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Chun-Wei Li

Publications and source records attributed to Chun-Wei Li.

9 recordsLinked to original sources

Semihydrodynamic injection for high salt stacking and sweeping on microchip electrophoresis and its application for the analysis of estrogen and estrogen binding.

In this work, a semihydrodynamic (SHD) injection method was introduced and coupled with high salt stacking and electrokinetic chromatography for the analysis of estrogen and estrogen binding using a simple cross microchannel. The SHD method allows all samples to be hydrodynamically injected and focused into the separation channel at a relatively high flow rate and without splitting and diffusion, leading to reproducible bias-free injections of larger sample volumes (up to 50 nL) within 3 s. Moreover, the injection method is initiated without voltage switching, leading to a reduced mixing effect. Such advantages are well suited for performing stacking and sweeping on a microchip. We investigated the stacking effect under continuous and discontinuous co-ion conditions as well as under sweeping conditions. Micellar sweeping effect alone was relatively weak (7-8 times), partly due to a lower sodium cholate concentration (30 mM) used for the running buffer. By combining the sweeping effect with high salt stacking, however, up to a 200-300-fold enhancement factor could be achieved, and the high-salt and low-surfactant contents for the running buffer were favorable for binding study under nonequilibrium conditions. To the best of our knowledge, this is the first demonstration of the hydrodynamic injection used for high salt sample stacking on a microchip, also for further combining micellar electrochromatography and affinity separation for the analysis of hydrophobic ligand binding using microchip electrophoresis.

Binding Sites↗

Early response of hepatocellular carcinoma to transcatheter arterial chemoembolization: choline levels and MR diffusion constants--initial experience.

PURPOSE: To prospectively investigate the apparent diffusion coefficient (ADC) and choline levels measured at hydrogen 1 ((1)H) magnetic resonance (MR) spectroscopy, to monitor therapeutic responses of hepatocellular carcinoma (HCC) to transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: Institutional review board approval was obtained, and all patients and control subjects provided informed consent. Histologically proved large HCCs (>3 cm in diameter) were evaluated in 20 patients (16 men and four women; mean age, 59 years; range, 34-80 years) before TACE and 2-3 days after TACE. A control group of eight adults (five men and three women; mean age, 43 years; range, 24-76 years) with normal livers was examined by using the same protocol. Hepatic choline levels were measured by means of an external phantom replacement method, quantifying the peak at 3.2 ppm at (1)H MR spectroscopy. ADCs were measured for all lesions. A Wilcoxon rank sum test was used to compare absolute choline concentrations and ADCs at baseline between HCCs and normal liver parenchyma. Changes in choline levels and ADCs in the tumors before and after TACE were analyzed by using the Wilcoxon signed rank test. RESULTS: The median preoperative choline level in patients with HCC (measured in 18 of the 20 patients) was 4.0 mmol/L (range, 0.0-17.2 mmol/L), which was significantly higher than that in patients with normal livers (n = 8) (median, 1.6 mmol/L; range, 0.0-2.1 mmol/L; P < .01). Among 18 patients with HCC, choline levels decreased significantly from before TACE to after TACE (P < .01). A significant increase in ADC from before TACE to after TACE in the 20 patients with HCC was also found (P < .01). CONCLUSION: Hepatic choline levels and ADCs may allow monitoring of therapeutic responses of HCC to TACE although larger, more definitive and quantitative studies with clinical end points are needed.

Adult↗

Electrophoretic mobility shift assay on poly(ethylene glycol)-modified glass microchips for the study of estrogen responsive element binding.

