Biomedical subjects

Zoe A Stewart

Publications and source records attributed to Zoe A Stewart.

5 recordsLinked to original sources

PubMed2015

Ferret and pig models of cystic fibrosis: prospects and promise for gene therapy.

Large animal models of genetic diseases are rapidly becoming integral to biomedical research as technologies to manipulate the mammalian genome improve. The creation of cystic fibrosis (CF) ferrets and pigs is an example of such progress in animal modeling, with the disease phenotypes in the ferret and pig models more reflective of human CF disease than mouse models. The ferret and pig CF models also provide unique opportunities to develop and assess the effectiveness of gene and cell therapies to treat affected organs. In this review, we examine the organ disease phenotypes in these new CF models and the opportunities to test gene therapies at various stages of disease progression in affected organs. We then discuss the progress in developing recombinant replication-defective adenoviral, adeno-associated viral, and lentiviral vectors to target genes to the lung and pancreas in ferrets and pigs, the two most affected organs in CF. Through this review, we hope to convey the potential of these new animal models for developing CF gene and cell therapies.

Animals↗

PubMed2006

Successful transplantation of cadaveric polycystic liver: case report and review of the literature.

The number of candidates awaiting liver transplantation continues to exceed the available donor organ pool. This steadily increasing donor organ shortage calls for the widening of selection criteria for potential donor organs. Strategies to increase the number of liver allografts include liver splitting, use of donors over 70 years, use of steatotic donor livers, and reutilization of liver allografts after brain death of the first recipient. We report the successful use of a polycystic donor liver and review the experience with this donor population. We propose that the selective use of polycystic donor livers containing small (<5 cm) cysts with preserved liver parenchyma is safe and appropriate.

Cadaver↗

PubMed2005

25-hydroxyvitamin D deficiency is a risk factor for symptoms of postoperative hypocalcemia and secondary hyperparathyroidism after minimally invasive parathyroidectomy.

BACKGROUND: Patients with primary hyperparathyroidism who undergo minimally invasive parathyroidectomy (MIP) may have postoperative symptoms of hypocalcemia or secondary hyperparathyroidism. This study sought to identify factors predictive of these events. METHODS: Between 1998 and 2004, 190 patients with primary hyperparathyroidism underwent MIP with excision of a single adenoma. Age, gender, race, prior head and neck surgery, use of preoperative thyroid hormone or calcium-channel blockers, preoperative levels of calcium, 25-hydroxyvitamin D (25[OH]D) and intact parathyroid hormone (iPTH), the presence of osteopenia or osteoporosis, intraoperative iPTH levels, and adenoma weight were evaluated by univariate analysis as predictors of postoperative symptoms of hypocalcemia and secondary hyperparathyroidism. RESULTS: None of the following were predictors of postoperative symptoms of hypocalcemia: age, gender, race, prior head and neck surgery, preoperative medications, preoperative calcium and iPTH levels, osteopenia or osteoporosis, intraoperative iPTH levels, or adenoma weight. However, patients with postoperative symptoms of hypocalcemia had significantly lower preoperative 25[OH]D levels (P = .01). Further, higher preoperative iPTH levels (P < .01) and lower preoperative 25[OH]D levels (P = .05) were associated with secondary hyperparathyroidism postoperatively. CONCLUSIONS: A low preoperative 25[OH]D level is associated with postoperative symptoms of hypocalcemia and secondary hyperparathyroidism in patients undergoing MIP. One might consider instituting empiric calcium supplementation postoperatively in patients with low 25[OH]D levels.

Adenoma↗

PubMed2003

Cell-cycle dysregulation and anticancer therapy.

Cell-cycle dysregulation is a hallmark of tumor cells. The ability of normal cells to undergo cell-cycle arrest after damage to DNA is crucial for the maintenance of genomic integrity. The biochemical pathways that stop the cell cycle in response to cellular stressors are called checkpoints. Defective checkpoint function results in genetic modifications that contribute to tumorigenesis. The regulation of checkpoint signaling also has important clinical implications because the abrogation of checkpoint function can alter the sensitivity of tumor cells to chemotherapeutics. Here, we provide an overview of the mechanisms that regulate the cell cycle, current anticancer therapies that target checkpoint signaling pathways, and strategies for the development of novel chemotherapeutic agents.

Antineoplastic Agents↗

PubMed2002

Analysis of cell-cycle checkpoint pathways in head and neck cancer cell lines: implications for therapeutic strategies.

OBJECTIVE: To determine the mechanism of action of paclitaxel (Taxol) and carboplatin in cell lines of head and neck squamous cell carcinoma (HNSCC). DESIGN: Four HNSCC cell lines were treated with paclitaxel and carboplatin, alone or in combination, and evaluated for cell-cycle position by means of flow cytometry, for molecular determinants of cell cycle by means of Western blotting and kinase analysis, and for anchorage-independent growth by means of soft-agar assays. RESULTS: Paclitaxel was more effective at inducing apoptosis and inhibiting anchorage-independent cell growth, compared with carboplatin. The activity of paclitaxel was correlated with an elevation of cyclin B1/CDC2 activity, prolonged mitotic arrest, and Bcl-2 phosphorylation. In contrast, carboplatin arrested cells before mitosis. Combination treatment with both agents, simultaneously or sequentially, was more effective at inhibiting cell growth than either single agent. Cellular outcome was the same regardless of which drug was used first. The order of addition of these 2 drugs differentially affected cell-cycle position. Paclitaxel pretreatment arrested cells in mitosis, whereas carboplatin pretreatment or cotreatment resulted in premitotic arrest. CONCLUSIONS: To our knowledge, this study is the first to explore how paclitaxel and carboplatin, alone or in combination, differentially affect cell-cycle checkpoint response and HNSCC cell growth. These results provide molecular validation for the current clinical use of both drugs in combination and set the stage for analyses of patient tumor specimens.

Antineoplastic Agents↗