{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:38:31Z","timestamp":1791891511679,"version":"4.3.4"},"reference-count":100,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health of Ukraine","award":["0123U100711"],"award-info":[{"award-number":["0123U100711"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Despite efforts in osteosarcoma (OS) research, the role of inductive moderate hyperthermia (IMH) in delivering and enhancing the antitumor effect of liposomal doxorubicin formulations (LDOX) remains unresolved. This study investigated the effect of a combination treatment with LDOX and IMH on Saos-2 human OS cells. We compared cell viability using a trypan blue assay, apoptosis and reactive oxygen species (ROS) measured by flow cytometry and pro-apoptotic Bax protein expression examined by immunocytochemistry in response to IMH (42 MHz frequency, 15 W power for 30 min), LDOX (0.4 \u03bcg\/mL), and LDOX plus IMH. The lower IC50 value of LDOX at 72 h indicated increased accumulation of the drug in the OS cells. LDOX plus IMH resulted in a 61% lower cell viability compared to no treatment. Moreover, IMH potentiated the LDOX action on the Saos-2 cells by promoting ROS production at temperatures of &lt;42 \u00b0C. There was a 12% increase in cell populations undergoing early apoptosis with a less heterogeneous distribution of Bax after combination treatment compared to those treated with LDOX (p &lt; 0.05). Therefore, we determined that IMH could enhance LDOX delivery and its antitumor effect via altered membrane permeabilization, ROS generation, and a lower level of visualized Bax heterogeneity in the Saos-2 cells, suggesting the potential translation of these findings into in vivo studies.<\/jats:p>","DOI":"10.3390\/ph17010133","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T05:46:44Z","timestamp":1705643204000},"page":"133","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Combination Treatment with Liposomal Doxorubicin and Inductive Moderate Hyperthermia for Sarcoma Saos-2 Cells"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6319-4215","authenticated-orcid":false,"given":"Valerii E.","family":"Orel","sequence":"first","affiliation":[{"name":"National Cancer Institute, 33\/43 Zdanovska Str., 03022 Kyiv, Ukraine"},{"name":"National Technical University of Ukraine \u201cIgor Sikorsky Kyiv Polytechnic Institute\u201d, 16\/2 Yangel Str., 03056 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatoliy G.","family":"Diedkov","sequence":"additional","affiliation":[{"name":"National Cancer Institute, 33\/43 Zdanovska Str., 03022 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasyl V.","family":"Ostafiichuk","sequence":"additional","affiliation":[{"name":"National Cancer Institute, 33\/43 Zdanovska Str., 03022 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleksandra O.","family":"Lykhova","sequence":"additional","affiliation":[{"name":"R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, 45 Vasylkivska Str., 03022 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denys L.","family":"Kolesnyk","sequence":"additional","affiliation":[{"name":"R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, 45 Vasylkivska Str., 03022 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3653-0823","authenticated-orcid":false,"given":"Valerii B.","family":"Orel","sequence":"additional","affiliation":[{"name":"National Cancer Institute, 33\/43 Zdanovska Str., 03022 Kyiv, Ukraine"},{"name":"National Technical University of Ukraine \u201cIgor Sikorsky Kyiv Polytechnic Institute\u201d, 16\/2 Yangel Str., 03056 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga Yo.","family":"Dasyukevich","sequence":"additional","affiliation":[{"name":"National Cancer Institute, 33\/43 Zdanovska Str., 03022 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleksandr Yu.","family":"Rykhalskyi","sequence":"additional","affiliation":[{"name":"National Cancer Institute, 33\/43 Zdanovska Str., 03022 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1432-2097","authenticated-orcid":false,"given":"Serhii A.","family":"Diedkov","sequence":"additional","affiliation":[{"name":"National Cancer Institute, 33\/43 Zdanovska Str., 03022 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna B.","family":"Prosvietova","sequence":"additional","affiliation":[{"name":"National Technical University of Ukraine \u201cIgor Sikorsky