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Find video protocols related to scientific articles indexed in Pubmed.
Botulinum toxin for salivary disorders in the treatment of head and neck cancer.
Anticancer Res.
PUBLISHED: 11-05-2014
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During the treatment of head and neck cancer (HNC), salivary problems may impair a patient's healing process. Botulinum toxin (BoNT) is accepted as an effective treatment option for reducing salivary flow. We aimed to describe the features of patients treated with BoNT to determine the effects of BoNT.
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Amplification options in unilateral aural atresia: an active middle ear implant or a bone conduction device?
Otol. Neurotol.
PUBLISHED: 08-15-2014
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There is no consensus on treatment of patients with congenital unilateral aural atresia. Currently, 3 intervention options are available, namely, surgical reconstruction, application of a bone-conduction device (BCD), or application of a middle ear implant.
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Immune imbalance in nasal polyps of Caucasian chronic rhinosinusitis patients is associated with a downregulation of E-selectin.
J Immunol Res
PUBLISHED: 05-19-2014
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Chronic rhinosinusitis with nasal polyps (CRSwNP) in Caucasians is a chronic Th2 inflammatory disease of the nasal and paranasal mucosa and the recruitment of leukocytes to the site of inflammation is poorly understood. We studied mRNA and protein expression profiles of adhesion molecules in nasal polyp and associated inferior turbinate tissues using molecular, biochemical, and immunohistological methods. Analysis showed a strongly decreased E-selectin expression in nasal polyps with a significant difference between eosinophil and neutrophil counts in nasal polyps and balanced counts in inferior turbinates. E-selectin expression is known to be downregulated in a Th2 milieu and has an essential role in immunosurveillance by locally activating neutrophil arrest and migratory function. A downregulation of E-selectin may come along with an immune imbalance in Caucasian nasal polyps due to a significant inhibition of neutrophil recruitment. Therefore, we suggest that an upregulation of E-selectin and the associated influx of neutrophils may play a significant role in the resolution of inflammation as well as for the pathophysiology of nasal polyps of Caucasian chronic rhinosinusitis patients.
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The complement receptors CD46, CD55 and CD59 are regulated by the tumour microenvironment of head and neck cancer to facilitate escape of complement attack.
Eur. J. Cancer
PUBLISHED: 05-05-2014
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Membrane-bound complement restriction proteins (mCRPs) CD46, CD55 and CD59 enable tumour cells to evade complement dependent cytotoxicity and antibody-dependent killing mechanisms. But less is known about the role of these mCRPs in head and neck cancer.
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The MEK1/2-ERK1/2 pathway is activated in chronic rhinosinusitis with nasal polyps.
Arch. Immunol. Ther. Exp. (Warsz.)
PUBLISHED: 03-09-2014
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Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease that has a considerable impact on the quality of life. Alterations in signalling pathways may contribute to the ongoing inflammation and proliferation in CRSwNP. The MEK1/2-ERK1/2 pathway transmits signals from many extracellular molecules to regulate cellular processes. We examined tissue samples from nasal polyps and the inferior turbinate of patients with CRSwNP and the inferior turbinate from subjects with healthy mucosa. The expressions of MEK1/2, ERK1/2, and their active phosphorylated forms pMEK1/2 and pERK1/2 were analysed using DNA microarray, quantitative real-time PCR, protein array, Western hybridisation, and immunohistochemistry. We detected increased MEK1/2 protein expression in nasal polyps compared to the inferior turbinates of patients with CRSwNP or healthy mucosa. We also found a higher amount of MEK1/2 in the inferior turbinates of patients with CRSwNP compared to those with healthy mucosa. Most importantly, we observed a significant increase in the phosphorylation of MEK1/2 and ERK1/2 in nasal polyps compared to both types of controls. We observed activation of the MEK1/2-ERK1/2 pathway in nasal polyps. Interestingly, we did not see the same activation pattern in different tiers of the MEK1/2-ERK1/2 signalling cascade. One explanation for this result is that the components enhance the complex MEK-ERK cascade in a distinct manner, enabling a wide variety of functions. The MEK1/2-ERK1/2 pathway appears to play a pivotal role in the pathogenesis of CRSwNP.
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Evaluation of the prognostic role of tumor cell podoplanin expression in locally advanced squamous cell carcinoma of the head and neck.
Strahlenther Onkol
PUBLISHED: 03-05-2014
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To investigate the potential prognostic role of tumor cell podoplanin expression in patients treated with resection followed by irradiation or chemoradiotherapy for locally advanced squamous cell carcinoma of the head and neck (SCCHN).
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Stem cell profiling in head and neck cancer reveals an Oct-4 expressing subpopulation with properties of chemoresistance.
Oral Oncol.
PUBLISHED: 01-07-2014
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In the past decade cancer, including head and neck squamous cell cancer (HNSCC), is increasingly being regarded as a stem cell associated disease which arises from cells with the property of stemness. According to the cancer stem cell (CSC) theory, only a specific subpopulation of cancer cells has the ability to initiate and perpetuate cancer growth, especially under treatment. In this article we describe a subpopulation of cells within HNSCC that expresses the stemness factor Oct-4, which leads to apoptotic resistance after exposure to chemotherapeutic agents.
