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Biomedical subjects

R Puntoni

Publications and source records attributed to R Puntoni.

At least 19 recordsLinked to original sources
PubMed2005

Incidence of pleural mesothelioma in Liguria Region, Italy (1996-2002).

In this study, incidence of pleural malignant mesothelioma (PMM) in the Liguria Region (Italy) (approximately 1.6 million inhabitants), in the presence of asbestos exposure was investigated. New PMM cases recorded by the Mesothelioma Registry of Liguria, from 1996 to 2002 and interviews reported on a standardised questionnaire were analysed according to demographical and etiological characteristics. Nine hundred and forty five PMM cases were recorded (757 males and 188 females); the age standardised (European population) incidence rates per 100,000 were 8.51 and 1.43, respectively. The rates among the four provinces ranged between 1.18 and 13.7 for males and 0.68 and 1.44 for females. The questionnaire was evaluated for 786 PMM cases (or next-of-kin). Higher incidence rates were reported in the provinces with larger industrial and harbour areas, including shipyards (construction and repair), dockyards, building activities, chemical and heavy industrial activities. Asbestos exposure was unlikely or unknown for 57.5% females and 15% males. A major role of environmental asbestos exposure in the etiology of PMM is hypothesised for females and for a minor proportion of males.

Adult↗
PubMed2001

Study of pretreatment serum levels of HER-2/neu oncoprotein as a prognostic and predictive factor in patients with advanced nonsmall cell lung carcinoma.

BACKGROUND: HER-2/neu tissue overexpression is found in nearly 15% of patients with nonsmall cell lung carcinoma and is reported to affect prognosis adversely in surgical series. However, the prognostic role of serum HER-2/neu oncoprotein, particularly in patients with advanced lung carcinoma, remains unknown. This study was designed to assess the potential value of measuring serum levels of HER-2/neu oncoprotein in predicting response to treatment and survival in patients with locally advanced and metastatic nonsmall cell lung carcinoma. METHODS: Baseline serum HER-2/neu levels (fm/mL) were studied using an enzyme-linked immunosorbent assay method in 84 patients with newly diagnosed, advanced nonsmall cell lung carcinoma who underwent chemotherapy. RESULTS: The patients enrolled in the study included 76 males and 8 females, with a median age of 62 years (range, 36-73 years) and a median performance status of 1. Fifty patients (59.5%) had nonsquamous histology, and 34 patients (40.5%) had squamous cell carcinoma. Thirty-four patients (40.5%) had Stage III disease, and 50 patients (59.5%) had Stage IV disease. The mean baseline value of HER-2/neu in the whole series was 56.1 fm/mL (range, 13.0-103.8 fm/mL). HER2 immunohistochemistry on paraffin embedded tissue was performed in 18 patients. HER-2/neu tissue overexpression was found in only one patient, who also showed high serum levels (102 fm/mL). No correlation was observed between protein serum quantitation and gender, age, histology, stage, performance status, leukocyte count, or smoking. Nonresponding and responding patients exhibited similar oncoprotein levels (median, 57.6 fm/mL vs. 51.9 fm/mL, respectively). The overall survival rate was 42.5% at 1 year and 12% at 2 years, with a median survival duration of 10 months. At univariate analysis, high HER-2/neu serum levels were associated with an unfavorable survival outcome. Using a cut-off point for HER-2/neu of 73.0 fm/mL (corresponding to the 80th percentile of protein concentration), the survival of patients who had higher serum levels of HER-2/neu was significantly worse compared with patients who had lower serum levels (median, 7.1 months vs. 10.9 months; P = 0.004). Multivariate analysis confirmed the independent predictive value of serum HER-2/neu concentration as a negative prognostic factor (P = 0.02). CONCLUSIONS: High pretreatment levels of HER-2/neu oncoprotein are associated with an adverse prognostic impact on survival in patients with locally advanced or metastatic nonsmall cell lung carcinoma.

Adult↗
PubMed2001

Validation of biomarkers as early predictors of disease.

The development and validation of biomarkers that link environmental exposures to the pathogenesis of human disease is a leading priority in the field of environmental research. The validation of biomarkers as early predictors of clinical disease can enhance health risk assessment and contribute to effective new disease prevention policies in environmental and occupational settings. The process of validating biomarkers involves dealing with a range of characteristics that include the intrinsic qualities of the biomarker, its determinants, and the analytic procedure. We discuss here a three phase approach to validation. The final phase, consisting of longitudinal studies, is reached after the biomarker has been determined to be technically reliable and after the effect of external variables on the association with the outcome has been evaluated. We provide some examples of biomarkers reputed to be early predictors of cancer and cardiovascular disease (CVD). We then present original data to support the potential of DNA adducts to predict cancer and show, through re-evaluation of the Italian database on cytogenetic biomarkers, a lack of association between the frequency of chromosomal aberrations in circulating lymphocytes and CVD mortality rates -- a finding that should not be considered conclusive. In general, whenever a biomarker has been determined to be a valid predictor of disease, it should be used in risk assessment and public health policy.

