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Biomedical subjects

C Sun

Publications and source records attributed to C Sun.

At least 19 recordsLinked to original sources
PubMed2006

Androgen receptor mutation (T877A) promotes prostate cancer cell growth and cell survival.

Alteration of the AR functions due to amplification, overexpression and somatic mutation of the AR itself or altered interaction of AR with other cell growth regulatory proteins, may contribute to a significant subset of advanced prostate cancer (CaP). Very little is known about the pathways impacted by AR dysfunctions, although CaP associated AR alterations suggest the biological role of the AR dysfunction in disease progression. Comparative evaluations of wild type (wt) AR and mutant (mt) ARs in appropriate experimental models should provide a better understanding of the functional impact of AR alterations in CaP. Here, we provide direct evidence showing cell growth/cell survival promoting effects of the widely studied CaP associated AR mutation (T877A). In contrast to Ad-wtAR or Ad-control infected LNCaP or LAPC4 cells, Ad-mtAR (T877A) infected LNCaP or LAPC4 cells continued to grow in the androgen-deprived medium and exhibited an androgen independent AR-transcription factor activity. Further, Ad-mtAR (T877A) infected LNCaP or LAPC4 cells exhibited enhanced cell growth in the presence of lower concentrations of the synthetic androgen, R1881. Of note, Ad-mtAR (T877A) infected LNCaP cells showed striking resistance to cell growth inhibition/apoptosis mediated by the wt p53. Taken together, these findings provide novel insights into the AR dysfunctions resulting from the T877A mutation and functionally similar AR alterations may provide selective cell growth/survival advantage for CaP progression. These observations have important implications for developing biology-based prognostic biomarkers and therapeutic strategies for CaP showing such AR dysfunctions.

Apoptosis↗
PubMed2006

Quantitative expression profile of PSGR in prostate cancer.

PSGR is a novel member of the G-protein-coupled olfactory receptor family. Our initial report showed predominant expression of the PSGR in human prostate gland and significant alterations of PSGR expression in primary prostate cancer (CaP) specimens. The aim of this study was to provide in-depth evaluations of the expression profile of PSGR in prostatic epithelial cells of CaP patients and to evaluate the association of PSGR expression characteristics with clinico-pathologic features. In total, 220 RNA specimens, from laser capture microdissected paired benign and malignant prostatic epithelial cells of 110 CaP patients, were analyzed for PSGR expression by quantitative real-time PCR. The differential expression of PSGR between the prostatic epithelial cells of malignant and benign glands was statistically significant (P<0.0001). Comparison of PSGR expression between paired benign and tumor cells revealed prostate tumor cell-specific overexpression in 67.2% of tumor specimens (74 of 110), decreased expression in 20.9% of tumor specimens (23 of 110) and no difference of PSGR expression between tumor and normal cells in 11.8% of specimens (13 of 110). In representative cases, PSGR expression patterns were independently confirmed by in situ RNA hybridization. The PSGR overexpression associated with higher percentage of pathologic stage, pT3, and a higher level of preoperative serum PSA. CaP cells of African-American CaP patients exhibited about two-fold increase of PSGR expression in comparison to the Caucasian American CaP patients. Strikingly high-percentage CaP cells overexpress PSGR warrants further studies of PSGR expression alterations to define subsets of CaPs.

Black or African American↗
PubMed2006

Preparation of novel cationic copolymer microspheres and evaluation of their function by in vitro and in vivo tests as pH-sensitive drug carrier systems.

Novel pH-sensitive copolymer microspheres containing methylacrylic acid and styrene cross-linking with divinylbenzene were synthesized by free radical polymerization. The microspheres that were formed were then characterized by Fourier-Transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), size analysis, and X-ray analysis. The copolymer microspheres showed pulsatile swelling behavior when the pH of the media changed. The pH-sensitive microspheres were loaded with diltiazem hydrochloride (DH). The release characteristics of the free drug and the drug-loaded microspheres were studied under both simulated gastric conditions and intestinal pH conditions. The in vivo evaluation of the pulsatile preparation was subsequently carried out using beagle dogs as experimental subjects. The results demonstrated that the drug release exhibited a pulsatile character both in vitro and in vivo.

