Thomas Schneider

Otto-von-Guericke-Universität Magdeburg, Magdeburg, Saxony-Anhalt, Germany

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Publications (30)84.86 Total impact

  • J H Tapia-Pérez · R Zilke · T Schneider
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    ABSTRACT: We analyzed the relationship between statin continuation or discontinuation and outcome after spontaneous intracerebral hemorrhage (ICH). From a databank with 447 data sets, we selected patients with hypertensive or anticoagulation--related hemorrhage (volume 10-250 mL). Of 323 patients available for analysis, 63 were taking statins. This group was divided into those who discontinued (n = 18) or continued therapy (n = 45). Statin users were matched by age, sex, and National Institutes of Health Stroke Scale (NIHSS) status in 1:4 ratio to nonusers. Mortality after 30 days, 3 months, and 12 months was analyzed using Cox regression. The Glasgow Outcome Scale (GOS) scores at discharge and at least 6 months after ICH onset were recorded. baseline characteristics of patients with continued and discontinued statin use were not different. Patients who discontinued statin therapy were very similar to their matched--cases; however, the control--matched cases for patients who continued statins had lower incidences of diabetes mellitus and cardiovascular diseases. In multivariate analysis, statin discontinuation was associated with a 6.9--fold (95% CI 2.09-23.13, p = 0.002) higher risk of death within the first 30 days after ICH onset compared to patients who continued therapy. Patients who discontinued also had an increased risk of death within 30 days of ICH onset compared to their matched--controls (HR = 3.87, 95% CI 1.69-8.87, p = 0.001). The continued statin group displayed only a slight reduction in mortality risk after 3 month (HR = 0.67, 95% CI 0.37-1.21, p = 0.19) compared to matched--controls, but the chance to be discharge with a better neurological ((NIHSS <15) was increased among patients with continued statin use (51% versus 33%, p=0.02). The continued use of statins after an ICH led to a small mortality reduction, whereas discontinuing statins might be related to increased mortality. Randomized clinical trials are needed to define the role of statin use in the management of acute ICH.
    Journal of neurosurgical sciences 12/2014; · 0.78 Impact Factor
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    ABSTRACT: Background Granular cell astrocytomas (GCAs) are rarely encountered aggressive glial neoplasms. Treatment options comprise surgery, radiotherapy, and chemotherapy. Due to the small number of cases, a standard therapeutic regimen for GCA does not exist. Material and Methods We report on the case of a 64-year-old woman with GCA subjected to tumor biopsy followed by radiochemotherapy with temozolomide. We provide clinical, histopathologic, and magnetic resonance imaging findings as well as a complete follow-up. To assess the relation of age, gender, time of publication, and different treatment options with survival we performed log-rank tests and calculated Cox regression models and hazard ratios in data from all available reports on GCA. Results A significant difference in survival rates in favor of adjuvant therapy (radiotherapy or radiochemotherapy) at 12 months was found. Age > 70 years at the time of diagnosis had a significantly unfavorable impact on survival at 12 months. Although not statistically significant, a tendency toward higher probability of survival at 12 months was found in cases reported after 2002. In surgically treated patients, we could not find a significant impact of extent of resection on survival. A significant impact of gender on survival was not found. Conclusion Adjuvant therapy is significantly related to a higher probability of survival at 12 months and may therefore be recommended for patients with a GCA. Further analysis of these rare neoplasms is warranted.
    07/2014; 76(01). DOI:10.1055/s-0034-1382781
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    ABSTRACT: Letter to the editor: abstract no available.
