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Natters, Austria

Aschauer G.,Internal Medicine I | Greil R.,Paracelsus Medical University | Linkesch W.,Medical University of Graz | Nosslinger T.,Hanusch Hospital | And 7 more authors.
Clinical Lymphoma, Myeloma and Leukemia | Year: 2015

Background Lenalidomide has demonstrated remarkable efficacy for therapy of lower-risk myelodysplastic syndromes (MDS) associated with 5q-. The present evaluation aimed to describe the characteristics and outcomes of low-risk MDS patients treated with lenalidomide in Austria. Patients and Methods For this retrospective, multicenter, observational analysis of MDS patients who received lenalidomide, data were collected at various hospitals in Austria over a period of 3 years. MDS classification, previous and current MDS therapies, and outcome and safety of lenalidomide were evaluated. Results Forty-six percent of the patients (n = 23) had a 5q- syndrome, while 12% (n = 6) exhibited 5q- plus additional aberrations or isolated 5q- but ≥ 5% blasts in the bone marrow (10%, n = 5). The remaining 32% of patients (n = 16) had MDS with other World Health Organization classifications. Seventy percent belonged to lower International Prognostic Scoring System risk classes. Sixteen centers participated, involving a total of 50 patients. Most frequently used lenalidomide doses were 10 mg and 5 mg on days 1 to 21 of a 28-day cycle. Seventy-five percent of the patients received 11 months of treatment, with a median therapy period of 3.5 months; median follow-up was 3.9 months (range, 0-26 months). Response rate, defined as transfusion independence during the 2 months after lenalidomide therapy, was 64%. Median overall survival was not reached. Conclusion Lenalidomide was well tolerated and is an effective and well-tolerated option for therapy of patients with 5q- syndrome but also lower-risk MDS patients with other World Health Organization classifications in clinical practice. © 2015 Elsevier Inc.

Sterlacci W.,Innsbruck Medical University | Fiegl M.,Innsbruck Medical University | Hilbe W.,Innsbruck Medical University | Jamnig H.,Hospital Natters | And 6 more authors.
Journal of Thoracic Oncology | Year: 2010

Introduction: A large group of interacting molecular factors, involved in epithelialmesenchymal transition, epidermal growth factor receptor (EGFR) signaling, and G1 mitotic phase, are shown to play an important role in cancerogenesis and progression of non-small cell lung cancer (NSCLC). Since success concerning potential correlations, structural and numeric gene aberrations, and biological risk assessment of these molecular factors are still lacking, combined analysis of a multitude of intertwined factors is currently a promising approach. Methods: Cyclins (D1, D2, D3, and E), p21, p27, EGFR, Snail, E-cadherin, β-catenin, phosphatidylinositol-3′ kinase, phosphatase and tensin homologue, phosphorylated Akt, and phosphorylated signal transducer, and activator of transcription-3 were analyzed by immunohistochemistry in 405 surgically resected NSCLC, using a standardized tissue microarray platform. In addition, the gene status of EGFR and cyclin D1 was examined by fluorescence in situ hybridization. Extensive clinical data were acquired, enabling detailed clinicopathologic correlation during a postoperative follow-up period of up to 14 years. Results: The protein overexpressions of nuclear p27, cyclin D1, cyclin D3, E-cadherin, and EGFR as assessed by immunohistochemistry were all associated with a significant reduction in overall survival time. In addition, cyclin D1 proved especially important, being the only independent molecular tumor-related factor with prognostic significance by multivariable analysis. In analogy to EGFR, recurrent numeric gene aberrations, particularly high-level amplifications, of cyclin D1 were obvious. Conclusions: The results emphasize that deregulation of controlling factors of the early G1 phase is of significant oncogenic relevance and may represent a potential treatment target in NSCLC. © 2010 by the International Association for the Study of Lung Cancer.

Sterlacci W.,University Teaching Hospital Feldkirch | Wolf D.,Innsbruck Medical University | Savic S.,University of Basel | Hilbe W.,Innsbruck Medical University | And 4 more authors.
Human Pathology | Year: 2012

