論文 - 安田　浩之

Bronchoscopic Microsampling is a Useful Complementary Diagnostic Tool for Detecting Lung Cancer

Yasuda Hiroyuki, Soejima Kenzo, Nakayama Sohei, Kawada Ichiro, Nakachi Ichiro, Yoda Satoshi, Satomi Ryosuke, Ikemura Shinnosuke, Terai Hideki, Sato Takashi, Watanabe Hideo, Naoki Katsuhiko, Hayashi Yuichiro, Ishizaka Akitoshi

Lung Cancer 72 （ 1 ） 32 - 38 2011年04月

ISSN  0169-5002

　概要を見る

<p>Purpose: Bronchoscopic microsampling (BMS) is a novel and direct method with which to obtain epithelial lining fluid (ELF) from the lungs. Analysis of DNA hypermethylation of tumor suppressor genes (TSGs) is expected to be a sensitive tool for the early detection of lung cancer. It has been reported that the existence of EGFR mutations and EML4-ALK gene rearrangements are related to the sensitivity of corresponding kinase inhibitors. We aimed to evaluate the suitability of ELF as a sample for analyzing molecular changes specific for lung cancer. Patients and methods: We collected ELF from 61 lung cancer patients by BMS from the airway close to the peripheral lung nodule and purified the nucleic acids. We performed methylation specific PCR in each ELF as well as matched serum and tumor tissue for TSGs for DNA methylation analysis. We also examined EGFR mutations and EML4-ALK rearrangement. Results: The sensitivity for detecting DNA hypermethylation in ELF vs serum was 74.1% vs 18.5%. We found 60.1% of patients had at least one hypermethylation in ELF, while only 27.9% had it in serum. Of note, DNA hypermethylation was detected even in stage I patients (60.0%) and the detection rate was almost the same level in each stage. We also found the sensitivity for detecting EGFR mutation in ELF vs serum was 58.3% vs 8.3%. We detected an EML4-ALK fusion gene using ELF in one patient. Conclusions: BMS is an alternative method to detect cancer specific genetic and epigenetic alterations and will be a useful complementary diagnostic tool for lung cancer. Summary: Investigation of genetic and epigenetic changes associated with lung cancer has clinical importance for its diagnosis and management. The clinical usefulness of bronchoscopic microsampling (BMS) in lung cancer has not yet been evaluated. This study demonstrates that BMS could be useful for detecting lung cancer specific molecular changes and valuable for early diagnosis and determination of treatment options for lung cancer. © 2010 Elsevier Ireland Ltd.</p>

• Access to Document (DOI)

A phase I study of S-1 and irinotecan combination therapy in previously treated advanced non-small cell lung cancer patients

安田 浩之

CANCER CHEMOTHERAPY AND PHARMACOLOGY 67 （ 3 ） 717 - 722 2011年03月

研究論文（学術雑誌）,  ISSN  0344-5704

• Access to Document (DOI)

Distinct epigenetic regulation of tumor suppressor genes in putative cancer stem cells of solid tumors

安田 浩之

INTERNATIONAL JOURNAL OF ONCOLOGY 37 （ 6 ） 1537 - 1546 2010年12月

研究論文（学術雑誌）,  ISSN  1019-6439

• Access to Document (DOI)

Distinct epigenetic regulation of tumor suppressor genes in putative cancer stem cells of solid tumors

Yasuda Hiroyuki, Soejima Kenzo, Watanabe Hideo, Kawada Ichiro, Nakachi Ichiro, Yoda Satoshi, Nakayama Sohei, Satomi Ryosuke, Ikemura Shinnosuke, Terai Hideki, Sato Takashi, Suzuki Sadafumi, Matsuzaki Yumi, Naoki Katsuhiko, Ishizaka Akitoshi

International Journal of Oncology 37 （ 6 ） 1537 - 1546 2010年12月

ISSN  1019-6439

　概要を見る

<p>Epigenetic gene regulation plays essential roles in differentiation of embryonic and tissue stem cells. In these benign undifferentiated cells, some polycomb targeted genes are kept in a state of DNA hypomethylation and they have a distinct chromatin signature termed bivalent chromatin structure to maintain their plasticity. We hypothesized that cancer stem cells (CSC), the malignant counterpart of these cells, are also under the control of epigenetics like benign stem cells. We compared the DNA methylation and chromatin structure in 10 tumor suppressor genes between CSC and differentiated cancer cells of MCF7 and Huh7 cells. We found that the level of DNA methylation was indeed significantly lower in CSC, while surprisingly, the bivalent chromatin structure was more ubiquitously seen in differentiated cancer cells compared to CSC. However, repressive marks of chromatin structure, namely H3K27me3 and EZH2, were significantly lower in CSC. As a consequence, CSC remained in a higher transcriptionally active chromatin state compared to differentiated cancer cells. We found that the differentiation of CSCs is also epigenetically regulated. These findings could help towards a comprehensive understanding of CSC, and also improve the development of eradicative therapies against human malignancies.</p>

• Access to Document (DOI)

The Combination of Multiple Receptor Tyrosine Kinase Inhibitor and Mammalian Target of Rapamycin Inhibitor Overcomes Erlotinib Resistance in Lung Cancer Cell Lines through c-Met Inhibition

安田 浩之

MOLECULAR CANCER RESEARCH 8 （ 8 ） 1142 - 1151 2010年08月

研究論文（学術雑誌）,  ISSN  1541-7786

• Access to Document (DOI)

