Faculty Profiles - TOYOOKA Shinichi

TAE226, a Bis-Anilino Pyrimidine Compound, Inhibits the EGFR-Mutant Kinase Including T790M Mutant to Show Anti-Tumor Effect on EGFR-Mutant Non-Small Cell Lung Cancer Cells Reviewed

Hiroki Otani, Hiromasa Yamamoto, Munenori Takaoka, Masakiyo Sakaguchi, Junichi Soh, Masaru Jida, Tsuyoshi Ueno, Takafumi Kubo, Hiroaki Asano, Kazunori Tsukuda, Katsuyuki Kiura, Shinji Hatakeyama, Eiji Kawahara, Yoshio Naomoto, Shinichiro Miyoshi, Shinichi Toyooka

PLOS ONE 10 ( 6 ) e0129838 2015.6

Language：English Publishing type：Research paper (scientific journal) Publisher：PUBLIC LIBRARY SCIENCE

TAE226, a bis-anilino pyrimidine compound, has been developed as an inhibitor of focal adhesion kinase (FAK) and insulin-like growth factor-I receptor (IGF-IR). In this study, we investigated the effect of TAE226 on non-small-cell lung cancer (NSCLC), especially focusing on the EGFR mutational status. TAE226 was more effective against cells with mutant EGFR, including the T790M mutant, than against cells with wild-type one. TAE226 preferentially inhibited phospho-EGFR and its downstream signaling mediators in the cells with mutant EGFR than in those with wild-type one. Phosphorylation of FAK and IGF-IR was not inhibited at the concentration at which the proliferation of EGFR-mutant cells was inhibited. Results of the in vitro binding assay indicated significant differences in the affinity for TAE226 between the wild-type and L858R (or delE746_A750) mutant, and the reduced affinity of ATP to the L858R (or delE746_A750) mutant resulted in good responsiveness of the L858R (or delE746_A750) mutant cells to TAE226. Of interest, the L858R/T790M or delE746_A750/T790M mutant enhanced the binding affinity for TAE226 compared with the L858R or delE746_A750 mutant, resulting in the effectiveness of TAE226 against T790M mutant cells despite the T790M mutation restoring the ATP affinity for the mutant EGFR close to that for the wild-type. TAE226 also showed higher affinity of about 15-fold for the L858R/T790M mutant than for the wild-type one by kinetic interaction analysis. The antitumor effect against EGFR-mutant tumors including T790M mutation was confirmed in mouse models without any significant toxicity. In summary, we showed that TAE226 inhibited the activation of mutant EGFR and exhibited anti-proliferative activity against NSCLCs carrying EGFR mutations, including T790M mutation.

DOI： 10.1371/journal.pone.0129838

Radiofrequency Ablation of Lung Metastases from Adenoid Cystic Carcinoma of the Head and Neck: Retrospective Evaluation of Nine Patients Reviewed

Toshihiro Iguchi, Takao Hiraki, Hideo Gobara, Hiroyasu Fujiwara, Yusuke Matsui, Shinichi Toyooka, Kazunori Nishizaki, Susumu Kanazawa

JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY 26 ( 5 ) 703 - 708 2015.5

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Purpose: To retrospectively evaluate the outcomes of radiofrequency (RF) ablation of lung metastases from head and neck adenoid cystic carcinoma (ACC).
Materials and Methods: Nine patients (two men and seven women; mean age, 61.6 y) with 45 lung metastases (mean diameter, 1.1 cm; range, 0.4-2.7 cm) from head and neck ACC underwent RF ablation in 30 sessions. Primary endpoints were technical success, technique effectiveness, and procedural complications. Secondary endpoints included overall survival (OS).
Results: RF ablation was technically successful for all 45 metastases. The median tumor follow-up period was 37.1 months (range, 12.9-128.3 mo). Local progression occurred in six tumors, two of which were treated again and subsequently showed complete response. Major complications (pneumothorax requiring chest tube placement) occurred in five sessions (16.7%). The median patient follow-up period was 61.6 months (range, 20.5-134.5 mo). Two patients died of disease progression at 38.9 and 61.6 months after RF ablation, respectively, whereas the other seven remained alive at the end of the study. OS rates from the initial RF ablation were 100% at 3 years and 83.3% at 5 years (mean survival time, 106.4 mo). OS rates from the treatment of the primary site were 100% at 5 years and 62.5% at 10 years (mean survival time, 210.1 mo).
Conclusions: Radiofrequency ablation is an acceptable and effective local treatment for lung metastases from head and neck ACC. However, further study is needed to evaluate its effect on patient survival.

