A mutation analysis of the BRCA1 gene in 140 families from southeast France with a history of breast and/or ovarian cancer.

A mutation analysis of the BRCA1 gene in 140 French families with a history of breast cancer or breast-ovarian cancer revealed several deleterious germline mutations, as well as rare sequence variants. The 19 genetics variants were of 15 different types, two of which had not been reported in the Breast cancer Information Core (BIC) database. Five distinct truncating mutations, leading to putative nonfunctional proteins, were identified out of 140 index cases (3.

Establishment of two new human bladder carcinoma cell lines, CAL 29 and CAL 185. Comparative study of cell scattering and epithelial to mesenchyme transition induced by growth factors.

We describe here two new human urothelial carcinoma cell lines, CAL 29 and CAL 185, established from two patients with high-grade tumours and which display very different properties in vitro. We have shown that CAL 29 cells were tumorigenic in mice and expressed characteristic features of both cell scattering and transition from epithelial to mesenchymal phenotype (EMT) after triggering by the EGF receptor ligands, TGFalpha and EGF. At the opposite, the CAL 185 cells were not tumorigenic in mice and neither scattered nor expressed vimentin intermediary filaments in the presence of growth factors.

Expression of vascular endothelial growth factor-b in human astrocytoma.

Growth of human malignant gliomas is stringently dependent on an angiogenic process that probably involves vascular endothelial growth factor (VEGF). Expressions of mRNA coding for the different forms of VEGF were analyzed in surgical specimens from human astrocytomas. Low levels of placental growth factor (PGF) and VEGFC mRNA were observed in polymerase chain reaction, but not in Northern blot experiments.

Screening of human bladder carcinomas for the presence of Ha-ras codon 12 mutation.

Contradictory results were obtained from previous studies aiming at defining the frequency of Ha-ras codon 12 mutations in bladder tumors. Differences in the sensitivities of the methods used could account for this discrepancy. In this study, we reevaluated the frequency of Ha-ras codon 12 mutations in a series of 87 human bladder tumors using a combination of two different methods.

Establishment, characterisation and partial cytokine expression profile of a new human osteosarcoma cell line (CAL 72).

Permanent human osteosarcoma cell lines are important tools for the study of bone cancer. As representative of an osteoblastic phenotype, they partly reflect their normal osteoblastic counterparts and, thus, may represent appropriate models to investigate the mechanisms involved in bone remodelling and in haematopoietic differentiation. In the present work, we describe a new human cell line, CAL 72, obtained from an osteosarcoma of the knee of a 10-year-old boy.

Human breast-cancer metastasis formation in a nude-mouse model: studies of hyaluronidase, hyaluronan and hyaluronan-binding sites in metastatic cells.

Few animal models are available to study metastasis formation. The purpose of the present study was to obtain a useful model of metastasis formation in nude mice in an attempt to analyze the stroma reaction and in particular the production and the expression of hyaluronan (HA), hyaluronidase, and HA-binding sites by cultivated cells, and HA and hyaluronectin (HN) in the invasive areas of tumors. Nude mice were subjected to i.

Epidermal growth factor receptor and labeling index are independent prognostic factors in glial tumor outcome.

The aim of this study was to perform a multivariate analysis including clinical and biological prognostic factors on glial tumor outcome. Seventy-nine patients were analyzed (48 men and 31 women; mean age = 56 years, range = 16-77 years): 7 had a benign glial tumor (grades 1 and 2), 21 had an anaplastic glial tumor (grade 3), and 51 had a glioblastoma (grade 4). Median follow-up was 17.

[Production of hyaluronidase by cultured human tumor cells].

The presence of hyaluronidase was detected at pH 3.8 in eight out of twelve human cancer cell line culture media. Eight cell lines derived from primary tumours and four from metastases.

Establishment and characterization of a new cell line derived from a human chondrosarcoma.

A new human cell line, CAL 78, derived from a dedifferentiated chondrosarcoma of the muscle of the thigh has been established in culture. Fibroblastoid morphology, vimentin expression and lack of epithelial antigens are in agreement with mesodermic origin of these cells. The xenograft of CAL 78 cells in nude mouse showed the characteristics of hyaline cartilaginous differentiation.

Non-specifically labelled cells that simulate bone marrow metastases in patients with non-metastatic breast cancer.

Aims: To determine whether the presence of disseminated bone marrow tumour cells at diagnosis is a prognostic factor for breast cancer patients at high risk of recurrence or bone metastasis, and to assess their presence as a criterion for evaluation of the potential benefits of adjuvant chemotherapy.

