Biomedical subjects

Yan Sun

Publications and source records attributed to Yan Sun.

At least 163 records · Page 9Linked to original sources

PubMed2003

[The effect of insulin on chemotherapeutic drug sensitivity in human esophageal and lung cancer cells].

OBJECTIVE: To discuss the effect of insulin, as a metabolic promoter, on chemotherapeutic drug sensitivity in human esophageal and lung cancer cells. METHODS: Human esophageal cancer cells NEC and human lung adenocarcinoma cells GLC were cultured and then inoculated into the wells. MTT was added. Chemotherapeutic drugs, etopside, cisplatin, or 5-fluoto-uracilum was added to examine their cytotoxity activity. Then insulin of the final concentration of 5 mU/ml was added 8 hours before etopside (30 - 40 micro g/ml), cisplatin (2.5 micro g/ml), or 5-Fu (50 micro g/ml) was added. MTT A value was tested by colorimetry to evaluate the number of cancer cells, cell activity, and metabolism status so as to reflect the cytotoxity of the anti-tumor agent. Insulin was added into the suspension of cancer cells. Flow cytometry was used to detect the cell-cycle progresses. RESULTS: Insulin alone did not inhibit the cell growth and mildly promoted the cell metabolism with the concentration > 5 mU/ml. Insulin (2.0 - 15.0 mU/ml) enhanced the chemocytotoxity of etopside (30 micro g/ml) on human esophageal and lung cancer cells as indicated by MTT colorimetry. GLC cell cycle assay showed that the S phase block induced by etopside, cisplatin and 5-FU and the G(2)/M block induced by 5-FU were enhanced by insulin with the increased block rates of 80% and 90% respectively. The increased block rate induced by insulin in NEC cells was lower than in GLC cells. CONCLUSION: A reversible metabolic promoter, insulin enhances the cytotoxity of the chemotherapeutic agents. It is possible to increase the growth and metabolism of cancer cells first so as to enhance the chemosensibility, and then administer chemotherapeutic agents, thus improving their therapeutic effects.

Adenocarcinoma↗

PubMed2003

Peptides targeting caspase inhibitors.

Here we report on the identification of peptides targeting the X-inhibitor of apoptosis protein (XIAP). XIAP functions as a caspase inhibitor and is a member of the inhibitors of apoptosis (IAP) family of proteins. IAPs are often overexpressed in cancers and leukemias and are associated with an unfavorable clinical prognosis. We have selected peptides from a phage library by using recombinant full-length human XIAP or a fragment containing only the baculovirus IAP repeat 2 (BIR2) domain. A consensus motif, C(D/E/P)(W/F/Y)-acid/basic-XC, was recovered from two independent screenings by using different libraries. Phage-displaying variations of the consensus sequence bound specifically to the BIR2 domain of XIAP but not to other IAPs. The interaction was specific as it could be blocked by the cognate synthetic peptides in a dose-dependent manner. Phage displaying the XIAP-binding motif CEFESC bound to the BIR2 domain of XIAP with an estimated dissociation constant of 1.8 nm as determined by surface plasmon resonance. Protein-protein interaction assays revealed that caspase-3 and caspase-7 (but not caspase-8) blocked the binding of the CEFESC phage to XIAP, indicating that this peptide targets a domain within XIAP that is related to the caspase-binding site. In fact, the sequence EFES is homologous to a loop unique to the executioner caspase-3 and caspase-7 that are targeted by XIAP. Finally, we demonstrated that an internalizing version of the XIAP-binding peptide identified in our screenings (PFKQ) can induce programmed cell death in leukemia cells. Peptides interacting with XIAP could serve as prototypes for the design of low molecular weight modulators of apoptosis.

Amino Acid Motifs↗

PubMed2003

The KRAB domain of zinc finger gene ZNF268: a potential transcriptional repressor.

Nearly one-third of Krupple-type C2H2 zinc finger proteins have a krupple-associated box (KRAB) domain, which may act as a transcriptional repressor. ZNF268, which was novelty isolated from early human embryo, is a typical krupple-type C2H2 zinc finger protein with a conserved KRAB domain. In this report, the KRAB domain of ZNF268 is identified to localize in the nucleus and has transcriptional repressor activity.

Amino Acid Sequence↗

PubMed2003

Codon 249 mutation in exon 7 of p53 gene in plasma DNA: maybe a new early diagnostic marker of hepatocellular carcinoma in Qidong risk area, China.

