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1.
Urologe A ; 58(5): 529-534, 2019 May.
Artigo em Alemão | MEDLINE | ID: mdl-30887058

RESUMO

Until 2018, patients with nonmetastatic castration-resistant prostate cancer (nmCRPC/M0CRPC) did not have a generally acknowledged standard of care therapy. As a result, these patients were often managed in a nonstandardized individual fashion and comparative analyses were lacking. In the current narrative review, we give an overview on the respective entities of nmCRPC and summarize novel treatment options that arose from the publication of the results of the SPARTAN and PROSPER trials and their subanalyses. We critically address the role that novel imaging modalities, namely 68Ga-PSMA-PET/CT (68Ga prostate-specific membrane antigen positron emission tomography/computed tomography) will play in the diagnosis of nmCRPC and raise the question whether incidence rates of true nmCRPC will significantly decline in the nearer future.


Assuntos
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Antígenos de Superfície , Glutamato Carboxipeptidase II , Humanos , Masculino
2.
Urologe A ; 58(5): 524-528, 2019 May.
Artigo em Alemão | MEDLINE | ID: mdl-30859231

RESUMO

In the prostate-specific antigen (PSA) era, most prostate cancers (PCa) are diagnosed in a localized stage and a plethora of therapeutic options are warranted in different clinical settings and disease stages of localized PCa. In the current narrative review, we give an overview of the current controversies in the therapeutic landscape of localized PCa and focus on organ-sparing approaches, percutaneous radiotherapy, brachytherapy as well as retropubic and robot-assisted prostatectomy by summarizing studies that have been published within the last two years.


Assuntos
Braquiterapia/métodos , Prostatectomia/métodos , Neoplasias da Próstata/terapia , Biópsia , Humanos , Masculino , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia
3.
Urologe A ; 58(3): 329-340, 2019 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-30824971

RESUMO

Prostate cancer is a heterogeneous disease. In cases of low-risk prostate cancer, active surveillance represents an attractive alternative treatment. Significant complications of a definitive treatment can therefore be delayed or completely avoided. Despite strict inclusion criteria for active surveillance, the diagnosis of low-risk prostate cancer can be inaccurate and there is therefore a risk of missing the optimal point in time for definitive treatment. Multimodal diagnostics and continuous aftercare are therefore crucial.


Assuntos
Biópsia Guiada por Imagem , Neoplasias da Próstata , Humanos , Imagem por Ressonância Magnética , Masculino , Imagem Multimodal , Neoplasias da Próstata/diagnóstico por imagem , Conduta Expectante
4.
Urologe A ; 58(2): 197-206, 2019 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-30734059

RESUMO

Ureteral injuries account for less than 3% of genitourinary injuries. Most of them are caused iatrogenically during abdominal surgery. The symptoms are often non-specific and do not aid in diagnosis. The later the injury is detected, the more often complications occur. Therefore, in such situations it is important to consider the possibility of ureteral injury and initiate further diagnostic steps as soon as possible. A variety of diagnostic tests are available. In addition to the direct inspection of the ureters and retrograde ureteropyelography, computed tomography (CT) urography is routinely used. Based on the time of diagnosis as well as the extent and the localization of the injury, the further procedure can be determined. For minor injuries, the insertion of a ureteral splint is usually the treatment of choice. In the case of higher grade damage, operative reconstruction by one of several possible surgical procedures is indicated.


Assuntos
Ureter , Humanos , Doença Iatrogênica , Stents , Tomografia Computadorizada por Raios X , Ureter/diagnóstico por imagem , Ureter/lesões , Urografia
5.
World J Urol ; 37(7): 1415-1420, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30341450

