Therapeutic efficacy of glucan in a murine model of hepatic metastatic disease
Therapeutic efficacy of glucan in a murine model of hepatic metastatic disease
复制标题
葡聚糖在小鼠肝转移疾病模型中的治疗效果
作者：
David L. Williams;E. Sherwood;R. McNamee;Ernest L. Jones;N. di Luzio
评价了葡聚糖（一种颗粒状β-1，3-葡聚糖免疫调节剂）改变网状细胞肉瘤小鼠肝转移和存活率的能力。将肉瘤M5076细胞（1 × 105个细胞）皮下注射到同系C57 BL/6 J雄性小鼠中。第20天，组织病理学研究表明存在肝微转移。此时，静脉内给予葡聚糖（每只小鼠0.45 mg）或葡萄糖。治疗以3天间隔持续至第50天。到攻毒后第36天，与对照组相比，葡聚糖给药组的肝转移（大体和组织病理学）显著减少。原发性肿瘤的生长也发生了显著抑制。在第36天测量溴磺酞的血浆清除率，表明葡聚糖治疗维持了肝实质细胞功能的完整性，而在对照小鼠中观察到溴磺酞清除率降低4倍。葡聚糖治疗小鼠的长期存活率为28%（p < 0.05）。相比之下，对照小鼠在攻击后第42天显示100%死亡率。评价葡聚糖抗转移作用机制的研究表明，葡聚糖给药后8天，离体肝巨噬细胞在体外对肉瘤细胞的细胞毒性显著高于正常枯否细胞。此时，葡聚糖处理小鼠的腹膜和脾脏巨噬细胞的细胞毒性活性未发生变化。此外，颗粒葡聚糖与不同群体的正常或肿瘤细胞在体外共孵育表明，葡聚糖对肉瘤和黑色素瘤细胞具有直接的细胞生长抑制作用，相反，对正常脾和骨髓细胞具有增殖作用。这些研究表明，葡聚糖治疗性给药将：（i）显著抑制肝转移;（ii）抑制原发性肿瘤的生长;（iii）可能通过增加枯否细胞杀肿瘤活性以及葡聚糖对肉瘤细胞的直接细胞抑制作用来提高长期生存率。
Glucan, a particulate β‐1,3‐polyglucose immunomodulator, was evaluated for its ability to modify hepatic metastases and survival in mice with reticulum cell sarcoma. Sarcoma M5076 cells were injected subcutaneously (1 × 105 cells) into syngeneic C57BL/6J male mice. On Day 20, histopathological studies indicated the presence of hepatic micrometastases. At this time, glucan (0.45 mg per mouse) or dextrose was administered intravenously. Therapy was continued at 3‐day intervals up to Day 50. By Day 36 postchallenge, the glucan‐treated group, when compared to the control group, showed a marked decrease in hepatic metastases, both grossly and histopathologically. A significant inhibition in the growth of the primary tumor also occurred. Plasma clearance of bromosulfophthalein measured on Day 36, denoted that glucan therapy maintained hepatic parenchymal cell functional integrity, while a 4‐fold impairment in bromosulfopthalein removal was observed in control mice. Glucan‐treated mice showed a 28% (p < 0.05) long‐term survival. In contrast, control mice showed a 100% mortality by Day 42 postchallenge. Studies to evaluate the mechanism of the anti‐metastatic action of glucan indicated that 8 days after glucan administration, isolated hepatic macrophages were significantly more cytotoxic to sarcoma cells in vitro than were normal Kupffer cells. At this time, the cytotoxic activity of peritoneal and splenic macrophages from glucan‐treated mice were unaltered. Additionally, co‐incubation of particulate glucan with diverse populations of normal or tumor cells in vitro indicated that glucan exerted a direct cytostatic effect on sarcoma and melanoma cells and, in contrast, had a proliferative effect on normal spleen and bone marrow cells. These studies denote that glucan, administered therapeutically will: (i) significantly inhibit hepatic metastases; (ii) inhibit the growth of the primary tumor, and (iii) enhance long‐term survival possibly by increased Kupffer cell tumoricidal activity as well as a direct cytostatic effect of glucan on sarcoma cells.
抑制巨噬细胞激活剂在体外和体内诱导的网状细胞肉瘤 (M5076) 的生长。
影响因子：
11.2
作者：
Talmadge,JE;Hart,IR
通讯作者：
Hart,IR
癌症转移中的肿瘤细胞多样性和宿主反应——第二部分——宿主免疫反应和转移治疗。
影响因子：
2.6
作者：
Nicolson,GL;Poste,G
通讯作者：
Poste,G