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Biomedical subjects

Wei-Jan Chen

Publications and source records attributed to Wei-Jan Chen.

9 recordsLinked to original sources

Overexpression of CLIC1 in human gastric carcinoma and its clinicopathological significance.

Gastric cancer is the second most common cancer worldwide and the fifth leading cause of cancer-related death in Taiwan. Identification of biomarkers is essential to improve patient survival. Fifty aberrantly expressed proteins were identified using 2-DE combined with MALDI TOF MS and were grouped based on their function. The overexpression of proteins was confirmed using real-time quantitative RT-PCR, Western blot, and immunohistochemical analysis. The clinicopathological correlations and prognostic significance of these aberrantly expressed proteins were evaluated to determine the novel gastric cancer biomarkers. In this study, expression of chloride intracellular channel 1 (CLIC1) is significantly up-regulated in 67.9% of gastric patients and was selected for further study. The CLIC1 expression in tumor tissues was increased by 1.95-fold (range, 0.01-6.19-fold) compared with that expressed by adjacent noncancerous mucosa. Elevated CLIC1 expression was strongly correlated with lymph node metastasis, lymphatic invasion, perineural invasion, and pathological staging. Additionally, the 5-year survival rate for the low CLIC1 expression group (n = 28; <1.72-fold) was higher than that for the high CLIC1 expression group (n = 28; >or=1.72-fold) (log rank, p = 0.0300). Experimental results indicate that overexpression of CLIC1 is a potential prognostic marker for gastric cancer.

Adult↗

Propylthiouracil, independent of its antithyroid effect, produces endothelium-dependent vasodilatation through induction of nitric oxide bioactivity.

OBJECTIVE: Propylthiouracil (PTU), independent of its antithyroid effect, is recently found to have a potent antiatherosclerotic effect. The aim of this study is to investigate whether PTU has a beneficial effect on endothelial function. METHODS AND RESULTS: Ninety patients with a history of hyperthyroidism receiving either PTU (n=45) or methimazole (MMI) (n=45) during the euthyroid status were enrolled in this study. Brachial artery endothelium-dependent (flow-mediated dilatation [FMD]) and endothelium-independent (nitroglycerin-mediated dilatation) responses were assessed by high-resolution ultrasound image. Data for these two groups were compared with those of 41 healthy control subjects. The FMD values were significantly increased in patients maintained on PTU versus those in the MMI and control groups (9.3+/-4.4%, 3.4+/-2.5%, and 3.6+/-3.4%, respectively; P<0.01). Nitroglycerin-mediated dilatation had no significant difference between the PTU, MMI, and control groups (17.4+/-7.5%, 15.9+/-6.1%, and 17.5+/-6.8%, respectively; P=0.455). On multivariate analysis, no significant relationship was found between the FMD and thyroid hormone index levels. To further elucidate whether PTU has a direct effect on endothelial function, the effect of PTU on isolated segments of Sprague-Dawley rat aorta was studied. Vasodilatation induced by PTU was endothelium-dependent and could be blocked by pretreatment with nitric oxide (NO) inhibitors. PTU also increased NO formation in aortic segments. CONCLUSIONS: This study demonstrated that PTU produced endothelium-dependent vasodilatation through thyroid-independent and NO-mediated mechanisms that may contribute to its beneficial effect on atherosclerosis.

Adult↗

Indirect regulation of human dehydroepiandrosterone sulfotransferase family 1A member 2 by thyroid hormones.

