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1.
HNO ; 2024 May 30.
Artigo em Alemão | MEDLINE | ID: mdl-38829524

RESUMO

BACKGROUND: With targeted inhibition of type 2 inflammation, biologics represent the standard add-on therapy for inadequately controlled severe forms of chronic rhinosinusitis with nasal polyps (CRSwNP). Despite standardization with paper-based checklists, the documentation of medical history and current findings pertinent to indication criteria are a significant challenge for physicians. Through development of an application based on structured reporting, the current study aimed to improve documentation quality and simplify the decision-making process. Previously available paper checklists served as a comparison. METHODS: For this study, a digital incremental tool was programmed to record current findings and check for fulfilment of indication criteria. The tool was compared with other checklists in terms of completeness, time required, and readability. RESULTS: A total of 20 findings were collected for each of the three documentation options and included in the analysis. Documentation with the two paper-based checklists had comparable information content: 17.5 ± 5.1/21.7 ± 7.6 points out of a maximum of 43 points; p > 0.05. Documentation using the digital application led to a significant increase in information content compared to all paper-based documentation. The average score was 38.25 ± 3.7 (88.9% of maximum; p < 0.001). On average, user satisfaction was high (9.6/10). Use of the digital application was initially more time consuming, but as more cases were documented, the time taken improved significantly. CONCLUSION: In the future, structured reporting using apps could replace paper-based reporting for the indication of biologic therapy in CRSwNP patients and offer additional benefits in terms of data quality and traceability of results. The increasing volume of documentation in the future, the progress of digitalization, and the possibility of networking between individual centers make introduction of the app in the near future both likely and economical.

2.
Acta Otolaryngol ; 144(3): 237-242, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38781053

RESUMO

BACKGROUND: Large Language Models (LLMs) might offer a solution for the lack of trained health personnel, particularly in low- and middle-income countries. However, their strengths and weaknesses remain unclear. AIMS/OBJECTIVES: Here we benchmark different LLMs (Bard 2023.07.13, Claude 2, ChatGPT 4) against six consultants in otorhinolaryngology (ORL). MATERIAL AND METHODS: Case-based questions were extracted from literature and German state examinations. Answers from Bard 2023.07.13, Claude 2, ChatGPT 4, and six ORL consultants were rated blindly on a 6-point Likert-scale for medical adequacy, comprehensibility, coherence, and conciseness. Given answers were compared to validated answers and evaluated for hazards. A modified Turing test was performed and character counts were compared. RESULTS: LLMs answers ranked inferior to consultants in all categories. Yet, the difference between consultants and LLMs was marginal, with the clearest disparity in conciseness and the smallest in comprehensibility. Among LLMs Claude 2 was rated best in medical adequacy and conciseness. Consultants' answers matched the validated solution in 93% (228/246), ChatGPT 4 in 85% (35/41), Claude 2 in 78% (32/41), and Bard 2023.07.13 in 59% (24/41). Answers were rated as potentially hazardous in 10% (24/246) for ChatGPT 4, 14% (34/246) for Claude 2, 19% (46/264) for Bard 2023.07.13, and 6% (71/1230) for consultants. CONCLUSIONS AND SIGNIFICANCE: Despite consultants superior performance, LLMs show potential for clinical application in ORL. Future studies should assess their performance on larger scale.


Assuntos
Otolaringologia , Humanos , Alemanha , Idioma , Competência Clínica , Benchmarking
3.
Ultrasound Int Open ; 9(1): E26-E32, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37808417

RESUMO

Purpose Ultrasound examinations are often criticized for having higher examiner dependency compared to other imaging techniques. Compared to free-text reporting, structured reporting (SR) of head and neck sonography (HNS) achieves superior time efficiency as well as report quality. However, there are no findings concerning the influence of SR on the interrater reliability (IRR) of HNS. Materials and Methods Typical pathologies (n=4) in HNS were documented by video/images by two certified head and neck ultrasound instructors. Consequently, structured reports of these videos/images were created by n=9 senior physicians at departments of otolaryngology or maxillofacial surgery with DEGUM instructors on staff. Reports (n=36) were evaluated regarding overall completeness and IRR. Additionally, user satisfaction was assessed by a visual analog scale (VAS). Results SR yielded very high report completeness (91.8%) in all four cases with a substantial IRR (Fleiss' κ 0.73). Interrater agreement was high at 87.2% with very good user satisfaction (VAS 8.6). Conclusion SR has the potential to ensure high-quality examination reports with substantial comparability and very high user satisfaction. Furthermore, big data collection and analysis are facilitated by SR. Therefore, process quality, workflow, and scientific output are potentially enhanced by SR.

