Experimental rat lung tumor model with intrabronchial tumor cell implantation. (57/243)

PURPOSE: The objective of this study was to develop a rat lung tumor model for anticancer drug testing. METHODS: Sixty-two female Wistar rats weighing 208 +/- 20 g were anesthetized intraperitoneally with 2.5% tribromoethanol (1 ml/100 g live weight), tracheotomized and intubated with an ultrafine catheter for inoculation with Walker's tumor cells. In the first step of the experiment, a technique was established for intrabronchial implantation of 10(5) to 5 x 10(5) tumor cells, and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from high-resolution computed tomography (HRCT) with findings from necropsia and determining time of survival. RESULTS: The tumor take rate was 94.7% for implants with 4 x 10(5) tumor cells, HRCT and necropsia findings matched closely (r=0.953; p<0.0001), the median time of survival was 11 days, and surgical mortality was 4.8%. CONCLUSION: The present rat lung tumor model was shown to be feasible: the take rate was high, surgical mortality was negligible and the procedure was simple to perform and easily reproduced. HRCT was found to be a highly accurate tool for tumor diagnosis, localization and measurement and may be recommended for monitoring tumor growth in this model.  (+info)

High susceptibility of activated lymphocytes to oxidative stress-induced cell death. (58/243)

The present study provides evidence that activated spleen lymphocytes from Walker 256 tumor bearing rats are more susceptible than controls to tert-butyl hydroperoxide (t-BOOH)-induced necrotic cell death in vitro. The iron chelator and antioxidant deferoxamine, the intracellular Ca2+ chelator BAPTA, the L-type Ca2+ channel antagonist nifedipine or the mitochondrial permeability transition inhibitor cyclosporin A, but not the calcineurin inhibitor FK-506, render control and activated lymphocytes equally resistant to the toxic effects of t-BOOH. Incubation of activated lymphocytes in the presence of t-BOOH resulted in a cyclosporin A-sensitive decrease in mitochondrial membrane potential. These results indicate that the higher cytosolic Ca2+ level in activated lymphocytes increases their susceptibility to oxidative stress-induced cell death in a mechanism involving the participation of mitochondrial permeability transition.  (+info)

Imaging transgene activity in vivo. (59/243)

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Evaluation of the purified fraction of Wilbrandia (c.f.) verticillata for antitumour activity. (60/243)

Cucurbitacins are known to produce cytotoxic and anticancer activities. Two novel norcucurbitacin glucosides (Wv1 and Wv2) have recently been isolated from a purified fraction obtained from the rhizome of Wilbrandia verticillata. The present study evaluates the cytotoxic and antitumour activities of these norcucurbitacins. We have found a regular cytotoxicity in KB cells (Cy50 = 12 micrograms/ml) as well as a significant inhibition in the Walker 256 carcinosarcoma growth (approximately 75%).  (+info)

A fetal protein in chromatin of Novikoff hepatoma and Walker 256 carcinosarcoma tumors that is absent from normal and regenerating rat liver. (61/243)

Antibodies to chromatin proteins of Novikoff hepatoma cells formed precipitin bands in the double-diffusion immunoprecipitation assay with chromatin proteins of Novikoff hepatoma, Walker 256 carcinosarcoma, and 18-day fetal rat liver. The antigen used for preparation of antiserum was the chromatin proteins initially extracted with 3 M NaCl-7 M urea and soluble after dialysis to 0.14 M NaCl-0.35 M urea. The chromatin proteins used for analytical studies were extracted with 0.6 M NaCl containing 0.01 M Tris-HCl (pH 8) and 100 muM phenylmethylsulfonyl fluoride. Corresponding chromatin proteins of normal and 18-hr regenerating rat liver, heart, and kidney did not form precipitin bands. The antigen was purified from the chrmatin of Novikoff hepatoma cells by exclusion chromatography on Sephadex G-150 and preparative nondenaturing polyacrylamide gel electrophoresis. Its migration on denaturing sodium dodecyl sulfate-polyacrylamide gels corresponded to a molecular weight of 26,000. Amino acid analysis showed that the ratio of acidic to basic amino acids was 1.4 to 1.0. Evidence for its homogeneity included its migration as a single protein spot on two-dimensional polyacrylamide gel electrophoresis and its single lysine amino-terminal amino acid. This protein is a glycoprotein, as shown by the presence of 15 moles of galactosamine per mole of antigen. These studies demonstrate the presence of a fetal glycoprotein in the chromatin of two tumors that may have an important role in determining their gene products.  (+info)

The oophorectomy effect on Walker 256 tumor inoculated into the vagina and uterine cervix of female rats. (62/243)

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In vivo measurements of intratumoral metabolism, modulation, and pharmacokinetics of 5-fluorouracil, using 19F nuclear magnetic resonance spectroscopy. (63/243)

In vivo 19F nuclear magnetic resonance spectroscopy was used to monitor and measure 5-fluorouracil and some of its cytotoxic anabolites directly in rats bearing the Walker 256 adenocarcinoma by using a 4.7-T horizontal bore magnet. A two-compartment subsystem model was used to estimate intratumoral transfer parameters. The apparent rate of formation of the nucleosides/tides in the tumor, K21, changed following methotrexate pretreatment, from a value of 6.4 +/- 2.4 to 15.5 +/- 5.0. These values were statistically significant to P less than 0.01. This 2-compartment model was validated by excising the tumors and measuring the 19F content of the acid soluble and the RNA fractions. The increase of the mean K21 value (2.4) estimated in vivo correlated favorably with the increase of the levels of the fluorinated nucleosides/nucleotides (2.2) observed by in vitro analysis. The in vitro measurements also revealed that the increase in the fluorinated nucleosides was accompanied with a similar increase in 5-fluorouracil incorporation into the RNA fraction, which suggests that increases or decreases in the relative intensity of the fluorinated nucleoside/nucleotide signals observed in vivo could be indicative of similar changes of the nuclear magnetic resonance invisible fluorinated RNA. The present study documents that it is now possible to estimate the pharmacokinetic behavior of 5-fluorouracil and of its active metabolites at its target site, tumor tissue, by using noninvasive measurements. Such measurements may provide useful means of assessing, during treatment, the possible effect of 5-fluorouracil on the tumor, and its response to treatment, both when used by itself as well as a function of biochemical modulation.  (+info)

Nuclear protein phosphokinases in normal and neoplastic tissues. (64/243)

Protein phosphokinases were isolated from the nuclei of normal and fetal liver and neoplastic tissues. Chromatography on phosphocellulose columns resolved the normal and fetal liver kinases into five reproducible fractions. Each of the fractions differed in optimal divalent cation and substrate requirements. Hepatic proliferation was accompanied by quantitative changes in the kinase activity profiles (with endogenous phosphoprotein as natural substrate). An additional phosphoprotein kinase activity stimulated by Mn2+ was found in the nuclei of malignant cells. This tumor-specific kinase could not be detected either in tumor cytoplasm or in fetal or regenerating liver nuclei. Mn2+-dependent phosphoprotein kinase from Novikoff hepatoma phosphorylated only one major protein band detectable by polyacrylamide gel electrophoresis. This substrate could not be detected in chromatin of normal tissues.  (+info)