RESUMO

PURPOSE: To analyze and compare preoperative patient characteristics and postoperative results in men with stress urinary incontinence (SUI) selected for an adjustable male sling system or an artificial urinary sphincter (AUS) in a large, contemporary, multi-institutional patient cohort. METHODS: 658 male patients who underwent implantation between 2010 and 2012 in 13 participating institutions were included in this study (n = 176 adjustable male sling; n = 482 AUS). Preoperative patient characteristics and postoperative outcomes were analyzed. For statistical analysis, the independent T test and Mann-Whitney U test were used. RESULTS: Patients undergoing adjustable male sling implantation were less likely to have a neurological disease (4.5% vs. 8.9%, p = 0.021), a history of urethral stricture (21.6% vs. 33.8%, p = 0.024) or a radiation therapy (22.7% vs. 29.9%, p = 0.020) compared to patients that underwent AUS implantation. Mean pad usage per day (6.87 vs. 5.82; p < 0.00) and the ratio of patients with a prior incontinence surgery were higher in patients selected for an AUS implantation (36.7% vs. 22.7%; p < 0.001). At maximum follow-up, patients that underwent an AUS implantation had a significantly lower mean pad usage during daytime (p < 0.001) and nighttime (p = 0.018). Furthermore, the patients' perception of their continence status was better with a subjective complete dry rate of 57.3% vs. 22.0% (p < 0.001). CONCLUSIONS: Patients selected for an AUS implantation showed a more complex prior history and pathogenesis of urinary incontinence as well as a more severe grade of SUI. Postoperative results reflect a better continence status after AUS implantation, favoring the AUS despite the more complicated patient cohort.


Assuntos
Slings Suburetrais , Incontinência Urinária por Estresse/cirurgia , Esfíncter Urinário Artificial , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Idoso , Estudos de Coortes , Humanos , Masculino , Medidas de Resultados Relatados pelo Paciente , Seleção de Pacientes , Radioterapia/estatística & dados numéricos , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Estreitamento Uretral/epidemiologia
6.
Urologe A ; 57(1): 29-33, 2018 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-29209754

RESUMO

BACKGROUND: The development of a stricture of the vesicourethral anastomosis is a serious complication after radical prostatectomy. Strictures occur in 5-8% of patients after radical prostatectomy. SYMPTOMS: Usually the clinical symptoms include an irritative and obstructive component similar to benign prostatic hyperplasia. In rare cases, patients suffer from partial or complete stress incontinence as a result of the anastomotic stricture. DIAGNOSTICS: The diagnostic workup is similar to the procedure for urethral strictures. In addition to uroflowmetry, a cystourethrogram (CUG) or, if necessary, a micturating cystourethrogram (MCU) can be performed. A urethrocystoscopy can be performed to ensure the diagnosis. THERAPY: In most cases, endoscopic procedures were performed for treatment. Beside a transurethral dilation of the stricture or the Sachse urethrotomy, the most common procedure is transurethral resection to treat the stricture. However, all procedures are associated with a high recurrence rate. In recurrent strictures, open surgical procedures, usually a perineal reanastomosis, should performed early. CONCLUSION: Endourological procedures like transurethral resection are a good treatment option, but due to the high recurrence rates, open surgical procedures should be discussed and if necessary should be performed early.


Assuntos
Anastomose Cirúrgica , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Estreitamento Uretral/etiologia , Estreitamento Uretral/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Anastomose Cirúrgica/efeitos adversos , Constrição Patológica , Humanos , Masculino , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/cirurgia , Uretra
7.
Urologe A ; 57(1): 6-10, 2018 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-29189873

RESUMO

Urethral stricture is a narrowing of the urethra due to scar tissue. It causes obstructive voiding dysfunction and can lead to long-term damage of the entire urinary tract. The probability of therapeutic success is dampened by a high rate of recurrence. Therefore, a careful taking of the patient's history and further diagnostics are crucial for finding the appropriate form of therapy. This review highlights the clinical presentation and diagnostic workup of urethral strictures.