Biomarkers↗
PubMed2001

Occupational exposure to carbon black and risk of bladder cancer.

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.

Adult↗
PubMed2001

Analysis of 13 (32)P-DNA postlabeling studies on occupational cohorts exposed to air pollution.

Industrial and urban workers may be exposed to significant levels of air pollutants resulting from the incomplete combustion of organic matter. The authors performed a meta-analysis of 13 DNA-adduct studies ((32)P-DNA postlabeling technique) on occupational cohorts exposed to air pollution. The association between levels of DNA adducts and air pollution exposure was significant both in heavily exposed industrial workers and in less severely exposed urban workers. Moreover, in an analysis using the seven studies that reported measuring levels of benzo[a]pyrene (B(a)P), a typical marker of exposure, DNA adduct levels in exposed workers (versus those in referents) were significantly correlated with air levels of B(a)P. The relation between DNA adducts and B(a)P was found to be linear at low doses and sublinear at high doses, indicating that DNA adduct formation tends to reach some kind of saturation point at higher levels of exposure to the chemical mixtures present in fumes. When the authors examined the efficiency of DNA adduct production associated with increasing air pollution exposures, the production of DNA adducts per unit of exposure was significantly decreased at higher B(a)P exposure levels. These findings suggest that linear downward extrapolations based on DNA adduct levels associated with B(a)P concentrations of > or =20 ng/m(3) might be affected by underestimation bias.

Air Pollutants, Occupational↗
PubMed2001

A historical cohort mortality study among shipyard workers in Genoa, Italy.

BACKGROUND: 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. METHODS: 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. RESULTS AND CONCLUSIONS: 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.

Adult↗
PubMed2001

Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma.

Vascular endothelial growth factor (VEGF), a potent mitogen for vascular endothelium, is expressed in malignant pleural mesothelioma (MM). The present report examines the effect of VEGF on MM growth. Four MM cell lines produced significantly higher VEGF levels than normal mesothelial cells (1946+/-14 pg/ml vs. 180+/-17 pg/ml; p<0.001). In addition, MM cells expressed the tyrosine kinase-related VEGF receptors Flt-1 and KDR. Recombinant human VEGF phosphorylated both Flt-1 and KDR and increased proliferation of all four MM cell lines in a dose-dependent fashion. Neutralizing antibodies against either VEGF, Flt-1 or KDR significantly reduced MM cellular proliferation. In addition, expression of VEGF, Flt-1, and KDR was observed in MM biopsies. Moreover, higher VEGF levels were found in the pleural effusions of MM patients than in the effusions of patients with non-malignant pleural disease (1885.7+/-894.9 pg/ml vs. 266.9+/-180.5 pg/ml; p<0.001). Linear regression analysis showed a significant inverse correlation between serum VEGF levels and MM patient survival (r=0.72; p<0.01). No correlation was found between tumour vessel density and either serum (r=0.26; p=0.42) or pleural effusion (r=0.35; p=0.26) VEGF levels. These results indicate that VEGF, via activation of its tyrosine kinase receptors, may be a key regulator of MM growth. In addition, VEGF production could have an impact on patient survival, not only by promoting tumour angiogenesis but also by directly stimulating tumour growth.

Adult↗
PubMed2001

Smoking reduction in smokers compliant to a smoking cessation trial with nicotine patch.

The aim of this retrospective analysis was to assess the extent of smoking reduction in smokers who were compliant to a smoking cessation trial with nicotine patch, and failed to completely quit smoking. Out of 297 smokers in total, 237 participants received active treatment (60 received placebo). Eighty treated subjects attended all the scheduled visits and were classified as either abstainers (nonsmokers), regular smokers or occasional smokers. Compared to the remaining 157 participants, these 80 subjects had significantly lower mean baseline daily cigarette consumption (24 versus 30; p < 0.001), expired carbon monoxide levels (25 versus 33 ppm; p < 0.001), plasma nicotine and cotinine levels, and Fagerström Tolerance Questionnaire score (5.7 versus 7.0; p < 0.001). All subjects received active treatment for up to 18 weeks (full dose for 12 weeks plus tapering dose for 6 weeks), with follow-up visits scheduled up to 1 yr. A statistically significant reduction in cigarette consumption (versus baseline) was observed among both the occasional (-99%) and regular (-77%) smokers between week 1 and week 52 (p < 0.001). Concomitant smoking and patch use was well tolerated since adverse events were infrequent, mild and transient. Thus, in addition to those subjects who successfully quit smoking, a further group of subjects who attended all the follow-up visits during the smoking cessation trial significantly reduced their mean daily cigarette consumption.