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Biological impact of superparamagnetic iron oxide nanoparticles for magnetic particle imaging of head and neck cancer cells.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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As a tomographic imaging technology, magnetic particle imaging (MPI) allows high spatial resolution and sensitivity, and the possibility to create real-time images by determining the spatial distribution of magnetic particles. To ensure a prospective biosafe application of UL-D (University of Luebeck-Dextran coated superparamagnetic nanoparticles), we evaluated the biocompatibility of superparamagnetic iron oxide nanoparticles (SPIONs), their impact on biological properties, and their cellular uptake using head and neck squamous cancer cells (HNSCCs).
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Increased Activation and Differentiated Localization of Native and Phosphorylated STAT3 in Nasal Polyps.
Int. Arch. Allergy Immunol.
PUBLISHED: 06-21-2013
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Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial disease; the underlying mechanisms of cell signalling are not fully understood. STAT3 (signal transducer and activator of transcription 3) is a phosphokinase and a key signalling molecule implicated in cell cycle regulation. We studied the distribution and expression of STAT3 to examine the role of STAT3 in the pathogenesis of CRSwNP. Methods: We investigated tissue samples of the nasal polyps and inferior turbinate of patients with CRSwNP as well as samples of the inferior turbinate of subjects without chronic sinusitis. The expression levels of STAT3 and its activated form pSTAT3 were analysed using Western blotting, protein array, DNA microarray and immunohistochemistry. Results: No significant differences were found in STAT3-mRNA levels between the samples of nasal polyps and inferior turbinates of the same patient. However, the amount of pSTAT3 was increased in the polyp tissue compared to the inferior turbinates from both CRSwNP patients and control subjects (p < 0.01), indicating an activation of STAT3 in polyps. We identified a varying distribution pattern of pSTAT3; pSTAT3 was primarily found in superficial epithelial cells but not in the basal layer of the epithelium of the turbinate, whereas pSTAT3 was located in all layers of the epithelium of the polyp and mostly noted in the basal layer. Conclusions: Our results of the activation and varying localisation of STAT3 and its phosphorylated form in nasal polyps suggest that pSTAT3 plays a crucial role in the proliferative development of nasal polyps. © 2013 S. Karger AG, Basel.
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Cytokine changes in response to radio-/chemotherapeutic treatment in head and neck cancer.
Anticancer Res.
PUBLISHED: 06-11-2013
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Radiation and systemic chemotherapy are standard treatment strategies for advanced or metastatic head and neck cancer. However, little is known about the implications and changes in the tumor microenvironment, including the T-helper (TH)1/TH2 balance in response to these treatment regimens. The aim of the current study was to unravel the effects of chemotherapeutic drugs and radiation on cytokine changes.
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Perioperative image-adapted brachytherapy for the treatment of paranasal sinus and nasal cavity malignancies.
Brachytherapy
PUBLISHED: 05-23-2013
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Sinonasal malignancies are a rare group of cancers often associated with late presentation and poor prognosis. In the past, there was little progress regarding survival rate, and often, multimodal treatment regimens are required. The aim of this study was to evaluate the clinical outcome of perioperative image-adapted brachytherapy (IABT) as part of a multidisciplinary treatment regimen for the therapy of sinonasal cancer.
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Phase I/II clinical study on safety and antivascular effects of paclitaxel encapsulated in cationic liposomes for targeted therapy in advanced head and neck cancer.
Head Neck
PUBLISHED: 04-18-2013
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The purpose of this phase I/II clinical trial was to test safety and effectiveness of 2 doses of vascular targeting cationic liposomes encapsulating paclitaxel (EndoTAG-1 [ET]) in human head and neck squamous cell carcinoma (HNSCC).
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Grading system for the selection of patients with congenital aural atresia for active middle ear implants.
Neuroradiology
PUBLISHED: 03-19-2013
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Active middle ear implants (aMEI) are being increasingly used for hearing restoration in congenital aural atresia. The existing gradings used for CT findings do not meet the requirements for these implants. Some items are expendable, whereas other important imaging factors are missing. We aimed to create a new grading system that could describe the extent of the malformation and predict the viability and challenges of implanting an aMEI.
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CpG-Induced IFN-? production of plasmacytoid dendritic cells: time and dosage dependence and the effect of structural modifications to the CpG backbone.
Nucleic Acid Ther
PUBLISHED: 02-15-2013
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Plasmacytoid dendritic cells (pDCs) represent a highly specialized immune cell subset and are considered to be the main sentinels against viral infections and play an important role in the development of immune tolerance. pDCs are able to recognize cytosine-phosphate-guanosine (CpG) motifs within microbial DNA, which are unmethylated CG dinucleotides in a certain sequence context and trigger the secretion of interferon (IFN)-? and other proinflammatory cytokines. Here we used the typical class A CpG oligodeoxynucleotide (ODN) 2216, the B-class ODN 2006, and the newly synthesized CpG ODN TM64 to explore the potency and kinetics of IFN-? stimulation of pDC. TM64 CpG ODN has a hexanucleotide sequence TCGTGT that leads to an increased cellular uptake and features a CpG nucleotide within the sequence that leads to a potent specific B-cell stimulation, thus characteristics similar to a class B CpG. Our data reveals that all CpGs act as both dosage- and time-dependent stimuli of IFN-? secretion. The relationship between concentration of the stimulant and the secreted amount of IFN-? is not linear and results in a plateau formation, with saturation kinetics. Alteration to the backbone can change duration and quantity of overall IFN-? secretion.
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Influence of silicone gel on standardized postoperative scars.
