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1.
HNO ; 69(8): 633-641, 2021 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-33502578

RESUMEN

BACKGROUND: From spring 2020, SARS-CoV­2 began to spread worldwide, with what is now known as the first wave of the pandemic, starting in March 2020. This resulted in restructuring and shift of resources at many hospitals. The aim of our work was to detect the effects of the pandemic on the german Oto-Rhino-Laryngology (ORL) university hospitals in terms of research, student teaching and further specialist training. MATERIAL AND METHODS: The chairmen of the 39 ORL university hospitals in Germany were asked about the effects of the pandemic on research, student teaching and ORL specialist training (residency) in the period from March to April 2020 using a structured online survey. RESULTS: All 39 chairmen took part in the survey. Of these, 74.4% (29/39) stated that their research activities had deteriorated as a result of the pandemic. In 61.5% (24/39) pandemic-related research issues were addressed. All hospitals reported a restriction for in-house teaching and 97.5% (38/39) introduced new digital teaching methods. During the observation period, 74.4% of the chairmen did not see ORL specialist training (residency)at risk. CONCLUSION: Our results provide an insight into the heterogeneous effects of the pandemic. The fast processing of pandemic-related research topics and the introduction of innovative digital concepts for student teaching impressively demonstrates the great innovative potential and the ability of the ORL university hospitals to react quickly in order to maintain their tasks in research, student teaching and ORL specialist training in the best possible way even during the pandemic.


Asunto(s)
COVID-19 , Otolaringología , Alemania/epidemiología , Hospitales Universitarios , Humanos , Pandemias , SARS-CoV-2 , Estudiantes , Enseñanza
2.
Laryngorhinootologie ; 99(10): 694-706, 2020 10.
Artículo en Alemán | MEDLINE | ID: mdl-32767296

RESUMEN

INTRODUCTION: Since December 2019, the SARS-CoV-2 virus has been rapidly spreading worldwide. In Germany, an exponential increase in the number of infections was registered at the beginning of March 2020 and led to a call of the Ministry of Health to create more capacity for intensive medical treatment in hospitals. The aim of the present study was to determine the effects of the SARS-CoV-2 pandemic on Oto-Rhino-Laryngology (ORL) university hospitals regarding patient care. MATERIALS AND METHODS: An online survey was sent out to all chairmen of the 39 ORL university hospitals in Germany. The answers to the questions referred to the defined period from March 15th to April 15th 2020 and were carried out using the online survey tool "SurveyMonkey". 87 questions focused on general information, health care, and structural effects in the respective institution. RESULTS: All chairmen of the 39 university hospitals in Germany participated in the survey. The collected data prove the considerable impact on organizational, structural and medical aspects of patient care. For example, the surveyed clinics reported a decrease in outpatient cases by 73.8 % to 26.2 ±â€Š14.2 % and in surgical treatments by 65.9 % to 34.1 ±â€Š13.9 %. In contrast, emergency treatment remained unchanged or even increased in 80 % of the facilities and surgical treatment of emergency patients remained unchanged or even increased in more than 90 %. Emergency outpatient and surgical treatment of patients was provided throughout the pandemic in all facilities. In total, about 35 000 outpatients and about 12 000 surgical cases were postponed. As a result of the acute structural changes, the potential danger of falling below current treatment standards was seen in individual areas of patient care. DISCUSSION: The assessment of the impact of the SARS-CoV-2 pandemic is heterogeneous. The majority of the chairmen are critically aware of the risk of falling below current medical treatment standards or guidelines. In the phase of an exponential increase in the number of infections, significant changes in treatment processes had to be accepted for understandable reasons. However, with the currently significantly reduced number of infections, falling below treatment standards and guidelines should not be allowed to remain constant and tolerated. SUMMARY: This study shows a differentiated picture with regard to the effects of the SARS-CoV-2 pandemic on outpatient, inpatient and operative patient care at the ORL university hospitals in Germany and illustrates the importance of these institutions for ensuring patient care during this critical phase.