DOI： 10.1016/j.jvir.2014.11.040

Lower lobe origin is a poor prognostic factor in locally advanced non-small-cell lung cancer patients treated with induction chemoradiotherapy. Reviewed International journal

Kazuhiko Shien, Shinichi Toyooka, Junichi Soh, Katsuyuki Hotta, Kuniaki Katsui, Takahiro Oto, Susumu Kanazawa, Katsuyuki Kiura, Hiroshi Date, Shinichiro Miyoshi

Molecular and clinical oncology 3 ( 3 ) 706 - 712 2015.5

Language：English Publishing type：Research paper (scientific journal)

The AIM of this study was to identify prognostic factors in patients receiving trimodality therapy for locally advanced non-small-cell lung cancer (NSCLC). Among patients who underwent induction chemoradiotherapy (CRT) followed by surgery between 1999 and 2011 at our institution, 76 NSCLC patients with clinical (c) N2/3 stage III were enrolled in this retrospective study. Induction CRT consisted of docetaxel and cisplatin with concurrent 40-60 Gy radiation therapy. In total, 76 patients were assessed (53 men and 23 women) with 43 adenocarcinomas and 33 non-adenocarcinomas. Of the 76 patients, 44 had cStage IIIA and 32 had cStage IIIB disease. The primary tumors were located in the right upper lobe (N=33), right middle lobe (N=5), right lower lobe (N=11), left upper lobe (N=20s) and left lower lobe (N=7). For all 76 patients, lower lobe tumors were associated with a significantly shorter overall survival (OS) and disease-free survival (DFS) compared to non-lower lobe tumors (OS, P=0.022; and DFS, P=0.0007). When the analysis was limited to pathologically proven N2/3 disease prior to induction CRT (n=36), lower lobe location, compared to other locations, tended to be a poor prognostic factor (OS, P=0.068; and DFS, P=0.0075). Our results indicated that a lower lobe tumor origin is associated with unfavorable prognosis in NSCLC patients treated with induction CRT, strongly suggesting the significance of appropriate patient selection in order to maximize the benefits of trimodality therapy.

DOI： 10.3892/mco.2015.509

Percutaneous Radiofrequency Ablation of Lung Cancer Presenting as Ground-Glass Opacity Reviewed

Toshihiro Iguchi, Takao Hiraki, Hideo Gobara, Hiroyasu Fujiwara, Yusuke Matsui, Junichi Soh, Shinichi Toyooka, Katsuyuki Kiura, Susumu Kanazawa

CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY 38 ( 2 ) 409 - 415 2015.4

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

We retrospectively evaluated the outcomes of lung cancer patients presenting with ground-glass opacity (GGO) who received radiofrequency ablation (RFA).
Sixteen patients (5 men and 11 women; mean age, 72.6 years) with 17 lung cancer lesions showing GGO (mean long axis diameter, 1.6 cm) underwent a total of 20 percutaneous computed tomography (CT) fluoroscopy-guided RFA sessions, including three repeated sessions for local progression. Lung cancer with GGO was defined as a histologically confirmed malignant pulmonary lesion with a GGO component accounting for > 50 % of the lesion on high-resolution CT. Procedure outcomes were evaluated.
There were no major complications. Pneumothorax occurred in 15 of 20 treatment sessions: 14 were asymptomatic, and 1 required chest tube placement but resolved satisfactorily within 48 h. Minor pulmonary hemorrhage occurred in two and mild pneumonitis in one. The median tumor follow-up period was 61.5 (range 6.1-96.6) months. The effectiveness rates of the primary and secondary techniques were 100 and 100 % at 1 year, 93.3 and 100 % at 2 years, and 78.3 and 92.3 % at 3 years, respectively. The median patient follow-up period was 65.6 (range 6.1-96.6) months. One patient died owing to recurrent other cancer 11.7 months after RFA, whereas the other 15 remained alive. Overall survival and disease-specific survival rates were 93.3 and 100 % at 1 year and 93.3 and 100 % at 5 years, respectively.
RFA for lung cancer with GGO was safe and effective, and resulted in promising survival rates.