4.
Front Cell Neurosci ; 17: 1189980, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37448696

RESUMO

Introduction: Preservation of residual hearing remains a great challenge during cochlear implantation. Cochlear implant (CI) electrode array insertion induces changes in the microvasculature as well as nitric oxide (NO)-dependent vessel dysfunction which have been identified as possible mediators of residual hearing loss after cochlear implantation. Methods: A total of 24 guinea pigs were randomized to receive either a CI (n = 12) or a sham procedure (sham) by performing a cochleostomy without electrode array insertion (n = 12). The hearing threshold was determined using frequency-specific compound action potentials. To gain visual access to the stria vascularis, a microscopic window was created in the osseous cochlear lateral wall. Cochlear blood flow (CBF) and cochlear microvascular permeability (CMP) were evaluated immediately after treatment, as well as after 1 and 2 h, respectively. Finally, cochleae were resected for subsequent immunohistochemical analysis of the iNOS expression. Results: The sham control group showed no change in mean CBF after 1 h (104.2 ± 0.7%) and 2 h (100.8 ± 3.6%) compared to baseline. In contrast, cochlear implantation resulted in a significant continuous decrease in CBF after 1 h (78.8 ± 8.1%, p < 0.001) and 2 h (60.6 ± 11.3%, p < 0.001). Additionally, the CI group exhibited a significantly increased CMP (+44.9% compared to baseline, p < 0.0001) and a significant increase in median hearing threshold (20.4 vs. 2.5 dB SPL, p = 0.0009) compared to sham after 2 h. Intriguingly, the CI group showed significantly lower iNOS-expression levels in the organ of Corti (329.5 vs. 54.33 AU, p = 0.0003), stria vascularis (596.7 vs. 48.51 AU, p < 0.0001), interdental cells (564.0 vs. 109.1 AU, p = 0.0003) and limbus fibrocytes (119.4 vs. 18.69 AU, p = 0.0286). Conclusion: Mechanical and NO-dependent microvascular dysfunction seem to play a pivotal role in residual hearing loss after CI electrode array insertion. This may be facilitated by the implantation associated decrease in iNOS expression. Therefore, stabilization of cochlear microcirculation could be a therapeutic strategy to preserve residual hearing.

5.
Diagnostics (Basel) ; 13(4)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36832149

RESUMO

In Germany, progress assessments in head and neck ultrasonography training have been carried out mainly theoretically and lack standardisation. Thus, quality assurance and comparisons between certified courses from various course providers are difficult. This study aimed to develop and integrate a direct observation of procedural skills (DOPS) in head and neck ultrasound education and explore the perceptions of both participants and examiners. Five DOPS tests oriented towards assessing basic skills were developed for certified head and neck ultrasound courses on national standards. DOPS tests were completed by 76 participants from basic and advanced ultrasound courses (n = 168 documented DOPS tests) and evaluated using a 7-point Likert scale. Ten examiners performed and evaluated the DOPS after detailed training. The variables of "general aspects" (6.0 Scale Points (SP) vs. 5.9 SP; p = 0.71), "test atmosphere" (6.3 SP vs. 6.4 SP; p = 0.92), and "test task setting" (6.2 SP vs. 5.9 SP; p = 0.12) were positively evaluated by all participants and examiners. There were no significant differences between a basic and advanced course in relation to the overall results of DOPS tests (p = 0.81). Regardless of the courses, there were significant differences in the total number of points achieved between individual DOPS tests. DOPS tests are accepted by participants and examiners as an assessment tool in head and neck ultrasound education. In view of the trend toward "competence-based" teaching, this type of test format should be applied and validated in the future.