AIM: One of the characteristics of hepatocellular carcinoma (HCC) in Qidong area is the selective mutation resulting in a serine substitution at codon 249 of the p53 gene (1, 20), and it has been identified as a "hotspot" mutation in heptocellular carcinomas occurring in populations exposed to aflatoxin and with high prevalence of hepatitis B virus carriers (2,3,9, 10,16,24). We evaluated in this paper whether this "hotspot" mutation could be detected in cell-free DNA circulating in plasma of patients with hepatocellular carcinoma and cirrhosis in Qidong, China, and tried to illustrate the significance of the detection of this molecular biomarker. METHODS: We collected blood samples from 25 hepatocellular carcinoma patients, 20 cirrhotic patients and 30 healthy controls in Qidong area. DNA was extracted and purified from 200 microl of plasma from each sample. The 249(Ser) p53 mutation was detected by restriction digestion analysis and direct sequencing of exon-7 PCR products. RESULTS: We found in exon 7 of p53 gene G-T transversion at the third base of codon 249 resulting 249(Arg) - 249(Ser) mutation in 10/25 (40 %) hepatocellular carcinoma cases, 4/20 (20 %) cirrhotics, and 2/30 (7 %) healthy controls. The adjusted odds ratio for having the mutation was 22.1(95 % CI, 3.2-91.7) for HCC cases compared to controls. CONCLUSION: These data show that the 249(Ser) p53 mutation in plasma is strongly associated with hepatocellular carcinoma in Qidong patients. We found this mutation was also detected, although it was at a much lower frequency, in plasma DNA of Qidong cirrhotics and healthy controls; We consider that these findings, together with the usual method of HCC diagnosis, will give more information in early diagnosis of HCC, and 249(Ser) p53 mutation should be developed to a new early diagnostic marker for HCC.

Adult↗

PubMed2003

[Cloning, expression and alternative splicing of a novel isoform of human TCP11b gene].

Based on homology analysis and RT-PCR, a novel isoform of human TCP11 gene was isolated. It encodes a 503 amino acid protein that is highly homologous to the mouse 566 amino acid protein Tcp-11. Tcp-11 is important to sperm function because it may be the receptor of fertilization promoting peptide (FPP). Complicated alternative splicing was found to exist between TCP11a and TCP11b genes. The gene has been mapped to human chromosome band 6p21 by fluorescence in situ hybridization. Results of Northern blot and RT-PCR analysis of RNA extracted from human tissues revealed that the gene was expressed in fertile adult testes only, but neither in azoospermic patient testes, fetal testes nor in other human tissues. Our results suggest that TCP11b gene may be important to human sperm function and male fertility.

Alternative Splicing↗

PubMed2003

[Study on the association of cholesteryl ester transfer protein gene mutations with the susceptibility to coronary atherosclerotic heart disease].

OBJECTIVE: To determine the frequencies of 4 mutations of cholesteryl ester transfer protein (CETP) gene in Chinese population and to investigate the association of the mutations with lipid metabolism and the susceptibility to coronary atherosclerotic heart disease (CHD). METHODS: The target fragments of CETP gene were amplified and analyzed by PCR-restriction fragment length polymorphism technique in 209 unrelated control individuals and 203 CHD patients. The test for Hardy-Weinberg equilibrium was performed using HWE program and statistical analysis was implemented in statistical package SPSS. RESULTS: IVS14A and 451Q mutant genes were not found in either control group or patient group. The frequencies of 405V mutant allele were 0.443 and 0.413 in controls and patients, respectively, while 442G mutant gene frequencies were 0.007 and 0.025, respectively. The observed allele frequencies of I405V and D442G mutation were in accord with Hardy-Weinberg equilibrium. The frequency of 442G mutant gene in patients was significantly higher than that in controls (P=0.043). Compared with the CHD patients without D442G mutation, the 442G heterozygous CHD patients exhibited a significant increase in plasma TC and LDL-C concentration (P=0.017; P=0.041). CONCLUSION: IVS14A and 451Q mutants of CETP gene were rare in Chinese population and 442G mutant gene was possibly one of the susceptibility factors to CHD in Chinese.

Aged↗

PubMed2003

Identification of a novel human zinc finger protein gene ZNF313.

A novel human zinc finger protein gene that contains both ring finger and C(2)H(2) domain was first isolated by mRNA differential display between the testes of fertile adults and azoospermic patients followed by rapid amplification of cDNA ends (RACE). Total 6 exons of the human gene span a 17,484 bp genomic DNA sequence that was mapped to chromosome 20q13 by fluorescence in situ hybridization. The mature processed mRNA encodes a 228-amino acid protein with a C(3)HC(4) ring finger and three C(2)H(2) domains. Genomic analysis of the human gene identified two polyadenylation signals in exon 6 resulting in alternative 3'-untranslated regions. Results of Northern blot and RT-PCR of RNAs extracted from multiple tissues revealed that the gene has two transcripts of which the shorter transcript was expressed abundantly in fertile adult testes, but much less in testes of azoospermic patient, fetus as well as other human tissues. These data suggest that the gene may play a role in human spermatogenesis and male fertility.