DOI： 10.1007/s00270-014-0926-x

胸腔鏡下拡大胸腺摘除術を施行した重症筋無力症の1例

悪性胸膜中皮腫におけるDNAコピー数の増加(DNA copy number gains in malignant pleural mesothelioma)

古川公之, 豊岡伸一, 林達朗, 山本寛斉, 宗淳一, 橋田真輔, 枝園和彦, 浅野博昭, 岡部和倫, 佃和憲, 三好新一郎

日本呼吸器外科学会雑誌 29 ( 3 ) O56 - 6 2015.4

局所進行性肺癌に対する胸骨正中切開アプローチの利用可能性(Feasibility of median sternotomy approach for locally advanced lung cancer)

佐藤博紀, 豊岡伸一, 岡田真典, 伊賀徳周, 牧佑歩, 三好健太郎, 山本寛斉, 杉本誠一郎, 宗淳一, 山根正修, 大藤剛宏, 三好新一郎

日本呼吸器外科学会雑誌 29 ( 3 ) O39 - 1 2015.4

尾山貴徳, 野田卓男, 谷本光隆, 牧佑歩, 宗淳一, 豊岡伸一, 三好新一郎, 柴田敬, 井上拓志, 吉永治美

日本小児外科学会雑誌 51 ( 2 ) 279 - 279 2015.4

局所進行非小細胞肺癌に対する根治的放射線化学療法後手術の治療成績

宗淳一, 豊岡伸一, 諏澤憲, 岡田真典, 牧佑歩, 伊賀徳周, 三好健太郎, 山本寛斉, 杉本誠一郎, 山根正修, 大藤剛宏, 伊達洋至, 三好新一郎

日本呼吸器外科学会雑誌 29 ( 3 ) RO2 - 2 2015.4

EGFR Mutation Testing Practices within the Asia Pacific Region Results of a Multicenter Diagnostic Survey Reviewed

Yasushi Yatabe, Keith M. Kerr, Ahmad Utomo, Pathmanathan Rajadurai, Van Khanh Tran, Xiang Du, Teh-Ying Chou, Ma. Luisa D. Enriquez, Geon Kook Lee, Jabed Iqbal, Shanop Shuangshoti, Jin-Haeng Chung, Koichi Hagiwara, Zhiyong Liang, Nicola Normanno, Keunchil Park, Shinichi Toyooka, Chun-Ming Tsai, Paul Waring, Li Zhang, Rose McCormack, Marianne Ratcliffe, Yohji Itoh, Masatoshi Sugeno, Tony Mok

JOURNAL OF THORACIC ONCOLOGY 10 ( 3 ) 438 - 445 2015.3

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Introduction: The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR mutation-positive non-small-cell lung cancer (NSCLC) patients necessitates accurate, timely testing. Although EGFR mutation testing has been adopted by many laboratories in Asia, data are lacking on the proportion of NSCLC patients tested in each country, and the most commonly used testing methods.
Methods: A retrospective survey of records from NSCLC patients tested for EGFR mutations during 2011 was conducted in 11 Asian Pacific countries at 40 sites that routinely performed EGFR mutation testing during that period. Patient records were used to complete an online questionnaire at each site.
Results: Of the 22,193 NSCLC patient records surveyed, 31.8% (95% confidence interval: 31.2%-32.5%) were tested for EGFR mutations. The rate of EGFR mutation positivity was 39.6% among the 10,687 cases tested. The majority of samples were biopsy and/or cytology samples (71.4%). DNA sequencing was the most commonly used testing method accounting for 40% and 32.5% of tissue and cytology samples, respectively. A pathology report was available only to 60.0% of the sites, and 47.5% were not members of a Quality Assurance Scheme.
Conclusions: In 2011, EGFR mutation testing practices varied widely across Asia. These data provide a reference platform from which to improve the molecular diagnosis of NSCLC, and EGFR mutation testing in particular, in Asia.

DOI： 10.1097/JTO.0000000000000422

Pneumocephalus and Chylothorax Complicating Vertebrectomy for Lung Cancer Reviewed

Seiichiro Sugimoto, Masato Tanaka, Ken Suzawa, Hitoshi Nishikawa, Shinichi Toyooka, Takahiro Oto, Toshifumi Ozaki, Shinichiro Miyoshi

ANNALS OF THORACIC SURGERY 99 ( 4 ) 1425 - 1428 2015.3

Language：English Publisher：ELSEVIER SCIENCE INC

Pneumocephalus is a rare, but potentially fatal complication of thoracic surgery. We describe a case of successful management of pneumocephalus complicated by persistent chylothorax developing after en bloc partial vertebrectomy performed after induction chemoradiotherapy for lung cancer invading the spine. Surgical treatment should be considered for pneumocephalus complicated by any condition requiring persistent chest drainage. (C) 2015 by The Society of Thoracic Surgeons

