Sebastian Stier

St. Vincenz Krankenhaus Limburg, Frankfurt, Hesse, Germany

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Publications (31)134.49 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Background. In several large studies an association between certain single-nucleotide polymorphisms (SNP) of the calpain-10 gene (CAPN10) with type 2 diabetes mellitus (T2D) has been identified. Since T2D and gestational diabetes mellitus (GDM) seem to be linked pathophysiologically, we examined the frequencies of CAPN10-polymorphisms in women with GDM. Methods. By using real-time PCR assisted melting curve analysis samples of 204 women with GDM and 297 controls were tested for variations of SNP-43, -44, -63 and Indel-19 of CAPN10. Results. Since the genotype frequencies found in SNP-44 among the controls did not meet the Hardy-Weinberg-Equilibrium, the further analysis was performed with SNP-43, -63 and Indel-19 only. Herein, the distribution of neither genotype nor allele nor haplogenotype-combination nor haplotype showed a significant difference between both groups. Conclusions. Variations of SNP-43, -63 and Indel-19 of CAPN10 were not associated with an increased risk of developing GDM.
    Scandinavian journal of clinical and laboratory investigation 11/2013; · 1.38 Impact Factor
  • Thomas Neuhaus, Yon-Dschun Ko, Sebastian Stier
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    ABSTRACT: BACKGROUND: Persistent and intractable hiccups are a rather rare, but distressing gastrointestinal symptom found in palliative care patients. Although several recommendations for treatment are given, hiccups often persist. CASE REPORTS: We describe a new pharmacological approach for successfully treating hiccups in four cancer patients. In the first patient, chronic and intractable hiccups lasted for more than 18 months, but disappeared immediately after swallowing a viscous 2 % lidocaine solution for treatment of mucositis. Based on this experience, we successfully treated three further patients suffering from singultus using a lidocaine-containing gel. To our knowledge, this is the first report about managing hiccups by oral application of a lidocaine solution.
    Supportive Care in Cancer 07/2012; 20(11):3009-11. · 2.09 Impact Factor
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    ABSTRACT: The aetiology of sarcoidosis is unclear. Single nucleotide polymorphisms (SNPs) in transforming growth factor (TGF)-β2 and -β3 have been reported to be associated with the development of lung fibrosis in patients with sarcoidosis. SNPs in TGF-β2 (rs1891467) and TGF-β3 (rs3917200) were investigated in 296 patients with sarcoidosis (acute/self remitting, n = 70 (including 62 patients with Löfgren's syndrome); chronic, n = 168; acute/chronic, n = 58) by real-time PCR. 32 patients showed radiological signs of lung fibrosis. The genotype frequencies were compared among the sarcoidosis groups as well as to 377 healthy controls. We found a significant association with the G-allele in rs1891467 in TGF-β2 and an acute/self remitting course of sarcoidosis compared to a chronic course (p = 0.001). The results were even more evident for patients with Löfgren's syndrome (p<0.001). Moreover, we could demonstrate a borderline significance between TGF-β3 (rs3917200) and lung fibrosis (p = 0.050). Carriers of the G-allele in rs1891467 might be protected from developing a chronic course. Moreover, there is evidence that rs3917200 is involved in the development of lung fibrosis in sarcoidosis. This study is the first in sarcoidosis patients to suggest a genetic implication of TGF-β2 as a protective factor in the course of sarcoidosis.
