DTo investigate the impact of the 2 major DNA repair machineries on cellular survival in response to irradiation with the 2 types of ionizing radiation.
Anna Subiel, Giuseppe Schettino et al
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Radiation Research
Quantitative multiparametric MRI assessment of glioma response to radiotherapy in a rat model
BACKGROUND: The inability of structural MRI to accurately measure tumor response to therapy complicates care management for patients with gliomas. The purpose of this study was to assess the potential of several noninvasive functional and molecular MRI biomarkers for...
Theranostic gold nanoparticles modified for durable systemic circulation effectively and safely enhance the radiation therapy of human sarcoma cells and tumors
Radiation therapy (RT) is an integral component of the treatment of many sarcomas and relies on accurate targeting of tumor tissue. Despite conventional treatment planning and RT, local failure rates of 10% to 28% at 5 years have been reported for locally advanced,...
Hematopoietic Stem and Progenitor Cell Migration After Hypofractionated Radiation Therapy in a Murine Model.
To characterize the recruitment of bone marrow (BM)-derived hematopoietic stem and progenitor cells (HSPCs) within tumor microenvironment after radiation therapy (RT) in a murine, heterotopic tumor model.
Jonathan Kane, Sarah A. Krueger, Joshua T. Dilworth, John T. Torma, George D. Wilson, Brian Marples, Gerard J. Madlambayan
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microRNA-34a promotes DNA damage and mitotic catastrophe
Efficient and error-free DNA repair is critical for safeguarding genome integrity, yet it is also linked to radio- and chemoresistance of malignant tumors. miR-34a, a potent tumor suppressor, influences a large set of p53-regulated genes and contributes to...
Functional interrogation of adult hypothalamic neurogenesis with focal radiological inhibition
The functional characterization of adult-born neurons remains a significant challenge. Approaches to inhibit adult neurogenesis via invasive viral delivery or transgenic animals have potential confounds that make interpretation of results from these studies difficult....
Review of backscatter measurement in kilovoltage radiotherapy using novel detectors and reduction from lack of underlying scattering material
Lack of underlying material can lead to dose reduction in kilovoltage radiotherapy treatments because of backscatter reduction. Conversely, the use of lead shielding can lead to large dose enhancement close to the lead interface. GAFCHROMIC film has been shown to be...
Combined treatment effects of radiation and immunotherapy: studies in an autochthonous prostate cancer model.
PURPOSE: To optimize the combination of ionizing radiation and cellular immunotherapy using a preclinical autochthonous model of prostate cancer. METHODS AND MATERIALS: Transgenic mice expressing a model antigen under a prostate-specific promoter were treated using a...
Proteasome Inhibitors Block DNA Repair and Radiosensitize Non-Small Cell Lung Cancer.
Despite optimal radiation therapy (RT), chemotherapy and/or surgery, a majority of patients with locally advanced non-small cell lung cancer (NSCLC) fail treatment. To identify novel gene targets for improved tumor control, we performed whole genome RNAi screens to identify knockdowns that most reproducibly increase NSCLC cytotoxicity. These screens identified several proteasome subunits among top hits, including the topmost hit PSMA1, a component of the core 20 S proteasome. Radiation and proteasome inhibition showed synergistic effects. Proteasome inhibition resulted in an 80-90% decrease in homologous recombination (HR), a 50% decrease in expression of NF-κB-inducible HR genes BRCA1 and FANCD2, and a reduction of BRCA1, FANCD2 and RAD51 ionizing radiation-induced foci. IκBα RNAi knockdown rescued NSCLC radioresistance. Irradiation of mice with NCI-H460 xenografts after inducible PSMA1 shRNA knockdown markedly increased murine survival compared to either treatment alone. Proteasome inhibition is a promising strategy for NSCLC radiosensitization via inhibition of NF-κB-mediated expression of Fanconi Anemia/HR DNA repair genes.
Cron KR, Zhu K, Kushwaha DS, Hsieh G, Merzon D, Rameseder J, Chen CC, D’Andrea AD, Kozono D.
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