J Dtsch Dermatol Ges
PUBLISHED: 02-05-2013
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Silicone gel is one therapeutic approach in the treatment and prevention of excessive scarring. The likely mechanism of action is the hydration of the tissue. This should lead to reduced angiogenesis and capillary blood flow. The efficacy is still controversial and the evidence base, insufficient. The aim of this prospective and standardized study is to investigate silicone gel in the preventive treatment of scars.
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Phosphorylation of STAT3 in head and neck cancer requires p38 MAPKinase, whereas phosphorylation of STAT1 occurs via a different signaling pathway.
Anticancer Res.
PUBLISHED: 11-24-2011
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STAT proteins work as signal transducers as well as transcription and activator proteins. In head and neck cancer both STAT1 and STAT3 are overexpressed. STAT3 contributes to malignant transformation and regulates tumor promoting cytokines, whereas STAT1 is purported to act antagonistically as a tumor suppressor. Since our previous data determined p38 MAPK to be a potent regulator of interleukin-6 (IL-6) and IL-8 expression in permanent head and neck squamous cell carcinoma (HNSCC) cell lines, we investigated the influence of this pathway on STAT3 and STAT1. Down-regulation of p38 MAPK expression levels by siRNA strongly reduces phosphorylation of STAT3 tyrosine 705 without any effects on phosphorylation of STAT3 serine 727 and STAT1. Analyzing the effect of silencing of ERK1/2 MAPK revealed that this MAPK strongly influences IL-6 and IL-8 expression, but is not involved in either activation of STAT1 or STAT3. Our data indicate STAT3 as a potent promoter of HNSCC progression.
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Biodistribution of 131I-labeled anti-CK8 monoclonal antibody in HNSCC in xenotransplanted SCID mice.
Anticancer Res.
PUBLISHED: 10-04-2011
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A new promising approach to improve the outcome of head and neck squamous cell carcinoma (HNSCC) is the application of radio-labeled antibodies directed against tumor-associated antigens. Cytokeratin 8 (CK8), an intermediate filament forming protein, is shown to be de novo expressed in dysplastic lesions as well as in HNSCC. Therefore like the epithelial cell adhesion molecule CK8 seems to be a suitable anchor molecule for targeted radioimmunotherapy (RIT). The aim of this study was to investigate the biodistribution of a radio-labeled Cytokeratin 8-specific monoclonal antibody (mAb) in a SCID (severe combined immunodeficiency disease) mouse model.
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Innate signaling in otitis media: pathogenesis and recovery.
Curr Allergy Asthma Rep
PUBLISHED: 04-20-2011
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Otitis media (OM) is the most prevalent childhood disease in developed countries. Involvement of innate immunity mediated by Toll-like receptors (TLRs) in OM has been implicated primarily in cell lines and by association studies of innate immune gene polymorphisms with OM prevalence. However, the precise role of innate immunity in OM is incompletely understood. We review recent research that has advanced our understanding of how innate immunity in the middle ear is mediated by the interaction of pathogen molecules with receptors such as the TLRs, leading to the activation of adaptor molecules and production of proinflammatory cytokines. TLR genes and signaling molecules are upregulated in OM in a murine model. Deletion of several key innate immune genes results in persistent OM in mice, coupled with an inability to clear bacterial infection from the middle ear. It is concluded that an intact innate immune signaling system is critical to recovery from bacterial OM.
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Evaluation and development of a predictive model for ultrasound-guided investigation of neck metastases.
Eur Arch Otorhinolaryngol
PUBLISHED: 04-11-2011
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Ultrasound investigations for the correct identification of lymph node metastases depend on the experience and qualifications of the investigator; thus, model that provides better preoperative evaluation is desired. Data from 290 patients with an upcoming neck dissection were analyzed to compare the preoperative ultrasound assessment of neck metastases with the pathologically proven postoperative neck status. In total, 364 data sets with 200 malignant and 164 benign lymph nodes were explored. The minimal and maximal transverse diameters and their ratio were shown to be especially good parameters for sensitivity, whereas the echostructure and the presence of a hilum were good for specificity. A model incorporating the evaluated markers is presented. The model provides better judgement of neck lymph nodes in a more objective manner. Using logistic regression, five parameters were identified to predict metastases.
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The number of CD161 positive Th17 cells are decreased in head and neck cancer patients.
Cell. Immunol.
PUBLISHED: 03-07-2011
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Despite lots of research efforts, the pathology of head and neck cancer remains elusive. Accumulating evidence suggests that the innate and adaptive immunity plays an important role in HNSCC (Head and Neck Squamous Cell Carcinoma) development. Recently, a new T helper cell subset additional to the classical Th1 and Th2 cells was identified called Th17 cells, due to their secretion of IL-17. However, Th17 cells also produce additional proinflammatory cytokines and many other cytokines are involved in their differentiation and expansion. It was shown that Th17 cells play a prominent role in host defense but are also associated with the development of autoimmune diseases. The role of Th17 cells in cancer pathogenesis remains nebulous.
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Stem cells in squamous head and neck cancer.
Crit. Rev. Oncol. Hematol.