    European Respiratory Journal 12/2010; 38(1):169-75. · 6.36 Impact Factor
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    ABSTRACT: Brain metastases represent an important cause of morbidity in patients with lung cancer and are associated with a mean survival of less than 6 months. Thus, new regimens improving the outcome of these patients are urgently needed. On the basis of promising data raised in a phase I/II trial, we initiated an open, randomised, prospective, multicentric phase III trial, comparing whole brain radiation therapy (WBRT; 20 x 2 Gy) alone with WBRT+topotecan (RCT; 0.4 mg m(-2) day(-1) x 20). A total of 320 patients with CNS-metastases due to SCLC or NSCLC were projected. The primary end point was overall survival, whereas second end points were local response and progression-free survival. However, until the cutoff date of study completion (i.e., a study duration of 34 months), only a total of 96 (RCT:47, WBRT:49) patients had been recruited, and so an analysis was performed at that time point. Although the numbers of grade 3/4 non-haematological toxicities (besides alopecia 115 (RCT/WBRT: 55 out of 60) were evenly distributed, the 25 haematological events occurred mainly in the combined treatment arm (24 out of 1). Local response, evaluated 2 weeks after treatment, was assessable in 44 (RCT/WBRT: 23 out of 21) patients, showing CR in eight (3 out of 5), PR in 17 (11 out of 6), SD in 14 (8 out of 6) and PD in five (1 out of 4) patients (all differences n.s.). Neither OAS (RCT/WBRT: median (days)): 87 out of 95, range 3-752/4-433; HR 1.32; 95% CI (0.83; 2.10)) nor PFS (median (days)): 71 out of 66, range, 3-399/4-228; HR 1.28, 95% CI (0.73; 2.43) differed significantly. On the basis of these results and the slow recruitment, a continuation of the study did not seem reasonable. The available data show no significant advantage for concurrent radiochemotherapy for patients with lung cancer; however, the recruited number of patients is too low to exhibit a small advantage of combined treatment.
    British Journal of Cancer 02/2009; 100(2):291-7. · 5.08 Impact Factor
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    ABSTRACT: The combination of simvastatin, an HMG-CoA reductase inhibitor, and ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, decreases cholesterol synthesis and absorption and reduces circulating LDL-cholesterol concentrations. The molecular mechanisms underlying the pronounced lipid-lowering effects of this combination have not been fully elucidated in humans. One center, prospective, randomized, parallel three-group study in 72 healthy men (mean age 32+/-9 years, mean body mass index 25.7+/-3.2 kg/m(2)). Each group of twenty-four subjects received a 14-day treatment with either ezetimibe (10mg/day), simvastatin (40 mg/day) or their combination. Lipid levels, the ratio of non-cholesterol sterols to cholesterol concentrations (used as markers of cholesterol synthesis and absorption), cell surface LDL receptor (LDLR) protein as well as LDLR and HMG-CoA reductase gene expression in mononuclear blood cells were measured at baseline and at the end of the study. LDL-C decreased in all groups. Simvastatin decreased, ezetimibe increased and their combination had no effect on HMG-CoA reductase activity. Simvastatin and the combination of ezetimibe and simvastatin increased the HMG-CoA reductase and LDLR gene expression while ezetimibe had no effect. The cell surface LDLR protein expression remained unchanged in all groups. The combination of ezetimibe and simvastatin increased the expression of the serine protease proprotein convertase subtilisin/kexin 9 (PCSK9), an enzyme shown to down-regulate LDLR protein levels. The co-administration of ezetimibe and simvastatin abrogates the ezetimibe-induced increase in cholesterol synthesis and up-regulates the LDLR gene but not protein expression, an effect possibly mediated through a parallel upregulation of PCSK9 expression.
    Atherosclerosis 06/2008; 198(1):198-207. · 3.71 Impact Factor
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    ABSTRACT: Outcomes in patients with brain metastases undergoing whole-brain radiotherapy (WBRT) are hardly encouraging, and an improvement in results is therefore needed. One possible approach is the addition of chemotherapeutics. However the data presented thus far are also disappointing. A promising substance in this setting could become topotecan, which is known to cross the blood-brain barrier and additionally offers radiosensitizing effects. Therefore we performed a phase I/II trial to evaluate the feasibility of a concurrent radiochemotherapy regimen. From January 1999 to July 2001, a total of 75 patients (10 in phase I and 65 in phase II) were included. The WBRT was applied with a fraction size of 2 Gy/day for a total of 40 Gy. Topotecan was administered as a 30-min infusion with 0.2 to 0.5 mg/m(2)/day for 5 days over 4 weeks within 2 h to radiation therapy. Because of the higher toxic rates seen in patients receiving 0.5 mg/m(2)/day, the recommended dosage for phase II was 0.4 mg/m(2)/day. In this group Grade 3/4 hematologic and nonhematologic side effects occurred in 19% and 21% of the patients, respectively. The overall response rate was 72% with an overall survival of 17 weeks and 30 weeks among the responders. Based on the moderate toxicity profile presented here we recommend to perform a phase III trial to confirm the promising phase I/II data.