Asunto(s)
Infecciones por Coronavirus , Otolaringología , Pandemias , Neumonía Viral , Síndrome Respiratorio Agudo Grave/epidemiología , Síndrome Respiratorio Agudo Grave/terapia , Betacoronavirus , COVID-19 , Alemania , Hospitales Universitarios , Humanos , SARS-CoV-2
3.
South Med J ; 110(6): 408-411, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28575898

RESUMEN

OBJECTIVES: This study evaluated the effectiveness of the Center for Executive Medicine (CEM) concierge primary care practice on preventive colorectal cancer (CRC) screening rates relative to local and national comparator data. METHODS: We performed an electronic medical record search encompassing our entire patient population who are between the ages of 50 and 75 years to determine the rate of CRC screening. We compared this rate with the average rate of Medicare Advantage plans reported by our Independent Physician Association (IPA) in 2015 and national health plans reported by the National Committee for Quality Assurance in 2014. RESULTS: The CEM had a CRC screening rate of 90.2%, which was significantly higher than local IPA Medicare Advantage plans (63.3%) and National Committee for Quality Assurance national plans (57.7%-66.5%). CEM members were significantly more likely than were IPA members to undergo screening (odds ratio 1.425, 95% confidence interval 1.348-1.507, P < 0.0001). CONCLUSIONS: These results suggest that the CEM practice strategy and processes increase CRC screening rates.


Asunto(s)
Neoplasias Colorrectales/diagnóstico , Consejería Médica , Detección Precoz del Cáncer/estadística & datos numéricos , Anciano , Registros Electrónicos de Salud , Femenino , Humanos , Cobertura del Seguro , Seguro de Salud , Masculino , Persona de Mediana Edad , Sangre Oculta
4.
Eur J Appl Physiol ; 116(9): 1841-53, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27465126

RESUMEN

BACKGROUND: Investigations of the effect of beverages containing carbohydrates, only, on the sodium and fluid balance during intermittent exercise of high intensity are rare. Therefore, we compared the effects of water and carbohydrate supplementation on plasma, blood volume, and electrolyte shifts during intermittent exercise. METHODS: Ten male subjects performed an intermittent exercise test twice. In one trial, tap water (4 ml/kg/15 min) was consumed (Plac trial). In the other trial, the same amount of water supplemented with maltodextrin to achieve a 9.1 % carbohydrate solution (CHO trial) was ingested. Training schedule: warm-up at 50 % for 15 min. Afterwards, power changed between 100 % of the maximum power from a previous incremental test minus 10 and 10 W for each 30 s. Venous blood was sampled to measure electrolytes, osmolality, [protein], hct, [Lactate], [glucose], [Hb] and catecholamines. Hydration status was evaluated by BIA before and after exercise. RESULTS: After beverage ingestion [glucose] was significantly higher in CHO until the end of the trial. Starting with similar resting values, osmolality increased significantly more during CHO (p = 0.002). PV decreased by 5 % under both conditions, but recovered partly during exercise under Plac (p = 0.002). [Na+] and [Cl(-)] decreased with Plac during exercise (both p < 0.001) but remained constant during exercise with CHO. CONCLUSIONS: Sole carbohydrate supplementation seems to stabilise plasma [Na+]. This cannot be explained simply by a cotransport of glucose and [Na+], because that should lead to a recovery of the blood and plasma volume under CHO. In contrast, this was found during exercise with Plac.


Asunto(s)
Carbohidratos de la Dieta/metabolismo , Suplementos Dietéticos , Entrenamiento de Intervalos de Alta Intensidad/métodos , Resistencia Física/fisiología , Sodio/sangre , Equilibrio Hidroelectrolítico/fisiología , Adulto , Carbohidratos de la Dieta/administración & dosificación , Humanos , Masculino , Acondicionamiento Físico Humano/métodos , Resistencia Física/efectos de los fármacos , Esfuerzo Físico/efectos de los fármacos , Esfuerzo Físico/fisiología , Equilibrio Hidroelectrolítico/efectos de los fármacos
5.
Pest Manag Sci ; 80(8): 4044-4054, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38563464

