RESUMO
Gendered differences in relative ACE2 expression in the nasal epithelium.
Assuntos
Enzima de Conversão de Angiotensina 2 , Mucosa Nasal , Humanos , Enzima de Conversão de Angiotensina 2/metabolismo , Mucosa Nasal/metabolismo , Masculino , Feminino , Fatores SexuaisRESUMO
BACKGROUND: Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) is involved in DNA demethylation and transcriptional regulation, plays a key role in the maintenance of stem cell pluripotency, and is dysregulated in malignant cells. The identification of cancer stem cells (CSCs) driving tumor growth and metastasis is the primary objective of biomarker discovery in aggressive prostate cancer (PCa). In this context, we analyzed TET1 expression in PCa. METHODS: A large-scale immunohistochemical analysis of TET1 was performed in normal prostate (NOR) and PCa using conventional slides (50 PCa specimens) and tissue microarrays (669 NOR and 1371 PCa tissue cores from 371 PCa specimens). Western blotting, RT-qPCR, and 450 K methylation array analyses were performed on PCa cell lines. Genome-wide correlation, gene regulatory network, and functional genomics studies were performed using publicly available data sources and bioinformatics tools. RESULTS: In NOR, TET1 was exclusively expressed in normal cytokeratin 903 (CK903)-positive basal cells. In PCa, TET1 was frequently detected in alpha-methylacyl-CoA racemase (AMACR)-positive tumor cell clusters and was detectable at all tumor stages and Gleason scores. Pearson's correlation analyses of PCa revealed 626 TET1-coactivated genes (r > 0.5) primarily encoding chromatin remodeling and mitotic factors. Moreover, signaling pathways regulating antiviral processes (62 zinc finger, ZNF, antiviral proteins) and the pluripotency of stem cells were activated. A significant proportion of detected genes exhibited TET1-correlated promoter hypomethylation. There were 161 genes encoding transcription factors (TFs), of which 133 were ZNF-TFs with promoter binding sites in TET1 and in the vast majority of TET1-coactivated genes. CONCLUSIONS: TET1-expressing cells are an integral part of PCa and may represent CSCs with oncogenic potential.
Assuntos
Oxigenases de Função Mista/análise , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas/análise , Idoso , Metilação de DNA/genética , Expressão Gênica/genética , Expressão Gênica/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Oxigenases de Função Mista/sangue , Oxigenases de Função Mista/genética , Proteínas Proto-Oncogênicas/sangue , Proteínas Proto-Oncogênicas/genéticaRESUMO
BACKGROUND: The urokinase plasminogen activator (uPA) system is one of the best-investigated protease systems, both under physiological and pathological conditions, including various types of cancer. However, effects of co-expression of members of the uPA system in soft-tissue sarcoma (STS) patients at the protein level in both tumour tissue and serum have not been investigated yet. METHODS: We examined 82 STS patients for protein levels of uPA, PAI-1and uPAR in tumour tissue and serum by ELISA. RESULTS: A significant correlation between high antigen levels of uPA, PAI-1 or uPAR in tumour tissue, and of uPAR in serum, with poor outcome of STS patients was found for the first time. Most strikingly, we observed an additive effect of combined uPA, PAI-1 or uPAR levels in tumour tissue extracts with uPAR levels in serum on patients' prognosis. High uPA/uPAR, PAI-1/uPAR and uPAR/uPAR antigen levels in tumour tissue/serum were associated with a 5.9-fold, 5.8-fold and 6.2-fold increased risk of tumour-related death (P=0.003, 0.001 and 0.002, respectively) compared with those patients who displayed low levels of the respective marker combination. CONCLUSION: As expression of members of the uPA system in tumour tissue and serum is additively correlated with prognosis of STS patients, our results suggest that combinations of these biomarkers can identify STS patients with a higher risk of tumour-related death.
