{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T17:37:53Z","timestamp":1781113073343,"version":"3.54.1"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,8,20]],"date-time":"2005-08-20T00:00:00Z","timestamp":1124496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2005,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lung cancer, the leading cause of cancer\u2010related deaths in both men and women, is the consequence of disordered apoptosis, induction of which may have therapeutic utility. Hyperthermia has been identified as a stimulus for apoptosis. We investigated the mechanism of hyperthermia\u2010induced cell death in ras\u2010transformed lung cells. Effect of hyperthermia (43\u00b0C for 180 min) was compared between two cell lines, an immortalized (sv\u201040) normal human bronchial epithelial (BEAS2\u2010B) and its malignant transformed (<jats:italic>H\u2010ras<\/jats:italic>transfected) counterpart (BZR\u2010T33). Survival after hyperthermia: 7\u2010d growth culture BEAS2\u2010B, 1.03\u2009\u00b1\u20090.007 and BZR\u2010T33, 0.39\u2009\u00b1\u20090.008 (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05); clonogenic assays BEAS2\u2010B, 0.76\u2009\u00b1\u20090.003 and BZR\u2010T33, 0.41\u2009\u00b1\u20090.004 (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Hoechst positive (apoptotic) cells: BEAS2\u2010B, 11\u2009\u00b1\u20093% and BZR\u2010T33, 78\u2009\u00b1\u20095% (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). TUNEL, DNA fragmentation, and Annexin\u2010V all corroborate this result. Western blot comparing the effect of hyperthermia in BZR\u2010T33 cells to BEAS2\u2010B cells revealed: TRAIL and FAS\u2010L displayed significant increases (threefold and twofold, respectively); caspase\u20103 showed a decrease in uncleaved form and an increase in cleaved form, and a 50\u2010fold increase in activity effectively blocked with the caspase\u20103 inhibitor DEVD\u2010fmk; caspase\u20109 showed near depletion of uncleaved; poly (ADP\u2010ribose) polymerase (PARP) degradation was clearly visible during heating. After hyperthermia, gene expression demonstrates a 5.7\u2010fold increase in TRAIL and insignificant changes in tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), FAS\u2010L, and caspases 3, 8, 9 in transformed cells. Data demonstrated that hyperthermia induces apoptosis in transformed cells, and that apoptosis is mediated by caspase\u20103 as a result of activation of cell\u2010death membrane receptors of the tumor\u2010necrosis\u2010factor family. In summary, these data suggest that hyperthermia could become an additional modality in the multidisciplinary approach to the treatment of lung cancer. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.20124","type":"journal-article","created":{"date-parts":[[2005,8,21]],"date-time":"2005-08-21T06:16:54Z","timestamp":1124605014000},"page":"111-121","source":"Crossref","is-referenced-by-count":35,"title":["A mechanism of hyperthermia\u2010induced apoptosis in ras\u2010transformed lung cells"],"prefix":"10.1002","volume":"44","author":[{"given":"Roger A.","family":"Vertrees","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gokul C.","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela M.","family":"Coscio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwu","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph B.","family":"Zwischenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Boor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,8,20]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"4","volume-title":"Cancer Facts and Figures","author":"American Cancer Society","year":"2004"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001622-200207000-00002"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.117.4_suppl_1.163S"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2003.10.111"},{"key":"e_1_2_6_6_2","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1177\/000313480006600607","article-title":"Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for disseminated peritoneal cancer of gastrointestinal origin","volume":"66","author":"Loggie BW","year":"2000","journal-title":"Am Surg"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10434-001-0771-4"},{"key":"e_1_2_6_8_2","first-page":"1051","article-title":"Quantitative differentiation of both free 3\u2032\u2010OH and 5\u2032\u2010OH DNA ends between heat\u2010induced apoptosis and necrosis","volume":"46","author":"Hayashi R","year":"1998","journal-title":"J Anat Biol"},{"key":"e_1_2_6_9_2","first-page":"R1447","article-title":"Hyperthermia protects mice against the lethal effects of endotoxin","volume":"265","author":"Hotchkiss R","year":"1993","journal-title":"Am J Physiol"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1996.0070"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-4975(00)01421-1"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81728-6"},{"key":"e_1_2_6_13_2","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.4049\/jimmunol.152.4.1751","article-title":"Fas antigen and 55\u2010kD TNF