Animals↗
PubMed2006

Oval cells in hepatitis B virus-positive and hepatitis C virus-positive liver cirrhosis: histological and ultrastructural study.

AIMS: It is still not clear whether oval cells demonstrate diverse morphology, immunophenotype or quantity in different human liver diseases. The aim of this study was to investigate these differences in hepatitis B virus (HBV)-positive and hepatitis C virus (HCV)-positive human liver cirrhosis (HLC). METHODS AND RESULTS: Thirty-eight cases of HBV+ HLC and 32 cases of HCV+ HLC were investigated by light microscopy and immunohistochemistry for Hepatocyte, CK19, stem cell factor (SCF) and CD34. Five cases were also examined by transmission electron microscopy. Oval cells of similar morphology could be found in proliferating bile ductules in both groups. These cells coexpressed CK19 and Hepatocyte, but did not express SCF or CD34. Some of these cells exhibited a trend towards differentiation. There was no difference in the amount of oval cells between the two groups. The oval cell number was found to increase significantly with the progression of inflammation. A similar stem-like cell was not seen in the normal liver. CONCLUSIONS: There are bipotential oval cells in both HBV+ and HCV+ HLC. The lack of difference in oval cells between the two groups suggests that they might play a similar biological role in the histogenesis of different liver diseases.

Adult↗
PubMed2005

Ultrafast quenching of ferromagnetism in InMnAs induced by intense laser irradiation.

Time-resolved magneto-optical Kerr spectroscopy of ferromagnetic InMnAs reveals two distinct demagnetization processes--fast (<1 ps) and slow (approximately 100 ps). Both components diminish with increasing temperature and are absent above the Curie temperature. The fast component rapidly grows with pump power and saturates at high fluences (>10 mJ/cm(2)); the saturation value indicates a complete quenching of ferromagnetism on a subpicosecond time scale. We attribute this fast dynamics to spin heating through p-d exchange interaction between photocarriers and Mn ions, while the approximately 100 ps component is interpreted as spin-lattice relaxation.

Journal Article↗
PubMed2005

Protection of PC12 cells from hydrogen peroxide-induced injury by EPS2, an exopolysaccharide from a marine filamentous fungus Keissleriella sp. YS4108.

A number of studies indicate that free radicals are involved in the neurodegeneration in Parkinson's and Alzheimer's diseases. EPS2, an exopolysaccharide with a mean molecular weight of 1.3 x 10(5) Da, was isolated by ion-exchange and sizing chromatography from the culture of Keissleriella sp. YS4108, a marine filamentous fungus. Compositionally, it is composed of galactose, glucose, rhamnose, mannose and glucuronic acid in an approximate proportion of 50:8:1:1:0.4. The protective effects of EPS2 on peroxide hydrogen (H2O2)-induced cell lesion, level of lipid peroxidation, antioxidant enzyme activities were investigated in the rat pheochromocytoma line PC12 cells. Following a 1-h exposure of the cells to H2O2, a significant reduction in cell survival and activities of glutathione peroxidase (GSH-Px) and catalase (CAT), as well as increased levels in malondialdehyde (MDA) production and lactate dehydrogenase (LDH) release were observed. However, preincubation of the cells with EPS2 prior to H2O2 exposure elevated the cell survival and GSH-Px and CAT activities, and decreased the level of MDA and LDH activity in a dose-dependent manner. In conclusion, EPS2 possesses pronounced protective effects against H2O2-induced cell toxicity. The finding is of a higher value in searching for new therapeutic agent for treating oxidative damage-derived neurodegenerative disorders.

Animals↗
PubMed2005

Characterization of interactions of Na+/H+ exchanger regulatory factor-1 with the parathyroid hormone receptor and phospholipase C.

