Combination of ultrasound and molecular testing in malignancy risk estimate of Bethesda category IV thyroid nodules: results from a single-institution prospective study.

PURPOSE: Malignancy prediction in indeterminate thyroid nodules is still challenging. We prospectively evaluated whether the combination of ultrasound (US) risk stratification and molecular testing improves the assessment of malignancy risk in Bethesda Category IV thyroid nodules. METHODS: Ninety-one consecutively diagnosed Bethesda Category IV thyroid nodules were prospectively evaluated before surgery by both ACR- and EU-TIRADS US risk-stratification systems and by a further US-guided fine-needle aspiration cytology (FNAC) for the following molecular testing: BRAFV600E, N-RAS codons 12/13, N-RAS codon 61, H-RAS codons 12/13, H-RAS codon 61, K-RAS codons 12/13, and K-RAS codon 61 point-mutations, as well as PAX8/PPARγ, RET/PC1, and RET/PTC 3 rearrangements. RESULTS: At histology, 37% of nodules were malignant. No significant association was found between malignancy and either EU- or ACR-TIRADS. In total, 58 somatic mutations were identified, including 3 BRAFV600E (5%), 5 N-RAS 12/13 (9%), 13 N-RAS 61 (22%), 7 H-RAS 12/13 (12%), 11 H-RAS 61 (19%), 6 K-RAS 12/13 (10%), 8 K-RAS 61 (14%) mutations and 2 RET/PTC1 (4%), 0 RET/PTC 3 (0%), 3 PAX8/PPARγ (5%) rearrangements. At least one somatic mutation was found in 28% and 44% of benign and malignant nodules, respectively, although malignancy was not statistically associated with the outcome of the mutational test. However, the combination of ACR-, but not EU-, TIRADS with the presence of at least one somatic mutation, was significantly associated with malignant histology (P = 0.03). CONCLUSION: US risk stratification and FNAC molecular testing may synergistically contribute to improve malignancy risk estimate of Bethesda category IV thyroid nodules.

A comparison between the effects of over-expression of miRNA-16 and miRNA-34a on cell cycle progression of mesothelioma cell lines and on their cisplatin sensitivity.

The prognosis of patients affected by malignant pleural mesothelioma (MPM) is presently poor and no therapeutic strategies have improved their survival yet. Introduction of miRNA mimics to restore their reduced or absent functionality in cancer cells is considered an important opportunity and a combination of miR's might be even more effective. In the present study, miR-16 and miR-34a were transfected, singularly and in combination, in MPM cell lines H2052 and H28, and their effects on cell proliferation and sensitivity to cisplatin are reported. Interestingly, the overexpression of both miRs, alone or combined, slows down the cell cycle progression, modulates the p53 and HMGB1 expression and increases the sensitivity of cells to cisplatin, producing a marked impairment of cell proliferation and strengthening the apoptotic effect of the drug. However, the co-overexpression of the two miRs results more effective only in the regulation of the cell cycle, but does not enhance the sensitivity of MPM cells to cisplatin. Consequently, although the potential of miR-16 and miR-34a is confirmed, we must conclude that their combination does not improve the response of MPM to chemotherapy.

A 5-year retrospective longitudinal study on the incidence and the risk factors of osteonecrosis of the jaws in patients treated with zoledronic acid for bone metastases from solid tumors.

BACKGROUND: The aim of this study was to evaluate the incidence and the risk factors of osteonecrosis of the jaw (ONJ) in a group of patients treated with zoledronic acid (ZA) for bone metastases from solid tumors and enrolled in a preventive dental program. MATERIAL AND METHODS: This 5-year retrospective longitudinal study included all consecutive oncological patients who underwent at least one infusion with ZA between 2004 and 2011 for bone metastases due to solid neoplasms. RESULTS: Of the 156 patients enrolled in the study, 17 developed ONJ (10.89%). At the multivariate analysis, severe periodontal disease (P=0.025), tooth extraction (P<0.0001) and starting the preventive dental program after the beginning of ZA therapy (P=0.02) were the only factors which showed a significant association with the occurrence of ONJ. CONCLUSIONS: This study demonstrated the importance of beginning dental prevention before zoledronic acid exposure in reducing ONJ occurrence, especially in the long term. The results of this research show that control of periodontal disease and an increase in the time between tooth extraction and the first ZA administration are recommended in order to reduce the risk of ONJ development.

