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Internal MedicineRespiratory Medicine

Introduction

Our research projects include clinical and basic research on various types of pulmonary diseases. The target diseases are lung cancer, interstitial pneumonia, pulmonary infections, asthma, chronic obstructive pulmonary disease (COPD), etc. The aim of our projects is to create new treatment strategies for patients with these pulmonary diseases to improve their outcomes. We are actively involved in next-generation therapies including gene therapies, molecular target therapies, and immunomodulatory treatment.

Research Projects

1. Oncology [Basic Science]...

PIs: T. Hase, MD. PhD.; I. Tanaka, MD. PhD.
Aim of my research is clarifying molecular pathogenesis of lung cancer and malignant pleural mesothelioma (MPM) and then translating such knowledge into the clinic by developing new early detection, chemoprevention, and therapeutic strategies. Main project I have been working on as a principal investigator is to identify therapeutic targets that substantially contribute to malignant phenotypes of lung cancer and MPM. So far, we have identified several such targets that include ZEB1, EpCAM, TIMELESS and BMAL1. Now, we are setting up genome-wide approaches to identify more vital targets for the two diseases.

2. Oncology [Clinical Study]

PI: M. Morise, MD, PhD.
Lung cancer is the leading cause of death worldwide and the number of patients with MPM has been increasing. In addition, elderly patients have been becoming major population of these malignancies, and the optimal treatment selection in those has not been fully established because of their heterogeneity in feasibility of systemic chemotherapy.
Our research is aimed to establish the algorithm of optimal treatment selection in elderly patients with thoracic malignancies. As of today, we performed the multicenter cohort study clarifying the non-fit population for platinum-based combination chemotherapy in elderly patients with advanced non-small cell lung cancer (presented in European Society for Medical Oncology, 2014). In the study, non-hematological toxicity such as chemotherapy induced nausea and vomiting (CINV) was the major reason of early treatment termination without progressive disease.
We are also investigating the new strategy to control CINV, which is an important issue especially in elderly patients with thoracic malignancy as mentioned above. We are now planning to conduct a prospective cohort study identifying unproven useful bio-markers for predicting the risk of CINV.

3. Microenvironment of Lung fibrosis and Lung Cancer

PIs: N. Hashimoto, MD, PhD.; K.Sakamoto MD PhD.
Heterogeneity of fibroblasts such as bone-marrow progenitors and endothelial-derived fibroblasts through endothelial-mesenchymal transition (Endo-MT) is shown in pulmonary fibrosis. Heterogeneity of fibroblast provides tissue micornvironment under which pulmonary fibrosis itself progresses. The patients with emphysema and pulmonary fibrosis often have lung cancer. Emphysema/fibrosis might provides tissue microenvironment, in which many signaling are active, and consequently affect development of lung cancer and its malignant phenotypes such as epithelial/endothelial-mesenchymal transition (EMT). Now I am projecting the research to establish new therapeutic strategy targeting for the shared mechanism in development of emphysema/fibrosis and cancer. We are searching the critical molecules to negatively regulate tissue microenvironment, consequently controlling not only chronic lung disease but also lung cancer.

4. Allergy and Immunology

PI: K. Wakahara, MD, PhD.
The immune system usually protects us against disease. However, in lung diseases such as asthma, COPD, interstitial pneumonia and cancer, aberrant immune system can be either a trigger or a modifier of the disease progressions.
Our projects:
We are trying to examine inflammatory phenotypes of various lung/airway diseases. Inflammatory cells obtained from lung, BALF, sputum and blood are analyzed by multicolor flow cytometry. Identifying rare but pathogenic cell populations within local site gives us new insights of the lung diseases.
We are trying to clarify the role of basophils on airway inflammation. Basophils are rare leukocytes involved in allergic diseases. We previously showed that basophils can exacerbate allergic airway inflammation by direct stimulation of effector T cells. Furthermore, our observations suggest that basophils enhance inflammation beyond Th2.
We are seeking appropriate asthma management in clinic. Inhaled corticosteroid and long acting beta 2 stimulant reduce the rates of death and hospitalization due to asthma. However, natural history of this common disease and long term effects of such medications are not well defined. We are studying long term change of lung function in asthmatic patients to evaluate our treatment.

5. Respiratory Tract Infections

PI: Y. Shindo, MD, PhD.
"Creation of the Optimal Treatment Strategy for Respiratory Tract Infections"
Pneumonia is a common disease and one of the lethal diseases. In order to achieve the appropriate initial treatment, appropriate assessment and classification of patients with pneumonia at diagnosis is essential.
Our group is currently taking a multidimensional approach to pneumonia, including clinical epidemiology, microbiological epidemiology, and basic research on infection immunity and immunotherapies. As one of the representative work, we performed a multicenter prospective study on adult patients with pneumonia in Japan (Shindo Y, et al. Am J Respir Crit Care Med 2013; 188: 985-995). This study identified six important risk factors for drug-resistant pathogens and proposed a new clinical predictive rule for initial antibiotic selection. Furthermore, we clarified the risk factors for mortality in pneumonia patients who received appropriate antibiotic treatment (Shindo Y, et al. Lancet Infect Dis 2015; 15: 1055-1065). This study elucidated patients who may need adjunctive therapy other than antibiotic treatment. Using pathogens identified from patients with pneumonia, molecular epidemiological research has been also performed with microbiologists (Ito R, et al. J Clin Microbiol 2015; 53:879-886). In addition, our member is working on basic research on immunotherapies and immunological mechanisms with US researchers, in connection with the findings of our clinical research (Shindo Y, et al. J Leukoc Biol 2016 (in press)). Our group is going to develop these multidimensional research to create the future treatment strategy for pneumonia and other respiratory tract infections.

