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1.
HNO ; 69(12): 952-960, 2021 Dec.
Article in German | MEDLINE | ID: mdl-33586050

ABSTRACT

BACKGROUND: The e­cigarette has become increasingly popular in recent years. However, the question of toxicity is not yet clear and there is global uncertainty regarding the use of e­cigarettes. This is intensified by the fact that there is a lack of declaration of the liquid ingredients. OBJECTIVE: The present paper investigates propylene glycol, a major component of the liquids, for possible acute inflammatory reactions as well as cytotoxic and genotoxic effects on human nasal mucosa cells. MATERIALS AND METHODS: The nasal mucosa cells from 10 volunteers were cultivated at the air-liquid interface and then exposed to different concentrations of propylene glycol. The analysis was carried out using the trypan blue test, comet assay, micronucleus test, and interleukin (IL)-6 and IL­8 sandwich ELISA. RESULTS: The trypan blue test showed no reduction in vitality. No increase in IL­6 and IL­8 concentrations were detected in the sandwich ELISA. In the comet assay, the Olive tail moment showed a dose-dependent increase in DNA fragmentation compared to the negative control at all examined concentrations. A difference between the pure substance and the negative control was shown in the micronucleus test. CONCLUSION: Possibly repairable dose-dependent DNA fragmentation and profound DNA alterations at high concentrations of propylene glycol warrant enhanced genotoxicological studies. These should include long-term exposure studies and assessment of further ingredients of the liquids. Consequently, the manufacturers need to be forced to declare the latter.


Subject(s)
Electronic Nicotine Delivery Systems , Nasal Mucosa/drug effects , Propylene Glycols/toxicity , Vaping/adverse effects , Cells, Cultured , Comet Assay , Humans , Inflammation , Micronucleus Tests , Nasal Mucosa/cytology
2.
HNO ; 68(1): 8-13, 2020 Jan.
Article in German | MEDLINE | ID: mdl-31511908

ABSTRACT

BACKGROUND: While an abundant number of studies concerning tobacco smoke and chewing tobacco show carcinogenic potential, there is little data on the consequences of snuff, especially on the cellular level. Therefore, the mutagenic effect of snuff is difficult to estimate and the WHO assessment of snuff being not carcinogenic is based on very limited data. OBJECTIVES: This paper investigates the potential cytotoxic and genotoxic effects of snuff on human lymphocytes and nasal mucosa cells. MATERIALS AND METHODS: Two types of snuff were used: one without menthol and one with a high degree of menthol. The necessary nasal mucosa cells and lymphocytes were collected from 10 subjects undergoing nasal obstruction surgery and incubated for one hour with a snuff-DMSO mixture (range 0.01-2000 µg/ml). Methods included the trypan blue test, the comet assay, and the micronucleus test. RESULTS: The trypan blue test showed no decrease in cell viability for either cell type. The comet assay revealed a significant increase in the Olive Tail Moment for lymphocytes starting at 100 µg/ml and at 1000 µg/ml for nasal mucosa cells. There was no significant increase in micronuclei according to the micronucleus test. No differences between these two types of tobacco were observed. CONCLUSION: The present study demonstrated genotoxic damage, such as DNA strand breaks, which may be repaired, but no non-repairable elevated micronuclei. The present findings cast doubts on the WHO assessment that snuff is not carcinogenic. However, for a sound assessment of the risk potential of snuff, further research on various genotoxic endpoints in human cells is warranted.


Subject(s)
Lymphocytes , Nasal Mucosa , Tobacco, Smokeless , Comet Assay , DNA Damage , Humans , Lymphocytes/drug effects , Nasal Mucosa/drug effects , Tobacco, Smokeless/adverse effects
3.
Laryngorhinootologie ; 95(11): 774-782, 2016 Nov.
Article in German | MEDLINE | ID: mdl-27128640

ABSTRACT

Objective: Voice feminization is an important step in the therapy of male-to-female transsexualism. Approaches are conservative voice therapy and surgical interventions. The most powerful parameter of gender perception is the fundamental frequency. Besides the vocal pitch, there are other parameters influencing gender perception of a voice, e. g. intonation, prosody or formant frequencies. Material and methods: In 21 male to female transgender persons after surgical elevation of the vocal pitch the Voice Handicap Index (VHI), the Life Satisfaction Questionnaire (FLZ) and a new addendum were used. A new algorithm for voice feminization in male-to-female transsexualism was deduced. Results: After elevation of the vocal pitch, the self-confidence of the male-to-female transgender persons has increased. Despite of an elevated pitch some persons were not satisfied with their voice. Conclusion: Surgical intervention changes only the pitch of a voice. To change other parameters, conservative voice therapy is necessary. If the transgender persons are able to reach a satisfying female voice with conservative voice therapy alone, surgical intervention is not indicated.


