Publications (49)249.32 Total impact
-
Article: A historical cohort mortality study among shipyard workers in Genoa, Italy.
[show abstract] [hide abstract]
ABSTRACT: A historical cohort mortality study was conducted among 3984 shipyard workers assigned to ship repair, refitting, and construction in the harbor of Genoa, Italy, between 1960 and 1981. These workers were exposed to asbestos fibers, welding fumes and gases, silica dust, polycyclic aromatic hydrocarbons, and solvents. Workers were classified in 20 different job-titles depending upon the type of activity. Standardized mortality ratios (SMRs) were computed using male residents of the Province of Genoa as the referent population. For the whole cohort significantly increased SMRs were detected for all causes, all cancers, liver, larynx, lung, pleural and bladder cancers, respiratory tract diseases, and cirrhosis of the liver. The analysis by job-title showed increased SMRs not only for pleural cancer, but also for lung, laryngeal cancers and respiratory tract diseases in occupations entailing heavy asbestos exposure. Bladder and liver cancers and liver cirrhosis mortality also appeared to be related to occupational exposure.American Journal of Industrial Medicine 11/2001; 40(4):363-70. · 1.63 Impact Factor -
Article: Occupational exposure to carbon black and risk of bladder cancer.
[show abstract] [hide abstract]
ABSTRACT: Exposure to carbon black has been linked to risk of lung and bladder cancer. We therefore investigated the frequency of these cancers in a group of 2286 longshoremen who were exposed occupationally to carbon-black dust. We identified 208 cancers (standardised incidence ratio 96, 95% CI 83-109), 53 lung cancers (108, 81-141), and 32 bladder cancers (130, 89-184). Longshoremen exposed to high concentrations of carbon black (n=14) had a significantly increased frequency of bladder cancer (204, 112-343). We conclude that the increase in bladder cancer in longshoremen is probably related to high exposure to carbon black.The Lancet 09/2001; 358(9281):562. · 38.28 Impact Factor -
Article: Exposure to agrochemicals and DNA adducts in Western Liguria, Italy.
[show abstract] [hide abstract]
ABSTRACT: Pesticides are used to control pests and improve agricultural production. Despite their selectivity of action, a number of agrochemicals have been reported to be genotoxic using the (32)P-DNA postlabeling assay. Greenhouse floriculturists are suspected of being heavily exposed to agrochemicals during loading, mixing, and application of pesticides, as well as during manual activities by continuous contact with flowers and ornamental plants. We analyzed the DNA adduct formations in the white blood cells (WBCs) of 57 nonsmoker greenhouse floriculturists and 33 nonsmoker age-matched referents residing in the Western Liguria Region, Italy-the most important Italian greenhouse floriculture area. The averages of DNA adducts, expressed as relative adduct labeling (RAL), were 8.50 x 10(9) +/- 1.98 (SE) in floriculturists and 2.17 x 10(9) +/- 1.05 (SE) in referents. DNA adducts were significantly higher in floriculturists than in controls after adjustment for age and gender (P = 0.007). A specific adduct pattern, with up to six different spots, was observed in 60% of floriculturists, while no adducts were generally detected in controls. Our study represents an important contribution to the correct evaluation of the potential health risk associated with floriculture activity and supports the adoption of measures ensuring pesticide exposure reduction in greenhouses.Environmental and Molecular Mutagenesis 02/1999; 34(1):52-6. · 3.71 Impact Factor -
Article: Urinary excretion of 1-hydroxypyrene as a marker for exposure to urban air levels of polycyclic aromatic hydrocarbons.
