論文 - 相馬　智也

口腔扁平上皮癌においてFOXA1発現はxCT依存的腫瘍成長を抑制する

岡崎 章悟, 中野 友暉, 吉川 桃子, 相馬 智也, 莇生田 整治, 後飯塚 僚, 佐谷 秀行, 永野 修

日本癌学会総会記事 （(一社)日本癌学会）  80回   [E11 - 3] 2021年09月

ISSN  0546-0476

Undifferentiated carcinoma of the mandible detected simultaneously with the liver: A case report

Seiji Asoda, Mayu Morita, Tomoya Soma, Hitoshi Sato, Toshihiro Hasegawa, Taneaki Nakagawa, Akinori Hashiguchi, Hiromasa Kawana

Oral and Maxillofacial Surgery Cases （Elsevier BV）  7 （ 3 ） 100228 - 100228 2021年08月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2214-5419

　概要を見る

We herein report a rare case of undifferentiated carcinoma that originated in the mandible with the same pathological findings as seen in the liver. A 64-year-old man underwent surgery for a hepatic tumor in October 2006, and the pathological diagnosis was undifferentiated carcinoma. The patient was referred to our department in January 2007, when whole-body positron emission tomography/computed tomography showed the uptake of fluorodeoxyglucose in the right mandibular ramus. The patient underwent right hemimandibulectomy in April 2007. The resected tumor was also undifferentiated carcinoma. In May 2014, seven years after the lower mandibular operation, the tumor recurred at the site corresponding to the right mandibular ramus after resection, and tumor resection and right neck dissection were performed. As a result of the histopathological examination, the undifferentiated carcinoma findings were the same as before. There have been no signs of local recurrence or metastases for over six years since the second mandibular surgery.

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Synoviolin is not a pathogenic factor for auto-inflammatory diseases.

Matsumoto T, Sato Y, Kobayashi T, Ito E, Soma T, Kimura A, Miyamoto K, Kobayashi S, Harato K, Matsumoto M, Nakamura M, Niki Y, Miyamoto T

Biochemical and biophysical research communications （Elsevier BV）  558   183 - 188 2021年04月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0006-291X

　概要を見る

Auto-inflammatory syndromes are rare diseases characterized by arthritis and joint destruction, symptoms similar to but distinct from rheumatoid arthritis (RA). Therapeutic targets have not been well characterized for auto-inflammatory syndromes, although the E3 ligase Synoviolin was previously shown to be a novel therapeutic target for RA. Here, we show that Synoviolin loss has little impact on a model of auto-inflammatory diseases. We previously established such a model, the hIL-1 cTg mouse, in which IL-1 signaling was constitutively activated, and animals exhibit symptoms recapitulating auto-inflammatory syndromes such as major joint dominant arthritis. Here, we crossed hIL-1 cTg with Synoviolin flox'd mice to yield hIL-1 cTg/Synoviolin cKO mice. Synoviolin gene expression was ablated in adult hIL-1 cTg/Synoviolin cKO mice by injection of pIpC to activate Mx1 promoter-driven Cre recombinase. However, symptoms seen in hIL-1 cTg mice such as arthritis and joint destruction were not alleviated by targeting Synoviolin, ruling out Synoviolin as a therapeutic target for auto-inflammatory disease. Our results indicate that although similar, RA and auto-inflammatory diseases are different diseases, and treatment strategies should differ accordingly.

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Treatment with an active vitamin D analogue blocks hypothalamic dysfunction-induced bone loss in mice.

Eri Ito, Yuiko Sato, Tami Kobayashi, Satoshi Nakamura, Yosuke Kaneko, Tomoya Soma, Tatsuaki Matsumoto, Atushi Kimura, Kana Miyamoto, Hideo Matsumoto, Morio Matsumoto, Masaya Nakamura, Kazuki Sato, Takeshi Miyamoto

Biochemical and biophysical research communications （Elsevier BV）  542   48 - 53 2021年01月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0006-291X

