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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As our understanding of the molecular pathways driving tumorigenesis improves and more druggable targets are identified, we have witnessed a concomitant increase in the development and production of novel molecularly targeted agents. Radiotherapy is commonly used in...
DNA repair and G2-phase cell cycle checkpoint responses are involved in the manifestation of hyper-radiosensitivity (HRS). The low-dose radioresponse of MSH2 isogenic endometrial carcinoma cell lines was examined. Defects in cell cycle checkpoint activation and the DNA damage response in irradiated cells (0.2 Gy) were evaluated. HRS was expressed solely in MSH2+ cells and was associated with efficient activation of the early G2-phase cell cycle checkpoint. Maintenance of the arrest was associated with persistent MRE11, γH2AX, RAD51 foci at 2 h after irradiation. Persistent MRE11 and RAD51 foci were also evident 24 h after 0.2 Gy. MSH2 significantly enhances cell radiosensitivity to low dose IR.
Lynn Martin, Brian Marples, Anthony M Davies, Anne Atzberger, Connla Edwards, Thomas Lynch, Donal Hollywood and Laure Marignol
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The current Small Animal Radiation Research Platform (SARRP) is poor for localizing small soft tissue targets for irradiation or tumor models growing in a soft tissue environment. Therefore, an imaging method complementary to x-ray CT is required to localize the soft tissue target’s Center of Mass (CoM) to within 1 mm. In this paper, we report the development of an integrated x-ray/bioluminescence imaging/tomography (BLI/BLT) system to provide a pre-clinical, high resolution irradiation system. This system can be used to study radiation effects in small animals under the conebeam computed tomography (CBCT) imaging guidance by adding the bioluminescence imaging (BLI) system as a standalone system which can also be docked onto the SARRP. The proposed system integrates two robotic rotating stages and an x-ray source rated at maximum 130 kVp and having a small variable focal spot. A high performance and low noise CCD camera mounted in a light-tight housing along with an optical filter assembly is used for multiwavelength BL imaging and tomography. A three-mirror arrangement is implemented to eliminate the need of rotating the CCD camera for acquiring multiple views. The mirror system is attached to a motorized stage to capture images in angles between 0-90o (for the standalone system). C
S. Eslami ; Y. Yang ; J. Wong ; M. S. Patterson ; I. Iordachita
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In this study, we investigated the accuracy of using off-line bioluminescence imaging (BLI) and tomography (BLT) to guide irradiation of small soft tissue targets on a small animal radiation research platform (SARRP) with on-board cone beam CT (CBCT) capability. A...
PURPOSE: We have established a high-throughput Gafchromic film dosimetry protocol for narrow kilo-voltage beams in homogeneous and heterogeneous media for small-animal radiotherapy applications. The kV beam characterization is based on extensive Gafchromic film...
Preclinical studies of cranial radiation therapy (RT) using animal brain tumor models have been hampered by technical limitations in the delivery of clinically relevant RT. We established a bioimageable mouse model of glioblastoma multiforme (GBM) and an image-guided radiation delivery system that facilitated precise tumor localization and treatment and which closely resembled clinical RT. Our novel radiation system makes use of magnetic resonance imaging (MRI) and bioluminescent imaging (BLI) to define tumor volumes, computed tomographic (CT) imaging for accurate treatment planning, a novel mouse immobilization system, and precise treatments delivered with the Small Animal Radiation Research Platform. We demonstrated that, in vivo, BLI correlated well with MRI for defining tumor volumes. Our novel restraint system enhanced setup reproducibility and precision, was atraumatic, and minimized artifacts on CT imaging used for treatment planning. We confirmed precise radiation delivery through immunofluorescent analysis of the phosphorylation of histone H2AX in irradiated brains and brain tumors. Assays with an intravenous near-infrared fluorescent probe confirmed that radiation of orthografts increased disruption of the tumor blood-brain barrier (BBB). This integrated model system, which facilitated delivery of precise, reproducible, stereotactic cranial RT in mice and confirmed RT’s resultant histologic and BBB changes, may aid future brain tumor research.
Baumann BC, Benci JL, Santoiemma PP, Chandrasekaran S, Hollander AB, Kao GD, Dorsey JF.
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PURPOSE: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, and radiation is one of the main treatment modalities. However, cure rates remain low despite best available therapies. Immunotherapy is a promising modality that could work...
The commercially available X-ray fluoroscopy quality assurance phantom, the Leeds test object TOR18FG, was found to be suitable to assess T-ray image quality in the range (0.1-0.4) THz at a depth of 0.5 cm. Previous to this only custom made phantoms, made especially...