Biomedical subjects

Chun Li

Publications and source records attributed to Chun Li.

89 records · Page 5Linked to original sources

PubMed2002

Improving metabolic stability of phosphodiesterase-4 inhibitors containing a substituted catechol: prevention of reactive intermediate formation and covalent binding.

A detailed study directed towards metabolic stability optimization of the alkoxy substituents on the catechol moiety of CDP-840 is reported. Replacement of the methoxy and cyclopentyloxy substituents by cyclobutyloxy and/or difluromethoxy groups resulted in the discovery of potent and selective PDE4 inhibitors where the formation of reactive metabolites that could covalently bind to microsomal protein was significantly reduced or eliminated.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2002

[Analysis of telomerase activity in esophageal carcinoma using microdissection telomeric repeat amplification protocol assay].

OBJECTIVE: To investigate the changes of telomerase activities in atypical hyperplasia of esophageal mucosal epithelium and esophageal squamous cell carcinoma (SCC) and to study the association of telomerase activity with differentiation, invasiveness, and lymphatic metastasis of cancer. METHODS: The telomerase activities of esophageal SCC tissues, adjacent tissue with dysplasia, and normal mucosal epithelium from surgical edge of 45 cases were detected by microdissection-TRAP (Telomeric Repeat Amplification Protocol)-silver assay. RESULTS: The telomerase activity rates were 79.3% (23/29) in atypical displastic epithelium, 82.2% (37/45) in SCC tissue, and only 5% (2/40) in normal epithelium. The difference of telpmerase activity between dysplastic and normal esophageal epithelia was highly significant (P < 0.01). In the same cancer tissue the differences of telomerase activity among cancer nests to different degrees of defferentiation and to different depths were not significant (P > 0.05). The positive rate of telomerase activity was significantly higher in cases with lymphatic metastasis than in cases without lymphatic metastasis (P < 0.05). CONCLUSION: The telomerase activities is increased in esophageal SCC tissue and adjacent atypical dysplastic tissue. The telomerase activity in SCC tissue is related to lymphatic metastasis but not related to cancer differentiation.

Adult↗

PubMed2002

[Inhibitory action of CPU86035 on L-type calcium current in single ventricular myocyte of guinea pig].

OBJECTIVE: To investigate the effects of CPU86035, a recently synthesized tetrahydroberberine derivative, on the L-type calcium currents (I(Ca.L)) in single guinea pig ventricular myocytes. METHODS: The effect of CPU86035 of different concentrations (50 approximately 250 micromomol/L) on I(Ca.L) in enzymatically dispersed single guinea pig ventricular myocytes was investigated by using whole-cell patch-clamp technique. RESULTS: (1) CPU86035 concentration-dependently inhibited I(Ca.L), with the IC50 at 75 micromol/L. (2) The inhibition of CPU86035 on I(Ca.L) was dependent on the holding potential (HP). 75 micromol/L CPU86035 inhibited I(Ca.L) by 49% +/- 2% at HP = -40 mV, and 64% +/- 4% at HP = -80 mV. (3) The homeostatic activation curve of ICa.L shifted to the right toward more positive potentials in the presence of CPU86035, with a V(1/2) of 15.4 mV +/- 0.8 mV compared with that of 15.4 +/- 0.8 mV in the control. (4) The homeostatic inactivation curve of I(Ca.L) shifted to the right toward more positive potentials in the presence of CPU86035, with a V(1/2) of -12.6 mV +/- 2.7 mV compared with that of -19.1 mV +/- 2.5 mV in the control. (5) The recovery from inactivation became slower in the presence of CPU86035. CONCLUSION: CPU86035 strongly inhibits the calcium channel, probably by binding to the channel in resting stage.

Animals↗

PubMed2002

Superior therapeutic profile of poly-L-glutamic acid-paclitaxel copolymer compared with taxol in xenogeneic compartmental models of human ovarian carcinoma.

