The lack of sufficient well-defined tumor-associated antigens is still a drawback on the way to a cytotoxic T-lymphocyte-based immunotherapy of renal cell carcinoma (RCC). We are trying to define a larger number of such targets by a combined approach involving HLA ligand characterization by mass spectrometry and gene expression profiling by oligonucleotide microarrays. Here, we present the results of a large-scale analysis of 13 RCC specimens. We were able to identify more than 700 peptides, mostly from self-proteins without any evident tumor association. However, some HLA ligands derived from previously known tumor antigens in RCC. In addition, gene expression profiling of tumors and a set of healthy tissues revealed novel candidate RCC-associated antigens. For several of them, we were able to characterize HLA ligands after extraction from the tumor tissue. Apart from universal RCC antigens, some proteins seem to be appropriate candidates in individual patients only. This underlines the advantage of a personalized therapeutic approach. Further analyses will contribute additional HLA ligands to this repertoire of universal as well as patient-individual tumor antigens.
MAGE derived HLA ligands have repeatedly been shown to elicit T-cell responses against tumor cells. In renal cell carcinoma (RCC), however, only few T-cell epitopes from cancer testis antigens have been described. To identify potential candidates, we applied a combined approach of microarray/qPCR expression analysis and sequencing of HLA ligands from RCC by mass spectrometry. We analyzed the expression of 21 MAGE genes in ten RCC samples and two glioblastoma samples and could identify the first MHC class I ligand NIGDEALIGRW from MAGED4 presented by HLA-A*25 on RCC solid tumor tissue. MAGED4 was expressed in 30% of RCC and both glioblastoma samples. Among the other MAGE family members only MAGEB2 and -C1 and the broadly expressed MAGED1, -D2, -F1 and -H1 were expressed in RCC. Ligands from MAGED4 could thus be interesting tumor-associated antigens in a subset of RCC, even though the identified ligand is presented by a rather rare allele.
Background Focused cardiac ultrasound (FCU) is a helpful tool to rapidly identify right ventricular (RV) causes of hemodynamic instability and facilitate the initiation of therapy. The clinical value of existing course models often remains unclear. This study investigated the effects of a one‐day FCU training on the visual estimation skills of RV characteristics. Methods Four residents were included as the study group after completing a standardized one‐day FCU training. Four gender‐matched controls did not take part in the training. All residents graded image quality, RV systolic function, and RV dimensions in a test comprising 35 ultrasound clips. Results The study and control group did not differ in ICU or ultrasound experience. Overall, training participants were able to distinguish between good and insufficient image quality significantly better than the control group (agreement 80.0% vs 61.4%, p = 0.04). The agreement for the estimation of RV function and RV dimensions was not different between the groups (63.2% vs 60.5%, p = 0.66 and 64.3% vs 67.1%, p = 0.18, respectively). Descriptively, only small differences were found between the groups for the estimation of RV function and RV dimensions in subgroups of patients with normal versus reduced systolic RV function or normal versus enlarged RV dimensions, respectively. Both groups struggled in identifying RV enlargement (34.6% vs 46.2%). Discussion In this study, a single one‐day FCU training had no impact on residents’ skills to visually assess systolic RV function or RV dimensions. Improvements of current training modalities or continuous teaching models are needed to optimize residency programs and patient care.
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