Assuntos
Estreitamento Uretral/diagnóstico , Humanos , Masculino , Recidiva , Uretra , Estreitamento Uretral/etiologia
8.
Mol Psychiatry ; 23(2): 422-433, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-27843151

RESUMO

The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10-7. Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10-7. In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Transtornos Relacionados ao Uso de Álcool/genética , Metilação de DNA/efeitos dos fármacos , Adulto , Grupo com Ancestrais do Continente Africano/genética , Idoso , Consumo de Bebidas Alcoólicas/metabolismo , Transtornos Relacionados ao Uso de Álcool/metabolismo , Biomarcadores/sangue , Ilhas de CpG/genética , Epigênese Genética , Etanol/sangue , Etanol/metabolismo , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade
9.
Int Urol Nephrol ; 49(12): 2137-2142, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28900840

RESUMO

OBJECTIVES: According to current guidelines, radical cystectomy (RC) should be combined with an extended pelvic lymphadenectomy (PLND) as therapeutic and staging instrument. Objective of this study was to analyze the influence of PLND on survival rates and complication rates in a selected group of elderly patients with a minimum age of 80 years. MATERIALS AND METHODS: In this single-center retrospective analysis, we evaluated 102 patients who underwent RC due to UCB from 2004 to 2015 at our institution. In 74 patients (73%), RC was combined with PLND; in 28 cases (27%), RC was performed without PLND. Impact of PLND on cancer specific survival (CSS), overall survival (OS) and progression-free survival (PFS) was analyzed using log-rank test and COX regression model. RESULTS: In univariate analysis of the data, we were not able to show a significant impact of PLND on CSS (p = 0.606), OS (p = 0.979) or PFS (p = 0.883). Also in multivariate analysis of the data, we were not able to identify PLND as an independent prognostic parameter on survival rates of patients undergoing RC, neither for CSS (p = 0.912) nor OS (p = 0.618) or PFS (p = 0.900). CONCLUSIONS: Our small and single-center study was not able to demonstrate a significant independent influence of PLND on CSS, OS and PFS in octogenarians undergoing RC due to UCB. There is no doubt that RC should usually be combined with PLND, but the results of this small data set with a selected patient cohort indicate that RC without PLND might be an option in selected cases of elderly patients.


Assuntos
Carcinoma de Células de Transição/cirurgia , Cistectomia , Excisão de Linfonodo , Complicações Pós-Operatórias/etiologia , Neoplasias da Bexiga Urinária/cirurgia , Idoso de 80 Anos ou mais , Cistectomia/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Excisão de Linfonodo/efeitos adversos , Masculino , Duração da Cirurgia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida
10.
Urologe A ; 56(7): 933-944, 2017 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-28573413

RESUMO

In the era of personalized medicine and precision oncology, innovative genetic biomarkers are of emerging interest to close the diagnostic and prognostic gap that is left by current clinicopathologic risk classifiers. The current review article summarizes evidence regarding prognostic and predictive genetic biomarkers that are currently in widespread clinical use at initial diagnosis as well as following definitive treatment of prostate cancer. We give a brief summary about basic principles of biomarker research studies and present current data for the Progensa PC3 test, TMPRSS2:ERG gene fusion, ConfirmMDx, Prolaris gene panel, OncotypeDX Genomic Prostate score, and Decipher classifier. Evidence regarding those genetic biomarkers has heavily increased recently. However, there is still a lack of large, multicentric and prospective clinical validation studies. Furthermore, comparative studies that investigate the prognostic value of various genetic biomarkers are needed.


Assuntos
Marcadores Genéticos/genética , Neoplasias da Próstata/genética , Humanos , Masculino , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Medicina de Precisão , Valor Preditivo dos Testes , Prognóstico , Neoplasias da Próstata/diagnóstico
11.
Urologe A ; 56(5): 599-603, 2017 May.
Artigo em Alemão | MEDLINE | ID: mdl-28314971

