Chicoine M R, Won E K, Zahner M C
Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Neurosurgery. 2001 Mar;48(3):607-14; discussion 614-5. doi: 10.1097/00006123-200103000-00032.
Anecdotal reports documented extended survival times for patients who developed infections at the site of resection of malignant gliomas. Hypothesized mechanisms for this phenomenon include immune responses triggered by lipopolysaccharide (LPS). This investigation assessed whether LPS could produce tumor regression in an in vivo model of malignant glioma.
Delayed brain tumor cells (2 x 10(6)) were injected subcutaneously into female BALB/c mice. LPS (300-500 microg) was injected intratumorally or subcutaneously at a contralateral site on Days 10, 17, and 24. Control animals received phosphate-buffered saline intratumorally or subcutaneously. Mice were killed on Day 28, and tumors were removed. Mean tumor masses for control animals and the two LPS-treated groups (intratumoral or contralateral subcutaneous treatment) were compared. Histological assessments of treated and control tumors were performed.
Complete or nearly total tumor regression was achieved in all 20 mice with subcutaneous delayed brain tumor cell tumors treated intratumorally with 400 microg of LPS (mean tumor mass of 0.09 +/- 0.38 g versus 2.42 +/- 2.46 g for control animals, P < 0.0001). Intratumoral administration of 300 microg of LPS or subcutaneous injection of 300 or 400 microg of LPS at a contralateral site resulted in less consistent regression of subcutaneous tumors. Administration of 500 microg of LPS resulted in tumor regression similar to that observed with lower doses but was limited by treatment-related deaths in 40% of animals. Histological assessment revealed lymphocytic infiltration of LPS-treated tumors.
Intratumoral injections of LPS caused dramatic regression of subcutaneously implanted delayed brain tumor cell mouse gliomas. Investigation of this antitumoral effect may improve treatment responses for patients with malignant gliomas.
轶事报道记录了恶性胶质瘤切除部位发生感染的患者生存期延长。这种现象的假设机制包括脂多糖（LPS）引发的免疫反应。本研究评估了LPS在恶性胶质瘤体内模型中是否能使肿瘤消退。
将延迟的脑肿瘤细胞（2×10⁶）皮下注射到雌性BALB/c小鼠体内。在第10、17和24天，将LPS（300 - 500微克）瘤内注射或在对侧部位皮下注射。对照动物接受瘤内或皮下注射磷酸盐缓冲盐水。在第28天处死小鼠并切除肿瘤。比较对照动物和两个LPS治疗组（瘤内或对侧皮下治疗）的平均肿瘤质量。对治疗和对照肿瘤进行组织学评估。
所有20只皮下植入延迟脑肿瘤细胞肿瘤且接受400微克LPS瘤内注射的小鼠均实现了完全或几乎完全的肿瘤消退（平均肿瘤质量为0.09±0.38克，而对照动物为2.42±2.46克，P<0.0001）。瘤内注射300微克LPS或在对侧部位皮下注射300或400微克LPS导致皮下肿瘤消退的一致性较差。注射500微克LPS导致的肿瘤消退与较低剂量观察到的相似，但40%的动物因治疗相关死亡而受限。组织学评估显示LPS治疗的肿瘤有淋巴细胞浸润。
瘤内注射LPS可使皮下植入延迟脑肿瘤细胞的小鼠胶质瘤显著消退。对这种抗肿瘤作用的研究可能会改善恶性胶质瘤患者的治疗反应。
