PDT dose parameters impact tumoricidal durability and cell death pathways in a 3D ovarian cancer model.

PDT dose parameters impact tumoricidal durability and cell death pathways in a 3D ovarian cancer model.
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DOI:
10.1111/php.12065
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发表时间:
2013-07
影响因子:
3.3
通讯作者:
Hasan T
Hasan T
中科院分区:
生物学3区
文献类型:
--
作者:
Rizvi I;Anbil S;Alagic N;Celli J;Zheng LZ;Palanisami A;Glidden MD;Pogue BW;Hasan T

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The successful implementation of photodynamic therapy (PDT)-based regimens depends on an improved understanding of the dosimetric and biological factors that govern therapeutic variability. Here, the kinetics of tumor destruction and regrowth are characterized by systematically varying benzoporphyrin derivative (BPD)-light combinations to achieve fixed PDT doses (M × J/cm2). Three endpoints were used to evaluate treatment response: 1.) Viability evaluated every 24 hours for 5 days post-PDT; 2.) Photobleaching assessed immediately post-PDT; and 3.) Caspase-3 activation determined 24-hours post-PDT. The specific BPD-light parameters used to construct a given PDT dose significantly impact not only acute cytotoxic efficacy, but also treatment durability. For each dose, PDT with 0.25 μM BPD produces the most significant and sustained reduction in normalized viability compared to 1 μM and 10 μM BPD. Percent photobleaching correlates with normalized viability for a range of PDT doses achieved within BPD concentrations. To produce a cytotoxic response with 10 μM BPD that is comparable to 0.25 μM and 1 μM BPD a reduction in irradiance from 150 mW/cm2 to 0.5 mW/cm2 is required. Activated caspase-3 does not correlate with normalized viability. The parameter-dependent durability of outcomes within fixed PDT doses provides opportunities for treatment customization and improved therapeutic planning.
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