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A Courdi

Publications and source records attributed to A Courdi.

At least 37 records · Page 2Linked to original sources
PubMed1996

[CAL 54, a new cell line derived from a human renal carcinoma: characterization and radiosensitivity].

A new cell line (CAL 54) was isolated from a malignant pleural effusion of a patient with renal carcinoma. CAL 54 is a continuous and stable cell line. Immunochemical staining showed simultaneous expression of cytokeratin, epithelial membrane antigen and vimentin. Cytometric flow analysis of DNA content reveals one major hyperdiploid population. Histological aspect of the tumor induced in the nude mouse showed well differentiated adenocarcinoma with papillary structure. Radiation response of these cells was evaluated by the colony-forming method and the data were fitted with the linear-quadratic model. Survival at 2 Gy (SF2) was 0.28 and the mean inactivation dose (D) = 1.50 Gy, ranking this cell line among the radiation sensitive cells. CAL 54 may be an informative cell line to investigate radiation effects in the management of renal tumours.

Aged↗
PubMed1995

Micronucleus induction and reproductive death in a human cell line exposed to low-energy argon beam.

Little is known about the action of charged particles of very high linear energy transfer (LET) on human cells and, in particular, the relationship between DNA damage and reproductive death. The aim of this study was to measure the biological efficiency of a low-energy argon beam (E = 7.1 MeV/nucleon, LET = 1590 keV/micron) produced at GSI, Darmstadt, on a human melanoma cell line (CAL4) established in our Institute. Two different methods were used: the micronucleus (MN) test and the colony-forming assay. The MN test, using the cytochalasin-block method, is a measure of genotoxic damage. MN are scored in binucleate cells (BNC) and are formed from acentric fragments or whole chromosomes that have not been incorporated into daughter nuclei at mitosis. The colony-forming assay quantifies reproductive death. Parallel experiments were run with cobalt gamma-rays for comparison. After Co irradiation, the MN-free BNC dose-response curve coincided with that of the loss of colony-forming ability, suggesting the potential of the former as a predictive test of cell killing. After Ar irradiation, there was a dissociation between the two effects, especially at high doses: cell death was greater than the frequency of BNC with MN. The inactivation cross-section was 74 microns2; it was 39 microns2 for MN yield. Therefore, the relative biological effectiveness (RBE) was higher for cell killing than for MN yield (0.8 and 0.5, respectively at a Co dose of 3 Gy). The total MN count in BNC followed the same pattern of response as the fraction of BNC with MN.(ABSTRACT TRUNCATED AT 250 WORDS)

Argon↗
PubMed1995

Micronucleus induction in 10 human tumour cells after high- and low-dose radiation.

A number of data measuring survival of animal or human cells to low LET ionizing radiation have demonstrated that these cells may be hypersensitive to doses below 1 Gy, possibly due to the absence of an inducible repair mechanism, which is observed at higher doses. The production of micronuclei (MN) in cells exposed to ionizing radiation reflects genotoxic damage. Moreover, the micronucleus assay is sensitive to low radiation doses. We have exposed 10 human tumour cell lines to doses ranging between 0.12 and 4 Gy. Using cytochalasin B to block the cells in a binucleate phase, we have scored the fraction of binucleate cells (BNC) expressing MN, as well as the number of MN per BNC, as a function of gamma-ray dose. Experimental points were fitted with a binomial equation. Doses from 1 to 4 Gy were fitted separately from those below 1 Gy, and the initial slopes after both fits were compared. Taken together, the initial slopes of MN induction after low-dose (LD) irradiation were not different from those after high-dose (HD) irradiation. Only in one cell line was a significant increase in MN production detected after LD irradiation. This cell line had the shallowest linear term after HD irradiation. It appeared that the likeliness of expressing hypersensitivity at LD was correlated with the quadratic term of MN induction at HD, which does not contradict an inducible repair hypothesis. However, the failure of observation of a significant hypersensitivity at LD for nine cell lines, and the high variability of response at LD suggests that this occasional effect may be influenced by other factors as well.

Humans↗
PubMed1994

The depth-dependent radiation response of human melanoma cells exposed to 65 MeV protons.

