Biomedical subjects

Yang Gao

Publications and source records attributed to Yang Gao.

At least 37 records · Page 2Linked to original sources

PubMed2005

Serum neopterin for early assessment of severity of severe acute respiratory syndrome.

Neopterin and C-reactive protein (CRP) concentrations were determined in serum samples from 129 severe acute respiratory syndrome (SARS) patients and 156 healthy blood donors. In the patients with confirmed SARS, an early neopterin elevation was detected already at the day of onset of symptoms and rose to a maximum level of 45.0 nmol/L 3 days after the onset. All SARS patients had elevated neopterin concentrations (>10 nmol/L) within 9 days after the onset. The mean neopterin concentrations were 34.2 nmol/L in acute sera of SARS patients, 5.1 nmol/L in convalescent sera, and 6.7 nmol/L in healthy controls. In contrast, the mean CRP concentrations in both acute and convalescent sera of SARS patients were in the normal range (<10 mg/L). Serum neopterin level in SARS patients was associated with fever period and thus the clinical progression of the disease, while there was no significant correlation between the CRP level and the fever period. Serum neopterin may allow early assessment of the severity of SARS. The decrease of neopterin level was found after steroid treatment, which indicates that blood samples should be collected before steroid treatment for the neopterin measurement.

Adrenal Cortex Hormones↗

PubMed2005

Clinical patterns and characteristics of uveitis in a tertiary center for uveitis in China.

PURPOSE: To address the clinical pattern and characteristics of uveitis in a tertiary center for uveitis in China and compare the similarity and difference in the distribution of uveitis entities between China and other countries. METHODS: A retrospective study was performed on the patients with uveitis referred to the Zhongshan Ophthalmic Center from January 1996 to December 2003. The clinical data including category, etiology, gender, and the age of the patients at uveitis presentation were analyzed and compared with studies published previously from other countries. RESULTS: There were 902 male and 850 female patients in our series. The mean age of these patients at uveitis presentation was 33.8 +/- 16.5 years. Anterior uveitis (800, 45.6%) was the most common anatomical entity, followed by panuveitis (727, 41.5%), posterior uveitis (119, 6.8%), and intermediate uveitis (106, 6.1%). Further classification with the etiology criteria revealed 16 entities in anterior uveitis, with idiopathic anterior uveitis being the most common entity (473, 27.0%). Twelve entities were identified in panuveitis, of which Behçet disease (289, 16.5%) and Vogt-Koyanagi-Harada (VKH) syndrome (278, 15.9%) were the predominant ones. No specific entity was recognized in the intermediate uveitis group. Although a number of specific entities were identified in posterior uveitis, toxoplasmosis was noted in only two patients in this group. CONCLUSIONS: Idiopathic anterior uveitis, Behçet disease, and VKH syndrome are the most common entities of uveitis in China. Ocular toxoplasmosis, ocular histoplasmosis, and birdshot retinochoroidopathy are less common or absent in China.

Adolescent↗

PubMed2005

An intelligent adaptive control scheme for postsurgical blood pressure regulation.

This paper presents an adaptive modeling and control scheme for drug delivery systems based on a generalized fuzzy neural network (G-FNN). The proposed G-FNN is a novel intelligent modeling tool, which can model unknown nonlinearities of complex drug delivery systems and adapt to changes and uncertainties in these systems online. It offers salient features, such as dynamic fuzzy neural topology, fast online learning ability and adaptability. System approximation formulated by the G-FNN is employed in the adaptive controller design for drug infusion in intensive care environment. In particular, this paper investigates automated regulation of mean arterial pressure (MAP) through intravenous infusion of sodium nitroprusside (SNP), which is one attractive application in automation of drug delivery. Simulation studies demonstrate the capability of the proposed approach in estimating the drug's effect and regulating blood pressure at a prescribed level.

Artificial Intelligence↗

PubMed2005

Monoclonal antibody-based antigen capture enzyme-linked immunosorbent assay reveals high sensitivity of the nucleocapsid protein in acute-phase sera of severe acute respiratory syndrome patients.