6. Bronchoscopy and Intervention

PI: S. Okachi, MD.
I am mainly engaged in clinical practice and clinical research of respiratory medicine. In particularly, I am concerned with bronchoscopy. We perform more than 300 cases of fiberoptic bronchoscopy every year. From January to December 2014, we performed 57 cases of EBUS-TBNA (Endobronchial Ultrasound-guided Transbronchial Needle Aspiration) for mediastinal lymphnodes and 140 cases of EBUS-GS (Endobronchial Ultrasonography with a Guide Sheath) for pulmonary lesions. We perform other procedures such as local anesthetic thoracoscopy or bronchial occlusion using EWS (Endoscopic Watanabe Spigot) in daily practice. As clinical research, we have investigated efficacy and safety of midazolam for sedation during bronchoscopy (Respir Investig. 2014), echoic features of lymph nodes with sarcoidosis determined by endobronchial ultrasound (Intern Med. 2013), safety and usefulness of EBUS-TBNA in older patients (Geriatr Gerontol Int. 2013), and so on. We are aiming to perform safer, more accurate and more painless bronchoscopic procedures through clinical practice and research.

Faculty Members

FacultyPositionDepartment
Naozumi Hashimoto, MD, PhD. Associate Professor Respiratory Medicine
Keiko Wakahara, MD, PhD. Lecturer Respiratory Medicine
Masahiro Morise, MD, PhD. Assistant Professor Respiratory Medicine; Center for Medical Education
Yuichiro Shindo, MD, PhD. Assistant Professor Respiratory Medicine
Tetsunari Hase, MD, PhD. Assistant Professor Respiratory Medicine
Koji Sakamoto, MD, PhD. Assistant Professor Respiratory Medicine
Shotaro Okachi, MD, PhD. Assistant Professor Respiratory Medicine
Ichidai Tanaka, MD, PhD. Assistant Professor Respiratory Medicine
Kazuhide Sato, MD, PhD. Designated assistant professor Institute for Advanced Research Respiratory Medicine
Akira Ando, MD Assistant Professor Respiratory Medicine

