K Hörmann

Universität Heidelberg, Heidelburg, Baden-Württemberg, Germany

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Publications (575)687.29 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The majority of patients affected by chronic rhinosinusitis (CRS) suffer from eosinophilic infiltration. We hypothesised that polihexanide and polyethylene glycol as an antiseptic might alter the eosinophil-associated IL-5 and eotaxin-3 expression in CRS and also the expression of MMP-9, being involved in the tissue-remodelling in CRS. After obtaining samples from 10 CRS patients with (CRSwNP) and without nasal-polyposis (CRSsNP) and 2 patients with inverted-papilloma undergoing functional endoscopic sinus surgery (FESS), the expression of interleukin-5, eotaxin-3 and MMP-9 were evaluated by an ELISA assay with and without the tested agent. CRSwNP showed a significantly increased expression of IL-5. Polihexanide seems not to alter the attraction of eosinophils in patients with CRS via IL-5 expression. Also elevated levels of MMP-9 could not be reduced to normal values. But there exists statistically significant evidence that the self-amplification process of eosinophils via eotaxin-3 could be influenced by the administration of polihexanide.
    In vivo (Athens, Greece) 07/2014; 28(4):489-494. · 0.97 Impact Factor
  • J. Ulrich Sommer · Richard Birk · Karl Hörmann · Boris A Stuck ·
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    ABSTRACT: The forces of specific muscle groups have been well described for nearly all parts of the human body. Interestingly, data for the tongue and its forces are rare. In light of ongoing development of systems for managing the tongue (retaining, advancing, suspending or stabilizing), especially in patients with obstructive sleep apnea, knowledge of the maximum tongue force is important for the conceptual design of those systems. The maximum tongue force in a sagittal direction was documented using a custom-built device that included a tongue clamp and a piezoelectric sensor to capture force measurements. Once positioned securely in the device, participants were asked to move the tongue in a posterior sagittal direction, with maximum force, in each of three test positions. Forty-nine healthy volunteers (29 male) were included in the study. Tongue force measurements were collected three times in three different tongue positions. Thirty-three participants had repeated measurements to investigate any potential learning effect. The maximum force of the human tongue in a posterior sagittal direction showed high inter-individual variation and ranged from 3.2 to 52.4 Newton (N; mean 14.1 ± 7.5 N), when measured from a "neutral protrusion or resting" tongue position. The "retracted" and "maximal protrusion" testing positions yielded lower maximum tongue forces. Men (m) showed statistically significantly higher tongue forces than women (w) (m: 16.0 ± 8.4 N, w: 11.0 ± 4.3 N), and there was a positive correlation with BMI and a negative correlation with age. Comparing the first measurement session with the second session (per patient) showed higher mean maximum forces in the second session, but with no statistical significance. The maximum tongue force data showed substantial inter- and intra-individual variability and gender dependency. Some male individuals produced very high forces. These forces should be considered for the future conception and development of tongue management systems and the mechanical stress to which these systems may be exposed.
    Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 06/2014; 271(11). DOI:10.1007/s00405-014-3103-6 · 1.55 Impact Factor
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    ABSTRACT: Unlabelled: Precise assessment of lymph node metastases is critical to the treatment outcome and overall survival of patients with head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to investigate the effect of time-of-flight (TOF) technique on the diagnostic performance of (18)F-FDG PET/CT for assessment of lymph node metastases in HNSCC patients. Methods: In 39 patients with an initial diagnosis of HNSCC, preoperative staging (18)F-FDG PET/CT was performed to assess lymph node metastases before surgery and histologic verification. Potential lymph node metastases were evaluated and documented separately for the right and left neck in accordance with the head and neck lymph node level classification. Two experienced readers measured lesion volume and uptake for every PET-positive lymph node. Sensitivity, specificity, image quality, and the PET characterization of the lesion (benign or malignant) were compared between different reconstruction methods (TOF PET and standard high-definition PET) and matrices for both readers. Results: TOF PET significantly increased the maximal standardized uptake value (SUVmax) but had no significant effect on lesion volume. However, a higher SUVmax did not result in a significant increase in small-lesion detection. Sensitivity and image quality were slightly improved with TOF PET but not significantly so. Matrix, on the other hand, had a significant effect on detected lesion numbers, sensitivity, and image quality. Conclusion: For preoperative assessment of lymph node metastases in HNSCC, (18)F-FDG PET/CT using TOF technique increases SUVmax in lesions and improves image quality but has no significant impact on small-lesion detectability.