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Estrogen deficiency can be caused by ovarian dysfunction in females. Mechanisms underlying osteoporosis in this condition have been characterized in animal models, such as ovariectomized mice and rats, although it remains unclear how hypothalamic dysfunction promotes osteoporosis. Here, we show that administration of a gonadotropin-releasing hormone antagonist (GnRHa) significantly decreases uterine weight, a manifestation of hypothalamic dysfunction, and promotes both cortical and trabecular bone loss in female mice in vivo. We also report that osteoclast number significantly increased in mice administered GnRHa, and that the transcription factor hypoxia inducible factor 1 alpha (HIF1α) accumulated in those osteoclasts. We previously reported that treatment of mice with the active vitamin D analogue ED71, also known as eldecalcitol, inhibited HIF1α accumulation in osteoclasts. We show here that in mice, co-administration of ED71 with GnRHa significantly rescued the reduced cortical and trabecular bone mass promoted by GnRHa administration alone. GnRHa-dependent HIF1α accumulation in osteoclasts was also blocked by co-administration of ED71. We conclude that hypothalamic dysfunction promotes HIF1α accumulation in osteoclasts and likely results in reduced bone mass. We conclude that treatment with ED71 could serve as a therapeutic option to counter osteoporotic conditions in humans.

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Food restriction reduces cortical bone mass and serum insulin-like growth factor-1 levels and promotes uterine atrophy in mice.

Eri Ito, Yuiko Sato, Tami Kobayashi, Satoshi Nakamura, Yosuke Kaneko, Tomoya Soma, Tatsuaki Matsumoto, Atushi Kimura, Kana Miyamoto, Hideo Matsumoto, Morio Matsumoto, Masaya Nakamura, Kazuki Sato, Takeshi Miyamoto

Biochemical and biophysical research communications （Elsevier BV）  534   165 - 171 2021年01月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0006-291X

　概要を見る

Low energy availability in female athletes often causes hypothalamic amenorrhea and osteoporosis, in turn promoting stress fractures. Mechanisms underlying these conditions remain unclear. Here we show that model mice subjected to food restriction (FR) or FR-plus-voluntary running exercise exhibit significantly reduced bone mineral density, cortical bone parameters and uterine weight than do control mice, and that these parameters worsen in the FR-plus-exercise group. Relative to controls, FR and FR-plus-exercise groups showed significantly lower mineral apposition rate and osteoclast number and significantly reduced serum insulin-like growth factor-1 (IGF1) levels. Outcomes were rescued by ED71 or 1.25(OH)2D3 treatment. Thus, we conclude that administration of active vitamin D analogues represents a possible treatment to prevent these conditions.

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Development of a microsurgery‐assisted robot for high‐precision thread traction and tension control, and confirmation of its applicability

Satoshi Hangai, Takahiro Nozaki, Tomoya Soma, Hidetaka Miyashita, Seiji Asoda, Masaki Yazawa, Kazuki Sato, Hiromasa Kawana, Kouhei Ohnishi, Eiji Kobayashi

The International Journal of Medical Robotics and Computer Assisted Surgery （Wiley）  17 （ 2 ） e2205 2020年11月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1478-5951

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Background: Microsurgery requires high skills for suturing using fragile threads, often within narrow surgical fields. Precise tension is required for good healing and to avoid the risk of thread breakage. Methods: To meet the demands, we developed a novel assist robot utilizing high-precision sensorless haptic technology. The robot adopts a cable-driven mechanism to maintain a distance from the surgical area and enhances compatibility with surgical equipment such as microscopes. The robot performance was verified through in vitro and in vivo experiments using a rat model. Results: The realization of precise tension control was confirmed in both experiments. In particular, in the in vivo experiments, the developed robot succeeded to produce a knot with an accurate tension of 0.66% error. Conclusions: The developed robot can realize to control traction force precisely. This technology might open up the window for a full assist robot for microsurgery with haptic feeling.

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Tooth extraction in mice administered zoledronate increases inflammatory cytokine levels and promotes osteonecrosis of the jaw.

