Molecular and Immunohistochemical Analysis of the Prognostic Value of Cell-Cycle Regulators in Urothelial Neoplasms of the Bladder

Yurakh, A.O.; Ramos, David; Calabuig, Silvia; Löpez‐Guerrero, José Antonio; Rubio, José; Solsona, E.; Romanenko, Alina; Vozianov, Alexander; Pellı́n, Antonio; Llombart‐Bosch, Antonio

doi:10.1016/j.eururo.2006.03.027

Cited by 71 publications

(44 citation statements)

References 41 publications

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“…Malats et al [33] reviewed the published p53 studies and noted that altered p53 expression was an independent prognostic factor for tumor recurrence in nine of 34 reports, for progression in 12 of 24, and for survival in 10 of 35. Several recent small studies reported no association between p53 immunohistochemistry and outcome [34,35]. In a large tissue microarray study containing specimens from over 400 bladder cancer patients, however, the proportion of altered p53 gradually increased from normal urothelium to non-muscle-invasive bladder cancer to carcinoma in situ to muscle-invasive bladder cancer, and was highest in metastatic lymph node specimens [36][37][38].…”

Section: The P53 Signaling Pathwaymentioning

confidence: 94%

Molecular markers in bladder cancer

Shariat

Karam

Lerner

2008

Current Opinion in Urology

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Molecular biology is paramount to our understanding of bladder cancer pathogenesis. The search for new markers, and elucidating cross-talk between markers in different pathways, is warranted. Molecular markers have the potential benefit of improving detection, prognosis and treatment of bladder cancer. In addition, understanding the molecular profile of the individual patient could usher us into a new era of improving prediction of the natural history of the disease and providing a more personalized and tailored treatment. Prospective trials are still needed, however, to objectively establish the true benefit of these markers in prognostic and therapeutic arenas.

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Section: The P53 Signaling Pathwaymentioning

confidence: 94%

Molecular markers in bladder cancer

Shariat

Karam

Lerner

2008

Current Opinion in Urology

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“…Also, CDK4 and CDK6 are amplified and/or overexpressed in a variety of human tumors [10,11]. Moreover loss of heterozygosity at 9p21, the chromosomal region that encompasses the INK4a-ARF and INK4b loci, is one of the most commonly affected regions in human cancers and occurs in over half of bladder tumors and might have prognostic value [12].…”

Section: Cyclin-dependent Kinases and Cancermentioning

confidence: 99%

Cyclin-dependent kinase inhibitors as potential targeted anticancer agents

2009

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Cyclin-dependent kinases (CDKs) are core components of the cell cycle machinery that govern the transition between phases during cell cycle progression. Genes involved in cell cycle are frequently mutated in human cancer and deregulated CDK activity represents a hallmark of malignancy. This knowledge provides a rationale for regarding CDKs and their associated molecules as potential targets for new drug development in anticancer research. The present article will review the most relevant CDK inhibitors with emphasis on the newer molecules in clinical development and the biological rationale of this therapeutic approach.

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“…It has also been reported that RB1 [58,59] and P15 [67,82] can be hypermethylated in bladder cancer. This reciprocal relationship between RB1 and CDKN2A alterations underscores the importance of this pathway in bladder cancer development and as a potential target [31][32][33][34]73].…”

Section: -55mentioning

confidence: 94%

Hypermethylation in bladder cancer: biological pathways and translational applications

Sänchez‐Carbayo

2012

Tumor Biol.

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A compelling body of evidences sustains the importance of epigenetic mechanisms in the development and progression of cancer. Assessing the epigenetic component of bladder tumors is strongly improving our understanding of their biology and clinical behavior. In terms of DNA methylation, cancer cells show genome-wide hypomethylation and site-specific CpG island promoter hypermethylation. In the context of other epigenetic alterations, this review will focus on the hypermethylation of CpG islands in promoter regions, as the most widely described epigenetic modification in bladder cancer. CpG islands hypermethylation is believed to be critical in the transcriptional silencing and regulation of tumor suppressor and crucial cancer genes involved in the major molecular pathways controlling bladder cancer development and progression. In particular, several biological pathways of frequently methylated genes include cell cycle, DNA repair, apoptosis, and invasion, among others. Furthermore, translational aspects of bladder cancer methylomes described to date will be discussed towards their potential application as bladder cancer biomarkers. Several tissue methylation signatures and individual candidates have been evidenced, that could potentially stratify tumors histopathologically, and discriminate patients in terms of their clinical outcome. Tumor methylation profiles could also be detected in urinary specimens showing a promising role as non-invasive markers for cancer diagnosis towards an early detection and potentially for the surveillance of bladder cancer patients in a near future. However, the epigenomic exploration of bladder cancer has only just begun. Genome-scale DNA methylation profiling studies will further highlight the relevance of the epigenetic component to gain knowledge of bladder cancer biology and identify those profiles and candidates better correlating with clinical behavior.

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Molecular and Immunohistochemical Analysis of the Prognostic Value of Cell-Cycle Regulators in Urothelial Neoplasms of the Bladder

Cited by 71 publications

References 41 publications

Molecular markers in bladder cancer

Molecular markers in bladder cancer

Cyclin-dependent kinase inhibitors as potential targeted anticancer agents

Hypermethylation in bladder cancer: biological pathways and translational applications

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