[show abstract] [hide abstract]
ABSTRACT: A cross-sectional study was conducted among 94 traffic police officers from the Municipality Police of Genoa, Italy, exposed to airborne pollutants and 52 referent subjects exposed to indoor air pollution levels to investigate the relationships between exposure to ambient air polycyclic aromatic hydrocarbons (PAHs) and urinary excretion of 1-hydroxypyrene (1-OH-P). The effects of smoking, lifestyle factors such as exposure to ETS, and diet, along with the role played by the cytochrome P4501A1 (CYP1A1), and glutathione S-transferase M1 and theta metabolic susceptibility gene polymorphisms were examined. The geometric mean of benzo(a)pyrene air measurements (an index compound of PAH levels) was 70 times higher in traffic police officers (3.67 ng/m3) than in referents (0.05 ng/m3). The urinary concentration of 1-OH-P was clearly associated with cigarette smoking and, to a lesser extent, with exposure to ETS and particulate PAH pollution. No association was detected between 1-OH-P excretion and diet. Women exhibited a higher excretion level than did men, and an apparent effect of age was due to differences in cigarette smoking habits. Exposure to PAHs resulted in higher levels of 1-OH-P excretion in all groups except heavy smokers. Overall, no significant role of any metabolic polymorphism was detected. However, stratification of study subjects according to their smoking habits revealed higher levels of excretion of 1-OH-P in subjects smoking < or =15 cigarettes/day carrying the CYP1A1 polymorphism. No such effect was seen either with nonsmokers or with people smoking more than 15 cigarettes/day. These findings are suggestive of a gene-environment interaction, in which subjects with the CYP1A1 polymorphism, relative to subjects without it, have higher levels of 1-OH-P in their urine at low doses of exposure to PAHs.Cancer Epidemiology Biomarkers & Prevention 02/1998; 7(2):147-55. · 4.12 Impact Factor -
Article: 32P-postlabeling detection of aromatic adducts in the white blood cell DNA of nonsmoking police officers.
[show abstract] [hide abstract]
ABSTRACT: Atmosphere in urban areas may be polluted by a number of combustion sources, including industries, vehicle traffic, and residential heating. Traffic police constitute a group of workers that is highly exposed to urban pollutants, especially those from motor vehicle exhaust. We conducted a biomonitoring study to simultaneously measure in 34 nonsmoking police officers and in 36 nonsmoking office workers, as referents, the individual benzo(a)pyrene [B(a)P] exposure using personal samplers and the formation of DNA adducts in peripheral WBCs using 32P-postlabeling techniques. Our results show that the police officers were exposed to significantly higher levels of B(a)P than were referents (P < 0.0001). No seasonal variation of the atmospheric levels of B(a)P was found throughout the year. The median relative adduct labeling x 10(-8) values of the controls and exposed police officers were 0.94 (range, 0.1-3.7) and 1.3 (range, 0.1-5.5), respectively, using the nuclease P1 technique. Although the DNA adduct levels of police officers were globally higher than those of referents (P < 0.05), the difference was entirely due to the summer difference [median values 0.80 (range, 0.1-1.8) and 2.8 (range, 0.7-5.5), respectively (P < 0.001)]. In winter, the DNA adduct levels were substantially identical, and in midseason, there was only a very small increase in police officers, with respect to controls (statistically not significant). Moreover, a more significant seasonal variation of bulky aromatic DNA adduct levels was observed in WBC DNA samples of police officers (P < 0.05) compared to those of referents. The seasonal variation of bulky aromatic adduct levels could be correlated with the reported seasonal variation of aryl hydrocarbon hydroxylase inducibility in human lymphocytes.Cancer Epidemiology Biomarkers & Prevention 01/1998; 7(1):3-11. · 4.12 Impact Factor -
Article: Sister chromatid exchange induction in peripheral blood lymphocytes of traffic police workers.
