Bladder tumor model

Nag S, Blatnik A, Soloway M. Enhancement of high intensity iodine-125 brachytherapy by cis-platinum in a murine bladder tumor model. J Urol 1984 131 1225-1228. 

It was demonstrated that curcumin effectively inhibits tumor implantation and growth in a murine bladder tumor model [Anand et al., 2008]. Another study demonstrated that dietary curcumin treatment reduced risk for kidney cancer metastasis in rats [Frank et al., 2003]. 

The polymer formulations containing anticancer agents (paclitaxel and cis-platin) were evaluated in vivo in heterotrophic (mouse bladder tumor) and orphotrophic (rat prostate cancer) models. Single administration of polymer-pactlitaxel formulation intratumorally in a mouse bladder tumor model increased the survival rate of the animals compared to untreated animals and to animals treated with paclitaxel dispersion (conventional administration method) (27). The optimal load of paclitaxel in the polymer was established as 10% w/w. Mice treated with this formulation showed median survival rate (MSR) of... 

S. linuma, G. Wagnieres, K. Schomacker, M. Bamberg, T. Hasan (1995). The importance of fluence rate in photodynamic therapy with ALA-induced PPIX and BPD-MA in a rat bladder tumor model. In T.J. Dougherty (Ed.), Optical Methods for Tumor Treatment and Detection Mechanisms and Techniques in PDTIV (Proc SPIE., Vol. 2392, pp. 136-140). 

Selman SH, Keck RW (2011) A comparative study of the inhibiting effects of mitomycin C and polyphenolic catechins on tumor cell implantation/growth in a rat bladder tumor model. J Urol 186 702-706... 

Pretreatment of human T24 bladder or human colorectal adenocarcinoma cells with 5-FU followed by CGP 41251 showed a synergistic drug interaction in both cell lines (Fabbro et al., 1999). CGP 41251 or 5rFU were ineffective as a single agent against COLO 205 tumors up to 200 mg/kg/day p.o. and 75 mg/kg/week i. v., respectively. Combination of both compounds at these concentrations showed significant antitumor activity in this tumor model (Fabbro et al., 1999). 

In addition to inflammation, another potential role for natural COX and LOX dual inhibitors is in the prevention and treatment of cancers [80], Over expression of COX-2 has been demonstrated in various different human malignancies. COX-2 inhibitors have also been shown to be efficacious in the treatment of animal models of skin, breast and bladder tumors. While the mechanism of action remains to be completely defined, the over expression of COX-2, in excess of production of prostaglandin E2 and 5-hydroxyeicosatetraenoic acid (5-HETE) have been shown to inhibit apoptosis and increase the invasiveness of tumerogenic cell types [81,82]. It is probable that the enhanced production of PGE2 and 5-HETE promotes cellular proliferation, and consequently, increases angiogenesis [83]. 

Urinary bladder tumors (iV-butyl-N-(4-hydroxybutyl)nitrosamine-induced rat model) [42]... 

Figure 2a. Dose/response curves of best fit in the observed range for bladder tumors from sodium saccharin. (Gamma and Armitage-Doll models too close to Weibull to distinguish.)...

Promotion in the urinary bladder is similar to other models since the lesions go through the stages of hyperplasia, hyperplastic nodules and later form carcinomas. Cell proliferation in the urinary bladder is an essential part of the promotion process (Hicks and Chowaniec, 1977). Focal hyperplasia, dysplasia and a high number of mitotic figures in transitional cells and urothelium are common in animals fed dietary saccharin (Chowaniec and Hicks, 1979). Male and female rats administered saccharin in the drinking water consumed less water and voluntarily less diet than if saccharin was mixed in the diet, and they did not develop bladder tumors (Chowaniec and Hicks, 1979). While increased cell proliferation is an essential component of the promotional process, hyperplasia may not be a sufficient stimulus for promotion. Isoproterenol given to rats caused urothelia hyperplasia but did not enhance MNU initiated bladder tumors (Hicks, 1980). Clearly, other biochemical properties of saccharin have to be investigated since hyperplasia... 

Most of the epidemiological data on the association of bladder tumors and the environment are centered on coffee consumption and artificial sweeteners. From case-control studies, there appears to be no causal relationship between coffee consumption and bladder tumor incidence (NAS, 1982 Omenn, 1982). Experimental animal models would predict that saccharin should promote tumors in the human. However, to this date there is no epidemiologic data that would indicate an increased tumor rate associated with populations consuming quantities of artificial sweeteners (Saccharin and Bladder Cancer, 1980 NAS, 1982). Perhaps the time frame is not correct or the dose is too low to demonstrate an effect in the human population. Further studies, especially on diabetic populations, are required to ascertain if artificial sweeteners can serve as promoters in human bladder cancer. 

The orthotopic bladder cancer model was verified by the histological section, as shown in Figure 6. The result shows apparent tumor in the bladder lumen with EGFR over expression in the tumors. Most important of all, all of the tumors were superficial without muscle invasiveness. The superficial bladder cancer is the most suitable time for initiation of adjuvant intravesical therapies. 

Preliminary in vitro and animal studies of the effects of silymarin and silybinin have been carried out with several cancer cell lines. In murine models of skin cancer, silybinin and silymarin were said to reduce tumor initiation and promotion. Induction of apoptosis has also been reported using silymarin in a variety of malignant human cell lines (eg, melanoma, prostate, leukemia cells, bladder transitional-cell papilloma cells, and hepatoma cells). Inhibition of cell growth and proliferation by inducing a Gx cell cycle arrest has also been claimed in cultured human breast and prostate cancer cell lines. The use of milk thistle in the clinical treatment of cancer has not yet been adequately studied but preliminary trials are under way. 

Fig. 9 Representative images of mIn-TA 138 at 0.5,1, and 2 h post injection in the c-neu On-comouse model. Arrows indicate the presence of radioactivity in tumors or the bladder. Theimages have not been filtered...

Ex vivo models, such as mouse bladder (Poste et al., 1980) or human amnion (Russo et al., 1986) either denuded of epithelium and/or reseeded with endothelial cells (Foltz et al., 1982) may be considered too simplified systems. According to Kim et al. (1998), these recapitulate poorly the structure of the blood vessels and, in particular, small vessels. .. where most of the cancer cell invasion is believed to take place . These authors describe an interesting alternative where cells are inoculated on the chick chorioallantoic membrane (CAM) of an artificially created air sac in chick embryo. To detect and quantitate tumor cells actively penetrated in the ventral lower CAM , genomic DNA is extracted and used as a template for human Alu sequence identification by PCR. These sequences, unique to human and higher primate DNA, are repetitive... 

While the majority of studies on tumor promotion have focused on mouse skin, there are cancers in other organs that are applicable to this model. Bladder... 

In many of the rodent models involving formation of urinary solids, there is associated cytotoxicity, regenerative proliferation, and ultimately the induction of tumors of the urothelium, usually of the urinary bladder but occasionally of the kidney pelvis or ureters (Shirai et al. 1989). Cytotoxicity and regenerative... 

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