PUBLISHED: 03-07-2011
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The initiation and metastasis of head and neck squamous cell carcinomas (HNSCC) and other cancers have recently been related to the presence of cancer stem cells (CSC). CSC are cancer initiating, sustaining and are mostly quiescent. Specific markers that vary considerably depending on tumor type or tissue of origin characterize putative CSC. Compared to the bulk tumor mass, CSC are less sensitive to chemo- and radiotherapy and may also have low immunogenicity. Therapeutic targeting of CSC may improve clinical outcome of HNSCC which has two distinct etiologies: infection of epithelial stem cells by high-risk types of the human papillomavirus, or long-term tobacco and alcohol abuse. Recent knowledge on the role of CSC in HNSCC is reviewed and where necessary parallels to CSC of other origin are drawn to give a more comprehensive picture.
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Established and novel NF-?B inhibitors lead to downregulation of TLR3 and the proliferation and cytokine secretion in HNSCC.
Oral Oncol.
PUBLISHED: 01-24-2011
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The transcriptional activation of NF-?B signalling has been identified as a major pathway involved in inflammation and tumor aggressiveness in a number of human cancers. Here we identify the impact of miscellaneous known and so far unknown NF-?B inhibitors originating from different drug classes on the function and proliferation of HNSCC. In detail: HNSCC cell lines were exposed to Acetylsalicylic Acid (ASA), Celecoxib, Dexamethasone, Curcumin and EPs 7630. Our major interest was to detect upstream alterations in cell signalling after applying NF-?B inhibiting substances. The inhibition of NF-?B signalling leads to an upstream regulation of Toll-like-receptor 3 (TLR3), a predominant receptor driving cell expansion. We find a marked downregulation of TLR3 and IKK complex, documenting upstream responses to NF-?B inhibition by every agent tested. In a second step we further analyse proliferation, cytokine production and alterations in the expression of downstream proteins such as cyclin D1 and c-Myc. Our data demonstrate decreased proliferation in response to incubation with aforementioned agents. Modulation of TLR3 and NF-?B expression is accompanied by altered profiles of IL-6 and IL-8 which are relevant cytokines in HNSCC progression. Proto-oncogenes cyclin D1 and c-myc are downregulated by all substances. Apart from the interplay of cytokines and TLR3, we substantiated EPs 7630 as a new and natural NF-?B inhibitor.
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Plasmacytoid dendritic cell subpopulations in head and neck squamous cell carcinoma.
Oncol. Rep.
PUBLISHED: 01-19-2011
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Human plasmacytoid dendritic cells (PDCs) are present in solid tumor tissue and metastatic cervical lymph nodes (CLN) in head and neck squamous cell carcinoma (HNSCC). We recently showed that classical PDC functions are heavily disturbed in the tumor microenvironment. In this study we present a new approach to the subject by introducing 3 PDC subsets in HNSCC, characterized by the surface markers CD25, CD56 and CD203c. The first subset, positive for CD25, is significantly induced by HNSCC in vitro and present in metastatic lymph nodes in vivo. This subset can be phenotypically subdivided into matured cells and into a group expressing early T cell markers. Functionally this subgroup is associated with the secretion of IL-8. The second subset, positive for CD56, constitutes 4-5% of all PDCs and is significantly down-regulated by HNSCC. Furthermore, this population sporadically expresses perforin/granzyme B and is absent in metastatic lymph nodes. The third subset, positive for the basophile marker CD203c, is inducible by crosslinking BDCA-2 in the presence of HNSCC and IL-4. Future studies will have to clarify the in vivo relevance of the different PDC subsets in HNSCC.
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mTOR inhibitors show promising in vitro activity in bladder cancer and head and neck squamous cell carcinoma.
Oncol. Rep.
PUBLISHED: 01-14-2011
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Bladder cancer and head and neck squamous cell carcinoma (HNSCC) are frequent but lack efficient therapies especially in advanced disease. Almost no studies on mTOR function and inhibition in these tumor entities have been reported. We examined the gene and protein expression levels of mTOR and its activated form (pmTOR) in three human bladder carcinoma cell lines (RT-4, T24, EJ28) and three HNSCC cell lines (PCI-1, PCI-13, BHY). Furthermore, the consequences of mTOR inhibition by mTOR-specific siRNAs and the mTOR inhibitor temsirolimus were analysed in vitro using immunohistochemical Ki-67 staining, mTOR and pmTOR western blot analysis, MTT assay, as well as cell cycle analysis with flow cytometry. Especially pmTOR protein expression levels showed marked differences between cell lines. siRNA transfection was associated with dose-dependent target protein reduction but not proliferation inhibition or apoptosis. On the contrary, temsirolimus significantly reduced cell viability and induced apoptosis and cell cycle arrest. According to these data, bladder cancer and HNSCC are promising tumor entities for mTOR inhibition with temsirolimus.
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The role of DNA sensing and innate immune receptor TLR9 in otitis media.
Innate Immun
PUBLISHED: 01-14-2011
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Otitis media (OM), a common infectious disease in children, is associated with bacterial middle ear (ME) infection. Toll-like receptors (TLRs) are important mediators of innate immune responses, and TLR9 specifically recognizes the unmethylated cytidine-phosphate-guanosine (CpG) motifs in bacterial DNA. Additional sensors of foreign DNA have recently been identified. The role of DNA sensing and TLR9 was investigated in a murine model of OM induced by non-typeable Haemophilus influenzae (NTHi). Expression of genes related to DNA-sensing pathways involved in innate immunity was assessed via DNA microarray, qPCR and immunohistochemistry. Middle ear responses to NTHi were examined in wild-type and TLR9(-/-) mice by histopathology and bacterial culture. Expression of TLR9 signaling genes was modestly up-regulated during OM, as was TLR9 protein in both ME mucosal cells and infiltrating leukocytes. However, genes known to be regulated by CpG DNA were dramatically up-regulated, as were genes involved in DNA sensing by DIA, Pol-III and AIM2. Toll-like receptor 9 deletion significantly prolonged the inflammatory response induced by NTHi in the ME and delayed bacterial clearance. The results suggest that DNA sensing via TLR9 plays a role in OM pathogenesis and recovery. Alternative forms of DNA sensing may also contribute to OM.
