A subset of malignant mesothelioma tumors retain osteogenic potential

Malignant mesothelioma (MM) is an aggressive serosal tumor associated with asbestos exposure. We previously demonstrated that mesothelial cells differentiate into cells of different mesenchymal lineages and hypothesize that osseous tissue observed in a subset of MM patients is due to local differentiation of MM cells. In this study, the capacity of human and mouse MM cells to differentiate into osteoblast-like cells was determined in vitro using a functional model of bone nodule formation and in vivo using an established model of MM. Human and murine MM cell lines cultured in osteogenic medium expressed alkaline phosphatase and formed mineralized bone-like nodules. Several human and mouse MM cell lines also expressed a number of osteoblast phenotype markers, including runt-related transcription factor 2 (RUNX2), osteopontin, osteonectin and bone sialoprotein mRNA and protein. Histological analysis of murine MM tumors identified areas of ossification within the tumor, similar to those observed in human MM biopsies. These data demonstrate the ability of MM to differentiate into another mesenchymal cell type and suggest that MM cells may contribute to the formation of the heterologous elements observed in MM tumors

Diffusion weighted imaging of the breast:Performance of standardized breast tumor tissue selection methods in clinical decision making

Objectives In breast diffusion weighted imaging (DWI) protocol standardization, it is recently shown that no breast tumor tissue selection (BTTS) method outperformed the others. The purpose of this study is to analyze the feasibility of three fixed-size breast tumor tissue selection (BTTS) methods based on the reproducibility, accuracy and time-measurement in comparison to the largest oval and manual delineation in breast diffusion weighted imaging data. Methods This study is performed with a consecutive dataset of 116 breast lesions (98 malignant) of at least 1.0 cm, scanned in accordance with the EUSOBI breast DWI working group recommendations. Reproducibility of the maximum size manual (BTTS1) and of the maximal size round/oval (BTTS2) methods were compared with three smaller fixed-size circular BTTS methods in the middle of each lesion (BTTS3, 0.12 cm(3) volume) and at lowest apparent diffusion coefficient (ADC) (BTTS4, 0.12 cm(3); BTTS5, 0.24 cm(3)). Mean ADC values, intraclass-correlation-coefficients (ICCs), area under the curve (AUC) and measurement times (sec) of the 5 BTTS methods were assessed by two observers. Results Excellent inter- and intra-observer agreement was found for any BTTS (with ICC 0.88-0.92 and 0.92-0.94, respectively). Significant difference in ADCmean between any pair of BTTS methods was shown (p = Conclusion The performance of fixed-size BTTS methods, as a potential tool for clinical decision making, shows equal AUC but shorter ADC measurement time compared to manual or oval whole lesion measurements. The advantage of a fixed size BTTS method is the excellent reproducibility. A central fixed breast tumor tissue volume of 0.12 cm(3) is the most feasible method for use in clinical practice

Umbilical cord-mesenchymal stem cells induce a memory phenotype in CD4+ T cells

Inflammation is a physiological state where immune cells evoke a response against detrimental insults. Finding a safe and effective treatment for inflammation associated diseases has been a challenge. In this regard, human mesenchymal stem cells (hMSC), exert immunomodulatory effects and have regenerative capacity making it a promising therapeutic option for resolution of acute and chronic inflammation. T cells play a critical role in inflammation and depending on their phenotype, they can stimulate or suppress inflammatory responses. However, the regulatory effects of hMSC on T cells and the underlying mechanisms are not fully elucidated. Most studies focused on activation, proliferation, and differentiation of T cells. Here, we further investigated memory formation and responsiveness of CD4+ T cells and their dynamics by immune-profiling and cytokine secretion analysis. Umbilical cord mesenchymal stem cells (UC-MSC) were co-cultured with either αCD3/CD28 beads, activated peripheral blood mononuclear cells (PBMC) or magnetically sorted CD4+ T cells. The mechanism of immune modulation of UC-MSC were investigated by comparing different modes of action; transwell, direct cell-cell contact, addition of UC-MSC conditioned medium or blockade of paracrine factor production by UC-MSC. We observed a differential effect of UC-MSC on CD4+ T cell activation and proliferation using PBMC or purified CD4+ T cell co-cultures. UC-MSC skewed the effector memory T cells into a central memory phenotype in both co-culture conditions. This effect on central memory formation was reversible, since UC-MSC primed central memory cells were still responsive after a second encounter with the same stimuli. The presence of both cell-cell contact and paracrine factors were necessary for the most pronounced immunomodulatory effect of UC-MSC on T cells. We found suggestive evidence for a partial role of IL-6 and TGFβ in the UC-MSC derived immunomodulatory function. Collectively, our data show that UC-MSCs clearly affect T cell activation, proliferation and maturation, depending on co-culture conditions for which both cell-cell contact and paracrine factors are needed