Tomoya Soma, Ryotaro Iwasaki, Yuiko Sato, Tami Kobayashi, Satoshi Nakamura, Yosuke Kaneko, Eri Ito, Hiroyuki Okada, Hisato Watanabe, Kana Miyamoto, Morio Matsumoto, Masaya Nakamura, Seiji Asoda, Hiromasa Kawana, Taneaki Nakagawa, Takeshi Miyamoto

Journal of bone and mineral metabolism （Journal of Bone and Mineral Metabolism）  39 （ 3 ） 372 - 384 2020年11月

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り,  ISSN  09148779

　概要を見る

INTRODUCTION: Osteonecrosis of the jaw (ONJ) occurring after invasive dental treatment often adversely affects patients' activities of daily living. Long-term administration of strong anti-bone resorptive agents such as bisphosphonates prior to invasive dental treatment is considered an ONJ risk factor; however, pathological mechanisms underlying ONJ development remain unclear. MATERIALS AND METHODS: We developed an ONJ mouse model in which a tooth is extracted during treatment with the bisphosphonate zoledronate. RESULTS: We observed induction of apoptosis in osteocytes, resulting in formation of empty lacunae in jaw bones at sites of tooth extraction but not in other bones of the same mice. We also observed elevated levels of inflammatory cytokines such as TNFα, IL-6 and IL-1 in jaw bone at the extraction site relative to other sites in zoledronate-treated mice. We also report that treatment in vitro with either zoledronate or an extract from Porphyromonas gingivalis, an oral bacteria, promotes expression of inflammatory cytokines in osteoclast progenitor cells. We demonstrate that gene-targeting of either TNFα, IL-6 or IL-1 or treatment with etanercept, a TNFα inhibitor, or a neutralizing antibody against IL-6 can antagonize ONJ development caused by combined tooth extraction and zoledronate treatment. CONCLUSIONS: Taken together, the cytokine storm induced by invasive dental treatment under bisphosphonate treatment promotes ONJ development due to elevated levels of inflammatory cytokine-producing cells. Our work identifies novel targets potentially useful to prevent ONJ.

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Clear cell carcinoma in the retromolar area: A case report

Yuta Yasui, Seiji Asoda, Tomoya Soma, Hidetaka Miyashita, Toshihiro Hasegawa, Takehito Ouchi, Takeshi Karube, Takazumi Yasui, Katsuhiro Onizawa, Taneaki Nakagawa, Hiromasa Kawana

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology （Elsevier BV）  32 （ 6 ） 507 - 513 2020年08月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2212-5558

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Clear cell carcinoma (CCC) is a malignant neoplasm of epithelial origin classified in the 2017 World Health Organization (WHO) classification as a low-grade salivary gland tumor consisting of glycogen-rich clear cytoplasm. We report a case of a 34-year-old woman presented in our department following the complaint of a mass in her right retromolar area. The tumor measured 10-mm in diameter and was elastic and hard mass. Spontaneous pain or tenderness and desensitization of the tongue were not observed. Marginal resection of the mandible was performed under general anesthesia. The lesion was located in the minor salivary gland that is mainly composed of mucus glands and had a relatively clearly defined circular shape. However, there was no film fabrication in the surrounding resions. Additionally, atypical cells comprising a clear cytoplasm and irregularly shaped pyknotic nuclei were growing in sheet form or island form, and markedly hyalinized fascicles were observed between the alveolar walls of the atypical cells. Immunohistochemical stains revealed these tumor cells to be positive for epithelial cell markers but negative for myoepithelial ones. Considering the above findings, the tumor was diagnosed as CCC. The patient is currently free from disease 37 months after surgery.

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Pimozide combined with paclitaxel demonstrates a significant antitumor effect in head and neck squamous cell carcinoma

Nakamura Shintaro, Ozawa Hiroyuki, Yamasaki Juntaro, Okazaki Shogo, Yoshikawa Momoko, Soma Tomoya, Asoda Seiji, Nagano Osamu, Sekimizu Mariko, Saito Shin, Yoshihama Keisuke, Mikoshiba Takuya, Ogawa Kaoru, Saya Hideyuki

CANCER RESEARCH 80 （ 16 ）  2020年08月

ISSN  0008-5472

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Vitamin D protects against immobilization-induced muscle atrophy via neural crest-derived cells in mice.

