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Title: Current status of molecular testing for the diagnosis of bone tumors
Authors: David Suster1, Saul Suster2
Affiliations: 1Mount Sinai Medical Center and Icahn School of Medicine, New York, NY 10029, USA.
2Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Abstract: Genetic events have been increasingly found to play a pivotal role in the process of carcinogenesis in bone and soft tissue tumors. In recent years, numerous advances have been made in the characterization of some of the molecular alterations involved in the histogenesis of bone tumors. Such findings play a significant role in the diagnosis and characterization of such lesions. In addition to serving to confirm the diagnosis in difficult or equivocal cases, they may also have some bearing for the prognosis and management of these patients, particularly in this era of personalized medicine in which specific treatment plans can be devised with the use of targeted therapies. This review will explore the principal new findings in the field of molecular genetics of bone tumors and their current impact on the management of these patients.
Type: Research Article
Title: Multiplexed bioluminescence imaging of cancer cell response to hypoxia and inflammation in a bone metastasis mouse model during treatment with zoledronic acid
Authors: Shinae Kizaka-Kondoh
Affiliations: School of Life Science and Technology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
Abstract: Therapeutic agents suppressing bone remodeling have been clinically approved to delay metastatic progression and skeletal-related events in patients with bone metastasis. However, the therapeutic agents including zoledronic acid (ZA) are insufficient to regress established bone metastasis. Therefore, new treatment strategies are desired, and elucidating the status of metastatic bone cancer cells during metastatic progression can help develop strategies. Here, we have developed a unique multiplexed bioluminescence reporter system (MRS) by using three luciferase reporter genes, which allows noninvasive, quantitative and long-term monitoring of tumor growth and the activities of NF-κB and hypoxia-inducible factor (HIF), key transcriptional factors in response to inflammation and hypoxia, respectively. PC-3/MRS, a human prostate cancer cell line that stably retains MRS, was applied to an intra-caudal artery injection bone metastasis model using immune-deficient mice. We demonstrated long-term (< 1 month) noninvasive monitoring of MRS signals emanating from bone metastasis in hind limbs. In addition, MRS imaging revealed that ZA treatment suppresses NF-κB and HIF activities as well as the growth of bone metastasis. Taken together, MRS successfully visualized activities of NF-κB and HIF in PC-3/MRS in bones and could be a powerful tool to develop new therapeutic strategies for bone metastasis.
Title: Photodynamic therapy as an alternative tool against osteosarcoma: concepts and recent advances
Authors: Lucas D. Dias1, Júlia M. Veronese2
Affiliations: 1São Carlos Institute of Physics, University of São Paulo, São Carlos, Brazil.
2Faculty of Medicine, University of Gurupi, Gurupi, Brazil.
Abstract: Osteosarcoma is one of the most common primary malignancies of bone in childhood and adolescence. This disease shows a poor prognosis for patients with metastatic or recurrent disease (survival < 20%). In this sense, a novel approach to treat this disease has been evaluated, namely, photodynamic therapy. This alternative and efficient therapeutic tool is based on use of a photosensitizing molecule, molecular oxygen, and an appropriate source light yielding oxidative species able to combat cancer cells. In this review, some of the important biochemical and clinical events involved in osteosarcoma as well as concepts and clinical applications of photodynamic therapy will be reported and discussed. Moreover, we review the last 5 years (2015-2019) regarding the application of photodynamic therapy against osteosarcoma.
Title: Proximal humeral reconstructive options in orthopedic oncology
Authors: Sridhar Pinnamaneni, Timothy A. Damron
Affiliations: Department of Orthopedic Surgery, Upstate Medical University, Upstate Bone and Joint Center, East Syracuse, NY 13057, USA.
Abstract: Proximal humeral reconstructive options following radical resection of proximal humeral primary and metastatic bone malignancies have evolved over time. With the relatively recent advent of the reverse total shoulder arthroplasty (rTSA), this technique has been increasingly employed in this setting over hemi-arthroplasty techniques. An array of options, including proximal humeral allograft-prosthetic composites (including both rTSA and hemi's), megaprostheses, and osteoarticular allografts will be reviewed from the perspective of their indications, techniques, complications, and published results. An extensive case-based pictorial presentation will illustrate these options.
Title: Targeting EZH2 for the treatment of soft tissue sarcomas
Authors: Magdalena Karolak1, Ian Tracy1, JanetShipley2, Zoë S Walters1
Affiliations: 1Translational Epigenomics Team, Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
2Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, UK.
Abstract: Soft tissue sarcomas (STS) are a heterogenous group of rare malignancies of mesenchymal origin, affecting both children and adults. The majority of STS have a poor prognosis and advanced stage at the time of diagnosis. Standard treatments for STS largely constitute tumour resection with chemotherapy and/or radiotherapy, and there has been little significant advancement in the application of novel therapies for treatment of these tumours. The current multimodal approach to therapy often leads to long-term side effects, and for some patients, resistance to cytotoxic agents leads to local recurrence and/or metastasis. There is, therefore, a need for novel therapeutic strategies for the treatment of STS. Recent advances in epigenetics have implicated the histone methyltransferase, EZH2, in the development and progression of diseases such as breast cancer, lymphoma and more recently STS. Here we will discuss the current literature surrounding EZH2 in soft tissue tumours, including high expression of EZH2 in STS and correlation of EZH2 with specific features of malignancy (metastasis, histological grade, prognosis). The effects of targeting EZH2 using RNA interference and small molecule inhibitors will also be reviewed and the potential for the use of EZH2 inhibition in therapeutic strategies for STS patients will be discussed.