The tumor microenvironment comprises various cellular components and associated subcellular molecules with antitumor and protumor effects. Because respective targeted treatment strategies are arising, it is important to characterize the exact role of these parameters. This study provides a comprehensive analysis of key immunologic factors in the tumor microenvironment of 383 surgically resected non-small cell lung cancer specimens. CD4, CD8, forkhead box protein P3, transforming growth factor β, Casitas B-cell lymphoma-b, programed death 1, T-cell-restricted intracellular antigen 1, granzyme B, mast cell tryptase, and stromal cell-derived factor 1 were analyzed by immunohistochemistry using a standardized tissue microarray platform. Extensive clinical data enabled detailed clinicopathologic correlations over a postoperative follow-up period of 15 years. Among the immunologic variables focused on, transforming growth factor β expression was the only prognostically relevant factor. Transforming growth factor β was more frequently expressed in adenocarcinoma as compared with other histologic subtypes. Expression of transforming growth factor β in tumor-infiltrating lymphocytes or in tumor cells was associated with significantly reduced postoperative survival time especially in patients with squamous cell carcinoma (P =.035 and P =.046, respectively). In these patients, the amount of transforming growth factor β-positive tumor-infiltrating lymphocytes represented the only independent immunologic parameter with prognostic significance by multivariat analysis (P =.021; hazard ratio, 2.602; 95% confidence interval, 1.159-5.844). These results should help to identify patients who are most suitable for therapeutic strategies aiming to block the transforming growth factor β signaling pathway. © 2012 Elsevier Inc. All rights reserved.

Lass-Florl C.,Innsbruck Medical University | Mutschlechner W.,Innsbruck Medical University | Aigner M.,Innsbruck Medical University | Grif K.,Innsbruck Medical University | And 15 more authors.
Journal of Clinical Microbiology | Year: 2013

Prospective studies addressing the clinical value of broad-range PCR using the internal transcribed spacer region (ITS) for diagnosis of microscopy-negative fungal infections in nonselected patient populations are lacking. We first assessed the diagnostic performance of ITS rRNA gene PCR compared with that of routine microscopic immunofluorescence examination. Second, we addressed prospectively the impact and clinical value of broad-range PCR for the diagnosis of infections using samples that tested negative by routine microscopy; the corresponding patients' data were evaluated by detailed medical record reviews. Results from 371 specimens showed a high concordance of>80% for broad-range PCR and routine conventional methods, indicating that the diagnostic performance of PCR for fungal infections is comparable to that of microscopy, which is currently considered part of the "gold standard." In this prospective study, 206 specimens with a negative result on routine microscopy were analyzed with PCR, and patients' clinical data were reviewed according to the criteria of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. We found that broad-range PCR showed a sensitivity, specificity, positive predictive value, and negative predictive value of 57.1%, 97.0%, 80%, and 91.7%, respectively, for microscopy-negative fungal infections. This study defines a possible helpful role of broad-range PCR for diagnosis of microscopy-negative fungal infections in conjunction with other tests. Copyright © 2013, American Society for Microbiology. All Rights Reserved.

Fuchs D.,Innsbruck Medical University | Jamnig H.,Hospital Natters | Heininger P.,Hospital Natters | Klieber M.,Innsbruck Medical University | And 6 more authors.
Journal of Breath Research | Year: 2012

Isoprene (2-methylbuta-1,3-diene) represents a precursor molecule of isoprenoids (steroids, terpens), and available data suggest that isoprene is related to cholesterol biosynthesis. Breath concentrations of isoprene have been reported to be altered in a number of clinical conditions. However, the physiological meaning of isoprene changes has not yet been established. Utilizing proton-transfer-mass spectroscopy, we analyzed isoprene concentrations (m/z 69, tentatively identified as isoprene) in breath samples in Tedlar bags collected from 79 lung cancer patients (23 females, 56 males). Results were compared to the concentrations of immune activation marker neopterin (ELISA, BRAHMS, Hennigsdorf, Germany), lipid parameters (routine enzymology) and C-reactive protein (CRP). Isoprene concentrations were median 92.5 ppb (25th-75th percentile: 79-131 ppb). There was no relationship with staging, grading or age, but isoprene concentrations correlated significantly with total cholesterol (rs = 0.281, p < 0.01) and LDL cholesterol (rs = 0.236, p < 0.05). There was no significant relationship between exhaled isoprene concentrations and HDL cholesterol (rs = 0.048), triglycerides (rs = 0.164) and CRP (rs = -0.115; all not significant). A significant inverse correlation existed between isoprene and neopterin concentrations (rs = -0.215, p < 0.05); the latter also correlated with total cholesterol (rs = -0.343, p = 0.001), HDL cholesterol (rs = -0.273, p = 0.01), LDL cholesterol (rs = -0.236, p < 0.05) and CRP (rs = 0.230, p < 0.05) but not with triglycerides (rs = 0.035, not significant). Results suggest that immune activation might play a role in the decline of isoprene which is probably related to lipid metabolic changes. Interestingly, similar relationships between elevated neopterin and decreased lipid concentrations have been reported earlier in other clinical conditions, e.g. in patients with HIV-1 infection. © 2012 IOP Publishing Ltd.

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