Using reverse-phase HPLC after pyridylamination, we quantified the concentrations of major neutral oligosaccharides in the milk of sixteen Japanese women collected at 4, 10, 30 and 100 d postpartum. In colostrum and mature milk (30 d lactation), lacto-N-fucopentaose (LNFP) I was the most abundant oligosaccharide, followed by 2 0 -fucosyllactose (2 0 -FL) + lacto-N-difucotetraose (LNDFT), LNFP II + lacto-N-difucohexaose II (LNDFH II), and 3-fucosyllactose (3-FL). Together these accounted for 73 % of the total weight of neutral oligosaccharides in colostrum and mature milk. Changes in concentration occurred during the course of lactation. LNFP I and 2 0 -FL + LNDFT increased from 4 to 10 d postpartum, and then declined by 100 d. LNFP II + LNDFH II steadily increased during the first 30 d and then declined. In contrast, 3-FL increased steadily throughout the entire 100 d of study. Large differences were observed between our data and previously published data in Italian women, in terms of both the concentration and temporal changes of each oligosaccharide. These differences may be caused by different assay methodology, although racial differences cannot be ruled out.
It has been suggested that histologic subtype of ovarian cancer is a factor that determines the chemoresponsiveness of tumor. In this study, we wanted to clarify the prognostic significance of histologic subtype and its correlation to expression of chemoresistance-related proteins (CRPs) in ovarian cancer. A total of 93 stage II-IV ovarian cancers, where the proportion of serous, endometrioid, mucinous, and clear cell subtype was 61.3%, 14.0%, 7.5%, and 17.2%, respectively, were investigated for glutathione S-transferase-pi (GST-pi), MDR (multidrug resistance)-1, and p53 expression using immunohistochemistry. GST-pi expression was detected in 62.4% of the tumors and was not related to histologic subtype of tumor. MDR-1 expression was observed in 12.9% of the tumors tested and was more frequently detected in clear cell adenocarcinomas than other histologic subtypes of tumor (10/ 16 vs. 2 / 77, P < 0.001). P53 expression was found in 49.1% of serous, 53.8% of endometrioid, and 50% of mucinous adenocarcinomas. In contrast, none of 16 clear cell adenocarcinomas showed positive p53 staining. In univariate analysis, no direct correlations were found between CRPs and overall survival. Histology of mucinous/clear cell tumors (P = 0.0063), as well as FIGO stage III/IV (P = 0.0091) and residual tumor >or= 2 cm (P = 0.0045), was found to have independent prognostic value in multivariate analysis. In conclusion, histologic subtype proved to be the significant independent prognostic factor in addition to FIGO stage and residual tumor in stage II-IV ovarian cancer. GST-pi, MDR-1, and p53 expression pattern is closely related to histologic subtype of ovarian cancer, although they are not significant predictors of survival.
The concentrations of three galactosyllactoses found in the milk of 24 Japanese women were determined using normal phase high-performance liquid chromatography of the 2-aminopyridyl (PA) derivatives of the oligosaccharides. The milk was collected at 4, 10, 30 and 100 days post partum. The concentration of 6 -galactosyllactose (6 -GL) was maximal at 4 days post partum, and then decreased, whereas the concentrations of 3 -and 4 -galactosyllactose (3 -GL and 4 -GL) did not change during the course of lactation. In human milk, 6 -GL was the main oligosaccharide among these galactosyllactoses at 4 days post partum, in contrast to bovine milk in which 3 -GL has been reported to be predominant. The concentrations of these galactosyllactoses in human milk were much lower than those reported for 2 -fucosyllacose, 3-fucosyllactose, lacto-Nfucopentaose I , II and III, and 3 -and 6 -N -acetylneuraminyllactose.
The concentrations of the six major sialyl oligosaccharides found in the milk of 24 Japanese women were determined using reverse phase high performance liquid chromatography of the 3-methyl-1-phenyl-5-pyrazolone derivatives of the oligosaccharides. The milk was collected at 4, 10, 30 and 100 days postpartum. The concentrations of all six oligosaccharides decreased during the course of lactation. The concentrations of 6'-sialyllactose, sialyllacto-N-tetraose b and disialyllacto-N-tetraose decreased only after 10 days postpartum, whereas those of sialyllacto-N-tetraose a and sialyllacto-N-neotetraose c as well as 3'-sialyllactose decreased from 4 days postpartum. Large differences were observed between present data and those previously reported for Italian women, both in terms of the content and in the variation pattern of each oligosaccharide during the course of lactation. These differences may be caused by the different ethnicity of the donors as well as the assay methods used in the studies. formed through the actions of various sialyltransferases.4) The sialyl oligosaccharides are generally believed to be of biological significance for human infants.7) Breast-fed infants appear to have fewer or less severe gastrointestinal and respiratory infections during the first year of life than formula-fed infants.8 It is thought that the sialyl saccha rides act as growth factors for beneficial intestinal bacteria such as Bifidobacterium.9) The reduction in pH of the in fant colon resulting from lactose fermentation by Bifido bacterium causes inhibition of the growth of Escherichia coli and other pathogenic organisms.The Sialyl milk oligosaccharides also inhibit the attach ment of pathogenic organisms8,10-12) such as Helicobacter pylori and of cholera toxin, to intestinal epithelial cells and the binding of rotavirus to the colon.In addition, sialic acid in milk oligosaccharides has been thought to be used as a material for the synthesis of brain gangliosides and sialyl glycoproteins.7) Breast milk may be an important source of sialic acid for newborn in fants, whose livers may not be able to synthesize suffi cient sialic acid. 13)The sialic acid content of bovine milk is much lower than that of human milk.14) This implies that sialyl oligo saccharides should be added to infant formulas based on bovine milk constituents. Although the total sialic acid content of human milk at several lactation periods has * Corresponding author . Abbreviations: HPLC, high-performance liquid chromatography; HPAEC, high-pH anion-exchange chromatography; PMP, 3-methyl-1-phenyl-5-pyrazolone; Glc, D-glucose; Gal, D-galactose; G1cNAc, N-acetyl-D-glucosamine; Fuc, L-fucose; NeuAc, N-acetylneuraminic acid; Xyl, D-xylose; 3'-SL, 3'-sialyllactose; 6'-SL, 6'-sialyllactose; LSTa, sialyllacto-N-tetraose a; LSTb, sialyllacto-N tetraose b; LSTc, sialyllacto-N-neotetraose c; DSLNT, disialyllacto-N-tetraose; 3'S3FL, 3'-sialyl-3-fucosyllactose; LNT, lacto-N-tetraose; LNnT, lacto-N-neotetraose. 462 J. Appl. Glycosci., Vol. 50, No. 4 (2003) be...
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