Radiation therapy with positively charged particles implies that the Bragg peak be spread out to deliver a homogeneous dose to the tumour. The spread-out Bragg peak (SOBP) has a higher linear energy transfer (LET) than the entrance beam. In addition, there is an LET gradient from proximal to distal SOBP. The aim of this study is to find out whether these small LET variations lead to differences in radiation response. Human melanoma cells (CAL4) were exposed to 65 MeV proton beams produced by the cyclotron Medicyc at five different positions: 2 mm depth corresponding to the entrance, 15, 20, 25 and 26.8 mm depth corresponding to four different positions in the half-modulated SOBP. Survival curves were generated using the in vitro colony method and fitted with the linear-quadratic model. Survival differences were observed at high doses; they were statistically significant at a dose of 8 Gy. With respect to the entrance position (2 mm), the relative biological effectiveness (RBE) at 1% survival was 1.09, 1.12, 1.19 and 1.27 at 15, 20, 25 and 26.8 mm in the SOBP, respectively. Whereas RBE values in the SOBP greater than 1.0 relative to the entrance beam represent a small biological advantage to be added to the well-known physical advantage of high energy proton beams; the RBE gradient along the SOBP would imply that the distal end of the tumour would receive a higher biologically equivalent dose than the proximal end, despite a homogeneous physical dose, especially at the high doses per fraction given in ocular melanomas. Although the increase in effectiveness with depth is mild, it should be kept in mind during eye treatment planning, in case a critical target is present at the extreme end of the SOBP.

Cell Survival↗
PubMed1994

Immunohistochemical determination of nuclear antigens by colour image analysis: application for labelling index, estrogen and progesterone receptor status in breast cancer.

The immunohistochemical evaluation of 5-bromo-2'-deoxyuridine (BrdU) labelling index, estrogen (ER) and progesterone receptor (PR) status was carried out on the automated computer-assisted image analysis station BIOCOM 500. Special software has been developed to measure nuclear antigens using the immunoperoxidase method with the Harris hematoxylin counterstain. The analysis was based on the different light adsorption spectra of the chromogen diaminobenzidine and Harris's hematoxylin coloration when exposed to light of differing wavelengths. The results obtained by image analysis were compared to previously validated methods. The thymidine labelling index performed by manual procedures and BrdU incorporation performed by image analysis were comparable (linear correlation coefficient r = 0.76, P < 0.001). Comparison of image analysis and dextran coated charcoal assay for ER and PR content revealed excellent sensitivities and specificities (linear correlation coefficient r = 0.87, P < 0.001 for ER and r = 0.93, P < 0.001 for PR). These data suggest that automated image analysis offers a reliable and reproducible procedure for measuring nuclear antigens.

Antigens, Neoplasm↗
PubMed1993

[Forum on tissue expansion. Tissue expansion and radiotherapy. Changes in epidermal mitotic index induced by expansion and/or irradiation in the rat].

In order to study the influence of irradiation during skin expansion, an experimental protocol using 15 laboratory rats was undertaken. The present experiment was designed to evaluate the mitotic activity of the epidermis by in vitro autoradiography. The mitotic activity was assessed by the Labelling Index. Experimental data concerning expansion were shown to be consistent with the literature. When a high dose of radiation was delivered to the skin during expansion, a significant increase was observed in the mitotic activity of the epidermis. The range of variation was equivalent to that expected in normal skin. This is the first experimental result in favour of irradiation during skin expansion. However, no conclusion can be drawn concerning the clinical applications (immediate breast reconstruction using tissue expansion) due to the limitations of the present experiment.

Animals↗
PubMed1992

Inherent radiosensitivity and split-dose recovery in plateau-phase cultures of 10 human tumour cell lines.