Bibliography

  • 2016
    1. Asano S, Mizuno S, Okachi S, Aso H, Wakahara K, Hashimoto N, Ito S, Kozaki Y, Katsuno T, Maruyama S, Hasegawa Y. Antineutrophil Cytoplasmic Antibody-associated Vasculitis Superimposed on Infection-related Glomerulonephritis Secondary to Pulmonary Mycobacterium avium Complex Infection. Intern Med. 2016; 55: 2439-2445.
    2. Harada T, Nakamura Y, Sato K, Nagaya T, Choyke PL, Seto Y, Kobayashi H. Surgical tissue handling methods to optimize ex vivo fluorescence with the activatable optical probe γ-glutamyl hydroxymethyl rhodamine green. Contrast Media Mol Imaging. 2016; 11: 572-578.
    3. Harada T, Nakamura Y, Sato K, Nagaya T, Okuyama S, Ogata F, Choyke PL, Kobayashi H. Near-infrared photoimmunotherapy with galactosyl serum albumin in a model of diffuse peritoneal disseminated ovarian cancer. Oncotarget. 2016; 7: 79408-79416.
    4. Inoue T, Ito S, Ando M, Nagaya M, Aso H, Mizuno Y, Hattori K, Nakajima H, Nishida Y, Niwa Y, Kodera Y, Koike M, Hasegawa Y. Changes in exercise capacity, muscle strength, and health-related quality of life in esophageal cancer patients undergoing esophagectomy. BMC Sports Sci Med Rehabil 2016; 8: 34.
    5. Ito S, Furuya K, Sokabe M, Hasegawa Y. Cellular ATP release in the lung and airway. AIMS Biophys 2016; 3: 571-584.
    6. Mizuno Y, Ito S, Hattori K, Nagaya M, Inoue T, Nishida Y, Onishi Y, Kamei H, Kurata N, Hasegawa Y, Ogura Y. Changes of muscle strength and six-minute walk distance before and after living donor liver transplantation. Transplantat Proc 2016; 48: 3348-3355.
    7. Mukoyama N, Yoshimi A, Goto A, Kotani H, Ishikawa K, Miyazaki N, Miyazaki M, Yamada K, Kikkawa F, Hasegawa Y, Ozaki N, and Noda Y. An Analysis of Behavioral and Genetic Risk Factors for Chemotherapy-Induced Nausea and Vomiting in Japanese Subjects. Biological and Pharmaceutical Bulletin 2016; 39: 11.
    8. Nagaya T, Nakamura Y, Sato K, Harada T, Choyke PL, Kobayashi H. Improved micro-distribution of antibody-photon absorber conjugates after initial near infrared photoimmunotherapy (NIR-PIT). J Control Release. 2016; 232: 1-8. 
    9. Nagaya T, Nakamura Y, Sato K, Harada T, Choyke PL, Kobayashi H. Near infrared photoimmunotherapy of B-cell lymphoma.Mol Oncol. 2016; 10: 1404-1414.
    10. Nagaya T, Nakamura Y, Sato K, Zhang YF, Ni M, Choyke PL, Ho M, Kobayashi H. Near infrared photoimmunotherapy with an anti-mesothelin antibody. Oncotarget. 2016;7 : 23361-9.
    11. Nakamura Y, Bernardo M, Nagaya T, Sato K, Harada T, Choyke PL, Kobayashi H. MR imaging biomarkers for evaluating therapeutic effects shortly after near infrared photoimmunotherapy. Oncotarget. 2016; 7: 17254-64.
    12. Nakamura Y, Harada T, Nagaya T, Sato K, Okuyama S, Choyke PL, Kobayashi H. Dynamic fluorescent imaging with the activatable probe, γ-glutamyl hydroxymethyl rhodamine green in the detection of peritoneal cancer metastases: Overcoming the problem of dilution when using a sprayable optical probe. Oncotarget. 2016; 7: 51124-51137.
    13. Nakamura Y, Nagaya T, Sato K, Harada T, Okuyama S, Choyke PL, Yamauchi T, Kobayashi H. Alterations of filopodia by near infrared photoimmunotherapy: evaluation with 3D low-coherent quantitative phase microscopy. Biomed Opt Express. 2016; 7: 2738-48. 
    14. Nishimura K, Ogasawara M, Makita M, Nakayasu K, Hasegawa Y, Mituma S Vitamin D and Diagnosis of COPD in a Working Population. Journal of Pulmonary & Respiratory Medicine. 2016; 6, 359.
    15. Okachi S, Imai N, Imaizumi K, Iwano S, Ando M, Hase T, Aso H, Morise M, Wakahara K, Ito S, Hashimoto N, Sato M, Kondo M, Hasegawa Y. Factors Affecting the Diagnostic Yield of Transbronchial Biopsy Using Endobronchial Ultrasonography with a Guide Sheath in Peripheral Lung Cancer. Intern Med. 2016; 55: 1705-1712.
    16. Omote N, Kondoh Y, Taniguchi H, Kimura T, Kataoka K, Hasegawa R, Hasegawa Y. Acute respiratory distress syndrome due to severe pulmonary tuberculosis treated with extracorporeal membrane oxygenation: a case report and review of the literature. Respiratory Medicine Case Reports. 2016; 19: 31-33.
    17. Sato K, Choyke PL, Kobayashi H. Selective Cell Elimination from Mixed 3D Culture Using a Near Infrared Photoimmunotherapy Technique. J Vis Exp. 2016 Mar 14;109.
    18. Sato K, Gorka AP, Nagaya T, Michie MS, Nakamura Y, Nani RR, Coble VL, Vasalatiy OV, Swenson RE, Choyke PL, Schnermann MJ, Kobayashi H. Effect of charge localization on the in vivo optical imaging properties of near-infrared cyanine dye/monoclonal antibody conjugates. Mol Biosyst. 2016; 12: 3046-56.
