Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22
Filtrar
1.
Eur Arch Otorhinolaryngol ; 278(9): 3551-3558, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33677653

RESUMEN

PURPOSE: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) replicates predominantly in the upper respiratory tract and is primarily transmitted by droplets and aerosols. Taking the medical history for typical COVID-19 symptoms and PCR-based SARS-CoV-2 testing have become established as screening procedures. The aim of this work was to describe the clinical appearance of SARS-CoV-2-PCR positive patients and to determine the SARS-CoV-2 contact risk for health care workers (HCW). METHODS: The retrospective study included n = 2283 SARS-CoV-2 PCR tests from n = 1725 patients with otorhinolaryngological (ORL) diseases performed from March to November 2020 prior to inpatient treatment. In addition, demographic data and medical history were assessed. RESULTS: n = 13 PCR tests (0.6%) were positive for SARS-CoV-2 RNA. The positive rate showed a significant increase during the observation period (p < 0.01). None of the patients had clinical symptoms that led to a suspected diagnosis of COVID-19 before PCR testing. The patients were either asymptomatic (n = 4) or had symptoms that were interpreted as symptoms typical of the ORL disease or secondary diagnoses (n = 9). CONCLUSION: The identification of SARS-CoV-2-positive patients is a considerable challenge in clinical practice. Our findings illustrate that taking a medical history alone is of limited value and cannot replace molecular SARS-CoV-2 testing, especially for patients with ORL diseases. Our data also demonstrate that there is a high probability of contact with SARS-CoV-2-positive patients in everyday clinical practice, so that the use of personal protective equipment, even in apparently "routine cases", is highly recommended.


Asunto(s)
COVID-19 , Enfermedades Otorrinolaringológicas , Prueba de COVID-19 , Humanos , ARN Viral , Estudios Retrospectivos , SARS-CoV-2
2.
Eur Arch Otorhinolaryngol ; 278(4): 1237-1245, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32895799

RESUMEN

INTRODUCTION: Based on current knowledge, the SARS-CoV-2 is transmitted via droplet, aerosols and smear infection. Due to a confirmed high virus load in the upper respiratory tract of COVID-19 patients, there is a potential risk of infection for health care professionals when performing surgical procedures in this area. The aim of this study was the semi-quantitative comparison of ENT-typical interventions in the head and neck area with regard to particle and aerosol generation. These data can potentially contribute to a better risk assessment of aerogenic SARS-CoV-2-transmission caused by medical procedures. MATERIALS AND METHODS: As a model, a test chamber was created to examine various typical surgical interventions on porcine soft and hard tissues. Simultaneously, particle and aerosol release were recorded and semi-quantitatively evaluated time-dependently. Five typical surgical intervention techniques (mechanical stress with a passive instrument with and without suction, CO2 laser treatment, drilling and bipolar electrocoagulation) were examined and compared regarding resulting particle release. RESULTS: Neither aerosols nor particles could be detected during mechanical manipulation with and without suction. The use of laser technique showed considerable formation of aerosol. During drilling, mainly solid tissue particles were scattered into the environment (18.2 ± 15.7 particles/cm2/min). The strongest particle release was determined during electrocoagulation (77.2 ± 30.4 particles/cm2/min). The difference in particle release between electrocoagulation and drilling was significant (p < 0.05), while particle diameter was comparable. In addition, relevant amounts of aerosol were released during electrocoagulation (79.6% of the maximum flue gas emission during laser treatment). DISCUSSION: Our results demonstrated clear differences comparing surgical model interventions. In contrast to sole mechanical stress with passive instruments, all active instruments (laser, drilling and electrocoagulation) released particles and aerosols. Assuming that particle and aerosol exposure is clinically correlated to the risk of SARS-CoV-2-transmission from the patient to the physician, a potential risk for health care professionals for infection cannot be excluded. Especially electrocautery is frequently used for emergency treatment, e.g., nose bleeding. The use of this technique may, therefore, be considered particularly critical in potentially infectious patients. Alternative methods may be given preference and personal protective equipment should be used consequently.


