Biological similarities between murine chemical-induced and natural human bladder carcinogenesis

Palmeira, Carlos; Oliveira, Paula A.; Lameiras, Catarina; Amaro, Teresina; Silva, Victor Menezes; Lopes, Carlos Renato; Santos, Lúcio Lara

doi:10.3892/ol_00000066

Cited by 11 publications

(10 citation statements)

References 14 publications

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“…The CIS surrounding normal-appearing urothelium shows a high frequency of abnormal DNA content, p53 mutated protein expression, and a high proliferative status. [11,14] Our studies revealed histopathological and biological similarities between the rodent urothelium carcinogenesis process and the corresponding process in humans. [11] The more aggressive lesions identified in rats showed a higher rate of DNA aneuploidy, p53 immunoexpression, and Ki-67 labeling index.…”

Section: Chemically Induced Ubcmentioning

confidence: 77%

“…[8][9][10] Rodents are exceptionally suited for these types of studies because rats and mice do not develop spontaneous urinary bladder tumors under normal conditions. [11] The occurrence of non-neoplastic urothelial lesions, such as inflammation and hyperplasia, is also uncommon in these species. [12] In our studies, C3H/He mice were exposed to BBN, a complete genotoxic carcinogen metabolically derived from a compound found in tobacco smoke.…”

Section: Chemically Induced Ubcmentioning

confidence: 99%

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What we have learned from urinary bladder cancer models

Bernardo¹,

Costa²,

Palmeira³

et al. 2015

J Cancer Metastasis Treat

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Urinary bladder cancer (UBC) is a heterogeneous disease with highly variable clinical outcomes and responses to chemotherapy. Despite some advances in the molecular understanding of UBC, this knowledge still has not been translated to the clinic in terms of improvements in the prognosis and treatment of patients. Suitable urinary bladder tumor models representative of the human disease in terms of histology and behavior are needed to study factors involved in tumor initiation, progression and metastasis. Further, accurate model systems would facilitate identification of new therapeutic targets and predictive markers that could lead to optimization of existing therapies and development of new ones. Many established cancer cell lines derived from human urinary bladder tumors representing different grades and stages have been used as experimental models for UBC study. These cell lines reflect some of the genetic and morphologic alterations observed in human urothelial carcinoma and serve as simplified models to study the behavior of cancer cells in vitro. However, their translational potential is limited due to the artificial conditions, in which the cells are maintained, grown and tested. Animal models offer a more complex and realistic model for the establishment, development, and progression of tumors as well as to evaluate new therapeutic approaches. Over the years, the authors' group has worked with several UBC cell lines, established and characterized chemically induced UBC models, and patient-derived xenografts models. In this study, the authors will provide a summary of the UBC models developed by their group, analyze their translational potential and weaknesses, and define areas that remain to be explored.

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Section: Chemically Induced Ubcmentioning

confidence: 77%

Section: Chemically Induced Ubcmentioning

confidence: 99%

What we have learned from urinary bladder cancer models

Bernardo¹,

Costa²,

Palmeira³

et al. 2015

J Cancer Metastasis Treat

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show abstract

“…A large scale GeLC-MS/MS strategy was used to analyze the urinary proteome of rats with chemically induced urothelial carcinoma, a well-established animal model of bladder cancer 16 . Indeed, BBN-induced tumors in rats are equivalent to the non-muscleinvasive urothelial carcinoma clinically observed in humans 14,24,25 . Animal models of urothelial carcinoma offer several advantages in medical research 16 as the possibility to follow-up tumors development and relate it with urine proteome dynamics.…”

Section: Discussionmentioning

confidence: 99%

Comparative proteomic analyses of urine from rat urothelial carcinoma chemically induced by exposure to N-butyl-N-(4-hydroxybutyl)-nitrosamine

et al. 2015

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Bladder cancer is estimated to be the ninth most common malignancy with a high rate of recurrence and progression despite therapy, early diagnosis being crucial for timely intervention. Using a well-established animal model of urothelial carcinoma, we performed a comprehensive analysis of urine proteome profile from healthy animals and animals with urothelial carcinoma at two time-points of disease pathogenesis. GeLC-MS/MS, followed by bioinformatics analysis of unique proteins and the ones present in significantly distinct levels among groups, highlighted the biological processes involved in disease pathogenesis such as, for instance, response to selenium and to drugs, neutral lipid metabolism at earlier stages of disease, and inflammation, immune response and wound healing at advanced stages. Proteins from up-regulated biological processes might be seen as putative disease biomarkers. These include, for example, cadherins, lipoproteins, and glysosyltransferases, which may be included in multimarker strategies. Taken together, the data support the application of urine proteomics for the identification of the biological processes modulated by bladder cancer in an integrative perspective. The present exploratory urinary proteomic analysis might be seen as an important starting point for studies targeting urinary proteins in human, aiming at the implementation of novel laboratory approaches for the detection and successful management of urothelial carcinoma.

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“…To overcome the lack of studies in this area, this work intended to implement humane endpoints in a rat model of urinary bladder cancer chemically-induced by BBN. This model is widely used by investigators to study the pathophysiology of this disease due to their similarities to human urinary bladder cancer (32). According to our knowledge this is the first study that examined a rat male model of BBN-induced urinary bladder tumors during a long period of time (35 weeks).…”

Section: Discussionmentioning

confidence: 99%