Kinetics of mouse jejunum radiosensitization by 2',2'-difluorodeoxycytidine (gemcitabine) and its relationship with pharmacodynamics of DNA synthesis inhibition and cell cycle redistribution in crypt cells.

Gemcitabine (dFdC), a deoxycitidine nucleoside analogue, inhibits DNA synthesis and repair of radiation-induced chromosome breaks in vitro, radiosensitizes various human and mouse cells in vitro and shows clinical activity in several tumours. Limited data are however available on the effect of dFdC on normal tissue radiotolerance and on factors associated with dFdC's radiosensitization in vivo. The purpose of this study was to determine the effect of dFdC on mouse jejunum radiosensitization and to investigate the kinetics of DNA synthesis inhibition and cell cycle redistribution in the jejunal crypts as surrogates of radiosensitization in vivo. For assessment of jejunum tolerance, the mice were irradiated on the whole body with 60Co gamma rays (3.5-18 Gy single dose) with or without prior administration of dFdC (150 mg kg-1). Jejunum tolerance was evaluated by the number of regenerated crypts per circumference at 86 h after irradiation. For pharmacodynamic studies, dFdC (150 or 600 mg kg-1) was given i.p. and jejunum was harvested at various times (0-48 h), preceded by a pulse BrdUrd labelling. Labelled cells were detected by immunohistochemistry on paraffin-embedded sections. DNA synthesis was inhibited within 3 h after dFdC administration. After an early wave of apoptosis (3-6 h), DNA synthesis recovered by 6 h, and crypt cells became synchronized. At 48 h, the labelling index returned almost to background level. At a level of 40 regenerated crypts, radiosensitization was observed for a 3 h time interval (dose modification factor of 1.3) and was associated with DNA synthesis inhibition, whereas a slight radioprotection was observed for a 48-h time interval (dose modification factor of 0.9) when DNA synthesis has reinitiated. In conclusion, dFdC altered the radioresponse of the mouse jejunum in a schedule-dependent fashion. Our data tend to support the hypothesis that DNA synthesis inhibition and cell cycle redistribution are surrogates for radiosensitization. More data points are however required before a definite conclusion can be drawn

Feasibility study combining low dose rate (192)Ir brachytherapy and external beam radiotherapy aiming at delivering 80-85 Gy to prostatic adenocarcinoma.

peer reviewedBACKGROUND: Increasing the radiation dose to prostatic adenocarcinoma has provided higher local control rates. A total of 80 Gy seem necessary to achieve this goal but patient set-up and prostate motion remain difficult problems to solve in conformal radiotherapy. Brachytherapy which overcomes these points could be an alternative way to external beam boost fields. We wanted to transpose the irradiation models largely used in cervix cancer treatment combining external beam radiotherapy and low dose rate brachytherapy. MATERIALS AND METHODS: In 71 patients with 19.5 and 13 ng/ml mean and median PSA levels, respectively, a dose escalation from 74 to 85 Gy was performed in four groups. RESULTS: Shifting from intraoperative placement of sources vectors (Group I) to positioning under ultrasound controls (groups II-IV), improving the implantation shape and optimizing radiation delivery to urethral bed have reduced the total dose to rectal wall under 65 Gy and to urethra under 100 Gy. Rectal/prostate dose ratio was lowered from 0.7 (Groups I-II) to 0.58 (Groups III-IV) while avoiding problems resulting from pelvic bone arch interference, prostate volume or seminal vesicles location. The mean and median follow-up periods are 28 and 18 months. In Groups III and IV 85% of patients without hormonotherapy treated with 80-85 Gy normalized PSA under 1 ng/ml within 6 months. No severe late effect has been noted for patients implanted under echographic control. CONCLUSIONS: The method described allows to deliver 85 Gy. Longer follow-up is however needed but the levels of dose delivered are not expected to induce prohibitive side effects

The Effects of the Atmospheric Pressure Changes on Seismic Signals or How to Improve the Quality of a Station