7.
Eur Arch Otorhinolaryngol ; 280(7): 3157-3169, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36635424

RESUMO

PURPOSE: The aim of the study was to develop the German Hearing in Noise Test (HINT) with female speaker by fulfilling the recommendations by International Collegium of Rehabilitative Audiology (ICRA) for using a female speaker to create new multilingual speech tests and to determine norms and to compare these norms with German male speech tests-the male speakers HINT and the Oldenburg Sentence Test (OLSA). METHODS: The HINT with a female speaker consists of the same speech material as the male speaking HINT. After recording the speech material, 10 normal hearing subjects were included to determine the performance-intensity function (PI function). 24 subjects were part of the measurements to determine the norms and compare them with the norms of male HINT and OLSA. Comparably, adaptive, open-set methods under headphones (HINT) and sound field (OLSA) were used. RESULTS: Acoustic phonetic analysis demonstrated significant difference in mean fundamental frequency, its range and mean speaking rate between both HINT speakers. The calculated norms by three of the tested four conditions of the HINT with a female speaker are not significantly different from the norms with a male speaker. No significant effect of the speaker's gender of the first HINT measurement and no significant correlation between the threshold results of the HINT and the OLSA were determined. CONCLUSIONS: The Norms for German HINT with a female speaker are comparable to the norms of the HINT with a male speaker. The speech intelligibility score of the HINT does not depend on the speakers' gender despite significant difference of acoustic-phonetic parameters between the female and male HINT speaker's voice. Instead, the speech intelligibility rating must be seen as a function of the used speech material.


Assuntos
Ruído , Percepção da Fala , Humanos , Masculino , Feminino , Limiar Auditivo , Mascaramento Perceptivo , Testes Auditivos , Inteligibilidade da Fala , Teste do Limiar de Recepção da Fala/métodos
9.
Eur Arch Otorhinolaryngol ; 280(2): 651-659, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35792917

RESUMO

BACKGROUND: For patients with single sided deafness (SSD) or severe asymmetric sensorineural hearing loss (ASHL), cochlear implantation remains the only solution to restore bilateral hearing capacity. Prognostically, the duration of hearing loss in terms of audiological outcome is not yet clear. Therefore, the aim of this study was to retrospectively investigate the influence of subjective deafness duration on postoperative speech perception after cochlear implantation for SSD as well as its impact on quality of life. MATERIALS AND METHODS: The present study included a total of 36 adults aged 50.2 ± 15.5 years who underwent CI for SSD/ASHL at our clinic between 2010 and 2015. Patients were audiometrically assessed at 3 and 12-36 months postoperatively. Test results were correlated with self-reported duration of deafness. Quality of life was assessed by questionnaire. RESULTS: Mean duration of deafness was 193.9 ± 185.7 months. The side-separated hearing threshold showed an averaged target range between 30 and 40 dB HL. Freiburg monosyllable test increased from 0% pre-operatively to 20% after 3 months (p = 0.001) and to 50% after 12-36 months (p = 0.002). There was a significant correlation between audiometric outcome and subjective deafness duration at 12-36 months postoperatively (r = - 0.564; p = 0.02) with a cutoff for open-set monosyllable recognition at a duration of deafness of greater than 408 months. Quality of life was significantly improved by CI. CONCLUSIONS: CI implantation in unilaterally deafened patients provides objective and subjective benefits. Duration of deafness is unlikely to be an independent negative predictive factor and thus should not generally be considered as contraindication.


Assuntos
Implante Coclear , Implantes Cocleares , Surdez , Perda Auditiva Neurossensorial , Perda Auditiva Unilateral , Percepção da Fala , Adulto , Humanos , Perda Auditiva Unilateral/cirurgia , Inteligibilidade da Fala , Surdez/cirurgia , Surdez/reabilitação , Estudos Retrospectivos , Qualidade de Vida , Resultado do Tratamento , Audição , Perda Auditiva Neurossensorial/cirurgia
10.
MethodsX ; 8: 101540, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34754808

RESUMO

This article contains supporting information on data collection for the research article entitled "Aircraft noise exposure drives the activation of white blood cells and induces microvascular dysfunction in mice" by Eckrich et al. We found that noise-induced stress triggered microvascular dysfunction via involvement of innate immune-derived reactive oxygen species. In this article, we present the instrumentation of mice with dorsal skinfold chambers for in vivo microscopic imaging of blood flow, interaction of leukocytes with the vascular wall (also by fluorescent labelling of blood cells) and vessel diameter. In addition, we explain the preparation of cerebral arterioles for measurement of vascular reactivity in vitro.•visualization of noise-dependent effects in dorsal skinfold chamber.•in vivo microscopy of noise-dependent activation of white blood cells.•analysis of noise-dependent microvascular dysfunction in dorsal skinfold chamber and cannulated cerebral arterioles.