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Expression of the T cell receptor ?? on a CD123+ BDCA2+ HLA-DR+ subpopulation in head and neck squamous cell carcinoma.
PLoS ONE
PUBLISHED: 01-11-2011
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Human Plasmacytoid Dendritic Cells (PDCs) infiltrating solid tumor tissues and draining lymph nodes of Head and Neck Squamous Cell Carcinoma (HNSCC) show an impaired immune response. In addition to an attenuated secretion of IFN-? little is known about other HNSCC-induced functional alterations in PDCs. Particular objectives in this project were to gain new insights regarding tumor-induced phenotypical and functional alterations in the PDC population. We showed by FACS analysis and RT-PCR that HNSCC orchestrates an as yet unknown subpopulation exhibiting functional autonomy in-vitro and in-vivo besides bearing phenotypical resemblance to PDCs and T cells. A subset, positive for the PDC markers CD123, BDCA-2, HLA-DR and the T cell receptor ?? (TCR-??) was significantly induced subsequent to stimulation with HNSCC in-vitro (p?=?0.009) and also present in metastatic lymph nodes in-vivo. This subgroup could be functionally distinguished due to an enhanced production of IL-2 (p?=?0.02), IL-6 (p?=?0.0007) and TGF-? (not significant). Furthermore, after exposure to HNSCC cells, mRNA levels revealed a D-J-beta rearrangement of the TCR-beta chain besides a strong enhancement of the CD3? chain in the PDC population. Our data indicate an interface between the PDC and T cell lineage. These findings will improve our understanding of phenotypical and functional intricacies concerning the very heterogeneous PDC population in-vivo.
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Implication of stem cells in the biology and therapy of head and neck cancer.
GMS Curr Top Otorhinolaryngol Head Neck Surg
PUBLISHED: 01-01-2011
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The progress which has been made in the therapy of patients with head and neck cancer in recent years mainly concern the HPV associated HNSCC and the quality of life. The overall survival of patients carrying non HPV associated HNSCC during the last thirty years has not experienced any significant improvement and must be referred to as static [1], [2]. The problem of the illness remains unchanged in the frequent and poorly controllable relapse situation. The locoregionally originating tumours or lymph node metastases show a considerably poorer response towards current therapies. Likewise for a number of patients a formation of distant metastases seems to develop during the course of the illness. Those distant metastases are also therapeutically rather difficult to control. Therefore the mortality of the non HPV induced head and neck cancer remains unchanged. The term "stem cell" describes the entity cell, which acts as a reservoir for new cells in order to replace defective or necrotic cells. A fundamental characteristic of stem cells is the constant ability to multiply into different type of cells, which subsequently do not proliferate. With the insight of new knowledge within the regenerative medicine and the ability of stem cells of self regenerating proliferation and their multipotency in the differentiation, the origin of cancer attains a new distinction. If you look on the tumour as a malignant wound it becomes obvious, that the regeneration or the composition of additional tissue depends on the presence and differentiation of stem cells. The wound healing, which is a regeneration of tissue depends not only on stationary stem cells. In fact stem cells are attracted for "homing" in the defective areas by despatch of various messengers, which then form and replace the vascular tree or other tissue [3], [4].Next to those stem cells, which functionally help to form tumour tissue, a small entity of "real cancer stem cells" in solid tumours is expected. Those occur in tumours and they have typical stem cell characteristics like self-regeneration and the potential of differentiation and are potentially responsible for tumour growth. With their ability of self-regeneration they would have the ability to form a complete tumour out of every single cell. That tumour would histologically look like the tumour those cells initially originated from. Of particular interest regarding those currently still elusive cancer stem cells is their resistance towards current therapies like radiotherapy or chemotherapy. Those insights now get a completely new meaning in tumour biology: Does a cancer stem cell exist, which is able to initiate and keep up tumour growth despite all possible therapeutic interventions? This presentation will outline the current views regarding cancer stem cells in non HPV associated HNSCC and it will highlight problems, which are currently researched on. The objective must be to understand the biology of those cells in a way that make an extended range of therapeutics possible. A therapy, which specifically targets cancer stem cells, could improve the chances of recovery.
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Dexamethasone and N-acetyl-cysteine attenuate Pseudomonas aeruginosa-induced mucus expression in human airways.
Pulm Pharmacol Ther
PUBLISHED: 07-28-2010
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Infection with Pseudomonas aeruginosa (PA) induces mucus hypersecretion in airways. Therapeutic options to attenuate excessive mucus expression are sparse.
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Propofol in bronchoalveolar lavage during anaesthesia.
Clin. Chim. Acta
PUBLISHED: 07-22-2010
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The lung protecting effect of propofol requires methods to measure the propofol concentration of the epithelial line fluid covering the alveolar surface. We hypothesized that (1) propofol can be determined in bronchoalveolar lavage (BAL) by reversed phase high performance liquid chromatography with fluorescence detection. (2) Positive end-expiratory pressure (PEEP) ventilation may have an effect on propofol concentration in BAL (cpB).