Seismic investigations are mainly limited by seismic noise. Two microbarometers have been installed in the seismic vault of two different GEOSCOPE stations, one at SSB and the other at TAM. All vertical components and most of the horizontal components show a significant correlation with pressure. In order to correct the seismic signals from the atmospheric pressure noise, a transfer function between the pressure data and the seismic data is inverted. Results show that, after correction, the noise levels reached on the horizontal components are similar between the two stations, and the vertical components display noise levels below the low-noise model as defined by Peterson (1993). This technique reduces part of the noise and allows detection of small earthquakes and a better extraction of normal modes. The analysis of the lowest normal modes of the Earth excited by the M_S = 8.2 Macquarie Island earthquake is given to illustrate the perspectives of the method

Adjuvant high-dose medroxyprogesterone acetate for early breast cancer: 13 years update in a multicentre randomized trial

The authors updated their report on a randomized trial initiated in 1982 comparing, in early breast cancer, high-dose IM Medroxyprogesterone acetate (HD-MPA) adjuvant hormonotherapy during 6 months with no hormonotherapy; node-positive patients also received 6 courses of IV CMF (day 1, day 8; q.4 weeks). 246 node-negative (NN) and 270 node-positive (NP) patients had been followed for a median duration of 13 years. Previous results were confirmed in this analysis on mature data. In NN patients, relapse-free survival (RFS) was improved in the adjuvant hormonotherapy arm, regardless of age while overall survival (OAS) was also increased in younger (less then 50 years) patients. In the whole group of NP patients, no difference was seen regarding RFS or OAS. However, an age-dependant opposite effect was observed: younger patients (< 50) experienced a worse and significant outcome of relapse-free and overall survivals when receiving adjuvant HD-MPA while older patients (> = 50) enjoyed a significant improvement of their relapse-free survival. For both NN and NP patients, differences in overall survivals observed in older women with a shorter follow-up, were no longer detected. © 2001 Cancer Research Campaign http://www.bjcancer.co

Radiobiological intercomparison of clinical neutron beams for growth inhibition in Vicia faba bean roots.

Relative biological effectiveness (RBE) and oxygen enhancement ratio (OER) values of different neutron beams produced at the variable energy cyclotron "Cyclone" of Louvain-la-Neuve (Belgium) were determined. The neutrons were obtained by bombarding a beryllium target with 34-, 45-, 65-, or 75-MeV protons or with 50-MeV deuterons. The biological system was growth inhibition in Vicia faba bean roots. Taking the p(65) + Be neutron beam as a reference, RBE values were found equal to 1.36 +/- 0.2, 1.20 +/- 0.1, 1.00 (ref), 0.98 +/- 0.1, and 1.18 +/- 0.1, respectively; the doses corresponding to 50% growth inhibition were 0.39, 0.44, 0.53, 0.54, and 0.45 Gy. For the same beams, OER values were found equal to 1.55 +/- 0.1, 1.38 +/- 0.1, 1.29 +/- 0.1, 1.41 +/- 0.1, and 1.60 +/- 0.2, respectively

Clonal Rearrangement of the T-cell Receptor Beta-chain Gene in the Pleural Fluid of a Patient With Thymoma

Thymoma is generally considered as an epithelial malignancy surrounded by lymphocytes not belonging to the tumour. This report documents a case of malignant thymoma associated with a lymphocytic pleural effusion. The pleural lymphocytes were mature T-cells, a small proportion of which were shown to have a monoclonal rearrangement of the beta-chain of the T-cell receptor. On the contrary, the lymphocytes of peripheral blood exhibited a germline configuration. The nature of the monoclonal population found in the pleural fluid is discussed and if the cells are of thymic origin their clonal configuration may point to a neoplastic nature of lymphocytes infiltrating malignant thymoma. Alternatively, he clonal T-cell subpopulation may result from an aberrant immunological response to the thymoma