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Articles 1 - 4 of 4
Full-Text Articles in Medicine and Health Sciences
Right Treatment Wrong Time: Immunotherapy Administration Post-Radiotherapy Decreases Tumor Burden In A Preclinical Model Of Brain Metastasis, Kathryn Elizabeth Blethen
Right Treatment Wrong Time: Immunotherapy Administration Post-Radiotherapy Decreases Tumor Burden In A Preclinical Model Of Brain Metastasis, Kathryn Elizabeth Blethen
Graduate Theses, Dissertations, and Problem Reports
This dissertation (a) provided an in-depth literature review of methods to modulate the blood-brain and blood-tumor barriers to increase drug delivery and efficacy in brain metastases, (b) evaluated the effects of whole-brain radiation therapy on the blood-brain barrier in immunocompetent and immunocompromised mouse models and proposed a mechanism by which the immune response to radiation disrupts the blood-brain barrier, and (c) developed a syngeneic lung cancer brain metastasis model to determine the impact of coordinated immunotherapy administration with radiotherapy. The blood-brain barrier is an impediment to drug delivery to the brain. The inherent leakiness of the blood-tumor barrier does not …
Exploiting Modulation Of The Blood-Brain And Blood-Tumor Barrier Permeability By Translational Focused Ultrasound For Therapeutic Delivery To Cns Metastases, Tasneem A. Arsiwala
Exploiting Modulation Of The Blood-Brain And Blood-Tumor Barrier Permeability By Translational Focused Ultrasound For Therapeutic Delivery To Cns Metastases, Tasneem A. Arsiwala
Graduate Theses, Dissertations, and Problem Reports
Transcranial low-intensity focused ultrasound is a unique technology to modulate the integrity of tight endothelial junctions and transiently increase BBB/BTB permeability to enhance therapeutic delivery. Despite promising early studies, present literature lacks agreement on key experimental conditions, which restricts our knowledge and the technique's widespread translation. This dissertation first provides a critical review of the current gaps in knowledge regarding the universal use of LiFUS in preclinical and clinical use. We then identify key parameters for translational and predictable opening of the BBB using a 3T MRI coupled with a clinical device. Our investigation highlights that passive permeability of the …
A Role For Endothelial Tissue-Nonspecific Alkaline Phosphatase In Blood-Tissue Barrier Health And Disease, Allison L. Brichacek
A Role For Endothelial Tissue-Nonspecific Alkaline Phosphatase In Blood-Tissue Barrier Health And Disease, Allison L. Brichacek
Graduate Theses, Dissertations, and Problem Reports
Sepsis is a disorder that targets the microcirculation with significant effects at blood-tissue barriers such as the blood-brain barrier (BBB) and gut-vascular barrier (GVB). Intestinal barrier dysfunction is thought to be one of the most important contributors to multi-organ dysfunction in sepsis. As a common site of infection, the impaired gut allows the dissemination of bacteria, which exacerbates the disease pathophysiology, and can lead to long-term morbidity and mortality. The mechanisms that influence altered barrier permeability in the GVB in sepsis and other inflammatory disorders are not well understood. Tissue-nonspecific alkaline phosphatase (TNAP) enzyme activity, which has been shown to …
Targeting The Cerebrovasculature In Sepsis: A Focus On The Brain Microvascular Endothelium, Divine C. Nwafor
Targeting The Cerebrovasculature In Sepsis: A Focus On The Brain Microvascular Endothelium, Divine C. Nwafor
Graduate Theses, Dissertations, and Problem Reports
The blood-brain barrier (BBB) is a critical interface between the systemic circulation and the brain. It is a specialized multicellular unit composed of brain microvascular endothelial cells (BMECs), pericytes, a basement membrane, and astrocytic end foot processes. BMECs are a principal component of the BBB that provide the structural framework needed for the stringent transport of molecules into the brain. BMEC dysfunction permits the trafficking of neurotoxins from systemic circulation into the brain, which ultimately exacerbates BBB dysfunction and neuroinflammation. Studies have shown that BBB dysfunction is a key determinant of cognitive decline in sepsis. However, there are critical knowledge …