Satoshi Nakamura, Yuiko Sato, Tami Kobayashi, Yosuke Kaneko, Eri Ito, Tomoya Soma, Hiroyuki Okada, Kana Miyamoto, Akihito Oya, Morio Matsumoto, Masaya Nakamura, Arihiko Kanaji, Takeshi Miyamoto

Scientific reports （Scientific Reports）  10 （ 1 ） 12242 - 12242 2020年07月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2045-2322

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Vitamin D deficiency is a recognized risk factor for sarcopenia development, but mechanisms underlying this outcome are unclear. Here, we show that low vitamin D status worsens immobilization-induced muscle atrophy in mice. Mice globally lacking vitamin D receptor (VDR) exhibited more severe muscle atrophy following limb immobilization than controls. Moreover, immobilization-induced muscle atrophy was worse in neural crest-specific than in skeletal muscle-specific VDR-deficient mice. Tnfα expression was significantly higher in immobilized muscle of VDR-deficient relative to control mice, and was significantly elevated in neural crest-specific but not muscle-specific VDR-deficient mice. Furthermore, muscle atrophy induced by limb immobilization in low vitamin D mice was significantly inhibited in Tnfα-deficient mice. We conclude that vitamin D antagonizes immobilization-induced muscle atrophy via VDR expressed in neural crest-derived cells.

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A case of spindle cell/pleomorphic lipoma on inferior border of the mandible

Kanako Munakata, Seiji Asoda, Shin Usuda, Hidetaka Miyashita, Tomoya Soma, Toshihiro Hasegawa, Chiharu Ogawa, Sadao Ohyama, Tomohiro Yamauchi, Miho Kawaida, Kaori Kameyama, Taneaki Nakagawa, Hiromasa Kawana

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology （Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology）  32 （ 1 ） 49 - 52 2020年01月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2212-5558

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© 2019 Asian AOMS(+) ASOMP(+) JSOP(+) JSOMS(+) JSOM(+) and JAMI Spindle cell lipomas and pleomorphic lipomas are uncommon and distinct variants of benign lipomas. Although spindle cell lipomas and pleomorphic lipomas were originally considered different entities, the recent WHO classification defines them as spindle cell/pleomorphic lipoma (SCL/PL). This is because of their similar clinical features and the existence of intermediate histopathological features between them. A 77-year-old male presented to our clinic with a painless swelling on the left inferior border of the mandible. Computed tomography revealed a clearly defined mass in the subcutaneous lesion. With a histopathological diagnosis of myxolipoma, demonstrated by biopsy, excisional surgery was performed under general anesthesia. The histopathology revealed SCL/PL with the presence of spindle cells and mature adipocytes. No tumor recurrence had been noted at two year after surgery.

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Clinical study of octacalcium phosphate and collagen composite in oral and maxillofacial surgery

Tadashi Kawai, Shinji Kamakura, Keiko Matsui, Masayuki Fukuda, Hiroshi Takano, Mitsuyoshi Iino, Shigeo Ishikawa, Hiromasa Kawana, Tomoya Soma, Eisaku Imamura, Hideki Kizu, Aya Michibata, Izumi Asahina, Keiichiro Miura, Norifumi Nakamura, Toshiro Kibe, Osamu Suzuki, Tetsu Takahashi

Journal of Tissue Engineering （SAGE Publications）  11   204173141989644 - 204173141989644 2020年01月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2041-7314

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Octacalcium phosphate and its collagen composite have been recognized as bone substitute materials possessing osteoconductivity and biodegradation properties. We evaluated the effectiveness of octacalcium phosphate and its collagen composite used for bone augmentation in major oral and maxillofacial surgeries in a clinical trial. Octacalcium phosphate and its collagen composite were used in cases of sinus floor elevation in 1- and 2-stage, socket preservation, cyst, and alveolar cleft procedures. A total of 60 patients were evaluated for effectiveness after the implantation of octacalcium phosphate and its collagen composite. Although sinus floor elevation in 1-stage, cyst, and alveolar cleft cases met the criteria for the judgment of success, sinus floor elevation in 2-stage and socket preservation groups did not meet the criteria in the initial evaluation. However, an additional evaluation for reconfirmation revealed the effectiveness of octacalcium phosphate and its collagen composite in those groups, and all evaluation results ultimately indicated the success of this clinical trial. Therefore, this clinical trial suggested that application of octacalcium phosphate and its collagen composite for oral and maxillofacial surgery was safe and effective and that octacalcium phosphate and its collagen composite could be a bone substitute candidate instead of autologous bone.

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Oral administration of N-acetyl cysteine prevents osteoarthritis development and progression in a rat model.

