Hiromasa Kawana

Keio University, Edo, Tōkyō, Japan

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Publications (22)29.95 Total impact

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    ABSTRACT: Chronic inflammation is frequently associated with tumorigenesis in elderly people. By contrast, young people without chronic inflammation often develop tumors considered independent of chronic inflammation but driven instead by mutations. Thus, whether inflammation has a significant role in tumor progression in tumors driven by mutations remains largely unknown. Here we show that TNFα is required for the tumorigenesis of osteosarcoma, the most common tumor in children and adolescents. We show that transplantation of AX osteosarcoma cells, which harbor mutations driving c-Myc overexpression and Ink4a-deficiency, in wild-type mice promotes lethal tumorigenesis accompanied by ectopic bone formation and multiple metastases, phenotypes seen in osteosarcoma patients. Such tumorigenesis was completely abrogated in TNFα-deficient mice. AX cells have the capacity to undergo osteoblastic differentiation; however, that activity was significantly inhibited by TNFα treatment, suggesting that TNFα maintains AX cells in an undifferentiated state. TNFα inhibition of AX cell osteoblastic differentiation occurred through ERK activation, and a pharmacological TNFα inhibitor effectively inhibited both AX cell tumorigenesis and increased osteoblastic gene expression and increased survival of tumor-bearing mice. Lethal tumorigenesis of AX cells was also abrogated in IL-1α/IL-1β doubly deficient mice. We found that both TNFα and IL-1 maintained AX cells in an undifferentiated state via ERK activation. Thus, inflammatory cytokines are required to promote tumorigenesis even in mutation-induced tumors, and TNFα/IL-1 and ERK may represent therapeutic targets for osteosarcoma.Oncogene advance online publication, 16 December 2013; doi:10.1038/onc.2013.545.
    Oncogene 12/2013; · 7.36 Impact Factor
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    ABSTRACT: The targeting of antioxidant systems that allow stem-like cancer cells to avoid the adverse consequences of oxidative stress might be expected to improve the efficacy of cancer treatment. Here we show that head and neck squamous cell carcinoma (HNSCC) cells that express variant isoforms of CD44 (CD44v) rely on the activity of the cystine transporter subunit xCT for control of their redox status. xCT inhibition selectively induces apoptosis in CD44v-expressing tumor cells without affecting CD44v-negative differentiated cells in the same tumor. In contrast to CD44v-expressing undifferentiated cells, CD44v-negative differentiated cells manifest epidermal growth factor receptor (EGFR) activation and rely on EGFR activity for their survival. Combined treatment with inhibitors of xCT-dependent cystine transport and of EGFR resulted in a synergistic reduction of EGFR-expressing HNSCC tumor growth. Thus, xCT-targeted therapy may deplete CD44v-expressing undifferentiated HNSCC cells and concurrently sensitize the remaining differentiating cells to available treatments including EGFR-targeted therapy.
    Cancer Research 01/2013; · 8.65 Impact Factor
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    ABSTRACT: We report a case of auricular malformation treated by placement of an osseointegrated implant-supported epithesis using telenavigation and model simulation. A 66-year-old male suffering from auricular malformation and atresia auris of his right ear since birth visited our department in October 2006. The patient desired placement of an ear epithesis supported by osseointegrated implants. Computed tomographic (CT) scans were obtained for use in the navigation system as a prerequisite for the telenavigation and the operative plan was designed in consultation with an overseas oral and maxillofacial surgeon having rich experience in telenavigation surgery. We also constructed a preoperative simulation model and a mirror model of the unaffected left ear based on laser lithography to produce successful operation and symmetrical form of a symmetrical ear epithesis as contrast with identical to that on the left side. The osseointegrated implant surgery was carried out under telenavigation guidance. As a result, safe and accurate positioning of the implants was achieved and a symmetrical and elaborate epithesis could be fabricated.
    Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology. 01/2013;
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    ABSTRACT: An estimation of bone density is important for dental implant. CT value has been used in clinical and diagnostic as a quantitative evaluation method of bone density. In this paper, a method for estimating the CT value is proposed by modeling the relation between the cutting force and the CT value. The cutting force is calculated by the thrust force of the linear motor and the torque of the rotary motor. The estimated CT value can be obtained in real time by comparing between the force from reaction force observer and the formula of CT value with the pre-estimated parameters. The validity of the proposal was confirmed through experiments using wood mentioned in Misch's bone density classification. The experimental results indicated that the error of CT value estimation was ±91 HU and the estimation accuracy was 84 %.
    Industrial Electronics Society, IECON 2013 - 39th Annual Conference of the IEEE; 01/2013
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    ABSTRACT: Bone defects caused by traumatic bone loss or tumor dissection are now treated with auto- or allo-bone graft, and also occasionally by artificial bone transplantation, particularly in the case of large bone defects. However, artificial bones often exhibit poor affinity to host bones followed by bony union failure. Thus therapies combining artificial bones with growth factors have been sought. Here we report that platelet derived growth factor bb (PDGFBB) promotes a significant increase in migration of PDGF receptor α (PDGFRα)-positive mesenchymal stem cells/pre-osteoblastic cells into artificial bone in vivo. Growth factors such as transforming growth factor beta (TGFβ) and hepatocyte growth factor (HGF) reportedly inhibit osteoblast differentiation; however, PDGFBB did not exhibit such inhibitory effects and in fact stimulated osteoblast differentiation in vitro, suggesting that combining artificial bones with PDGFBB treatment could promote host cell migration into artificial bones without inhibiting osteoblastogenesis.
    Biochemical and Biophysical Research Communications 04/2012; 421(4):785-9. · 2.41 Impact Factor
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    ABSTRACT: Drilling is used in the medical field, especially in oral surgery and orthopaedics. In recent years, oral surgery involving dental implants has become more common. However, the risky drilling process causes serious accidents. To prevent these accidents, supporting systems such as robotic drilling systems are required. A telerobotic-assisted drilling system is proposed. An acceleration-based four-channel bilateral control system is implemented in linear actuators in a master-slave system for drill feeding. A reaction force observer is used instead of a force sensor for measuring cutting force. Cutting force transmits from a cutting material to a surgeon, who may feel a static cutting resistance force and vigorous cutting vibrations, via the master-slave system. Moreover, position scaling and force scaling are achieved. Scaling functions are used to achieve precise drilling and hazard detection via force sensation. Cutting accuracy and reproducibility of the cutting force were evaluated by angular velocity/position error and frequency analysis of the cutting force, respectively, and errors were > 2.0 rpm and > 0.2 mm, respectively. Spectrum peaks of the cutting vibration were at the theoretical vibration frequencies of 30, 60 and 90 Hz. The proposed telerobotic-assisted drilling system achieved precise manipulation of the drill feed and vivid feedback from the cutting force.
    International Journal of Medical Robotics and Computer Assisted Surgery 01/2012; 8(2):221-9. · 1.49 Impact Factor
  • Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 03/2011; 69(3):808-12. · 1.58 Impact Factor
  • Journal of Oral and Maxillofacial Surgery - J ORAL MAXILLOFAC SURG. 01/2011; 69(9).
  • Y. Kasahara, K. Ohnishi, H. Kawana
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    ABSTRACT: Recent years, a dental implant surgery has been focused and has been widely prevalent. At present, the limited doctor had acquired the skill for the surgery. It is because of that the dental implant surgery has risks of an accident. Therefore, the high quality skill for the surgery is required. A dental hand-piece (dental drill) is used to make the hole which is for insertion of an artificial tooth root. The wear of drill makes the surgery more difficult and it increases the risks of accident. It is because an exact and safe operation is disturbed by wear of drill. To prevent the accidents, an monitoring technology of a cutting force and a cutting power is desired. In this paper, a cutting power estimation system is proposed. The proposed system achieves the estimation of the cutting power without a torque sensor and a force sensor. To estimate the cutting power, dynamics of two-dimensional cutting based on a cutting theory in a manufacturing industry is introduced. A measurement of cutting force is achieved by disturbance observer (DOB). In the experiment, an evaluation of the drill wear is tried as one of the applications of the proposed method.
