Markus Loeffler

University of Leipzig, Leipzig, Saxony, Germany

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Publications (369)2092.42 Total impact

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    ABSTRACT: The 'Fragebogen zum Essverhalten' (FEV) is the German version of the Three-factor-Eating-Questionnaire (TFEQ). This questionnaire covers three domains of eating behaviour ('cognitive restraint', 'disinhibition' and 'hunger') as well as common problems (e.g. craving for sweets). So far, there is a lack of normative data of the FEV especially for the middle-aged and older population. Aim of this study therefore was to provide age- and gender-specific norms of the FEV for the general population aged 40-79 years. We studied 3,144 participants of the ongoing large community-based Leipzig Research Center for Civilization Diseases (LIFE) Health Care Study. We provided age- (four age groups: 40-49, 50-59, 60-69, and 70-79 years) and gender-specific percentile ranks and T-scores for the three domains of the FEV as well as age- and gender-specific frequencies of the common problems in eating behaviour. Females scored significantly higher than males in all three domains of the FEV (p<0.001). Older individuals showed significantly higher mean scores than the younger ones in the domain of cognitive restraint, but lower mean scores in disinhibition and hunger (p<0.001). 45.1% of the males and 69.9% of the females reported specific problems in eating. The main problem in both genders was craving for sweets (38.6%). Eating in response to stress was mostly reported in younger individuals. The present study offers current normative data for the FEV in the middle-aged and older general population that can be applied in clinical and non-clinical settings. Information on eating behaviour can be helpful in understanding body weight modulation, and thus, may help to improve interventive and preventive programs for overweight, obesity, and eating disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Appetite 04/2015; DOI:10.1016/j.appet.2015.04.044 · 2.52 Impact Factor
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    ABSTRACT: Cerebral gliomas of World Health Organization (WHO) grade II and III represent a major challenge in terms of histological classification and clinical management. Here, we asked whether large-scale genomic and transcriptomic profiling improves the definition of prognostically distinct entities. We performed microarray-based genome- and transcriptome-wide analyses of primary tumor samples from a prospective German Glioma Network cohort of 137 patients with cerebral gliomas, including 61 WHO grade II and 76 WHO grade III tumors. Integrative bioinformatic analyses were employed to define molecular subgroups, which were then related to histology, molecular biomarkers, including isocitrate dehydrogenase 1 or 2 (IDH1/2) mutation, 1p/19q co-deletion and telomerase reverse transcriptase (TERT) promoter mutations, and patient outcome. Genomic profiling identified five distinct glioma groups, including three IDH1/2 mutant and two IDH1/2 wild-type groups. Expression profiling revealed evidence for eight transcriptionally different groups (five IDH1/2 mutant, three IDH1/2 wild type), which were only partially linked to the genomic groups. Correlation of DNA-based molecular stratification with clinical outcome allowed to define three major prognostic groups with characteristic genomic aberrations. The best prognosis was found in patients with IDH1/2 mutant and 1p/19q co-deleted tumors. Patients with IDH1/2 wild-type gliomas and glioblastoma-like genomic alterations, including gain on chromosome arm 7q (+7q), loss on chromosome arm 10q (-10q), TERT promoter mutation and oncogene amplification, displayed the worst outcome. Intermediate survival was seen in patients with IDH1/2 mutant, but 1p/19q intact, mostly astrocytic gliomas, and in patients with IDH1/2 wild-type gliomas lacking the +7q/-10q genotype and TERT promoter mutation. This molecular subgrouping stratified patients into prognostically distinct groups better than histological classification. Addition of gene expression data to this genomic classifier did not further improve prognostic stratification. In summary, DNA-based molecular profiling of WHO grade II and III gliomas distinguishes biologically distinct tumor groups and provides prognostically relevant information beyond histological classification as well as IDH1/2 mutation and 1p/19q co-deletion status.
