55 research outputs found
Advances in Biological Understanding of Tumor Radiation Resistance
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Radiation-induced and obesity dependent NK cell activities against metastatic breast cancer cells
<p><strong>Theoretical framework:</strong> Radiation therapy (RT) is one of the leading therapeutic approaches used in the management of metastatic breast cancer (BC). However, currently existing RT schedules are limited in their efficacy due to the impossibility to reach a curative radiation dose for killing of aggressive and radiation resistant carcinoma cells. Although high-LET irradiation could more efficiently eradicate therapy resistant carcinoma cells in comparison with photon-based RT, it is unclear whether it could also better mobilize immune cells for elimination of undifferentiated and radioresistant cancer stem cells (CSCs). Currently, overweight and obesity is an increasing problem that can diminish an efficacy of RT and alter immune response in patients with metastatic BC. Unfortunately, it is still unknown how adipocytes can contribute to the crosstalk between carcinoma and immune cells upon low- and high-LET radiation exposure.</p>
<p><strong>Research objectives:</strong> elucidation of the role of obese microenvironment in the regulation of cytotoxic activities of low- and high-LET ionizing radiations and NK cells against BC cells with enhanced metastatic properties. </p>
<p><strong>Methods:</strong> Low- and high-LET irradiation of luminal A and B BC cells with different invasive and migratory abilities, and NK cells in presence or absence of adipocytes obtained from pre-, menopausal, and postmenopausal women with different BMIs, will be used to determine adipocyte-dependent differences in radiation responses, alterations in pro-metastatic properties, and modulation of metabolic activities of the investigated BC cells.</p>
<p><strong>Level of originality and innovation:</strong> of the research project consists in an integrated approach of the evaluation of the crosstalk between metastatically-active luminal A BC and NK cells upon photon, proton, and carbon ion irradiation and obese circumstances. There are no reports on adipocyte responses to these kinds of irradiation. It is also unknown whether radiation response and susceptibility to NK lysis of BC cells with enhanced invasive and metastatic capacities can be affected by adipocytes during cell exposure to different kinds of irradiation. Pre-clinical data received during conducting of this project, can be translated into the clinical practice for the development of NK cell-based treatment approaches and novel targeted therapeutics modulating an influence of adipose tissues in luminal BC patients in the context of radiotherapy. </p>
<p><strong>Primary researchers involved:</strong> This is a joint project involving the researchers with different expertises: PI Ira Skvortsova (Austria) and her team (EXTRO-Lab members, Medical University of Innsbruck, Austria); collaborators: Christian Ploner (Medical University of Innsbruck, Austria), Slavisa Tubin (MedAustron, Wr. Neustadt, Austria); Monica Marchese, Olga Kofanova (IBBL, Luxembourg); Alessandra Bisio and Yari Ciribilli (CIBIO, University of Trento, Italy); Anahid Jewett (UCLA School of Dentistry, Los Angeles, USA).</p>
Predicting and Understanding Cancer Response to Treatment
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Book review: “Worlds of Japanese Culture” by Elena L. Skvortsova and Alexander L. Lutsky
The article examines the contents of the book “Worlds of Japanese Culture” by E.L. Skvortsova and A.L. Lutsky (Moscow, St. Petersburg: Center for Humanitarian Initiatives, 2025. 582 p. Series “Tree of Meanings.” ISBN 978-5-98712-499-4). The review outlines the main topics addressed by the authors of the book: the development of Japanese philosophy and sociology in the modern period, the problems faced by Japanese society in the 21st century, the essence and characteristic features of Japanese civilization. According to the author of the review, the book is a valuable contribution to the study of modern philosophy and culture of Japan as a whole
ETV7 regulates breast cancer stem-like cell features by repressing IFN-response genes
Abstract Cancer stem cells (CSCs) represent a population of cells within the tumor able to drive tumorigenesis and known to be highly resistant to conventional chemotherapy and radiotherapy. In this work, we show a new role for ETV7, a transcriptional repressor member of the ETS family, in promoting breast cancer stem-like cells plasticity and resistance to chemo- and radiotherapy in breast cancer (BC) cells. We observed that MCF7 and T47D BC-derived cells stably over-expressing ETV7 showed reduced sensitivity to the chemotherapeutic drug 5-fluorouracil and to radiotherapy, accompanied by an adaptive proliferative behavior observed in different culture conditions. We further noticed that alteration of ETV7 expression could significantly affect the population of breast CSCs, measured by CD44+/CD24low cell population and mammosphere formation efficiency. By transcriptome profiling, we identified a signature of Interferon-responsive genes significantly repressed in cells over-expressing ETV7, which could be responsible for the increase in the breast CSCs population, as this could be partially reverted by the treatment with IFN-β. Lastly, we show that the expression of the IFN-responsive genes repressed by ETV7 could have prognostic value in breast cancer, as low expression of these genes was associated with a worse prognosis. Therefore, we propose a novel role for ETV7 in breast cancer stem cells’ plasticity and associated resistance to conventional chemotherapy and radiotherapy, which involves the repression of a group of IFN-responsive genes, potentially reversible upon IFN-β treatment. We, therefore, suggest that an in-depth investigation of this mechanism could lead to novel breast CSCs targeted therapies and to the improvement of combinatorial regimens, possibly involving the therapeutic use of IFN-β, with the aim of avoiding resistance development and relapse in breast cancer
Cancer Stem Cells: What Do We Know about Them?
During past decades, survival rates in cancer patients have drastically improved due to the successful development of novel, promising chemical compounds and therapeutic schedules [...
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