11.
J Histochem Cytochem ; 69(11): 731-739, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34666550

RESUMO

In the vertebrate cochlea, the reticular lamina seals the organ of Corti against the endolymph filled scala media. After noise exposure, fast alterations in the endothelial nitric oxide synthase (eNOS) expression level were identified in this cochlear structure. Minor amounts of nitric oxide (NO) produced by eNOS or applied by NO donors such as S-nitroso-N-acetyl-penicillamine (SNAP) might protect this vulnerable part of the organ of Corti, on the line of gap junctions of supporting cells and cochlear microcirculation. In n=5 anesthetized guinea pigs, SNAP was intravenously applied in two concentrations. Six untreated animals served as controls. The cochleae were removed and prepared for immunoelectron microscopy using specific gold-labeled anti-eNOS antibodies. The density of the gold particles was quantified for seven cellular regions in the reticular lamina at the ultrastructural level. Following SNAP application, a significant increase in eNOS expression (+176%) was detected compared with controls (p=0.012). The increase occurred mainly in actin-rich cuticular structures and the prominent microtubules bundles. Correlation analysis revealed three clear and five moderate cellular associations for controls, whereas only one clear and one moderate after SNAP application. Thus, application of the NO donor SNAP resulted in an increase in eNOS expression in distinct regions of the reticular lamina.


Assuntos
Doadores de Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Órgão Espiral/metabolismo , Lâmina Espiral/metabolismo , Animais , Cobaias , Masculino
12.
Redox Biol ; 46: 102063, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34274810

RESUMO

Epidemiological studies showed that traffic noise has a dose-dependent association with increased cardiovascular morbidity and mortality. Whether microvascular dysfunction contributes significantly to the cardiovascular health effects by noise exposure remains to be established. The connection of inflammation and immune cell interaction with microvascular damage and functional impairment is also not well characterized. Male C57BL/6J mice or gp91phox-/y mice with genetic deletion of the phagocytic NADPH oxidase catalytic subunit (gp91phox or NOX-2) were used at the age of 8 weeks, randomly instrumented with dorsal skinfold chambers and exposed or not exposed to aircraft noise for 4 days. Proteomic analysis (using mass spectrometry) revealed a pro-inflammatory phenotype induced by noise exposure that was less pronounced in noise-exposed gp91phox-/y mice. Using in vivo fluorescence microscopy, we found a higher number of adhesive leukocytes in noise-exposed wild type mice. Dorsal microvascular diameter (by trend), red blood cell velocity, and segmental blood flow were also decreased by noise exposure indicating microvascular constriction. All adverse effects on functional parameters were normalized or improved at least by trend in noise-exposed gp91phox-/y mice. Noise exposure also induced endothelial dysfunction in cerebral microvessels, which was associated with higher oxidative stress burden and inflammation, as measured using video microscopy. We here establish a link between a pro-inflammatory phenotype of plasma, activation of circulating leukocytes and microvascular dysfunction in mice exposed to aircraft noise. The phagocytic NADPH oxidase was identified as a central player in the underlying pathophysiological mechanisms.


Assuntos
Leucócitos , Proteômica , Aeronaves , Animais , Leucócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Estresse Oxidativo
13.
Ultraschall Med ; 42(4): 411-417, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32052386

RESUMO

PURPOSE: Correct differentiation between malignant and benign incidentally found cystic renal lesions has critical implications for patient management. In several studies contrast-enhanced ultrasound (CEUS) showed higher sensitivity with respect to the accurate characterization of these lesions compared to MRI, but the cost-effectiveness of CEUS has yet to be investigated. The aim of this study was to analyze the cost-effectiveness of CEUS as an alternative imaging method to MRI for the characterization of incidentally found cystic renal lesions. MATERIALS AND METHODS: A decision model including the diagnostic modalities MRI and CEUS was created based on Markov simulations estimating lifetime costs and quality-adjusted life years (QALYs). The recent literature was reviewed to obtain model input parameters. The deterministic sensitivity of diagnostic parameters and costs was determined and probabilistic sensitivity analysis using Monte-Carlo Modelling was applied. Willingness-to-pay (WTP) was assumed to be $ 100 000/QALY. RESULTS: In the base-case scenario, the total costs for CEUS were $9654.43, whereas the total costs for MRI were $9675.03. CEUS resulted in an expected effectiveness of 8.06 QALYs versus 8.06 QALYs for MRI. Therefore, from an economic point of view, CEUS was identified as an adequate diagnostic alternative to MRI. Sensitivity analysis showed that results may vary if CEUS costs increase or those of MRI decrease. CONCLUSION: Based on the results of the analysis, the use of CEUS was identified as a cost-effective diagnostic strategy for the characterization of incidentally found cystic renal lesions.