    Acta Neuropathologica 03/2015; DOI:10.1007/s00401-015-1409-0 · 9.78 Impact Factor
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    ABSTRACT: Background Reference intervals for leukocyte subsets from peripheral blood are helpful for the understanding of disease states and therapy effects. Methods We performed in-depth immunophenotyping for 608 healthy German adults from the Leipzig region from 40 to 79 years by 10-color flow cytometry (FCM) to gain reference information for various leukocyte subsets including subsets of granulocytes, monocytes and lymphocytes. Results First, we derived gender- and age-specific reference intervals for males and females from 40 to 59 and from 60 to 79 years, respectively. Second, we further investigated the influence of gender and age on leukocyte counts. We found significantly higher cell counts for monocytes (p<.001) and NK cells (p<.001) in men, whereas women had higher counts for B cells (p<.001), Th cells (p<.001) and regulatory T cells (p=.008). Furthermore, with increasing age, a decrease in Tc cells (about 8% within five years) and an increase in NK cells (less than 4% within five years) were observed. Conclusion In future research, it should be investigated whether these are real ageing effects that can be confirmed in longitudinal studies. Furthermore, it is important to understand if the Tc cell count drop is functionally compensated by the increase of NK cells. This article is protected by copyright. All rights reserved. Copyright © 2015 Clinical Cytometry Society.
    Cytometry Part B Clinical Cytometry 02/2015; DOI:10.1002/cyto.b.21234 · 2.28 Impact Factor
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    ABSTRACT: Prognostically-relevant risk factors in patients with diffuse large B-cell lymphoma (DLBCL) have predominantly been evaluated in elderly populations. We tested whether previously described risk factors are also valid in younger, poor-prognosis DLBCL patients. Paraffin-embedded samples from 112 patients with de novo DLBCL, enrolled in the R-MegaCHOEP trial of the German High Grade Non-Hodgkin Lymphoma Study Group (DSHNHL) were investigated using immunohistochemistry (MYC, FOXP1, LMO2, GCET1, CD5, CD10, BCL2, BCL6, IRF4/MUM1) and fluorescence in situ hybridization (MYC, BCL2, BCL6). MYC, BCL2 and BCL6 breaks occurred in 14%, 21% and 31%, respectively. In the majority of cases, MYC was simultaneously rearranged with BCL2 and/or BCL6. The adverse impact of MYC rearrangements was confirmed, but the sole presence of BCL2 breaks emerged as a novel prognostic marker associated with inferior overall survival (OS) (p=0.002). Combined over-expression of MYC and BCL2 showed only limited association with inferior OS. All immunohistochemical cell of origin (COO) classifiers applied failed to predict survival time. DLBCL tumors with significant proportion of immunoblastic and/or immunoblastic-plasmacytoid cells had inferior OS, independently from from BCL2 break. Younger, poor-prognosis DLBCL patients, therefore, display different biological risk factors compared to an elderly population, with BCL2 translocations emerging as a powerful negative prognostic marker.Leukemia accepted article preview online, 17 February 2015. doi:10.1038/leu.2015.43.
    Leukemia 02/2015; DOI:10.1038/leu.2015.43 · 9.38 Impact Factor
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    ABSTRACT: Background Although the growth-factor G-CSF is widely used to prevent granulotoxic side effects of cytotoxic chemotherapies, its optimal use is still unknown since treatment outcome depends on many parameters such as dosing and timing of chemotherapies, pharmaceutical derivative of G-CSF used and individual risk factors. We showed in the past that a pharmacokinetic and ¿dynamic model of G-CSF and human granulopoiesis can be used to predict the performance of yet untested G-CSF schedules. However, only a single chemotherapy was considered so far.In the present paper, we propose a comprehensive model of chemotherapy toxicity and combine it with our cell kinetic model of granulopoiesis. Major assumptions are: proportionality of cell numbers and cell loss, delayed action of chemotherapy, drug, drug-dose and cell stage specific toxicities, no interaction of drugs and higher toxicity of drugs at the first time of application. Correspondingly, chemotherapies can be characterized by a set of toxicity parameters which can be estimated by fitting the predictions of our model to clinical time series data of patients under therapy. Data were either extracted from the literature or were received from cooperating clinical study groups.ResultsModel assumptions proved to be feasible in explaining granulotoxicity of 10 different chemotherapeutic drugs or drug-combinations applied in 33 different schedules with and without G-CSF. Risk groups of granulotoxicity were traced back to differences in toxicity parameters.Conclusion We established a comprehensive model of combined G-CSF and chemotherapy action in humans which allows us to predict and compare the outcome of alternative G-CSF schedules. We aim to apply the model in different clinical contexts to optimize and individualize G-CSF treatment.