Accurate and timely diagnosis of severe acute respiratory syndrome coronavirus (SARS-CoV) infection is a critical step in preventing another global outbreak. In this study, 829 serum specimens were collected from 643 patients initially reported to be infected with SARS-CoV. The sera were tested for the N protein of SARS-CoV by using an antigen capture enzyme-linked immunosorbent assay (ELISA) based on monoclonal antibodies against the N protein of SARS-CoV and compared to 197 control serum samples from healthy donors and non-SARS febrile patients. The results of the N protein detection analysis were directly related to the serological analysis data. From 27 SARS patients who tested positive with the neutralization test, 100% of the 24 sera collected from 1 to 10 days after the onset of symptoms were positive for the N protein. N protein was not detected beyond day 11 in this group. The positive rates of N protein for sera collected at 1 to 5, 6 to 10, 11 to 15, and 16 to 20 days after the onset of symptoms for 414 samples from 298 serologically confirmed patients were 92.9, 69.8, 36.4, and 21.1%, respectively. For 294 sera from 248 serological test-negative patients, the rates were 25.6, 16.7, 9.3, and 0%, respectively. The N protein was not detected in 66 patients with cases of what was initially suspected to be SARS but serologically proven to be negative for SARS and in 197 serum samples from healthy donors and non-SARS febrile patients. The specificity of the assay was 100%. Furthermore, of 16 sera collected from four patients during the SARS recurrence in Guangzhou, 5 sera collected from 7 to 9 days after the onset of symptoms were positive for the N protein. N protein detection exhibited a high positive rate, 96 to 100%, between day 3 and day 5 after the onset of symptoms for 27 neutralization test-positive SARS patients and 298 serologically confirmed patients. The N protein detection rate continually decreased beginning with day 10, and N protein was not detected beyond day 19 after the onset of symptoms. In conclusion, an antigen capture ELISA reveals a high N protein detection rate in acute-phase sera of patients with SARS, which makes it useful for early diagnosis of SARS.

Antibodies, Monoclonal↗

PubMed2005

Vasoactive intestinal peptide ameliorates synovial cell functions of collagen-induced arthritis rats by down-regulating NF-kappaB activity.

The objectives of this work were to observe the multiple immuno-regulating effects of vasoactive intestinal peptide (VIP) on synovial cells of collagen induced arthritis (CIA) rats and to determine whether the transcriptional factor-kappaB (NF-kappaB) signal pathway was involved. CIA was induced using female Wistar rats by native bovine type II collagen (C II) emulsified with complete Freund's adjuvant (CFA). Synovial cells from the knees of the CIA rats were cultivated, and the effects of VIP and VIP receptor inhibitor ([D-P-Cl-Phe(6),Leu(17)]-VIP, I) on proliferation and apoptosis of the synovial cells were assayed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carcoxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), flow cytometry, and DNA integrity. The effects of VIP and [D-P-Cl-Phe(6), Leu(17)]-VIP on mRNA expression of several cytokines in the synovial cells including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), regulated upon activation, normal T-cell expressed and secreted (RANTES), inducible NO synthase (iNOS), matrix metalloproteinase-2 (MMP-2) and MMP-9 were estimated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Effects of VIP and [D-P-Cl-Phe(6), Leu(17)]-VIP on NF-kappaB activity were analyzed using luciferase gene reporter assays. Effects of VIP and [D-P-Cl-Phe(6),Leu(17)]-VIP on p65NF-kappaB expression of the synovial cells were examined by Western blot. Seventy-five percent of the induced rats developed CIA. VIP has multiple effects on synovial cells of CIA rats including decreasing proliferation, inducing apoptosis, and down-regulating mRNA expression of several inflammatory factors. VIP was found to play immuno-regulating roles through the down-regulation of the activity and expression of NF-kappaB, whereas VIP receptor blockade was found to counteract all the effects. In conclusion, VIP was found to ameliorate synovial cell functions of CIA rats through binding with receptors and further down-regulating NF-kappaB signal pathway, suggesting VIP is a potential anti-inflammatory and anti-rheumatic agent of CIA by blocking NF-kappaB.

Animals↗

PubMed2005

[The effects of 4 laboratory test kits in early detecting of severe acute respiratory syndrome coronavirus].

OBJECTIVE: To compare the 4 test kits on severe acute respiratory syndrome coronavirus (SARS-CoV) gene, antigen and antibody for early diagnose of SARS patients. METHODS: Three enzyme linked immunosorbent assay (ELISA) kits were used to detect SARS-CoV IgG, IgM and N protein and fluorescent polymerase chain reaction (F-PCR) kit was used to detect SARS-CoV RNA. RESULTS: In 162 serum samples, 90.2% (55/61) became N protein positive in 1 - 5 days and 92.8% (13/14) became positive IgM and IgG in 15 - 18 days after the onset of disease, respectively. On 82 gorgling samples, the positive rates of F-PCR were 56.3% (14/24) in 1 - 5 days and 71.4% (10/14) in 6 - 9 days after the onset. CONCLUSION: Other than F-PCR, N protein had good effect in the early detection on dubious patients which could lead to effective prevention and control of the epidemic.

