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Find video protocols related to scientific articles indexed in Pubmed.
Oncological outcomes of advanced muscle-invasive bladder cancer with a micropapillary variant after radical cystectomy and adjuvant platinum-based chemotherapy.
World J Urol
PUBLISHED: 09-02-2014
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To assess the oncological outcomes of radical cystectomy (RC) and adjuvant chemotherapy to treat muscle-invasive bladder cancer (MIBC) with a micropapillary component (MPC), and to compare outcomes with those from pure urothelial carcinoma (PUC).
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Inflammatory Biomarkers and Bladder Cancer Prognosis: A Systematic Review.
Eur. Urol.
PUBLISHED: 08-20-2014
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Host immune response has an impact on tumour development and progression. There is interest in the use of inflammatory biomarkers (InfBMs) in cancer care. Although several studies assessing the potential prognostic value of InfBMs in cancer have been published in the past decades, they have had no impact on the management of patients with urothelial bladder carcinoma (UBC).
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EGFR as a potential therapeutic target for a subset of muscle-invasive bladder cancers presenting a basal-like phenotype.
Sci Transl Med
PUBLISHED: 07-11-2014
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Muscle-invasive bladder carcinoma (MIBC) constitutes a heterogeneous group of tumors with a poor outcome. Molecular stratification of MIBC may identify clinically relevant tumor subgroups and help to provide effective targeted therapies. From seven series of large-scale transcriptomic data (383 tumors), we identified an MIBC subgroup accounting for 23.5% of MIBC, associated with shorter survival and displaying a basal-like phenotype, as shown by the expression of epithelial basal cell markers. Basal-like tumors presented an activation of the epidermal growth factor receptor (EGFR) pathway linked to frequent EGFR gains and activation of an EGFR autocrine loop. We used a 40-gene expression classifier derived from human tumors to identify human bladder cancer cell lines and a chemically induced mouse model of bladder cancer corresponding to human basal-like bladder cancer. We showed, in both models, that tumor cells were sensitive to anti-EGFR therapy. Our findings provide preclinical proof of concept that anti-EGFR therapy can be used to target a subset of particularly aggressive MIBC tumors expressing basal cell markers and provide diagnostic tools for identifying these tumors.
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Predicting the risk of harboring high-grade disease for patients diagnosed with prostate cancer scored as Gleason ? 6 on biopsy cores.
World J Urol
PUBLISHED: 06-15-2014
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Biopsy and final pathological Gleason score (GS) are inconstantly correlated with each other. The aim of the current study was to develop and validate a predictive score to screen patients diagnosed with a biopsy GS ? 6 prostate cancer (PCa) at risk of GS upgrading.
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MET is a potential target across all papillary renal cell carcinomas: result from a large molecular study of pRCC with CGH array and matching gene expression array.
Clin. Cancer Res.
PUBLISHED: 03-21-2014
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Papillary renal cell carcinomas (pRCC) are the most common nonclear cell RCC subtype. Germline mutations of the MET oncogene at 7q31 have been detected in patients with hereditary type I pRCC and in 13% of sporadic type I pRCC. Recent report of MET inhibition strengthened the role of c-Met inhibition across pRCC.
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DNA comparison between operative and biopsy specimens to investigate stage pT0 after radical prostatectomy.
World J Urol
PUBLISHED: 03-05-2014
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The aim was to eliminate, by DNA comparison, any identity mismatch between operative and biopsy specimens and to analyse the determinants of all pT0 prostate cancers occurred in a single institution.
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Prediction of recurrence of non muscle-invasive bladder cancer by means of a protein signature identified by antibody microarray analyses.
Proteomics
PUBLISHED: 02-05-2014
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About 70% of newly diagnosed cases of bladder cancer are low-stage, low-grade, non muscle-invasive. Standard treatment is transurethral resection. About 60% of the tumors will recur, however, and in part progress to become invasive. Therefore, surveillance cystoscopy is performed after resection. However, in the USA and Europe alone, about 54 000 new patients per year undergo repeated cystoscopies over several years, who do not experience recurrence. Analysing in a pilot study resected tumors from patients with (n = 19) and without local recurrence (n = 6) after a period of 5 years by means of an antibody microarray that targeted 724 cancer-related proteins, we identified 255 proteins with significantly differential abundance. Most are involved in the regulation and execution of apoptosis and cell proliferation. A multivariate classifier was constructed based on 20 proteins. It facilitates the prediction of recurrence with a sensitivity of 80% and a specificity of 100%. As a measure of overall accuracy, the area under the curve value was found to be 91%. After validation in additional sample cohorts with a similarly long follow-up, such a signature could support decision making about the stringency of surveillance or even different treatment options.
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Long-term impact of positive surgical margins on biochemical recurrence after radical prostatectomy: Ten years of follow-up.