DOI： 10.1016/j.athoracsur.2014.05.098

Hsp90 inhibitor NVP-AUY922 enhances the radiation sensitivity of lung cancer cell lines with acquired resistance to EGFR-tyrosine kinase inhibitors Reviewed

Shinsuke Hashida, Hiromasa Yamamoto, Kazuhiko Shien, Tomoaki Ohtsuka, Ken Suzawa, Yuho Maki, Masashi Furukawa, Junichi Soh, Hiroaki Asano, Kazunori Tsukuda, Shinichiro Miyoshi, Susumu Kanazawa, Shinichi Toyooka

ONCOLOGY REPORTS 33 ( 3 ) 1499 - 1504 2015.3

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is a critical issue that needs to be overcome in the treatment of patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations. EGFR and AKT are client proteins of the 90-kDa heat shock protein (Hsp90). Therefore, it was hypothesized that the use of Hsp90 inhibitors might allow the resistance to EGFR-TKIs to be overcome. Furthermore, Hsp90 inhibitors are known to function as radiosensitizers in various types of cancer. In the present study, we evaluated the radiosensitizing effect of the novel Hsp90 inhibitor, NVP-AUY922 (AUY), on NSCLC cell lines harboring EGFR activating mutations and showing acquired resistance to EGFR-TKIs via any of several mechanisms. We used HCC827 and PC-9, which are NSCLC cell lines harboring EGFR exon 19 deletions, and gefitinib-resistant sublines derived from the same cell lines with T790M mutation, MET amplification or stem-cell like properties. AUY was more effective against the gefitinib-resistant sublines with T790M mutation and MET amplification than against the parental cell lines, although the subline with stem cell-like properties showed more than a 10-fold higher resistance to AUY than the parental cell line. AUY exerted a significant radiosensitizing effect on the parental cell line and the MET-amplified subline through inducing G(2)/M arrest and inhibition of non-homologous end joining (NHEJ). In contrast, the radiosensitizing effect of AUY was limited on the subline with stem cell-like properties, in which it did not induce G(2)/M arrest or inhibition of NHEJ. In conclusion, combined inhibition of Hsp90 plus radiation was effective, and therefore a promising treatment alternative for overcoming major EGFR-TKI resistance, such as that induced by T790M mutation or MET amplification. However, other approaches are required to overcome minor resistance to EGFR-TKIs, such as that observed in cells with stem cell-like properties.

DOI： 10.3892/or.2015.3735

Long-Term Survival following Percutaneous Radiofrequency Ablation of Colorectal Lung Metastases Reviewed

Yusuke Matsui, Takao Hiraki, Hideo Gobara, Toshihiro Iguchi, Hiroyasu Fujiwara, Takeshi Nagasaka, Shinichi Toyooka, Susumu Kanazawa

JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY 26 ( 3 ) 303 - 310 2015.3

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Purpose: To retrospectively evaluate long-term survival outcomes of radiofrequency (RF) ablation of colorectal lung metastases and evaluate factors associated with improved survival.
Materials and Methods: Eighty-four patients (46 male and 38 female; median age, 65 y) with 172 colorectal lung metastases (median size, 1.2 cm) underwent 113 RF ablation sessions. Thirteen patients had viable extrapulmonary recurrences at the time of RF ablation. The primary endpoint was patient survival. Prognostic factors associated with survival were determined by univariate and multivariate analyses. Secondary endpoints were local tumor progression and adverse events (per National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0).
Results: During follow-up (median duration, 37.5 mo), 36 patients (42.9%) died. The estimated overall survival (OS) rates were 95.2%, 65.0%, and 51.6% at 1, 3, and 5 years, respectively (median OS time, 67.0 mo). Multivariate analysis revealed that a carcinoembryonic antigen (CEA) level of at least 5 ng/mL before RE ablation (P = .03) and the presence of viable extrapulmonary recurrences at the time of RF ablation (P = .001) were independent negative prognostic factors. The local tumor progression rate was 14.0% (24 of 172 tumors). Grade 3 adverse events were observed after two sessions (1.8%), and grade 415 adverse events were not observed.
Conclusions: RF ablation of colorectal lung metastases provided favorable long-term survival With a low incidence of severe adverse events. Independent prognostic factors were a high CEA level before RF ablation and the presence of viable extrapulmonary recurrences at the time of RF ablation.

