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S Parodi

Publications and source records attributed to S Parodi.

At least 19 recordsLinked to original sources

Differences in the epidemic rise and decrease of prostate cancer among geographical areas in Southern Europe. an analysis of differential trends in incidence and mortality in France, Italy and Spain.

This is a population-based study aimed at evaluating incidence and mortality trends for prostate cancer in France, Italy and Spain, during the prostate-specific antigen (PSA) era, considering elderly people aged 70 years and over and younger adults aged between 40 and 69 years. Trends were estimated by a log-linear Poisson regression model and expressed as an Estimated Annual Percent Change (EAPC). Incidence increased sharply in almost all areas. Spain showed the lowest increases. Incidence started to rise around 1985 in France and after 1990 in Italy and Spain. Mortality increased until the late 1980s in all countries, then declined in France and Italy (-2.5% in 40-69 year age group), but not in Spain. Younger people showed a much higher rise in incidence than the elderly, while mortality decreased mainly in the younger adults. The decrease in mortality was more marked in those areas and the younger age group where the rise in incidence was higher and started earlier, i.e. in France and in younger people, suggesting that the PSA test may have had a positive effect on mortality, although other clinical advances also have to be taken into account.

Adult↗

Lymphohaematopoietic system cancer incidence in an urban area near a coke oven plant: an ecological investigation.

AIMS: To evaluate the incidence risk of lymphohaematopoietic cancers for the 1986-94 period in Cornigliano, a district of Genoa (Italy), where a coke oven is located a few hundred metres from the residential area. METHODS: The whole of Genoa and one of its 25 districts (Rivarolo) were selected as controls. The trend of risk around the coke oven was evaluated via Stone's method, while the geographic pattern of such risks across the Cornigliano district was evaluated by computing full Bayes estimates of standardised incidence ratio (FBE-SIR). RESULTS: In males, elevated relative risks (RR) were observed for all lymphohaematopoietic cancers (RR 1.7 v Rivarolo and 1.6 v Genoa), for NHL (RR 2.4 v Rivarolo and 1.7 v Genoa), and for leukaemia (RR 2.4 v Rivarolo and 1.9 v Genoa). In females, statistically non-significant RR were observed. In males no excess of risk was found close to the coke oven. In females, a rising risk for NHL was observed approaching the plant, although statistical significance was not reached, while the risk for leukaemia was not evaluable due to the small number of cases. Analysis of the geographic pattern of risk suggested the presence of a cluster of NHL in both sexes in the eastern part of the district, where a foundry had been operational until the early 1980s. A cluster of leukaemia cases was observed in males in a northern part of the area, where no major sources of benzene seemed to be present. CONCLUSIONS: The estimated risks seem to be slightly or not at all related to the distance from the coke oven. The statistically significant higher risks observed in males for NHL and leukaemia, and the clusters of leukaemia in males and of NHL in both sexes deserve further investigations in order to trace the exposures associated with such risks.

Benzene↗

Intracystic epidermal growth factor level is predictive of breast-cancer risk in women with gross cystic disease of the breast.

Women affected by gross cystic disease of the breast have an increased risk of breast cancer. We report here the incidence of breast cancer by cyst type and intracystic epidermal growth factor (EGF) concentration. Our retrospective study included 504 women who had at least 1 cyst aspiration between 1985 and 1993. Cyst fluids were processed for electrolyte concentration (n = 378), EGF concentration (n = 347) or both (n = 337). Age-standardized incidence ratios (SIRs) were estimated using the population of the Genoa Cancer Registry. A multivariate Poisson regression model was used to estimate relative risks (RRs) when the study groups were compared directly. By June 1999, 19 invasive breast cancers had developed in the cohort of women. The age SIR of breast cancer calculated for the whole cohort was 3.32 (95% confidence interval 2.00-5.18). The ratio was not affected by age and was only moderately increased in women with a positive family history of breast cancer and type I cysts (i.e., those with a Na+/K+ ratio <3). However, it was significantly increased in women with high EGF concentrations. Direct comparisons confirmed that age, cyst type and family history only moderately increased the RR, whereas EGF concentration was a strong predictor of risk. Our results confirm that women affected by palpable cysts have an increased risk of developing breast cancer and suggest that the risk is higher in women with high intracystic EGF concentrations.

Adult↗

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↗

Mortality trend for multiple sclerosis in Italy (1974-1993).