Asunto(s)
Aerosoles/efectos adversos , COVID-19/prevención & control , COVID-19/transmisión , Electrocoagulación , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Terapia por Láser , Procedimientos Quirúrgicos Otorrinolaringológicos/efectos adversos , Animales , COVID-19/virología , Humanos , Procedimientos Quirúrgicos Otorrinolaringológicos/métodos , Procedimientos Quirúrgicos Otorrinolaringológicos/normas , Pandemias , SARS-CoV-2 , Porcinos
3.
Cells ; 8(10)2019 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-31569361

RESUMEN

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and often has a poor prognosis. The present study investigated the role of the low affinity nerve growth factor receptor CD271 as a putative therapy target in HNSCC. Neurotrophins that bind to CD271 also have a high affinity for the tropomyosin receptor kinase family (Trk), consisting of TrkA, TrkB, and TrkC, which must also be considered in addition to CD271. A retrospective study and functional in vitro cell line tests (migration assay and cell sorting) were conducted in order to evaluate the relevance of CD271 expression alone and with regard to Trk expression. CD271 and Trks were heterogeneously expressed in human HNSCC. The vast majority of tumors exhibited CD271 and TrkA, whereas only half of the tumors expressed TrkB and TrkC. High expression of CD271-positive cells predicted a bad clinical outcome of patients with HNSCC and was associated with distant metastases. However, the human carcinomas that also expressed TrkC had a reduced correlation with distant metastases and better survival rates. In vitro, CD271 expression marked a subpopulation with higher proliferation rates, but proliferation was lower in tumor cells that co-expressed CD271 and TrkC. The CD271 inhibitor LM11A 31 suppressed cell motility in vitro. However, neither TrkA nor TrkB expression were linked to prognosis or cell proliferation. We conclude that CD271 is a promising candidate that provides prognostic information for HNSCC and could be a putative target for HNSCC treatment.


Asunto(s)
Neoplasias de Cabeza y Cuello/patología , Proteínas del Tejido Nervioso/metabolismo , Receptor trkC/metabolismo , Receptores de Factor de Crecimiento Nervioso/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Análisis de Supervivencia
5.
Oncol Lett ; 10(4): 2289-2294, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26622836

RESUMEN

In head and neck squamous cell carcinoma (HNSCC), aldehyde dehydrogenase 1 family, member A1 (ALDH1A1) and hyaluronan receptor cluster of differentiation 44 (CD44) are often used as cancer stem cell (CSC) markers. The aim of the present study was to examine the relevance of these proteins for HNSCC in general and for the identification of CSCs. Tumors from 48 patients with primary HNSCC were analyzed for the expression of ALDH1A1 and CD44. Additionally, the association of the proteins with the proliferation rate and epidermal growth factor receptor (EGFR) expression was analyzed. ALDH1A1 was expressed in 54.2% of the carcinoma samples while CD44 was expressed in 89.6% of the carcinoma samples. Most notably, these proteins were often not expressed exclusively in a subpopulation, but also in the majority of tumor cells (ALDH1A1: 30.8% of ALDH1A1+ tumors; CD44: 65.1% of CD44+ tumors). Furthermore, patients with ALDH1A1+ tumors exhibited worse survival rates. CD44 and EGFR expression patterns were overlapping within the tumors and the expression rates were significantly connected. Ki-67+ tumor cells often expressed CD44. ALDH1A1 and CD44 expression patterns only partly overlapped. Consequently, ALDH1A1 and CD44 play significant roles in carcinogenesis and tumor progression. Within the present study, CD44 appeared to interact with EGFR and was more often expressed in primary HNSCC than the marker ALDH1A1. However, ALDH1A1 was a better marker to define a subpopulation of tumor cells. Finally, neither ALDH1A1 nor CD44, alone or combined, were sufficient to determine the CSC population in HNSCC.