    BMC Systems Biology 12/2014; 8(1):5. DOI:10.1186/s12918-014-0138-7 · 2.85 Impact Factor
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    ABSTRACT: Objective: To test for a possible effect of the apolipoprotein E epsilon 4 (APOE ε4) allele on memory performance and executive functioning (EF) in cognitively intact elderly. Method: The authors studied 202 randomly selected and cognitively intact older adults (65+ years) of the Leipzig Research Center for Civilization Diseases Health Care Study. Intact global cognitive functioning was defined using a Mini-Mental Status Examination (MMSE) score ≥28. Performance in memory was assessed with the CERAD Word List and Constructional Praxis Recall, performance in EF with the Trail Making Test Part B (TMT-B). Multivariable linear regressions were used to evaluate the association between cognitive performance and APOE status, controlled for covariates. Results: Among the cognitively intact older adults, 21.3% (n = 43) were carriers of the APOE ε4 allele. Carriers did not differ significantly from noncarriers in terms of age, gender, intelligence level, or performance in memory but showed a significantly lower TMT-B performance as a measure of EF (TMT-B M time/SD = 105.6/36.2 vs. 91.9/32.7 s; Mann-Whitney U = 4,313.000; p = .009). The association between lower TMT-B performance and APOE ε4 genotype remained significant in multivariable linear regression analysis. Similar findings were found for the subsample of those 78 elderly, who reached a perfect MMSE-score of 30. Conclusions: A lower EF performance in cognitively intact older APOE ε4 allele carriers might be related to an early Alzheimer's dementia (AD) prodrome. In this case, a stronger focus on first subtle changes in EF may help to improve early AD detection in those being at genetic risk. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
    Neuropsychology 11/2014; DOI:10.1037/neu0000147 · 3.43 Impact Factor
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    ABSTRACT: The prognosis of glioblastoma, the most malignant type of glioma, is still poor, with only a minority of patients showing long-term survival of more than three years after diagnosis. To elucidate the molecular aberrations in glioblastomas of long-term survivors, we performed genome- and/or transcriptome-wide molecular profiling of glioblastoma samples from 94 patients, including 28 long-term survivors with >36 months overall survival (OS), 20 short-term survivors with <12 months OS, and 46 patients with intermediate OS. Integrative bioinformatic analyses were used to characterize molecular aberrations in the distinct survival groups considering established molecular markers such as isocitrate dehydrogenase 1 or 2 (IDH1/2) mutations, and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Patients with long-term survival were younger and more often had IDH1/2-mutant and MGMT-methylated tumors. Gene expression profiling revealed over-representation of a distinct (proneural-like) expression signature in long-term survivors that was linked to IDH1/2 mutation. However, IDH1/2-wildtype glioblastomas from long-term survivors did not show distinct gene expression profiles and included proneural, classical and mesenchymal glioblastoma subtypes. Genomic imbalances also differed between IDH1/2-mutant and IDH1/2-wildtype tumors, but not between survival groups of IDH1/2-wildtype patients. Thus, our data support an important role for MGMT promoter methylation and IDH1/2 mutation in glioblastoma long-term survival and corroborate the association of IDH1/2 mutation with distinct genomic and transcriptional profiles. Importantly, however, IDH1/2-wildtype glioblastomas in our cohort of long-term survivors lacked distinctive DNA copy number changes and gene expression signatures, indicating that other factors might have been responsible for long survival in this particular subgroup of patients. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 10/2014; 135(8). DOI:10.1002/ijc.28836 · 5.01 Impact Factor
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    ABSTRACT: Follicular lymphoma (FL) with a t(14;18) is a B-cell neoplasm clinically characterized by multiple recurrencies. In order to investigate the clonal evolution of this lymphoma we studied paired primary and relapse tumor samples from 33 patients with recurrent non-transformed t(14;18)-positive FL. We reconstruct phylogenetic trees of the evolution by taking advantage of the AID-mediated somatic hypermutation (SHM) active in the germinal center reaction using sequences of the clonal VHDHJH rearrangements of the immunoglobulin heavy chain (IGH) locus. Mutational analysis of the IGH locus showed evidence for ongoing somatic mutation and for counter-selection of mutations affecting the BCR conformation during tumor evolution. We further followed evolutionary divergence by targeted sequencing of gene loci affected by aberrant SHM as well as of known driver genes of lymphomagenesis, and by array based genome-wide chromosomal imbalance and DNA methylation analysis. We observed a wide spectrum of evolutionary patterns ranging from almost no evolution to divergent evolution within recurrent non-transformed t(14;18) FL. Remarkably, we observed a correlation of the magnitude of evolutionary divergence across all genetic and epigenetic levels suggesting co-evolution. The distribution of coding mutations in driver genes and the correlation with SHM suggest CREBBP and AID to be potential modifiers of genetic and epigenetic co-evolution in FL.Leukemia accepted article preview online, 16 July 2014; doi:10.1038/leu.2014.209.