Yosuke Kaneko, Nobuharu Tanigawa, Yuiko Sato, Tami Kobayashi, Satoshi Nakamura, Eri Ito, Tomoya Soma, Kana Miyamoto, Shu Kobayashi, Kengo Harato, Morio Matsumoto, Masaya Nakamura, Yasuo Niki, Takeshi Miyamoto

Scientific reports （Scientific Reports）  9 （ 1 ） 18741 - 18741 2019年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2045-2322

　概要を見る

The number of osteoarthritis patients is increasing with the rise in the number of elderly people in developed countries. Osteoarthritis, which causes joint pain and deformity leading to loss of activities of daily living, is often treated surgically. Here we show that mechanical stress promotes accumulation of reactive oxygen species (ROS) in chondrocytes in vivo, resulting in chondrocyte apoptosis and leading to osteoarthritis development in a rat model. We demonstrate that mechanical stress induces ROS accumulation and inflammatory cytokine expression in cultured chondrocytes in vitro and that both are inhibited by treatment with the anti-oxidant N-acetyl cysteine (NAC). In vivo, osteoarthritis development in a rat osteoarthritis model was also significantly inhibited by oral administration of NAC. MMP13 expression and down-regulation of type II collagen in chondrocytes, both of which indicate osteoarthritis, as well as chondrocyte apoptosis in osteoarthritis rats were inhibited by NAC. Interestingly, osteoarthritis development in sham-operated control sides, likely due to disruption of normal weight-bearing activity on the control side, was also significantly inhibited by NAC. We conclude that osteoarthritis development in rats is significantly antagonized by oral NAC administration. Currently, no oral medication is available to prevent osteoarthritis development. Our work suggests that NAC may represent such a reagent and serve as osteoarthritis treatment.

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Acute odontogenic infection combined with crowned dens syndrome: a case report.

Tomoya Soma, Seiji Asoda, Moemi Kimura, Kanako Munakata, Hidetaka Miyashita, Taneaki Nakagawa, Hiromasa Kawana

Journal of medical case reports （Journal of Medical Case Reports）  13 （ 1 ） 143 - 143 2019年05月

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り

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BACKGROUND: Calcium pyrophosphate dihydrate crystal deposition disease is a condition in which calcium pyrophosphate dihydrate crystal is deposited in joint cartilage and ligaments. Calcium pyrophosphate dihydrate crystal deposition disease that involves calcification around the odontoid process of the second cervical vertebra is called crowned dens syndrome. Crowned dens syndrome is accompanied by fever in addition to acute and intense neck, posterior head, and temporal pain; thus, distinguishing crowned dens syndrome may be difficult in the presence of odontogenic infection. To the best of our knowledge, this is the first report describing a patient with crowned dens syndrome with coexisting odontogenic infection. CASE PRESENTATION: A 75-year-old Japanese woman was examined in the Emergency Department of this hospital due to a chief complaint of worsened buccal swelling on the left side. An odontogenic infection was considered, and she underwent her first examination. She presented with a body temperature of 37.4 °C, marked swelling and tenderness of her left lower eyelid through to her left cheek, and pain on the left temporal area. Blood tests revealed a leukocyte count of 6700/μL and a C-reactive protein level of 7.15 mg/dL. There was swelling and pain around the gingiva and acute purulent apical periodontitis of left maxillary second premolar. Cellulitis of the left cheek was diagnosed. After performing drainage of the pus, antibiotic treatment was initiated. Although her clinical symptoms improved, blood tests on day 9 of hospitalization revealed a leukocyte count of 6500/μL and a C-reactive protein level of 25.62 mg/dL, which were indicative of worsening symptoms. Computed tomography was performed to evaluate remote infection and images revealed a calcification around the odontoid process of her second cervical vertebra. When she was referred to the Orthopedic Surgery Department, pseudogout of the cervical spine was diagnosed. Subsequently, oral acetaminophen was initiated, and both her leukocyte count and C-reactive protein improved markedly. CONCLUSIONS: In the presence of persistent fever and abnormally high leukocyte and C-reactive protein indicative of an inflammatory reaction, coexistence of pseudogout should be considered. In particular, when symptoms of temporal pain are present, the possibility of pseudogout of the cervical spine must be considered in the differential diagnosis.

