IgG and IgM glycosylation patterns in patients undergoing image-guided tumor ablation.

BACKGROUND: Image-guided tumor ablation is a technique whereby needle-like applicators are placed directly into solid tumors under guidance typically with computed tomography or ultrasound. Changes in IgG and IgM antibody glycosylation were studied during ablation-induced immune response to cancer, and the use of glycosylation as a biomarker for diagnosis, prognosis and disease treatment was examined. METHODS: Plasma from 27 tumor patients was collected immediately before, after and for 6 months following ablation. IgG and IgM antibodies were isolated by use high-throughput chromatography, and analyzed by hydrophilic liquid chromatography. Thorough identification of glycan structures in each chromatography peak was performed by nano-liquid chromatography electrospray ionization mass spectrometry. RESULTS: Although antibody glycosylation was found to vary with cancer type, discernable patterns of change based on the successful treatment of tumors by ablation were not identified. One patient with renal clear cell carcinoma and poor disease outcome had unexpectedly high amount of oligomannose IgG glycans during the whole period of monitoring. In contrast, IgM antibodies did not follow the same pattern. CONCLUSIONS: These findings suggest that glycosylation patterns are indicative of an immune system that is unable to prevent different types of cancer, rather than products of the immunostimulatory response to the ablation of tumor itself. Analyses of the outcome effect suggested that IgG glycosylation and IgM glycosylation are not associated with tumor ablation. GENERAL SIGNIFICANCE: Present work opens a new way for parallel determination of glycosylation changes of both IgG and IgM antibodies by use of high-throughput methods, and their future use as biomarkers for disease diagnosis and prognosis. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.

Nuclear Magnetic Resonance-Assisted Prediction of Secondary Structure for RNA: Incorporation of Direction-Dependent Chemical Shift Constraints.

Knowledge of RNA structure is necessary to determine structure-function relationships and to facilitate design of potential therapeutics. RNA secondary structure prediction can be improved by applying constraints from nuclear magnetic resonance (NMR) experiments to a dynamic programming algorithm. Imino proton walks from NOESY spectra reveal double-stranded regions. Chemical shifts of protons in GH1, UH3, and UH5 of GU pairs, UH3, UH5, and AH2 of AU pairs, and GH1 of GC pairs were analyzed to identify constraints for the 5' to 3' directionality of base pairs in helices. The 5' to 3' directionality constraints were incorporated into an NMR-assisted prediction of secondary structure (NAPSS-CS) program. When it was tested on 18 structures, including nine pseudoknots, the sensitivity and positive predictive value were improved relative to those of three unrestrained programs. The prediction accuracy for the pseudoknots improved the most. The program also facilitates assignment of chemical shifts to individual nucleotides, a necessary step for determining three-dimensional structure.

Solitary painful osseous metastases: correlation of imaging features with pain palliation after radiofrequency ablation--a multicenter american college of radiology imaging network study.

PURPOSE: To identify the correlation of pre- and postablation imaging features with pain relief, pain intensity, and patient mood after radiofrequency (RF) ablation of solitary painful osseous metastases. MATERIALS AND METHODS: This prospective, multicenter group trial was approved by each institutional review board. Participants were enrolled between November 1, 2001, and April 6, 2006. Written informed consent was obtained from all subjects, and patient confidentiality protocols were followed in compliance with HIPAA. Computed tomography (CT)-guided RF ablation and contrast material-enhanced 1-month follow-up CT and/or magnetic resonance imaging were performed in 49 subjects (24 men, 25 women; age range, 34-83 years) with a confirmed malignant solitary bone lesion of maximum dimension of 8 cm or smaller that was causing intractable pain. Pain intensity and patient mood were measured before and after RF ablation. Tumor imaging features were recorded. Unadjusted and adjusted linear mixed-effects models, with a random intercept for each subject, were used to model patient mood, pain relief, and pain intensity scores at three times after ablation as a function of each tumor characteristic. RESULTS: Decreased postablation tumor pain correlated with preablation tumor volume (P = .02) and pathologic fracture (P = .01), while pain relief correlated with pathologic fracture (P = .03) and percentage of bone-tumor interface (BTI) ablated (P = .02). Conversely, presence of an irregular rim after ablation (P = .02) and rim thickness (P = .01) correlated with increased pain. There was no evidence in this study that RF ablation of larger tumor percentage or larger volume leads to better pain relief or decreased pain (P > .05). CONCLUSION: Existing pathologic fracture and smaller tumor size appear to be predictive parameters of success when selecting patients for palliative RF ablation of painful solitary osseous metastases. Successful palliation also appears to be related to the percentage of BTI ablated.