Scand J Urol
PUBLISHED: 07-24-2013
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Abstract Objective. Positive surgical margins (PSMs) in men undergoing radical prostatectomy (RP) for prostate cancer are associated with an increased risk of biochemical recurrence. This study evaluated the long-term (>10 year) impact of PSMs on biochemical recurrence after RP in adjuvant treatment-naïve pT2-pT4 N0 men and determined predictors of prostate-specific antigen (PSA) failure. Material and methods. The institutional registry of 1276 patients who underwent RP at Henri Mondor Hospital from 1988 to 2001 was reviewed, identifying 403 patients with regular follow-up at the time of analysis. The study included 108 patients with PSMs who did not receive neoadjuvant or adjuvant therapy before PSA relapse. Median follow-up was 12.2 years. PSA failure was defined by a PSA rising by more than 0.2 ng/ml and biochemical recurrence-free survival (RFS) was estimated using the Kaplan-Meier method. Cox proportional hazard regression models were used to analyse clinicopathological variables associated with biochemical recurrence. Results. Biochemical recurrence 10 years after RP was 33.5% for patients regardless of the margin status. The 10-year biochemical RFS was 73% in men with negative margins compared to 49% in the case of PSM (p < 0.001). In multivariate analysis, margin status was a significantly predictive for PSA failure (hazard ratio 1.46, p = 0.04). After stratification by pathological stage, margin status was significantly predictive for biochemical RFS in pT2 (p < 0.001) and pT3a (p < 0.001), whereas the impact of PSM did not reach significance in pT3b (p = 0.16). Conclusions. After 10-year follow-up, PSMs remain an independent risk factor of biochemical RFS after RP with less relevant impact in pT3b disease. Randomized prospective trials are needed to determine the place of adjuvant versus delayed radiotherapy.
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Patient selection and pathological outcomes using currently available active surveillance criteria.
BJU Int.
PUBLISHED: 06-07-2013
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To establish the rate of higher risk criteria in various definitions of an active surveillance population.
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Cross modulation between the androgen receptor axis and protocadherin-PC in mediating neuroendocrine transdifferentiation and therapeutic resistance of prostate cancer.
Neoplasia
PUBLISHED: 04-14-2013
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Castration-resistant prostate cancers (CRPCs) that relapse after androgen deprivation therapies (ADTs) are responsible for the majority of mortalities from prostate cancer (PCa). While mechanisms enabling recurrent activity of androgen receptor (AR) are certainly involved in the development of CRPC, there may be factors that contribute to the process including acquired neuroendocrine (NE) cell-like behaviors working through alternate (non-AR) cell signaling systems or AR-dependent mechanisms. In this study, we explore the potential relationship between the AR axis and a novel putative marker of NE differentiation, the human male protocadherin-PC (PCDH-PC), in vitro and in human situations. We found evidence for an NE transdifferentiation process and PCDH-PC expression as an early-onset adaptive mechanism following ADT and elucidate AR as a key regulator of PCDH-PC expression. PCDH-PC overexpression, in turn, attenuates the ligand-dependent activity of the AR, enabling certain prostate tumor clones to assume a more NE phenotype and promoting their survival under diverse stress conditions. Acquisition of an NE phenotype by PCa cells positively correlated with resistance to cytotoxic agents including docetaxel, a taxane chemotherapy approved for the treatment of patients with metastatic CRPC. Furthermore, knockdown of PCDH-PC in cells that have undergone an NE transdifferentiation partially sensitized cells to docetaxel. Together, these results reveal a reciprocal regulation between the AR axis and PCDH-PC signals, observed both in vitro and in vivo, with potential implications in coordinating NE transdifferentiation processes and progression of PCa toward hormonal and chemoresistance.
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Concomitant High-Grade Prostatic Intraepithelial Neoplasia Is Associated with Good Prognosis Factors and Oncologic Outcome after Radical Prostatectomy.
Urol. Int.
PUBLISHED: 04-13-2013
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Objectives: To assess correlations between concomitant high-grade prostatic intraepithelial neoplasia (HGPIN), pathological features and oncologic outcomes after radical prostatectomy (RP). Material and Methods: We prospectively collected a single-institution database of 2,351 patients who underwent RP between 1998 and 2011. Results: 1,272 (54.1%) patients had HGPIN on specimens. The mean follow-up was 28 months. Presence of HGPIN was significantly associated with a favorable preoperative risk status and with pathological factors of poor prognosis in RP specimens. Patients without HGPIN had a worse biochemical recurrence-free survival compared with those with HGPIN in RP specimen (log-rank test: p = 0.015). The 3-year RFS rate was 73.9% for the HGPIN group versus 67.2%. The absence of HGPIN was also significantly correlated with the use of androgen deprivation treatment during the follow-up (p < 0.001). In Cox multivariate analysis, taking into account the other prognostic pathological factors, HGPIN was not an independent predictive factor for PSA failure (p = 0.868). Conclusion: HGPIN is associated with factors of good prognosis but fails to show independent significance when classical pathological prognostic factors are taken into account.
