Author of

• 12409

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  P3.03 - Poster Session 3 - Technology and Novel Development (ID 152)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12410

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    P3.03-001 - The overxpression of TS protein induced by NPe6-PDT (ID 1339)

    09:30 - 09:30  |  Author(s): Y. Shimada
    • Abstract

    Background
    Malignant pleural mesothelioma(MPM) is a locally aggressive disease characterized by a poor prognosis and increasing. MPM tumors are usually related to asbestos exposure, and the incidence is anticipated to peak between 2020 and 2030 because of the lag time between asbestos expousere and the development of the malignancy. MPM is difficult to detect at an early stage, and surgical and radiotherapeutic approaches are ineffective when used independently, because MPM spreads diffusely in the surrounding chest wall. No universally accepted treatment approach currently exists.

    Methods
    We examined whether combination treatment consisting of pemetrexed chemotherapy and photodynamic therapy (PDT) using the photosensitizer, NPe6, enhanced the antitumor effect in vitro and in vivo models. We also investigated preclinical treatment schedules. Four human malignant mesothelioma cell line, (MSTO-211H, H2052, H2452and H28) were assayed using the WST assy after treatment with pemetrexed and NPe6-PDT. The treatment schedule for the combination treatment was examined using nude mice.

    Results
    In nude mice injected with MSTO-211H cells and then treared using a combination of pemetrexed and NPe6-PDT (10 mg/kg NPe6, 10 J/cm2 laser irradiation), the tumor volume decreased by 50% but subsequently increased, reaching the pretreatment value after 14 days. Pemetrexed treatment followed by NPe6-PDT resulted in an 80% reduction in the tumor size and inhibited re-growth. NPe6-PDT followed by pemetrexed treatment resulted in a 60% reduction in tumor size but did not inhibit re-growth.

    Conclusion
    Pemetrexed reportedly inhibits multiple enzymes in the folate metabolic pathway, with TS being the main target. In non-small cell lung cancer cell line, high baseline TS expression levels confer resistance to pemetrexed, and the TS level is correlated with pemetrexed efficacy in a variety of solid tumors. These results suggest that the overexpression of TS protein induced by NPe6-PDT may be associated with the failure of pemetrexed to exert a tumoricidal action. Therefore, we concluded that NPe6-PDT followed by pemetrexed did not enhance tumor cell lethality in the in vivo model. Combination treatment, consisting of pemetrexed followed by NPe6-PDT, should be further investigated as a new treatment modality for malignant pleural mesothelioma. In the future, this combination treatment may contribute to a reduction in local recurrence and a prolonged survival period in patients with malignant pleural mesothelioma.