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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 for 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. Dias
Affiliations: Coimbra Chemistry Centre, CQC, Departament of Chemistry, Faculdade de Ciências e Tecnologia, Universidad de Coimbra, Coimbra 3004⁻535, Portugal.
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, novel approaches to treat this disease have 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: Phosphoinositide signal transduction pathway and osteosarcoma metastases
Authors: Vincenza Rita Lo Vasco
Affiliations: Morphology Section, Department of Biomedical, Metabolic Sciences and Neuroscience, University of Modena and Reggio Emilia, Modena, Italy.
Abstract: Metastasis spreading confers worse prognosis to the clinical outcome in patients affected with osteosarcoma, the most common primary bone tumour in childhood and adolescence. The identification of the molecules involved in spreading might help to understand the mechanisms of tumour dissemination, opening the way to novel therapeutic strategies. The activation of ezrin-radixin-moesin (ERM) family proteins was proposed to occur after interaction with molecules belonging to Phosphoinositide signal transduction pathway. The Phosphatydil inositol (4,5) bisphosphate (PIP2), a crucial molecule in PI pathway, was indicated to be involved in the stabilization of ERM proteins or a more efficient receptor binding. The levels of PIP2 in the pathway represent a critical element for regulation of a number of cell events. PIP2 levels are regulated by means of enzymes, including the PI-specific Phospholipase C family. The reduction of PIP2 levels induces ERM protein dissociation from the membrane. PI-PLC enzymes contribute to regulate this event (Brown 2001). The role of PI signal transduction molecules in osteosarcoma metastases will be discussed.
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.