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Träfflista för sökning "WFRF:(Lerner Seth P) ;lar1:(lu)"

Sökning: WFRF:(Lerner Seth P) > Lunds universitet

  • Resultat 1-6 av 6
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1.
  • Kamoun, Aurélie, et al. (författare)
  • A Consensus Molecular Classification of Muscle-invasive Bladder Cancer
  • 2020
  • Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 77:4, s. 420-433
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Muscle-invasive bladder cancer (MIBC) is a molecularly diverse disease with heterogeneous clinical outcomes. Several molecular classifications have been proposed, but the diversity of their subtype sets impedes their clinical application. Objective: To achieve an international consensus on MIBC molecular subtypes that reconciles the published classification schemes. Design, setting, and participants: We used 1750 MIBC transcriptomic profiles from 16 published datasets and two additional cohorts. Outcome measurements and statistical analysis: We performed a network-based analysis of six independent MIBC classification systems to identify a consensus set of molecular classes. Association with survival was assessed using multivariable Cox models. Results and limitations: We report the results of an international effort to reach a consensus on MIBC molecular subtypes. We identified a consensus set of six molecular classes: luminal papillary (24%), luminal nonspecified (8%), luminal unstable (15%), stroma-rich (15%), basal/squamous (35%), and neuroendocrine-like (3%). These consensus classes differ regarding underlying oncogenic mechanisms, infiltration by immune and stromal cells, and histological and clinical characteristics, including outcomes. We provide a single-sample classifier that assigns a consensus class label to a tumor sample's transcriptome. Limitations of the work are retrospective clinical data collection and a lack of complete information regarding patient treatment. Conclusions: This consensus system offers a robust framework that will enable testing and validation of predictive biomarkers in future prospective clinical trials. Patient summary: Bladder cancers are heterogeneous at the molecular level, and scientists have proposed several classifications into sets of molecular classes. While these classifications may be useful to stratify patients for prognosis or response to treatment, a consensus classification would facilitate the clinical use of molecular classes. Conducted by multidisciplinary expert teams in the field, this study proposes such a consensus and provides a tool for applying the consensus classification in the clinical setting.
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  • Lawrentschuk, Nathan, et al. (författare)
  • Prevention and Management of Complications Following Radical Cystectomy for Bladder Cancer
  • 2010
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 57:6, s. 983-1001
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: This review focuses on the prevention and management of complications following radical cystectomy (RC) for bladder cancer (BCa). Objective: We review the current literature and perform an analysis of the frequency, treatment, and prevention of complications related to RC for BCa. Evidence acquisition: A Medline search was conducted to identify original articles, reviews, and editorials addressing the relationship between RC and short- and long-term complications. Series examined were published within the past decade. Large series reported on multiple occasions (Lee [1], Meyer [2], and Chang and Cookson [3]) with the same cohorts are recorded only once. Quality of life (QoL) and sexual function were excluded. Evidence synthesis: The literature regarding prophylaxis, prevention, and treatment of complications of RC in general is retrospective, not standardised. In general, it is of poor quality when it comes to evidence and is thus difficult to synthesise. Conclusions: Progress has been made in reducing mortality and preventing complications of RC. Postoperative morbidity remains high, partly because of the complexity of the procedures. The issues of surgical volume and standardised prospective reporting of RC morbidity to create evidence-based guidelines are essential for further reducing morbidity and improving patients' QoL. (C) 2010 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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4.
  • Choi, Woonyoung, et al. (författare)
  • Genetic Alterations in the Molecular Subtypes of Bladder Cancer : Illustration in the Cancer Genome Atlas Dataset
  • 2017
  • Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 72:3, s. 354-365
  • Forskningsöversikt (refereegranskat)abstract
    • Context: Recent whole genome mRNA expression profiling studies revealed that bladder cancers can be grouped into molecular subtypes, some of which share clinical properties and gene expression patterns with the intrinsic subtypes of breast cancer and the molecular subtypes found in other solid tumors. The molecular subtypes in other solid tumors are enriched with specific mutations and copy number aberrations that are thought to underlie their distinct progression patterns, and biological and clinical properties. Objective: The availability of comprehensive genomic data from The Cancer Genome Atlas (TCGA) and other large projects made it possible to correlate the presence of DNA alterations with tumor molecular subtype membership. Our overall goal was to determine whether specific DNA mutations and/or copy number variations are enriched in specific molecular subtypes. Evidence: We used the complete TCGA RNA-seq dataset and three different published classifiers developed by our groups to assign TCGA's bladder cancers to molecular subtypes, and examined the prevalence of the most common DNA alterations within them. We interpreted the results against the background of what was known from the published literature about the prevalence of these alterations in nonmuscle-invasive and muscle-invasive bladder cancers. Evidence synthesis: The results confirmed that alterations involving RB1 and NFE2L2 were enriched in basal cancers, whereas alterations involving FGFR3 and KDM6A were enriched in luminal tumors. Conclusions: The results further reinforce the conclusion that the molecular subtypes of bladder cancer are distinct disease entities with specific genetic alterations. Patient summary: Our observation showed that some of subtype-enriched mutations and copy number aberrations are clinically actionable, which has direct implications for the clinical management of patients with bladder cancer. We analyzed the prevalence of the most common genomic alterations in the bladder cancer molecular subtypes. The results have important implications for our understanding of bladder cancer etiology and the development of molecular subtype-specific therapies.
