Biomedical subjects

Peter Fong

Publications and source records attributed to Peter Fong.

5 recordsLinked to original sources

PubMed2006

5,6-Dimethylxanthenone-4-acetic acid in the treatment of refractory tumors: a phase I safety study of a vascular disrupting agent.

This phase I safety study aimed to identify the optimal dose of the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) for combination studies. Using a crossover design, 15 patients with refractory tumors were allocated randomly to receive six sequential doses of DMXAA (300, 600, 1,200, 1,800, 2,400, and 3,000 mg m(-2)), each given once-weekly as a 20-minute i.v. infusion. The drug was generally well tolerated. Transient, moderate increases in the heart rate-corrected cardiac QT interval occurred at the two highest doses. DMXAA produced transient dose-dependent increases in blood pressure. Transient, dose-related visual disturbances occurred at the two highest doses. No significant changes in K(trans) and k(ep) were observed but V(e), a secondary dynamic contrast-enhanced magnetic resonance imaging variable, increased significantly after giving DMXAA. At 1,200 mg m(-2), the Cmax and the area under the concentration-time curve over 24 hours for total and free DMXAA plasma concentrations were 315 +/- 25.8 microg/mL, 29 +/- 6.4 microg/mL x d, 8.0 +/- 1.77 microg/mL, and 0.43 +/- 0.07 microg/mL x d, respectively. Plasma levels of the vascular damage biomarker 5-hydroxyindoleacetic acid increased in the 4 hours after treatment in a dose-dependent fashion up to 1,200 mg m(-2), with a plateau thereafter. Doses in the range of 1,200 mg m(-2) have been selected for further studies (phase II combination studies with taxanes and platins are under way) because this dose produced no significant effect on heart rate-corrected cardiac QT interval, produced near maximum levels of 5-hydroxyindoleacetic acid, achieved DMXAA plasma concentrations within the preclinical therapeutic range, and was well tolerated.

Adult↗

PubMed2006

Development of a model system for preliminary evaluation of tissue-engineered vascular conduits.

BACKGROUND/PURPOSE: The ability to construct tissue-engineered neovessels for use as arterial or venous grafts holds great promise for the advancement of pediatric surgical disciplines. Although the feasibility of tissue engineering vascular grafts has been demonstrated, the long-term function, safety, and efficacy of these grafts as well as their capacity to grow and adapt remain largely unknown. In an attempt to further characterize and develop this technology, we used severe combined immunodeficiency beige (SCID/bg) mouse recipients, chosen because such animals accept xenogenic human cells, to create a small animal model that would allow a rapid and cost-effective preliminary evaluation of the function of tissue-engineered vascular grafts. METHODS: Eight CB-17 SCID/bg female mice underwent vascular graft placement. Four of these mice received aortic interposition grafts, 1 mouse received an inferior vena cava interposition graft, and 3 mice underwent aortocaval graft insertion. All grafts were fashioned from decellularized ovine arteriole tissue engineering scaffolds. Grafts were evaluated for patency using clinical examination, ultrasound interrogation, and micro-computed tomography. Animals were killed at various time points after implantation, and grafts were harvested and analyzed histologically using standard hematoxylin and eosin staining. RESULTS: All grafts were patent based on clinical examination for up to 35 days. Patency was confirmed in 5 grafts using ultrasound interrogation. Patency was confirmed in 4 grafts using micro-computed tomography. One animal that underwent arteriovenous grafting had to be euthanized secondary to high-output cardiac failure on postoperative day 2. The remaining animals were killed between postoperative days 12 and 35. Histologic evaluation of the specimens demonstrated patent grafts with cellular ingrowth into the tissue engineering scaffold. CONCLUSIONS: From these results, we conclude that the use of the SCID/bg mouse model for preliminary evaluation of new tissue engineering methodologies for construction of vascular conduits is feasible. Use of this model has the added advantage of evaluating nonautologous and even xenograft tissues, including human cells.

Animals↗

PubMed2005

Development of a parathyroid hormone-controlled release system as a potential surgical treatment for hypoparathyroidism.

BACKGROUND/PURPOSE: The aim of this study was to develop a surgically implantable controlled release delivery system for parathyroid hormone (PTH) that will maintain calcium homeostasis without the adverse side effects of long-term calcium and vitamin D replacement and can be used for the treatment of hypoparathyroidism. METHODS: Biodegradable poly(lactide-co-glycolide) (PLGA) microspheres loaded with PTH were made using a modification of the double emulsion (water/oil/water) solvent evaporation technique. To simulate the release of PTH from microspheres after implantation in an animal, the in vitro release profile for the PTH microspheres was determined by incubating the PTH microspheres in phosphate-buffered saline, serially sampling the effluent, and determining the concentration of PTH in the effluent over time using an enzyme-linked immunosorbent assay. RESULTS: (1) PTH was successfully incorporated into PLGA microspheres. (2) Controlled release of PTH was demonstrated in vitro over a 3-week period. (3) Release of physiological significant concentrations of PTH was achieved using this methodology. CONCLUSIONS: Controlled release of physiological concentrations of PTH can be achieved using PLGA microsphere encapsulation.

Biocompatible Materials↗

PubMed2005

Histone deacetylase inhibitors: emerging anticancer therapeutic agents?

Histone deacetylase inhibitors are novel anticancer agents in clinical development that target the family of histone deacetylase (HDAC) enzymes responsible for deacetylating core nucleosomal histones and other proteins. The precise mechanisms resulting in the antiproliferative biologic effects of these agents are not yet known, but there are several proposed mechanistic models, including transcriptional and nontranscriptional processes. Clinical experience with these agents indicates that they are generally well tolerated, and anticancer activity has been observed in early clinical trials in several tumor types including non-small-cell lung cancer. The development of these agents continues, with an emphasis on the discovery of HDAC isoform-selective compounds. Successful future development relies on clearer understanding of the dominant mechanisms involved in the observed antiproliferative effects.

Carcinoma, Non-Small-Cell Lung↗

PubMed2004

Potential tissue-engineering applications for neonatal surgery.

Tissue engineering attempts to build neotissue from its cellular building blocks. This neotissue can then be used for reconstructive surgical applications such as replacement of a congenitally abnormal heart valve or repair of a craniofacial abnormality. Since its inception in the late 1980s, tissue engineering has sparked the interests of physicians and scientists alike because of its great potential. Significant progress has been made in this burgeoning branch of science. This article reviews some of the ongoing preclinical and clinical tissue engineering research as it applies to neonatology.

Animals↗