Bone and soft tissue tumors, particularly malignant diseases, markedly affect patients' lives. Our orthopedic oncology group belongs to four senior staff and three PhD students, treating tumors of the bone and soft tissues arising in the extremities and the trunk. Diagnosis and treatment of bone and soft tissue tumors demand knowledge and expertise due to difficulties in pathological diagnosis, as well as specialized treatments, such as systemic chemotherapy, imaging-based surgical resection, and limb salvage surgery. In these days, the number of cases treated for bone metastasis has increased in our department because overall survival of cancer patients has improved with the development of new therapeutics, such as targeted therapies and immune checkpoint inhibitors. Taking advantage of the multidisciplinary expertise of university hospitals, our goal is to improve treatment outcomes in patients with refractory tumors.
Recent advances in diagnostic imaging and surgical margin assessment have improved treatment outcomes in patients, as indicated by the increases in survival and functional preservation. However, because a number of cases are still difficult to treat, a breakthrough in research would significantly improve treatment outcomes in patients. We focus on basic research with the ultimate goal of translating our findings into clinical practice. Our current research interests are in the following areas:
Transcutaneous application of carbon dioxide for treatment of bone and soft tissue sarcomas and metastatic bone tumors
Hypoxia in malignant tumors regulates tumor pathogenesis, disease progression, and metastasis. We previously demonstrated that the transcutaneous application of carbon dioxide reduces hypoxic conditions and enhances therapeutic responses using mouse models of malignant fibrous histiocytoma and lung metastasis in osteosarcoma. We are currently investigating the antitumor effects of the transcutaneous application of carbon dioxide and the underlying inhibitory mechanisms of bone destruction in a mouse model of bone metastasis using breast cancer cell lines.
Antitumor effects of survivin inhibition and smac mimetics in bone and soft tissue sarcoma
Suppression of survivin, which belongs to the inhibitor of apoptosis protein (IAP) family, has been implicated in increased cell death and enhanced chemosensitivity. We are currently investigating the role of survivin in bone and soft tissue sarcoma as a potential therapeutic target. In addition, we are investigating the use of a mimetic of smac, an endogenous antagonist of the IAP family, in bone and soft tissue sarcoma and its synergistic effects with existing chemotherapeutics.
Antitumor effects of AICAR in bone and soft tissue sarcoma
Malignant tumors have long been known to rely on glycolysis for energy metabolism instead of mitochondrial oxidative phosphorylation; however, the underlying mechanisms of the metabolic switch remain unclear. We are currently investigating the antitumor effect of AICAR, an AMPK agonist that promotes mitochondrial proliferation, by regulating mitochondrial biogenesis.
The effect of a novel drug delivery system using Low Adhesive Scaffold Collagen (LASCol) as a drug carrier for the treatment of bone metastasis
This research is conducted in collaboration with the Faculty of Biology-Oriented Science and Technology, Kinki University, where the drug carrier was developed. The ultimate goal of this research is to develop an innovative treatment for bone metastasis using a novel drug delivery system.