AIM: Gold nanoparticles have attracted significant interest in cancer diagnosis and treatment. Herein, we evaluated the theranostic potential of dithiolated diethylenetriamine pentaacetic acid (DTDTPA) conjugated AuNPs (Au@DTDTPA) for CT-contrast enhancement and...
Area of Interest
FLIP: A Targetable Mediator of Resistance to Radiation in Non-Small Cell Lung Cancer
Resistance to radiotherapy due to insufficient cancer cell death is a significant cause of treatment failure in non-small cell lung cancer (NSCLC). The endogenous caspase-8 inhibitor FLIP is a critical regulator of cell death that is frequently overexpressed in NSCLC...
Resistance of Nonmelanoma Skin Cancer to Nonsurgical Treatments. Part II: Photodynamic Therapy, Vismodegib, Cetuximab, Intralesional Methotrexate, and Radiotherapy.
A wide range of treatments is now available for nonmelanoma skin cancer, including 5-fluorouracil, ingenol mebutate, imiquimod, diclofenac, photodynamic therapy, methotrexate, cetuximab, vismodegib, and radiotherapy. All are associated with high clinical and...
Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy
The anecdotal reports of promising results seen with immunotherapy and radiation in advanced malignancies have prompted several trials combining immunotherapy and radiation. However, the ideal timing of immunotherapy with radiation has not been clarified. Tumor...
Synergy of radiotherapy and PD-1 blockade in Kras-mutant lung cancer
Radiation therapy (RT), a critical modality in the treatment of lung cancer, induces direct tumor cell death and augments tumor-specific immunity. However, despite initial tumor control, most patients suffer from locoregional relapse and/or metastatic disease...
Tumor-derived CCL2 mediates resistance to radiotherapy in pancreatic ductal adenocarcinoma
Purpose: Local tumor growth is a major cause of morbidity and mortality in nearly 30% of patients with pancreatic ductal adenocarcinoma (PDAC). Radiotherapy (RT) is commonly used for local disease control in PDAC, but efficacy is limited. We studied the impact of...
A preclinical murine model for the early detection of radiation-induced brain injury using magnetic resonance imaging and behavioral tests for learning and memory: with applications for the evaluation of possible stem cell imaging agents and therapies.
Stem cell therapies are being developed for radiotherapy-induced brain injuries (RIBI). Magnetic resonance imaging (MRI) offers advantages for imaging transplanted stem cells. However, most MRI cell-tracking techniques employ superparamagnetic iron oxide particles (SPIOs), which are difficult to distinguish from hemorrhage. In current preclinical RIBI models, hemorrhage occurs concurrently with other injury markers. This makes the evaluation of the recruitment of transplanted SPIO-labeled stem cells to injury sites difficult. Here, we developed a RIBI model, with early injury markers reflective of hippocampal dysfunction, which can be detected noninvasively with MRI and behavioral tests. Lesions were generated by sub-hemispheric irradiation of mouse hippocampi with single X-ray beams of 80 Gy. Lesion formation was monitored with anatomical and contrast-enhanced MRI and changes in memory and learning were assessed with fear-conditioning tests. Early injury markers were detected 2 weeks after irradiation. These included an increase in the permeability of the blood-brain barrier, demonstrated by a 92 ± 20 % contrast enhancement of the irradiated versus the non-irradiated brain hemispheres, within 15 min of the administration of an MRI contrast agent. A change in short-term memory was also detected, as demonstrated by a 40.88 ± 5.03 % decrease in the freezing time measured during the short-term memory context test at this time point, compared to that before irradiation. SPIO-labeled stem cells transplanted contralateral to the lesion migrated toward the lesion at this time point. No hemorrhage was detected up to 10 weeks after irradiation. This model can be used to evaluate SPIO-based stem cell-tracking agents, short-term.
Ngen EJ, Wang L, Gandhi N, Kato Y, Armour M, Zhu W, Wong J, Gabrielson KL, Artemov D.
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Hypoxia Potentiates the Radiation-Sensitizing Effect of Olaparib in Human Non-Small Cell Lung Cancer Xenografts by Contextual Synthetic Lethality.
We proposed to exploit hypoxia-inducible factor (HIF)-1alpha overexpression in prostate tumours and use this transcriptional machinery to control the expression of the suicide gene cytosine deaminase (CD) through binding of HIF-1alpha to arrangements of hypoxia response elements. CD is a prodrug activation enzyme, which converts inactive 5-fluorocytosine to active 5-fluorouracil (5-FU), allowing selective killing of vector containing cells.
Laure Marignol, Ruth Foley, Thomas Southgate, Mary Coffey, Donal Hollywood and Mark Lawler
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The effect of irradiation on tumor microenvironment and bone marrow cell migration in a pre-clinical tumor model.
To characterize the tumor microenvironment after standard radiation therapy (SRT) and pulsed radiation therapy (PRT) in Lewis lung carcinoma (LLC) allografts.
Jonathan L Kane, Sarah A Krueger, Alaa Hanna, Thomas R Raffel, George D Wilson, Gerard J Madlambayan and Brian Marples
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