Urinary biomarkers of exposure and of oxidative damage in children exposed to low airborne concentrations of benzene.

The aim of this work was to evaluate the oxidative damage to nucleic acids in children (5-11 years) associated with exposure to environmental pollutants and tobacco smoke (ETS). For each subject, urinary sampling was done twice (evening and next morning) to measure by tandem LC-MS-MS such oxidated products of nucleic acids as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and 8-oxo-7,8-dihydroguanine (8-oxoGua). Methyl tert-butyl ether (U-MTBE), benzene (U-Benz), and its metabolites (t,t-muconic and S-phenylmercapturic acids, t,t-MA and S-PMA, respectively) were determined as biomarkers of exposure to air pollution, and cotinine as a biomarker of exposure to ETS. Biomarkers of exposure (S-PMA and U-MTBE) and of DNA oxidation (8-oxodGuo) were dependent on the urbanization and industrialization levels and increased in the evening sample as compared to next morning (p<0.05). In both evening and next morning samples, 8-oxodGuo and 8-oxoGuo correlated with each other (r=0.596 and r=0.537, respectively, p<0.01) and with biomarkers of benzene exposure, particularly S-PMA (r=0.59 and r=0.45 for 8-oxodGuo and r=0.411 and r=0.383 for 8-oxoGuo, p<0.01). No such correlations were observed for U-MTBE and cotinine. Multiple linear regression analyses showed that 8-oxodGuo was positively associated with S-PMA at both sampling times (ß=0.18 and ß=0.14 for evening and next morning sampling, respectively; p<0.02) and weakly with U-MTBE (ß=0.07, p=0.020) only in the evening urines. These results suggest that the selected biomarkers of exposure to benzene, particularly S-PMA, are good tracers of exposure to complex mixtures of oxidative pollutants and that the associated oxidative damage to nucleic acids is detectable even at very low levels of exposure.

Porphyrin conjugated SiC/SiOx nanowires for X-ray-excited photodynamic therapy.

The development of innovative nanosystems opens new perspectives for multidisciplinary applications at the frontier between materials science and nanomedicine. Here we present a novel hybrid nanosystem based on cytocompatible inorganic SiC/SiOx core/shell nanowires conjugated via click-chemistry procedures with an organic photosensitizer, a tetracarboxyphenyl porphyrin derivative. We show that this nanosystem is an efficient source of singlet oxygen for cell oxidative stress when irradiated with 6 MV X-Rays at low doses (0.4-2 Gy). The in-vitro clonogenic survival assay on lung adenocarcinoma cells shows that 12 days after irradiation at a dose of 2 Gy, the cell population is reduced by about 75% with respect to control cells. These results demonstrate that our approach is very efficient to enhance radiation therapy effects for cancer treatments.

Exhaled breath analysis in suspected cases of non-small-cell lung cancer: a cross-sectional study.

