RADIATION & RISK
Bulletin of the National Radiation and Epidemiological Registry
since 1992
About the Journal : 2018 : vol. 27, No. 4 : Reactions of normal and tumor cells and tissues to hyperthermia in combination with ionizing radiation. Review

Reactions of normal and tumor cells and tissues to hyperthermia in combination with ionizing radiation. Review

«Radiation and Risk», 2018, vol. 27, No. 4, pp.141-154

DOI: 10.21870/0131-3878-2018-27-4-141-154

Authors

Kabakov A.E. – Head of Lab., C. Sc., Biol.
Lebedeva T.V. – Lead. Researcher, C. Sc., Biol.
Anokhin Yu.N. – Head of Dep., C. Sc., Med. Contacts: 1, Studgorodok, Obninsk, Kaluga region, Russia, 249036. Tel.: +7-910-542-97-30; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .

1A. Tsyb MRRC, Obninsk
2Obninsk Institute for Nuclear Power Engineering, Obninsk

Abstract

The review presents an analysis of literature data on the modifying effect of hyperthermia (HT) on the radiation response of normal and tumor cells and tissues, as well as on the use of HT to increase the radiosensitivity of tumors. The analyzed data indicate that the radiosensitizing effects of HT are manifested in the additive or synergistic enhancement of cytotoxicity in irradiated bioobjects. The degree of such enhancement depends on the level of heating, radiation dose, the sequence of the exposures and the interval between them, types of tissue, etc. The radiosensitizing effects of HT are manifested not only on tumors, but also on normal cells and tissues too. This circumstance requires determination of the therapeutic gain factor in different cases of application of the thermotherapy of tumors. Heatshock proteins (HSPs), which are one of the factors of tumor resistance to thermo, chemo and radiotherapy, are actively involved in cellular reactions to HT and radiation exposure. It is shown that the functioning of HSP90 is necessary for the postradiation repair of nuclear DNA breaks. In addition, HSP90, HSP70 and HSP27 are powerful suppressors of apoptosis and help the stressed cell to reactivate or degrade stressdenatured proteins. In the case of a combination of HT and radiation, these HSPs form complexes with denatured intracellular proteins and can no longer act as radioprotectors and blockers of apoptosis. Thus, recruitment of HSPs to protect against the proteotoxic effects of HT occurs to the detriment of HSPmediated radioresistance of cancer cells and, consequently, contributes to their radiosensitization. However, the induction and transient increase in the levels of HSP90, HSP70 and HSP27 in cells that have survived HT can make them for some period thermotolerant and more radioresistant that should be taken into consideration in the case of consequtive combining HT and radiation therapy.

Key words
Ionizing radiation, heat shock proteins, radiosensitivity, hyperthermia, extra- and intracellular рО2 and pH, blood flow, thermal sensitivity, therapeutic gain, therapy of tumors, thermotolerance.

References

1. Yarmonenko S.P., Vaynson A.A. Radiobiology of humans and animals. Moscow, Izd. Vysshaya shkola, 2004, 549 p. (In Russian).

2. Kurpeshev O.K. Patterns of radiosensitizing and damaging effects of hyperthermia on normal and tumor tissues. Dr. med. sci. ref. dis. Obninsk, 1989. 37 p. (In Russian).

3. Kurpeshev O.K., Tsyb A.F., Mardynsky Yu.S., Berdov B.A. Chemoresistance of tumors: mechanisms of development and ways to overcome. Part 3. How to overcome chemoresistance of tumors. Rossijskij onkologicheskij zhurnal – Russian Journal of Oncology, 2003, no. 2, pp. 50-52. (In Russian).

4. Datta N.R., Ordonez S.G., Gaipl U.S., Paulides M.M., Crezee H., Gellermann J., Marder D., Puric E., Bodis S. Local hyperthermia combined with radiotherapy and-/or chemotherapy: recent advances and promises for the future. Cancer Treat. Rev., 2015, vol. 41, no. 9, pp. 742-753. DOI: 10.1016/J.CTRV.2015.05.009.