Subject(s)
Algorithms , Patient Satisfaction , Transgender Persons , Voice Quality , Female , Humans , Male , Transsexualism
4.
Oncol Rep ; 35(1): 219-26, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26530463

ABSTRACT

Human mesenchymal stem cells (hMSCs) have been applied therapeutically in numerous clinical trials. The pro-angiogenic effects of hMSCs, as well as their strong tumor tropism, have been shown both in vitro and in vivo. Some studies suggest using hMSCs as potential drug-carriers for tumor therapy. In previous investigations by our group, the pro-tumorigenic effects of hMSCs on head and neck squamous cell carcinoma (HNSCC) were shown. However, the influence of hMSCs on tumor vascularization as well as the possibility of its inhibition are yet to be elucidated. The cytokine patterns of the HNSCC cell line FaDu, native hMSCs (hMSCs-nat), hMSCs differentiated into adipocytes (hMSCs-adip) and osteocytes (hMSCs-ost) were evaluated. Human umbilical vein endothelial cells (HUVECs) were co-cultured with FaDu cells, hMSCs-nat, hMSCs-adip and hMSCs-ost. The capillary tube formation assay was applied. Furthermore, the migration capability of hMSCs-nat, hMSCs-adip and hMSCs-ost towards FaDu cells was measured in a Transwell system. Spheroids were cultured from hMSCs-nat, FaDu cells and DiI-labeled HUVECs. FaDu cells, hMSCs-nat, hMSCs-adip and hMSCs-ost released a wide range of cytokines and growth factors, e.g., IL-6, IL-8, IL-10, GRO and MCP. In the capillary tube formation assay, HUVECs generated significantly longer tubes after co-cultivation with hMSCs-nat as compared to HUVECs alone and FaDu. Differentiation into adipocytes and osteocytes counteracted the tube formation. The adipogenic differentiation did not alter hMSC motility, whereas osteogenic differentiation significantly inhibited hMSC migration. Generation of multi-cellular spheroids from hMSCs-nat, FaDu cells and DiI-labeled HUVECs was possible. Florescence microscopy revealed that all HUVECs were present in the spheroid core. Taken together, hMSCs-nat have a pro-angiogenic effect. The effects are counteracted by the differentiation of hMSCs towards osteogenic and adipogenic lineages. The differentiation of stem cells into different lineages may be a promising solution to generating carriers for cancer therapy without pro-tumorigenic properties.


Subject(s)
Adipogenesis , Mesenchymal Stem Cells/cytology , Neovascularization, Physiologic , Osteogenesis , Carcinoma, Squamous Cell/blood supply , Carcinoma, Squamous Cell/immunology , Cell Differentiation , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cells, Cultured , Coculture Techniques , Cytokines/metabolism , Head and Neck Neoplasms/blood supply , Head and Neck Neoplasms/immunology , Human Umbilical Vein Endothelial Cells , Humans , In Vitro Techniques , Mesenchymal Stem Cells/immunology , Spheroids, Cellular/cytology , Spheroids, Cellular/immunology , Squamous Cell Carcinoma of Head and Neck
5.
Laryngorhinootologie ; 93(6): 369-80, 2014 Jun.
Article in German | MEDLINE | ID: mdl-24863908

ABSTRACT

Adipose-derived Stromal Cells (ASC) - Basics and Therapeutic Approaches in Otorhinolaryngology Mesenchymal stem cells from adipose tissue can be easily harvested with less discomfort, low donor-site morbidity and high amount compared to bone marrow-derived stem cells. Due to their multilineage differentiation potential in various cell types, immunmodulatory properties and their capability to enhance wound healing, ASC are a promising cell source for tissue engineering approaches and regenerative medicine. They are characterized by the expression of specific surface marker proteins and their differentiation potential into the mesenchymal lineages. Whereas only preclinical studies are published for otorhinolaryngology-related therapeutic options using ASC, various diseases, for instance graft-versus-host disease, have already been treated with ASC in single cases or clinical trials. Safety and genomic stability of ASC as well as the risk of spontaneous malignant transformation are still disputed. This review summarizes the current literature on characterization and anatomic localization of ASC. In addition, beside the presentation of preclinical studies concerning therapeutic approaches in otorhinolaryngology as well as of current clinical applications, the issue of safety of ASC in human stem cell therapy is discussed.


