{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:15:51Z","timestamp":1792268151833,"version":"4.4.0"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,2,15]]},"abstract":"<jats:p>\n                    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent endogenous activator of the cell death pathway and functions by activating the cell surface death receptors 4 and 5 (DR4 and DR5). TRAIL is nontoxic\n                    <jats:italic>in vivo<\/jats:italic>\n                    and preferentially kills neoplastically transformed cells over normal cells by an undefined mechanism. Radiotherapy is a common treatment for breast cancer as well as many other cancers. Here we demonstrate that ionizing radiation can sensitize breast carcinoma cells to TRAIL-induced apoptosis. This synergistic effect is p53-dependent and may be the result of radiation-induced up-regulation of the TRAIL-receptor DR5. Importantly, TRAIL and ionizing radiation have a synergistic effect in the regression of established breast cancer xenografts. Changes in tumor cellularity and extracellular space were monitored\n                    <jats:italic>in vivo<\/jats:italic>\n                    by diffusion-weighted magnetic resonance imaging (diffusion MRI), a noninvasive technique to produce quantitative images of the apparent mobility of water within a tissue. Increased water mobility was observed in combined TRAIL- and radiation-treated tumors but not in tumors treated with TRAIL or radiation alone. Histological analysis confirmed the loss of cellularity and increased numbers of apoptotic cells in TRAIL- and radiation-treated tumors. Taken together, our results provide support for combining radiation with TRAIL to improve tumor eradication and suggest that efficacy of apoptosis-inducing cancer therapies may be monitored noninvasively, using diffusion MRI.\n                  <\/jats:p>","DOI":"10.1073\/pnas.030545097","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:07Z","timestamp":1027679707000},"page":"1754-1759","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":430,"title":["Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy"],"prefix":"10.1073","volume":"97","author":[{"given":"Arul M.","family":"Chinnaiyan","sequence":"first","affiliation":[{"name":"Center for Molecular Imaging and Departments of Pathology, Radiation Oncology, Radiology, and Biochemistry, University of Michigan Medical School, 1301 Catherine Road, MSI Room 4237, Ann Arbor, MI 48109-0602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uttara","family":"Prasad","sequence":"additional","affiliation":[{"name":"Center for Molecular Imaging and Departments of Pathology, Radiation Oncology, Radiology, and Biochemistry, University of Michigan Medical School, 1301 Catherine Road, MSI Room 4237, Ann Arbor, MI 48109-0602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunita","family":"Shankar","sequence":"additional","affiliation":[{"name":"Center for Molecular Imaging and Departments of Pathology, Radiation Oncology, Radiology, and Biochemistry, University of Michigan Medical School, 1301 Catherine Road, MSI Room 4237, Ann Arbor, MI 48109-0602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Hamstra","sequence":"additional","affiliation":[{"name":"Center for Molecular Imaging and Departments of Pathology, Radiation Oncology, Radiology, and Biochemistry, University of Michigan Medical School, 1301 Catherine Road, MSI Room 4237, Ann Arbor, MI 48109-0602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murthy","family":"Shanaiah","sequence":"additional","affiliation":[{"name":"Center for Molecular Imaging and Departments of Pathology, Radiation Oncology, Radiology, and Biochemistry, University of Michigan Medical School, 1301 Catherine Road, MSI Room 4237, Ann Arbor, MI 48109-0602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas L.","family":"Chenevert","sequence":"additional","affiliation":[{"name":"Center for Molecular Imaging and Departments of Pathology, Radiation Oncology, Radiology, and Biochemistry, University of Michigan Medical School, 1301 Catherine Road, MSI Room 4237, Ann Arbor, MI 48109-0602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian D.","family":"Ross","sequence":"additional","affiliation":[{"name":"Center for Molecular Imaging and Departments of Pathology, Radiation Oncology, Radiology, and Biochemistry, University of Michigan Medical School, 1301 Catherine Road, MSI Room 4237, Ann Arbor, MI 48109-0602"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alnawaz","family":"Rehemtulla","sequence":"additional","affiliation":[{"name":"Center for Molecular Imaging and Departments of Pathology, Radiation Oncology, Radiology, and Biochemistry, University of Michigan Medical School, 1301 Catherine Road, MSI Room 4237, Ann Arbor, MI 48109-0602"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,2,4]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199810013391407"},{"key":"e_1_3_3_2_2","volume-title":"Radiobiology for the Radiologist","author":"Hall E","year":"1988","unstructured":"E Hall Radiobiology for the Radiologist (Lippincott, Philadelphia, 1988)."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/09553008914551691"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0360-3016(91)90320-4"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81874-7"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1305"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/smim.1996.0055"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60672-0"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90071-3"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.14.7795"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81266-0"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81265-9"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.5.2926"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5327.815"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5327.818"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)00135-5"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(06)00422-2"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/5517"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(99)80034-9"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(92)90116-O"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.167.3.1067"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1994.1349"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/364806a0"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6926"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5430.998"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/28412"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.neo.7900009"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5309.111"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9120(97)00049-0"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(90)90029-U"},{"key":"e_1_3_3_31_2","first-page":"2095","volume":"54","author":"Haldar S","year":"1994","unstructured":"S Haldar, M Negrini, M Monne, S Sabbioni, C M Croce Cancer Res 54, 2095\u20132097 (1994).","journal-title":"Cancer Res"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.9.4961"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.41.25783"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910340202"},{"key":"e_1_3_3_35_2","first-page":"1593","volume":"58","author":"Sheikh M S","year":"1998","unstructured":"M S Sheikh, T F Burns, Y Huang, G S Wu, S Amundson, K S Brooks, A J Fornace, W S el-Deiry Cancer Res 58, 1593\u20131598 (1998).","journal-title":"Cancer Res"},{"key":"e_1_3_3_36_2","volume-title":"Medicine","author":"Fishman M","year":"1991","unstructured":"M Fishman, A Hoffman, R Klausner, M Thaler Medicine (Lippincott, Philadelphia, 1991)."},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3798106"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.240.4860.1796"},{"key":"e_1_3_3_39_2","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.4049\/jimmunol.161.6.2833","volume":"161","author":"Griffith T S","year":"1998","unstructured":"T S Griffith, W A Chin, G C Jackson, D H Lynch, M Z Kubin J Immunol 161, 2833\u20132840 (1998).","journal-title":"J Immunol"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.32.20131"},{"key":"e_1_3_3_41_2","first-page":"3129","volume":"56","author":"Gao Q","year":"1996","unstructured":"Q Gao, S H Hauser, X L Liu, D E Wazer, H Madoc-Jones, V Band Cancer Res 56, 3129\u20133133 (1996).","journal-title":"Cancer Res"},{"key":"e_1_3_3_42_2","first-page":"1853","volume":"14","author":"Hachiya M","year":"1994","unstructured":"M Hachiya, A Chumakov, C W Miller, M Akashi, J Said, H P Koeffler Anticancer Res 14, 1853\u20131859 (1994).","journal-title":"Anticancer Res"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.12.12.5581-5592.1992"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.030545097","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T08:14:28Z","timestamp":1682151268000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.030545097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,2,4]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2000,2,15]]}},"alternative-id":["10.1073\/pnas.030545097"],"URL":"https:\/\/doi.org\/10.1073\/pnas.030545097","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,2,4]]},"assertion":[{"value":"1999-08-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-12-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-02-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}