The radiation response of 10 human tumour cell lines, eight of them established in our Institute, was analysed. Single dose acute survival curves were constructed and fitted with the linear-quadratic (LQ) model. The mean inactivation dose (D) was also calculated, together with D(o) and n. In order to measure both split-dose recovery and delayed plating recovery of plateau-phase cells, confluent cultures were subjected to two doses of 2 Gy 24 h apart, and plated 24 h later, simulating clinical fractionation. Survival of these cells (S2 x 2) was compared to that following 4 Gy given to cells plated at low density and an overall recovery factor (RF) was derived, including both types of recovery. S2 x 2 and RF were compared to the intrinsic radiosensitivity parameters. The three melanoma cell lines differed in radiation response, and the three squamous cell carcinoma cell lines were rather radioresistant. The neuroblastoma cell line was highly sensitive, yet it expressed the highest beta and the highest RF. Using a non-parametric correlation test, S2 x 2 was found to be related to D, whereas RF was not related to the radiosensitivity parameters. However, the two cell lines with the lowest D and the lowest S2 expressed the highest RF. These results suggest that radiosensitive cell lines may have a considerable capacity to recover if confluent cultures are exposed to fractionated irradiation. The overall recovery factor (RF) used here is proposed as a useful measure of cellular recovery.

Cell Survival↗
PubMed1992

The labelling index in carcinoma of the uterine cervix: its correlation with tumour sterilization.

The pre-treatment labelling index (LI) was measured in 72 patients with carcinoma of the cervix. It was not correlated with patient age, stage of the disease or histological grade. 46 patients underwent hysterectomy after intracavitary irradiation with or without external radiotherapy. The mean LI in patients with tumour sterilization or microscopic residue was significantly higher than in patients with gross disease. These results suggest that tumours with low LI may be difficult to sterilize with conventional therapeutic measures, or that doomed cells may require several weeks to be eliminated in tumours with low LI.

Adenocarcinoma↗
PubMed1991

[Characterization of a human cell line from an anaplastic carcinoma of the thyroid gland].

A new cell line derived from a thyroid anaplastic carcinoma, CAL 62, has been established in culture. This line is constituted by highly tumorigenic cells. Their epithelial phenotype is stable in culture. Immunochemical staining for human thyroglobulin is negative. Cytogenetic analysis showed a gain of chromosome 20, the translocation i (14q), and breakpoints of centrometric chromatine. These results are similar to those previously reported by other investigators. CAL 62 radiosensibility has been studied. The survival curve of the in vitro irradiated cells has been adjusted with a linear-quadratic model. This cell line is thus showed to be radioresistant. Cell line CAL 62 constitutes an appropriate model for in vitro studies of thyroid anaplastic carcinoma.

Aged↗
PubMed1990

Pharmacokinetics of cisplatin given at a daily low dose as a radiosensitiser.

A total of 25 patients with inoperable cervical cancer were treated by daily radiotherapy (2 Gy); sensitisation was obtained by administration of 5 mg cisplatin 30 min before each irradiation session. The total cumulative dose of cisplatin varied between 50 and 150 mg. A complete kinetic profile (0-24 h) of platinum (Pt) was established after the first dose and at the end of treatment for 22 patients. Pt was quantified by atomic absorption spectrophotometry using Zeeman-effect background correction for trace analysis. The total Pt AUC0-24h increased from 1.53 +/- 0.77 to 7 +/- 3.55 micrograms.h.ml-1 between the start and the end of treatment (P less than 0.001). Ultrafilterable Pt (Pt UF) rose from 0.079 +/- 0.038 to 0.138 +/- 0.095 microgram.h.ml-1 (P less than 0.01). Elimination half-lives were unchanged for total Pt but rose for Pt UF; these kinetic modifications in Pt UF did not correlate with any significant change in individual serum creatinine levels. No clear correlation was found between the cumulative cisplatin dose and tumor levels measured in 13 patients, and the tumor cisplatin dose did not correlate with response to treatment. Patients with hematological toxicity were characterised by an increase in their residual Pt UF level during treatment. Overall, our findings strengthen the notion of Pt UF kinetic variability during repeated treatment.

Adult↗
PubMed1990

Alternate day treatment and late effects: the concept of an effective dose per fraction.