Kyiv Polytechnic Institute\u201d, 16\/2 Yangel Str., 03056 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1750-1172-2-6","article-title":"Osteosarcoma (osteogenic sarcoma)","volume":"2","author":"Picci","year":"2007","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1051\/sicotj\/2017028","article-title":"Osteosarcoma: A comprehensive review","volume":"4","author":"Misaghi","year":"2018","journal-title":"Sicot J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/s41572-022-00416-z","article-title":"Osteosarcoma","volume":"8","author":"Beird","year":"2022","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/s10552-015-0607-3","article-title":"Bone cancer incidence by morphological subtype: A global assessment","volume":"26","author":"Valery","year":"2015","journal-title":"Cancer Causes Control."},{"key":"ref_5","unstructured":"Heymann, D. (2022). Bone Sarcomas and Bone Metastases\u2014From Bench to Bedside, Academic Press. [3rd ed.]."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.cyto.2017.05.024","article-title":"Cytokines in immunogenic cell death: Applications for cancer immunotherapy","volume":"97","author":"Showalter","year":"2017","journal-title":"Cytokine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1172\/JCI72931","article-title":"Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation","volume":"124","author":"Ichikawa","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Susa, M., Iyer, A.K., Ryu, K., Hornicek, F.J., Mankin, H., Amiji, M.M., and Duan, Z. (2009). Doxorubicin loaded polymeric nanoparticulate delivery system to overcome drug resistance in osteosarcoma. BMC Cancer, 9.","DOI":"10.1186\/1471-2407-9-399"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.1039\/D0TB00327A","article-title":"Human serum albumin-based doxorubicin prodrug nanoparticles with tumor pH-responsive aggregation-enhanced retention and reduced cardiotoxicity","volume":"8","author":"Zhang","year":"2020","journal-title":"J. Mater. Chem. B"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.drup.2016.10.003","article-title":"New insights and evolving role of pegylated liposomal doxorubicin in cancer therapy","volume":"29","author":"Gabizon","year":"2016","journal-title":"Drug Resist. Updat."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yi, G.Y., Kim, M.J., Kim, H.I., Park, J., and Baek, S.H. (2022). Hyperthermia treatment as a promising anti-cancer strategy: Therapeutic targets, perspective mechanisms and synergistic combinations in experimental approaches. Antioxidants, 11.","DOI":"10.3390\/antiox11040625"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Orel, V.B., Papazoglou, A.S., Tsagkaris, C., Moysidis, D.V., Papadakos, S., Galkin, O.Y., Orel, V.E., and Syvak, L.A. (2023). Nanotherapy based on magneto-mechanochemical modulation of tumor redox state. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 15.","DOI":"10.1002\/wnan.1868"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8572","DOI":"10.1039\/C8CS00162F","article-title":"Liposomes and polymersomes: A comparative review towards cell mimicking","volume":"47","author":"Rideau","year":"2018","journal-title":"Chem. Soc. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Otagiri, M., and Chuang, V. (2016). Albumin in Medicine, Springer.","DOI":"10.1007\/978-981-10-2116-9"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lee, D. (2018). Radionanomedicine. Biological and Medical Physics, Biomedical Engineering, Springer.","DOI":"10.1007\/978-3-319-67720-0"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3178","DOI":"10.1016\/j.ejca.2014.10.004","article-title":"First-line anthracycline-based chemotherapy for angiosarcoma and other soft tissue sarcoma subtypes: Pooled analysis of eleven European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group trials","volume":"50","author":"Young","year":"2014","journal-title":"Eur. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Shi, P., Cheng, Z., Zhao, K., Chen, Y., Zhang, A., Gan, W., and Zhang, Y. (2023). Active targeting schemes for nano-drug delivery systems in osteosarcoma therapeutics. J. Nanobiotechnol., 21.","DOI":"10.1186\/s12951-023-01826-1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"805978","DOI":"10.3389\/fonc.2022.805978","article-title":"Recent advances in nanoplatforms for the treatment of osteosarcoma","volume":"12","author":"Wu","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"903","DOI":"10.2165\/00002018-200124120-00004","article-title":"A comparison of liposomal formulations of doxorubicin with drug administered in free form: Changing toxicity profiles","volume":"24","author":"Waterhouse","year":"2001","journal-title":"Drug Saf."