The Na(+)/H(+) exchanger regulatory factor-1 (NHERF1) is a molecular scaffold important for the signaling of the G-protein coupled receptor for the parathyroid hormone (PTH1R). The two PDZ (PSD-95, Discs-large, ZO1) domains of NHERF1 through association with the C-termini of PTH1R and phospholipase C enhance the signaling pathway associated with PTH. To examine these interactions, we have produced the individual PDZ1 and PDZ2 domains as well as the tandem PDZ1-PDZ2 domains (PDZ12) of NHERF1 and have characterized the binding affinities of the C-terminal motifs of PTH1R and PLCbeta using fluorescence anisotropy. Circular dichroism indicates that the PDZ1 and PDZ2 are properly folded. Based on fluorescence anisotropy we find that the C-terminus of PTH1R, containing ETVM, has similar affinities (approximately 10 microm) for both PDZ1 and PDZ2. The PTH1R displayed reduced binding affinity for the tandem PDZ12 (16 microm) compared with the individual domains or a solution of equal molar concentrations of PDZ1 and PDZ2 (5.8 microm), suggesting negative cooperativity between the PDZ domains or intervening region. The C-termini of PLCbeta (both beta1 and beta2 isozymes were examined, containing DTPL and ESRL, respectively) displayed a diminished affinity for PDZ2 (approximately 30 microm) over that of PDZ1 (approximately 8 microm). Finally, we demonstrate trans PDZ1-PDZ2 association that is enhanced in the presence of the C-terminus of PTH1R or PLCbeta, suggesting oligomerization of NHERF as a mode for enhancing the signaling associated with PTH.

Animals↗
PubMed2004

Orientation bias of the extraclassical receptive field of the relay cells in the cat's dorsal lateral geniculate nucleus.

The spatial properties of the extraclassical receptive fields (ECRF) of neurons responding to a stimulus restricted to it and its interaction with the classical receptive field (CRF) in visual information processing were investigated in 74 relay cells in the dorsal lateral geniculate nucleus (LGNd) of anesthetized cats. The results demonstrate that the ECRF of most relay cells in the LGNd responded preferentially to a grating stimulus of low spatial frequency through a mechanism of spatial summation. These biased cells showed a significant orientation bias which was relatively smaller than that of the CRF. The preferred orientations of the ECRF were not correlated with those of the CRF in most relay cells. The orientation biased ECRFs and CRFs interacted with each other in a non-linear way, resulting in a great diversity of response properties. Overall, the CRF played a more significant role than the ECRF in determining a cell's orientation bias and preferred orientation. The ECRF mostly showed a modulatory role mainly in suppressing and/or in partially facilitating the neural response to stimulation in the CRF although in some cases, the ECRF did determine a cell's responsiveness and orientation sensitivity. These results suggest that the ECRF might contribute to the ability of the LGNd neurons to detect some complex features such as texture segmentation and provide a subcortical contribution to the integrative field of visual cortical cells through receiving inputs from retinal ganglion cells with similar orientation biased extended surrounds [Neuroscience 98 (2000) 207].

Action Potentials↗
PubMed2004

Gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with antitumor activity against breast cancer in vivo.

Gliotoxin is a natural mycotoxin with immunosuppressive and antimicrobial activity. Inhibition of farnesyltransferase (IC50 80 microM) and geranylgeranyltransferase I (IC50 17 microM) stimulated interest in the potential antitumor activity of this epidithiodioxopiperazine. Gliotoxin inhibited proliferation of six breast cancer cell lines in culture with mean +/- SD IC50 289 +/- 328 microM (range 38-985 microM); intracellular farnesylation of Lamin B and geranylgeranylation of Rap1A were inhibited in a dose-dependent manner. In randomized controlled studies using the N-methyl-N-nitrosourea rat mammary carcinoma model, gliotoxin had pronounced antitumor activity in vitro and little systemic toxicity when administered to 10 animals at 10 mg/kg by subcutaneous injection weekly for 4 wk compared with 10 controls. Single doses up to 25 mg/kg were well tolerated. The present studies confirm that gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with pronounced antitumor activity and favorable toxicity profile against breast cancer in vitro and in vivo.