Previous preclinical studies with ectopic tumor models have demonstrated remarkable improvements in the therapeutic profile of paclitaxel, formulated as a copolymer with poly-L-glutamic acid, compared with paclitaxel in the clinical formulation, Taxol. In this study, we evaluated these formulations in two human ovarian carcinoma xenograft models, NMP-1 and HEY, in nude mice. i.p. implantation in female nude mice of either cell line gave rise to progressive disease within the peritoneum, in the parenchyma of visceral organs, and eventually at extraperitoneal sites; the resultant, increasing morbidity then required host sacrifice. i.p. administration of multiple-dose Taxol at its maximum tolerated dose 1 week after tumor implantation afforded minimal or no increased survival compared with controls in either model. Consistent with the predictions of drug copolymer behavior, paclitaxel, as the poly-L-glutamic acid-paclitaxel copolymer, displayed much less toxicity than Taxol in these hosts. When evaluated for antitumor efficacy in both the Taxol-resistant NMP-1 and HEY models, significant improvement in survival, and even some cures, were observed after a single i.p. treatment with this copolymer. The observed antitumor response correlated with histopathological analysis of peritoneal and extraperitoneal tumor burden in comparing control HEY mice sacrificed near the onset of morbidity with mice receiving paclitaxel copolymer. We conclude that both the i.p. NMP-1 and HEY models have significant value in establishing the efficacy of candidate agents, which might address Taxol-resistant human ovarian carcinoma. Furthermore, the poly-L-glutamic acid-paclitaxel copolymer has a superior therapeutic profile in these Taxol-resistant compartmental models.

Animals↗

PubMed2002

Telomerase activity analysis of esophageal carcinoma using microdissection-TRAP assay.

OBJECTIVES: To investigate telomerase activity in esophageal squamous cell carcinoma (SCC) and its preneoplasia lesions, and to study the relationships between telomerase activity and cancer differentiation, cancer invasiveness, and lymphatic metastasis. METHODS: Telomerase activity in esophageal SCC tissues, adjacent dysplasia tissues and normal epithelia from the surgical edge were assessed by microdissection-TRAP (telomeric repeat amplification protocol)-silver staining assay. RESULTS: Telomerase activity was detected in 37 (82.2%) of 45 esophageal tumors, 23 (79.3%) of 29 dysplasias, and 2 (5%) of 40 normal epithelia. There was a significant difference in activity between dysplasia and normal epithelium, as well as between tumor and normal epithelium. Twenty-six (92.9%) of 28 tumors with lymphatic metastasis had detectable telomerase activity compared to 11 (64.7%) of 17 non-lymphatic metastasis tumors. These relationships were statistically significant (P < 0.05), but the one between telomerase activity and tumor grade was not. CONCLUSION: Telomerase activity was high both in esophageal SCC and their preneoplasia lesions. The telomerase activity in SCC tissue was related to lymphatic metastasis, but not to cancer differentiation.

Adult↗

PubMed2002

[Chemical composition of fructus Liquidambaris--lulutong].

AIM: To study the chemical composition in the fruits of Liquidambar formana Hance. METHODS: Various column chromatographic techniques were used to separate and purify the constituents. Their physical and chemical properties and spectral data were measured for structural elucidation. RESULTS: Eleven compounds were isolated and identified as beta-sitosterol (1), 3-oxo-11 alpha, 12 alpha-epoxyleanan-28, 13 beta-olide (2), 3-oxo-12 alpha-hydroxy-oleanan-28, 13 beta-olide (3), 3 alpha-acetyloxy-25-hydroxyolean-12-en-28-oic acid (4), oleanolic acid (5), ursolic acid (6), daucosterol (7), betulonic acid (8), gallic acid (9), nonacosane (10) and n-triacontanoic acid (11). CONCLUSION: Among the isolated constituents, compound 4 is new compound, compound 3 is firstly isolated from the natural product and compound 5, 6, 7, 9, 10 and 11 are isolated from LuLuTong for the first time.

