Multidrug resistant variants of two human osteosarcoma cell lines (U-2 OS and Saos-2) were selected by continuous exposure to doxorubicin. The in vitro and in vivo growth characteristics of these sublines as well as the expression of osteoblastic markers and of some surface antigens were analyzed. Resistant variants showed a higher doubling time and a lower cloning efficiency, and a lower metastatic ability after i.v. injection than corresponding parental cell lines. All the sublines showed overexpression of p-glycoprotein (referred to as p170). The level of expression of this protein in the different cell lines was directly related to the degree of resistance as shown by the in vitro sensitivity to doxorubicin and other multidrug-related drugs. In sublines showing the highest levels of resistance (over 300-fold), p170 overexpression was associated with mdr 1 gene amplification. These are the first multidrug resistant human osteosarcoma cell lines ever reported. They may be used as a model for further investigations into the mechanisms of drug resistance in osteosarcoma and as a standard for the assessment of chemosensitivity in clinical samples.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Malignant pleural mesothelioma. Multivariate analysis of prognostic factors on 113 patients.

We report on clinical features of 113 cases of pathologically confirmed Malignant Pleural Mesothelioma, observed in Genoa (Italy) between 1979 and 1985. Overall median survival was 10 months. Among the pretreatment variables studied (age, sex, asbestos exposure, pathological type, chest pain and dyspnea at the time of diagnosis), the only one of prognostic value in the univariate analysis was the histological subtype: median survivals were 12, 7 and 4 months for the patients in the epithelial, mixed, and fibrosarcomatous groups, respectively (p = 0.0012). A multivariate analysis confirmed the independent predictive power of the histotype (p = 0.0022). A review of literature data concerning prognostic factors in Malignant Pleural Mesothelioma is presented.

Adult↗