    Journal of Nuclear Medicine Technology 06/2014; 42(3). DOI:10.2967/jnmt.114.141192
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    ABSTRACT: In ENT, polyhexanide-containing solutions are used to treat nasal infections caused by multiresistant bacteria like methicillin-resistant Staphylococcus aureus. Many forms of commercial nasal solutions containing polyhexanide exist, such as gels or solutions for topical use. Data regarding the influence of polyhexanide on ciliary beat frequency (CBF) are lacking to date. We tested the CBF of nasal ciliated epithelial cells under the influence of a commercially available polyhexanide-containing solution (Lavasept(®) Concentrate) in a therapeutic concentration (0.04, 0.02 %). In addition, we tested the concentrations of 0.1 and 0.01 %. Cells were visualized with a phase contrast microscope, and the CBF was measured with the SAVA system's region of interest method. Ringer's solution and macrogol served as negative controls. A therapeutic concentration of Lavasept significantly reduced CBF in a time- and concentration-dependent manner. After 1 min, the CBF was reduced from 8.90 ± 1.64 to 5.00 ± 3.72 Hz with a concentration of 0.04 % (p value = 0.001). After 10 min, all cilia stopped beating. After 5 min, a 0.02 % solution of Lavasept concentrate decreased CBF significantly from 8.64 ± 1.71 to 3.30 ± 3.27 Hz (p value < 0.001). In conclusion, CBF of human nasal epithelia is significantly reduced with the use of the polyhexanide-containing solution Lavasept in some therapeutic concentrations. Due to our findings in this study, Lavasept should be used on ciliated mucosa only with caution and in a concentration of 0.02 %.
    Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 06/2014; 272(2). DOI:10.1007/s00405-014-3112-5 · 1.55 Impact Factor
  • J Stern-Straeter · K Hörmann ·
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    ABSTRACT: Due to the enormous expansion of knowledge in the fields of stem cell research and biomaterials, skeletal muscle tissue engineering represents a rapidly developing field of biomedical research. This article provides a general overview of skeletal muscle tissue engineering, including a discussion of recent findings and future research perspectives. Additionally, the results of myogenic differentiation of human mesenchymal stem cells and satellite cells are presented.
    HNO 06/2014; 62(6):415-22. DOI:10.1007/s00106-014-2863-z · 0.58 Impact Factor
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    ABSTRACT: It has been suggested that personality traits may be prognostic for the severity of suffering from tinnitus. Resilience as measured with the Wagnild and Young resilience scale represents a positive personality characteristic that promotes adaptation to adverse life conditions including chronic health conditions. Aim of the study was to explore the relation between resilience and tinnitus severity. In a cross-sectional study with a self-report questionnaire, information on tinnitus-related distress and subjective tinnitus loudness was recorded together with the personality characteristic resilience and emotional health, a measure generated from depression, anxiety, and somatic symptom severity scales. Data from 4705 individuals with tinnitus indicate that tinnitus-related distress and to a lesser extent the experienced loudness of the tinnitus show an inverse correlation with resilience. A mediation analysis revealed that the relationship between resilience and tinnitus-related distress is mediated by emotional health. This indirect effect indicates that high resilience is associated with better emotional health or less depression, anxiety, and somatic symptom severity, which in turn is associated with a less distressing tinnitus. Validity of resilience as a predictor for tinnitus-related distress is supported but needs to be explored further in longitudinal studies including acute tinnitus patients.