RESUMEN

BACKGROUND: The hydraulic spray delivery (HSD)-based solid set canopy delivery system (SSCDS) emitter configuration has been optimized for agrochemical applications in vertical shoot position (VSP) vineyards. It uses cost-prohibitive emitters, and their placement restricts the mechanical pruning activities. Therefore, this study focused on optimizing the spray performance of a pneumatic spray delivery (PSD)-based SSCDS variant that addresses the earlier issues. Three PSD-SSCDS emitter configurations (C1-C3) were designed using modified low-cost emitters (E1: modified flat fan, E2: 90° modular flat fan) for agrochemical applications in VSP vineyards. C1 had an E1 installed on trellis posts at 1.67 m above ground level. C2 had a pair of E2 installed per vine at 0.3 m below the cordon, while C3 combined the emitter placement of C1 and C2. The spray deposition (ng cm-2) and coverage (%) were quantified (mean ± standard error) using mylar cards and water-sensitive paper samplers placed within the canopy, respectively. RESULTS: Spray deposition for C1, C2, and C3 was 301.12 ± 63.30, 347.9 ± 66.29, and 837.6 ± 92.53 ng cm-2, respectively. Whereas spray coverage for corresponding configurations was 18.02 ± 2.63, 8.98 ± 1.84, and 28.84 ± 2.46%, respectively. CONCLUSIONS: Overall, configuration C3 provided significantly higher spray deposition and coverage than C1 and C2. Substantially reduced system installation cost and emitter density per hectare with improved spray performance were achieved by C3 compared to earlier optimized HSD-SSCDS configuration in the VSP vineyards. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Asunto(s)
Vitis , Agroquímicos/farmacología , Granjas , Plaguicidas
6.
Biochim Biophys Acta ; 1822(9): 1343-57, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22240198

RESUMEN

Peroxisomes are remarkably dynamic, multifunctional organelles, which react to physiological changes in their cellular environment and adopt their morphology, number, enzyme content and metabolic functions accordingly. At the organelle level, the key molecular machinery controlling peroxisomal membrane elongation and remodeling as well as membrane fission is becoming increasingly established and defined. Key players in peroxisome division are conserved in animals, plants and fungi, and key fission components are shared with mitochondria. However, the physiological stimuli and corresponding signal transduction pathways regulating and modulating peroxisome maintenance and proliferation are, despite a few exceptions, largely unexplored. There is emerging evidence that peroxisomal dynamics and proper regulation of peroxisome number and morphology are crucial for the physiology of the cell, as well as for the pathology of the organism. Here, we discuss several key aspects of peroxisomal fission and proliferation and highlight their association with certain diseases. We address signaling and transcriptional events resulting in peroxisome proliferation, and focus on novel findings concerning the key division components and their interplay. Finally, we present an updated model of peroxisomal growth and division. This article is part of a Special Issue entitled: Metabolic Functions and Biogenesis of Peroxisomes in Health and Disease.


Asunto(s)
Peroxisomas/fisiología , Animales , Dinaminas , GTP Fosfohidrolasas/deficiencia , GTP Fosfohidrolasas/genética , Humanos , Membranas Intracelulares/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas Asociadas a Microtúbulos/deficiencia , Proteínas Asociadas a Microtúbulos/genética , Dinámicas Mitocondriales , Proteínas Mitocondriales/deficiencia , Proteínas Mitocondriales/genética , PPAR alfa/fisiología , Trastorno Peroxisomal/genética , Trastorno Peroxisomal/metabolismo , Peroxisomas/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Transducción de Señal
7.
Graefes Arch Clin Exp Ophthalmol ; 251(8): 2063-70, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23456173