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Permanent up-regulation of regulatory T-lymphocytes in patients with head and neck cancer.
Int. J. Mol. Med.
PUBLISHED: 06-02-2010
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Various immune functions of different types of immune cells are strongly impaired in patients with head and neck squamous cell carcinoma (HNSCC). Regulatory T-lymphocyte cells (Tregs) have been suggested to be involved in the immunomodulation of immune responses and contribute to HNSCC progression and immune escape. Naturally occurring CD4+ CD25+ Tregs represent a small fraction within the different subsets of regulatory T cells, which are known to inhibit numerous immune functions of different types of immune cells. In this study, the cellular ratio of CD4+ CD25(high) Tregs to the entire population of CD4+ T-lymphocytes was analyzed with respect to different stages of tumor progression and disease. Our data indicate a significantly high increased abundance of CD4+ CD25(high) CD127(low) Tregs in the peripheral blood of patients with HNSCC, which in addition show modulated expression levels of various functional proteins. Surprisingly, increased Treg levels were found even in patients with no active disease several years after tumor resection, with no significant correlation to the individual tumor stage. Additionally, increased levels of chemokine CCL22, which mediates migration of Tregs to the tumor, and upregulation of the corresponding receptor protein CCR4 were observed in HNSCC. Our data strongly suggest that HNSCC leads to a permanent shift of Treg levels with hardly recognizable recovery rates.
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Metastases of squamous cell carcinoma of the head and neck show increased levels of nucleotide excision repair protein XPF in vivo that correlate with increased chemoresistance ex vivo.
Int. J. Oncol.
PUBLISHED: 04-08-2010
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Nucleotide excision repair (NER) is a key node of resistance of tumour cells to the anticancer drug cisplatin. Testicular germ cell tumours (TGCT) show exquisite sensitivity towards cisplatin, and this has been connected to low levels of the NER proteins ERCC1 and XPF. Tumours of some patients with advanced head and neck squamous cell carcinoma (HNSCC) regress well under cisplatin chemotherapy but prediction of responsiveness is poor. Little is known about the levels of ERCC1-XPF in HNSCC tissues and cell lines. We investigated mRNA and protein levels of ERCC1 and XPF in 13 HNSCC cell lines and seven testis tumour cell lines and examined the correlation between levels of ERCC1 and XPF and cellular resistance towards cisplatin. No significant difference in mRNA expression of either ERCC1 or XPF in the HNSCC cell lines compared to the testis tumour cell lines was observed. Significantly higher XPF protein levels were found in HNSCC cell lines compared to testis tumour cell lines resulting in cellular cisplatin resistance. The data indicate a contribution of XPF protein for the cisplatin resistance observed in HNSCC cell lines. Subsequently, XPF and ERCC1 protein expression was investigated in cancer tissue of 34 patients. XPF levels were significantly higher in metastases of HNSCC patients than in primary cancer tissue. These findings indicate a contribution of XPF protein for the observed chemoresistance in some HNSCC tissue. XPF protein may be a predictive marker for cisplatin responsiveness of metastases in HNSCC patients.
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Application of the Vibrant Soundbridge in bilateral congenital atresia in toddlers.
Acta Otolaryngol.
PUBLISHED: 01-29-2010
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The Vibrant Soundbridge offers an excellent audiologic rehabilitation for toddlers with microtia and atresia. It provides direct stimulation of the cochlea and straightforward adaption to the given anatomical structures. The posterior atresia incision preserves the physical integrity of the tissue layers around the ear remnant, which is essential for an aesthetic auricular reconstruction.
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Cytokine release of human NK cells solely triggered with Poly I:C.
Cell. Immunol.
PUBLISHED: 01-07-2010
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Natural killer (NK) cells play a crucial role in innate immunity as effectors against tumor cells and pathogen-infected cells. Our data show for the first time that NK cells produce high levels of cytokines interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in response to stimulation with the artificial RNA analogue Poly I:C without additional cytokines or contact to other types of immune cells. An incubation period of 48 h is necessary to induce cytokine release by Poly I:C. These data suggest Poly I:C as a competent direct activator and immunomodulator of NK cell functions.
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Sleep apnoea in patients after treatment of head neck cancer.
Acta Otolaryngol.
PUBLISHED: 10-30-2009
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The prevalence of sleep apnoea among patients following treatment of head and neck carcinomas seems to be slightly higher than in the normal population. The possible importance of tumour treatment features, especially transient tracheostoma, needs further assessment.
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A prospective evaluation of psychosocial outcomes following ear reconstruction with rib cartilage in microtia.
