Establishment, characterization, chemosensitivity, and radiosensitivity of two different cell lines derived from a human breast cancer biopsy.

In vitro culture of a human breast cancer biopsy fragment gave rise to two permanent cell lines, CAL 18 A and CAL 18 B, which were differentiated by both morphological and ultrastructural analysis. The karyotypic and growth properties of these two cell lines also differed, providing further evidence of cell heterogeneity within a given tumor. Both cell lines lost their hormone receptors in vitro. CAL 18 A cells grew in agar and were tumorigenic after inoculation into nude mice; neither of these properties was observed in CAL 18 B cells. The chemosensitivity of 12 antineoplastic drugs was assessed by a short-term assay, using inhibition of tritiated thymidine incorporation by the cells after contact with the drugs as the end point. Only a few drugs were active at moderate concentrations. The overall responses of both cell lines were similar. The cell survival curves, established by the colony method following a single dose of radiation, were also very similar, despite the greater heterogeneity of CAL 18 B cells. The two cell lines appear to be interrelated, since CAL 18 B cells were occasionally observed to emerge from CAL 18 A clones, suggesting that malignant cell redifferentiation may occur spontaneously in vitro.

Conservative treatment of breast cancer: a report on 108 patients.

Between 1975 and 1980, 108 breast cancers (T1 and small T2) were treated at the Centre Antoine-Lacassagne (Nice, France) by a combination of conservative surgery and irradiation. Ninety-two of these patients underwent axillary node dissection; 17% of them presented with nodal involvement. All irradiation was given by telecobalt: 45 Gy to the entire breast, 60 Gy to the site of the tumor. All cosmetic results were acceptable. Intramammary recurrences were rare (6%) and independent of the tumor site or size or of any nodal involvement. Solitary metastases (not associated with a local recurrence) were extremely rare (4%) and were observed in patients who had had no nodal involvement. The actuarial survival rate at 5 years is 90%.

Development and use of a computer system in a radiotherapy department: SISGRAD.

SISGRAD, the interactive computer system of the Antoine-Lacassagne Cancer Center Radiotherapy Department, has been operational since January 1982. It completes the computerized dosimetry system installed several years earlier and is fully integrated with the institution's central network. SISGRAD is in charge of surveillance of the radiotherapy treatments given by the Center's three radiotherapy units (1400 patients per year); it is also used for administrative purposes in the Department and physically connects all of the Department's operating stations. SISGRAD consists of a series of microcomputers connected to a common mass memory; each microcomputer is used as an intelligent console. SISGRAD was developed to guarantee that the treatments comply with prescriptions, to supply extemporaneous dosimetric data, to improve administrative work, and to supply banks with data for statistical analysis and research. SISGRAD actively intervenes to guarantee treatment quality and helps to improve therapy-related security factors. The present text describes the results of clinical use over a 4-year period. The consequences of integration of the system within the Department are analyzed, with special emphasis being placed on SISGRAD's role in the prevention and detection of errors in treatment prescription and delivery.

CT measurement of lung density: the role of patient position and value for total body irradiation.

To obtain more precise data on pulmonary doses in preparation for total body irradiation, the lung density of patients was systematically analyzed in treatment positions using data obtained by computed tomography (CT). With the patient supine, the lung density was not significantly different for the right and left lungs. In contrast, considerable differences were noted between the two lungs in lateral decubitus positions owing to variations in ventilation and perfusion. The relative electron density of lung was also found to decrease with age, dropping to pe = 0.160 at 71 years.

Plasma levels of 7-hydroxymethotrexate after high-dose methotrexate treatment.

Thirteen patients with cancer being treated with high-dose methotrexate (MTX) chemotherapy (350-5,000 mg/6 h IV were entered in this study. Plasma levels of MTX and 7-OHMTX, its main circulating metabolite, were measured by an HPLC technique. 7-OHMTX appears rapidly in the blood, reaching a maximum 6-12 h after the beginning of treatment. The elimination of 7-OHMTX is slower than that of MTX, but the elimination half-lives (24-48 h) are not significantly different: 25.2 h for 7-OHMTX versus 20.3 h for MTX. In all cases, 24 h after starting infusion plasma levels of 7-OHMTX exceeded those of MTX. There was a positive and significant correlation between the dose administered and peak plasma 7-OHMTX. Finally, 7-OHMTX formation was shown to be relatively stable throughout the treatment.

Comparative study of gamma glutamyl transferase, alkaline phosphatase and its alpha 1 isoenzyme as biological indicators of liver metastases.

Biological detection of liver metastases represents an important factor in the surveillance of the course of cancerous affections. The authors present a report on a potential new indicator, the isoenzyme of alkaline phosphatase migrating to the alpha 1 region (alpha 1 ALP). In comparison to those tests considered the most sensitive at present-gamma glutamyl transferase and total alkaline phosphatase-this alpha 1 isoenzyme appears more sensitive and more specific, capable of detecting 97% of liver metastases with a specificity of 90%.

In vitro study of the cell populations in two cases of Kaposi's sarcoma.

Despite numerous studies, the histogenesis of Kaposi's sarcoma remains unclear. In connection with the culture of two Kaposi's sarcomas, the morphological, ultrastructural, and immunological properties of the various cell types observed are discussed. Cloning in agar, loss of contact inhibition, and karyotyping were used to determine which cells had undergone malignant transformation. Findings for both cases revealed that endothelial cells had undergone neoplastic transformation. Fibroblastic cell lines were isolated from both sarcoma fragments; although their growth characteristics distinguished them from normal fibroblasts (increased growth and possibility of culture in soft agar), cytogenetic investigations on both lines confirmed that they were genetically normal, and occurred along with malignant cells as a accessory compartment within lesions. Endothelial cells appear to be the sole origin of Kaposi's sarcoma, and may release factors which alter fibroblastic growth.

