The role of peroxisome proliferator-activated receptor γ in bladder cancer in relation to angiogenesis and progression

Possati, L; Rocchetti, Romina; Talevi, Simona; Beatrici, Valerio; Margiotta, Chiara; Ferrante, Luigi; Calza, R; Sagrini, David; Ferri, Albertino

doi:10.1016/s0306-3623(01)00116-1

Cited by 26 publications

(31 citation statements)

References 19 publications

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“…Degradation of these structures during invasion should cause a release of bFGF into the tumour, thus encouraging further tumour growth and progression. In our experience, bFGF has a more direct role in papillary tumour growth and progression: we found bFGF expression almost exclusively in those papillary bladder cancers exhibiting a high tendency to relapse or progress towards invasive forms [6] .…”

Section: Introductionsupporting

confidence: 94%

“…We analyzed the immunohistochemical expression of PPAR ␥ in 75 human bladder tumour specimens, and found that it was expressed more signifi cantly in papillary tumours than in solid cancers. Its presence was associated with statistical signifi cance to a low incidence of tumour recurrence or progression, but coexpression of PPAR ␥ and bFGF seemed to play a worsening role [6] .…”

Section: Introductionmentioning

confidence: 99%

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Antiangiogenic Drugs for Chemotherapy of Bladder Tumours

Rocchetti

Talevi²,

Margiotta³

et al. 2005

Chemotherapy

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Background: Bladder cancers have different angiogenic pathways distinguishing not only papillary from solid tumours, but even papillary superficial from papillary invasive ones, thus representing selective targets for antiangiogenic drugs. Methods: The bacterial wall component tecogalan, inhibiting basic fibroblast growth factor (bFGF), the fumagillin derivative TNP-470, inhibiting vascular endothelial growth factor (VEGF), the distamycin A derivative PNU153429, and the tetracycline minocycline were administered to nude mice injected with the human bladder cancer cell lines 639V, causing bFGF-expressing papillary superficial tumours, or T24, causing VEGF-expressing papillary invasive tumours. Results: Tecogalan had no effect even on 639V tumour growth, where bFGF was unaffected. TNP-470 only had an effect on T24 tumours, delaying tumour appearance and growth and lowering VEGF; these effects were augmented by adding minocycline. PNU153429 had no effect on 639V tumours, and a slight effect on T24 tumours. Conclusion: TNP-470 may represent a selective drug for the treatment of VEGF-expressing invasive papillary bladder tumours.

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Section: Introductionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Antiangiogenic Drugs for Chemotherapy of Bladder Tumours

Rocchetti

Talevi²,

Margiotta³

et al. 2005

Chemotherapy

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“…Although a positive correlation was observed between PPARγ expression and tumor grade and progression in one study of human bladder tumors,the authors demonstrated a PPARγ agonistmediated potent anti-proliferative effect on the same bladder tumor cells in vitro (Yoshimura et al, 2003b). Moreover, no positive correlation between PPARγ expression and tumor grade, stage, onset, or number was observed by others in a separate study (Possati et al, 2002). Rather, the presence of PPARγ expression was higher in papillary than in solid (more advanced) tumors and was associated with a low incidence of tumor recurrence or progression.…”

Section: Discussionmentioning

confidence: 99%

Urothelial Carcinogenesis in the Urinary Bladder of Male Rats Treated with Muraglitazar, a PPARα/γ Agonist: Evidence for Urolithiasis as the Inciting Event in the Mode of Action

et al. 2006

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Muraglitazar, a PPARα/γ agonist, dose-dependently increased urinary bladder tumors in male Harlan Sprague-Dawley (HSD) rats administered 5, 30, or 50 mg/kg/day for up to 2 years. To determine the mode of tumor development, male HSD rats were treated daily for up to 21 months at doses of 0, 1, or 50 mg/kg while being fed either a normal or 1% NH 4 Cl-acidified diet. Muraglitazar-associated, time-dependent changes in urine composition, urothelial mitogenesis and apoptosis, and urothelial morphology were assessed. In control and treated rats fed a normal diet, urine pH was generally ≥ 6.5, which facilitates formation of calcium-and magnesium-containing solids, particularly in the presence of other prolithogenic changes in rat urine. Urinary citrate, an inhibitor of lithogenesis, and soluble calcium concentrations were dose dependently decreased in association with increased calcium phosphate precipitate, crystals and/or microcalculi; magnesium ammonium phosphate crystals and aggregates; and calcium oxalate-containing thin, rod-like crystals. Morphologically, sustained urothelial cytotoxicity and proliferation with a ventral bladder predilection were noted in treated rats by month 1 and urinary carcinomas with a similar distribution occurred by month 9. Urothelial apoptotic rates were unaffected by muraglitazar treatment or diet. In muraglitazar-treated rats fed an acidified diet, urine pH was invariably < 6.5, which inhibited formation of calcium-and magnesium-containing solids. Moreover, dietary acidification prevented the urothelial cytotoxic, proliferative, and tumorigenic responses. Collectively, these data support an indirect pharmacologic mode of urinary bladder tumor development involving alterations in urine composition that predispose to urolithiasis and associated decreases in urine-soluble calcium concentrations.

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“…Lastly, PPARγ may also target vascular neogenesis in bladder cancer, a disease whose vascular phenotype has previously been shown to respond well to anti-angiogenic drugs. 97 Possati et al 98 analyzed the expression of PPARγ and angiogenic factors in 75 human bladder tumor specimens and the results were compared to the clinical and pathological characteristics of the disease. They found that the expression of platelet-derived endothelial cell growth factor (PDECGF), an angiogenic factor, is significantly associated with tumor recurrence and poor prognosis.…”

Section: Role In Cancer Biologymentioning

confidence: 99%

“…However, the concomitant expression of PPARγ was associated with significantly low incidence of tumor recurrence or progression suggesting a protective effect of PPARγ against PDECGF. 98 Although PPARγ have shown important role in carcinogenesis, a better understanding of its mechanism of action in bladder tumors is needed. As previously mentioned, Chaffer et al 75 investigated the effects of a range of endogenous and synthetic PPARγ ligands on proliferation, growth arrest and apoptosis in a series of transitional cell carcinoma (TCC) of the bladder with increasing metastatic potential.…”

Section: Role In Cancer Biologymentioning

confidence: 99%