Lung cancer is one of the most frequently diagnosed cancers worldwide and is still the leading cause of cancer-related deaths. There is a considerable interest in finding diagnostic methods in the disease's earliest stages. A complementary approach to imaging techniques could be provided by exhaled breath gas phase and exhaled breath condensate (EBC) analysis. The aim of this study was to quantify various biomarkers in the exhaled breath gas phase and EBC in suspected cases of non-small-cell lung cancer (NSCLC). The study involved 138 subjects with suspected lung cancer, 71 of whom had a subsequent diagnosis of NSCLC. The diagnostic power of a combination of hydrogen peroxide (H2O2)-EBC, and exhaled pentane, 2-methyl pentane, hexane, ethyl benzene, heptanal, trans-2-nonenal in distinguishing NSCLC and non-NSCLC subjects was poor-to-fair (area under the curve (AUC) = 0.68), similar to that of smoking history alone (expressed as pack-years, AUC = 0.70); a further improvement was observed when smoking history was combined with exhaled compounds (AUC = 0.80). The diagnostic power was increased in those patients with little or no past smoke exposure (AUC = 0.92) or where past smoke exposure was up to 30 pack-years (AUC = 0.85). Exhaled substances had a good accuracy in discriminating suspected cancerous cases only in those subjects with a modest smoking history (≤ 30 pack-years), but the inclusion of other exhaled biomarkers may increase the overall accuracy, regardless of tobacco smoke.

Ethnicity-related variations of left ventricular remodeling in adolescent amateur football players.

Adult and adolescent elite black athletes display - as compared with their white counterparts - excessively increased left ventricle (LV) wall thickness (LVWT), mass (LVM), and relative wall thickness (RWT). To investigate such ethnicity-related differences in non-professional adolescent athletes, 138 male, amateur football players [age 14.0 ± 1.7 years, 42 West-African blacks (BA) and 96 Italian whites (WA)] underwent an echocardiographic study of LV diameters, LVWT, maximal wall thickness (MWT), LVM, and RWT as remodeling index. BA vs WA exhibited greater thickness of septum and posterior wall, higher MWT (10.3 ± 1.7 vs 8.8 ± 1.1 mm), and higher LVM (117 ± 27 vs 101 ± 20 g/m(2)) and RWT (0.44 ± 0.07 vs 0.35 ± 0.04). Age, systolic blood pressure, body mass index, and ethnicity predicted MWT and LVM, whereas ethnicity was the sole strong predictor of RWT. The greater MWT, LVWT, and LVM of 14-year-old, amateur-level BA vs WA indicates that ethnicity substantially affects LV structure in adolescent, non-professional athletes. In contrast with MWT and LVM, elevated RWT was predicted by black ethnicity only. We suggest that concentric-type LV remodeling is a peculiar LV phenotype in adolescent African athletes.

Cytocompatibility and cellular internalization mechanisms of SiC/SiO2 nanowires.

First evidence of in vitro cytocompatibility of SiC/SiO2 core-shell nanowires is reported. Different internalization mechanisms by adenocarcinomic alveolar basal epithelial cells, monocytic cell line derived from an acute monocytic leukemia, breast cancer cells, and normal human dermal fibroblasts are shown. The internalization occurs mainly for macropinocytosis and sporadically by direct penetration in all cell models considered, whereas it occurred for phagocytosis only in monocytic leukemia cells. The cytocompatibility of the nanowires is proved by the analysis of cell proliferation, cell cycle progression, and oxidative stress on the cells treated with NWs as compared to controls. Reactive oxygen species generation was detected as an early event that then quickly run out with a rapid decrease only in adenocarcinomic alveolar basal epithelial and human dermal fibroblasts cells. In all the cell lines, the intracellular presence of NWs induce the same molecular events but to a different extent: peroxidation of membrane lipids and oxidation of proteins. The NWs do not elicit either midterm (72 h) or long-term (10 days) cytotoxic activity leading to irreversible cellular damages or death. Our results are important in view of a possible use of SiC/SiO2 core-shell structures acting as biomolecule-delivery vectors or intracellular electrodes.

Synergistic interactions between PBDEs and PCBs in human neuroblastoma cells.

Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants. Exposure to these chemicals has been associated with developmental neurotoxicity, endocrine dysfunction, and reproductive disorders. Humans and wildlife are generally exposed to a mixture of these environmental pollutants, highlighting the need to evaluate the potential effects of combined exposures. In this study, we investigated the cytotoxic effects of the combined exposure to two PBDEs and two PCBs in a human neuronal cell line. 2,2',4,4'-Tetrabromodiphenyl ether, 2,2',4,4',5-pentabromodiphenyl ether, PCB-126 (3,3',4,4',5-pentachlorobiphenyl; a dioxin-like PCB), and PCB-153 (2,2',4,4',5,5'-hexachlorobiphenyl; a non-dioxin-like PCB) were chosen, because their concentrations are among the highest in human tissues and the environment. The results suggest that the nature of interactions is related to the PCB structure. Mixtures of PCB-153 and both PBDEs had a prevalently synergistic effect. In contrast, mixtures of each PBDE congener with PCB-126 showed additive effects at threshold concentrations, and synergistic effects at higher concentrations. These results emphasize the concept that the toxicity of xenobiotics may be affected by possible interactions, which may be of significance given the common coexposures to multiple contaminants.

[New perspectives in biomonitoring of metallic elements: the example of hexavalent chromium]. / Nuove prospettive nel monitoraggio biologico degli elementi metallici: l'esempio del cromo esavalente.

Plating industry is an important productive sector in all the national territory, because of its contribution to a high number of industrial products and crafts. In the chrome plating sector there is a specific chemical risk due to the exposure to compounds containing hexavalent Chromium [Cr(VI)]. Exhaled breath condensate (EBC) has been used to study both acute and long term exposure to Cr(VI) in chrome plating workers. Cr-EBC correlates with specific oxidative stress biomarkers. Moreover, both total Cr and its hexavalent fraction can be measured in EBC, which therefore is a promising biological fluid to assess the absorbed dose at the target organ level, the pulmonary reduction kinetics of Cr(VI) and in general its local pneumotoxic effects. EBC collection and analysis could give additional information to the traditional measures performed during biomonitoring.

Association between environmental exposure to benzene and oxidative damage to nucleic acids in children.

OBJECTIVES: To evaluate the association between environmental exposure to benzene and oxidative damage to nucleic acids in children, also considering the role of Environmental Tobacco Smoke (ETS). METHODS: 396 children living in central Italy were recruited in districts with different urbanization and air pollution. All biomarkers were determined in spot urine samples by mass spectrometric techniques to assess exposure [benzene (U-Benz), and its metabolites (t,t-muconic and S-phenylmercapturic acids, t,t-MA and S-PMA, respectively), cotinine] and nucleic acid oxidation [8-oxo-7, 8-dibydro-2'-deoxyguanosine (8-oxodGuo), 8-oxo-7, 8-dihydroguanosine (8-oxoGuo), and 8-oxo-7, 8-dihydroguanine (8-oxoGua)]. RESULTS: Biomarkers of exposure and nucleic acid oxidation increased with urbanization and were correlated with each other (r > 0.18, p < 0.005). In a multiple linear regression model, benzene exposure, assessed by S-PMA and t,t-MA, was associated (p < 0.0001) with both 8-oxodGuo (R2 = 0.392) and 8-oxoGuo (R2 = 0.193) in all areas of residence, with similar slopes. CONCLUSIONS: (i) Biomarkers of exposure to benzene increased as a function of environmental air pollution and urbanization level; (ii) U-Benz clearly distinguished both exposure to ETS and areas of residence, whereas benzene metabolites were associated only with the latter; (iii) the variance of 8-oxodGuo and 8-oxoGuo was accounted for by environmental benzene exposure, thus suggesting that benzene is a good tracer of other components of complex mixtures of pollutants causing oxidative damage to nucleic acids.

[Sleep disorders, risk of accidents and traffic accidents in a group of drivers of public transport]. / Disturbi del sonno, rischio infortunistico e incidenti stradali in un gruppo di autisti di mezzi pubblici.