Antibodies, Viral↗

PubMed2005

[Clinical value of esophageal mucosal iodine stain during esophagoscopy for patients without swallowing symptoms].

OBJECTIVE: To investigate the clinical value of esophageal mucosal iodine stain during esophagoscopy for patients with early esophageal carcinoma or precancerous lesions without swallowing symptoms, through analyzing the correlation between endoscopic findings and pathological results of biopsy on the suspicious spots. METHODS: For 366 patients examined by iodine stain during esophagoscopy, the position, size, shape and boundary of all visible unstained lesions were recorded and multiple biopsies were taken on the unstained spots. RESULTS: Before iodine stain, 462 lesions had been discovered in 366 patients. However, 478 abnormal lesions stained in 341 patients were detected after iodine stain, the remaining 25 gave no abnormal findings. More than 1/3 of patients were found to have more than 2 abnormally stained lesions. 28.4% of them (104 cases) had moderate or severe dysplasia or early esophageal cancer. The sensitivity of iodine stain in this series was 89.8%. CONCLUSION: Iodine stain is very useful in detecting occult early esophageal carcinoma and precancerous lesions. The degree of coloration and the margin of suspicious spots are closely correlated with the pathological results.

Adult↗

PubMed2005

[Apoptosis and apoptosis-related genes in experimental autoimmune inner ear disease].

OBJECTIVE: To investigate the protein and mRNA expression patterns of apoptosis-related genes, together with evidence of apoptosis, in relation to experimental autoimmune inner ear disease (AIED). METHODS: Male C57BL/6 mice at 4 weeks age (n = 80) were randomly assigned to one of the five group (n = 16). The inbred mice were given a single subcutaneous injection of diluted solution of pertussis and an emulsion containing equal parts of complete Freund adjuvant (CFA) and inner ear antigens (IEAg) extracted form guinea pig. The animals were sacrificed for inner ear examination at a defined time after the immunization (7, 14, 21 or 28 days). An autoimmune inner ear diseases model was established. Apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (d-UTP) nick end-laying (TUNEL) method. Using immunohistochemical techniques and reverse transcriptase polymerase chain reaction to clarify the profile of Fas, FasL, and bcl-2. RESULTS: Under normal conditions, no TUNEL-positive cell was observed in the cochlea except for a few positive cells in the supporting cells of Corti's organ and macula sacculi. Inner ear antigens administration induced TUNEL-positive reactions in a wide variety of cells such as inner hair cells, supporting cells, stria vascularis and spiral ligament fibrocytes. No positive staining was evident in outer hair cells, spiral ganglion cells and Scarpa's ganglion cells during the whole period. Fas proteins were expressed in a wide range of cells in inner ear. The levels of Fas mRNA were no significant differences between normal and AIED mice. FasL and bcl-2 proteins could be detected in spiral ganglion cells and Scarpa's ganglion cells both in normal and AIED mice. FasL positive cells increased in number in inner ear of AIED mice. bcl-2 positive cells were not detectable in inner hair cells, stria vascularis and spiral ligament both in normal and AIED mice. The mRNA of three kinds of apoptosis-related genes was detectable in the normal and AIED mice. FasL mRNA was expressed at low levels in normal, being maximal at 14 d post inoculation and decreased gradually to steady levels by 2 weeks. The levels of bcl-2 mRNA increased significantly during the period of AIED. CONCLUSION: Apoptosis mediated by Fas/FasL signal system may play a role in the initiation and maintenance of AIED. bcl-2 has a crucial role in the regulation of the process of apoptosis in the inner ear of AIED mice.

Animals↗

PubMed2005

[Multicenter controlled study on transient asthma-stopping action of acupuncture at "Qingchuan point"].

OBJECTIVE: To test and verify the transient therapeutic effect of acupuncture at point "Qingchuan" on bronchial asthma. METHODS: Two hundred cases of bronchial asthma at acute attack stage were divided into a trial group of 100 cases treated with acupuncture at point "Qingchuan" and a control group of 100 cases treated with acupuncture at Dingchuan (EX-B1). RESULTS: The total effective rate was 92.60% and the effect occurred within 42-860 seconds after acupuncture in the trial group, and 81.0% and within 114-126 seconds in the control group, respectively, with very significant differences between the two groups (P < 0.01, P < 0.001). CONCLUSION: Acupuncture at point "Qingchuan" can significantly improve asthmatic state in the patient of bronchial asthma with action of rapidly stopping asthma.