5. Kurpeshev О.К., Mardynsky Yu.S., Maksimov S.A., Medvedev V.S. Combined treatment of patients with oral cancer by “conditional and dynamical” regime of fractional radiotherapy and loco-regional hyperthermia. Sibirskoe meditsinskoe obozrenie – Siberian Medical Review, 2011, vol. 67, no. 1, pp. 80-84. (In Russian).

6. Berdov B.A, Kurpeshev O.K, Mardynsky Yu.S. The effect of hyperthermia and hyperglycemia on the efficacy of radiation therapy for cancer patients. Rossijskij onkologicheskij zhurnal – Russian Journal of Oncology, 1996, no. 1, pp. 12-16. (In Russian).

7. Kurpeshev O.K., Mardynskiy Yu.S. Radiomodifiers in Radiotherapy of Tumors. Terapevticheskaya radiologiya – Therapeutic Radiology. Eds.: A.F. Tsyb, Yu.S. Mardynsky. Moscow, 2010, pp. 13-43. (In Russian).

8. Van der Zee J., Vujaskovic Z., Kondo M., Sugahara T. Clinical hyperthermia. Part I. The Kadota Fund International Forum 2004 – Clinical group consensus. Int. J. Hyperthermia, 2008, vol. 24, no. 2, pp. 111-122.

9. Pankratov V.A., Andreev V.G., Rozhnov V.A. Gulidov I.A., Barishev V.V., Buyakova M.E., Vdovina S.N., Kurpeshev O.K., Podlesnikh N.I. Concurrent chemo- and radiation therapy in conservative alone and combined treatment of patients with locally advanced laryngeal and laryngopharyngeal cancers. Sibirskij onkologicheskij zhurnal ‒The Siberian Journal of Oncology, 2007, vol. 21, no. 1, pp. 18-22. (In Russian).

10. Kurpeshev O.K., Ragulin Yu.A., Mozerov S.A., Orlova A.V., Lebedeva T.V. Possibilities of local hyperthermia in treatment for edematous breast cancer patients. Voprosy onkologii – Problems in Oncology, 2016, vol. 62, no. 5, pp. 680-687. (In Russian).

11. Barlev N.A. Hot and toxic: hyperthermia and anti-mitotic drugs in cancer therapy. Cell Cycle, 2013, vol. 12, no. 16, p. 2533.

12. Mehtala J.G., Torregrosa-Allen S., Elzey B.D., Jeon M., Kim Ch., Wei A. Synergistic effects of cisplatin chemotherapy and gold nanorod-mediated hyperthermia on ovarian cancer cells and tumors. Nanomedicine (London), 2014, vol. 9, no. 13, pp. 1939-1955. doi:10.2217/nnm.13.209.

13. Oei A.L., Vriend L.E.M., Crezee J., Franken N.A.P. Effects of hyperthermia on DNA repair pathways: one treatment to inhibit them all. Radiat. Oncol., 2015, vol. 10, pp. 165-178. DOI: 10.1186/s13014-015-0462-0. 14. Zhu S., Wang J., Xie B., Luo Zh., Lin X., Liaoe D.J. Culture at a higher temperature mildly inhibits cancer cell growth but enhances chemotherapeutic effects by inhibiting cell-cell collaboration. PLoS ONE, 2015, vol. 10, no. 10, e0137042. DOI: 10.1371/journal.

15. Pandita T.K., Pandita S., Bhaumik S.R. Molecular parameters of hyperthermia for radiosensitization. Crit. Rev. Eukaryot. Gene Expr., 2009, vol. 19, no. 3, pp. 235-251.

16. Hyperthermic oncology from bench to bedside. Eds.: S. Kokura, T. Yoshikawa, T. Ohnishi. Springer, 2016, 444 p.

17. Mladenov E., Magin S., Soni A., Iliakis G. DNA double-strand break repair as determinant of cellular radiosensitivity to killing and target in radiation therapy. Front. Oncol., 2013, no. 3, p. 113. DOI: 10.3389/fonc.2013.00113.