receptor signal apoptosis through distinct pathways","volume":"152","author":"Wong GH","year":"1994","journal-title":"J Immunol"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.949602"},{"key":"e_1_2_6_15_2","first-page":"805","article-title":"Tumor chemosensitization strategies based on apoptosis manipulations","volume":"2","author":"Shabbits JA","year":"2003","journal-title":"Mol Can Therap"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81590-1"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81589-5"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.neo.7900203"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.23.2032"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.8.5308"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010384200"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0955-0674(95)80063-8"},{"key":"e_1_2_6_23_2","first-page":"400","article-title":"A dominant role for the c\u2010Jun NH2\u2010terminal kinase in oncogenic ras\u2010induced morphologic transformation of human lung carcinoma cells","volume":"60","author":"Xiao L","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-2219"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(04)00113-8"},{"key":"e_1_2_6_26_2","first-page":"3397","article-title":"Expression of TRAIL and TRAIL death receptors in stage III non\u2010small cell lung cancer","volume":"9","author":"Spierings DCJ","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-5846(03)00016-2"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3975607"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.2940010303"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/81.8.587"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.2307\/3579088"},{"key":"e_1_2_6_32_2","first-page":"47","article-title":"Expression of ras proto\u2010oncogene proteins in normal human tissues","volume":"1","author":"Furth ME","year":"1987","journal-title":"Oncogene"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108947200"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-4975(01)02673-X"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdf280"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.2307\/3577617"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.2307\/3577755"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1667\/0033-7587(2001)155[0050:GPDAIA]2.0.CO;2"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1245\/ASO.2003.08.006"},{"key":"e_1_2_6_41_2","first-page":"345","article-title":"Whole body hyperthermia with carboplatin (CBDCA) for treatment of advanced or metastatic GI adenocarcinomas","volume":"40","author":"Nagle VLJ","year":"1999","journal-title":"Proc Am Assoc CA Res"},{"key":"e_1_2_6_42_2","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/S0022-5223(19)38032-8","article-title":"Treatment of far\u2010advanced bronchogenic carcinoma by extracorporeally induced systemic hyperthermia","volume":"78","author":"Parks LC","year":"1979","journal-title":"J Thorac Cardiovasc Surg"},{"key":"e_1_2_6_43_2","first-page":"4515","article-title":"Thermal response of oncogene\u2010transfected rat cells","volume":"50","author":"Li GC","year":"1990","journal-title":"Cancer Res"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01212608"},{"key":"e_1_2_6_45_2","first-page":"995","article-title":"Transformation by viral oncogenes increased sensitivity to heat in rat 3Y1 fibroblasts","volume":"13","author":"Mitsudomi T","year":"1993","journal-title":"Anticancer Res"},{"key":"e_1_2_6_46_2","first-page":"2887","article-title":"Synergistic inhibition of human lung cancer cell growth by adenovirus\u2010mediated wild\u2010type p53 gene transfer in combination with docetaxel and radiation therapeutics in vitro and in vivo","volume":"7","author":"Nishizaki M","year":"2001","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1746.2001.02426.x"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10069"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1016119328968"},{"key":"e_1_2_6_50_2","first-page":"87","article-title":"Control of ras activation","volume":"27","author":"Downward J","year":"1996","journal-title":"Cancer Surv"},{"key":"e_1_2_6_51_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1093\/oso\/9780198599456.003.0016","volume-title":"Guidebook to the Small GTPases","author":"Marshall C","year":"1995"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.32.22532"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmc.20124","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.20124","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T06:09:54Z","timestamp":1706508594000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.20124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,8,20]]},"references-count":51,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2005,10]]}},"alternative-id":["10.1002\/mc.20124"],"URL":"https:\/\/doi.org\/10.1002\/mc.20124","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"value":"0899-1987","type":"print"},{"value":"1098-2744","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,8,20]]}}}