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This report emphasizes the need for interdisciplinary collaboration in diagnosing and treating pediatric obstructive sleep apnea (OSA). OSA, affecting 1% to 4% of children, often results from adenotonsillar hypertrophy, craniofacial disorders, or obesity. While adenotonsillectomy is the primary treatment, about 75% of children, especially those with craniofacial disorders or obesity, continue to experience OSA symptoms post-surgery. To address these cases, several medical fields emphasize the necessity and demand for interdisciplinary collaboration in managing pediatric OSA. Therefore, the authors aimed to develop the Pediatric Obstructive Sleep Apnea Diagnostic Examination Form (POSADEF). This form, based on clinical experience and the literature, captures craniofacial and functional characteristics linked to pediatric OSA. A case study of an eight-year-old girl with OSA, who was unsuccessfully treated with adenotonsillectomy, underlines the importance of the diagnostic examination form. The orthodontic assessment revealed craniofacial disorders and subsequent treatment with maxillary expansion and functional appliance therapy resolved her OSA symptoms. This case demonstrates the value of POSADEF in enabling comprehensive evaluation and treatment across medical disciplines. POSADEF is designed to assist health care professionals in diagnosing craniofacial and orofacial anomalies contributing to pediatric OSA. [ABSTRACT FROM AUTHOR]

Objectives: Obstructive sleep apnea (OSA) is a common sleep disorder, which is associated with recurrent oxygen desaturation during sleep. It has already been shown that nocturnal hypoxia may lead to cochlear dysfunction in patients with OSA. Less is known whether hypoxia during sleep also impacts vestibular function in those patients. Thus, the aim of the presented study was to assess a potential vestibulotoxic effect of nightly desaturations with hypoxia in patients with OSA by investigating a possible correlation between respiratory parameters and vestibular function tests. Methods: A total of 56 patients were included in the study and underwent a fully attended cardiorespiratory polysomnography (PSG). Vestibular function was assessed using video head impulse test to evaluate horizontal semicircular canal function and cervical vestibular evoked myogenic potentials (cVEMPs) and ocular vestibular evoked myogenic potentials (oVEMPs) to measure otolith function. Descriptive data analysis was conducted and correlation analysis between selected PSG parameters and the results of vestibular testing was performed using Kendall τ coefficient. Results: A significant correlation between vestibular function and respiratory polysomnographic parameters could not be demonstrated in the study (P >.05) but cVEMP and oVEMP results showed a trend toward a correlation with oxygen desaturation indices and apnea–hypopnea index. Additionally, otolith hypofunction was more prevalent in patients with hypertension as well as OSA. Conclusion: The results of our study show that there is no significant correlation between vestibular function and sleep apnea parameters, although otolith dysfunction might be more prevalent in patients with OSA and hypertension. [ABSTRACT FROM AUTHOR]

Background/Aim: Cocaine is a widely used recreational drug and is known for its nasal complications including epithelial, cartilage and bone damage. The aim of the study was to analyze the impact of cocaine on ciliary beat frequency (CBF) of human nasal epithelial cells and therefore better understand its side effects on nasal mucosa. Materials and Methods: Nasal epithelial cells of 21 healthy subjects were harvested and exposed in vitro to cocaine hydrochloride solutions ranging from 0.875% to 7%. Highspeed video footage was acquired with phase contrast microscopy and CBF was analyzed with Sissons-Ammons Video Analysis (SAVA) software. Results: All tested concentrations led to a significant reduction in CBF compared to the control. Effects increased over time and with concentration. A mechanical inhibition of cilia by cocaine crystals was also observed. Conclusion: We assume that CBF reduction is part of the pathomechanism leading to nasal complications in cocaine abuse. Considering these results, clinical usage of cocaine should be critically evaluated and restricted to select cases only. [ABSTRACT FROM AUTHOR]

