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Finkelmeier, Fabian ; Canli, Özge ; Peiffer, Kai-Henrik ; Walter, Dirk Henning ; Tal, Andrea Oliver ; Koch, Christine ; Pession, Ursula ; Vermehren, Johannes ; Trojan, Jörg ; Zeuzem, Stefan ; Piiper, Albrecht ; Greten, Florian ; Grammatikos, Georgios ; Waidmann, Oliver
Background and aims: Expression of carbonic anhydrase IX (CA9), an enzyme expressed in response to hypoxia, acidosis and oncogenic alterations, is reported to be a prognostic factor in HCC patients. Here we evaluated serum CA9 levels in HCC and cirrhosis patients.
Methods: HCC and cirrhosis patients were prospectively recruited and CA9 levels were determined. CA9 levels were compared to stages of cirrhosis and HCC stages. The association of the CA9 levels and overall survival (OS) was assessed. Furthermore, immunohistochemical CA9 expression in HCC and cirrhosis was evaluated.
Results: 215 patients with HCC were included. The median serum CA9 concentration in patients with HCC was 370 pg/ml and significantly higher than in a healthy cohort. Patients with advanced cancer stages (BCLC and ALBI score) had hid significant higher levels of CA9 in the serum. HCC patients with high serum CA9 concentrations (>400 pg/ml) had an increased mortality risk (hazard ratio (HR) 1.690, 95% confidence interval (CI) 1.017–2.809, P = 0.043). Serum CA9 concentration in cirrhotic patients did not differ significantly from HCC patients. Higher CA9 levels in cirrhotic patients correlated with portal hypertension and esophageal varices. Patients with ethanol induced cirrhosis had the highest CA9 levels in both cohorts. Levels of CA9 did not correlate with immunohistochemical expression.
Conclusions: We conclude that a high CA9 level is a possible prognostic indicator for a poor outcome in HCC patients. The high CA9 levels are probably mainly associated with portal hypertension. Ductular reactions might be a possible source of serum CA9.
Bleicher, Marcus ; Amelin, Nikolai ; Bass, Steffen A. ; Brandstetter, Mathias ; Dumitru, Adrian Bogdan ; Ernst, Christoph ; Gerland, Lars ; Konopka, Jens ; Spieles, Christian ; Weber, Henning ; Winckelmann, Luke Andreas ; Stöcker, Horst ; Greiner, Walter
The microscopic phasespace approach URQMD is used to investigate the stopping power and particle production in heavy systems at SPS and RHIC energies. We find no gap in the baryon rapidity distribution even at RHIC. For CERN energies URQMD shows a pile up of baryons and a supression of multi-nucleon clusters at midrapidity.
Schlenk, Richard Friedrich ; Lübbert, Michael ; Benner, Axel ; Lamparter, Alexander ; Krauter, Jürgen ; Herr, Wolfgang ; Martin, Hans ; Salih, Helmut Rainer ; Kündgen, Andrea ; Horst, Heinz August ; Brossart, Peter ; Götze, Katharina ; Nachbaur, David ; Wattad, Mohammed ; Köhne, Claus-Henning ; Fiedler, Walter ; Bentz, Martin ; Wulf, Gerald ; Held, Gerhard ; Hertenstein, Bernd ; Salwender, Hans ; Gaidzik, Verena I. ; Schlegelberger, Brigitte ; Weber, Daniela ; Döhner, Konstanze ; Ganser, Arnold ; Döhner, Hartmut
The aim of this clinical trial was to evaluate the impact of all-trans retinoic acid (ATRA) in combination with chemotherapy and to assess the NPM1 status as biomarker for ATRA therapy in younger adult patients (18-60 years) with acute myeloid leukemia (AML). Patients were randomized for intensive chemotherapy with or without open-label ATRA (45 mg/m2, days 6-8; 15 mg/m2, days 9-21). Two cycles of induction therapy were followed by risk-adapted consolidation with high-dose cytarabine or allogeneic hematopoietic cell transplantation. Due to the open label character of the study, analysis was performed on an intention-to-treat (ITT) and a per-protocol (PP) basis. One thousand one hundred patients were randomized (556, STANDARD; 544, ATRA) with 38 patients treated vice versa. Median follow-up for survival was 5.2 years. ITT analyses revealed no difference between ATRA and STANDARD for the total cohort and for the subset of NPM1-mutated AML with respect to event-free (EFS; p = 0.93, p = 0.17) and overall survival (OS; p = 0.24 and p = 0.32, respectively). Pre-specified PP analyses revealed better EFS in NPM1-mutated AML (p = 0.05) and better OS in the total cohort (p = 0.03). Explorative subgroup analyses on an ITT basis revealed better OS (p = 0.05) in ATRA for genetic low-risk patients according to ELN recommendations. The clinical trial is registered at clinicaltrialsregister.eu (EudraCT Number: 2004-004321-95).