{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:48:39Z","timestamp":1760233719206,"version":"build-2065373602"},"reference-count":58,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T00:00:00Z","timestamp":1613520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","award":["201820136"],"award-info":[{"award-number":["201820136"]}],"id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We evaluated the abscopal effect of re-implantation of liquid nitrogen-treated tumor-bearing bone grafts and the synergistic effect of anti-PD-1 (programmed death-1) therapy using a bone metastasis model, created by injecting MMT-060562 cells into the bilateral tibiae of 6\u20138-week-old female C3H mice. After 2 weeks, the lateral tumors were treated by excision, cryotreatment using liquid nitrogen, excision with anti-PD-1 treatment, and cryotreatment with anti-PD-1 treatment. Anti-mouse PD-1 4H2 was injected on days 1, 6, 12, and 18 post-treatment. The mice were euthanized after 3 weeks; the abscopal effect was evaluated by focusing on growth inhibition of the abscopal tumor. The re-implantation of frozen autografts significantly inhibited the growth of the remaining abscopal tumors. However, a more potent abscopal effect was observed in the anti-PD-1 antibody group. The number of CD8+ T cells infiltrating the abscopal tumor and tumor-specific interferon-\u03b3 (IFN-\u03b3)-producing spleen cells increased in the liquid nitrogen-treated group compared with those in the excision group, with no significant difference. The number was significantly higher in the anti-PD-1 antibody-treated group than in the non-treated group. Overall, re-implantation of tumor-bearing frozen autograft has an abscopal effect on abscopal tumor growth, although re-implantation of liquid nitrogen-treated bone grafts did not induce a strong T-cell response or tumor-suppressive effect.<\/jats:p>","DOI":"10.3390\/ijms22041973","type":"journal-article","created":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T21:35:42Z","timestamp":1613597742000},"page":"1973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Abscopal Effect of Frozen Autograft Reconstruction Combined with an Immune Checkpoint Inhibitor Analyzed Using a Metastatic Bone Tumor Model"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8037-6213","authenticated-orcid":false,"given":"Noritaka","family":"Yonezawa","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Demura","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4762-5932","authenticated-orcid":false,"given":"Satoshi","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Miwa","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsuhito","family":"Yoshioka","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, National Hospital Organization Kanazawa Medical Center, Kanazawa, Ishikawa 920-8650, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8583-4615","authenticated-orcid":false,"given":"Kazuya","family":"Shinmura","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriaki","family":"Yokogawa","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaki","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norihiro","family":"Oku","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Kitagawa","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Handa","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6373-9265","authenticated-orcid":false,"given":"Ryohei","family":"Annen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Kurokawa","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazumi","family":"Fushimi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa 920-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eishiro","family":"Mizukoshi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa 920-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,17]]},"reference":[{"key":"ref_1","first-page":"395","article-title":"Studies in cryo-immunology. I. The production of antibodies to uro-genital tissue in consequence of freezing treatment","volume":"12","author":"Yantorno","year":"1967","journal-title":"Immunology"},{"key":"ref_2","first-page":"149","article-title":"Studies in cryo-immunology. II. Tissue and species specificity of the autoantibody response and comparison with iso-immunization","volume":"14","author":"Shulman","year":"1968","journal-title":"Immunology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1302\/0301-620X.87B2.15325","article-title":"Reconstruction using an autograft containing tumour treated by liquid nitrogen","volume":"87","author":"Tsuchiya","year":"2005","journal-title":"J. Bone Jt. Surg. Br. Vol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Murakami, H., Demura, S., Kato, S., Nishida, H., Yoshioka, K., Hayashi, H., Inoue, K., Ota, T., Shinmura, K., and Yokogawa, N. (2013). Increase of IL-12 following Reconstruction for Total En Bloc Spondylectomy Using Frozen Autografts Treated with Liquid Nitrogen. