Biomedical subjects

Franck Couillaud

Publications and source records attributed to Franck Couillaud.

5 recordsLinked to original sources

PubMed2007

MMP-7 (matrilysin) expression in human brain tumors.

Matrix metalloproteinases (MMP) which degrades protein components of the extra-cellular matrix and basement membrane seems to be largely involved in cancer invasiveness. MMP proteolitic activity essentially comes from stromal cells but matrilysin (MMP-7) is produced by the tumor itself. Thus, MMP-7 is investigated to address the particular invasive behavior of human glioma. Both MMP-7 mRNA and protein were clearly identified in human glioma. MMP-7 mRNA expression was highly variable within our glioma population. When analyzing MMP-7 mRNA expression in different primary brain tumors, we found highly variable levels of expression not related to their invasive behavior. In successive biopsies obtained in the same patients with glioblastoma, MMP-7 mRNA was quantified and appeared variable, but intra-individual variations were lower than inter-individual differences. With a xenograft model of U87 human tumors in RAG2/gamma(c) immune-deficient mice, the strict tumor origin of MMP-7 was shown. Additionally, MMP-7 expression by U87 cells which is low in culture was stimulated by these cells while forming tumors and the level of expression was higher when the tumor cells were implanted within the brain. These data provide some consistent information about cross-talk occurring between the tumor and the surrounding stroma to regulate MMP-7 expression.

Animals↗

PubMed2006

Gene expression and gene therapy imaging.

The fast growing field of molecular imaging has achieved major advances in imaging gene expression, an important element of gene therapy. Gene expression imaging is based on specific probes or contrast agents that allow either direct or indirect spatio-temporal evaluation of gene expression. Direct evaluation is possible with, for example, contrast agents that bind directly to a specific target (e.g., receptor). Indirect evaluation may be achieved by using specific substrate probes for a target enzyme. The use of marker genes, also called reporter genes, is an essential element of MI approaches for gene expression in gene therapy. The marker gene may not have a therapeutic role itself, but by coupling the marker gene to a therapeutic gene, expression of the marker gene reports on the expression of the therapeutic gene. Nuclear medicine and optical approaches are highly sensitive (detection of probes in the picomolar range), whereas MRI and ultrasound imaging are less sensitive and require amplification techniques and/or accumulation of contrast agents in enlarged contrast particles. Recently developed MI techniques are particularly relevant for gene therapy. Amongst these are the possibility to track gene therapy vectors such as stem cells, and the techniques that allow spatiotemporal control of gene expression by non-invasive heating (with MRI guided focused ultrasound) and the use of temperature sensitive promoters.

Animals↗

PubMed2006

Diversity of contactin mRNA in human brain tumors.

In order to address the molecular signature of human glioma, we investigated the polymorphism of 5'UTR of the mRNA of Contactin, an adhesion molecule which plays a role in the invasive behavior of these tumors. Contactin mRNA is identified by RT-PCR and a strategy based on rapid amplification of cDNA ends (RACE) reveals different 5'UTRs resulting from both an alternative use of two types of leader exons and a splicing mechanism within the 5'UTR. The spliced exon is an Alu-containing element specific to the primate lineage, thus indicating a recent evolution of regulatory processes specific to the simian line that occurs on this gene. Each 5'UTR exhibits different transcription/translation efficiencies and contains features that allow translation to occur independently of the classic cap-dependent mechanism. These data illustrate the complex regulation of Contactin expression in human brain tumors occurring at both transcriptional and translation levels. The different 5'UTRs are differentially expressed in diverse types of human tumors. Thus, the polymorphism occurring within the non-coding part of the Contactin mRNA reveals new opportunities to explore deregulation that occurs during the oncogenic process.

5' Untranslated Regions↗

PubMed2005

Polymorphism of the untranslated regions of the F3/contactin mRNA in the rat nervous system.

F3/contactin is a neural adhesion molecule implicated in various physiological processes. In rat brain tissues, we cloned various mRNA with the same coding region but differing in 3' and 5'UTR. The 3'UTR presents two polyadenylation signals. At the 5' end, we identified two leader exons, multiple transcription initiation sites and splicing events, leading to at least 19 different 5'UTR. The F3/contactin rat gene differs from the mouse gene for two reasons: (1) it contains two additional untranslated exons that are alternatively spliced and (2) it lacks the homologue mouse untranslated exon 0.

Alternative Splicing↗

PubMed2005

Spatial and temporal control of expression of therapeutic genes using heat shock protein promoters.

Heat-shock protein promoters, particularly hsp70, have been used for gene therapy strategies because of their efficiency and the possibility of induction by external heat. This review describes some of the characteristics of hsp70 promoters that make them attractive for use in gene therapy. The human hsp70B promoter is especially promising because of its dose response effect with regard to temperature. Spatial and temporal control of transgene expression using hsp70 promoters necessitates non-invasive methods of local heat deposition and accurate local control of temperature. Special emphasis is given to Focused Ultrasound heating guided by Magnetic Resonance temperature mapping.

Cell Line, Tumor↗