    19. Sato K, Gorka AP, Nagaya T, Michie MS, Nani RR, Nakamura Y, Coble VL, Vasalatiy O, Swenson RE Choyke PL, Schnermann MJ, Kobayashi H. Role of Fluorophore Charge on the In Vivo Optical Imaging Properties of Near-Infrared Cyanine Dye/Monoclonal Antibody Conjugates. Bioconjug Chem. 2016; 27: 404-13.
    20. Sato K, Sato N, Xu B, Nakamura Y, Nagaya T, Choyke PL, Hasegawa Y, Kobayashi H. Spatially selective depletion of tumor-associated regulatory T cells with near infrared photoimmunotherapy. Sci Transl Med. 2016; 8: 352ra110.
    21. Sato K, Watanabe R, Hanaoka H, Nakajima T, Choyke PL, Kobayashi H. Comparative effectiveness of light emitting diodes (LEDs) and Lasers in near infrared photoimmunotherapy. Oncotarget. 2016;7 :14324-35.
    22. Sokai R, Ito S, Iwano S, Uchida A, Aso H, Kondo M, Ishiguro N, Kojima T, Hasegawa Y. Respiratory mechanics measured by forced oscillation technique in rheumatoid arthritis-related pulmonary abnormalities: frequency-dependence, heterogeneity and effects of smoking. SpringerPlus 2016; 5: 335.
    23. Suzuki M, Cao K, Kato S, Komizu Y, Mizutani N, Tanaka K, Arima C, Tai MC, Yanagisawa K, Togawa N, Shiraishi T, Usami N, Taniguchi T, Fukui T, Yokoi K, Wakahara K, Hasegawa Y, Mizutani Y, Igarashi Y, Inokuchi J, Iwaki S, Fujii S, Satou A, Matsumoto Y, Ueoka R, Tamiya-Koizumi K, Murata T, Nakamura M, Kyogashima M, Takahashi T. Targeting ceramide synthase 6-dependent metastasis-prone phenotype in lung cancer cells. J Clin Invest. 2016; 126: 254-265.
    24. Takahashi K, Taniguchi H, Ando M, Sakamoto K, Kondoh Y, Watanabe N, Kimura T, Kataoka K, Suzuki A, Ito S, Hasegawa Y. Mean pulmonary arterial pressure as a prognostic indicator in connective tissue disease associated with interstitial lung disease: a retrospective cohort study. BMC Pulm Med 2016; 16: 55.
  • 2015
    1. Shindo Y, Ito R, Kobayashi D, Ando M, Ichikawa M, Goto Y, Fukui Y, Iwaki M, Okumura J, Yamaguchi I, Yagi T, Tanikawa Y, Sugino Y, Shindoh J, Ogasawara T, Nomura F, Saka H, Yamamoto M, Taniguchi H, Suzuki R, Saito H, Kawamura T, and Hasegawa Y, on behalf of the Central Japan Lung Study Group. Risk factors for 30-day mortality in patients with pneumonia who receive appropriate initial antibiotics: an observational cohort study. Lancet Infect Dis 2015; 15: 1055-1065.
    2. Yamashita R, Sato M, Kakumu T, Hase T, Yogo N, Maruyama E, Sekido Y, Kondo M, Hasegawa Y. Growth inhibitory effects of miR-221 and miR-222 in non-small cell lung cancer cells. Cancer Med. 2015;4:551-564.
    3. Kusunose M, Hashimoto N, Kimura M, Ogata R, Aoyama D, Sakamoto K, Miyazaki S, Ando A, Omote N, Imaizumi K, Kawabe T, Hasegawa Y Direct regulation of TGFβ-induced EMT by the protein phosphatase activity of unphosphorylated PTEN in lung cancer cells. Cancer Science 2015; 106:1693-1704.
    4. Okachi S, Wakahara K, Kato D, Umeyama T, Yagi T, Hasegawa Y. Massive mediastinal cryptococcosis in young immunocompetent patient. Respirol Case Rep. 2015; 3: 95-98.
    5. Osuka S, Hashimoto N, Sakamoto K, Wakai K, Yokoi K, Hasegawa Y. Risk stratification by the lower limit of normal of FEV1/FVC for postoperative outcomes in patients with COPD undergoing thoracic surgery. Respir Investig 2015; 53:117-123.
    6. Andruska A, Micek S, Shindo Y, Hampton N, Colona B, McCormick S, Kollef M. Pneumonia pathogen characterization is an independent determinant of hospital readmission. Chest 2015; 148: 103-111.
    7. Enomoto Y, Kenmotsu H, Watanabe N, Baba T, Murakami H, Yoh K, Ogura T, Takahashi T, Goto K, Kato T. Efficacy and Safety of Combined Carboplatin, Paclitaxel, and Bevacizumab for Patients with Advanced Non-squamous Non-small Cell Lung Cancer with Pre-existing Interstitial Lung Disease: A Retrospective Multi-institutional Study. Anticancer Res. 2015;35:4259-4263.
    8. Hanaoka H, Nakajima T, Sato K, Watanabe R, Phung Y, Gao W, Harada T, Kim I, Paik CH, Choyke PL, Ho M, Kobayashi H. Photoimmunotherapy of hepatocellular carcinoma-targeting Glypican-3 combined with nanosized albumin-bound paclitaxel. Nanomedicine (Lond). 2015;10:1139-1147.
    9. Hanaoka H, Nagaya T, Sato K, Nakamura Y, Watanabe R, Harada T, Gao W, Feng M, Phung Y, Kim I, Paik CH, Choyke PL, Ho M, Kobayashi H. Glypican-3 targeted human heavy chain antibody as a drug carrier for hepatocellular carcinoma therapy. Mol Pharm. 2015;12:2151-2157.
    10. Ito R, Shindo Y, Kobayashi D, Ando M, Jin W, Wachino J, Yamada K, Kimura K, Yagi T, Hasegawa Y, and Arakawa Y. Molecular Epidemiological Characteristics of Klebsiella pneumoniae Associated with Bacteremia among Patients with Pneumonia. J Clin Microbiol 2015; 53: 879-886.