    Leukemia 07/2014; 29(2). DOI:10.1038/leu.2014.209 · 9.38 Impact Factor
  • Leukemia 07/2014; DOI:10.1038/leu.2014.213 · 9.38 Impact Factor
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    ABSTRACT: Molecular changes associated with the progression of glioblastoma after standard radiochemotherapy remain poorly understood. We compared genomic profiles of 27 paired primary and recurrent IDH1/2 wild-type glioblastomas by genome-wide array-based comparative genomic hybridization. By bioinformatic analysis, primary and recurrent tumor profiles were normalized and segmented, chromosomal gains and losses identified taking the tumor cell content into account, and difference profiles deduced. Seven of 27 (26%) pairs lacked DNA copy number differences between primary and recurrent tumors (equal pairs). The recurrent tumors in 9/27 (33%) pairs contained all chromosomal imbalances of the primary tumors plus additional ones, suggesting a sequential acquisition of and/or selection for aberrations during progression (sequential pairs). In 11/27 (41%) pairs, the profiles of primary and recurrent tumors were divergent, i.e., the recurrent tumors contained additional aberrations but had lost others, suggesting a polyclonal composition of the primary tumors and considerable clonal evolution (discrepant pairs). Losses on 9p21.3 harboring the CDKN2A/B locus were significantly more common in primary tumors from sequential and discrepant (nonequal) pairs. Nonequal pairs showed ten regions of recurrent genomic differences between primary and recurrent tumors harboring 46 candidate genes associated with tumor recurrence. In particular, copy numbers of genes encoding apoptosis regulators were frequently changed at progression. In summary, approximately 25% of IDH1/2 wild-type glioblastoma pairs have stable genomic imbalances. In contrast, approximately 75% of IDH1/2 wild-type glioblastomas undergo further genomic aberrations and alter their clonal composition upon recurrence impacting their genomic profile, a process possibly facilitated by 9p21.3 loss in the primary tumor. © 2014 Wiley Periodicals, Inc.
    Genes Chromosomes and Cancer 07/2014; 53(7). DOI:10.1002/gcc.22169 · 3.84 Impact Factor
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    ABSTRACT: The prognosis of glioblastoma, the most malignant type of glioma, is still poor, with only a minority of patients showing long-term survival of more than three years after diagnosis. We aimed to elucidate the poorly characterized molecular aberrations in glioblastomas of longterm survivors.
    Neuro-Oncology 07/2014; 16 Suppl 3:iii46-iii47. DOI:10.1093/neuonc/nou209.19 · 5.29 Impact Factor
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    ABSTRACT: Carriers of mismatch repair (MMR) gene mutations have a high lifetime risk for colorectal and endometrial cancers, as well as other malignancies. As mutation analysis to detect these patients is expensive and time-consuming, clinical criteria and tumour-tissue analysis are widely used as pre-screening methods. The aim of our study was to evaluate the performance of commonly applied clinical criteria (the Amsterdam I and II Criteria, and the original and revised Bethesda Guidelines) and the results of tumour-tissue analysis in predicting MMR gene mutations. We analyzed 3671 families from the German HNPCC Registry and divided them into nine mutually exclusive groups with different clinical criteria. A total of 680 families (18.5%) were found to have a pathogenic MMR gene mutation. Among all 1284 families with microsatellite instability-high (MSI-H) colorectal cancer, the overall mutation detection rate was 53.0%. Mutation frequencies and their distribution between the four MMR genes differed significantly between clinical groups (p<0.001). The highest frequencies were found in families fulfilling the Amsterdam Criteria (46.4%). Families with loss of MSH2 expression had higher mutation detection rates (69.5%) than families with loss of MLH1 expression (43.1%). MMR mutations were found significantly more often in families with at least one MSI-H small-bowel cancer (p<0.001). No MMR mutations were found among patients under 40-years-old with only colorectal adenoma. Familial clustering of Lynch syndrome-related tumours, early age of onset, and familial occurrence of small-bowel cancer were clinically relevant predictors for Lynch syndrome. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 07/2014; 135(1). DOI:10.1002/ijc.28650 · 5.01 Impact Factor