RESUMEN

BACKGROUND: The establishment of long-term uveal melanoma (UM) cell lines is difficult. However, studying living cells and their behaviour in the presence of other cells and the extracellular matrix is important in terms of understanding tumour biology and malignant behaviour. We have established three UM cell lines and report a first characterisation of these cell lines. METHODS: Three established UM cell lines (UMT2, UMT26 and UMT33) were analysed according to their morphologic characteristics, melanocytic differentiation, adhesion on different extracellular matrices and proliferative activity. Copy number changes of chromosomes 1, 3, 6 and 8 were studied by multiplex ligation-dependent probe amplification (MLPA). Oncogenic mutations in UM involving exons 4 and 5 of GNAQ and GNA11, respectively, were analysed by sequencing. RESULTS: All cell lines grew in suspension. UMT2 cells were homogeneous, UMT26 and UMT33 cells heterogeneous with regard to cell size and pigmentation. All UM cell lines revealed a melanocytic differentiation. UMT2 and 33 adhered on various extracellular matrices, while UMT26 only adhered to basal membrane extract (BME). This difference corresponded to the different expression of various integrins. Ki67 was expressed by 89% of UMT2 and 95% of UMT33 cells, which thus were in a proliferative stage, while only 2% of UMT26 cells revealed immunostaining for this proliferation marker. The doubling time of UMT2 was 3 days, 12 days for UMT33, and circa 3-4 months for UMT26. MLPA revealed disomy 3 in UMT2 and monosomy 3 in UMT33. The same point mutation was found in UMT2, 26 and 33, in exon 5 of GNA11 at codon 209 (p.Q209L). CONCLUSIONS: The establishment of UM cell lines under serum-free conditions is possible. Characterisation of UMT2, 26, and 33 revealed obvious differences in cytomorphology, melanocytic differentiation, adhesion on extracellular matrices, and proliferative activity. UMT2, 26 and 33 showed the same oncogenic mutation in exon 5 of GNA11.


Asunto(s)
Medio de Cultivo Libre de Suero , Melanoma/patología , Neoplasias de la Úvea/patología , Anciano , Biomarcadores de Tumor/metabolismo , Diferenciación Celular , Línea Celular Tumoral , Proliferación Celular , Variaciones en el Número de Copia de ADN , Análisis Mutacional de ADN , ADN de Neoplasias/genética , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Subunidades alfa de la Proteína de Unión al GTP/genética , Subunidades alfa de la Proteína de Unión al GTP Gq-G11 , Humanos , Masculino , Melanoma/genética , Reacción en Cadena de la Polimerasa Multiplex , Mutación , Neoplasias de la Úvea/genética , Neoplasias de la Úvea/metabolismo
8.
Minerva Urol Nefrol ; 65(4): 235-48, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24091477

RESUMEN

The incidence of muscle-invasive bladder cancer (MIBC) is increasing. Many different and multimodal novel treatment options were brought on the way since the beginning of a new era in the early 1980s, when the neobladder as a common option for urinary diversion had been induced. In addition to open radical cystectomy and urinary diversion, recently, minimal invasive surgery has been implemented in experienced centers and led to promising results in short term follow-up, awaiting confirmation in larger cohorts. Pelvic lymphnode dissection can cure patients with low metastatic load. Expansion of pelvic lymphonodal dissection and its influence on survival was discussed intensively with trends to a moderate enlargement of the standard field. Outcome in nodal positive disease is remaining poor, while 90% of patients with multiple lymphnode metastases will suffer from systemic progress 5 years after diagnosis. In the last decade, treatment regimens based on neoajuvant or adjuvant chemotherapy were published with different results on efficiency. To decide whether to treat with surgery alone, or to offer perioperative systemic cytostatic therapy, is one of the unanswered questions. Furthermore, bladder preserving techniques are still optional for patients with small unifocal lesions or the medically unfit cohort. This review summarizes current data and aims to help guiding through several available recommendations on therapy and management of MIBC.


Asunto(s)
Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/terapia , Terapia Combinada , Cistectomía/métodos , Humanos , Escisión del Ganglio Linfático , Procedimientos Quirúrgicos Mínimamente Invasivos , Músculo Liso , Invasividad Neoplásica , Tratamientos Conservadores del Órgano , Derivación Urinaria
9.
Br J Cancer ; 107(11): 1853-63, 2012 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-23169338