3' Untranslated Regions↗

PubMed2003

[Study on the association of lecithin cholesterol acyltransferase gene polymorphisms with the lipid metabolism in coronary atherosclerotic heart disease].

OBJECTIVE: To examine the distribution of 3 polymorphisms of lecithin cholesterol acyltransferase gene in Chinese population and the association of these polymorphisms with lipid metabolism in patients with atherosclerotic heart disease (CHD). METHODS: Genotypes and frequencies of 3 sites were examined by PCR-restriction fragment length polymorphism technique in 209 unrelated normal control individuals and 203 CHD patients. RESULTS: The observed allele frequencies conform well to Hardy-Weinberg equilibrium. The frequency of 608T allele was significantly higher in controls than that in patients (P=0.034). Compared with the CHD patients without 608T, the CHD patients with 608T exhibited a significant increase in plasma HDL-C concentration (P=0.015). 911T/C and 1188C/T polymorphisms were not found in either group. CONCLUSION: 608T polymorphism of LCAT gene was associated with higher plasma HDL-C level in CHD patients, while 911T/C and 1188C/T polymorphisms maybe very rare in Chinese population.

Alleles↗

PubMed2003

[Clinical investigation of outbreak of nosocomial severe acute respiratory syndrome].

OBJECTIVE: To summarize and analyze the clinical manifestation, diagnosis and therapeutic strategy of severe acute respiratory syndrome (SARS), and its characteristics of outbreak in hospital via infection transmission cluster associated with SARS patients. METHODS: (1) Two hospitalized community acquired SARS cases with their clinical data and epidemiologically linked transmission clusters in our hospital were analyzed; (2) The clinical data from 41 SARS cases were summarized. RESULTS: (1) The contagiousness of SARS virus in SARS patients was extremely strong, especially in their acute stage. (2) The majority of clinical manifestations were fever (100% cases), and there were no obvious respiratory symptoms in more than half of the patients (53.7%) at early SARS stage (day 1 to day 3), accompanied by leucopenia(52.6%) and lymphopenia (68.4%). (3) Timely administration of Ribavirin, Methylprednisolone, immunoenhancer (such as interferon alpha-2b, thymosin-alpha1) to SARS patients was efficacious to certain extent in controlling the development of the disease. CONCLUSION: It is very important for clinicians to pay great attention to protect themselves from infection of SARS. Early discovery of SARS, early isolation of SARS patients, and early treatment are very helpful to improving patient's prognosis and controlling SARS overspread.

Adult↗

PubMed2003

[Cloning, expression, and alternative splicing of the novel isoform of hTCP11 gene].

OBJECTIVE: To identify a novel isoform of hTCP11 gene and investigate its expression and alternative splicing. METHODS: According to the sequence of human ESTs which are highly homologous to hTCP11a, primers for PCR were synthesized. Then, the amplified fragments were cloned and sequenced; some methods including BLAST, ClustalW and RT-PCR were used for genomic analysis, study of alternative splicing and gene expression among multiple tissues and different testis tissues. RESULTS: A novel isoform of hTCP11 gene was isolated. It encodes a 440 amino acid protein that is highly homologous to the mouse 566 amino acid protein which is important to sperm function because it encodes the receptor for fertilization promoting peptide (FPP). Among TCP11a, TCP11b and TCP11c, the complicated alternative splicing was found. RT-PCR analysis of RNA extracted from human tissues revealed that the gene is only expressed in fertile adult testes, but not in azoospermic patient testes, fetal testes or other human tissues. CONCLUSION: Our results along with the mouse Tcp-11 function suggest that the isoforms of TCP11 gene play important roles in sperm function and fertility.

Adult↗

PubMed2003

[Long-term results of multimodality therapy of testicular germ cell tumor].

