Liver tumor model

The third hypothesis put forth to explain the anti-carcinogenic effects of DR holds that selective removal of initiated cells takes place in DR. It has been shown in the liver tumor model that increased apoptosis and decrease in the rate of cell proliferation in DR animals play an important role in decreasing spontaneous as well as chemical-induced tumors. Similar enhancement in apoptosis has been shown in brain tumor model. The increase in apoptosis is a mechanism devised by the DR animals to cope up with the decreased availability of food. The damaged and weak cells are efficiently removed in the DR animal, which also helps in... 

Popp, J. A., and Goldsworthy, T. L. (1989). Defining fod of cellular alteration in short-term and medium-term rat liver tumor models. Toxicol Pathol 17(4 Pt 1), 561—568. 

An antitumor bioactivity glycoprotein is also purified from earthworm (E. fetida) recently [82], It is assayed by using a liver tumor model (H22) of mice the results show that significant antitumor effects and the life-prolonged rate was 65.4% in cultured H22 of mice [82]. Furthermore, it has been proved that EFE can enhance the curative effects by both radiation therapy and chemotherapy [83,84],... 

J.P. Rovers, A.E. Saamack, M. de lode, H.J. Sterenborg, O.T. Terpstra, M.F. Grahn (2000). Biodistribution and bioactivity of terapegylated meta-tetra(hydroxyphenyl) chlorin in a rat liver tumor model. Photochem. PhotobioL, 71, 211-217. 

Moroz, P. Jones, S.K. Winter, J. Gray, B.N. (2001), Targeting liver tumors with hyperthermia ferromagnetic embolization in a rabbit liver tumor model. J. Surg. 

Intravenous injection of isosorbide dinitrite, an organic NO donor (0.2 mg/kg), increased partial oxygen pressure in tumor tissues by 79% via increase in tumor perfusion compared with treatmait with vehicle in the transplantable murine liver tumor model (Jordan et al. 2(XX)). These findings demonstrated that increase in oxygenation by NO may enhance radiosensitivity. 

A simple example might make this clearer. Suppose it were known that a 100 mg dose of chemical Z produced an extra 10% incidence of liver tumors in rats. Suppose further that we studied the pharmacokinetics of compound Z and discovered that, at the same 100 mg dose, 10 mg of the carcinogenic metabolite of Z was present in the liver. The usual regulatory default would instruct us to select the 100 mg dose as the point-of-departure for low dose extrapolation, and to draw a straight line to the origin, as in Figure 8.1. We are then further instructed to estimate the upper bound on risk at whatever dose humans are exposed to - let us say 1 mg. If the extra risk is 10% at 100 mg, then under the simple linear no-threshold model the extra risk at 1 mg should be 10% 100 = 0.1% (an extra risk of... 

Leander P, Golman K, Strande P, Klaveness J, Besjakov J, Fait K (1993) A comparison between lEEC, a new biodegradable particulate contrast medium, and iohexol in a tumor model of computed tomography imaging of the liver. Invest Radiol 28 513... 

Poly(alkyl cyanoacrylate) nanoparticles accumulate in the liver (60-90% of the injected dose) and the spleen upon iv injection, with the macrophages in the liver being their major target. Nanoparticles loaded with doxorubicin have shown a markedly enhanced therapeutic index in a number of animal tumor models. 

In the rodent liver initiation-promotion model, phenobarbital is a tumor promoter. Phenobarbital is a hepatic mitogen, and recent evidence indicates that it activates the transcription factor, constitutive androstane nuclear receptor (CAR). Additionally, CAR was found to be essential for liver tumor promotion in pheno-barbital-treated mice. In phenobarbital promoted preneoplastic foci and hepatic tumors, phenobarbital can also suppress apoptosis and accelerate the growth of the foci or tumor. Withdrawal of phenobarbital treatment is accompanied by an increase in apoptosis. Similar results involving the inhibition of apoptosis have been reported for nafenopin, a peroxisome proliferator and hepatic tumor promoter. 

A number of the chemicals administered were found to induce cancer in rats and mice. Some chemicals, particularly agricultural products, were negative in the rat models but induced liver tumors in mice. With either type of response, a chemical that induced cancer in any test was labeled a carcinogen, and by extrapolation was considered to be a human cancer risk without questioning its relevance or the imderlying mechanism. 

The second group conducted by Gould was interested in investigating preventive anti-cancer monoterpenes. Their investigations concerned chemopreventive efficacy of d-limonene in relation to rodent mammary [116-118], skin [119] and liver [120] tumor model systems [121]. 

Use of in vivo 19F MR spectroscopy to directly measure the pharmocokinetics of 5-FU in liver tumors and metastases enabled identification of drug mechanism of action and investigation of tumor pathophysiology. Similar studies were undertaken to evaluate the ability of a range of medications to modulate the in vivo effectiveness of fluorouracil and its prodrugs [3-5, 7-10], These studies have served as a model for other in vivo drug MR... 

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