Different dose rate-dependent responses of human melanoma cells and fibroblasts to low dose fast neutrons.

Purpose: To analyze the dose rate influence in hyper-radiosensitivity (HRS) of human melanoma cells to very low doses of fast neutrons and to compare to the behaviour of normal human skin fibroblasts.

Materials And Methods: We explored different neutron dose rates as well as possible implication of DNA double-strand breaks (DSB), apoptosis, and energy-provider adenosine-triphosphate (ATP) levels during HRS.

Results: HRS in melanoma cells appears only at a very low dose rate (VLDR), while a high dose rate (HDR) induces an initial cell-radioresistance (ICRR).

Simulation of neutron interactions at the single-cell level.

We recently reported that the exposure of cancer cells to 14 MeV neutrons at a very low dose rate (0.8 mGy min(-1)) produced a marked increase in cell killing at 5 cGy, followed by a plateau in survival and chromosomal damage. Simulation of the energy deposition events in irradiated cells may help to explain these unusual cell responses.

Simulation code for the interaction of 14 MeV neutrons on cells.

The structure of the survival curve of melanoma cells irradiated by 14 MeV neutrons displays unusual features at very low dose rate where a marked increase in cell killings at 0.05 Gy is followed by a plateau for survival from 0.1 to 0.

Comparisons of carboplatin and cisplatin as potentiators of 5-fluorouracil and radiotherapy in the mouse L1210 leukaemia model.

Background: Carboplatin (CBDCA), an analogue of cisplatin (CDDP), has synergistic antitumour activity in combination with 5-fluorouracil (5-FU) and radiotherapy and is better tolerated than CDDP by patients. In an in vivo model, we evaluated the doses of CBDCA and CDDP required to obtain, in these combinations, equal curative effects.

Materials And Methods: Groups of 6-week-old B6D2F1 mice were injected with L1210 leukaemia.

Effects of low-dose neutrons applied at reduced dose rate on human melanoma cells.

Human melanoma cells that are resistant to gamma rays were irradiated with 14 MeV neutrons given at low doses ranging from 5 cGy to 1.12 Gy at a very low dose rate of 0.8 mGy min(-1) or a moderate dose rate of 40 mGy min(-1).

[Cell cycle regulation after exposure to ionizing radiation].

When cells are exposed to ionizing radiation, they initiate a complex response that includes the arrest of cell cycle progression in G1 and G2, apoptosis and DNA repair. DNA is an important subcellular target of ionizing radiation, but oxydative damage to plasma membrane lipids initiates signal transduction pathways that activate apoptosis and that may play a role in cell cycle regulation. How is DNA damage converted into intracellular signals for cell cycle arrest? The ataxia telangectasia mutant (ATM) protein and/or the DNA-dependent protein kinase (DNA-PK), that are both activated by DNA damage, may initiate cell cycle arrest by activating the p53 tumor suppressor protein.

[Gene transfer and radiotherapy].

Recent studies have shown that experimental tumors could be treated more efficiently with ionizing radiation if genetic material was transfered into tumor cells. Several approaches have been reported, and among them, the first one consisted of increasing the apoptotic response to radiation by modulating genes involved in the regulation of the apoptotic pathway. Indeed the modulation of p53 and bcl-2 gene expression has recently been used successfully in several experimental models to increase the apoptotic death after radiation.

High-dose therapy and autologous bone marrow transplantation in first complete or partial remission for poor prognosis Hodgkin's disease.

We report the experience of three French centres which evaluated high-dose therapy (HDT) as consolidation therapy for poor prognosis Hodgkin's disease (HD). From March 1986 to April 1990, 23 consecutive patients with poor prognosis stage IV HD underwent HDT followed by autologous bone marrow transplantation (ABMT) after achieving either complete remission (CR1) or good partial response (GPR1) (reduction mass> 75%). The median age was 31 years (range 18 to 55 years), 14 were male.

The hematopoietic stem cell transplantation in Hodgkin's disease: questions and controversies.

Most patients with Hodgkin's disease (HD) are cured with chemotherapy and/or radiotherapy. However, half of those with advanced stage disease (IIIB, IV) do not respond adequately to treatment or relapse. Salvage therapy used in such cases gives from 10% to 50% complete remission but only 10% long term survival.

[Prognostic value of beta-2-microglobulin in Hodgkin disease in young adults].

From 1977 to 1989, we measured serum beta-2-microglobulin (beta 2-MG) levels from 64 unselected and untreated patients, between 18 to 50-year-old, affected by Hodgkin's disease. Serum beta 2-MG level was measured by radioimmunoassay (Phadebas beta 2 microtest). Then, all patients received a chemotherapy such as MOPP or alternating MOPP/ABVD followed or not by radiotherapy.

Clinical relevance of immunohistochemical detection of multidrug resistance P-glycoprotein in breast carcinoma.

In 20 women with breast carcinoma, 17 of whom had locally advanced cancer and 3 of whom had confirmed metastases, the expression of P-glycoprotein was evaluated before the start of a chemotherapy regimen that included multidrug resistance-related drugs. With the use of the C494 monoclonal antibody in an avidin-biotin-immunoperoxidase technique, P-glycoprotein was detected in 17 of 20 tumor samples. Results were expressed in a semiquantitative manner, taking into account the number of positive tumor cells (N index) and the specific staining intensity (I index).

