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Oncolytic virotherapy is a novel antitumor treatment for inducing lytic cell death in tumor cells without affecting normal cells. Based on the Ad5 genome, we have generated three types of telomerase-specific replication-competent oncolytic adenoviruses: OBP-301 (Telomelysin), green fluorescent protein (GFP)-expressing OBP-401 (TelomeScan), and tumor suppressor p53-armed OBP-702. These viruses drive the expression of the adenoviral E1A and E1B genes under the control of the hTERT (human telomerase reverse transcriptase-encoding gene) promoter, providing tumor-specific virus replication. This review focuses on the therapeutic potential of three hTERT promoter-driven oncolytic adenoviruses against bone and soft-tissue sarcoma cells with telomerase activity. OBP-301 induces the antitumor effect in monotherapy or combination therapy with chemotherapeutic drugs via induction of autophagy and apoptosis. OBP-401 enables visualization of sarcoma cells within normal tissues by serving as a tumor-specific labeling reagent for fluorescence-guided surgery via induction of GFP expression. OBP-702 exhibits a profound antitumor effect in OBP-301-resistant sarcoma cells via activation of the p53 signaling pathway. Taken together, telomerase-specific oncolytic adenoviruses are promising antitumor reagents that are expected to provide novel therapeutic options for the treatment of bone and soft-tissue sarcomas.<\/jats:p>","DOI":"10.3390\/cancers12020478","type":"journal-article","created":{"date-parts":[[2020,2,24]],"date-time":"2020-02-24T03:33:43Z","timestamp":1582515223000},"page":"478","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Bone and Soft-Tissue Sarcoma: A New Target for Telomerase-Specific Oncolytic Virotherapy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4658-1050","authenticated-orcid":false,"given":"Hiroshi","family":"Tazawa","sequence":"first","affiliation":[{"name":"Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama 700-8558, Japan"},{"name":"Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Hasei","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuya","family":"Yano","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3610-8211","authenticated-orcid":false,"given":"Shunsuke","family":"Kagawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan"},{"name":"Minimally Invasive Therapy Center, Okayama University Hospital, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshifumi","family":"Ozaki","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyoshi","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/rmv.386","article-title":"The impact of adenovirus infection on the immunocompromised host","volume":"13","author":"Kojaoghlanian","year":"2003","journal-title":"Rev. Med. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.2217\/14796694.2.1.137","article-title":"Current developments in adenovirus-based cancer gene therapy","volume":"2","author":"Rein","year":"2006","journal-title":"Future Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1517\/14712598.2013.845662","article-title":"Advances in adenovirus-mediated p53 cancer gene therapy","volume":"13","author":"Tazawa","year":"2013","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_4","first-page":"3395","article-title":"The development of conditionally replicative adenoviruses for cancer therapy","volume":"6","author":"Curiel","year":"2000","journal-title":"Clin. Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/mt.2009.266","article-title":"Current issues and future directions of oncolytic adenoviruses","volume":"18","author":"Yamamoto","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/cgt.2011.7","article-title":"Clinical development directions in oncolytic viral therapy","volume":"18","author":"Eager","year":"2011","journal-title":"Cancer Gene Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/nbt.2287","article-title":"Oncolytic virotherapy","volume":"30","author":"Russell","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1517\/17425247.2016.1158707","article-title":"Redirecting adenovirus tropism by genetic, chemical, and mechanical modification of the adenovirus surface for cancer gene therapy","volume":"13","author":"Yoon","year":"2016","journal-title":"Expert. Opin. Drug Deliv."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/89901","article-title":"Replication-selective virotherapy for cancer: Biological principles, risk management and future directions","volume":"7","author":"Kirn","year":"2001","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S1470-2045(01)00618-0","article-title":"Oncolytic biotherapy: A novel therapeutic plafform","volume":"3","author":"Hawkins","year":"2002","journal-title":"Lancet Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1038\/nrc948","article-title":"Oncolytic viruses","volume":"2","author":"Chiocca","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.canlet.2007.02.002","article-title":"Oncolytic viruses in cancer therapy","volume":"254","author":"Heikkila","year":"2007","journal-title":"Cancer Lett."