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J M Denis

Publications and source records attributed to J M Denis.

13 recordsLinked to original sources
PubMed2004

Cisplatin enhances the cytotoxicity of fast neutrons in a murine lymphoma cell line.

The utilization of high linear energy transfer (LET) radiations, such as fast neutrons or carbon ions (hadrontherapy), offers promising perspectives in radiotherapy. While it is well known that by combining radiotherapy and chemotherapy, important therapeutic advantages can be obtained to cure cancer, there have been, so far, very few investigations on the effects of treatments combining an irradiation with high-LET particles and cancer drugs. The present study was therefore undertaken to examine the effects of exposure to 65 MeV fast neutrons combined with cisplatin in a murine T cell lymphoma (RDM4) in vitro. The cells were irradiated at doses ranging from 2 to 8 Gy without or with addition of cisplatin shortly before the irradiation, at concentrations between 0.3 and 12.5 micro M. These treatments were applied concomitantly. Proliferation and apoptosis were assessed at different time intervals thereafter. The combination of irradiation with cisplatin was found to be more cytotoxic than either treatment alone. Furthermore, the cytotoxicity induced by this cotreatment resulted not only from apoptosis but also from other forms of cell death.

Animals↗
PubMed2002

Induction of apoptosis by high linear energy transfer radiation: role of p531.

The involvement of the tumor suppressor p53 gene in the sensitivity of many cell types towards low linear energy transfer (LET) radiation is now well established. However, little information is available on the relationship between p53 status of tumor cells and their ability to undergo apoptosis following exposure to high-LET radiation. Here we present the results of experiments carried out with the human lymphoblastoid cell line TK6 and its p53 knock-out counterpart NH32. Cells were irradiated at doses ranging from 0.25 to 8 Gy with fast neutrons (65 MeV), carbon ions (95 MeV/nucleon), and X rays (15 MV). For both cell lines, the occurrence of apoptosis, determined by the quantification of hypodiploid particles as well as the activation of several caspases, was compared with their sensitivity towards high-LET radiation. Results indicate that p53 is involved in the response of TK6 cells to fast neutrons and carbon ions, as measured by cell proliferation and occurrence of apoptosis. However, p53-deficient cells are still able to undergo apoptosis following irradiation. This suggests that heavy ions and fast neutrons induce cellular damage that is not under the control of p53. The involvement of executioner caspases in high-LET radiation induced apoptosis was also evaluated by use of specific inhibitors.

Apoptosis↗
PubMed2002

Involvement of TP53 in apoptosis induced in human lymphoblastoid cells by fast neutrons.

We investigated the involvement of TP53 in apoptosis induced by fast neutrons in cells of three human B-lymphoblast cell lines derived from the same donor and differing in TP53 status: TK6 (wild-type TP53), WTK1 (mutant TP53) and NH32 (knockout TP53). Cells were exposed to X rays or to fast neutrons at doses ranging from 0.5 to 8 Gy. Apoptosis was determined by measurements of the sub-G0 /G1-phase DNA content and by the externalization of phosphatidylserine. Fast neutrons induced extensive apoptosis in TK6 cells, as shown by the formation of hypodiploid particles, the externalization of phosphatidylserine, and the activation of caspases. In contrast, cell death was triggered at a significantly lower rate in cells lacking functional TP53. However, TP53-independent cell death also expressed the morphological and biochemical hallmarks of apoptosis. Proliferation tests and clonogenic assays showed that fast neutrons can nevertheless kill WTK1 and NH32 cells efficiently. The absence of functional TP53 only delays radiation-induced cell death, which is also mediated by caspases. These results indicate that fast-neutron irradiation activates two pathways to apoptosis and that the greater relative biological effectiveness of fast neutrons reflects mainly an increase in clonogenic cell death.

Apoptosis↗
PubMed2001

Experimental p(wall) and p(cel) correction factors for ionization chambers in low-energy clinical proton beams.

Current dosimetry protocols for clinical protons using ionization chambers do not take into account ionization chamber-dependent perturbation correction factors. In the present investigation, the relative response of 17 cylindrical ionization chambers was evaluated at three proton beam qualities: at two points in a modulated beam and one point in a non-modulated beam, all with an incident energy of 75 MeV. Thirteen of the ionization chambers had a Farmer-type geometry but consisted of different combinations of wall and central electrode materials. All ionization chambers were calibrated in terms of air kerma as well as in terms of absorbed dose to water in a 60Co beam. The relative response of the ionization chambers was compared with results of Monte Carlo simulations of proton and secondary electron transport in the phantom and the ionization chamber geometry. The results of the measurements for cylindrical ionization chambers show relative perturbation effects that are limited to 0.5-1%, resulting in perturbation correction factors that are larger than unity compared with an NE2571 ionization chamber. The experimental relative wall and total perturbation correction factors agree with Monte Carlo calculated values, indicating that the differences between the responses of different ionization chambers are due to secondary electron effects. This conclusion is supported by the comparison of our results with those from other investigators after re-analysis of their data. The central electrode perturbation correction factor for an aluminium electrode in a Farmer-type geometry was found to be unity within the experimental uncertainties.