Acupuncture Points↗

PubMed2005

Beta-endorphin prevents collagen induced arthritis by neuroimmuno-regulation pathway.

OBJECTIVE: To observe the effects and mechanisms of beta-endorphin (beta-END) preventing collagen induced arthritis (CIA) by neuroimmuno-regulating pathway. METHODS: Female wistar (Ws) rats were used in this study. CIA was induced by Native bovine type II collagen emulsified with complete Freund's adjuvant (CFA). Beta-END was administered i.p. to CIA rats every other day from the 14th day (secondary immunization) to the 35th day after primary immunization. Clinical assessments were performed by two independent, blinded examiners every other day. Pathological and radiological observations were taken on the 35th day after the primary immunization. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), regulated upon activation, normal T-cell expressed and secreted (RANTES), inducible NO syntheses (iNOS), matrix metalloproteinase-2 (MMP-2) and MMP-9 mRNA expression of synovium tissues of CIA rats was estimated by quantitative RT-PCR. The frequency of spleen Th1 and Th2 cells were assessed by fluorescence activated cell sorter (FACS) assay. RESULTS: Clinical manifestation of rats with CIA were significantly abrogated or ameliorated by treatment with beta-END. Beta-END treatment in vivo could down-regulate mRNA expression of several pro-inflammatory cytokines, chemokines and MMPs in CIA synovial, and polarize Th1/Th2 balance to Th2. CONCLUSION: Beta-END alleviates CIA through both depressing Th1 responses and down-regulating proinflammatory and other rheumatic factors, suggesting beta-END is a promising anti-inflammatory and anti-rheumatic agent in treating CIA.

Analysis of Variance↗

PubMed2004

Structure analysis of the protein transduction domain of human Period1 and its mutant analogs.

Human Period1 (hPer1) has been proved to be able to translocate into cells in a protein transduction manner. The segment of amino acids 830-845 of hPer1 is its protein transduction domain (PTD). In order to explore the membrane penetrating mechanism of hPer1-PTD and the physico-chemical properties necessary in the process, Ala scanning mutation method was used to investigate the variation in the peptide internalization. To further investigate the related physico-chemical requirements, the three dimensional structures of hPer1-PTD and its mutant analogs were simulated by Rosetta method. The electrostatic potentials and energies of these structures were calculated using the Delphi algorithm to solve Poisson-Boltzman equation. The hydrophobicity was assessed by the percentage of the nonpolar area in SAS (solvent accessible surface (SAS)). It has been proved that the Arg836 was the key residue for peptide internalization. When this Arg mutated into Ala, the peptide could not cross the membrane. The large enough area with positive charge was the decisive factor for hPer1-PTD. The alpha-helical structure seemed to play an assistant role so as to enable the positive charge connected in spatial arrangement.

Amino Acid Sequence↗

PubMed2004

Genetic structure of Hmong-Mien speaking populations in East Asia as revealed by mtDNA lineages.

Hmong-Mien (H-M) is a major language family in East Asia, and its speakers distribute primarily in southern China and Southeast Asia. To date, genetic studies on H-M speaking populations are virtually absent in the literature. In this report, we present the results of an analysis of genetic variations in the mitochondrial DNA (mtDNA) hypervariable segment 1 (HVS1) region and diagnostic variants in the coding regions in 537 individuals sampled from 17 H-M populations across East Asia. The analysis showed that the haplogroups that are predominant in southern East Asia, including B, R9, N9a, and M7, account for 63% (ranging from 45% to 90%) of mtDNAs in H-M populations. Furthermore, analysis of molecular variance (AMOVA), phylogenetic tree analysis, and principal component (PC) analysis demonstrate closer relatedness between H-M and other southern East Asians, suggesting a general southern origin of maternal lineages in the H-M populations. The estimated ages of the mtDNA lineages that are specific to H-M coincide with those based on archeological cultures that have been associated with H-M. Analysis of genetic distance and phylogenetic tree indicated some extent of difference between the Hmong and the Mien populations. Together with the higher frequency of north-dominating lineages observed in the Hmong people, our results indicate that the Hmong populations had experienced more contact with the northern East Asians, a finding consistent with historical evidence. Moreover, our data defined some new (sub-)haplogroups (A6, B4e, B4f, C5, F1a1, F1a1a, and R9c), which will direct further efforts to improve the phylogeny of East Asian mtDNAs.

