Biomedical subjects

Y Xie

Publications and source records attributed to Y Xie.

At least 181 records · Page 10Linked to original sources

PubMed2000

HSP70 and heat shock factor 1 cooperate to repress Ras-induced transcriptional activation of the c-fos gene.

Heat shock protein 70 (HSP70) is a molecular chaperone involved in protein folding and resistance to the deleterious effects of stress. Here we show that HSP70 suppresses transcription of c-fos, an early response gene that is a key component of the ubiquitous AP-1 transcription factor complex. HSP70 repressed Ras-induced c-fos transcription only in the presence of functional heat shock factor1 (HSF1). This suggests that HSP70 functions as a corepressor with HSF1 to inhibit c-fos gene transcription. Therefore, besides its known function in the stress response, HSP70 also has the property of a corepressor and combines with HSF1 to antagonize Fos expression and may thus impact multiple aspects of cell regulation.

Animals↗

PubMed2000

RSK2 represses HSF1 activation during heat shock.

Heat shock transcription factor 1(HSF1) activation is a multistep process. The conversion of a latent cytoplasmic form to a nuclear, DNA binding state appears to be activated by nonsteroidal anti-inflammatory drugs. In previous studies, we showed that HSF 1 is phosphorylated by the protein kinase RSK2 in vitro and that this effect is inhibited by nonsteroidal anti-inflammatory drugs at the concentration that leads to the activation of HSF1 in vivo (Stevenson et al 1999). In the present study, using cells from a patient with Coffin-Lowry syndrome (deficient in RSK2), we demonstrate that RSK2 slightly represses activation of HSF1 in vivo at 37 degrees C. In Coffin-Lowry syndrome cells, HSF1-HSE DNA binding activity after treatment with sodium salicylate was slightly higher than that in untreated cells, indicating that although RSK2 is involved in HSF1 regulation, it is not the unique protein kinase that suppresses HSF1-HSE binding activity at 37 degrees C. However, heat shock treatment resulted in significantly higher HSF1-HSE binding activity in Coffin-Lowry syndrome cells as compared with normal controls, suggesting that RSK2 represses HSF1-HSE binding activity during heat shock.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

Downregulation of LAR tyrosine phosphatase prevents apoptosis and augments NGF-induced neurite outgrowth.

The identity of the protein tyrosine phosphatases (PTPs) regulating cell death and responses to neurotrophins during neural development remain unknown. To determine if the leukocyte common antigen-related (LAR) PTP regulates these processes, PC12 cells were made LAR-deficient via stable transfection with an LAR antisense transgene. LAR-deficient cells demonstrated a stable novel phenotype, including a two-fold increase in nerve growth factor- but not fibroblast growth factor-induced neurite outgrowth. Upon serum-deprivation, LAR-deficient cells exhibited a two- to three-fold decrease in cell death. The findings that an endogenous PTP promotes cell death and counter-regulates neurotrophin actions introduce a major new receptor gene family to neurotrophic processes and suggest novel strategies for preventing cell death and augmenting neurotrophin function.

Animals↗

PubMed2000

Detailed allelic loss mapping on 7q32 in nasopharyngeal carcinoma.

OBJECTIVE: The present research group had found high frequency of loss of heterozygosity(LOH) of D7S500-D7S495 on chromosome band 7q32 in nasopharyngeal carcinoma, this study was conducted to further find the deletion region. METHODS: Higher density of loci on 7q32 in 30 tumors was studied by using microsatellite analysis. RESULTS: The frequency of LOH was 63.3%. The highest frequency of LOH was identified at the loci of D7S500-D7S509-D7S495, among which a common deletion of D7S509 was found. CONCLUSION: A putative tumor suppressor gene may be present around D7S509.

Chromosomes, Human, Pair 7↗

PubMed2000

Effects of Bcl-2 and Bcl-XL protein levels on chemoresistance of hepatoblastoma HepG2 cell line.