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Risk of repeat biopsy and prostate cancer detection after an initial extended negative biopsy: longitudinal follow-up from a prospective trial.
BJU Int.
PUBLISHED: 03-04-2013
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WHATS KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Even after a negative set of prostate biopsies, the risk of undetected prostate cancer remains clinically significant. Predictive markers of such a risk are undefined. In addition to PSA and PSAD, low prostate volume and %fPSA are interesting time-varying risk factors and are relevant in biopsy decision-making.
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PI3K/AKT pathway activation in bladder carcinogenesis.
Int. J. Cancer
PUBLISHED: 02-21-2013
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The PI3K/AKT pathway is considered to play a major role in bladder carcinogenesis, but its relationships with other molecular alterations observed in bladder cancer remain unknown. We investigated PI3K/AKT pathway activation in a series of human bladder urothelial carcinomas (UC) according to PTEN expression, PTEN deletions and FGFR3, PIK3CA, KRAS, HRAS, NRAS and TP53 gene mutations. The series included 6 normal bladder urothelial samples and 129 UC (Ta n = 25, T1 n = 34, T2-T3-T4 n = 70). Expression of phospho-AKT (pAKT), phospho-S6-Ribosomal Protein (pS6) (one downstream effector of PI3K/AKT pathway) and PTEN was evaluated by reverse phase protein Array. Expression of miR-21, miR-19a and miR-222, known to regulate PTEN expression, was also evaluated. pAKT expression levels were higher in tumors than in normal urothelium (p < 0.01), regardless of stage and showed a weak and positive correlation with pS6 (Spearman coefficient RS = 0.26; p = 0.002). No association was observed between pAKT or pS6 expression and the gene mutations studied. PTEN expression was decreased in PTEN-deleted tumors, and in T1 (p = 0.0089) and T2-T3-T4 (p < 0.001) tumors compared to Ta tumors; it was also negatively correlated with miR-19a (RS = -0.50; p = 0.0088) and miR-222 (RS = -0.48; p = 0.0132), but not miR-21 (RS = -0.27; p = 0.18) expression. pAKT and PTEN expressions were not negatively correlated, and, on the opposite, a positive and moderate correlation was observed in Ta (RS = 0.54; p = 0.0056) and T1 (RS = 0.56; p = 0.0006) tumors. Our study suggests that PI3K/AKT pathway activation occurs in the entire spectrum of bladder UC regardless of stage or known most frequent molecular alterations, and independently of low PTEN expression.
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An essential role for decorin in bladder cancer invasiveness.
EMBO Mol Med
PUBLISHED: 02-19-2013
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Muscle-invasive forms of urothelial carcinomas are responsible for most mortality in bladder cancer. Finding new treatments for invasive bladder tumours requires adequate animal models to decipher the mechanisms of progression, in particular the way tumours interact with their microenvironment. Herein, using the murine bladder tumour cell line MB49 and its more aggressive variant MB49-I, we demonstrate that the adaptive immune system efficiently limits progression of MB49, whereas MB49-I has lost tumour antigens and is insensitive to adaptive immune responses. Furthermore, we unravel a parallel mechanism developed by MB49-I to subvert its environment: de novo secretion of the proteoglycan decorin. We show that decorin overexpression in the MB49/MB49-I model is required for efficient progression, by promoting angiogenesis and tumour cell invasiveness. Finally, we show that these results are relevant to muscle-invasive human bladder carcinomas, which overexpress decorin together with angiogenesis- and adhesion/migration-related genes, and that decorin overexpression in the human bladder carcinoma cell line TCCSUP is required for efficient invasiveness in vitro. We thus propose decorin as a new therapeutic target for these aggressive tumours.
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Prediction of the risk of harboring prostate cancer by a prebiopsy nomogram based on extended biopsy protocol.
Urol. Int.
PUBLISHED: 01-05-2013
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We aimed to build a nomogram allowing to predict the probability of prostate cancer (PC) after an initial 21-core biopsy and with readily available clinical data.
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Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets.