High-resolution, High-sensitivity, Low-frequency uGMRT View of Coma Cluster of Galaxies

We present high-resolution, high-sensitivity upgraded Giant Metrewave Radio Telescope observations of the Coma cluster (A1656) at 250-500 MHz and 550-850 MHz. At 250-500 MHz, 135 sources have extensions >0.'45 (with peak-to-local-noise ratio >4). Of these, 24 sources are associated with Coma-member galaxies. In addition, we supplement this sample of 24 galaxies with 20 ram pressure stripped (RPS) galaxies from (Chen et al. 2020, eight are included in the original extended radio source sample) and an additional five are detected and extended. We present radio morphologies, radio spectra, spectral index maps, and equipartition properties for these two samples. In general, we find the equipartition properties lie within a narrow range (e.g., Pmin = 1-3 × 10- 13 dynes cm-2). Only NGC 4874, one of the two brightest central Coma cluster galaxies, has a central energy density and pressure about five times higher and a radio source age about 50% lower than that of the other Coma galaxies. We find a diffuse tail of radio emission trailing the dominant galaxy of the merging NGC 4839 group that coincides with the slingshot tail seen in X-rays. The southwestern radio relic, B1253+275, has a large extent ≍32' × 10' (≃1.08 × 0.34 Mpc2). For NGC 4789, whose long radio tails merge into the relic and may be a source of its relativistic seed electrons, we find a transverse radio spectral gradient, a steepening from southwest to northeast across the width of the radio source. Finally, radio morphologies of the extended and RPS samples suggest that these galaxies are on their first infall into Coma on (predominantly) radial orbits

Incidence of cancer in the area around Amsterdam Airport Schiphol in 1988–2003: a population-based ecological study

BACKGROUND: Amsterdam Airport Schiphol is a major source of complaints about aircraft noise, safety risks and concerns about long term adverse health effects, including cancer. We investigated whether residents of the area around Schiphol are at higher risk of developing cancer than the general Dutch population. METHODS: In a population-based study using the regional cancer registry, we estimated the cancer incidence during 1988–2003 in residents of the area surrounding Schiphol. We defined a study area based on aircraft noise contours and 4-digit postal code areas, since historical data on ambient air pollution were not available and recent emission data did not differ from the background urban air quality. RESULTS: In residents of the study area 13 207 cancer cases were diagnosed, which was close to the expected number, using national incidence rates as a reference (standardized incidence ratio [SIR] 1.02). We found a statistically significantly increased incidence of hematological malignancies (SIR 1.12, 95% confidence interval [CI]: 1.05, 1.19), mainly due to high rates for non-Hodgkin lymphoma (SIR 1.22, 95% CI: 1.12, 1.33) and acute lymphoblastic leukemia (SIR 1.34, 95% CI: 0.95, 1.83). The incidence of cancer of the respiratory system was statistically significantly decreased (SIR 0.94, 95% CI: 0.90, 0.99), due to the low rate in males (SIR 0.89). In the core zone of the study area, cancer incidence was slightly higher than in the remaining ring zone (rate ratio of the core zone compared to the ring zone 1.05, 95% CI 1.01, 1.10). This was caused by the higher incidence of cancer of the respiratory system, prostate and the female genital organs in the core zone in comparison to the ring zone. CONCLUSION: The overall cancer incidence in the Schiphol area was similar to the national incidence. The moderately increased risk of hematological malignancies could not be explained by higher levels of ambient air pollution in the Schiphol area. This observation warrants further research, for example in a study with focus on substances in urban ambient air pollution, as similar findings were observed in Greater Amsterdam