The ratio between apoptotic promoters and repressors in the Bcl-2 family determines the chemosensitivity of cells to apoptotic stimuli. This study examines the chemoresistance of a transfected human hepatoblastoma HepG2 cell-line during Taxol and Doxorubicin application. Sense bcl-2, and anti-sense bcl-XL gene fragments were separately inserted into HepG2 cells via stable transfection. The expression profile of the Bcl-2 family proteins was determined by Western blot analysis. Chemosensitivity of the transfected cells was measured by Trypan blue exclusion assay and XTT reduction assay during drug application. In the absence of Bax protein, HepG2 cells with elevated Bcl-2 protein levels did not exhibit any significant increase in chemosensitivity towards the drugs. Transfected cells with reduced Bcl-XL levels became more sensitive to the drugs, and a significant difference in IC50 values was observed. The chemosensitivity of HepG2 cells to Taxol and Doxorubicin was not affected by Bcl-2 levels, while reduction of Bcl-XL levels rendered the cells more sensitive to the drugs. This suggests that the Bcl-2 protein alone could not protect HepG2 cells from drug-induced apoptosis, and that the Bcl-XL protein may be a target for gene therapy in hepatoblastoma treatment.

Antineoplastic Agents↗

PubMed2000

Inhibition of N-linked glycosylation down-regulates insulin-like growth factor-1 receptor at the cell surface and kills Ewing's sarcoma cells: therapeutic implications.

The insulin-like growth factor-1 receptor (IGF-1R) has been shown to be of critical importance for tumor development and tumor cell survival of various types of malignancies. We have previously demonstrated that an adequate N-linked glycosylation of IGF-1R is required for its translocation to the cell surface in melanoma cells. This raises the possibility of using glycosylation inhibitors as therapeutic agents against IGF-1R-dependent malignancies. In this study we show that inhibition of N-linked glycosylation using tunicamycin or the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor lovastatin resulted in down-regulation of IGF-1R at the cell surface in Ewing's sarcoma cell lines (RD-ES and ES-1 cells). The down-regulation of plasma membrane-bound IGF-1R was correlated with a drastic decrease in IGF-1R autophosphorylation, suggesting biochemical inactivation of the receptor. Whereas RD-ES and ES-1 cells responded differently with regard to DNA synthesis, the decrease in IGF-1R expression was accompanied by a rapid and substantial decrease in survival of both cell lines. Our data suggest that relatively untoxic HMG-CoA reductase inhibitors (e.g. lovastatin) could have therapeutic significance in IGF-1R-dependent neoplasms like Ewing's sarcoma.

Antineoplastic Agents↗

PubMed2000

[Molecular cloning of a novel gene located on chromosome 3p25.3 and an analysis of its expression in nasopharyngeal carcinoma].

OBJECTIVE: To obtain the novel genes associated with human nasopharyngeal carcinoma(NPC) on chromosome 3p24-26. METHODS: Twenty epithelial-derived expressed sequence tags(EST) were selected from chromosome 3p24-26 where loss of heterozygosity(LOH) frequently occurs in NPC tissues. Primers were designed based on the sequences of these ESTs. RT-PCR was used to amply their corresponding cDNA fragments from NPC cell line HNE1 and primary cultures of normal nasopharyngeal epithelial cells. The differential expression of two ESTs, T93093 and R41598, was confirmed by Northern blot. Then, expression of EST T93093 was further detected in 7 normal nasopharyngeal and 19 NPC biopsies. cDNA library screening was used to get its full cDNA sequence and the sequence of this novel gene was analyzed by bioinformatics. RESULTS: Thirteen ESTs(T62511, N39155, N68660, R61275, T95314, R06143, H52697, H66521, AA128685, AA284537, N52379, AA054180, and H98090) showed the similar expression level and 5 ESTs(R00732, R07573, R98052, H91759, H17566) showed no expression in both types of cells. EST T93093 was down-expressed, whereas EST R41598 up-expressed in NPC HNE1 cells. The EST T93093 was also found to be down-expressed in 26.3%(5/19) of NPC biopsies. The full length cDNA of this gene was obtained and named NAG-7, which is located at chromosome 3p25.3. Its 1677 bp full length cDNA has a potential open reading frame(ORF) predicting a 94 amino acid protein with a molecular weight of 11023.87 Dalton. Bioinformatics analysis of the NAG-7 gene shows that it is a transmembrane protein containing a protein kinase C(PKC) phosphorylation site and a myristyl site. It has no significant homology to any reported genes in database of GenBank(AF086709). CONCLUSION: NAG-7 is a novel gene down-expressed in NPC, which may be involved in the development of NPC.

Chromosome Mapping↗

PubMed2000

Aberrant Fanconi anaemia protein profiles in acute myeloid leukaemia cells.

