Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim was to determine whether proton magnetic resonance spectroscopy (MRS) could grade human colorectal cells of differing malignant potential. A cell model of tumour development and progression comprising 2 non-tumorigenic adenoma lines and 4 carcinoma lines of increasing tumorigenicity was chosen. A gradual reduction in cellular differentiation and an accumulation of genetic alterations from adenoma to carcinoma characterized the selected cell lines. One-dimensional and 2-dimensional MRS showed that reduced differentiation in the cell model correlated with an increase in the levels of lipid, metabolites, the glycosylation intermediate uridine diphospho-N-acetylglucosamine and cell-surface fucosylation. Mutations involving the K-ras, APC and DCC genes are present both in adenoma- and in carcinoma-derived lines in this model, but the first evidence of an abnormality in the p53 gene was concomitant with the cells' ability to grow as a tumour in athymic nude mice. This genetic change coincided with the detection, by MRS, of UDP-hexose (ribose moiety, 2D MRS cross peak between H2 at 4.38 ppm and HI at 5.99 ppm) and the appearance of an additional fucosyl resonance (cross peak between-CH3 at 1.41 and H5 at 4.30 ppm) in the least tumorigenic of the carcinoma cell lines. An increase in complexity of the fucosylation spectral pattern was observed with further cellular de-differentiation and increased tumorigenicity. Collectively these data support the existence of an adenoma-carcinoma sequence.
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PMID:Correlation of cellular differentiation in human colorectal carcinoma and adenoma cell lines with metabolite profiles determined by 1H magnetic resonance spectroscopy. 792 26

Oligonucleotides containing 2'-O-aminopropyl-substituted RNA have been synthesized. The 2'-O-(aminopropyl)adenosine (APA), 2'-O-(aminopropyl)cytidine (APC), 2'-O-(aminopropyl)-guanosine (APG), and 2'-O-(aminopropyl)uridine (APU) have been prepared in high yield from the ribonucleoside, protected, and incorporated into an oligonucleotide using conventional phosphoramidite chemistry. Molecular dynamics studies of a dinucleotide in water demonstrates that a short alkylamine located off the 2'-oxygen of ribonucleotides alters the sugar pucker of the nucleoside but does not form a tight ion pair with the proximate phosphate. A 5-mer with the sequence ACTUC has been characterized using NMR. As predicted from the modeling results, the sugar pucker of the APU moiety is shifted toward a C3'-endo geometry. In addition, the primary amine rotates freely and is not bound electrostatically to any phosphate group, as evidenced by the different sign of the NOE between sugar proton resonances and the signals from the propylamine chain. Incorporation of aminopropyl nucleoside residues into point-substituted and fully modified oligomers does not decrease the affinity for complementary RNA compared to 2'-O-alkyl substituents of the same length. However, two APU residues placed at the 3'-terminus of an oligomer gives a 100-fold increase in resistance to exonuclease degradation, which is greater than observed for phosphorothioate oligomers. These structural and biophysical characteristics make the 2'-O-aminopropyl group a leading choice for incorporation into antisense therapeutics. A 20-mer phosphorothioate oligonucleotide capped with two phosphodiester aminopropyl nucleotides targeted against C-raf mRNA has been transfected into cells via electroporation. This oligonucleotide has 5-10-fold greater activity than the control phosphorothioate for reducing the abundance of C-raf mRNA and protein.
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PMID:2'-O-aminopropyl ribonucleotides: a zwitterionic modification that enhances the exonuclease resistance and biological activity of antisense oligonucleotides. 897 41

The alpha-gal epitope (Galalpha1-3Galbeta1-(3)4GlcNAc-R) is abundantly synthesized on glycolipids and glycoproteins of non-primate mammals and New World monkeys by the glycosylation enzyme alpha1,3galactosyltransferase (alpha1,3GT). In humans, apes and Old World monkeys, this epitope is absent because the alpha1,3GT gene was inactivated in ancestral Old World primates. Instead, humans, apes and Old World monkeys produce the anti-Gal antibody, which specifically interacts with alpha-gal epitopes and which constitutes approximately 1% of circulating immunoglobulins. Anti-Gal has functioned as an immunological barrier, preventing the transplantation of pig organs into humans, because anti-Gal binds to the alpha-gal epitopes expressed on pig cells. The recent generation of alpha1,3GT knockout pigs that lack alpha-gal epitopes has resulted in the elimination of this immunological barrier. Anti-Gal can be exploited for clinical use in cancer immunotherapy by targeting autologous tumour vaccines to APC, thereby increasing their immunogenicity. Autologous intact tumour cells from haematological malignancies, or autologous tumour cell membranes from solid tumours are processed to express alpha-gal epitopes by incubation with neuraminidase, recombinant alpha1,3GT and with uridine diphosphate galactose. Subsequent immunization with such autologous tumour vaccines results in in vivo opsonization by anti-Gal IgG binding to these alpha-gal epitopes. The interaction of the Fc portion of the vaccine-bound anti-Gal with Fcgamma receptors of APC induces effective uptake of the vaccinating tumour cell membranes by the APC, followed by effective transport of the vaccinating tumour membranes to the regional lymph nodes, and processing and presentation of the tumour-associated antigen (TAA) peptides. Activation of tumour-specific T cells within the lymph nodes by autologous TAA peptides may elicit an immune response that in some patients will be potent enough to eradicate the residual tumour cells that remain after completion of standard therapy. A similar expression of alpha-gal epitopes can be achieved by transduction of tumour cells with an adenovirus vector (or other vectors) containing the alpha1,3GT gene, thus enabling anti-Gal-mediated targeting of the vaccinating transduced cells to APC. Intratumoral delivery of the alpha1,3GT gene by various vectors results in the expression of alpha-gal epitopes. Such expression of the xenograft carbohydrate phenotype is likely to induce anti-Gal-mediated destruction of the tumour lesion, similar to rejection of xenografts by this antibody. Opsonization of the destroyed tumour cell membranes by anti-Gal IgG further targets them to APC, thus converting the tumour lesion, treated by the alpha1,3GT gene, into an in situ autologous tumour vaccine.
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PMID:The alpha-gal epitope and the anti-Gal antibody in xenotransplantation and in cancer immunotherapy. 1626 20