Cancer Discov
PUBLISHED: 12-15-2011
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Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer that most commonly evolves from preexisting prostate adenocarcinoma (PCA). Using Next Generation RNA-sequencing and oligonucleotide arrays, we profiled 7 NEPC, 30 PCA, and 5 benign prostate tissue (BEN), and validated findings on tumors from a large cohort of patients (37 NEPC, 169 PCA, 22 BEN) using IHC and FISH. We discovered significant overexpression and gene amplification of AURKA and MYCN in 40% of NEPC and 5% of PCA, respectively, and evidence that that they cooperate to induce a neuroendocrine phenotype in prostate cells. There was dramatic and enhanced sensitivity of NEPC (and MYCN overexpressing PCA) to Aurora kinase inhibitor therapy both in vitro and in vivo, with complete suppression of neuroendocrine marker expression following treatment. We propose that alterations in Aurora kinase A and N-myc are involved in the development of NEPC, and future clinical trials will help determine from the efficacy of Aurora kinase inhibitor therapy.
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Evaluation of combined oncologic and functional outcomes after robotic-assisted laparoscopic extraperitoneal radical prostatectomy: trifecta rate of achieving continence, potency and cancer control.
Urol. Oncol.
PUBLISHED: 06-29-2011
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Outcomes of continence, erectile function, and oncologic control are well-described in isolation especially for the retropubic open approach. However, only few series have yet reported combined results after radical prostatectomy. To determine the proportion of men who are continent, potent, and cancer-free (trifecta rate) 2 years after robot-assisted laparoscopic radical prostatectomy (RALRP).
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Kidney cancer pathology in the new context of targeted therapy.
Pathobiology
PUBLISHED: 06-14-2011
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The outcome in metastatic renal cancer remains poor with an overall survival at 5 years of less than 10%. However, molecular pathology in kidney cancer has developed extensively in the few last years, providing a basis for new systemic therapies including antiangiogenic drugs and mTOR inhibitors. Use of these targeted therapies in metastatic disease has improved the prognosis but still in a too-limited range, with a lack of consistent predictive biomarkers. The multiple entities of renal tumors add complexity to the research of biomarkers and the design of clinical trials. This review aims to focus on pathways in renal cancer (VHL/HIF, mTOR, c-MYC, c-MET, and immune response) in the respective tumor subtypes, accounting for the effects of targeted therapies and providing the framework to search for relevant predictive biomarkers and propose new trials. This overview underscores that the pathways are often intermingled and common (at least partially) to the different tumor subtypes.
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The risk of upstaged disease increases with body mass index in low-risk prostate cancer patients eligible for active surveillance.
Eur. Urol.
PUBLISHED: 06-11-2011
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Obese patients have a greater risk of adverse pathologic features and biochemical recurrence after radical prostatectomy (RP). The impact of body mass index (BMI) on the risk of reclassification and deferred treatment in active surveillance (AS) programs has not been thoroughly assessed.
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Toward a standardized urine proteome analysis methodology.
Proteomics
PUBLISHED: 02-16-2011
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Urine is an easily accessible bodily fluid particularly suited for the routine clinical analysis of disease biomarkers. Actually, the urinary proteome is more diverse than anticipated a decade ago. Hence, significant analytical and practical issues of urine proteomics such as sample collection and preparation have emerged, in particular for large-scale studies. We have undertaken a systematic study to define standardized and integrated analytical protocols for a biomarker development pipeline, employing two LC-MS analytical platforms, namely accurate mass and time tags and selected reaction monitoring, for the discovery and verification phase, respectively. Urine samples collected from hospital patients were processed using four different protocols, which were evaluated and compared on both analytical platforms. Addition of internal standards at various stages of sample processing allowed the estimation of protein extraction yields and the absolute quantification of selected urinary proteins. Reproducibility of the entire process and dynamic range of quantification were also evaluated. Organic solvent precipitation followed by in-solution digestion provided the best performances and was thus selected as the standard method common to the discovery and verification phases. Finally, we applied this protocol for platforms cross-validation and obtained excellent consistency between urinary protein concentration estimates by both analytical methods performed in parallel in two laboratories.
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Mid-term oncological control after laparoscopic radical cystectomy in men: a single-centre experience.
BJU Int.
PUBLISHED: 02-14-2011
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• To assess the mid-term (3 years of follow-up) oncological control of laparoscopic radical cystectomy (LRC) for high-grade muscle-invasive bladder cancer in a well studied male population.
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A novel epigenetic phenotype associated with the most aggressive pathway of bladder tumor progression.
J. Natl. Cancer Inst.
PUBLISHED: 12-20-2010
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Epigenetic silencing can extend to whole chromosomal regions in cancer. There have been few genome-wide studies exploring its involvement in tumorigenesis.
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Low pretreatment total testosterone (< 3 ng/mL) predicts extraprostatic disease in prostatectomy specimens from patients with preoperative localized prostate cancer.
BJU Int.
PUBLISHED: 11-02-2010
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• To investigate the relationship between pretreatment testosterone levels and pathological specimen characteristics, by prospectively examining serum androgen concentrations in a well-studied cohort of patients who underwent radical prostatectomy (RP) for localized prostate cancer.