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A case of platelet transfusion refractoriness occurring after platelet transfusion for tooth extraction in myelodysplastic syndromes patient

Tomoya Soma, Seiji Asoda, Ryotaro Iwasaki, Hidetaka Miyashita, Mariko Inoue, Yuka Yamada, Kimio Uchiyama, Taneaki Nakagawa, Hiromasa Kawana

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology （Elsevier BV）  30 （ 6 ） 496 - 499 2018年11月

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り,  ISSN  2212-5558

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Myelodysplastic syndrome is an acquired hematopoietic disorder showing symptoms of pre-leukemia and refractory anemia. In the tooth extraction process of such cases, bleeding tendency due to pancytopenia, infection etc., becomes a problem. As such, a cautious approach is required. We have confirmed platelet transfusion refractoriness prior to tooth extraction in a myelodysplastic syndrome patient, and hereby report a case of tooth extraction following human leukocyte antigen (HLA)-compatible concentrated platelet transfusion. The patient was a 55-year-old female who was examined at our department due to a request for the extraction of tooth No. 36. Following consultation at the Hematology Department, platelet transfusion was performed as a pretreatment upon hospitalization. Increased body temperature, chills, shivers, and feelings of discomfort in the pharynx were observed. A close examination was performed due to a lack of increase in platelet count, and revealed platelet transfusion refractoriness caused by anti-HLA antibodies. Therefore, the patient was re-hospitalized and transfused with a platelet concentrate-HLA preparation. One hour later, an increase in platelet count was confirmed and the tooth extraction was performed. There was no evidence of bleeding or infection following extraction, and the prognosis was good.

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Dedifferentiated parosteal osteosarcoma of the maxilla: a case report and review of the literature.

Hidetaka Miyashita, Kazunari Yoshida, Tomoya Soma, Kaori Kameyama, Aya Sasaki, Masanori Hisaoka, Masaki Yazawa, Hideo Morioka, Moe Takahashi, Taneaki Nakagawa, Hiromasa Kawana

Journal of medical case reports （Journal of Medical Case Reports）  12 （ 1 ） 235 - 235 2018年08月

研究論文（学術雑誌）, 共著, 査読有り

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BACKGROUND: Parosteal osteosarcomas are usually low-grade tumors, however, sometimes they transform to high-grade tumors, which is named dedifferentiation. This phenomenon has been reported in long bones. Recently, we encountered a patient with dedifferentiated parosteal osteosarcoma occurring in the maxilla. Here, we report a first case of dedifferentiated parosteal osteosarcoma of the head and neck region. CASE PRESENTATION: A 45-year-old Japanese woman with a refractory bone lesion in the maxilla presented to our hospital. A biopsy showed atypical spindle cell proliferation involving dedifferentiated high-grade component, which was diagnosed as dedifferentiated parosteal osteosarcoma. Three cycles of neoadjuvant chemotherapy using ifosfamide and pirarubicin were performed followed by sub-total maxillectomy. Histopathological results showed that neoadjuvant chemotherapy was effective for high-grade component. The decision to perform adjuvant chemotherapy (cisplatin and pirarubicin) was made because distant metastasis has been reported, even in cases with dedifferentiated parosteal osteosarcoma in which complete necrosis of high-grade component was achieved due to neoadjuvant chemotherapy. There was no recurrence 15 months after surgery. CONCLUSIONS: Dedifferentiated parosteal osteosarcoma can occur in the head and neck region. Chemotherapy including anthracycline anticancer agent could be effective for high-grade component of dedifferentiated parosteal osteosarcoma.

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Recurrent Spindle Cell Carcinoma Shows Features of Mesenchymal Stem Cells

T. Ouchi, S. Morikawa, S. Shibata, M. Takahashi, M. Yoshikawa, T. Soma, H. Miyashita, W. Muraoka, K. Kameyama, H. Kawana, Y. Arima, H. Saya, H. Okano, T. Nakagawa, S. Asoda

Journal of Dental Research （SAGE Publications Inc.）  97 （ 7 ） 779 - 786 2018年07月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1544-0591