Citrus junos as a host of citrus bacterial canker

Following a request from the European Commission, the European Food Safety Authority (EFSA) Plant Health (PLH) Panel analysed a dossier submitted by the Japanese authorities in order to clarify the host status of Citrus junos with regard to Xanthomonas citri pv. citri and Xanthomonas citri pv. aurantifolii, causal agents of citrus bacterial canker, and to indicate whether C. junos fruit could represent a pathway for the introduction of citrus bacterial canker into the European Union. In a previous opinion in the year 2014, the EFSA PLH Panel concluded that commercial fresh citrus fruit is generally pathway and that no commercially important Citrus species or variety can be considered as immune to citrus bacterial canker. In the current assessment, the EFSA PLH Panel analysed the two scientific papers provided by the Japanese authorities, as well as 16 additional papers identified through a systematic literature review. The PLH Panel considered that the conclusions of its previous opinion remain valid and that convergent lines of evidence provide sufficient demonstration that C. junos is a host of X. citri pv. citri and X. citri pv. aurantifolii. Therefore, there is no reason to consider the C. junos fruit differently from other citrus species. Consequently, the assessment of the general citrus fruit pathway from the 2014 opinion still applies. Uncertainties on these conclusions are a result of the scarce scientific evidence published on this subject in addition to the methodological and reporting limitations of the published papers

Photodynamic Therapy of Tumors Can Lead to Development of Systemic Antigen-Specific Immune Response

Background: The mechanism by which the immune system can effectively recognize and destroy tumors is dependent on recognition of tumor antigens. The molecular identity of a number of these antigens has recently been identified and several immunotherapies have explored them as targets. Photodynamic therapy (PDT) is an anti-cancer modality that uses a non-toxic photosensitizer and visible light to produce cytotoxic reactive oxygen species that destroy tumors. PDT has been shown to lead to local destruction of tumors as well as to induction of anti-tumor immune response. Methodology/Principal Findings: We used a pair of equally lethal BALB/c colon adenocarcinomas, CT26 wild-type (CT26WT) and CT26.CL25 that expressed a tumor antigen, β-galactosidase (β-gal), and we treated them with vascular PDT. All mice bearing antigen-positive, but not antigen-negative tumors were cured and resistant to rechallenge. T lymphocytes isolated from cured mice were able to specifically lyse antigen positive cells and recognize the epitope derived from beta-galactosidase antigen. PDT was capable of destroying distant, untreated, established, antigen-expressing tumors in 70% of the mice. The remaining 30% escaped destruction due to loss of expression of tumor antigen. The PDT anti-tumor effects were completely abrogated in the absence of the adaptive immune response. Conclusion: Understanding the role of antigen-expression in PDT immune response may allow application of PDT in metastatic as well as localized disease. To the best of our knowledge, this is the first time that PDT has been shown to lead to systemic, antigen- specific anti-tumor immunity.United States. National Cancer Institute (grant RO1CA/AI838801)United States. National Cancer Institute (grant R01AI050875

Selective cancer-germline gene expression in pediatric brain tumors

Cancer-germline genes (CGGs) code for immunogenic antigens that are present in various human tumors and can be targeted by immunotherapy. Their expression has been studied in a wide range of human tumors in adults. We measured the expression of 12 CGGs in pediatric brain tumors, to identify targets for therapeutic cancer vaccines. Real Time PCR was used to quantify the expression of genes MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MAGE-C2, NY-ESO-1 and GAGE-1,2,8 in 50 pediatric brain tumors of different histological subtypes. Protein expression was examined with immunohistochemistry. Fifty-five percent of the medulloblastomas (n = 11), 86% of the ependymomas (n = 7), 40% of the choroid plexus tumors (n = 5) and 67% of astrocytic tumors (n = 27) expressed one or more CGGs. Immunohistochemical analysis confirmed qPCR results. With exception of a minority of tumors, the overall level of CGG expression in pediatric brain tumors was low. We observed a high expression of at least one CGG in 32% of the samples. CGG-encoded antigens are therefore suitable targets in a very selected group of pediatric patients with a brain tumor. Interestingly, glioblastomas from adult patients expressed CGGs more often and at significantly higher levels compared to pediatric glioblastomas. This observation is in line with the notion that pediatric and adult glioblastomas develop along different genetic pathways