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In multivariate analysis, GS of the regular prostatectomy specimen was the only statistically significant parameter for pT2R1 prostate cancer.
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PURPOSE: To clarify the value of targeted versus off-target biopsies in men with a suspicion of prostate cancer (PC) and a visible lesion in multi-parametric magnetic resonance imaging (mpMRI) using transperineal robot-assisted biopsy. METHODS: Fifty-five consecutive men with one non-palpable suspicious lesion in mpMRI after negative 12-core transrectal ultrasound-guided biopsy were enrolled in 2014-2015. Lesions were scored using the Prostate Imaging Reporting and Data System. A robot-assisted system was utilized to collect four robot-assisted targeted transperineal biopsy cores (RA-TB) within the lesion using mpMRI-TRUS elastic fusion. Untargeted transperineal 14-core biopsy was performed only outside the lesion (RA-UB). Histological grade was compared in biopsies and available prostatectomy specimens. RESULTS: Overall, 34 of 55 patients (62%) were diagnosed with PC based on biopsy. 85% of cancers were clinically significant PC (csPC) defined as GS ≥ 7. 85% of biopsy-proven cancers were detected with RA-TB alone. RA-UB identified only one additional patient with csPC and lead to upgrading in five biopsy cases (14.7%). Pathological evaluation of 14 prostatectomy specimens showed upgrading in 2 patients (14.3%), while all other patients were correctly classified by RA-TB without need of additional RA-UB. Mean procedure duration was 43 (±6) min, and only minor complications according to Clavien-Dindo were recorded during 30-day follow-up. CONCLUSIONS: This is the first report of transperineal robot-assisted elastic mpMRI-TRUS fusion biopsy. RA-TB of positive MR lesions enabled reliable detection of csPC, while RA-UB in MRI-negative regions is of minor importance.
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Imagen por Resonancia Magnética , Próstata , Neoplasias de la Próstata , Robótica/métodos , Ultrasonografía Intervencional , Anciano , Humanos , Biopsia Guiada por Imagen/instrumentación , Biopsia Guiada por Imagen/métodos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/instrumentación , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Próstata/diagnóstico por imagen , Próstata/patología , Prostatectomía/métodos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Reproducibilidad de los Resultados , Ultrasonografía Intervencional/instrumentación , Ultrasonografía Intervencional/métodosRESUMEN
PURPOSE: To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with positive surgical margin (R1) and no adjuvant/neoadjuvant therapy. METHODS: A multicenter data analysis of 956 patients with pT2R1N0/Nx tumors was performed. Patients underwent radical prostatectomy between 1994 and 2009. No patients received neoadjuvant or adjuvant therapy. All prostate specimens were re-evaluated according to a well-defined protocol. The association of pathological and clinical features, in regard to BCR, was calculated using various statistical tests. RESULTS: With a mean follow-up of 48 months, BCR was found in 25.4 %. In univariate analysis, multiple parameters such as tumor volume, PSA, Gleason at positive margin were significantly associated with BCR. However, in multivariate analysis, Gleason score (GS) of the prostatectomy specimen was the only significant parameter for BCR. Median time to recurrence for GS ≤ 6 was not reached; 5-year BCR-free survival was 82 %; and they were 127 months and 72 % for GS 3+4, 56 months and 54 % for GS 4 + 3, and 27 months and 32 % for GS 8-10. The retrospective approach is a limitation of our study. CONCLUSIONS: Our study provides data on the BCR in pT2R1-PCa without adjuvant/neoadjuvant therapy and thus a rationale for an individual's risk stratification. The data support patients and physicians in estimating the individual risk and timing of BCR and thus serve to personalize the management in pT2R1-PCa.
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Calicreínas/sangre , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/diagnóstico , Antígeno Prostático Específico/sangre , Prostatectomía , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/cirugía , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasia Residual , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: Renal oncocytomas are assigned as benign tumours, and their detailed molecular mechanism is poorly characterised. Activation of the PKB/Akt pathway is assumed to contribute to the pathogenesis and progression of malignant disease. For oncocytomas, hardly any data are available for Akt signalling parameters. Aim of the present work was to determine the alterations of Akt parameters PTEN, phosphorylated Akt (p-Akt) and p27(Kip1) in oncocytoma to better understand the dedifferentiation of renal tumours. METHODS: By tissue microarray analysis 15 oncocytoma, 18 clear cell renal cell carcinoma (ccRCC) and the corresponding benign tissue were investigated. Significant expression differences between PTEN, p-Akt and p27(Kip1) were determined by immunohistochemistry using One-way ANOVA with all pairs Tukey-Kramer as post hoc analyses. To investigate Akt parameter interactions in the oncocytoma, linear regression analyses were performed. RESULTS: Expression of all proteins was significantly different between the groups and in all groups the lowest for oncocytoma: PTEN: 32.9 ± 13.0 versus 75.5 ± 8.0 versus 123.7 ± 8.8; p < 0.001 for oncocytoma, benign parenchyma and ccRCC and 2.7 ± 1.2 versus 40.8 ± 9.5 versus 143.6 ± 12.2; p < 0.001 for p27(Kip1). p-Akt expression was significantly different between oncocytoma and ccRCC (67.3 ± 15.7 vs. 144.0 ± 26.6; p < 0.05). CONCLUSION: All three investigated parameters were the lowest in oncocytoma when compared to ccRCC. Expression of PTEN and p27(Kip1) seems to be exceedingly associated with malignant conditions of ccRCC. These findings might contribute to the understanding of tumorous signalling of the PKB/Akt axis in renal tumours.