Assuntos
Neoplasias Renais , Imageamento por Ressonância Magnética , Meios de Contraste , Análise Custo-Benefício , Humanos , Rim/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Ultrassonografia
14.
PLoS One ; 15(11): e0242804, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33253265

RESUMO

Computed tomography (CT) scans represent the gold standard in the planning of functional endoscopic sinus surgeries (FESS). Yet, radiologists and otolaryngologists have different perspectives on these scans. In general, residents often struggle with aspects involved in both reporting and operation planning. The aim of this study was to compare the completeness of structured reports (SR) of preoperative CT images and structured operation planning (SOP) to conventional reports (CR) and conventional operation planning (COP) to potentially improve future treatment decisions on an individual level. In total, 30 preoperative CT scans obtained for surgical planning of patients scheduled for FESS were evaluated using SR and CR by radiology residents. Subsequently, otolaryngology residents performed a COP using free texts and a SOP using a specific template. All radiology reports and operation plannings were evaluated by two experienced FESS surgeons regarding their completeness for surgical planning. User satisfaction of otolaryngology residents was assessed by using visual analogue scales. Overall radiology report completeness was significantly higher using SRs regarding surgically important structures compared to CRs (84.4 vs. 22.0%, p<0.001). SOPs produced significantly higher completeness ratings (97% vs. 39.4%, p<0.001) regarding pathologies and anatomical variances. Moreover, time efficiency was not significantly impaired by implementation of SR (148 s vs. 160 s, p = 0.61) and user satisfaction was significantly higher for SOP (VAS 8.1 vs. 4.1, p<0.001). Implementation of SR and SOP results in a significantly increased completeness of radiology reports and operation planning for FESS. Consequently, the combination of both facilitates surgical planning and may decrease potential risks during FESS.


Assuntos
Endoscopia , Doenças dos Seios Paranasais/cirurgia , Radiologia , Adulto , Feminino , Humanos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Doenças dos Seios Paranasais/diagnóstico por imagem , Doenças dos Seios Paranasais/patologia , Tomografia Computadorizada por Raios X
15.
Sci Rep ; 10(1): 18585, 2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-33122780

RESUMO

The chorioallantoic-membrane (CAM)-assay is an established model for in vivo tumor research. Contrary to rodent-xenograft-models, the CAM-assay does not require breeding of immunodeficient strains due to native immunodeficiency. This allows xenografts to grow on the non-innervated CAM without pain or impairment for the embryo. Considering multidirectional tumor growth, limited monitoring capability of tumor size is the main methodological limitation of the CAM-assay for tumor research. Enclosure of the tumor by the radiopaque eggshell and the small structural size only allows monitoring from above and challenges established imaging techniques. We report the eligibility of ultrasonography for repetitive visualization of tumor growth and vascularization in the CAM-assay. After tumor ingrowth, ultrasonography was repetitively performed in ovo using a commercial ultrasonographic scanner. Finally, the tumor was excised and histologically analyzed. Tumor growth and angiogenesis were successfully monitored and findings in ultrasonographic imaging significantly correlated with results obtained in histological analysis. Ultrasonography is cost efficient and widely available. Tumor imaging in ovo enables the longitudinal monitoring of tumoral development, yet allowing high quantitative output due to the CAM-assays simple and cheap methodology. Thus, this methodological novelty improves reproducibility in the field of in vivo tumor experimentation emphasizing the CAM-assay as an alternative to rodent-xenograft-models.