},{"key":"ref_13","first-page":"3181","article-title":"A telomerase-dependent conditionally replicating adenovirus for selective treatment of cancer","volume":"63","author":"Wirth","year":"2003","journal-title":"Cancer Res."},{"key":"ref_14","first-page":"191","article-title":"Development of a Conditional Replication Competent Adenovirus, Controlled by the Human Telomerase Promoter (hTERT)","volume":"35","author":"Kim","year":"2003","journal-title":"Cancer Res. Treat. Off. J. Korean Cancer Assoc."},{"key":"ref_15","first-page":"7936","article-title":"Replication of an adenoviral vector controlled by the human telomerase reverse transcriptase promoter causes tumor-selective tumor lysis","volume":"63","author":"Lanson","year":"2003","journal-title":"Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/sj.onc.1207033","article-title":"A novel oncolytic adenovirus targeting to telomerase activity in tumor cells with potent","volume":"23","author":"Zou","year":"2004","journal-title":"Oncogene"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1158\/1078-0432.CCR-1075-3","article-title":"Telomerase-specific replication-selective virotherapy for human cancer","volume":"10 Pt 1","author":"Kawashima","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_18","first-page":"73","article-title":"Midkine promoter-based conditionally replicative adenovirus for malignant glioma therapy","volume":"12","author":"Kohno","year":"2004","journal-title":"Oncol. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1002\/jgm.1486","article-title":"Complete regression of human malignant mesothelioma xenografts following local injection of midkine promoter-driven oncolytic adenovirus","volume":"12","author":"Kubo","year":"2010","journal-title":"J. Gene Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00535-004-1490-y","article-title":"Promoter-controlled infectivity-enhanced conditionally replicative adenoviral vectors for the treatment of gastric cancer","volume":"40","author":"Ono","year":"2005","journal-title":"J. Gastroenterol."},{"key":"ref_21","first-page":"729","article-title":"Oncolytic adenoviral vectors which employ the survivin promoter induce glioma oncolysis via a process of beclin-dependent autophagy","volume":"34","author":"Ulasov","year":"2009","journal-title":"Int. J. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1111\/j.1349-7006.2008.00878.x","article-title":"Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers","volume":"99","author":"Kyo","year":"2008","journal-title":"Cancer Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1038\/nm1404","article-title":"In vivo imaging of lymph node metastasis with telomerase-specific replication-selective adenovirus","volume":"12","author":"Kishimoto","year":"2006","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1016\/j.ejca.2011.12.020","article-title":"A novel apoptotic mechanism of genetically engineered adenovirus-mediated tumour-specific p53 overexpression through E1A-dependent p21 and MDM2 suppression","volume":"48","author":"Yamasaki","year":"2012","journal-title":"Eur. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer statistics, 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"CA Cancer J. Clin."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/2045-3329-2-14","article-title":"The epidemiology of sarcoma","volume":"2","author":"Burningham","year":"2012","journal-title":"Clin. Sarcoma Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Miwa, S., Yamamoto, N., Hayashi, K., Takeuchi, A., Igarashi, K., and Tsuchiya, H. (2019). Therapeutic Targets for Bone and Soft-Tissue Sarcomas. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010170"},{"key":"ref_28","first-page":"4776","article-title":"Telomerase activity in soft-tissue and bone sarcomas","volume":"6","author":"Aogi","year":"2000","journal-title":"Clin. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1097\/00043426-200210000-00006","article-title":"Ewing sarcoma family of tumors express adenovirus receptors and are susceptible to adenovirus-mediated oncolysis","volume":"24","author":"Rice","year":"2002","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/j.1349-7006.2003.tb01354.x","article-title":"Expression of the coxsackievirus and adenovirus receptor in musculoskeletal tumors and mesenchymal tissues: Efficacy of adenoviral gene therapy for osteosarcoma","volume":"94","author":"Kawashima","year":"2003","journal-title":"Cancer Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3831","DOI":"10.1158\/1078-0432.CCR-03-0345","article-title":"High-level expression of the coxsackievirus and adenovirus receptor messenger RNA in osteosarcoma, Ewing\u2019s sarcoma, and benign neurogenic tumors among musculoskeletal tumors","volume":"10","author":"Gu","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/ng0198-65","article-title":"Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas","volume":"18","author":"Nakayama","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_33","first-page":"1558","article-title":"Expression of human telomerase subunits and correlation with telomerase activity in cervical cancer","volume":"58","author":"Takakura","year":"1998","journal-title":"Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1158\/1078-0432.217.11.1","article-title":"A