Background: The role of Cytokeratin fraction 21-1 (CYFRA 21-1) as a tumour marker for head and neck cancer is still a matter of research. The aim of the present study was to evaluate the clinical impact of CYFRA 21-1 for patients with oropharyngeal squamous cell carcinoma (OSCC). Patients and methods: Data of 180 patients with an initial diagnosis of OSCC of any stage between 2003 and 2017 were retrospectively analysed regarding the association between pretherapeutic CYFRA 21-1 levels, clinical characteristics, overall and disease-free survival. Additionally, the potential of CYFRA 21-1 for the detection of recurrent disease in the follow-up was evaluated. The cut-off value was set at 3.3 ng/ml. The median follow-up time was 2.85 years. Results: A significant correlation of the CYFRA 21-1 concentration at the time of diagnosis and the N-stage was detected (p = 0.01). Patients with CYFRA 21-1 levels > 3.3 ng/ml at first diagnosis showed a significantly shorter overall survival. In the case of disease-progression, a significant increase of CYFRA 21-1 value was found compared to post-therapeutic CYFRA 21-1 levels (9.1 ng/ml versus 5.1 ng/ml; p < 0.01). CYFRA 21-1 level after treatment showed only a low sensitivity of 32% and a specificity of 78% for tumour recurrence. Conclusion: CYFRA 21-1 correlates with the tumour stage and, therefore, the survival of OSCC patients. Posttreatment CYFRA21-1 seems not to be a suitable predictor of tumour recurrence in the further course of the disease. However, a sudden increase of CYFRA 21-1 during follow-up may indicate a tumour recurrence in the individual patient. [ABSTRACT FROM AUTHOR]

Background: We investigated the expression patterns of cluster of differentiation (CD) 44 and amphiregulin (AREG), two signaling molecules essential for cell proliferation and differentiation, under the influence of selective tyrosine kinase inhibitors (TKIs) in human papillomavirus (HPV)+ and HPV- squamous carcinoma cell lines. Materials and Methods: The protein expression of CD44 and AREG was determined by sandwich enzymelinked immunosorbent assay in HPV- cell lines UMSCC-11A and UMSCC-14C, and HPV+ CERV-196 cells after TKI treatment. Results: The expression of AREG and CD44 was dependent on the cell line's HPV status. AREG expression increased after incubation with nilotinib in HPV+ tumor cells. The expression of CD44 was significantly influenced by all drugs; its expression under selective epidermal growth factor receptor inhibition was mostly reduced, whereas nilotinib led to an exceptional increase of CD44 expression. Conclusion: The selective drug treatment options significantly influenced the expression of CD44 and AREG in HPV- and HPV+ tumor cells, constituting the need for personalized treatment options. [ABSTRACT FROM AUTHOR]

The results of surgical repair of extensive muscle tissue defects are still of primary concern, leaving patients with residual cosmetic and functional impairments. Therefore, skeletal muscle tissue engineering attempts to grow functional neo‑tissue from human stem cells to promote tissue regeneration and support defect closure. Despite intensive research efforts, the goal of stable induction of myogenic differentiation in expanded human stem cells by using clinically feasible stimuli, has not yet been reached to a sufficient extent. Therefore, the present study investigated the differentiation potential of static magnetic fields (SMFs), using co‑cultures of human satellite cells and human mesenchymal stem cells (MSCs). It has previously been demonstrated that SMFs may act as a promising myogenic stimulus. Tests were performed on co‑cultures with and without SMF exposure, using growth medium [high growth factor concentrations (GM)] and differentiation medium [low growth factors concentrations (DM)]. AlamarBlue® assay‑based cell proliferation analysis revealed no significant difference between co‑cultures with, vs. without SMF stimulation, regardless of growth factor concentrations in the cell culture medium. To determine the degree of differentiation in co‑cultures under stimulation with SMFs, semi‑quantitative gene expression measurements of the following marker genes were performed: Desmin, myogenic factor 5, myogenic differentiation antigen 1, myogenin, adult myosin heavy chain 1 and skeletal muscle α1 actin. In neither GM nor DM was a steady, significant increase in marker gene expression detected. Verifying the gene expression findings, immunohistochemical antibody staining against differentiation markers revealed that SMF exposure did not enhance myogenic maturation. Therefore, SMF treatment of human satellite cell/MSC co‑cultures did not result in the desired increase in myogenic differentiation. Further studies are required to identify a suitable stimulus for skeletal muscle tissue engineering. [ABSTRACT FROM AUTHOR]