In order to evaluate the prevalence of sleep disorders and visuomotor performance, a survey was conducted on 253 drivers of public transport company, aged between 25 and 64 years. Biometric data (BMI, neck circumference and waist, PA) were collected and three questionnaires were administered to investigate sleep disorders. Simple and multiple choice reaction times were administered using a computerized test battery. Records on road accidents in the period 2005-2011 and all accidents in the period 2002-2010 were analyzed. On the basis of clinical and anamnestic questionnaire, workers were divided into two groups: 194 drivers (group 1) without suspicion of sleep disorders and 59 drivers (group 2) with suspected sleep disorders, and 41 with suspected obstructive sleep apnea syndrome (OSAS). The drivers with suspicion of sleep disorders, in particular those with suspected diagnosis of OSAS, showed reaction times significantly prolonged as compared to the drivers of the group 1. In group 2, a higher incidence of (all) accidents was found, whereas the incidence of road accidents was significantly increased only in drivers with suspected OSAS. In addition to the sleep disorders, the use of drugs altering vigilance (antihistamines and benzodiazepines) were significant determinants. In-depth clinical examinations are in progress to confirm the suspected diagnosis of sleep disorders.

[Acute lead poisoning: a singular case of hemolytic anemia and lead colic]. / Intossicazione acuta da piombo: un caso singolare di anemia emolitica e colica saturnina.

BACKGROUND: Acute lead poisoning due to food intake is exceptional in adults and often associated with mental illness OBJECTIVES: to describe a case report of acute lead intoxication with haemolytic anemia and lead colic. METHODS: A 41-year old male patient was admitted to hospital for abdominal pain and persistent constipation. Abdominal X-ray showed a radiopaque mass in the caecum and progressive anaemia was observed The patient was discharged with a diagnosis of bowel obstruction. Due to persistence of the symptoms he was again hospitalized; abdominal X-ray showed diffuse radiopaque particles in the colon and haemoglobin (hb) had dropped to 8.7 g/dl. Blood levels of lead and zinc protoporphryin were 106.7 microg/dl and 6.6 microg/gHb, respectively. The timely start of chelating therapy led to a rapid return to normal peripheral blood counts and a decline in blood lead levels. RESULTS: Although acute lead poisoning due to intake with food is exceptional in adults and often associated with mental illness, in this case, it was not possible to clarify the route and vehicle of ingestion of the toxic. Lead body burden was shown as a caecal mass, probably as a result of ingesting a single bolus of lead dust which, considering the size and density of the mass, was estimated as weighing several grammes. This acute lead intake induced an acute haemolysis due to enhanced fragility of the erythrocyte membrane. CONCLUSIONS: In the course of acute lead intoxication, the critical organ is not the bone marrow, but rather the red blood cell, leading to haemolysis and anaemia.

[Biological monitoring and exposure to silica: application of new dose and effect biomarkers]. / Monitoraggio biologico ed esposizione a silice: applicazione di nuovi indicatori di dose e di effetto.

Si-CAE was measured in 16 composite marble industry workers furthermore, a spirometry was performed and 8oxoGua, 8oxoGuo 8oxodGuo, SP-A, SP-D, CC16 and HO-1 were dosed. A lower spirometric values (FEV1 and FVC) were observed among workers compared with controls and the following markers were increased: Si-CAE, 8oxoGuo and HO-1 expression. This study shows that exposure to silica can increase the levels of Si-CAE, which can be used to estimate the dose to the target. Finally, nonspecific spirometric abnormalities and an increase in biomarkers of effect were observed.

[Early molecular diagnosis of lung cancer: a method to rule out the disease]. / Diagnosi molecolare precoce del tumore polmonare: un metodo per escludere la malattia.

Aim of this study was the determination of new markers for the diagnosis of lung cancer. 61 patients with non-small cell lung cancer (NSCLC) and 42 controls were enrolled. In the NSCLC patients the following markers were increased: H2O2 in exhaled breath condensate, pentane, hexane, nonenal, trans-2-heptanal, trans-2-nonenal in exhaled breath, while pentanal was decreased. Using multivariate statistical models, a sensitivity of 73.8% and a specificity of 76.8% were calculated. This study shows that with this non-invasive test followed by a most powerful test on positives (e.g. PET) it is possible to decrease the number of false positives.

