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Articles 1 - 6 of 6
Full-Text Articles in Medicine and Health Sciences
Decreased Kidney Mitochondrial Content And Pgc-1Α Following Repeated Low-Dose Cisplatin-Induced Kidney Injury., Andrew Joseph Orwick
Decreased Kidney Mitochondrial Content And Pgc-1Α Following Repeated Low-Dose Cisplatin-Induced Kidney Injury., Andrew Joseph Orwick
Electronic Theses and Dissertations
Cisplatin is highly effective and one of the most commonly used chemotherapeutic agents in the treatment of a number of different solid organ tumors. Unfortunately, the dose-limiting nephrotoxicity occurs in up to 30% of patients, which requires alterations to treatment regimens that are often less effective. The kidney’s function is to provide fluid homeostasis, and this is an energy-intensive process. Proper renal function is dependent on functional mitochondria. PGC-1α regulates mitochondrial number, respiratory capacity, and mitochondrial proteins in proximal tubule cells. We delivered low-dose cisplatin to mice via intraperitoneal injections once a week for 4 weeks. The mice were then …
Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller
Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller
Electronic Theses and Dissertations
The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug …
A Clinically Relevant Mouse Model Of Cisplatin-Induced Kidney Injury., Cierra Nichole Sharp
A Clinically Relevant Mouse Model Of Cisplatin-Induced Kidney Injury., Cierra Nichole Sharp
Electronic Theses and Dissertations
Cisplatin is a potent chemotherapeutic used for the treatment of many solid cancers, including testicular, ovarian, and lung cancer. Cisplatin causes many adverse side effects, of which nephrotoxicity leading to acute kidney injury is dose-limiting. Approximately 30% of patients will develop nephrotoxicity with cisplatin, and will either have their next dose of cisplatin lowered, skipped, or be switched to a less nephrotoxic chemotherapeutic altogether. These outcomes are not ideal when trying to treat cancer. Previously, it was believed that patients could recover from cisplatin-induced acute kidney injury with little to no lasting effects, but recent longitudinal studies have shown this …
Inhibition Of Chemotherapeutic-Induced Apoptosis In Esophageal Squamous Cancer Cells By The Keystone Periodontal Pathogen, Porphyromonas Gingivalis., Atul Kumar Agrawal
Inhibition Of Chemotherapeutic-Induced Apoptosis In Esophageal Squamous Cancer Cells By The Keystone Periodontal Pathogen, Porphyromonas Gingivalis., Atul Kumar Agrawal
Electronic Theses and Dissertations
Recent evidence has shown that P. gingivalis, a Gram-negative, anaerobic oral bacterium, is negatively associated with the presence and outcome of esophageal squamous cell carcinoma (ESCC). While potential underlying mechanisms are yet to be established, P. gingivalis infection is known to inhibit apoptosis in gingival epithelial cells. Therefore, we hypothesized that P. gingivalis may also inhibit of the induction of apoptosis in human ESCC cells exposed to the commonly employed anti-ESCC chemotherapeutic agent, cisplatin. The capacity of P. gingivalis, at variant multiplicities of infection, to suppress cisplatin-induced necrosis and apoptosis in EC9706 ESCC cells was established by lactate …
Developing A More Clinically-Relevant Mouse Model Of Cisplatin-Induced Nephrotoxicity., Cierra N. Sharp
Developing A More Clinically-Relevant Mouse Model Of Cisplatin-Induced Nephrotoxicity., Cierra N. Sharp
Electronic Theses and Dissertations
Cisplatin is a nephrotoxic chemotherapeutic that causes acute kidney injury (AKI) in 30% of patients. Although recovery can occur after one episode of cisplatin-induced AKI, studies have indicated multiple episodes may lead to the development of chronic kidney disease (CKD), an irreversible disease with no current treatments. The standard mouse model of cisplatin-induced AKI consists of one, high dose of cisplatin (> 20 mg/kg) that is lethal to the animal three days later. This model doesn’t accurately reflect the repeated dosing regimen patients receive, and doesn’t allow for long-term outcome studies of pathologies associated with CKD. We have developed a …
Suramin Protects From Cisplatin-Induced Acute Kidney Injury., Tess Dupre
Suramin Protects From Cisplatin-Induced Acute Kidney Injury., Tess Dupre
Electronic Theses and Dissertations
In rodent models, suramin improves recovery following acute kidney injury (AKI). We hypothesized that suramin would be useful in protection against cisplatin-induced AKI. This hypothesis was tested by pre-treating C57BL/6j mice with suramin prior to cisplatin. Our data indicates that suramin protects the kidney from injury by decreasing cisplatininduced decreases in kidney function. Renal histology indicated that suramin significantly protected from cisplatin-induced AKI. Data indicate that suramin pretreatment attenuated mRNA expression of pro-inflammatory cytokines and chemokines following cisplatin treatment, while also decreasing markers of cell stress and cell death. We utilized the same experimental design with 10-month old FVB mice …