 cases were documented as cN0 and 606 as cN1. Abnormal axillary nodes under US were detected in 1,152 cases, among which 821 were proven to have positive nodes by FNAC. The positive FNAC results enabled 11.7% of cN0 patients (373/3,175) to avoid unnecessary SLNB. All 331 cases with abnormal US but negative FNAC results, and the 2,629 cases with normal US underwent SLNB procedure for nodal staging, and metastatic nodes were identified in 745 patients. The sensitivity of PE was 32.2%, with a specificity of 95.5%, a PPV of 83.5%, a NPV of 65%, and an accuracy of 69.3%. The sensitivity, specificity, PPV, NPV, and accuracy of axillary US alone were 58.6, 89.4, 79.6, 75.3, and 76.7%, respectively. Combining axillary US with FNAC resulted in sensitivity, specificity, PPV, NPV, and accuracy of 52.4, 100, 100, 74.8, and 80.3%, respectively. Our study demonstrated that US-FNAC is a feasible and effective triage during axillary staging for newly diagnosed breast cancer patients.

Obesity is associated with many severe chronic diseases and deciphering its development and molecular mechanisms is necessary for promoting treatment. Previous studies have revealed that mitochondrial content is down-regulated in obesity, diabetes, and nonalcoholic fatty liver disease (NAFLD) and proposed that NAFLD and diabetes are mitochondrial diseases. However, the exact mechanisms underlying these processes remain unclear. In this study, we discovered that resistin down-regulated the content and activities of mitochondria, enhanced hepatic steatosis, and induced insulin resistance (IR) in mice. The time course indicated that the change in mitochondrial content was before the change in fat accumulation and development of insulin resistance. When the mitochondrial content was maintained, resistin did not stimulate hepatic fat accumulation. The present mutation study found that the residue Thr464 of the p65 subunit of nuclear factor kappa B was essential for regulating mitochondria. A proximity ligation assay revealed that resistin inactivated peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC-1a) and diminished the mitochondrial content by promoting the interaction of p65 and PGC-1a. Signaling-transduction analysis demonstrated that resistin down-regulated mitochondria by a novel protein kinase C/protein kinase G/p65/PGC-1a-signaling pathway. Conclusion: Resistin induces hepatic steatosis through diminishing mitochondrial content. This reveals a novel pathway for mitochondrial regulation, and suggests that the maintenance of normal mitochondrial content could be a new strategy for treatment of obesity-associated diseases.

Glioma is among the most fatal brain tumors characterized by a highly malignancy and rapid progression and early metastasis. Dysregulation of long non-coding RNA differentiation antagonizing non-protein coding RNA (LncRNA DANCR) is associated with the development, progression and metastasis of various cancers. In the present study, we investigated functional role of LncRNA DANCR in the malignancy of glioma. The results showed that LncRNA DANCR was increased in glioma tissues and cells compared with normal brain tissues and cells. DANCR expression was positively correlated with the malignancy and poor prognosis of glioma patients. DANCR contained a binding site of miR-33a-5p. miR-33a-5p was decreased in glioma tissues and cells compared with normal brain tissues and cells. Downregulation of miR-33a-5p was positively correlated with the malignancy and poor prognosis of glioma patients. In glioma tissues, the expression of DANCR was negatively correlated with the expression of miR-33a-5p. Downregulation of DANCR increased miR-33a-5p expression. miR-33a-5p mimic reduced the luciferase of DANCR-WT but not DANCR-MUT. DANCR pull-down showed the expression of miR-33a-5p. miR-33a-5p mimic enhanced knockdown of DANCR -induced inhibition of cell proliferation, migration, and EMT, and increase of apoptosis. Anti-miR-33a-5p reversed the effects of si- DANCR on cell malignancy. Knockdown of DANCR remarkably reduced the increase of tumor volumes in xenograft mouse models. In tumor tissues, knockdown of DANCR increased the expression of miR-33a-5p, reduced EMT and increased apoptosis. Our study provides novel insights in the functions of LncRNA DANCR-miR-33a-5p axis in tumorigenesis of glioma.

Despite improvements in surgical resection and adjuvant chemotherapy, the prognosis and outcomes of patients with osteosarcoma remains poor due to the occurrence of metastasis or relapse. Monocyte chemoattractant protein-1-induced protein-1 (MCPIP1), a zinc-finger RNA-binding protein, is known to regulate inflammatory responses and repress breast cancer growth. However, the regulation of MCPIP1 by microRNAs has not been clearly elucidated in osteosarcoma. In this study, we found that miR-421 expression was upregulated and MCPIP1 expression was downregulated in the osteosarcoma specimens from patients. Moreover, MCPIP1 expression was inversely correlated with miR-421 expression in the clinical samples. Furthermore, the upregulation of miR-421 and downregulation of MCPIP1 resulted in poor overall survival and severe disease progression, respectively, in the patients with osteosarcoma. Bioinformatics analysis and luciferase reporter gene assays confirmed that miR-421 specifically targets and binds to the 3ʹ-UTR of MCPIP1. The overexpression of miR-421 induced cell proliferation, invasion, and migration, and the release of proinflammatory IL-6 in cultured human osteosarcoma cells. Additionally, the administration of miR-421 to tumorbearing mice facilitated osteosarcoma growth by downregulating MCPIP1 expression. Taken together, these findings indicate that miR-421 is able to promote the development of osteosarcoma by regulating MCPIP1 expression, and can be a potential therapeutic target for osteosarcoma.