J Plast Reconstr Aesthet Surg
PUBLISHED: 08-24-2009
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Little is known about the psychosocial improvement of microtic patients following reconstruction with rib cartilage. Furthermore, no data exist on detailed follow-ups of patients who refused ear repair. To the best of our knowledge, this is the first report of a prospective evaluation of psychosocial outcomes with a validated instrument in ear reconstruction with rib cartilage. Twenty-one patients, who had undergone rib-cartilage reconstruction to treat a congenital auricular defect, were evaluated prospectively for psychosocial changes using a clinically validated questionnaire. In addition, patients were asked to judge the new auricle and thoracic scar. Twenty-three patients, who decided against an ear reconstruction following consultation, were analysed for the reasons behind their refusal. Almost 66% of the treated patients were able to integrate the new ear into their body concept. If faced with the same surgery decision again, 88% would still choose to undergo ear reconstruction with rib cartilage. There were strong postoperative improvements in psychosocial attitude (p=0.02). In our sample, patients who declined ear repair showed higher values of psychosocial attitude (p=0.006) compared with the preoperative results in treated patients. Our study shows that the clinically known improvement of psychosocial aspects can be documented by a validated psychological test. The patients expectations and surgical limits of the reconstruction with rib cartilage need detailed discussion prior to surgery to prevent dissatisfaction despite surgical success. Our data help to accept a childs denial as these patients have a good psychosocial standing even with an unrepaired microtia.
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Decreased levels of circulating regulatory NK cells in patients with head and neck cancer throughout all tumor stages.
Anticancer Res.
PUBLISHED: 08-08-2009
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Natural killer (NK) cells play a crucial role in innate immunity as effectors against tumor cells and pathogen-infected cells. Human NK cells can be subdivided into two functional subsets, the immunoregulatory CD56(bright) NK cells and the cytotoxic CD56(dim) NK cells. NK-mediated host defence against tumor cells is strongly impaired in patients with head and neck squamous cell carcinoma (HNSCC).
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Effect of head and neck cancer supernatant and CpG-oligonucleotides on migration and IFN-alpha production of plasmacytoid dendritic cells.
Anticancer Res.
PUBLISHED: 08-08-2009
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Plasmacytoid dendritic cells (PDCs) infiltrating solid tumor tissues and draining lymph nodes of head and neck squamous cell carcinoma (HNSCC) show an impaired immune response. Immunosuppressive cytokines secreted by HNSCC have been recognized to account for reduced interferon-alpha (IFN-alpha) production, whereas the influence on PDC migration has not yet been investigated.
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Glandular tissue from human pancreas and salivary gland yields similar stem cell populations.
Eur. J. Cell Biol.
PUBLISHED: 01-23-2009
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Stem cells derived from pancreatic tissue are well characterized and exhibit a broad plasticity as they can differentiate beyond lineage boundaries into many cell types. The aim of this study was the comparative characterization of pancreatic stem cells with one other derivate of the embryonic foregut, namely salivary glands, for the existence of similar stem cell populations. The expression of stem cell markers as well as lineage-specific markers was detected by reverse transcription polymerase chain reaction, flow cytometry and immuncytochemical staining. The isolated cells from salivary glands and pancreas grew adherently in vitro and could be maintained for up to 55 and 46 population doublings, respectively. Cells from both tissues showed a comparable phenotype. They expressed different embryonic and adult stem cell markers and had the ability to differentiate spontaneously into cells representing the three embryonic germ layers. Additionally, the directed differentiation of glandular stem cells into the mesodermal lineage was achieved, yielding adipogenic, osteogenic and chondrogenic cells from salivary gland stem cells as well as osteogenic and chondrogenic cells from pancreatic stem cells. Here, we compared two stem cell populations from different glandular tissues which showed similar phenotypes and analogous properties. During embryonic development the two exocrine glands originate from the foregut, which might be the explanation for these intriguing resemblances.
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Tumour-derived prostaglandin E and transforming growth factor-beta synergize to inhibit plasmacytoid dendritic cell-derived interferon-alpha.
Immunology
PUBLISHED: 01-11-2009
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In previous studies we reported that plasmacytoid dendritic cells (PDC) infiltrating head and neck cancer tissue are functionally impaired, but the molecular basis for the functional deficiency remained unclear. Here we demonstrate that tumour-derived prostaglandin E2 (PGE(2)) and transforming growth factor-beta (TGF-beta) increase interleukin-8 (IL-8) but synergistically inhibit interferon-alpha (IFN-alpha) and tumour necrosis factor (TNF) production of Toll-like receptor 7 (TLR7)- and Toll-like receptor 9 (TLR9)-stimulated PDC. The inhibitory effect of PGE(2) could be mimicked by the induction of cyclic AMP (cAMP) and by inhibitors of cyclooxygenase. The contribution of tumour-derived TGF-beta was confirmed by the TGF-beta antagonist SB-431542. Suppression of tumour-derived PGE(2) and TGF-beta restored TLR-induced IFN-alpha production of PDC. Additionally, PGE(2)- and TGF-beta-treated PDC display a tolerogenic phenotype because of a downregulation of CD40 accompanied by an upregulation of CD86. Finally, in TLR-stimulated PDC, PGE(2) and TGF-beta reduce the CCR7:CXCR4 ratio, suggesting that PDC are impaired in their ability to migrate to tumour-draining lymph nodes but are retained in stromal cell-derived factor 1 (SDF-1)-expressing tissues. Based on these data, cyclooxygenase inhibitors and TGF-beta antagonists may improve TLR7- and TLR9-based tumour immunotherapy.
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Application of the Vibrant Soundbridge to unilateral osseous atresia cases.
Laryngoscope
PUBLISHED: 01-02-2009
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Patients with high-grade atresia-microtia suffer from a combined malformation of the outer and middle ears, typically leading to a severe hearing impairment. Long-term results of middle ear reconstruction with tympanoplasty are often insufficient due to persistent air-bone gaps, and new techniques in hearing rehabilitation are required. The objective of this research is to evaluate the active middle ear implant, the Vibrant Soundbridge (VSB), for hearing rehabilitation of patients with unilateral osseous aural atresia.
