Cancer biochemistry biophysics最新文献

Current evidences clearly point out that an increase in lipid peroxidation influences lipid metabolism in cancer patients. Several investigations recognize selenium as a potent antioxidant, as well as an anticarcinogen, in both animal and human systems. Selenium was administered to Wistar rats bearing mammary tumor induced by 7,12-dimethylbenz(a)anthracene (DMBA) to study alterations in the concentration of lipid profiles and in the activities of some lipid metabolising enzymes. Control and tumor-bearing rats administered with selenium, were fed 5 mg sodium selenite/kg diet from the day of tumor induction. Plasma total lipids, total cholesterol, free fatty acids, triglycerides, phospholipids, VLDL and LDL cholesterol were significantly lower in selenium-treated rats bearing tumors, whereas, plasma ester cholesterol and HDL cholesterol were significantly greater due to selenium administration in DMBA induced-tumor rats. Total lipase and lecithin: cholesterol acyltransferase registered greater activities in plasma of selenium administered rats with tumor, while the activity of preheparin lipoprotein lipases in plasma of rats bearing tumors was lower due to selenium administration. These observations clearly indicate the effect of selenium in correcting the abnormalities of lipid metabolism in tumor-induced rats.

The intraperitoneal administration of pristane (2,6,10,14-tetramethylpentadecane) induces peritoneal plasmacytomas in genetically susceptible BALB/c mice. The purpose of this study was to estimate the disposition of an amount of intraperitoneally injected pristane that would conventionally be used in a tumor induction protocol. The distribution of 3H-labeled pristane in various tissues was monitored by liquid scintillation counting at different times after injection. The data show that pristane is present in the blood and detectable in all tested tissues during an observation period of one to 64 days. The levels of pristane fluctuate in some tissues such as lymph node and bone marrow but show a clear tendency to accumulate in others such as liver, spleen and kidney. Evidence is also presented for the in vivo metabolism of pristane based on the observed urinary excretion of tritium and on the high levels of radioactivity in the gall bladder fluid. It is concluded that intraperitoneally administered pristane is distributed throughout the mouse and is stored in tissues in sufficient amounts to allow interactions with the cells residing there.

Brefeldin A (NSC 89671), a macrocyclic lactone, blocks cellular protein transport by disturbing the association and dissociation of the Golgi apparatus with a 110-kD protein which is regulated by GTP. Brefeldin also induces retrograde transport from the Golgi membrane to the endoplasmic reticulum, which is mediated by microtubules which also require GTP for their biosynthesis. The anti-cancer action of taxol is exerted by enhancing tubulin polymerization in microtubule assembly; tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 28693) acts through decreasing cellular GTP concentrations. Therefore, we tested the hypothesis that taxol (paclitaxel, NSC 125975) or tiazofurin might provide synergism with brefeldin. In human breast carcinoma MDA-MB-435 cells in the growth inhibition assays for brefeldin, taxol and tiazofurin, the IC50s were 41 nM, 6 nM and 13 microM, respectively. When brefeldin and taxol were given simultaneously, addition (brefeldin 10 nM with taxol 2 to 8 nM) or synergism (brefeldin 30 nM with taxol 2 to 8 nM) was observed. When brefeldin and tiazofurin were given simultaneously, or tiazofurin was followed 12 h later by brefeldin, addition was observed. The protocols yielding synergism and addition should be of value in the design of clinical trials for breast carcinoma.

Erythrocytes from the circulation of rats bearing intraperitoneal Yoshida ascites sarcoma, as well as the red cells contaminating the tumor fluid, exhibit higher concanavalin A (Con A)-mediated agglutination than the cells from normal animals. Two proteins have been purified earlier from the ascites fluid that can impart high agglutinability on the cells in vitro. We report here that the erythrocytes from the tumor-bearing rats exhibit reduced electrophoretic mobility compared to the cells from normal animals (P < 0.001), which correlates with the increase in their Con A-agglutinability (r = 0.998). The two purified proteins also cause reduction in the electrophoretic mobility of erythrocytes (P < 0.01). Thus the modification of the host cell surface observed in tumor-bearing rats arises due to non-specific binding of tumor products that reduce the host cell surface charge.

In this study, fibronectin and sialic acid concentrations were determined in plasma from patients with pituitary adenoma, meningioma and glioma, and, from controls. The mean plasma fibronectin levels in patients with pituitary adenoma, meningioma and glioma (p < 0.001) appeared to be significantly lower than controls. On the contrary, the mean plasma sialic acid values in patients with pituitary adenoma (p < 0.01), and glioma (p < 0.001) were significantly higher as compared to normal plasmas. The mean plasma sialic acid values in patients with meningioma were not different from those in controls. Also, the mean fibronectin levels in patients with glioma were found to be significantly higher than those in patients with meningioma (p < 0.05).

