Combining proton or photon irradiation with epothilone B : An in vitro study of cytotoxicity in human cancer cells

Recently, the use of proton beams in cancer therapy is becoming widespread, and tumour treatment modalities combining radiosensitizing chemical agents with irradiation are under investigation in order to achieve greater tumour local control and reduce the probability of distant failures. The combined treatment modality of radiation and the clinically relevant microtubule-stabilizing compound epothilone B is a promising approach for anticancer therapy. In the present study, we investigated the cytotoxicity of a spread out Bragg peak (SOBP) proton beam, as well as of 6 MV photons, in human glioblastoma (U251 MG) and lung adenocarcinoma (A549) cells pretreated for 24 h, or not, with epothilone B at concentrations of 0.125 and 0.075 nM respectively. Proton irradiation was performed at the middle position of an actively modulated SOBP (12\u201318 cm depth in water) and cell survival was evaluated by a colony forming assay. For both cell lines, survival curves after proton or photon irradiation alone showed linear quadratic behaviour with proton RBE (relative biological effectiveness), compared with photons at 10% survival, of 1.5 \ub1 0.2. Treatment of cells with epothilone B at subnanomolar concentration has an anticlonogenic effect. Furthermore, differently from the results found with radiation alone, the survival curves for the combined treatment epothilone B\u2013radiation showed a linear trend and analysis of the interaction of the two cytotoxic agents indicated a slight synergism. These data provide a radiobiological basis for further experiments, as well as clinical studies

Tamoxifen reduces plasma homocysteine levels in healthy women.

Treatment with tamoxifen is associated with reduced incidence of myocardial infarction. As plasma homocysteine is an independent risk factor for cardiovascular disease, we studied the effects of tamoxifen on plasma homocysteine in 66 healthy women participating in the Italian prevention trial of breast cancer who were randomized in a double-blind manner to tamoxifen 20 mg day(-1) or placebo for 5 years. They were aged between 35 and 70 years, had undergone previous hysterectomy for non-malignant conditions and had no contraindications to the use of tamoxifen. Plasma levels of total homocysteine (tHcy) were measured at randomization and after 2 and 6 months. The mean +/- s.d. plasma levels of tHcy were 7.59 +/- 1.71 micromol l(-1), 7.25 +/- 1.61 and 7.09 +/- 1.33 in the tamoxifen group and 8.07 +/- 2.06, 7.93 +/- 1.77 and 8.12 +/- 2.04 in the placebo group at 0, 2 and 6 months (P = 0.008 for the between-group difference over time). The higher the baseline tHcy level, the greater was the lowering effect of tamoxifen. No statistically significant effect of age, body mass index or smoking habit on baseline tHcy levels and its variation over time was found. In conclusion, tamoxifen (20 mg day(-1) for 6 months) decreased plasma tHcy levels in healthy women. This effect may contribute to its protective effect on myocardial infarction

Studies of Fricke-PVA-GTA xylenol orange hydrogels for 3D measurements in radiotherapy dosimetry

The Fricke gels (FG) composition has been modified over the years in order to improve their dosimetric characteristic for spatial dose evaluation in radiotherapy. Some problems, in particular those related to the diffusion of ferric ions in the gel matrix, have limited the clinical use of FG and still represent significant challenges for the scientific community working in the field of gel dosimetry. In this work, FG based on poly-vinyl alcohol (PVA) as the gelling agent, glutaraldehyde (GTA) as a cross-linker and FG based on gelatine loaded with silicate nano-clay (laponite) were developed with the aim to overcome the diffusion drawbacks affecting the traditional FG. Neither the sensitivity to the radiation dose nor the diffusion coefficient were significantly altered by the addition of laponite into the Fricke xylenol orange gel formulation employed. By contrast, lower diffusion rates were obtained with PVA-GTA gels, suggesting that this matrix could have a promising use in the field of 3D dosimetry

Shape resonance spectrum of cytosine-guanine pairs.

