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Biomedical subjects

Z Fan

Publications and source records attributed to Z Fan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Antitumor effect of an HER2-specific antibody-toxin fusion protein on human prostate cancer cells.

BACKGROUND: HER2/neu has been implicated in the oncogenesis of human prostate cancer. Clinical studies have suggested that overexpression of HER2 may be one of the indicators of poor prognosis in prostate cancer patients. METHODS: We used Western blot analysis to examine the expression of HER2 in a panel of established human prostate cancer cell lines and used an MTT assay to evaluate the cytotoxicity on these cells of a recombinant fusion protein consisting of an HER2-specific single-chain antibody and the Pseudomonas exotoxin A, scFv(FRP5)-ETA. RESULTS: LNCaP cells express high levels of HER2 protein. Exposure of LNCaP cells to scFv(FRP5)-ETA caused remarkable cell death. In contrast, PC3M cells, which express an undetectable level of HER2 protein, were resistant to scFv(FRP5)-ETA-induced cytotoxicity. MDA PCa 2a, MDA PCa 2b, and DU145 cells express low-to-medium levels of HER2 protein and showed an HER2 level-dependent response to scFv(FRP5)-ETA-induced cytotoxicity. The scFv(FRP5)-ETA-induced cytotoxicity of LNCaP cells could be inhibited by an anti-HER2 monoclonal antibody (mAb), which downregulated the levels of HER2 protein, indicating the specificity of scFv(FRP5)-ETA in inducing cytotoxicity in LNCaP cells. Using an apoptosis ELISA, we demonstrated that scFv(FRP5)-ETA induced apoptosis in LNCaP cells. The apoptosis was inhibited by the presence of dihydrotestosterone (DHT) in culture medium. Exposure of LNCaP cells to scFv(FRP5)-ETA caused reduction in the level of the prostate-specific antigen (PSA). CONCLUSIONS: Our data suggest that scFv(FRP5)-ETA might be a useful agent for the treatment of human prostate cancer cells with high levels of HER2 expression.

ADP Ribose Transferases↗
PubMed2001

Synergistic interaction between an anti-p185HER-2 pseudomonas exotoxin fusion protein [scFv(FRP5)-ETA] and ionizing radiation for inhibiting growth of ovarian cancer cells that overexpress HER-2.

OBJECTIVES: The HER-2 proto-oncogene is overexpressed in 15-30% of ovarian cancers, providing a target for therapy in a fraction of patients. We previously described the ability of a recombinant single-chain anti-p185HER-2-Pseudomonas exotoxin A fusion protein, scFv(FRP5)-ETA, to inhibit growth of cancer cells in culture and tumor xenografts in vivo. We have also described synergistic interaction between an anti-p185HER-2-ricin A chain immunotoxin and ionizing radiation for inhibiting growth of ovarian and breast cancer cells that overexpress HER-2. Our objective in this report was to evaluate the in vitro and in vivo effects of scFv(FRP5)-ETA against SKOv3 ovarian cancer cells that have been transfected to express >10(6) p185HER-2 receptors per cell (clone-9002-18). METHODS: Inhibition of clonogenic growth was measured in vitro by limiting dilution analysis. Inhibition of tumor growth was measured in vivo using heterografts established with the same ovarian cancer cell lines. RESULTS: Clone-9002-18 cells were substantially more sensitive than parental SKOv3 cells to the cytotoxic effects of scFv(FRP5)-ETA. Exotoxin fusion protein induced apoptosis in clone-9002-18 cells, but did not affect parental SKOv3 cells. Treatment of clone-9002-18 cells with 200- to 2000-cGy external beam irradiation in combination with scFv(FRP5)-ETA produced synergistic elimination of clonogenic tumor cells in culture. In vivo, subcutaneous or intraperitoneal growth of tumor xenografts in nu/nu mice was significantly inhibited (P = 0.004) by treatment for 10 days with scFv(FRP5)-ETA or with 131I-labeled-520C9 anti-p185HER-2 radionuclide conjugate, but additive effects were not observed with combined treatment. CONCLUSION: ScFv(FRP5)-ETA deserves further evaluation for intraperitoneal therapy of ovarian cancers that overexpress p185HER-2.

ADP Ribose Transferases↗
PubMed2001

Histone-like proteins from fish are lethal to the parasitic dinoflagellate Amyloodinium ocellatum.

Antimicrobial proteins were purified from acid extracts of rainbow trout (Oncorhynchus mykiss) and sunshine bass (Morone saxatilis male x M. chrysops female) skin, gill and spleen by reverse-phase HPLC. Mass spectrometry and amino acid sequence data suggest that these proteins are closely related to histone H2B and histone H1 and thus they were designated histone-like proteins (HLPs). These proteins were lethal to Amyloodinium ocellatum, which is one of the most important parasitic agents affecting fish. Antibiotic concentrations as low as 12.5 microg/ml were inhibitory. Activity was directed against the trophont (feeding) stage of the parasite, while the disseminative (dinospore) stage was unaffected. Thus, HLPs act unlike typical drugs used to treat amyloodiniosis, which usually target the dinospore. Both the ability of the parasite to infect host cells, as well as the ability to grow and differentiate after infection were severely inhibited. This is in contrast to magainin 2, which was similarly toxic to both the dinospore and trophont stages. These findings provide further evidence that histone-like proteins may be important defensive molecules in fish.