RESUMEN

BACKGROUND: Resistance to cisplatin-based chemotherapy is associated with poor prognosis in testicular germ cell cancer, emphasising the need for new therapeutic approaches. In this respect, the therapeutic concept of anti-angiogenesis is of particular interest. In a previous study, we presented two novel anti-angiogenic compounds, HP-2 and HP-14, blocking the tyrosine kinase activity of angiogenic growth factor receptors, such as vascular endothelial growth factor receptor-2 (VEGFR-2), and related signalling pathways in testicular cancer. In this study, we investigated the efficacy of these new compounds in platinum-resistant testicular germ cell tumours (TGCTs), in vitro and in vivo. METHODS AND RESULTS: Drug-induced changes in cell proliferation of the cisplatin-sensitive TGCT cell line 2102EP and its cisplatin-resistant counterpart 2102EP-R, both expressing the VEGFR-2, were evaluated by crystal violet staining. Both compounds inhibited the growth of cisplatin-resistant TGCT cells in a dose-dependent manner. In combination experiments with cisplatin, HP-14 revealed additive growth-inhibitory effects in TGCT cells, irrespective of the level of cisplatin resistance. Anti-angiogenic effects of HP compounds were confirmed by tube formation assays with freshly isolated human umbilical vein endothelial cells. Using TGCT cells inoculated onto the chorioallantoic membrane of fertilised chicken eggs (chicken chorioallantoic membrane assay), the anti-angiogenic and anti-proliferative potency of the novel compounds was also demonstrated in vivo. Gene expression profiling revealed changes in the expression pattern of genes related to DNA damage detection and repair, as well as in chaperone function after treatment with both cisplatin and HP-14, alone or in combination. This suggests that HP-14 can revert the lost effectiveness of cisplatin in the resistant cells by altering the expression of critical genes. CONCLUSION: The novel compound HP-14 effectively inhibits the growth of cisplatin-resistant TGCT cells and suppresses tumour angiogenesis. Thus, HP-14 may be an interesting new agent that should be further explored for TGCT treatment, especially in TGCTs that are resistant to cisplatin.


Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Antineoplásicos/farmacología , Cisplatino/uso terapéutico , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias Testiculares/tratamiento farmacológico , Animales , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Embrión de Pollo , Resistencia a Antineoplásicos , Perfilación de la Expresión Génica , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/patología , Neovascularización Patológica/tratamiento farmacológico , Neoplasias Testiculares/patología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/análisis
10.
Strahlenther Onkol ; 188(12): 1096-101, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23128897

RESUMEN

BACKGROUND: Biochemical recurrence after radical prostatectomy (RP) is associated with risk indicators, including Gleason score, preoperative PSA level, tumor stage, seminal vesicle invasion, and positive surgical margins. The 5-year biochemical progression rate among predisposed patients is as high as 50-70%. Post-RP treatment options include adjuvant radiotherapy (ART, for men with undetectable PSA) or salvage radiotherapy (SRT, for PSA persisting or re-rising above detection threshold). Presently, there are no published randomized trials evaluating ART vs. SRT directly. METHODS: Published data on ART and SRT were reviewed to allow a comparison of the two treatment approaches. RESULTS: Three randomized phase III trials demonstrated an almost 20% absolute benefit for biochemical progression-free survival after ART (60-64 Gy) compared to a "wait and see" policy. The greatest benefit was achieved in patients with positive margins and pT3 tumors. SRT can be offered to patients with elevated PSA after RP. In 30-70% of SRT patients, PSA will decrease to an undetectable level, thus giving a second curative chance. The rate of side effects for both treatments is comparably low. The role of irradiation of pelvic lymph nodes and the additional use of hormone therapy and radiation dose are discussed. CONCLUSION: It remains unclear whether early SRT initiated after PSA failure is equivalent to ART. Where SRT is indicated, it should be started as early as possible.