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    ABSTRACT: The pathogenesis of diffuse large B cell lymphomas (DLBCL) is only partly understood. We analyzed 148 DLBCL by single nucleotide polymorphism (SNP)-chips to characterize genomic imbalances. Seventy-nine cases were of the germinal center B-cell like (GCB) type of DLBCL, 49 of the activated B-cell like (ABC) subtype and 20 were unclassified DLBCL. Twenty-four regions of recurrent genomic gains and 38 regions of recurrent genomic losses were identified over the whole cohort, with a median of 25 imbalances per case for ABC-DLBCL and 19 per case for GCB-DLBCL. Several recurrent copy number changes showed differential frequencies in the GCB- and ABC-DLBCL subgroups, including gains of HDAC7A predominantly in GCB-DLBCL (38% of cases) and losses of BACH2 and CASP8AP2 predominantly in ABC-DLBCL (35%), hinting at disparate pathogenetic mechanisms in these entities. Correlating gene expression and copy number revealed a strong gene dosage effect in all tumors, with 34% of probesets showing a concordant expression change in affected regions. Two new potential tumor suppressor genes emerging from the analysis, CASP3 and IL5RA, were sequenced in 10 and 16 candidate cases, respectively. However, no mutations were found, pointing to a potential haploinsufficiency effect of these genes, considering their reduced expression in cases with deletions. This work thus describes differences and similarities in the landscape of genomic aberrations in the DLBCL subgroups in a large collection of cases, confirming already known targets, but also discovering novel copy number changes with possible pathogenetic relevance. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 07/2014; DOI:10.1002/ijc.29072 · 5.01 Impact Factor
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    ABSTRACT: The intestinal epithelium is permanently renewed during homoeostasis. Stable function of its stem cells is ensured by interaction with a specific tissue compartment, the so-called 'intestinal stem cell niche'. The essential regulatory principles of this niche are still under debate. In order to approach this question, we have introduced several single cell-based models of the spatiotemporal stem cell organization in murine intestinal crypts and organoids. In the present article, we provide a brief review of these models. Starting with pedigree models reproducing cell kinetics, over the last few years, we have successively improved these models by refining the biomechanical representation of the system and introducing environmentally controlled lineage specification. Our current models of the intestinal crypt are capable of linking a broad spectrum of experimental observations encompassing spatially confined cell proliferation, directed cell migration, multiple cell lineage decisions and clonal competition. Our model of intestinal organoids provides for the first time a description of a self-organizing intestinal stem cell niche. It suggests that this niche is established by secretory activity of specified cells and in addition requires a defined spatial organization, which sensitively depends on tissue biomechanics.
    Biochemical Society Transactions 06/2014; 42(3):671-7. DOI:10.1042/BST20140015 · 3.24 Impact Factor
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    ABSTRACT: Background The level of mental demands in the workplace is rising. The present study investigated whether and how mental demands at work are associated with cognitive functioning in the general population. Methods The analysis is based on data of the Health Study of the Leipzig Research Centre for Civilization Disease (LIFE). 2,725 participants aged 40–80 years underwent cognitive testing (Trail-Making Test, Verbal Fluency Test) and provided information on their occupational situation. Participants over the age of 65 years additionally completed the Mini-Mental State Examination. Mental demands at work were rated by a standardized classification system (O*NET). The association between mental demands and cognitive functioning was analyzed using Generalized Linear Modeling (GENLIN) adjusted for age, gender, self-regulation, working hour status, education, and health-related factors. Results Univariate as well as multivariate analyses demonstrated significant and highly consistent effects of higher mental demands on better performance in cognitive testing. The results also indicated that the effects are independent of education and intelligence. Moreover, analyses of retired individuals implied a significant association between high mental demands at work of the job they once held and a better cognitive functioning in old age. Conclusions In sum, our findings suggest a significant association between high mental demands at work and better cognitive functioning. In this sense, higher levels of mental demands – as brought about by technological changes in the working environment – may also have beneficial effects for the society as they could increase cognitive capacity levels and might even delay cognitive decline in old age.
