Filamin A regulates focal adhesion disassembly and suppresses breast cancer cell migration and invasion

The actin cross-linking protein filamin A reduces migration, invasion, and metastasis of breast cancer cells

Protective effect of Salidroside on hypoxia‐related liver oxidative stress and inflammation via Nrf2 and JAK2/STAT3 signaling pathways

Abstract High‐altitude hypoxia‐induced oxidative stress and inflammation played an essential role in the incidence and development of liver injury. Salidroside (Sal), a phenylpropanoid glycoside extracted from the plant Rhodiola rosea, has recently demonstrated antioxidant, anti‐inflammatory, and antihypoxia properties. Herein, we hypothesized that salidroside may alleviate hypoxia‐induced liver injury via antioxidant and antiinflammatory‐related pathways. A high‐altitude hypoxia animal model was established using hypobaric chamber. Male SD rats were randomly divided into the control group, hypoxia group, control +Sal group, and hypoxia +Sal group. Salidroside treatment significantly inhibited hypoxia‐induced increases of serum and hepatic pro‐inflammatory cytokines release, hepatic ROS production and MDA contents; attenuated hypoxia‐induced decrease of hepatic SOD, CAT, and GSH‐Px activities. Furthermore, salidroside treatment also potentiated the activation of Nrf2‐mediated anti‐oxidant pathway, as indicated by upregulation of n‐Nrf2 and its downstream HO‐1 and NQO‐1. In vitro study found that blocking the Nrf2 pathway using specific inhibitor ML385 significantly reversed the protective effect of salidroside on hypoxia‐induced liver oxidative stress. In addition, salidroside treatment significantly inhibited hepatic pro‐inflammatory cytokines release via JAK2/STAT3‐mediated pathway. Taken together, our findings suggested that salidroside protected against hypoxia‐induced hepatic oxidative stress and inflammation via Nrf2 and JAK2/STAT3 signaling pathways

Prognostic significance of microRNA-20a-5p levels which promotes proliferation and invasion by targeting cyclin G2 in small cell lung cancer

MicroRNA-20a-5p (miR-20a-5p) has been shown to function as a tumor promoter factor in several cancers. However, its role in small cell lung cancer (SCLC) remains unclear. In this study, we have made an attempt to measure the tumor tissue levels of miR-20a-5p in patients with SCLC using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The biological function of miR-20a-5p in SCLC cells was investigated in vitro and in vivo studies, including cell proliferation, migration assays and tumorigenicity in nude mice. Meanwhile，we conducted the luciferase reporter assay to verify the biological relationship between miR-20a-5p and CCNG2. The expression of miR-20a-5p was significantly upregulated in human SCLC compared to that in normal tissues. Kaplan-Meier analysis indicated that patients with high expression of miR-20a-5p are closely related with the shorter survival of SCLC. Further, multivariate analysis showed that miR-20a-5p was an independent prognostic factor. Increasing miR-20a-5p expression promotes the proliferation, migration and invasion of the NCI-H446 cells in vitro and in vivo. Dual-luciferase reporter gene assay demonstrated that miR-20a-5p directly targets CCNG2. These findings suggest that miR-20a-5p levels might be a novel diagnostic and prognostic marker of SCLC. Inhibiting miR-20a-5p could be a promising therapeutic strategy for SCLC

High-grade encapsulated papillary carcinoma of the breast is clinicopathologically distinct from low/intermediate-grade neoplasms in Chinese patients

Encapsulated papillary carcinoma (EPC) of the breast is typically of low-to-intermediate grade (LTIG) with favorable prognosis. Rarely, high-grade (HG) EPC cases have been documented in recent years. Herein we compared the morphological, immunohistochemical, and clinical features of LTIG EPC to those of HG EPC. Of the 30 EPC patients, 25 were diagnosed as LTIG and five as HG (median age: 60 and 36 years, respectively); 80% of the HG EPCs exhibited predominantly solid architecture with prominent lymphoplasmacytic infiltrates, more crowded and thicker papillae, and greater stratification and irregular arrangement of malignant epithelial cells. Coexisting invasive components were observed in 32% and 80% of LTIG and HG cases, respectively. HG EPC was negative for hormone receptor staining. Additionally, 48% of LTIG EPC cases were moderately positive for human epidermal growth factor receptor 2 (Her-2) immunostaining (2+); among them, one case showed Her-2 gene amplification by fluorescence in situ hybridization. The basal-like markers cytokeratin 5/6 and epidermal growth factor receptor were detected in two and five HG cases, respectively. HG EPC was also characterized by a significantly high Ki-67 index (median: 85%, P<0.001). No local recurrence or distant metastasis was noted during the follow-up. HG EPC typically exhibited a solid architecture with a concurrent invasive component as well as a triple-negative and basal-like immunophenotype in young women. HG EPC might be indicative of high proliferative activity and potential aggressiveness

BRAF V600E and TERT Promoter Mutations in Papillary Thyroid Carcinoma in Chinese Patients

<div><p>Background</p><p>The BRAF V600E and telomerase reverse transcriptase (TERT) promoter mutations have been reported in papillary thyroid carcinoma (PTC). The aim of this retrospective cross-sectional study was to add further information regarding the prevalence of the BRAF V600E and TERT promoter mutations in Chinese PTC and their clinicopathological associations.</p><p>Methods</p><p>We detected the BRAF V600E mutation and TERT promoter mutations in 455 Chinese PTC patients and analyzed the association of these mutations with several clinicopathological features.</p><p>Results</p><p>The BRAF V600E mutation was detected in 343 (75.4%) of 455 cases and was significantly associated with older age (p<0.001) and conventional subtype (p = 0.003). TERT promoter mutations were detected in 19 (4.4%) of 434 PTCs and were associated with older age (p<0.001), larger tumor size (p = 0.024), and advanced TNM stage(p<0.001). Of the 19 patients that were positive for TERT promoter mutations, 18 (94.7%) also harbored the BRAF V600E mutation.</p><p>Conclusion</p><p>We determined the prevalence and clinicopathological associations of BRAF V600E and TERT promoter mutations in Chinese PTC patients. TERT promoter mutations but not the BRAF V600E mutation were associated with more advanced TNM stage upon diagnosis.</p></div

Cell swelling, softening and invasion in a three-dimensional breast cancer model

Control of the structure and function of three-dimensional multicellular tissues depends critically on the spatial and temporal coordination of cellular physical properties, yet the organizational principles that govern these events and their disruption in disease remain poorly understood. Using a multicellular mammary cancer organoid model, we map here the spatial and temporal evolution of positions, motions and physical characteristics of individual cells in three dimensions. Compared with cells in the organoid core, cells at the organoid periphery and the invasive front are found to be systematically softer, larger and more dynamic. These mechanical changes are shown to arise from supracellular fluid flow through gap junctions, the suppression of which delays the transition to an invasive phenotype. These findings highlight the role of spatiotemporal coordination of cellular physical properties in tissue organization and disease progression.National Cancer Institute (Grant 1U01CA202123

Clinicopathological associations of BRAF V600E and TERT promotermutations.

<p>Clinicopathological associations of BRAF V600E and TERT promotermutations.</p