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Bayreuth, Germany

Pachmann K.,Friedrich - Schiller University of Jena | Camara O.,Friedrich - Schiller University of Jena | Kohlhase A.,Friedrich - Schiller University of Jena | Rabenstein C.,Transfusion Center Bayreuth | And 3 more authors.
Journal of Cancer Research and Clinical Oncology

Purpose: In malignant tumors, predictive markers have been developed with respect to targeted therapies. One of the first targeted therapies was the hormone-blocking treatment of tumors of the male and female reproductive system. A typical therapy in breast cancer is the use of the selective estrogen receptor modulator, tamoxifen. However, only some of the patients, positive for the target molecules, respond to the selected therapy. It would, therefore, be highly desirable to have a tool to promptly assess the therapeutic efficacy of the applied agent in the individual patient. Methods: Longitudinal observation of CETC provides a unique tool for monitoring therapy response. About 178 patients with breast cancer were followed prospectively during hormone therapy, requiring only 1 ml of peripheral blood, using a fluorochrome-labeled antibody against surface-epithelial antigen. Image analysis allowed CETC numbers to be calculated in relation to blood volume and monitoring over the entire course of treatment. Results: A more than tenfold increase in CETC during therapy was a strong indicator of looming relapse (P = 0.0001 hazard ratio 5.5; 95% confidence interval 1,297-23,626), and a Cox regression analysis of age, tumor size, receptor expression, nodal status and previous treatment resulted in a regression model, in which CETC behavior was the parameter with the highest independent correlation to relapse-free survival. Conclusions: The change in the number of CETC (increase or decrease) may, in the future, be used to guide therapy in order to change to other available treatment options in good time. © 2010 The Author(s). Source

Pizon M.,Transfusion Center Bayreuth | Zimon D.S.,Transfusion Center Bayreuth | Pachmann U.,Transfusion Center Bayreuth | Pachmann K.,Friedrich - Schiller University of Jena

Background: Circulating epithelial tumor cell (CETC) analysis is a promising diagnostic field for estimating the risk for metastatic relapse and progression in patients with malignant disease. CETCs characterization can be used as a liquid biopsy for prognostic and predictive purposes in breast and other cancers. IGF-IR and VEGFR-2 play an important role in tumor growth and the progression of cancer disease. The purpose of the current study was therefore to investigate their expression on CETCs. Methods: CETCs were determined from the blood of 50 patients suffering from breast cancer. The number of vital CETCs and the expression of IGF-IR and VEGFR-2 were investigated using the maintrac® method. Results: IGF-IR and VEGFR-2 expression on the surface of CETCs were detected in 84% of patients. A statistically high correlation was found between IGF-IR and VEGFR-2 (r = 0.745 and p<0.001) on the CETCs. The co-expression of both receptors was confirmed in some experiments and ranged between 70% and 100%. Statistically significant correlations were observed between the number of CETCs and IGF-IR (r = 0.315 and p<0.05) and VEGFR-2 (r = 0.310 and p<0.05) expression. The presence of CETCs and the level of IGF-IR and VEGFR-2 expression were not associated with tumor stage, hormone receptor status or nodal/distant metastasis. Summary: In this study, a parallel and co-expression of IGF-IR and VEGFR-2 was examined on the surface of CETCs in breast cancer patients for the first time. Characterization of CETCs may be a promising approach for the rational design of targeted anticancer therapies. © 2013 Pizon et al. Source

Hekimian K.,Friedrich - Schiller University of Jena | Stein E.-L.,Transfusion Center Bayreuth | Pachmann U.,Transfusion Center Bayreuth | Pachmann K.,Friedrich - Schiller University of Jena
Clinical Chemistry and Laboratory Medicine

Background: The epithelial cell adhesion molecule (EpCAM) embedded in the plasma membrane of circulating epithelial tumor cells (CETC) is used for detection and enrichment of circulating tumor cells in peripheral blood and as a target for anti-epithelial antibodies elicited during immune response in anti-tumor immunization. Although an efficient immune response against EpCAM can be generated, the clinical application of such approaches has not been successful so far and the detection of circulating epithelial cells is highly variable. One reason for these discrepancies may be that not all circulating tumor cells are equally accessible for the specific antibody. A possible reason might be masking of EpCAM by glycoproteins or membrane lipoproteins preventing antibody binding. Methods: We have tested the application of detergents as demasking agents known to be successful in demasking red blood cell epitopes and determined how and in which way they affect integral membrane proteins and membrane lipids. Results: The results showed that the polysorbate Tween®20, a non-ionic detergent like organic solvent is able to demask EpCAM on CETC and makes it better accessible to its specific antibody retaining at the same time full cell viability. Conclusions: The data presented in this study suggest that EpCAM is present on part of circulating tumor cells in a masked form and that it is possible to demask EpCAM on CETC of breast cancer patients using Tween®20 treatment. But further studies are needed to elucidate the mechanism of demasking. © 2012 by Walter de Gruyter Berlin Boston. Source

Pizon M.,Clinic of Bayreuth | Pizon M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Friedel N.,Clinic of Bayreuth | Pizon M.,Transfusion Center Bayreuth | And 3 more authors.
Journal of Cardiothoracic Surgery

Background: Epicardial ablation concomitant to cardiac surgery is an easy and safe approach to treat atrial fibrillation (AF), but its efficacy in longstanding persistent (LsPe) AF remains intermediate. Although larger left atrial size has been associated with worse outcome after ablation, biochemical predictors of success are not well established. The aim of this study was to evaluate relationship between biochemical marker, echo-characteristic and cardiac rhythm in 6 months follow-up after epicardial ultrasound (HIFU) ablation.Methods: We included 78 consecutive patients, who underwent elective cardiac surgery. 42 patients with AF (11.9% paroxysmal, 23.8% persistent, 64.3% LsPeAF) underwent concomitant HIFU ablation (AF ablation group), 16 with AF underwent cardiac surgery without ablation (AF control) and 20 had preoperatively normal sinus rhythm (SR control). We measured plasma ANP secretion before, on postoperative day (POD) 1, POD 7 as well as 3 and 6 months after surgery. Moreover, we estimated cardiac rhythm and atrial mechanical function by Atrial Filling Fraction (AFF) and A-wave velocity in follow-up.Results: Baseline ANP levels were higher in patients with LsPeAF, as compared to the paroxysmal and permanent AF and to the SR control group. Patients with LsPeAF (n = 27) who converted to SR had preoperatively smaller left atrial diameter (LAD) and LA area (p < 0.05) and higher ANP level (p = 0.009) than those who remained in AF at 6 months after ablation. Multivariate regression analysis revealed that only preoperative ANP level was an independent predictor of cardiac rhythm after ablation. Patients with LsPeAF and preoperative ANP >7.5 nmol/l presented with SR in 80%, in contrast to those with ANP <7.5 nmol/l who converted to SR in 20%. We detected gradual increase of AFF and A-velocity at 6 months after ablation (p < 0.05) solely in AF ablation group. ANP levels were increased on POD 1 in ablation group (p < 0.05), without changes in further follow-up.Conclusion: Our results indicate that preoperative ANP levels may be a new biochemical predictor of successful epicardial ablation in patients with concomitant LsPeAF. HIFU ablation caused a significant improvement of atrial mechanical function and gradual increase of AFF and did not associate with alteration of atrial endocrine secretion at 6 months follow-up. © 2013 Pizon et al.; licensee BioMed Central Ltd. Source

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