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  • American Association for Cancer Research (AACR)  (2)
  • 1
    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
    RVK:
    RVK:
    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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  • 2
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 18, No. 5 ( 2019-05-01), p. 947-956
    Abstract: Anaplastic thyroid carcinoma (ATC) is a rare but aggressive undifferentiated tumor that frequently metastasizes to the brain. The multiple kinase inhibitor lenvatinib and sorafenib have been approved to treat unresectable differentiated thyroid cancer, and lenvatinib has been approved in Japan to treat ATC. This study compared the effects of lenvatinib and sorafenib in mouse models of central nervous system metastases of ATC. Immunodeficient mice were inoculated with ATC cells, and the effects of lenvatinib and sorafenib were evaluated in subcutaneous- and brain metastasis–mimicking models. Drug distribution was evaluated by imaging tandem mass spectrometry (ITMS). Neither lenvatinib nor sorafenib affected the viability of ATC cell lines, whereas both inhibited VEGF secretion by ATC cells. In the subcutaneous tumor model, both lenvatinib and sorafenib inhibited growth and were associated with reduced tumor microvessel density. In the brain metastasis–mimicking model, lenvatinib, but not sorafenib, inhibited the growth of ATC cells and reduced microvessel density in brain lesions. ITMS showed that lenvatinib was well-distributed in both subcutaneous and brain lesions, whereas the distribution of sorafenib was lower in brain than in subcutaneous lesions. These results demonstrate that lenvatinib is well-distributed in mouse models of ATC, and inhibited the growth of ATC brain lesions predominantly by inhibiting angiogenesis, suggesting that lenvatinib is highly potent against ATC brain metastases.
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 2062135-8
    SSG: 12
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