Single and double strand breaks in DNA can be caused by low-energy electrons, the most abundant secondary products of the interaction of ionizing radiation to the biological matter. Attachment of these electrons to biomolecules lead to the formation of transient negative ions (TNIs) [1], often referred to as resonances, a process that may lead to significant vibrational excitation and dissociation. In the present study, we employ the parallel version [2] of the Schwinger Multichannel Method implemented with pseudopotentials [3] to obtain the shape resonance spectrum of cytosine-guanine (CG) pairs, with special attention to π* transient anion states. Recent experimental studies pointed out a quasi-continuum vibrational excitation spectrum for electron collisions against formic acid dimers [4], suggesting that electron attachment into π* valence orbitals could induce proton transfer in these dimers. In addition, our previous studies on the shape resonance spectra of the hydrogen-bonded complexes comprising formic acid and formamide units indicated interesting electron delocalization (localization) effects arising from the presence (absence) of inversion symmetry centers in the complexes [5]. In the present work, we extend the studies on hydrogen-bonded complexes to the CG pair, where localization of ¼¤ anions would be expected, based on the previous results.\ud References\ud [1]. B. Boudaïffa, P. Cloutier, D. Hunting, M. A. Huels, L. Sanche, Science 287, 1658 (2000).\ud [2]. J. S. dos Santos, R. F. da Costa , M. T. do N. Varella, J. Chem. Phys. 136, 084307 (2012).\ud [3]. M. H. F. Bettega, L. G. Ferreira, M. A. P. Lima, Phys. Rev. A 47, 1111 (1993).\ud [4]. M. Allan, Phys. Rev. Lett. 98, 123201 (2007).\ud [5]. T. C. Freitas, S. dA. Sanchez, M. T. do N. Varella, M. H. F. Bettega, Phys. Rev. A 84, 062714 (2011).CNPqFAPESPFundação Araucári

Genotypic variability and antifungal susceptibility of Candida spp. isolated from hospital surfaces and hands of healthcare professionals

Objectives Candida spp. are responsible for 9095% of hematogenous fungal infections. In Brazil and Latin America, C. albicans is the most common specie, followed by C. parapsilosis and C. tropicalis. Infections caused by Candida spp. may have their origin in exogenous sources, transmitted to patients via contaminated infusions, biomedical devices or even by the hands of the hospital staff members. Molecular biology techniques such as Randomly Amplified Polymorphic DNA (RAPD) can show that the strains found in anatomical sites or abi- otic surfaces have the same pattern genome.Moreover, in the last decades it has been observed increasing the number of yeasts isolated from hospital environment resistant to antifungals. Thus, the aim of this study was to determine the susceptibility to antifungals and intraspecies similarity among isolates of different hospital surfaces and hands of healthcare professionals. Methods The study was conducted with 25 isolates of Candida spp.: 5 strains of C. albicans and 5 strains of C. parapsilosis isolated from hospital surfaces. 5 strains of C. albicans, 5 strains of C. parapsilosis and 5 strains of C. tropicalis isolated from hands of healthcare professionals. Professionals and surfaces belonged to intensive care units. The minimal inhibitory concentration (MIC) was determined to voriconazole (VOR), fluconazole (FLZ), amphotericin B (AMB) and micafungin (MFG) according to M27-A3 of the Clinical and Labora- tory Standards Institute (CLSI). To determine the intra-species similarity, 3 primers were used: P4 (50 -AAGAGCCCGT-30 ), OPA-18 (50AGCTGACCGT30) and OPE-18 (50GGACTGCAGA 30). RAPD pro- files were analyzed using BioNumerics software version 4.6. The study was approved by the Ethics in research involving human subjects, CAAE 0448.0.093.000-11 protocol. Results In relation to susceptibility testing (Table 1), it is important to highlight that C. parapsilosis showed 80% of MFG resistance. C. albicans and C. tropicalis showed reduced susceptibility to VOR, and resistence of the AMB was observed for C. albicans (20%). All amplifi- cations revealed distinct polymorphic bands. Genetic distances between each of the isolates were calculated and cluster analysis was used to generate a dendrogram showing relationships between them. The analysis of all primers showed similarity greater than 80% between strains of hands and hospital surfaces for intraspecies. Conclusion Our work shows that, healthy people and hospital surfaces may be colonized by different species yeast. Furthermore, the strains studied had relative resistance to antifungal drugs most frequently used in clinical practice. Finally, there was a high similarity between samples from hands (hospital staff members) and surfaces, providing an infection risk to susceptible individuals. Healthy people working in hospitals can carry yeasts on their hands with the same potential virulence, and which therefore offer the same risk of infection. This information should be considered when preventive measures are established. Attention to the colonization of hands and surfaces should not be restricted to high-risk units such as NICUs, but should also include other sections of hospitals

