PARP inhibitors affect growth, survival and radiation susceptibility of human alveolar and embryonal rhabdomyosarcoma cell lines

PARP inhibitors (PARPi) are used in a wide range of human solid tumours but a limited evidence is reported in rhabdomyosarcoma (RMS), the most frequent childhood soft-tissue sarcoma. The cellular and molecular effects of Olaparib, a specific PARP1/2 inhibitor, and AZD2461, a newly synthesized PARP1/2/3 inhibitor, were assessed in alveolar and embryonal RMS cells both as single-agent and in combination with ionizing radiation (IR)

Malassezia furfur bloodstream infection: still a diagnostic challenge in clinical practice

The opportunistic fungus Malassezia furfur (M. furfur) can cause either cutaneous or systemic infections. We report a case of M. furfur fungemia in a 22-year-old male with T-cell Acute Lymphoblastic Leukemia (T-ALL) who developed concomitant Bacillus cereus (B. cereus) septicemia. The fungal infection was diagnosed by microscopic examination and culture-based methods, while automated blood culture systems and molecular approaches failed in identifying the fungus. Despite appropriate therapy, the patient died 18 days after the hospitalization

Otx015 epi‐drug exerts antitumor effects in ovarian cancer cells by blocking gnl3‐mediated radioresistance mechanisms: Cellular, molecular and computational evidence

Ovarian cancer (OC) is the most aggressive gynecological tumor worldwide and, notwithstanding the increment in conventional treatments, many resistance mechanisms arise, this leading to cure failure and patient death. So, the use of novel adjuvant drugs able to counteract these pathways is urgently needed to improve patient overall survival. A growing interest is focused on epigenetic drugs for cancer therapy, such as Bromodomain and Extra‐Terminal motif inhibitors (BETi). Here, we investigate the antitumor effects of OTX015, a novel BETi, as a single agent or in combination with ionizing radiation (IR) in OC cellular models. OTX015 treatment significantly reduced tumor cell proliferation by triggering cell cycle arrest and apoptosis that were linked to nucleolar stress and DNA damage. OTX015 impaired migration capacity and potentiated IR effects by reducing the expression of different drivers of cancer resistance mechanisms, including GNL3 gene, whose expression was found to be significantly higher in OC biopsies than in normal ovarian tissues. Gene specific knocking down and computational network analysis confirmed the centrality of GNL3 in OTX015‐mediated OC antitumor effects. Altogether, our findings suggest OTX015 as an effective option to improve therapeutic strategies and overcome the development of resistant cancer cells in patients with OC

Transitional ‘hospital to home’ care of older patients: healthcare professionals’ perspectives

Author's accepted version (postprint).This is an Accepted Manuscript of an article published by Wiley in Scandinavian Journal of Caring Sciences on 27/08/2020.Available online: https://onlinelibrary.wiley.com/doi/epdf/10.1111/scs.12904acceptedVersio

Treatment cost and life expectancy of diffuse large B-cell lymphoma (DLBCL) : a discrete event simulation model on a UK population-based observational cohort

Background Diffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma. Previous studies examining the cost of treating DLBCL have generally focused on specific first-line therapy alone; meaning that their findings can neither be extrapolated to the general patient population nor to other points along the treatment pathway. Based on empirical data from a representative population-based patient cohort, the objective of this study was to develop a simulation model that could predict costs and life expectancy of treating DLBCL. Methods All patients newly diagnosed with DLBCL in the UK’s population-based Haematological Malignancy Research Network (www.hmrn.org) in 2007 were followed until 2013 (n=271). Mapped treatment pathways, alongside cost information derived from the National Tariff 2013/14, were incorporated into a patient level simulation model in order to reflect the heterogeneities of patient characteristics and treatment options. The NHS and social services perspective was adopted, and all outcomes were discounted at 3.5% per annum. Results Overall, the expected total medical costs were £22,122 for those treated with curative intent, and £2,930 for those managed palliatively. For curative chemotherapy, the predicted medical costs were £14,966, £23,449 and £7,376 for first, second, and third line treatments, respectively. The estimated annual cost for treating DLBCL across the UK was around £88-92 million. Conclusions This is the first cost modelling study using empirical data to provide ‘real world’ evidence throughout the DLBCL treatment pathway. Future application of the model could include evaluation of new technologies/treatments to support healthcare decision makers, especially in the era of personalised medicine

The genomes of four tapeworm species reveal adaptations to Parasitism

Tapeworms (Cestoda) cause neglected diseases that can be fatal and are difficult to treat, owing to inefficient drugs. Here we present an analysis of tapeworm genome sequences using the human-infective species Echinococcus multilocularis, E. granulosus, Taenia solium and the laboratory model Hymenolepis microstoma as examples. The 115- to 141-megabase genomes offer insights into the evolution of parasitism. Synteny is maintained with distantly related blood flukes but we find extreme losses of genes and pathways that are ubiquitous in other animals, including 34 homeobox families and several determinants of stem cell fate. Tapeworms have specialized detoxification pathways, metabolism that is finely tuned to rely on nutrients scavenged from their hosts, and species-specific expansions of non-canonical heat shock proteins and families of known antigens. We identify new potential drug targets, including some on which existing pharmaceuticals may act. The genomes provide a rich resource to underpin the development of urgently needed treatments and control.Fil: Tsai, Isheng J.. Wellcome Trust Genome Campus; Estados Unidos. University of Miyazaki; JapónFil: Zarowiecki, Magdalena. Wellcome Trust Genome Campus; Estados UnidosFil: Holroyd, Nancy. Wellcome Trust Genome Campus; Estados UnidosFil: Garciarrubio, Alejandro. Universidad Nacional Autónoma de México; MéxicoFil: Sanchez Flores, Alejandro. Wellcome Trust Genome Campus; Estados Unidos. Universidad Nacional Autónoma de México; MéxicoFil: Camicia, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Cucher, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Kamenetzky, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Macchiaroli, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Rosenzvit, Mara Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Liu, Kan. Chinese Academy of Sciences; República de ChinaFil: Luo, Xuenong. Chinese Academy of Agricultural Sciences; ChinaFil: Luo, Yingfeng. Chinese Academy of Sciences; República de ChinaFil: Nichol, Sarah. Wellcome Trust Genome Campus; Estados UnidosFil: Paps, Jordi. University of Oxford; Reino UnidoFil: Parkinson, John. University of Toronto; CanadáFil: Pouchkina Stantcheva, Natasha. Natural History Museum; Reino UnidoFil: Riddiford, Nick. Natural History Museum; Reino UnidoFil: Salinas, Gustavo. Universidad de la República; UruguayFil: Wasmuth, James D.. University of Calgary; CanadáFil: Zamanian, Mostafa. McGill University; CanadáFil: Zheng, Yadong. Chinese Academy of Agricultural Sciences; ChinaFil: The Taenia Solium Genome Consortium. No especifica;Fil: Cai, Xuepeng. Chinese Academy of Agricultural Sciences; ChinaFil: Soberón, Xavier. Universidad Nacional Autónoma de México; México. Instituto Nacional de Medicina Genómica; MéxicoFil: Olson, Peter D.. Natural History Museum; Reino UnidoFil: Laclette, Juan P.. Universidad Nacional Autónoma de México; MéxicoFil: Brehm, Klaus. Universität Würzburg; AlemaniaFil: Berriman, Matthew. Wellcome Trust Genome Campus; Estados Unido