Assuntos
Inibidor 1 de Ativador de Plasminogênio/análise , Receptores de Ativador de Plasminogênio Tipo Uroquinase/análise , Sarcoma/diagnóstico , Ativador de Plasminogênio Tipo Uroquinase/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Técnicas e Procedimentos Diagnósticos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangue , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Prognóstico , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Sarcoma/sangue , Sarcoma/metabolismo , Sarcoma/mortalidade , Análise de Sobrevida , Ativador de Plasminogênio Tipo Uroquinase/sangue , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Adulto JovemRESUMO
Even in times of kyphoplasty and vertebroplasty, braces remain an efficient option in the treatment of osteoporotic hyperkyphosis due to imminent or manifest vertebral wedging with the obligatory pain and fracture risk of adjacent vertebraes. In the same fashion, acute osteoporotic fractures with considerable backpain can be treated with an adequate orthosis besides analgetics and osteological drugs. Essential is the careful selection of the right brace for a given type of osteoporotic fracture: Overall brace-frames (Stagnara type) should be used only in highly unstable or multiple osteoporotic fractures with impact onto the spinal canal where surgery is not possible. These brace frames should be administered only for the shortest possible period (8-12 weeks) to reduce muscle atrophy and immobilization. However, in the typical stable osteoporotic wedge fracture, light weight constructions like the Jewett or Bähler-Vogt brace or - in less severe cases - dynamic braces (e.g. TorsoStretch brace or SpinoMedActive brace) should be used to minimize muscle atrophy and demineralisation. Brace treatment at its best though, can be only one step in the cascade of measures to fight demineralisation and the clinical consequences: General physiotherapy, analgetics and specific osteological drugs and minerals add essentially to the treatment.
Assuntos
Fraturas Espontâneas/reabilitação , Aparelhos Ortopédicos , Osteoporose/reabilitação , Fraturas da Coluna Vertebral/reabilitação , Idoso , Dor nas Costas/reabilitação , Braquetes , Terapia Combinada , Ensaios Clínicos Controlados como Assunto , Desenho de Equipamento , Terapia por Exercício , Feminino , Fraturas Espontâneas/diagnóstico , Humanos , Cifose/diagnóstico , Cifose/reabilitação , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Osteoporose/diagnóstico , Satisfação do Paciente , Fraturas da Coluna Vertebral/diagnósticoRESUMO
Back pain is a very common clinical picture. The causes are often not only somatic, which generally has led to a biopsychosocial understanding of this disease. Therefore, it is necessary to employ a multimodal treatment approach to achieve effective and longer-lasting relief. Such a concept requires the cooperation of multiple disciplines in a sophisticated and strongly organized manner. In our clinic we have developed a clinical pathway for conservative back pain treatment that avoids the use of too much time by careful coordination of the therapy elements. It has proven to be a successful tool for the efficient treatment of patients with primarily somatically caused back pain. The following article describes this clinical pathway.
Assuntos
Dor nas Costas/diagnóstico , Dor nas Costas/terapia , Procedimentos Clínicos/organização & administração , Atenção à Saúde/organização & administração , Modelos Organizacionais , Ortopedia/organização & administração , Alemanha , HumanosRESUMO
The annual symposium of the German Research Association for Bladder Carcinoma (DFBK) was organized on February 7th and 8th, 2020, in Düsseldorf. On the first day, eight international guest speakers invited by the DFBK and the Department of Urology of the Heinrich Heine University Düsseldorf presented the current state of research on bladder cancer (BC). Topics were genomic changes and molecular classification in non-muscle-invasive and muscle-invasive BC, prospects and limits of proteome technology in urine diagnostics, function of chromatin regulators in bladder carcinogenesis, cellular reactions to aneuploidy, organoid technology and biobanking, as well as novel aspects of immunotherapy for BC. The second day was dedicated to new results and ideas of the DFBK members on BC pathomechanisms, diagnostics and therapeutic approaches, and most importantly, discussions on the further development of collaborative projects. Additional information is available at http://www.forschungsverbund-blasenkarzinom.de.
Assuntos
Bancos de Espécimes Biológicos , Imunoterapia , Neoplasias da Bexiga Urinária/terapia , Congressos como Assunto , Humanos , Pesquisa , Sociedades Médicas , Neoplasias da Bexiga Urinária/diagnóstico , Urologia/tendênciasRESUMO
Cancer stem cells can play an important role in tumorigenesis and tumor progression. However, it is still difficult to detect and isolate cancer stem cells. An alternative approach is to analyse stem cell-associated gene expression. We investigated the coexpression of three stem cell-associated genes, Hiwi, hTERT and survivin, by quantitative real-time-PCR in 104 primary soft-tissue sarcomas (STS). Multivariate Cox's proportional hazards regression analyses allowed correlating gene expression with overall survival for STS patients. Coexpression of all three stem cell-associated genes resulted in a significantly increased risk of tumor-related death. Importantly, tumors of patients with the poorest prognosis were of all four tumor stages, suggesting that their risk is based upon coexpression of stem cell-associated genes rather than on tumor stage.