Administration, Cutaneous↗
PubMed2000

Mesothelioma and lung tumors attributable to asbestos among petroleum workers.

BACKGROUND: Asbestos exposure has been definitively found to be associated with both mesothelioma and lung cancer. Nevertheless, in the overall population of oil refinery workers potentially exposed to asbestos, many studies clearly show a definitely increased risk of mesothelioma, but no proven excess of lung cancer after comparison to the general population. Through the presentation of new data and the re-appraisal of two recent and independent epidemiological studies conducted in Liguria, Italy, and Ontario, Canada, we attempt to shed light on this apparently paradoxical finding. METHODS: Lung cancer mortality was studied among maintenance workers exposed to asbestos, and among two other subgroups of refinery employees: blue collar and white collar workers. The comparison with blue collar workers was performed in order to take into account the role of healthy worker effect, smoking habit, and the socioeconomic level. The comparison with white collar workers was performed to control for other occupational lung carcinogens. RESULTS AND CONCLUSIONS: Results reveal a consistency between the two studies and show that 96-100% of the mesotheliomas and 42-49% of the lung tumors arising among maintenance workers were attributable to asbestos exposure. Our new analysis, estimating two cases of asbestos-related lung cancer for each case of mesothelioma, confirms published findings on the magnitude of asbestos-related tumors in oil refineries.

Asbestos↗
PubMed2000

Simian virus-40 sequences are a negative prognostic cofactor in patients with malignant pleural mesothelioma.

Several biochemical and clinical factors have been shown to correlate with survival in human malignant pleural mesothelioma (MM). Nevertheless, average survival of 4 to 10 months from diagnosis is sometimes not sufficient for full expression of these factors. Several studies have reported SV40 sequences in MM, suggesting a possible pathogenic role. We investigated whether the presence of these sequences had any effect on MM patient survival. For this study, we used polymerase chain reaction and Southern blot analysis to search for and identify SV40 DNA in biopsy samples from 83 MM patients. These cases were divided according to histology: 62/83 (74. 7%) had epithelioid morphology (EMM) and 21/83 (25.3%) had either biphasic or sarcomatous morphology (B/SMM). SV40 positivity was significantly associated with B/SMM growth pattern (chi-squared test = 5.03, P = 0.025). Kaplan-Meier univariate analysis confirmed the independent effect of histology on MM survival (log-rank test = 13.9, P < 0.001) and showed a trend for increased survival in SV40-negative patients (log-rank test = 2.83, P = 0.09). Most importantly, Cox's regression model showed that SV40-positive status affected the predictive value of histology on patient survival. In particular, when SV40 expression was added to the B/SMM histotype, Cox's regression model showed a significant increase in hazard ratio (HR) with respect to SV40-negative B/SMM (HR = 4.25, 95% CI = 2.00-9. 00, likelihood ratio test = 14.31, P < 0.001). We conclude that SV40 expression is significantly associated with B/SMM histology and represents an important prognostic cofactor when associated with the tumor subtype in MM patients.

Adult↗
PubMed2000

Effects of nicotine replacement therapy on markers of oxidative stress in cigarette smokers enrolled in a smoking cessation program.

Twenty healthy, asymptomatic long-term cigarette smokers (8 males, 12 females; mean age: 43 +/- 9 years) were selected at random from a larger series receiving nicotine replacement therapy (NRT) for 12 weeks to study the effects of NRT on plasma markers of oxidative stress. Plasma aliquots, obtained at baseline (T0) and after 12 weeks (T12) of NRT, were used to measure malondialdeyde (MDA) and total Trolox-equivalent antioxidant capacity (TEAC). In subjects who completely quit smoking ('quitters', n = 10), MDA was higher at T0 (1.08 mumol/l, interquartile range 0.85-1.16) than at T12 (0.71 mumol/l, range 0.32-0.92; p < 0.01), and TEAC was lower at T0 (1.20 mM, range 1.11-1.31) than at T12 (1.43 mM, range 1.31-1.49; p < 0.05). In subjects who had only reduced the number of cigarettes smoked per day ('reducers', n = 10), differences between the T0 and T12 levels of MDA (0.81 [0.75-0.96] vs. 0.76 [0.58-0.84] mumol/l) and TEAC (1.28 [1.05-1.50] vs. 1.25 [1.09-1.42] mM) were not significant. At T0, MDA and cotinine levels correlated in reducers (r = 0.79, p < 0.05) and, though not significantly, in quitters (r = 0.50, p = 0.12). At T12 this relationship between MDA and cotinine was still present in the reducers (r = 0.70, p < 0.05), while the scatter of points in quitters was completely dispersed (r = (0.09). These results show that smoking cessation but not smoking reduction is associated with decreased markers of oxidative stress in the plasma of active cigarette smokers.