  • J H Tapia-Pérez · S Gehring · R Zilke · T Schneider
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    ABSTRACT: Spontaneous intracerebral hemorrhage (ICH) can be a devastating event. Increased glucose levels in the plasma may be related to poor outcomes; however, the precise association remains unclear. We retrospectively assessed 116 patients with hypertensive ICH. Glucose level in the plasma was assessed at days 0, 1, and 3. Outcome variables were mortality within 7 and 30days and the National Institutes of Health Stroke Scale (NIHSS) score at day 14 after ICH onset. Twenty deaths had occurred by day 7, and the 30-day mortality rate was 31.9%. Hyperglycemia at day 0 was significantly more common in patients who died within 7days or 30days. Hyperglycemia at day 1 was more common in patients with an NIHSS score >15 on admission and at day 14. No differences in glucose levels were found between diabetic and non-diabetic patients. Among non-diabetic patients, higher glucose levels were related to poorer outcomes (death or an NIHSS score >15). In multivariate analysis, glucose levels >140mg/dL at day 1 were related to the 30-day mortality (hazard ratio=2.65; 95% confidence interval [CI]=1.15-6.12, p=0.02), and glucose levels >160mg/dL at day 1 were associated with an NIHSS score >15 at day 14 (odds ratio=3.08; 95% CI=0.9-10.5, p=0.07). White blood cell counts were directly associated with poorer outcomes and significantly correlated to glucose levels. Initially increased glucose levels and increased levels within 24h of ICH onset were related to poorer outcomes. Altered glucose metabolism may be due to inflammatory cell activation. Further studies are needed to clarify the association between immune activation and glucose metabolism after ICH onset.
    Clinical neurology and neurosurgery 03/2014; 118C:37-43. DOI:10.1016/j.clineuro.2013.12.018 · 1.25 Impact Factor
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    ABSTRACT: Meningiomas are frequent intracranial or spinal neoplasms which recur frequently and can show aggressive clinical behaviour. We elucidated the impact of the integrin inhibitor cilengitide on migration, proliferation and radiosensitization of meningioma cells. We analyzed integrin expression in tissue microarrays of human meningiomas and the anti-meningioma properties of cilengitide in cell cultures, subcutaneous and intracranial nude mouse models by measuring tumor volumes and survival times. αvβ5 was the predominantly expressed integrin heterodimer in meningiomas, while αvβ3 was mainly detected in tumor blood vessels. Application of up to 100µg/ml cilengitide resulted in only mildly reduced proliferation/survival of meningioma cell lines. Effects on cell survival could be enhanced by irradiation. One µg/ml cilengitide was sufficient to significantly inhibit meningioma cell migration and invasion in vitro. A daily dosage of 75 mg/kg did neither affect tumor volumes nor overall survival (p = 0.813, log-rank test), but suppressed brain invasion in a significant fraction of treated animals. A combination of 75 mg/kg cilengitide daily and irradiation (2 x 5 Gy) led to a 67% reduction of MRI estimated tumor volumes in the intracranial model (p<0.01), whereas the corresponding reduction reached by irradiation alone was only 55% (p<0.05). These data show that a monotherapy with cilengitide is not likely to achieve major responses in rapidly growing malignant meningiomas, although brain invasion may be reduced due to the strong anti-migratory properties of the drug. The combination with radiotherapy warrants further attention.