Asia, Southeastern↗

PubMed2004

Gene transfer of cocaine hydrolase suppresses cardiovascular responses to cocaine in rats.

We previously found that injection of a cocaine hydrolase (CocE) engineered from human butyrylcholinesterase will transiently accelerate cocaine metabolism in rats while reducing physiological and behavioral responses. To investigate more extended therapeutic effects, CocE cDNA was incorporated into a replication-incompetent type-5 adenoviral vector with a cytomegalovirus promoter. In rats dosed with this agent (2.2 x 10(9) plaque-forming units), the time course of expression was characterized by reverse transcription polymerase chain reaction for CocE mRNA and by radiometric assay for enzyme activity. Liver and plasma showed comparable expression, beginning 2 days after vector administration and peaking between 5 and 7 days. Plasma CocE content was up to 100 mU/ml, with total cocaine hydrolyzing activity 3000-fold greater than in "empty vector" or untreated controls. This level of expression approximated that found immediately after i.v. injection of purified hydrolase, 3 mg/kg, a dose that shortened cocaine halflife and blunted cardiovascular effects. Sucrose density gradient analysis showed that 96% of the circulating CocE activity was associated with tetrameric enzyme forms, expected to be stable in vivo. Consistent with this expectation, CocE from vector-treated rats showed a plasma t(1/2) of 33 h when reinjected into naive rats. Transduction of another mutant butyrylcholinesterase, Applied Molecular Evolution mutant 359 (AME(359)), caused plasma cocaine hydrolase activity to rise 50,000-fold. At the point of peak AME(359) expression, cocaine was cleared from the blood too rapidly for accurate measurement, and pressor responses to the injection of drug were greatly impaired.

Animals↗

PubMed2004

Genetic evidence supports demic diffusion of Han culture.

The spread of culture and language in human populations is explained by two alternative models: the demic diffusion model, which involves mass movement of people; and the cultural diffusion model, which refers to cultural impact between populations and involves limited genetic exchange between them. The mechanism of the peopling of Europe has long been debated, a key issue being whether the diffusion of agriculture and language from the Near East was concomitant with a large movement of farmers. Here we show, by systematically analysing Y-chromosome and mitochondrial DNA variation in Han populations, that the pattern of the southward expansion of Han culture is consistent with the demic diffusion model, and that males played a larger role than females in this expansion. The Han people, who all share the same culture and language, exceed 1.16 billion (2000 census), and are by far the largest ethnic group in the world. The expansion process of Han culture is thus of great interest to researchers in many fields.

Agriculture↗

PubMed2004

Alterations of intercellular communication in neonatal cardiac myocytes from connexin43 null mice.

OBJECTIVE: To compare gap junction expression and intercellular coupling in wildtype neonatal cardiac myocytes to those from mice lacking the most abundant cardiac gap junction protein (connexin43, Cx43). METHODS: Northern and Western blots compared connexin mRNA and protein levels, immunocytochemistry evaluated connexin distribution in neonatal Cx43 null(-/-), heterozygous(+/-) and wildtype(+/+) mouse hearts. Ca(2+) imaging, dye coupling and electrophysiological methods evaluated intercellular communication. RESULTS: Similar levels of Cx40 and Cx45 were detected in all genotypes, although in adult cardiac tissue from wildtype mice, Cx43 expression was higher than in heterozygotes. After culturing dissociated cells for 3-4 days, cardiocytes beat spontaneously; in Cx43(+/+) and (+/-) cultures, the beating was generally quite synchronous. In Cx43(-/-) mice, interbeat intervals were on average twice as long and more variable than in Cx43(+/+) or Cx43(+/-) cultures. Junctional conductance was lower by about 60% in Cx43(-/-) as compared to Cx43(+/-) and (+/+) littermates; Lucifer Yellow dye coupling was virtually absent in Cx43(-/-) cardiomyocytes but was comparably strong in wildtype and heterozygous siblings. Macroscopic junctional conductance measurements on Cx43(-/-) cardiocytes showed slightly stronger voltage sensitivity in these cells than in Cx43(+/+) cardiocytes. Unitary junctional conductance measurements revealed distinct populations of channels contributing to macroscopic conductance for Cx43(+/+) and Cx43(-/-) genotypes. CONCLUSIONS: In Cx43-deficient cardiac myocytes, the expression of other connexins only partially compensates for the functional loss, with dye coupling and spontaneous beating being strongly impaired.

Animals↗

PubMed2004

An engineered cocaine hydrolase blunts and reverses cardiovascular responses to cocaine in rats.

