研究者詳細 - 安田　浩之

論文 - 安田　浩之

分割表示 111 件中 81 - 100 件目／全件表示 >>

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

安田浩之

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 45 （ 4 ） 356 - 361 2015年04月

研究論文（学術雑誌）, ISSN 0368-2811

Access to Document (DOI)

Characterization of the cell of origin and propagation potential of the fibroblast growth factor 9-induced mouse model of lung adenocarcinoma

安田浩之

JOURNAL OF PATHOLOGY 235 （ 4 ） 593 - 605 2015年03月

研究論文（学術雑誌）, ISSN 0022-3417

Access to Document (DOI)

Multiple roles of extracellular fibroblast growth factors in lung cancer cells

Suzuki Takahiro, Yasuda Hiroyuki, Funaishi Koji, Arai Daisuke, Ishioka Kota, Ohgino Keiko, Tani Tetsuo, Hamamoto Junko, Ohashi Ayano, Naoki Katsuhiko, Betsuyaku Tomoko, Soejima Kenzo

International Journal of Oncology 46 （ 1 ） 423 - 429 2015年01月

ISSN 1019-6439

Cancer cells are surrounded by the extracellular fluid, matrix, and stroma cells. Little is known about how extracellular components such as growth factor ligands affect the biology of lung cancer cells. The objective of this study was to determine whether extracellular fibroblast growth factors (FGFs) can affect the biology of lung cancer cells and to understand how extracellular FGFs affect the biology of lung cancer cells, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cells. Out of the 23 reported FGFs, we focused on FGF2, FGF9 and FGF10. We examined the effect of FGFs on proliferation, treatment sensitivity, and apoptosis of NSCLC (PC9) and SCLC (H69, H82 and H146) cells in vitro. To determine which FGF was the most clinically relevant, we also examined FGF2 and FGF9 concentrations in the serum of patients with lung cancer. We found that extracellular FGFs can affect proliferation, treatment sensitivity, and apoptosis of lung cancer cells in a cell-specific manner. Our results indicate that extracellular FGFs affect the biology of lung cancer cells through multiple functions.

Access to Document (DOI)

Long-term exposure to gefitinib induces acquired resistance through DNA methylation changes in the EGFR-mutant PC9 lung cancer cell line

Terai Hideki, Soejima Kenzo, Yasuda Hiroyuki, Sato Takashi, Naoki Katsuhiko, Ikemura Shinnosuke, Arai Daisuke, Ohgino Keiko, Ishioka Kota, Hamamoto Junko, Kanai Yae, Betsuyaku Tomoko

International Journal of Oncology 46 （ 1 ） 430 - 436 2015年01月

ISSN 1019-6439

This study was designed to identify epigenetically regulated genes and to clarify the contribution of epigenetic alteration to acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-T KIs). We established a gefitinib-resistant lung cancer cell line, PC9, which was originally gefitinib-sensitive, by serial long-term exposure to gefitinib. RNA and DNA were collected from both gefitinib-sensitive and -resistant PC9 cells, and comprehensive DNA methylation and mRNA expression analyses were performed using Infinium HumanMethylation27 Bead Arrays and Agilent SurePrint G3 Human Gene Expression 8x60K Array, respectively. DNA methylation was increased in 640 genes in gefitinib-resistant cells compared to parental cells. Among them, we selected 29 candidate genes that presented a decrease in mRNA expression in resistant PC9. We further studied four of the selected genes (C10orf116, IGFBP3, KL, and S100P) and found that KL or S100P silencing by siRNA induced a decrease in gefitinib sensitivity compared to that in the negative control in PC9. In conclusion, KL and S100P could be potential targets to overcome resistance to EGFR-TKIs.

Access to Document (DOI)

Methylation-induced downregulation of TFPI-2 causes TMPRSS4 overexpression and contributes to oncogenesis in a subset of non-small-cell lung carcinoma

安田浩之

CANCER SCIENCE 106 （ 1 ） 34 - 42 2015年01月

研究論文（学術雑誌）, ISSN 1347-9032

Access to Document (DOI)

FOXD1 Expression Is Associated with Poor Prognosis in Non-small Cell Lung Cancer

安田浩之

ANTICANCER RESEARCH 35 （ 1 ） 261 - 268 2015年01月

研究論文（学術雑誌）, ISSN 0250-7005

A phase II study of biweekly paclitaxel and carboplatin in elderly patients with advanced non-small cell lung cancer