S-1/Radiation併用療法によってCRが得られたGefitinib抵抗性の非小細胞肺癌術後再発の1例

藤本 博行, 小山 孝彦, 水渡 哲史, 橋本 浩平, 亀山 洋樹, 安田 浩之, 石塚 広司

癌と化学療法 （(株)癌と化学療法社）  37 （ 2 ） 295 - 298 2010年02月

ISSN  0385-0684

　概要を見る

症例は35歳、女性。肺腺癌c-T2N2M0に対して術前CDDP+DOCを3コース施行。NCの効果判定で左肺下葉切除術およびND2a系統的縦隔リンパ節郭清術を施行した。p-T2N2M0であった。術後療法としてgefitinibを投与。2ヵ月間の内服後の評価で気管分岐下リンパ節の腫脹とSLXの上昇を認めたため、gefitinibの投与を中止した。術後4ヵ月より縦隔へ放射線を総量50Gy照射した。術後5ヵ月よりS-1化学療法を施行した。S-1は100mg/dayで1日二分割投与、4週投与2週休薬とした。S-1の増量は行わず、6コースの化学療法を施行した。縦隔リンパ節腫脹は消失、SLXも正常化し、complete response(CR)となった。その後UFT内服にて外来経過観察中であり術後36ヵ月以上経過するが、現在のところ再発の徴候はない。(著者抄録)

FDG-PET imaging of benign pulmonary diseases

Terai Hideki, Soejima K., Naoki K., Kawada I., Nakachi I., Satomi R., Nakayama S., Yoda S., Ikemura S., Sato T., Ishizaka A., Yasuda H.

Japanese Journal of Clinical Radiology 55 （ 1 ） 163 - 172 2010年

ISSN  0009-9252

　概要を見る

<p>The usefulness of fluorodeoxyglucose (FDG) -positron emission tomography (PET) has been established for the diagnosis of cancer. However, we often experience false positive as well as false negative cases in clinical practice. Examining those will be useful to understand more adequate use of FDG-PET. So we evaluated all the PET/CT results (n=467) conducted from April 2003 to March 2008 and selected 54 cases diagnosed eventually as benign pulmonary diseases. As a whole, the PET positive rate in the benign disease was 48.1% (26/54). In contrast, 149 cases with primary lung cancer examined in the same period yielded the positive rate of 86.6% (129/146). We analyzed the changes of PET positive rate by the shape or the size of the shadow, and by the disease. And we summarized false positive results from FDG-PET study and classified them into seven categories (inflammation, interstitial lung disease, pneumoconiosis, radiation pneumonia, granulomatous disease, large vessel vasculitis, mediastinal disease).</p>

A case of complete response treated by S-1 with concurrent radiotherapy for a gefitinib-resistant non-small cell lung cancer patient

Fujimoto, H., Oyama, T., Suito, T., Hashimoto, K., Kameyama, Y., Yasuda, H., Ishizuka, H.

Japanese Journal of Cancer and Chemotherapy 37 （ 2 ）  2010年

Deregulation of histone lysine methyltransferases contributes to oncogenic transformation of human bronchoepithelial cells.

Hideo Watanabe, Kenzo Soejima, Hiroyuki Yasuda, Ichiro Kawada, Ichiro Nakachi, Satoshi Yoda, Katsuhiko Naoki, Akitoshi Ishizaka

Cancer cell international 8   15 - 15 2008年11月

　概要を見る

BACKGROUND: Alterations in the processing of the genetic information in carcinogenesis result from stable genetic mutations or epigenetic modifications. It is becoming clear that nucleosomal histones are central to proper gene expression and that aberrant DNA methylation of genes and histone methylation plays important roles in tumor progression. To date, several histone lysine methyltransferases (HKMTs) have been identified and histone lysine methylation is now considered to be a critical regulator of transcription. However, still relatively little is known about the role of HKMTs in tumorigenesis. RESULTS: We observed differential HKMT expression in a lung cancer model in which normal human bronchial epithelial (NHBE) cells expressing telomerase, SV40 large T antigen, and Ras were immortal, formed colonies in soft agar, and expressed specific HKMTs for H3 lysine 9 and 27 residues but not for H3 lysine 4 residue. Modifications in the H3 tails affect the binding of proteins to the histone tails and regulate protein function and the position of lysine methylation marks a gene to be either activated or repressed. In the present study, suppression by siRNA of HKMTs (EZH2, G9A, SETDB1 and SUV39H1) that are over-expressed in immortalized and transformed cells lead to reduced cell proliferation and much less anchorage-independent colony growth. We also found that the suppression of H3-K9, G9A and SUV39H1 induced apoptosis and the suppression of H3-K27, EZH2 caused G1 arrest. CONCLUSION: Our results indicate the potential of these HKMTs in addition to the other targets for epigenetics such as DNMTs and HDACs to be interesting therapeutic targets.

• Access to Document (DOI)

Clinical evaluation of the deep venous thrombosis and pulmonary embolism after total joint arthroplasty

Sui, O., Kubo, A., Yasuda, H., Hirohashi, N., Yoshikawa, Y., Kato, Y., Inoue, T., Tonai, T.

Japanese Journal of Clinical Radiology 52 （ 1 ）  2007年

20.無気肺を契機に発見され高周波スネアにて切除した気管支内過誤腫の1例(第116回 日本呼吸器内視鏡学会関東支部会)

堀口 速史, 安田 浩之, 石井 誠, 鈴木 雄介, 赤塚 誠哉, 小林 紘一

気管支学 （特定非営利活動法人 日本呼吸器内視鏡学会）  28 （ 4 ） 327 - 327 2006年

• Access to Document (DOI)