The binding of estrogen receptor (ER) to estrogen response element (ERE) is essential for genomic pathways of estrogens and gel-based electrophoretic mobility shift assay (EMSA) is commonly used for analyzing ERE binding. Gel-based EMSA, however, requires the use of hazard radio isotopes and they are slow, labor-intensive and difficult to quantify. Here, we present quantitative affinity assays based on microchip electrophoresis using PEG-modified glass microchannels, which bear neutral surfaces against the adsorption of acidic DNA molecules and basic ER proteins. We first demonstrated the feasibility of the method by measuring binding constants of recombinant ERalpha and ERbeta with a consensus ERE sequence (cERE, 5'-GGTCAGAGTGACC-3') as well as with an ERE-like sequence (ERE 1576, 5'-GACCGGTCAGCGGACTCAC-3'). Changes in mobility as a function of protein-DNA molar ratios were plotted and the dissociation constants were determined based on non-linear curve fitting. The minimum amount of ER proteins required for one assay was around 0.2 ng and the run time for one chip analysis was less than 2 min. We further measured the estrogenic compound-mediated dissociation constants with recombinant ER proteins as well as with the extracted ERbeta from treated and untreated A549 bronchioloalveolar carcinoma cells. Dissociation constants determined by this method agree with the fact that agonist compounds such as 17beta-estradiol (1.70 nM), diethylstilbestrol (0.14 nM), and genistein (0.80 nM) assist ERE binding by decreasing the constants; while antagonist compounds such as testosterone (140.4 nM) and 4-hydroxytamoxifen (10.5 nM) suppress the binding by increasing the dissociation constant.

Base Sequence↗

Quantification of choline compounds in human hepatic tumors by proton MR spectroscopy at 3 T.

The quantification of choline-containing compounds (Cho) in hepatic tumors by (1)H MR spectroscopy (MRS) is of great interest because such compounds have been linked to malignancy. In this study, a practical external phantom replacement method for the absolute quantification of hepatic metabolites is demonstrated. We performed experiments at 3 T using a body coil, and used an external phantom containing choline chloride for calibration. We first tested the quantification strategy to confirm its suitability in vivo using a phantom of known concentration and normal brain tissue. The results obtained after coil loading and T(1) and T(2) effects were corrected for were consistent with the known concentration and previously published values. To demonstrate its feasibility, we applied the technique to liver studies conducted on five normal volunteers and four patients with hepatocellular carcinoma, and one patient (also in the latter group) who had undergone post-transcatheter arterial chemoembolization (TACE). The Cho concentrations in the four patients were estimated to be 3.4, 6.3, 7.4, and 14.0 mM, respectively. These values are substantially higher than those obtained from the healthy volunteers (1.3 +/- 0.9 mM (mean +/- SD)). The results indicate that the proposed method is accurate and requires fewer tedious procedures for MRS; therefore, it may be a promising technique for evaluating response to treatment in liver cancer.

Brain↗

Thermodynamic studies of pressure-induced retention of peptides in reversed-phase liquid chromatography.

The pressure-induced retention of peptides on reversed-phase HPLC was studied by systematically changing organic solvent composition and temperature at both low (19 bar) and high (318 bar) pressures using a homologous series of hydrophobic poly-L-phenylalanine (n = 2-7) as the model compound. Based on van' t Hoff plots under different organic solvent compositions and pressures, the enthalpy change for the solute (deltaH) was determined. Moreover, both the enthalpy and entropy change for each phenylalanine residue (deltadeltaH and deltadeltaS), which corresponds to solute retention on a microenvironment along the depth of C18 chain, were also calculated by direct subtractions. Results indicate that under acetonitrile (ACN) compositions above 35%, the pressure caused deltadeltaS value to change from a negative to a positive value and both deltaH and deltadeltaH to change from a negative to a less negative value, all leading to a thermodynamic state closer to those under 35% acetonitrile composition. This implies that the pressure-induced retention observed in this study was an entropy-favored but enthalpy-unfavored process and was explained by pressure-induced desorption of solvent molecules that were associated with the stationary phase or with the peptide solute. Under 35% acetonitrile composition, however, it was found that neither deltadeltaH nor deltadeltaS value was significantly changed by the pressure. Whereas, both deltaH value and the intercept of van't Hoff plots under 35% acetonitrile composition were increased by pressure. This indicates that under low organic solvent composition, 35%, most of the acetonitrile molecules adsorbed on the surface of the stationary phase and only little solvent molecules were dissolved in the bulk stationary phase where the phenylalanine residues were partitioned. This study has provided new thermodynamic insights to the pressure-induced retention for peptides and proteins.