[show abstract] [hide abstract]
ABSTRACT: Traffic police workers, as a population exposed to urban atmosphere, were compared with a control population exposed to indoor air pollution levels. Sister chromatid exchanges (SCEs) as a biomarker of effect were measured in peripheral blood lymphocytes of 54 exposed subjects and 35 controls, and environmental concentration of polynuclear aromatic hydrocarbon (PAH) tracer compounds was detected by personal air samplers. The mean exposure level to benzo[a]pyrene in our group of traffic policemen (3.4 mg/m3) was in the range that has been estimated in urban areas in Europe during the last 10 years. No difference in SCE levels was found between exposed workers (7.36, SD 1.35) and controls (7.47, SD 1.28). No correlation was observed between SCE/cell and airborne PAH concentration in the traffic worker population. A positive regression of SCE on exposure estimate was found only in the non-smoking group of police workers. Our findings suggest that exposure to urban air pollution does not induce relevant cytogenetic effects.Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 12/1997; 394(1-3):37-44. · 2.85 Impact Factor -
Article: Cytogenetic biomonitoring in traffic police workers: micronucleus test in peripheral blood lymphocytes.
[show abstract] [hide abstract]
ABSTRACT: Atmospheric pollution represents a relevant environmental hazard which has been associated with considerable excess mortality, morbidity, and increased rates of respiratory diseases in humans. To date, more than 3,000 environmental chemical compounds have been identified in the ambient atmosphere, including a variety of mutagenic and/or carcinogenic agents, such as polycyclic aromatic hydrocarbons (PAHs), aromatic amines, and heterocyclic compounds. Positive associations between cytogenetic markers and airborne levels of PAHs have been reported by experimental and human studies. Traffic has been implicated as the major determinant for the concentration of PAHs and, therefore, for the genotoxic activity of urban air. A biomonitoring study has been conducted in 82 italian traffic police workers exposed to air pollutants and 34 control subjects (matched by age, gender, and smoking habits) not exposed to traffic pollutants. The aim of this study was to assess the cytogenetic effects, such as micronucleus frequency in peripheral blood lymphocytes, and to estimate the association with individual exposure to PAH. Statistical analysis of the frequency of micronuclei in binucleated cells showed higher mean levels in referent subjects (4.03%) than in traffic police officers (3.73%). Smoking showed no effect on the frequency of micronuclei. The study failed to detect any association between micronucleus frequency and individual level of benzo(a)pyrene, considered a marker of exposure to PAHs. These findings indicate that exposure to urban air pollutants does not result in increased levels of micronuclei in peripheral white blood cells.Environmental and Molecular Mutagenesis 02/1997; 30(4):396-402. · 3.71 Impact Factor -
Article: Airborne levels of polycyclic aromatic hydrocarbons: 32P-postlabeling DNA adducts and micronuclei in white blood cells from traffic police workers and urban residents.
[show abstract] [hide abstract]
ABSTRACT: An epidemiologic study on 94 traffic police officers exposed to airborne polycyclic aromatic hydrocarbons (PAH) and 52 age-matched urban residents working in confined spaces considered as referent subjects without occupational exposure to PAH was conducted to characterize individual exposure to benzo(a)pyrene (BaP), benzo(b)-, and benzo(k)fluoranthene (BbF and BkF) and the occurrence of DNA adducts and micronuclei in white blood cells (WBC). The study's findings indicated that mean concentrations of PAH in the city air were 10 to 30 times higher among the traffic police officers compared with referent subjects (4.55 +/- 3.44 ng/m3 and 0.15 +/- 0.30 ng/m3 of BaP among police officers and referents, respectively). 32P-postlabeling DNA adducts in WBC obtained from police officers (1.48 +/- 1.35 RAL/10(8)) were significantly higher than in referent subjects (1.01 +/- 0.63 RAL/10(8), P = 0.007), suggesting a possible role of exposure to airborne PAH in the DNA damage. The frequency of micronuclei was significantly increased (P = 0.02) in referent subjects (4.49 +/- 2.0% cells) compared with police officers (3.75 +/- 1.65% cells) due to the large proportion of females in the former group. Comparison of the mean micronuclei frequencies among 82 male police officers (3.73 +/- 1.6% cells) and referents (4.03 +/- 1.61% cells) failed to reveal a statistically significant difference (P = 0.38). Our findings support the evidence of a noxious effect of the exposure to airborne PAH found in large cities on the occurrence of DNA adducts in WBC, whereas there seems to be no effect on the cytogenetic risk assessed as micronuclei frequency.Journal of Environmental Pathology Toxicology and Oncology 02/1997; 16(2-3):157-62. · 1.00 Impact Factor -
Article: Cisplatin combined with the new cisplatin-procaine complex DPR: in vitro and in vivo studies.