DOI： 10.1016/j.jvir.2014.11.013

Transfissural Route Used for Preoperative Localization of Small Pulmonary Lesions with a Short Hook Wire and Suture System Reviewed

Toshihiro Iguchi, Takao Hiraki, Hideo Gobara, Hiroyasu Fujiwara, Yusuke Matsui, Seiichiro Sugimoto, Shinichi Toyooka, Takahiro Oto, Shinichiro Miyoshi, Susumu Kanazawa

CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY 38 ( 1 ) 222 - 226 2015.2

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

We retrospectively evaluated the results of the transfissural route for preoperative localization with a short hook wire and suture system for video-assisted thoracoscopic surgery (VATS).
Eleven patients with 11 tumors underwent CT-guided transfissural placement of a hook wire before VATS. This route was selected for all patients, because the distance between the tumor and interlobar fissure was much shorter than the required distance traversed using the conventional approach. Complications were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0.
The hook wire was successfully placed using the transfissural route in all but one case. Of these ten successful placements, two tumors needed a second puncture for optimal placement, because the CT scan showed that the first hook wire was not properly placed in the lung. In one patient, we did not attempt replacement after the first placement was incorrect. In ten successful procedures, the mean distance traversed in the parenchyma of the unaffected lung lobe was 27.9 mm. The distance between the pleura and placed hook wire was significantly shorter than the estimated distance between the pleura and hook wire using the conventional route (mean 16.3 vs. 40.9 mm; P = 0.0002). Grade 1 adverse events occurred (11 pneumothoraxes and 4 pulmonary hemorrhages). No grade 2 or higher adverse event was observed.
The transfissural route used for preoperative localization before VATS is useful for selected patients because this route may allow for more limited lung parenchyma resection.

DOI： 10.1007/s00270-014-0862-9

呼吸器外科領域における周術期管理について

宗淳一, 豊岡伸一, 足羽孝子, 小林求, 福田智美, 村田尚道, 井上真一郎, 牧佑歩, 三好新一郎

臨床呼吸生理 47 21 - 25 2015.2

Language：Japanese Publisher：臨床呼吸生理研究会

呼吸器外科領域における周術期管理について検討した。術前評価不足や抗凝固薬中止忘れなど、術前評価や準備不足により中止となった症例はPERIO導入により減少した。PERIO群は従来群に比較して有意に術後歩行開始日数が早かった。63歳以上呼吸器外科手術症例において、嚥下チーム介入群では術後肺炎の発症が減少した。せん妄発症率はD-mac群で有意に低下し、せん妄発症リスク因子数が多い症例でせん妄発症予防効果が顕著であった。特に75歳以上の患者で有意な低下を認めた。82歳以上の原発性肺癌手術症例における包括評価方式(DPC)と出来高方式による入院費差額の年次推移を比較し、PERIO、嚥下チーム、せん妄対策チームの導入により、経時的にDPC差額が増額した。

Validity of using lobe-specific regional lymph node stations to assist navigation during lymph node dissection in early stage non-small cell lung cancer patients Reviewed

Shinichiro Miyoshi, Kazuhiko Shien, Shinichi Toyooka, Kentaroh Miyoshi, Hiromasa Yamamoto, Seiichiro Sugimoto, Junichi Soh, Makio Hayama, Masaomi Yamane, Takahiro Oto

SURGERY TODAY 44 ( 11 ) 2028 - 2036 2014.11

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

Purpose The validity of our proposed lobe-specific regional lymph node stations (LSRLNS) was evaluated as a method for navigation during lymphadenectomy in patients with early stage non-small cell lung cancer (NSCLC).
Methods A total of 725 NSCLC patients with c-T2N1M0 or less extensive disease who had undergone a curative operation with complete mediastinal lymph node dissection (MLND) were studied. The LSRLNS were #2, #3, #4 and #10 for the right upper lobe, #11i, #11s, #7 and #8 for the right lower lobe, #4, #5 and #6 for the left superior division, #11, #5 and #7 for the left lingular division and #11, #7 and #8 for the left lower lobe.
Results If the LSRLNS were used for pathological examinations during surgery, 599 p-N0 and 39 p-N1 patients diagnosed with no metastasis would have been subjected to a selective MLND, while 20 p-N1 and 65 p-N2 patients who had a diagnosis of metastasis would have been navigated to a complete MLND. Two p-N2 patients with a diagnosis of no metastasis would have inappropriately undergone a selective MLND, resulting in the false negative rate at 0.3 %.
Conclusion Intra-operative pathological examination using our LSRLNS may accurately reveal the status of metastasis, and appropriately lead to a selective or complete MLND in patients with c-T2N1M0 or less extensive disease.