Subject(s)
Adipose Tissue/cytology , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/cytology , Otorhinolaryngologic Diseases/therapy , Tissue Engineering/methods , Animals , Cell Differentiation/genetics , Cell Differentiation/physiology , Chromosome Aberrations , Chromosomes, Human, Pair 8 , Genomic Instability , Humans , Karyotyping , Patient Safety , Tissue and Organ Harvesting/methods , Trisomy
6.
Cells Tissues Organs ; 198(5): 327-37, 2013.
Article in English | MEDLINE | ID: mdl-24356396

ABSTRACT

Interactions of human mesenchymal stem cells (hMSC) with tumors are controversially discussed since there is evidence for both tumor progression as well as tumor inhibition by hMSC. The objective of the present study is to investigate whether hMSC support cell motility and cytokine secretion in a head and neck squamous cell carcinoma cell line (HLaC 78). A spheroid model was generated in which the ultrastructure of spheroids was analyzed using scanning electron microscopy (SEM). The migration capability was monitored in a monolayer as well as in a spheroid model. The variation in migration and secretion of interleukin (IL)-6, IL-8 and vascular endothelial growth factor (VEGF), as well as the expression of the multidrug resistance gene (MDR-1) was investigated. Finally, the alteration in the cell cycle was analyzed by flow cytometry. SEM showed a tight cell-cell contact with extensive secretion of extracellular matrix. The migration and invasion capability of HLaC 78 was enhanced by hMSC. Cancer cell motility was also increased by hMSC as well as secretion of the cytokines IL-6, IL-8 and VEGF. hMSC did not induce the expression of MDR-1 in HLaC 78, and there was no alteration in the cell cycle of HLaC 78 after cocultivation with hMSC. Our results confirm the important role of hMSC in cancer biology since both an enhancement of cell motility as well as cytokine secretion could be shown. However, based on these findings and those in the current literature, caution must be applied when using hMSC as a carrier for tumor therapy in cancer treatment.


Subject(s)
Carcinoma, Squamous Cell/pathology , Cell Communication/physiology , Cell Movement/physiology , Cytokines/metabolism , Head and Neck Neoplasms/pathology , Mesenchymal Stem Cells/cytology , Carcinoma, Squamous Cell/metabolism , Cell Line, Tumor , Head and Neck Neoplasms/metabolism , Humans , Mesenchymal Stem Cells/metabolism , Spheroids, Cellular/pathology , Squamous Cell Carcinoma of Head and Neck
7.
Cells Tissues Organs ; 197(5): 384-98, 2013.
Article in English | MEDLINE | ID: mdl-23485626

ABSTRACT

INTRODUCTION: Adipose tissue-derived stem cells (ASCs) have become the primary focus of tissue engineering research. To understand their functions and behavior in in vitro and in vivo models, it is mandatory to track the implanted cells and distinguish them from the resident or host cells. A common labeling method is the use of fluorescent dyes, e.g. the lipophilic carbocyanine dye, DiI. This study aimed to analyze potential DNA damage, toxicity and impairment of the functional properties of human ASCs after labeling with DiI. METHODS: Cytotoxicity was measured using the MTT assay and DNA damage was determined by means of the comet assay. Potential apoptotic effects were determined using the annexin V-propidium iodide test. Differentiation potential was evaluated by trilineage differentiation procedures in labeled and unlabeled ASCs. Proliferation as well as migration capability was analyzed, and the duration and stability of DiI labeling in ASCs during in vitro expansion was observed over a period of 35 days. RESULTS: DiI labeling did not cause genotoxic effects 15, or 30 min or 24 h after the labeling procedure, and there were no cytotoxic effects until 72 h afterwards. No impairment of proliferation or migration capability or differentiation potential could be determined. However, after 35 days, only 37% of labeled cells could be detected using the fluorescence microscope, which indicates a decrease in staining stability during in vitro expansion. CONCLUSION: DiI is a convenient method for ASCs labeling which causes no toxic effects and does not impair the proliferation, migration or differentiation potential of ASCs after the labeling procedure.


