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C Chang

Publications and source records attributed to C Chang.

At least 55 records · Page 3Linked to original sources
PubMed2001

From transforming growth factor-beta signaling to androgen action: identification of Smad3 as an androgen receptor coregulator in prostate cancer cells.

Although transforming growth factor-beta (TGF-beta) has been identified to mainly inhibit cell growth, the correlation of elevated TGF-beta with increasing serum prostate-specific antigen (PSA) levels in metastatic stages of prostate cancer has also been well documented. The molecular mechanism for these two contrasting effects of TGF-beta, however, remains unclear. Here we report that Smad3, a downstream mediator of the TGF-beta signaling pathway, functions as a coregulator to enhance androgen receptor (AR)-mediated transactivation. Compared with the wild-type AR, Smad3 acts as a strong coregulator in the presence of 1 nM 5alpha-dihydrotestosterone, 10 nM 17beta-estradiol, or 1 microM hydroxyflutamide for the LNCaP mutant AR (mtAR T877A), found in many prostate tumor patients. We further showed that endogenous PSA expression in LNCaP cells can be induced by 5alpha-dihydrotestosterone, and the addition of the Smad3 further induces PSA expression. Together, our findings establish Smad3 as an important coregulator for the androgen-signaling pathway and provide a possible explanation for the positive role of TGF-beta in androgen-promoted prostate cancer growth.

Androgens↗
PubMed2001

Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase.

Smad proteins are key intracellular signaling effectors for the transforming growth factor-beta superfamily of peptide growth factors. Following receptor-induced activation, Smads move into the nucleus to activate transcription of a select set of target genes. The activity of Smad proteins must be tightly regulated to exert the biological effects of different ligands in a timely manner. Here, we report the identification of Smurf2, a new member of the Hect family of E3 ubiquitin ligases. Smurf2 selectively interacts with receptor-regulated Smads and preferentially targets Smad1 for ubiquitination and proteasome-mediated degradation. At higher expression levels, Smurf2 also decreases the protein levels of Smad2, but not Smad3. In Xenopus embryos, ectopic Smurf2 expression specifically inhibits Smad1 responses and thereby affects embryonic patterning by bone morphogenetic protein signals. These findings suggest that Smurf2 may regulate the competence of a cell to respond to transforming growth factor-beta/bone morphogenetic protein signaling through a distinct degradation pathway that is similar to, yet independent of, Smurf1.

Acetylcysteine↗
PubMed2001

Trends in cardiac morbidity and mortality after endoluminal abdominal aortic aneurysm repair; discussion 999-1000.

HYPOTHESIS: The adverse cardiac event rate following endoluminal abdominal aortic aneurysm (EAAA) repair has decreased as experience in performing the procedure has increased. Aneurysm complexity affects the rate of adverse cardiac events. DESIGN AND PATIENTS: Data from 173 consecutive patients undergoing EAAA repair from 2 successive periods were compared. There were 82 patients in the early group (group 1) and 91 patients in the later group (group 2). MAIN OUTCOME MEASURES: Myocardial infarction, congestive heart failure, unstable angina, major dysrhythmias, death. RESULTS: The cardiac event rate was 8.5% for group 1 vs 16.5% for group 2 (P =.16). Predictors of adverse cardiac events on multivariate analysis were the use of 4 or more graft extensions (P =.04), female sex (P =.01), and number of Eagle risk factors (P<.001). There were 2 postoperative deaths (2.4%) in group 1 and 4 (4.4%) in group 2 (P =.7). CONCLUSIONS: Following EAAA repair: (1) adverse cardiac events were found to correlate with use of 4 or more graft extensions, female sex, and the number of Eagle risk factors; (2) cardiac morbidity and mortality remain significant despite greater experience and improved technology; and (3) operative mortality remains acceptably low.

Aged↗
PubMed2001

Localization of androgen receptor expression in human bone marrow.

Androgens have been shown to modulate the haematopoietic and immune systems and have been used clinically for stimulating haematopoiesis in bone marrow failure conditions. To identify the bone marrow cell types as potential targets of androgens, an androgen receptor (AR)-specific antibody was used to localize the AR in normal human bone marrow biopsies. The results show that AR was ubiquitously expressed in the bone marrow of both males and females. Furthermore, the AR expression pattern did not change with age. Stromal cells, macrophages, endothelial cells, myeloblasts, myelocytes, neutrophils, and megakaryocytes expressed AR. In contrast, AR was not detected in the lymphoid and erythroid cells, or in eosinophils. These results indicate that androgens may exert direct modulating effects on a wide spectrum of bone marrow cell types via AR-mediated responses.