Thyroid hormone, T(3), regulates cell metabolism, differentiation, and development. cDNA microarrays were performed to study the mechanism of target gene regulation after T(3) treatment in a thyroid hormone receptor-alpha (TRalpha)-overexpressing hepatoma cell line (HepG2-TRalpha). The differentially expressed target genes are several metabolic enzymes, including dehydroepiandrosterone-sulfotransferase family 1A member 2 (SULT2A1). Enzyme SULT2A1 was elevated roughly 5-fold at the protein level and 9-fold increase at the mRNA level after 48 h T(3) treatment in HepG2-TRalpha cells. Cycloheximide inhibited T(3)-induced SULT2A1 expression, suggesting that regulation was indirect. SULT2A1 has been reported to be regulated by the two transcription factors, steroidogenic factor 1 (SF1) and GATA, in the human adrenal gland. T(3) induced a 2.5- to 3.5-fold elevation of SF1 at the protein level and a 6.2-fold increase at the RNA level in HepG2-TRalpha cells. About seven SF1 binding sites exist on the SULT2A1 gene. To identify and localize the critical SF1 binding site, series of deletion mutants of SULT2A1 promoter fragments in pGL2 plasmid were constructed. The promoter activity of the SULT2A1 gene was enhanced about 2.8- to 7.1-fold by T(3). The -228 SF1 binding site was identified as the most critical site because deleting this region reduced T(3)-induced expression. Transcription factor SF1 application enhanced the -228 but not -117 reporter plasmid activities. SULT2A1 and SF1 up-regulation at protein and RNA levels in thyroidectomized rats occurred after T(3) application. In summary, this work demonstrated that the SULT2A1 gene was mediated by SF1 and indirectly regulated by T(3). Further study is required to elucidate the physiological importance of SULT2A1 induction mediated by T(3).

Animals↗

Mediation of the inhibitory effect of thyroid hormone on proliferation of hepatoma cells by transforming growth factor-beta.

Thyroid hormone (triiodothyronine, T3) regulates growth, development and differentiation. To examine the influence of T3 on hepatoma cell growth, thyroid receptor (TR)alpha1 or TRbeta1 over-expressing HepG2 cell lines were used. Growth of the HepG2-TR stable cell line was inhibited by over 50% following treatment with T3. However, transforming growth factor (TGF)-beta neutralizing antibody, but not the control antibody can reverse the cell growth inhibition effect of T3. Flow cytometric analysis indicated that the growth inhibition was apparent at the transition point between the G1 and S phases of the cell cycle. The expression of major cell cycle regulators was used to provide further evidence for the growth inhibition. Cyclin-dependent kinase 2 (cdk2) and cyclin E were down-regulated in HepG2-TR cells. Moreover, p21 protein or mRNA levels were up-regulated by around 5-fold or 7.3-fold respectively following T3 treatment. Furthermore, phospho-retinoblastoma (ppRb) protein was down-regulated by T3. The expression of TGF-beta was studied to delineate the repression mechanism. TGF-beta was stimulated by T3 and its promoter activity was enhanced six- to eight-fold by T3. Furthermore, both T3 and TGF-beta repressed the expression of cdk2, cyclin E and ppRb. On the other hand, TGF-beta neutralizing but not control antibody blocked the repression of cdk2, cyclin E and ppRb by T3. These results demonstrated that T3 might play a key role in liver tumor cell proliferation.

Blotting, Northern↗

Tunable deep-ultraviolet source generated by scattering off adiabatically prepared Raman coherence in hydrogen gas.

We demonstrate a tunable deep-ultraviolet coherent source generated by the beating of a tunable UV laser and strongly driven vibrational Raman coherence in hydrogen. The total energy conversion efficiency reaches a maximum of 50% at the phase side of the Raman coherence. The generated spectrum of Raman sidebands tunes with the input and extends from 435 to 146 nm for an input at 282 nm.

Journal Article↗

The 4051-Angstroms band of C3 (A 1Piu-X 1Sigmag +, 000-000): perturbed low-J lines and lifetime measurements.

Rotational analyses have been carried out at high resolution for the 000-000 and 000-100 bands of the A (1)Pi(u)-X (1)Sigma(g) (+) transition of supersonic jet-cooled C(3). Two different spectra have been recorded for each band, using time gatings of 20-150 and 800-2300 ns. At the shorter time delay the spectra show only the lines observed by many previous workers. At the longer time delay many extra lines appear, some of which have been observed previously by [McCall et al.Chem. Phys. Lett. 374, 583 (2003)] in cavity ring-down spectra of jet-cooled C(3). Detailed analysis of these extra lines shows that at least two long-lived states perturb the A (1)Pi(u), 000 state. One of these appears to be a (3)Sigma(u) (-) vibronic state, which may possibly be a high vibrational level of the b (3)Pi(g) state, and the other appears to be a P = 1 state with a low rotational constant B. Our spectra also confirm the reassignment by McCall et al. of the R(0) line of the 000-000 band, which is consistent with the spectra recorded towards a number of stars that indicate the presence of C(3) in the interstellar medium. Fluorescence lifetimes have been measured for a number of upper-state rotational levels. The rotational levels of the A (1)Pi(u) state have lifetimes in the range of 230-190 ns, decreasing slightly with J; the levels of the perturbing states have much longer lifetimes, with some of them showing biexponential decays. An improved value has been obtained for the nu(1) vibrational frequency of the ground state, nu(1) = 1224.4933 +/- 0.0029 cm(-1).

