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BACKGROUND: Patients suffering from squamous cell carcinoma of the larynx (LSCC) with lymphatic metastasis have a relatively poor prognosis and often require radical therapeutic management. The mechanisms which drive metastasis to the lymph nodes are largely unknown but may be promoted by a pro-angiogenic tumor microenvironment. In this study, we examined whether the number of microvessels and the expression level of vascular endothelial growth factor (VEGF) in the primary tumor are correlated with the degree of lymph node metastasis (N-stage), tumor staging (T) and survival time in LSCC patients. METHODS: Tissue-Microarrays of 97 LSCC patients were analyzed using immunohistochemistry. The expression of VEGF was scored as intensity of staining (low vs high) and the number of CD31-positive vessels (median ≥7 vessels per visual field) was counted manually. Scores were correlated with N-stage, T-stage and 5-year overall survival rate. RESULTS: A high expression of angiogenic biomarkers was not associated with poor overall survival in the overall cohort of patients. Instead high CD31 count was associated with early stage cancer (p = 0.004) and in this subgroup high VEGF expression correlated with poor survival (p = 0.032). Additionally, in early stage cancer a high vessel count was associated with an increased recurrence rate (p = 0.004). CONCLUSION: Only in the early stage subgroup a high expression of angiogenic biomarkers was associated with reduced survival and an increased rate of recurrence. Thus, biomarkers of angiogenesis may be useful to identify high risk patients specifically in early stage LSCC.
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Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/secundario , Neoplasias Laríngeas/patología , Recurrencia Local de Neoplasia/patología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Carcinoma de Células Escamosas/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Laríngeas/metabolismo , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/metabolismo , Estadificación de Neoplasias , Neovascularización Patológica , Tasa de SupervivenciaRESUMEN
Two hypotheses-that elevated night-time temperatures due to climate warming would enforce post-fire dormancy of Proteaceae seed due to low moisture, and that periods without rain during summer would exceed desiccation periods tolerated by Proteaceae seedlings-were tested empirically. Enforced dormancy, i.e., the inability to germinate due to an environmental restraint, was tested by measuring seed germination in 11 Proteaceae species in experimental mesocosms whose soils were artificially elevated by 1.4 and 3.5 °C above ambient by far-red wavelength filtered infrared lamps. Diminished totality of germination and velocities were observed in 91 and 64%, respectively, of the Proteaceae species tested. Drought resilience was tested in one-year-old seedlings of 16 Proteaceae species by withholding water from potted plants during summer in a greenhouse. The most drought-resilient Proteaceae species displayed the lowest initial transpiration rates at field capacity, the smallest declines in transpiration rate with decreasing soil water content, and the lowest water losses by transpiration. Projected drought periods leading to the complete cessation of transpiration in all Proteaceae species greatly exceeded the number of days without rain per month during summer in the current distribution ranges of those species. It was therefore concluded that enforced seed dormancy induced by elevated night-time temperatures is the post-fire recruitment stage of Proteaceae that is most sensitive to climate warming.
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Adaptación Fisiológica , Sequías , Calor , Latencia en las Plantas/fisiología , Proteaceae/fisiología , Estaciones del Año , Semillas/fisiología , Incendios , Germinación , Calentamiento Global , Proteaceae/crecimiento & desarrollo , Lluvia , Plantones/crecimiento & desarrollo , Plantones/fisiología , Semillas/crecimiento & desarrollo , Suelo , Sudáfrica , Estrés Fisiológico , AguaRESUMEN
BACKGROUND: Patients suffering from vestibular schwannoma can choose between four modalities of management: (1) wait-and-scan, (2) tumour resection, (3) radiosurgery and (4) fractionated radiotherapy. METHOD: This study is based on postal questionnaire survey of 739 vestibular schwannoma patients (survey response rate, 78%). It not only investigates the decision-making of patients, especially the medical consultation, but also further influences on the therapy decision and the patients' evaluation of possible side-effects of the treatment. RESULTS: Only a minority of the patients was informed about radiosurgery and radiotherapy at all. CONCLUSION: The praxis of patient counselling of acoustic neuroma patients in Germany is far from the ideal condition of medical consultation: The most important shortcoming is that it is unilateral: About 69% of the patients are informed about only one treatment option, generally surgery. Furthermore, information about side effects is usually insufficient. We recommend to advice all patients on all treatment options by an interdisciplinary team. The counselling should firstly be based on evidence-based medicine and secondly respond to the patients' individual life situation and preferences.