Adolescent↗
PubMed2001

Ethylene hormone receptor action in Arabidopsis.

Small gaseous molecules play important roles in biological signaling in both animal and plant physiology. The hydrocarbon gas ethylene has long been known to regulate diverse aspects of plant growth and development, including fruit ripening, leaf senescence and flower abscission. Recent progress has been made toward identifying components involved in ethylene signal transduction in the plant Arabidopsis thaliana. Ethylene is perceived by five receptors that have similarity to two-component signaling proteins. The hydrophobic amino-terminus of the receptors binds ethylene, and mutations in this domain both prevent ethylene binding and confer ethylene insensitivity to the plant; the carboxyl-terminal portion of the receptors has similarity to bacterial his tidine protein kinases. Genetic data suggest a model in which ethylene binding inhibits receptor signaling, yet precisely how these receptors function is unclear. Two of the receptors have been found to associate with a negative regulator of ethylene responses called CTR1, which appears to be a mitogen-activated protein kinase (MAPK) kinase kinase.

Animals↗
PubMed2001

Improving relative anisotropy measurement using directional correlation of diffusion tensors.

A method employing directional correlation of the diffusion tensor, directional-correlation weighted relative anisotropy (DRA), was developed to improve the accuracy of estimated relative anisotropy (RA). The intravoxel directional correlation was established on the same voxel between two identically acquired diffusion tensor images, and the correlation coefficient derived from tensor dot product was employed as the weighting factor applied in the calculation of RA. The effect of noise influence was reduced since the random noise between repeated scans is not directionally correlated. The RA and the inter- and intravoxel DRA estimations were examined on rat brains in vivo. The background noise alters the direction of eigenvectors and the magnitude of eigenvalues. The dispersion angle between repeatedly obtained eigenvectors, representing the extent of directional alteration of eigenvectors, depends on the tissue anisotropy as well as the signal-to-noise ratio (SNR) of the source images. Current results demonstrate that the intravoxel DRA improves the accuracy of RA estimation, increases the relative contrast of gray and white matter, and avoids the partial volume effect commonly seen in the intervoxel operations.

Animals↗
PubMed2001

Apoptosis and Fas-ligand expression correlate to the histopathological grade of gastric smooth muscle tumors.

BACKGROUND: Apoptosis is associated with the tumor grade in various types of carcinomas or lymphomas, but less is understood about the association of apoptosis in mesenchymal tumors. In the prior studies, expression of apoptotic regulatory proteins, Bcl-2, Fas and its ligand, Fas-ligand, has been related to apoptotic index (AI) and histopathological grade of tumors. Our study investigated the incidence of apoptosis in gastric smooth muscle tumor and the correlation of the apoptotic index (AI) with the histopathological grade of the tumors. We evaluated the relationship of apoptotic regulatory proteins to the AI and tumor grade. METHODS AND MATERIALS: Using immunohistochemistry and the terminal deoxynucleotidyl transferase (TdT)-mediated digoxigenin-dUTP nick end-labeling (TUNEL) assay, we analyzed the expression of Bcl-2, Fas, Fas-ligand, and AI in 26 cases of gastric smooth muscle tumors. RESULTS: The incidence of greater than 10 apoptotic cells per 10 high-power fields (HPFs) was 73% (19/26 cases). The AI was significantly associated with malignant tumors (P = 0.006) and mitotic counts (P = 0.006) but not with tumor size. Bcl-2, Fas, and Fas-ligand were detected in 13 (50%), 14 (53.8%), and 19 (73%) cases, respectively. Interestingly, Fas-ligand was significantly correlated to malignancy (P = 0.006), mitotic counts (P = 0.006), and AI (P = 0.035) but not to tumor size. Fas expression was significantly associated with high levels of AI (P = 0.014). In contrast, Bcl-2 expression was inversely associated with AI (P = 0.004). Expression of Bcl-2 and Fas did not show a statistically significant correlation with tumor grade, mitotic counts, or tumor size. CONCLUSION: Apoptosis and Fas-ligand expression are statistically correlated to the histopathological grade of gastric smooth muscle tumors. This suggests that detection of apoptotic cells and Fas-ligand expression using the TUNEL assay or immunohistochemistry are useful for the evaluation of the malignant potential of gastric smooth muscle tumors.

Adult↗
PubMed2001

Ministernotomy versus full sternotomy in congenital heart defects: a prospective randomized study.