Asunto(s)
Prostatectomía , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Tiempo de Tratamiento , Biomarcadores de Tumor/sangre , Terapia Combinada , Supervivencia sin Enfermedad , Estudios de Seguimiento , Adhesión a Directriz , Humanos , Irradiación Linfática , Imagen por Resonancia Magnética , Masculino , Clasificación del Tumor , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Neoplasia Residual/patología , Neoplasia Residual/radioterapia , Neoplasia Residual/cirugía , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Radioterapia Adyuvante/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Terapia Recuperativa/métodos
11.
Biochim Biophys Acta ; 1803(8): 881-97, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20347886

RESUMEN

Peroxisomes represent so-called "multipurpose organelles" as they contribute to various anabolic as well as catabolic pathways. Thus, with respect to the physiological specialization of an individual organ or animal species, peroxisomes exhibit a functional diversity, which is documented by significant variations in their proteome. These differences are usually regarded as an adaptational response to the nutritional and environmental life conditions of a specific organism. Thus, human peroxisomes can be regarded as an in part physiologically unique organellar entity fulfilling metabolic functions that differ from our animal model systems. In line with this, a profound understanding on how peroxisomes acquired functional heterogeneity in terms of an evolutionary and mechanistic background is required. This review summarizes our current knowledge on the heterogeneity of peroxisomal physiology, providing insights into the genetic and cell biological mechanisms, which lead to the differential localization or expression of peroxisomal proteins and further gives an overview on peroxisomal biochemical pathways, which are specialized in different animal species and organs. Moreover, it addresses the impact of proteome studies on our understanding of differential peroxisome function describing the utility of mass spectrometry and computer-assisted algorithms to identify peroxisomal target sequences for the detection of new organ- or species-specific peroxisomal proteins.


Asunto(s)
Peroxisomas , Proteoma , Animales , Ácidos Grasos/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Humanos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Oxidación-Reducción , Peroxisomas/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
13.
Br J Cancer ; 103(1): 18-28, 2010 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-20551952

RESUMEN

BACKGROUND: Testicular germ cell tumour (TGCT) is the most common cause of death from solid tumours in young men and especially for platinum-refractory patients novel treatment approaches are urgently needed. Using an in silico screening approach for the detection of novel cancer drugs with inhibitory effects on the tyrosine kinase activity of growth factors (e.g., VEGFR, PDGFR), we identified two compounds (HP-2 and HP-14) with antiangiogenic and antiproliferative potency, which were evaluated in endothelial cell models and TGCT cells. RESULTS: HP-2 and HP-14 effectively inhibited the growth of VEGFR-2-expressing TGCT cell lines (Tera-1, Tera-2 and 2102EP) and endothelial cell models, while they failed to supress the growth of VEGFR-2-lacking tumour cells. cDNA-microarrays revealed an inhibition of the expression of several growth factor receptors and related signal transduction molecules. Vascular endothelial growth factor (VEGF)-induced cell migration was also potently inhibited. Cell cycle-regulating proteins such as p21 and p27 were upregulated, leading to an S-phase arrest. Additional in vivo evaluations confirmed the antiangiogenic potency and good tolerability of the novel substances. CONCLUSION: Our data show that the identified novel compounds inhibit the growth of TGCT cells and decrease angiogenic microvessel formation. The mode of action involves cell cycle arresting effects and changes in the expression pattern of several angiogenic genes. The novel compounds may qualify as new candidates for targeted treatment of TGCT and merit further evaluation.


Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Neoplasias Testiculares/tratamiento farmacológico , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Perfilación de la Expresión Génica , Humanos , Masculino , Neoplasias de Células Germinales y Embrionarias/patología , Receptores de Factores de Crecimiento Endotelial Vascular/genética , Neoplasias Testiculares/patología
15.
J Cell Biol ; 141(1): 115-33, 1998 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-9531552

RESUMEN

We studied basolateral-to-apical transcytosis of three classes of apical plasma membrane (PM) proteins in polarized hepatic WIF-B cells and then compared it to the endocytic trafficking of basolaterally recycling membrane proteins. We used antibodies to label the basolateral cohort of proteins at the surface of living cells and then followed their trafficking at 37 degreesC by indirect immunofluorescence. The apical PM proteins aminopeptidase N, 5'nucleotidase, and the polymeric IgA receptor were efficiently transcytosed. Delivery to the apical PM was confirmed by microinjection of secondary antibodies into the bile canalicular-like space and by EM studies. Before acquiring their apical steady-state distribution, the trafficked antibodies accumulated in a subapical compartment, which had a unique tubulovesicular appearance by EM. In contrast, antibodies to the receptors for asialoglycoproteins and mannose-6-phosphate or to the lysosomal membrane protein, lgp120, distributed to endosomes or lysosomes, respectively, without accumulating in the subapical area. However, the route taken by the endosomal/lysosomal protein endolyn-78 partially resembled the transcytotic pathway, since anti-endolyn-78 antibodies were found in a subapical compartment before delivery to lysosomes. Our results suggest that in WIF-B cells, transcytotic molecules pass through a subapical compartment that functions as a second sorting site for a subset of basolaterally endocytosed membrane proteins reaching this compartment.