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064818"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1007\/s00586-013-3056-2","article-title":"Reconstruction using a frozen tumor-bearing vertebra in total en bloc spondylectomy can enhance antitumor immunity","volume":"23","author":"Murakami","year":"2013","journal-title":"Eur. Spine J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1007\/s10776-002-0626-3","article-title":"Effects of liquid nitrogen treatment on the proliferation of osteosarcoma and the biomechanical properties of normal bone","volume":"8","author":"Yamamoto","year":"2003","journal-title":"J. Orthop. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1302\/0301-620X.90B9.20671","article-title":"Re-implantation of tumour tissue treated by cryotreatment with liquid nitrogen in-duces anti-tumour activity against murine osteosarcoma","volume":"90","author":"Nishida","year":"2008","journal-title":"J. Bone Jt. Surg. Br."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"110411","DOI":"10.1016\/j.msec.2019.110411","article-title":"Scaffold strategies for modulating immune microenvironment during bone regeneration","volume":"108","author":"He","year":"2020","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.actbio.2015.12.003","article-title":"Titanium surface characteristics, including topography and wettability, alter macrophage activation","volume":"31","author":"Hotchkiss","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"712810","DOI":"10.1155\/2015\/712810","article-title":"Attenuating Immune Response of Macro-phage by Enhancing Hydrophilicity of Ti Surface","volume":"2015","author":"Dai","year":"2015","journal-title":"J. Nanomater."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/j.1600-0501.2011.02172.x","article-title":"Early osseointegration to hydrophilic and hydrophobic implant surfaces in humans","volume":"22","author":"Lang","year":"2011","journal-title":"Clin. Oral Implant. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Shinmura, K., Murakami, H., Demura, S., Kato, S., Yoshioka, K., Hayashi, H., Inoue, K., Ota, T., Yokogawa, N., and Ishii, T. (2018). A histological examination of spinal reconstruction using a frozen bone autograft. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191679"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1056\/NEJMoa1112824","article-title":"Immunologic Correlates of the Abscopal Effect in a Patient with Melanoma","volume":"366","author":"Postow","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.ijrobp.2005.06.032","article-title":"Combining radiotherapy and immunotherapy: A revived part-nership","volume":"63","author":"Demaria","year":"2005","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1158\/1078-0432.728.11.2","article-title":"Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer","volume":"11","author":"DeMaria","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5379","DOI":"10.1158\/1078-0432.CCR-09-0265","article-title":"Fractionated but Not Single-Dose Radiotherapy Induces an Immune-Mediated Abscopal Effect when Combined with Anti\u2013CTLA-4 Antibody","volume":"15","author":"Dewan","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"E6","DOI":"10.3171\/2014.11.FOCUS14716","article-title":"Stereotactic radiosurgery and immunotherapy for metastatic spinal melanoma","volume":"38","author":"Caruso","year":"2015","journal-title":"Neurosurg. Focus"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4180","DOI":"10.18632\/oncotarget.24105","article-title":"Cryoablation inhibition of distant untreated tumors (abscopal effect) is immune mediated","volume":"10","author":"Yang","year":"2018","journal-title":"Oncotarget"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.jvir.2018.12.004","article-title":"Abscopal Effect following Cryoablation of Breast Cancer","volume":"30","author":"Kumar","year":"2019","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s00586-015-4077-9","article-title":"Disappearance of lung adenocarcinoma after total en bloc spon-dylectomy using frozen tumor-bearing vertebra for reconstruction","volume":"25","author":"Sugita","year":"2016","journal-title":"Eur. Spine J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00586-018-5831-6","article-title":"Lung metastases regression with increased CD8+ T lymphocyte infiltration following preoperative spinal embolization and total en bloc spondylectomy using tumor-bearing frozen autograft in a patient with spinal metastatic leiomyosarcoma","volume":"28","author":"Yonezawa","year":"2019","journal-title":"Eur. Spine J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1007\/s00262-016-1858-x","article-title":"Optimized magnitude of cryosurgery facilitating anti-tumor immunoreaction in a mouse model of Lewis lung cancer","volume":"65","author":"Takahashi","year":"2016","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1111\/j.1464-410X.2005.05502.x","article-title":"The molecular basis of cryosurgery","volume":"95","author":"Baust","year":"2005","journal-title":"Bju Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cryobiol.2008.10.126","article-title":"Cryo-immunology: