Tomomi Ichikawa

Publications (7)5.19 Total impact

• Article: The Sirt1 Activator SRT1720 Suppresses Inflammation in an OVA-induced Mouse Model of Asthma.

  Tomomi Ichikawa, Ryuji Hayashi, Kensuke Suzuki, Shingo Imanishi, Kenta Kambara, Seisuke Okazawa, Minehiko Inomata, Toru Yamada, Yu Yamazaki, Yukiko Koshimizu, Toshiro Miwa, Shoko Matsui, Isao Usui, Masaharu Urakaze, Yuji Matsuya, Masakiyo Sasahara, Kazuyuki Tobe
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  ABSTRACT: SUMMARY AT A GLANCE: We investigated the effect of Sirt1 activator SRT1720 on an inflammatory model of asthma. SRT1720 suppressed inflammatory cell infiltration and cytokine production in an OVA-challenged mouse model. SRT1720 and resveratrol also directly suppressed OVA-induced splenocyte proliferation and TNFα and IL-6 production. SRT1720 has potential as a therapeutic drug for asthma. ABSTRACT: Background and Objective:  In asthma, reduced histone deacetylase (HDAC) activity and enhanced histone acetyltransferase (HAT) activity in the lungs have been reported. However, the precise function of Sirtuin 1 (Sirt1), a class III HDAC, and the effect of the Sirt1 activator SRT1720 on allergic inflammation have not been fully elucidated. Methods:  We investigated the effect of SRT1720, a synthetic activator of Sirt1, in a ovalbumin (OVA)-induced asthma mouse model. We also examined the effect of SRT1720 and resveratrol on OVA stimulation in splenocytes from OVA-sensitized and challenged mice. Results:  In OVA-sensitized and challenged mice (OVA-mice) compared with saline-sensitized and challenged mice (control-mice), Sirt1 mRNA expression in the lungs was decreased (P =0.02) while cellular infiltration, airway eosinophilia and bronchoalveolar lavage (BAL) fluid levels of Interleukin (IL)-4, IL-5 and IL-13 were increased (P< 0.01). In OVA-mice, SRT1720 treatment decreased total and eosinophil cell counts and IL-5 and IL-13 levels in the BAL fluid compared with the vehicle treatment (P< 0.05). In OVA-mice, SRT1720 treatment also decreased inflammatory cell lung infiltrates histologically (P =0.002). Both SRT1720 and resveratrol suppressed OVA-induced cell proliferation and IL-6 (P< 0.05) and tumor necrosis factor alpha (TNFα) (P< 0.05) production in splenocytes (P< 0.01). Conclusions:  The Sirt1 activator SRT1720 suppressed inflammatory cell infiltration and cytokine production in an OVA-induced mouse model of asthma. SRT1720 and resveratrol suppressed OVA-induced splenocyte proliferation and TNFα and IL-6 production. Sirt1 activators might have beneficial effects in asthmatics by suppressing inflammation. © 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.
  Respirology 10/2012; · 2.42 Impact Factor
• Article: Miliary brain metastasis presenting with calcification in a patient with lung cancer: a case report.