Fruit↗

PubMed2001

Studies on Mixed Monolayers and Langmuir-Blodgett Films of Schiff-Base Complex Cu(SBC(18))(2) and Calix

Mixed monolayers of Schiff-base complex Cu(SBC(18))(2) with an octadecyl hydrocarbon chain and Calix[4]arene without a long alkyl chain at an air/water interface were studied in ultrapure water at different temperatures. Interface behavior and thermodynamic estimation of the mixed monolayer indicate that a strong intermolecular interaction exists between the mixed components (Cu(SBC(18))(2) and calix[4]arene) and the two-dimensional miscibility decreases with the molar fraction of Cu(SBC(18))(2). It is noticeable that the calix[4]arene monolayer can be transferred successfully onto solid substrates due to the introduction of Cu(SBC(18))(2). FTIR transmission and UV-Vis absorption spectra of mixed LB films provide further evidence of molecular interaction between the headgroups. Copyright 2001 Academic Press.

Journal Article↗

PubMed2001

Microstructure and Ion Exchange in Stearic Acid Langmuir-Blodgett Films Studied by Fourier Transform Infrared-Attenuated Total Reflection Spectroscopy.

Fourier transform infrared-attenuated total reflection (FTIR-ATR) spectra have been recorded of 11-layer Langmuir-Blodgett (LB) films of stearic acid deposited at various surface pressures (0.1, 15, and 35 mN/m), and the molecular orientation angles were evaluated quantitatively, which supplied insight into the molecular order with the alkyl chains tightly packed like crystal in the LB films deposited at the zero and higher surface pressures. These experimental results indicate that, in the Langmuir film as the precursor of LB films, stearic acid molecules self-aggregate to form two-dimensional crystalline domains already even at the zero surface pressure, which results in the inhomogeneity of monolayer. The analysis of dependence of nu(C=O) intensity on the surface pressure, surface density, and subphase temperature leads to the conclusion that the defects in LB films originate from the Langmuir film and be conserved upon deposition. Annealing below 50 degrees C and cooling could improve the monolayer homogeneity, and thus a defect-free or low-defect LB films can be deposited. Furthermore, ion exchange conducted in the LB films, on the other hand, confirms the existence of structure defects in LB films of stearic acid. The polar plane microstructure, lateral transport along the polar planes and the coordination types of stearic acid/cation system may be the rate-limiting process. The results have implication on the possible uses of stearic acid LB films as ion-exchange materials or sensors. Copyright 2001 Academic Press.

Journal Article↗

PubMedDate not supplied

Probing for integrin alpha v beta3 binding of RGD peptides using fluorescence polarization.

Integrin alpha(v)beta(3) is an adhesion molecule involved in tumor invasion, angiogenesis, and metastasis. There is substantial interest in developing novel agents that bind to integrin alpha(v)beta(3). Here we report the synthesis and characterization of a fluorescent integrin alpha(v)beta(3) probe and its use in a nonradioactive, simple, sensitive fluorescence polarization (FP) assay to quantify binding to integrin alpha(v)beta(3). For assay validation, the FP assay was compared to a cell adhesion assay. In the two assays, probe binding to integrin alpha(v)beta(3) showed a similar dependence on probe concentration. The FP assay was successfully applied to measure the binding affinity to integrin alpha(v)beta(3) of several cyclic peptides containing the Arg-Gly-Asp (RGD) motif. The FP assay we describe here may be appropriate for high-throughput screening for integrin alpha(v)beta(3)-binding ligands used for anti-integrin therapy or noninvasive imaging of integrin expression.

Cell Adhesion↗

PubMedDate not supplied

Synthesis and characterization of poly(L-glutamic acid) gadolinium chelate: a new biodegradable MRI contrast agent.

Most currently evaluated macromolecular contrast agents for magnetic resonance imaging (MRI) are not biodegradable. The goal of this study is to synthesize and characterize poly(l-glutamic acid) (PG) gadolinium chelates as biodegradable blood-pool MRI contrast agents. Two PG chelates of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) were synthesized through the use of difunctional and monofunctional DTPA precursors. The conjugates were characterized with regard to molecular weight and molecular weight distribution, gadolinium content, relaxivity, and degradability. Distributions of the polymeric MRI contrast agents in various organs were determined by intravenous injection of (111)In-labeled polymers into mice bearing murine breast tumors. MRI scans were performed at 1.5 T in mice after bolus injection of the polymeric chelates. PG-Hex-DTPA-Gd, obtained from aminohexyl-substituted PG and DTPA-dianhydride, was partially cross-linked and was undegradable in the presence of cathepsin B. On the other hand, PG-Bz-DTPA-Gd synthesized directly from PG and monofunctional p-aminobenzyl-DTPA(acetic acid-tert-butyl ester) was a linear polymer and was degradable. The relaxivities of the polymers at 1.5 T were 3-8 times as great as that of Gd-DTPA. Both polymers had high blood concentrations and were primarily accumulated in the kidney. However, PG-Bz-DTPA-Gd was gradually cleared from the body and had significantly less retention in the blood, the spleen, and the kidney. MRI with PG-Bz-DTPA-Gd in mice showed enhanced vascular contrast at up to 2 h after the contrast agent injection. The ability of PG-Bz-DTPA-Gd to be degraded and cleared from the body makes it a favorable macromolecular MRI contrast agent.