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Adenoma Oxifílico/metabolismo , Carcinoma de Células Renales/metabolismo , Neoplasias Renales/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/fisiología , Adenoma Oxifílico/diagnóstico , Adenoma Oxifílico/patología , Anciano , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/patología , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Masculino , Análisis por Micromatrices , Persona de Mediana Edad , Fosfohidrolasa PTEN/metabolismo , FosforilaciónRESUMEN
Selenoprotein P (SePP) is central to selenium (Se) metabolism in the mammalian organism. Human SePP contains 10 Se atoms that are covalent constituents of the polypeptide chain incorporated as the rare amino acid selenocysteine (Sec). Since hepatocytes secrete SePP into plasma, SePP is commonly regarded as a Se transport protein, although SePP mRNA is expressed in many organs. Gene targeting of SePP in mice leads to neurological dysfunction resulting from Se deficiency and associated reduction of selenoenzyme activities in the brain. However, more recent data revealed that isolated hepatic SePP deficiency does not alter brain Se levels, suggesting a role for SePP locally expressed in the brain. Some of the best characterized and most abundant selenoenzymes, glutathione peroxidases, thioredoxin reductases, and methionine sulfoxide reductase B, play major roles in the cellular defense against reactive oxygen species. Therefore, it was hypothesized that reduced brain Se bioavailability may be involved in the pathogenesis of neurodegenerative disease and normal ageing. We present evidence that human CSF contains SePP and that the human brain expresses SePP mRNA. Moreover, SePP-like immunoreactivity localizes to neurons and ependymal cells and thus appears strategically situated for maintenance and control of Se-dependent anti-oxidative defense systems.
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Encéfalo/metabolismo , Epéndimo/metabolismo , Regulación de la Expresión Génica , Neuronas/metabolismo , Proteoma/biosíntesis , Selenoproteína P/biosíntesis , Selenoproteína P/metabolismo , Adulto , Animales , Antioxidantes/metabolismo , Encéfalo/citología , Células COS , Línea Celular Tumoral , Chlorocebus aethiops , Epéndimo/química , Regulación de la Expresión Génica/fisiología , Humanos , Sueros Inmunes/metabolismo , Inmunohistoquímica , Recién Nacido , Ratones , Neuronas/química , Proteoma/química , Selenio/sangre , Selenio/fisiología , Selenoproteína P/inmunologíaRESUMEN
While clear cell, papillary and chromophobic renal cell carinoma (RCC) represent the most common malignant renal neoplasms, the evaluation and classification of rare renal carcinomas has currently come into focus. One of these is the leiomyomatous RCC, which shows morphologic similarities to clear cell RCCs, however exhibiting additional, atypical smooth muscle differentiation. We report the clinical case of a patient simultaneously presenting with leiomyomatous and papillary RCC and discuss new tumor entities of RCC.
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Carcinoma de Células Renales/clasificación , Carcinoma de Células Renales/patología , Neoplasias Renales/clasificación , Neoplasias Renales/patología , Leiomioma/clasificación , Leiomioma/patología , Adulto , Carcinoma de Células Renales/diagnóstico por imagen , Diagnóstico Diferencial , Humanos , Neoplasias Renales/diagnóstico por imagen , Leiomioma/diagnóstico por imagen , Masculino , Terminología como AsuntoRESUMEN
Bone sialoprotein (BSP) regulates bone metabolism by directly influencing the activity of osteoblasts and osteoclasts. A significant correlation between the tissue expression of BSP in tumors and the occurrence of bone metastases was found in different cancers. Aim of this study was to identify the BSP expression in renal cell carcinomas (RCC) according to their stage of metastatic disease. Tissue samples of patients with RCC who underwent partial resection or nephrectomy were separated into three groups, each with 10 patients showing either no metastases (group I), only soft tissue metastases (group II) or bone metastases (group III) at date of surgery. Immunohistochemical analysis of BSP expression in tumor tissue and corresponding renal parenchyma was performed and evaluated with an established semiquantitative scoring system. BSP expression was detected both in tumor tissue and renal parenchyma. Concerning the expression in malignant tissue, no significant difference could be found between the three groups whereas the corresponding renal parenchyma showed a staining score of 164, 198 and 224 for group I, II and III (P = 0.07). RCC staged T3 showed only a little higher BSP expression than those staged T1/2 (P < 0.21), while the corresponding parenchyma of T3 tumors showed significantly higher expressions (P = 0.02). This pilot study revealed a correlation between expression of BSP and tumor staging and type of metastases, especially for osseous metastases in RCC. Alternation of BSP expression could be detected particularly in renal parenchyma and linked to the type of metastases.