BACKGROUND: Although the ministernotomy is extensively used in the repair of congenital heart defects all over the world, whether this approach has additional advantages over the conventional full sternotomy is not well established. This prospective study was designed to evaluate the effects of lower ministernotomy in the repair of congenital heart defects. METHODS: One hundred patients who underwent repair of atrial or ventricular septal defects were randomly divided into two groups: lower ministernotomy group (n = 50), and full sternotomy group (n = 50). The clinical indexes of each procedure were recorded and analyzed. RESULTS: The age, sex, and types of cardiac defects were comparable between the two groups. Ischemic times, bypass times, intensive care unit stay, and ventilation duration were similar in both groups. The procedure time (from skin to skin) was longer in the lower ministernotomy group than in the full sternotomy group (p < 0.001). There was less drainage in the lower ministernotomy group than in the full sternotomy group for the first 24 hours after operation (186 +/- 99 mL/m2 versus 237 +/- 134 mL/m2, p = 0.03) but no significant difference in transfusions between the two groups. The hospital stay was shorter in the lower ministernotomy group than in the full sternotomy group (6.5 +/- 1.2 days versus 7.5 +/- 1.8 days, p = 0.02). CONCLUSIONS: Ministernotomy is as safe and effective as a full sternotomy in the repair of simple congenital heart defects in older children and adults. Furthermore, this small incision reduces the postoperative drainage, shortens hospital stay, and provides better cosmetic results. Operative times are longer.

Adolescent↗
PubMed2001

MR staging of clinical stage I and IIa cervical carcinoma: a reappraisal of efficacy and pitfalls.

The purpose of this study was to evaluate the diagnostic efficacy and pitfalls of magnetic resonance (MR) imaging in preoperative staging of cervical cancer. MR imaging was performed to determine the tumor staging for 31 patients with cervical carcinoma emphasizing tumor size, parametrial invasion, vaginal invasion and lymph node metastases. Tumor size was 3.23+/-1.75 cm (mean+/-standard deviation) at MR imaging compared with 2.79+/-1.76 cm at surgical-pathologic evaluation. The discrepancy between the tumor size determined by MR imaging and the measured surgical specimens was consistent in tumors larger than 1 cm. In assessing parametrial invasion, vaginal invasion and lymph node metastases, MR imaging had an accuracy of 96.7 and 87%. In determining stage of disease and differentiating operable (< or =stage IIA) from advanced disease (> or =stage IIB), MR imaging had an accuracy of 83.8 and 96.7%. Pitfalls leading to staging errors included difficulties in differentiating cancer foci from surrounding tissue edema and excluding vaginal invasion in the presence of large cervical cancer. In conclusion, MR imaging is accurate in the evaluation of parametrial invasion and useful in the differentiation of operable from advanced disease. The ability of MR imaging to exclude vaginal invasion in the presence of large cervical cancer and differentiate cancer foci from surrounding tissue edema is not as reliable.

Adenocarcinoma↗
PubMed2001

Potential anti-androgenic activity of roxithromycin in skin.

Since acne formation is a multistep process accelerated by androgens, we examined whether a new anti-acne antibiotic roxithromycin (RXM) may act as anti-androgen using transient transfection assays in human skin fibroblasts. The result showed no significant effect of 0.5, 1 and 5 microg/ml RXM on 10(-9) M R1881-induced androgen receptor (AR) transcriptional activity. While the cotransfection of exogenous ARA55, a novel AR coactivator, increased AR transactivation up to 2.59-fold, this increase was attenuated by 5 microg/ml RXM to 64.7%. Semiquantitative RT-PCR results showed that 0.1 mM H(2)O(2) treatment increased ARA55 mRNA expression level, indicating that reactive oxygen species increase the expression of ARA55 in skin. These results suggest that RXM may serve as anti-androgen only in the hypersensitive state to androgen, but not in the physiological state, through modulating end-organ hypersensitive condition to androgen possibly involving the pathway from reactive oxygen species to ARA55.

Androgen Antagonists↗
PubMed2001

The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis.

Metalloproteases are important in many aspects of biology, ranging from cell proliferation, differentiation and remodeling of the extracellular matrix (ECM) to vascularization and cell migration. These events occur several times during organogenesis in both normal development and during tumor progression. Mechanisms of metalloprotease action underlying these events include the proteolytic cleavage of growth factors so that they can become available to cells not in direct physical contact, degradation of the ECM so that founder cells can move across tissues into nearby stroma, and regulated receptor cleavage to terminate migratory signaling. Most of these processes require a delicate balance between the functions of matrix metalloproteases (MMPs) or metalloprotease-disintegrins (ADAMs) and natural tissue inhibitors of metalloproteases (TIMPs). In this review, we discuss recent progress in identifying an essential role for metalloproteases in axon outgrowth, as an example of a focal invasive event. We also discuss the evolving concept of how MMPs might regulate stem cell fate during tumor development.

