Thierry Dufour

Antisense anti IGF-I cellular therapy of malignant tumours: Immune response in cancer patients

The treatment of cancer by antisense anti-IGF-I cellular therapy inducing immune response has evoked interest among many promising strategies. Here, we reported some results obtained from patients with cancer, mainly glioblastoma treated by this strategy, which was also extended to patients with colon carcinoma, ovary cystadenocarcinoma and prostate adenocarcinoma. It was shown that, in the phase I of clinical trial, patients vaccinated with their own tumour cells treated by antisense IGF-I presented a slight increase of temperature. Their peripheral blood lymphocytes showed a shift in the percentage of CD8 effector cells as judged by expression of cell surface markers CD8+ CD28+. Particularly, in two treated patients with glioblastoma, the survival time was 19 and 24 months respectively in comparison to the range of 12 to 15 months observed in the case of classical treatment such as surgery, radiation or chemotherapy. These results, although preliminary, gave indication that the reported strategy could deserve consideration owing to its safety. Furthermore, the increase in the percentage of peripheral blood monomorphonucleated cells (PBMNCs) with effector phenotype, i.e., CD8+ CD28+ in vaccinated patients might explain their prolonged survival time.

Effect of limiting the cathode surface on direct current microhollow cathode discharge in helium

This paper describes how to light several microdischarges in parallel without having to individually ballast each one. The V-I curve of a microhollow cathode discharge is characterized by a constant voltage in the normal glow regime because the plasma is able to spread over the cathode surface area to provide the additional secondary electrons needed. If one limits the cathode surface area, the V-I characteristic can be forced into an abnormal glow regime in which the operating voltage must increase with the current. It is then possible to light several microdischarges mounted in parallel without ballasting them individually.

A new putative target for antisense gene therapy of glioma: Glycogen synthase

The treatment of malignant brain gliomas remains a challenge, despite the availability of the classical triad of surgery, radiotherapy, and chemotherapy. There is thus the need for investigations into other forms of treatment strategies, such as gene therapy. Using antisense technology we have targeted glycogen metabolism, since malignant astrocytes present a high content of glycogen. In vitro rat C6‑glioma cells, transfected with antisense glycogen synthase (C6‑AS cells) exhibited a decreased expression of glycogen synthase and reduced activity of glycogen synthesis, along with attenuated invasiveness. In vivo tumors induced by C6‑AS cells in nude mice exhibited a significant reduction in tumor growth compared with controls. This reduction could be mediated by the induction of MCH‑I expression. The inhibition of glycogen synthesis by antisense glycogen synthase validates a putative target and a new approach for further study to advance the much‑needed efficacy of intervention strategies for malignant gliomas.

Ignition and extinction phenomena in helium micro hollow cathode discharges

Micro hollow cathode discharges (MHCD) were produced using 250 µm thick dielectric layer of alumina sandwiched between two nickel electrodes of 8 µm thickness. A through cavity at the center of the chip was formed by laser drilling technique. MHCD with a diameter of few hundreds of micrometers allowed us to generate direct current discharges in helium at up to atmospheric pressure. A slowly varying ramped voltage generator was used to study the ignition and the extinction periods of the microdischarges. The analysis was performed by using electrical characterisation of the V-I behaviour and the measurement of He*(3S1) metastable atoms density by tunable diode laser spectroscopy. At the ignition of the microdischarges, 2 µs long current peak as high as 24 mA was observed, sometimes followed by low amplitude damped oscillations. At helium pressure above 400 Torr, an oscillatory behaviour of the discharge current was observed just before the extinction of the microdischarges. The same type of instability in the extinction period at high pressure also appeared on the density of He*(3S1) metastable atoms, but delayed by a few µs relative to the current oscillations. Metastable atoms thus cannot be at the origin of the generation of the observed instabilities.

RF impedance measurements of DC atmospheric micro-discharges

AbstractThe available diagnostics for atmospheric micro-plasmas remain limited andnrelatively complex to implement; so we present a radio-frequency techniquenfor diagnosing a key parameter here. The technique allows one to estimatenthe dependencies of the electron density by measuring the RF-impedance ofnthe micro-plasma and analyzing it with an appropriate equivalent circuit.nThis technique is inexpensive, can be used in real time and gives reasonablenresults for argon and helium DC micro-plasmas in holes over a wide pressurenrange. The electron density increases linearly with current in the expectednrange consistent with normal glow discharge behavior.