    International Journal of Radiation OncologyBiologyPhysics 08/2007; 68(3):839-44. · 4.52 Impact Factor
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    ABSTRACT: Jo-1 syndrome is an autoimmune disease with autoantibodies against the histidyl tRNA synthetase. Characteristic clinical findings include inflammatory myopathy and interstitial lung disease. We present the first case of a patient with Jo-1 syndrome (positive Jo-1 autoantibodies, myositis, interstitial alveolitis) who developed Hodgkin's lymphoma of nodular-sclerosing type. Thus, patients with Jo-1 syndrome and immunosuppressive therapy similar to other patients with autoimmune disease are at risk to develop lymphomas and should therefore be monitored carefully.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 08/2007; 451(1):101-4. · 2.68 Impact Factor
  • Atherosclerosis Supplements - ATHEROSCLER SUPPL. 01/2007; 8(1):61-61.
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    ABSTRACT: IGF2 and H19 are imprinted genes in normal human tissue, but many studies have observed a loss of imprinting (LOI) of these genes in tumors as an epigenetic alteration of the DNA, that leads to a biallelic expression predisposing cells to carcinogenesis and tumor growth. The aim of this study was to test the reliability of LightCycler-assisted Real-time PCR in detecting LOI of IGF2 and H19 in 39 patients with testicular germ cell tumors by comparing these results with the analysis generated by the golden standard restriction fragment length polymorphism (RFLP). With LightCycler-assisted Real-time PCR for IGF2 44% and for H19 49% of the patients were found to be heterozygous. This was consistent with the results obtained by RFLP, but surprisingly RFLP failed in more than 7% of the patients. In detecting LOI (for IGF2 in 41% and for H19 in 68% of the informative patients) the approach by RFLP was superior, since the results derived from LightCycler-assisted Real-time PCR showed reliable results in 76 and 10% of the samples concerning IGF2 and H19, respectively. Again, no discrepancy between the results obtained by the two methods occurred. In sum, LightCycler-assisted Real-time PCR is a sufficiently working approach for the rapid and reliable detection of heterozygosity of IGF2 or H19 gene and identification of LOI of IGF2 and thus may be helpful in conducting large epidemiological studies. However, for the identification of LOI of the H19 gene in this cohort it possesses only restrictive use.
    Archive für Toxikologie 11/2006; 80(10):713-8. · 5.22 Impact Factor
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    ABSTRACT: Parathyroid hormone (parathyroid hormone) has been shown to be capable of exerting anabolic effects on bone when administered intermittently. We hypothesized that parathyroid hormone will modulate the response of periodontal ligament cells in terms of anabolic effects with respect to proliferation, differentiation and the production of key regulatory factors of bone remodeling such as osteoprotegerin and receptor activator of nuclear factor kappaB ligand (RANKL) in a maturation-state dependent manner. Periodontal ligament cells were cultured from human bicuspids obtained from six patients. Following characterization, confluent and preconfluent periodontal ligament cells were challenged with parathyroid hormone (1-34) for 0, 1, 3, 6 or 24 h within three incubation cycles of 48 h each. At harvest, the cell number, alkaline phosphatase specific activity and osteocalcin, osteoprotegerin and RANKL production were determined by means of semiquantitative polymerase chain reaction (PCR) and immunoassays. Dermal fibroblasts and MG63 osteoblast-like cells served as a reference. Intermittent parathyroid hormone treatment of confluent periodontal ligament cells caused a significant increase in proliferation (+32% maximum) whereas alkaline phosphatase activity, osteocalcin and osteoprotegerin decreased at the transcriptional and translational level (-59.7% maximum). In preconfluent periodontal ligament cells, parathyroid hormone induced a decrease in proliferation (-66.3% maximum) but an increase in differentiation and osteoprotegerin production (+49.2% maximum). RANKL was hardly detectable and unaffected by parathyroid hormone treatment. Similar results were obtained in MG63 cells, whereas parathyroid hormone stimulation did not alter any of the parameters examined in dermal fibroblasts. These results indicate that human periodontal ligament cells respond to an intermittent parathyroid hormone exposure with changes in proliferation, differentiation and osteoprotegerin production in a maturation-state dependent manner and therefore might be regulatorily involved in periodontal regeneration.