OBJECTIVE: To study the clinical characteristics, outcome, prognostic factors and survival of patients with testicular germ cell tumors (TGCTs). METHODS: 107 TGCT patients received chemotherapy after orchiectomy. The median age of the patients was 32 years. 30.8% (33/107) patients had seminomas with 14 (42.4%) stage I lesions. Seventy-four patients had non-seminomatous germ cell tumors (NSGCTT) with 21 (28.4%) stage I lesions. The response rate was analyzed with chi(2) test. The survival rate was calculated with Kaplan-Meier method and log-rank test. Therapy including chemotherapy, radiation and necessary salvage operation were performed after orchiectomy. RESULTS: Clinical stage and pathological type were the main prognostic factors. The 3-, 5- and 10-year survival rates were 75.8%, 73.5%, 73.5% for all patients, 100%, 96.8%, 96.8% for seminoma and 63.5%, 61.7%, 61.7% for NSGCTTs, respectively. Sixty-four patients were evaluable for response. Seventeen (26.6%) patients achieved CR by chemotherapy alone and an additional 8 patients (12.5%) achieved CR by chemotherapy plus salvage operation or radiation. The 5-year survival rates were 91.7% and 26.2% for patients who achieved CR or not. CONCLUSION: The long-term outcome for stage I germ cell tumors is excellent. The treatment outcome and survival in patients with metastatic TGCTs can be greatly improved by adopting multi-modality therapy with combined chemotherapy as the chief means.

Adolescent↗

PubMed2003

[Result of phase II clinical trial of herceptin in advanced Chinese breast cancer patients].

OBJECTIVE: To observe the clinical efficacy and adverse effects of herceptin for advanced Chinese breast cancer patients. METHODS: Thirty-one pathologically proved advanced breast cancer women were treated by herceptin. In the first week, a loading dose 4 mg/kg was administered by intravenous infusion and from the second week, a routine dose of 2 mg/kg was given every week for at least 3 months. RESULTS: There were 2 CR, 6 PR, 7 SD, and 16 PD among 31 patients after treatment by herceptin, the response rate being 25.8%. In factors influencing the prognosis, age and general condition were factors favoring the results, and pathological type, site of metastasis, grade of her-2 over expression and prior treatment were irrelevant to the results. The adverse effects were mild but different from those of the common anticancer drugs. CONCLUSION: Herceptin is effective and well tolerated by the Chinese breast cancer patients.

Adult↗

PubMed2003

[The study of autonomic nervous activities in patients with obstructive sleep apnea syndrome].

OBJECTIVE: To explore the nocturnal variation of autonomic nervous system (ANS) in patients with obstructive sleep apnea syndrome (OSAS) and the transformation after surgery. METHOD: Sixty-one subjects with OSAS were recruited to undergo 7-hour nocturnal polysomnography(PSG) in sleep lab. Sixteen subjects with OSAS were performed PSG before and after UPPP. Sixteen subjects without OSAS were included as controls. Power spectrum analysis of heart rate variability (HRV) was performed in each subject. RESULT: The nocturnal of ANS activities were abnormal in patients with OSAS, especially the enhancement of sympathetic nervous activity. It increased gradually along with aggravating condition. The activities of sympathetic and vagus nerve were decreased significantly. CONCLUSION: There are abnormal ANS activities in patients with OSAS. Effective treatment of OSAS by surgery will significantly reduce the parameters of ANS, and redress the abnormality of heart rate and blood pressure.

Adult↗

PubMed2003

[Cloning and fusion expression of bovine enterokinase light chain gene in Escherichia coli].

The objective of the study was to obtain the gene of bovine enterokinase light chain, which would be used in the cleavage and purification of fusion proteins. The fragment of bovine enterokinase light chain cDNA was obtained by RT-PCR from a sold bovine's duodenal mucosa, then cloned into the pUCmT cloning vector and sequenced. Compared with the sequence deposited in GenBank,the cloned gene sequence is correct. Then the interested gene fragment was inserted into the pET39b expression plasmid. The recombinant vector pET39b-EKL was transformed into E.coli BL21(DE3) and induced by IPTG. It was confirmed that the nucleotide sequence was correct on the conjunction site between the recombinant DNA 5'terminal multi-cloning site and recombinant fragment after the analysis of the nucleotide sequence. SDS-PAGE analysis indicated that target product was about 65 kDa which occupied 28% of the total protein. A pure fusion protein was obtained by nickel chelating chromatogram using His*Binding Resin. After desalting and changing buffer, the crude kinase was incubated at 21 degrees overnight and demonstrated a high autocatalytic cleavage activity. This investigation would be able to lay a foundation for enterokinase activity research and farther application of expression products on a large scale.

English Abstract↗

PubMed2003

[Study on the degradation pathway of biphenyl by Rhodococcus pyridinovorans R04].