Alkyl and Aryl Transferases↗
PubMed2004

The nuclear oxysterol receptor LXRalpha is expressed in the normal human breast and in breast cancer.

The liver X> or = receptor alpha (LXRalpha) is a nuclear receptor with a key role in bile acid biosynthesis and cholesterol metabolism. The present study investigated the expression and function of LXRalpha in the normal and malignant human breast. LXRalpha mRNA transcripts were detected by RT-PCR in nine breast carcinoma cell lines. The nucleotide sequence of the cloned PCR product was identical to the corresponding human LXRalpha cDNA sequence. Expression of LXRalpha protein was confirmed by immunoblot analysis of breast cancer cell lysates. LXRalpha mRNA was expressed in 14/15 (93%) of normal human breast mammoplasty specimens and in 11/15 (73%) of primary breast carcinomas. Oxysterol and nonsteroidal LXRalpha agonists at low micromolar concentrations inhibited proliferation of breast carcinoma cell lines in culture. The importance of LXRalpha signaling in cholesterol homeostasis and the observed expression of LXRalpha in normal breast tissue suggest that this nuclear oxysterol receptor has an important physiological function in the breast. LXRalpha gene expression is regulated by dietary fatty acids implicated in breast carcinogenesis and detection of LXRalpha expression in breast cancer cell lines and breast tumors in the present study indicates that LXRalpha may also be important in breast carcinogenesis. Inhibition of breast cancer cell proliferation suggests that pharmacological LXRalpha agonists may have potential preventive and/or therapeutic antitumor activity in breast cancer.

Breast↗
PubMed2003

FLAG chemotherapy followed by allogeneic stem cell transplant using nonmyeloablative conditioning induces regression of myelofibrosis with myeloid metaplasia.

A 38-year-old woman with agnogenic myeloid metaplasia complicated by the poor prognostic factors of severe osteosclerosis, prominent hepatosplenomegaly, and profound anemia was treated with FLAG chemotherapy to decrease her organomegaly before undergoing a nonmyeloablative allogeneic stem cell transplant from a matched-sibling donor. The patient's pre- and post transplant course were complicated by an autoimmune disorder and her post transplant course was complicated by severe hepatic and gastrointestinal GVHD. A technetium-99m sulfur colloid scan 4 months post transplant and bone marrow studies 8 months post transplant demonstrated intramedullary hematopoiesis, complete resolution of marrow fibrosis, and partial resolution of osteosclerosis.

Adult↗
PubMed2003

Pre-neutralization of C5a-mediated effects by the monoclonal antibody 137-26 reacting with the C5a moiety of native C5 without preventing C5 cleavage.

Complement C5a is aetiologically linked to inflammatory tissue damage in conditions like septicaemia, immune complex diseases and ischaemia-reperfusion injury. We here describe a monoclonal antibody (mAb), 137-26, that binds to the C5a moiety of human C5 and neutralizes the effects of C5a without interfering with C5 cleavage and the subsequent formation of lytic C5b-9 complex. Mouse anti-human C5 mAbs were generated and the reactivity with C5 and C5a was detected by ELISA and surface plasmon resonance. The inhibition of C5a binding to C5a receptor was studied using a radioligand binding assay. The effects of the antibody on C5a functions were examined using isolated neutrophils and a novel human whole blood model of inflammation. Haemolytic assays were used to study the effect on complement-mediated lysis. mAb 137-26 reacted with both solid- and solution-phase C5 and C5a in a dose-dependent manner with high affinity. The antibody competed C5a binding to C5a receptor and inhibited C5a-mediated chemotaxis of neutrophils. Furthermore, the antibody effectively abrogated complement-dependent E. coli-induced CD11b up-regulation and oxidative burst in neutrophils of human whole blood. mAb 137-26 was more potent than a C5a receptor antagonist and a previously described anti-C5a antibody. mAb 137-26 did not inhibit complement-mediated lysis, nor did it activate complement itself. Together, mAb 137-26 binds both the C5a moiety of native C5 and free C5a, thereby effectively neutralizing the biological effects of C5a. The antibody may have therapeutic potential in inflammatory diseases where C5a inhibition combined with an operative lytic pathway of C5b-9 is particularly desired.