Subject(s)
Adipose Tissue/cytology , Carbocyanines/metabolism , Carbocyanines/toxicity , DNA Damage , Stem Cells/cytology , Annexin A5/metabolism , Cell Death/drug effects , Cell Differentiation/drug effects , Cell Lineage/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Comet Assay , Humans , Phenotype , Propidium/metabolism , Staining and Labeling , Stem Cells/drug effects , Stem Cells/metabolism , Trypan Blue/metabolism
8.
Toxicol Lett ; 218(3): 207-14, 2013 Apr 26.
Article in English | MEDLINE | ID: mdl-23410960

ABSTRACT

Various hypotheses on the origin of cancer stem cells (CSCs) exist, including that CSCs develop from transformed human bone marrow mesenchymal stem cells (hBMSC). Since the polyether antibiotic salinomycin selectively kills CSCs, the present study aims to elucidate the effects of salinomycin on normal hBMSC. The immunophenotype of hBMSC after salinomycin exposure was observed by flow cytometry. The multi-differentiation capacity of hBMSC was evaluated by Oil Red O and van Kossa staining. Cytotoxic effects of salinomycin were monitored by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) assay. Furthermore, spheroid formation and migration capacity were assessed. There were no differences in the immunophenotype and multi-differentiation capacity of hBMSC induced by salinomycin treatment. Cytotoxic effects were observed at concentrations of 30 µM and above. Neither the migration capability nor the ability to form spheroids was affected. Essential functional properties of hBMSC were unaffected by salinomycin. However, dose-dependent cytotoxicity effects could be observed. Overall, low dose salinomycin showed no negative effects on hBMSC. Since mesenchymal stem cells from various sources respond differently, further in vitro studies are needed to clarify the effect of salinomycin on tissue-specific stem cells.


Subject(s)
Bone Marrow Cells/drug effects , Mesenchymal Stem Cells/drug effects , Pyrans/toxicity , Bone Marrow Cells/immunology , Bone Marrow Cells/pathology , Cell Differentiation/drug effects , Cell Line , Cell Movement/drug effects , Cell Shape/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Flow Cytometry , Humans , Immunophenotyping/methods , Mesenchymal Stem Cells/immunology , Mesenchymal Stem Cells/pathology
9.
Sleep Breath ; 17(1): 253-8, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22411172

ABSTRACT

PURPOSE: The influence of short-term severe thyroid hormone deficiency on sleep is currently still unknown. Several studies have demonstrated an effect of long-term hypothyroidism on sleep disorders due to anatomical changes of the pharynx or body mass. The aim of this preliminary study, however, is to evaluate the changes in sleep patterns of patients with short-term hypothyroidism to elucidate the isolated effect of thyroid hormone withdrawal before anatomical changes can potentially occur. METHODS: Ten patients with differentiated thyroid carcinoma were enrolled in this study. Two patients discontinued the study and one patient was finally excluded due to obesity, so that the datasets of seven patients were available for study analysis. During the course of carcinoma treatment, each patient had previously undergone total thyroidectomy and I-131 remnant ablation. Polysomnographic measurements were performed twice: (1) over the course of two consecutive nights during severe thyroid hormone deficiency after levothyroxine withdrawal and prior to further diagnostics and therapy and (2) during euthyroidism after substitution with levothyroxine. RESULTS: Comparison of the Epworth Sleepiness Scale during hypo- and euthyroidism for each patient revealed no statistically significant difference. Furthermore, the comparison of polysomnographic parameters like (1) apnea-hypopnea index, (2) the duration of various sleep stages, (3) duration of rapid eye movement sleep, (4) latency until rapid eye movement sleep, (5) total sleep time, (6) periodic leg movements, and (7) arousal index showed no statistically significant differences between the hypothyroid or euthyroid state. CONCLUSIONS: We conclude that, in this preliminary experimental setting, short-term severe thyroid hormone deficiency per se does not cause sleep disturbances and a feeling of fatigue as described in other studies may be due to changes in perception or brain metabolism during hypothyroidism.