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Toma de Decisiones , Fraccionamiento de la Dosis de Radiación , Neuroma Acústico/radioterapia , Neuroma Acústico/cirugía , Participación del Paciente , Radiocirugia , Adulto , Anciano , Anciano de 80 o más Años , Conducta Cooperativa , Toma de Decisiones/ética , Ética Médica , Medicina Basada en la Evidencia/ética , Femenino , Alemania , Humanos , Consentimiento Informado/ética , Comunicación Interdisciplinaria , Masculino , Persona de Mediana Edad , Grupo de Atención al Paciente/ética , Educación del Paciente como Asunto/ética , Complicaciones Posoperatorias/etiología , Radiocirugia/ética , Estudios Retrospectivos , Adulto JovenRESUMEN
The capability of Pseudomonas aeruginosa and Staphylococcus aureus to form biofilm on varying CI component materials differs in the presence and absence of bioactive glass (BAG). The application of BAG induces significant changes in biofilm morphology which can be visualized via scanning electron microscopy (SEM). Bacterial biofilm formation on medical devices, such as cochlear implants (CI), can lead to chronic infections. Interestingly, BAG of type S53P4 seems to be a promising tool for use in the reduction of biofilm development. Primarily, four bacterial species known to cause implant-related infections, P.aeruginosa (ATCC9027), S. aureus (ATCC6538), Staphylococcus epidermidis (ATCC12228) and Streptococcus pyogenes (ATCC19615) were analyzed regarding their capacity to form biofilm on CI components manufactured from three kinds of material: silicone, platinum and titanium. Subsequently, P. aeruginosa and S. aureus biofilms were visualized using scanning electron microscopy, comparing BAG-treated biofilm with non-treated biofilm. The four bacterial species presented biofilm-forming capabilities in a species and surface dependent manner. Metal CI components allowed for the greatest proliferation of biofilm. S. aureus and P. aeruginosa showed the highest rate of biofilm formation on polystyrene surfaces. For both species, SEM revealed altered biofilm morphology after treatment of S53P4 BAG. This study indicates that bacterial biofilm formation and structure on CI components is dependent on the surface composition, altering between metal and silicone surfaces. After application of BAG, changes in biofilm morphology on CI components were observed. These data highlight the impact of BAG on bacterial biofilm morphology.
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Bacterias/efectos de los fármacos , Fenómenos Fisiológicos Bacterianos/efectos de los fármacos , Biopelículas/efectos de los fármacos , Implantes Cocleares/microbiología , Vidrio , Microscopía Electrónica de Rastreo , Imagen Molecular , Antibacterianos/farmacología , Bacterias/ultraestructura , Biopelículas/crecimiento & desarrolloRESUMEN
HYPOTHESIS: Biofilm formation on cochlear implant (CI) surfaces differs between bacterial species and can be reduced by the application of S53P4 bioactive glass. BACKGROUND: The formation of bacterial biofilms on medical devices, such as cochlear implants, can lead to chronic infections resulting in the need for implant removal. In this study, various surfaces of three CI implant kits from different manufacturers were examined for bacterial biofilm formation and reduction of a pre-existing biofilm by the application of bioactive glass. METHODS: Biofilm formations of 4 bacterial species causing implant-related infections were tested on 17 different surfaces: Pseudomonas aeruginosa (ATCC9027), Staphylococcus aureus (ATCC6538), Staphylococcus epidermidis (ATCC12228), and Streptococcus pyogenes (ATCC19615). For P. aeruginosa and S. aureus biofilm reduction after application of S53P4 bioactive glass was evaluated. RESULTS: All tested microbial species formed biofilms on the examined CI surfaces in a strain-dependent manner. For S. aureus, a significantly higher biofilm formation on metal components compared with silicone was found whereas the other strains did not show a material specific biofilm formation. Application of S53P4 bioactive glass resulted in a significant reduction of P. aeruginosa and S. aureus mature biofilm. CONCLUSION: The four bacteria species displayed biofilm formation on the CI surfaces in a species- and material-specific manner. The results show that bioactive glass can reduce biofilm formation on CI materials in vitro. Future studies are necessary to confirm the results in vivo.
