Results of a clinical multicentric randomized phase-ii study of nonsmall cell lung-cancer treated with vinorelbine Cisplatin versus vinorelbine alone.

From July 1992 to December 1993, 62 patients with non-small cell lung cancer (NSCLC) were admitted to a multicentric randomized study. The patients were treated with vinorelbine (V) alone at a dose of 25 mg/m(2)/i.v. weekly or with V at a dose of 25 mg/m(2)/i.v. on day 1 and 8 plus cisplatin at a dose of 80 mg/m(2)/i.v. on day 1 every 3-4 weeks (VP). An objective response was observed in 42% of patients treated with VP versus 12.5% of those treated with vinorelbine alone (p=0.038). There was no significant difference in the median survival duration between the two groups (38 versus 30 weeks for VP and V, respectively). Toxicity was tolerable but more severe in the VP regimen. These data suggest that V is an active agent in NSCLC and that the VP regimen may yield results comparable to other cisplatin combinations for treatment of these tumors.

Seroprevalence of chronic Chlamydia pneumoniae infection in patients affected by chronic stable asthma.

OBJECTIVE: To evaluate the seroprevalence of Chlamydia pneumoniae and age, gender and smoking habits in stable asthmatic patients. METHODS: Over a period of 3 months, 197 adult patients affected by intermittent-to-severe chronic asthma were enrolled from 16 respiratory disease units in the south of Italy. As a control group, we tested 185 healthy, non-asthmatic subjects matched for age and gender, recruited among hospital staff. All patients were submitted to clinical examination, spirometry and blood collection for C. pneumoniae serology. The presence of infection was investigated by microimmunofluorescence (Micro-IF Test) for C. pneumoniae-specific IgG, IgM and IgA antibodies. RESULTS: C. pneumoniae IgG titers > or =1 : 64 were detected in 30.4% of asthmatics and in 30.8% of controls. Correlation of age, gender and smoking habit with C. pneumoniae seropositivity was evaluated by linear regression analysis. Age was significantly associated with C. pneumoniae IgG titer > or =1 : 64 when seropositive asthmatics were tested. Moreover, C. pneumoniae seroprevalence was higher among smokers with a diagnosis of chronic asthma. CONCLUSIONS: The seroprevalence of C. pneumoniae in stable asthmatics was comparable with the controls; therefore, the study does not support the association between C. pneumoniae antibody titers and stable asthma. However, the analysis for likely confounders such as age, gender and smoking status suggests a possible association of enhanced susceptibility to C. pneumoniae infection with age and smoking habitus.

Malignant mesothelioma in subjects with Marfan's syndrome and Ehlers-Danlos syndrome: only an apparent association?

Malignant mesothelioma is a rare neoplasm which could be favored by an hereditary predisposing factor. So far, malignant mesothelioma have never been described in patients with hereditary diseases of the connective tissue. Here, we report some cases of mesothelioma affecting subjects who were not exposed to inhalation of asbestos. One of these subjects was affected by Ehlers-Danlos syndrome, whereas in two brothers, mesothelioma was associated with Marfan's syndrome. The observation of the same histologic subtype of mesothelioma in two brothers and the coexistence of two pathologic conditions of mesodermal origin indicate the presence of hereditary factors predisposing to the cancerogenic action of even small amounts of asbestos. Structural alterations of collagen and primary immunodeficiency may represent the host factor inducing development of the neoplasm. We conclude that the association between these rare disorders of the connective tissue and mesothelioma may not be coincidental, but could be the result of the exposition to small amounts of asbestos in predisposed individuals.

Sensitivity of human glioma cells to cytotoxic heteroconjugates.

Several anti-human glioma cytotoxic conjugates were studied in vitro. Monoclonal antibodies (MAbs) to the GE2 glioma-associated antigen (anti-GE 2) and MAbs to HLA-DR antigens (D1/12) or human diferric transferrin (Tfn) were linked to the potent cytotoxin ricin (anti-GE 2-ricin) or to its A subunit (anti-GE 2-RTA, D1/12-RTA, Tfn-RTA). Anti-GE 2-RTA had low cytotoxic activity in both the absence and the presence of lysosomotropic substances inhibiting intracellular degradation. Anti-GE 2-ricin was about 1,000 times more toxic than RTA alone, but showed only 14-fold target specificity. D1/12-RTA was about 20 times more toxic than RTA and its cytotoxic effect increased about 6- to 7-fold when cell-surface HLA-DR antigen expression was enhanced by IFN-gamma treatment. Human diferric Tfn linked to RTA demonstrated the highest cytotoxic activity, being about 5,000 times more toxic than RTA alone for glioma cells and about 6,000 times more toxic for Jurkat cells in the presence of the carboxylic ionofore monensin. Ricin toxin was only about 5 times more toxic for Jurkat and glioma cells than Tfn-RTA-monensin. Tfn-RTA was over 100,000 times more potent than the chemotherapeutic agent BCNU in reducing glioma cell survival in vitro. Addition of 80% human pooled cerebrospinal fluid (CSF) reduced Tfn-RTA toxicity about 10-fold. Kinetics of Tfn-RTA cytotoxicity at non-saturating concentrations indicated that over 80% of target cells could be killed within 8-10 hr in the absence and within 10-12 hr in the presence of human pooled CSF.

Human glioma cell lines: tumour associated antigens distribution and sensitivity to antibody-toxin or ligand-toxin conjugates. A preliminary report.

We have investigated the phenotype of seven human glioma cell lines established in vitro from primary tumour explants. Indirect immunofluorescence and flow cytofluorimetry revealed a heterogeneous distribution of surface GE 2 and CG 12 Tumour Associated Antigens (TAA). In one group of cell lines TAA were detected both at the cell surface and in the cytosol, whereas in a second group of glioma cell lines TAA were found only in the cytosol. We have also investigated the sensitivity of glioma-derived cell lines to antibody-toxin and ligand-toxin conjugates (Immunotoxins). Monoclonal antibodies anti GE 2 antigen linked to ricin toxin A subunit (RTA) showed poor cytotoxicity, which increased about 50 fold when the whole toxin was linked to anti GE 2 monoclonals. Treatment with human recombinant interferon gamma (IFN-gamma) greatly augmented the percentage of HLA-DR+ cells and the amount of HLA-DR antigens per cell. IFN-gamma treatment resulted in a net increase of sensitivity to anti HLA-DR Immunotoxins (IT). Human diferric transferrin linked to RTA exhibited a potent cytotoxic effect against human glioma-derived cells when used in the presence of the lysosomotropic carboxylic ionophore monensin.