    Journal of Periodontal Research 03/2006; 41(1):62-72. · 1.99 Impact Factor
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    ABSTRACT: In East Germany, uranium mining was undertaken on a large scale from 1946 to 1990. Poor working conditions led to a high level of exposure to ionizing radiation and quartz dust. This analysis evaluates the histopathology of lung carcinoma in uranium miners in relation to radon exposure and silicosis. A database developed for autopsy cases ascertained in a pathological tissue repository of German uranium miners was used to estimate odds ratios for developing lung carcinoma by major cell type with regard to radon exposure and silicosis. Silicosis information was extracted from autopsy protocols. Working level months (WLM) were calculated with a job-exposure matrix to assess lifetime radon exposure. Risk estimates were based on 3414 male miners who died from small cell lung carcinoma (SCLC, n = 1446), squamous cell carcinoma (SqCC, n = 1006), or adenocarcinoma (AC, n = 962) between 1957 and 1990. SCLC and SqCC seem more likely to be associated with high radon exposure than AC. Mean cumulative radon exposure was 868 (SD 631) WLM in SCLC, 871 (SD 652) WLM in SqCC, and 743 (SD 598) WLM in AC. Silicosis prevalence was 26% in SCLC, 38% in SqCC, and 30% in AC. In silicotics, AC and SqCC had a relatively higher frequency at the expense of SCLC. SCLC occurred earlier than AC and SqCC. High radon exposure was associated with a higher relative frequency of SCLC and SqCC than AC. Silicosis tended to increase the appearance of SqCC and AC.
    Cancer 03/2006; 106(4):881-9. · 5.20 Impact Factor
  • Diabetologie Und Stoffwechsel - DIABETOL STOFFWECHS. 01/2006; 1.
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    ABSTRACT: The purpose of this study was to determine the maximum tolerated dose, toxicity profile and anti-tumor activity of paclitaxel in combination with gemcitabine when administered to patients with unresectable locally recurrent or metastatic squamous cell carcinoma of the head and the neck (SCCHN). Twenty-seven patients were treated in a phase I-II study with gemcitabine at a dose of 800 mg/m on days 1 and 8, escalating to a dose of 1,000 mg/m, plus escalating doses of paclitaxel (100, 135 and 175 mg/m) on day 2. Treatment consisted of 6 cycles repeated every 3 weeks. The main toxicity was myelosuppression. Other toxicities were mild and manageable. Due to grade 4 neutropenia at higher doses the recommended dose level of the gemcitabine/paclitaxel combination was 1,000/135 mg/m. Four patients achieved a partial response and no patient had a complete remission, giving an overall response rate of 14.8%. The median time of survival was 24 weeks. We conclude that the combination of paclitaxel and gemcitabine is tolerated, but shows insufficient clinical activity in patients with recurrent and/or metastatic SCCHN to warrant further testing.
    Anti-Cancer Drugs 12/2005; 16(10):1115-21. · 2.23 Impact Factor
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    ABSTRACT: Bone-marrow-derived cells can contribute nuclei to skeletal muscle fibers. However, serial sectioning of muscle in mdx mice implanted with GFP-labeled bone marrow reveals that only 20% of the donor nuclei chronically incorporated in muscle fibers show dystrophin (or GFP) expression, which is still higher than the expected frequency of "revertant" fibers, but there is no overall increase above controls over time. Obviously, the vast majority of incorporated nuclei either never or only temporarily turn on myogenic genes; also, incorporated nuclei eventually loose the activation of the beta-actin::GFP transgene. Consequently, we attempted to enhance the expression of dystrophin. In vivo application of the chromatin-modifying agents 5-azadeoxycytidine and phenylbutyrate as well as local damage by cardiotoxin injections caused a small increase in dystrophin-positive fibers without abolishing the appearance of "silent" nuclei. The results thus confirm that endogenous repair processes and epigenetic modifications on a small-scale lead to dystrophin expression from donor nuclei. Both effects, however, remain below functionally significant levels.
