【Research and Results】Orthopaedic Oncology

神戸大学医学部整形外科 Kobe University Orthopaedic Surgery

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黒田良祐 教授 Prof. Ryosuke Kuroda

スタッフ Staff

整形外科教室の歩み Department of Orthopaedic Surgery

研究・業績 Research and Results

臨床研修を希望される方へ To Residents,Fellows,and Student

患者様へご案内 To Patients

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  Research and Results
Japanese

Greeting
Staff
 
Research and Results Sports & Lower Extremity Spine Adults Reconstruction
Orthopaedic Oncology Upper Extremity Trauma Reumatology
Division of Orthopaedic Oncology /
Research
Results

 
  ▲Division of Orthopaedic Oncology
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.

【Clinical Research】


Because bone and soft tissue sarcomas involve various tissue types and are uncommon compared with other cancers, establishing treatment strategies in a single facility with a limited number of patients is challenging. Nationwide clinical studies are necessary to establish standard treatments for bone and soft tissue sarcoma; to this end, we have been participating in the Japan Clinical Oncology Group (JCOG) since September 2014 to conduct clinical trials.

【Basic Research】

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.


Greeting
Staff
 
Research and Results Sports & Lower Extremity Spine Adults Reconstruction
Orthopaedic Oncology Upper Extremity Trauma Reumatology
Division of Orthopaedic Oncology /
Results
Research

Original Article

(1) Morishita M, Kawamoto T, Hara H, Onishi Y, Ueha T, Minoda M, Katayama E,Takemori T, Fukase N, Kurosaka M, Kuroda R, Akisue T. AICAR induces mitochondrial apoptosis in human osteosarcoma cells through an AMPK-dependent pathway. Int J Oncol. 2017 Jan;50(1):23-30

(2) Fujimoto T, Andoh T, Sudo T, Fujita I, Fukase N, Takeuchi T, Sonobe H, Inoue M, Hirose T, Sakuma T, Moritake H, Sugimoto T, Kawamoto T, Fukumori Y, Yamamoto S, Atagi S, Sakurai Y, Kurosaka M, Ono K, Ichikawa H, Suzuki M. Potential of boron neutron capture therapy (BNCT) for malignant peripheral nerve sheath tumors (MPNST). Appl Radiat Isot.2015 Dec :106:220-5

(3) Andoh T, Fujimoto T, Suzuki M, Sudo T, Sakurai Y, Tanaka H, Fujita I, Fukase N,他10名.Boron neutron capture therapy (BNCT) as a new approach for clear cell sarcoma (CCS) treatment: Trial using a lung metastasis model of CCS. Appl Radiat Isot. 2015 Dec;106:195-201.

(4) Minoda M, Kawamoto T, Ueha T, Kamata E, Morishita M, Harada R, Toda M, Onishi Y, Hara H, Kurosaka M, Akisue T. Antitumor effect of YM155, a novel small-molecule survivin suppressant, via mitochondrial apoptosis in human MFH/UPS. Int J Oncol.2015 Sep:47 (3) 891-99

(5) Onishi Y, Akisue T, Kawamoto T, Ueha T, Hara H, Toda M, Harada R, Minoda M, Morishita M, Sasaki R, Nishida K, Kuroda R, Kurosaka M. Transcutaneous application of CO2 enhances the antitumor effect of radiation therapy in human malignant fibrous histiocytoma. Int J Oncol. 2014 Aug;45(2):732-8.

(6) Onishi Y, Ueha T, Kawamoto T, Hara H, Toda M, Harada R, Minoda M, Kurosaka M, Akisue T. Regulation of mitochondrial proliferation by PGC-1α induces cellular apoptosis in musculoskeletal malignancies. Sci Rep. 2014 Jan 29;4:3916.

(7) Toda M, Kawamoto T, Ueha T, Kishimoto K, Hara H, Fukase N, Onishi Y, Harada R, Minoda M, Kurosaka M, Akisue T. 'Decoy' and 'non-decoy' functions of DcR3 promote malignant potential in human malignant fibrous histiocytoma cells. Int J Oncol. 2013 Sep;43(3):703-12.

(8) Harada R, Kawamoto T, Ueha T, Minoda M, Toda M, Onishi Y, Fukase N, Hara H, Sakai Y, Miwa M, Kuroda R, Kurosaka M, Akisue T. Reoxygenation using a novel CO2 therapy decreases the metastatic potential of osteosarcoma cells. Exp Cell Res. 2013 Aug 1;319(13):1988-97.