  Minehiko Inomata, Ryuji Hayashi, Kenta Kambara, Seisuke Okazawa, Shingo Imanishi, Tomomi Ichikawa, Kensuke Suzuki, Toru Yamada, Toshiro Miwa, Tatsuhiko Kashii, Shoko Matsui, Kazuyuki Tobe, Masakiyo Sasahara
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  ABSTRACT: Miliary brain metastasis is an extremely rare form of brain metastasis which can present with atypical imaging findings. We report the case of a patient with miliary brain metastasis of lung cancer showing calcification in metastatic lesions. A 68-year-old Japanese woman was diagnosed with lung adenocarcinoma. Brain computed tomography revealed multiple small calcified lesions in both cerebral hemispheres. Mutation of the epidermal growth factor receptor gene (exon 21, L858R) in lung cancer cells was detected, and treatment with gefitinib was initiated. A partial response was observed; however, the patient was readmitted to our hospital because of regrowth of the primary lesion and complaints of nausea, headache, and difficulty walking. Brain magnetic resonance imaging revealed scattered tiny nodules enhanced by gadolinium. A diagnosis of leptomeningeal carcinomatosis was made on the basis of cerebrospinal fluid cytology. The patient's general status worsened, and she died 356 days after the day of first medical examination. Upon autopsy, the brain was found to be edematous and swollen. Lung carcinoma cells were diffusely disseminated on the meningeal surface. Metastatic foci of small nodular form, accompanied by calcifications, were also found in the brain parenchyma. We diagnosed miliary metastasis of lung carcinoma. To the best of our knowledge, this is the third report of calcified miliary brain metastasis confirmed by autopsy. We describe calcified lesions that increased in size during the clinical course of nine months. Brain computed tomography findings that reveal multiple small calcified lesions in patients with malignancy should raise suspicion of miliary brain metastasis.
  Journal of Medical Case Reports 09/2012; 6(1):279.
• Article: SRT1720, a SIRT1 activator, promotes tumor cell migration, and lung metastasis of breast cancer in mice.

  Kensuke Suzuki, Ryuji Hayashi, Tomomi Ichikawa, Shingo Imanishi, Toru Yamada, Minehiko Inomata, Toshiro Miwa, Shoko Matsui, Isao Usui, Masaharu Urakaze, Yuji Matsuya, Hirofumi Ogawa, Hiroaki Sakurai, Ikuo Saiki, Kazuyuki Tobe
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  ABSTRACT: Silent information regulator 2 (SIR2) is a highly conserved protein, the mammalian orthologue of which, SIRT1, exhibits histone deacetylase activity. SIRT1 is involved not in only longevity due to caloric restriction but in a variety of diseases such as diabetes, cardiovascular dysfunction and neurodegeneration. However, accumulating evidence shows that SIRT1 is overexpressed in various types of malignant cells, and its inhibitors suppress the growth of tumor cells. The relationship between SIRT1 and metastasis remains to be clarified. Here, we examined the effect of SRT1720, a SIRT1 activator, on lung metastasis of breast cancer cells. 4T1 breast cancer cells were subcutaneously implanted into syngeneic BALB/c mice and SRT1720 was administered alone or with an antitumor agent, cisplatin. As expected, cisplatin decreased the lung metastasis score, whereas SRT1720 increased metastasis irrespective of cisplatin. In the primary tumors, cisplatin suppressed the mRNA level of angiopoietin-like protein 4 (angptl4), a lung metastasis-promoting gene product of breast cancer, but SRT1720 reduced the effectiveness of cisplatin. The results obtained with animal experiments were in accordance with those in human cancer cells; SRT1720 significantly increased the amount of VEGF secreted from MDA-MB-231 cells. Moreover, a transendothelial cell migration assay showed that SRT1720 promotes the migration of MDA-MB-231 cells across an endothelial cell layer despite the presence of cisplatin. These findings imply that SRT1720 promotes the pulmonary metastasis of breast cancer cells and SIRT1 may be an important target for suppressing metastasis to the lung.
  Oncology Reports 06/2012; 27(6):1726-32. · 1.84 Impact Factor
• Article: A history of ischemic heart disease is a common cause of wheezing in the elderly of a Japanese local community.