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Class III beta-tubulin expression predicts prostate tumor aggressiveness and patient response to docetaxel-based chemotherapy.
Cancer Res.
PUBLISHED: 11-02-2010
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Expression of class III ?-tubulin (?III-tubulin) correlates with tumor progression and resistance to taxane-based therapies for several human malignancies, but its use as a biomarker of tumor behavior in prostate cancer (PCa) remains largely unexplored. Here, we describe ?III-tubulin immunohistochemical staining patterns of prostate tumors obtained from a broad spectrum of PCa patients, some of whom subsequently received docetaxel therapy for castration-resistant PCa (CRPC). Elevated ?III-tubulin expression was significantly associated with tumor aggressiveness in PCa patients with presumed localized disease, as it was found to be an independent marker of biochemical recurrence after treatment. Additionally, ?III-tubulin expression in tumor cells was an independent predictor of lower overall survival for patients receiving docetaxel-based chemotherapy for CRPC. Manipulation of ?III-tubulin expression in human PCa cell lines using a human ?III-tubulin expression vector or ?III-tubulin small interfering RNA altered cell survival in response to docetaxel treatment in a manner that supports a role for ?III-tubulin expression as a mediator of PCa cell resistance to docetaxel therapy. Our findings suggest a role for ?III-tubulin as candidate theranostic biomarker to predict the response to docetaxel-based chemotherapy as well as to target for treatment of docetaxel-resistant CRPC.
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Expression of follicle-stimulating hormone receptor in tumor blood vessels.
N. Engl. J. Med.
PUBLISHED: 10-22-2010
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In adult humans, the follicle-stimulating hormone (FSH) receptor is expressed only in the granulosa cells of the ovary and the Sertoli cells of the testis. It is minimally expressed by the endothelial cells of gonadal blood vessels.
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Transforming growth factor ?-receptor II protein expression in benign prostatic hyperplasia is associated with prostate volume and inflammation.
BJU Int.
PUBLISHED: 09-14-2010
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To assess transforming growth factor ?-receptor II (TGFBRII) protein expression in benign prostatic hyperplasia (BPH) using immunohistochemistry analysis, and to compare the analysis with phenotypic properties.
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Impact of the primary Gleason pattern on biochemical recurrence-free survival after radical prostatectomy: a single-center cohort of 1,248 patients with Gleason 7 tumors.
World J Urol
PUBLISHED: 09-03-2010
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We aimed to evaluate the impact of the primary Gleason pattern on biochemical recurrence-free survival (RFS) after radical prostatectomy (RP) in a single-center cohort of patients with Gleason 7 tumors.
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Identification of a novel biomarker signature associated with risk for bone metastasis in patients with renal cell carcinoma.
Int. J. Biol. Markers
PUBLISHED: 06-15-2010
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When renal cell carcinoma (RCC) metastasizes to bone (a frequent site of systemic spread of this cancer) it becomes highly resistant to radiation therapy and chemotherapy. A better understanding of the biology of bone metastasis in RCC may permit to identify biomarkers for early detection of subclinical disease and better stratification of patients prior to treatment. We therefore investigated in this study, using a multiplex real-time RT-PCR assay, the expression of a panel of 16 biomarkers involved in angiogenesis and tumor invasion; the panel was applied to primary tumors and normal tissues obtained from clear-cell RCC patients with and without bone metastases. We identified a novel combination of biomarkers associated with the risk of bone metastasis. Among the transcripts of the genes studied, VEGFR-1, VEGFR-2, HIF-1alpha, uPA , and PA I-1 overexpression in tumor tissues was significantly associated with the presence of bone metastasis (p=0.02, p=0.02, p<0.0001, p=0.04, and p=0.03, respectively). No differences were found in the expression of these transcripts in the corresponding normal tissues. This preliminary study provides a promising tool that may help in the management of RCC patients with bone metastasis. Indeed, these predictive markers could be useful to identify subclinical disease, improve staging, and guide treatment decisions.
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Abrogation of de novo lipogenesis by stearoyl-CoA desaturase 1 inhibition interferes with oncogenic signaling and blocks prostate cancer progression in mice.
Mol. Cancer Ther.