robust assay for alternative lengthening of telomeres in tumors shows the significance of alternative lengthening of telomeres in sarcomas and astrocytomas","volume":"11","author":"Henson","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_35","first-page":"813","article-title":"Efficient oncolysis by a replicating adenovirus (ad) in vivo is critically dependent on tumor expression of primary ad receptors","volume":"61","author":"Douglas","year":"2001","journal-title":"Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/sj.cgt.7700284","article-title":"Coxsackievirus-adenovirus receptor expression in ovarian cancer cell lines is associated with increased adenovirus transduction efficiency and transgene expression","volume":"8","author":"You","year":"2001","journal-title":"Cancer Gene Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1089\/thy.2005.15.977","article-title":"Variable expression of coxsackie-adenovirus receptor in thyroid tumors: Implications for adenoviral gene therapy","volume":"15","author":"Marsee","year":"2005","journal-title":"Thyroid Off. J. Am. Thyroid Assoc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1038\/sj.cgt.7700947","article-title":"Expression of the coxsackievirus- and adenovirus receptor in gastrointestinal cancer correlates with tumor differentiation","volume":"13","author":"Korn","year":"2006","journal-title":"Cancer Gene Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/cgt.2008.103","article-title":"Expression and function of the coxsackie and adenovirus receptor in Barrett\u2019s esophagus and associated neoplasia","volume":"16","author":"Anders","year":"2009","journal-title":"Cancer Gene Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1158\/1078-0432.CCR-10-2066","article-title":"Preclinical evaluation of telomerase-specific oncolytic virotherapy for human bone and soft tissue sarcomas","volume":"17","author":"Sasaki","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.urology.2005.02.033","article-title":"Loss of coxsackie and adenovirus receptor expression is associated with features of aggressive bladder cancer","volume":"66","author":"Matsumoto","year":"2005","journal-title":"Urology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/sj.bjc.6604876","article-title":"Loss of the coxsackie and adenovirus receptor contributes to gastric cancer progression","volume":"100","author":"Anders","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/cgt.2009.49","article-title":"Downregulation of the coxsackie and adenovirus receptor in cancer cells by hypoxia depends on HIF-1alpha","volume":"17","author":"Kuster","year":"2010","journal-title":"Cancer Gene Ther."},{"key":"ref_44","first-page":"6328","article-title":"Enhanced adenovirus transgene expression in malignant cells treated with the histone deacetylase inhibitor FR901228","volume":"61","author":"Kitazono","year":"2001","journal-title":"Cancer Res."},{"key":"ref_45","first-page":"5394","article-title":"The histone deacetylase inhibitor FK228 preferentially enhances adenovirus transgene expression in malignant cells","volume":"9","author":"Goldsmith","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.yexcr.2005.10.026","article-title":"Histone deacetylase inhibitor FR901228 enhances the antitumor effect of telomerase-specific replication-selective adenoviral agent OBP-301 in human lung cancer cells","volume":"312","author":"Watanabe","year":"2006","journal-title":"Exp. Cell Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.virusres.2018.08.012","article-title":"Tropism and transduction of oncolytic adenovirus 5 vectors in cancer therapy: Focus on fiber chimerism and mosaicism, hexon and pIX","volume":"257","author":"Stepanenko","year":"2018","journal-title":"Virus Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1111\/j.1349-7006.2007.00665.x","article-title":"Establishment of biological and pharmacokinetic assays of telomerase-specific replication-selective adenovirus","volume":"99","author":"Hashimoto","year":"2008","journal-title":"Cancer Sci."},{"key":"ref_49","first-page":"333","article-title":"Oncolytic adenovirus-induced autophagy: Tumor-suppressive effect and molecular basis","volume":"67","author":"Tazawa","year":"2013","journal-title":"Acta Med. Okayama"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.1002\/ijc.27589","article-title":"Genetically engineered oncolytic adenovirus induces autophagic cell death through an E2F1-microRNA-7-epidermal growth factor receptor axis","volume":"131","author":"Tazawa","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5295","DOI":"10.1038\/onc.2014.452","article-title":"C-Jun N-terminal kinases are required for oncolytic adenovirus-mediated autophagy","volume":"34","author":"Klein","year":"2015","journal-title":"Oncogene"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1080\/15384047.2018.1491503","article-title":"The role of JNK phosphorylation as a molecular target to enhance adenovirus replication, oncolysis and cancer therapeutic efficacy","volume":"19","author":"Wechman","year":"2018","journal-title":"Cancer Biol. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"682","DOI":"10.18632\/genesandcancer.155","article-title":"JNK-signaling: A multiplexing hub in programmed cell death","volume":"8","author":"Dhanasekaran","year":"2017","journal-title":"Genes Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"28953","DOI":"10.1038\/srep28953","article-title":"Ablation of MCL1 expression by virally induced microRNA-29 reverses chemoresistance in human osteosarcomas","volume":"6","author":"Osaki","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1111\/cas.13316","article-title":"Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction","volume":"108","author":"Yamakawa","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3451","DOI":"10.1158\/1078-0432.CCR-08-1616","article-title":"Zoledronic acid inhibits both the osteolytic and osteoblastic components of osteosarcoma lesions in a mouse model","volume":"15","author":"Labrinidis","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/ijc.25051","article-title":"Zoledronic acid protects against osteosarcoma-induced bone destruction but lacks efficacy against pulmonary metastases in a syngeneic rat model","volume":"127","author":"Labrinidis","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1158\/1535-7163.MCT-12-0869","article-title":"Dual programmed cell death pathways induced by p53 transactivation overcome resistance to oncolytic adenovirus in human osteosarcoma cells","volume":"12","author":"Hasei","year":"2013","journal-title":"Mol. Cancer Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/1061186X.2014.950668","article-title":"The critical role of bisphosphonates to target bone cancer metastasis: An overview","volume":"23","author":"Singh","year":"2015","journal-title":"J. Drug Target."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13569-016-0046-2","article-title":"Zoledronic acid in metastatic osteosarcoma: Encouraging progression free survival in four consecutive patients","volume":"6","author":"Conry","year":"2016","journal-title":"Clin. Sarcoma Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/gt.2011.213","article-title":"A simple detection system for adenovirus receptor expression using a telomerase-specific replication-competent adenovirus","volume":"20","author":"Sasaki","year":"2013","journal-title":"Gene Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1007\/s00432-010-0969-6","article-title":"Efficient virotherapy for osteosarcoma by telomerase-specific oncolytic adenovirus","volume":"137","author":"Li","year":"2011","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3172","DOI":"10.1172\/JCI38609","article-title":"A simple biological imaging system for detecting viable human circulating tumor cells","volume":"119","author":"Kojima","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1136\/gutjnl-2014-306957","article-title":"Fluorescence virus-guided capturing system of human colorectal circulating tumour cells for non-invasive companion diagnostics","volume":"64","author":"Shigeyasu","year":"2015","journal-title":"Gut"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s10549-011-1603-2","article-title":"A novel approach using telomerase-specific replication-selective adenovirus for detection of circulating tumor cells in breast cancer patients","volume":"128","author":"Kim","year":"2011","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/bjc.2012.276","article-title":"Circulating tumour cells detected by a novel adenovirus-mediated system may be a potent therapeutic marker in gynaecological cancers","volume":"107","author":"Takakura","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Ito, H., Inoue, H., Sando, N., Kimura, S., Gohda, K., Sato, J., Murakami, K., Ito, S., Odaka, N., and Satodate, H. (2012). Prognostic impact of detecting viable circulating tumour cells in gastric cancer patients using a telomerase-specific viral agent: A prospective study. BMC Cancer, 12.","DOI":"10.1186\/1471-2407-12-346"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.3892\/ol.2014.1940","article-title":"Circulating tumor cells as a prognostic factor in patients with small cell lung cancer","volume":"7","author":"Igawa","year":"2014","journal-title":"Oncol. Lett."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.3892\/or.2014.3436","article-title":"Detection and preliminary evaluation of circulating tumor cells in the peripheral blood of patients with eight types of cancer using a telomerase-specific adenovirus","volume":"32","author":"Yabusaki","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"34884","DOI":"10.18632\/oncotarget.16818","article-title":"Sensitive detection of viable circulating tumor cells using a novel conditionally telomerase-selective replicating adenovirus in non-small cell lung cancer patients","volume":"8","author":"Togo","year":"2017","journal-title":"Oncotarget"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1158\/0008-5472.CAN-13-0813","article-title":"Detection of brain tumor cells in the peripheral blood by a telomerase promoter-based assay","volume":"74","author":"Macarthur","year":"2014","journal-title":"Cancer Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"683","DOI":"10.4161\/cbt.28412","article-title":"Application of a telomerase-based circulating tumor cell (CTC) assay in bladder cancer patients receiving postoperative radiation therapy: A case study","volume":"15","author":"Ju","year":"2014","journal-title":"Cancer Biol. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/cncr.28975","article-title":"Tracking viable circulating tumor cells (CTCs) in the peripheral blood of non-small cell lung cancer (NSCLC) patients undergoing definitive radiation therapy: Pilot study results","volume":"121","author":"Dorsey","year":"2015","journal-title":"Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.1111\/cas.13760","article-title":"Integrated fluorescent cytology with nano-biologics in peritoneally disseminated gastric cancer","volume":"109","author":"Watanabe","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1186\/s13046-018-0981-2","article-title":"The epithelial-to-mesenchymal transition induced by tumor-associated macrophages confers chemoresistance in peritoneally disseminated pancreatic cancer","volume":"37","author":"Kuwada","year":"2018","journal-title":"J. Exp. Clin. Cancer Res. CR"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e1671760","DOI":"10.1080\/2162402X.2019.1671760","article-title":"Intraperitoneal cancer-immune microenvironment promotes peritoneal dissemination of gastric cancer","volume":"8","author":"Sakamoto","year":"2019","journal-title":"Oncoimmunology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1158\/1078-0432.CCR-08-2690","article-title":"Telomerase-specific virotheranostics for human head and neck cancer","volume":"15","author":"Kurihara","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3001","DOI":"10.1158\/1535-7163.MCT-09-0556","article-title":"Selective metastatic tumor labeling with green fluorescent protein and killing by systemic administration of telomerase-dependent adenoviruses","volume":"8","author":"Kishimoto","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"14514","DOI":"10.1073\/pnas.0906388106","article-title":"In vivo internal tumor illumination by telomerase-dependent adenoviral GFP for precise surgical navigation","volume":"106","author":"Kishimoto","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/cgt.2009.44","article-title":"Intraperitoneal administration of telomerase-specific oncolytic adenovirus sensitizes ovarian cancer cells to cisplatin and affects survival in a xenograft model with peritoneal dissemination","volume":"17","author":"Takakura","year":"2010","journal-title":"Cancer Gene Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/nrc3566","article-title":"Fluorescence-guided surgery with live molecular navigation\u2014A new cutting edge","volume":"13","author":"Nguyen","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nrclinonc.2013.123","article-title":"Image-guided cancer surgery using near-infrared fluorescence","volume":"10","author":"Vahrmeijer","year":"2013","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1586\/14737140.2016.1121109","article-title":"Current status and future perspectives of fluorescence-guided surgery for cancer","volume":"16","author":"DeLong","year":"2016","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"314","DOI":"10.3389\/fonc.2017.00314","article-title":"Fluorescence-Guided Surgery","volume":"7","author":"Nagaya","year":"2017","journal-title":"Front. Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Yano, S., Takehara, K., Miwa, S., Kishimoto, H., Hiroshima, Y., Murakami, T., Urata, Y., Kagawa, S., Bouvet, M., and Fujiwara, T. (2016). Improved Resection and Outcome of Colon-Cancer Liver Metastasis with Fluorescence-Guided Surgery Using In Situ GFP Labeling with a Telomerase-Dependent Adenovirus in an Orthotopic Mouse Model. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148760"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1038\/mt.2015.63","article-title":"Experimental Curative Fluorescence-guided Surgery of Highly Invasive Glioblastoma Multiforme Selectively Labeled With a Killer-reporter Adenovirus","volume":"23","author":"Yano","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e000096","DOI":"10.1136\/bmjresp-2015-000096","article-title":"Precise navigation surgery of tumours in the lung in mouse models enabled by in situ fluorescence labelling with a killer-reporter adenovirus","volume":"2","author":"Yano","year":"2015","journal-title":"BMJ Open Respir. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"75635","DOI":"10.18632\/oncotarget.12314","article-title":"Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence","volume":"7","author":"Yano","year":"2016","journal-title":"Oncotarget"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"18558","DOI":"10.18632\/oncotarget.6670","article-title":"Adenoviral targeting of malignant melanoma for fluorescence-guided surgery prevents recurrence in orthotopic nude-mouse models","volume":"7","author":"Yano","year":"2016","journal-title":"Oncotarget"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1002\/jor.23073","article-title":"Eradication of osteosarcoma by fluorescence-guided surgery with tumor labeling by a killer-reporter adenovirus","volume":"34","author":"Yano","year":"2016","journal-title":"J. Orthop. Res. Off. Publ. Orthop. Res. Soc."