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"419","DOI":"10.2165\/00003088-200342050-00002","article-title":"Pharmacokinetics of pegylated liposomal Doxorubicin: Review of animal and human studies","volume":"42","author":"Gabizon","year":"2003","journal-title":"Clin. Pharmacokinet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13569-018-0107-9","article-title":"A phase II study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcomas","volume":"8","author":"Trucco","year":"2018","journal-title":"Clin. Sarcoma Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zabielska-Koczyw\u0105s, K., and Lechowski, R. (2017). The use of liposomes and nanoparticles as drug delivery systems to improve cancer treatment in dogs and cats. Molecules, 22.","DOI":"10.3390\/molecules22122167"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1023\/A:1006429907449","article-title":"Phase II trial of liposomal doxorubicin (Doxil) in advanced soft tissue sarcomas","volume":"18","author":"Chidiac","year":"2000","journal-title":"Investig. New Drugs"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2100152","DOI":"10.1002\/adtp.202100152","article-title":"Nanodelivery systems face challenges and limitations in bone diseases management","volume":"4","author":"Giordano","year":"2021","journal-title":"Adv. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"230","DOI":"10.7150\/ntno.61280","article-title":"Mild hyperthermia accelerates doxorubicin clearance from tumour-extravasated temperature-sensitive liposomes","volume":"6","author":"Kostarelos","year":"2022","journal-title":"Nanotheranostics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1080\/02656730600582956","article-title":"Hyperthermia mediated liposomal drug delivery","volume":"22","author":"Ponce","year":"2006","journal-title":"Int. J. Hyperth."},{"key":"ref_27","first-page":"585","article-title":"Effect of thermosensitive liposomal doxorubicin with hyperthermia on primary tumor and lung metastases in hamster osteosarcoma","volume":"19","author":"Shimose","year":"2001","journal-title":"Int. J. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Vaupel, P., Piazena, H., Notter, M., Thomsen, A.R., Grosu, A.L., Scholkmann, F., Pockley, A.G., and Multhoff, G. (2023). From localized mild hyperthermia to improved tumor oxygenation: Physiological mechanisms critically involved in oncologic thermo-radio-immunotherapy. Cancers, 15.","DOI":"10.3390\/cancers15051394"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Rotundo, S., Brizi, D., Flori, A., Giovannetti, G., Menichetti, L., and Monorchio, A. (2022). Shaping and focusing magnetic field in the human body: State-of-the art and promising technologies. Sensors, 22.","DOI":"10.3390\/s22145132"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1080\/02656736.2021.1914354","article-title":"Non-thermal membrane effects of electromagnetic fields and therapeutic applications in oncology","volume":"38","author":"Wust","year":"2021","journal-title":"Int. J. Hyperth."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/bem.20372","article-title":"The effects of pulsed electromagnetic fields on the cellular activity of SaOS-2 cells","volume":"29","author":"Martino","year":"2008","journal-title":"Bioelectromagnetics"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Cmoch, A., Podszywalow-Bartnicka, P., Palczewska, M., Piwocka, K., Groves, P., and Pikula, S. (2014). Stimulators of mineralization limit the invasive phenotype of human osteosarcoma cells by a mechanism involving impaired invadopodia formation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0109938"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.envres.2018.01.038","article-title":"Role of radical pairs and feedback in weak radio frequency field effects on biological systems","volume":"163","author":"Barnes","year":"2018","journal-title":"Environ. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1533033818806003","DOI":"10.1177\/1533033818806003","article-title":"Efficacy of combined regional inductive moderate hyperthermia and chemotherapy in patients with multiple liver metastases from breast cancer","volume":"17","author":"Klimanov","year":"2018","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1533033820963599","DOI":"10.1177\/1533033820963599","article-title":"Efficacy of combination neoadjuvant chemotherapy and regional inductive moderate hyperthermia in the treatment of patients with locally advanced breast cancer","volume":"19","author":"Loboda","year":"2020","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"127","DOI":"10.3109\/02656730903335995","article-title":"Thermochemotherapy in patients with extremity high-risk soft tissue sarcomas (HR-STS)","volume":"26","author":"Schlemmer","year":"2010","journal-title":"Int. J. Hyperth."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1080\/10717540590932007","article-title":"Mechanochemically activated doxorubicin nanoparticles in combination with 40 MHz frequency irradiation on A-549 lung carcinoma cells","volume":"12","author":"Orel","year":"2005","journal-title":"Drug Deliv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"920","DOI":"10.3109\/02656736.2015.1094147","article-title":"Low-melting-point polymeric nanoshells for thermal-triggered drug release under hyperthermia condition","volume":"31","author":"Dabbagh","year":"2015","journal-title":"Int. J. Hyperth."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Bala, V.-M., Lampropoulou, D.I., Grammatikaki, S., Kouloulias, V., Lagopati, N., Aravantinos, G., and Gazouli, M. (2024). Nanoparticle-Mediated Hyperthermia and Cytotoxicity Mechanisms in Cancer. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010296"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jconrel.2013.03.011","article-title":"Mild hyperthermia triggered doxorubicin release from optimized stealth thermosensitive liposomes improves intratumoral drug delivery and efficacy","volume":"168","author":"Li","year":"2013","journal-title":"J. Control. Release"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1080\/03639045.2022.2102648","article-title":"In vitro and in vivo activity of thermosensitive liposomes loaded with doxorubicin and cisplatin","volume":"48","author":"Maswadeh","year":"2022","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.7150\/thno.14960","article-title":"Investigation of particle accumulation, chemosensitivity and thermosensitivity for effective solid tumor therapy using thermosensitive liposomes and hyperthermia","volume":"6","author":"Lokerse","year":"2016","journal-title":"Theranostics"},{"key":"ref_43","first-page":"365","article-title":"Efficacy of doxorubicin thermosensitive liposomes (40 degrees C) and local hyperthermia on rat rhabdomyosarcoma","volume":"20","author":"Morita","year":"2008","journal-title":"Oncol. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Liu, P., Xu, L.X., and Zhang, A. (September, January 30). Enhanced efficacy of anti-tumor liposomal doxorubicin by hyperthermia. Proceedings of the 2006 International Conference of the IEEE Engineering in Medicine and Biology Society, New York, NY, USA.","DOI":"10.1109\/IEMBS.2006.259729"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1016\/j.nano.2015.06.007","article-title":"In vitro experiments showing enhanced release of doxorubicin from Doxil\u00ae in the presence of ammonia may explain drug release at tumor site","volume":"11","author":"Silverman","year":"2015","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2891","DOI":"10.1007\/s11095-017-2272-6","article-title":"Helder EphA2 targeted doxorubicin-nanoliposomes for osteosarcoma treatment","volume":"34","author":"Haghiralsadat","year":"2017","journal-title":"Pharm. Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kullenberg, F., Degerstedt, O., Calitz, C., Pavlovi\u0107, N., Balgoma, N., Gr\u00e5sj\u00f6, K., Sj\u00f6gren, E., Hedeland, M., Heindryckx, F., and Lennern\u00e4s, H. (2021). In vitro cell toxicity and intracellular uptake of doxorubicin exposed as a solution or liposomes: Implications for treatment of hepatocellular carcinoma. Cells, 10.","DOI":"10.3390\/cells10071717"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Smith, L.A., Cornelius, V.R., Plummer, C.J., Levitt, G., Verrill, M., Canney, P., and Jones, A. (2010). Cardiotoxicity of anthracycline agents for the treatment of cancer: Systematic review and meta-analysis of randomised controlled trials. BMC Cancer, 10.","DOI":"10.1186\/1471-2407-10-337"},{"key":"ref_49","first-page":"970","article-title":"Liposomal doxorubicin attenuates cardiotoxicity via induction of interferon-related DNA damage resistance","volume":"116","author":"Lukovic","year":"2020","journal-title":"Cardiovasc. Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Chen, L., Lan, J., Li, Z., Zeng, R., Wang, Y., Zhen, L., Jin, H., Ding, Y., and Zhang, T. (2022). A novel diosgenin-based liposome delivery system combined with doxorubicin for liver cancer therapy. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14081685"},{"key":"ref_51","first-page":"3656","article-title":"Effect of adriamycin and analogs on the nuclear fluorescence of propidium iodide-stained cells","volume":"38","author":"Krishan","year":"1978","journal-title":"Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.3892\/ol.2014.1935","article-title":"Molecular mechanisms of chemoresistance in osteosarcoma (Review)","volume":"7","author":"He","year":"2014","journal-title":"Oncol. Lett."},{"key":"ref_53","first-page":"3743","article-title":"Characterization of osteosarcoma cell lines MG-63, Saos-2 and U-2 OS in comparison to human osteoblasts","volume":"24","author":"Pautke","year":"2004","journal-title":"Anticancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"707","DOI":"10.4161\/cbt.28557","article-title":"Pegylated liposomal doxorubicin in the management of ovarian cancer: A systematic review and metaanalysis of randomized trials","volume":"15","author":"Staropoli","year":"2014","journal-title":"Cancer Biol. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ho, M.-W., Popp, F.-A., and Warnke, U. (1994). Bioelectrodynamics and Biocommunication, World Scientific.","DOI":"10.1142\/2267"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Shi, J., Ma, Y., Zhu, J., Chen, Y., Sun, Y., Yao, Y., Yang, Z., and Xie, J. (2018). A review on electroporation-based intracellular delivery. Molecules, 23.","DOI":"10.3390\/molecules23113044"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Lai, H., and Levitt, B.B. (2023). Cellular and molecular effects of non-ionizing electromagnetic fields. Rev. Environ. Health.","DOI":"10.1515\/reveh-2023-0023"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/0360-3016(94)90572-X","article-title":"Hyperthermia induces doxorubicin release from long-circulating liposomes and enhances their anti-tumor efficacy","volume":"29","author":"Ning","year":"1994","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3109\/02656736.2015.1091093","article-title":"The future of biology in driving the field of hyperthermia","volume":"32","author":"Dewhirst","year":"2016","journal-title":"Int. J. Hyperth."},{"key":"ref_60","first-page":"842","article-title":"Annexin V imaging of acute doxorubicin cardiotoxicity (apoptosis) in rats","volume":"45","author":"Bennink","year":"2004","journal-title":"J. Nucl. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/s41420-023-01483-1","article-title":"The dual role of ferroptosis in anthracycline-based chemotherapy includes reducing resistance and increasing toxicity","volume":"9","author":"Zhao","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1080\/15368378.2021.1958342","article-title":"Effects induced by a 50 Hz electromagnetic field and doxorubicin on Walker-256 carcinosarcoma growth and hepatic redox state in rats","volume":"40","author":"Orel","year":"2021","journal-title":"Electromagn. Biol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/1756-9966-30-87","article-title":"Apoptosis in cancer: From pathogenesis to treatment","volume":"30","author":"Wong","year":"2011","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0925-4439(02)00094-7","article-title":"Preferential targeting of apoptosis in tumor versus normal cells","volume":"1587","author":"Woynarowska","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1179064417730559","DOI":"10.1177\/1179064417730559","article-title":"Upregulated heat shock proteins after hyperthermic chemotherapy point to induced cell survival mechanisms in affected tumor cells from peritoneal carcinomatosis","volume":"10","author":"Grimmig","year":"2017","journal-title":"Cancer Growth Metastasis"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/febs.14186","article-title":"Bax, Bak and beyond\u2014Mitochondrial performance in apoptosis","volume":"285","year":"2018","journal-title":"FEBS