6.
Anticancer Res ; 33(8): 3481-5, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23898123

RESUMEN

BACKGROUND/AIM: A change in epidemiology of head and neck squamous cell carcinoma (HNSCC) has been noticed: while overall incidence has decreased, the incidence of oropharyngeal SCC (OSCC) has been increasing over the past decades. A growing body of evidence suggests a causative role of the human papillomavirus (HPV) as an independent risk factor in development of OSCC. The aim of this study was to determine the HPV status in all OSCC specimens collected in our biological database since 1988, correlating the results with overall survival, and to compare them with the current literature data. PATIENTS AND METHODS: A total of 104 tumor samples were obtained and included in this study. Patient records were reviewed. HPV status was determined by a two-step polymerase chain reaction (PCR) combined with p16 immunohistochemistry. Statistical analysis was performed with BiAS™. RESULTS: Overall 12 (12%) of the 104 tumor samples were HPV-positive. Most of the patients had advanced disease [(UICC) stage III or IV)]: 91.7 % in the HPV-positive group versus 78.2% in the HPV-negative group. Multivariate analysis showed that HPV status (p=0.04), UICC stage (p=0.01) and age at initial diagnosis (p=0.0006) were all independent determinants of overall survival. A positive HPV status (hazard ratio=0.52; 95%) was associated with a 48% increase of overall survival compared to patients with HPV-negative tumors. CONCLUSION: Our findings confirm a prevalence of HPV-positive tumors within OSCC. Due to its epidemiologic and prognostic relevance, HPV status should be considered an important part of tumor staging. For this purpose, HPV detection via two-step PCR combined with p16 immunohistochemistry seems reliable.


Asunto(s)
Carcinoma de Células Escamosas/virología , Neoplasias de Cabeza y Cuello/patología , Estimación de Kaplan-Meier , Neoplasias Orofaríngeas/virología , Papillomaviridae/fisiología , Carcinoma de Células Escamosas/patología , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/patología , Estudios Retrospectivos
7.
Anticancer Res ; 33(3): 913-6, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23482761

RESUMEN

UNLABELLED: Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most common type of cancer worldwide; 600,000 new cases are diagnosed every year. Infected with high-risk human papilloma virus (HPV) types are particularly linked to oropharyngeal cancer. Among over 100 different HPV types, HPV-16 and HPV-18 are detected in the majority of HPV-positive SCCHNs. The p16 gene is often mutated in SCCHN, its overexpression is caused by the viral E7 protein. Consequently, p16 is assumed to be an indirect marker of HPV-induced SCCHN. The aim of the present study was to determine the role of p16 expression as a predictive marker of HPV infection in SCCHN tumors in a retrospective single-center study. MATERIALS AND METHODS: Oropharyngeal tumor samples from 45 patients (34 males, 11 females) were analyzed. Tumor samples were examined for HPV infection using a two-step PCR. p16 staining by immunohistochemistry was then performed. RESULTS: Samples with strong p16 signal were typed HPV-16-positive. Out of 14 tumor samples with HPV-positive PCR results, 13 samples contained the high risk variant HPV-16. In one sample, HPV-6 DNA was detected. All HPV-16-positive tumors overexpressed p16 (p16(+++)), whereas the HPV-6 sample was p16-negative. CONCLUSION: p16 is not a surrogate marker for replacing PCR testing, but both methods in combination, PCR and immunohistochemistry, could lead to a higher diagnostic validation.


Asunto(s)
Carcinoma de Células Escamosas/virología , Neoplasias de Cabeza y Cuello/virología , Neoplasias de la Boca/virología , Proteínas de Neoplasias/análisis , Papillomaviridae/aislamiento & purificación , Biomarcadores , Inhibidor p16 de la Quinasa Dependiente de Ciclina , ADN Viral/análisis , Femenino , Humanos , Masculino , Proteínas de Neoplasias/fisiología , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello
8.
Mol Clin Oncol ; 1(2): 286-290, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24649162