Animals↗
PubMed2001

Induction of Tie-1 and Tie-2 receptor protein expression after cerebral ischemia-reperfusion.

Tie-1 and Tie-2 are receptor tyrosine kinases (RTKs) that are exclusively expressed in endothelial cells and play important roles in endothelial cell biology. The authors have reported previously the temporal profiles of Tie-1 and Tie-2 mRNA expression after focal cerebral ischemia-reperfusion. In the current study, the localization of Tie-1/Tie-2 mRNA and proteins were further investigated in the same focal ischemia model. In situ hybridization showed that, after 60-minute ischemia and 72-hour reperfusion, both Tie-1 and Tie-2 mRNA appeared as capillary-like structures in the ischemic middle cerebral artery (MCA) cortex. Western blot analysis showed a biphasic expression of Tie-1 protein in the same region. The first peak, spanning the ischemic and early reperfusion period. was of low intensity and short-lived. The second peak was of greater intensity and spanning the period from 72 to 168 hours after reperfusion. Similarly, Tie-2 expression at the protein level also exhibited a biphasic pattern. Immunohistochemical studies, after 72 hours of reperfusion, showed that although Tie-1 and Tie-2 were detected within the ischemic cortex, they actually were expressed in different populations of endothelial cells in different regions. In agreement with the in situ hybridization study, Tie-1 immunoreactivity appeared as capillary-like structures in cortical layers 2 to 4. Similar capillary-like appearance of Tie-2 immunoreactivity was noted in the outer cortical layers. In addition, Tie-2 immunoreactivity also was observed in cortical layer 6b, where de novo large vessel formation was noted. Cellular colocalization experiments revealed that Tie-2 is expressed in proximity to its antagonist, Angpo-2, as well as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in cortical layer 1, where active vessel remodeling was noted. Interestingly, bFGF only partially colocalized with VEGF, suggesting differential roles for these angiogenic factors during vessel remodeling. Tie-1 protein, to a lesser degree, also colocalized with Angpo-2, bFGF, and VEGF in cortical layer 1. Magnetic resonance imaging (MRI) showed increased regional cerebral blood flow (CBF) corresponding to the expression of these angiogenesis gene products. Together, these findings suggest that the evolving expression of angiogenesis genes underlie the robust vascular remodeling after ischemia and reperfusion.

Angiopoietin-2↗
PubMed2001

The Arabidopsis eer1 mutant has enhanced ethylene responses in the hypocotyl and stem.

By screening for enhanced ethylene-response (eer) mutants in Arabidopsis, we isolated a novel recessive mutant, eer1, which displays increased ethylene sensitivity in the hypocotyl and stem. Dark-grown eer1 seedlings have short and thick hypocotyls even in the absence of added ethylene. This phenotype is suppressed, however, by the ethylene biosynthesis inhibitor 1-aminoethoxyvinyl-glycine. Following ethylene treatment, the dark-grown eer1 hypocotyl response is greatly exaggerated in comparison with the wild type, indicating that the eer1 phenotype is not simply due to ethylene overproduction. eer1 seedlings have significantly elevated levels of basic-chitinase expression, suggesting that eer1 may be highly sensitive to low levels of endogenous ethylene. Adult eer1 plants display exaggerated ethylene-dependent stem thickening, which is an ethylene response previously unreported in Arabidopsis. eer1 also has enhanced responsiveness to the ethylene agonists propylene and 2,5-norbornadiene. The eer1 phenotype is completely suppressed by the ethylene-insensitive mutation etr1-1, and is additive with the constitutive ethylene-response mutation ctr1-3. Our findings suggest that the wild-type EER1 product acts to oppose ethylene responses in the hypocotyl and stem.

Alkenes↗
PubMed2001

CD4+ T helper 1 cells facilitate regression of murine Lyme carditis.