The identification of molecular targets in the therapy of human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is a primary aim of cancer research. Matrix metalloproteinase 9 (MMP-9) and vascular endothelial growth factor receptor (VEGFR) have important roles in the development of HNSCC. The tyrosine kinase inhibitors, nilotinib, dasatinib, erlotinib and gefitinib are well established in the targeted therapy of tumors other than HNSCC. The present study aimed to investigate the alteration of MMP-9 and VEGFR-1 expression patterns following treatment with these tyrosine kinase inhibitors in p16-positive and -negative squamous carcinoma cells. MMP-9 and VEGFR-1 expression was evaluated using an ELISA in HNSCC 11A, HNSCC 14C and p16-positive CERV196 tumor cell lines, following treatment with nilotinib, dasatinib, erlotinib and gefitinib. A statistically significant reduction in MMP-9 and VEGFR-1 expression was observed in the p16-negative HNSCC 11A cells following treatment with all inhibitors (P<0.05). VEGFR-1 expression was significantly increased in p16-positive SCC cells following treatment with nilotinib, dasatinib, erlotinib and gefitinib (P<0.05). The expression of MMP-9 and VEGFR-1 was significantly altered by treatment with nilotinib, dasatinib, erlotinib and gefitinib in vitro. The results of the present study are attributed to the efficacy of the tested drugs and present potential compensatory strategies of cancer cells to avoid the antiangiogenic properties of the tested tyrosine kinase inhibitors in vitro. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that vascular endothelial growth factor (VEGF) is upregulated in patients with hereditary hemorrhagic telangiectasia (HHT). The use of Bevacizumab as an anti-angiogenic treatment agent seems promising. The purpose of the present in vitro study was to determine the efficacy and potential toxicity levels of bevacizumab on cell proliferation and VEGF concentrations in endothelial cells of HHT patients. In this in vitro study, endothelial cells from patients with HHT and HUVECs (control) were incubated with different concentration levels of bevacizumab (2, 4, 6, 8 or 10 mg/ml). After 24, 48 or 72 h, the cell proliferation was assessed by Alamar Blue® Assay and the VEGF levels in the cell culture supernatants were measured by VEGF-ELISA. All endothelial cells incubated with bevacizumab showed an initial decrease in cell proliferation. Cell proliferation recovered within 72 h in cell cultures incubated with concentration levels of up to 4 mg/ml bevacizumab, whereas those incubated with higher concentration levels showed a continuous decline in cell proliferation. VEGF expression decreased after 24 h in cell cultures incubated with bevacizumab concentration levels of 2 and 4 mg/ml but increased again after 48 h. Cell cultures incubated with bevacizumab concentration levels of 10 mg/ml showed a constant decline in VEGF expression without any tendency for recovery. Translating these results into daily clinical practice, the present study suggests that the intranasal submucosal injection of bevacizumab in HHT patients should not exceed a concentration level of 4 mg/ml. Overall, higher bevacizumab concentration levels not only reduce VEGF expression but pose a higher risk of toxic effects on endothelial cells as they jeopardize cell proliferation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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, immunohisto-chemical 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 ml 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. [ABSTRACT FROM AUTHOR]

Objective: Head-and-neck cancer patients run a high risk of peri- or post-treatment malnutrition that can severely affect the therapy outcome. However, little is known about malnutrition under the pre-treatment condition. Therefore, this study aimed to provide a systematic description of the pre-treatment nutritional status and risk of malnutrition in this population., Material and Methods: Before the onset of the oncological therapy, nutritional status of 102 head-and-neck cancer patients was assessed by body mass index (BMI), their risk of malnutrition by "Nutritional Risk Screening" (NRS). Tumour stage and site, patients' age and sex as well as oropharyngeal dysphagia were