A combined approach to investigate the toxicity of an industrial landfill's leachate: chemical analyses, risk assessment and in vitro assays.

Solid wastes constitute an important and emerging problem. Landfills are still one of the most common ways to manage waste disposal. The risk assessment of pollutants from landfills is becoming a major environmental issue in Europe, due to the large number of sites and to the importance of groundwater protection. Furthermore, there is lack of knowledge for the environmental, ecotoxicological and toxicological characteristics of most contaminants contained into landfill leacheates. Understanding leachate composition and creating an integrated strategy for risk assessment are currently needed to correctly face the landfill issues and to make projections on the long-term impacts of a landfill, with particular attention to the estimation of possible adverse effects on human health and ecosystem. In the present study, we propose an integrated strategy to evaluate the toxicity of the leachate using chemical analyses, risk assessment guidelines and in vitro assays using the hepatoma HepG2 cells as a model. The approach was applied on a real case study: an industrial waste landfill in northern Italy for which data on the presence of leachate contaminants are available from the last 11 years. Results from our ecological risk models suggest important toxic effects on freshwater fish and small rodents, mainly due to ammonia and inorganic constituents. Our results from in vitro data show an inhibition of cell proliferation by leachate at low doses and cytotoxic effect at high doses after 48 h of exposure.

In vivo comparative study of the cytotoxicity of a liposomal formulation of cisplatin (lipoplatin™).

PURPOSE: Cisplatin is one of the most effective cytotoxic agents in the treatment of solid malignancies, but its use is limited by several side effects. Among them, peripheral neurotoxicity can be dose limiting. A liposomal formulation of cisplatin, Lipoplatin™, was developed to reduce the systemic toxicity of cisplatin but without preventing its efficacy. The aim of this study was to use an animal model to establish, through a multimodal approach, whether chronic treatment with two different schedules of Lipoplatin™, selected within the range of its anticancer effective dose, is less neurotoxic than cisplatin administration. METHODS: Female Wistar rats were treated intraperitoneally with cisplatin at a dose of 4 mg/kg or with Lipoplatin™ at doses delivering 12 or 24 mg/kg of cisplatin once weekly for 4 weeks. General toxicity was assessed by daily observation, body weight change, hematological and blood chemistry analysis, and histopathology of liver and kidney. The onset of peripheral neurotoxicity was assessed by measuring tail nerve conduction velocity (NCV), morphological and morphometric analysis of dorsal root ganglia (DRG), and morphological analysis of the sciatic nerve. RESULTS: Cisplatin induced a statistically significant reduction in body weight, the development of renal failure, and impairment in NCV with pathological alterations in the DRG and sciatic nerve. By contrast, Lipoplatin™ was markedly less nephrotoxic, and no significant weight gain reduction was observed in animals treated with both doses of the drug. Moreover, the lowest dose induced less severe damage to the peripheral nervous system with a moderate decrease in NCV and mild pathological alterations in DRG and the sciatic nerve. CONCLUSIONS: The results suggest that Lipoplatin™ 12 mg/kg is less neurotoxic than cisplatin 4 mg/kg, thus opening up the possibility of using this new formulation in future studies where its anticancer activity and the peripheral neurotoxicity will be assessed in parallel.

Higher survival of refractory metastatizing breast cancer after thermotherapy and autologous specific antitumoral immunotherapy.

46 women (average 54.3 yrs) with refractory metastatizing breast cancer were treated with thermotherapy and autologous specific immunotherapy (rhIL-2 ex vivo activated cells). Metastases involved one organ in 69%; in particular, bone, lung, liver. The PS after treatment was satisfactory in 41%; the outcome was better in those cases with metastases to one site. The women remaining alive were 31/46; 67% of thermoimmunotherapy treated patients were alive after a maximum survival time of 85 months (median 24 months). The 36 months of control showed a 5-fold higher survival rate in our series when challenged with that of compared women undergoing only chemotherapy (p < .001).

Therapeutic hyperthermia in cancer and AIDS: an updated survey.

The aim of this paper is to update with personal contributions the progress thus far accomplished in the clinical application of hyperthermia (HT) in cancer and chronic infectious diseases. The HT treatment has been successfully developed since the 1970s in cancer patients in whom it showed positive results consisting of complete or partial clinical remissions. Its rationale was based on the fact that core temperatures of > or = 42 degrees C induce cytotoxic effects that are higher in malignant cells than in normal cells. HT could be applied by different methods according to type, stage, and localization of the malignancies. Thus, systemic whole-body HT (WBH), through invasive or noninvasive techniques, was first used in disseminated cancers; local perfusion, infusion, and interstitial HTs have been applied in limb, skin, subcutaneous, or intracavitary tumors. The observation of a macrophagic lysosomal exocytosis and subsequent cancer cell death induced by HT, suggested that its mechanism of action involves an immune reaction. This suggested the possibility of associating HT with cytotoxic agents, antibiotics, antiviral drugs, and antioxidants, including beta-carotene (BC). The association of HT with BC at high doses are synergistic in patients with AIDS-related complex (ARC) and improve its symptoms, preventing the progress of the disease into the severe stage of AIDS; the same synergism helped also to increase the survival time in patients with severe AIDS.

Hyperthermia in the treatment of brain metastases from lung cancer. Experience on 17 cases.

Medium or long-term survival in metastatic "non oat cell" lung tumors is seldom possible only if surgery can eradicate the lesion. Out of 17 patients treated with hyperthermia plus nitrosoureas 16 (94%) responded, with clinical improvement, radiological regression or disease stabilization. The survival time of the improved patients was 12.7 months. Hyperthermia in combination with nitrosoureas seems to allow clinically and radiologically satisfactory responses in lung tumors metastatic to the brain.

Is metastatic breast cancer, refractory to usual therapy, curable?

Breast cancer with metastatic disease is presently incurable. Significantly shorter survival rates are seen in premenopausal women despite usual therapies when compared to survival rates in older women. Median survival rates of 24-30 months are documented in large-scale prospective clinical trials of previously untreated women with metastatic breast cancer regardless of the protocol employed (chemotherapy, hormone therapy). High dose chemotherapy followed by autologous stem cell rescue (bone marrow or peripheral blood) is associated with significant response and possibly improved survival in chemosensitive patients with metastatic disease without visceral metastases though with significant toxicities and cost (median survival rate of 20 months). Patients with refractory disease have dismal results regardless of therapy (median survival rates of 8-9 months in a number of prospective trials with or without stem cell rescue). The use of alpha-interferon in such patients has not improved response. Whole body hyperthermia is of benefit in the presence of liver metastases although median survival rate is in the range of 12 months. New treatment approaches with curative intent are clearly required. We report fifty-nine patients with metastatic breast cancer refractory to common therapies who were treated with whole body hyperthermia (40 degrees C) with low dose chemotherapy and immunomodulation: five presented with brain metastases; 13 with multiple bone metastases; 8 with liver metastases; 10 with lung metastases; and 23 with multiple soft tissue metastases. Fifteen were premenopausal; 44 postmenopausal. Twenty-three achieved complete remission. Fourteen have been sustained with patients remaining alive from 17-80 months (median, 40 months). Nine failed after 20-40 months of being disease-free (mean, 32 months).(ABSTRACT TRUNCATED AT 250 WORDS)