会議発表用資料 Gene expression profiling identifies molecular targets to enhance the cytotoxicity of Auger electron radioimmunotherapy

Hasegawa, Sumitaka  ,  Furukawa, Takako  ,  Saga, Tsuneo

2015-10-10
内容記述
Auger electron (AE)-emitters such as I-125 and In-111 are highly cytotoxic when they decay in the nucleus because of their high local energy deposition. The use of antibody modified with nuclear localizing signal (NLS) has been proposed to achieve the efficient delivery of AE-emitters into tumor cell nucleus. [In-111]trastuzumab-NLS is a promising radiopharmaceutical in AE radioimmunotherapy for targeted killing of HER2-positive cancers. However, for further improvement of its therapeutic efficacy, better understanding of cellular response to [In-111]trastuzumab-NLS is required. We performed DNA microarray analysis in HER2-overexpressing human breast cancer SKBR3 cells treated with [In-111]trastuzumab-NLS and identified the modulation of NF-kB signaling activity as a molecular signature of [In-111]trastuzumab-NLS treatment. Thirty-eight of genes in NF-kB targets were transcriptionally altered by [In-111]trastuzumab-NLS treatment. Furthermore, bortezomib, a NF-kB pathway modulator drug, significantly enhanced the cytotoxicity of [In-111]trastuzumab-NLS in SKBR3 cells in comparison to monotherapy of [In-111]trastuzumab-NL
第74回日本癌学会学術総会

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