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Biomedical subjects

G Milhaud

Publications and source records attributed to G Milhaud.

At least 271 records · Page 15Linked to original sources
PubMedDate not supplied

Treatment of medullary thyroid carcinoma by combined expression of suicide and interleukin-2 genes.

Inherited medullary thyroid carcinomas (MTC) are aggressive and resistant to conventional chemo- and radiotherapies. We evaluated a novel strategy for treatment of MTC, combining "suicide" and interleukin-2 (IL-2) gene therapies. Tumors were produced in Wag/Rij rats by orthotopic injection of the rMTC 6-23 cell line, and/or derivatives expressing the herpes simplex virus 1 thymidine kinase (HSV1-TK) gene (rMTC-TK). Ganciclovir, a nucleoside analog selectively transformed to a toxic metabolite by HSV1-TK, totally eradicated rMTC-TK tumors in 60% of the animals. 1:1 rMTC and rMTC-TK mixed tumors were also strongly inhibited by ganciclovir (P < 0.05), indicating the occurrence of an efficient "bystander" effect in vivo. Double labelling of rMTC cell membranes and apoptotic nuclei revealed that, as with the TK+ cells, some TK- cells died by apoptosis. A 1:1 mixture of rMTC and rMTC-TK cells was administered to produce established tumors and then rMTC cells, transfected to express the IL-2 gene (rMTC-IL2), were inoculated. Combined ganciclovir and IL-2 treatment improved the inhibition of tumor growth compared to that following ganciclovir alone (86% compared to 54%, P < 0.05). This treatment also significantly enhanced macrophage activation and tumor infiltration by CD8+ and CD4+ T lymphocytes. These results open an avenue for combining suicide and immunoregulatory gene therapies for MTC management in man.

Animals↗
PubMedDate not supplied

Renal calcitonin receptors in the ageing Wistar rat.

Ageing can affect both the secretion of a hormone and the number of its specific receptors. An autoradiographic method was used to quantify renal binding sites for calcitonin (CT) in Wistar rats aged 1, 3, 6, 12 and 18 months. In 1-month-old rats, high densities of calcitonin binding sites were observed in the outer cortex and in the outer medulla. However, an increasing number of rats presenting very low calcitonin binding site density in the outer medulla (that we called 'deficient') appeared during ageing. Ageing also involved a gradual decrease in calcitonin receptor densities in the kidney outer medulla in the non-'deficient' rats. The basal calcitonin concentrations in plasma did not vary with age. The increase in plasma calcitonin in response to a calcium injection increased with age, but this increase was not cor- related with the decrease in binding site density. In 18-month-old rats suffering from C cell hyperplasia or carcinoma, both basal and stimulated levels of calcitonin were increased (basal: x 3; stimulated: x 5), but no major modification in calcitonin binding site densities was observed. Thus in the Wistar rat, receptor density is apparently age-regulated and a relative increase in endogenous CT level is without effect on receptor density.

Journal Article↗
PubMedDate not supplied

Expression of CGRP mRNAs in the pink salmon, Oncorhynchus gorbuscha.

We report the isolation of calcitonin gene-related peptide (CGRP) mRNAs and expression of these RNAs in different tissues in the pink salmon, Oncorhynchus gorbuscha. Hybridization of poly(A+) RNAs indicated a mature CGRP RNA of 1.1 kb. The CGRP-like immunoreactivity occurring in tissues and plasma had the same relative molecular weight as the synthetic molecule. Variations in CGRP plasma levels were observed during migration, spawning, and postspawning states. These data suggest that CGRP may play an important role during the reproductive cycle of salmon.

Animals↗
PubMedDate not supplied

Bivalent hapten-bearing peptides designed for iodine-131 pretargeted radioimmunotherapy.

Pretargeting with bispecific antibodies has been used successfully for tumor detection and is now considered for radioimmunotherapy. The advantages of bivalent haptens have been demonstrated in this context. A series of bivalent molecules allowing efficient labeling with radioactive iodine has been designed for use with this new technology. They were based on the histamine-hemisuccinate hapten and prepared by solid phase peptide synthesis. Simultaneous binding of two antibody molecules to one bivalent hapten was possible with low steric hindrance when the two hapten groups were attached to the lateral chains of lysine residues separated by a single amino acid. Bispecific antibodies to the hapten and to carcinoembryonic antigen were shown to mediate specific binding of the haptens to tumor cells in vitro. These experiments demonstrated that the bivalent hapten AG3.0, with a lysyl-D-tyrosyl-lysine connecting chain, possessed the best binding properties. This peptide was used to target iodine-125 to human colon cancer xenografts in nude mice. High tumor uptake and tumor to normal tissue ratios were observed. This peptide thus appears as a good candidate for further development. Asymmetric bivalent haptens, with one histamine-hemisuccinate and one diethylenetriaminepentaacetic acid group, have also been prepared and shown to be capable of binding simultaneously two specific antibody molecules. These peptides should be useful to target radioiodine to cells characterized by the expression of two different antigenic markers.

Animals↗
PubMedDate not supplied

[Calcitonin an XXVI. Value of replacement doses in daily practice].

Calcitonin and insulin are nowadays the most largely prescribed peptide hormones. It is therefore surprising that for some authors the relevant dosage of calcitonin remains a matter of concern. The dose-effect relationship was established twenty years ago, taking into account the kinetic analysis of calcium metabolism and the clinical data, enabling to assess effective dose of calcitonin. Our clinical experience concerning regularly followed-up patients confirms that the replacement dose of calcitonin is necessary and sufficient for managing the disorders of bone and calcium metabolism. Long-term calcitonin replacement treatment: represents a therapeutic approach preserving the integrity and the sensitivity of the hormone receptors, is devoid of the undesirable effects due to pharmacologic doses of the hormone. Therefore the compliance to the treatment is very high. Replacement therapy should become the rule governing the use of calcitonin.

Animals↗