RESUMEN

Inhibition of the polo-like-kinase-1 (PLK-1) has been shown to be effective in several haematological and solid tumor models. In this systemic in vitro study, the antitumor effect of BI2536, a small molecule inhibitor of PLK-1, in combination with cisplatin and docetaxel was examined in nine squamous cell carcinoma cell lines, most of which had a head and neck origin (SCCHN). Dose escalation studies were conducted with nine SCCHN cell lines using BI2536, cisplatin and docetaxel in cell line-specific concentrations. Growth inhibitory and proapoptotic effects were measured quantitatively using cytohistology and a Human Apoptose Array kit. BI2536 in combination with cisplatin and docetaxel showed a markedly higher antiproliferative and apoptotic activity in the SCCHN cell lines investigated (P≤0.008), compared with single agent cisplatin or docetaxel alone. The findings of this study showed that the addition of PLK-1-inhibitor BI2536 to conventional chemotherapeutic drugs led to a statistically higher antiproliferative and apoptotic effect in SCCHN cell lines compared with cisplatin or docetaxel alone. Inaugurating BI2536 in the clinical setting might enhance the antitumoral activity of conventional drugs, possibly leading to less toxic side effects of cancer therapy.

9.
Oncol Lett ; 4(6): 1305-1308, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23226805

RESUMEN

Inhibition of the proteasome with Bortezomib as well as inhibition of Polo-like-kinase-1 (PLK-1) has been shown to be effective in many solid tumour models and also in squamous cell carcinoma of the head and neck (SCCHN) cell lines. For the first time, we systematically examined the antitumour effect of Bortezomib in combination with BI2536 in SCCHN in an in vitro study. Dose escalation studies were performed with nine SCCHN cell lines using Bortezomib and BI2536 as single agent and combination treatments. Growth-inhibitory and pro-apoptotic effects were measured quantitatively using cytohistology and Human Apoptose Array kit. The combination of Bortezomib and BI2536 showed significant anti-proliferative and apoptotic activity in all SCCHN cell lines investigated (P=0.008) compared to both the untreated control group and Bortezomib alone. A combination treatment regime consisting of the proteasome inhibitor, Bortezomib, and the inhibitor of PLK-1, BI2536, leads to an enhanced anti-proliferative and apoptotic effect in SCCHN cell lines, compared to single agent treatment with Bortezomib alone.

10.
Oncol Lett ; 4(5): 1043-1046, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23162648

RESUMEN

Recent studies have shown BI2536 and bortezomib to be effective in squamous cell carcinoma of the head and neck (SCCHN) cell lines. In this systemic in vitro study, we examined the antitumor effect of the small molecules BI2536 and bortezomib in combination with cisplatin or docetaxel in nine squamous cell carcinoma cell lines, most of head and neck origin. Dose escalation studies were performed with these cell lines using bortezomib, BI2536, cisplatin and docetaxel in cell line-specific concentrations. Growth inhibitory and proapoptotic effects were measured quantitatively using cytohistology and the Human Apoptosis Array kit. The combination of bortezomib and BI2536 with cisplatin or docetaxel showed a significantly higher antiproliferative and apoptotic activity in all SCCHN cell lines investigated compared with single agent cisplatin or docetaxel alone (P≤0.021). Combination of conventional chemotherapeutic drugs, such as cisplatin and docetaxel, with small molecules in the clinical setting may enhance the antitumor activity of these agents and may lead to less toxic side-effects and a more effective cancer therapy.

11.
Oncol Rep ; 28(3): 785-90, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22825751

RESUMEN

One challenge of squamous cell carcinoma of the head and neck (SCCHN) chemotherapy is a small percentage of tumor cells that arrest in the G0 phase of the cell cycle and are thus not affected by chemotherapy. This could be one reason for tumor recurrence at a later date. The recruitment of these G0-arresting cells into the active cell cycle and thus, proliferation, may increase the efficacy of chemotherapeutic agents. The aim of this study was to investigate whether stimulation with recombinant epidermal growth factor (EGF) or serotonin leads to an increased tumor cell proliferation in xenografts. Detroit 562 cells were injected into NMRI-Foxn1nu mice. Treatment was performed with 15 µg murine or human EGF, or 200 µg serotonin. The control mice were treated with Lactated Ringer's solution (5 mice/group). Tumor size was measured on days 4, 8 and 12 after tumor cell injection. The EGF stimulated mice showed a significantly higher tumor growth compared to the serotonin-stimulated mice and the untreated controls. In the present study, we show that it is possible to stimulate tumor cells in xenografts by EGF and thus, enhance cell proliferation, resulting in a higher tumor growth compared to the untreated control group. In our future investigations, we plan to include a higher number of mice, an adjustment of the EGF dosage and cell subanalysis, considering the heterogeneity of SCCHN tumors.


