|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.
||▲Division of Orthopaedic
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.
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
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
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.
|Division of Orthopaedic
(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.
(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
(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.
(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.
(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.
(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.