analysed as possible influence factors. The latter was quantified by the Flexible Endoscopic Evaluation of Swallowing (FEES)., Results: According to BMI, malnutrition (undernutrition) was found in 6% of patients, a risk of malnutrition (NRS) in 27% of patients, and oropharyngeal dysphagia in 15%. In a linear regression, only oropharyngeal dysphagia was identified as a significant influence factor for the risk of malnutrition ( β = 0.380/3.776; p < .001)., Conclusions: Pre-treatment risk of malnutrition was found in a quarter of head-and-neck cancer patients. For the early identification of this risk and for the introduction of measures that would help to avoid it, a pre-treatment examination of swallowing functions and a systematic malnutrition screening by means of NRS are recommended., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background/aim: The rise of targeted therapies in the treatment of head and neck squamous cell carcinoma (HNSCC) has considerably widened the treatment range. Matrix metalloproteinases (MMPs) are key regulators of the tumor development of many cancer entities, which makes them a promising target for new treatment options. We examined the expression patterns of MMP2 and MMP14 in human papillomavirus (HPV)-positive and -negative SCC lines after treatment with small molecule tyrosine kinase inhibitors (TKIs) and a mechanistic target of rapamycin (mTOR) inhibitor in vitro., Materials and Methods: Cells of two human HPV-negative cell lines (UMSCC-11A/-14C) and one HPV-positive cell line (CERV196) were incubated with 20 μmol/l of erlotinib, gefitinib, nilotinib, dasatinib, or everolimus for 24-96 h. Cell proliferation was assessed by proliferation assay and the protein concentrations of MMP2 and MMP14 by sandwich enzyme-linked immunosorbent assay. For statistical analysis, the results were compared with those of untreated SCC cells., Results: MMP2 and MMP14 were expressed in all three tested cell lines; expression levels were highest in the UMSCC-14C cell line. The tested TKIs significantly (p<0.05) reduced MMP2 expression in the UMSCC-14C cell line. In the HPV-positive cell line, the drugs led to an increase in MMP2 and MMP14 expression., Conclusion: Dysregulations in MMP signaling are involved in tumorigenesis and metastasis of HNSCCs; MMP2 has been noted as a potential biomarker. The expression of MMP2 and MMP14 is influenced effectively by small molecule TKIs and everolimus. Based on our data, future research should concentrate on a better understanding of the interplay between tumor microenvironment and tumor cells in vitro and in vivo., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

We present the case of an otherwise healthy 19-year-old student who has been affected by vocal cord dysfuntion (VCD) since she is fourteen. 3 years after that diagnosis she has also been coughing blood at an increasing rate (1-3 times per week). We postulate that the haemoptoe is the result of breathing against a closed airway which can lead to excessively high negative intrathoracic pressures. Which, in turn, rapture alveolar capillaries. After bilateral injection of Botulinum toxin injection into the muscles vocalis, VCD as well as haemoptoe episodes ceased for three months., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Objective:  Dysphagia constitutes a frequent post-operative functional impairment in head-and-neck cancer patients. This impairment can result in aspiration/penetration and limitations of oral intake. Therefore, often it requires a therapeutic intervention. In this study, prevalence of post-operative dysphagia and its associations with the tumour stage, localisation, patients' age, and biological sex were analysed for the inpatient treatment setting., Material and Methods:  A total of 201 adult head-and-neck cancer patients (mean age 63 years) were analysed prospectively by FEES in two university hospitals in regard to their penetration/aspiration, limitations of oral intake, and need for therapeutic interventions directly after the operative tumour treatment. Additionally, the influence of the same patients' characteristics on these three parameters were analysed by means of univariate and multivariate statistical methods., Results:  Out of 201 patients, 66.7 % needed a therapeutic intervention because of their dysphagia, 57.2 % needed a nasogastral or PEG tube due to limitations of oral intake, 45.3 % had an aspiration. In the latter subgroup, 38.5 % had a silent aspiration. Higher tumour stage, patients' higher