(9) Fujimoto T, Andoh T, Sudo T, Fujita I, Moritake H, Sugimoto T, Sakuma T, Akisue T, Kawabata S, Kirihata M, Suzuki M, Sakurai Y, Ono K, Fukumori Y, Kurosaka M, Ichikawa H. Boron neutron capture therapy (BNCT) selectively destroys human clear cell sarcoma in mouse model. Appl Radiat Isot. 2013 Mar;73:96-100.

(10) Onishi Y, Kawamoto T, Ueha T, Kishimoto K, Hara H, Fukase N, Toda M, Harada R, Minoda M, Sakai Y, Miwa M, Kurosaka M, Akisue T. Transcutaneous application of carbon dioxide (CO2) induces mitochondrial apoptosis in human malignant fibrous histiocytoma in vivo. PLoS One. 2012;7(11):e49189.

(11) Onishi Y, Kawamoto T, Kishimoto K, Hara H, Fukase N, Toda M, Harada R, Kurosaka M, Akisue T. PKD1 negatively regulates cell invasion, migration and proliferation ability of human osteosarcoma. Int J Oncol. 2012 Jun;40(6):1839-48.

(12) Kawamoto T, Fan C, Gaivin RJ, Levine MA, Lietman SA. Decreased SH3BP2 inhibits osteoclast differentiation and function. J Orthop Res. 2011 Oct;29(10):1521-7.

(13) Fukase N, Kawamoto T, Kishimoto K, Hara H, Okada Y, Onishi Y, Toda M, Kurosaka M, Akisue T. Protein kinase Cδ in tumorigenesis of human malignant fibrous histiocytoma. Oncol Rep. 2011 Nov;26(5):1221-6.

(14) Andoh T, Fujimoto T, Sudo T, Fujita I, Imabori M, Moritake H, Sugimoto T, Sakuma Y, Takeuchi T, Kawabata S, Kirihata M, Akisue T, Yayama K, Kurosaka M, Miyatake S, Fukumori Y, Ichikawa H. Boron neutron capture therapy for clear cell sarcoma (CCS): biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models. Appl Radiat Isot. 2011 Dec;69(12):1721-4.

(15) Fujimoto T, Andoh T, Sudo T, Fujita I, Imabori M, Moritake H, Sugimoto T, Sakuma Y, Takeuchi T, Sonobe H, Epstein AL, Akisue T, Kirihata M, Kurosaka M, Fukumori Y, Ichikawa H. Evaluation of BPA uptake in clear cell sarcoma (CCS) in vitro and development of an in vivo model of CCS for BNCT studies. Appl Radiat Isot. 2011 Dec;69(12):1713-6.


Case Report


(1) Hara H, Akisue T, Kawamoto T, Onishi Y, Fujioka H, Nishida K, Kuroda R, Kurosaka M, Akisue T. Reconstruction of the Midfoot Using a Free Vascularized Fibular Graft After En Bloc Excision for Giant Cell Tumor of the Tarsal Bones: A Case Report. J Foot Ankle Surg. 2015 Jul S1067-2516(15):183-0

(2) Fukui T, Kawamoto T, Hitora T, Yamagami Y, Akisue T, Yamamoto T. Polyostotic fibrous dysplasia with epiphyseal involvement in long bones: a case report. Case Rep Orthop. 2013;2013:715402.

(3) Hara H, Akisue T, Kawamoto T, Kurosaka M. Sequential MR Images and Radiographs of Epiphyseal Osteomyelitis in the Distal Femur of an Infant. Case Rep Radiol. 2013;2013:672815.

(4) Akisue T, Nishida K, Kishimoto K, Kawamoto T, Hara H, Hirata H, Kuroda R, Kurosaka M. Intraosseous epidermoid cyst in the femur arising after open fracture: A case report. JBJS Case Connect 2013 Oct 09; 3 (4): e120.

(5) Kishimoto K, Fujioka H, Akisue T, Kokubu T, Hara H, Nagura I, Inui A, Toyokawa N, Doita M, Kurosaka M. Reconstruction of the elbow joint with extracorporeal irradiated bone graft associated with low intensity pulsed ultrasound in malignant soft tissue tumor. J Shoulder Elbow Surg. 2012 Apr;21(4):e1-4.

(6) Akisue T, Kishimoto K, Kawamoto T, Hara H, Kurosaka M. Dedifferentiated chondrosarcoma with a high-grade mesenchymal component mimicking a gastrointestinal stromal tumor. Open J Pathol 2012 2: 90-95.

(7) Matsuzaki T, Akisue T, Kishimoto K, Kishimoto S, Imabori M, Hara H, Okada Y, Hitora T, Kuroda R, Kurosaka M, Yamamoto T. Intra-articular nodular fasciitis of the knee: a rare cause of recurrent hemarthrosis. Rheumatol Int. 2012 Jun;32(6):1691-4.


 
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