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Biomarcadores de Tumor/metabolismo , Neoplasias Óseas/secundario , Carcinoma de Células Renales/metabolismo , Sialoproteína de Unión a Integrina/metabolismo , Neoplasias Renales/metabolismo , Neoplasias Óseas/metabolismo , Carcinoma de Células Renales/patología , Humanos , Inmunohistoquímica , Neoplasias Renales/patología , Proyectos Piloto , Estudios RetrospectivosRESUMEN
BACKGROUND: Electrosurgical vessel sealing produces seals that can withstand intraluminal pressures well above the physiological range. In many cases it is more efficient than other methods, such as sutures, hemoclips, and ultrasonic coagulation devices, but bears lateral thermal damage as a side effect. The overall aim of this study was to compare the thermal lateral damage (TL) in vivo versus ex vivo using two different bipolar vessel sealing instruments in an epigastric vein animal model. MATERIAL AND METHODS: A total of 96 thermofusions of bilateral epigastric veins were carried out in a prospective, randomized and controlled study design. The laparoscopic BiClamp (type Maryland) and the bipolar clamp Kelly model Clermont-Ferrand were used for ex vivo versus in vivo investigation. After exposure of the two bilateral epigastric veins the proximal sections were bilaterally coagulated in vivo with the two different instruments. For ex vivo coagulation, the uncoagulated section of the vein was removed and coagulated ex vivo. The TL was investigated by infrared measurement, light microscope and histological analysis. RESULTS: The comparison of the extent of coagulation damage between ex vivo and in vivo coagulation did not differ significantly: no differences between in vivo and ex vivo measurements were found for the Kelly clamp. In the case of the Maryland clamp only a significant greater TL in vivo was shown for stereomicroscopic measurements. CONCLUSIONS: Ex vivo TL results are comparable with in vivo results. This might prospectively spare in vivo studies with respect to TL and might facilitate the design of future experiments for the development of bipolar electrocoagulation devices.
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Electrocoagulación/efectos adversos , Animales , Electrocoagulación/métodos , Femenino , Calor/efectos adversos , Laparoscopía , Estudios Prospectivos , Distribución Aleatoria , Porcinos , Venas/cirugíaRESUMEN
In the treatment of advanced bladder cancer (BC), attention has recently focused on small molecule therapy concerning EGFR and the downstream Akt signalling pathway. Cellular deregulation processes are poorly understood, and biological determinants for the selection of therapy and monitoring are currently not available. The proteins PTEN, p-Akt and p27(Kip1) are suggested to be potentially significant biomarkers of Akt signalling. In this study, we investigated the expression of these proteins in advanced BC. PTEN, p-Akt and p27(Kip1) expression was determined immunohistochemically in 86 T2-4 BC specimens using a tissue microarray technique. Staining was documented with regard to intensity, cellular frequency and a multiplied staining score. Staining characteristics of the three proteins were correlated by regression analysis with the parameters of tumour stage and grade. A positive correlation was observed in the expression scores of PTEN and p-Akt, p-Akt and p27(Kip1) as well as PTEN and p27(Kip1) (p<0.02 for all combinations). The positive correlation between PTEN and p-Akt resulted mainly due to the strong correlation of PTEN intensity with p-Akt (p=0.0003 and p=0.0006 to p-Akt frequency and intensity, respectively). A positive correlation between p-Akt and p27(Kip1) was noted for p-Akt frequency as well as intensity (p<0.05 for all combinations). The positive correlation between PTEN and p27(Kip1) resulted due to the correlation of PTEN intensity alone with p27(Kip1) (p<0.03 for p27(Kip1) frequency and intensity), whereas no significance was noted for PTEN frequency. No correlation was found between T or G and expression of the proteins. However, activation of Akt in BC is known to occur independently of PTEN protein loss and appears not to cause a decrease of p27(Kip1). However, a direct regulatory impact of PTEN on p27(Kip1) was found. PTEN intensity, rather than frequency, appears to be a superior biomarker. These results may provide information to support research into protein profiling-predicted targeted therapy for BC. Correlations to benign urothelium, superficial BC specimens and follow-up data remain to be investigated.