PUBLISHED: 06-08-2010
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Increased de novo fatty acid (FA) synthesis is one hallmark of tumor cells, including prostate cancer. We present here our most recent results showing that lipid composition in human prostate cancer is characterized by an increased ratio of monounsaturated FA to saturated FA, compared with normal prostate, and evidence the overexpression of the lipogenic enzyme stearoyl-CoA desaturase 1 (SCD1) in human prostate cancer. As a new therapeutic strategy, we show that pharmacologic inhibition of SCD1 activity impairs lipid synthesis and results in decreased proliferation of both androgen-sensitive and androgen-resistant prostate cancer cells, abrogates the growth of prostate tumor xenografts in nude mice, and confers therapeutic benefit on animal survival. We show that these changes in lipid synthesis are translated into the inhibition of the AKT pathway and that the decrease in concentration of phosphatidylinositol-3,4,5-trisphosphate might at least partially mediate this effect. Inhibition of SCD1 also promotes the activation of AMP-activated kinase and glycogen synthase kinase 3alpha/beta, the latter on being consistent with a decrease in beta-catenin activity and mRNA levels of various beta-catenin growth-promoting transcriptional targets. Furthermore, we show that SCD1 activity is required for cell transformation by Ras oncogene. Together, our data support for the first time the concept of targeting the lipogenic enzyme SCD1 as a new promising therapeutic approach to block oncogenesis and prostate cancer progression.
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Soluble isoforms of vascular endothelial growth factor are predictors of response to sunitinib in metastatic renal cell carcinomas.
PLoS ONE
PUBLISHED: 04-22-2010
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Angiogenesis is the target of several agents in the treatment of malignancies, including renal cell carcinoma (RCC). There is a real need for surrogate biomarkers that can predict selection of patients who may benefit from antiangiogenic therapies, prediction of disease outcome and which may improve the knowledge regarding mechanism of action of these treatments. Tyrosine kinase inhibitors (TKI) have proven efficacy in metastatic RCC (mRCC). However, the molecular mechanisms underlying the clinical response to these drugs remain unclear.
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The role of tumor-free status in repeat resection before intravesical bacillus Calmette-Guerin for high grade Ta, T1 and CIS bladder cancer.
J. Urol.
PUBLISHED: 04-20-2010
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We evaluated the outcome of repeat transurethral bladder tumor resection for high risk nonmuscle invasive bladder cancer before induction and maintenance bacillus Calmette-Guerin.
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Analysis of the copy number profiles of several tumor samples from the same patient reveals the successive steps in tumorigenesis.
Genome Biol.
PUBLISHED: 04-12-2010
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We present a computational method, TuMult, for reconstructing the sequence of copy number changes driving carcinogenesis, based on the analysis of several tumor samples from the same patient. We demonstrate the reliability of the method with simulated data, and describe applications to three different cancers, showing that TuMult is a valuable tool for the establishment of clonal relationships between tumor samples and the identification of chromosome aberrations occurring at crucial steps in cancer progression.
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Evaluation of combined oncological and functional outcomes after radical prostatectomy: trifecta rate of achieving continence, potency and cancer control--a literature review.
Urology
PUBLISHED: 03-02-2010
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The first objective of radical prostatectomy is cancer control. However, the success of RP should be also measured by the long-term morbidity outcomes and by the maintenance of quality of life. We performed a review of the literature for combined results of continence, erectile function, and cancer control after radical prostatectomy. Since 2003 and the first report of "trifecta," only 7 series have yet reported such combined results (trifecta rate range: 20%-76%). The preoperative risk (DAmico) predicted for quality of life outcomes and biochemical recurrence is an aggregate endpoint, the trifecta.
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Inflammation in benign prostatic hyperplasia: a 282 patients immunohistochemical analysis.
Prostate
PUBLISHED: 08-12-2009
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Prostatic inflammation could be a key component in prostate enlargement and benign prostatic hyperplasia (BPH) progression. Our aim was to characterize inflammatory cells infiltrate within BPH tissue and to correlate inflammation and clinical data.
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Pathological findings and prostate specific antigen outcomes after radical prostatectomy in men eligible for active surveillance--does the risk of misclassification vary according to biopsy criteria?
J. Urol.
PUBLISHED: 06-07-2009
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We compared the pathological findings and prostate specific antigen outcome after radical prostatectomy in men eligible for active surveillance according to 3 biopsy inclusion criteria.
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Is robot assistance affecting operating room time compared with pure retroperitoneal laparoscopic radical prostatectomy?
J. Endourol.
PUBLISHED: 05-29-2009
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To compare operating room times between retroperitoneal robot-assisted laparoscopic radical prostatectomy (RALRP) and pure retroperitoneal laparoscopic radical prostatectomy (LRP).
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Predicting tumour location in radical prostatectomy specimens: same-patient comparisons of 21-sample versus sextant biopsy.
BJU Int.
PUBLISHED: 05-18-2009
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To determine the value of a 21-sample biopsy protocol in predicting tumour localization in radical prostatectomy (RP) specimens, compared with sextant biopsies.
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The role of biopsy core number in selecting prostate cancer patients for active surveillance.
Eur. Urol.
PUBLISHED: 05-06-2009
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Studies offer wide variations in inclusion criteria for active surveillance (AS) in prostate cancer (PCa), but the role of the biopsy core number has not been thoroughly assessed.
