Biomedical subjects

Fan Yuan

Publications and source records attributed to Fan Yuan.

22 records · Page 2Linked to original sources

PubMed2003

Systemic dissemination of viral vectors during intratumoral injection.

Intratumoral injection is a routine method for local viral gene delivery that may improve interstitial transport of viral vectors in tumor tissues and reduce systemic toxicity. However, the concentration of transgene products in normal organs, such as in the liver, may still exceed normal tissue tolerance if the products are highly toxic. The elevated concentration in normal tissues is likely to be caused by the dissemination of viral vectors from the tumor. Therefore, we investigated transgene expression in the liver, the serum, and a mouse mammary carcinoma (4T1) in mice after intratumoral injection of adenoviral vectors for mouse interleukin-12, luciferase, enhanced green fluorescence protein, or beta-galactosidase. We also performed numerical simulations of virus transport in tumors after intratumoral injection, based on the Krogh cylinder model. Our experimental data and numerical simulations demonstrated that virus dissemination was significant in mice and it occurred mainly during the intratumoral injection. To reduce virus dissemination, we mixed these vectors with a viscous alginate solution and injected the mixture into the tumors. Our data showed that the alginate solution could significantly reduce virus dissemination while having minimal effects on transgene expression in tumors and on interleukin-12-induced tumor growth delay. These data suggest that virus dissemination is a potential problem in local viral gene therapy of cancer and that the dissemination could be significantly reduced by the alginate solution without compromising the efficacy of gene therapy.

Adenoviridae↗

PubMed2002

An equivalent length model of microdialysis sampling.

One of the critical issues in microdialysis sampling is how to predict the extraction fraction (E(d)), based on transport properties of analytes in both tissues and probes. A one-dimensional (1-D) model has been used widely in previous studies to predict E(d) at the steady state. However, this model is valid only for long probes. To this end, an equivalent length (EL) model was developed for probes with any length used in experiments. The key idea in the model was to replace the probe length (L) in the 1-D model with an equivalent length (L(E)) when calculating transport resistance in surrounding tissues. The length difference, (L(E)-L), was assumed to be proportional to the penetration depth of analytes (Gamma). The proportionality constant (lambda) was determined through minimizing the errors in predicted E(d). We found that, the EL model could accurately predict E(d) when lambda=0.369. The maximum error in EL model predictions was <6%, for model constants varying in the same ranges as those in microdialysis experiments. This error was one order of magnitude smaller than that in 1-D model predictions.

Algorithms↗

PubMed2002

Intravital fluorescence facilitates measurement of multiple physiologic functions and gene expression in tumors of live animals.

The purpose of this report is to present an overview of the use of fluorescence imaging in vivo, with particular emphasis on oncology. It is important to note, however, that many of the methods described herein have been applied to the study of non-malignant tissues as well. Modern medicine and biology research has benefited greatly from an ever-expanding assortment of fluorescent markers and labels. These markers and labels have allowed investigators to observe the behavior and properties of cell and molecular entities of interest in the context of complicated biological systems such as a mammalian cell or a whole mouse. Methods developed to image fluorescence in whole mice have been valuable in studying patterns of tumor growth and metastases. Alternatively, more detailed information and a wide variety of endpoints can be obtained using "intravital" preparations. This review focuses on use of fluorescence imaging for intravital preparations. For detail on fluorescence imaging of whole animals, refer to reviews on this subject [1,2]. For oncologic applications, studies have focused primarily on window chamber preparations that allow for real-time visualization of tumor growth, vascularity, vascular responses to stimulation, vascular permeability, vascular orientation, flow instability, and the like. These endpoints have been used to show that there are functional differences between tumor and normal tissues with respect to these functions under baseline conditions and after therapeutic manipulation. Examples of some of these differences are provided in this review as a means to illustrate how they can be used.

Animals↗

PubMedDate not supplied

A clinical model of dermal wound angiogenesis.

Full-thickness dermal biopsies were performed in healthy volunteers to establish the range of angiogenic responses in wound healing in a normal population. Four-millimeter punch biopsies were made in the forearms of 15 healthy volunteers. Each wound was evaluated microscopically 4-5 times per week for 2 weeks. A semiquantitative wound scoring system to evaluate the neovasculature at the wound periphery was investigated. A vascular score was calculated for each wound at each observation. Two independent observers analyzed the microscopic wound images using the scoring system. At the end of the 14-day period, repeat biopsies were performed on some of the volunteers, and the granulation tissue was stained with anti-CD31. The Kaplan-Meier method was used to estimate the distribution of the time to reach predetermined target average vascular scores. A mixed-effects regression model indicated that time, age, and observer were predictors for the average vascular score outcome. The pattern and time course for wound neovascularization was highly reproducible in this group of healthy volunteers, and the assay was feasible and well tolerated. This wound angiogenesis model may be useful for monitoring the effects of antiangiogenic agents on normal wound neovascularization.

Adult↗