Ravindranath Mepur H, Wood Thomas F, Soh Daniel, Gonzales Alexandra, Muthugounder Sakunthala, Perez Carlos, Morton Donald L, Bilchik Anton J
Laboratory of GlycoImmunotherapy, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404-2302, USA.
Cryobiology. 2002 Aug;45(1):10-21. doi: 10.1016/s0011-2240(02)00102-5.
Cryosurgical ablation (CSA) of tumors induces disruptive necrosis. Necrosis may release tumor gangliosides into circulation and they may augment serum antiganglioside antibodies depending on the nature of gangliosides released. The hypothesis is tested by determining the level of serum total gangliosides (STG) and their antibody titers in the sera of colon cancer patients with cryoablated liver tumors. As controls, we examined the sera of patients who underwent radiofrequency ablation (RFA) and regular surgery (RS), none of which cause disruptive necrosis. The STG level (expressed as lipid-bound sialic acids, LBSA) is higher (p(2)<0.001) in 35 patients (stage IV) than in 38 healthy case-controls (median 23.48 mg/dL, Q-range 7.1 vs 16.04 mg/dL, Q-range 4.5). The mean STG level increased significantly to 31.2+/-6.0mg/dL (p(2)<0.03) after CSA. Concomitantly, the IgM titer against colon cancer-associated gangliosides (GM(2), GD(1a), GT(1b)), increased significantly, but no increase was observed against normal tissue gangliosides (GM(3) or GM(1)). Also after RFA and RS, no such increase was observed either in the level of STG or in IgM titer against tumor gangliosides. The results suggest that CSA-induced necrosis might have acted as an adjuvant, because purified gangliosides without exogenous adjuvants even after repeated immunization failed to elicit antibody response. The post-CSA decline in the STG level correlated with the increase in the antibodies, suggesting a homeostatic role of the antibodies.
肿瘤的冷冻手术消融（CSA）会导致破坏性坏死。坏死可能会将肿瘤神经节苷脂释放到循环系统中，并且根据所释放神经节苷脂的性质，它们可能会增加血清抗神经节苷脂抗体。通过测定冷冻消融肝脏肿瘤的结肠癌患者血清中的血清总神经节苷脂（STG）水平及其抗体滴度来验证这一假设。作为对照，我们检测了接受射频消融（RFA）和常规手术（RS）患者的血清，这两种手术均不会导致破坏性坏死。35例患者（IV期）的STG水平（以脂质结合唾液酸，LBSA表示）高于38例健康对照（中位数23.48mg/dL，四分位间距7.1对16.04mg/dL，四分位间距4.5）（p(2)<0.001）。CSA后，平均STG水平显著升高至31.2±6.0mg/dL（p(2)<0.03）。同时，针对结肠癌相关神经节苷脂（GM(2)、GD(1a)、GT(1b)）的IgM滴度显著升高，但针对正常组织神经节苷脂（GM(3)或GM(1)）未观察到升高。同样在RFA和RS后，STG水平或针对肿瘤神经节苷脂的IgM滴度均未观察到此类升高。结果表明，CSA诱导的坏死可能起到了佐剂的作用，因为即使反复免疫，没有外源性佐剂的纯化神经节苷脂也未能引发抗体反应。CSA后STG水平的下降与抗体的增加相关，表明抗体具有稳态作用。