Assuntos
Carcinoma Hepatocelular/patologia , Membrana Corioalantoide/patologia , Neoplasias Hepáticas/patologia , Neovascularização Patológica/patologia , Ultrassonografia/métodos , Animais , Bioensaio , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/diagnóstico por imagem , Galinhas , Modelos Animais de Doenças , Xenoenxertos , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Neovascularização Patológica/diagnóstico por imagem , Células Tumorais Cultivadas
16.
Med Ultrason ; 22(4): 445-450, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-32905561

RESUMO

AIMS: Reporting of head and neck ultrasound (HNU) has been outlined to be a major obstacle during ultrasound training due to a lack of standardized structure, content and terminology. Consequently, overall report quality differs significantly between various examiners posing a severe risk factor for information loss and miscommunication. Therefore, the present study's purpose is to compare the overall quality of free text reports (FTR) and structured reports (SR) of HNU at various stages of training in order to determine the optimal educational level to implement SR. MATERIAL AND METHODS: Typical pathologies in HNU were reported upon using SR and FTR by medical students, junior residents and senior residents. The reports were assessed for overall quality, time efficiency and readability. Additionally, user satisfaction was determined using a questionnaire. RESULTS: SRs exhibited a significantly superior report quality (93.1% vs. 45.6%, p<0.001) at all training levels. Overall time efficiency was significantly better for SRs, especially at the stages of medical school and early residency (89.4 s vs. 160.2 s., p<0.001). Using structured reporting also increased user satisfaction significantly (VAS 8.6 vs. 3.9, p<0.001). CONCLUSIONS: Implementing structured reporting of HNU results in a superior report quality at all training stages. Greatest benefits for time efficiency are achieved by implementation during medical school. Therefore, structured reporting of HNU should be implemented early on in the training of HNU.


Assuntos
Internato e Residência , Estudantes de Medicina , Ultrassonografia , Cabeça/diagnóstico por imagem , Humanos , Pescoço/diagnóstico por imagem , Ultrassonografia/métodos
17.
J Proteomics ; 226: 103886, 2020 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-32621938

RESUMO

Despite improvements of radiotherapy and better outcomes of cancer patients resistances still limit the therapeutic success. The combined treatment of tumors by the use of irradiation as well as targeted therapies is a promising approach. By the use of a proteomic screening of lung and head and neck cancer cell lines we identified the heat shock protein HSP27 as a potential target protein for a combined treatment strategy. Overall expression of HSP27 was distinctly lower in HNSCCUM-02T cells which have a high HSP27 phosphorylation ratio, whereas A549 cells revealed the opposite. Irradiation and inhibition of HSP27 phosphorylation by MKII inhibition resulted in a significantly reduced viability in both cell lines. While irradiation impaired migration only in HNSCCUM-02T cells, MKII inhibition exerted that effect in both cell lines. In contrast, knockdown of HSP27 compromised the viability only in A549 cells. Additionally, MKII inhibition counteracts radiation-induced phosphorylation of HSP27 which causes an additive toxicity and reduced migratory capacity in HNSCCUM-02T when combined. Inhibition of HSP27 expression and phosphorylation in combination with radiotherapy may be an effective treatment option to overcome resistances.


Assuntos
Proteínas de Choque Térmico HSP27 , Neoplasias , Linhagem Celular Tumoral , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico , Humanos , Fosforilação , Proteômica , RNA Interferente Pequeno
18.
Anticancer Res ; 38(2): 699-706, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29374693

RESUMO

BACKGROUND/AIM: Head and neck squamous cell carcinomas (HNSCC) are characterized by aggressiveness, early recurrence and lymph node metastasis. Therefore, there is an urgent need to identify new biomarkers and drug targets. MATERIALS AND METHODS: Neck dissection specimens from 11 patients diagnosed with hypopharyngeal cancer were analyzed for their lymphatic vessel density (LVD) by lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) immunostaining, expression of eukaryotic initiation factor 4E (eIF4E) and levels of secreted protein acidic and rich in cysteine (SPARC) using immunoblot analysis. RESULTS: Compared to lymph node biopsies of healthy controIs, LVD was significantly increased in metastatic lymph nodes as well as in advanced primary tumors. Overexpression of eIF4E and SPARC was demonstrated in all hypopharyngeal cancer specimens. Notably, we observed that increased LVD significantly correlated with the expression of eIF4E as well as SPARC levels. CONCLUSION: eIF4E- and SPARC-associated signaling pathways may be associated with lymphangiogenesis and could be exploited to counteract the spread of hypopharyngeal cancer cells.


Assuntos
Neoplasias Hipofaríngeas/metabolismo , Neoplasias Hipofaríngeas/patologia , Linfangiogênese/fisiologia , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Osteonectina/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço
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