Animals↗
PubMed2003

Platelet FcgammaRIIA His131Arg polymorphism and platelet function: antibodies to platelet-bound fibrinogen induce platelet activation.

The His131Arg polymorphism of platelet FcgammaRIIA affects the binding affinity of certain IgG subclasses. The Arg131 allele has been associated with (auto)immune thrombocytopenia and heparin-induced thrombocytopenia in some studies. Because FcgammaRIIA can transmit platelet activation signals, we studied platelet responsiveness from 73 healthy donors to determine if this polymorphism modulated platelet function. Platelet function was studied by agonist and shear-induced activation, and standard aggregation. FcgammaRIIA was genotyped by allele-specific PCR. Compared with His131, the Arg131 allele was associated with significantly greater binding of activation-dependent antibodies. This effect was most prominent for the receptor-induced binding site (RIBS) antibodies F26 (P < 0.0001) and RIBS1 (P = 0.0057), and the ligand-induced binding site antibody LIBS1 (P = 0.0367). Unexpectedly, Arg131-positive platelets did not show greater fibrinogen binding, platelet aggregation or shear-induced platelet activation. We considered whether enhanced Fc binding and FcgammaRIIA cross-linking were responsible for those discrepancies. The increased binding of the two RIBS antibodies to the Arg131 isoform was abolished by blocking FcgammaRIIA, and the FcgammaRIIA genotype effect on F26 IgG binding was lost when F26 F(ab')2 fragments were used. Furthermore, intact F26 and RIBS1 IgG directly and specifically induced P-selectin expression, and this effect was greatest in Arg131-positive platelets. We concluded that (a) the His131Arg polymorphism of FcgammaRIIA does not affect intrinsic platelet reactivity; (b) RIBS antibodies are able to cross-link FcgammaRIIA and activate platelets, and this activation has a modest effect on Arg131 platelets; and (c) flow cytometric based platelet assays may need to compensate for this FcgammaRIIA His131Arg effect on platelet activation.

Adult↗
PubMed2002

Trace analysis of dissolved polychlorinated organic compounds in the water of the Yangtse River (Nanjing, China).

Eighteen organochlorine contaminants from the water samples of the Yangtse River have been qualitatively and quantitatively analyzed. The analysis of polychlorinated organic compounds (PCOCs) extracted by C18 Solid Phase Extract (SPE) was performed using HP6890 gas chromatograph coupled by ECD detector. The analytical results demonstrate that the analytical methods are reliable based on the fact that most of the recoveries for the targeted compounds are 60-90%. Most of the concerned contaminants, i.e. chlorinated pesticides and PCBs were found in the water samples of the Yangtse River, but their concentration was very low, <2.97 ng l(-1), which is far less than 1 microg l(-1)--the standard of drinking water of China. It is apparent that the PCOCs were in high concentration during the dry season, and in low concentration during the rainy season. The situation of PCOCs contamination in the water of the Yangtse River in 1999 was greatly improved in comparison with 10 years ago.

China↗
PubMed2001

Biphasic effects of orchidectomy on calcitonin gene-related peptide synthesis and release.

We hypothesize that the decline of male gonadal hormones may play a role in age-related decrease of calcitonin gene-related peptide (CGRP) synthesis and release. Orchidectomized rats were raised with or without testosterone replacement and CGRP levels in serum and some tissues as well as the perfusate from the isolated mesenteric arterial bed (MAB) were measured at 1, 2 and 4 months after orchidectomy. CGRP levels of serum and tissues, and CGRP release from MAB were significantly elevated after 1 month and decreased after 4 months in orchidectomized rats. The changes were restored by testosterone replacement. Our results indicate that the age-related decline of testosterone might contribute to the age-related decrease of CGRP synthesis and release.

Animals↗