    IECON 2010 - 36th Annual Conference on IEEE Industrial Electronics Society; 12/2010
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    ABSTRACT: Burkitt's lymphoma is a malignant lymphoma of high malignancy grade and accounts for less than 1% of all cases of malignant lymphoma. Patients with malignant lymphoma in the oral and maxillofacial region including Burkitt's lymphoma, frequently present with gingival swelling, or a tumor mass/ulcers as the initial symptoms. We present an extremely rare case with bilateral mental nerve paralysis as the initial symptom without not only regional tumor but also brain and nose-pharyngeal area. This report indicates that the unexplained oral abnormalities such as inferior alveolar nerve hypoesthesia must be considered, potentially prodromal symptoms of Burkitt's lymphoma.
    Asian Journal of Oral and Maxillofacial Surgery 09/2010; 22(3):180–184.
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    ABSTRACT: Case report. To report 3 cases of malignant tumors in the upper cervical spine that were treated surgically by a combination of posterior tumor resection and stabilization and anterior tumor resection through a mandible-splitting approach after failed ion-beam radiation therapy. Few clinical reports have described in detail the postoperative complications associated with transoral surgical resection of tumors in the upper cervical spine after unsuccessful ion-beam radiation therapy. Three patients with malignant tumors in the upper cervical spine who had undergone ion-beam radiotherapy and experienced tumor recurrence were treated by a combination of posterior and anterior surgery through a mandible-splitting approach. One patient (patient 1, a 32-year-old man) had a hemangioendothelioma at the C2 and C3 level, whereas the other 2 patients (patient 2, a 66-year-old woman and patient 3, a 65-year-old man) had a chordoma at the C2 and C3 level. The intralesional but macroscopic total resection of the tumors was achieved in all 3 patients. However, serious complications developed after surgery, including deep wound infection, cerebrospinal fluid leakage, and meningitis in patient 1, prolonged swallowing difficulty, subsidence of the strut graft, and recurrence in patient 2, and deep wound infection and discitis causing progressive paralysis in patient 3. All patients underwent salvage surgery, including debridement of the wound in patient 1, posterior reinforcement using instrumentation and posterior tumor resection for the recurrent tumor in patient 2, and anterior debridement of the wound with a pedicle flap using the pectoral major muscle in patient 3 to address these problems. Patients 1 and 3 had no signs of recurrence at the time of a follow-up examination. Severe complications, mainly associated with the disturbance in healing of the retropharyngeal wall, were observed in all 3 patients. A preventive method, such as primary repair of the retropharyngeal wall using muscular/musculocutaneous flaps, should be considered for patients undergoing resection through a transoral approach after ion-beam irradiation.
    Spine 05/2010; 35(11):E505-9. · 2.16 Impact Factor
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    ABSTRACT: During oral rehabilitation by dental implantation for mandibles reconstructed with plate and screws, intensified stresses can develop at the implant-bone interfaces and fixation screw-bone interfaces that might cause complications at these interfaces. The present study aims to evaluate the stresses occurring at these sites using the finite element method. Ten computer-aided design models simulating 10 mandibles were produced and were termed normal models. Simulation surgery was performed on these normal models, where parts of the models were removed and replaced by fibula or reconstruction plates plus screws. Depending on the replaced part (body [B] or body and symphysis [BS]) and the reconstruction materials (fibula [Fib] or reconstruction plate [Plate]), the modified models were termed B-Fib, B-Plate, BS-Fib, and BS-Plate models, respectively. For each model, an implant was embedded in the first molar region. Stresses occurring at the implant-bone interfaces and fixation screw-bone interfaces on mastication were calculated using the finite element method and compared among the model groups. The stresses at the implant-bone interfaces showed no statistically significant differences among the 5 model groups. With the B-Plate and BS-Plate models, stresses at the fixation screw-bone interfaces were nearly twice as intense as those at the implant-bone interfaces. If it is allowed that complication risks correlate with stresses, fixation screws are more subject to failure than implants in performing implantation for mandibles reconstructed with a plate and fixation screws. Therefore, the fixation screws deserve special attention in performing oral rehabilitation for such patients.
    Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 03/2010; 109(3):346-56. · 1.50 Impact Factor
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    ABSTRACT: The surgical strategy for tumors located in or extending from the intracranial space to the infratemporal fossa was analyzed in 12 cases with various pathologies. A case of mandibular nerve schwannoma, which extended 1 cm below the external orifice of the foramen ovale, was completely removed via the epidural subtemporal approach without zygomatic osteotomy with partial removal of the middle cranial base. The inferior margin of infratemporal tumor could be accessed via the transcranial route with zygomatic or orbitozygomatic osteotomy without complications including facial nerve injury in nine cases, and the lowest level of the infratemporal tumors was approximately 4.5 cm below the outer surface of the middle cranial base. In five of these 9 cases (2 schwannomas, 1 myxoma, 1 chondrosarcoma, and 1 malignant peripheral nerve sheath tumor), the tumors were localized in the infratemporal fossa, and in the other 4 cases (2 meningiomas, 1 glioblastoma, and 1 ameloblastoma), the tumors extended to both the intracranial space and the infratemporal fossa. In two cases (recurrent jugular schwannoma and mandibular osteosarcoma), a combined transcranial and transcervical approach (mandibular swing approach) was essential, because the resection line of the lower margin was too far from the middle cranial base. These results indicate that the transcranial approach, with or without zygomatic or orbitozygomatic osteotomy (zygomatic infratemporal fossa approach), is safe and effective for removal of some infratemporal tumors, and that a combined transcranial and transcervical approach is useful for removing infratemporal tumors with extensive downward extension.
    Neurologia medico-chirurgica 12/2009; 49(12):580-6. · 0.49 Impact Factor
  • International Journal of Oral and Maxillofacial Surgery - INT J ORAL MAXILLOFAC SURG. 01/2009; 38(5):588-588.
  • Neurologia Medico-chirurgica - NEUROL MED-CHIR. 01/2009; 49(12):580-586.
  • International Journal of Oral and Maxillofacial Surgery - INT J ORAL MAXILLOFAC SURG. 01/2009; 38(5):559-560.
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    ABSTRACT: The balance between osteoclast and osteoblast activity is central for maintaining the integrity of bone homeostasis. Here we show that mice lacking dendritic cell specific transmembrane protein (DC-STAMP), an essential molecule for osteoclast cell–cell fusion, exhibited impaired bone resorption and upregulation of bone formation by osteoblasts, which do not express DC-STAMP, which led to increased bone mass. On the contrary, DC-STAMP over-expressing transgenic (DC-STAMP-Tg) mice under the control of an actin promoter showed significantly accelerated cell–cell fusion of osteoclasts and bone resorption, with decreased osteoblastic activity and bone mass. Bone resorption and formation are known to be regulated in a coupled manner, whereas DC-STAMP regulates bone homeostasis in an un-coupled manner. Thus our results indicate that inhibition of a single molecule provides both decreased osteoclast activity and increased bone formation by osteoblasts, thereby increasing bone mass in an un-coupled and a tissue specific manner.
    Biochemical and Biophysical Research Communications 12/2008; · 2.41 Impact Factor
  • Journal of Cranio-maxillofacial Surgery - J CRANIO MAXILLOFAC SURG. 01/2008; 36.
  • International Journal of Oral and Maxillofacial Surgery - INT J ORAL MAXILLOFAC SURG. 01/2007; 36(11):1089-1089.
  • Journal of Cranio-maxillofacial Surgery - J CRANIO MAXILLOFAC SURG. 01/2006; 34:150-150.