Soejima Kenzo, Naoki Katsuhiko, Ishioka Kota, Nakamura Morio, Nakatani Michie, Kawada Ichiro, Watanabe Hideo, Nakachi Ichiro, Yasuda Hiroyuki, Satomi Ryosuke, Nakayama Sohei, Yoda Satoshi, Ikemura Sinnosuke, Terai Hideki, Sato Takashi, Ohgino Keiko, Arai Daisuke, Tani Tetsuo, Kuroda Aoi, Nishino Makoto, Betsuyaku Tomoko

Cancer Chemotherapy and Pharmacology （Springer Science and Business Media LLC） 75 （ 3 ） 513 - 519 2015年

ISSN 0344-5704

Purpose: The number of elderly patients with advanced non-small cell lung cancer (NSCLC) is increasing. Although several studies have suggested the benefit of chemotherapy with a platinum doublet for elderly patients with advanced NSCLC, this treatment is still controversial in this age group. To evaluate the efficacy and tolerability of combination chemotherapy with biweekly paclitaxel and carboplatin for elderly patients with advanced NSCLC, we conducted a multicenter, non-randomized, open label, phase II trial. Methods: We recruited patients aged ≥70 years with clinical stage IIIB and IV NSCLC and ECOG performance status (PS) of 0-2. Patients received paclitaxel (90 mg/m2) and carboplatin (AUC = 2.5) on day 1 and 15, every 4 weeks. The primary endpoint was overall response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: Sixty-five patients (median age 79 years; range 70-87 years) were enrolled. Forty-nine patients were men, and 48 were stage IV. The PS was 0, 1, and 2 in 28, 33, and 4 patients, respectively. The histological type of NSCLC was non-squamous in 69.3 % and squamous cell carcino

Access to Document (DOI)

β-catenin contributes to lung tumor development induced by EGFR mutations

Nakayama Sohei, Sng Natasha, Carretero Julian, Welner Robert, Hayashi Yuichiro, Yamamoto Mihoko, Tan Alistair J., Yamaguchi Norihiro, Yasuda Hiroyuki, Li Danan, Soejima Kenzo, Soo Ross A., Costa Daniel B., Wong Kwok Kin, Kobayashi Susumu S.

Cancer Research 74 （ 20 ） 5891 - 5902 2014年10月

ISSN 0008-5472

The discovery of somatic mutations in EGFR and development of EGFR tyrosine kinase inhibitors (TKI) have revolutionized treatment for lung cancer. However, resistance to TKIs emerges in almost all patients and currently no effective treatment is available. Here, we show that β-catenin is essential for development of EGFR-mutated lung cancers. β-Catenin was upregulated and activated in EGFR-mutated cells. Mutant EGFR preferentially bound to and tyrosine phosphorylated β-catenin, leading to an increase in β-catenin-mediated transactivation, particularly in cells harboring the gefitinib/erlotinib-resistant gatekeeper EGFR-T790M mutation. Pharmacologic inhibition of β-catenin suppressed EGFR-L858R-T790M mutated lung tumor growth, and genetic deletion of the β-catenin gene dramatically reduced lung tumor formation in EGFR-L858R-T790M transgenic mice. These data suggest that b-catenin plays an essential role in lung tumorigenesis and that targeting the β-catenin pathway may provide novel strategies to prevent lung cancer development or overcome resistance to EGFR TKIs.

Access to Document (DOI)

Identification and Characterization of ALK Kinase Splicing Isoforms in Non-Small-Cell Lung Cancer

安田浩之

JOURNAL OF THORACIC ONCOLOGY 9 （ 2 ） 248 - 253 2014年02月

研究論文（学術雑誌）, ISSN 1556-0864

Access to Document (DOI)

Dual ALK and EGFR inhibition targets a mechanism of acquired resistance to the tyrosine kinase inhibitor crizotinib in ALK rearranged lung cancer

Yamaguchi Norihiro, Lucena-Araujo Antonio R., Nakayama Sohei, de Figueiredo-Pontes Lorena L., Gonzalez David A., Yasuda Hiroyuki, Kobayashi Susumu, Costa Daniel B.