RESUMO

BACKGROUND: Recent improvements in imaging diagnostics has led to a rising incidence of oligometastatic prostate cancer and, most notably, an increasing incidence of nodal-only biochemical recurrences. In this clinical setting, systemic therapy is still the treatment of choice. However, there is increasing evidence for surgical approaches in this challenging clinical setting. AIM OF THE STUDY: In this comprehensive review article, current evidence regarding surgical approaches of primary nodal metastases, nodal-only biochemical recurrence following radical prostatectomy, and osseous metastatic prostate cancer will be discussed. RESULTS: If nodal metastasis is clinically suspected, a significant survival benefit was observed in retrospective studies if radical prostatectomy and extended pelvic lymphadenectomy was performed within a multimodal therapeutic setting. Salvage lymphadenectomy as a therapeutic option for nodal-only biochemical recurrence is clinically feasible and can postpone systemic therapy significantly. However, since most patients do not have a lasting PSA response, a survival benefit of this therapeutic approach is questionable based on current evidence. Regarding osseous metastatic prostate cancer, the surgical approach has an inferior position compared to conservative management and radiotherapy. CONCLUSION: Evidence regarding a surgical approach towards oligometastatic prostate cancer is increasing. However, current evidence is mainly based on retrospective studies that were conducted in the pre-PSMA-PET/CT era.


Assuntos
Tomada de Decisão Clínica/métodos , Excisão de Linfonodo/métodos , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/cirurgia , Medicina Baseada em Evidências , Humanos , Masculino , Metástase Neoplásica , Neoplasias da Próstata/diagnóstico por imagem , Resultado do Tratamento
12.
Urologe A ; 56(7): 857-860, 2017 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-28349187

RESUMO

Primary prostatic sarcomas are rare, reportedly comprising less than 1% of all prostate malignancies. Most patients present with lower urinary tract symptoms due to bladder outlet obstruction. Prostate-specific antigen (PSA) is typically normal. Histological confirmation and staging by a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the pelvis and abdomen are essential for diagnosis and treatment planning. The differential diagnosis includes sarcomatoid prostate cancer or benign spindle cell tumors. Primary prostatic sarcomas are often aggressive and require multimodal treatment with surgery and (neo)adjuvant radiation and/or chemotherapy. The risk of local recurrence is high and the long-term prognosis is poor.


Assuntos
Neoplasias da Próstata/diagnóstico , Sarcoma/diagnóstico , Quimiorradioterapia Adjuvante , Terapia Combinada , Diagnóstico Diferencial , Endossonografia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Próstata/patologia , Prostatectomia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Sarcoma/mortalidade , Sarcoma/patologia , Sarcoma/terapia , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Obstrução do Colo da Bexiga Urinária/diagnóstico , Obstrução do Colo da Bexiga Urinária/etiologia , Obstrução do Colo da Bexiga Urinária/mortalidade , Obstrução do Colo da Bexiga Urinária/patologia
13.
World J Urol ; 34(5): 703-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26376992

RESUMO

PURPOSE: Different blood parameters have shown to be associated with patient's oncological outcome. There is only limited knowledge about the prognostic relevance of routine blood parameters in patients undergoing radical cystectomy for transitional cell carcinoma (TCC). Therefore, we retrospectively analyzed the influence of preoperative C-reactive protein (CRP) and hemoglobin (Hb) levels on overall survival (OS) and cancer-specific survival (CSS). MATERIALS AND METHODS: Preoperative CRP and Hb levels were available in 664 patients who underwent RC due to TCC from 2004 to 2013 at our institution. More men than women (77 vs. 23 %) underwent surgery with a median age of 70 years (35-97). Median follow-up time was 24 months (max. 108). Outcome was analyzed using Kaplan-Meier method, log-rank test, and Cox regression models. RESULTS: Median CRP level was 0.5 mg/dl (0.1-28.3), and median Hb level was 13.4 g/dl (6.7-17.9). Patients with CRP value above the median died significantly earlier due to their disease than those with CRP below the median (median CSS 19 vs. 70 months; p < 0.001). Patients with preoperative Hb level below the median had significantly worse outcome than those with Hb level above the median (median CSS 25 vs. 78 months; p < 0.001). In multivariate analysis, CRP and Hb levels were independent prognostic parameters regarding CSS/OS (CRP p = 0.016/p = 0.004; Hb p = 0.006/p = 0.004, respectively). CONCLUSIONS: In our single-center study, preoperative CRP and Hb levels were found to be independent prognostic factors, indicating impaired outcome in patients undergoing RC for TCC. These findings could be used for individual risk stratification and optimization of therapeutic strategies.