Metabolites of Rhodococcus pyridinovorans R04 from biphenyl were analyzed by GC-MS. The results demonstrated that biphenyl was degraded via a route of 2,3-dihydro-2,3-dihydroxybiphenyl and 2,3-dihydroxybiphenyl. 4-Benzoylbutyric acid and 1-phenylethanone were also found in the GC-MS analysis, which indicated there were other pathways beside the main route.

Bacterial Proteins↗

PubMed2002

Particle size and density distributions of two dense matrices in an expanded bed system.

The size and density distributions of two commercial media, that is, Streamline particles and 6% agarose coated steel beads (6AS), in an expanded bed system has been studied with a glass column (26 mm I.D.) modified by side ports. The Streamline particles have a broad size distribution but a relatively uniform density, while the 6AS beads have both broad size and density distributions. The effect of liquid-phase flow velocity, liquid viscosity and settled bed height on the particle size and density distributions is investigated. It is found that the radial mean particle size and density of the two matrices are uniform, while axial classifications are obvious in the expanded beds. For the Streamline, the volume-weighted mean particle size decreases linearly with increasing expanded bed height. For the 6AS beads, however, the mean particle size is even in the axial direction, but the particle density decreases exponentially with the increase of bed height. Moreover, the mean particle size of the Streamline or the density of the 6AS beads is well expressed as a function of the normalized bed height (that is, the ratio of the distance from bed bottom to the expanded bed height). The liquid flow-rate, liquid viscosity and settled bed height influence the mean axial size or density distribution by affecting the expanded bed height.

Chromatography, Liquid↗

PubMed2002

Operational intensification by direct product sequestration from cell disruptates: application of a pellicular adsorbent in a mechanically integrated disruption-fluidised bed adsorption process.

A novel prototype adsorbent, designed for intensified fluidised bed adsorption processes, was assembled by the emulsification coating of 4% (w/v) porous agarose upon a zirconia-silica solid core. The adsorbent, designated ZSA (particle density 1.75 g/ml, maximum pellicle depth 40 microm), was subjected to physical and biochemical comparison with the performance of two commercial adsorbents (Streamline and Macrosorb K4AX). Bed expansion qualities and hydrodynamic characteristics (N, D(axl) and B(o)) of ZSA demonstrated a marked robustness in the face of elevated velocities (up to 550 cm/h) and biomass loading (up to 30% (ww/v)) disrupted yeast cells. Cibracron Blue derivatives of the pellicular prototype (ZSA-CB), evaluated in the batch and fluidised bed recovery of glyceraldehyde 3-phosphate dehydrogenase (G3PDH) from unclarified yeast disruptates, exhibited superior capacities and adsorption/desorption performance to the commercial derivatives. These advanced physical and biochemical properties facilitated a demonstration of the direct, mechanical coupling of bead-milling and fluidised bed adsorption in a fully integrated process for the accelerated recovery of G3PDH from yeast. The generic application of such pellicular adsorbents and integrated processes to the recovery of labile, intracellular products is discussed.

Adsorption↗

PubMed2002

Preparation and characterization of vanadyl complexes with bidentate maltol-type ligands; in vivo comparisons of anti-diabetic therapeutic potential.

A series of 2-alkyl-3-hydroxy-4-pyrone oxovanadium(IV) compounds has been synthesized, characterized, and tested for bioactivity as potential insulin-enhancing agents. The vanadyl complexes, bis(maltolato)oxovanadium(IV), BMOV, bis(ethylmaltolato)oxovanadium(IV), BEOV, and bis(isopropylmaltolato)oxovanadium(IV), BIOV, were compared against vanadyl sulfate for glucose-lowering ability, when administered i.p. to STZ-diabetic rats, at a one-time dose of 0.1 mmol kg(-1)body weight. Blood levels of vanadium were determined at regular intervals, to 72 h, following i.p. injection. All complexes tested exceeded vanadyl sulfate in glucose-lowering ability; this effect was not correlated, however, with blood vanadium levels. Analysis of the pharmacokinetics of the disappearance of [ethyl-1-(14)C]BEOV after an oral gavage dose (50 mg kg(-1), 0.144 mmol kg(-1), in a 10 mL kg(-1) volume of 1% CMC solution) indicated clearly that metal ion-ligand dissociation took place relatively soon after oral ingestion of the complex. Half-lives of fast phase uptake and slow phase disappearance for (14)C and V were calculated from a two-compartment model for whole blood, plasma, liver, kidney, bone, small intestine, and lung, ranging from 17 min ( t(1/2)alpha for (14)C, liver) to 30 days ( t(1/2)beta for V, bone). Curves of disappearance of plasma and whole blood (14)C and V diverged dramatically within the first hour after administration of the vanadium complex.

Administration, Oral↗