Asunto(s)
Carcinoma de Células Escamosas/patología , Factor de Crecimiento Epidérmico/farmacología , Neoplasias de Cabeza y Cuello/patología , Proteínas Recombinantes/farmacología , Serotonina/farmacología , Secuencia de Aminoácidos , Animales , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Factor de Crecimiento Epidérmico/fisiología , Receptores ErbB/metabolismo , Femenino , Neoplasias de Cabeza y Cuello/metabolismo , Humanos , Antígeno Ki-67/metabolismo , Ratones , Datos de Secuencia Molecular , Trasplante de Neoplasias , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Serotonina/fisiología , Carga Tumoral
12.
Oncol Lett ; 4(1): 175-177, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22807983

RESUMEN

Inhibition of the Polo-like-kinase-1 (PLK1) has been shown to be effective in a number of solid tumor models. In this in vitro study, we examined the antitumor effect of BI2536, a small molecule inhibitor of PLK1, in squamous cell carcinoma of the head and neck (SCCHN) cell lines. Dose escalation studies were performed with nine SCCHN cell lines using BI2536. Growth inhibitory and proapoptotic effects were measured quantitatively using cytohistology and a Human Apoptosis Array Kit. BI2536 demonstrated a significant antiproliferative and apoptotic activity in all nine SCCHN cell lines investigated (p<0.009). Our results indicate that inhibition of PLK1 by BI2536 leads to an antiproliferative and apoptotic effect in SCCHN cell lines. In vivo and in the clinical setting, the application of BI2536 may support the antitumoral activity of conventional drugs that are in current use and could decrease the systemic toxicity of these drugs.

13.
In Vivo ; 26(4): 593-8, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22773573

RESUMEN

BACKGROUND/AIM: Besides late diagnosis, tumor metastasis and cancer relapse are the main reasons for the poor prognosis of patients with head and neck cancer. Several investigations have shown that tumor is of heterogeneous molecularity consisting of several subpopulations, with a broad range of biological behaviors. The ability and potential of tumor to infiltrate into vessels and into neighbouring organs, as well as the resistance to chemotherapeutical cancer therapy may be caused by cancer stem cells (CSCs). The aim of the present study was to illuminate the role and behaviour of (CD44) and (ALDH1A1) as tumor stem cell markers in a xenograft mouse model of squamous cell carcinoma. MATERIALS AND METHODS: Five female NMRI-Foxn1nu mice were injected with five million Detroit 562 cells (100 µl). After sacrifice of the mice, tumors were excised. Then ALDH1A1, CD44, (EGFR), CD31 and Ki 67 were detected as molecular markers for tumor stem cells by immunohistopathology and immunofluorescence. RESULTS: The amount of putative CSC marker proteins CD44 and ALDH1A1 vary. ALDH1A1high tumor cells express low levels of CD44 and EGFR. The CD44+high expressers also exhibit expression of high levels of the EGFR. CSCs must be sub-classified depending on their expression of marker proteins. CONCLUSION: We assume that CSCs can also be sub-classified into migratory and stationary CSCs. ALDH1A1high/CD44low/EGFRlow tumor cells may be stationary and quiescent, whereas ALDH1A1-/CD44high/EGFRhigh expressers have a migratory, invasive nature. It is likely that a regulatory mechanism, as yet unknown, controls this conversion, from quiescent to active cancer stem cells.