Assuntos
Proteína C-Reativa/análise , Carcinoma de Células de Transição/sangue , Carcinoma de Células de Transição/cirurgia , Cistectomia , Hemoglobinas/análise , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/mortalidade , Cistectomia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/mortalidade
14.
Urologe A ; 54(12): 1779-83, 2015 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-26582381

RESUMO

BACKGROUND: Neuroendocrine carcinoma of the prostate (NEPC) is a rare, androgen-independent variant of prostate cancer with increasing incidence of over the past few years. It commonly progresses rapidly and is associated with a poor prognosis. Based on a different tumor biology compared to adenocarcinomas of the prostate, standard therapeutic approaches for prostate cancer are ineffective. To date, no specific treatment for NEPC exists. OBJECTIVES: The purpose of this work is to provide an overview of current histopathologic characteristics, histomorphologic classifications, and current as well as future treatment options for NEPC. MATERIALS AND METHODS: The literature was reviewed and clinical trials focusing on the above mentioned objectives are discussed. RESULTS: Current histomorphologic classifications aim to differentiate between NEPC including its variants and neuroendocrine transdifferentiated adenocarcinoma of the prostate. Regarding conventional chemotherapy, platinum-based schemes are still widely used. Antiangiogenetic drugs represent potential alternatives and are currently under clinical investigation. CONCLUSIONS: Histomorphological subtypes distinguish themselves in terms of aggressiveness, prognosis, and preferred therapeutic approaches. Treatment of NEPC differs fundamentally compared to adenocarcinoma of the prostate. There is only limited data available for the treatment of NEPC.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Antineoplásicos/administração & dosagem , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/terapia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Diagnóstico Diferencial , Medicina Baseada em Evidências , Humanos , Masculino , Resultado do Tratamento
15.
Urologe A ; 54(1): 52-61, 2015 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-25503722

RESUMO

INTRODUCTION: Retroperitoneal fibrosis (RPF) is a rare chronic inflammatory disease which is characterized by fibrotic tissue in the retroperitoneal space. There have only been a few studies on serum markers of this disease. The main goal of the current investigation was to identify biological markers which are increased in the serum of patients suffering from RPF and which may correlate with the extent of fibrosis. MATERIAL AND METHODS: The serum of 42 patients with primary and yet untreated retroperitoneal fibrosis was examined for biomarkers known to be specific for fibrotic diseases and compared to a control group. In addition, patients were stratified according to the extent and volume of the retroperitoneal mass using cross-sectional imaging. To estimate the discriminatory power of the evaluated biomarkers, receiver operating characteristic (ROC) curves were created. RESULTS: Independent of the extent of fibrosis, calprotectin, fibrinogen, osteopontin, matrix metallopeptidase 9 (MMP-9), tenascin C and TIMP metallopeptidase inhibitor 1 (TIMP-1) were significantly increased (p<0.01) in patients suffering from RPF compared to the control group. Connective tissue growth factor (CTGF) was significantly elevated (p<0.01) in patients with high RPF burden only but monocyte chemoattractant protein 1 (MCP-1) and heart-type fatty acid binding protein (H-FABP) showed no increase in serum levels. The discriminatory power of these parameters was ranked by the ROC analysis which demonstrated an area under the curve (AUC) >0.87 for MMP-9, TIMP-1, osteopontin, tenascin C, asymmetric dimethylarginine (ADMA), fibrinogen and calprotectin and an AUC <0.64 for MMP-2, CTGF, H-FABP and MCP-1. CONCLUSION: Several biomarkers of fibrogenesis were significantly elevated in patients suffering from RPF as compared to a control group. These biomarker candidates will be further evaluated for their potential to allow a differentiation between other diseases or if they could be used for disease monitoring.