Fanconi anaemia (FA) is an autosomal recessive disease strongly predisposing to bone marrow failure and acute myeloid leukaemia (AML). Four FA genes, corresponding to complementation groups A, C, F and G, have been cloned, but the molecular functions of the corresponding proteins are unknown. The high risk of AML in FA patients suggests that the 'FA pathway' helps to prevent AML in non-FA individuals. We examined 10 AML cell lines, as well as primary cells from 15 AML patients representing the French-American-British subclasses M1-M5a, for possible deficiencies in the 'FA pathway'. Cellular lysates were analysed for the presence of the FA proteins FANCA, FANCC, FANCF and FANCG, as well as the complexes reported to be formed between these proteins, using immunoprecipitation and Western blot analysis. Aberrant protein profiles were observed in five of the 10 cell lines and in 11 of the 15 primary AML samples. Aberrations, that included absence or reduced presence of FA proteins and/or their complexes, were noted in the subclasses M1-M4, but not in M5a (n = 3). Our results suggest that a significant proportion of general AML is characterized by a disturbance of the 'FA pathway' that may represent an early event in the development of this type of leukaemia.

Acute Disease↗

PubMed2000

[Detection of differentially expressed genes in hepatocellular carcinoma using DNA microarray].

Large scale gene expression profiles between normal hepatocytes and hepatocellular carcinomas are detected with high throughput microarray. DNA microarrays were made by spotting PCR products of 4,096 human cDNAs onto a specially treated glass slides. The probes were prepared by labelling normal tissue mRNA and cancer tissue mRNA with Cy3-dUTP and Cy5-dUTP separately through reverse transcription. The arrays were then hybridized against the cDNA probe mixture and the fluorescent signals were scanned. The obtained data were analyzed from 4 repeated experiments. There are 903 genes of which the average ratios between Cy3 signal and Cy5 signal are greater than 3.0. These genes identified through this approach are potential candidates for hepatocellular carcinoma diagnosis and therapy.

Carcinoma, Hepatocellular↗

PubMed2000

[Research on the relationship between expression of VEGF and high altitude pulmonary edema].

OBJECTIVE: To investigate the relationship between the expression of VEGF and the incidence of high altitude pulmonary edema (HAPE) and the mechanism of high altitude acclimatization-adaptation. METHODS: Pulmonary artery endothelial cells (PAEC) of rat were cultured. The expression of VEGF in PAEC was detected using RT-PCR and ELISA. Rats were divided randomly into five groups by weight: control, acute hypoxia (exposed to a simulated 8,000 m altitude for 4 hours), and three intermittent hypoxia groups (exposed to a simulated 3,000 m or 5,000 m altitude for 2 weeks, 4 hours a day, then to a simulated 8,000 m altitude for 4 hours). VEGF in the lung was detected using immunohis to chemistry and slot hybridization, and the changes of pathology in the lung were observed. VEGF in the blood plasma of rats, in men who immigrated to high altitude at different times, and in those who suffered from high altitude pulmonary edema were measured using ELISA. RESULTS: The expression of VEGF in PAEC was increased under hypoxia condition (1% O2) (P < 0.01). In the blood plasma and lung of rats during hypoxia, levels of VEGF and VEGF mRNA were higher than that in the control group. VEGF in acute hypoxia group was increased significantly compared with that in the intermittent hypoxia groups. Leakage of fluid in the lung of rats was observed in the acute hypoxia group. The longer the rats acclimatized, the lower the level of VEGF expressed, and the less the fluid leaked in the lung. The same tendency could be seen in humans. The level of VEGF in patients with high altitude pulmonary edema pre-therapy was higher than that measured post-therapy. CONCLUSIONS: Hypoxia could stimulate the expression of VEGF, and the upregulated expression of VEGF is one of the most important factors of incidence of high altitude pulmonary edema.

Altitude Sickness↗

PubMed2000

Anti-hepatoma activity of taxol in vitro.

AIM: To investigate the in vitro anti-hepatoma activity of taxol against SMMC-7721 human hepatoma cells. METHODS: The hepatoma cell growth was measured by MTT-microculture tetrazolium assay. Cell-cycle kinetics and apoptosis were analyzed by flow cytometry and microscopic examination. RESULTS: Taxol inhibited the hepatoma cell growth in concentration- and time-dependent manners with IC50 of 18.96 nmol.L-1. Marked cell accumulation in G2/M phase and multinucleated cells were also observed after treatment with taxol 10 nmol.L-1. In addition, taxol at 10 nmol.L-1 could induce the apoptosis of hepatoma cells. CONCLUSION: Taxol suppresses the growth of SMMC-7721 human hepatoma cells in vitro by causing cell-cycle arrest, aberrant mitosis, and apoptosis of the human hepatoma cells.

