0000000000846870

AUTHOR

Giulia Federici

TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells

Metastatic growth in breast cancer (BC) has been proposed as an exclusive property of cancer stem cells (CSCs). However, formal proof of their identity as cells of origin of recurrences at distant sites and the molecular events that may contribute to tumor cell dissemination and metastasis development are yet to be elucidated. In this study, we analyzed a set of patient-derived breast cancer stem cell (BCSC) lines. We found that in vitro BCSCs exhibit a higher chemoresistance and migratory potential when compared with differentiated, nontumorigenic, breast cancer cells (dBCCs). By developing an in vivo metastatic model simulating the disease of patients with early BC, we observed that BCSCs…

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Key EU DEMO plant and building layout criteria

Abstract An early attention to the layout of both plant site and its buildings is essential in a complex plant under preliminary design as DEMO in order to meet the assigned targets, namely i) the licensing requirements ii) a good availability in delivery electricity to the grid. The layout definition has to follow several criteria that become more complex and stringent for nuclear buildings, e.g. functional, maintenance, fire protection, safety, human factors, shielding, and remote handling. The criterion As Low As Reasonable Achievable, with respect to the dose to the staff, has to be applied in design, operation, maintenance and decommissioning phases. The tokamak building, where several…

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Feasibility of D-D start-up under realistic technological assumptions for EU-DEMO

Abstract One of the main issues in view of the realization of a DEMOnstration fusion reactor is the availability of a sufficient external supply of tritium (T) to start operation. T is an unstable nuclide, which is almost absent in nature and is currently available as by-product in e.g. CANDU, whose operation in the next decades (both in terms of life extension of existing reactors and construction of new ones) is at the moment under debate. During DEMO operation, T will be generated on-site by breeding blanket, employing the neutrons originating from D-T reaction. However, it is considered that a certain initial amount of T is needed to start operation, the so-called start-up inventory. An…

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Erythropoietin activates cell survival pathways in breast cancer stem-like cells to protect them from chemotherapy

Abstract Recombinant erythropoietin (EPO) analogs [erythropoiesis-stimulating agents (ESA)] are clinically used to treat anemia in patients with cancer receiving chemotherapy. After clinical trials reporting increased adverse events and/or reduced survival in ESA-treated patients, concerns have been raised about the potential role of ESAs in promoting tumor progression, possibly through tumor cell stimulation. However, evidence is lacking on the ability of EPO to directly affect cancer stem–like cells, which are thought to be responsible for tumor progression and relapse. We found that breast cancer stem–like cells (BCSC) isolated from patient tumors express the EPO receptor and respond to …

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Proliferation state and polo-like kinase1 dependence of tumorigenic colon cancer cells.

Abstract Tumor-initiating cells are responsible for tumor maintenance and relapse in solid and hematologic cancers. Although tumor-initiating cells were initially believed to be mainly quiescent, rapidly proliferating tumorigenic cells were found in breast cancer. In colon cancer, the proliferative activity of the tumorigenic population has not been defined, although it represents an essential parameter for the development of more effective therapeutic strategies. Here, we show that tumorigenic colon cancer cells can be found in a rapidly proliferating state in vitro and in vivo, both in human tumors and mouse xenografts. Inhibitors of polo-like kinase1 (Plk1), a mitotic kinase essential fo…

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