Assuntos
Citocinas/sangue , Fibrose Retroperitoneal/sangue , Fibrose Retroperitoneal/diagnóstico , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fibrose Retroperitoneal/terapia , Sensibilidade e Especificidade
16.
Allergy ; 69(9): 1171-80, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24866380

RESUMO

BACKGROUND: Genomewide association and epigenetic studies found a region within the RAD50 gene on chromosome 5q31 to be associated with total serum IgE levels and asthma. In mice, this region harbors a locus control region for nearby TH 2 cytokines, which is characterized by four Rad50 DNase I hypersensitive sites (RHS4-7). Among these, RHS7 seems to have the strongest impact on TH 2 differentiation. We investigated whether within the human homolog of RHS7, functional polymorphisms exist, which could affect DNA methylation or gene expression in the 5q31 locus and might have an influence on asthma status or IgE regulation. METHODS: The human RHS7 region was fine mapped using 1000 genomes database information. In silico analysis and electrophoretic mobility shift assays were used to assess SNP function. Allele-specific effects on DNA methylation were evaluated in cord blood (n = 73) and at age of 4.5 years (n = 61) by pyrosequencing. Allele-specific effects on RAD50, IL4, and IL13 expression were analyzed in 100 subjects. Associations with asthma and IgE levels were investigated in the MAGICS/ISAAC II population (n = 1145). RESULTS: Polymorphism rs2240032 in the RHS7 region is suggestive of allele-specific transcription factor binding, affects methylation of the IL13 promoter region and influences RAD50 and IL4 expression (lowest P = 0.0027). It is also associated with total serum IgE levels (P = 0.0227). CONCLUSION: A functional relevant polymorphism in the TH 2 locus control region, equivalent to RHS7 in mice, affects DNA methylation and gene expression within 5q31 and influences total serum IgE on the population level.


Assuntos
Asma/genética , Metilação de DNA , Regulação da Expressão Gênica/imunologia , Região de Controle de Locus Gênico/genética , Polimorfismo de Nucleotídeo Único , Células Th2/imunologia , Adulto , Asma/imunologia , Criança , Metilação de DNA/imunologia , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/imunologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/imunologia , Ensaio de Desvio de Mobilidade Eletroforética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Imunoglobulina E/sangue , Interleucina-13/genética , Interleucina-13/imunologia , Região de Controle de Locus Gênico/imunologia , Masculino , Reação em Cadeia da Polimerase
17.
Allergy ; 69(5): 632-42, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24661001

RESUMO

BACKGROUND: Type 2 immune responses directed by Th2 cells and characterized by the signature cytokines IL4, IL5, and IL13 play major pathogenic roles in atopic diseases. Single nucleotide polymorphisms in the human Th2 cytokine locus in particular in a locus control region within the DNA repair gene RAD50, containing several RAD50 DNase1-hypersensitive sites (RHS), have been robustly associated with atopic traits in genome-wide association studies (GWAS). Functional variants in IL13 have been intensely studied, whereas no causative variants for the IL13-independent RAD50 signal have been identified yet. This study aimed to characterize the functional impact of the atopy-associated polymorphism rs2240032 located in the human RHS7 on cis-regulatory activity and differential binding of transcription factors. METHODS: Differential transcription factor binding was analyzed by electrophoretic mobility shift assays (EMSAs) with Jurkat T-cell nuclear extracts. Identification of differentially binding factors was performed using mass spectrometry (LC-MS/MS). Reporter vector constructs carrying either the major or minor allele of rs2240032 were tested for regulating transcriptional activity in Jurkat and HeLa cells. RESULTS: The variant rs2240032 impacts transcriptional activity and allele-specific binding of SMAD3, SP1, and additional putative protein complex partners. We further demonstrate that rs2240032 is located in an RHS7 subunit which itself encompasses repressor activity and might be important for the fine-tuning of transcription regulation within this region. CONCLUSION: The human RHS7 critically contributes to the regulation of gene transcription, and the common atopy-associated polymorphism rs2240032 impacts transcriptional activity and transcription factor binding.