Methods: Multiple bone marrow aspirates from 72 breast cancer patients free from metastasis were obtained during surgery at the time of diagnosis and were tested immunologically by alkaline phosphatase antialkaline phosphatase technique with a panel of three antiepithelial monoclonal antibodies (MoAb) KL1, EMA, and HMFG2.

Results: In nine of 72 patients, with each MoAb tested, numerous strongly positive cells always isolated were observed.

[GC12, marker of cells of mesodermal origin. Value and application to cytodiagnosis of serous effusions].

Monoclonal antibody GC12 was examined for its value in cytopathologic diagnosis. Its sensitivity and specificity in staining reactive mesothelial cells in serous effusions was determined using the indirect immuno alkaline phosphatase anti-alkaline phosphatase technique. Smears prepared from 78 serous effusions (15 benign, 54 malignant, 9 atypical) were immunostained with GC12 and five other monoclonal antibodies: KL1 directed against cytokeratins, D33 against desmin, E29 against epithelial membrane antigen, Calam 27 against epithelial surface antigen and NEO 723 reactive with carcinoembryonic antigen.

[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.

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.

Chromosomes in gliomatosis cerebri.

Gliomatosis cerebri is a rare brain tumor which histologically resembles a diffuse cerebral astrocytoma. It can simultaneously infiltrate multiple sites in the cerebrum, cerebellum, brainstem, and spinal cord. This remarkable diffuseness has led to the idea that gliomatosis cerebri does not derive from a solitary focus but must arise from a broad field of glial cells.

Cytogenetics of malignant gliomas. II. The sex chromosomes with reference to X isodisomy and the role of numerical X/Y changes.

Sex chromosomal monosomy with total loss of an X or Y is frequently observed in malignant gliomas. Beyond that, not much is known about the behavior of the sex chromosomes in these tumors. We noted loss of the X from 3 of 13 gliomas from women (23%) compared to loss of the Y from 16 of 28 gliomas from men (57%).

Cytogenetics of malignant gliomas: I. The autosomes with reference to rearrangements.

Autosomal chromosome abnormalities are far from always detectable and, when detected, far from fully consistent in malignant gliomas. In 15 of 41 malignant gliomas, we found autosomal chromosome aberrations ranging from solitary trisomy to a wildly abnormal polyploid complement. The sequence of chromosome events appears to proceed from the normal to the near-diploid state (via structural and numerical changes) to near-tetraploidy (via polyploidization), and finally toward near-triploidy (via chromosome loss and additional rearrangements).

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.

Immunophenotyping and metastatic localization of breast cancer.

Monoclonal antibody SM 92 is involved in the immunophenotype of gastrointestinal and liver cells, SM 43 in ovarian cells, and SM 13 in lung cells. Based on a study of 61 breast adenocarcinoma patients, we found that tumors reacting with SM 92 appear associated with liver metastases, SM 43 with ovarian metastases, and SM 13 with lung metastases. These associations are highly significant.

Effects of tamoxifen on potential doubling time of human breast cancer cell line determined by image cytometry of double fluorescent BrdU and DNA labeling.

Tamoxifen is extensively used for the treatment of human breast cancer. However, the mechanisms by which antiestrogens regulate the growth of estrogen receptor positive tumors have not been totally defined. A new methodology, using automated image analysis BIOCOM 500, was developed for determining potential doubling time (Tpot) of tumors.

Characterization of cal39, a new human cell-line derived from a vulvar squamous-cell carcinoma.

We have obtained a permanent cell line from a squamous cell carcinoma of the vulva. These cells, named CAL39, exhibited morphological, ultrastructural, and immunochemical characteristics of epithelial cells. They were tumorigenic in nude mice.

[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.

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.

Effects of prolonged exposure to cisplatin on cytotoxicity and intracellular drug concentration.

The present study was designed to analyse the cytotoxic effect of cisplatin in vitro as a function of various exposure times (up to 120 h), keeping constant the parameter C x T (product of the drug concentration per time). Intracellular drug concentrations were measured in parallel following analysis of cisplatin influx and efflux characteristics. A head and neck cancer cell line was selected to represent the spectrum of cisplatin antitumour activity.

[Cytotoxic effects of the combination of a new nitrosourea, fotemustine, combined with 5-fluorouracil and folinic acid depend on the sequence of their administration].

The present study was designed to analyse the cytotoxic effects of the combination of fotemustine plus 5-fluorouracil (5-FU) and folinic acid (FA). Two human tumor cell lines were used; one line was derived from colon cancer (WIDR) and the other from a non-small cell lung cancer (CAL 12). Cytotoxic effects were assessed by the MTT semi-automated test in 96-well incubation plates.

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.