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1.
Diagnostics (Basel) ; 14(15)2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39125469

RESUMO

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.

2.
Anticancer Res ; 42(7): 3403-3411, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35790279

RESUMO

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.


Assuntos
Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Everolimo/farmacologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Metaloproteinase 14 da Matriz , Metaloproteinase 2 da Matriz , Inibidores de Proteínas Quinases/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Microambiente Tumoral
3.
Laryngorhinootologie ; 101(8): 652-659, 2022 08.
Artigo em Alemão | MEDLINE | ID: mdl-35500596

RESUMO

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 (ß = 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.


Assuntos
Transtornos de Deglutição , Neoplasias de Cabeça e Pescoço , Desnutrição , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Detecção Precoce de Câncer , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Desnutrição/diagnóstico , Desnutrição/etiologia , Desnutrição/prevenção & controle , Estado Nutricional
4.
HNO ; 70(7): 533-539, 2022 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-35122104

RESUMO

BACKGROUND: The swallowing and nutritional status of head-and-neck cancer patients after oncological therapy have been extensively researched. However, the same topics are seldom scrutinized before the onset of oncological therapy, although they can influence treatment success in the long term. OBJECTIVE: This study focusses on a systematic assessment of swallowing function and nutritional status in head-and-neck cancer patients prior to oncological therapy. MATERIALS AND METHODS: In 102 patients, penetration/aspiration (PA scale), limitations of oral intake (Functional Oral Intake Scale, FOIS), and the need for further intervention (NFI) were endoscopically assessed to objectively quantify swallowing function. The subjective evaluation of swallowing function was carried out with the gEAT-10 (German EAT-10) questionnaire, nutritional status was assessed by body mass index (BMI). Possible impact factors for swallowing function and BMI were analyzed by univariate and multivariate methods. RESULTS: PAS, FOIS, and NFI values were abnormal in ≤ 15% of patients. BMI was more often too high than too low. Objectively assessed swallowing functions depended predominantly on tumor stage and showed moderate correlations with gEAT-10. The latter mostly yielded a "fail" result. The nutritional status depended on the patients' biological sex and NFI. CONCLUSION: In the pre-treatment setting, neither dysphagia nor malnutrition were found in most patients. Impaired swallowing was associated with higher tumor stages, malnutrition with female sex and NFI. A systematic pre-treatment assessment of swallowing and nutritional status in head-and-neck cancer patients appears necessary for modern oncological therapy and optimal patient outcome.


Assuntos
Transtornos de Deglutição , Neoplasias de Cabeça e Pescoço , Desnutrição , Deglutição , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Desnutrição/diagnóstico , Desnutrição/etiologia , Desnutrição/terapia , Inquéritos e Questionários
5.
Eur Arch Otorhinolaryngol ; 279(1): 493-499, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34117898

RESUMO

PURPOSE: No standardized treatment regimen exists for juvenile recurrent parotitis (JRP). The investigators hypothesized that irrigation with saline only without local anesthesia will be an effective and beneficial option. METHODS: Using a retrospective study design, a series of children with typical symptoms of JRP who were treated with at least one irrigation therapy were evaluated. This treatment consisted of irrigation of the affected gland with 3-10 ml saline solution without any type of anesthesia. The outcome variables were patient/parent satisfaction, frequency and duration of acute JRP episodes, and the need for antibiotics before and after irrigation therapy. RESULTS: The case series was composed of six boys aged 3.3-7.7 years who experienced one to eight sessions of irrigation therapy. The period of follow-up was 9-64 months. We observed a total resolution of symptoms in two children and an improvement in the other four. No relevant side effects were seen. CONCLUSION: Our results suggest that irrigation therapy is a reasonable, simple, and minimally invasive treatment alternative for JRP. In contrast to sialendoscopy or sialography, there is no need for general anesthesia or radiation exposure.


Assuntos
Anestesia , Parotidite , Criança , Endoscopia , Humanos , Masculino , Parotidite/terapia , Satisfação do Paciente , Estudos Retrospectivos , Sialografia
6.
Laryngorhinootologie ; 101(4): 320-326, 2022 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-34187052

RESUMO

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.


Assuntos
Transtornos de Deglutição , Neoplasias de Cabeça e Pescoço , Adulto , Deglutição , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
7.
Eur Arch Otorhinolaryngol ; 278(3): 893-900, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33111155

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) is a sleep disorder with a prevalence of 9-38%. The underlying pathology in OSA is a collapse of the upper airway. Especially in more severely affected patients, this collapse is often located at the level of the tongue base. Therefore, various implantable systems (anchors and ligament techniques) were developed to prevent or overcome this collapse. These systems are exposed to various forces. Different models have been developed to measure these forces and data comparing forces in healthy individuals with OSA patients are rare. PURPOSE: Purpose of the study was to evaluate possible differences in tongue forces between healthy individuals and patients with OSA. METHOD: To evaluate maximum isometric tongue forces, we conducted a matched pair design study including 20 healthy individuals and 20 patients suffering from OSA. Maximum isometric tongue forces were measured in an anterior/posterior direction with the help of self-designed new device that clamps the tongue. RESULTS: We could show that the maximum isometric force does not differ significantly in healthy individuals (10.7 ± 5.2N) from patients with OSA (14.4 ± 6.3N). CONCLUSION: Currently there are no indications that maximum isometric tongue force does differ in healthy individuals and patients with OSA. Higher, as well as lower, tongue forces in patients with OSA seem not to differ from healthy subjects and therefore may not be needed to consider, in the development of tongue management devices, for OSA patients.