    11. Kawakami K, Iwano S, Hashimoto N, Hasegawa Y, Naganawa S. Evaluation of emphysema using three-dimensional computed tomography: association with postoperative complications in lung cancer patients. Nagoya J Med Sci. 2015; 77:113-122.
    12. Kim J, Sato M, Choi JW, Kim HW, Yeh BI, Larsen JE, Minna JD, Cha JH, Jeong Y. Nuclear Receptor Expression and Function in Human Lung Cancer Pathogenesis. PLoS One. 2015 Aug 5;10:e0134842.
    13. Kondoh Y, Johkoh T, Fukuoka J, Arakawa H, Tanaka T, Watanabe N, Sakamoto K, Kataoka K, Kimura T, Taniguchi H. Broader criteria of undifferentiated connective tissue disease in idiopathic interstitial pneumonias. Respir Med. 2015;109:389-396.
    14. Koriyama H, Ishii G, Yoh K, Neri S, Morise M, Umemura S, Matsumoto S, Niho S, Ohmatsu H, Tsuboi M, Goto K, Ochiai A. Presence of podoplanin-positive cancer-associated fibroblasts in surgically resected primary lung adenocarcinoma predicts a shorter progression-free survival period in patients with recurrences who received platinum-based chemotherapy. J Cancer Res Clin Oncol. 2015;141:1163-70.
    15. Minezawa T, Okamura T, Yatsuya H, Yamamoto N, Morikawa S, Yamaguchi T, Morishita M, Niwa Y, Takeyama T, Mieno Y, Hoshino T, Uozu S, Goto Y, Hayashi M, Isogai S, Matsuo M, Nakanishi T, Hashimoto N, Okazawa M, Imaizumi K. Bronchus sign on thin-section computed tomography is a powerful predictive factor for successful transbronchial biopsy using endobronchial ultrasound with a guide sheath for small peripheral lung lesions: a retrospective observational study. BMC Medical Imaging 2015; 21;15-21.
    16. Morise M, Hishida T, Takahashi A, Yoshida J, Ohe Y, Nagai K, Ishii G. Clinicopathological significance of cancer stem-like cell markers in high-grade neuroendocrine carcinoma of the lung. J Cancer Res Clin Oncol. 2015;141:2121-30.
    17. Nagaya T, Sato K, Harada T, Nakamura Y, Choyke PL, Kobayashi H. Near Infrared Photoimmunotherapy Targeting EGFR Positive Triple Negative Breast Cancer: Optimizing the Conjugate-Light Regimen. PLoS One. 2015;10:e0136829.
    18. Omote N, Taniguchi H, Kondoh Y, Watanabe N, Sakamoto K, Kimura T, Kataoka K, Johkoh T, Fujimoto K, Fukuoka J, Otani K, Nishiyama O, Hasegawa Y. Lung-dominant connective tissue disease: clinical, radiologic and histologic features. Chest. 2015;148:1438-1446.
    19. Sarfati M, Wakahara K, Chapuy L, Delespesse G. Mutual interaction of basophils and T cells in choronic infalammatory diseases. Front Immunol. 2015; 6:399. [Review]
    20. Sato K, Hanaoka H, Watanabe R, Nakajima T, Choyke PL, Kobayashi H. Near infrared photoimmunotherapy in the treatment of disseminated peritoneal ovarian cancer. Mol Cancer Ther. 2015;14:141-150.
    21. Sato K, Nagaya T, Choyke PL, Kobayashi H. Near infrared photoimmunotherapy in the treatment of pleural disseminated NSCLC: preclinical experience. Theranostics 2015; 5: 698-709.
    22. Sato K, Nakajima T, Choyke PL, Kobayashi H. Selective cell elimination in vitro and in vivo from tissues and tumors using antibodies conjugated with a near infrared phthalocyanine. RSC Adv. 2015;5:25105-25114.
    23. Sato K, Nagaya T, Nakamura Y, Harada T, Choyke PL, Kobayashi H. Near infrared photoimmunotherapy prevents lung cancer metastases in a murine model. Oncotarget. 2015:19747-19758.
    24. Sato K, Nagaya T, Mitsunaga M, Choyke PL, Kobayashi H. Near infrared photoimmunotherapy for lung metastases. Cancer Lett. 2015;365:112-121.
    25. Sato K, Nagaya T, Nakamura Y, Harada T, Nani RR, Shaum JB, Gorka AP, Kim I, Paik CH, Choyke PL, Schnermann MJ, Kobayashi H. Impact of C4'-O-Alkyl Linker on in Vivo Pharmacokinetics of Near-Infrared Cyanine/Monoclonal Antibody Conjugates. Mol Pharm. 2015;12:3303-3311.
    26. Shindo Y, Unsinger J, Burnham C, Green J, and Hotchkiss R. Interleukin 7 and anti-programmed cell death 1 antibody have differing effects to reverse sepsis-induced immunosuppression. Shock 2015; 43: 334-343.
    27. Udagawa H, Ishii G, Morise M, Umemura S, Matsumoto S, Yoh K, Niho S, Ohmatsu H, Tsuboi M, Goto K, Ochiai A, Ohe Y. Comparison of the expression levels of molecular markers among the peripheral area and central area of primary tumor and metastatic lymph node tumor in patients with squamous cell carcinoma of the lung. J Cancer Res Clin Oncol. 2015;141:1417-25.
    28. Wakayama H, Hashimoto N, Matsushita Y, Matsubara K, Yamamoto N, Hasegawa Y, Ueda M, Yamamoto A. Factors secreted from dental pulp stem cells show multifaceted benefits for treating acute respiratory distress syndrome in mice. Cytotherapy 2015; 17: 1119-1129.
