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  • 1
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 8548-8548
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 8548-8548
    Abstract: 8548 Background: Programmed death-ligand 1 (PD-L1) and human leukocyte antigen (HLA) class-I, expressed on tumor cells (TCs), are important regulators in cancer immunity. The current study was conducted to assess prognostic impact of PD-L1 status in correlation with HLA class-I status in lung adenocarcinoma. Methods: A total of 94 patients with completely resected pathologic stage I lung adenocarcinoma were retrospectively reviewed. PD-L1 expression on TCs was evaluated with immunohistochemistry, in correlation with several clinicopathological and molecular features including HLA class-I expression on tumor TCs. Results: Seventeen patients (18.1%) had tumor with positive PD-L1 expression (percentage of TCs expressing PD-L1, ≥ 5%), and the incidence was higher in smokers with higher smoking index and in poorly differentiated tumor. There was no significant correlation between HLA class-I expression and PD-L1 expression. PD-L1-positivity was a significant factor to predict a poor survival (5-year survival rate, 66.7% versus 85.9%; P = 0.048), which was enhanced in tumor with normal HLA class-I expression (p = 0.029) but disappeared in tumor with reduced HLA class-I expression. Conclusions: The prognostic impact of PD-L1 expression on TCs in early-stage resectable lung adenocarcinoma was distinct according to HLA class-I expression on TCs.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. e23045-e23045
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 1721-1721
    Abstract: Background: Circulating tumor cells (CTCs) are tumor cells shed from primary tumor and circulate in the peripheral blood. CTCs, as a surrogate of distant metastasis, can be potentially useful in diagnosis and monitoring therapeutic effects in malignant tumors. Among a variety of systems for detection of CTCs, the “Cellsearch” is the only approved system for clinical use. However, EpCAM-negative tumor cells, such as those originating from non-epithelial cells and those undergoing epithelial-mesenchymal transition (EMT) cannot be captured with the “CellSearch” that is an EpCAM-based isolation system. Therefore, we have developed a novel polymeric microfluidic device (“Universal” CTC-chip) that can capture CTCs with or without EpCAM expression (AACR 2015). In the present study, we examined CTCs-detection performance of the CTC-chip in patients with thoracic malignant tumors (lung cancer [LC] as an “EpCAM-positive” tumor and malignant pleural mesothelioma [MPM] as an “EpCAM-negative” tumor) in comparison with that of the CellSearch. Methods: Peripheral blood sampled from each patient was divided and subjected to quantitative evaluation of CTCs with the CTC-chip as well as with the “CellSearch”. The CTC-chip, coated with an anti-EpCAM antibody, was used to capture CTCs in the blood samples (n=19) from lung cancer patients. To capture CTCs in the samples (n=11) from MPM patients, the CTC-chip was coated with an antibody against podoplanin that is expressed on the mesothelioma. After immuno-staining for cytokeratin and CD45 on the chip, a captured cell containing Hoechst-positive nucleus and cytokeratin-positive/ CD45-negative cytoplasm was judged as a CTC. The CTC-count for each sample was represented as the number per 7.5mL of the blood. Results: The median CTC-count detected with the CTC-chip in LC was 50 (range, 0-270), which was significantly higher than that (the median CTC-count, 0; range, 0-47) with the CellSearch (p & lt;0.01). In the peripheral blood sampled from MPM patients, CTC was detected in only one patient using the CellSearch, but was detected in all 11 patients with the median CTC-count of 144 (range 0-470). Conclusion: The “universal” CTC-chip achieved higher performance in detection of CTCs of thoracic malignant tumors as compared with the CellSearch. The updated data will be presented at the AACR annual meeting 2017. Citation Format: Kazue Yoneda, Taiji Kuwata, Yasuhiro Chikaishi, Kenichi Kobayashi, Sakiko Yura, Hiroki Matsumiya, Masatoshi Kanayama, Akihiro Taira, Yusuke Nabe, Shinji Shinohara, Masaru Takenaka, Soichi Oka, Ayako Hirai, Yuko Tashima, Naoko Imanishi, Koji Kuroda, Fumihiro Tanaka. Detection of CTCs in thoracic malignant tumors with "universal" CTC-chip [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1721. doi:10.1158/1538-7445.AM2017-1721
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 3149-3149