Antineoplastic Agents, Phytogenic↗

PubMed2000

[Isolation, identification and certain characteristics of a Hantaan virus proposed as candidate virus for killed vaccine].

OBJECTIVE: Isolation and identification of a Hantaan virus from HFRS patient's serum for killed vaccine development. METHODS: This virus temporally called FT14 detected by IFAT, RT-PCR. Partial sequence of M segment was determined by Sanger' a dideoxy chain termination method. RESULTS: The antigenicity and PCR amplification of the newly isolated virus FT14 proved that it belongs to virus of HTN type. Antiserum to the virus can neutralize many strains of Hantaan virus from different areas. The partial sequence of M segment of FT14, as compared with other HTN strains, showed great differences among nucleotide sequences, while the deduced amino acid sequence is comparatively conservative. The titer of the virus reached its peak at 9 days post inoculation in vitro, then the peak titer could last for a long time. CONCLUSIONS: This virus strain FT14 would be a good candidate virus for killed vaccine development.

Amino Acid Sequence↗

PubMed2000

Soluble cell adhesion molecules in patients with acute coronary syndrome.

OBJECTIVE: To observe the changes in serum soluble intercellular adhesion molecule type-1 (ICAM-1), vascular cell adhesion molecule type-1 (VCAM-1), E-selectin and von Willebrand factor (vWf) in patients with acute coronary syndrome. METHODS: Serial venous blood samples were taken from 21 patients with acute myocardial infarction (AMI) before and 4, 8, 12, 24, 48 and 72 h after thrombolytic treatment or direct PTCA. One blood sample was drawn from 16 patients with unstable angina and 16 control subjects. Serum concentrations of ICAM-1, VCAM-1, E-selectin and vWf were determined using a double antibody sandwich enzyme-linked immunosorbent assay. RESULTS: Serum levels of ICAM-1, VCAM-1, E-selectin and vWf were higher in patients with acute coronary syndrome than in controls. Patients with AMI and successful reperfusion therapy had a significant reduction in the serum concentration of ICAM-1 and E-selectin at 24 and 48 h, VCAM-1 at 24 and 72 h and vWf at 12, 24, 48 and 72 h, but had peak in serum levels of ICAM-1 and E-selectin at 4 h. The number of diseased coronary arteries was not related to the levels of ICAM-1, VCAM-1 and E-selecin. CONCLUSION: The serum concentration of soluble cell adhesion molecules was elevated significantly in patients with acute coronary syndrome. Successful reperfusion therapy was associated with a reduction in the serum concentrations of soluble cell adhesion molecules in patients with AMI.

Aged↗

PubMed2000

A cDNA located on chromosome 7q32 shows loss of expression in epithelial cell line of nasopharyngeal carcinoma.

OBJECTIVE: To isolate and clone the tumor suppressor gene on chromosomal region 7q32 correlated with the carcinogenesis of human nasopharyngeal carcinoma (NPC). METHODS: The genotypes of polymorphic microsatellite markers on 7q32 in DNA from 24 biopsies of nasopharyngeal carcinoma and matched normal blood cells were identified. The expression levels of 20 expressed sequence tags (ESTs) on 7q32 between human nasopharyngeal carcinoma epithelial 1 (HNE1) and primary cultures of normal nasopharyngeal epithelial (PNNE) cells were compared using differential RT-PCR and Northern hybridization. The quantity of AA070437 DNA and mRNA was detected by differential PCR and differential RT-PCR, respectively. RESULTS: Loss of heterozygosity (LOH) was found in 25%-46% of NPC biopsies. AA070437 EST expression was down-regulated in HNE1 cell compared to PNNE cells. The down-regulation of AA070437 was found in 30.7% of NPC biopsies and allelic loss of AA070437 was observed in 29.1% of NPC biopsies. CONCLUSION: Our results show that AA070437 EST is negatively related with the occurrence of human NPC and may represent a candidate tumor suppressor gene of NPC on 7q32.

Chromosomes, Human, Pair 7↗

PubMed2000

[Effect of fixed appliance on periodontal status of patients with malocclusion].