The MEDICYC programme.

The major goal of MEDICYC, the medical cyclotron programme of the Antoine-Lacassagne Cancer Center (Nice, France) is radiotherapy based on protons and fast neutrons. This cyclotron has also been designed to meet the medical requirements for the Center's Nuclear Medicine Department. Technical specifications and anticipated applications are discussed. The construction of the machine is nearly finished and a first axially injected beam is scheduled for early 1987.

Prospects for the application of fast neutrons in cancer therapy. Radiobiological bases and survey of the clinical data.

The rationale for introducing fast neutrons in therapy initially was a reduction in the Oxygen Enhancement Ratio (OER). The recent radiobiological developments indicate that, more generally, fast neutrons tend to reduce the difference in radiosensitivity between cell lines, or related to the degree of oxygenation (Oxygen Gain Factor), the position of the cells in the mitotic cycle (Kinetics Gain Factor), etc. The reduction of the differences in radiosensitivity brings a benefit for certain types of tumours (normally resistant to photons), but a disadvantage for other types of tumours (those which can currently be controlled by photon treatment). A review of the available clinical data is presented. The tumour types or sites for which a benefit has been observed are discussed: locally advanced tumours of the salivary glands, paranasal sinuses, some tumours of the head and neck area with metastatic lymph nodes, slowly growing, well differentiated soft tissue sarcomas, inoperable/recurrent melanomas, locally extended (C, D1) prostatic adenocarcinomas. Selection of the patients suitable for neutron therapy remains the main problem. Collaboration between neutron therapy centres is essential to accelerate the acquisition of sufficient clinical data needed in order to improve patient selection, as well as the optimum modality of application of fast neutrons.

[Labelling index in breast cancer and in upper respiratory and digestive tract cancer (author's transl)]. / L'index de marquage dans les cancers du sein et des voies aéro-degestives supérieures.

The labelling index (LI) of 96 breast adenocarcinomas and of 43 upper respiratory and digestive tract cancers has been measured. For the two histological groups, the distribution of individual values is found to be log-normal, with a mean value depending on the tumour type. Our data have been compared with other authors results. The dispersion of individual values within a same histological type suggests that the LI is interesting as an individual value depending on the patient and his own cancer. For breast adenocarcinomas the LI values obtained have been separated in two groups depending upon the patient age, the age of 53 has been chosen to separate premenopausal from post-menopausal patients. A test of significance showed that the two corresponding log-normal distributions were different, even at the 0.01 level of significance, a mean LI value thus characterizing each distribution.

[Host-tumor relationship as a function of the orosomucoid-prealbumin ratio]. / Etude de la relation hôte-tumeur par le rapport orosomucoïde sur préalbumine.

Of the various prognostic factors for cancer, biological parameters of the Host/Tumour relationship allow objective evaluation of the conflict between the organism and the disease. Alpha 1-acid glycoprotein (Orosomucoïd), which belongs to the Acute Phase Reactant's Proteins, and prealbumin, a highly sensitive nutritional protein, are two compounds whose blood levels vary in inverse proportion during perceptible-stage cancers: alpha 1-acid glycoprotein concentrations increase while prealbumin values drop. The ratio of the blood levels of these two parameters provides a more sensitive index than either parameter taken alone. Study of the orosomucoïd/prealbumin ratio (ROP) in a population of 132 patients and 63 controls revealed a good association between the ratio values and the different stages of the disease. The highest values corresponded to patients with active disease; normal levels were obtained for patients in partial or complete remission. During the course of disease, the orosomucoïd/prealbumin ratio is more reliable than the sedimentation rate. Furthermore, when measured at the onset of the disease, this ratio is an undeniable prognostic element, independent of the stage of disease extension.

[Viability of human cancer cells in culture after exposure to diagnostic ultrasound]. / Viabilité de cellules cancéreuses humaines en culture après exposition aux ultrasons émis par un appareil de diagnostic.

Reports have appeared in the literature regarding biological damage to human cells following exposure to diagnostic ultrasound. We have examined the effects of diagnostic ultrasound (Sonel 400, C.G.R.) on human cell lines established in our laboratory. We report here that exposure to diagnostic ultrasound, at maximum exposure intensity and at exposure time as long as 60 minutes, produces no cell lysis as determined by vital dye exclusion ability, and as confirmed by electron microscopy. However, the exposure to ultrasound produced by an apparatus delivering an acoustic power higher than the diagnostic levels (Sonoscope-Alcatel) can cause the complete lysis of the same cells.

[Conservative treatment of cancer of the breast. Apropos of 108 cases]. / Traitement conservateur du cancer du sein. A propos de 108 cas.

Between 1975 and 1980, 108 cancers of the breast (T1 and small T2) were treated by associated conservative surgery and radiotherapy. Axillary glands were curetted in 92 patients; 17% showed lymph node invasion. Radiotherapy was by telecobalt: 45 grays to the whole breast and 60 grays to the tumor bed. Esthetic results were satisfactory. Intramammary recurrence was rare (6%) and was independent of site or size of tumor and of degree of lymph node involvement. Metastases not associated with local recurrence were very rarely observed (4% of cases) and were present only in patients without glandular involvement. The 5-year actuarial survival rate was 95%.