Combination of cell delivery and thermoinducible transcription for in vivo spatiotemporal control of gene expression: a feasibility study.

Purpose: To demonstrate the feasibility of combining in situ delivery of genetically modified cells into the rat kidney, to induce expression of a reporter gene under transcriptional control of a heat-inducible promoter activated with magnetic resonance (MR)-guided focused ultrasonography (US), and to demonstrate in vivo the local expression of the synthesized protein.

Materials And Methods: Experiments were conducted in agreement with the European Commission guidelines and directives of the French Research Ministry. C6 cells were genetically modified by incorporating the firefly luciferase (LucF) gene under transcriptional control of a heat-sensitive promoter (human heat shock protein 70B).

Image-guided, noninvasive, spatiotemporal control of gene expression.

Spatiotemporal control of transgene expression is of paramount importance in gene therapy. Here, we demonstrate the use of magnetic resonance temperature imaging (MRI)-guided, high-intensity focused ultrasound (HIFU) in combination with a heat-inducible promoter [heat shock protein 70 (HSP70)] for the in vivo spatiotemporal control of transgene activation. Local gene activation induced by moderate hyperthermia in a transgenic mouse expressing luciferase under the control of the HSP70 promoter showed a high similarity between the local temperature distribution in vivo and the region emitting light.

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.

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.

Cellular distribution of interleukin-1alpha-immunoreactivity after MPTP intoxication in mice.

In young rodents, peripheral injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) results in a dopaminergic nigrostriatal denervation (during the first week after injection), followed by a spontaneous dopaminergic reinnervation. Sprouting from residual neurons has been proposed to account for this event. It has been shown that an inflammatory process takes place during striatal dopaminergic denervation but its consequences remain controversial.