Lung Cancer 83 （ 1 ） 37 - 43 2014年01月

ISSN 0169-5002

Introduction: The multitargeted tyrosine kinase inhibitor (TKI) crizotinib is active against ALK translocated non-small-cell lung cancer (NSCLC); however acquired resistance invariably develops over time. ALK mutations have previously been implicated in only a third of resistant tumors. We sought to evaluate alternative mechanisms of resistance and preclinical strategies to overcome these in a cell line driven by EML4-ALK. Methods: We selected the NSCLC cell line NCI-H3122 (H3122: EML4- ALK E13;A20) and derived resistant variants that were able to grow in the presence of 1. μM crizotinib. These were analyzed for ALK mutations, sensitivity to crizotinib in combination with other TKIs, and for activation of alternative tyrosine kinases. Results: All H3122 crizotinib resistant (CR) clones lacked amplification or mutations in the kinase domain of ALK. To evaluate if possible alternative kinases functioned as "bypass" tracks for downstream signaling activation in these resistance cells, we performed of phosho-receptor tyrosine kinase array that demonstrated that CR clones had higher phospho-EGFR signals than H3122 cells before and after exposure to crizotinib. A functional approach of dual ALK TKI (with crizotinib) with combinatory TKI inhibition was used as a secondary screen for possible targets. Crizotinib. +. erlotinib (reversible EGFR TKI) and crizotinib. +. afatinib (irreversible EGFR/ERBB2 TKI) were able to inhibit the growth of H3122 CR clones, confirming EGFR activation as a mechanism of resistance. The removal of crizotinib from the culture media re-sensitized CR cells to crizotinib. Conclusions: We identified activation of EGFR as a mechanism of resistance to crizotinib in preclinical models of ALK translocated NSCLC. If EGFR activation is confirmed as a predominant mechanism of ALK TKI-induced resistance in patient-derived tumors, the use of ALK plus EGFR TKIs could be explored for this important cohort of NSCLCs. © 2013 Elsevier Ireland Ltd.

Access to Document (DOI)

Expression of fibroblast growth factor 9 is associated with poor prognosis in patients with resected non-small cell lung cancer

安田浩之

LUNG CANCER 83 （ 1 ） 90 - 96 2014年01月

研究論文（学術雑誌）, ISSN 0169-5002

Access to Document (DOI)

The efficacy, safety, and pharmacokinetics of biapenem administered thrice daily for the treatment of pneumonia in the elderly

Namkoong Ho, Kameyama Youjyu, Yasuda Hiroyuki, Nakayama Sohei, Kaneko Hiroshi, Kawashima Chieko, Terajima Tomoko, Maezawa Kayoko, Hayashi Takeshi, Sandoh Mitsuru, Ishii Makoto, Tasaka Sadatomo, Kanayama Akiko, Kobayashi Intetsu, Betsuyaku Tomoko, Kizu Junko, Iwata Satoshi, Sato Yoshitake, Hasegawa Naoki

Journal of Infection and Chemotherapy 20 （ 6 ） 356 - 360 2014年

ISSN 1341-321X

Biapenem has been widely used to treat bacterial pneumonia; however, there is little information concerning its efficacy and safety in elderly patients. Based on pharmacokinetic-pharmacodynamic theory, administration of biapenem thrice rather than twice daily would be expected to be more effective because of longer time above the minimum inhibitory concentration. In this study, we aimed to evaluate the efficacy, safety, and pharmacokinetics of biapenem (300 mg) administered thrice daily in pneumonic patients aged 65 years or older. Biapenem was effective in 22 of 25 patients, as assessed by the improvement in clinical symptoms and/or the eradication of the causative organisms, and caused no serious adverse events. The pharmacokinetic profile was established based on simulations using a modeling program. Among 17 patients whose causative organisms were detected, time above the minimum inhibitory concentration was estimated to be 100% in 16 patients, all of whom showed clinical improvement. The results of this study confirmed the efficacy and safety of 300 mg of biapenem administered thrice daily for the treatment of pneumonia in elderly patients. © 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Access to Document (DOI)

Claudin-1 is a novel target of miR-375 in non-small-cell lung cancer

Yoda Satoshi, Soejima Kenzo, Hamamoto Junko, Yasuda Hiroyuki, Nakayama Sohei, Satomi Ryosuke, Terai Hideki, Ikemura Shinnosuke, Sato Takashi, Naoki Katsuhiko, Betsuyaku Tomoko

