Relationships between EGFR Mutation Status of Lung Cancer and Preoperative Factors - Are they Predictive?

Usuda, Katsuo,Sagawa, Motoyasu,Motono, Nozomu,Ueno, Masakatsu,Tanaka, Makoto,Machida, Yuichiro,Matoba, Munetaka,Taniguchi, Mitsuru,Tonami, Hisao,Ueda, Yoshimichi,Sakuma, Tsutomu Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2

Background: The epidermal growth factor receptor (EGFR) mutation status of lung cancer is important because it means that EGFR-tyrosine kinase inhibitor treatment is indicated. The purpose of this prospective study is to determine whether EGFR mutation status could be identified with reference to preoperative factors. Materials and Methods: One hundred-forty eight patients with lung cancer (111 adenocarcinomas, 25 squamous cell carcinomas and 12 other cell types) were enrolled in this study. The EGFR mutation status of each lung cancer was analyzed postoperatively. Results: There were 58 patients with mutant EGFR lung cancers (mutant LC) and 90 patients with wild-type EGFR lung cancers (wild-type LC). There were significant differences in gender, smoking status, maximum tumor diameter in chest CT, type of tumor shadow, clinical stage between mutant LC and wild-type LC. EGFR mutations were detected only in adenocarcinomas. Maximum standardized uptake value (SUVmax:$3.66{\pm}4.53$) in positron emission tomography-computed tomography of mutant LC was significantly lower than that ($8.26{\pm}6.11$) of wild-type LC (p<0.0001). Concerning type of tumor shadow, the percentage of mutant LC was 85.7% (6/7) in lung cancers with pure ground glass opacity (GGO), 65.3%(32/49) in lung cancers with mixed GGO and 21.7%(20/92) in lung cancers with solid shadow (p<0.0001). For the results of discriminant analysis, type of tumor shadow (p=0.00036) was most significantly associated with mutant EGFR. Tumor histology (p=0.0028), smoking status (p=0.0051) and maximum diameter of tumor shadow in chest CT (p=0.047) were also significantly associated with mutant EGFR. The accuracy for evaluating EGFR mutation status by discriminant analysis was 77.0% (114/148). Conclusions: Mutant EGFR is significantly associated with lung cancer with pure or mixed GGO, adenocarcinoma, never-smoker, smaller tumor diameter in chest CT. Preoperatively, EGFR mutation status can be identified correctly in about 77 % of lung cancers.

ASTRONOMY FOR DEVELOPMENT; APPROACHES IN ASIA

USUDA-SATO, KUMIKO,TOMITA, AKIHIKO The Korean Astronomical Society 2015 天文學論叢 Vol.30 No.2

As task force members, we present the International Astronomical Union (IAU) Office of Astronomy for Development (OAD) and its task forces. Each task force calls for proposals every year and reviews the submitted proposals. From the point of view of "Astronomy for a Better World", the vision of the OAD, our aim is to reach diverse people including those such as the visually impaired. Our efforts meet one of the goals of the OAD and some OAD-funded projects.

Diffusion Weighted Imaging Can Distinguish Benign from Malignant Mediastinal Tumors and Mass Lesions: Comparison with Positron Emission Tomography

Usuda, Katsuo,Maeda, Sumiko,Motono, Nozomu,Ueno, Masakatsu,Tanaka, Makoto,Machida, Yuichiro,Matoba, Munetaka,Watanabe, Naoto,Tonami, Hisao,Ueda, Yoshimichi,Sagawa, Motoyasu Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: Diffusion-weighted magnetic resonance imaging (DWI) makes it possible to detect malignant tumors based on the diffusion of water molecules. It is uncertain whether DWI is more useful than positron emission tomography-computed tomography (PET-CT) for distinguishing benign from malignant mediastinal tumors and mass lesions. Materials and Methods: Sixteen malignant mediastinal tumors (thymomas 7, thymic cancers 3, malignant lymphomas 3, malignant germ cell tumors 2, and thymic carcinoid 1) and 12 benign mediastinal tumors or mass lesions were assessed in this study. DWI and PET-CT were performed before biopsy or surgery. Results: The apparent diffusion coefficient (ADC) value ($1.51{\pm}0.46{\times}10^{-3}mm^2/sec$) of malignant mediastinal tumors was significantly lower than that ($2.96{\pm}0.86{\times}10^{-3}mm^2/sec$) of benign mediastinal tumors and mass lesions (P<0.0001). Maximum standardized uptake value (SUVmax) ($11.30{\pm}11.22$) of malignant mediastinal tumors was significantly higher than that ($2.53{\pm}3.92$) of benign mediastinal tumors and mass lesions (P=0.0159). Using the optimal cutoff value (OCV) $2.21{\times}10^{-3}mm^2/sec$ for ADC and 2.93 for SUVmax, the sensitivity (100%) by DWI was not significantly higher than that (93.8%) by PET-CT for malignant mediastinal tumors. The specificity (83.3%) by DWI was not significantly higher than that (66.7%) for benign mediastinal tumors and mass lesions. The accuracy (92.9%) by DWI was not significantly higher than that (82.1%) by PET-CT for mediastinal tumors and mass lesions. Conclusions: There was no significant difference between diagnostic capability of DWI and that of PET-CT for distinguishing mediastinal tumors and mass lesions. DWI is useful in distinguishing benign from malignant mediastinal tumors and mass lesions.

