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Biomedical subjects

Sheng Tong

Publications and source records attributed to Sheng Tong.

3 recordsLinked to original sources

Quantitative comparison of the inhibitory effects of GW5638 and tamoxifen on angiogenesis in the cornea pocket assay.

GW5638 is a novel tissue-selective estrogen receptor (ER) modulator. Structurally, it is a derivative of tamoxifen that is known for its inhibitory effects on angiogenesis in an ER-independent manner. Therefore, it is possible that GW5638 has the same effects as tamoxifen on angiogenesis. To test this hypothesis, we used the rat cornea pocket assay and developed a new method that could precisely determine the total projected area of microvessels induced by basic fibroblast growth factor (bFGF) in the cornea. Animals in the study were treated with corn oil (control group), tamoxifen, or GW5638. After treatment, we observed that both GW5638 and tamoxifen could inhibit angiogenesis in the cornea (P<0.05) and that the inhibitory effects were not mediated by blocking functions of estrogen. Meanwhile, GW5638 had minimal effects on the body weight of animals whereas tamoxifen significantly reduced the body weight. Based on these observations, we concluded that GW5638 was as effective as tamoxifen in antiangiogenic treatment but less toxic than tamoxifen.

Angiogenesis Inhibitors↗

Targeting tumor microvessels using doxorubicin encapsulated in a novel thermosensitive liposome.

Liposomal drugs accumulate only in perivascular regions in tumors after i.v. injection. Thus, they cannot kill tumor cells in deeper tissue layers. To circumvent this problem, we investigated effects of doxorubicin (DOX) encapsulated in a lysolecithin-containing thermosensitive liposome (LTSL) on tumor microcirculation because damaging microvessels would stop nutrient supply to deeper tumor cells. We used LTSL-DOX in combination with hyperthermia to treat a human squamous carcinoma xenograft (FaDu) implanted in dorsal skinfold chambers in nude mice. Before the treatment, the RBC velocity in tumors was 0.428 +/- 0.037 mm/s and the microvascular density was 3.93 +/- 0.44 mm/mm(2). At 24 hours after the treatment, they were reduced to 0.003 +/- 0.003 mm/s and 0.86 +/- 0.27 mm/mm(2), respectively. The same treatment, however, caused only 32% decrease in the RBC velocity and no apparent change in microvascular networks in normal s.c. tissues over the same period. LTSL and LTSL-DOX alone had no effect on tumor microcirculation, and LTSL plus hyperthermia caused only a transient decrease in the RBC velocity in tumors. At 24 hours after treatments, tumor microcirculation in all these control experiments was insignificantly different from that before the treatments. We also examined apoptosis of cells in tumors at different time points after LTSL-DOX plus hyperthermia treatment and observed few apoptotic cells in tumor microvessels. In conclusion, the rapid release of DOX during hyperthermia could make the drug to shutdown tumor blood flow while have only minor effects on normal microcirculation in s.c. tissues.

Animals↗

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↗