Oxidative potential, cytotoxicity, and intracellular oxidative stress generating capacity of PM10: a case study in South of Italy

Long and short-term exposure to atmospheric particulate matter (PM) has detrimental effects on human health. The effective mechanisms leading to PM toxicity are still not fully understood, even if it is known that physical-chemical properties, strongly influenced by sources and atmospheric processes, are known to play an important role. In this work, PM10 samples were collected, at an urban background site in southern Italy, to determine cytotoxicity (using MTT test on A549 cells), genotoxicity (using the comet assay), and intracellular oxidative stress on A549 cells exposed for 24h to aqueous extracts of PM10 samples. Organic carbon (OC) and elemental carbon (EC) content of PM10 and acellular determination of oxidative potential with DTT assay was performed with the objective to compare results of acellular and cellular biological assays. Cellular (OSGCV and MTTV) and acellular (OPDTTV) outcomes, normalised in volume, are well correlated (statistical significant results) with carbon content suggesting that combustion sources play an important role in deter-mining cellular oxidative stress and cytotoxicity of PM10. Even if the number of data is limited, genotoxicity results are well correlated (Pearsons > 0.95) with OSGCV and MTTV and a weaker, but statistically significant correlation was observed with OPDTTV. OSGCV is well correlated with the cell mortality observed with MTTV test and a lower, but still statistical significant correlation is observed between MTTV and OPDDTV. A statistically significant correlation was found between OPDTTV and OSGCV results. When the outcomes of cellular and acellular assay are compared normalised in mass (i.e. intrinsic values), the correlations become significantly weaker suggesting that the different sources acting on the site produces particulate matter with different toxicological potential influ-encing differently the biological tests studie

Lack of Activity of Docetaxel in Soft Tissue Sarcomas: Results of a Phase II Study of the Italian Group on Rare Tumors

Purpose. The prognosis of advanced soft tissue sarcoma is poor, only a few drugs showing some activity with response rates around 15– 25%. Consequently drug development seems mandatory to improve treatment outcome. Following previous favourable EORTC experience, the Italian Group on Rare Tumors started a phase II study with docetaxel to confirm the activity of this drug in soft tissue sarcoma

Correlation of Oxidative Potential with Ecotoxicological and Cytotoxicological Potential of PM10 at an Urban Background Site in Italy

: It is known that exposure to atmospheric particulate matter (PM) has detrimental effects on health. However, specific mechanisms of toxicity are still not fully understood depending on several physical and chemical properties of PM. In recent years, there has been a growing evidence that oxidative stress is an important mechanism of PM toxicity leading to the hypothesis to use acellular evaluation of oxidative potential (OP) as a global indicator of potential health effects of PM. However, when OP data are correlated with the outcomes of in vitro (or in vivo) toxicological tests, there are contrasting results. In this work an analysis of PM10 health effect indicators was done, using the acellular DTT assay to retrieve OPDTT, the Microtox® test on Vibrio fischeri bacterium to assess the ecotoxicological potential, and the in vitro MTT assay on the human cell line A549 to estimate the cytotoxicological potential. The objective was to evaluate the correlation among acellular OPDTT and the results from toxicological and ecotoxicological bioassays and how these health-related indicators are correlated with atmospheric PM10 concentrations collected at an urban background site in Southern Italy. Results indicated that both bioassays showed time-dependent and dose-dependent outcomes. Some samples presented significant ecotoxic and cytotoxic response and the correlation with PM10 concentration was limited, suggesting that these health endpoints depend on PM10 chemical composition and not only on exposure concentrations. OPDTT showed a statistically significant correlation with PM10 concentrations. MTT and Microtox outcomes were not correlated suggesting that the two toxicological indicators are sensitive to different physical-chemical properties of PM10. Intrinsic oxidative potential OPDTTM (DTT activity normalised with PM10 mass) was correlated with mortality observed with MTT test (normalized with PM10 mass), however, it was not correlated with Microtox outcome

A case series of low dose bevacizumab and chemotherapy in heavily pretreated patients with epithelial ovarian cancer

