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Junichi Murakami



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    P2.06 - Mesothelioma (Not CME Accredited Session) (ID 955)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.06-38 - Mesothelioma Stem Cells May Be the Critical Factor of Treatment Failure (ID 11344)

      16:45 - 18:00  |  Author(s): Junichi Murakami

      • Abstract

      Background

      Cancer cell repopulation during treatments of chemotherapy or radiotherapy is a major factor resulting in treatment failure. It has been indicated that cancer stem cells (CSC) may play critical roles during this process. The goal of our study is to characterise mesothelioma stem cells (MSC) and evaluate the prognostic values in those patients with malignant pleural mesothelioma (MPM). The eventual aim would be to design specific target therapy against MSC and develop novel approaches in clinical practice.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We have screened a group of genes that are most likely MSC-specific. Further characterization of the selected genes will be of critical importance in tumorigenesis, progression and prognosis. Murine mesothelioma AB12 and RN5 cells treated with either chemotherapy or γ-ray irradiation in culture, were used to compare gene expression profiles. The selected genes were confirmed by real-time PCR, flow cytometry and immunostaining. In vivo models, peritoneal lavage was collected at different time points after RN5 cell injection, to perform magnetic ranking cytometry with antibody-nanoparticle conjugates, and microarray assay. The expression of Tnfsf18 and Ngfr (CD271) genes associated with prognosis was evaluated in tumor tissues from MPM patients treated with SMART vs pre-SMART protocols, as SMART protocol has already shown significant clinical benefit. Image analysis was performed using Apero Imagescope program.

      4c3880bb027f159e801041b1021e88e8 Result

      The proportion of MSC significantly increased after RN5 parental cells were treated with either chemotherapy, or γ-ray irradiation, or in combination, while MSC showed more resistance to the above treatments, suggesting that chemoradiation resulted in MSC enrichment. Upregulation of genes Tnfsf18, Serpinb9b, Ly6a (Sca-1), Ngf, and Nppb were confirmed. CD271, the receptor of NGF, was shown to be upregulated after chemoradiation, especially after γ-ray radiation with a dose of 10Gy. Mesothelial precursors captured with magnetic nanoparticles conjugated to anti-Msln and trapped in the microfluidic device in the presence of a magnetic field showed an increase over time from 2-8weeks. Image analysis of human section slides indicated that total positive area of CD271 staining was significantly lower in those who were treated with SMART protocol than those with pre-SMART protocol (p<0.0025). Similar results were obtained in the high, medium and low positive areas from the SMART group, and p values are 0.0013, 0.0017 and 0.0035, respectively, when compared with the pre-SMART group.

      8eea62084ca7e541d918e823422bd82e Conclusion

      MSC-specific genes like CD271 and Tnfsf18 might be used as potential prognostic indicators and therapeutic targets.

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