Novel Electron Spectroscopy of Tenuously and Weakly Bound Negative Ions

A novel method is proposed that uses very slow electron elastic collisions with atoms to identify their presence through the observation of tenuously bound (electron impact energy, E<0.1 eV) and weakly bound (E<1 eV) negative ions, formed as Regge resonances during the collisions.Comment: 4pages, 3figure

Experimental and theoretical electron-scattering cross- section data for dichloromethane

We report on a combination of experimental and theoretical investigations into the elastic differential cross sections (DCSs) and integral cross sections for electron interactions with dichloromethane, CH₂Cl₂, in the incident electron energy over the 7.0-30 eV range. Elastic electron-scattering cross-section calculations have been performed within the framework of the Schwinger multichannel method implemented with pseudopotentials (SMCPP), and the independent-atom model with screening-corrected additivity rule including interference-effects correction (IAM-SCAR+I). The present elastic DCSs have been found to agree reasonably well with the results of IAM-SCAR+I calculations above 20 eV and also with the SMC calculations below 30 eV. Although some discrepancies were found for 7 eV, the agreement between the two theoretical methodologies is remarkable as the electron-impact energy increases. Calculated elastic DCSs are also reported up to 10000 eV for scattering angles from 0⁰ to 180⁰ together with total cross section within the IAM-SCAR+I framework

BNCT dosimetry: peculiarities and methods

Dosimetry in tissue exposed to the epithermal neutron beams utilized for BNCT is complex, due to the multiplicity of the possible neutron reactions and consequently of the secondary radiation that contains photons, charged particles and recoil nuclei. Owing to the different radiobiological effectiveness of the various components of the absorbed dose, it is necessary to attain the evaluation of each of them. In addition, the spatial distributions of these dose components changes considerably with size and shape of the irradiated volume. Therefore, BNCT dosimetry requires suitably developed calculations and experimental methods. In this work, Monte Carlo simulations in phantoms of different sizes and shapes have been developed. Experimental methods for separating the dose components, mainly based on gel dosimeters and thermoluminescence detectors, have been applied. Moreover, the change in the absorbed dose resulting from the addition of 157Gd was investigated. Both measurements and calculations have been done with the BNCT epithermal beam of the LVR-15 reactor

Role of maternal diet in the risk of childhood acute leukemia: a systematic review and meta-analysis

Many studies have investigated the etiology of acute leukemia, one of the most common types of cancer in children; however, there is a lack of clarity regarding preventable risk factors. This systematic review and meta-analysis aimed to summarize the current evidence regarding the role of maternal dietary factors in the development of childhood leukemia. All epidemiological studies published until July 2022 that evaluated maternal dietary risk factors for childhood acute leukemia were identified in two electronic databases (PubMed and Web of Science) without limits of publication year or language. A total of 38 studies (1 prospective cohort study, 34 case-control studies and 3 studies with pooled analysis) were included. The published risk estimates were combined into a meta-analysis, using the Generic Inverse Variance method. The maternal consumption of fruits (two or more daily servings vs. less) was inversely associated with acute lymphoblastic leukemia (odds ratio = 0.71; 95% CI, 0.59–0.86), whereas maternal coffee intake (higher than two cups per day vs. no consumption) was associated with an increased risk of acute lymphoblastic leukemia (odds ratio = 1.45; 95% CI, 1.12–1.89). Despite these findings, more high-quality research from cohort studies and the identification of causal factors are needed to develop evidence-based and cost-effective prevention strategies applicable at the population level. Review Registration: PROSPERO registration no. CRD42019128937

Time-resolved diffuse optical tomography for non-invasive flap viability assessment: Pre-clinical tests on rats

We present a new setup for time-resolved diffuse optical tomography based on multiple source-detector acquisitions analysed by means of the Mellin-Laplace transform. The proposed setup has been used to perform pre-clinical measurements on rats in order to show its suitability for non-invasive assessment of flap viability