A review of the literature and proposed mechanisms for stimulatory versus suppressive immune responses","volume":"58","author":"Sabel","year":"2009","journal-title":"Cryobiology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cryobiol.2020.02.010","article-title":"The future of cryoablation: An abscopal effect","volume":"97","author":"Chen","year":"2020","journal-title":"Cryobiology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3389\/fonc.2018.00085","article-title":"Immunotherapy Plus Cryotherapy: Potential Augmented Abscopal Effect for Advanced Cancers","volume":"8","author":"Abdo","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s13244-019-0727-5","article-title":"Cryoablation and immunotherapy: An overview of evidence on its synergy","volume":"10","author":"Aarts","year":"2019","journal-title":"Insights Imaging"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cryobiol.2018.04.013","article-title":"Percutaneous ablative cryoimmunotherapy for micrometastaic abscopal effect: No compli-cations","volume":"82","author":"Soule","year":"2018","journal-title":"Cryobiology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/s41391-018-0035-z","article-title":"Combining immune check-point blockade and cryoablation in an immunocompetent hormone sensitive murine model of prostate cancer","volume":"21","author":"Benzon","year":"2018","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.cryobiol.2013.04.004","article-title":"Cryotherapy protocols for metastatic breast cancer after failure of radical surgery","volume":"67","author":"Niu","year":"2013","journal-title":"Cryobiology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"659","DOI":"10.4149\/neo_2014_081","article-title":"Anti-tumor immunological response induced by cryoablation and anti-CTLA-4 antibody in an in vivo RM-1 cell prostate cancer murine model","volume":"61","author":"Li","year":"2014","journal-title":"Neoplasma"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1158\/0008-5472.CAN-11-1782","article-title":"Potent Induction of Tumor Immunity by Combining Tumor Cryoablation with Anti\u2013CTLA-4 Therapy","volume":"72","author":"Waitz","year":"2012","journal-title":"Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1002\/cam4.842","article-title":"Ultrasound imaging of splenomegaly as a proxy to monitor colon tumor development in Apcmin716\/+mice","volume":"5","author":"Hodgson","year":"2016","journal-title":"Cancer Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1006\/cryo.2001.2302","article-title":"In Vivo Destruction of Tumor Tissue by Cryoablation Can Induce Inhibition of Secondary Tumor Growth: An Experimental Study","volume":"42","author":"Joosten","year":"2001","journal-title":"Cryobiology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.cryobiol.2006.07.004","article-title":"Adoptive immunotherapy of breast cancer with lymph node cells primed by cry-oablation of the primary tumor","volume":"53","author":"Sabel","year":"2006","journal-title":"Cryobiology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s10549-004-3289-1","article-title":"Immunologic response to cryoablation of breast cancer","volume":"90","author":"Sabel","year":"2005","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/S0011-2240(03)00039-7","article-title":"Antitumor effects of residual tumor after cryoablation: The combined effect of residual tumor and a protein-bound polysaccharide on multiple liver metastases in a murine model","volume":"46","author":"Urano","year":"2003","journal-title":"Cryobiology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1006\/cryo.2001.2305","article-title":"Investigation of the mechanism and the effect of cryo-immunology in the copenhagen rat","volume":"42","author":"Hoffmann","year":"2001","journal-title":"Cryobiology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7465","DOI":"10.1158\/1078-0432.CCR-06-1840","article-title":"Enhancement of Immunologic Tumor Regression by Intratumoral Administration of Dendritic Cells in Combination with Cryoablative Tumor Pretreatment and Bacillus Calmette-Guerin Cell Wall Skeleton Stimulation","volume":"12","author":"Udagawa","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1016\/S0022-5347(01)64284-8","article-title":"Cryosurgical ablation of the normal ventral prostate plus adjuvant does not protect Copenhagen rats from dunning prostatic adenocarcinoma challenge","volume":"158","author":"Friedman","year":"1997","journal-title":"J. Urol."},{"key":"ref_41","first-page":"462","article-title":"Comparative immunologi-cal studies in rats following cryosurgery and surgical excision of 3-methylcholanthrene-induced primary autochthonous tumors","volume":"73","author":"Hayakawa","year":"1982","journal-title":"Gan"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.1365-2249.2010.04246.x","article-title":"Prolonged recurrence-free survival following OK432-stimulated dendritic cell transfer into hepatocellular carcinoma during transarterial embolization","volume":"163","author":"Nakamoto","year":"2010","journal-title":"Clin. Exp. