ABSTRACT
Aortic valve stenosis (AVS) and coronary artery disease (CAD) are accompanied by changes in the cardiac extra cellular matrix (cECM) including the re-expression of oncofetal fibronectin (Fn) and tenascin-C (Tn-C) variants. Human antibodies against these variants are usable for targeted therapy. Aim of the study was the comparative analysis of cECM remodelling in tissue samples from right atrial auricle (RAA) and left ventricular septum (LVS). RAA and LVS specimens from 30 patients (17 × AVS; 13 × AVS+CAD) were analysed with respect to histological changes and ECM remodelling using PCR based ECM gene expression profiling. Re-expression of ED-A(+) Fn and A1(+) Tn-C was investigated on the mRNA and on the protein level. For immunofluorescence, human recombinant small immunoprotein (SIP) format antibodies were used. There was a positive correlation of the grade of histological changes in RAA and corresponding LVS samples (r = 0.695). ECM gene expression levels were higher in LVS compared to RAA. For 24 genes, a corresponding relevant (>2.5-fold) up- or down-regulation in RAA and LVS occurred. Using SIP antibodies, a positive correlation of protein deposition levels in RAA and corresponding LVS (r = 0.818) could be shown for ED-A(+) Fn. Cardiac tissue remodelling is likely a process involving the entire heart reflected by intra-individually comparable histology and cECM changes in RAA and LVS samples. ED-A(+) Fn might be an excellent target for an antibody-mediated delivery of diagnostic or therapeutic agents. The RAA is a valuable and representative tool to evaluate cardiac remodelling and to plan individualized therapy.
Subject(s)
Aortic Valve Stenosis/genetics , Coronary Artery Disease/genetics , Fibronectins/genetics , Heart Atria/metabolism , Heart Ventricles/metabolism , Tenascin/genetics , Aged , Aortic Valve Stenosis/metabolism , Aortic Valve Stenosis/pathology , Coronary Artery Disease/metabolism , Coronary Artery Disease/pathology , Female , Fibronectins/metabolism , Gene Expression Profiling , Heart Atria/pathology , Heart Ventricles/pathology , Humans , Male , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tenascin/metabolism , Tissue DistributionABSTRACT
PURPOSE: To assess the importance of the information obtained from MRI for adaptive cervix cancer radiotherapy. PATIENTS AND METHODS: 49 patients with cervix cancer, treated by external-beam radiotherapy (EBRT) and MRI-assisted high-dose-rate brachytherapy +/- concomitant cisplatin, underwent MRI at diagnosis and at the time of brachytherapy fractions. 190 MRI examinations were performed. Pretreatment scans were correlated with clinical examination (CE) findings. Measurements in 3-D of the tumor extension and also of the distance from the tumor to the pelvic side wall were performed using both MRI and CE. The tumor volume regression induced initially by EBRT and the subsequent regression after each brachytherapy fraction were assessed. RESULTS: MRI and CE showed 92% agreement in overall parametrial staging and 73% agreement in terms of vaginal involvement. There was, however, disagreement in parametrial side (right/left) classification in 25% of the parametria examined. These were patients with unilateral displacement of the cervix and contralateral invasion of the parametrium. The mean tumor volume on the pretreatment MRI scan (GTVD) was 61 cm(3). At the time of the four brachytherapy fractions the mean was 16 cm(3), 10 cm(3), 9 cm(3), and 8 cm(3), defined as the GTVBT plus the gray zones in the parametria. CONCLUSION: CE and MRI findings agree well in terms of overall staging. The clinical assessment of side-specific parametrial invasion improved when having access to the additional knowledge obtained from MRI. The greatest decrease in tumor volume occurs during EBRT, whereas tumor regression between the first and subsequent brachytherapy fractions is minor.