Chromatography, High Pressure Liquid↗

In vivo proton magnetic resonance spectroscopy of large focal hepatic lesions and metabolite change of hepatocellular carcinoma before and after transcatheter arterial chemoembolization using 3.0-T MR scanner.

PURPOSE: To investigate the value of in vivo proton magnetic resonance spectroscopy (MRS) in the assessment of large focal hepatic lesions and to measure the metabolite change of hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) using 3.0-T scanner. MATERIALS AND METHODS: In this prospective study, 43 consecutive patients with large (not less than 3 cm in diameter) hepatic tumors and eight normal volunteer were included. MRS of the lesions in addition to uninvolved liver parenchyma was carried out using a whole-body 3.0-T scanner. Among the patients with proven HCC, eight lesions were evaluated before and two to five days after TACE. The choline-to-lipid (cho/lipid) ratio was measured by dividing the peak area of choline at 3.2 ppm by the peak area of lipid at 1.3 ppm. The sensitivity and specificity profiles of MRS in the diagnosis of malignant hepatic tumors were determined by plotting empirical receiver operating characteristic (ROC) curve. The mean cho/lipid ratios in different groups before and after TACE were also measured. RESULTS: The technical success rate for MRS was 90% (53/59). The ROC curve showed proton MRS has moderate discriminating ability in diagnosing malignant hepatic tumors, although the sensitivity was less than 50% while 1-specificity was less than 20%. The area under the curve was 0.71 (P < 0.05). The mean +/- 1 standard error (SE) of cho/lipid ratios for uninvolved liver (N = 8), benign tumor (N = 8), and malignant tumor (N = 21; 19 HCC, one angiosarcoma, and one lymphoma) were 0.06 +/- 0.02, 0.02 +/- 0.02, and 0.17 +/- 0.05, respectively. A significantly statistical difference (ANOVA planned contrast test, P = 0.01 and Games-Howell procedure, P = 0.03) was achieved in the mean cho/lipid ratio between malignant and benign tumors. The mean cho/lipid ratios were significantly decreased from 0.23 +/- 0.11 before TACE to 0.01 +/- 0.00 after the treatment (t = 2.01, P < 0.05, one-tail paired t-test; z = -2.37, P < 0.05, Wilcoxon Signed Ranks Test). CONCLUSION: In vivo proton MRS is technically feasible for the evaluation of focal hepatic lesions. The technique has potential in the detection of early metabolite change in malignant liver tumors after TACE but limitation still exists in clear differentiation between normal liver and benign and malignant tumor.

Adult↗

Evaluation of [Gd(Bz-TTDA)]2- as a potential contrast agent in MR imaging of the hepatobiliary system: an animal study.

PURPOSE: To evaluate the potential of a new lipophilic paramagnetic complex [Gd(Bz-TTDA)]2- [(4s)-4-benzyl-3,6,10-tri(carboxymethyl)-3,6,10-triazadodecandioic acid]2- designed for use as a hepatobiliary MR contrast agent. MATERIALS AND METHODS: MR imaging studies for normal and hepatocellular carcinoma (HCC) rat models were performed using a 1.5-T scanner. Sequential multislice T1-weighted turbo field echo (TFE) (TR/TE/flip angle: 15 msec/6.1 msec/25 degrees) coronal images of normal rats were obtained before and after intravenous injections of 0.1 mmol/kg [Gd(Bz-TTDA)]2- in study groups (N = 12) or 0.1 mmol/kg gadopentate dimeglumine (Gd-DTPA)2- in control groups (N = 12). Similar protocols of MR imaging with additional T2-weighted images were used for the rats with implanted HCC in both study and control groups (N = 12, in each group). MR images were analyzed to evaluate the time-enhancement change (% increase of signal-to-noise ratio [SI/N]) in normal liver, renal cortex, renal medulla, and tumors. The liver-lesion contrast-to-noise ratios (CNR) were also evaluated in study and control groups. The rats were killed immediately after the last MR scan to undergo autopsy and histopathologic observation. The acute toxicity test (medial lethal dose, LD50) in mice was also done. RESULTS: The liver enhancement in normal rats reached a plateau 5-50 minutes after injection of [Gd(Bz-TTDA)]2-, maintained for three hours, then gradually declined. Intensity of enhancement in liver, renal cortex, and medulla after injection of [Gd(Bz-TTDA)]2- was significantly higher than with Gd-DTPA. The efficacy of tumor characterization with injection of [Gd(Bz-TTDA)]2- was similar to that of Gd-DTPA at the early dynamic phase of the contrast study. However, the liver-lesion CNRs were significantly higher in the study group in the later phase, when tumor enhancement decreased and liver enhancement persisted. The dose of LD50 in acute toxicity test of [Gd(Bz-TTDA)]2- in mice was 7.5 mmol/kg. CONCLUSION: The preliminary results in this animal study indicated that [Gd(Bz-TTDA)]2- has the potential of becoming a reliable liver MR contrast agent.

