Abstract

Diverse functions of microRNAs have been investigated in tumorigenesis in osteosarcoma (OS), involving the regulation of proliferation, invasion, migration, apoptosis and drug resistance. MiR-367 was found to be an oncogene and increased in OS. However, the function of miR-367 in drug resistance in OS cells is still unknown. In this study, we found that miR-367 was up-regulated in OS tissues and OS cell cultures. Meanwhile, treatment with adriamycin (ADR) induced apoptosis of OS cells with upregulation of miR-367. Notably, KLF4 was demonstrated to be a direct target of miR-367 by gene reporter assay, and miR-367 significantly blocked both mRNA and protein level of KLF4. In addition, overexpression of miR-367 markedly suppressed the increase of KLF4 induced by ADR in OS cells, as well as Bax and cleaved caspase-3, which were significantly reversed by anti-miR-367 transfection. Taken together, our data demonstrates that miR-367 and KLF4 play important roles in OS treatment and ADR resistance, suggesting that miR-367 is a potential biomarker of chemotherapy resistance in OS and also probably a novel therapeutic target against OS.

Abstract

Liver X receptor (LXR) plays an important role in reverse cholesterol transport (RCT), and activation of LXR could reduce atherosclerosis. In the present study we used a cell-based screening method to identify new potential LXRβ agonists. A novel benzofuran-2-carboxylate derivative was identified with LXRβ agonist activity: E17110 showed a significant activation effect on LXRβ with an EC50 value of 0.72 μmol/L. E17110 also increased the expression of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) in RAW264.7 macrophages. Moreover, E17110 significantly reduced cellular lipid accumulation and promoted cholesterol efflux in RAW264.7 macrophages. Interestingly, we found that the key amino acids in the LXRβ ligand-binding domain had distinct interactions with E17110 as compared to TO901317. These results suggest that E17110 was identified as a novel compound with LXRβ agonist activity in vitro via screening, and could be developed as a potential anti-atherosclerotic lead compound.

Abstract

To investigate age-related persistence with bisphosphonates (BIS) in women with breast cancer (BC) and bone metastases. We included a dataset of 1541 patients diagnosed with BC and bone metastases and initially treated with BIS between 1994 and 2013. The primary outcome measure was the age-related rate of BIS discontinuation within 12 months after treatment initiation. Therapy discontinuation was defined as a period of at least 90 days without treatment. A multivariate Cox regression model was created to determine the influence of age on the risk of discontinuation. Health insurance coverage (private/statutory), type of care (gynecological/general), region (West/East Germany), depression, chemotherapy, hormone therapy, pain medication, antidepressants, and the number of co-medications were included as covariates. The mean ages in the group of women

Abstract

In an era of reduced peer-reviewed grant funding, performing academic bone oncology-related research has become increasingly challenging. Over the last 10 years we have held an annual meeting to bring together clinicians, clinician/scientists and basic biomedical researchers interested in the effects of cancer and its treatment on skeletal tissues. In the past these “Bone and the Oncologist New Updates Conference (BONUS)” meetings have served as critical catalyst for initiating productive research collaborations between attendees. The 2015 BONUS meeting format focused on potential key research themes that could form the basis of a coordinated national research strategy to tackle unmet clinical and research needs related to complications associated with cancer metastasis to bone. The three themes planned for discussion were: Is bone metastases-related pain the main issue facing patients? Are there new therapeutic targets for patients with bone metastases? How do we more firmly link basic science with clinical practice? We present a summary of lectures and commentaries from the attendees to serve as an example that other similarly motivated groups can model and share their experiences. It is our hope that these presentations will result in comments, feedback and suggestions from all those researchers interested in this important area.

Abstract

Osteosarcoma (OS) responds poorly to radiotherapy, but the mechanism is unclear. We found OS tumor tissues expressed high level of protein HIF-1α, a common biological marker indicative of hypoxia. It is known that hypoxic cells are generally radioresistant because of reduced production of irradiation-induced DNA-damaging reactive oxygen species (ROS) in the anaerobic condition. Here we report another mechanism how hypoxia induces radioresistance. In MG-63 human osteosarcoma cells, hypoxic pretreatment increased the cellular survival in irradiation. These hypoxia-exposed cells displayed compartmental recruitment of GFP-tagged LC3 and expression of protein LC3-II, and restored the radiosensitivity upon autophagy inhibition. The following immunohistochemistry of OS tumor tissue sections revealed upregulated LC3 expression in a correlation with HIF-1α protein level, implying the possibly causative link between hypoxia and autophagy. Further studies in MG-63 cells demonstrated hypoxic pretreatment reduced cellular and mitochondrial ROS production during irradiation, while inhibition of autophagy re-elicited them. Taken together, our study suggests hypoxia can confer cells resistance to irradiation through activated autophagy to accelerate the clearance of cellular ROS products. This might exist in human osteosarcoma as an additional mechanism for radioresistance.

Abstract

MicroRNA-223 (miR-223) has been shown to be a potential diagnostic and prognostic marker for several cancers. In addition, miR-223 has been reported to suppress osteosarcoma cell proliferation in vitro. However, the clinical value of miR-223 is still unknown. We detected the expression of miR-223 expression in the serum of osteosarcoma patients and in osteosarcoma cancer cells using RT-PCR. We compared the serum expression of miR-223 with the clinicopathological characteristics and survival of osteosarcoma patients. Finally, we explored the role of miR-223 on the invasion of osteosarcoma cancer cells using cell migration and invasion assays. We observed that the expression of miR-223 was significantly decreased in the serum of osteosarcoma patients and osteosarcoma cancer cells compared to healthy controls (P