    29. Watanabe N, Niho S, Kirita K, Umemura S, Matsumoto S, Yoh K, Ohmatsu H, Goto K.  Second-line docetaxel for patients with platinum-refractory advanced non-small cell lung cancer and interstitial pneumonia. Cancer Chemother Pharmacol. 2015;76(1):69-74.
    30. Watanabe N, Niho S, Kirita K, Umemura S, Matsumoto S, Yoh K, Ohmatsu H, Goto K. Vinorelbine and Cisplatin in Patients with Advanced Non-small Cell Lung Cancer with Interstitial Pneumonia. Anticancer Res. 2015;35:1697-1701.
    31. Watanabe N, Umemura S, Niho S, Kirita K, Matsumoto S, Yoh K, Ohmatsu H, Goto K. Docetaxel for platinum-refractory advanced thymic carcinoma. Jpn J Clin Oncol. 2015; 45:665-669.
    32. Watanabe R, Hanaoka H, Sato K, Nagaya T, Harada T, Mitsunaga M, Kim I, Paik CH, Wu AM, Choyke PL, Kobayashi H. Photoimmunotherapy targeting prostate-specific membrane antigen: are antibody fragments as effective as antibodies? J Nucl Med. 2015 Jan;56:140-144.
  • 2014
    1. Chapuy L, Bsat M, Mehta H, Rubio M, Wakahara K, Van VQ, Baba N, Cheong C, Yun TJ, Panzini B, Wassef R, Richard C, Tamaz R, Soucy G, Delespesse G, Sarfati M. Basophils increase in Crohn disease and ulcerative colitis and favor mesenteric lymph node memory TH17/TH1 response. J Allergy Clin Immunol. 2014; 134 (4): 978-981.
    2. Fukatsu A, Ishiguro F, Tanaka I, Kudo T, Nakagawa K, Shinjo K, Kondo Y, Fujii M, Hasegawa Y, Tomizawa K, Mitsudomi T, Osada H, Hata Y, Sekido Y. RASSF3 downregulation increases malignant phenotypes of non-small cell lung cancer. Lung Cancer 2014; 83: 23-29.
    3. Fukihara J, Watanabe N, Taniguchi H, Kondoh Y, Kimura T, Kataoka K, Matsuda T, Yokoyama T, Hasegawa Y. Clinical predictors of response to EGFR tyrosine kinase inhibitors in patients with EGFR-mutant non-small cell lung cancer. Oncology 2014; 86(2): 86-93.
    4. Hashimoto N, Matsuzaki A, Okada Y, Imai N, Iwano S, Wakai K, Imaizumi K, Yokoi K, Hasegawa Y. Clinical impact of prevalence and severity of COPD on the decision-making process for therapeutic management of lung cancer patients. BMC Pulm Med 2014; 14(1): 14.
    5. Kitano M, Iwano S, Hashimoto N, Matsuo K, Hasegawa Y, Naganawa S. Lobar analysis of collapsibility indices to assess functional lung volumes in COPD patients. Int J Chron Obstruct Pulmon Dis 2014; 9: 1347-1356.
    6. Morise M, Taniguchi H, Saka H, Shindoh J, Suzuki R, Kojima E, Hase T, Ando M, Kondo M, Saito H, Hasegawa Y. Phase II study of erlotinib for previously treated patients with EGFR wild-type non-small-cell lung cancer, following EGFR mutation status reevaluation with the Scorpion Amplified Refractory Mutation System. Mol Clin Oncol. 2014; 2: 991-996.
    7. Morise M, Niho S, Umemura S, Matsumoto S, Yoh K, Goto K, Ohmatsu H, Ohe Y. Low-dose irinotecan as a second-line chemotherapy for recurrent small cell lung cancer. Jpn J Clin Oncol. 2014; 44: 846-851.
    8. Murata N, Ito S, Furuya K, Takahara N, Naruse K, Aso H, Kondo M, Sokabe M, Hasegawa Y. Ca2+ influx and ATP release mediated by mechanical stretch in human lung fibroblasts. Biochem Biophys Res Commun 2014; 453: 101-105.
    9. Noble PD, Pascoe CD, Bo L, Ito S, Kistemaker LE, Tatler AL, Pera T, Brook BS, Gosens R, West AR. Airway smooth muscle in asthma: linking contraction and mechanotransduction to disease pathogenesis and remodeling. Pulm Pharmacol Ther 2014; 29: 96-107. [Review]
    10. Ogawa T, Imaizumi K, Hashimoto I, Shindo Y, Imai N, Uozu S, Shimokata T, Ito S, Hashimoto N, Sato M, Kondo M, Hasegawa Y. Prospective analysis of efficacy and safety of an individualized-midazolam-dosing protocol for sedation during prolonged bronchoscopy. Respir Investig 2014; 52: 153-159.
    11. Shindo Y, Hasegawa Y. Reply: HCAP Not Busy Being Born Is Busy Dying. Am J Respir Crit Care Med 2014; 189 (3): 366-367.
    12. Shindo Y, Hasegawa Y. Reply: Isolation of drug-resistant pathogens does not always require antibiotics of broad spectrum in pneumonia. Am J Respir Crit Care Med 2014; 189(6): 757-758.
    13. Suzuki A, Taniguchi H, Watanabe N, Kondoh Y, Kimura T, Kataoka K, Matsuda T, Yokoyama T, Sakamoto K, Nishiyama O, Hasegawa Y. Significance of pulmonary arterial pressure as a prognostic indicator in lung-dominant connective tissue disease. PLoS One 2014; 9(9): e108339.
    14. Takahara N, Ito S, Furuya K, Naruse K, Aso H, Kondo M, Sokabe M, Hasegawa Y. Real-time imaging of ATP release induced by mechanical stretch in human airway smooth muscle cells. Am J Respir Cell Mol Biol 2014; 51: 772-782.