Assuntos
Apneia Obstrutiva do Sono , Voluntários Saudáveis , Humanos , Língua
8.
In Vivo ; 34(6): 3285-3289, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33144435

RESUMO

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%. High-speed 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.


Assuntos
Cocaína , Contagem de Células , Cílios , Cocaína/farmacologia , Células Epiteliais , Humanos , Mucosa Nasal
9.
Anticancer Res ; 40(11): 6195-6203, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109556

RESUMO

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.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Everolimo/farmacologia , Papillomaviridae/fisiologia , Inibidores de Proteínas Quinases/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proteína Ligante Fas/metabolismo , Humanos , Proteínas de Neoplasias/metabolismo , Papillomaviridae/efeitos dos fármacos , Receptor fas/metabolismo
10.
Anticancer Res ; 40(10): 5621-5630, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988886

RESUMO

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.


Assuntos
Everolimo/farmacologia , Fatores de Crescimento de Fibroblastos/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Serina-Treonina Quinases TOR/genética , Linhagem Celular Tumoral , Dasatinibe/farmacologia , Cloridrato de Erlotinib/farmacologia , Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Gefitinibe/farmacologia , Papillomavirus Humano 16/efeitos dos fármacos , Papillomavirus Humano 16/patogenicidade , Humanos , Papillomaviridae/efeitos dos fármacos , Papillomaviridae/patogenicidade , Inibidores de Proteínas Quinases/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Serina-Treonina Quinases TOR/antagonistas & inibidores
11.
Cancer Genomics Proteomics ; 17(5): 579-585, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32859636

RESUMO

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.


Assuntos
Anfirregulina/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Receptores de Hialuronatos/genética , Infecções por Papillomavirus/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Alphapapillomavirus/isolamento & purificação , Anfirregulina/análise , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Linhagem Celular Tumoral , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Receptores de Hialuronatos/análise , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Medicina de Precisão/métodos , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
12.
Anticancer Res ; 40(7): 3847-3855, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620624

RESUMO

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.


Assuntos
Everolimo/farmacologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Papillomavirus Humano 16/isolamento & purificação , Infecções por Papillomavirus/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Receptor IGF Tipo 1/biossíntese , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Dasatinibe/farmacologia , Cloridrato de Erlotinib/farmacologia , Gefitinibe/farmacologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Infecções por Papillomavirus/virologia , Pirimidinas/farmacologia , Receptor IGF Tipo 1/antagonistas & inibidores , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia
13.
Eur Arch Otorhinolaryngol ; 277(9): 2561-2571, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32285192

RESUMO

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.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Pulmonares , Antígenos de Neoplasias , Biomarcadores Tumorais , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Humanos , Queratina-19 , Queratinas , Recidiva Local de Neoplasia/diagnóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Carcinoma de Células Escamosas de Cabeça e Pescoço
14.
Anticancer Res ; 40(2): 825-835, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014925

RESUMO

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 -ß 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/-ß 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.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Papillomavirus Humano 16/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Carcinoma de Células Escamosas/patologia , Humanos
15.
Eur Arch Otorhinolaryngol ; 276(12): 3467-3475, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31482332

RESUMO

PURPOSE: The clinical significance of cytokeratin fraction 21-1 (CYFRA 21-1) for patients with head and neck cutaneous squamous cell carcinoma (CSCC) is unknown. Thus, the aim of the study was to evaluate the clinical value of CYFRA 21-1 in the context of treatment and follow-up for these patients. METHODS: The clinical, histological and laboratory data of a total of 55 patients with the first diagnosis of head and neck cutaneous squamous cell carcinoma (T1-T4, N0-N2b, M0-1) between 2003 and 2017 were retrospectively analyzed. In 25 cases, the primary tumor could be treated successfully without residual or recurrent disease in the further course. The average follow-up period was 2.3 years. In all patients, pretherapeutic determination of CYFRA 21-1 was performed using the ECLIA test kit. The cut-off value was set at 3.3 ng/ml. RESULTS: In 18 patients (32.7%), regional recurrence was found in the course of treatment. Distant metastases could be observed in two patients (3.6%). In these cases, no significant increase of CYFRA 21-1 blood concentration was detected at the time of recurrence/metastasis. At the time of the first diagnosis, the mean value of CYFRA 21-1 blood concentration was 2.4 ng/ml; and in cases of regional recurrence or distant metastases, the initial mean CYFRA 21-1 concentration was 2.0 ng/ml. There was no statistically significant relationship between CYFRA 21-1 blood concentration and analyzed tumor characteristics. CONCLUSIONS: According to current knowledge, the tumor marker CYFRA 21-1 is not clinically significant for treatment and follow-up of patients with head and neck CSCC.