    Abstract: Aim: To investigate the prognostic impact of programmed death-ligand 1 (PD-L1) expression on tumor cells in correlation with neutrophil-to-lymphocyte ratio (NLR) in early-stage squamous cell carcinoma of the lung, as PD-L1 is a potent regulator of cancer immunity and NLR is a potential surrogate of immune status. Patients and methods: Eighty-three patients with completely resected pathologic stage I lung squamous cell carcinoma were retrospectively reviewed. Tumoral PD-L1 expression was evaluated with immunohistochemistry, and its prognostic impact was analyzed in correlation with NLR. Results: Forty-three patients (51.8%) had tumor with positive PD-L1 expression (percentage of tumor cells expressing PD-L1, ≥1%). There was no significant correlation between PD-L1 expression and NLR. PD-L1-positivity failed to provide a significant prognostic impact (overall survival [OS] rate at 5 years, 70.1% in PD-L1-negative patients versus 53.0% in PD-L1-positive patients; P=0.117). Among NLR-low ( & lt;2.2) patients, however, PD-L1-positivity was significantly correlated with a poor prognosis (OS rate at 5 years, 86.0% in PD-L1-negative patients versus 46.1% in PD-L1-positive patients; P=0.020). In contrast, among NLR-high (≥2.2) patients, PD-L1-positivity provided no prognostic impact (P=0.680). When NLR status and tumoral PD-L1 status were combined, “NLR-low and tumoral PD-L1-negative” was a significant and independent factor to predict a favorable recurrence-free survival (hazard ratio, 0.237 [95% confidence interval, 0.083 to 0.674]; P=0.007) and OS (hazard ratio, 0.260 [95% confidence interval, 0.091 to 0.745] ; P=0.012). Conclusions: The prognostic impact of PD-L1 expression on tumor cells was distinct according to NLR. “NLR-low and tumoral PD-L1-negative” patients showed a favorable prognosis. Citation Format: Kazue Yoneda, Taiji Kuwata, Masataka Mori, Masatoshi Kanayama, Ayako Hirai, Yuko Tashima, Naoko Imanishi, Koji Kuroda, Yoshinobu Ichiki, Fumihiro Tanaka. Prognostic impact of PD-L1 expression in correlation with neutrophil-to-lymphocyte ratio in squamous cell carcinoma of the lung [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3149.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 5
    In: Immunology Letters, Elsevier BV, Vol. 196 ( 2018-04), p. 155-160
    Type of Medium: Online Resource
    ISSN: 0165-2478
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2013171-9
    SSG: 12
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  • 6
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 3080-3080
    Abstract: Background. The CellSearch system is the most commonly used technique approved by the FDA to isolate and quantify circulation tumor cells (CTCs). However, in this system, the efficiency of CTC isolation is influenced by the epithelial cell adhesion molecule (EpCAM). Therefore, it is difficult to isolate CTCs in the setting of the epithelial to mesenchymal transition (EMT), malignant pleural mesothelioma and so on. We developed polymeric microfluidic devices for CTC isolation (CTC-chip) and compared the efficacy of CellSearch with CTC-chip using EpCAM-negative tumor cell lines of malignant pleural mesothelioma. Methods. In order to evaluate the accuracy of the number of CTCs, we used PBS samples and peripheral blood samples (blood samples) collected from healthy donors to which spiking the tumor cell lines ACC-MESO1 and ACC-MESO4. Both tumor cell lines (obtained from ATCC) were derived from malignant pleural mesothelioma, positive for mesothelin and podoplanin and negative for EpCAM. The recovery rate was evaluated using two methods. CellSearch was performed according to the normal method, while CTC-chip was performed using a two coating pattern with anti-mesothelin antibody (chip1) and anti-podoplanin antibody (chip2). Results. In the PBS samples, the recovery rate of captured ACC-MESO1 was 8.6%/98%/99% (CellSearch/chip 1/chip 2), while those of ACC-MESO4 was 21.1%/97%/99%, respectively. In the blood samples, the recovery rate of captured ACC-MESO1 was 1.2%/6.2%/13.3% (CellSearch/chip 1/chip 2), while that of ACC-MESO4 was 6.0%/3.7%/11.6%, respectively. Conclusions. Our experiments showed that the recovery rate of each sample was higher using CTC-chip than that obtained with CellSearch. Moreover, CTC-chip coated anti-podoplanin antibody exhibited a higher recovery rate than coated anti-mesothelin antibody. Future studies using experiments of CTC isolation in cancer patients with malignant pleural mesothelioma are thus required. Citation Format: Yasuhiro Chikaishi, Tomoko So, Masaru Takenaka, Soichi Oka, Ayako Hirai, Takashi Iwanami, Hidehiko Shimokawa, Kazue Yoneda, Yoshika Nagata, Hidetaka Uramoto, Takeshi Ohnaga, Fumihiro Tanaka. Comparison of CellSearch with polymeric microfluidic devices for CTC isolation using EpCAM-negative tumor cell lines of malignant pleural mesothelioma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3080. doi:10.1158/1538-7445.AM2014-3080
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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