Electrons↗
PubMed2001

[Induction of apoptosis of splenic lymphocytes in mice by accelerated carbon ions].

To assess the capacity of heavy ions to induce apoptosis in lymphocytes, mice have been irradiated with accelerated carbon ions (95 MeV/nucleon) at doses ranging from 0.1 to 4 Gy. Their spleens were removed 24 h later and gently dissociated to prepare a single cell suspension. Mononuclear cells were then maintained in culture at 37 degrees C, and the occurrence of apoptosis in these cells was analysed 24 h later. Lymphocytes were also irradiated in vitro, in the presence of Ac-DEVD-CHO, a potent caspase-3 and -7 inhibitor. Results from three experiments performed at the Grand Accelerateur National d'Ions Lourds (GANIL, Caen, France) are reported here. They indicate that carbon ions induce a marked, dose-dependent, reduction of the spleen weight and cellularity. However, in sharp contrast with spleen cells prepared from X-ray irradiated mice, only a slight increase of apoptosis is evidenced in cultured lymphocytes from mice irradiated with heavy ions. The significance of such results is discussed. So far, few data exist concerning the biological effects of heavy ions, in particular their capacity to induce apoptosis in lymphocytes; the present study provides useful clues for further investigations.

Animals↗
PubMed1998

Fast 2D phantom dosimetry for scanning proton beams.

A quality control system especially designed for dosimetry in scanning proton beams has been designed and tested. The system consists of a scintillating screen (Gd2O2S:Tb), mounted at the beam-exit side of a phantom, and observed by a low noise CCD camera with a long integration time. The purpose of the instrument is to make a fast and accurate two-dimensional image of the dose distribution at the screen position in the phantom. The linearity of the signal with the dose, the noise in the signal, the influence of the ionization density on the signal, and the influence of the field size on the signal have been investigated. The spatial resolution is 1.3 mm (1 s.d.), which is sufficiently smaller than typical penumbras in dose distributions. The measured yield depends linearly on the dose and agrees within 5% with the calculations. In the images a signal to noise ration (signal/1 s.d.) of 10(2) has been found, which is in the same order of magnitude as expected from the calculations. At locations in the dose distribution possessing a strong contribution of high ionization densities (i.e., in the Bragg peak), we found some quenching of the light output, which can be described well by existing models if the beam characteristics are known. For clinically used beam characteristics such as a Spread Out Bragg peak, there is at most 8% deviation from the NACP ionization chamber measurements. The conclusion is that this instrument is a useful tool for quick and reliable quality control of proton beams. The long integration-time capabilities of the system make it worthwhile to investigate its applicability in scanning proton beams and other dynamic treatment modalities.

Brachytherapy↗
PubMed1996

The multileaf collimator for fast neutron therapy at Louvain-la-Neuve.

The multileaf collimator of the fast neutron therapy facility at Louvain-la-Neuve is described, as well as some of the physics experiments performed in order to evaluate the attenuation of neutron beams in different materials and thus optimize the composition of the collimator leaves. The multileaf collimator consists of two sets of 22 leaves each, which can be moved independently. They are made of iron and their thickness is 95 cm. Seven borated polyethylene disks are located in the distal part of the leaves in order to absorb more efficiently the low-energy component of the neutron spectrum. The width of the leaves is 1 cm at their distal part. The leaves can move 11 cm outwards and 6 cm inwards from their reference position, and field sizes up to 25.7 x 24.8 cm, as well as irregular field shapes, can be obtained. The inner part of the leaves and their two sides are always focused on the target. The complete multileaf collimator can rotate around the beam axis, from -90 degrees to +90 degrees from the reference position. The width of the penumbra (80-20% isodoses) is 0.64 cm and 1.17 cm at the depth of the maximum buildup and at 10 cm in depth respectively, for a 10 x 10 cm field size. The collimator is adequate for the energy of the p(65)+Be neutron beam of Louvain-la-Neuve and has been adapted to the fixed vertical beam. It has been designed following the original plans of Scanditronix, adjusted and fully assembled at the workshop of the Centre de Recherches du Cyclotron (CRC). Systematic measurements were performed in order to optimize the design and the composition of the leaves. In particular the attenuations of the actual beam and of monoenergetic neutron beams were measured in different materials such as iron and polyethylene. Above (upstream) the multileaf collimator, a fixed pre-collimator (iron thickness 50 cm; section 1 x 1 m) defines a conical aperture aligned on the largest opening of the leaves. It contains the two transmission chambers and a 2 cm thick polyethylene layer used for hardening the beam.