[Treatment of malignant intracranial germ-cell tumors in children. 7 cases].

Seven children, aged from 9 to 16 years, with intracranial germ cell tumour received post-operative chemotherapy prior to radiotherapy. Treatment consisted of several courses of vinblastine, bleomycin and cisplatin alternating or not with courses of cyclophosphamide and actinomycin D. In the 6 children whose tumours secreted alphafoetoprotein or chorionic gonadotrophin, chemotherapy brought these markers down to normal.

Initial chemotherapy and low-dose radiation in limited fields in childhood Hodgkin's disease: results of a joint cooperative study by the French Society of Pediatric Oncology (SFOP) and Hôpital Saint-Louis, Paris.

To minimize the drawbacks of treatment we had shown in a previous study that it was possible after chemotherapy to limit the radiation fields to the involved areas only. Pursuing our policy of deescalation, we started in January 1982 a study in 29 French pediatric and hematologic centers, with two aims: (1) To compare the efficacy of 4 cycles of two different chemotherapeutic regimens (4 ABVD vs 2 MOPP + ABVD) in early stages (CSIA and II A) while other stages would receive 6 cycles of the same regimen (3 MOPP + 3 ABVD); (2) To evaluate the efficacy of irradiation given at a low dose (20 Gy) in the patients who had a minimum 70% reduction of the size of their nodes (good responders). From January 1982 to March 1987, 174 patients were entered in this study, of whom 157 completed their treatment program at the time of analysis.

Sequential combination of 5-fluorouracil, cis-platinum and irradiation. 1. Advanced head and neck cancers.

Based on the synergistic action of 5-fluorouracil (5-FUra), cis-dichlorodiamminoplatinum(II) (cis-DDP) and gamma-rays, which was suggested in experiments on murine tumours, a sequential treatment combining irradiation and chemotherapy for human solid tumours known to be resistant to conventional treatments has been developed. A pilot study was carried out on 30 patients with recurring head and neck cancers previously treated by radiotherapy and surgery. The good tolerance and the initial results justified applying this protocol to previously untreated cases.

Chemotherapy with low doses of radiation followed by definitive radiotherapy for advanced unresectable carcinoma of the head and neck.

Thirty-six patients with advanced unresectable carcinoma of the head and neck were treated with a combination of three courses of chemotherapy and low doses of radiation, followed after 3 weeks by definitive irradiation. Each course was repeated every 3 weeks with the following sequence. Cisplatin (20 mg/m2) was given in a 20-minute infusion, followed by a 2-hour infusion of 5-fluorouracil (400mg/m2), on days 1,2,5, and 6.

[Medical treatment of urothelial tumors of the bladder].

Intravesical chemotherapy is widely used in the management of superficial urinary bladder tumors. A complete response rate of 30 to 50% is observed in unresected tumors. Prophylactic instillations of the drugs after transurethral resection of the tumors seem able to delay recurrences.

[Ureteral dosimetry during gynecological curietherapy. Possible effects on the occurrence of postoperative ureteral complications].

The dosage of radiations delivered during gynaecological brachytherapy is usually calculated for the bladder and the rectum. A new technical approach is described in order to known the dose of radiation received by the terminal portion of the ureter. During placement of the Fletcher suit one of the ureters is catheterized by a special stent which appears on the X-rays control used for dosimetry.

A monoclonal antibody against LAV gag precursor: use for viral protein analysis and antigenic expression in infected cells.

A murine monoclonal antibody (MAb), named C.V.K.

[Psychosocial repercussions of the the treatment of Hodgkin's disease. Assessment by questionnaire with 150 patients].

One hundred and fifty patients, treated for Hodgkin's disease (stages I-IIIA) in a cooperative trial and remaining in complete remission after 2 to 7 years, answered a questionnaire dealing with psychosocial status and quality of life. Many informations were gathered and studied by multiparametric methods. Quality of life of patients appears determined by three kinds of parameters: patients' characteristics (age, sex, family and work status); stage of the disease determining the intensity and duration of treatment; practical conditions of treatment.

[Data collection from patients treated for Hodgkin's disease. Relation to quality of life].

One hundred and fifty patients treated for Hodgkin's disease (stage I to IIIA) in a cooperative trial, answered a questionnaire dealing partly with their information, after 2 to 7 years of complete remission. This information appears insufficient for the majority of patients (52%), at least as far as treatment and its complications are concerned. There are many significant relations with other parameters which suggest that a good level of information may improve quality of life of patients.

[Pre and postoperative chemotherapy of osteosarcoma with an adriamycin-cisplatin combination. Risks of a neoadjuvant chemotherapy which is not sufficiently effective].

The authors evaluated a new protocol of neoadjuvant chemotherapy for osteosarcoma, easier to manage and different from T10. The good results obtained with the postoperative ADR-CDDP association led us to undertake a pilot study between 1982 and 1984, using ADR-CDDP as preoperative chemotherapy. The records of sixteen patients were available for follow-up.