[show abstract] [hide abstract]
ABSTRACT: The administration of combinations of platinum compounds is considered as a useful alternative therapeutic strategy to avoid the complications of toxic events during cancer chemotherapy in order to obtain a therapeutic advantage. On the basis of previous in vitro and in vivo findings, suggesting an antitumour activity of the new cisplatin-derived compound cis-diamminechloro-[2-(diethylamino)ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate (DPR), we investigated the effectiveness of the combination of cisplatin (DDP) and DPR in vitro on murine leukaemic cells, which were either sensitive (P388) or resistant (L1210/DDP) to DDP, and on the murine M5076 reticulum cell sarcoma, and in vivo in BDF1 female mice transplanted with P388 leukaemic cells or cisplatin-resistant L1210/DDP leukaemic cells. The contemporaneous exposure in vitro to both platinum compounds gave a significantly higher cell growth inhibition than that expected on the basis of dose-response curves for single agents in all tumour models tested. In vivo, the combinations of DDP plus DPR elicited significant enhancement over the activity of the drugs alone both in the ascitic and solid P388 models. The combined treatment of 10 mg/kg DDP and 14 mg/kg DPR yielded 62.5% tumour-free mice compared with 6.2% with 10 mg/kg DDP alone, the best single agent. It is noteworthy that the combined application of DDP and DPR was also very effective in the solid cisplatin-resistant L1210/DDP model, inducing a significant reduction in the volume of tumour. A therapeutic advantage was achieved with combination treatments that had no effect on platinum-mediated body weight loss and were generally well tolerated by the mice. At equitoxic concentrations of DPR and carboplatin, the treatment with DDP plus DPR proved to have a higher efficacy against this tumour model compared to that observed after the combined treatment with DDP and carboplatin. In summary, the combination of DDP and DPR showed a therapeutic advantage over single drug treatment and has demonstrated promise at the preclinical level in its ability to circumvent acquired resistance to DDP both in vitro and in vivo.European Journal of Cancer 01/1997; 32A(13):2327-33. · 5.54 Impact Factor -
Article: Effect of the antiarrhythmic drug procainamide on the toxicity and antitumor activity of cis-diamminedichloroplatinum(II).
[show abstract] [hide abstract]
ABSTRACT: The class I antiarrhythmic drug procainamide (Pd) was tested on BDF1 mice for its chemoprotective activity against cis-diamminedichloroplatinum(II) (DDP) toxicity. Pd at the dose of 50 mg/kg protected mice against otherwise lethal doses of DDP (survivors at Day 14 after 25 mg/kg DDP or 25 mg/kg DDP-Pd treatment: 0% vs 100%) and greatly reduced the weight loss induced by DDP. Moreover, the increased plasma urea nitrogen levels caused by a single ip administration of DDP in water (8 or 16 mg/kg) as well as the tubular degenerative changes detected by light microscopy were prevented by Pd. Pd had no effect on the sensitivity of P388 leukemic cells to DDP in vitro, but the administration of DDP (16 mg/kg) and Pd (50 mg/kg) to BDF1 mice bearing P388 leukemic cells produced a significant increase in survivals compared to mice receiving ip DDP alone diluted in 0.9% NaCl solution. The increased efficacy of this combination therapy in P388 leukemic mice compared to a single DDP treatment at the same dose was observed both when the drugs were administered ip simultaneously (p = 0.042) and when DDP and Pd were given ip and iv, respectively (p = 0.018). Since procaine, which differs from Pd merely in the replacement of the amide by the ester linkage, has also been reported to significantly enhance DDP efficacy (M. Esposito et al., 1990, J. Natl. Cancer Inst. 82, 677-684.), a comparison of their effects in tumored mice exposed to DDP has been made. Although both drug combinations were superior to that of DDP alone, in terms of both survival time and numbers of cures, Pd treatment seems to offer better protection against DDP-induced lethality than did procaine.Toxicology and Applied Pharmacology 11/1996; 140(2):370-7. · 4.45 Impact Factor -
Article: (32)P-postlabeling detection of DNA adducts in peripheral white blood cells of greenhouse floriculturists from western Liguria, Italy.
