66 research outputs found

    Scurvy presenting as vulvar folliculitis, a case report and review of the literature

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    This case examines clinical features and care of a patient with scurvy presenting with vulvar folliculitis

    Where It’s at Really Matters: In Situ In Vivo Vascular Endothelial Growth Factor Spatially Correlates with Electron Paramagnetic Resonance pO2 Images in Tumors of Living Mice

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    Purpose: Tumor microenvironments show remarkable tumor pO_{2} heterogeneity, as seen in prior EPR pO_{2} images (EPROI). pO_{2} correlation with hypoxia response proteins is frustrated by large rapid pO2 changes with position. Procedures: To overcome this limitation, biopsies stereotactically located in the EPROI were used to explore the relationship between vascular endothelial growth factor A (VEGF) concentrations in living mouse tumors and the local EPROI pO_{2}. Results: Quantitative ELISA VEGF concentrations correlated (p = 0.0068 to 0.019) with mean pO_{2}, median pO_{2}, and the fraction of voxels in the biopsy volume with pO_{2} less than 3, 6, and 10 Torr. Conclusions: This validates EPROI hypoxic fractions at the molecular level and provides a new paradigm for the assessment of the relationship, in vivo, between hypoxia and hypoxia response proteins. When translated to human subjects, this will enhance understanding of human tumor pathophysiology and cancer response to therapy

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    Radiation oxygen biology with pulse electron paramagnetic resonance imaging in animal tumors

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    The reduced oxygen in tumors (hypoxia) generates radiation resistance and limits tumor control probability (TCP) at radiation doses without significant normal tissue complication. Modern radiation therapy delivery with intensity modulated radiation therapy (IMRT) enables complex, high dose gradient patterns, which avoid sensitive human tissues and organs. EPR oxygen images may allow selection of more resistant parts of a tumor to which to deliver more radiation dose to enhance TCP. EPR O(2) images are obtained using injected narrow line, low relaxation rate trityl spin probes that enable pulse radiofrequency EPR O(2) images of tumors in the legs of mice, rats, and rabbits, the latter exceeding 4 cm in size. Low relaxation rates of trityls have enabled novel T(1), rather than T(2), based oxymetry, which provides near absolute pO(2) imaging. Tomographic image formation and filtered back projection reconstruction are used to generate these images with fixed, linear stepped gradients. Images obtained both with T(2) and T(1) oxymetric images have demonstrated the complex in vivo mechanism explaining the unexpected efficacy of TNFerade, a radiation inducible adenoviral construct to locally produce TNF induced vascular as well as radiation damage [1,2]. The unexpected efficacy of large dose radiation fractions is seen to be due to an interaction between host microvasculature and tumor cells producing a prompt (15 minute) post radiation hypoxia, paralyzing tumor cell repair and sensitizing tumors. Finally, cure of tumors treated to a single 50% control dose shows a significant dependence on EPR O(2) image hypoxic fractions, best shown with the fraction of voxels less than 10 torr (HF10). We show that these O(2) images provide a quantitative basis for measuring tumor and normal tissue response to abnormally low O(2) levels. Measurements of vascular endothelial growth factor (VEGF) production in a specific syngeneic mouse fibrosarcoma , FSa vs. fraction of tissue voxels with pO(2) less than 10 torr produced a slope of 0.14 pgVEGF protein/mg total protein/% HF10. We argue that this quantification may be diagnostic of tumor vs. normal tissue, and it may be etiologic in the development of malignancy
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