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Background: The function of H3F3A G43W mutation, which has been observed in almost all GCTB, remains poorly characterized. Breakthrough in malignant GCTB has been trapped by the lack of clinical available drugs, limited canonical patient samples and paucity of fidelity preclinical models. Methods: Tumor samples obtained from a malignant GCTB was implanted in immunodeficient mice for the generation of PDX. Histological examination and short tandem repeat (STR) were used for inherited features analyses. An epigenetic/transcriptional targeted compound library was selected for drug screening. The in vivo effects of selected drug were validated in PDX model. Results: We established the PDX model with recurrent malignant GCTB specimens, histological examination and STR analyses revealed that PDX and their corresponding parental patients shared the same STRs and histologic features, suggesting common origins. ITF-2357 was the most significant compound with an IC50 lower than 0.1 uM. The results of the drug screening and in vivo PDX validation demonstrated that ITF-2357 might be a promising drug targeted H3F3A G34W mutation MGCTBs. Conclusion: Our study demonstrates that PDX model maintained the same histologic and genetic features as those in the original patient. targeting HDAC through ITF-2357 effectively overcomes malignant GCTB progression in vitro and in vivo. Translational potential statement: As PDX retain the principal histologic and genetic characteristics of the primary tumors, mad it a valuable research tool in predictive clinical efficacy. In this study, we first established a malignant GCTB PDX model, which might further accelerate the progress of drug development in malignant GCTB.

Given the huge cost, long research and development (R&D) time and uncertain side effects of discovering new drugs, drug repositioning of those approved to treat diseases clinically as new drugs for other pathological conditions, especially cancers, is a potential alternative strategy. Disulfiram (DSF), an old drug used to treat alcoholism, has been found to exhibit anticancer activity and improve chemotherapeutic efficacy in cancers by an increasing number of studies. In addition, the combination of DSF and copper may be a more effective therapeutic strategy. In this study, we report the toxicity of the disulfiram/copper (DSF/Cu) complex to human osteosarcoma (OS) both in vitro and in vivo. DSF/Cu significantly inhibited the proliferation and clonogenicity of OS cell lines. Furthermore, the generation of reactive oxygen species (ROS) was triggered by DSF/Cu, and cell arrest, autophagy and apoptosis were induced in an ROS-dependent manner. The underlying mechanism of this process was explored, and DSF/Cu may mainly inhibit OS by inducing apoptosis by activating the ROS/JNK pathway. DSF/Cu also inhibited OS growth in a xenograft model with low levels of organ-related toxicities. These results suggest that the DSF/Cu complex could be an efficient and safe option for the treatment of OS in the clinic. [ABSTRACT FROM AUTHOR]

There are more than 100 sarcoma subtypes, each of which is uncommon and challenging to diagnose. Most patients with locally advanced and unresectable sarcomas are still treated with cytotoxic chemotherapy and have low long-term survival. Therefore, novel therapeutic methods are needed to improve the prognosis of patients with sarcomas. Immunotherapy is increasingly recognized as have an essential role in the treatment of malignant tumors. Emerging strategies, such as immune checkpoint inhibitors, vaccines, and adoptive cell therapies have been investigated for the treatment of sarcomas. Advances in these immunotherapies have provided a better understanding of how immuno-oncology can be best applied to the treatment of sarcomas, including their potential as adjuvant therapies in combination strategies. In this review, we discuss the immune microenvironment and how it relates to immunoresponsiveness, focusing on the advances in immunotherapy (immune checkpoint inhibitors, vaccines and adoptive cell therapies), the use of which will hopefully lead to improved outcomes for patients with sarcomas., Competing Interests: None., (AJTR Copyright © 2020.)

Osteoporosis is a common metabolic bone disease characterized by low bone mineral density (BMD) and microarchitectural deterioration of bone tissue, which leads to decreased bone strength and increased fracture risk. Osteoporosis mainly results from a disruption of the balance between bone formation mediated by osteoblasts and bone resorption mediated by osteoclasts. At present, the molecular mechanisms underlying osteoporosis are still not fully understood. Long noncoding RNAs (lncRNAs) are RNA molecules that exceed 200 nucleotides (nt) in length and have limited or no protein-coding capacity. Over the past decade, numerous lncRNAs have been demonstrated to participate in multiple biological processes and to play essential roles in the pathogenesis of various diseases. In this review, we summarize recent progress in research on lncRNAs in osteoporosis and mainly focus on their regulatory roles in osteogenesis and osteoclastogenesis. Moreover, we briefly discuss the potential clinical applications of lncRNAs in osteoporosis., Competing Interests: None., (AJTR Copyright © 2020.)

Schwann cells can be used to promote peripheral nerve repair. However, it is challenging to obtain abundant autologous Schwann cells without sacrificing nerve integrity. In this study, we isolated Schwann cells from murine inguinal adipose tissue and identified the cell phenotype and function in vivo and in vitro. Through H&E and immunofluorescence staining, we detected tiny nerve fibers and Schwann cells in adipose tissue. We evaluated the phenotype of spindle-shaped cells (Schwann cell-like cells, SCLCs) isolated from adipose tissue using immunofluorescence staining and real-time RT-PCR. The results showed that SCLCs expressed specific Schwann cell markers. Analysis of conditioned SCLC culture media showed that, similar to Schwann cells isolated from sciatic nerves, SCLCs secreted NGF and BDNF. SCLCs were harvested from CAG-EGFP transgenic mice and combined with silicone nerve conduits to repair sciatic nerve defects in wild-type mice. Six months post-surgery, we found EGFP-positive SCLCs forming myelin sheaths in the same way as sciatic nerve-derived Schwann cells. This research indicates the existence of Schwann cells in adipose tissue and identifies the spindle-shaped cells isolated from adipose tissue as Schwann cells using in vitro and in vivo evaluations. Thus, SCLCs might be promising seed cells for peripheral nerve tissue engineering., Competing Interests: None.