[show abstract] [hide abstract]
ABSTRACT: Pesticides are widely used in agriculture to enhance crop yields and to control disease vectors. Floriculturists work frequently in greenhouses and may be exposed to high levels of pesticides, which may result in adverse health effects. To evaluate the relationship between exposure to pesticides and DNA adduct formation in peripheral WBCs of Italian floriculturists, the nuclease P1 modification of a (32)P-postlabeling assay was used to analyze WBC DNA from floriculturists (n = 26) and matched controls (n = 22). DNA adduct-positive samples were more frequent in floriculturists (11/26; 42%) than in matched controls (2/22; 9%) (P < 0.01). Slightly higher frequencies of DNA adduct-positive samples were observed in floriculturists > or = 44 years of age (53%) and in female floriculturists (57%). Floricultural practice was found to be associated with a significantly higher DNA adduct-positive rate in WBCs (rate ratio, 5.12; 95% confidence interval, 1.1-23.7) after allowing for the effects of age and gender. These two latter covariates were not significantly associated with DNA adduct-positive rates. The quantitative levels of DNA adducts were significantly higher in floriculturists than in matched controls according to the Mann-Whitney nonparametric statistic (P = 0.0052). The median adduct level for positive samples among floriculturists was 1.5/10(8) bases. A specific, well-visible spot, named alpha adduct, was detected in 7 out of the 11 DNA adduct-positive samples from floriculturists but in none of the (22 + 20) referent samples (P = 0.0004). The presence of pesticide-related DNA adducts was confirmed clearly using the butanol extraction procedure. Six of 8 floriculturists and 0 of 10 referents were found positive with this method. The median adduct level for positive samples was 6.0/10(8) bases. Two strong spots close to the origin could be identified in all six positive floriculturists, using the butanol extraction procedure. No association between DNA adducts and use of specific pesticides was observed.Cancer Epidemiology Biomarkers & Prevention 06/1996; 5(5):361-9. · 4.12 Impact Factor -
Article: Treatment of stage IIIB non-small-cell lung cancer with surgery followed by infusion of tumor infiltrating lymphocytes and recombinant interleukin-2: a pilot study.
[show abstract] [hide abstract]
ABSTRACT: Stage IIIb non-small-cell lung cancer (NSCLC) has a poor prognosis. The median survival is approximately 6 months, and only 30% of patients are alive 1 year after diagnosis. The need for effective treatment is evident. The aim of this study was to evaluate whether the infusion of tumor-infiltrating lymphocytes (TILs), isolated from resected tumor, expanded in vitro and injected together with recombinant Interleukin-2, is feasible and may at least partially modify the poor prognosis in these patients. The infusion of TILs, derived from surgically resected NSCLC and expanded in vitro, together with subcutaneous (s.c.) injections of recombinant interleukin-2 (rIL-2) was attempted in a group of 11 patients. Treated patients were infused i.v. with in vitro expanded TILs (from 4 to 70 x 10(9) cells), and rIL-2 was injected s.c. at doses varying from 61 to 378 x 10(6) IU. Toxic side effects (fever and, in some cases, hypotension) were observed and limited the dose of rIL-2 infused. Follow-up was continued for 40 months. The mean survival time was 13.8 months. Three of five TIL-treated patients with residual disease have no evident disease after 1 year, and two of them are still alive and have no evidence of disease after 40 months. This pilot study suggests that the infusion of in vitro expanded TILs, derived from surgical samples, is feasible and seems to prolong overall survival and to control the residual disease in patients with advanced NSCLC.Journal of immunotherapy with emphasis on tumor immunology: official journal of the Society for Biological Therapy 06/1996; 19(3):224-30. -
Article: [Genotoxic damage in subjects exposed to automobile exhaust: preliminary results].