18. Harnicek D., Kampmann E., Lauber K., Hennel R., Cardoso Martins A.S., Guo Y., Belka C., Mortl S., Gallmeier E., Kanaar R., Mansmann U., Hucl T., Lindner L.H., Hiddemann W., Issels R.D. Hyperthermia adds to trabectedin effectiveness and thermal enhancement is associated with BRCA2 degradation and impairment of DNA homologous recombination repair. Cancer, 2016, vol. 139, no. 2, pp. 467-479.

19. Van den Tempel N., Laffeber C., Odijk H., van Cappelen W.A., van Rhoon G.C., Franckena M., Kanaar R. The effect of thermal dose on hyperthermia-mediated inhibition of DNA repair through homologous recombination. Oncotarget, 2017, vol. 8, no. 27, pp. 44593-44604. DOI: 10.18632/oncotarget.17861.

20. Schmitt C.A. Cellular senescence and cancer treatment. Biochim. Biophys. Acta (BBA) – Reviews on Cancer, 2007, vol. 1775, pp. 5-20.

21. Song C.W., Griffin R., Shakil A. Tumor pO2 increased by mild temperature hyperthermia. Hyperthermic Oncology (Roma), 1996, vol. II, pp. 783-785.

22. Herman T.S., Teicher B.A., Holden S.A., Collins L.S. Interaction of hyperthermia and radiation in murine cells: hypoxia and acidosis in vitro, tumor subpopulations in vivo. Cancer Res., 1989, vol. 49, pp. 3338-3343.

23. Robinson J.E., Wisenberg M.J., McCready W.A. Radiation and hyperthermal response of normal tissue in situ. Radiology, 1974, vol. 113, no. 1, pp. 195-198.

24. Stewart F.A., Denekamp J. The therapeutic advantage of combined heat and X-rays on a mouse fibrocarcinoma. Brit. J. Radiol., 1978, vol. 51, no. 604, pp. 307-316.

25. Dewey W.C. The search for critical targets damaged by heat. Radiat. Res., 1989, vol. 20, pp. 191-204.

26. Crile G.J. Heat as an adjunct to the treatment of cancer. Clevland Clin., 1961, no. 28, pp. 75-89.

27. Overgaard K., Overgaard J. Radiation sensitizing effect of heat. Acta Radiol., 1974, vol. 13, no. 6, pp. 501-511.

28. Hume S.P., Field S.B. Hyperthermic sensitization of mouse intestine to damage by X-rays: the effect of sequence and temporal separation of the two treatments. Brit. J. Radiol., 1978, vol. 51, no. 604, pp. 302-307.

29. Myers R., Field R.B. The response of the rat tail on to combined heat and X-rays. Br. J. Radiol., 1977, vol. 52, pp. 581-586.

30. Hill S.A., Denekamp J. The Respons of Six mouse Tumours to Combined Heat and X-rays; Implications for Therapy. Brit. J. Radiol., 1979, vol. 52, pp. 209-218.

31. Overgaard J. Simultaneous and sequential hyperthermia and radiation treatment of an experimental tumor and its surrounding normal tissue in vivo. Int. J. Radiation Oncol. Biol. Phys., 1981, vol. 6, no. 11, pp. 1507-1517.

32. Overgaard J. Fractionated radiation and hyperthermia: experimental and clinical studies. Cancer, 1981, vol. 48, no. 5, pp. 1116-1123.

33. Jansen W., Scuren E., Breur K. Thermal enhancement of the radiation response of the skin and mammary carcinoma in mice. Cancer Therapy by Hyperthermia and Radiation. Eds: Streffer C. et al. Baltimore-Munich, 1978, pp. 255-256.

34. Stewart F.A., Denekamp J. Loss of therapeutic advantage for combined heat and X-rays with fractionation. Nat. Cancer Inst. Monorgr. Washington, 1982, no. 61, pp. 291-293.

35. Kabakov A.E., Kudryavtsev V.A. Heat shock proteins as molecular targets for anticancer therapy: approaches, agents, and trends. Heat shock proteins. Classifications, functions, and applications. Ed.: S. Usmani. New York, Nova Science Publishers, 2013, pp. 25-56.