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Biopelículas/crecimiento & desarrollo , Implantes Cocleares/microbiología , Vidrio , Infecciones Relacionadas con Prótesis , Infecciones Relacionadas con Prótesis/prevención & control , Infecciones por Pseudomonas/prevención & control , Pseudomonas aeruginosa , Infecciones Estafilocócicas/prevención & control , Staphylococcus aureus , Staphylococcus epidermidisRESUMEN
Very few B cells in germinal centers (GCs) and extrafollicular (EF) regions of lymph nodes express CD30. Their specific features and relationship to CD30-expressing Hodgkin and Reed/Sternberg (HRS) cells of Hodgkin lymphoma are unclear but highly relevant, because numerous patients with lymphoma are currently treated with an anti-CD30 immunotoxin. We performed a comprehensive analysis of human CD30+ B cells. Phenotypic and IgV gene analyses indicated that CD30+ GC B lymphocytes represent typical GC B cells, and that CD30+ EF B cells are mostly post-GC B cells. The transcriptomes of CD30+ GC and EF B cells largely overlapped, sharing a strong MYC signature, but were strikingly different from conventional GC B cells and memory B and plasma cells, respectively. CD30+ GC B cells represent MYC+ centrocytes redifferentiating into centroblasts; CD30+ EF B cells represent active, proliferating memory B cells. HRS cells shared typical transcriptome patterns with CD30+ B cells, suggesting that they originate from these lymphocytes or acquire their characteristic features during lymphomagenesis. By comparing HRS to normal CD30+ B cells we redefined aberrant and disease-specific features of HRS cells. A remarkable downregulation of genes regulating genomic stability and cytokinesis in HRS cells may explain their genomic instability and multinuclearity.
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Subgrupos de Linfocitos B/inmunología , Enfermedad de Hodgkin/inmunología , Antígeno Ki-1/metabolismo , Subgrupos de Linfocitos B/clasificación , Subgrupos de Linfocitos B/patología , Genes de las Cadenas Pesadas de las Inmunoglobulinas , Genes myc , Centro Germinal/inmunología , Centro Germinal/patología , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/patología , Humanos , Cambio de Clase de Inmunoglobulina , Región Variable de Inmunoglobulina/genética , Memoria Inmunológica , Inmunofenotipificación , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Mutación , Células de Reed-Sternberg/inmunología , Células de Reed-Sternberg/patología , Transcriptoma , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/metabolismoRESUMEN
OBJECTIVES: Whether the origin of severe hearing loss in Refsum's syndrome is caused by cochlear impairment or retrocochlear degeneration remains unclear. This case report aims to investigate hearing performance before and after cochlear implantation to shed light on this question. Also, identification of new mutations causing Refsum's syndrome would be helpful in generating additional means of diagnosis. METHODS: A family of 4 individuals was subjected to genetic testing. Two siblings (56 and 61 years old) suffered from severe hearing and vision loss and received bilateral cochlear implants. Genetic analysis, audiological outcome, and clinical examinations were performed. RESULTS: One new mutation in the PHYH gene (c.768del63bp) causing Refsum's disease was found. Preoperative distortion product otoacoustic emissions (DPAOEs) were absent. Postoperative speech perception in Freiburger speech test was 100% for bisyllabic words and 85% (patient No. 1) and 65% (patient No. 2), respectively, for monosyllabic words. Five years after implantation, speech perception remained stable for bisyllabic words but showed decreasing capabilities for monosyllabic words. DISCUSSION: A new mutation causing Refsum's disease is presented. Cochlear implantation in case of severe hearing loss leads to an improvement in speech perception and should be recommended for patients with Refsum's disease, especially when the hearing loss is combined with a severe loss of vision. Decrease of speech perception in the long-term follow-up could indicate an additional retrocochlear degeneration.
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Implantación Coclear , Pérdida Auditiva Sensorineural/cirugía , Oxigenasas de Función Mixta/genética , Enfermedad de Refsum/genética , Audiometría de Respuesta Evocada , Audiometría de Tonos Puros , Femenino , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Sensorineural/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Emisiones Otoacústicas Espontáneas , Enfermedad de Refsum/complicaciones , Hermanos , Percepción del HablaRESUMEN
The cellular microenvironment in classical Hodgkin lymphoma (cHL) is dominated by a mixed infiltrate of inflammatory cells with typically only about 1% Hodgkin and Reed/Sternberg (HRS) tumor cells. T cells are usually the largest population of cells in the cHL microenvironment, encompassing T helper (Th) cells, regulatory T cells (Tregs), and cytotoxic T cells. Th cells and Tregs presumably provide essential survival signals for HRS cells. Tregs are also involved in rescuing HRS cells from antitumor immune responses. An understanding of the immune evasion strategies of HRS cells is not only relevant for a characterization of the pathophysiology of cHL but is also clinically relevant, given the current treatment approaches targeting checkpoint inhibitors. Here, we characterized the cHL-specific CD4+ T-cell infiltrate regarding its role in immune evasion. Global gene expression analysis of CD4+ Th cells and Tregs isolated from cHL lymph nodes and reactive tonsils revealed that Treg signatures were enriched in CD4+ Th cells of cHL. Hence, HRS cells may induce Treg differentiation in Th cells, a conclusion supported by in vitro studies with Th cells and cHL cell lines. We also found evidence for immune-suppressive purinergic signaling and a role of the inhibitory receptor-ligand pairs B- and T-cell lymphocyte attenuator-herpesvirus entry mediator and CD200R-CD200 in promoting immune evasion. Taken together, this study highlights the relevance of Treg induction and reveals new immune checkpoint-driven immune evasion strategies in cHL. Cancer Immunol Res; 5(12); 1122-32. ©2017 AACR.