Diagnostic Performance of Whole-Body Diffusion-Weighted Imaging Compared to PET-CT Plus Brain MRI in Staging Clinically Resectable Lung Cancer

Usuda, Katsuo,Sagawa, Motoyasu,Maeda, Sumiko,Motono, Nozomu,Tanaka, Makoto,Machida, Yuichiro,Matoba, Takuma Matsui Munetaka,Watanabe, Naoto,Tonami, Hisao,Ueda, Yoshimichi,Uramoto, Hidetaka Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.6

Background: Precise staging of lung cancer is usually evaluated by PET-CT and brain MRI. Recently, however, whole-body diffusion-weighted magnetic resonance imaging (WB-DWI) has be applied. The aim of this study is to determine whether the diagnostic performance of lung cancer staging by WB-DWI is superior to that of PET-CT+brain MRI. Materials and Methods: PET-CT + brain MRI and WB-DWI were used for lung cancer staging before surgery with 59 adenocarcinomas, 16 squamous cell carcinomas and 6 other carcinomas. Results: PET-CT + brain MRI correctly identified the pathologic N staging in 67 patients (82.7%), with overstaging in 5 (6.2%) and understaging in 9 (11.1%), giving a staging accuracy of 0.827. WB-DWI correctly identified the pathologic N staging in 72 patients (88.9%), with overstaging in 1 (1.2%) and understaging in 8 patients (9.9%), giving a staging accuracy of 0.889. There were no significant differences in accuracies. PET-CT + brain MRI correctly identified the pathologic stages in 56 patients (69.1%), with overstaging in 7 (8.6%) and understaging in 18 (22.2%), giving a staging accuracy of 0.691. WB-DWI correctly identified the pathologic stages in 61 patients (75.3%), with overstaging in 4 (4.9%) and understagings in16(19.7%), giving a staging accuracy of 0.753. There were no significant difference in accuracies. Conclusions: Diagnostic efficacy of WB-DWI for lung cancer staging is equivalent to that of PET-CT + brain MRI.

Recurrence and Metastasis of Lung Cancer Demonstrate Decreased Diffusion on Diffusion-Weighted Magnetic Resonance Imaging

Usuda, Katsuo,Sagawa, Motoyasu,Motomo, Nozomu,Ueno, Masakatsu,Tanaka, Makoto,Machida, Yuichiro,Maeda, Sumiko,Matoba, Munetaka,Tonami, Hisao,Ueda, Yoshimichi,Sakuma, Tsutomu Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

Background: Diffusion-weighted magnetic resonance imaging (DWI) is reported to be useful for detecting malignant lesions. The purpose of this study is to clarify characteristics of imaging, detection rate and sensitivity of DWI for recurrence or metastasis of lung cancer. Methods: A total of 36 lung cancer patients with recurrence or metastasis were enrolled in this study. While 16 patients underwent magnetic resonance imaging (MRI), computed tomography (CT) and positron emission tomography-computed tomography (PET-CT), 17 underwent MRI and CT, and 3 underwent MRI and PET-CT. Results: Each recurrence or metastasis showed decreased diffusion, which was easily recognized in DWI. The detection rate for recurrence or metastasis was 100% (36/36) in DWI, 89% (17/19) in PET-CT and 82% (27/33) in CT. Detection rate of DWI was significantly higher than that of CT (p=0.0244) but not significantly higher than that of PET-CT (p=0.22). When the optimal cutoff value of the apparent diffusion coefficient value was set as $1.70{\times}10^{-3}mm^2/sec$, the sensitivity of DWI for diagnosing recurrence or metastasis of lung cancer was 95.6%. Conclusions: DWI is useful for detection of recurrence and metastasis of lung cancer.