Animals↗

Characterization of bone and soft-tissue tumors with in vivo 1H MR spectroscopy: initial results.

PURPOSE: To determine if in vivo detection of choline by using hydrogen 1 (1H) magnetic resonance (MR) spectroscopy with dynamic contrast material-enhanced MR imaging can help differentiate between benign and malignant musculoskeletal tumors. MATERIALS AND METHODS: MR imaging was performed in 36 consecutive patients with bone and soft-tissue tumors larger than 1.5 cm in diameter. Examinations were performed at 1.5 T with a surface coil appropriate for the location of the lesions. Single-voxel 1H MR spectroscopy was performed by using a point-resolved spectroscopic sequence with echo times of 40, 135, and 270 msec. The volume of interest within lesions was positioned on the areas of early enhancement (<8 seconds after arterial enhancement) according to the findings of dynamic contrast-enhanced MR imaging with subtraction. The criterion for determining whether choline was present in a lesion was a clearly identifiable peak at 3.2 ppm in at least two of the three spectra acquired at echo times. MR spectroscopic results and histopathologic findings were determined in blinded fashion and compared with kappa statistics. P <.001 was considered to indicate a significant difference. RESULTS: Choline was detected in 18 of 19 patients with malignant tumors and in three of 17 patients with benign lesions. The three benign lesions included one perineurioma, one giant cell tumor, and one abscess. Choline was not detected in 14 patients with benign lesions nor in one patient with a densely ossifying low-grade parosteal osteosarcoma. In vivo 1H MR spectroscopy characterized bone and soft-tissue tumors, resulting in a sensitivity of 95%, specificity of 82%, and accuracy of 89% (P <.001). CONCLUSION: Choline can be reliably detected in large malignant bone and soft-tissue tumors by using a multiecho point-resolved spectroscopic protocol. 1H MR spectroscopy can help differentiate malignant from benign musculoskeletal tumors by revealing the presence or absence of water-soluble choline metabolites.

Adolescent↗

Poly(dimethylsiloxane)-based microfluidic device with electrospray ionization-mass spectrometry interface for protein identification.

An easy method to fabricate poly(dimethylsiloxane) (PDMS)-based microfluidic chips for protein identification by tandem mass spectrometry is presented. This microchip has typical electrophoretic microchannels, a flow-through sampling inlet, and a sheathless nanoelectrospray ionization (ESI) interface. The surface of the microchannel was modified with 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) and the generated electroosmotic flow under acidic buffer condition used for the separation was found to be more stable compared to that generated by the microchannel without modification. The feasibility of the device for flow-through sampling, separation, and ESI-MS/MS analysis was demonstrated by the analysis of a standard mixture composed of three tryptic peptides. Results show that four peaks corresponding to three peptide standards and acetylated products of the standard peptide were well resolved and the deduced sequences were consistent with those expected. Furthermore, the compatibility of this device with other miniaturized devices to integrate the whole process was also explored by connecting a miniaturized enzymatic digestion cartridge and a desalting cartridge in series to the sampling inlet of the microchip for the identification of a model protein, beta-casein.

Amino Acid Sequence↗