Ines M Costa, George Firth, Jana Kim, Giuseppe Schettino, Gilbert O Fruhwirth, Samantha Y.A. Terry

In vitro and preclinical systematic dose-effect studies of Auger electron- and beta particle-emitting radionuclides and external beam radiation for cancer treatment

Despite a rise in clinical use of radiopharmaceutical therapies, the biological effects of radionuclides and their relationship with absorbed radiation dose are poorly understood. Here, we set out to define this relationship for Auger electron-emitters [99mTc]TcO4 and [123I]I, and β−-particle-emitter [188Re]ReO4. Studies were carried out using genetically-modified cells that permitted direct radionuclide comparisons.

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Roarke A. Kamber, Yoko Nishiga, Bhek Morton, Allison M. Banuelos, Amira A. Barkal, Felipe Vences-Catalán, Mingxin Gu, Daniel Fernandez, Jose A.Seoane, David Yao, Katherine Liu, Sijie Lin, Kaitlyn Spees, Christina Curtis, Livnat Jerby-Arnon, Irving L. Weissman, Julien Sage, Michael C. Bassik

Inter-cellular CRISPR screens reveal regulators of cancer cell phagocytosis

Monoclonal antibody therapies targeting tumor antigens drive cancer cell elimination in large part by triggering macrophage phagocytosis of cancer cells1–7. However, cancer cells evade phagocytosis using mechanisms that are incompletely understood. Here we develop a platform for unbiased identification of factors that impede antibody-dependent cellular phagocytosis (ADCP) using complementary genome-wide CRISPR knockout and overexpression screens in both cancer cells and macrophages. In cancer cells, beyond known factors such as CD47, we identify many regulators of susceptibility to ADCP, including the poorly characterized enzyme adipocyte plasma membrane-associated protein (APMAP).

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L.M. Smith, H.E. Greenwood, W.E. Tyrrell, R.S. Edwards, V. de Santis, F. Baark, G. Firth, M. Tanc, S. Y. A. Terry, A. Herrmann, R. Southworth, T. H. Witney

The chicken chorioallantoic membrane as a low-cost, high-throughput model for cancer imaging

Mouse models are invaluable tools for radiotracer development and validation. They are, however, expensive, low throughput, and are constrained by animal welfare considerations. Here, we assessed the chicken chorioallantoic membrane (CAM) as an alternative to mice for preclinical cancer imaging studies.

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Satoshi Yamaga, Atsushi Murao, Gaifeng Ma, Max Brenner, Monowar Aziz, and Ping Wang.

Radiation upregulates macrophage TREM-1 expression to exacerbate injury in mice

Exposure to high-dose ionizing radiation causes tissue injury, infections and even death due to immune dysfunction. The triggering receptor expressed on myeloid cells-1 (TREM-1) has been demonstrated to critically amplify and dysregulate immune responses. However, the role of TREM-1 in radiation injury remains unknown. Extracellular cold-inducible RNA-binding protein (eCIRP), a new damage-associated molecular pattern, is released from activated or stressed cells during inflammation. We hypothesized that ionizing radiation upregulates TREM-1 expression via eCIRP release to worsen survival.

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Laurel B. Darragh, Jacob Gadwa, Tiffany T. Pham, Benjamin Van Court, Brooke Neupert, Nicholas A. Olimpo, Khoa Nguyen, Diemmy Nguyen, Michael W. Knitz, Maureen Hoen, Sophia Corbo, Molishree Joshi, Yonghua Zhuang, Maria Amann, Xiao-Jing Wang, Steven Dow, Ross M. Kedl, Von Samedi, Mary-Keara Boss & Sana D. Karam

Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors

In the setting of conventional radiation therapy, even when combined with immunotherapy, head and neck cancer often recurs locally and regionally. Elective nodal irradiation (ENI) is commonly employed to decrease regional recurrence. Given our developing understanding that immune cells are radiosensitive, and that T cell priming occurs in the draining lymph nodes (DLNs), we hypothesize that radiation therapy directed at the primary tumor only will increase the effectiveness of immunotherapies

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I. Chiver, E. B. dos Santos, S. Valle, F. Lallemand, C. A. Cornil, G. F. Ball & J. Balthazart

Effects of the depletion of neural progenitors by focal X-ray irradiation on song production and perception in canaries

The song control nucleus HVC of songbirds has emerged as a widespread model system to study adult neurogenesis and the factors that modulate the incorporation of new neurons, including seasonal state, sex differences or sex steroid hormone concentrations. However, the specific function of these new neurons born in adulthood remains poorly understood. We implemented a new procedure based on focal X-ray irradiation to deplete neural progenitors in the ventricular zone adjacent to HVC and study the functional consequences.

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I. Gertsenshteyn, B. Epel, M. Giurcanu, E. Barth, J. Lukens, K. Hall, J. F. Martinez, M. Grana, M. Maggio, R. C. Miller, S. V. Sundramoorthy, M. Krzykawska-Serda, E. Pearson, B. Aydogan, R. R. Weichselbaum, V. M. Tormyshev, M. Kotecha, and H. J. Halpern.

Absolute Oxygen-Guided Radiation Therapy Improves Tumor Control in Three Preclinical Tumor Models

Clinical attempts to find benefit from specifically targeting and boosting resistant hypoxic tumor subvolumes have been promising but inconclusive. While a first preclinical murine tumor type showed significant improved control with hypoxic tumor boosts, a more thorough investigation of efficacy from boosting hypoxic subvolumes defined by electron paramagnetic resonance oxygen imaging (EPROI) is necessary. The present study confirms improved hypoxic tumor control results in three different tumor types using a clonogenic assay and explores potential confounding experimental conditions.

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L.M. Wang R. Yadav, M. Serban, O. Arias, J. Seuntjens, N. Ybarra

Validation of an orthotopic non-small cell lung cancer mouse model, with left or right tumor growths, to use in conformal radiotherapy studies

Orthotopic non-small cell lung cancer (NSCLC) mice models are important for establishing translatability of in vitro results. However, most orthotopic lung models do not produce localized tumors treatable by conformal radiotherapy (RT). Here we report on the performance of an orthotopic mice model featuring conformal RT treatable tumors following either left or right lung tumor cell implantation.

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J. Caravaca, R. Peter, J. Yang, C. Gunther, J. Antonio Camara Serrano, C. Nostrand, V. Sterri and Y. Seo

Comparison and calibration of dose delivered by 137Cs and X-ray irradiators in mice

The Office of Radiological Security, U.S. Department of energy's National Nuclear Security Administration, is implementing a radiological risk reduction program which seeks to minimize or eliminate the use of high activity radiological sources, including 137Cs, by replacing them with non-radioisotopic technologies, such as x-ray irradiators. The main goal of this paper is to evaluate the equivalence of the dose delivered by gamma- and x-ray irradiators in mice sing experimental measurements and Monte Carlo simulations.

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J.S Eakins, B. Afrough, R.Hewson

Monte Carlo modelling of an x-ray chamber for providing inactivation exposures to viruses

The Monte Carlo radiation transport code MCNP6 has been used to model dosimetry for biological pathogen samples

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