Diagnostic Performance of Diffusion Weighted Imaging of Malignant and Benign Pulmonary Nodules and Masses: Comparison with Positron Emission Tomography

Usuda, Katsuo,Sagawa, Motoyasu,Motono, Nozomu,Ueno, Masakatsu,Tanaka, Makoto,Machida, Yuichiro,Maeda, Sumiko,Matoba, Munetaka,Kuginuki, Yasuaki,Taniguchi, Mitsuru,Tonami, Hisao,Ueda, Yoshimichi,Sakuma Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

Background: Diffusion-weighted imaging (DWI) makes it possible to detect malignant tumors based on the diffusion of water molecules. However, it is uncertain whether DWI has advantages over FDG-PET for distinguishing malignant from benign pulmonary nodules and masses. Materials and Methods: One hundred-forty-three lung cancers, 17 metastatic lung tumors, and 29 benign pulmonary nodules and masses were assessed in this study. DWI and FDG-PET were performed. Results: The apparent diffusion coefficient (ADC) value ($1.27{\pm}0.35{\times}10^{-3}mm^2/sec$) of malignant pulmonary nodules and masses was significantly lower than that ($1.66{\pm}0.58{\times}10^{-3}mm^2/sec$) of benign pulmonary nodules and masses. The maximum standardized uptake value (SUVmax: $7.47{\pm}6.10$) of malignant pulmonary nodules and masses were also significantly higher than that ($3.89{\pm}4.04$) of benign nodules and masses. By using optimal cutoff values for ADC ($1.44{\times}10^{-3}mm^2/sec$) and for SUVmax (3.43), which were determined with receiver operating characteristics curves (ROC curves), the sensitivity (80.0%) of DWI was significantly higher than that (70.0%) of FDG-PET. The specificity (65.5%) of DWI was equal to that (65.5%) of FDG-PET. The accuracy (77.8%) of DWI was not significantly higher than that (69.3%) of FDG-PET for pulmonary nodules and masses. As the percentage of bronchioloalveolar carcinoma (BAC) component in adenocarcinoma increased, the sensitivity of FDG-PET decreased. DWI could not help in the diagnosis of mucinous adenocarcinomas as malignant, and FDG-PET could help in the correct diagnosis of 5 out of 6 mucinous adenocarcinomas as malignant. Conclusions: DWI has higher potential than PET in assessing pulmonary nodules and masses. Both diagnostic approaches have their specific strengths and weaknesses which are determined by the underlying pathology of pulmonary nodules and masses.

Diagnostic Performance of Diffusion - Weighted Imaging for Multiple Hilar and Mediastinal Lymph Nodes with FDG Accumulation

Usuda, Katsuo,Maeda, Sumiko,Motono, Nozomu,Ueno, Masakatsu,Tanaka, Makoto,Machida, Yuichiro,Matoba, Munetaka,Watanabe, Naoto,Tonami, Hisao,Ueda, Yoshimichi,Sagawa, Motoyasu Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: It is sometimes difficult to assess patients who have multiple hilar and mediastinal lymph nodes (MHMLN) with FDG accumulation in PET-CT. Since it is uncertain whether diffusion-weighted magnetic resonance imaging (DWI) is useful in the assessment of such patients, its diagnostic performance was assessed. Materials and Methods: Twenty-three patients who had three or more stations of hilar and mediastinal lymph nodes with SUVmax of 3 or more in PET-CT were included in this study. Results: For diagnosis of disease, there were 20 malignancies (lung cancers 17, malignant lymphomas 2 and metastatic lung tumor 1), and 3 benign cases (sarcoidosis 2 and benign disease 1). For diagnosis of lymph nodes, there were 7 malignancies (metastasis of lung cancer 7 and malignant lymphoma 1) and 16 benign lymphadenopathies (pneumoconiosis/silicosis 7, sarcoidosis 4, benign disease 4, and atypical lymphocyte infiltration 1). The ADC value ($1.57{\pm}0.29{\times}10^{-3}mm^2/sec$) of malignant MHMLN was significantly lower than that ($1.99{\pm}0.24{\times}10^{-3}mm^2/sec$) of benign MHMLN (P=0.0437). However, the SUVmax was not significantly higher ($10.0{\pm}7.34$ as compared to $6.38{\pm}4.31$) (P=0.15). The sensitivity (86%) by PET-CT was not significantly higher than that (71%) by DWI for malignant MHMLN (P=1.0). The specificity (100%) by DWI was significantly higher than that (31%) for benign MHMLN (P=0.0098). Furthermore, the accuracy (91%) with DWI was significantly higher than that (48%) with PET-CT for MHMLN (P=0.0129). Conclusions: Evaluation by DWI for patients with MHMLN with FDG accumulation is useful for distinguishing benign from malignant conditions.