Adult↗
PubMed2000

Analysis of erythrocyte glycophorin-A variants by flow cytometry in lung disease patients detects the effect of tobacco smoke.

The glycophoryn A (GPA) assay evaluates somatic in vivo mutations. It is considered a cumulative biodosimeter for genotoxic exposures and is under evaluation in cancer risk assessment. GPA, a polymorphic membrane protein of the erythrocytes, determines the MN blood groups. The NO and NN variant frequencies (VF) may be detected in MN subjects (about 50% of the population) by flow cytometry using two differently labelled antibodies. We explored if GPA NO and NN VF might be relevant to the assessment of individual lung cancer risk and susceptibility, in a small population with a high prevalence of heavy tobacco smokers: 8 lung cancer patients and 16 subjects with non-malignant lung diseases associated with increased risk of lung cancer. There was a wide interindividual variability and complete overlap between non-neoplastic and neoplastic patients. A significant positive correlation was seen with smoking duration in NO VF (p = 0.04, age-adjusted). Current smokers (n = 12) displayed higher NO values than never (n = 1) or ex-smokers (n = 11), 36.3 +/- 18.2 and 21.0 +/- 13.2, respectively (p < 0.01). No association was shown with occupational exposure. The present exploratory study suggests that assessment of individual lung cancer risk and susceptibility by the GPA assay does not seem to be feasible. The assay appears to provide a biomarker of longterm exposure to tobacco smoke.

Aged↗
PubMed1999

Exposure to agrochemicals and DNA adducts in Western Liguria, Italy.

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.

Adult↗
PubMed1999

Platelet-vessel wall interactions with third-generation oral contraceptives: no evidence of detrimental effects.

Because of the association of oral contraceptives (OC) and cigarette smoking with an increased thrombotic risk, we evaluated thromboxane (TX) and prostacyclin urinary (u) metabolites, as in vivo indices of platelet-vessel wall interactions, in women assigned to third generation OC. Twenty-eight women (15 smokers) underwent a 6-month trial of 30 microg ethinylestradiol plus 0.150 mg desogestrel. Cotinine plasma levels were elevated only in persons classified as smokers and serum TXB2 determination confirmed the absence of cyclooxygenase inhibition throughout the study. u-TXB2 and 11-dehydro-TXB2 were higher in smokers than in non-smokers. OC decreased u-11-dehydro-TXB2 both in smokers (from (pg/micromol creatinine) 35.1+/-6.9 to 15.8+/-2.8; P<0.025) and non-smokers (from 31.7+/-9.8 to 20.6+/-4.8, P = N.S.). u-6-keto-prostaglandin(PG)F1alpha excretion, also higher in smokers compared to non-smokers, was also reduced after OC in smokers (from (pg/micromol creatinine) 24.3+/-5.2 to 14.8+/-2.3; P<0.05). Smokers also had a trend to higher u-2,3-dinor-6-keto-PGF1alpha, marginally reduced by OC. Thus, the OC regimen used here improves - if anything - platelet vessel wall interactions as assessed by prostanoid production in vivo. The prothrombotic tendency associated with the use of OC in smokers does not appear to be mediated by changes in platelet-vessel wall interactions.

6-Ketoprostaglandin F1 alpha↗
PubMed1998

Socioeconomic status and survival of gastric cancer patients.

Survival differences in cancer patients according to socioeconomic status (SES) have been reported for several organs, but the relationship with gastric cancer prognosis has not been conclusively defined. The present study analysed the survival of 122 incident, histologically confirmed gastric cancer patients diagnosed between 1985 and 1987 in Genoa, Italy and enrolled in a multicentric case-control study on gastric cancer occurrence and dietary habits. Adjusting for age at diagnosis, tumour stage, histopathological grading and surgery (i.e. curative gastric resection), Cox's proportional hazards regression model showed statistically significant hazard ratio (HR) (relative risk) estimates below unity for education (> 5 versus < or = 5 years of schooling, HR = 0.40, P = 0.003) and occupation (higher versus lower income job, HR = 0.59, P = 0.030). Also, the same final regression model revealed a positive prognostic effect for origin (Southern Italy migrants versus Genoa natives) (HR = 0.56, P = 0.039) and female gender (HR = 0.58, P = 0.020). High SES, origin from lower risk area for gastric cancer occurrence and female gender are positive prognostic categories for gastric cancer patients.

Adult↗