Differential Radiomodulating Action of Olea europaea L. cv. Caiazzana Leaf Extract on Human Normal and Cancer Cells: A Joint Chemical and Radiobiological Approach.

The identification of a natural compound with selectively differential radiomodulating activity would arguably represent a valuable asset in the striving quest for widening the therapeutic window in cancer radiotherapy (RT). To this end, we fully characterized the chemical profile of olive tree leaf polyphenols from the Caiazzana cultivar (OLC), autochthonous to the Campania region (Italy), by ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HR-MS). Oleacein was the most abundant molecule in the OLC. Two normal and two cancer cells lines were X-ray-irradiated following 24-h treatment with the same concentration of the obtained crude extract and were assessed for their radioresponse in terms of micronucleus (MN) induction and, for one of the normal cell lines, of premature senescence (PS). Irradiation of pre-treated normal cells in the presence of the OLC reduced the frequency of radiation-induced MN and the onset of PS. Conversely, the genotoxic action of ionising radiation was exacerbated in cancer cells under the same experimental conditions. To our knowledge, this is the first report on the dual action of a polyphenol-rich olive leaf extract on radiation-induced damage. If further confirmed, these findings may be pre-clinically relevant and point to a substance that may potentially counteract cancer radioresistance while reducing RT-associated normal tissue toxicity.

The Proton-Boron Reaction Increases the Radiobiological Effectiveness of Clinical Low- and High-Energy Proton Beams: Novel Experimental Evidence and Perspectives.

Protontherapy is a rapidly expanding radiotherapy modality where accelerated proton beams are used to precisely deliver the dose to the tumor target but is generally considered ineffective against radioresistant tumors. Proton-Boron Capture Therapy (PBCT) is a novel approach aimed at enhancing proton biological effectiveness. PBCT exploits a nuclear fusion reaction between low-energy protons and 11B atoms, i.e. p+11B→ 3α (p-B), which is supposed to produce highly-DNA damaging α-particles exclusively across the tumor-conformed Spread-Out Bragg Peak (SOBP), without harming healthy tissues in the beam entrance channel. To confirm previous work on PBCT, here we report new in-vitro data obtained at the 62-MeV ocular melanoma-dedicated proton beamline of the INFN-Laboratori Nazionali del Sud (LNS), Catania, Italy. For the first time, we also tested PBCT at the 250-MeV proton beamline used for deep-seated cancers at the Centro Nazionale di Adroterapia Oncologica (CNAO), Pavia, Italy. We used Sodium Mercaptododecaborate (BSH) as 11B carrier, DU145 prostate cancer cells to assess cell killing and non-cancer epithelial breast MCF-10A cells for quantifying chromosome aberrations (CAs) by FISH painting and DNA repair pathway protein expression by western blotting. Cells were exposed at various depths along the two clinical SOBPs. Compared to exposure in the absence of boron, proton irradiation in the presence of BSH significantly reduced DU145 clonogenic survival and increased both frequency and complexity of CAs in MCF-10A cells at the mid- and distal SOBP positions, but not at the beam entrance. BSH-mediated enhancement of DNA damage response was also found at mid-SOBP. These results corroborate PBCT as a strategy to render protontherapy amenable towards radiotherapy-resilient tumor. If coupled with emerging proton FLASH radiotherapy modalities, PBCT could thus widen the protontherapy therapeutic index.

Effects of irradiation conditions on the radiation sensitivity of microorganisms in the presence of OH-radical scavengers.

PURPOSE: The purpose of the paper was to investigate the protective effect of some scavengers of OH radicals (hydroxyl radicals) on the radiation sensitivity of bacteria (in some cases also yeast) under normoxic (in air) or hypoxic (suboxic) conditions and to compare the obtained results with those published earlier for the yeast, all in a wide interval of irradiation conditions. Another aim was to investigate a possible impact of the reaction order of the reaction between the scavengers and the OH radicals on the protection of the cells. MATERIALS AND METHODS: In order to study the protective effect of OH scavengers we used various concentrations of methanol and potassium formate (in some cases also ethanol) in isotonic salt solutions. These solutions containing living bacteria (Escherichia coli) or yeast (Saccharomyces cerevisiae) were irradiated with 60Co radiation using various doses and dose rates. Irradiation was performed in air, in some cases under the hypoxic conditions. The number of surviving cells was determined prior to and after irradiation in suspension with and without scavengers. The surviving fractions after irradiation with and without scavenger were evaluated. RESULTS: The surviving fraction of bacterial cells increases linearly with increasing concentration of both scavengers. The fraction of surviving cells does not increase with increasing concentration of the scavengers under suboxic conditions. The protective effect Ϭ increases linearly with increasing scavenging efficiency and this dependence is much sharper under normoxic conditions than under suboxic ones. The specific protection k is much higher for the methanol than for the potassium formate. CONCLUSIONS: The basic characteristics of the impact of scavengers of OH radicals on radiation sensitivity of both bacteria and yeast are the same in a wide interval of doses and dose rates. The specific protection effect is much higher under the normoxic conditions. This protective effect is inversely proportional to the rate constant of the reaction between the scavenger and the OH radicals. It seems to be obvious that the presence of oxygen during irradiation is a necessary condition for the protective action of the scavengers which may be partially controlled by some transport processes and may be connected with the radiation sensitivity of the cells. On the other hand, the change of the reaction order of the reaction of the scavenger with the OH radicals has turned out to be unimportant.