Lung Cancer 85 （ 3 ） 366 - 372 2014年

ISSN 0169-5002

Objectives: We previously reported low expression of miR-375 in squamous-cell carcinoma (SCC) and high expression in adenocarcinoma (AC) of the lung. miR-. 375's target genes and its function in non-small-cell lung cancer (NSCLC) have not been elucidated. Therefore, the present study was designed to identify the targets of miR-375 and to characterize its function in NSCLC. Materials and methods: Candidate targets of miR-375 were determined using a prediction database and previous data on differential gene expression between SCC and AC. We evaluated miR-375 and target-gene expression levels in 12 NSCLC cell lines. The effect of miR-375 overexpression and knockdown was evaluated in NSCLC cell lines by transfecting them with an miR-375 precursor or inhibitor. A luciferase-reporter assay was performed to confirm a direct interaction between miR-375 and its target gene. Further, a wound-healing assay was performed to evaluate the effect of miR-375 overexpression on the migration of SK-MES-1 cells. Finally, to assess the clinical relevance, 63 clinical NSCLC samples were analyzed. Results: Claudin-1 (CLDN1) has 4 putative miR-375 target sites in its 3'-untranslated region, and this gene was determined to be a target of miR-375. CLDN1 messenger RNA and protein expression were attenuated by overexpression of miR-375 and increased by knockdown of miR-375 in NSCLC cell lines. In a luciferase-reporter assay, miR-375 overexpression resulted in a 3-fold repression of luciferase activity (P<. 0.001). Cell migration was promoted by miR-375 overexpression, suggesting a high potential for invasion and metastasis in NSCLC expressing high levels of miR-375. In clinical NSCLC samples, there was a negative correlation between miR-375 and CLDN1 expression (r = -0.35, P = 0.005). In addition, high miR-375 expression was correlated with a shorter survival time among the clinical samples (P = 0.043). Conclusion: CLDN1 is a novel target of miR-375, and high miR-375 expression shortens survival in NSCLC.

Access to Document (DOI)

Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer

Yasuda Hiroyuki, Park Eunyoung, Yun Cai Hong, Sng Natasha J., Lucena-Araujo Antonio R., Yeo Wee Lee, Huberman Mark S., Cohen David W., Nakayama Sohei, Ishioka Kota, Yamaguchi Norihiro, Hanna Megan, Oxnard Geoffrey R., Lathan Christopher S., Moran Teresa, Sequist Lecia V., Chaft Jamie E., Riely Gregory J., Arcila Maria E., Soo Ross A., Meyerson Matthew, Eck Michael J., Kobayashi Susumu S., Costa Daniel B.

Science Translational Medicine 5 （ 216 ） 2013年12月

ISSN 1946-6234

Epidermal growth factor receptor (EGFR) gene mutations (G719X, exon 19 deletions/insertions, L858R, and L861Q) predict favorable responses to EGFR tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). However, EGFR exon 20 insertion mutations (∼10% of all EGFR mutations) are generally associated with insensitivity to available TKIs (gefitinib, erlotinib, and afatinib). The basis of this primary resistance is poorly understood. We studied a broad subset of exon 20 insertion mutations, comparing in vitro TKI sensitivity with responses to gefitinib and erlotinib in NSCLC patients, and found that most are resistant to EGFR TKIs. The crystal structure of a representative TKI-insensitive mutant (D770-N771insNPG) reveals an unaltered adenosine triphosphate-binding pocket, and the inserted residues form a wedge at the end of the C helix that promotes the active kinase conformation. Unlike EGFR-L858R, D770-N771insNPG activates EGFR without increasing its affinity for EGFR TKIs. Unexpectedly, we find that EGFR-A763-Y764insFQEA is highly sensitive to EGFR TKIs in vitro, and patients whose NSCLCs harbor this mutation respond to erlotinib. Analysis of the A763-Y764insFQEA mutant indicates that the inserted residues shift the register of the C helix in the N-terminal direction, altering the structure in the region that is also affected by the TKI-sensitive EGFR-L858R. Our studies reveal intricate differences between EGFR mutations, their biology, and their response to EGFR TKIs.