NEAR-INFRARED HIGH-RESOLUTION SPECTROSCOPY OF THE OBSCURED AGN IRAS 01250+2832

Shirahata, M.,Usuda, T.,Oyabu, S.,Nakagawa, T.,Yamamura, I. The Korean Astronomical Society 2012 天文學論叢 Vol.27 No.4

We provide a new physical insight on the hot molecular clouds near the nucleus of the heavily obscured AGN IRAS 01250+2832, based on the results of near-infrared high-resolution spectroscopy of gaseous CO ro-vibrational absorption lines with Subaru/IRCS. The detected CO absorption lines up to highly excited rotational levels reveal that hot dense molecular clouds exist around the AGN under the peculiar physical conditions.

Establishment and application of information resource of mutant mice in RIKEN BioResource Research Center

Masuya Hiroshi,Usuda Daiki,Nakata Hatsumi,Yuhara Naomi,Kurihara Keiko,Namiki Yuri,Iwase Shigeru,Takada Toyoyuki,Tanaka Nobuhiko,Suzuki Kenta,Yamagata Yuki,Kobayashi Norio,Yoshiki Atsushi,Kushida Tatsu 한국실험동물학회 2021 Laboratory Animal Research Vol.37 No.1

Online databases are crucial infrastructures to facilitate the wide effective and efficient use of mouse mutant resources in life sciences. The number and types of mouse resources have been rapidly growing due to the development of genetic modification technology with associated information of genomic sequence and phenotypes. Therefore, data integration technologies to improve the findability, accessibility, interoperability, and reusability of mouse strain data becomes essential for mouse strain repositories. In 2020, the RIKEN BioResource Research Center released an integrated database of bioresources including, experimental mouse strains, Arabidopsis thaliana as a laboratory plant, cell lines, microorganisms, and genetic materials using Resource Description Framework-related technologies. The integrated database shows multiple advanced features for the dissemination of bioresource information. The current version of our online catalog of mouse strains which functions as a part of the integrated database of bioresources is available from search bars on the page of the Center ( https://brc.riken.jp ) and the Experimental Animal Division ( https://mus.brc.riken.jp/ ) websites. The BioResource Research Center also released a genomic variation database of mouse strains established in Japan and Western Europe, MoG + ( https://molossinus.brc.riken.jp/mogplus/ ), and a database for phenotype-phenotype associations across the mouse phenome using data from the International Mouse Phenotyping Platform. In this review, we describe features of current version of databases related to mouse strain resources in RIKEN BioResource Research Center and discuss future views.

Activation-induced Apoptosis of Peripheral Lymphocytes Treated with 7-hydroxystaurosporin, UCN-01

Fukumoto, H.,Tamura, T.,Kamiya, Y.,Usuda, J.,Suzuki, T.,Kanazawa, F.,Kuh, H J.,Ohe, Y.,Saijo, N.,K. Nishio 가톨릭대학교 2000 Bulletin of The Catholic Research Institutes of Me Vol.28 No.-

7-hydroxystaurosporine (UCN-01) is a new anticancer agent which exerts an inhibitory effect on cell cycle check points and is currently under phase I clinical trials in US and Japan. Preliminary clinical data indicated that UCN-01 remained in plasma at high concentrations for long periods of time. this unavoidable high plasma drug exposure is likely to lead to hematological toxicties in patients. In the present study, cultured human peripheral blood lymphocytes (PBLs) were used to evaluate the possible hematological toxicities of UCN-01 treatment. UCN-01 treatment. UCN-01 induces apoptosis, and the induction of apoptosis-related surface markers were also examined to investigate the involvement of these molecules in UCN-01-induced apoptosis in PBLs. In vitro viability of PBLs was decreased by high dose of UCN-01 (25 microM, 3-day exposure). This effect of UCN-01 was significantly suppressed by the presence of human serum, suggesting that some specific inhibitory factor(s) in human serum may antagonize the lympholytic effect of UCN-01. The percentage of annexin V-positive PI-negative cells increased with exposure to UCN-01 in a time- and dose-dependent manner; by up to 30.3% after exposure to 25 microM UCN-01 for 3 day. At the same time, the expression of both interleukin-2 receptor (IL-2R, CD25) and Fas (CD95), analyzed by flow cytometry, was induced. Con A-stimulated PBLs were more sensitive to UCN-01-induced apoptosis than non-stimulated lymphocytes and UCN-01 increased the sFas-L released into culture medium from con A-stimulated PBLs. Therefore, lymphocyte depletion mediated by activation-induced apoptosis is likely to occur in patients treated with UCN-01 at high doses. (Investigational New Drugs 17(4):335-341, 1999)