Asunto(s)
Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/patología , Inmunofenotipificación , Células Madre Neoplásicas/patología , Animales , Carcinoma de Células Escamosas/inmunología , Femenino , Neoplasias de Cabeza y Cuello/inmunología , Ratones , Modelos Biológicos , Trasplante Heterólogo
14.
Artículo en Inglés | MEDLINE | ID: mdl-22558056

RESUMEN

THE INNER EAR IS OUR MOST SENSITIVE SENSORY ORGAN AND CAN BE SUBDIVIDED INTO THREE FUNCTIONAL UNITS: organ of Corti, stria vascularis and spiral ganglion. The appropriate stimulus for the organ of hearing is sound, which travels through the external auditory canal to the middle ear where it is transmitted to the inner ear. The inner ear houses the hair cells, the sensory cells of hearing. The inner hair cells are capable of mechanotransduction, the transformation of mechanical force into an electrical signal, which is the basic principle of hearing. The stria vascularis generates the endocochlear potential and maintains the ionic homeostasis of the endolymph. The dendrites of the spiral ganglion form synaptic contacts with the hair cells. The spiral ganglion is composed of neurons that transmit the electrical signals from the cochlea to the central nervous system. In recent years there has been significant progress in research on the molecular basis of hearing. An increasing number of genes and proteins related to hearing are being identified and characterized. The growing knowledge of these genes contributes not only to greater appreciation of the mechanism of hearing but also to a deeper understanding of the molecular basis of hereditary hearing loss. This basic research is a prerequisite for the development of molecular diagnostics and novel therapies for hearing loss.

15.
In Vivo ; 24(4): 603-6, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20668332

RESUMEN

PURPOSE: To report the experience with AdOnco, a computerized database for head and neck cancer patients. PATIENTS AND METHODS: AdOnco is a Filemaker Pro 6.0 based database integrated into the local network of the host ENT department. It is used by the physicians as a clinical and scientific documentation system to store and retrieve information about all patients with head and neck cancer referred to the host oncology center. This study reviews the achievements to date of AdOnco and, as an example of its enormous data evaluation potential, presents survival curves of patients with laryngeal cancer undergoing laser resection. RESULTS: Over a period of six years, the data of 881 patients with head and neck cancer were entered into the AdOnco database. CONCLUSION: AdOnco has proven to be a useful patient database and documentation system which has become an integral and essential part of daily clinical routine and also a valuable research tool.


Asunto(s)
Neoplasias de Cabeza y Cuello/patología , California , Bases de Datos Factuales , Documentación/métodos , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/cirugía , Neoplasias de Cabeza y Cuello/terapia , Humanos , Neoplasias Laríngeas/mortalidad , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/cirugía , Sistemas de Registros Médicos Computarizados , Estudios Retrospectivos , Tasa de Supervivencia , Sobrevivientes
16.
J Neurooncol ; 98(1): 31-9, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-19937367

RESUMEN

The expression of neurotrophic factors, such as artemin, glial cell line-derived neurotrophic factor (GDNF), neurturin, transforming growth factors (TGF)-beta1/beta2 and brain-derived neurotrophic factor (BDNF), is enhanced in vestibular schwannomas compared to peripheral nerves. Furthermore, this upregulation may correlate with mitotic activity. Vestibular schwannoma arising from Schwann cells of the vestibular nerve are mostly benign and slow-growing. Most of the pathogenic mechanisms regulating the vestibular schwannoma growth process are unknown. An impaired growth regulation and imbalance between mitosis and apoptosis can be assumed. However, molecular mechanisms interfering with regulation of the vestibular schwannoma growth also modulated by mitogenic factors have to be identified. Neurotrophic factors are involved in regulation of developmental processes in neuronal tissues and regeneration after peripheral nerve trauma and also reveal mitogenic effects on glial cell populations. Gene expression profiles of artemin, BDNF, GDNF, TGF-beta1/beta2 and Ret were determined in the vestibular schwannoma in comparison to the peripheral nerve tissues by using semiquantitative RT-PCR. The expression data were correlated to the proliferation-associated Ki-67 labelling index. A significant higher BDNF expression was observed in the vestibular schwannoma, whereas gene expression of artemin and GDNF was upregulated in peripheral nerves. The correlation between LI and BDNF, TGF-beta1 and Ret was found to be significant in the vestibular schwannoma. Our results demonstrate a coherence between BDNF expression and proliferative activity in the vestibular schwannoma. Based on these results, we propose a pivotal role for BDNF in modulating the vestibular schwannoma growth.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/genética , Proliferación Celular , Regulación Neoplásica de la Expresión Génica/fisiología , Neuroma Acústico/genética , ARN Mensajero/metabolismo , Regulación hacia Arriba/fisiología , Adulto , Anciano , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Femenino , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Humanos , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neuroma Acústico/patología , Nervios Periféricos/metabolismo , Estadística como Asunto/métodos , Estadísticas no Paramétricas , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta2/genética , Factor de Crecimiento Transformador beta2/metabolismo , Adulto Joven
17.
J Assoc Res Otolaryngol ; 10(2): 173-90, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19247714

