Decreased mortality of Norman murine sarcoma in mice treated with the immunomodulator, Acemannan.

Molecular biotherapy Pub Date : 1991-06-01
S Y Peng, J Norman, G Curtin, D Corrier, H R McDaniel, D Busbee
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Abstract

An extract from the parenchyma of Aloe barbadensis Miller shown to contain long chain polydispersed beta (1,4)-linked mannan polymers with random O-acetyl groups (acemannan, Carrisyn) was found to initiate the phagocyte production of monokines that supported antibody dependent cellular cytotoxicity and stimulated blastogenesis in thymocytes. Acemannan, in both enriched and highly purified forms, was administered intraperitoneally to female CFW mice into which murine sarcoma cells had been subcutaneously implanted. The rapidly growing, highly malignant and invasive sarcoma grew in 100% of implanted control animals, resulting in mortality in 20 to 46 days, dependent on the number of cells implanted. Approximately 40% of animals treated with acemannan at the time of tumor cell implantation (1.5 x 10(6) cells) survived. Tumors in acemannan-treated animals exhibited vascular congestion, edema, polymorphonuclear leukocyte infiltration, and central necrosing foci with hemorrhage and peripheral fibrosis. The data indicate that in vivo treatment of peritoneal macrophages stimulates the macrophage production of monokines, including interleukin-1 and tumor necrosis factor. The data further indicate that sarcomas in animals treated i.p. with acemannan at the time of tumor cell implantation were infiltrated by immune system cells, became necrotic, and regressed. The combined data suggest that acemannan-stimulated synthesis of monokines resulted in the initiation of immune attack, necrosis, and regression of implanted sarcomas in mice.

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用免疫调节剂阿塞曼南治疗的小鼠诺曼鼠肉瘤死亡率降低。
从芦荟薄壁组织中提取的提取物含有长链多分散的β(1,4)连接甘露聚糖聚合物和随机o -乙酰基(葡甘露聚糖,Carrisyn),发现可以启动吞噬细胞产生单因子,支持抗体依赖性细胞毒性和刺激胸腺细胞的囊胚发生。将浓缩和高度纯化的阿塞曼南注射到皮下植入小鼠肉瘤细胞的雌性CFW小鼠腹腔内。这种快速生长、高度恶性和侵袭性的肉瘤在100%被植入的对照动物体内生长,在20至46天内死亡,死亡时间取决于植入的细胞数量。在肿瘤细胞植入(1.5 x 10(6)个细胞)时,约有40%的动物接受阿西甘露聚糖治疗后存活。acemanan治疗动物的肿瘤表现为血管充血、水肿、多形核白细胞浸润、中央坏死灶伴出血和周围纤维化。数据表明,腹膜巨噬细胞的体内处理刺激巨噬细胞产生单因子,包括白细胞介素-1和肿瘤坏死因子。这些数据进一步表明,在肿瘤细胞植入时,用阿赛甘露聚糖处理的动物体内的肉瘤被免疫系统细胞浸润、坏死并消退。综合数据表明,紫杉醇刺激的单因子合成导致小鼠植入式肉瘤的免疫攻击、坏死和消退。
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