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Glycogen synthase kinase 3 in chronic rhinosinusitis: two faces of a single enzyme in one disease.
Ann. Allergy Asthma Immunol.
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The origin and pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) remain unclear. Glycogen synthase kinase 3 (GSK-3) is a unique multitasking kinase involved in the regulation of inflammation and apoptosis and is an important messenger in the downstream signaling of interleukin 6.
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Functional characterization of novel mutations affecting survivin (BIRC5)-mediated therapy resistance in head and neck cancer patients.
Hum. Mutat.
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Survivin (BIRC5) is an acknowledged cancer therapy-resistance factor and overexpressed in head and neck squamous cell carcinomas (HNSCC). Driven by its nuclear export signal (NES), Survivin shuttles between the nucleus and the cytoplasm, and is detectable in both cellular compartments in tumor biopsies. Although predominantly nuclear Survivin is considered a favorable prognostic disease marker for HNSCC patients, the underlying molecular mechanisms are not resolved. Hence, we performed immunohistochemical and mutational analyses using laser capture microdissection on HNSCC biopsies from patients displaying high levels of nuclear Survivin. We found somatic BIRC5 mutations, c.278T>C (p.Phe93Ser), c.292C>T (p.Leu98Phe), and c.288A>G (silent), in tumor cells, but not in corresponding normal tissues. Comprehensive functional characterization of the Survivin mutants by ectopic expression and microinjection experiments revealed that p.Phe93Ser, but not p.Leu98Phe inactivated Survivins NES, resulted in a predominantly nuclear protein, and attenuated Survivins dual cytoprotective activity against chemoradiation-induced apoptosis. Notably, in xenotransplantation studies, HNSCC cells containing the p.Phe93Ser mutation responded significantly better to cisplatin-based chemotherapy. Collectively, our results underline the disease relevance of Survivins nucleocytoplasmic transport, and provide first evidence that genetic inactivation of Survivins NES may account for predominantly nuclear Survivin and increased therapy response in cancer patients.
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Phase I clinical study of vascular targeting fluorescent cationic liposomes in head and neck cancer.
Eur Arch Otorhinolaryngol
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The aim of this first-time-in-human non-randomized dose-escalating prospective phase I clinical trial was to analyze safety of two doses of fluorescent rhodamine-labeled cationic liposomes (LDF01) in head and neck squamous cell carcinoma (HNSCC). Patients had resectable UICC stadium I-IV A HNSCCs. LDF01 was administered before tumor resection under general anesthesia as an intravenous infusion with effective lipid doses of 0.5 or 2 mg/kg b.w., respectively. In addition to clinical monitoring for safety assessment, tumor biopsies were taken during the surgical procedure for fluorescence histological analysis. Eight patients were assigned to the two dose groups. During safety follow-up no clinically relevant adverse events occurred. Fluorescence histology revealed some evidence of favorable selectivity of LDF01 for tumor microvessels in the high-dose group. LDF01 is safe applied as infusion at both tested dose levels. Furthermore, LDF01 can be detected in the vicinity of tumor cells and could be assigned to the microvessel target in individual HNSSC cases. Detailed analysis of targeting properties of LDF01 has to be performed in upcoming clinical phase II trials.
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The Lübeck flowchart for functional and aesthetic rehabilitation of aural atresia and microtia.
Otol. Neurotol.
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Current strategies for functional rehabilitation of microtia-atresia patients with bone-anchored implants or surgical atresia repair have been extended by the feasibility of active middle ear implants. The aim of the present research is to evaluate a new flowchart of the treatment of these patients that considers active middle ear implants.
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Laryngeal chondrosarcoma with unusual dissemination to the humerus.
ORL J. Otorhinolaryngol. Relat. Spec.
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We report the case of an 81-year-old woman admitted to our clinic with a 16-month history of hoarseness due to unilateral vocal cord immobilization, slowly progressive dysphagia and an episode of painless swelling of the right arm. Radiological and histological workup revealed a medium-grade conventional chondrosarcoma of the cricoid cartilage with paratracheal spread and dissemination to the lung and the humeral bone. To our knowledge, this is the first humeral bone metastasis of laryngeal chondrosarcoma reported in the literature. The course of the presented case underlines the need for an early and detailed clinical and radiological workup of vocal cord immobilization.
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Human mesenchymal stromal cells from adipose tissue of the neck.
Eur Arch Otorhinolaryngol
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Mesenchymal stromal cells (MSC) have been introduced into the field of tissue-engineered airway transplantation. Since patients with extensive tracheal defects often require an open tracheotomy, this study investigated if MSC could be obtained from the adipose tissue of the neck during this procedure. Cells were isolated by plastic adherence from the adipose tissue of 8 patients. Cell isolates were analyzed for (i) proliferation, (ii) the expression of CD marker molecules and (iii) multilineage differentiation. The isolated spindle-shaped cells showed a high proliferation capacity and the flow cytometric analysis revealed a distinct population meeting the criteria for MSC. Using classical MSC cultivation protocols the characterized cells showed adipogenic, chondrogenic and osteogenic differentiation for all analyzed cell isolates. This study was able to demonstrate that sufficient amounts of stem/progenitor cells can be easily isolated from adipose tissue of the neck obtained during open tracheotomy. These cells may be a source for future tracheal replacement therapies.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.