    15. Takahashi K, Saito H, Hasegawa Y, Ando M, Yamamoto M, Kojima E, Sugino Y, Kimura T, Nomura F, Ogasawara T, Shindoh J, Yoshida N, Suzuki R. First-line gefitinib therapy for elderly patients with non-small cell lung cancer harboring EGFR mutation: Central Japan Lung Study Group 0901. Cancer Chemother Pharmacol. 2014; 74(4): 721-727.
    16. Takashima K, Matsushima M, Hashimoto K, Nose H, Sato M, Hashimoto N, Hasegawa Y, Kawabe T. Protective effects of intratracheally administered quercetin on lipopolysaccharide-induced acute lung injury. Respiratoy Research 2014; 15(1): 150.
    17. Umemura S, Mimaki S, Makinoshima H, Tada S, Ishii G, Ohmatsu H, Niho S, Yoh K, Matsumoto S, Takahashi A, Morise M, Nakamura Y, Ochiai A, Nagai K, Iwakawa R, Kohno T, Yokota J, Ohe Y, Esumi H, Tsuchihara K, Goto K. Therapeutic priority of the PI3K/AKT/mTOR pathway in small cell lung cancers as revealed by a comprehensive genomic analysis. J Thorac Oncol. 2014; 9: 1324-1331.
    18. Watanabe N, Taniguchi H, Kondoh Y, Kimura T, Kataoka K, Nishiyama O, Kondo M, Hasegawa Y. Chemotherapy for extensive-stage small-cell lung cancer with idiopathic pulmonary fibrosis. Int J Clin Oncol 2014; 19(2): 260-265.
    19. Watanabe N, Nakahara Y, Taniguchi H, Kimura T, Kondoh Y, Kataoka K, Sakamoto K. Crizotinib-induced acute interstitial lung disease in a patient with EML4-ALK positive non-small cell lung cancer and chronic interstitial pneumonia. Acta Oncol 2014; 53:158-160.
    20. Watanabe N, Sakamoto K, Taniguchi H, Kondoh Y, Kimura T, Kataoka K, Ono K, Fukuoka J, Nishiyama O, Hasegawa Y. Efficacy of combined therapy with cyclosporin and low-dose prednisolone in interstitial pneumonia associated with connective tissue disease. Respiration 2014; 87(6): 469-477.
    21. Wu W, Ichihara G, Hashimoto N, Hasegawa Y, Hayashi Y, Tada-Oikawa S, Suzuki Y, Chang J, Kato M, D'Alessandro-Gabazza CN, Gabazza EC, Ichihara S. Synergistic Effect of Bolus Exposure to Zinc Oxide Nanoparticles on Bleomycin-Induced Secretion of Pro-Fibrotic Cytokines without Lasting Fibrotic Changes in Murine Lungs. Int J Mol Sci. 2014; 16(1): 660-676.
  • 2013
    1. Aoyama D, Hashimoto N, Sakamoto K, Kohnoh T, Kusunose M, Kimura M, Ogata R, Imaizumi K, Kawabe T, Hasegawa Y. Involvement of TGFβ-induced phosphorylation of the PTEN C-terminus on TGFβ-induced acquisition of malignant phenotypes in lung cancer cells. Plos One 2013;8(11): e81133.
    2. Aso H, Ito S, Mori A, Suganuma N, Morioka M, Takahara N, Kondo M, Hasegawa Y. Differential regulation of airway smooth muscle cell migration by E-prostanoid receptor subtypes. Am J Respir Cell Mol Biol 2013;48(3):322-329.
    3. Baba N, Van VQ, Wakahara K, Rubio M, Fortin G, Panzini B, Soucy G, Wassef R, Richard C, Tamaz R, Lahaie R, Bernard EJ, Caussignac Y, Leduc R, Lougnarath R, Bergeron C, Racicot MA, Bergeron F, Panzini MA, Demetter P, Franchimont D, Schäkel K, Weckbecker G, Kolbinger F, Heusser C, Huber T, Welzenbach K, Sarfati M. CD47 fusion protein targets CD172a+ cells in Crohn's disease and dampens the production of IL-1β and TNF. J Exp Med 2013;210(6):1251-1263.
    4. Billington CK, Ojo OO, Penn RB, Ito S. cAMP regulation of airway smooth muscle function. Pulm Pharmacol Ther 2013;6:112-120. [Review]
    5. Hashimoto I, Imaizumi K, Hashimoto N, Furukawa H, Noda Y, Kawabe T, Honda T, Ogawa T, Matsuo M, Imai N, Ito S, Sato M, Kondo M, Shimokata K, Hasegawa Y. Aqueous fraction of Sauropus androgynus might be responsible for bronchiolitis obliterans. Respirology 2013;18(2):340-347.
    6. Imai N, Imaizumi K, Ando M, Shimokata T, Ogawa T, Ito S, Hashimoto N, Sato M, Kondo M, Hasegawa Y. Echoic features of lymph nodes with sarcoidosis determined by endobronchial ultrasound. Intern Med 2013;52(13):1473-1478.
    7. Kimura M, Taniguchi H, Kondoh Y, Kimura T, Kataoka K, Nishiyama O, Aso H, Sakamoto K, Hasegawa Y. Pulmonary hypertension as a prognostic indicator at the initial evaluation in idiopathic pulmonary fibrosis. Respiration 2013;85(6):456-463.
    8. Nakagawa T, Takeuchi S, Yamada T, Ebi H, Sano T, Nanjo S, Ishikawa D, Sato M, Hasegawa Y, Sekido Y, Yano S. EGFR-TKI resistance due to BIM polymorphism can be circumvented in combination with HDAC inhibition. Cancer Res 2013;73(8):2428-2434.
    9. Nakagawa T, Takeuchi S, Yamada T, Ebi H, Sano T, Nanjo S, Ishikawa D, Sato M, Hasegawa Y, Sekido Y, Yano S. EGFR-TKI resistance due to BIM polymorphism can be circumvented in combination with HDAC inhibition. Cancer Res 2013;73(8):2428-2434.
    10. Nishimura K, Mitsuma S, Kobayashi A, Yanagida M, Nakayasu K, Hasegawa Y, Jones PW. COPD and disease-specific health status in a working population. Respir Res 2013;14:61.
