Showing papers by "Timothy L. Ratliff published in 2009"

Phase I Clinical Trial of an Adenovirus/Prostate-Specific Antigen Vaccine for Prostate Cancer: Safety and Immunologic Results

Abstract: Purpose: We performed a phase I clinical trial of adenovirus/prostate-specific antigen (PSA) vaccine in men with measurable metastatic hormone-refractory disease. Experimental Design: Men with measurable metastatic disease received one vaccine injection. Toxicity, immune responses, changes in PSA doubling times, and patient survival were assessed. Thirty-two patients with hormone-refractory metastatic prostate cancer were treated with a single s.c. vaccine injection at one of three dose levels, either as an aqueous solution or suspended in a Gelfoam matrix. All patients returned for physical and clinical chemistry examinations at regular intervals up to 12 months after injections. Results: The vaccine was deemed safe at all doses in both administration forms. There were no serious vaccine-related adverse events; the most prevalent were localized erythema/ecchymoses and cold/flu-like symptoms. Anti-PSA antibodies were produced by 34% of patients and anti-PSA T-cell responses were produced by 68%. PSA doubling time was increased in 48%, whereas 55% survived longer than predicted by the Halabi nomogram. Conclusions: The adenovirus/PSA vaccine was proven safe with no serious vaccine-related adverse events. The majority of vaccinated patients produced anti-PSA T-cell responses and over half survived longer than predicted by nomogram. Although the latter data are only derived from a small number of patients in this phase I trial, they are encouraging enough to pursue further studies. (Clin Cancer Res 2009;15(23):7375–80)

Platelet influence on T- and B-cell responses

Abstract: Understanding the adaptive immune response is an area of research critically important in medicine. Several positive regulators of B- and T-cell activation exist to eliminate pathogens, in which CD40 ligand (CD154) plays a fundamental role. It is well documented that CD154 expressed by CD4 T helper cells can be critical in the proper activation of dendritic cells for the productive stimulation of CD8 T cells and is required for proper T-dependent B-cell immunity. However, platelets are an abundant and systemic source of CD154. While classically known to be important for hemostasis and inflammation, several lines of evidence suggest that platelet-derived ligands can modulate the adaptive immune compartment.

Early microrecanalization of vas deferens following biodegradable graft implantation in bilaterally vasectomized rats.

Abstract: We evaluated a biodegradable graft for reconstruction of rat vasa deferentia with long obstructed or missing segments A total of 47 Sprague-Dawley rats underwent bilateral vasectomy and were divided into groups according to length of the vas deferens affected (05, 1, 15 cm) After 8 weeks, poly-(D,L-lactide) (PDLA) grafts were used to reconnect the vas deferens Grafts and adjoining vasa deferentia were excised 8 and 12 weeks later and evaluated microscopically At 8 weeks, microscopic changes included a robust inflammatory response around the grafts All grafts were still intact but in the early stages of degradation No microtubules, indicative of vas deferens recanalization, were identified One specimen showed evidence of healing and neovascularization at the interface zone between the vas deferens and the graft At 12 weeks, grafts were further degraded but still present Microscopic evaluation showed decreased inflammation Seven specimens showed neovascularization at the interface zone; two of these showed distinct epithelialized vas deferens microcanals at the graft edges One specimen showed a microcanal spanning the entire 05-cm graft A time period of 8 weeks is not ample enough for vas deferens regeneration in the setting of a biodegradable PDLA graft; however, early evidence of re-growth was seen at 12 weeks A longer healing time should permit further biodegradation of the graft, as well as re-growth and possible eventual reconnection of the vas deferens, allowing passage of sperm These findings suggest a potential role for biodegradable grafts in the reconstruction of vas deferens with long obstructed segments

Mass-sensing BioCD Protein Array towards Clinical Application: Prostate Specific Antigen Detection in Patient Sera

Abstract: Mass-sensing biosensor arrays for protein detection require no fluorophores or enzyme labels. However, few mass biosensor protein arrays have demonstrated successful application in high background samples, such as serum. In this paper, we test the BioCD as a mass biosensor based on optical interferometry of antibodies covalently attached through Schiff-base reduction. We use the BioCD to detect prostate specific antigen (PSA, a biomarker of prostate cancer) in patient sera in a 96-well anti-PSA microarray. We have attained a 4 ng/ml detection limit in full serum and have measured PSA concentrations in three patient sera.