Biomedical subjects

Jean-Marc Simon

Publications and source records attributed to Jean-Marc Simon.

8 recordsLinked to original sources

PubMed2005

Successful combination of local CpG-ODN and radiotherapy in malignant glioma.

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) display broad immunostimulating activity and are currently under clinical trial in various malignancies, including recurrent glioblastomas. Combining CpG-ODN with another therapy that could induce antigen release might enhance tumor-specific immune response. We investigated whether radiotherapy (RT) could be associated advantageously to intratumoral injections of CpG-ODN. Fisher rats bearing 9L glioma were treated with various combinations of RT and CpG-28, an oligonucleotide with good immunostimulating activity. RT and CpG-28 induced complete tumor remission in one-third of the animals. When both treatments were combined, complete tumor remission was achieved in two-thirds of the animals (p < 0.001 when compared to non-treated rats, p < 0.03 when compared to CpG-28 alone). Such efficacy was not observed in nude mice, underlying the role of T cells in antitumor effects. The combination of both treatments appeared optimal when the delay between RT and CpG-28 administration was <3 days (from 100% survival for a 3 days delay, to 57% survival for a 21 days delay, p < 0.05). Tumor infiltration by immune cells and expression within tumors of the CpG receptor, TLR9, were not modified by irradiation. These results support an attractive strategy of sequential radiotherapy and immunotherapy by CpG-ODN and have potential implications for future clinical trials with CpG-ODN.

Animals↗

PubMed2005

Sticking probability on zeolites.

The sticking coefficient, i.e., the probability that, on hitting the surface of a nanoporous particle (zeolite), a molecule shall be able to enter the intracrystalline space, is a key quantity for the application of such materials in heterogeneous catalysis and molecular sieving. On the basis of pulsed field gradient NMR diffusion measurements and molecular dynamics simulations, typical values of this probability are found to be close to one. They exceed previous estimates on the basis of IR uptake measurements by many orders of magnitude.

Journal Article↗

PubMed2005

[Concomitant radiotherapy with chemotherapy in patients with glioblastoma].

Glioblastomas are the most frequent and the most aggressive primary brain tumors in adults. Therapeutic strategy is challenging because of radioresistance and chemoresistance explaining the poor prognosis (median survival of 12 months). Standard therapy consisted until recently of surgery and postoperative radiotherapy while the impact of chemotherapy (investigated as adjuvant, neo adjuvant therapy or concomitant with irradiation) was a matter of debate. However a recent phase III study has concluded to the benefit of adjuvant temozolomide administered during and after radiotherapy. This strategy is yet to become a standard.

Antineoplastic Agents↗

PubMed2005

[Combined radiotherapy and hormone therapy in non metastatic adenocarcinoma of prostate].

Non metastatic adenocarcinoma of prostate can be cured in the vast majority of cases with surgery and/or external or interstitial radiotherapy. Failures are much more frequent when tumours are locally advanced. For this reason, new strategies have been designed, among them combined radiotherapy and hormonotherapy, in most cases with a LHRH analog, neoadjuvant and/or concomitant and/or adjuvant. Analysis of results of recent randomised trials comparing this association and exclusive radiotherapy allows for validating concept of combined radiotherapy and hormono therapy in locally advanced adenocarcinoma of prostate, while many questions should be more clearly answered.

Androgen Antagonists↗

PubMed2004

Monte Carlo versus molecular dynamics simulations in heterogeneous systems: an application to the n-pentane liquid-vapor interface.

The Monte Carlo (MC) and molecular dynamics (MD) methodologies are now well established for computing equilibrium properties in homogeneous fluids. This is not yet the case for the direct simulation of two-phase systems, which exhibit nonuniformity of the density distribution across the interface. We have performed direct MC and MD simulations of the liquid-gas interface of n-pentane using a standard force-field model. We obtained density and pressure components profiles along the direction normal to the interface that can be very different, depending on the truncation and long range correction strategies. We discuss the influence on predicted properties of different potential truncation schemes implemented in both MC and MD simulations. We show that the MD and MC profiles can be made in agreement by using a Lennard-Jones potential truncated via a polynomial function that makes the first and second derivatives of the potential continuous at the cutoff distance. In this case however, the predicted thermodynamic properties (phase envelope, surface tension) deviate from experiments, because of the changes made in the potential. A further readjustment of the potential parameters is needed if one wants to use this method. We conclude that a straightforward use of bulk phase force fields in MD simulations may lead to some physical inconsistencies when computing interfacial properties.