36. Kudryavtsev V.A., Khokhlova A.V., Mosina V.A., Selivanova E.I., Kabakov A.E. Induction of Hsp70 in tumor cells treated with inhibitors of the Hsp90 activity: a predictive marker and promising target for radiosensitization. PLoS ONE, 2017, vol. 12, no. 3, e0173640. DOI: 10.1371/journal.pone.0173640.

37. Kennedy D., Jager R., Mosser D.D., Samali A. Regulation of apoptosis by heat shock proteins. IUBMB Life, 2014, vol. 66, no. 5, pp. 327-338.

38. Vabulas R.M., Raychaudhuri S., Hayer-Hartl M., Hartl F.U. Protein folding in the cytoplasm and the heat shock response. Cold Spring Harb. Perspect. Biol., 2010, no. 2, a004390.

39. Kabakov A.E., Malyutina Y.V., Latchman D.S. Hsf1-mediated stress response can transiently enhance cellular radioresistance. Radiat. Res., 2006, vol. 165, pp. 410-423.

40. Griffin R.J., Dings P.M., Jamshidi-Parsian A., Song C.W. Mild temperature hyperthermia and radiation therapy: role of tumour vascular thermotolerance and relevant physiological factors. Int. J. Hyperthermia, 2010, vol. 26, no. 3, pp. 256-263. 41. Liu T., Ye Y.-W., Zhu A.-L., Yang T.Zh., Fu Y., Wei Ch.-Q., Liu Q., Zhao Ch.-Lin., Wang G.-J., Zhang X.-Fu. Hyperthermia combined with 5-fluorouracil promoted apoptosis and enhanced thermotolerance in human gastric cancer cell line SGC-7901. Onco Targets Ther., 2015, vol. 8, pp. 1265-1270. DOI: 10.2147/OTT.S78514.

42. Bettaieb A., Averill-Bates D.A. Thermotolerance induced at a mild temperature of 40°C alleviates heat shock-induced ER stress and apoptosis in HeLa cells. Biochim. Biophys. Acta, 2015, vol. 1853, no. 1, pp. 52–62. DOI: 10.1016/j.bbamcr.2014.09.016.

43. Kolesnikova A.I., Kalsina S.Sh., Lepekhina L.A. Thermosensitivity of clonogenic cells and induction of thermotolerance in them. Meditsinskaya radiologiya – Medical Radiology, 1987, vol. 32, no. 1, pp. 67-69. (In Russian).

44. Bresler S.Ye., Beketova A.G., Noskin L.A., Rosenberg O.A., Stepanova I.M., Suslov A.V. Thermoinduced radioresistance of cells. Radiobiologiya – Radiobiology, 1984, no. 5, pp. 579-583. (In Russian).

45. Miyakoshi R.E.J., Heki S., Kano E. Cellular responses to hyperthermia and radiation in Chinese hamster cells. Modification of Radiosensitivity in Cancer Treatment. Ed:. T. Sugahara. Tokyo-New York-London-Monreal, Academic Press, 1984, pp. 335-350.

46. Hettinga J.V.E., Lemstra W., Konings A.W.T., Kampinga H.H. Cisplatin sensitivity and thermochemosensitisation in thermotolerant cDDP-sensitive and -resistant cell lines. Br. J. Cancer, 1995, vol. 71, pp. 498-504.

47. Kregel K.C. Invited review: heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance. J. Appl. Physiol., 2002, vol. 92, pp. 2177-2186.

48. Li G.C., Mivechi N.F., Weitzel G. Heat shock proteins, thermotolerance, and their relevance to clinical hyperthermia. Int. J. Hyperthermia, 1995, vol. 11, no. 4, pp. 459-488.

49. Eng J.W.-L., Reed C.B., Kokolus K.M., Repasky E.A. Housing temperature influences the pattern of heat shock protein induction in mice following mild whole body hyperthermia. Int. J. Hyperthermia, 2014, vol. 30, no. 8, pp. 540-546. DOI: 10.3109/02656736.2014.981300.

50. Kudryavtsev V.A., Makarova Y.M., Kabakov A.E. Thermosensitization of tumor cells with inhibitors of chaperone activity and expression. Biomeditsinskaya khimiya – Biomedical Chemistry (Moscow), 2012, vol. 58, no. 6, pp. 662-672. (In Russian).

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