age and male sex were shown to be significant influence factors for dysphagia, tumour localisation showed only a marginally significant result., Conclusions:  The study demonstrated a clinical importance and relevance of the consequent and systematic treatment of post-operative dysphagia in head-and-neck cancer patients in the acute care units as a constituent of a modern oncological therapy., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Background: Head and neck squamous cell cancer (HNSCC) affects the oral cavity and the pharynx. The aim of the study was to investigate the effects of selective tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib, nilotinib and dasatinib and the mammalian target of rapamycin (mTOR) inhibitor everolimus on the expression of apoptosis-related proteins caspase-3, FAS cluster of differentiation (CD)-95 and FAS ligand in human papilloma virus (HPV)-dependent squamous cancer., Materials and Methods: Two HPV-negative cell lines (UMSCC-11A/-14C) and one HPV-positive cell line (CERV196) were incubated with TKIs or everolimus and protein concentrations of target proteins were analyzed with enzyme-linked immunosorbent assay (ELISA)., Results: Caspase-3 was affected by the tested TKIs in HPV-positive SCC, whereas FAS CD95 and FAS ligand were influenced in HPV-negative SCC., Discussion: This is the first study to analyze the influence of TKIs and everolimus on key proteins of apoptosis. Our results provide novel information contributing to a better understanding of the cell biology of HPV-dependent HNSCC and might contribute to the discovery of novel pharmaceutical treatment strategies for HNSCC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Targeted therapies in the treatment of head and neck squamous cell carcinoma (HNSCC) are subject to extensive research. Different mutations of genes belonging to the fibroblast growth factor (FGF) family have been detected in HNSCC. In this study, we examined the expression of FGF1 and FGF2 after treatment with small-molecule tyrosine kinase inhibitors (TKIs) and an inhibitor of mechanistic target of rapamycin (mTOR) in vitro using human papillomavirus (HPV)-positive and -negative SCC lines., Materials and Methods: Cells of two human HPV-negative cell lines (UMSCC-11A/-14C) and one HPV-positive cell line (CERV196) were incubated with 20 μmol/l of erlotinib, gefitinib, nilotinib, dasatinib, or everolimus for 24-96 h. Cell proliferation was assessed by proliferation assay and the protein concentrations of FGF1 and FGF2 by sandwich enzyme-linked immunosorbent assay. For statistical analysis, the results were compared with those for untreated HPV-negative SCC cells., Results: FGF1 and FGF2 were detected in all three tested cell lines. The tested TKIs significantly (p<0.05 reduced) FGF1 expression in the UMSCC-11A cell line within the first 24 h. At later time points, the tested TKIs and everolimus significantly (p<0.05) increased FGF1 and FGF2 expression in HPV-negative and -positive cancer cell lines. The effect was stronger in the HPV-positive cell line., Conclusion: Alterations in FGF signalling are considered to be relevant drivers of tumourigenesis in some HNSCCs. Our results show that the expression of FGF1 and -2 can be influenced effectively by small-molecule TKIs and everolimus. Based on our data, future research should include combinations of specific FGF inhibitors, mTOR inhibitors and other TKIs in the treatment of HNSCC and research on FGF-mediated drug escape mechanisms., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: We investigated the expression patterns of cluster of differentiation (CD) 44 and amphiregulin (AREG), two signaling molecules essential for cell proliferation and differentiation, under the influence of selective tyrosine kinase inhibitors (TKIs) in human papillomavirus (HPV) + and HPV - squamous carcinoma cell lines., Materials and Methods: The protein expression of CD44 and AREG was determined by sandwich enzyme-linked immunosorbent assay in HPV - cell lines UMSCC-11A and UMSCC-14C, and HPV + CERV-196 cells after TKI treatment., Results: The expression of AREG and CD44 was dependent on the cell line's HPV status. AREG expression increased after incubation with nilotinib in HPV + tumor cells. The expression of CD44 was significantly influenced by all drugs; its expression under selective epidermal growth factor receptor inhibition was mostly reduced, whereas nilotinib led to an exceptional increase of CD44 expression., Conclusion: The selective