Assuntos
Antígenos de Neoplasias/sangue , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Queratina-19/sangue , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Adulto , Assistência ao Convalescente , Idoso , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Progressão da Doença , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Neoplasias Cutâneas/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue
16.
Anticancer Res ; 38(5): 2723-2731, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29715092

RESUMO

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.


Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Neoplasias/biossíntese , Infecções por Papillomavirus/patologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-kit/biossíntese , Quinases da Família src/biossíntese , Proteína Tirosina Quinase CSK , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Linhagem Celular Tumoral , Indução Enzimática/efeitos dos fármacos , Feminino , Neoplasias de Cabeça e Pescoço/enzimologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas c-kit/genética , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/secundário , Neoplasias Cutâneas/virologia , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Quinases da Família src/genética
17.
Cancer Genomics Proteomics ; 15(3): 175-184, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29695399

RESUMO

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.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Dasatinibe/farmacologia , Cloridrato de Erlotinib/farmacologia , Gefitinibe , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Pirimidinas/farmacologia , Quinazolinas/farmacologia , Células Tumorais Cultivadas
18.
Mol Med Rep ; 17(3): 3813-3820, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29286120

RESUMO

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 neo­tissue 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 co­cultures 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 co­cultures with and without SMF exposure, using growth medium [high growth factor concentrations (GM)] and differentiation medium [low growth factors concentrations (DM)]. AlamarBlue® assay­based cell proliferation analysis revealed no significant difference between co­cultures with, vs. without SMF stimulation, regardless of growth factor concentrations in the cell culture medium. To determine the degree of differentiation in co­cultures under stimulation with SMFs, semi­quantitative 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 co­cultures did not result in the desired increase in myogenic differentiation. Further studies are required to identify a suitable stimulus for skeletal muscle tissue engineering.


Assuntos
Expressão Gênica/efeitos da radiação , Campos Magnéticos , Células-Tronco Mesenquimais/efeitos da radiação , Mioblastos/efeitos da radiação , Engenharia Tecidual , Actinas/genética , Actinas/metabolismo , Biomarcadores/metabolismo , Miosinas Cardíacas/genética , Miosinas Cardíacas/metabolismo , Diferenciação Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Técnicas de Cocultura , Meios de Cultura/química , Meios de Cultura/farmacologia , Desmina/genética , Desmina/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos da radiação , Proteína MyoD/genética , Proteína MyoD/metabolismo , Mioblastos/citologia , Mioblastos/metabolismo , Fator Regulador Miogênico 5/genética , Fator Regulador Miogênico 5/metabolismo , Miogenina/genética , Miogenina/metabolismo , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Cultura Primária de Células
19.
Head Neck ; 39(12): 2481-2487, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28990261

RESUMO

BACKGROUND: After tracheostomy, the airway lacks an essential mechanism for warming and humidifying the inspired air with the consequent functional impairment and discomfort. The purpose of this study was to compare airway hydration with cold-air nebulization versus heated high-flow humidification on medical interventions and tracheal ciliary beat frequency (CBF). METHODS: Newly tracheostomized patients (n = 20) were treated either with cold-air nebulization or heated humidification. The number of required tracheal suctioning procedures to clean the trachea and tracheal CBF were assessed. RESULTS: The number of required suctions per day was significantly lower in the heated humidification group with medians 3 versus 5 times per day. Mean CBF was significantly higher in the heated humidification group (6.36 ± 1.49 Hz) compared to the cold-air nebulization group (3.99 ± 1.39 Hz). CONCLUSION: The data suggest that heated humidification enhanced mucociliary transport leading to a reduced number of required suctioning procedures in the trachea, which may improve postoperative patient care.


Assuntos
Manuseio das Vias Aéreas/métodos , Temperatura Baixa , Temperatura Alta , Oxigenoterapia/métodos , Traqueostomia/métodos , Administração por Inalação , Adulto , Idoso , Estudos de Coortes , Feminino , Alemanha , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores , Estudos Prospectivos , Estatísticas não Paramétricas , Resultado do Tratamento
20.
Anticancer Res ; 37(9): 4827-4836, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28870902

RESUMO

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.


Assuntos
Comunicação Celular/efeitos dos fármacos , Quimiocina CXCL12/farmacologia , Modelos Biológicos , Células-Tronco Neoplásicas/patologia , Papillomaviridae/fisiologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Imunofluorescência , Humanos , Receptores de Hialuronatos/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Receptores CXCR4/metabolismo
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