Delayed effects of accelerated heavy ions on the induction of HPRT mutations in V79 hamster cells.

Fundamental research on the harmful effects of ionizing radiation on living cells continues to be of great interest. Recently, priority has been given to the study of high-charge and high-energy (HZE) ions that comprise a substantial part of the galactic cosmic ray (GCR) spectra that would be encountered during long-term space flights. Moreover, predictions of the delayed genetic effects of high linear energy transfer (LET) exposure is becoming more important as heavy ion therapy use is increasing. This work focuses mainly on the basic research on the delayed effects of HZE ions on V79 Chinese hamster cells, with emphasis on the induction of HPRT mutations after prolonged expression times (ET). The research was conducted under various irradiation conditions with accelerated ions 18O (E=35.2MeV/n), 20Ne (E=47.7MeV/n and 51.8MeV/n), and 11B (E=32.4MeV/n), with LET in the range from 49 to 149 keV/µm and with 60Co γ-rays. The HPRT mutant fractions (MF) were detected in irradiated cells in regular intervals during every cell culture recultivation (every 3days) up to approximately 40days (70-80 generations) after irradiation. The MF maximum was reached at different ET depending on ionizing radiation characteristics. The position of the maximum was shifting towards longer ET with increasing LET. We speculate that the delayed mutations are created de novo and that they are the manifestation of genomic instability. Although the exact mechanisms involved in genomic instability initiation are yet to be identified, we hypothesize that differences in induction of delayed mutations by radiations with various LET values are related to variations in energy deposition along the particle track. A dose dependence of mutation yield is discussed as well.

Influence of various scavengers of •OH radicals on the radiation sensitivity of yeast and bacteria.

PURPOSE: To quantitatively investigate the influence of various •OH (hydroxyl radical) scavengers on the radiation sensitivity of yeast and bacteria, particularly to define the relationship between the protective effect of a scavenger and its •OH scavenging efficiency. MATERIALS AND METHODS: In order to study the protective effect of •OH scavengers we used various concentrations of four scavengers (methanol, potassium formate, ethanol and ascorbic acid) in isotonic salt solutions. These solutions containing live yeast (Saccharomyces cerevisiae) or bacteria (Escherichia coli) were irradiated with (60)Co isotope γ -radiation using two different doses and dose rates. The number of surviving cells was determined prior to and after irradiation both in suspension with and without scavengers. The surviving fractions after irradiation with and without the scavenger were evaluated. RESULTS AND CONCLUSIONS: The main results of the paper were: The surviving fraction increased approximately linearly within the measured interval with increasing concentration of the scavenger. The same dependences were found for the protecting effect depending on the scavenging efficiency. The slopes of these dependences (k) were found to be characteristic for each scavenger. The k value determined the degree in which the scavenging of •OH radicals participated in the protection of living cells. The protective effects of scavengers at the same scavenging efficiency were different and unique for each scavenger. No simple relation was found between the efficiency of scavenger k and the rate constant kOH of the reactions between scavengers and •OH radicals. Our results suggest that the studied scavengers effectively protected yeast and bacteria against ionizing radiation. Although the scavenging of •OH radicals seems to be important for protection of living cells, it is clearly not the only process on which the protection is based.

[Health behaviours in children and youth aged 7 to 16 years]. / Zachowania zdrowotne dzieci i mlodziezy w wieku 7-16 lat.

The study aimed at describing selected health behaviors of 470 subjects aged 7 to 16 years from Jedlina Zdrój. The frequency of the meals eaten and physical activity were estimated by means of a standardized multiple choice questionnaire. In both sexes the number of hours spent on physical activity rose significantly with age. The time of physical activity in older boys was significantly higher than in their female peers. Similarly, the percentage of children skipping breakfast and the second breakfast increased with age. The amount of fruit and vegetables eaten decreased with age of the subjects. At school milk was drunk by very few boys only.

Factors influencing survival after bypass procedures in patients with advanced pancreatic adenocarcinomas.

BACKGROUND: Patients with occult metastasis or locally nonresectable pancreatic cancer found during surgical exploration have a limited life expectancy. We sought to define markers in these patients that could predict survival and thus aid decision making for selection of the most appropriate therapeutic palliative option. METHODS: In a prospective 4-year single-center study, 136 consecutive patients with obstructive pancreatic cancer and intraoperative diagnosis of nonresectable or disseminated pancreatic cancer underwent a palliative surgical bypass procedure. Potential factors predicting survival were evaluated. RESULTS: Ninety-eight patients had metastatic disease and 38 locally advanced disease. Surgical morbidity rate was 16 %, re-operation rate 1%, and overall in-hospital mortality 4%. Univariate analysis showed American Society of Anesthesiologists (ASA) score, pain, operation time, presence of metastasis, and levels of leukocytes, albumin, C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9 were associated significantly with survival. The multivariate analysis identified ASA score, presence of liver metastasis, pain, CA 19-9, and CEA levels as independent indicators for poor survival. Patients with none or 1 of these risk factors had a median survival of 13.5 months, whereas patients with 4 or 5 risk factors had a median survival of 3.5 months. CONCLUSIONS: The clinical markers identified predict poor outcome for patients with palliative bypass surgery and therefore aid the appropriate selection of either surgical bypass or endoscopic stenting in these patients.