Assuntos
Citocinas/genética , Regulação da Expressão Gênica , Hipersensibilidade Imediata/genética , Hipersensibilidade Imediata/metabolismo , Região de Controle de Locus Gênico , Proteína Smad3/metabolismo , Fator de Transcrição Sp1/metabolismo , Células Th2/metabolismo , Transcrição Genética , Alelos , Sítios de Ligação , Ordem dos Genes , Humanos , Hipersensibilidade Imediata/imunologia , Desequilíbrio de Ligação , Motivos de Nucleotídeos , Polimorfismo de Nucleotídeo Único , Matrizes de Pontuação de Posição Específica , Regiões Promotoras Genéticas , Ligação Proteica , Sequências Reguladoras de Ácido Nucleico
18.
Urologe A ; 53(3): 339-40, 342, 344-5, 2014 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-24522693

RESUMO

Postprostatectomy incontinence (PPI) is one of the most feared complications of radical prostatectomy with major impact on quality of life and social well-being. In recent years due to improved surgical techniques a reduction of the postoperative incontinence rate was achieved. However, due to the increasing number of radical prostatectomies performed for prostate cancer, a substantial and increasing number of patients are suffering from postoperative stress urinary incontinence. If conservative treatment fails, surgical therapy is recommended. For decades, the artificial urinary sphincter was the reference standard for moderate to severe postoperative male stress urinary incontinence. However, patients' demand on minimally invasive treatment options is high. Age or advanced prostate cancer should not be an exclusion criterion for surgical treatment of persistent PPI.


Assuntos
Saúde do Homem , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Prostatectomia/efeitos adversos , Slings Suburetrais , Incontinência Urinária por Estresse/etiologia , Incontinência Urinária por Estresse/cirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Humanos , Masculino , Procedimentos Cirúrgicos Reconstrutivos/instrumentação , Procedimentos Cirúrgicos Reconstrutivos/métodos , Procedimentos Cirúrgicos Urológicos Masculinos/instrumentação
19.
Urologe A ; 52(4): 497-503, 2013 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-23483268

RESUMO

The diagnostic approach to prostate cancer is still a big challenge for the treating physician. Regarding an individualized and risk-adapted evaluation of different therapeutic options, precise diagnostic tools are crucial to accurately distinguish between localized and advanced prostate cancer. Imaging of advanced prostate cancer is currently changing due to numerous technical innovations. While choline-based hybrid positron emission tomography-computed tomography (PET/CT) has been established as an important diagnostic tool in clinical imaging of advanced prostate cancer, well-investigated methods, such as magnetic resonance imaging (MRI) and bone scintigraphy are currently expanding the diagnostic potential due to technical improvements. The specific use of imaging for advanced prostate cancer may help to offer the patient a well-tailored oncologic therapy. Further research is needed to evaluate whether this individualized therapy can consistently improve the prognosis of patients suffering from advanced prostate cancer.


Assuntos
Aumento da Imagem/métodos , Imagem por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada por Raios X , Humanos , Masculino , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
J Chromatogr B Analyt Technol Biomed Life Sci ; 879(17-18): 1393-401, 2011 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-21176889

RESUMO

In order to develop a generic positive ionization ESI LC-MS method for a variety of interesting substance classes, a new derivatization strategy for carboxylic acids was developed. The carboxylic acid group is labeled with the bromine containing 4-APEBA reagent based on carbodiimide chemistry. The derivatization reaction can be carried out under aqueous conditions, thereby greatly simplifying sample preparation. In this paper, the derivatization of carboxylic acids is exemplified for the determination of prostanoids and non-steroidal anti-inflammatory drugs (NSAID). Optimization of the derivatization conditions was studied. In order to prove the applicability of the presented approach, we applied the described protocol to urine samples from complex regional pain syndrome (CRPS) patients and were able to detect several prostanoids not visible in the urine of healthy volunteers. Further, the determination of the non-steroidal anti-inflammatory drug ibuprofen in a urine sample was possible.


Assuntos
Compostos de Anilina/química , Anti-Inflamatórios não Esteroides/urina , Ácidos Carboxílicos/química , Síndromes da Dor Regional Complexa/urina , Ibuprofeno/urina , Prostaglandinas/urina , Compostos de Amônio Quaternário/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Espectrometria de Massas em Tandem/métodos
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