Subject(s)
Hypothyroidism/physiopathology , Iodine Radioisotopes/therapeutic use , Polysomnography , Postoperative Complications/physiopathology , Sleep Apnea, Obstructive/physiopathology , Sleep Stages/physiology , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/surgery , Thyroidectomy , Adult , Aged , Arousal/physiology , Disorders of Excessive Somnolence/drug therapy , Disorders of Excessive Somnolence/physiopathology , Female , Humans , Hypothyroidism/drug therapy , Male , Middle Aged , Postoperative Complications/drug therapy , Sleep Apnea, Obstructive/drug therapy , Surveys and Questionnaires , Thyroxine/therapeutic use
10.
Toxicol Lett ; 207(1): 89-95, 2011 Nov 10.
Article in English | MEDLINE | ID: mdl-21864657

ABSTRACT

Current pollution limits indicating potential harm to human health caused by nitrogen dioxide have prompted a variety of studies on the cytotoxicity and genotoxicity of nitrogen dioxide (NO2) in vitro. The present study focuses on toxic effects of NO2 at the WHO defined 1-h limit value of 200 µg NO2/m(3) air, equivalent to 0.1 ppm NO2. Nasal epithelial mucosa cells of 10 patients were cultured as an air-liquid interface and exposed to 0.1 ppm NO2 for 0.5 h, 1 h, 2 h and 3 h and synthetic air as negative control. After exposure, analysis of genotoxicity was performed by the alkaline single cell microgel electrophoresis (comet) assay and by the micronucleus test. Depression of proliferation and cytotoxic effects were checked by the micronucleus assay and the trypan blue exclusion assay. The experiments demonstrated significant DNA fragmentation even at the shortest exposure duration of half an hour in the comet assay. The amount of DNA fragmentation significantly increased with extended NO2 exposure durations. The amount of DNA fragmentation increased with extended exposure durations to synthetic air at a significantly lower level as compared to NO2 exposure. Micronucleus inductions were seen only at the longest exposure duration of 3h. There were no changes in proliferation seen in the micronucleus assay under any experimental setup. Moreover, no signs of necrosis, apoptosis or changes in viability were detected. Data demonstrate genotoxicity of NO2 at concentrations found in the urban atmosphere during short exposure durations. DNA alterations in the micronucleus assay at an exposure time of 3h indicate a significant DNA alteration possibly being hazardous to humans.


Subject(s)
DNA Fragmentation/drug effects , Nasal Mucosa/drug effects , Nitrogen Dioxide/toxicity , Cell Survival/drug effects , Comet Assay , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Humans , Micronucleus Tests , Nasal Mucosa/cytology , Nasal Mucosa/metabolism , Statistics, Nonparametric
11.
Eur Arch Otorhinolaryngol ; 268(8): 1219-1225, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21327733

ABSTRACT

In 2003, osteonecrosis of the jaw was described as an intraoral complication of bisphosphonate therapy. More recently, cases of avascular necrosis of the hip were reported in patients with long-lasting bisphosphonate therapy. Thus, it was the aim of the present study to analyze cases of benign osteonecrosis of the external ear canal and to retrospectively identify a possible relationship to long-lasting bisphosphonate therapy. 13 patients with osteonecrosis of the external ear canal operated on between 2005 and 2009 were included. Patient histories were reviewed for possible previous or current bisphosphonate therapy. Three patients with osteonecrosis of the external ear canal and long-term bisphosphonate therapy could be identified. They had been treated either for breast cancer or multiple myeloma. Certainly, the jaw is an area of increased risk for developing osteonecrosis with its high mechanical stress and intraoral bacterial flora. However, osteonecrosis of the hips and the external ear canal in patients receiving long-term bisphosphonate therapy necessitate further investigation of a possible systemic, bisphosphonate-related phenomenon.


Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw/diagnosis , Diphosphonates/adverse effects , Ear Canal/pathology , Administration, Oral , Aged , Bone Density Conservation Agents/administration & dosage , Bone Density Conservation Agents/adverse effects , Diphosphonates/administration & dosage , Ear Canal/drug effects , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasms/drug therapy , Prognosis , Retrospective Studies , Time Factors
12.
Article in English | MEDLINE | ID: mdl-20367549

ABSTRACT

Numerous manufacturing techniques for autogenous fibrin glue used as scaffold material have been described. As there is no consensus regarding the influence of chemical additives on cell biology, it was the aim of this study to establish a method for manufacturing autologous fibrin glue without any additives. The serum part was separated from whole blood. After fibrinogen precipitation, centrifugation was performed to obtain the fibrinogen pellet. Various experimental series were run to examine influences of various temperatures or substituting centrifugation for sedimentation. The method as described here is effective, simple, and performed without any additives, which could potentially influence cell biology.