J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mito.2008.10.003","article-title":"Putative partners in Bax mediated cytochrome-c release: ANT, CypD, VDAC or none of them?","volume":"9","author":"Kumarswamy","year":"2009","journal-title":"Mitochondrion"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6753","DOI":"10.1074\/jbc.M310145200","article-title":"Reactive oxygen species are required for hyperoxia-induced Bax activation and cell death in alveolar epithelial cells","volume":"279","author":"Buccellato","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0079-6107(02)00008-1","article-title":"Mechanical stress-induced apoptosis in the cardiovascular system","volume":"78","author":"Wernig","year":"2002","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.1529\/biophysj.108.135483","article-title":"Monte Carlo simulation of cell death signaling predicts large cell-to-cell stochastic fluctuations through the type 2 pathway of apoptosis","volume":"95","author":"Raychaudhuri","year":"2008","journal-title":"Biophys. J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1007\/s10495-010-0515-7","article-title":"Bcl-2 inhibits apoptosis by increasing the time-to-death and intrinsic cell-to-cell variations in the mitochondrial pathway of cell death","volume":"15","author":"Skommer","year":"2010","journal-title":"Apoptosis"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"9584","DOI":"10.1039\/C7CP00401J","article-title":"The role of conformational heterogeneity in regulating the apoptotic activity of BAX protein","volume":"19","author":"Kao","year":"2017","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.trecan.2020.12.006","article-title":"Illuminating non-genetic cellular heterogeneity with imaging-based spatial proteomics","volume":"7","author":"Gnann","year":"2021","journal-title":"Trends Cancer."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1016\/j.str.2017.06.009","article-title":"Conformational heterogeneity in the activation mechanism of Bax","volume":"25","author":"Barnes","year":"2017","journal-title":"Structure"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Ibraheem, A., and Manteghi, M. (2014, January 6\u201311). Performance of electrically coupled loop antenna inside human body at different frequency bands. Proceedings of the 2014 IEEE Antennas and Propagation Society International Symposium (APSURSI), Memphis, TN, USA.","DOI":"10.1109\/APS.2014.6904815"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1080\/15368378.2022.2073547","article-title":"Magnetic fields and apoptosis: A possible mechanism","volume":"41","author":"Tofani","year":"2022","journal-title":"Electromagn. Biol. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1016\/j.bbamcr.2016.09.012","article-title":"Activation of apoptosis signalling pathways by reactive oxygen species","volume":"1863","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s40744-016-0050-2","article-title":"Osteosarcoma overview","volume":"4","author":"Lindsey","year":"2017","journal-title":"Rheumatol. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/jbmr.5650020310","article-title":"Characterization of a human osteoblastic osteosarcoma cell line (SAOS-2) with high bone alkaline phosphatase activity","volume":"2","author":"Murray","year":"1987","journal-title":"J. Bone Miner. Res."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Dvorakova, J., Wiesnerova, L., Chocholata, P., Kulda, V., Landsmann, L., Cedikova, M., Kripnerova, M., Eberlova, L., and Babuska, V. (2023). Human cells with osteogenic potential in bone tissue research. Biomed. Eng. Online, 22.","DOI":"10.1186\/s12938-023-01096-w"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s12943-019-0992-4","article-title":"Tumor microenvironment-driven non-cell-autonomous resistance to antineoplastic treatment","volume":"18","author":"Qu","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_82","unstructured":"Capes-Davis, A., and Freshney, R.I. (2021). Freshney\u2019s Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications, Wiley-Blackwell. [8th ed.]."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3954","DOI":"10.1021\/acsabm.9b00526","article-title":"Nonlinear Magnetochemical effects in nanotherapy of Walker-256 carcinosarcoma","volume":"2","author":"Orel","year":"2019","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.cplett.2006.11.003","article-title":"Computer simulation of magnetic properties of human blood","volume":"432","author":"Cano","year":"2006","journal-title":"Chem. Phys. Lett."