Asunto(s)
Polaridad Celular/fisiología , Hígado/fisiología , Lisosomas/fisiología , Proteínas de la Membrana/metabolismo , 5'-Nucleotidasa/metabolismo , Animales , Anticuerpos , Antígenos CD13/metabolismo , Membrana Celular/fisiología , Endocitosis , Técnica del Anticuerpo Fluorescente Indirecta , Células Híbridas , Cinética , Hígado/citología , Neoplasias Hepáticas Experimentales , Lisosomas/ultraestructura , Microscopía Electrónica , Ratas , Receptores Fc/metabolismo
16.
J Inherit Metab Dis ; 32(2): 163-80, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19067229

RESUMEN

Mitochondria and peroxisomes are ubiquitous subcellular organelles, which fulfil an indispensable role in the cellular metabolism of higher eukaryotes. Moreover, they are highly dynamic and display large plasticity. There is growing evidence now that both organelles exhibit a closer interrelationship than previously appreciated. This connection includes metabolic cooperations and cross-talk, a novel putative mitochondria-to-peroxisome vesicular trafficking pathway, as well as an overlap in key components of their fission machinery. Thus, peroxisomal alterations in metabolism, biogenesis, dynamics and proliferation can potentially influence mitochondrial functions, and vice versa. In this review, we present the latest progress in the emerging field of peroxisomal and mitochondrial interrelationship with a particular emphasis on organelle dynamics and its implication in diseases.


Asunto(s)
Mitocondrias/fisiología , Enfermedades Mitocondriales/metabolismo , Trastorno Peroxisomal/metabolismo , Peroxisomas/fisiología , Animales , Humanos , Mitocondrias/metabolismo , Enfermedades Mitocondriales/genética , Trastorno Peroxisomal/genética , Peroxisomas/metabolismo
17.
Tumour Biol ; 29(5): 323-9, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18984978

RESUMEN

BACKGROUND: The polycomb group (PCG) proteins are epigenetic transcriptional repressors involved in the control of cellular proliferation and oncogenesis. This study aimed at examining whether mRNA tumor levels of the PCG family members BMI1, SUZ12, RING1, and CBX7 relate to histopathological parameters in urothelial carcinomas of the bladder and whether they may provide prognostic information following tumor resection. METHODS: The relative gene expression of BMI1, SUZ12, RING1, and CBX7 was analyzed by real-time RT-PCR in tumor tissue obtained from 93 patients with urothelial carcinoma of the bladder undergoing surgical treatment. Expression data was correlated with pathological variables and outcome. RESULTS: PCG family members BMI1, SUZ12, RING1, and CBX7 are commonly expressed in urothelial carcinomas of the bladder. The relative CBX7 mRNA expression levels gradually decreased from superficial (pTa) to invasive (pT1) and finally to muscle-invasive (> or =pT2) tumors (p = 0.008). Furthermore, CBX7 expression was statistically significantly correlated with tumor grade (p = 0.04). No correlation of mRNA levels with histopathological tumor features or tumor recurrence was observed for the other PCG components investigated. CONCLUSION: Expression levels of CBX7 inversely correlate with the progression of tumor stage and grade in urothelial carcinomas of the bladder, suggesting that downregulation of CBX7 indicates aggressive urothelial carcinoma phenotype.