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Prognostic significance of microscopic bladder neck invasion in prostate cancer.
BJU Int.
PUBLISHED: 04-10-2009
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To assess the prognostic significance of microscopic bladder neck invasion (BNI+) after radical prostatectomy (RP).
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Extensive biopsies and transurethral prostate resection in men with previous negative biopsies and high or increasing prostate specific antigen.
J. Urol.
PUBLISHED: 02-25-2009
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We determined the diagnostic role of an extensive biopsy protocol associated with transurethral prostate resection in patients with persistently increased or increasing prostate specific antigen without evidence of prostate cancer after 2 or more extended negative sets of biopsies.
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High-grade prostatic intraepithelial neoplasia and atypical small acinar proliferation on initial 21-core extended biopsy scheme: incidence and implications for patient care and surveillance.
World J Urol
PUBLISHED: 02-10-2009
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To evaluate the incidence of high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP) in an initial 21-core extended biopsy scheme and to determine the prostate cancer detection rate in the repeated biopsy.
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A meta-analysis of the relationship between FGFR3 and TP53 mutations in bladder cancer.
PLoS ONE
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TP53 and FGFR3 mutations are the most common mutations in bladder cancers. FGFR3 mutations are most frequent in low-grade low-stage tumours, whereas TP53 mutations are most frequent in high-grade high-stage tumours. Several studies have reported FGFR3 and TP53 mutations to be mutually exclusive events, whereas others have reported them to be independent. We carried out a meta-analysis of published findings for FGFR3 and TP53 mutations in bladder cancer (535 tumours, 6 publications) and additional unpublished data for 382 tumours. TP53 and FGFR3 mutations were not independent events for all tumours considered together (OR?=?0.25 [0.18-0.37], p?=?0.0001) or for pT1 tumours alone (OR?=?0.47 [0.28-0.79], p?=?0.0009). However, if the analysis was restricted to pTa tumours or to muscle-invasive tumours alone, FGFR3 and TP53 mutations were independent events (OR?=?0.56 [0.23-1.36] (p?=?0.12) and OR?=?0.99 [0.37-2.7] (p?=?0.35), respectively). After stratification of the tumours by stage and grade, no dependence was detected in the five tumour groups considered (pTaG1 and pTaG2 together, pTaG3, pT1G2, pT1G3, pT2-4). These differences in findings can be attributed to the putative existence of two different pathways of tumour progression in bladder cancer: the CIS pathway, in which FGFR3 mutations are rare, and the Ta pathway, in which FGFR3 mutations are frequent. TP53 mutations occur at the earliest stage of the CIS pathway, whereas they occur would much later in the Ta pathway, at the T1G3 or muscle-invasive stage.
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External validation of extranodal extension and lymph node density as predictors of survival in node-positive bladder cancer after radical cystectomy.
Ann. Surg. Oncol.
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Prognostic factors in pathologic node-positive patients after radical cystectomy are debated. Extranodal extension (ENE) and lymph node density (LND) are strong predictors of survival. The aim of this study was to assess factors predictive of survival and to evaluate the prognostic significance of the tumor, node, metastasis staging system (TNM) nodal classification in a retrospective cohort of node-positive bladder cancers after radical cystectomy.
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Plasma 25-hydroxyvitamin D(3) and bladder cancer risk according to tumor stage and FGFR3 status: a mechanism-based epidemiological study.
J. Natl. Cancer Inst.
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Previous evidence suggests that 25-hydroxyvitamin D(3) [25(OH)D(3)] protects against several cancers. However, little is known regarding urothelial bladder cancer (UBC). We analyzed the association between plasma 25(OH)D(3) and overall risk of UBC, as well as according to stage and FGFR3 molecular subphenotypes.
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Analysis of outcomes after radical prostatectomy in patients eligible for active surveillance (PRIAS).
BJU Int.
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To identify the risk of failure of active surveillance (AS) in men who had the Prostate Cancer Research International: Active Surveillance (PRIAS) criteria and had undergone radical prostatectomy (RP), by studying as primary endpoints the risk of unfavourable disease in RP specimens (stage >T2 and/or Gleason score >6) and of biochemical progression after RP.
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Deregulation of Rab and Rab effector genes in bladder cancer.
