The influence of bovine lactoferrin (bLF) on colon carcinogenesis was investigated in male F344 rats treated with azoxymethane (AOM). Following three weekly injections of AOM, the animals received 2 or 0.2% bLF for 36 weeks. No effects indicative of toxicity were noted, but significant reduction in both the incidence and number of adenocarcinomas of the large intestine was observed with both doses. Thus, the incidences of adenocarcinomas in the groups receiving 2% and 0.2% bLF were 15% and 25%, respectively, in contrast to the 57.5% control value (P < 0.01 and P<0.05, respectively). The results indicate that bLF might find application for chemoprevention of colon cancer.
Orotate phosphoribosyl transferase (OPRT) is the main enzyme that involves in phosphoribosylation of 5-fluorouracil (5-FU), an essential step that leads to tumor growth inhibition. In our study, the prognostic relevance of OPRT, thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in resectable colorectal cancer (CRC) patients treated by oral 5-FU were compared to further clarify the prognostic value of OPRT. Tumor tissue was collected from 90 CRC patients and the patients were followed for 5.2 years (Median). TS, DPD and OPRT activities in the extract of tumor tissue were determined enzymatically. The cut-off value of OPRT (0.147 nmol/(min mg), TS (0.044 pmol/mg) and DPD (72.10 pmol/ (min mg) were determined by maximal v 2 method. Among these 5-FU metabolic enzymes, only high OPRT group demonstrated significantly better disease-free survival (DFS) (p 5 0.0152) and better overall survival (p 5 0.0078). In Cox regression analysis, node status (p < 0.0005) and OPRT (p 5 0.044) were significant factors for DFS. OPRT activity in tumor tissue was a predictor of prognosis in resectable CRC patients treated by oral 5-FU-based adjuvant chemotherapy, and was useful to pick-up high risk patients independent from known prognosis factors. ' 2006 Wiley-Liss, Inc.Key words: orotate phosphoribosyl transferase; thymidylate synthasel; dihydropyrimidine dehydrogenase; oral 5-fluorouracil; adjuvant chemotherapy; colorectal cancer 5-fluorouracil (5-FU) is widely used all over the world for the treatment of a variety of tumors, and it is especially a key drug in the treatment of colorectal cancer (CRC). In western countries, 5-FU injection has been evolved as a constituent of multidrug chemotherapy, as represented by biochemical modulation of leucovorin. In Japan, in contrast, oral form of the drug was developed for the convenient administration, and has been used widely in adjuvant chemotherapy. In this connection, the usefulness of chemotherapy with oral fluoropyrimidine has been recently reported in adjuvant chemotherapy of CRC. 1,2 The analysis of correlation between 5-FU metabolic enzymes and antitumor effect has been widely investigated to predict the effect of 5-FU. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are such enzymes and the association to 5-FU efficacy has been frequently reported in the literature. TS plays a part in DNA synthesis from thymidine and known be inhibited by forming ternary complex together with 5-fluorodeoxyuridine monophosphate (FdUMP) and active folic acid when 5-FU is administered. 3,4 High TS activity in tumor cells often associate with low 5-FU sensitivity and low TS activity associate with high sensitivity. 5 It has been reported that patients with high DPD activity in the tumor showed low 5-FU sensitivity, whereas those with low DPD activity showed high 5-FU sensitivity. 6 Also, Salonga et al. have studied the impact of the enzymes on the 5-FU efficacy and then clarified that a combination of two enzyme activities, TS and DPD, is useful to predict the res...
Oxidation of low-density lipoprotein (LDL) by reactive oxygen species (ROS) and reactive nitrogen species (RNS) has been suggested to be involved in the onset of atherosclerosis. Oolong tea contains unique polyphenols including oolonghomobisflavan A (OFA). In this study, the effects of OFA on LDL oxidation by ROS and RNS were investigated in vitro. OFA suppressed formation of cholesterol ester hydroperoxides in LDL oxidized by peroxyl radical and peroxynitrite, and formation of thiobarbituric acid reactive substances in LDL oxidized by Cu. In addition, OFA inhibited fragmentation, carbonylation, and nitration of apolipoprotein B-100 (apo B-100) in the oxidized LDL, in which heparin-binding activity of apo B-100 was protected by OFA. Our results suggest that OFA exhibits antioxidant activity against both lipid peroxidation and oxidative modification of apo B-100 in LDL oxidized by ROS and RNS. Polyphenols in oolong tea may prevent atherosclerosis by reducing oxidative stress.
Platelet concentrate product derived from plateletpheresis from a single donor is preferable in terms of reducing the risks of adverse reactions in platelet transfusion. This study evaluated the status of platelet transfusion and the efficacy and safety of plateletpheresis machines. The average number of donors of platelet product per patient has been decreasing and recently reached nearly 1.0; however, some patients still receive multiple random donor platelet products. Platelet collection efficacy was comparable between the Haemonetics Component Collection System (CCS) and the Multi Component System (Multi). However, the CCS has been shown to be effective in terms of processed blood volume and procedure time, especially in donors with lower hematocrits. These results suggest that the CCS may be preferable and safer for donors with lower hematocrits and lighter body weights. Blood centers should collect platelets more effectively to achieve platelet transfusion with the use of platelets derived from a single donor using effective equipment.
The complement-dependent bactericidal factor, Ra-reactive factor, binds specifically to Ra polysaccharide, which is common to some strains of Gram-negative enterobacteria, and its is a complex of proteins composed of a polysaccharide-binding component and a component that is presumably responsible for the complement activation. The former component consists of two different 28-kDa polypeptides, P28a and P28b. We determined the partial amino acid sequences of P28a and P28b, and the results indicated that these polypeptides were similar to two species of mannose-binding protein, MBP-C and MBP-A (alternative names, liver and serum mannan-binding proteins, respectively), which have been isolated from rat liver and/or serum [Drickamer, K., Dordal, M. S., & Reynolds, L. (1986) J. Biol. Chem. 261, 6878-6887; Oka, S., Itoh, N., Kawasaki, T., & Yamashina, I. (1987) J. Biochem. 101, 135-144]. Thus, we cloned the respective cDNAs, using as probes synthetic oligonucleotides for which the sequences had been deduced from the amino acid sequences of P28a and P28b and of rat MBP cDNAs. The primary structures of P28a and P28b deduced from the cloned cDNAs are homologous to one another. They have three domains, a short NH2-terminal domain, a collagen-like domain, and a domain homologous to regions of some carbohydrate-binding proteins, as has been reported for rat MBPs. Southern and Northern blotting analyses using these cDNAs indicated that the P28a and P28b polypeptides are the products of two unique mouse genes which are expressed in hepatic cells.
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