A Study of an anti-angiogenic thcropy targetting integrins expressed on angiogenesis endotherial cells

白细胞介素12（IL-12）在不同的模型中被证明能诱导有效的抗肿瘤和抗转移免疫反应。IL-12也有抗血管生成的作用。本研究的目的是利用生命显微镜系统阐明IL-12对人胰腺癌的抗血管生成作用。我们使用严重联合免疫缺陷小鼠（SCID）。采用皮肤折叠腔模型，评估胰腺癌细胞PK-1或IL-12基因工程PK-1 （IL-12/PK-1）植入后肿瘤生长和血管生成情况。通过活体显微镜记录新生血管的图像并离线分析。研究了抗ifny和抗il -12抗体的作用。注射抗亚洲蓟GM1抗体阻断自然免疫。在体外实验中，虽然没有注射asialo GMI抗体来阻断PK-1与IL-12/PK-1在自然免疫曲线上的差异，但IL-12/PK-1的生长明显受到抑制。皮褶腔研究显示IL-12/PL-1对肿瘤和血管发生有较强的抑制作用。IL-12抗体允许IL-12/PK-1植入后肿瘤发展。结果表明，IL-12具有抑制血管生成的作用，可抑制胰腺癌的生长。IL-12局部给药系统有望成为治疗胰腺癌的新策略。内皮细胞上表达的CD62E （B-selectin， SLAM,1）可与其在肿瘤细胞表面的配体sLeas和sLex结合。e -选择素的可溶性形式也被发现促进炎症和肿瘤血管生成。为了研究CD62E在肿瘤微环境中的作用。我们从小鼠C-26结肠腺cardoma细胞株中分离出CD62B cDNA，通过FACScan检测发现该细胞株表达CD62B。将CD62E cDNA转染到不表达CD62B的黑色素瘤细胞株（B16 /B）中。B16/E系与B16系体外生长无显著差异。在SCID小鼠透明腔内生长时，B16/E肿瘤的生长速度快于B16肿瘤，并且伴有快速的新生血管形成。将一种新的合成选择性拮抗剂KB-R9188每天（10 mg/kg）给予SCID小鼠20天，B16/B肿瘤的生长水平与B16肿瘤相当。CD62E是一种血管生成因子。少

Interleukin 12(IL-12) was proved to induce a potent antitumor and antimetastasis immune response in different models. It had also been reported that IL-12 possess anti-angiogenesis effect. The aim of this study is to clarify the anti-angiogenesis effect of IL-12 on human pancreatic carcinoma using a vital microscope system. We used severe combined immune-deficient mice (SCID). Skinfold chamber models was used to evaluate tumor growth and angiogenesis after implantation of PK-1 (pancreatic carinoma cells) or IL-12 genetically engineered PK-1 (IL-12/PK-1). Images of neovascularization were recorded though intravital microscopy and analyzed off-line. The effects of anti-IFNy and anti-IL-12 antibodies were investigated. Anti-asialo GM1 antibodi was injected to block the natural immunity. Although there was no asialo GMI antibody was injected to block the natural immunity differences in growth curve in vitro between PK-1 and IL-12/PK-.1, the growth of IL-12/PK-1 was inhibited significantly … More as compared with PK-1 in vivo. Skinfold chamber studies showed a strong inhibition on tumor an giogenesis of IL-12/PL-1. IL-12 antibodies administration allowed tumor development after IL-12/PK-1 implantation. It is demonstrated that anti-angiogenesis effect of IL-12 prevented the growth of panaoreatic cancer. Local delivery system of IL-12 is expected to a new strategy for pancreatic cancer.CD62E (B-selectin, SLAM,1) expressed on endothelial cells can bind to its ligands sLeas and sLex on the surface of tumor cells. The soluble form of E-selectin was also found to promote inflammation and tumor angiogenesis. In order to study the role of CD62E in tumor microenviroment. we isolated CD62B cDNA from murine C-26 colon adcnocardnoma cell line which we found to express CD62B by FACScan. CD62E cDNA was transfected into mudne B16 melanoma cell line (B 16/B) which does not express CD62B.There was no difference between the in vibo growth of B16/E and B16 lines. The B16/E tumors grew faster than B16 tumors paralleled by rapid neovascularization when tumors were grown within the transparent chambers in SCID mice. When a new synthetic antagonist of selections, KB-R9188 was administered i-p-daily (10 mg/kg) for 20 days to SCID mico, the growth of B16/B tumores was leveled to that of B16 tumors. CD62E is revealed as an angiogenic factor. Less