Belgium↗
PubMed1996

[Water calorimetry measurements in a 85 MeV clinical proton beam].

The importance of water calorimetry in clinical proton beam dosimetry has increased for various reasons: there has been an increasing interest in proton therapy from the radiotherapy world; existing dosimetry protocols for clinical proton beams recommend calorimetry as the primary dosimetry method (ie, AAPM and ECHED); water has recently become the reference material for dose specification. For the water calorimetric dose evaluation, the water calorimeter developed in Ghent was used. Ionometry was performed following the ECHED protocol. The study resulted in a calorimetric to ionometric dose ratio of 0.974 +/- 0.009. The discrepancy should in our opinion be attributed to the (Wle)p,air value of 35.2 J/C implemented in the protocol, possibly next to ion chamber dependent effects for which indications are found in the ionometry measurements.

Calorimetry↗
PubMed1996

Response analysis of TLD-300 dosimeters in heavy-particle beams.

In vivo dosimetry is recommended as part of the quality control procedure for treatment verification in radiation therapy. Using thermoluminescence, such controls are planned in the p(65) + Be neutron and 85 MeV proton beams produced at the cyclotron at Louvain-La-Neuve and dedicated to therapy applications. A preliminary study of the peak 3 (150 degrees C) and peak 5 (250 degrees C) response of CaF2:Tm (TLD-300) to neutron and proton beams aimed to analyse the effect of different radiation qualities on the dosimetric behaviour of the detector irradiated in phantom. To broaden the range of investigation, the study was extended to an experimental 12C heavy ion beam (95 MeV/nucleon). The peak 3 and 5 sensitivities in the neutron beam, compared to 60Co, varied little with depth. A major change of peak 5 sensitivity was observed for samples positioned under five leaves of the multi-leaf collimator. While peak 3 sensitivity was constant with depth in the unmodulated proton beam, peak 5 sensitivity increased by 15%. Near the Bragg peak, peak 3 showed the highest decrease of sensitivity. In the modulated proton beam, the sensitivity values were not significantly smaller than those measured in the unmodulated beam far from the Bragg peak region. The ratio of the heights of peak 3 and peak 5 decreased by 70% from the 60Co reference radiation to the 12C heavy-ion beam. This parameter was strongly correlated with the change of radiation quality.

Carbon↗
PubMed1996

Water calorimetry and ionization chamber dosimetry in an 85-MeV clinical proton beam.

In recent years, the increased use of proton beams for clinical purposes has enhanced the demand for accurate absolute dosimetry for protons. As calorimetry is the most direct way to establish the absorbed dose and because water has recently been accepted as standard material for this type of beam, the importance of water calorimetry is obvious. In this work we report water calorimeter operation in an 85-MeV proton beam and a comparison of the absorbed dose to water measured by ionometry with the dose resulting from water calorimetric measurements. To ensure a proper understanding of the heat defect for defined impurities in water for this type of radiation, a relative response study was first done in comparison with theoretical calculations of the heat defect. The results showed that pure hypoxic water and hydrogen-saturated water yielded the same response with practically zero heat defect, in agreement with the model calculations. The absorbed dose inferred from these measurements was then compared with the dose derived from ionometry by applying the European Charged Heavy Particle Dosimetry (ECHED) protocol. Restricting the comparison to chambers recommended in the protocol, the calorimeter dose was found to be 2.6% +/- 0.9% lower than the average ionometry dose. In order to estimate the significance of chamber-dependent effects in this deviation, measurements were performed using a set of ten ionization chambers of five different types. The maximum internal deviation in the ionometry results amounted to 1.1%. We detected no systematic chamber volume dependence, but observed a small but systematic effect of the chamber wall thickness. The observed deviation between calorimetry and ionometry can be attributed to a combination of the value of (Wair/e)p for protons, adopted in the ECHED protocol, the mass stopping power ratios of water to air for protons, and possibly small ionization chamber wall effects.

Calorimetry↗
PubMed1979

[Bone scanning in children: technic and indications. Apropos of 50 cases].

In children, radionuclide skeletal imaging with 99m Tc M. D.P. has been performed in 50 cases. Scans are done immediately, 20 minutes and three hours after injection. Osteomyelitis has been studied in 24 cases, Legg Perthes disease and benign bone tumors in the others. The scintigraphic patterns are very sensitive but not characteristic. However this exam seems to be essential in some orthopedic disorders of children.

Adolescent↗