[show abstract] [hide abstract]
ABSTRACT: The associations between selected biomarkers of biologically effective dose (32P-post-labelling-DNA adducts), early biological effects (Micronuclei, MN) and sister chromatid exchanges (SCE) and individual measurements of exposure to benzo(a)pyrene (a surrogate index of exposure to polynuclear aromatic hydrocarbons, PAHs) are investigated in a study being conducted among traffic police workers and referent subjects in the City of Genova, Italy. Preliminary findings show B(a)P mean values of 1.33 ng/m3, SD = 1.35 ng/m3 and 0.06, SD = 0.17 in traffic police workers and referent subjects, respectively. Micronuclei mean levels in peripheral blood lymphocytes of 26 traffic police workers and 25 referents were 3.30, DS = 1.24 e 3.90, DS = 1.50 (per 1,000 binucleated cells). Eleven subjects (61%) out of 18 had detectable levels of DNA adducts (32P-post-labelling technique, range 1.8-9.0 Relative Adduct Level (RAL) per 10(9) nucleotides).Epidemiologia e prevenzione 04/1995; 19(62):120-3. · 0.65 Impact Factor -
Article: Mortality among silicotics in Genoa, Italy, from 1961 to 1987.
[show abstract] [hide abstract]
ABSTRACT: A historical cohort mortality study conducted among 515 silicotic subjects revealed higher than expected risks for all causes [standardized mortality ratio (SMR) 1.89], respiratory tract diseases (SMR 8.89), silicotuberculosis (SMR 27.00), respiratory tract cancers (SMR 3.14), and lung cancer (SMR 3.50). Mortality from cardiovascular diseases was lower than that expected (SMR 0.51). Lung cancer risk increased with duration of occupational exposure (SMR 2.80, 2.99, and 5.02 for 14, 15-29, and 30 years of employment, respectively). Lung cancer risk was higher for the silicotics without tuberculosis (SMR 3.72) than for those with tuberculosis (SMR 2.83). Indirect adjustment for smoking habits, including number of cigarettes smoked per day, showed that smoking would have been responsible for a maximum risk of 1.77. Thus smoking may have explained 50% of the observed excess mortality from lung cancer.Scandinavian journal of work, environment & health 02/1995; 21 Suppl 2:77-80. · 3.12 Impact Factor -
Article: Cancer, cardiovascular mortality, and diet in Italy and the Czech Republic.
[show abstract] [hide abstract]
ABSTRACT: A descriptive study aimed at comparing mortality and dietary patterns in Italy and the Czech Republic was conducted in the period 1970-1990. Mortality from all causes, all cancers, selected site specific cancers and cardiovascular diseases were found to be generally higher in the Czech Republic than in Italy. The North-South gradients observed within Italy have diminished in the course of the last twenty years, mostly due to a less contained decrease of the mortality from cardiovascular diseases and to a marked increase in cancer mortality for Southern regions compared to Central and Northern regions. The mediterranean diet with many health promoting, possibly protective components, mostly of vegetable origin, is consumed in most parts of Italy, particularly in the South. In contrast, a Central European diet abounding in animal products and lacking in fresh fruit and vegetables is generally followed in the Czech Republic. These differences in diet may play a role in the origin of the observed differences in mortality patterns. Some factors other than diet, such as smoking habits, alcohol consumption, endogenous factors, and occupation, that are not considered here, are known to be involved in the causation of some types of cancer. The results of this study are compatible with the hypothesis of a relevant role played by dietary and other life-style habits in the etiopathogenesis of neoplastic and cardiovascular diseases.Neoplasma 02/1995; 42(5):275-83. · 1.44 Impact Factor -
Article: Multiple regression analysis of cytogenetic human data.