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"13133","DOI":"10.18632\/oncotarget.3811","article-title":"Targeting tumors with a killer-reporter adenovirus for curative fluorescence-guided surgery of soft-tissue sarcoma","volume":"6","author":"Yano","year":"2015","journal-title":"Oncotarget"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nbt1175","article-title":"A genetically encoded photosensitizer","volume":"24","author":"Bulina","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1158\/1535-7163.MCT-15-0344","article-title":"Targeted Photodynamic Virotherapy Armed with a Genetically Encoded Photosensitizer","volume":"15","author":"Takehara","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1080\/15384101.2016.1249548","article-title":"Eradication of melanoma in vitro and in vivo via targeting with a Killer-Red-containing telomerase-dependent adenovirus","volume":"16","author":"Takehara","year":"2017","journal-title":"Cell Cycle"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.cell.2009.04.037","article-title":"Blinded by the Light: The Growing Complexity of p53","volume":"137","author":"Vousden","year":"2009","journal-title":"Cell"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"a001008","DOI":"10.1101\/cshperspect.a001008","article-title":"TP53 mutations in human cancers: Origins, consequences, and clinical use","volume":"2","author":"Olivier","year":"2010","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1002\/cncr.26390","article-title":"Sarcomas in TP53 germline mutation carriers: A review of the IARC TP53 database","volume":"118","author":"Ognjanovic","year":"2012","journal-title":"Cancer"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1093\/carcin\/bgp331","article-title":"In vivo analysis of p53 tumor suppressor function using genetically engineered mouse models","volume":"31","author":"Attardi","year":"2010","journal-title":"Carcinogenesis"},{"key":"ref_99","first-page":"1","article-title":"p53 Replacement Therapy for Cancer. Recent results in cancer research. Fortschritte der Krebsforschung","volume":"209","author":"Tazawa","year":"2016","journal-title":"Progres dans les Recherches sur le Cancer"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1158\/1535-7163.MCT-10-0205","article-title":"Preclinical evaluation of differentially targeting dual virotherapy for human solid cancer","volume":"9","author":"Sakai","year":"2010","journal-title":"Mol. Cancer Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/mt.2009.262","article-title":"A phase I study of telomerase-specific replication competent oncolytic adenovirus (telomelysin) for various solid tumors","volume":"18","author":"Nemunaitis","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1016\/S1470-2045(17)30624-1","article-title":"Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): A multicentre, two-cohort, single-arm, open-label, phase 2 trial","volume":"18","author":"Tawbi","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13073-017-0424-2","article-title":"Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden","volume":"9","author":"Chalmers","year":"2017","journal-title":"Genome Med."},{"key":"ref_104","first-page":"977","article-title":"Characteristics of mismatch repair deficiency in sarcomas","volume":"32","author":"Doyle","year":"2019","journal-title":"Modern Pathol. Off. J. U. S. Can. Acad. Pathol. Inc."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e947872","DOI":"10.4161\/21624011.2014.947872","article-title":"Healing after death: Antitumor immunity induced by oncolytic adenoviral therapy","volume":"3","author":"Jiang","year":"2014","journal-title":"Oncoimmunology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/1476-4598-12-103","article-title":"Oncolytic viruses as therapeutic cancer vaccines","volume":"12","author":"Bartlett","year":"2013","journal-title":"Mol. Cancer"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3389\/fonc.2014.00074","article-title":"Oncolytic Immunotherapy: Dying the Right Way is a Key to Eliciting Potent Antitumor Immunity","volume":"4","author":"Guo","year":"2014","journal-title":"Front. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Tazawa, H., Kuroda, S., Hasei, J., Kagawa, S., and Fujiwara, T. (2017). Impact of Autophagy in Oncolytic Adenoviral Therapy for Cancer. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071479"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1158\/0008-5472.CAN-18-1086","article-title":"Multiregion Sequencing Reveals the Genetic Heterogeneity and Evolutionary History of Osteosarcoma and Matched Pulmonary Metastases","volume":"79","author":"Wang","year":"2019","journal-title":"Cancer Res."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/2\/478\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:58:49Z","timestamp":1760173129000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/2\/478"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,18]]},"references-count":109,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["cancers12020478"],"URL":"https:\/\/doi.org\/10.3390\/cancers12020478","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,18]]}}}