Structural characterization of the N-linked oligosaccharides in bile salt-stimulated lipase originated from human breast milk. (1/1911)

The detailed structures of N- glycans derived from bile salt-stimulated lipase (BSSL) found in human milk were determined by combining exoglycosidase digestion with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The N- glycan structures were conclusively determined in terms of complexity and degree of fucosylation. Ion-exchange chromatography with pulsed amperometric detection, together with mass-spectral analysis of the esterified N- glycans, indicated the presence of monosialylated structures. The molecular mass profile of esterified N- glycans present in BSSL further permitted the more detailed studies through collision-induced dissociation (CID) and sequential exoglycosidase cleavages. The N- glycan structures were elucidated to be complex/dibranched, fucosylated/complex/dibranched, monosialylated/complex/dibranched, and monosialylated/fucosylated/dibranched entities.  (+info)

Primary yolk sac tumour of the liver in adulthood. (2/1911)

Primary yolk sac tumour of the liver is exceedingly rare. A 28 year old woman presented with a cystic liver mass and a markedly raised serum alpha-fetoprotein concentration. She underwent a partial hepatectomy for a suspected hepatocellular carcinoma but histological examination of the tumour revealed the classical morphological and immunohistochemical features of a yolk sac tumour. There was no evidence of an extrahepatic primary source. Review of this case, together with the six previously reported adult cases of primary yolk sac tumours of the liver, revealed several features of the tumour that may aid differentiation from hepatocellular carcinoma, with potential therapeutic implications.  (+info)

Phase II trial of primary chemotherapy followed by reduced-dose radiation for CNS germ cell tumors. (3/1911)

PURPOSE: A prospective phase II study was initiated to assess the response rate, survival, and late effects of treatment in patients with newly diagnosed CNS germ cell tumors (GCT), using etoposide plus cisplatin followed by radiation therapy prescribed by extent of disease, histology, and response to chemotherapy. PATIENTS AND METHODS: Seventeen patients aged 8 to 24 years with histologically proven CNS GCT received etoposide (100 mg/m2/d) plus cisplatin (20 mg/m2/d) daily for 5 days every 3 weeks for four cycles, followed by radiation therapy. Nine patients had germinomas; eight had mixed GCT. Four patients (three with germinomas and one with mixed GCT) presented with leptomeningeal dissemination. RESULTS: Radiographically, 14 of 17 patients were assessable for response; 11 patients experienced complete regression, and three had major partial regression before radiation. Six of seven assessable patients with elevated CSF levels of alpha-fetoprotein or betahuman chorionic gonadotropin had normalization with chemotherapy alone; all normalized with combined chemotherapy and radiation therapy. All 17 patients are alive without evidence of disease (median follow-up, 51 months). One patient developed a relapse in the spinal leptomeninges and was rendered free of disease with spinal radiation more than 5 years ago. One patient developed carotid stenosis requiring surgery. Thus far, only minimal long-term deterioration in neurocognitive function has been detected as a consequence of protocol treatment. CONCLUSION: Conventional-dose intravenous chemotherapy with etoposide and cisplatin can effect tumor regression in a high proportion of patients with CNS GCT, including those with leptomeningeal metastases. Acute and long-term toxicities are acceptable. Progression-free survival and overall survival are excellent.  (+info)

Several new targets of antitumor agents. (4/1911)

Alpha-fetoprotein (AFP), as a hepatoma-promoting factor, has become a new target of anti-hepatoma agents. It is a new approach for the treatment of tumors to inhibit or block oncogene expression. Informational drugs are being developed for gene therapy applications as inhibitors of oncogene expression. The induction of tumor cell differentiation is another new strategy of drug therapy of tumors. Common action mode of many antitumor drugs is to induce apoptosis of tumor cells. Suicide genes, as targeting therapy of tumors, improve the present chemotherapy, exhibiting broad application prospects.  (+info)

Complementary adenoviral vectors for oncolysis. (5/1911)