Murine Lyme borreliosis, caused by infection with the spirochete Borrelia burgdorferi, results in acute arthritis and carditis that regress as a result of B. burgdorferi-specific immune responses. B. burgdorferi-specific antibodies can attenuate arthritis in mice deficient in both B cells and T cells but have no effect on carditis. Because macrophages comprise the principal immune cell in carditis, T-cell responses that augment cell-mediated immunity may be important for carditis regression. To investigate this hypothesis, we examined the course of Lyme carditis in mice selectively deficient in B cells or alphabeta T cells. Our results show that carditis regresses in B-cell-deficient B10.A(k) mice but not in alphabeta T-cell-deficient mice, independently of the mouse strain background. Despite prominent macrophage infiltrates, hearts from B. burgdorferi-infected alphabeta T-cell-deficient mice had less mRNA for tumor necrosis factor alpha as measured by reverse transcription-PCR compared to infected control mice. Anti-inflammatory cytokine mRNA levels were equivalent. Adoptive transfer of gamma interferon-secreting CD4+ T cells into infected alphabeta T-cell-deficient mice promoted carditis resolution. These results show that alphabeta T cells can promote resolution of murine Lyme carditis and are the first demonstration of a beneficial role for CD4+ T helper 1 cells in this disease.

Animals↗
PubMed2001

Quercetin cumulatively enhances copper induction of metallothionein in intestinal cells.

Wilson's disease, a genetic copper-overload condition, is currently treated with zinc because of the ability of zinc to induce metallothionein. We are interested in nonmetal chemicals that may alter intestinal copper metabolism and thus help to alleviate copper toxicity. Previously, we have shown that quercetin, a dietary flavonoid, can chelate copper. This study further examined the interaction of quercetin and copper in intestinal epithelial cells. We found that quercetin enhanced metallothoinein induction by copper and the effect was dose dependent. Quercetin also exerted a cumulative effect after repeated exposure. Repeated low-dose treatment (3-10 microM) of cells with quercetin can lead to the same effect on metallothoinein as one higher concentration treatment (100 microM). This property of quercetin is distinct from its chemical interaction with copper, but both can contribute to a reduction of copper toxicity. Among other flavonoids tested, two other copper chelators, catechin and rutin, did not increase copper induction of metallothionein, whereas genistein, an isoflavone that does not interact with copper chemically, increased copper induction of metallothionein. The effect of quercetin on copper metabolism is unique. Quercetin decreased zinc-stimulated metallothionein expression and had no effect on the cadmium induction of metallothionein. The clinical application of our observation needs to be explored.

Cadmium↗
PubMed2001

Role of chaperones in nuclear translocation and transactivation of steroid receptors.

Molecular chaperones assist proteins to reach their mature and functional conformation. It has become apparent in recent years that chaperones function as part of a multiprotein heterocomplex that is potentially involved not only in protein folding, but also in intracellular trafficking and in targeting proteins for degradation. In the case of steroid receptors, the activity of the chaperone heterocomplex, as well as the proteins comprising the heterocomplex, has an effect on the observed ligand-dependent transcriptional activity of the receptor. The direct interaction between chaperones and steroid receptors makes them potential therapeutic targets in a number of pathologic conditions. In the case of cancers with steroid receptor involvement, such as breast and prostate cancer, the inhibition of chaperone activity may inhibit tumor cell growth. Conversely, enhancement of chaperone activity may be beneficial in disorders of protein misfolding, as in the case of androgen receptor aggregates found in Spinal and Bulbar Muscular Atrophy.

Biological Transport↗
PubMed2001

Gender difference in cytoprotection induced by estrogen on female and male bovine aortic endothelial cells.

Before menopause, women have a lower risk of cardiovascular diseases than men. Studies attribute this gender difference to estrogenic protection in the female cardiovascular system. We have demonstrated that 17beta-estradiol (E2) protects female bovine aortic endothelial cells against oxidative injury, probably through the induction of antioxidant enzyme activities. In this study, we examined whether E2 confers a differential protection on male and female cells. Bovine aortic endothelial cells from both genders were preconditioned for 24 h with E2 (1 nM to 10 microM), and their resistance to paraquat (1 mM, 3 h), a superoxide generator, was measured using an MTT assay. In contrast to the protection observed in female bovine aortic endothelial cells, there was no protective effect by E2 on male bovine aortic endothelial cells at physiologic concentrations. However, E2 at 1-10 microM attenuated paraquat's toxicity in both male and female cells, probably through its direct antioxidant activity. E2 at 1 nM increased in female, but not in male, cells the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, which was associated with decreased levels of reactive oxygen species during subsequent paraquat exposure. This suggests that antioxidant enzyme induction plays some role in E2-augmented oxidative resistance in female endothelial cells.

Animals↗