Subject(s)
Aprotinin/chemistry , Fibrin Tissue Adhesive , Fibrinogen , Tissue Engineering/methods , Tissue Scaffolds , Cartilage/chemistry , Centrifugation , Fibrin Tissue Adhesive/chemistry , Fibrinogen/chemistry , Gels/chemistry , Humans
13.
Toxicol Appl Pharmacol ; 245(2): 219-25, 2010 Jun 01.
Article in English | MEDLINE | ID: mdl-20214917

ABSTRACT

Cytotoxicity and genotoxicity of nitrogen dioxide (NO(2)) as part of urban exhaust pollution are widely discussed as potential hazards to human health. This study focuses on toxic effects of NO(2) in realistic environmental concentrations with respect to the current limit values in a human target tissue of volatile xenobiotics, the epithelium of the upper aerodigestive tract. Nasal epithelial cells of 10 patients were cultured as an air-liquid interface and exposed to 0.01 ppm NO(2), 0.1 ppm NO(2), 1 ppm NO(2), 10 ppm NO(2) and synthetic air for half an hour. After exposure, genotoxicity was evaluated by the alkaline single-cell microgel electrophoresis (Comet) assay and by induction of micronuclei in the micronucleus test. Depression of proliferation and cytotoxic effects were determined using the micronucleus assay and trypan blue exclusion assay, respectively. The experiments revealed genotoxic effects by DNA fragmentation starting at 0.01 ppm NO(2) in the Comet assay, but no micronucleus inductions, no changes in proliferation, no signs of necrosis or apoptosis in the micronucleus assay, nor did the trypan blue exclusion assay show any changes in viability. The present data reveal a possible genotoxicity of NO(2) in urban concentrations in a screening test. However, permanent DNA damage as indicated by the induction of micronuclei was not observed. Further research should elucidate the effects of prolonged exposure.


Subject(s)
Environmental Exposure/adverse effects , Nasal Mucosa/drug effects , Nitrogen Dioxide/toxicity , Cell Survival/drug effects , Dose-Response Relationship, Drug , Epithelial Cells/drug effects , Epithelial Cells/ultrastructure , Humans , Mutagenicity Tests
14.
Histopathology ; 53(5): 567-77, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18983466

ABSTRACT

AIMS: To evaluate the prognostic impact of expression of receptor tyrosine kinases epidermal growth factor receptor (EGFR), HER2, and C-KIT in relation to established clinicopathological parameters in salivary gland carcinomas. METHODS AND RESULTS: Immunohistochemistry for EGFR, HER2, C-KIT and the proliferation marker Ki67 was performed in 101 cases of salivary gland carcinoma and related to long-term clinical follow-up. Immunopositivity of C-KIT was common in adenoid cystic carcinoma (92%). Lack of C-KIT expression occurred in salivary duct carcinoma (P < 0.001) and was associated with high-grade tumours (P = 0.002), positive lymph nodes (P = 0.002) and high expression of Ki67 (P = 0.001). HER2 was typically expressed in salivary duct carcinomas (83%), but was not associated with any other parameter. EGFR overexpression occurred independently of histological type and clinical parameters. On univariate survival analysis, overexpression of EGFR (P = 0.011) and lack of C-KIT (P = 0.014) were associated with worse prognosis, whereas HER2 was of no prognostic significance. On multivariate analysis, the strongest negative predictor of survival was high proliferative activity measured by Ki67 (P = 0.002), followed by presence of residual tumour (P = 0.006), overexpression of EGFR (P = 0.026) and advanced tumour stage (P = 0.041). CONCLUSIONS: The expression of receptor tyrosine kinases confers additional prognostic impact on disease-specific survival. EGFR overexpression is an independent negative prognostic factor.