    06/2014; 2014(Article ID 370307). DOI:10.1155/2014/370307
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    ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer worldwide. The growth and invasion of HNSCC are strongly influenced by the extracellular matrix (ECM), which is modified by matrix metalloproteinases (MMPs). The MMP family is still relevant to cancer research, as it promotes malignant transformation, cell proliferation and modulation of angiogenesis even in the early stages of cancer. The proteolytic processing of bioactive molecules by MMP-14 (MT1-MMP) causes severe abnormalities in connective tissue, defective angiogenesis and premature death. MMP-2 (gelatinase A) and MMP-14 also play a role in degradation of basement membrane and cell carcinoma invasion. Imatinib blocks the PTK receptor c-kit and forestalls its PTK activity. The aim of the present study was to investigate the expression pattern of MMP-14 and MMP-2 in human papilloma virus (HPV)-negative and p16-positive SCC and to evaluate the chemosensitivity of the tumour cells to the chemotherapeutic agents, imatinib and 5-fluorouracil (5-FU). We incubated the SCC cell lines with imatinib (18 and 30 µmol/ml) and 5-FU (1 and 5 µmol/ml) and detected MMP-14 and MMP-2 by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) after 48, 72, 120, 192 and 240 h. We detected expression of MMP-2 and MMP-14 in all incubated tumour cell lines. With imatinib in particular, we found a reliable trend towards decreased MMP-2 and MMP-14 expression levels in p16-positive and p16-negative SCC tumour cell lines in addition to an induced apoptotic effect. We found statistically significant imatinib-induced suppression of MMP-2- and MMP-14, dependent on the incubation time and the cell line. We detected a significant suppression of MMP-2 and MMP-14 especially in p16-negative HNSCC14C cells after prolonged treatment time with imatinib. Dose escalation of imatinib and 5-FU had no statistically significant effect on the expression of MMP-2 or MMP-14. The p16-positive SCC cells exhibited higher expression of total protein. We detected a significant suppression of MMP-2 and MMP-14 in all the incubated SCC cell lines, partially after treatment with imatinib. We found higher suppression of MMP-2 in the CERV196 cells after incubation with imatinib. We detected a reliable trend towards increased chemosensitivity of p16-positive tumour cells in vitro after treatment with imatinib. Extended studies and clinical trials are needed to further investigate these findings in HPV-associated HNSCC.
    Oncology Reports 05/2014; DOI:10.3892/or.2014.3225 · 2.30 Impact Factor
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    ABSTRACT: Tissue engineering is a promising research field, which aims to create new functional muscle tissue in vitro, by utilizing the myogenic differentiation potential of human stem cells. The objective of the present study was to determine the effect of static magnetic fields (SMF), combined with the use of the myogenic differentiation enhancing hepatocyte growth factor (HGF), on human satellite cell cultures, which are one of the preferred stem cell sources in skeletal muscle tissue engineering. We performed almarBlue® proliferation assays and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) for the following myogenic markers: desmin (DES), myogenic factor 5 (MYF5), myogenic differentiation antigen 1 (MYOD1), myogenin (MYOG), myosin heavy chain (MYH) and α1 actin (ACTA1) to detect the effects on myogenic maturation. Additionally, immunohistochemical staining (ICC) and fusion index (FI) determination as independent markers of differentiation were performed on satellite cell cultures stimulated with HGF and HGF + SMF with an intensity of 80 mT. ICC verified the muscle phenotype at all time points. SMF enhanced the proliferation of satellite cell cultures treated with HGF. RT-PCR analysis, ICC and FI calculation revealed the effects of HGF/SMF on the investigated differentiation markers and stimulation with HGF and SMF verified the continuing maturation, however no significant increase in analysed markers could be detected when compared with control cultures treated with serum cessation. In conclusion, HGF or HGF + SMF stimulation of human satellite cell cultures did not lead to the desired enhancement of myogenic maturation of human satellite cell cultures compared with cell cultures stimulated with growth factor reduction.
    Molecular Medicine Reports 03/2014; 9(6). DOI:10.3892/mmr.2014.2083 · 1.55 Impact Factor
  • A Freuschle · J Brom · K Hörmann · J D Schultz ·
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    ABSTRACT: Keloids are fibroproliferative extreme variants of an impaired wound healing, developing a tumour-like growth. In the ENT area keloids arise mainly at auricle. Often caused by piercings or trauma. They grow bulging excessively over the original scar edges and adopt sometimes bizarre morphologies. The patients complain often of dysesthesias such as burning pain, severe itching and are suffering often from stigmatization. The huge number of therapy methods, for the treatment of keloids described in the literature (silicon therapy, compression, intralesional corticoids, intra- or extralesional surgical excision, kryosurgery, radiatio, Interferon- or Bleomycin-therapy) emphasize the enormous challenge for the treating doctor, particularly in facial plastic surgery.