There is increasing evidence that human plasma butyrylcholinesterase can lower the toxicity of cocaine overdose. Recently, with structure-based protein engineering, we converted this enzyme into a more efficient cocaine hydrolase (CocE). When tested in rats, CocE shortened cocaine's plasma half-life and decreased drug accumulation in heart and brain. Here, we have investigated the potential of CocE to antagonize cardiovascular responses to cocaine. Anesthetized rats were instrumented for continuous recording of blood pressure from the femoral artery. Cocaine (7 mg/kg i.v.) caused blood pressure to rise within 30 s by 25 to 37 mmHg, but pressure returned to baseline within 60 s. These transient pressor responses were prolonged up to 5 min when vagal reflexes were blocked with atropine (1 mg/kg). Under such conditions, pretreatment with CocE (3 mg/kg i.v.) reduced cocaine's pressor effect, whereas delayed treatment with CocE rapidly restored normal mean blood pressure. CocE had no hemodynamic effects in control animals not treated with cocaine. The finding that CocE can oppose pre-established physiologic actions of cocaine suggests that similar or improved hydrolases might help rescue patients from the life-threatening toxicity of drug overdose.

Animals↗

PubMed2004

Sequence-dependent DNA immobilization: specific versus nonspecific contributions.

We present results of the first systematic study on in situ sequence-dependent kinetics for short single-strand oligonucleotide surface immobilization. By measuring film coverage for both thiolated and nonthiolated homo-oligomers as a function of adsorption time, we determine the relative contribution of specific thiol-surface and nonspecific DNA-surface interactions to the overall mechanism of DNA-thiol attachment to gold. We find that sequence-dependent nonspecific surface interactions play a significant role in DNA-thiol immobilization, influencing not only the kinetics but also the extent of oligomer adsorption. For example, sequences that initially form strong, rapid nonspecific contacts with the surface hinder long-time thiol adsorption (i.e., poly(dA)-thiol). In contrast, sequences with nucleotides that initially bind slowly and weakly to the surface (i.e., poly(dT)-thiol) do not obstruct further thiol adsorption, resulting in higher film coverage and Langmuir immobilization kinetics. This view of the DNA-thiol immobilization mechanism is further supported by sequence-dependent rinsing losses observed for thiolated DNA strands but not for analogous nonthiolated strands. Nonthiolated strands contact the surface strongly in a more horizontal orientation, whereas thiolated strands attain a more upright orientation that allows vertical DNA-DNA base-stacking. The results clearly illustrate the importance and interplay of competitive specific and nonspecific forces in forming DNA-thiol films. The specific coverage attained and the time dependence of the adsorption process depend on the prevailing sequence composition.

DNA↗

PubMed2004

Suppression of 6A8 alpha-mannosidase gene expression reduced the potentiality of growth and metastasis of human nasopharyngeal carcinoma.

Suppression of alpha-mannosidases by chemicals has been shown to reduce the potentiality of growth and metastasis of various tumors. In our study, the effect of 6A8 alpha-mannosidase (MAN 6A8), recently discovered in our laboratory, on malignant behaviors of tumor cells was examined. Since the suppressive effect of chemicals on alpha-mannosidase is not specific, antisense technique was used to specifically inhibit expression of the MAN 6A8 in human nasopharyngeal carcinoma cells, CNE-2L2. Two cell clones, AS1 and AS2, with pronounced suppression of MAN 6A8 expression were developed. Wild-type (W), mock-transduced (M) and irrelevant DNA-transduced (IR) CNE-2L2 cells with normal expression of the enzyme were used as controls. Malignant behaviors of the cells were examined. Significant inhibition of growth of AS cells in vitro measured by MTT assay, colony formation and anchorage-independent colony formation was found. Pronounced inhibition of formation of tumors from AS cells inoculated into nude mice and metastasis was also observed. W, M and IR cells cultured in plate wells appeared dispersed with a fibroblastic or epithelial morphology, whereas AS cells were in compact sheets with an epithelioid organization. Since E-cadherin is the key factor in homophilic adhesion of epithelial cells, its expression on the surface of CNE-2L2 cells was determined. E-cadherin expression on AS cells was enhanced, whereas it was markedly diminished on W, M and IR cells. In addition, lamellipodia, which play an important role in cell spreading and mobility, almost disappeared on AS cells. The results demonstrate a significant suppressive effect of reduced expression of MAN 6A8 on malignant behaviors of CNE-2L2 cells.

Animals↗