    Clinical Cancer Research 08/2013; 19(19). DOI:10.1158/1078-0432.CCR-12-0299 · 8.19 Impact Factor
  • Benjamin Voellger · Christian Mawrin · Thomas Schneider
    03/2013; DOI:10.1530/endoabs.32.P943
  • J H Tapia-Pérez · R Rupa · R Zilke · S Gehring · B Voellger · T Schneider
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    ABSTRACT: Spontaneous intracerebral hemorrhage (ICH) often represents a devastating event despite maximal therapeutic efforts. Statins are drugs primarily used as cholesterol reducers with several pleiotropic effects that may result in neuroprotection. In this study, we assessed the continued use of statins after acute ICH. From January 2008 to October 2010, we analyzed a retrospective cohort of 178 patients with acute ICH. Patients with head injury, cerebral tumors, hemorrhage after ischemic stroke, and having a National Institute Health Stroke Scale (NIHSS) score of greater than 30 points on admission were excluded. In 29 patients, statins were continued within the first 24 h after onset of ICH and, subsequently, given daily until discharge, whereas 149 nonusers were used as controls. Inpatient mortality, NIHSS, and Glasgow Outcome Score (GOS) at discharge as well as mortality after 10 days, 3 months, and 6 months were recorded as outcomes. Additionally, changes of C-reactive protein (CRP) and white blood cell (WBC) counts, as well as aspartate transaminase and alanine transaminase levels were assessed. Except for the number of hypertensive and diabetic patients, characteristics on admission were similar between both groups. No mortality was observed in statin users, whereas 19 controls (12.7 %) died (p = 0.04) until discharge; after 10 days, 3 months, and 6 months, a similar trend was found. After 6 months, statin use was associated to lower mortality in regression models (OR = 0.32, 95 % CI = 0.11-0.95, p = 0.04). In the same way, statin use was related to NIHSS reduction (-3.53, 95 % CI = -7.59 to 0.42, p = 0.07). In mixed models, changes of WBC counts and CRP levels were associated with statin use. The hepatic enzymes were similar between groups. The continued use of statins after ICH could be associated to early neurological improvement and may reduce mortality within 6 months. Immunomodulation as a pleiotropic effect of statins may represent one of the underlying mechanisms.
    Neurosurgical Review 10/2012; 36(2). DOI:10.1007/s10143-012-0431-0 · 1.86 Impact Factor
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    Laboratory Investigation 12/2011; 91:1766-1776. · 3.83 Impact Factor
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    ABSTRACT: The mitochondrial protein frataxin (FXN) is known to be involved in mitochondrial iron homeostasis and iron-sulfur cluster biogenesis. It is discussed to modulate function of the electron transport chain and production of reactive oxygen species (ROS). FXN loss in neurons and heart muscle cells causes an autosomal-dominant mitochondrial disorder, Friedreich's ataxia. Recently, tumor induction after targeted FXN deletion in liver and reversal of the tumorigenic phenotype of colonic carcinoma cells following FXN overexpression were described in the literature, suggesting a tumor suppressor function. We hypothesized that a partial reversal of the malignant phenotype of glioma cells should occur after FXN transfection, if the mitochondrial protein has tumor suppressor functions in these brain tumors. In astrocytic brain tumors and tumor cell lines, we observed reduced FXN levels compared with non-neoplastic astrocytes. Mitochondrial content (citrate synthase activity) was not significantly altered in U87MG glioblastoma cells stably overexpressing FXN (U87-FXN). Surprisingly, U87-FXN cells exhibited increased cytoplasmic ROS levels, although mitochondrial ROS release was attenuated by FXN, as expected. Higher cytoplasmic ROS levels corresponded to reduced activities of glutathione peroxidase and catalase, and lower glutathione content. The defect of antioxidative capacity resulted in increased susceptibility of U87-FXN cells against oxidative stress induced by H(2)O(2) or buthionine sulfoximine. These characteristics may explain a higher sensitivity toward staurosporine and alkylating drugs, at least in part. On the other hand, U87-FXN cells exhibited enhanced growth rates in vitro under growth factor-restricted and hypoxic conditions and in vivo using tumor xenografts in nude mice. These data contrast to a general tumor suppressor function of FXN but suggest a dual, pro-proliferative but chemosensitizing role in astrocytic tumors.
