Abscopal antitumor immune effects of magnet-mediated hyperthermia at a high therapeutic temperature on Walker-256 carcinosarcomas in rats - PubMed (original) (raw)

doi: 10.3892/ol.2014.1803. Epub 2014 Jan 15.

Li Zhang 2, Yingrui Shi 3, Sara Javidiparsijani 4, Guirong Wang 4, Xiao Li 5, Weiwei Ouyang 6, Jumei Zhou 3, Lingyun Zhao 5, Xiaowen Wang 5, Xiaodong Zhang 5, Fuping Gao 5, Jingshi Liu 7, Junming Luo 8, Jintian Tang 5

Affiliations

Abscopal antitumor immune effects of magnet-mediated hyperthermia at a high therapeutic temperature on Walker-256 carcinosarcomas in rats

Hui Wang et al. Oncol Lett. 2014 Mar.

Abstract

The abscopal effect has previously been described in various tumors and is associated with radiation therapy and hyperthermia, with possible underlying mechanisms explaining each observed case. In the present study, we aimed to investigate the antitumor effects of magnet-mediated hyperthermia on Walker-256 carcinosarcomas in rats at two different temperature ranges (42-46°C and 50-55°C). We also aimed to identify whether a higher therapeutic temperature of magnetic-mediated hyperthermia improves the abscopal antitumor effects, where localised irradiation of the tumor causes not only the irradiated tumor to shrink, but also tumors located far from the area of irradiation. Following induction of carcinosarcoma in both sides of the body, magnet-mediated hyperthermia was applied to one side only, leaving the other side as a control. The changes in tumor growth were observed. Our results demonstrated that magnet-mediated hyperthermia at a higher temperature inhibited the growth of carcinosarcoma at the site of treatment. Furthermore, the growth of the carcinosarcoma on the untreated side was also inhibited. The expression levels of proliferating cell nuclear antigen were decreased in the hyperthermia group, which was more significant in the higher temperature test group. Flow cytometric analysis showed an increased number of CD4- and CD8-positive T cells, and enzyme-linked immunosorbent assay showed increased levels of interferon-γ and interleukin-2 in the higher temperature group. These results suggested that magnet-mediated hyperthermia at a higher temperature (50-55°C) can improve the abscopal antitumor effects and stimulate a greater endogenous immune response in carcinosarcoma-bearing rats.

Keywords: Walker-256 carcinosarcoma; abscopal effect; magnet-mediated hyperthermia; temperature; tumor immunity.

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Figures

Figure 1

Figure 1

The electric current of the alternating magnetic fields was controlled and the temperature of the thermoseeds was maintained within the ranges of (A) 42–46°C (H1 group) and (B) 50–55°C (H2 group). In these two hyperthermia-treated groups, the rectal temperature was maintained at 35–37°C. Following the thermal treatment, tumor growth in the H1 and H2 groups of rats was inhibited, particulary in the H2 group, and was observed on both sides of the rats. Tumor diameter was measured every 2 days to determine the growth curves of tumors on both the (C) heated side and (D) unheated side. Group C, untreated control; group M, magnetic field control; group T, thermoseed control; group H1, thermoseeds heated to 42–46°C for 30 min; group H2, thermoseeds heated to 50–55°C for 10 min.

Figure 2

Figure 2

Pathological observation and immunohistochemistry in the control group (C), and hyperthermia groups 1 (H1) and 2 (H2). In the control group, both sides of the tumor tissue contained typical tumor cells (A1, B1, both unheated); in the H1 group, the tumor cells exposed to heat exhibited large areas of necrosis and karyorrhexis (C1, heated side; D1, unheated side); in the H2 group, tumor cells showed a large area of necrosis. The unheated side showed more necrosis than the heated side (E1, heated side; F1, unheated side). Compared with groups C, M and T, the PCNA index was significantly decreased in the H1 group (C2, heated side; D2, unheated side) and the H2 group (E2, heated side; F2, unheated side) (P<0.05). Compared with the H1 group, the PCNA index in the H2 group was significantly decreased (P<0.01), but there was no significant difference in the PCNA indexes between groups C, M and T (P>0.05). PCNA, proliferating cell nuclear antigen.

Figure 3

Figure 3

Immunohistochemistry analysis indicated that (A) PCNA expression was decreased significantly in the hyperthermia groups, H1 and H2, compared with that of the control. Compared with groups C, M and T, the PCNA index was significantly decreased (P<0.05). Compared with the H1 group, the PCNA index in the H2 group was significantly decreased (P<0.05). (B) The levels of cytokines in the five groups. IFN-γ and IL-2 were significantly higher in the H1 and H2 groups compared with the three control groups (P<0.05); and there was also a significant difference between the H1 and H2 group (P<0.01). Levels of cytokines, IFN- γ and IL-2, were markedly increased in the H2 group. PCNA, proliferating cell nuclear antigen; IFN-γ, interferon-γ; IL-2, interleukin-2; group C, untreated control; group M, magnetic field control; group T, thermoseed control; group H1, thermoseeds heated to 42–46°C for 30 min; group H2, thermoseeds heated to 50–55°C for 10 min.

Figure 4

Figure 4

Compared with group C, the survival time of the rats in groups H1 and H2 was significantly prolonged (P<0.05), and there was a significant difference in the survival time between groups H1 and H2 (P<0.05). Group C, untreated control; group M, magnetic field control; group T, thermoseed control; group H1, thermoseeds heated to 42–46°C for 30 min; group H2, thermoseeds heated to 50–55°C for 10 min.

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