| Objective: Based on previous research results, in this study we hypothesized that the enhanced antitumor immunity induced by high intensity focused ultrasound (HIFU) in the treatment of malignancies would correlate with the reduced secretion of tumor-origin immunosuppressive factors, which can directly inhibit host immune function against tumor. The purpose of this study was to investigate the mechanism of the reversal of tumor-induced immunosuppression after HIFU. For assessing the effects of HIFU on immunosuppressive factors in patients with malignancies, vascular endothelial growth factor(VEGF), transforming growth factor-β1(TGF-β1), transforming growth factor-β2(TGF-β2), interleukin 6(IL-6), and interleukin 10 (IL-10) were examined in primary tumor, in metastasis-positive axillary lymph nodes, and in peripheral blood samples before and after HIFU treatment.Materials and Methods: (1) A total of 48 women with biopsy-provenbreast cancer were divided into HIFU group (n=23) and control group (n=25). All patients were treated by modified radical mastectomy, while the patients in HIFU group received HIFU treatment 1～2 weeks before surgery. After the operation, the specimens of tumor lesions and axillary lymph nodes were collected in both groups. SP immunohistochemical stain was used to detect the tumor expression of VEGF,TGF-β1,TGF-β2,IL-6, and IL-10 in primary tumor and in metastasis-positive axillary lymph nodes (HIFU, n=11; Control, n=12), respectively. The positive rate was qualitatively assessed in both groups, and the number of immunostained positive tumor cells was counted in a microscopic grid. Statistical significance of the data obtained was analyzed by the Fisher exact test and the Student t test. (2) Using sandwich ELISA technique, serum level of VEGF,TGF-β1,TGF-β2,IL-6, and IL-10 was measured in 15 patients with malignancies before and one week after HIFU treatment. Statistical difference was analyzed by using the Student t test.Results: (1) The positive rate of tumor-origin VEGF, TGF-β1, TGF-β2, IL-6, and IL -10 in primary tumor was 72%, 72%, 80%, 68%, and 84% in control group, respectively; while in HIFU group the positive rate was 30.4%, 56.5%, 69.6%, 47.8%, and 60.9%, respectively. The simultaneous positivity of the five immunosuppressive factors was 48% in control group, and 27.3% in HIFU group. The positivities of theseimmunosuppressive factors were lower in HIFU group than those in control group, and there were significant differences of VEGF, IL-6, and IL-10 between two groups (P<0.05). (2) The number of positive tumor cells of VEGF, TGF-β1, TGF-β2, IL-6, and IL-10 in primary tumor was 344.5±90.6/mm2, 355.7±111.4/mm2, 391.5±87.3/mm2, 399.1±95.8/mm2, and 327.2±140.8/mm2 in control group, respectively; while in HIFU group the number was 235.9±93.8/mm2, 243.7±69.2/mm2, 209.8±77.1/mm2, 303.1±99.4/mm2, and 238.1±79.8/mm2, respectively. The expressions of these immunosuppressive factors were significantly lower in HIFU group than those in control group (P<0.05). (3) The positive rate of tumor-origin VEGF, TGF-β1, TGF-β2, IL-6, and IL-10 in metastasis-positive axillary lymph nodes was lower in HIFU group than those in control group, and there was a significant difference of TGF-β2 between two groups (P<0.05). (4) The number of positive tumor cells of VEGF, TGF-β1, TGF-β2, IL-6, and IL-10 in metastasis-positive axillary lymph nodes was 410.6±36.9/mm2, 324.0±43.6/mm2, 366.4±130.2/mm2, 300.5±60.2/mm2, and 328.7±60.0/mm2 in control group, respectively; while in HIFU group, the number was 315.3±51.4/mm2, 243.1±52.0/mm2, 249.1±102.7/mm2, 217.9±57.7/mm2, and 212.0±49.5/mm2, respectively. The expressions of these immunosuppressive factors were lower in HIFU group than those incontrol group, and there were significant differences of VEGF, TGF-β1, IL-6, and IL-10 between two groups (P<0.05). (5) Fifteen patients with malignant tumors received one-session HIFU treatment. Before HIFU the serum level of VEGF, TGF-β1, TGF-?... |
PDF Full Text Request