Occupational asphyxiation by unknown compound(s): environmental and toxicological approach.

During a routine truck-tank washing operation, five healthy workers were found motionless inside an empty tanker. Four of them died inside the tanker while the fifth died the following day in hospital. Since the true nature of the fatal compound(s) were not known, a rigorous environmental and toxicological approach supported by autopsy findings was essential to clarify the cause of death. Environmental results indicated that H(2)S fumes arising from the liquid sulfur previously shipped were responsible for the serial deaths, also confirmed by a simulation performed on two similar truck-tanks. These environmental findings were supported by toxicological analyses through the measurement of thiosulfate, one of the main H(2)S metabolites. Abnormal thiosulfate concentrations from 1.1 to 186.2 mg/kg were revealed in all post-mortem biological samples (blood, lung, liver, kidney, brain and fat). Finally, the cluster analysis performed on thiosulfate body distribution contributed to establishing the time of death according to the accident scene reconstruction. This report presents valuable findings in correctly identifying the cause of death in gas asphyxiation cases by unknown compound(s).

Natural killer cell cytotoxicity is enhanced by very low doses of rIL-2 and rIFN-alpha in patients with renal cell carcinoma.

Very low doses of recombinant interleukin-2 (rIL-2) and interferon-alpha (rIFN-alpha) induce, in patients with advanced renal cell carcinoma (RCC) clinical response rate and median survival time comparable to other protocols, other than immunological response in terms of expansion of NK cells and cT lymphocytes. The aim of this pilot study was to verify whether very low dose immunotherapy can enhance NK cell cytotoxicity against tumoral target cells. Eight patients with advanced and 13 patients with localised disease received 4-week cycles of rIL-2 (total dose per week 7 MIU/m(2), s.c.) and rIFN-alpha (total dose per week 3.6 MUI/m(2), i.m.) according to the scheme proposed by Buzio et al. Neutrophils, monocytes, eosinophils, NK cells (CD56+bright, CD56+dimmer, CD3-CD56 +), NK-T cells (CD3+CD56+), Th-lymphocytes, cT-lymphocytes, HLA-DR+ and CD25+ lymphocytes and NK cell cytotoxicity were evaluated before and after cycle. The treatment led to the significant expansion of eosinophils (P < 0.001), NK cells (P < 0.001), CD56+bright (P < 0.001), CD56+dimmer (P < 0.001), Th-lymphocytes (P = 0.001), cT-lymphocytes (P = 0.014), HLA-DR+ (P = 0.007) and CD25+(P = 0.002) cells. Neutrophils significantly decreased (P = 0.001), whereas no significant effect was observed on monocytes (P = 0.22) or NK-T cells (P = 0.20). Patients with localised disease responded significantly better to treatment than metastatic patients in terms of the expansion of CD56+bright (P = 0.038), DR+ (P = 0.021), CD25+ (P = 0.006) and Th-lymphocytes (P = 0.014). The NK cell cytotoxicity was significantly increased by the immunotherapy in the whole population (P = 0.021) and similarly in the two groups of patients (P = 0.860); a reverse relation, even if not significant, was seen between the variation of NK-T cells and NK cells cytotoxicity (r = -0.39; P = 0.074).

[Non-invasive assessment of lung pathobiology in hairdressers]. / Valutazione non invasiva della patobiologia polmonare in una coorte di lavoratori del settore acconciatura.