    Laryngo-Rhino-Otologie 02/2014; 93(5). DOI:10.1055/s-0033-1358482 · 0.84 Impact Factor
  • A. Freuschle · J. Brom · K. Hörmann · J. Schultz ·

    Aktuelle Dermatologie 02/2014; 41(01/02):35-43. DOI:10.1055/s-0034-1365510
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    ABSTRACT: The treatment of diseases of the lingual tonsils is still under debate, and surgical interventions are often associated with significant morbidity and complications. The aim of the present study was to evaluate the safety of lingual tonsillectomy using cold ablation (coblation) as a new treatment of lingual tonsil diseases. In this retrospective, bicentric study, we included all patients between 2005 and 2012 who underwent cold ablation (Coblation(®)) of the lingual tonsils. We assessed the frequency of postoperative complications based on the patients' charts. A total of 108 patients (47 ± 13, 6 years) underwent lingual tonsillectomy using coblation. All patients were operated on under general anesthesia as inpatients. Intraoperative complications did not occur. Three patients (2.8 %) needed revision surgery due to postoperative hemorrhage, and in one of those cases, three revisions were necessary. There was no postoperative airway compromise and no need for tracheostomy. There was no hypoglossal nerve paralysis, but in the case needing multiple revisions, a weakness of the hypoglossal nerve persisted. In all the cases, oral intake was possible with adequate analgesia. Coblation of the tongue base is a safe procedure with a relatively low rate of postoperative complications. Postoperative hemorrhage is the most relevant complication that occurred in our series of patients. Future studies are needed to evaluate the efficacy of the procedure in the treatment of obstructive sleep apnea.
    Archives of Oto-Rhino-Laryngology 01/2014; 271(6). DOI:10.1007/s00405-013-2845-x · 1.55 Impact Factor
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    ABSTRACT: The cancer stem cell (CSC) theory implies that CSCs are surrounded by supportive stromal cells, which are known as the CSC niche. Stromal cell-derived factor-1 (SDF-1) shows a multitude of functional effects in head and neck squamous cell carcinoma (HNSCC) cells, including migration and polarization. Therefore, the SDF-1-CXCR4 axis may be involved in the pathophysiology of the progression, recurrence and metastasis of malignant diseases of the head and neck. In the present study, the CD44(+) HNSCC UM-SCC-11A cell line was used as a model for CSCs. The interaction between the UM-SCC-11A cells and the supportive microenvironmental cells, including fibrocytes, human umbilical vein endothelial cells (HUVECs) and human microvascular vein endothelial cells (HMVECs) was evaluated. All the cell types that were tested were shown to secrete different concentrations of SDF-1 into the surrounding culture medium [mean (m)fibro, 1243.3±156.2 pg/ml; mHMVEC, 1061.4±23.2 pg/ml; mHUVEC, 849.6±110.9 pg/ml]. The migration of the UM-SCC-11A cells towards the supportive cells was increased by a higher supply of SDF-1 (contrfibro, 315.23±61.55 μm; mfibro, 477.73±143.7 μm; Pfibro=0.003; contrHMVEC, 123.41±66.68 μm; mHMVEC, 249.04±111.95 μm; PHMVEC=0.004; contrHUVEC, 189.7±93.26 μm; mHUVEC, 260.82±161.58 μm). The amount of the UM-SCC-11A cells that migrated towards the differentiated fibrocytes was significantly higher than that which migrated towards the HMVECs or HUVECs (Pfibro/HMVEC=2.12E-11; Pfibro/HUVEC=2.28E-5). Cell-cell interaction by podia formation of the UM-SCC-11A cells was observed in all the supportive cell types that were tested. Broadly based cell-cell contacts were observed. By contrast, digitiform podia formations presented by the UM-SCC-11A cells were determined using fluorescence microscopy. The SDF-1-CXCR4 axis is postulated to be a crucial pathway in the interaction between CSCs and their surrounding supportive cells. Understanding the cell-cell interactions in the CSC niche using in vitro models may aid in gaining further insight into these mechanisms and finding new strategies of therapy in this field.
