High-efficiency deleter mice show that FLPe is an alternative to Cre- loxP

Hypoxia-induced Transcriptional Activation and Increased mRNA Stability of Vascular Endothelial Growth Factor in C6 Glioma Cells

Conjugates of oligonucleotides and modified oligonucleotides: a review of their synthesis and properties

Maintaining the integrity of the gastrointestinal tract, despite the continual presence of microbial flora and injurious agents, is essential. Epithelial continuity depends on a family of small, yet abundant, secreted proteins--the trefoil factors (TFFs). TFFs protect mucous epithelia from a range of insults and contribute to mucosal repair, although the signalling events that mediate these responses are only partially understood.

Trefoil factors: initiators of mucosal healing

The past several years have seen an explosive growth in the application of antisense oligodeoxynucleotides as modulators of gene expression. In this review, we discuss the various classes of compounds currently receiving attention. These include unmodified oligodeoxynucleotides, methylphosphonates, phosphorothioates, and α-oligonucleotides. The relative advantages and disadvantages of each class with regard to parameters such as ( a ) duplex stability ( b ) nuclease resistance, and ( c ) effectiveness of specific gene inhibition are noted. Oligodeoxynucleotides covalently linked to intercalating and other reactive groups are also described, as are possible mechanisms of oligodeoxynucleotide action. Finally, we consider potential future directions for this field and note that it holds the promise for specific gene therapy.

https://cancerres.aacrjournals.org/content/canres/48/10/2659.full.pdf

Oligodeoxynucleotides as inhibitors of gene expression: a review.

Approximately 50% of human breast tumors secrete a small cysteine-rich protein, pS2, of unknown function. pS2 protein was recently found to be homologous to a porcine protein with hormonogastric activity, pancreatic spasmolytic polypeptide (PSP), in which the 5-cysteine domain present in pS2 is tandemly duplicated. We have characterized cDNA species encoding PSP and its human and mouse counterparts, hSP and mSP. We show that hSP and pS2 are separately encoded in the genome, and that the two proteins are co-expressed in normal stomach epithelium. However, expression of hSP was not detected in breast tumors. Computer analysis revealed that the pattern of conserved cysteine residues in hSP and pS2, the P domain, is present at the N termini of two other mammalian proteins, intestinal sucrase-isomaltase and lysosomal alpha-glucosidase.

hSP, the domain-duplicated homolog of pS2 protein, is co-expressed with pS2 in stomach but not in breast carcinoma.

A new set of molecules made of an intercalating agent (oxazolopyridocarbazole, OPC) covalently linked through a polymethylene chain of various length to the 3' end of alpha-anomeric or beta-anomeric tetradeoxynucleotides (alpha- or beta-T4) have been synthesized The beta-thymidylate modified compound (beta-T4C5OPC) is able to interact with the complementary sequence, beta-poly (rA); this interaction is strongly stabilized compared to the parent compound, beta-oligo(dT)4 and is specific for poly (rA) The molecule synthesized from the unnatural alpha-anomer, alpha-T4C5OPC, is also able to interact with poly (rA) leading to the formation of an alpha-beta hybrid stabilized by the energy provided by the OPC moiety The stoechiometry of the binding reaction shows that an A-T pairing occurs in the alpha-beta heterohybrids Tm studies reveal that the alpha-beta heterohybrids are more stable than their beta-beta counterparts

α-DNA IV: α-anomeric and β-anomeric tetrathymidylates covalently linked to intercalating oxazolopyridocarbazole. Synthesis, physicochemical properties and poly (rA) binding

Ninety-one percent of breast tumors aberrantly express an epithelial tumor antigen (ETA) identified by monoclonal antibody H23. Vaccinia virus recombinants expressing tumor antigens have considerable promise in the active immunotherapy of cancer, and we have evaluated the potential of vaccinia recombinants expressing the secreted (S) and cell-associated (transmembrane, T) forms of H23 ETA to elicit immunity to tumor cells expressing ETA. Tumorigenic ras-transformed Fischer rat fibroblast lines FR-S and FR-T, expressing the S or T form of H23 ETA, respectively, were constructed for use in challenge experiments. Expression of H23 ETA in these lines was confirmed by Western blotting and immunofluorescence. When challenged by subcutaneous seeding of tumor cells, 97% (FR-S) and 91% (FR-T) of syngeneic Fischer rats rapidly developed tumors that failed to regress. Vaccination with recombinant vaccinia virus expressing ETA-T prior to challenge prevented tumor development in 82% of animals seeded with FR-T cells but in only 61% of animals seeded with FR-S. The vaccinia recombinant expressing the S form was a less effective immunogen, and vaccination protected only 29-30% of animals from developing tumors upon challenge with either FR-S or -T cells. The increased immunogenicity of the recombinant expressing ETA-T was reflected in elevated levels of ETA-reactive antibody in vaccinated animals, confirming that secreted antigens expressed from vaccinia virus are less effective immunogens than their membrane-associated counterparts.

https://www.pnas.org/content/pnas/87/23/9498.full.pdf

Claudie Gautier

Papers

hSP, the domain-duplicated homolog of pS2 protein, is co-expressed with pS2 in stomach but not in breast carcinoma.

α-DNA IV: α-anomeric and β-anomeric tetrathymidylates covalently linked to intercalating oxazolopyridocarbazole. Synthesis, physicochemical properties and poly (rA) binding

Vaccination against tumor cells expressing breast cancer epithelial tumor antigen.

A ubiquitous mammalian expression vector, pHMG, based on a housekeeping gene promoter.

Vaccinia recombinants expressing secreted and transmembrane forms of breast cancer-associated epithelial tumour antigen (ETA).