Journal Article↗

Protective effect of propylthiouracil independent of its hypothyroid effect on atherogenesis in cholesterol-fed rabbits: PTEN induction and inhibition of vascular smooth muscle cell proliferation and migration.

BACKGROUND: Propylthiouracil (PTU) is used to treat hyperthyroid patients by its hypothyroid effect. PTU also is found to have potent antioxidant and immunosuppressive effects. These findings suggest that PTU may play a role in the prevention of atherosclerosis. METHODS AND RESULTS: This study evaluates the effect of PTU on atherosclerotic change in rabbits fed a high-cholesterol diet. The pronounced atherosclerotic lesions in the aortas of rabbits fed a 2% cholesterol diet for 12 weeks were significantly attenuated by the concurrent addition of 0.1% PTU to the drinking water. However, exogenous supplementation of thyroid hormone in hypothyroid PTU-treated rabbits did not abrogate the protective effect of PTU on atherogenesis. Immunohistochemical analysis showed that PTU administration apparently reduced the intimal smooth muscle cell/macrophage ratio in the atherosclerotic plaques of rabbits fed a 2% cholesterol diet. In vitro, the addition of PTU to the medium of cultured rat vascular smooth muscle cells led to a dose-dependent inhibition of cell proliferation and migration. Furthermore, this study confirmed that PTU dose-dependently increased expression of PTEN, a tumor suppressor gene known to be involved in the coordinate inhibition of VSMC proliferation and migration. CONCLUSIONS: This study demonstrated that PTU inhibited the development of atherosclerosis through a thyroid-independent mechanism that may be explained, at least in part, by the ability of PTU to inhibit vascular smooth muscle cell proliferation and migration. Furthermore, PTEN induction, via disruption of the phosphatidylinsitol 3-kinase-mediated pathway, plays a crucial role in mediating the inhibitory action on vascular smooth muscle cell proliferation and migration.

Animals↗

Predictors of stable outcome in treating chronic heart failure patients with carvedilol.

Carverdilol has a variable outcome in treating patients with chronic heart failure. This prospective single-center study evaluated the predictors of clinical variables in determining favorable outcomes in treating chronic heart failure patients with carvedilol. The relation between clinical variables and maintenance doses of carvedilol was also determined. Seventy chronic heart failure patients (mean age, 62.2 years, 50 males and 20 females) with a left ventricular ejection fraction < 35% and functional class II-III were enrolled in the study. The patients were clinically followed-up for at least 24 months. Patients were considered to have a favorable outcome if they had no decreases in functional class or quality-of-life score, an increase in left ventricular ejection fraction>5%, were not admitted to hospital due to worsening heart failure, and free of cardiac mortality. Patients with favorable outcomes had a younger age (P = 0.021), higher baseline systolic blood pressure (P = 0.080), better baseline functional class (P = 0.001), and a higher tolerated dose of carvedilol (P = 0.026) than those in the unfavorable group. In this primarily Chinese cohort of chronic heart failure patients, those with favorable outcomes were likely to be young, have a high baseline systolic blood pressure, and good baseline functional class.

Adrenergic beta-Antagonists↗

An unusual case of dual coronary artery fistulas to main pulmonary artery.

Coronary artery fistula is an anomaly in which a coronary artery directly connects to a cardiac chamber or great vessel. Its incidence is around 0.1 to 1% in the adult population. Dual coronary artery fistulas are far less common and their incidence is estimated to be around 5% in patients with this anomaly. Closure of the fistulas is indicated in patients with myocardial ischemia, large left to right shunt, congestive heart failure or other complications. Herein, we report a 64 year-old man with dual coronary artery fistulas presenting with exertional chest pain. The fistulas were initially suspected on transesophageal echocardiogram because of abnormal flow with a mosaic pattern between the left anterior descending and main pulmonary arteries. Selective coronary angiogram confirmed the diagnosis and revealed fistulous connections from the proximal left anterior descending and ostial right coronary arteries to the main pulmonary artery. The patient became symptom-free after surgical closure of the fistulas.

Coronary Disease↗