    Journal of Occupational Medicine and Toxicology 05/2014; 9:23. DOI:10.1186/1745-6673-9-23 · 1.23 Impact Factor
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    ABSTRACT: Background Haematotoxicity of conventional chemotherapies often results in delays of treatment or reduction of chemotherapy dose. To ameliorate these side-effects, patients are routinely treated with blood transfusions or haematopoietic growth factors such as erythropoietin (EPO) or granulocyte colony-stimulating factor (G-CSF). For the latter ones, pharmaceutical derivatives are available, which differ in absorption kinetics, pharmacokinetic and -dynamic properties. Due to the complex interaction of cytotoxic effects of chemotherapy and the stimulating effects of different growth factor derivatives, optimal treatment is a non-trivial task. In the past, we developed mathematical models of thrombopoiesis, granulopoiesis and erythropoiesis under chemotherapy and growth-factor applications which can be used to perform clinically relevant predictions regarding the feasibility of chemotherapy schedules and cytopenia prophylaxis with haematopoietic growth factors. However, interactions of lineages and growth-factors were ignored so far. Results To close this gap, we constructed a hybrid model of human granulopoiesis and erythropoiesis under conventional chemotherapy, G-CSF and EPO applications. This was achieved by combining our single lineage models of human erythropoiesis and granulopoiesis with a common stem cell model. G-CSF effects on erythropoiesis were also implemented. Pharmacodynamic models are based on ordinary differential equations describing proliferation and maturation of haematopoietic cells. The system is regulated by feedback loops partly mediated by endogenous and exogenous EPO and G-CSF. Chemotherapy is modelled by depletion of cells. Unknown model parameters were determined by fitting the model predictions to time series data of blood counts and cytokine profiles. Data were extracted from literature or received from cooperating clinical study groups. Our model explains dynamics of mature blood cells and cytokines after growth-factor applications in healthy volunteers. Moreover, we modelled 15 different chemotherapeutic drugs by estimating their bone marrow toxicity. Taking into account different growth-factor schedules, this adds up to 33 different chemotherapy regimens explained by the model. Conclusions We conclude that we established a comprehensive biomathematical model to explain the dynamics of granulopoiesis and erythropoiesis under combined chemotherapy, G-CSF, and EPO applications. We demonstrate how it can be used to make predictions regarding haematotoxicity of yet untested chemotherapy and growth-factor schedules.
    Theoretical Biology and Medical Modelling 05/2014; 11(1):24. DOI:10.1186/1742-4682-11-24 · 1.27 Impact Factor
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    ABSTRACT: The epidermal growth factor receptor vIII mutant (EGFRvIII) is found in ∼50% of all EGFR-amplified glioblastomas and constitutes a tumor-specific therapeutic target. To assess molecular testing approaches and the prognostic role of EGFRvIII in patients treated according to current standards of care, we compared different EGFRvIII detection methods and correlated EGFRvIII status with outcome in a prospective patient cohort of the German Glioma Network. In total, 184 newly diagnosed glioblastoma patients were investigated for EGFR amplification and for expression of EGFR and EGFRvIII by immunohistochemistry. Further, the EGFRvIII status was additionally studied by multiplex ligation-dependent probe amplification (MLPA) analysis and reverse transcription-PCR (RT-PCR). Immunohistochemistry demonstrated EGFRvIII in 34 of 184 patients (18%). RT-PCR or MLPA analysis detected four additional EGFRvIII-positive patients. Overall, RT-PCR and immunohistochemistry were more sensitive for EGFRvIII detection than MLPA. EGFRvIII status was not associated with progression-free and overall survival. EGFRvIII also had no prognostic significance in the subgroup of patients who were free from progression after concomitant radiochemotherapy and thus would be eligible for the ongoing ACT IV EGFRvIII vaccination trial. Age, extent of resection and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status appeared to be less prognostic in EGFRvIII-positive patients. Thus, EGFRvIII positivity is not a major negative prognostic factor in glioblastoma patients treated according to current standards of care. Data from phase II EGFRvIII-targeted vaccination trials compare favorably with the present contemporary results, supporting the further exploration of EGVRvIII vaccination in newly diagnosed glioblastoma.
    International Journal of Cancer 05/2014; 134(10). DOI:10.1002/ijc.28576 · 5.01 Impact Factor
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    ABSTRACT: A proof-of-principle study was accomplished assessing the descriptive potential of two simple geometric measures (shape descriptors) applied to sets of segmented glands within images of 125 prostate cancer tissue sections. Respective measures addressing glandular shapes were (i) inverse solidity and (ii) inverse compactness. Using a classifier based on logistic regression, Gleason grades 3 and 4/5 could be differentiated with an accuracy of approx. 95%. Results suggest not only good discriminatory properties, but also robustness against gland segmentation variations. False classifications in part were caused by inadvertent Gleason grade assignments, as a-posteriori re-inspections had turned out.