Journal Article↗

PubMed2004

The GETUG 70 Gy vs. 80 Gy randomized trial for localized prostate cancer: feasibility and acute toxicity.

PURPOSE: To describe treatments and acute tolerance in a randomized trial comparing 70 Gy and 80 Gy to the prostate in patients with localized prostate cancer. METHODS AND MATERIALS: Between September 1999 and February 2002, 306 patients were randomized to receive 70 Gy (153 patients) or 80 Gy (153 patients) in 17 institutions. Patients exhibited intermediate-prognosis tumors. If the risk of node involvement was greater than 10%, surgical staging was required. Previous prostatectomy was excluded, and androgen deprivation was not admitted. The treatment was delivered in two steps. PTV1-including seminal vesicles, prostate, and a 1-0.5-cm margin-received 46 Gy given with a 4-field conformal technique. PTV2, reduced to prostate with the same margins, irradiated with at least 5 fields. Dose was prescribed according to ICRU recommendations in the 70 Gy group, but adapted at the 80 Gy level. RESULTS: All patients but one in the 80 Gy arm completed the treatment. In the 70 Gy arm, the mean dose to the PTV2 was 69.5 Gy. In the 80 Gy arm, the mean dose in the PTV2 was 78.5 Gy. Acute toxicity according to Radiation Therapy Oncology Group scale during treatment was reported in 306 patients. There was no statistically significant difference between the two arms: 12% had no toxicity, 80% complained of bladder toxicity, and 70% complained of rectal symptoms. Two months after the end of treatment, 43% of the 70 Gy level and 48% of the 80 Gy level complained of side effects, including 24% and 20% of sexual disorders. There was 6% and 2% of Grade 3 urinary and rectal toxicity. Five patients required a 10-29-day suspension of the treatment. Acute Grade 2 and 3 side effects were related to PTV and CTV1 size, which was the only independent predictive factor in multivariate analysis. Toxicity was not related to the center, age, arm of treatment, or selected data from dose-volume histogram of organ at risk. CONCLUSION: Treatments were completed in respect to constraints. Acute toxicity was acceptable. Intensity of toxicity depended on target volumes.

Aged↗

PubMed2004

Prednisone reduces muscle degeneration in dystrophin-deficient Caenorhabditis elegans.

Duchenne muscular dystrophy is a degenerative muscular disease caused by mutations in the dystrophin gene. There is no curative treatment against Duchenne muscular dystrophy. In several countries, the steroid prednisone (or analogs) is prescribed as a palliative treatment. In the model animal Caenorhabditis elegans, mutations of the dys-1 dystrophin-like gene lead to a muscular degenerative phenotype when they are associated with a mild MyoD mutation. This cheap and fast-growing model of dystrophinopathy may be used to screen for molecules able to slow muscle degeneration. In a blind screen of approximately 100 compounds covering a wide spectrum of targets, we found that prednisone is beneficial to the C. elegans dystrophin-deficient muscles. Prednisone reduces by 40% the number of degenerating cells in this animal. This result is a proof-of-principle for the use of C. elegans as a tool in the search for molecules active against the effects of dystrophin-deficiency. Moreover, since C. elegans is not susceptible to inflammation, this suggests that prednisone exerts a direct effect on muscle survival.

Animals↗

PubMed2002

Head and neck brachytherapy.

Experience accumulated over several decades in the treatment of head and neck tumors by irradiation has demonstrated the need for a high tumor dose to achieve local control. With external beam irradiation alone, it is difficult to spare adjacent normal tissues, resulting in undesirable late effects on the salivary glands, mandible, and muscles of mastication. Interstitial implantation is ideally suited to deliver a high dose limited to the volume of the primary tumor, thus maximizing tumor control while minimizing complications. A large experience has been accumulated with low dose rate (LDR) brachytherapy in treatment of carcinoma of oral cavity, oropharynx, and nasopharynx. Recent analysis of large clinical series provided data indicating that modalities of LDR brachytherapy should be optimized in treating these tumors for increasing therapeutic ratio. LDR brachytherapy is now challenged by high dose rate (HDR) brachytherapy and pulsed dose rate (PDR) brachytherapy. Preliminary results obtained with these 2 last modalities will be discussed.

Brachytherapy↗