Animals↗
PubMed2001

The MMT bag for emission source sampling: design and evaluation.

This paper presents the design and evaluation results for a metal-coated multilayer Tedlar (MMT) bag that was developed for the collection of source emissions. The applicability of the MMT bag was evaluated for a number of important greenhouse relevant gases: CO, CO2, CH4, N2O, and total hydrocarbons (THCs). The bag was tested for durability and stability for a range of concentrations of the tested compounds using both laboratory-prepared samples and real source samples. The results show that all tested compounds were more stable when stored in the MMT bag than when stored in a regular Tedlar bag. These compounds can be stored at room temperature for at least 3 months without significant changes in concentration. When properly packed, the MMT bag is durable and may be shipped by air. The MMT bag is lower in cost, lighter in weight, and easier to clean, and it requires less devices during the subsequent laboratory analysis compared with a stainless steel canister, which is often used to collect air and source samples.

Air Pollutants, Occupational↗
PubMed2001

Dermal fibroblasts genetically engineered to release nerve growth factor.

Current surgical strategies for repair of critical nerves involves the transfer of normal donor nerve from an uninjured body location. One possible alternative to autogenous tissue replacement is the development of engineered constructs to replace those elements necessary for axonal proliferation. Delivery of growth factors is one strategy to enhance synthetic nerve constructs. Thus, this study focused on the delivery of nerve growth factor (NGF) by genetic engineering to begin approaching the microenvironment dictated, in part, by Schwann's cells. Rat dermal fibroblasts (DFBs) were modified genetically to release rat NGF. The reporter gene LacZ was used to assess the optimum nonviral transfection method commercially available before NGF transfection. FuGENE6 provided the optimum transfection efficiency (24% maximum, 20.1 +/- 1.9% 5-day average) as measured by beta-galactosidase catalytic activity. NGF release from transfected DFBs was assessed over a 3-day period. Compared with control (no transfection) DFBs and DFBs transfected with vector alone, DFBs transfected with an expression vector encoding rat beta-NGF demonstrated significantly (p < 0.05) higher levels of NGF, with a 3-day maximum of 111 pg NGF per milliliter. When normalized to cell number, NGF-transfected DFBs released 1.2 pg NGF per milliliter/10(3) cells. The NGF-transfected DFBs demonstrated a maximal NGF release rate at day 1 (1.2 ng NGF/10(6) cells per day), followed by a markedly lower, sustained release rate at days 2 and 3 (0.44 ng NGF/10(6) cells per day and 0.48 ng NGF/10(6) cells per day respectively). The release rate curves for control and vector-transfected DFBs also exhibited a maximal NGF release rate at day 1, but were followed by a decreasing release rate, potentially representing in vitro degradation of NGF present in fetal bovine serum. Although not first with the development of growth factor delivery through fibroblasts, these findings suggest that rat DFBs can be modified genetically to act like Schwann's cells to deliver NGF.

Animals↗
PubMed2001

Differential roles of p21(Waf1) and p27(Kip1) in modulating chemosensitivity and their possible application in drug discovery studies.

In this study, the differential role of the cyclin-dependent kinase (CDK) inhibitors p21(Waf1) and p27(Kip1) in cell cycle regulation was proposed for use in screening natural or synthetic compounds for cell cycle-dependent (particularly M phase-dependent) antineoplastic activity. p21(Waf1) or p27(Kip1) was ectopically expressed with an ecdysone-inducible mammalian expression system in a human colon adenocarcinoma cell line. Induction of p21(Waf1) or p27(Kip1) expression inhibited the activities of CDK2 and completely arrested cells at G(1) phase of the cell cycle by p27(Kip1) and at G(1) and G(2) phases by p21(Waf1). We examined the sensitivity of these cells to several antineoplastic agents known to be cell cycle-dependent or -independent. Substantially increased resistance to cell cycle-dependent antineoplastic agents was found in the cells when the expression of p21(Waf1) or p27(Kip1) was induced. In contrast, only a desensitization to cell cycle-independent antineoplastic agents was found in the cells arrested by p21(Waf1) or p27(Kip1). Because p21(Waf1) induces an additional block at G(2) phase that inhibits cell entry into M phase, we further examined the difference between p21(Waf1)- and p27(Kip1)-induced cells in their sensitivity to D-24851, a novel M phase-dependent compound. We found that induction of p21(Waf1) after exposure of the cells to D-24851 conferred stronger resistance than did induction of p27(Kip1). Taken together, our results suggest that the differential effect of p21(Waf1) and p27(Kip1) on cell cycle regulation may be advantageous for screening chemical libraries for novel antineoplastic candidates that are cell cycle-dependent, and M phase-dependent in particular.