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This study investigated a case of spindle cell carcinoma (SpCC) in tongue pathological lesions. The patient experienced a local recurrence and distant metastasis after surgical intervention. Although standard chemotherapy was administered, a granulomatous mass continued to develop. This aggressive growth led to survival of the tumor. Secondary debulking surgery was performed to improve the patient’s quality of life at the request of the patient. Using a tissue sample derived from the secondary debulking surgery, we performed an analysis of the tumor’s cell surface antigens, differentiation potential, metastatic ability, and inhibition potential by anticancer reagents. In vitro analysis revealed that the cell population grown under adherent culture conditions expressed the mesenchymal stem cell (MSC) markers CD73, CD90, and CD105. The cell line established from this SpCC contained colony-forming unit fibroblasts (CFU-Fs) and exhibited multipotent differentiation into several mesenchymal lineages, including bone, cartilage, and fat. The SpCC cells also displayed vigorous mobilization. These characteristics suggested that they had the differentiation potential of mesenchymal cells, especially MSCs, rather than that of epithelial cells. The surgical specimen analyzed in this study resisted the molecular target reagent cetuximab, which is an epidermal growth factor receptor inhibitor. This clinical insight revealed that chemotherapy-resistant SpCC cells have different characteristics compared to most other cancer cells, which are sensitive to cetuximab. Our cell death assay revealed that SpCC cell death was induced by the anticancer drug imatinib, which is known to inhibit protein tyrosine kinase activity of ABL, platelet-derived growth factor receptor α (PDGFRα), and KIT. Here, we report recurrent SpCC with characteristics of MSCs and potential for treatment with imatinib.

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本態性血小板血症患者に発生した口底癌の1例

長谷川稔洋, 宗像花楠子, 小川千晴, 家崎憲博, 莇生田整治, 宮下英高, 相馬智也, 福田仁, 吉田俊一, 内田育宏, 寺尾保信, 大山定男

日本口腔腫瘍学会誌 （(一社)日本口腔腫瘍学会）  30 （ 4 ） 59‐166(J‐STAGE) - 166 2018年

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0915-5988

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The onset risk of carcinoma in patients continuing tacrolimus topical treatment for oral lichen planus: a case report

Mayu Morita, Seiji Asoda, Kazuyuki Tsunoda, Tomoya Soma, Taneaki Nakagawa, Masayori Shirakawa, Hirofumi Shoji, Hisao Yagishita, Takeji Nishikawa, Hiromasa Kawana

Odontology （Springer Tokyo）  105 （ 2 ） 262 - 266 2017年04月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1618-1247

　概要を見る

Oral lichen planus is a chronic inflammatory mucocutaneous disease. Topical use of steroids and other immuno-modulating therapies have been tried for this intractable condition. Nowadays, tacrolimus ointment is used more commonly as a choice for treatment. However, a number of discussions have taken place after tacrolimus was reported to be carcinogenic. This report describes a patient who applied tacrolimus ointment to the lower lip after being diagnosed with oral lichen planus in 2008, and whose lesion developed squamous cell carcinoma in 2010. Since the relationship between tacrolimus and cancer development has been reported in only a few cases, including this case report, the clinician must be careful selecting tacrolimus as a second-line treatment for oral lichen planus.

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IGF-II産生非膵島細胞腫瘍性低血糖症を発症した上顎歯肉癌の1例

宮下英高, 莇生田整治, 森泰昌, 山田有佳, 相馬 智也and 河奈裕正

日本口腔外科学会雑誌 62 （ 9 ） 448 - 453 2016年09月

共著,  ISSN  0021-5163

　概要を見る

72歳男。上顎左側歯肉の腫脹・疼痛を主訴に受診し、諸検査により歯肉癌(中分化型扁平上皮癌)と診断した。手術を勧めたが、同意が得られず、他院での治療を希望したため当科での治療はいったん終了としたが、他院を受診することなく、初診の4ヵ月後に当科を再受診した。腫瘍は増大しており、鼻腔や外側翼突筋に浸潤していた。手術は希望しなかったため化学放射線療法を行い、治療終了3週間後に突然見当識障害が出現した。血糖値の著明な低下を認めたため精査を行い、低血糖発作時にインスリンの過剰分泌を認めないことや、血中IGF-I分泌が抑制されていることに加え、大きな膵外腫瘍(歯肉癌)を認めていることからIGF-II産生非膵島細胞腫瘍性低血糖症と診断した。診断後に追加で歯肉癌生検標本のIGF-II免疫染色を行ったところ陽性であった。