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5.
  • Meeks, Joshua J., et al. (författare)
  • Tumor Subtyping : Making Sense of Heterogeneity with a Goal Toward Treatment
  • 2021
  • Ingår i: Bladder Cancer. - 2352-3727. ; 7:1, s. 1-11
  • Forskningsöversikt (refereegranskat)abstract
    • BACKGROUND: Bladder cancers have high total mutation burdens resulting in genomic diversity and intra-and inter-tumor heterogeneity that may impact the diversity of gene expression, biologic aggressiveness, and potentially response to therapy. To compare bladder cancers among patients, an organizational structure is necessary that describes the tumor at the histologic and molecular level. These 'molecular subtypes', or 'expression subtypes' of bladder cancer were originally described in 2010 and continue to evolve secondary to next generation sequencing (NGS) and an increasing public repository of well-annotated cohorts. OBJECTIVE: To review the history and methodology of expression-based subtyping of non-muscle invasive (NMIBC) and muscle invasive bladder cancer (MIBC). METHODS: A literature review was performed of primary papers from PubMed that described subtyping methods and their descriptive feature including search terms of 'subtype', and 'bladder cancer'. RESULTS: 21 papers were identified for review. Tumor subtyping developed from N = 2 to N = 6 subtyping schemes with most subtypes comprised of at least luminal and basal tumors. Most NMIBCs are luminal cancers and luminal MIBCs may be associated with less aggressive features, while one study of basal tumors identified a better clinical outcome with systemic chemotherapy. Tumors with a P53-like may have intrinsic resistance to chemotherapy. The heterogeneity of tumors, which is likely derived from stromal components and immune cell infiltration, affect subtype calls. CONCLUSION: Subtyping, while still evolving, is ready for testing in clinical trials. Improved patient selection with tumor subtyping may help with tumor classification and potentially match patient or tumor to therapy.
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6.
  • Seiler, Roland, et al. (författare)
  • Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy
  • 2017
  • Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 72:4, s. 544-554
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: An early report on the molecular subtyping of muscle-invasive bladder cancer (MIBC) by gene expression suggested that response to neoadjuvant chemotherapy (NAC) varies by subtype. Objective: To investigate the ability of molecular subtypes to predict pathological downstaging and survival after NAC. Design, setting, and participants: Whole transcriptome profiling was performed on pre-NAC transurethral resection specimens from 343 patients with MIBC. Samples were classified according to four published molecular subtyping methods. We developed a single-sample genomic subtyping classifier (GSC) to predict consensus subtypes (claudin-low, basal, luminal-infiltrated and luminal) with highest clinical impact in the context of NAC. Overall survival (OS) according to subtype was analyzed and compared with OS in 476 non-NAC cases (published datasets). Intervention: Gene expression analysis was used to assign subtypes. Outcome measurements and statistical analysis: Receiver-operating characteristics were used to determine the accuracy of GSC. The effect of GSC on survival was estimated by Cox proportional hazard regression models. Results and limitations: The models generated subtype calls in expected ratios with high concordance across subtyping methods. GSC was able to predict four consensus molecular subtypes with high accuracy (73%), and clinical significance of the predicted consensus subtypes could be validated in independent NAC and non-NAC datasets. Luminal tumors had the best OS with and without NAC. Claudin-low tumors were associated with poor OS irrespective of treatment regimen. Basal tumors showed the most improvement in OS with NAC compared with surgery alone. The main limitations of our study are its retrospective design and comparison across datasets. Conclusions: Molecular subtyping may have an impact on patient benefit to NAC. If validated in additional studies, our results suggest that patients with basal tumors should be prioritized for NAC. We discovered the first single-sample classifier to subtype MIBC, which may be suitable for integration into routine clinical practice. Patient summary: Different molecular subtypes can be identified in muscle-invasive bladder cancer. Although cisplatin-based neoadjuvant chemotherapy improves patient outcomes, we identified that the benefit is highest in patients with basal tumors. Our newly discovered classifier can identify these molecular subtypes in a single patient and could be integrated into routine clinical practice after further validation. Molecular subtypes in muscle-invasive bladder cancer appear have an impact on patient response to neoadjuvant chemotherapy (NAC); namely, patients with basal tumors showed the most benefit from NAC and should be prioritized for NAC. Moreover, these subtypes can be identified in a single sample by our discovered classifier.
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