Access to Document (DOI)

Identification of microRNAs differentially expressed between lung squamous cell carcinoma and lung adenocarcinoma

安田浩之

MOLECULAR MEDICINE REPORTS 8 （ 2 ） 456 - 462 2013年08月

研究論文（学術雑誌）, ISSN 1791-2997

Access to Document (DOI)

Activation of the FGF2-FGFR1 autocrine pathway

Terai Hideki, Soejima Kenzo, Yasuda Hiroyuki, Nakayama Sohei, Hamamoto Junko, Arai Daisuke, Ishioka Kota, Ohgino Keiko, Ikemura Shinnosuke, Sato Takashi, Yoda Satoshi, Satomi Ryosuke, Naoki Katsuhiko, Betsuyaku Tomoko

Molecular Cancer Research 11 （ 7 ） 759 - 767 2013年07月

ISSN 1541-7786

Patients with non-small cell lung cancer (NSCLC) that harbors epidermal growth factor receptor (EGFR) mutations initially respond to EGFR-tyrosine kinase inhibitors (TKI) but eventually experience relapse. Acquired resistance to EGFR-TKIs is strongly associated with patient mortality. Thus, elucidation of the mechanism of acquired resistance to EGFR-TKIs is of great importance. In this study, gefitinib-resistant cell line models were established by long-term exposure to gefitinib using the gefitinib-sensitive lung cancer cell lines, PC9 and HCC827. Expression analyses indicated that both FGFR1 and FGF2 were increased in PC9 gefitinib-resistant (PC9 GR) cells as compared with PC9 naïve (PC9 na) cells. Importantly, proliferation of gefitinib-resistant cells was dependent on the FGF2-FGFR1 pathway. Mechanistically, inhibition of either FGF2 or FGFR1 by siRNA or FGFR inhibitor (PD173074) restored gefitinib sensitivity in PC9 GR cells. These data suggest that FGF2-FGFR1 activation through an autocrine loop is a novel mechanism of acquired resistance to EGFR-TKIs. © 2013 American Association for Cancer Research.

Access to Document (DOI)

Frequent downregulation of the transcription factor Foxa2 in lung cancer through epigenetic silencing

Basseres Daniela S., D'Alò Francesco, Yeap Beow Y., Löwenberg Ester C., Gonzalez David A., Yasuda Hiroyuki, Dayaram Tajhal, Kocher Olivier N., Godleski John J., Richards William G., Meyerson Matthew, Kobayashi Susumu, Tenen Daniel G., Halmos Balázs, Costa Daniel B.

Lung Cancer 77 （ 1 ） 31 - 37 2012年07月

ISSN 0169-5002

Purpose: We sought to determine the mechanisms of downregulation of the airway transcription factor Foxa2 in lung cancer and the expression status of Foxa2 in non-small-cell lung cancer (NSCLC). Methods: A series of 25 lung cancer cell lines were evaluated for Foxa2 protein expression, FOXA2 mRNA levels, FOXA2 mutations, FOXA2 copy number changes and for evidence of FOXA2 promoter hypermethylation. In addition, 32 NSCLCs were sequenced for FOXA2 mutations and 173 primary NSCLC tumors evaluated for Foxa2 expression using an immunohistochemical assay. Results: Out of the 25 cell lines, 13 (52%) had undetectable FOXA2 mRNA. The expression of FOXA2 mRNA and Foxa2 protein were congruent in 19/22 cells (p= 0.001). FOXA2 mutations were not identified in primary NSCLCs and were infrequent in cell lines. Focal or broad chromosomal deletions involving FOXA2 were not present. The promoter region of FOXA2 had evidence of hypermethylation, with an inverse correlation between FOXA2 mRNA expression and presence of CpG dinucleotide methylation (p< 0.0001). In primary NSCLC tumor specimens, there was a high frequency of either absence (42/173, 24.2%) or no/low expression (96/173, 55.4%) of Foxa2. In 130 patients with stage I NSCLC there was a trend towards decreased survival in tumors with no/low expression of Foxa2 (HR of 1.6, 95%CI 0.9-3.1; p= 0.122). Conclusions: Loss of expression of Foxa2 is frequent in lung cancer cell lines and NSCLCs. The main mechanism of downregulation of Foxa2 is epigenetic silencing through promoter hypermethylation. Further elucidation of the involvement of Foxa2 and other airway transcription factors in the pathogenesis of lung cancer may identify novel therapeutic targets. © 2012 Elsevier Ireland Ltd.

Access to Document (DOI)

Preclinical rationale for use of the clinically available multitargeted tyrosine kinase inhibitor crizotinib in ROS1-translocated lung cancer

Yasuda Hiroyuki, De Figueiredo-Pontes Lorena L., Kobayashi Susumu, Costa Daniel B.

