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...
Exposure to hypoxia following irradiation increases radioresistance in prostate cancer cells.
Tumor hypoxia is a common feature of prostate tumors associated with the stabilization of hypoxia-inducible-factor 1alpha (HIF-1α) and poor prognosis following radiation therapy. Lack of oxygen at the time of irradiation is associated with radioresistance, but recent reports suggest radioresponse is also modulated by the dynamic nature of tumor hypoxia.
Derek Hennessey, Lynn Martin, Anne Atzberger, Thomas Lynch, Donal Hollywood and Laure Marignol
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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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Inhibition of Hsp27 Radiosensitizes Head-and-Neck Cancer by Modulating Deoxyribonucleic Acid Repair.
To present a novel method of tumor radiosensitization through Hsp27 knockdown using locked nucleic acid (LNA) and to investigate the role of Hsp27 in DNA double strand break (DSB) repair.
David M. Guttmann, Lori Hart, Kevin Du, Andrew Seletsky, Constantinos Koumenis
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Non-Melanoma Skin Cancer Incidence and Impact of Skin Cancer Screening on Incidence
Non-melanoma skin cancer (NMSC) is the most common malignancy, whose public health significance is often unrecognized. This analysis has two objectives: first, to provide up-to-date incidence estimates by sex, age group, histological type, and body site; and second,...