drug treatment options significantly influenced the expression of CD44 and AREG in HPV - and HPV + tumor cells, constituting the need for personalized treatment options., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The effects of tyrosine kinase inhibitors (TKI) in head and neck squamous cell cancer (HNSCC) are not fully understood. We investigated the effects of selective TKIs erlotinib, gefitinib, nilotinib, and dasatinib and the mTOR-inhibitor everolimus on the expression of insulin-like growth factor 1 receptor (IGF1R) in HPV-positive and HPV-negative squamous cancer cell lines., Materials and Methods: HPV-negative UMSCC-11A and UMSCC-14C cells and HPV-positive CERV196 cells were treated with TKIs or everolimus. Protein concentration of IGF1R was measured using ELISA., Results: IGF1R expression was significantly reduced by all tested TKIs and everolimus in both HPV-negative cancer cell lines. In HPV-positive squamous cancer cells we observed significant protein inhibition., Conclusion: The crosstalk between epidermal growth factor receptors and IGF1R could be of central interest for the development of novel medical approaches for individualized therapy., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Despite extensive research into new treatment options, the prognosis for head and neck squamous cell carcinoma remains poor. Platelet-derived growth factor (PDGF) is up-regulated in HNSCC and expression levels decrease after surgery, suggesting its role in tumour development. The influence of HPV on the PDGF/PDGF receptor (PDGFR) pathway remains unclear. In this study, we investigated the effect of small-molecule tyrosine kinase inhibitors (TKIs) on the expression of PDGF and its receptor in vitro using squamous cancer cell lines with different human papillomavirus 16 (HPV16) status., Materials and Methods: Two human HPV16-negative cell lines (UMSCC-11A/-14C) and one HPV16-positive cell line (CERV196) were used. Tumour cells were incubated with 20 μmol/l of TKIs nilotinib, dasatinib, afatinib, gefitinib and erlotinib for 24-96 h. Cell proliferation was assessed via proliferation assay and protein concentrations of PDGF-AA and BB and PDGFRα and -β via sandwich enzyme-linked immunosorbent assay. For statistical analysis, the results were compared with those from an untreated negative control., Results: PDGF-AA/BB and PDGFRα/-β were detected in all three tested cell lines. The addition of TKI led to a significant (p<0.05) decrease of PDGF/PDGFR at different time points and cell lines. The strongest effects were seen for the expression of PDGF-AA, which was consistently inhibited by most drugs. The effects of the TKI were independent of the HPV status., Conclusion: Proteins of this pathway can effectively be inhibited by small molecule TKIs. PDGF-AA seems to be a promising target for future studies with selective TKIs., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Targeted therapy in head and neck squamous cell carcinoma (HNSCC) is limited. HIF-1α and mTOR are involved in the formation of local tumor progression and distant metastasis. The present study analyzed the influence of well-established tyrosine kinase inhibitors nilotinib, dasatinib, erlotinib and gefitinib on the expression of HIF-1α and mTOR in p16-positive and -negative squamous cancer cells (SCC) in vitro in order to develop novel strategies in the treatment of HNSCC., Materials and Methods: Expression of HIF-1α and mTOR was analyzed by using Sandwich-ELISA in p16-negative and p16-positive SCC after treatment with nilotinib, dasatinib, erlotinib and gefitinib (20 μmol/l, 24-96 h of incubation)., Results: All substances significantly reduced mTOR expression in both, p16-negative and p16-positive SCC (p<0.05). HIF-1α expression was significantly reduced by all tested substances in p16-negative SCC. However, a statistically significant increase of HIF-1α was observed in p16-positive SCC., Conclusion: This is the first study to investigate the alteration of expression levels of HIF-1α and mTOR under selective tyrosine kinase inhibition in both p16-positive and -negative SCC. Our findings provide novel insights for a better understanding of HIF-1α and mTOR in the tumor biology of HNSCC and their interaction with selective small-molecule inhibitors., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Therapeutic options of locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) are limited. Src and cKIT are key protein regulators for local tumor progression. The aim of the study