Identifying Superficial, Muscle-Invasive, and Metastasizing Transitional Cell Carcinoma of the Bladder

Modlich, Olga; Prisack, Hans-Bernd; Pitschke, Gerald; Ramp, Uwe; Ackermann, R.; Bojar, Hans; Vögeli, Thomas-Alexander; Grimm, Marc‐Oliver

doi:10.1158/1078-0432.ccr-03-0134

Cited by 99 publications

(69 citation statements)

References 53 publications

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“…The growth rate can be obtained indirectly by assessment of bromodeoxyuridine (BrdU) incorporation or antigen Ki67 expression (Limas et al, 1993). Related features such the proliferation an invasive potential can be accessed by micro-array analysis (Modlich et al, 2004). …”

Section: Discussionmentioning

confidence: 99%

Mathematical Model of BCG Immunotherapy in Superficial Bladder Cancer

Bunimovich‐Mendrazitsky

2007

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Immunotherapy with Bacillus Calmette-Guérin (BCG)-an attenuated strain of Mycobacterium bovis (M. bovis) used for anti tuberculosis immunization-is a clinically established procedure for the treatment of superficial bladder cancer. However, the mode of action has not yet been fully elucidated, despite much extensive biological experience. The purpose of this paper is to develop a first mathematical model that describes tumor-immune interactions in the bladder as a result of BCG therapy. A mathematical analysis of the ODE model identifies multiple equilibrium points, their stability properties, and bifurcation points. Intriguing regimes of bistability are identified in which treatment has potential to result in a tumor-free equilibrium or a full-blown tumor depending only on initial conditions. Attention is given to estimating parameters and validating the model using published data taken from in vitro, mouse and human studies. The model makes clear that intensity of immunotherapy must be kept in limited bounds. While small treatment levels may fail to clear the tumor, a treatment that is too large can lead to an over-stimulated immune system having dangerous side effects for the patient.

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Section: Discussionmentioning

confidence: 99%

Mathematical Model of BCG Immunotherapy in Superficial Bladder Cancer

Bunimovich‐Mendrazitsky

2007

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“…Gene-chip studies have demonstrated that UC can be clustered into different tumor stages and grades based on the overall gene expression profile alone. 96,97 Several gene clusters that characterize superficial or invasive tumors have been identified. Superficial tumors, in general, showed increased expression levels of genes involved in protein synthesis and metabolism as well as several genes involved in cell-cycle progression.…”

Section: Gene Expression Profiling Of Bladder Carcinoma: a Pipeline Omentioning

confidence: 99%

Genetic alterations in urothelial bladder carcinoma

Mhawech‐Fauceglia

Cheney

Schwaller

2006

Cancer

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New oncogenes and tumor suppressor genes that play an important role in the pathogenesis of urothelial bladder carcinoma have been discovered. The objectives of this review were to summarize the most important oncogenes and tumor suppressor genes involved in urothelial carcinoma and to address their role in pathogenesis, their prognostic value, and their potential use as therapeutic targets.The collected data led the authors to propose a common pathway in which the fibroblastic growth factor receptor 3 (FGFR3) mutation seems to be the earliest genetic abnormality responsible for the transformation from normal tissue to atypia and dysplasia. Three different progression pathways were proposed: The first operative pathway is from dysplasia to superficial papillary pathologic Ta

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“…In recent years, genome-wide expression profiling by the use of microarray technology has contributed to extensive and new insights into the complex gene expression patterns and dysregulation of genes occurring in urothelial neoplasias (Thykjaer et al, 2001;Dyrskjt et al, 2003Dyrskjt et al, , 2004Dyrskjt et al, , 2005Mor et al, 2003;SanchezCarbayo et al, 2003;Modlich et al, 2004;Blaveri et al, 2005;Kim et al, 2005;Wild et al, 2005). Microarray analyses have not only delineated gene expression profiles distinct for different histological subtypes (Thykjaer et al, 2001;Dyrskjt et al, 2003Dyrskjt et al, , 2004Sanchez-Carbayo et al, 2003;Blaveri et al, 2005;Wild et al, 2005), but also gene expression signatures of importance for tumor recurrence and progression (Dyrskjt et al, 2003(Dyrskjt et al, , 2005Modlich et al, 2004;Wild et al, 2005), and patient survival (Blaveri et al, 2005;Kim et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of early-stage bladder carcinomas by expression profiles, FGFR3 mutation status, and loss of 9q

et al. 2006

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We used gene expression profiling, mutation analyses of FGFR3 and TP53, and LOH analyses of chromosome 9 and the TP53 region on chromosome arm 17p, to molecularly characterize 75 Ta and T1 bladder carcinomas. We identified four major cellular processes related to cell cycle, protein synthesis, immune response, and extra cellular components that contribute to the expressional heterogeneity of early-stage urothelial cell carcinoma (UCC). Activating FGFR3 mutations were found at the highest frequency in G1 tumors (80%), and showed a strong correlation with FGFR3 expression. In contrast, G3 tumors displayed mutations in less than 10% of the cases and a low level of FGFR3 expression. Even though LOH on chromosome 9 was not associated with any specific expression pattern, our data indicate that loss of chromosome 9 is associated with tumor development rather than initiation. The combined analyses suggest the existence of two types of UCC tumors, one which is characterized by FGFR3 mutation or expression, high expression of protein synthesis genes, and low expression of cell cycle genes. Furthermore, the presented data underscore FGFR3 receptor involvement in urothelial cell transformation as the presence of FGFR3 mutations has a major impact on the global gene expression profile of bladder carcinomas.

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Identifying Superficial, Muscle-Invasive, and Metastasizing Transitional Cell Carcinoma of the Bladder

Abstract: Conclusions: Gene expression profiling of human bladder cancers provides insight into the biology of bladder cancer progression and identifies patients with distinct clinical phenotypes.

Cited by 99 publications

References 53 publications

Mathematical Model of BCG Immunotherapy in Superficial Bladder Cancer

Mathematical Model of BCG Immunotherapy in Superficial Bladder Cancer

Genetic alterations in urothelial bladder carcinoma

Molecular characterization of early-stage bladder carcinomas by expression profiles, FGFR3 mutation status, and loss of 9q

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