Assuntos
Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Sarcoma/genética , Sarcoma/patologia , Proteínas Argonautas , Feminino , Humanos , Proteínas Inibidoras de Apoptose , Masculino , Proteínas Associadas aos Microtúbulos/genética , Proteínas de Neoplasias/genética , Prognóstico , Proteínas/genética , Sarcoma/etiologia , Survivina , Telomerase/genéticaRESUMO
Selected transcript markers as well as their combinations were analyzed on minimal prostate tissue specimens with regard to their diagnostic potential. Artificial prostate biopsies from RPE explants were used for evaluation and optimization of the techniques used followed by application to diagnostic prostate needle core biopsies. Minimal prostate specimens were cryopreserved and processed with standardized methods. The RNA amount of a half of each biopsy was sufficient for the analysis of 11 marker genes and one reference gene (TBP) using quantitative PCR assays.The relative transcript amounts obtained were included in several analyses including calculations for each single marker gene like median overexpression rate as well as marker combinations. Two optimized mathematical models based on relative expression levels of EZH2, hepsin, PCA3, prostein, and TRPM8 were evaluated with regard to their diagnostic potential. Compared to single marker analyses these models show higher sensitivity and specificity for prostate cancer detection.Thus biomolecular prostate cancer identification may represent a suitable diagnostic tool to supplement conventional techniques on prostate biopsies. Furthermore, an extension of this approach to PCa prognosis and the transfer to urine samples appear very promising.
Assuntos
Biomarcadores Tumorais/genética , Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Biópsia por Agulha Fina , Diagnóstico Diferencial , Diagnóstico Precoce , Perfilação da Expressão Gênica , Humanos , Masculino , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/genética , Hiperplasia Prostática/patologia , Transcrição Gênica/genéticaRESUMO
As individual risk assessment mainly depends on the correct prediction of the tumor's biological behavior, primary diagnosis plays a key role in the clinical management of prostate cancer patients. Prostate core needle biopsy, as a primary diagnostic tool, should not only confirm clinical suspicion but also supply the urologist with information which is necessary for risk-adapted therapy. The experience and competence of both the urologist and the pathologist are crucial for the quality of prostate core needle biopsy diagnosis. Optimized handling and submission of prostate core needle biopsy specimens by the urologist to the pathologist are of outstanding importance for improving the number of cancer cases detected. Increasing availability of molecular markers leads to the necessity of developing new tissue sampling procedures which allow prostate core needle biopsy specimens to be simultaneously studied histologically and by molecular approaches.
Assuntos
Biópsia por Agulha/normas , Neoplasias da Próstata/patologia , Biomarcadores Tumorais/análise , Comportamento Cooperativo , Humanos , Relações Interprofissionais , Masculino , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Padrões de Referência , Risco Ajustado , Manejo de EspécimesRESUMO
Telomerase, a ribonucleoprotein complex is activated in the vast majority of human malignancies, including prostate cancer. Its inhibition is a putative way to affect cancer proliferation and might be used in the therapy of tumors. We analysed the influence of antisense phosphorothioate oligonucleotides (PTO) against the reverse transcriptase subunit of telomerase on prostate cancer cell viability, telomerase activity and telomere length. DU145 prostate cancer cells were cultivated in PTO containing medium. The PTO-incorporation was confirmed by confocal laser scanning microscopy. Cell viability was measured by a WST-1 tetrazolium assay. After 15 days of antisense PTO treatment, a significant inhibition of cell viability occurred. Telomerase activity was determined by a telomeric repeat amplification protocol (TRAP) assay and telomere length by Southern blot analysis. Since the long-term telomerase antisense treatment reduces the viability of prostate cancer cells significantly, this antisense approach could be a new therapeutic strategy to treat patients with advanced prostate cancer.