BACKGROUND: Hairdressers are exposed to chemical agents with potentially irritant and sensitizing effects on airways. OBJECTIVES: To asses the presence of respiratory symptoms and biochemical and functional changes of the airways in a cohort of hairdressers. METHODS: Respiratory symptoms, lung function tests, fractional exhaled nitric oxide (FE(NO)50) and selected oxidative stress biomarkers [hydrogen peroxide (H2O2), malondialdehyde (MDA) and 4-hydroxynonenal (HNE)] in exhaled breath condensate (EBC) were assessed in 23 hairdressers on a rest day (Group 1); 12 workers (Group 2) were willing to perform the same tests at the beginning (BS) and at the end of a shift (ES) on the same working day. Eighteen subjects not occupationally exposed to airways irritants formed the control group. RESULTS: Most of the hairdressers reported respiratory symptoms during work; however, all (except one) showed normal spirometry indexes. FE(NO)50 levels were within the reference limits and did not change comparing BS vs. ES sampling. H2O2 and HNE values in EBC were higher in Group 1 (H2O2: 0,16 [0,05-0,19] microM; HNE: 0,94 [0,82-1,22] nM) than in controls (H2O2: 0,05 [0,02-0,09] microM; HNE: 0,61 [0,49-0,78] nM, p < 0,001). In Group 2, H2O2 and MDA levels were higher in EBC collected at ES (0,56 [0,23-3,62] mM and 5,21 [4,93-5,95] nM) in comparison with the BS values (0,11 [0,03-0,28] mM and 4,12 [3,46-5,16] nM, p < 0,001 and p < 0,02, respectively). CONCLUSIONS: Increased levels of oxidative stress biomarkers are detectable in EBC of hairdressers, without impairment in respiratory function. Exhaled biomarkers of oxidative stress may be sensitive end points for evaluating early biochemical changes in the airways of hairdressers.

[Molecular diagnosis of lung cancer]. / Diagnosi molecolare di tumore del polmone.

Individuals who have been exposed to lung carcinogenics are concerned by their greater risk of developing lung cancer, thus consult physicians with the expectation of undergoing screening tests. Controversy remains as to which screening procedures should be assessed. Previous studies of sputum cytology and chest X-rays showed no benefits in lung cancer mortality reduction. Screening of high risk individuals through computerized tomography scan appeared promising, but this radiological technique suffers from low specificity. Currently, the differential diagnosis is mainly based on additional imaging techniques, particularly positron emission tomography, which is expensive, and also shows limitations in terms of sensitivity and specificity. Therefore, purely morphological criteria seem to be insufficient to distinguish lung cancer at early stages from benign nodules with sufficient confidence, and false positives undergoing surgical resection seem to occur frequently. A molecular approach to the diagnosis of lung cancer through the analysis of biomarkers obtained by non invasive means could greatly improve the specificity of imaging procedures. Extremely sensitive mass spectrometric techniques are available to detect molecular alterations in accessible media, which characterise lung cancer at early stages, thereby reducing the rate of false positives, expected to be very out without a sound application of confirmatory diagnostic tests.

Methylmercury at low doses modulates the toxicity of PCB153 on PC12 neuronal cell line in asynchronous combination experiments.

Me-Hg and PCB153 are known neurotoxic contaminants which tend to accumulate in food, particularly in fish. Aim of this study was to perform asynchronous and combined exposure to Me-Hg and PCB153 in a neuronal rat cell line (PC12) to better characterise the antagonism observed at some combination concentrations. PC12 cells were treated with three concentrations of Me-Hg (0.1-0.5-1.0 microM) and PCB153 at one concentration (175 microM) in single and combined asynchronous exposures, using viability (MTT assay) as end-point. At all concentrations used, a statistically significant antagonistic effect was observed when Me-Hg preceded PCB153 exposure, while effect was additive when PCB153 preceded Me-Hg exposure. The antagonism is particularly evident at low concentrations of Me-Hg (0.1 microM). In conclusion, combined asynchronous exposure showed that whereas Me-Hg can modulate PCB153 toxicity, the opposite seems not to be true. Therefore, the use of asynchronous exposure could be a promising approach to study the mechanisms of toxicity of binary mixtures.