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Nun protein from coliphage HK022 binds to phage boxB RNA and functions, in contrast to phage lambda N protein, as a transcriptional terminator. The basic Nun-(10-44) peptide contains the boxB RNA binding arginine rich motif, ARM. The peptide binds boxB RNA and competes with the phage lambda ARM peptide N-(1-36) as indicated by nuclear magnetic resonance (NMR) spectroscopy titrations. In two-dimensional nuclear Overhauser enhancement spectroscopy experiments boxB RNA in complex with Nun-(20-44) exhibits the same pattern of resonances as it does in complex with N peptides containing the ARM, and we could show that Nun-(20-44) forms a bent alpha-helix upon binding to the boxB RNA. The structure of the boxB RNA-bound Nun-(20-44) was determined on the basis of 191 intra- and 30 intermolecular distance restraints. Ser-24 is anchored to the lower RNA stem, and stacking of Tyr-39 and A7 is clearly experimentally indicated. Arg-28 shows numerous contacts to the RNA stem. Leu-22, Ile-30, Trp-33, Ile-37, and Leu-41 form a hydrophobic surface, which could be a recognition site for additional host factors such as NusG. Such a hydrophobic surface area is not present in N-(1-36) bound to boxB RNA.
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Bacteriófago lambda/química , Colifagos/química , ARN Viral/química , Factores de Transcripción/química , Transcripción Genética , Proteínas Virales/química , Secuencia de Aminoácidos , Secuencia de Bases , Modelos Moleculares , Datos de Secuencia Molecular , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Homología de Secuencia de Aminoácido , Moldes GenéticosRESUMEN
The solution structure of a 15-mer nutRboxB RNA hairpin complexed with the 36-mer N-terminal peptide of the N protein (N36) from bacteriophage lambda was determined by 2D and 3D homonuclear and heteronuclear magnetic resonance spectroscopy. These 36 amino acids include the arginine-rich motif of the N protein involved in transcriptional antitermination of phage lambda. Upon complex formation with boxB RNA, the synthetic N36 peptide binds tightly to the major groove of the boxB hairpin through hydrophobic and electrostatic interactions forming a bent alpha helix. Four nucleotides of the GAAAA pentaloop of the boxB RNA adopt a GNRA-like tetraloop fold in the complex. The formation of a GAAA tetraloop involves a loop-closing sheared base pair (G6-A10), base stacking of three adenines (A7, A8, and A10), and extrusion of one nucleotide (A9) from the loop, as observed previously for the complex of N(1-22) peptide and the nutLboxB RNA [Legault, P., Li, J., Mogridge, J., Kay, L.E. & Greenblatt, J. (1998) Cell 93, 289-299]. Stacking of the bases is extended by the indole-ring of Trp18 which also forms hydrophobic contacts to the side-chains of Leu24, Leu25, and Val26. Based on the structure of the complex, three mutant peptides were synthesized and investigated by CD and NMR spectroscopy in order to determine the role of particular residues for complex formation. These studies revealed very distinct amino-acid requirements at positions 3, 4, and 8, while replacement of Trp18 with tyrosine did not result in any gross structural changes.
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Fragmentos de Péptidos/química , Proteínas de Unión al ARN/química , Ribonucleoproteínas/química , Secuencia de Aminoácidos , Proteínas Bacterianas/química , Dicroismo Circular , Escherichia coli/metabolismo , Regulación Viral de la Expresión Génica , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Datos de Secuencia Molecular , Mutación , Conformación de Ácido Nucleico , Oligorribonucleótidos/química , Estructura Secundaria de Proteína , ARN Viral/química , Proteínas Virales/química , Proteínas Reguladoras y Accesorias ViralesRESUMEN
Ferredoxins of the [Fe2S2] type function in photosynthetic electron transport as essential electron acceptors of photosystem I. The solution structure of the 97 amino acid ferredoxin from the thermophilic cyanobacterium Synechococcus elongatus was determined by nuclear magnetic resonance spectroscopy and restrained molecular dynamics calculations. The structure consists of a four-stranded parallel/ antiparallel beta-sheet, a short two-stranded antiparallel beta-sheet, and three short helices. The overall structure is similar to the structure of the ferredoxin from Anabaena. In contrast to related ferredoxins from mesophilic organisms, this thermostable protein contains a salt bridge inside a 17-amino acid hydrophobic core.