Assuntos
Oligonucleotídeos Antissenso/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , RNA , Telomerase/genética , Células Tumorais Cultivadas/efeitos dos fármacos , Southern Blotting , Morte Celular , Sobrevivência Celular/efeitos dos fármacos , Proteínas de Ligação a DNA , Regulação para Baixo , Humanos , Masculino , Microscopia Confocal , Microscopia de Contraste de Fase , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Telomerase/metabolismo , Telômero/química , Telômero/metabolismo , Tionucleotídeos/uso terapêutico , Células Tumorais Cultivadas/enzimologia , Células Tumorais Cultivadas/patologiaRESUMO
BACKGROUND: In previous studies we isolated a new cDNA fragment named C13 which is down-regulated in malignant prostate tissues. The corresponding gene is localized on chromosome 13q13 between the known tumour suppressor genes (TSG) BRCA-2 and RB-1. MATERIALS AND METHODS: Loss of heterozygosity (LOH) analyses were carried out in the region of C13 in order to investigate the importance of the new putative TSG for prostate cancer development. Using semiquantitative LOH analysis, we screened 21 prostate carcinoma patients of different tumour stages (pT2-pT4) for 14 microsatellite markers in the region of C13 (13q13) and in the flanking BRCA-2 and the RB-1 loci. RESULTS: For 18 (86%) patients LOH or allelic imbalances were found. We identified three to nine alterations in affected tumours per marker. An overall genetic alteration frequency per patient of 38% (86 of 225 informative cases) could be calculated. One important finding regarding the overall frequency of determined microsatellite instability is that the LOH/AI rate of 47% for the seven C13-associated markers was higher than for the four markers of the RB-1 locus (39%) and for the three BRCA-2 markers (25%). Surprisingly, defining LOH critical regions (LCR) for the investigated marker panel, eight of the ten affected LCR cases showed chromosomal imbalances simultaneously for the RB-1 and the C13 LOH markers. CONCLUSIONS: The high LOH rate for eight different microsatellite markers in and around the putative TSG locus C13 on chromosome 13q13 further supports an involvement of C13 in prostate tumourigenesis.
Assuntos
Cromossomos Humanos Par 13/genética , Perda de Heterozigosidade , Neoplasias da Próstata/genética , Idoso , Desequilíbrio Alélico , Mapeamento Cromossômico , DNA de Neoplasias/genética , Genes BRCA2 , Genes do Retinoblastoma/genética , Humanos , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologiaRESUMO
The German Bladder Cancer Association (DFBK) invited its members to the 3rd annual meeting 2012 in Hannover 4 years after the official founding. The meeting was directed to discuss the progress of ongoing and newly initiated projects and collaborations. In this article we will introduce current research activities and collaborations of the DFBK and would like to invite interested researchers to join this national interdisciplinary research association. The aim of the DFBK is to initiate interdisciplinary collaboration and to support scientific discussions among its members. For further information please visit our website at www.forschungsverbund-blasenkarzinom.de.
Assuntos
Oncologia/organização & administração , Sociedades Médicas/organização & administração , Neoplasias da Bexiga Urinária , Alemanha , Humanos , Objetivos OrganizacionaisAssuntos
Antineoplásicos/administração & dosagem , Materiais Biocompatíveis , Portadores de Fármacos , Nanotubos de Carbono , Neoplasias da Próstata/tratamento farmacológico , Próteses e Implantes , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Humanos , Masculino , Camundongos , Ratos , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismoAssuntos
Carcinoma de Células de Transição/tratamento farmacológico , Oligodesoxirribonucleotídeos Antissenso/uso terapêutico , RNA Interferente Pequeno/uso terapêutico , Células Tumorais Cultivadas/efeitos dos fármacos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Divisão Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Transplante de Neoplasias , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologiaAssuntos
Carcinoma de Células Renais/secundário , Perfilação da Expressão Gênica , Neoplasias Renais/genética , Neoplasias Pulmonares/secundário , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , DNA de Neoplasias/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Terapia a Laser , Pulmão/patologia , Pulmão/cirurgia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único/genética , PrognósticoAssuntos
Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Neoplasias da Próstata/genética , Fatores de Transcrição/genética , Biópsia , Humanos , Masculino , Prognóstico , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Sensibilidade e EspecificidadeRESUMO
One of the principal objects of the scientific research network "German Bladder Cancer Network" is to consolidate research activities on bladder cancer. An overview about directions of current projects on this research topic was given at the annual meeting of the German Association of Urology in Düsseldorf from September 22 to 25 September 2010. As representatives of the"German Bladder Cancer Network" we summarize and comment on some of the most interesting projects on bladder cancer presented at this meeting. A special focus will be on current developments in the field of uropathology and on different aspects in preclinical research on bladder cancer.