Animals↗

PubMedDate not supplied

New invariant of DNA sequences.

For a DNA sequence with n bases, one can always associate it with an n x n nonnegative real symmetric matrix whose diagonal entries are zero. Once the matrix is given, its leading eigenvalue is usually calculated and used as an invariant to characterize the DNA sequence. Let M be such a matrix, and lambda1 its leading eigenvalue. Then (1/n)//M//m1 and sqrt [(n-1)/n]//M//F are the lower and upper bounds of lambda1, respectively. Since their arithmetic average is an approximate value of lambda1 and simpler for calculation, we can use it as an alternative invariant to characterize the DNA sequence. The utility of the new parameter is illustrated on the DNA sequences of five species: human, chimpanzee, mouse, rat, and gallus.

Animals↗

PubMedDate not supplied

Nuclear medicine in the era of genomics and proteomics: lessons from annexin V.

In the past decade, genomics and proteomics have begun to develop many new targets for potential diagnostic and therapeutic agents. Among the life sciences, nuclear medicine is also deeply involved in the field of clinical investigation. Experience with radiolabeled annexin V highlights the many steps required to translate a good basic-science concept into the clinical setting. This model also emphasizes the value of synergy between basic and medical specialties in developing and optimizing a clinically useful product initially derived from basic investigation.

Annexin A5↗

PubMedDate not supplied

Quantifying molecular specificity of alphavbeta3 integrin-targeted optical contrast agents with dynamic optical imaging.

Dynamic fluorescence images were obtained from a subcutaneous human Kaposi's sarcoma tumor (KS1767) model immediately following the intravenous injection of an integrin-targeting cyanine dye conjugate, Cy5.5-c(KRGDf). The fluorescence images, acquired via an intensified charge-coupled device detection system, were used in conjunction with a pharmacokinetic (PK) model to determine kinetic properties of target binding in the presence and absence of a competitive ligand, free c(KRGDf). The results indicate that the conjugate dye behaves similarly in normal tissue to the free Cy5.5 dye while it possesses increased uptake in tumor tissue. The change in pharmacokinetic parameters obtained from dynamic imaging of Cy5.5-c(KRGDf) after administration of c(KRGDf) as a competitive ligand to the integrin receptor suggests that (i) the increased uptake of Cy5.5-c(KRGDf) is molecularly specific and that (ii) receptor turnover occurs within 24 h. In addition, PK analysis enables quantification of an in vivo c(KRGDf) binding constant attributable to integrin binding. In vivo pharmacokinetic analysis based on rapid and dynamic optical imaging may be potentially useful for evaluating the presence and turnover rate of disease markers that are potential targets of molecular medicine.

Animals↗

PubMedDate not supplied

Quality analysis of in vivo near-infrared fluorescence and conventional gamma images acquired using a dual-labeled tumor-targeting probe.