The prevalence of multiple sclerosis (MS) in Italy is one of the highest in Europe, estimated proportions ranging between 32 and 69 cases per 100,000. An update of mortality time trend analyses can help trace a picture of the evolution of the disease and contribute to the interpretation of differences related to latitude and gender. Standardized mortality ratios (SMR) were computed for the 1974-1993 calendar period, using the pooled data set as standard. World population was the standard used to estimate age-adjusted rates for all Italy, while for selected regions the 1991 Italian population was utilized. Time trend analysis was performed using the Poisson regression model and the variation of mortality rates in time was expressed as mean difference per cent per year. Age-adjusted rates per million inhabitants were 4.1 for males and 5.0 for females. Northern Italian regions showed higher MS mortality rates than Central and Southern regions and Sicily, particularly in females; the effect was less evident in Sardinia. Time trend analysis by area showed a mortality decrease in Northern Italy (-1.15%) that reached statistical significance for men. In central regions a slight increase of borderline statistical significance (+1.03%) was observed only in women. while in the South and Sicily a statistically significant increase was seen in both males (+2.14%) and females (+3.09%). The analysis of the time trend for all Italy did not reveal significant variations in male mortality; by contrast, a slight, but statistically significant, increase (+0.88%) was observed in female mortality. Analysis of age-adjusted MS mortality rates in each region suggested the presence of an effect due to latitude. The occurrence of an increasing trend in Southern Italian regions and Sicily deserves further investigation.

Female↗

Diagnostic value of CYFRA 21-1 tumor marker and CEA in pleural effusion due to mesothelioma.

STUDY OBJECTIVE: The aim of our study was to assess the clinical value of CYFRA 21-1 tumor marker and carcinoembryonic antigen (CEA) as diagnostic tools that are complementary to cytology in the diagnosis of malignant mesotheliomas. PATIENTS: We measured CEA and CYFRA 21-1 in the pleural effusions (PEs) and serum of 106 patients (benign lung disease, 34 patients; bronchogenic and metastatic carcinoma, 40 patients; mesothelioma, 32 patients). METHODS: CEA and CYFRA 21--1 levels were determined by means of two commercial enzyme immunoassays. RESULTS: The cutoff levels of CYFRA 21--1 and CEA in malignant PEs, selected on the basis of the best diagnostic efficacy, were 41.9 ng/mL and 5.0 ng/mL, respectively. In all neoplastic PEs, CYFRA 21--1 and CEA sensitivity was 78% and 30.6%, respectively, with a specificity of 80% and 91%, respectively. The sensitivity of CYFRA 21--1 and CEA in patients with mesothelioma was 87.5% and 3.1%, respectively. The results of the CYFRA 21--1 assay were positive in 17 of 19 cases of mesothelioma (89.5%) with a negative or uncertain cytology. The association of the tumor marker assay and the cytology allowed a correct diagnosis in 30 of 32 cases of mesothelioma (93.7%). CONCLUSION: This study suggests that CYFRA 21--1 would provide a useful parameter for the differential diagnosis between benign and malignant PE from mesothelioma when the result of cytology is negative or uncertain and the clinical context does not allow a more aggressive approach. Moreover, the association of CYFRA 21--1 with CEA could provide details for a differential diagnosis between mesotheliomas and carcinomas. In fact, an elevated CYFRA 21--1 level with a low CEA level is highly suggestive of mesothelioma, whereas high levels of CEA alone or high levels of both the markers suggest a diagnosis of malignant PE, excluding mesothelioma.

Antigens, Neoplasm↗

HPV16-E6 enhances mitoxantrone sensitivity in a human ovarian cancer line: an isolated instance or a trend?

A cellular isogenic system, in which wt-p53 expression level is challenged through human papilloma virus 16-E6 gene transfection, was previously developed in our laboratory. As an average trend, cancer lines bearing an inactivated p53 have a general tendency toward an increased resistance to chemotherapeutic agents. However, using the above isogenic system, the transfected line (A2780-N9) was found to be more sensitive to taxol than the parental one (A2780-WT). In a NCI meta-analysis study the average trend is that altered p53 status is related to cellular resistance to topoisomerase II inhibitors, while it is irrelevant in determining sensitivity/resistance to mitotic spindle poisons. We report that our E6 transfected line, previously shown to be hypersensitive to taxol, is also clearly hypersensitive to a topoisomerase II inhibitor (mitoxantrone). Differences in cytotoxicity are more evident after a shorter/more intense exposure, than after a milder/longer exposure, being A2780-WT 27-fold more resistant than the transfected clone in the former case. These differences seem to be related to the different activities ("cross-talks") of E6 protein, among which shortening of p53 half-life is only one aspect. After mitoxantrone treatment A2780-N9 cells display also an increased propensity to apoptosis. In addition, a literature survey of E6 effects in transfected cancer cell lines, seems to suggest that chemosensitization to different classes of antineoplastic agents is the rule rather than the exception in these E6-based isogenic systems.