[show abstract] [hide abstract]
ABSTRACT: Biomonitoring studies on cytogenetic outcomes in humans should be considered as epidemiological studies, rather than randomized trials. Under this light the emphasis given to the achievement of a significant p-value should be reduced, since this measure suffers from major limitations. The use of a point estimate (and its corresponding confidence interval) to measure the association between exposure and effect offers several advantages, including the adjustment for confounding, and the evaluation of possible interaction between factors. In most instances the use of multivariate statistical methods allows an efficient analysis of these studies, even in presence of a small sample size and several covariates. In this paper we re-analyzed four biomonitoring studies by using multivariate methods to estimate relative risks through statistical modeling. The use of multiple regression techniques allowed the computation of point estimates of association and their confidence intervals for each covariate evaluated by the studies considered; the estimate of the effect of confounding variables such as smoking habits, age and gender; and the presence of interaction between covariates. Measures of association estimated through univariate and multivariate statistical approaches are compared. The advantages of the latter technique are discussed.Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 09/1994; 313(1):69-80. · 2.85 Impact Factor -
Article: Plasma and tissue levels of some lanthanide elements in the human colorectal lesions
Journal of Radioanalytical and Nuclear Chemistry 01/1994; 174:23-28. · 1.52 Impact Factor -
Article: Tumour kinetics, response to chemotherapy and survival in primary ovarian cancer.
[show abstract] [hide abstract]
ABSTRACT: The analysis of thymidine labelling index (TLI) in relation to clinico-pathological variables and survival was carried out in 111 ovarian cancer patients. The significance of TLI in predicting response to aggressive first line chemotherapy regimens was examined. The overall median TLI value of 1.8% was used as a cut-off to discriminate slowly from highly proliferating cancers. 94 patients entered into two consecutive randomised trials, and were treated with six courses of cisplatin-based chemotherapy with or without doxorubicin. A significantly higher objective response of 60% was reported in the subset of patients with TLI > 1.8% as compared to 35% in patients with TLI < or = 1.8% (P = 0.03). In addition, patients achieving complete response had tumours with median TLI of 3.8% as compared to 2.4% for partial responders, 1.5% for patients with stable disease and 1.7% for those with progressive disease. A significant increase in tumour kinetics was observed in advanced cancers (P = 0.001), more undifferentiated tumours (P = 0.02) and postsurgical residual disease greater than 2 cm (P = 0.04). In univariate analysis, TLI failed to influence significantly clinical outcome: 26 versus 32 months median survival time for patients with high and low tumour TLI, respectively. In the Cox's regression model, the only independent prognostic variables were performance status and amount of residual disease after primary surgery (P = 0.000).European Journal of Cancer 01/1994; 30A(4):449-52. · 5.54 Impact Factor -
Article: [Separation and identifying features of the cardiac aglycones and glycosides of Nerium oleander L. flowers by thin-layer chromatography].