    Proceedings of the National Academy of Sciences 09/2005; 102(33):11852-7. · 9.74 Impact Factor
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    ABSTRACT: TNF-alpha plays a pivotal role in inflammation processes which are mainly regulated by endothelial cells. While TNF-alpha induces apoptosis of several cell types like tumor cells, endothelial cells are resistant to TNFa mediated cell death. The cytotoxic effects of TNF-alpha on most cells are only evident if RNA or protein synthesis is inhibited, suggesting that de novo RNA or protein synthesis protect cells from TNF-alpha cytotoxicity, presumably by NF-kappaB mediated induction of protective genes. However, the cytoprotective genes involved in NF-kappaB dependent endothelial cell survival have not been sufficiently identified. In the present study, the suppression subtractive hybridization (SSH) method was employed to identify rarely transcribed TNF-alpha inducible genes in human arterial endothelial cells related to cell survival and cell cycle. The TNF-alpha-induced expression of the RNA binding protein p54(nrb) and the 14-3-3 protein HS1 as shown here for the first time may contribute to the TNF-alpha mediated cell protection of endothelial cells. These genes have been shown to play pivotal roles in cell survival and cell cycle control in different experimental settings. The concerted expression of these genes together with other genes related to cell protection and cell cycle like DnaJ, p21(cip1) and the ubiquitin activating enzyme E1 demonstrates the identification of new genes in the context of TNF-alpha induced gene expression patterns mediating the prosurvival effect of TNF-alpha in endothelial cells.
    Journal of biochemistry and molecular biology 08/2005; 38(4):447-56. · 2.02 Impact Factor
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    ABSTRACT: Stem cells reside in a specialized niche that regulates their abundance and fate. Components of the niche have generally been defined in terms of cells and signaling pathways. We define a role for a matrix glycoprotein, osteopontin (OPN), as a constraining factor on hematopoietic stem cells within the bone marrow microenvironment. Osteoblasts that participate in the niche produce varying amounts of OPN in response to stimulation. Using studies that combine OPN-deficient mice and exogenous OPN, we demonstrate that OPN modifies primitive hematopoietic cell number and function in a stem cell-nonautonomous manner. The OPN-null microenvironment was sufficient to increase the number of stem cells associated with increased stromal Jagged1 and Angiopoietin-1 expression and reduced primitive hematopoietic cell apoptosis. The activation of the stem cell microenvironment with parathyroid hormone induced a superphysiologic increase in stem cells in the absence of OPN. Therefore, OPN is a negative regulatory element of the stem cell niche that limits the size of the stem cell pool and may provide a mechanism for restricting excess stem cell expansion under conditions of niche stimulation.
    Journal of Experimental Medicine 07/2005; 201(11):1781-91. · 13.21 Impact Factor
  • Praxis 06/2005; 94(20):803-9; quiz 810.
  • Praxis 01/2005; 93(50):2085-92.
  • Praxis. 01/2005; 94(20):803-810.
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    ABSTRACT: Galloyl group-containing catechins, such as epigallocatechin-3 gallate, inhibit receptor tyrosine kinase activity of several growth factor receptors. This study investigated the effects of epigallocatechin-3 gallate, as compared to epicatechin, on vascular endothelial growth factor-induced intracellular signaling and mitogenesis of human umbilical endothelial cells. Epigallocatechin-3 gallate concentration-dependently inhibited vascular endothelial growth factor-induced DNA synthesis, cell proliferation, autophosphorylation of vascular endothelial growth factor receptors-1 and -2, phosphorylation of extracellular signal-regulated kinases-1 and -2, and mRNA expression of the early growth response factor-1. In contrast, epicatechin was not effective. Thus, epigallocatechin-3 gallate may be an attractive candidate drug to inhibit tumour angiogenesis.
    European Journal of Pharmacology 02/2004; 483(2-3):223-7. · 2.59 Impact Factor

Publication Stats

985 Citations
134.49 Total Impact Points


  • 2012
    • St. Vincenz Krankenhaus Limburg
      Frankfurt, Hesse, Germany
    • Haematology Oncology Practice Altona
      Hamburg, Hamburg, Germany
  • 2007
    • Strahlentherapie Bonn-Rhein-Sieg
      Bonn, North Rhine-Westphalia, Germany
  • 2000–2005
    • Harvard Medical School
      Boston, Massachusetts, United States
    • University of Bonn
      • Medizinische Klinik und Poliklinik II
      Bonn, North Rhine-Westphalia, Germany
  • 2002
    • Massachusetts General Hospital
      Boston, Massachusetts, United States