Antineoplastic Agents↗

Direct in situ PCR allows rapid and sensitive detection of high risk human papillomavirus in cytologic specimens and formalin-fixed paraffin tissues by fluorescent labelling.

We developed a rapid, sensitive and robust high risk human papillomavirus (HR HPV) detection protocol based on direct in situ PCR technology and fluorochrome-modified nucleotides on cytologic specimens (cell smears) and on HPV infected tissues (CIN III). Reproducible results on both cytologic specimens and paraffin-embedded tissues were obtained, providing a powerful tool for clinical investigation on HR HPV infection. Quantitative PCR performed on the same tissue sections adjacent to those used for in situ techniques allowed us to establish the sensitivity of our methods, able to detect rare copies (about 15 in our paraffin-embedded tissues) of HPV.

Female↗

A retro-inverso peptide homologous to helix 1 of c-Myc is a potent and specific inhibitor of proliferation in different cellular systems.

In 1998 we reported that an L-peptide derived from H1 of c-Myc (Int-H1-S6A,F8A), linked to an internalization sequence from the third a-helix of Antennapedia, was endowed with an antiproliferative and proapoptotic activity toward a human mammary cancer cell line: The activity apparently depends upon the presence of the Myc motif. In the present work we have added new dimensions to our original findings. It is known that short retro-inverso (RI-) peptides can assume a 3D conformation very close to their corresponding L-forms and can be recognized by the same monoclonal antibody. We synthesized a RI-peptide form of our original L-peptide: It was much more resistant to serum peptidases than the original molecule (a half life of days rather than hours); in addition, the RI-form of the original Antennapedia internalization sequence was perfectly capable of carrying a D-peptide into human cells. We have studied three different potentially active peptides. L-peptides: Int-H1wt, Int-H1-S6A,F8A. D-peptides: RI-Int -H1-S6A,F8A. We have also studied three presumed control peptides: Int and RI-Int (no H1 motif), H1-S6A,F8A (no internalization sequence). Both 'active' and 'control' peptides have essentially confirmed our expectations, however, in cells treated with the higher concentration (10 mM) of the control peptide RI-Int, non-Myc related side effects could be detected. In order to investigate whether the antiproliferative activities displayed by some of our molecules were indeed related to an interference with the role of c-Myc (and molecules of the family), we chose an iso-amphipathic modified peptide of the H1 motif, with a proximity coefficient >50% and where the major change was at position 7 (F-->A). From a family of 73 H1 motifs belonging to (H1-Loop-H2) hu man sequences, the smallest evolutionary distance from our reference peptide was observed for the H1 of N-Myc, L-Myc, c-Myc, H1-S6A,F8A of c-Myc, and Max, in that order. Our reference peptide was therefore appropriate as a check of whether we were indeed observing activities related to Myc functions. Both Int-H1isoamph and the corresponding RI-Int-H1isoamph peptide were synthesized and studied. In terms of biological targets, we added to the human mammary cancer line of our previous work (MCF-7 cells) a colon cancer line (HCT-116 cells) and also a system of normal cells: human peripheral blood lymphocytes (PBLs) stimulated with phytohemoagglutinin (PHA). Peptides carrying an iso-amphipathic-modified H1 sequence were always very clearly (3-10 times) less active than the corresponding peptides carrying a conserved "H1 of Myc" motif. This finding was noted in five independent situations (all the cellular models considered at the present time): MCF-7 cells treated with L-peptides; MCF-7 cells treated with RI-peptides; HCT-116 cells treated with L-peptides; PBLs treated with L-peptides; PBLs treated with RI-peptides. Modulation of transcription levels of ornithine decarboxylase (ODC), p53, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in PBLs treated with our different molecules, was well compatible with an interference by our active peptides at the level of Myc transcriptional activity. We had already reported a similar observation in MCF-7 cells. On a molar basis, RI-peptides were about 5-10 times more potent and 30-35 times more stable in complete culture medium, than their corresponding L-forms. RI-Int can probably internalize longer peptido-mimetic molecules (for instance molecules mimetic of (H1-Loop-H2), or even more. These possibilities open the way to rodent studies and to more potent/selective Myc inhibitors-two steps closer to a potential drug.