    Proceedings of SPIE - The International Society for Optical Engineering 02/2014; DOI:10.1117/12.2043225 · 0.20 Impact Factor
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    ABSTRACT: Adult brainstem gliomas are rare primary brain tumors (<2% of gliomas). The goal of this study was to analyze clinical, prognostic and therapeutic factors in a large series of histologically proven brainstem gliomas. Between 1997 and 2007, 104 patients with a histologically proven brainstem glioma were retrospectively analyzed. Data about clinical course of disease, neuropathological findings and therapeutic approaches were analyzed. The median age at diagnosis was 41 years (range 18-89 years), median KPS before any operative procedure was 80 (range 20-100) and median survival for the whole cohort was 18.8 months. Histopathological examinations revealed 16 grade I, 31 grade II, 42 grade III and 14 grade IV gliomas. Grading was not possible in 1 patient. Therapeutic concepts differed according to the histopathology of the disease. Median overall survival for grade II tumors was 26.4 months, for grade III tumors 12.9 months and for grade IV tumors 9.8 months. On multivariate analysis the relative risk to die increased with a KPS < 70 by factor 6.7, with grade III/IV gliomas by the factor 1.8 and for age >= 40 by the factor 1.7. External beam radiation reduced the risk to die by factor 0.4. Adult brainstem gliomas present with a wide variety of neurological symptoms and postoperative radiation remains the cornerstone of therapy with no proven benefit of adding chemotherapy. Low KPS, age >= 40 and higher tumor grade have a negative impact on overall survival.
    BMC Cancer 02/2014; 14(1):115. DOI:10.1186/1471-2407-14-115 · 3.32 Impact Factor

Publication Stats

18k Citations
2,092.42 Total Impact Points

Institutions

  • 1995–2015
    • University of Leipzig
      • Institute of Medical Informatics, Statistics and Epidemiology
      Leipzig, Saxony, Germany
    • The Christie NHS Foundation Trust
      Manchester, England, United Kingdom
  • 2014
    • University of Zurich
      • Division of Neuropsychology
      Zürich, Zurich, Switzerland
  • 2013
    • Heinrich-Heine-Universität Düsseldorf
      • Institute of Neuropathology
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2012
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
  • 2009–2010
    • Asklepios Klinik St. Georg
      Hamburg, Hamburg, Germany
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
    • Ludwig-Maximilian-University of Munich
      • Faculty of Medicine
      München, Bavaria, Germany
  • 1985–2009
    • University of Cologne
      • • Department of Internal Medicine
      • • Institute of Medical Statistics, Epidemiology and Computer Science
      Köln, North Rhine-Westphalia, Germany
  • 2008
    • McMaster University
      Hamilton, Ontario, Canada
  • 2005–2008
    • Friedrich-Schiller-University Jena
      • Department of Anaesthesiology and Intensive Care Medicine
      Jena, Thuringia, Germany
    • Technische Universität Dresden
      Dresden, Saxony, Germany
    • Max Planck Institute for Mathematics in the Sciences
      Leipzig, Saxony, Germany
  • 2006
    • Charité Universitätsmedizin Berlin
      • Institute of Pathology
      Berlin, Land Berlin, Germany
  • 2001
    • Université de Technologie de Compiègne
      Compiègne, Picardie, France
    • Institut de Cancérologie Gustave Roussy
      • Department of Radiotherapy
      Villejuif, Île-de-France, France
    • University of Toronto
      Toronto, Ontario, Canada
  • 2000–2001
    • French National Centre for Scientific Research
      • Institute for Molecular and Cellular Biology (IBMC)
      Lutetia Parisorum, Île-de-France, France
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1998–2000
    • Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V.
      Leipzig, Saxony, Germany
  • 1999
    • University of Innsbruck
      • Institute of Biochemistry
      Innsbruck, Tyrol, Austria
  • 1990
    • Bergische Universität Wuppertal
      Wuppertal, North Rhine-Westphalia, Germany
  • 1989–1990
    • University of Groningen
      Groningen, Groningen, Netherlands