Journal of Thoracic Oncology 7 （ 7 ） 1086 - 1090 2012年07月

ISSN 1556-0864

INTRODUCTION: Most clinically available small-molecule kinase inhibitors are multi-targeted and can inhibit multiple kinases. Our driving hypothesis was that one of these multi-targeted tyrosine kinase inhibitors (TKIs) would have antiproliferative activity against ROS1 translocated non-small-cell lung cancer (NSCLC). METHODS: We selected NSCLC cell lines-A549 (KRAS G12S), NCI-H3255 (EGFR L858R), NCI-H3122 (EML4-ALK E13;A20), and HCC78 (SLC34A2-ROS1)-to evaluate the antiproliferative effects of submicromolar concentrations of the multitargeted TKIs imatinib, sorafenib, erlotinib, and crizotinib. RESULTS: Imatinib and sorafenib were unable to significantly inhibit proliferation of the aforementioned cell lines. Erlotinib only inhibited EGFR mutated NCI-H3255, as expected. Crizotinib displayed dose-dependent inhibition of anaplastic lymphoma kinase translocated NCI-H3122 and also ROS1-translocated HCC78. The SLC34A2-ROS1 translocated HCC78 cell line had phosphorylated levels of ROS1, AKT, and ERK inhibited by submicromolar doses of crizotinib, and subsequently underwent apoptosis. CONCLUSIONS: The ROS1-translocated HCC78 cell line was sensitive to inhibition by the multitargeted ALK/MET/RON/ROS1 inhibitor crizotinib. Preclinical data supports the clinical development of crizotinib for ROS1-translocated NSCLC. Copyright © 2012 by the International Association for the Study of Lung Cancer.

Access to Document (DOI)

EGFR exon 20 insertion mutations in non-small-cell lung cancer: preclinical data and clinical implications

安田浩之

LANCET ONCOLOGY 13 （ 1 ） E23 - E31 2012年01月

研究論文（学術雑誌）, ISSN 1470-2045

Access to Document (DOI)

The PCR-invader method (structure-specific 5 nuclease-based method), a sensitive method for detecting EGFR gene mutations in lung cancer specimens; Comparison with direct sequencing

Naoki Katsuhiko, Soejima Kenzo, Okamoto Hiroaki, Hamamoto Junko, Hida Naoya, Nakachi Ichiro, Yasuda Hiroyuki, Nakayama Sohei, Yoda Satoshi, Satomi Ryosuke, Ikemura Shinnosuke, Terai Hideki, Sato Takashi, Watanabe Koshiro

International Journal of Clinical Oncology 16 （ 4 ） 335 - 344 2011年08月

ISSN 1341-9625

Background: Several sensitive assays, including the PCR-invader method (structure-specific 5 nuclease-based method), have been used to detect EGFR mutations in non-small-cell lung cancer (NSCLC). However, validation has not been reported. We assessed the detection rate of EGFR mutation by the PCR-invader method and direct sequencing using same clinical specimens. Patients and methods: EGFR mutations were analyzed with the PCR-invader method and compared with direct sequencing using paraffin tissues and pleural and pericardial effusions from NSCLC patients. The relationships between the treatment responses and mutations were evaluated retrospectively. Results: Fifty-four samples from 42 NSCLC patients were studied. EGFR mutations were identified in 52% of the patients and 52% of the samples with the PCR-invader method, but only in 43% of the patients and in 35% of the samples by direct sequencing. In the samples obtained from the same patients at different sites and different times, EGFR mutations were coincident in nine out of ten patients by the PCR-invader method but in six out of ten patients by direct sequencing. Seventeen patients with EGFR mutations were treated with gefitinib; the response rate (RR) and disease control rate (DCR) were 41 and 94%, and median treatment duration was more than 6 months. Seven EGFR mutation-negative patients were treated with gefitinib; the RR and DCR were 0 and 14%, and median treatment duration was 1 month. Conclusion: The PCR-invader method was useful for detecting EGFR mutations in clinical lung cancer specimens and is more sensitive than direct sequencing. © 2011 Japan Society of Clinical Oncology.

Access to Document (DOI)

　前のページ - 次のページ　

安田 浩之

論文 - 安田 浩之

安田　浩之

論文 - 安田　浩之