title: Cryosurgical ablation of liver tumors in colon cancer patients increases the serum total ganglioside level and then selectively augments antiganglioside IgM.
abstract: 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.
authors.affiliation: Laboratory of GlycoImmunotherapy, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404-2302, USA. ravi@jwci.org
authors.forename: Mepur H
authors.initials: MH
authors.lastname: Ravindranath
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wood
authors.forename: Daniel
authors.initials: D
authors.lastname: Soh
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gonzales
authors.forename: Sakunthala
authors.initials: S
authors.lastname: Muthugounder
authors.forename: Carlos
authors.initials: C
authors.lastname: Perez
authors.forename: Donald L
authors.initials: DL
authors.lastname: Morton
authors.forename: Anton J
authors.initials: AJ
authors.lastname: Bilchik
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000276:immunology / Q000556:secondary* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000097:blood* / Q000276:immunology; D003080:Cold Temperature / Q000009:adverse effects; D003110:Colonic Neoplasms / Q000097:blood* / Q000276:immunology / Q000473:pathology; D003452:Cryosurgery / Q000009:adverse effects; D004564:Electrocoagulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005732:Gangliosides / Q000097:blood / Q000276:immunology*; D006498:Hepatectomy; D006706:Homeostasis; D006801:Humans; D007114:Immunization; D007075:Immunoglobulin M / Q000097:blood* / Q000276:immunology; D008099:Liver / Q000293:injuries / Q000473:pathology; D008113:Liver Neoplasms / Q000097:blood / Q000276:immunology / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009367:Neoplasm Staging; D000078702:Radiofrequency Therapy
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D005732:Gangliosides; D007075:Immunoglobulin M