[show abstract] [hide abstract]
ABSTRACT: The present work was aimed at extracting some cardiotonic glycosides from Nerium oleander L. (N.o.L.) flowers, free from phytosterols and their esters and at resolving themselves by thick- and thin-layer chromatography. This work may contribute to the scientific recognition of N.o.L. drugs in the field of forensic medicine. MATERIALS AND METHODS. Apparatus. Kieselgel F254 thin-layer (250 mu) and Kieselgel thick-layer (2 mm) glass plates were used. MATERIALS. Chromatographic solvents were used; detectors were p-toluene sulphonic acid (PTSA) and antimony trichloride (SbCl3). STANDARDS. The following standards were used: gitoxigenin, oleandrin, digitoxin, and stigmasterol. Standard solutions were prepared at a M-3 concentration. The solvent system is described in Table I. EXTRACT. The extract was prepared using a mixture of solvents (hexane-diethylether-acetic acis, 50:50:1 v/v). With this mixture we noted that, in thin-layer chromatography, the used standards remained at the origin, while phytosterols and their esters migrated. White flowers of N.o.L. were air dried in the shade at room temperature, powered, and macerated in hexane-diethylether acetic acid for 24 hours. After removal of the phytosterols the remacerating powder was further percolated using a chloroform-methanol mixture (1:1.7 v/v) in order to extract the aglycone and the cardiac glycosides. As the medium's thin-layer chromatogram showed the absence of corresponding spots to test samples, the chloroform-methanol media were combined and evaporated under vacuum. The residue was redissolved in the chloroform-methanol mixture. The obtained extract concentration consisted of 5 grammes of dried flowers in 1 milliliter of solution, called extract E (Fig. 1). RESULTS. The results are reported in Figures 2 and 4 and in Table II (see text for explanation of symbols). Extract E (Fig. 2) and the F1, F2, and F3 concentrated fractions were examined by thin-layer chromatography (Fig. 1 and 3). Only the F3 fraction revealed compounds with the same chromatographic path and colours (detected by PTSA and SbCL3) as the reference standards gitoxigenin, oleandrin, and digitoxin. This finding was confirmed by using five different solvent-systems (Fig. 4). DISCUSSION AND CONCLUSION. The present study shows that the cardiac steroids and other constituents of Nerium oleander's flowers are separated in three fractions by thick-layer chromatography free from phytosterols and their esters. This result may have useful implications in the fields of analytical toxicology and forensic medicine and potential application in clinical practice given that cytotoxic and antileukemic activities of the extracts from plants containing cardiac glucosides have been reported.Minerva medica 12/1993; 84(11):627-32. · 0.90 Impact Factor -
Article: Para-aminobenzoic acid suppression of cis-diamminedichloroplatinum(II) nephrotoxicity.
[show abstract] [hide abstract]
ABSTRACT: Concurrent administration of para-aminobenzoic acid (PABA) reduced the toxicity of cis-diamminedichloroplatinum(II) (DDP) in a dose-related manner in rats. When administered i.p. simultaneously with 7.5 mg/kg DDP, PABA (100 mg/kg) significantly reduced plasma urea nitrogen (PUN) and plasma creatinine levels as well as DDP-induced weight loss. Increasing doses of PABA (25, 50 and 100 mg/kg) correlated with progressively better parameters of renal activity and body wt and with lower levels of platinum in plasma and tissues in rats killed 5 days after drug administration. The formation of cisplatin-DNA adducts, the total platinum levels in kidney and testes and the DDP-induced tumor response were investigated in the presence and absence of PABA exposure in mice bearing P388 leukemic cells. Renal and testicular DNA-adducts in mice treated i.p. with 16 mg/kg DDP in normal saline were higher than those observed in mice receiving the same protocol and added PABA. Analysis of tissue platinum content demonstrated significantly lower platinum levels both in kidneys (P < 0.05) and testes (P < 0.01) of mice receiving DDP and PABA in normal saline compared to those receiving only DDP in normal saline. PABA did not affect the in vivo and in vitro antitumor activity of DDP against P388 leukemia, and there was no significant PABA-induced modification in the concentration of platinum both in the tumor cells and in DNA samples isolated from P388 leukemic cells of DDP-treated mice. We conclude that PABA may be a promising compound for reducing DDP-toxic side effects, including nephrotoxicity, without compromising its antitumor activity.Carcinogenesis 12/1993; 14(12):2595-9. · 5.70 Impact Factor
Top co-authors
Top Journals
Institutions
-
1988–1998
-
National Institute for Research on Cancer
Genova, Liguria, Italy
-
-
1991
-
Università degli Studi di Genova
- Dipartimento di Medicina sperimentale (DIMES)
Genova, Liguria, Italy
-