Amino Acid Motifs↗

Changes in the expression of cytokeratins and nuclear matrix proteins are correlated with the level of differentiation in human prostate cancer.

The nuclear matrix-intermediate filament complex (NM-IF) is a protein scaffold which spans the whole cell, and several lines of evidence suggest that this structural frame represents also a functional unit, which could be involved in the epigenetic control of cancer development. Here we report the characterization by high resolution two-dimensional gel electrophoresis and Western blot analysis of the NM-IF complex isolated from prostate cancer (PCa); tumor-associated proteins were identified by comparing the electrophoretic patterns with those of normal human prostate (NHP). Extensive changes in the expression of both the NM and IF proteins occur; they are, however, related in a different way to tumor progression. Poorly differentiated PCa (Gleason score 8-9) shows a strong down regulation of several constitutive cytokeratins (CKs 8, 18, and 19); their expression significantly (P < 0.05) decreases with respect to both NHP and benign prostatic hyperplasia (BPH) and, more interestingly, also with respect to moderately (Gleason score 6-7) and well (Gleason score 4-5) differentiated tumors. Moreover, we have identified a tumor-associated species which is present in all of the tumors examined, systematically absent in NHP and occurs only in a few samples of BPH; this polypeptide, of M(r) 48,000 and pI 6.0, represent a proteolytic fragment of CK8. At variance with these continuing alterations in the expression, the NM proteins undergo stepwise changes correlating with the level of differentiation. The development of less differentiated tumors is characterized by the appearance of several new proteins and by the decrease in the expression of others. Six proteins were found to be expressed with a frequency equal to one in poorly differentiated tumor, namely in all the samples of tumor examined, while in moderately and well differentiated tumors the frequency is less than one, and decreases with increasing the level of differentiation. When tumors of increasing Gleason score are compared with NHP a dramatic increase in the complexity of the protein patterns is observed, indicating that tumor dedifferentiation results in a considerable increase in the phenotypic diversity. These results suggest that tumor progression can be characterized using an appropriate subset of tumor-associated NM proteins.

Adenocarcinoma↗

Prostate cancer incidence and mortality trends among elderly and adult Europeans.

Prostate cancer is a common malignancy primarily of elderly men, with incidence rates rapidly increasing, owing to the population ageing and the introduction of more sensitive diagnostic procedures. Although the effectiveness of a screening test remains controversial, the decreasing mortality rates, which recently emerged in the USA, may be partly attributable to the changes of patterns of care, thus suggesting a potential effect of preventive measure. The object of this study is to examine time trends in incidence and mortality from prostate cancer in European Union (EU) countries, with particular attention to possible differences between the elderly (65 years old or over) and younger or middle age adults (35-64 years old). EUROCIM, the data base created by the European Network of Cancer Registries, provided the incidence and mortality data for the 12 EU Countries analysed (namely: Finland, Denmark, Scotland, England and Wales, Ireland and The Netherlands in Northern Europe; Austria, Germany and France in Central Europe; Italy, Spain and Portugal in Southern Europe), for the 1978-1994 period. Incidence and mortality time trends, expressed as mean difference per cent (MD%) per year, were estimated by a Poisson log-linear regression model. Higher resolution analyses were also carried out to check differences in time trends by age class within the two groups under study. Upward mortality trends occurred in several countries, excepting Ireland, Austria and Southern Europe, but only for younger and middle aged adults. Rates increased more rapidly in older age groups; a clear north-south gradient appeared both in the elderly and in younger adults; for the elderly, MD% higher than +1.5 for most countries of Northern Europe, MD% around +1 for Central Europe, and MD% less than +1 for Southern Europe were registered, with lower values for younger people. Incidence rates rose across the period considered, almost in all countries both for elderly and for younger and middle age adults, increasing more rapidly in younger age. Incidence trends showed a less clear geographic pattern than for mortality. In the younger group, high MD%, ranging in Northern Europe from +3.2 in Finland and England and Wales to +5.7 in The Netherlands, were observed, while in the South values ranged between +4.2 and +5.0. In Central Europe, very high MD%, ranging between +8.4 in France and +16.6 in Austria, were noted. No significant trends were observed for Denmark, Ireland and Portugal. For the elderly the increase was generally lower and no significant trend was observed in Germany and Portugal. Interaction between age and calendar period in the older group was observed for most of the considered countries. With reference to mortality, the MD% showed a tendency to rise, with increasing age, while no consistent pattern emerged for incidence. The observed incidence trends are probably a consequence of the different times in which the more recent detection methods were introduced in each country, and of the different policies adopted by each health care system towards the elderly. A comparison with the USA data suggests that in the next future a favourable downward mortality trend could be expected also in some EU Countries and, particularly, for younger age groups, even though prostatic cancer in old patients will remain a great burden, which National Health Care Systems will have to face in the next decades.