Replication-competent adenoviruses (Ads) were used for oncolytic virotherapy soon after they were discovered. Recently mutated and genetically engineered Ads have been shown to selectively lyse tumor cells. We have split the human Ad type 5 genome into two defective viruses that complement each other only in certain tumor cells. The genome of one of these vectors, GT5610, contains only the minimal viral elements required in cis for replication and packaging and the E1 viral genes with E1A under the control of the human alpha-fetoprotein promoter. This "controlled" vector has a capacity for 30 kilobases of foreign DNA. The supplemental vector, AdHbeta, contains all adenoviral genes except for E1. Both vectors were designed to carry heterologous reporter genes whose expression could be detected throughout the tumor. Coinfection of hepatocarcinoma cells that have the capacity to transcribe genes under the control of the alpha-fetoprotein promoter leads to cell lysis and copropagation. The oncolytic spread of these complementary vectors in vivo was demonstrated by the intratumoral injection of human hepatocarcinomas xenografted in severe combined immunodeficient (SCID) mice. This system presents safety and gene capacity features that could yield a therapeutic advantage over oncolysis by a single virus.  (+info)

The effects on fetal development of high alpha-fetoprotein and maternal smoking. (6/1911)

OBJECTIVES: This study determined the risk of impaired fetal growth resulting from the interaction between maternal smoking during pregnancy and unexplained elevated concentrations of maternal serum alpha-fetoprotein (MSAFP). METHODS: This observational study involved 123 pregnant smokers with unexplained second-trimester elevated concentrations of MSAFP, 827 smokers with normal levels, and 471 nonsmokers with raised levels. RESULTS: By logistic regression, coincident smoking and elevated MSAFP levels were found to be associated with increases in the low basic risks of prematurity, small-for-gestational-age births, low birthweight, and need for neonatal care. CONCLUSIONS: Maternal smoking has an adverse effect on fetal development in pregnancies with unexplained elevated MSAFP concentrations. Such pregnancies merit close surveillance.  (+info)

Size of lipid microdroplets effects results of hepatic arterial chemotherapy with an anticancer agent in water-in-oil-in-water emulsion to hepatocellular carcinoma. (7/1911)

We have initially prepared a new drug delivery system for hepatocellular carcinoma (HCC). Using sonication and a detergent, iodinated poppy seed oil (IPSO) can be mixed with an aqueous solution of epirubicin to make a water-in-oil emulsion. The water-in-oil emulsion is further passed through a microporous glass membrane and split into saline to make a long-term inseparable water-in-oil-in-water emulsion (W/O/W) that consists of IPSO microdroplets. To investigate the effect of the size of IPSO microdroplets on the efficacy of injection chemotherapy with W/O/W in patients with HCC, 32 HCC patients were randomly assigned and treated with W/O/W of small IPSO microdroplets (30 micrometers in diameter) containing 60 mg of epirubicin (n = 16, group A) or W/O/W of large IPSO microdroplets (70 micrometers) containing the same amounts of epirubicin (n = 16, group B). Effects were assessed by measuring the percentage of decline of the alpha-fetoprotein (AFP) level in a week from the AFP level immediately before the treatment. The decline was significantly larger in group B (50.5 +/- 19.8, mean +/- S.D.) compared with group A (18.9 +/- 33.1; p <.005). The size of IPSO microdroplets injected into the hepatic artery determines the decrease of serum AFP levels of the patients with HCC.  (+info)

The recombinant third domain of human alpha-fetoprotein retains the antiestrotrophic activity found in the full-length molecule. (8/1911)

Previous studies have shown that alpha-fetoprotein (AFP) interferes with estrogen (E2)-stimulated growth, including E2-stimulated breast cancer growth. In an effort to localize the antiestrotrophic portion of the molecule, the C-terminal one-third (200 amino acids) of human AFP, known as Domain III, was produced in a baculovirus expression system as a fusion protein containing an amino terminal histidine tag. The histidine tag was included to facilitate purification by metal ion affinity chromatography. The purified recombinant Domain III fusion protein was functionally similar to full-length natural AFP isolated from human cord sera or from cultured human hepatoma cells (HepG2) in that they all produced significant and quantitatively similar inhibition of E2-stimulated growth of immature mouse uterus. Furthermore, the dose-response profiles of the recombinant Domain III AFP and natural full-length AFP were similar. Preincubation of either protein in a molar excess of E2 lowered the minimally effective antiestrotrophic dose and produced a difference spectrum consistent with a change in conformation. These findings indicate that the antiestrotrophic activity of AFP is contained within the third domain of the molecule, and they have obvious implications for the production of biologically active peptides derived from this portion of the AFP molecule.  (+info)