DOI： 10.1007/s00595-013-0772-5

【肺癌:最新の分子標的療法】肺癌のマイクロRNA異常

牧佑歩, 山本寛斉, 宗淳一, 三好新一郎, 豊岡伸一

Pharma Medica 32 ( 11 ) 49 - 52 2014.11

A New Human Lung Adenocarcinoma Cell Line Harboring the EML4-ALK Fusion Gene Reviewed

Hideko Isozaki, Masayuki Yasugi, Nagio Takigawa, Katsuyuki Hotta, Eiki Ichihara, Akihiko Taniguchi, Shinichi Toyooka, Shinsuke Hashida, Toshiaki Sendo, Mitsune Tanimoto, Katsuyuki Kiura

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 44 ( 10 ) 963 - 968 2014.10

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

Objective: The echinoderm microtubule associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene was identified in patients with non-small cell lung cancer. To the best of our knowledge, there are only three cell lines harboring the EML4-ALK fusion gene, which have contributed to the development of therapeutic strategies. Therefore, we tried to establish a new lung cancer cell line harboring EML4-ALK.
Methods: A 61-year-old Japanese female presented with chest discomfort. She was diagnosed with left lung adenocarcinoma with T4N3M1 Stage IV. Although she was treated with chemotherapy, her disease progressed with massive pleural effusion. Because the EML4-ALK rearrangement was found in a biopsied specimen using fluorescence in situ hybridization, she was treated with crizotinib. She did well for 3 months.
Results: Tumor cells were obtained from the malignant pleural effusion before treatment with crizotinib. Cells continued to proliferate substantially for several weeks. The cell line was designated ABC-11. The EML4-ALK fusion protein and genes were identified in ABC-11 cells using fluorescence in situ hybridization and immunohistochemistry, respectively. ABC-11 cells were sensitive to crizotinib and next-generation ALK inhibitors (ceritinib and AP26113), as determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Phosphorylated ALK protein and its downstream signaling were suppressed by treatment with crizotinib in western blotting. Furthermore, we could transplant ABC-11 cells subcutaneously into BALB/c nu/nu mice.
Conclusions: We successfully established a new lung adenocarcinoma cell line harboring the EML4-ALK fusion gene. This cell line could contribute to future research of EML4-ALK-positive lung cancer both in vivo and in vitro.

DOI： 10.1093/jjco/hyu110

Percutaneous Radiofrequency Ablation for Pulmonary Metastases from Esophageal Cancer: Retrospective Evaluation of 21 Patients Reviewed

Yusuke Matsui, Takao Hiraki, Hideo Gobara, Hiroyasu Fujiwara, Toshihiro Iguchi, Yasuhiro Shirakawa, Toshiyoshi Fujiwara, Shinichi Toyooka, Susumu Kanazawa

JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY 25 ( 10 ) 1566 - 1572 2014.10

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Purpose: To evaluate retrospectively Outcomes after radiofrequency (RF) ablation for pulmonary Metastases from esophageal cancer.
Materials and Methods: This study included 21 consecutive patients who met inclusion. criteria (all men; mean age, 66.0 y) and had pulmonary metastases from esophageal cancer. There were 31 tumors (mean size, 1.7 cm) that Were treated with 27 planned ablation sessions. At the initial RF ablation sessions, 3 patients had viable extrapulmonary recurrences, and 18 patients had Viable recurrences confined to the lung. Primary study endpoints included patient survival and the determination of prognostic factors. Secondary endpoints included local efficacy and safety of the treatment. The log-rank test was used to identify prognostic factors. Adverse events Were evaluated according to,the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0.
Results: Median follow-up duration after the initial RF ablation was 22.4 months (range, 6.2-76.1 mo). Estimated overall survival rates were 85.7% at 1 year, 54.8% at 2 years, and 38.4% at 3 years after the initial RF ablation session. The presence of viable extrapulmonary recurrences at the initial RF ablation session was an unfavorable prognostic factor (P < .001). Local tumor progression was observed in 25.8% (8 of 31) of tumors and occurred 2.6-10.0 months (median, 4.8 mo) after RP ablation. Grade 3 adverse events occurred in 7.4% (2 of 27) of sessions, including pleural effusion requiring chest tube placement and pneumoderma requiring surgical intervention. No grade 4 or greater adverse events occurred.
Conclusions: RF ablation is a promising treatment option for patients with pulmonary metastases from esophageal cancer.

DOI： 10.1016/j.jvir.2014.06.030