Adult↗

The relationship between urban airborne pollution and short-term mortality: quantitative and qualitative aspects.

The influence of airborne pollution on mortality rates has been examined since the well known severe pollution episodes of Pennsylvania (1948) and London (1952). Three main epidemiological approaches are available: transversal studies, time series studies, prospective studies. The most frequently used method is the time series analysis, which retrospectively determines daily mortality rates as compared to daily pollution levels in a defined period. The vast majority of studies applying this approach confirm the existence of a positive correlation between mortality and airborne pollution. The relative risk of death during the most severely polluted days as compared to the least polluted days ranges between 1.02 and 1.13. Airborne pollution affects mortality as related to cardiovascular and chronic obstructive pulmonary diseases mainly in subjects previously affected by these pathologies. The dose-response mortality-pollution curve shows linear increments of mortality at low pollution levels, weak increments at high pollution levels. This phenomenon is attributed to the existence of subjects highly susceptible to pollution induced adverse health effects. These subjects, dying at low pollution levels, are not available to increase mortality rates at high pollution levels. Mortality is mainly related to the concentration of single pollutants, such as suspended particle matter, sulfur oxides, nitric oxides and ozone. Elderly are highly susceptible to pollution-induced mortality increases. Therefore, the study of mortality-pollution correlation is of particular interest in cities characterized by a relative prevalence of the elderly in the population. The latency period between pollution increases and related mortality increases falls in the 1-3 days interval range. The pollution-mortality relationship is influenced by many factors, such as the occurrence of exceedingly high or low environmental temperatures, influenza epidemics, etc. Many hypotheses has been raised to support the causality of the mortality-pollution association, including a direct effect of pollutants on cardiovascular and respiratory apparatus, and the release of inflammatory mediators affecting blood viscosity and pneumocytes homeostasis. On the whole, available data suggest that pollution is able to increase mortality only if associated to other risk factors determining an increased susceptibility in the exposed population.

Air Pollutants↗

Geographical variations of place of death among Italian communities suggest an inappropriate hospital use in the terminal phase of cancer disease.

This study aimed to assess geographic variations of place of death among Italian communities, to investigate the determinants of home death, and to examine trends in the proportion of home deaths over a period of 8 y. A cross-sectional analysis was performed on 13 provinces from two Italian regions (Liguria and Toscana), and the geographic variations and determinants of home death were studied for the 17,597 residents, who died of cancer in 1991. Trends for both the regions of the proportion of home deaths were examined for the period 1987 and 1995. A remarkable heterogeneity in the observed proportion of home deaths among the 13 provinces was observed, ranging between 31.4 and 40.4% in Liguria and between 37.7 and 73.3% in Toscana. The estimated proportion of home deaths after adjustment for age, gender, marital status, education, place of birth, characteristics of the living area, and cancer site remained substantially the same. The proportion of home deaths significantly increased with increasing age, and years of education. It was higher among females, married and widowed patients, native patients, and for residents in a semi-urban or rural areas. A significant decrease in the percentage of patients who died at home between 1987 and 1995 in both regions was observed. The wide geographical and social differences observed between and within the communities for the frequency of home deaths are not explained by the distribution of known determinants, and possibly suggest patterns of inappropriate hospital admissions in the terminal phase of disease.

Aged↗

Detection of ornithine decarboxylase mRNA in human breast cancer MCF-7 cells by in situ RT-PCR.

We have studied the expression of ornithine decarboxylase (ODC) mRNA by in situ hybridization and in situ RT-PCR in human breast cancer MCF-7 cell line. In situ RT-PCR demonstrated the overexpression of ODC mRNA, localized over the cytoplasm, while a very low signal was detected by in situ hybridization. Our findings indicate that in situ RT-PCR could represent a useful tool to study different levels of ODC expression in normal and tumor tissues. Since ODC expression is regulated by c-Myc oncoprotein, this model could be useful to monitor in vivo the effects of new anti-neoplastic molecules, specific inhibitors of c-Myc.

Breast Neoplasms↗

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↗