RESUMEN

Nonmammalian vertebrates regenerate lost sensory hair cells by means of asymmetric division of supporting cells. Inner ear or lateral line supporting cells in birds, amphibians, and fish consequently serve as bona fide stem cells resulting in high regenerative capacity of hair cell-bearing organs. Hair cell regeneration does not happen in the mammalian cochlea, but cells with proliferative capacity can be isolated from the neonatal cochlea. These cells have the ability to form clonal floating colonies, so-called spheres, when cultured in nonadherent conditions. We noticed that the sphere population derived from mouse cochlear sensory epithelium cells was heterogeneous, consisting of morphologically distinct sphere types, hereby classified as solid, transitional, and hollow. Cochlear sensory epithelium-derived stem/progenitor cells initially give rise to small solid spheres, which subsequently transition into hollow spheres, a change that is accompanied by epithelial differentiation of the majority of sphere cells. Only solid spheres, and to a lesser extent, transitional spheres, appeared to harbor self-renewing stem cells, whereas hollow spheres could not be consistently propagated. Solid spheres contained significantly more rapidly cycling Pax-2-expressing presumptive otic progenitor cells than hollow spheres. Islet-1, which becomes upregulated in nascent sensory patches, was also more abundant in solid than in hollow spheres. Likewise, hair cell-like cells, characterized by the expression of multiple hair cell markers, differentiated in significantly higher numbers in cell populations derived from solid spheres. We conclude that cochlear sensory epithelium cell populations initially give rise to small solid spheres that have self-renewing capacity before they subsequently convert into hollow spheres, a process that is accompanied by loss of stemness and reduced ability to spontaneously give rise to hair cell-like cells. Solid spheres might, therefore, represent the most suitable sphere type for cell-based assays or animal model transplantation studies aimed at development of cell replacement therapies.


Asunto(s)
Diferenciación Celular , Cóclea/citología , Epitelio/anatomía & histología , Células Madre/citología , Animales , Cadherinas/biosíntesis , Técnicas de Cultivo de Célula , Proliferación Celular , Cóclea/metabolismo , Epitelio/metabolismo , Proteínas de Homeodominio/biosíntesis , Inmunohistoquímica , Proteínas con Homeodominio LIM , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica de Rastreo , Factor de Transcripción PAX2/biosíntesis , Células Madre/metabolismo , Factores de Tiempo , Factores de Transcripción
18.
J Neurooncol ; 89(2): 131-9, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18431543

RESUMEN

Erythropoietin (Epo) expression is regulated via hypoxia-inducible factor (HIF)-1alpha-directed gene transcription. Activation of the erythropoietin receptor (EpoR) by Epo leads to elevated expression of the anti-apoptotic protein, bcl-2, which has recently been shown to promote angiogenesis in malignant tumors. Expression of HIF-1alpha, Epo, EpoR, and bcl-2 was studied by immunohistochemistry in a series of 20 olfactory neuroblastoma (ONB) samples. Data were correlated with microvessel density, proliferative activity, and apoptosis in the specimens and survival analysis was performed to investigate the prognostic value of the examined factors. Immunohistochemical analysis revealed robust expression of HIF-1alpha, Epo, EpoR, and bcl-2 in ONB. Ninety percent of the samples showed HIF-1alpha immunoreactivity and in 60% of the cases, bcl-2 immunoreactivity was observed. A significant positive correlation between the expression levels of HIF-1alpha and bcl-2 and the microvessel density was found. Survival analysis did not reveal any prognostic significance for the tested factors. Expression of HIF-1alpha, Epo, Epo-R, and bcl-2 may play a functional role in ONB pathogenesis. Our data suggest that bcl-2 may act as a stimulator of angiogenesis in ONB, and thus represents a novel target for anti-angiogenic treatment strategies in the therapy of ONB.