The Seventeenth Annual Interdisciplinary Cancer Research Workshop was held at the University of New Orleans on March 4, 1994. It was again sponsored by the Cancer Association of Greater New Orleans, a United Way Agency. As all the previous workshops in this highly successful series, it was organized by Peter Politzer (University of New Orleans), with the assistance of Anita H. Buckel (University of New Orleans) and James R. Jeter (Tulane University School of Medicine, New Orleans). The three invited speakers were Robert J. Coffey (Vanderbilt University, Nashville, TN), Suzanne A. W. Fuqua (University of Texas Health Science Center, San Antonio, TX), and Frank M. Torti (Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC). A one-hour-discussion period in the afternoon presented ample opportunity for an exchange of ideas and research findings among the speakers and the workshop participants. James R. Jeter served as the moderator of this lively discussion session.

The biosynthesis of a given glycosphingolipid is under the control of specific glycosyltransferases, while its catabolism is catalyzed by step-wise action of glycosidases. The net amount of glycolipids apparently result from the difference between these two processes. However, other parameters should be taken into consideration, such as intracellular recycling of catabolic products, membrane insertion, and membrane turnover. In order to establish a possible correlation between ganglioside expression in brain tumor and the activities of the enzymes involved in their metabolism, we analyzed the activities of specific sialyltransferases (SAT-1 and SAT-2), galactosyltransferase (GalT-4), N-acetylgalactosaminyltransferase (GalNAcT-1), and N-acetylglucosaminyltransferase (GlcNAcT-1) in 9 human meningiomas whose ganglioside pattern was characterized either by the predominance ganglioside GM3 (4 out of 9) or ganglioside GD3 (5 out of 9). The results indicated a strong correlation between the GM3/GD3 ratio and SAT-2 activity; to the contrary, SAT-1 activity did not show any correlation if compared with the Lc2/GM3 ratio. In all the samples where GM3 was the main ganglioside, little or no activity of GalNAcT-1 and GlcNAcT-1 was detectable.

Serum depletion of exponentially growing normal human fibroblasts resulted in a moderate depression of the activity of HMG-CoA reductase which occurred simultaneously to the onset of growth arrest of the cells. Specific inhibition of HMG-CoA reductase using mevinolin also resulted in growth arrest. PDGF counteracted the suppressive effect of serum depletion on HMG-CoA reductase activity and cell growth. The growth inhibitory effect of serum depletion and mevinolin was correlated to a decreased biosynthesis of dolichols, in particular of dolichol-20. If PDGF was present in the serum-free medium a high rate of dolichol synthesis was maintained. This effect was mediated not only through an increased HMG-CoA reductase activity. PDGF also increased the incorporation of mevalonate into dolichols, once again into dolichol-20 in particular. In contrast to HDF, the growth of virus-transformed human fibroblasts was not decreased following serum depletion. This was correlated to a sustained activity of HMG-CoA reductase and a sustained dolichol-20 synthesis. In order to block growth and dolichol synthesis of the transformed fibroblasts a stronger inhibition of HMG-CoA reductase activity was required than in the normal cells. Conditioned medium isolated from the transformed cells was found to maintain a high growth rate and a high HMG-CoA reductase activity in serum-depleted HDF. In addition, the incorporation of mevalonate into dolichols was increased. The present data raise the possibility that PDGF or related factors, through autocrine loops, may contribute to the maintenance of a high dolichol synthesis in tumor cells.

Fasting blood samples were taken from 64 tamoxifen-treated postmenopausal women with early stage breast cancer. The levels of erythrocyte lipid peroxidation and the status of erythrocyte detoxifying enzymes were analyzed in untreated and treated patients for 3 months and 6 months with tamoxifen. Erythrocyte membrane lipid peroxidation and membrane cholesterol, phospholipid were also determined in all the patients. The 3 months and 6 months tamoxifen-treated patients showed significantly decreased levels of erythrocyte, erythrocyte membrane lipid peroxide with concomitantly increased levels of detoxifying enzymes when compared with baseline values of untreated women. Erythrocyte membrane cholesterol and phospholipid levels were markedly decreased in tamoxifen-treated patients than in untreated women. An interesting finding of this study indicates that the lipid peroxide, as well as, the lipid lowering efficacy of tamoxifen, was increased in patients with greater levels of baseline lipid and lipid peroxides in their erythrocyte membrane. These results indicate that tamoxifen is a potent suppressor of lipid peroxide formation through the favorable effects on membrane lipids and protective enzyme system.

Cysteine conjugate beta-lyase, an enzyme that converts cysteine S-conjugates to free thiols, pyruvate and ammonia, is normally expressed primarily in the liver and kidney. In theory, this selective distribution affords the opportunity to target thiol-containing drugs to these organs and, perhaps, to tumors derived from them. To assess the potential for delivery of such drugs to kidney-derived tissue, we have used a typical beta-lyase substrate, S-(2-benzothiazolyl)-L-cysteine, to measure the beta-lyase activity in normal and tumor tissue of kidneys removed from patients with renal carcinoma. Although considerable heterogeneity in enzyme activity levels was observed in normal and tumor-derived samples, a high proportion of tumor samples had enzyme activity that was at least 50% of that observed in adjacent normal tissue. Frequently, hypoxanthine-guanine phosphoribosyltransferase activity was observed to be greater in the tumor than in normal tissue. These results may aid in the development of therapy for renal carcinomas.