Abstract Background The addition of bevacizumab to standard chemotherapy prolongs progression free survival in the first line treatment of epithelial ovarian cancer (EOC), but its cost/effectiveness is debated. We assessed the safety and activity of a lower dose of bevacizumab in pretreated advanced stage EOC. Methods We treated 15 patients, mostly with platinum resistant EOC, who had received a median of four prior cytotoxic regimens, with bevacizumab 5–7.5 mg/kg q21 days in combination with either carboplatin (n = 8), oral cyclofosfamide (n = 5) or weekly paclitaxel (n = 2). Bevacizumab was administered until disease progression. Tumor response was assessed by CA125 and fusion 18 F-FDG PET/contrast enhanced CT. Results The median number of bevacizumab cycles was 21 (range 3–59). The median baseline CA125 was 272 U/ml and decreased to 15.2 U/ml at nadir. Tumor response was 4 complete response (CR) (26.7%) and 7 partial response (PR) (46.7%) by chemotherapy (CT), with an overall response rate of 73.4% (95% CI, 51.0 – 95.8) according to Response Evaluation Criteria In Solid Tumors (RECIST), and 6 CR (40%) and 4 PR (26.7%) by PET, for an overall metabolic response rate of 67% (95%CI, 42.8 – 90.6) according to PET Response Criteria in Solid Tumors (PERCIST). Median progression free survival (PFS) was 21 months and median overall survival (OS) was 24 months. Grade 3 adverse events related to bevacizumab were hypertension (n = 2), proteinuria (n = 1) and epistaxis (n = 5). Treatment was delayed in five patients for nasal bleeding or uncontrolled hypertension. Conclusions Low-dose bevacizumab and chemotherapy was well tolerated and active in a heavily pretreated population of advanced EOC. Further studies should assess the activity of low dose bevacizumab in EOC.</p

Characterization and dating of waterlogged woods from an ancient harbor in Italy

Waterlogged wood samples of Ulmus sp. and Fraxinus sp. from the ancient harbor of Otranto in Southern Italy were radiocarbon dated by accelerator mass spectrometry (AMS) and examined for physical and chemical changes to assess the degree of degradation. The analyzed woods were dated to the 2nd half of the twelfth – 1st half of the thirteenth centuries AD. The results of all the used methods (maximum water content, basic density, shrinkage, XRD analysis and holocellulose content) indicated a low level of degradation in the inner part of the wooden find. The outer and middle part, on the other hand, showed a greater degradation level. An important result is the identification of a not homogeneous degradation in the different parts of the examined wooden block, which will affect the design of the consolidating treatmen

Apoptotic volume decrease (AVD) in A549 cells exposed to water-soluble fraction of particulate matter (PM10)

Exposure to atmospheric particulate matter (PM) is recognized as a human health risk factor of great concern. The present work aimed to study the cellular mechanisms underlying cytotoxic effects of airborne particulate matter <10 mu m in size (PM10), sampled in an urban background site from January to May 2020, on A549 cells. In particular, the study addressed if PM10 exposure can be a main factor in the induction of the Apoptotic Volume Decrease (AVD), which is one of the first events of apoptosis, and if the generation of intracellular oxidative stress can be involved in the PM10 induction of apoptosis in A549 cells. The cytotoxicity of PM10 samples was measured by MTT test on cells exposed for 24 h to the PM10 aqueous extracts, cell volume changes were monitored by morphometric analysis of the cells, apoptosis appearance was detected by annexin V and the induction of intracellular oxidative stress was evaluated by the ROS sensitive CM-H2DCFDA fluorescent probe. The results showed cytotoxic effects ascribable to apoptotic death in A549 cells exposed for 24 h to aqueous extracts of airborne winter PM10 samples characterized by high PM10 value and organic carbon content. The detected reduced cell viability in winter samples ranged from 55% to 100%. Normotonic cell volume reduction (ranging from about 60% to 30% cell volume decrease) after PM10 exposure was already detectable after the first 30 min clearly indicating the ability of PM10, mainly arising from biomass burning, to induce Apoptotic Volume Decrease (AVD) in A549 cells. AVD was prevented by the pre-treatment with 0.5 mM SITS indicating the activation of Clefflux presumably through the activation of VRAC channels. The exposure of A549 cells to PM10 aqueous extracts was able to induce intracellular oxidative stress detected by using the ROS-sensitive probe CM-H2DCFDA. The PM10induced oxidative stress was statistically significantly correlated with cell viability inhibition and with apoptotic cell shrinkage. It was already evident after 15 min exposure representing one of the first cellular effects caused by PM exposure. This result suggests the role of oxidative stress in the PM10 induction of AVD as one of the first steps in cytotoxicity