Asunto(s)
Estesioneuroblastoma Olfatorio/metabolismo , Estesioneuroblastoma Olfatorio/patología , Cavidad Nasal/patología , Neovascularización Patológica , Neoplasias Nasales/metabolismo , Neoplasias Nasales/patología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Adulto , Anciano , Apoptosis/fisiología , Eritropoyetina/genética , Eritropoyetina/metabolismo , Estesioneuroblastoma Olfatorio/mortalidad , Estesioneuroblastoma Olfatorio/terapia , Femenino , Regulación Neoplásica de la Expresión Génica/fisiología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Etiquetado Corte-Fin in Situ/métodos , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Neovascularización Patológica/metabolismo , Neoplasias Nasales/mortalidad , Neoplasias Nasales/terapia , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Receptores de Eritropoyetina/genética , Receptores de Eritropoyetina/metabolismo , Análisis de Supervivencia
19.
Eur Arch Otorhinolaryngol ; 265(4): 481-4, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17909827

RESUMEN

Hemangiopericytomas are malignant tumors arising from pericytic cells and account for less than 1% of all vascular neoplasms. We report a rare case of an extra- and intracranial dumbbell-shaped hemangiopericytoma originating from the soft tissue of the neck and penetrating the skull base with invasion into the posterior cranial fossa. The 59-year-old female patient presented with a large pulsating neck mass and reported weakness, abnormal fatigue and headache. MRI revealed an inhomogeneously enhancing tumor and cerebral angiography showed intensive vascularization. Preoperative embolization was performed in order to decrease the operative blood loss. The tumor was operated via a far lateral approach through an osteoclastic suboccipital craniotomy. Total resection of both the intra- and extracranial part of the neoplasm (grade I by Simpson) could be achieved. The histopathological analysis revealed a mesenchymal, hypervascular tumor with the classic staghorn vascular pattern. In this article, we discuss the clinical presentation and multidisciplinary management of hemangiopericytoma and describe the radiological and pathological features of this tumor entity.


Asunto(s)
Neoplasias de Cabeza y Cuello/patología , Hemangiopericitoma/patología , Angiografía Cerebral , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/cirugía , Hemangiopericitoma/diagnóstico por imagen , Hemangiopericitoma/cirugía , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Invasividad Neoplásica , Tomografía Computarizada por Rayos X
20.
Childs Nerv Syst ; 23(11): 1313-7, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17701413

RESUMEN

OBJECTIVES: Current multislice computed tomography (CT) technology can be used for diagnosis and surgical planning applying computer-assisted three-dimensional (3D) visualization and surgical simulation. The usefulness of a technique for surgical simulation of frontoorbital advancement is demonstrated here in a child with metopic synostosis. MATERIALS AND METHODS: Postprocessing of multi-slice CT data was performed using the software 3D slicer. 3D models were created for the purpose of surgical simulation. These allow planning the course of the osteotomies and individually placing the different bony fragments by an assigned matrix to simulate the surgical result. Photo documentation was obtained before and after surgery. Surgical simulation of the procedure allowed determination of the osteotomy course and assessment of the positioning of the individual bony fragments. CONCLUSIONS: Computer-assisted postprocessing and simulation is a useful tool for surgical planning in craniosynostosis surgery. The time-effort for segmentation currently limits the routine clinical use of this technique.


Asunto(s)
Craneosinostosis/cirugía , Hueso Frontal/cirugía , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional , Cirugía Asistida por Computador/métodos , Simulación por Computador , Craneosinostosis/patología , Estudios de Seguimiento , Hueso Frontal/anomalías , Humanos , Procesamiento de Imagen Asistido por Computador/instrumentación , Lactante , Masculino , Órbita/anomalías , Órbita/cirugía , Cirugía Asistida por Computador/instrumentación , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA