Biomedical subjects

Ching-Hsuan Tung

Publications and source records attributed to Ching-Hsuan Tung.

58 records · Page 4Linked to original sources

PubMedDate not supplied

A branched fluorescent peptide probe for imaging of activated platelets.

Novel fluorescent probes for thrombi and activated-platelet detection were developed that were based on the glycoprotein IIb/IIIa (GP-IIb/IIIa) binding sequence, Pro-Ser-Pro-Gly-Asp-Trp. Linear, Pro-Ser-Pro-Gly-Asp-Trp-Aha-Gly-Cys(Cy5.5)-NH(2) (1PF), and branched, (Pro-Ser-Pro-Gly-Asp-Trp-Aha)(2)-Lys-Gly-Cys(Cy5.5)-NH(2) (2PF), fluorescent-labeled peptide probes were synthesized. A third probe, also branched, (Pro-Ser-Pro-Gly-Glu-Trp-Aha)(2)-Lys-Gly-Cys(Cy5.5)-NH(2) (2CF), was synthesized as control. The platelet-binding activity of the probes was tested in clots generated from human platelet-rich plasma. Fluorescence reflectance imaging results showed that 2PF has a 16-fold increase in fluorescence intensity compared to the autofluorescence of clots. The linear conjugate, 1PF, and free dye did not show appreciable fluorescence enhancement. 2PF fluorescence was also found 5.5-fold higher than that of the control probe, 2CF. Overall, our results suggest that 2PF binds tightly to GP-IIb/IIIa and potentially can be used for in vivo imaging of thrombosis.

Blood Platelets↗

PubMedDate not supplied

In-vivo imaging of tumor associated urokinase-type plasminogen activator activity.

The ability to image tumor associated protease in vivo has biological and clinical implications. In the present study, we describe the development and validation of a urokinase-type plasminogen activator (uPA) sensitive fluorescence imaging probe. The activation of our probe is highly specific to uPA in both enzymatic and cellular-based assays. In two distinct in-vivo tumor models (human colon adenocarcinoma HT-29 and human fibrosarcoma HT-1080), the observed fluorescence changes correlate well with tumor associated uPA activity. The signal intensities of the tumors are about three-fold higher in animals with probe injections. Our results suggest a direct detection method for uPA activity in vivo and the approach can be used for monitoring tumor growth and development.

Adenocarcinoma↗

PubMedDate not supplied

Detection of dysplastic intestinal adenomas using a fluorescent folate imaging probe.

Macrophages have long been recognized as a prominent component of tumors. Activated macrophages overexpress folate receptors and we used this phenomenon to image inflammatory reactions in colon dysplasia using a fluorescent folate probe (FFP). APC(Delta468) mice injected with FFP showed fluorescent adenomas (target-to-background ratio, adenoma vs. adjacent normal mucosa, of 2.46 +/- 0.41), significantly higher (p < .001) than adenomas in animals injected with a non-folate-containing control probe. Fluorescence-activated cell-sorting analysis revealed a 3-fold higher content of Mac1-positive cells in colonic adenomas compared with normal adjacent mucosa (6.8% vs. 2.2%), and confirmed the source of FFP-positive cells to be primarily an F4/80-positive macrophage subpopulation. Taken together, these results indicate that probe potentially can be used to image dysplastic intestinal adenomas in vivo.

Adenoma↗

PubMedDate not supplied

A novel method for imaging apoptosis using a caspase-1 near-infrared fluorescent probe.

Here we describe a novel method for imaging apoptosis in cells using a near-infrared fluorescent (NIRF) probe selective for caspase-1 (interleukin 1beta-converting enzyme, ICE). This biocompatible, optically quenched ICE-NIRF probe incorporates a peptide substrate, which can be selectively cleaved by caspase-1, resulting in the release of fluorescence signal. The specificity of this probe for caspase-1 is supported by various lines of evidence: 1) activation by purified caspase-1, but not another caspase in vitro; 2) activation of the probe by infection of cells with a herpes simplex virus amplicon vector (HGC-ICE-lacZ) expressing a catalytically active caspase-1-lacZ fusion protein; 3) inhibition of HGC-ICE-lacZ vector-induced activation of the probe by coincubation with the caspase-1 inhibitor YVAD-cmk, but not with a caspase-3 inhibitor; and 4) activation of the probe following standard methods of inducing apoptosis with staurosporine, ganciclovir, or ionizing radiation in culture. These results indicate that this novel ICE-NIRF probe can be used in monitoring endogenous and vector-expressed caspase-1 activity in cells. Furthermore, tumor implant experiments indicate that this ICE-NIRF probe can be used to detect caspase-1 activity in living animals. This novel ICE-NIRF probe should prove useful in monitoring endogenous and vector-expressed caspase-1 activity, and potentially apoptosis in cell culture and in vivo.

Animals↗