    Laboratory Investigation 08/2011; 91(12):1766-76. DOI:10.1038/labinvest.2011.130 · 3.83 Impact Factor
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    ABSTRACT: Statins are inhibitors of the cholesterol synthesis pathway with pleiotropic effects, while thiazolidinediones (TDZ) are peroxisomal proliferator activator receptor γ (PPAR-γ) agonists with potent proapoptotic activity. For both groups of substances a cytotoxic effect against several human tumors is presumed. Direct comparison of several statins and TDZ has not been performed on meningioma cells until now. We compared the antiproliferative/cytotoxic effect of five statins, two TDZ, and their combinations on various human meningioma cell lines and nontumorous cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, cell cycle analysis, and caspase-3 assay. Simvastatin (SMV) and its combination with the TDZ pioglitazone (PGZ) turned out to be the most effective treatment. After 96 h the 50% inhibition concentration (IC(50)) of SMV in MTT assays for two more sensitive meningioma cell lines (one benign and one malignant) was below 0.9 μM, while the IC(50) was 2.8 μM or higher for two other meningioma lines. Fluorescence-activated cell sorting (FACS) analysis suggested that MTT results mostly represented cytotoxic rather than antiproliferative effects. Strong caspase-3 induction suggested participation of intrinsic apoptosis in meningioma cell death. In contrast, SMV showed no substantial effects on fibroblasts and astrocytes. Addition of 40 μM PGZ significantly decreased the fraction of clonogenic cells in soft-agar assays, as compared with 2.8 μM SMV alone. Taken together, SMV showed a significant cytotoxic effect against human meningioma cells, which was moderately enhanced by PGZ.
    Journal of Neuro-Oncology 05/2011; 102(3):383-93. DOI:10.1007/s11060-010-0351-1 · 2.79 Impact Factor
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    ABSTRACT: Glioblastoma multiforme is still a tumor with very poor prognosis. Statins are actually used for the treatment of dyslipidemias and thiazolidinediones for improving insulin sensitivity in diabetes. Statins are inhibitors of the cholesterol pathway, while thiazolidinediones are peroxisomal proliferator activator receptor γ (PPAR) agonists. For both, a potent pro-apoptotic activity has been suggested. We compared the antiglioma effect of simvastatin, atorvastatin, lovastatin, pravastatin, rosuvastatin, rosiglitazone, pioglitazone and their combinations at several concentrations on human glioblastoma cell lines U87, U 138, LN 405 and rat RG II. The cytotoxic effect was assessed using a cell proliferation assay after 48 and 144 h. Caspase 3 activity and the addition of isoprenoids and PPAR-y inhibitor GW9662 were assessed. Experiments were as well conducted under hypoxia for 24 h. We demonstrated a significant cytotoxic effect with a combination of statins plus pioglitazone. The effect was observed after 48 h and dramatically increased after 144 h. The combination of 2 types of statins (synthetic and natural) allowed a fivefold dose reduction. Statin effect was reversed with isoprenoids and partially with PPAR-γ antagonists, while thiazolidinediones effect was slightly affected by PPAR-γ antagonists. A marked increase in caspase 3 activity was achieved by combining atorvastatin with lovastatin. Cytotoxicity of the combination of statins and thiazolidinediones did not decrease under hypoxia. The assessed combination of statins with thiazolidinediones shows a synergistic cytotoxic effect against glioblastoma cells in vitro, which could represent a feasible therapeutic schema.
    Cancer Chemotherapy and Pharmacology 12/2010; 67(5):1193-201. DOI:10.1007/s00280-010-1535-2 · 2.57 Impact Factor
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    ABSTRACT: Primary brain tumors are among the ten most common causes of cancer-related death. There is no screening test for them, but timely diagnosis and treatment improve the outcome. Ideally, treatment should be provided in a highly specialized center, but patients reach such centers only on the referral of their primary care physicians or other medical specialists from a wide variety of fields. An up-to-date account of basic knowledge in this area would thus seem desirable, as recent years have seen major developments both in the scientific understanding of these tumors and in clinical methods of diagnosis and treatment. Selective search of the pertinent literature (PubMed and Cochrane Library), including the guidelines of the German Societies of Neurosurgery, Neurology, and Radiotherapy. Modern neuroradiological imaging, in particular magnetic resonance imaging, can show structural lesions at high resolution and provide a variety of biological and functional information, yet it is still no substitute for histological diagnosis. Gross total resection of gliomas significantly improves overall survival. New molecular markers can be used for prognostication. Chemotherapy plays a major role in the treatment of various different kinds of glioma. The median survival, however, generally remains poor, e.g., 14.6 months for glio-blastoma.