    11. Oguri T, Mitsuma A, Inada-Inoue M, Morita S, Shibata T, Shimokata T, Sugishita M, Nakayama G, Uehara K, Hasegawa Y, Ando Y. Genetic polymorphisms associated with oxaliplatin-induced peripheral neurotoxicity in Japanese patients with colorectal cancer. International Journal of clinical pharmacology and therapeutics 2013;51(6):475-481.
    12. Ohno T, Okamoto M, Hara T, Hashimoto N, Imaizumi K, Matsushima M, Nishimura M, Shimokata K, Hasegawa Y, Kawabe T. Detection of loci for allergic asthma using SMXA recombinant inbred strains of mice. Immunogenetics 2013; 65(1):17-24.
    13. Okachi S, Imai N, Imaizumi K, Hase T, Shindo Y, Sakamoto K, Aso H, Wakahara K, Hashimoto I, Ito S, Hashimoto N, Sato M, Kondo M, Hasegawa Y. Endobronchial ultrasound transbronchial needle aspiration in older people. Geriatr Gerontol Int. 2013;13(4):986-92.
    14. Osborne JK, Larsen JE, Gonzales JX, Shames DS, Sato M, Wistuba II, Girard L, Minna JD, Cobb MH. NeuroD1 regulation of migration accompanies the differential sensitivity of neuroendocrine carcinomas to TrkB inhibition. Oncogenesis 2013;19;2:e63
    15. Osborne JK, Larsen JE, Shields MD, Gonzales JX, Shames DS, Sato M, Kulkarni A, Wistuba II, Girard L, Minna JD, Cobb MH. NeuroD1 regulates survival and migration of neuroendocrine lung carcinomas via signaling molecules TrkB and NCAM. Proc Natl Acad Sci U S A. 2013;110(16): 6524-6529.
    16. Sato M, Larsen JE, Lee W, Sun H, Shames DS, Dalvi MP, Ramirez RD, Tang H, DiMaio JM, Gao B, Xie Y, Wistuba II, Gazdar AF, Shay JW, Minna JD. Human lung epithelial cells progressed to malignancy through specific oncogenic manipulations. Mol Cancer Res. 2013;11(6):638-50.
    17. Shindo Y, Ito R, Kobayashi D, Ando M, Ichikawa M, Shiraki A, Goto Y, Fukui Y, Iwaki M, Okumura J, Yamaguchi I, Yagi T, Tanikawa Y, Sugino Y, Shindoh J, Ogasawara T, Nomura F, Saka H, Yamamoto M, Taniguchi H, Suzuki R, Saito H, Kawamura T, Hasegawa Y. Risk Factors for Drug-Resistant Pathogens in Community-Acquired and Healthcare-Associated Pneumonia. Am J Respir Crit Care Med 2013;188:985-995.
    18. Sunaga N, Kaira K, Imai H, Shimizu K, Nakano T, Shames DS, Girard L, Soh J, Sato M, Iwasaki Y, Ishizuka T, Gazdar AF, Minna JD, Mori M. Oncogenic KRAS-induced epiregulin overexpression contributes to aggressive phenotype and is a promising therapeutic target in non-small-cell lung cancer. Oncogene. 2013;32(34):4034-42.
    19. Taga S, Taniguchi H, Watanabe N, Kondoh Y, Kimura T, Kataoka K, Aso H, Sakamoto K, Hasegawa Y. Predictors of the need to initiate noninvasive ventilation in stable outpatients with acute exacerbation of chronic obstructive pulmonary disease. Intern Med. 2013;52:1781-1786.
    20. Takahashi N, Kondo T, Fukuta M, Takemoto A, Takami Y, Sato M, Ando T, Hashimoto N, Suzuki T, Sato J, Yamamura M, Ban N. Selective IgA deficiency mimicking Churg-Strauss syndrome and hypereosinophilic syndrome: a case report. Nagoya J Med Sci 2013;75(1-2):139-46.
    21. Tsukuura H, Nishimura K, Taniguchi H, Kondoh Y, Kimura T, Kataoka K, Watanabe N, Hasegawa Y. Opioid Use in End-of-Life Care in Patients With Interstitial Pneumonia Associated With Respiratory Worsening. Journal of Pain Palliat Care Pharmacother 2013;27:214-219.
    22. Uchida A, Ito S, Suki B, Matsubara H, Hasegawa Y. Influence of cheek support on respiratory impedance measured by forced oscillation technique. Springer Plus 2013;2:342.
    23. Wakahara K, Van VQ, Baba N, Bégin P, Rubio M, Delespesse G, Sarfati M. Basophils are recruited to inflamed lungs and exacerbate memory Th2 responses in mice and humans. Allergy 2013; 68(2):180-9.
    24. Watanabe F, Taniguchi H, Sakamoto K, Kondoh Y, Kimura T, Kataoka K, Ogawa T, Arizono S, Nishiyama O, Hasegawa Y. Quadriceps weakness contributes to exercise capacity in nonspecific interstitial pneumonia. Respiratory medicine 2013;107:622-628.
    25. Watanabe N, Taniguchi H, Kondoh Y, Kimura T, Kataoka K, Nishiyama O, Kondo M, Hasegawa Y. Efficacy of chemotherapy for advanced non-small cell lung cancer with idiopathic pulmonary fibrosis. Respiration 2013;85-4:326-331.
    26. Yoshida K, Sato M, Hase T, Elshazley M, Yamashita R, Usami N, Taniguchi T, Yokoi K, Nakamura S, Kondo M, Girard L, Minna JD, Hasegawa Y. TIMELESS is overexpressed in lung cancer and its expression correlates with poor patient survival. Cancer Sci 2013;104(2):171-177.

Research Keywords

Lung cancer; malignant mesothelioma; interstitial pneumonia; pulmonary fibrosis; chronic obstructive pulmonary disease (COPD); asthma ; pneumonia; pulmonary infections; respiratory failure; gene therapy; molecular target therapy、 immunotherapy.