Subject(s)
Carcinoma/mortality , Carcinoma/pathology , ErbB Receptors/metabolism , Proto-Oncogene Proteins c-kit/metabolism , Salivary Gland Neoplasms/mortality , Salivary Gland Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Carcinoma/diagnosis , Female , Humans , Immunohistochemistry , Ki-67 Antigen/metabolism , Male , Middle Aged , Multivariate Analysis , Prognosis , Receptor, ErbB-2/metabolism , Salivary Gland Neoplasms/diagnosis , Survival Analysis
15.
J Dent Res ; 87(4): 378-80, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18362323

ABSTRACT

Bisphenol-A-glycidyldimethacrylate (BisGMA) is used in many resin-based dental materials. It was shown in vitro that BisGMA was released into the adjacent biophase from such materials during the first days after placement. In this study, the uptake, distribution, and excretion of [(14)C]BisGMA applied via gastric and intravenous administration (at dose levels well above those encountered in dental care) were examined in vivo in guinea pigs to test the hypothesis that BisGMA reaches cytotoxic levels in mammalian tissues. [(14)C]BisGMA was taken up rapidly from the stomach and intestine after gastric administration and was widely distributed in the body following administration by each route. Most [(14)C] was excreted within one day as (14)CO(2). The peak equivalent BisGMA levels in guinea pig tissues examined were at least 1000-fold less than known toxic levels. The peak urine level in guinea pigs that received well in excess of the body-weight-adjusted dose expected in humans was also below known toxic levels. The study therefore did not support the hypothesis.


Subject(s)
Bisphenol A-Glycidyl Methacrylate/pharmacokinetics , Dental Materials/pharmacokinetics , Animals , Bile/chemistry , Bisphenol A-Glycidyl Methacrylate/administration & dosage , Bisphenol A-Glycidyl Methacrylate/analysis , Blood , Carbon Dioxide/analysis , Carbon Radioisotopes , Cystic Duct , Dental Materials/analysis , Feces/chemistry , Guinea Pigs , Injections, Intravenous , Instillation, Drug , Jugular Veins , Male , Radiopharmaceuticals , Random Allocation , Time Factors , Tissue Distribution , Urine
16.
Eur Arch Otorhinolaryngol ; 265(10): 1239-44, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18317786

ABSTRACT

Until now only limited and controversial data are available concerning the presence of steroid hormone receptors in the human vocal fold. A sum of 140 slides from 104 patients were investigated including 25 Reinke's edemas, 19 cases of recurrent respiratory papillomatosis, 19 polyps, 10 epithelial hyperplasias without or with dysplasias, 4 carcinomas in situ, 20 laryngeal carcinomas as well as 7 fresh cadaver samples without macroscopic alterations. The median patient age was 58 years. Paraffin-embedded tissue was incubated with monoclonal antibodies for estrogen-alpha, androgen and progesterone. Androgen receptors were expressed most frequently, followed by estrogen receptors, whereas no progesterone receptors were identified. Receptor staining could be detected with different densities and locations within the different vocal fold pathologies, but not in the autopsy samples. Our study could clearly demonstrate the presence of hormone receptors in the human vocal fold. Androgen receptors were most frequently detected, especially in the basal and intermediate layer of the stratified epithelium and the lamina propria. Whether the high incidence of steroid hormone receptors in some vocal fold pathologies has implications on their pathogenesis must be evaluated by further studies.


Subject(s)
Receptors, Androgen/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Vocal Cords/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy , Child , Child, Preschool , Female , Humans , Immunohistochemistry , Laryngeal Diseases/metabolism , Laryngeal Diseases/pathology , Male , Middle Aged , Vocal Cords/pathology , Young Adult
17.
HNO ; 56(2): 205-10, 2008 Feb.
Article in German | MEDLINE | ID: mdl-18214406

ABSTRACT

BACKGROUND: This study evaluated the performance of oral brush biopsies using standard morphological analysis and haematoxylin and eosin (HE) staining for detecting oral squamous cell carcinomas and their respective precursor lesions PATIENTS AND METHODS: Brush biopsies were obtained in 169 consecutive patients who underwent routine biopsies and histological examination for clinically suspicious oral lesions. Air-dried smears were processed by acetone fixation and HE staining. Cytological assessment used well-established criteria of atypia to classify the specimen as either "tumor negative" (no signs of atypia, no malignant cells) or "tumor positive" (malignant cells, any sign of atypia or doubtful cells). RESULTS: Despite a sufficient number of cells, a definite cytological diagnosis could not be established in six cases. According to the criteria specified above, these specimens were classified as "tumor positive." The cytological analysis identified 49 out of 62 oral malignancies (sensitivity 79%). Seven out of 107 benign lesions were classified as false positive (specificity 93%). The positive and negative predictive values were each 88%. CONCLUSION: Oral brush biopsies will identify only about 80% of oral malignancies when the smears are processed by routine HE stains and are analysed via standard morphological criteria. Thus, this technique should not be used for diagnostic proof or to exclude malignant cells in a lesion suspicious for cancer. However, oral brush biopsy provides a versatile back-up strategy to uncover the true nature of the disease if a lesion is clinically considered benign by mistake.