was to investigate the therapeutic potential of targeted therapies in human squamous cell carcinoma (HNSCC) in vitro. Therefore, the influence of the selective tyrosine kinase inhibitors niotinib, dasatinib, erlotinib, gefitinib and afatinib on Src and cKIT expression in Human papilloma virus (HPV)-positive and HPV-negative squamous cancer cells (SCC) was analyzed in vitro., Materials and Methods: ELISA was performed to evaluate the expression of Src and cKIT under the influence of nilotinib, dasatinib, erlotinib, gefitinib and afatinib (10 μmol/l) in HPV-negative and HPV-positive SCC (24-96 h of incubation)., Results: Gefitinib significantly increased cKIT expression in HPV-positive and HPV-negative cells whereas nilotinib and afatinib decreased cKIT expression in HPV-positive SCC. The influence of tyrosine kinase inhibitors in HPV-negative SCC was marginal. Surprisingly, Src expression was significantly increased by all tested tyrosine kinase inhibitors in HPV-positive SCC., Conclusion: The results revealed beneficial and unexpected information concerning the interaction of selective tyrosine kinase inhibitors and the tumor biology of HNSCC., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Cancer stem cells (CSCs) are suspected of being a reason for limited therapy in head and neck squamous cell carcinoma (HNSCC). Stromal cell-derived factor-1α (SDF-1α) plays a critical role in the communication between CSCs and their microenvironment. We investigated the influence of SDF-1α on HPV+/HPV- SCC cell lines to find an approach of explanation for the superior prognosis of HPV+ HNSCCs., Materials and Methods: We evaluated the expression of CD44/CXCR4 on HPV+/HPV- SCC cell lines and monitored the influence of SDF-1α on proliferation, morphology and migration of HPV+/HPV- SCCs., Results: HPV- SCCs showed a significant increase of podia formation and an intensified migration towards SDF-1α. HPV+ SCCs rested nearly unaffected by SDF-1α., Conclusion: Weakened reaction to SDF-1α in HPV+ SCC could lead to an impaired communication between CSCs and their niche, that would result in an increased exposure of CSCs to the harming influence of e.g. chemotherapeutic agents., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

In the presented study video-head impulse test (vHIT) was performed in 72 patients with complaints of dizziness for more than 3 months who did not show any pathology in rotatory chair testing or caloric test, in order to analyzed high frequency vestibular-ocular-reflex (VOR). Retrospective data analyzed of rotatory chair testing, caloric tests and vHIT results were accomplished in 72 patients. Gain, gain variance and the occurrence of catch-up saccades were measured. 10 patients (n=10; 13.8%) showed pathologic vHOR results with reduced gain. In the remaining 62 patients, a median gain of 0.85 when tested to the right respectively 0.87 when tested to the left side was assed. Especially in patients with normal results in rotatory chair testing and caloric testing, who complain of persistent dizziness and imbalance, high frequency hVOR should also be evaluated using vHIT in order to objectify and document an isolated high frequency hVOR lesion., Competing Interests: Interessenkonflikt: Kein Interessenkonflikt angegeben., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The validation of potential molecular targets in head and neck squamous cell carcinoma (SCC) is mandatory. β-Catenin and E-cadherin are crucial for cancer progression through epithelial-mesenchymal transition. We analyzed the effect of the tyrosine kinase inhibitors nilotinib, dasatinib, erlotinib and gefitinib on β-catenin and E-cadherin expression in SCC with respect to human papillomavirus (HPV) status., Materials and Methods: Expression of β-catenin and E-cadherin in cell lines UMSCC 11A, UMSCC 14C and CERV196 under the influence of tyrosine kinase inhibitors were analyzed by enzyme-linked immunosorbent assay., Results: All agents reduced β-catenin and E-cadherin expression of HPV16-negative cells. Increased E-cadherin expression was observed after treatment with gefitinib and dasatinib in HPV16-positive cells., Conclusion: All substances, nilotinib, dasatinib, erlotinib and gefitinib have a significant impact on β-catenin and E-cadherin expression in both HPV16-positive and HPV16-negative cells in vitro. Alterations of β-catenin and E-cadherin could provide novel insights for future targeted therapies of head and neck SCC., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)