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"4115","DOI":"10.2298\/TSCI200109151P","article-title":"Thermodynamic properties of human tissues","volume":"24","author":"Popovic","year":"2020","journal-title":"Therm. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Zhbanov, A., and Yang, S. (2015). Effects of aggregation on blood sedimentation and conductivity. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129337"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Bronzino, J.D. (2006). Biomedical Engineering Fundamental, CRC Press. [3rd ed.].","DOI":"10.1201\/9781420003857"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1016\/j.stemcr.2023.05.004","article-title":"Nutritional requirements of human induced pluripotent stem cells","volume":"18","author":"Copley","year":"2023","journal-title":"Stem Cell Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/nprot.2006.179","article-title":"Sulforhodamine B colorimetric assay for cytotoxicity screening","volume":"1","author":"Vichai","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"A.3B.1","DOI":"10.1002\/0471142735.ima03bs21","article-title":"Trypan blue exclusion test of cell viability","volume":"21","author":"Strober","year":"1997","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"164","DOI":"10.3390\/cimb45010013","article-title":"Flow cytometry detection of anthracycline-treated breast cancer cells: An optimized protocol","volume":"45","author":"Catitti","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1038\/nprot.2009.143","article-title":"Expression, purification and use of recombinant annexin V for the detection of apoptotic cells","volume":"4","author":"Logue","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/978-1-60761-411-1_4","article-title":"Identification of ROS Using Oxidized DCFDA and Flow-Cytometry","volume":"594","author":"Eruslanov","year":"2010","journal-title":"Methods Mol. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1515\/ntrev-2016-0070","article-title":"Application of cryo-electron microscopy for investigation of Bax-induced pores in apoptosis","volume":"6","author":"Kuwana","year":"2017","journal-title":"Nanotechnol. Rev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/sj.cdd.4402025","article-title":"Elucidation of some Bax conformational changes through crystallization of an antibody-peptide complex","volume":"14","author":"Peyerl","year":"2007","journal-title":"Cell Death Differ."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1136\/jcp.48.9.876","article-title":"A \u201cquickscore\u201d method for immunohistochemical semiquantitation: Validation for oestrogen receptor in breast carcinomas","volume":"48","author":"Detre","year":"1995","journal-title":"Clin. Pathol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"13085","DOI":"10.1073\/pnas.202139299","article-title":"Metapopulation dynamics and spatial heterogeneity in cancer","volume":"99","author":"Costa","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1097\/RCT.0000000000001218","article-title":"Texture analysis of tumor and peritumoral tissues based on 18F-Fluorodeoxyglucose positron emission tomography\/computed tomography hybrid imaging in patients with rectal cancer","volume":"45","author":"Orel","year":"2021","journal-title":"J. Comput. Assist. Tomogr."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/j.2042-7158.2012.01567.x","article-title":"Doxorubicin: An update on anticancer molecular action, toxicity and novel drug delivery systems","volume":"65","author":"Tacar","year":"2013","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"643692","DOI":"10.3389\/fimmu.2021.643692","article-title":"Single-cell profiling to explore immunological heterogeneity of tumor microenvironment in breast cancer","volume":"12","author":"Yuan","year":"2021","journal-title":"Front. Immunol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/1\/133\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:45:50Z","timestamp":1760103950000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/1\/133"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,19]]},"references-count":100,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["ph17010133"],"URL":"https:\/\/doi.org\/10.3390\/ph17010133","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,19]]}}}