Subject(s)
Biopsy/methods , Carcinoma, Squamous Cell/pathology , Mouth Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity
18.
Eur Arch Otorhinolaryngol ; 264(12): 1497-508, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17628822

ABSTRACT

Keloids are abnormal wound reactions of connective tissue. Auricular keloids can develop as a result of, e.g., otoplasty, ear piercing, or skin trauma. A wide variety of therapeutic options exists, including surgery as primary treatment. Furthermore, there are medical, physical, radiotherapeutic and experimental options. The present paper focuses on the different techniques including the therapeutic outcome and quality rating for each chosen pathway. In addition to the experience of the university hospitals, a thorough review of the literature was performed in order to update and compare today's therapeutic options. Surgical techniques are customized to the lesion's specific localization and extent. They may include revision of otoplasty. With medical treatment, established modalities such as steroid injection have to be distinguished from experimental methods like interferon, 5-FU, verapamil, imiquimod, or mitomycin C. Radiation is generally accepted to be effective, especially applied accompanying surgery, but needs to be restricted due to possible side effects. Physical therapy, e.g., pressure in a variety of application modalities, has gained a profound position in the therapy of auricular keloids. The success rates of the different treatment modalities vary markedly, and the number of patients per study is considerably low. Resuming the results, a periodic follow-up and good patients' compliance are mandatory to early realize and treat auricular keloids. However, studies are needed to evaluate accepted and experimental therapies including larger number of patients.


Subject(s)
Ear , Keloid/therapy , Algorithms , Humans , Keloid/etiology , Keloid/pathology
19.
HNO ; 55 Suppl 1: E33-9, 2007 May.
Article in German | MEDLINE | ID: mdl-17415535

ABSTRACT

After condylar resection a decision on whether to proceed immediately to reconstruction has to be decided. In this paper, two patients who had undergone hemimandibulectomy including exarticulation, in one because of an expanded keratocystic odontogenic tumour and in the other because of oral squamous cell carcinoma, are presented. In one patient a metallic condylar reconstruction plate combined with an iliac crest graft was implanted for primary mandibular reconstruction, whereas in the other the part of the mandible that had been removed and the condylar head were not replaced. One patient was followed up for 5 years and the other for 6 years. Functional (max. incisal distance, protrusive and lateral excursions, occlusion and joint noises) and cosmetic results (scarring, facial nerve function), and also quality of life with and without primary mandibular replacement by a metallic condylar reconstruction plate are compared.


Subject(s)
Ilium/transplantation , Mandibular Condyle/surgery , Mandibular Neoplasms/surgery , Osteotomy/methods , Plastic Surgery Procedures/methods , Aged , Female , Humans , Patient Satisfaction , Recovery of Function , Transplantation, Homologous , Treatment Outcome
20.
Mund Kiefer Gesichtschir ; 10(6): 395-401, 2006 Nov.
Article in German | MEDLINE | ID: mdl-17028845

ABSTRACT

BACKGROUND: Tumorigenesis is based on initiation, promotion, and progression, whereas tobacco smoke is a decisive predisposing factor for squamous cell carcinomas of the upper aerodigestive tract. A variety of tobacco smoke compounds is known to potentially initiate tumors, but the alkaloid nicotine is generally considered to induce addiction only. However, there is growing evidence that nicotine may also contribute to early stages of tumorigenesis. In the present study, a possible direct genotoxic potential of nicotine is investigated. MATERIAL AND METHODS: Lymphatic tissue of the tonsilla palatina of eight donors was harvested during surgery and incubated with nicotine. DNA damage was measured with the comet assay. RESULTS: Genotoxic effects of nicotine could be demonstrated. DISCUSSION: The results suggest a direct contribution of nicotine to tumor initiation and carcinogenesis.


Subject(s)
Carcinoma, Squamous Cell/chemically induced , Mutagenicity Tests , Nicotine/toxicity , Otorhinolaryngologic Neoplasms/chemically induced , Carcinoma, Squamous Cell/pathology , Cell Transformation, Neoplastic/pathology , Comet Assay , DNA Damage , Dose-Response Relationship, Drug , Humans , Otorhinolaryngologic Neoplasms/pathology , Palatine Tonsil/drug effects , Palatine Tonsil/pathology
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