    Oncology letters 01/2014; 7(1):82-86. DOI:10.3892/ol.2013.1673 · 1.55 Impact Factor
  • R. Dollner · K. Hörmann · B.A. Stuck · O. Pfaar · L. Klimek ·

    Allergologie 01/2014; 37(01):11-19. DOI:10.5414/ALX01584 · 0.23 Impact Factor
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    ABSTRACT: Incidence of oropharyngeal head and neck squamous cell carcinoma (HNSCC) induced by the human papilloma virus (HPV) is rising. HNSCC is the sixth most common neoplasia worldwide. The survival rate remains poor, thus innovative therapy approaches are necessary. Everolimus, an inhibitor of the mammalian target of rapamycin, as well as the multi-tyrosine kinase inhibitors sorafenib (targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor and RAF) and sunitinib (targeting vascular endothelial growth factor receptor, platelet-derived growth factor receptor, stem cell factor receptor, RET proto-oncogene and colony-stimulating factor), have shown a remarkable antitumor effect against various tumor entities, with moderate side-effects. These drugs are administered orally, which should lead to higher patient compliance and less hospitalisation. Aim: This study sought to evaluate the expression of PDGFR α/β and hypoxia-inducible factor-1α (HIF-1α) and their alterations induced by everolimus, sorafenib and sunitinib in chemonaïve HPV-positive and HPV-negative HNSCC. To our knowledge, this is the first in vitro study to investigate such cases. We incubated HPV-positive CERV196 and HPV-negative HNSCC 11A and 14C cells for 2 to 8 days with increasing concentration of drugs. Expression of PDGFR α/β and HIF-1α was measured by enzyme-linked immunosorbent assay and compared to a chemonaïve controls. Our study showed that PDGFR α/β and HIF-1α were expressed in all three cell lines. Incubation with everolimus, sorafenib or sunitinib led to a decrease in PDGFR α/β and HIF-1α expression, depending on the HPV status. A statistically significant alteration of PDGFR α/β was detected in CERV196 only. Thus, HPV-positive HNSCC exhibited a higher sensitivity to the drugs used compared to HPV-negative HNSCC 11A and 14C tumor cells. A significant reduction of HIF-1α was measured for HNSCC 11A and 14C only. An escalation of drug concentration had no significant effect. We showed that these novel agents led to a significant reduction of PDGFR and HIF-1α, depending on the HPV status. HPV positivity is associated with increased chemosensitivity and may be associated with better locoregional control and overall patient survival compared to HPV negativity. Further studies are necessary to investigate the efficacy and safety of these agents in the treatment of HPV-positive and -negative HNSCC in vivo.
    Anticancer research 12/2013; 33(12):5385-93. · 1.83 Impact Factor
  • G.M. Bran · K. Hörmann · J. Gosepath ·
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    ABSTRACT: Die Korrektur komplexer Narben im Gesichtsbereich erfordert individuell angepasste, oft multimodale Therapiekonzepte. Der vorliegende Beitrag erläutert unterschiedliche Techniken zur Korrektur von Kontrakturen, atrophen Narben, Narben in behaarten Gesichtsbereichen und Keloiden im Bereich der Ohrmuscheln. Darüber hinaus werden adjuvante Verfahren innerhalb der einzelnen Themenkomplexe vorgestellt.
    HNO 12/2013; 61(12). DOI:10.1007/s00106-013-2720-5 · 0.58 Impact Factor
  • G M Bran · K Hörmann · J Gosepath ·
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    ABSTRACT: Correction of complex facial scars frequently requires individualized, multimodal strategies, which are composed of various therapeutic measures. This report provides information on techniques for correction of contractures, atrophic scars, scars within hair-bearing regions of the face and auricular keloids. Additionally, we present adjuvant procedures in a subject-related manner.