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Enfermedad de Hodgkin/inmunología , Evasión Inmune , Línea Celular Tumoral , Perfilación de la Expresión Génica , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/patología , Humanos , Evasión Inmune/genética , Evasión Inmune/inmunología , Activación de Linfocitos/genética , Activación de Linfocitos/inmunología , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Transducción de Señal , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Microambiente Tumoral/genética , Microambiente Tumoral/inmunologíaRESUMEN
Although Burkitt lymphomas and follicular lymphomas both have features of germinal center B cells, they are biologically and clinically quite distinct. Here we performed whole-genome bisulfite, genome and transcriptome sequencing in 13 IG-MYC translocation-positive Burkitt lymphoma, nine BCL2 translocation-positive follicular lymphoma and four normal germinal center B cell samples. Comparison of Burkitt and follicular lymphoma samples showed differential methylation of intragenic regions that strongly correlated with expression of associated genes, for example, genes active in germinal center dark-zone and light-zone B cells. Integrative pathway analyses of regions differentially methylated in Burkitt and follicular lymphomas implicated DNA methylation as cooperating with somatic mutation of sphingosine phosphate signaling, as well as the TCF3-ID3 and SWI/SNF complexes, in a large fraction of Burkitt lymphomas. Taken together, our results demonstrate a tight connection between somatic mutation, DNA methylation and transcriptional control in key B cell pathways deregulated differentially in Burkitt lymphoma and other germinal center B cell lymphomas.
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Linfoma de Burkitt/genética , Metilación de ADN , Linfoma Folicular/genética , Mutación , Transcriptoma/genética , Adolescente , Adulto , Anciano , Linfocitos B/metabolismo , Línea Celular Tumoral , Niño , Preescolar , Femenino , Genoma Humano/genética , Centro Germinal/metabolismo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-myc/genética , Transducción de Señal/genética , Translocación Genética , Adulto JovenRESUMEN
Background. Postoperative imaging after cochlear implantation is usually performed by conventional cochlear view (X-ray) or by multislice computed tomography (MSCT). MSCT after cochlear implantation often provides multiple metal artefacts; thus, a more detailed view of the implant considering the given anatomy is desirable. A quite new method is flat panel volume computed tomography. The aim of the study was to evaluate the method's clinical use. Material and Methods. After cochlear implantation with different implant types, flat panel CT scan (Philips Allura) was performed in 31 adult patients. Anatomical details, positioning, and resolution of the different electrode types (MedEL, Advanced Bionics, and Cochlear) were evaluated interdisciplinary (ENT/Neuroradiology). Results. In all 31 patients cochlear implant electrode array and topographical position could be distinguished exactly. Spatial resolution and the high degree of accuracy were superior to reported results of MSCT. Differentiation of cochlear scalae by identification of the osseous spiral lamina was possible in some cases. Scanning artefacts were low. Conclusion. Flat panel CT scan allows exact imaging independent of implant type. This is mandatory for detailed information on cochlear electrode position. It enables us to perform optimal auditory nerve stimulation and allows feed back on surgical quality concerning the method of electrode insertion.
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BACKGROUND: The cyclin B1/CDC2 complex governs entry into mitosis by regulating the G(2)/M checkpoint, and it can be repressed by the tumor suppressor p53. We aimed to determine cyclin B1 expression in squamous cell carcinomas of the head and neck (SCCHN) and correlate it with p53 status and clinicopathological parameters. PATIENTS AND METHODS: Cyclin B1 and p53 protein expression was analyzed by immunohistochemistry, and p53 mutation analyses were performed. RESULTS: Cytoplasmic expression of cyclin B1 was found in all 26 SCCHN studied. In contrast, nuclear staining was seen in the basal layers of normal mucosa. A total of 46% of tumors showed high cyclin B1 expression. p53 was overexpressed in 53.8% of cases, and of these 79% carried a p53 gene mutation. High cyclin B1 expression significantly correlated with the high tumor grade, but not with gender, tumor size, nodal status, local tumor recurrence or p53 expression. CONCLUSION: Cyclin B1 is frequently overexpressed in SCCHN, and its high expression is significantly associated with a high tumor grade. These data suggest that cyclin B1 may serve as a potential prognostic biomarker in SCCHN.