The cyclic peptide, cyclopentapeptide cyclo(lys-Arg-Gly-Asp-phe) (c(KRGDf)), which is known to target alpha(v)beta3 integrin, is dual-labeled with a radiotracer, (111)indium, for gamma scintigraphy as well as with a near-infrared dye, IRDye800, for continuous-wave (cw) imaging of alpha(v)beta3 positive human M21 melanoma in xenografts. Twenty-four hours after administration of the dual-labeled peptide at a dose equivalent to 90 microCi of (111)In and 5 nmol of near-infrared (NIR) dye, whole-body gamma scintigraphy and cw imaging was conducted. Image acquisition time was 15 min for the gamma scintigraphy images and 800 ms for the optical images acquired using an NIR sensitive intensified charge-coupled device. The results show that while the target-to-background ratio (TBR) of nuclear and optical imaging were similar for surface regions of interest and consistent with the origin of gamma and NIR radiation from a common targeted peptide, the signal-to-noise ratio (SNR) was significantly higher for optical than nuclear imaging. Furthermore, an analysis of SNR versus contrast showed greater sensitivity of optical over nuclear imaging for the subcutaneous tumor targets. While tomographic reconstructions are necessary to probe TBR, SNR, and contrast for interior tissues, this work demonstrates for the first time the direct comparison of molecular optical and planar nuclear imaging for surface and subsurface cancers.

Animals↗

PubMedDate not supplied

Near-infrared fluorescence optical imaging and tomography.

The advent of recent advances in near-infrared laser diodes and fast electro-optic detection has spawned a new research field of diagnostic spectroscopy and imaging based on targeting and reporting exogenous fluorescent agents. This review seeks to concisely address the physics, instrumentation, advancements in tomography, and near-infrared fluorescent contrast agent development that promises selective and specific molecular targeting of diseased tissues. As an example of one area of the field, recent work focusing on pharmacokinetic analysis of fluorophores targeting the epidermal growth factor receptor (EGFR) is presented in a human breast cancer xenograft mouse model to demonstrate specificity of molecularly targeted contrast agents. Finally, a critical evaluation of the limitations and the opportunities for future translation of fluorescence-enhanced optical imaging of deep tissues is presented.

Animals↗

PubMedDate not supplied

Imaging dose-dependent pharmacokinetics of an RGD-fluorescent dye conjugate targeted to alpha v beta 3 receptor expressed in Kaposi's sarcoma.

Dynamic fluorescence images were obtained from xenografts bearing a subcutaneous human Kaposi's sarcoma (KS1767) immediately following the intravenous injection of an integrin-receptor targeting Cy5.5-c(KRGDf) at a dose ranging from 0.75 to 6 nmol/mouse. The fluorescence images were acquired using an intensified charge-coupled device system and were analyzed with a three-compartment pharmacokinetic (PK) model to determine uptake parameters in the tumor and normal tissue regions of interest as a function of administered dose. Our results show that the uptake of Cy5.5-c(KRGDf) in tumor regions were: (i) significantly greater than the contralateral normal tissue regions; (ii) linearly increased with dose of Cy5.5-c(KRGDf) up to 1.5 nmol/mouse; and (iii) blocked by preinjection of c(KRGDf). Above doses of 1.5 nmol/mouse, the uptake no longer increased with dose, suggesting integrin receptor saturation. In normal tissues, the PK uptake parameters were not influenced by Cy5.5-c(KRGDf) dose nor by the preadministration of c(KRGDf).

Animals↗

PubMedDate not supplied

Improved excitation light rejection enhances small-animal fluorescent optical imaging.

Small-animal fluorescence-enhanced imaging involves the detection of weak fluorescent signals emanating from nanomolar to picomolar concentrations of exogenous or endogenously produced fluorophore concurrent with the rejection of an overwhelmingly large component of backscattered excitation light. The elimination of the back-reflected excitation light of the collected signal remains a major and often unrecognized challenge for further reducing the noise floor and increasing sensitivity of small-animal fluorescence imaging. Herein, we show that the combination of three-cavity interference and holographic super notch filters with appropriate imaging lenses to collimate light improves rejection of excitation light, enabling more accurate imaging. To assess excitation leakage, the "out-of-band (S(lambda x))" to "in-band (S(lambda m) - S(lambda x))" signal ratio from phantom studies and the target-to-background ratio (TBR) from in vivo animal imaging was acquired with and without collimating optics. The addition of collimating optics resulted in a 51% to 75% reduction in the ratio of (S(lambda x))/(S(lambda m) - S(lambda x)) for the phantom studies and an improvement of TBR from 11% to 31% and of signal-to-noise ratio from 11% to 142% for an integrin-targeting conjugate in human glioma xenografts.

Animals↗