    Deutsches Ärzteblatt International 11/2010; 107(45):799-807; quiz 808. DOI:10.3238/arztebl.2010.0799 · 3.61 Impact Factor
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    ABSTRACT: Statins are drugs used to control cholesterol disorders and prevent cardiovascular diseases. Their denominated pleiotropic effects have demonstrated a broad action spectrum that might profit some neurological and neurosurgical diseases. These effects are correlated to dose and kind of statin. We accomplished a systematic review in PubMed and MEDLINE about studies of statins and main neurosurgical diseases. If statins are administered after subarachnoid hemorrhage, a significant lower incidence of vasospasm as well as delayed ischemic deficits and decreased mortality could be found; the results of a large multicenter trial are expected. In other complex diseases as intracerebral hemorrhage or traumatic brain injury, the evidence for positive effects of a treatment with statin increased. Additionally, promising experimental results indicate that high statin doses are able to promote cell death in tumor cells, especially in gliomas. Moreover, experimental and observational studies suggest the ability of statins to modulate the immune system, by that they can reduce incidence and severity of sepsis. The origin of these multiple effects from neuroprotection to tumoral apoptosis is not totally explained so far. Recent data in literature are discussed in this review. More trials in humans are urgently required to finally determine if statins could contribute to the current management of neurosurgical diseases.
    Neurosurgical Review 07/2010; 33(3):259-70; discussion 270. DOI:10.1007/s10143-010-0259-4 · 1.86 Impact Factor
  • Neuropathology and Applied Neurobiology 09/2009; 36(1):86-9. DOI:10.1111/j.1365-2990.2009.01041.x · 4.97 Impact Factor
  • Thomas Schneider
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    ABSTRACT: Antisense oligonucleotides (AON), short oligonucleotides of DNA, which selectively bind to complementary mRNA inside the cytoplasm, can specifically block genes and production of designated proteins. The use of AP12009 against TGF-β2 has been the most frequently studied antisense therapy for brain tumors so far. Further oncogenes e.g. c-Met, RAS or Bcl-2, the growth factors VEGF, EGFR, IGF-1 or the enzyme telomerase have been suggested as such targets. Other antisense strategies deal with an immunological approach such as the use of AON with CpG motifs. Systemic therapy with AON is limited by its degradation in plasma and, in case of brain tumors, by the blood–brain-barrier. Many studies approach these problems with a construction of modified AON, with coupling to liposomes or nanoparticles or with direct administration into the brain via convection-enhanced delivery. All antisense strategies are promising options, but currently and in the foreseeable future there is no cure for malignant glioma by a single therapeutical regime. Possibly a combination of several strategies may be a more effective approach for these cruel tumors.
    08/2009: pages 425-451;
  • Aktuelle Neurologie 09/2008; 35. DOI:10.1055/s-0028-1087023 · 0.32 Impact Factor
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    ABSTRACT: We examined a "double-punch" approach to overcome the escape of glioblastoma cells to the immune surveillance: increasing the immune systems activation by an active specific immunization (ASI) with Newcastle-Disease-Virus infected tumor cells and blocking the TGF-beta production by delivery of TGF-beta antisense oligonucleotides using polybutyl cyanoacrylate nanoparticles (NPs). Gene delivery was first evaluated using the CMV-beta-gal plasmid as a reporter gene. Fischer rats received implantation of glioblastoma cells into the brain and were then treated with combined ASI/NP-anti-TGF-beta formulation. Massive staining of tumor cells was seen after NP delivery of the plasmid beta-galactosidase, indicating gene transfer by nanoparticles to tumor cells. When treated with NP-anti-TGF-beta after having been immunized, the rats survived longer than untreated controls, had reduced TGF-beta-levels and showed increased rates of activated CD25+ T cells. In summary, nanoparticles are useful to deliver plasmids and antisense oligonucleotides to brain tumors. A combined immunization/gene delivery of TGF-beta antisense oligonucleotides may be a promising approach for brain tumor therapy.
