{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T17:00:32Z","timestamp":1777482032001,"version":"3.51.4"},"reference-count":31,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Biotherapy and Radiopharmaceuticals"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:p>\n                    <jats:sup>111<\/jats:sup>\n                    In-labeled trastuzumab modified with nuclear localizing signal (NLS) peptides (\n                    <jats:sup>111<\/jats:sup>\n                    In-trastuzumab-NLS) efficiently delivers an Auger electron (AE) emitter\n                    <jats:sup>111<\/jats:sup>\n                    In into the cell nucleus and is thus a promising radiopharmaceutical in AE radioimmunotherapy (AE-RIT) for targeted killing of HER2-positive cancer. However, further improvement of its therapeutic efficacy is required. In this study, the authors show a transcriptomic approach to identify potential targets for enhancing the cytotoxic effects of\n                    <jats:sup>111<\/jats:sup>\n                    In-trastuzumab-NLS. They generated two types of\n                    <jats:sup>111<\/jats:sup>\n                    In-trastuzumab-NLS harboring different numbers of NLS peptides,\n                    <jats:sup>111<\/jats:sup>\n                    In-trastuzumab-NLS-S and -L. These radioimmunoconjugates (230 and 460\u2009kBq) showed a significant higher cytotoxicity to SKBR3 human breast cancer cells overexpressing HER2 compared to\n                    <jats:sup>111<\/jats:sup>\n                    In-trastuzumab. Microarray analysis revealed that NF-kB-related genes (38 genes) were significantly changed in transcription by\n                    <jats:sup>111<\/jats:sup>\n                    In trastuzumab-NLS-L (230\u2009kBq) treatment. Quantitative reverse transcription polymerase chain reaction confirmed the microarray data by showing transcriptional alternation of selected NF-\u03baB target genes in cells treated with\n                    <jats:sup>111<\/jats:sup>\n                    In-trastuzumab-NLS-L. Interestingly, bortezomib, a drug known as a NF-\u03baB modulator, significantly enhanced the cytotoxicity of\n                    <jats:sup>111<\/jats:sup>\n                    In-trastuzumab-NLS-L in SKBR3 cells. Taken together, the transcriptome data suggest the possibility that the modulation of NF-kB signaling activity is a molecular signature of\n                    <jats:sup>111<\/jats:sup>\n                    In-trastuzumab-NLS and coadministration of bortezomib may be efficacious in enhancement of AE-RIT with\n                    <jats:sup>111<\/jats:sup>\n                    In-trastuzumab-NLS.\n                  <\/jats:p>","DOI":"10.1089\/cbr.2015.1882","type":"journal-article","created":{"date-parts":[[2015,10,8]],"date-time":"2015-10-08T15:06:01Z","timestamp":1444316761000},"page":"349-358","source":"Crossref","is-referenced-by-count":14,"title":["Transcriptomic Signatures of Auger Electron Radioimmunotherapy Using Nuclear Targeting\n                    <sup>111<\/sup>\n                    In-Trastuzumab for Potential Combination Therapies"],"prefix":"10.1177","volume":"30","author":[{"given":"Huizi Keiko","family":"Li","sequence":"first","affiliation":[{"name":"National Institute of Radiological Sciences","place":["Japan"]},{"name":"Chiba University","place":["Japan"]},{"name":"Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukie","family":"Morokoshi","sequence":"additional","affiliation":[{"name":"National Institute of Radiological Sciences","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Daino","sequence":"additional","affiliation":[{"name":"Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takako","family":"Furukawa","sequence":"additional","affiliation":[{"name":"National Institute of Radiological Sciences","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadashi","family":"Kamada","sequence":"additional","affiliation":[{"name":"Chiba University","place":["Japan"]},{"name":"Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsuneo","family":"Saga","sequence":"additional","affiliation":[{"name":"National Institute of Radiological Sciences","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumitaka","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"National Institute of Radiological Sciences","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2015,10,1]]},"reference":[{"issue":"1","key":"e_1_3_3_2_2","first-page":"4S","article-title":"Radiobiologic principles in radionuclide therapy","volume":"46","author":"Kassis AI","year":"2005","unstructured":"Kassis AI, , Adelstein SJ. Radiobiologic principles in radionuclide therapy. J Nucl Med, 2005; 46 Suppl 1:4S.","journal-title":"J Nucl Med"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1118\/1.597227"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.2174\/157016310793360657"},{"key":"e_1_3_3_5_2","first-page":"827","article-title":"Nuclear localizing sequences promote nuclear translocation and enhance the radiotoxicity of the anti-CD33 monoclonal antibody HuM195 labeled with 111In in human myeloid leukemia cells","volume":"47","author":"Chen P","year":"2006","unstructured":"Chen P, , Wang J, , Hope K, et al. Nuclear localizing sequences promote nuclear translocation and enhance the radiotoxicity of the anti-CD33 monoclonal antibody HuM195 labeled with 111In in human myeloid leukemia cells. 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