Although most institutions treat all fields each day, some radiotherapists continue to adopt an alternate day schedule. The resulting daily variations of the dose per fraction in laterally located targets have been analyzed using the linear-quadratic model. Patients with breast carcinoma treated with definitive radiotherapy in 1974-1975 with one field a day were studied. An effective dose per fraction was derived, with a value higher than the average dose per fraction received by the reference point. The greater the fluctuations between the doses per fraction on successive days, the higher the effective dose per fraction. The corresponding cell survival due to alternate treatment as compared to survival with daily treatment depends on the alpha/beta ratio. For a late effect with low alpha/beta ratio, an alternate treatment may lead to almost 10-fold increase in cell kill in these lateral targets such as those responsible for subcutaneous sclerosis as compared to daily treatment of all fields with the same total dose. Taking the average effective dose per fraction in our series, the increase in cell kill was 4-fold. Acute effects would suffer less damage due to alternate treatment because of a high alpha/beta ratio. Treatment on an alternate schedule should be restricted to palliative radiotherapy.

Breast Neoplasms↗
PubMed1989

Cell proliferation kinetics in human solid tumors: relation to probability of metastatic dissemination and long-term survival.

A large number of studies have investigated the relationship between the long-term survival and the percentage of tumor cells in S phase assessed by autoradiography after tritiated thymidine labelling, image cytometry, flow cytometry or labelling with an halogenated analog of thymidine, in various types of human solid tumors. The survey of the results clearly shows that the S-phase fraction (SPF) is of high prognostic significance in several types of cancers, in particular in breast cancers, non-Hodgkin lymphomas, ovarian cancers, neuroblastoma, bladder cancers and lung cancers. SPF was found of high independent significance in 10 of the 11 studies in which multivariate analyses of prognostic factors had been carried out. Proliferation appears generally to be of higher prognostic significance than ploidy. In view of the wide differences in the biological characteristics of the tumors studied, it is likely that the association between a high proliferation rate and the degree of tumor aggressiveness is a general feature of human solid tumors. However, high proliferative rate of tumor cells is probably not the cause of tumor biological aggressiveness but a variable associated with it. The extent to which cells escape from the regulatory systems which control their proliferation appears to be a good index of tumor progression.

Autoradiography↗
PubMed1989

The labelling index: a prognostic factor in head and neck carcinoma.

The thymidine labelling index (LI), representing the percentage of cells in the DNA-synthesis phase, was measured in vitro prior to therapy in 87 patients with squamous cell carcinoma of the head and neck, who were treated between 1977 and 1982. The LI was not related to patient age, site of the tumour, clinical stage or histological grade. Overall survival was 44.5%. Univariate analysis demonstrated that survival was affected by the following factors: (1) age: patients older than 55 had a better outcome (p = 0.03); (2) site of the tumour (p = 0.005): laryngeal tumours had the best survival; (3) clinical stage (p = 0.05). Histological grade did not influence the survival (p = 0.41). Patients having a tumour LI higher than 15.5% (mean + 1 S.D.) had a significantly lower survival than patients with lower tumour LI (p = 0.008). A multivariate analysis using the Cox model showed that clinical stage and LI kept their prognostic impact with regard to survival. Finally, survival after relapse was lower in patients with a high tumour LI. These results demonstrate that a high tumour proliferation rate is an additional factor influencing the disease outcome in head and neck carcinoma. Patients with bad prognosis defined by this parameter could be offered a more energetic treatment.

Adult↗
PubMed1989

Factors affecting relapse in node-negative breast cancer. A multivariate analysis including the labeling index.

Between 1975 and 1982, 167 patients with carcinoma of the breast without axillary lymph node metastases were studied. The thymidine labeling index (LI), representing the percentage of cells in the DNA synthesis phase, was measured in all these patients. High LI values were more frequently encountered in young patients (P = 0.05), in low estrogen receptor (ER) tumor content (P = 0.007) and in high grade tumors (P = 0.0002). The overall 8-year relapse-free survival (RFS) was 68%. Univariate analysis demonstrated that RFS was influenced by histological grading (P = 0.03), ER (P = 0.03), PR (P = 0.02) and LI (P = 0.01). Multivariate analysis using the Cox regression model selected the LI as the single significant prognostic factor with regard to RFS (P = 0.037). These results emphasize the important role of cell proliferation kinetics in defining node-negative breast cancer patients with a high risk of relapse.

Adult↗