PLoS ONE
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Growing evidence indicates that Rab GTPases, key regulators of intracellular transport in eukaryotic cells, play an important role in cancer. We analysed the deregulation at the transcriptional level of the genes encoding Rab proteins and Rab-interacting proteins in bladder cancer pathogenesis, distinguishing between the two main progression pathways so far identified in bladder cancer: the Ta pathway characterized by a high frequency of FGFR3 mutation and the carcinoma in situ pathway where no or infrequent FGFR3 mutations have been identified. A systematic literature search identified 61 genes encoding Rab proteins and 223 genes encoding Rab-interacting proteins. Transcriptomic data were obtained for normal urothelium samples and for two independent bladder cancer data sets corresponding to 152 and 75 tumors. Gene deregulation was analysed with the SAM (significant analysis of microarray) test or the binomial test. Overall, 30 genes were down-regulated, and 13 were up-regulated in the tumor samples. Five of these deregulated genes (LEPRE1, MICAL2, RAB23, STXBP1, SYTL1) were specifically deregulated in FGFR3-non-mutated muscle-invasive tumors. No gene encoding a Rab or Rab-interacting protein was found to be specifically deregulated in FGFR3-mutated tumors. Cluster analysis showed that the RAB27 gene cluster (comprising the genes encoding RAB27 and its interacting partners) was deregulated and that this deregulation was associated with both pathways of bladder cancer pathogenesis. Finally, we found that the expression of KIF20A and ZWINT was associated with that of proliferation markers and that the expression of MLPH, MYO5B, RAB11A, RAB11FIP1, RAB20 and SYTL2 was associated with that of urothelial cell differentiation markers. This systematic analysis of Rab and Rab effector gene deregulation in bladder cancer, taking relevant tumor subgroups into account, provides insight into the possible roles of Rab proteins and their effectors in bladder cancer pathogenesis. This approach is applicable to other group of genes and types of cancer.
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SMARCB1/INI1 inactivation in renal medullary carcinoma.
Histopathology
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Renal medullary carcinoma (RMC), a rare and highly aggressive tumour which occurs in patients with sickle-cell disease, shares many clinicopathological features with collecting duct carcinoma (CDC). The molecular mechanisms underlying RMC and CDC are mainly unknown, and there is ongoing debate about their status as distinct entities. Loss of expression of SMARCB1/INI1, a chromatin remodelling regulator and repressor of cyclin D1 transcription, has been reported recently in RMC. The aim of our study was to investigate if such loss of expression is specific for RMC. SMARCB1/INI1 genetic alterations and cyclin D1 expression were also studied.
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CDKN2A homozygous deletion is associated with muscle invasion in FGFR3-mutated urothelial bladder carcinoma.
J. Pathol.
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The gene cyclin-dependent kinase inhibitor 2A (CDKN2A) is frequently inactivated by deletion in bladder carcinoma. However, its role in bladder tumourigenesis remains unclear. We investigated the role of CDKN2A deletion in urothelial carcinogenesis, as a function of FGFR3 mutation status, a marker for one of the two pathways of bladder tumour progression, the Ta pathway. We studied 288 bladder carcinomas: 177 non-muscle-invasive (123 Ta, 54 T1) and 111 muscle-invasive (T2-4) tumours. CDKN2A copy number was determined by multiplex ligation-dependent probe amplification, and FGFR3 mutations by SNaPshot analysis. FGFR3 mutation was detected in 124 tumours (43.1%) and CDKN2A homozygous deletion in 56 tumours (19.4%). CDKN2A homozygous deletion was significantly more frequent in FGFR3-mutated tumours than in wild-type FGFR3 tumours (p = 0.0015). This event was associated with muscle-invasive tumours within the FGFR3-mutated subgroup (p < 0.0001) but not in wild-type FGFR3 tumours. Similar findings were obtained for an independent series of 101 bladder carcinomas. The impact of CDKN2A deletions on recurrence-free and progression-free survival was then analysed in 89 patients with non-muscle-invasive FGFR3-mutated tumours. Kaplan-Meier survival analysis showed that CDKN2A losses (hemizygous and homozygous) were associated with progression (p = 0.0002), but not with recurrence, in these tumours. Multivariate Cox regression analysis identified CDKN2A loss as a predictor of progression independent of stage and grade. These findings highlight the crucial role of CDKN2A loss in the progression of non-muscle-invasive FGFR3-mutated bladder carcinomas and provide a potentially useful clinical marker for adapting the treatment of such tumours, which account for about 50% of cases at initial clinical presentation.
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Detailed biopsy pathologic features as predictive factors for initial reclassification in prostate cancer patients eligible for active surveillance.
Urol. Oncol.
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To evaluate the impact of detailed biopsy characteristics such as positive cores location or multifocality on the risk of initial reclassification in prostate cancer (CaP) patients eligible for active surveillance (AS).
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The value of urinary prostate cancer gene 3 (PCA3) scores in predicting pathological features at radical prostatectomy.
BJU Int.
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Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b Whats known on the subject? and What does the study add? PCA3 scores correlate to numerous histoprognostic factors, specifically tumour volume and positive surgical margins. These results may have a clinical impact in the near future on the selection of patients eligible to undergo active surveillance and nerve-sparing surgery.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.