    Journal of Neuroimmunology 04/2008; 195(1-2):21-7. DOI:10.1016/j.jneuroim.2007.12.005 · 2.79 Impact Factor
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    ABSTRACT: The molecular basis of tumorigenesis and tumor progression in meningiomas is not fully understood. Here we present results of conventional cytogenetic, fluorescence in situ hybridization (FISH), and comparative genetic hybridization (CGH) analyses in a patient with recurrent anaplastic meningioma. We found complex aberrant karyotype alterations previously described in anaplastic meningiomas, such as 1p, 14q aberration, and a possibly tetraploid karyotype. Loss of chromosome 22q was detected by conventional cytogenetic analysis. Additional chromosomal aberrations not previously reported included a near-triploid karyotype and alterations such as 4p+, 5p-, 7p+, 8q+, and gain of chromosome 19. FISH with LSI 9p21, CEP9, LSI PML/RARA, and CGH confirmed the karyotype complexity in this case. Our findings of several previously unreported cytogenetic alterations suggest that complex karyotype alterations are a characteristic feature in anaplastic meningiomas. High chromosomal complexity might be associated with a highly aggressive meningioma phenotype.
    Cancer Genetics and Cytogenetics 05/2007; 174(1):48-53. DOI:10.1016/j.cancergencyto.2006.10.008 · 1.93 Impact Factor
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    ABSTRACT: Recently, several in vitro studies have demonstrated production of the potent immunosuppressive cytokine transforming growth factor beta (TGF-beta)2 in glioblastoma cell lines. Systematic studies of the concentration of TGF-beta isoforms in the plasma of patients harboring intracerebral tumors do not exist. In the present study, the concentrations of TGF-beta1 and TGF-beta2 in platelet-poor plasma of 21 patients with glioblastoma before and after extensive resection were measured by specific ELISA systems and related to survival. The plasma concentrations of latent TGF-beta1 of patients with glioblastoma prior to surgery were significantly higher in comparison to healthy control probands, but not to patients with multiple sclerosis (MS). Furthermore, latent TGF-beta2 was found to be significantly increased in the plasma of patients with glioblastoma in comparison to healthy control probands and patients with MS. After extensive resection of the tumor, the value of latent TGF-beta2 evidently decreased. Interestingly, the concentration of latent TGF-beta2 prior to surgery was correlated with survival and a strong relationship was found between the survival and the difference of latent TGF-beta2 levels prior to surgery minus the TGF-beta2 concentrations 7 days after surgery. A higher difference in these plasma concentrations >6 ng/ml vs. <6 ng/ml clearly correlates with a longer survival time. In conclusion, this study suggests that glioblastoma does secret TGF-beta2 in vivo and that TGF-beta2 may play an important role in glioblastoma patients.
    Journal of Neuro-Oncology 09/2006; 79(1):61-5. DOI:10.1007/s11060-005-9116-7 · 2.79 Impact Factor
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    ABSTRACT: The FGFR4 codon 388 polymorphism (Arg(388), Arg/Gly(388) or Gly(388)) was determined in glioblastoma multiforme (GBM), anaplastic astrocytomas (AA), diffuse astrocytomas (DA), and control muscles. Arg(388) was rare in AA, GBM, muscles, and was absent in DA. The Arg/Gly(388) and the Gly(388) frequency was equal among GBM and controls. FGFR4 expression was not related to codon 388 in GBM, and no survival differences between Arg/Gly(388) and Gly(388) tumors were found. U87 cells (Arg/Gly(388)) did not show higher invasion than U138 cells (Gly(388)). This suggests that the FGFR4 codon 388 status does not play a major role in malignant gliomas.
    Cancer Letters 09/2006; 239(2):239-45. DOI:10.1016/j.canlet.2005.08.013 · 5.62 Impact Factor