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Marconi, R., Strolin, S., Bossi, G., and Strigari, L. (2017). A meta-analysis of the abscopal effect in preclinical models: Is the biologically effective dose a relevant physical trigger?. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171559"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1172\/JCI67313","article-title":"Irradiation and anti\u2013PD-L1 treatment synergistically promote antitumor immunity in mice","volume":"124","author":"Deng","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1158\/1078-0432.CCR-07-4485","article-title":"Enhancement of Antitumor Radiation Efficacy and Consistent Induction of the Abscopal Effect in Mice by ECI301, an Active Variant of Macrophage Inflammatory Protein-1\u03b1","volume":"14","author":"Shiraishi","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1126\/scitranslmed.aad7118","article-title":"PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy","volume":"8","author":"Zou","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_47","first-page":"1","article-title":"Checkpoint inhibitors in the treatment of cutaneous malignant melanoma","volume":"3","author":"Lutzky","year":"2014","journal-title":"Chin. Clin. Oncol."},{"key":"ref_48","first-page":"41","article-title":"Combination Immunotherapy Superior to Monotherapy in Patients with Melanoma","volume":"8","author":"Doyle","year":"2015","journal-title":"Am. Health Drug Benefits"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e00378-18","DOI":"10.1128\/mSphereDirect.00378-18","article-title":"Spleen Ty-rosine Kinase Inhibitor TAK-659 Prevents Splenomegaly and Tumor Development in a Murine Model of Epstein-Barr Vi-rus-Associated Lymphoma","volume":"22","author":"Cen","year":"2018","journal-title":"mSphere"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.antiviral.2012.05.003","article-title":"Dasatinib therapy results in decreased B cell proliferation, splenomegaly, and tumor growth in a murine model of lymphoma expressing Myc and Epstein-Barr virus LMP2A","volume":"95","author":"Dargart","year":"2012","journal-title":"Antivir. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"36663","DOI":"10.1038\/srep36663","article-title":"Inhibiting MDSC differentiation from bone marrow with phytochemical polyacetylenes drastically impairs tumor metastasis","volume":"6","author":"Wei","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1093\/intimm\/10.10.1563","article-title":"Immunological studies on PD-1 deficient mice: Implication of PD-1 as a negative regulator for B cell responses","volume":"10","author":"Nishimura","year":"1998","journal-title":"Int. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1016\/j.ijrobp.2011.09.049","article-title":"Maximizing Tumor Immunity with Fractionated Radiation","volume":"83","author":"Schaue","year":"2012","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s10585-007-9068-8","article-title":"Novel hyperthermia for metastatic bone tumors with magnetic materials by generating an alternating elec-tromagnetic field","volume":"24","author":"Matsumine","year":"2007","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1109\/JMMCT.2019.2959585","article-title":"A Multiphysic Model for the Hyperthermia Treatment of Residual Osteo-sarcoma Cells in Upper Limbs Using Magnetic Scaffolds","volume":"4","author":"Lodi","year":"2019","journal-title":"IEEE J. Multiscale Multiphys. Comput. Tech."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1359\/jbmr.1998.13.3.400","article-title":"The Mouse Mammary Tumor Cell Line, MMT060562, Produces Prostaglandin E2 and Leukemia Inhibitory Factor and Supports Osteoclast Formation In Vitro Via a Stromal Cell-Dependent Pathway","volume":"13","author":"Akatsu","year":"1998","journal-title":"J. Bone Min. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S8756-3282(98)00065-9","article-title":"Mouse Mammary Carcinoma Cell Line (BALB\/c-MC) Stimulates Osteoclast Formation From Mouse Bone Marrow Cells Through Cell-to-Cell Contact","volume":"23","author":"Ono","year":"1998","journal-title":"Bone"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/BF00391826","article-title":"Estimation of liver tumor volume using different formulas?An experimental study in rats","volume":"105","author":"Carlsson","year":"1983","journal-title":"J. Cancer Res. Clin. Oncol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/4\/1973\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:25:09Z","timestamp":1760160309000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/4\/1973"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,17]]},"references-count":58,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["ijms22041973"],"URL":"https:\/\/doi.org\/10.3390\/ijms22041973","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2021,2,17]]}}}