    HNO 12/2013; 61(12):997-1004. · 0.58 Impact Factor
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    ABSTRACT: The creation of functional muscles/muscle tissue from human stem cells is a major goal of skeletal muscle tissue engineering. Mesenchymal stem cells (MSCs) from fat/adipose tissue (AT-MSCs), as well as bone marrow (BM-MSCs) have been shown to bear myogenic potential, which makes them candidate stem cells for skeletal muscle tissue engineering applications. The aim of this study was to analyse the myogenic differentiation potential of human AT-MSCs and BM-MSCs cultured in six different cell culture media containing different mixtures of growth factors. The following cell culture media were used in our experiments: mesenchymal stem cell growth medium (MSCGM)™ as growth medium, MSCGM + 5-azacytidine (5-Aza), skeletal muscle myoblast cell growth medium (SkGM)-2 BulletKit™, and 5, 30 and 50% conditioned cell culture media, i.e., supernatant of human satellite cell cultures after three days in cell culture mixed with MSCGM. Following the incubation of human AT-MSCs or BM-MSCs for 0, 4, 8, 11, 16 or 21 days with each of the cell culture media, cell proliferation was measured using the alamarBlue® assay. Myogenic differentiation was evaluated by quantitative gene expression analyses, using quantitative RT-PCR (qRT-PCR) and immunocytochemical staining (ICC), using well-defined skeletal markers, such as desmin (DES), myogenic factor 5 (MYF5), myosin, heavy chain 8, skeletal muscle, perinatal (MYH8), myosin, heavy chain 1, skeletal muscle, adult (MYH1) and skeletal muscle actin-α1 (ACTA1). The highest proliferation rates were observed in the AT-MSCs and BM-MSCs cultured with SkGM-2 BulletKit medium. The average proliferation rate was higher in the AT-MSCs than in the BM-MSCs, taking all six culture media into account. qRT-PCR revealed the expression levels of the myogenic markers, ACTA1, MYH1 and MYH8, in the AT-MSC cell cultures, but not in the BM-MSC cultures. The muscle-specific intermediate filament, DES, was only detected (by ICC) in the AT-MSCs, but not in the BM-MSCs. The strongest DES expression was observed using the 30% conditioned cell culture medium. The detection of myogenic markers using different cell culture media as stimuli was only achieved in the AT-MSCs, but not in the BM-MSCs. The strongest myogenic differentiation, in terms of the markers examined, was induced by the 30% conditioned cell culture medium.
    International Journal of Molecular Medicine 11/2013; 33(1). DOI:10.3892/ijmm.2013.1555 · 2.09 Impact Factor
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    ABSTRACT: Signs of pharyngeal neurodegeneration have been detected in patients with obstructive sleep apnea (OSA). Along with this neurodegeneration, a decreased pharyngeal sensitivity to mechanical stimulation has been described. The decreased sensitivity may play a role in the pathophysiology of this disease. The aim of the study was to investigate the chemosensitivity of the pharyngeal mucosa in patients with OSA compared with controls. Healthy controls and patients with OSA (age: 30-60 years) were included. Testing of oropharyngeal chemosensitivity was performed with subjective intensity ratings of capsaicin (SIR, visual analogue scale 0-10), air puffs (presented with an olfactometer), and stimulation with CO2 at the posterior pharyngeal wall. A 2-point discrimination test at the soft palate, an intensity rating of capsaicin at the tongue, and a nasal lateralization test were performed. Twenty-six patients with OSA and 18 healthy controls were included. No differences were detected in the SIR of capsaicin at the tongue or in the nasal lateralization test. At the pharynx, a decreased sensitivity to capsaicin (OSA: 6.8±2.3; healthy control: 8.6±1.3), air puffs (OSA: 2.8±1.9; healthy control: 4.2±1.6), and stimulation with CO2 (OSA: 1.5±1.7; healthy control: 2.8±1.8) were demonstrated in patients with OSA (all P < 0.05). Two-point discrimination at the soft palate was reduced with statistical significance in the OSA group (OSA: 11.5±5.4mm; healthy control: 5.0±2.4mm). The results suggest reduced pharyngeal chemosensitivity in OSA patients in addition to the reduced mechanical pharyngeal sensitivity shown with 2-point discrimination. This demonstrates peripheral neurodegeneration in the context of this disease.
    Chemical Senses 07/2013; 38(7). DOI:10.1093/chemse/bjt031 · 3.16 Impact Factor
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    ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer worldwide. In several tumour entities, the tyrosine kinase receptor c-KIT is associated with tumour transformation in the epithelial tissue in cases of aberrant expression. Furthermore, tumour development and dissemination are a result of dysregulated cellular pathways such as the WNT/β-catenin pathway. β-Catenin is a multifunctional protein within the canonical WNT signalling pathway and a pivotal factor for the stabilization of cell-cell interactions. In malignant tissues, β-catenin triggers tumour proliferation and progression. The aim of this study is to investigate the expression patterns of c-KIT and β-catenin in human papillomavirus-negative and p16-positive SCC and to evaluate the chemosensitivity of the tumour cells to the chemotherapeutical agents docetaxel and 5-fluorouracil (5-FU). We incubated the tumour cell lines with docetaxel (5 μmol/ml) and 5-FU (1 μmol/ml) and detected β-catenin and c-KIT by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) after 48, 72, 120, 192 and 240 h. We found a reliable trend towards decreased β-catenin expression levels in p16-positive and p16-negative tumour cell lines when incubated with docetaxel, in addition to induced apoptotic effect. At best, 5-FU had a slight influence on the alteration of the expression of β-catenin. Dose escalation of docetaxel and 5-FU had no statistically significant effect on the expression of β-catenin or c-KIT. In HPV-negative HNSCC, a reduced expression level of β-catenin and c-KIT was detected in an incubation period-dependent manner. p16-transformed SCC (CERV196) cells were characterized by a reduced susceptibility to docetaxel induced alteration of β-catenin expression. We were unable to confirm the clinically-substantiated increased chemosensitivity of p16-positive tumour cells in vitro. Extended studies and clinical trials are needed to investigate these findings further in HPV-associated HNSCC.