OBJECTIVE: To determine if the fixed appliance will affect the periodontal health. METHODS: Sixteen patients with malocclusion were randomly selected. One week before the fixed appliance placement, plaque index (PLI), bleeding index (BI), pocket depth (PD) and subgingival plaque were assessed. The observed value was served as the baseline records. RESULTS: After the fixed appliance placement, significant differences were found in PLI, BI, PD and these values were significantly greater than the baseline. Subgingival microfloral shifted to a more disease-inducing microflora and there was a statistically significant increase in spirochetes and fusiform. CONCLUSION: Fixed appliance placement will affect the periodontal health. Therefore, it is very important to strengthen the oral hygiene instruction to the people who receive the treatment of fixed appliance.

Adolescent↗

PubMed2000

[The effect of artificial tears on corneal surface regularity in dry eye].

OBJECTIVE: To evaluate the regularity of corneal surface and the effect of artificial tears on the corneal surface regularity in dry eye. METHODS: The surface regularity index (SRI), surface asymmetry index (SAI), the indices of TMS-1 corneal topography system, and potential visual acuity (PVA) were used to investigate the corneal regularity and corneal vision in 33 normal subjects (64 eyes) and 22 dry eye patients (42 eyes) before and after instillation of artificial tears. RESULTS: The SRI and SAI were significantly elevated and the PVA was remarkably decreased in patients with dry eye compared to that of normal subjects (P < 0.001). The average amount of astigmatism was also significantly increased in dry eye compared to that in normal eyes (P = 0.02). In the patients with dry eye, the SRI and SAI were positively correlated with corneal fluorescein staining scores. The SRI, SAI and astigmatism were significantly reduced, the PVA was improved and the irregular topographic pattern was markedly decreased in the dry eyes after the usage of artificial tears. CONCLUSION: The dry eye has an irregular corneal surface and the indices of TMS-1, SRI and SAI can be used to objectively diagnose this disorder, evaluate the severity of the dry eye and the effect of artificial tears on it. Artificial tears can smooth the corneal surface and improve the visual acuity in patients with dry eye.

Aged↗

PubMed2000

[The abnormal expression of epidermal growth factor receptor family in pterygium].

OBJECTIVE: To evaluate the expression of type 1 growth factor receptor family [epidermal growth factor receptor (EGFR), ErbB2 and ErbB3] by the epithelium in pterygium so as to understand the pathogenesis of this disorder. METHODS: The immunofluorescent staining and Western blotting were performed in 15 patients with primary pterygium, compared to normal conjunctival epithelium, to determine the expression of EGFR, ErbB2 and ErbB3 proteins. RESULTS: The EGFR was present at the basal cells while the ErbB2 and ErbB3 were expressed by the superficial cells in normal conjunctival epithelium in immunofluorescent staining. Of 15 pterygia, 11 pterygia expressed the stains of EGFR, ErbB2 and ErbB3 in the full thickness of epithelium and with stronger staining compared to the control group, 4 of them showed the same staining pattern as that in the normal conjunctiva. Compared to normal conjunctiva, the stronger density of protein bands of EGFR, ErbB2 and ErbB3 was also demonstrated by western blotting in 11 pterygia with strong staining of these antibodies. CONCLUSIONS: The expression of EGFR, ErbB2 and ErbB3 is increased in pterygium, showing that the pterygium is a disorder with proliferation. The abnormal expression of EGFR, ErbB2 and ErbB3 by epithelium and their communicating with cytokines at stroma in pterygium may be one of the key pathogenetic factors in this disorder.

Adult↗

PubMed2000

[Immune responses of a recombined live Salmonella typhimurium SL3261 expressing a multi-epitope antigen of HCV].

A multi-epitope antigen gene of hepatitis C virus(HCV) was fused to beta-galactosidase gene and introduced into attenuated Salmonella typhimurium SL3261 to construct HCV recombined live vaccine candidate SL3261 (pWR/PCX). when the oral live bacteria were used to immunize mice or rabbits, specific anti-GZ-PCX IgG was detected at week 6 and the strongest antibody responses happened at week 12 at a titer of 1:800 and 1:25,600 in mice and rabbits, respectively, which showed significant difference compared with those of SL3261 and blank controls. Anti-GZ-PCX sIgA in mice's intestine and anti-LPS antibody in sera were also detected. The oral live bacteria elicited obvious DTH reaction and proliferation response of peripheral lymphocytes by GZ-PCX antigen. The body weight of immunized mice slightly decreased but no other toxic effects was observed, which showed the safety of oral immunization. The study of oral live HCV multi-epitope vaccine might be able to provide a new route for the researches of HCV vaccines.

Animals↗