  Minehiko Inomata, Yukio Kawagishi, Kotaro Tokui, Yasuaki Masaki, Chihiro Taka, Kenta Kambara, Seisuke Okazawa, Shingo Imanishi, Tomomi Ichikawa, Kensuke Suzuki, Toru Yamada, Minoru Iwata, Isao Usui, Shigeki Sumi, Hideki Origasa, Shoko Matsui, Ryuji Hayashi, Kazuyuki Tobe
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  ABSTRACT: We conducted a cross-sectional study to investigate which factors have a significant impact on wheezing and QOL in the elderly of a Japanese local community. In 2008, 527 participants (250 participants aged 45 to 64 years and 277 participants aged 65 to 88 years) responded to the questionnaire regarding wheezing and disease history. QOL was evaluated by the Short Form-8. The participants underwent airway reversibility testing. The plasma levels of IgE were measured. The plasma levels of N-terminal-pro-B-type natriuretic peptide were measured in twenty-one participants with a history of ischemic heart disease and in thirty-five age-matched participants without that history. Wheezing was reported by 50 (9.5%) participants and was associated with a lower score of QOL. In multivariate analysis, wheezing was associated with sex (OR 3.12, CI 1.10-9.67) and a history of bronchial asthma (OR 22.3, CI 6.50-84.0) among participants aged 45 to 64 years. Among participants aged 65 and over, wheezing was associated with a history of bronchial asthma (OR 4.86, CI 1.39-15.1) and ischemic heart disease (OR 5.12, CI 1.61-15.0). Participants with both a history of ischemic heart disease and wheezing showed higher levels of N-terminal-pro-B-type natriuretic peptide. Airway reversibility was only associated with a history of ischemic heart disease (OR 4.65, CI 1.26-17.6). It is suggested that bronchial asthma and heart disease are both significant causes of wheezing and affect the QOL in the elderly of a Japanese local community.
  Internal Medicine 01/2011; 50(24):2975-81. · 0.94 Impact Factor
• Article: [A case of hyper-IgE syndrome complicated by chronic necrotizing pulmonary aspergillosis].

  Hirokazu Taniguchi, Minehiko Inomata, Tomomi Ichikawa, Hitoshi Abo, Saburo Izumi
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  ABSTRACT: A 46-year-old man afflicted with recurring infection and bone fracture consulted our hospital because of general malaise and increase of sputum. He was given a diagnosis of chronic necrotizing pulmonary aspergillosis, and underwent right lower lobectomy. Six months later, chronic necrotizing pulmonary aspergillosis become exacerbated. Slightly improvement was obtained with voriconazole. Two months later, this disease become reactivated, and slightly improved with itraconazole and amphotericin B. Subsequently, hyper-IgE syndrome was diagnosed in him by pathognomonic face, recurring infection and bone fracture, chronic necrotizing pulmonary aspergillosis, elevated IgE, and eosinophilia. We suggested that the pathogenic cause of chronic necrotizing pulmonary aspergillosis in this case was hyper-IgE syndrome. After that, chronic necrotizing pulmonary aspergillosis was reexacerbated. We added micafungin, increased itraconazole, interferon gamma, and so on. As a result, his chest radiograph and symptoms improved slowly. Cases of hyper-IgE syndrome are rare.
  Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 05/2008; 46(4):302-7.
• Article: [A case of chest pain variant asthma].

  Hirokazu Taniguchi, Minehiko Inomata, Tomomi Ichikawa, Hitoshi Abo, Saburo Izumi
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  ABSTRACT: A 45-year-old woman afflicted with bronchial asthma consulted our hospital because of severe constricting pain at the sternal area. Her chest pain improved with montelukast, and she was diagnosed to have chest pain variant asthma. Chest pain variant asthma is rare.
  Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 12/2007; 45(11):866-8.
• Article: [Case of both T- and B-cell markers positive pyothorax-associated lymphoma].

  Hirokazu Taniguchi, Tomomi Ichikawa, Saburo Izumi
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  ABSTRACT: A 84-year-old man with a history of pulmonary tuberculosis admitted to our hospital due to painful swelling in right front chest wall. His chest CT shows a tumor at right chest wall and right chronic empyema. Histopathologic findings from biopsy revealed both T- and B-cell markers positive non-Hodgkin's lymphoma, and we diagnosed him pyothorax-associated lymphoma. Irradiation resulted in tumor shrinkage, and a pain of tumor disappeared. T- and B-cell markers positive pyothorax-associated lymphoma is rare.
  Kekkaku: [Tuberculosis] 10/2007; 82(9):711-4.