    Anticancer research 06/2013; 33(6):2457-65. · 1.83 Impact Factor
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    ABSTRACT: Purpose: Continuous positive airway pressure (CPAP) is the gold standard in the treatment of obstructive sleep apnea (OSA), but its impact on ciliary function is unclear to date. Furthermore, CPAP is associated with numerous side effects related to the nose and upper airway. Humidified CPAP is used to relieve these symptoms, but again, little is known regarding its effect on ciliary function of the nasal respiratory epithelium. Methods: In this prospective, randomized, crossover trial, 31 patients with OSA (AHI >15/h) were randomized to two treatment arms: nasal continuous positive airway pressure (nCPAP) with humidification or nCPAP without humidification for one night in each modality to assess short-term effects of ciliary beat frequency (CBF) and mucus transport time (MTT) and consecutively for 8 weeks in each modality to assess long-term effects in a crossover fashion. Results: The baseline CBF was 4.8 ± 0.6 Hz, and baseline MTT was 540 ± 221 s. After one night of CPAP with and without humidification, ciliary function increased moderately yet with statistical significance (p <0.05). The short-term groups with and without humidification did not differ statistically significant. Regarding long-term effects of CPAP, a statistically significant increase in ciliary function above the baseline level and above the short-term level was shown without humidification (7.2 ± 0.4 Hz; 402 ± 176 s; p <0.01). The increase above baseline level was even more pronounced with humidification (9.3 ± 0.7 Hz; 313 ± 95 s; p <0.01). There was a statistically significant difference between both groups at long-term assessment with regard to CBF (p <0.01). Conclusions: Independent of airway humidification, nCPAP has moderate effects on short-term ciliary function of the nasal respiratory epithelium. However, a significant increase in ciliary function-both in terms of an increased CBF and a decreased MTT-was detected after long-term use. The effect was more pronounced when humidification was used during nCPAP.
    Sleep And Breathing 05/2013; 18(1). DOI:10.1007/s11325-013-0853-0 · 2.48 Impact Factor

Publication Stats

5k Citations
687.29 Total Impact Points


  • 1995-2015
    • Universität Heidelberg
      • • Faculty of Medicine Mannheim and Clinic Mannheim
      • • Institute of Hygiene
      Heidelburg, Baden-Württemberg, Germany
    • Universität Mannheim
      Mannheim, Baden-Württemberg, Germany
  • 2014
    • Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e.V.
      Mannheim, Baden-Württemberg, Germany
  • 2009-2014
    • Universitätsmedizin Mannheim
      Mannheim, Baden-Württemberg, Germany
  • 2012
    • HELIOS Klinikum Berlin-Buch
      Berlín, Berlin, Germany
  • 1997-2010
    • Westpfalz-Klinikum GmbH
      Kaiserlautern, Rheinland-Pfalz, Germany
  • 2005-2009
    • The Australian Society of Otolaryngology Head & Neck Surgery
      Evans Head, New South Wales, Australia
    • BG Trauma Center Ludwigshafen
      Ludwigshafen, Rheinland-Pfalz, Germany
  • 2007
    • University of Münster
      Muenster, North Rhine-Westphalia, Germany
  • 2006
    • Universitätsklinikum Münster
      Muenster, North Rhine-Westphalia, Germany
  • 2001
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
  • 1993
    • Technische Universität Kaiserslautern
      • Department of Physics
      Kaiserlautern, Rheinland-Pfalz, Germany
  • 1987
    • University of Hamburg
      Hamburg, Hamburg, Germany
  • 1979
    • Institut für Interdisziplinäre Medizin Hamburg
      Hamburg, Hamburg, Germany