Effects Of High Intensity Focused Ultrasound On Tumor Vascular Growth Factor

Background: Tumor vascular growth factors play a very important role in tumor growth and its spread. Trauma might induce the production and/or release of tumor vascular growth factors. High intensity focused ultrasound (HIFU) as a non-invasive local therapy for cancers may have less effect on vascular growth factor than surgery. Part one: Effects of HIFU therapy on tumor vascular growth factors in the local areaObjective: 1 The aim of this part is to determine effects of HIFU therapy on the expression of VEGF, bFGF, TGFβ₁ and TGFα in the local area (center and edge) of B16 melanoma. Methods: B16 melanoma model was established in 60 C57BL/6J mice by injecting B16 melanoma cells subcutaneously. Animals were randomly divided into three groups: HIFU group(n＝20), surgery group(n＝20) and control group(n＝20). HIFU(10 MHz, 40W/cm²) wasperformed 10s each time and cumulative ultrasonic exposed duration was 250s³00s. Its purpose was to induce complete coagulative necrosis in tumors and 5mm margin that were confirmed histologically. In surgery group, tumors were resected and the resecting scope was the same as that of the HIFU group. And there is no treatment on the control group. Central (tumor tissues) and marginal tissues (skin tissues) locating at the targeted area in HIFU group, marginal tissues in surgery group and tumor tisssues and skin tissues beyond the distance of 5mm away from the tumor in control group were sampled; The expression of VEGF, bFGF, TGFβ₁ and TGFαwere detected by immunohistochemical assay in these specimens. Results: The positive expression rates of VEGF, bFGF, TGFβ₁ and TGFαin the tumor tissue of the control group are 80.0ï¼…, 50.0ï¼…, 65.0ï¼… and 80.0ï¼… respectively. The skin tissues in control group and the central tissues of targeted area in HIFU group were all negatively expressing. The positive expression rates of all these factors in the specimens taken at the edge of targeted area in HIFU group and surgery group were 100% and the positive cells were all the inflammation cells. There were significant differences on the tumor tissues and the skin tissues between the control group and other groups. And there was no difference on the skin tissue between HIFU group and surgery group after operation(p<0.05). Conclusion: B16 melanoma expressed these four tumor vascular growth factors; HIFU therapy can suppressed their expression on the tumor tissues; HIFU therapy can increase tumor vascular growth factors at the edge of the targeted area, which were mainly derived from infiltrating of the inflammation cells.Part two: Effect of HIFU therapy on VEGF in the serumObjective: The aim of this part is to determine effect of HIFU therapy on serum-VEGF level.Methods: B16 melanoma bearing mice were randomly divided into two groups: HIFU group (n=40) and surgery group(n=40). Another 40 mice were injected isovolumetric normal saline solution and were treated as the surgery group, which served as the control. Blood were sampled before and 1, 3 and 7 day after operation (0, 1, 3, 7). Serum-VEGF concetrations were measured by an ELISA assay. Results: serum-VEGF concetrations in groups HIFU and surgery decreased after operation (HIFU group: 47.72pg/ml vs 152.89pg/ml; surgery group: 62.55pg/ml vs 152.89pg/ml; p<0.01), while that in control group increased (35.45pg/ml vs 2.14pg/ml; p<0.01). The levels of these two groups didn't fall to normal even on the seventh postoperative day. The levels of the HIFU group on days 1, 3 and 7 postoperatively were all lower than that of the surgery group(79.16pg/ml vs 91.59pg/mlï¼›33.64pg/ml vs 49.39pg/mlï¼›30.37pg/ml vs 46.68pg/ml). but there wasn't significant difference (p>0.05). Conclusion: HIFU maybe has less effect on serum-VEGF than surgery.