Asunto(s)
Proteínas Portadoras/genética , Proteínas de Unión al ADN/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias de los Músculos/genética , Proteínas Nucleares/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genética , Neoplasias de la Vejiga Urinaria/genética , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de los Músculos/patología , Invasividad Neoplásica , Proteínas de Neoplasias , Estadificación de Neoplasias , Complejo Represivo Polycomb 1 , Complejo Represivo Polycomb 2 , Pronóstico , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Factores de Transcripción , Neoplasias de la Vejiga Urinaria/patología
18.
Urologe A ; 47(11): 1460-4, 2008 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-18813902

RESUMEN

Neoadjuvant and adjuvant therapeutic strategies are widely employed for a variety of cancer entities. The basic aim and the potential benefit for the patient are to eradicate micrometastases, with the downside being side effects and overtreatment. Neoadjuvant and adjuvant hormone therapy for prostate cancer have been investigated in a number of clinical studies. Based on these studies, the following recommendations can be given: there is currently no indication for neoadjuvant therapy prior to radical prostatectomy. Adjuvant therapy using LHRH analogs for patients with lymph node-positive tumors following radical prostatectomy can be considered but should be weighed against early"biochemical progression triggered" treatment. For locally advanced tumors the same is true (bicalutamide): adjuvant treatment has shown an advantage in clinically progression-free survival; however, no systematic comparison is available with early"biochemical progression triggered" treatment. Before radiotherapy 2 months of neoadjuvant LHRH analog treatment has shown a survival advantage in patients with locally advanced tumors and a low risk of systemic spread (Gleason <7). For high-risk patients, long-term (2-3 years) adjuvant LHRH analog treatment is indicated.


Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Terapia Neoadyuvante , Prostatectomía , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Antineoplásicos Hormonales/efectos adversos , Quimioterapia Adyuvante , Terapia Combinada , Supervivencia sin Enfermedad , Diagnóstico Precoz , Humanos , Masculino , Estadificación de Neoplasias , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Radioterapia Adyuvante , Ensayos Clínicos Controlados Aleatorios como Asunto
19.
Front Radiat Ther Oncol ; 41: 7-14, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18544980

RESUMEN

Radical prostatectomy for treatment of prostate cancer is a technically sophisticated operation. Simpler therapies have therefore been developed in the course of decades. The decisive advantage of a radical operation is the chance of a cure with minimal collateral damage. It is the only approach that enables precise tumor staging. The 10-year progression-free survival probability is approximately 85% for a localized tumor with negative resection margins. This high cure rate is unsurpassed by competitive treatment modalities. Nowadays, experienced surgeons achieve excellent functional results (for example, recovery of continence and erectile function) with minimum morbidity. Even in the locally advanced stage, results are very good compared to those obtained with other treatment modalities. Pathological staging enables stratified adjuvant therapy based on concrete information. The overall prognosis can thus be significantly improved.


Asunto(s)
Prostatectomía , Neoplasias de la Próstata/cirugía , Humanos , Masculino , Prostatectomía/efectos adversos , Prostatectomía/estadística & datos numéricos
20.
Front Radiat Ther Oncol ; 41: 49-57, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18544985

RESUMEN

Although hormone therapy is widely used in the management of prostate cancer, the optimal timing of its initiation remains a matter of debate. Many studies of the last decades have reported a small but significant survival benefit and a clear delay in the development of clinical symptoms after early initiation of therapy. Patients who have localized or locally advanced prostate cancer and are not suitable for curative options like radical prostatectomy or radiotherapy can best be managed by hormone therapy alone, which has already been recognized as the optimal treatment for metastatic disease. On the other hand, long-term hormone treatment will expose the patient to the risk of substantial adverse effects, including muscle wasting, chronic fatigue and osteoporosis. Prognostic and quality-of-life factors also have an impact on the treatment decision, particularly in patients most likely to profit from an extension of the remaining life span. Based on available evidence, early hormone therapy may be recommended for men with poorly differentiated tumors or advanced disease and for those infrequently seen by their physicians. This management can prevent prostate cancer from migrating to the bones, where treatment becomes extremely difficult and cure or even longterm control of the disease is an exception.


Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Neoplasias de la Próstata/tratamiento farmacológico , Ensayos Clínicos como Asunto , Humanos , Masculino , Neoplasias Hormono-Dependientes/sangre , Neoplasias Hormono-Dependientes/patología , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Tiempo
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