Acetamides↗
PubMed2001

Restoration of anti-human immunodeficiency virus type 1 (HIV-1) responses in CD8+ T cells from late-stage patients on prolonged antiretroviral therapy by stimulation in vitro with HIV-1 protein-loaded dendritic cells.

We demonstrate that dendritic cells loaded in vitro with human immunodeficiency virus type 1 (HIV-1) protein-liposome complexes activate HLA class I-restricted anti-HIV-1 cytotoxic T-lymphocyte and gamma interferon (IFN-gamma) responses in autologous CD8+ T cells from late-stage HIV-1-infected patients on prolonged combination drug therapy. Interleukin-12 enhanced this effect through an interleukin-2- and IFN-gamma-mediated pathway. This suggests that dendritic cells from HIV-1-infected persons can be engineered to evoke stronger anti-HIV-1 CD8+ T-cell reactivity as a strategy to augment antiretroviral therapy.

Anti-HIV Agents↗
PubMed2001

Time course of the MAPK and PI3-kinase response within 24 h of skeletal muscle overload.

Knowledge of the molecular mechanisms by which skeletal muscle hypertrophies in response to increased mechanical loading may lead to the discovery of novel treatment strategies for muscle wasting and frailty. To gain insight into potential early signaling mechanisms associated with skeletal muscle hypertrophy, the temporal pattern of mitogen-activated protein kinase (MAPK) phosphorylation and phosphatidylinositol 3-kinase (PI3-kinase) activity during the first 24 h of muscle overload was determined in the rat slow-twitch soleus and fast-twitch plantaris muscles after ablation of the gastrocnemius muscle. p38alpha MAPK phosphorylation was elevated for the entire 24-h overload period in both muscles. In contrast, Erk 2 and p54 JNK phosphorylation were transiently increased by overload, returning to the levels of sham-operated controls by 24 h. PI3-kinase activity was increased by muscle overload only at 12 h of overload and only in the plantaris muscle. In summary, sustained elevation of p38alpha MAPK phosphorylation occurred early in response to muscle overload, identifying this pathway as a potential candidate for mediating early hypertrophic signals in response to skeletal muscle overload.

Animals↗
PubMed2001

[Comprehensive assessment on environmental quality in vulnerable ecotone of Tarim River Basin].

Tarim River Basin (TRB) is one of ecological environment vulnerable areas. Due to the matching of material and energy existed in some problems, the different fragility characteristics occurred obviously. According to related principles of ecological environment quality assessment, combined with ecological environment situation of Tarim River Basin, 20 indexes were selected, and the indicator system for synthetically ecological environment assessment was built. Moreover, ecological fragility index was set up, which can be used to indicate the degree of ecological environment quality in Tarim River Basin. The results were as follows: Aksu River Basin belongs to improved area. Yerkart River Basin and the upper reaches of TRB belongs to balance areas and Hetian River Basin and the middle reaches of TRB belongs to maladjustment areas. The lower reaches of TRB belongs to severe damage area. The assessment results are consonant with actual situation, which play an important function in ecological environment construction.

China↗
PubMed2001

An analysis of therapeutic effect of drug acupoint application in 209 cases of allergic asthma.

Both therapies of traditional crude herb moxibustion and drug acupoint application were used in 209 cases of allergic asthma to compare their long-term and short-term therapeutic effects and to analyze the relationship between clinic therapeutic effects of both therapies and differential types of the disease. The results showed that the short-term total effective rate in the group of drug acupoint application was higher than that in the group of traditional crude herb moxibustion, the therapeutic effects of drug acupoint application being closely related to differential types. Analysis also shows the best short-term therapeutic effect was in the type of heat in the lung while the poorest effect in the type of deficiency of the kidney-yang.

Acupuncture Points↗
PubMed2001

[The inhibitory effect of oxymatrine on hepatitis C virus in vitro].

OBJECTIVE: To study the inhibitory effect of oxymatrine on HCV in vitro. METHODS: SMMC-7721 cells transfected with pBK-HCV using lipofectin transfection protocal were treated with oxymatrine. bDNA signal amplification assay and MTT colorimetric assay were used for intracellular HCV RNA and cytotoxicity. RESULTS: The stable HCV expression cell model established here could be used as a tool for medicine screen. Oxymatrine at the concentration of 100~1000 mug/ml could significantly decrease the level of intracellular HCV RNA. No cytotoxicity was shown in such concentrations. CONCLUSIONS: Oxymatrine has an anti-HCV potential activity in vitro.

Alkaloids↗
PubMed2001

Molecular genetic profiling of Gleason grade 4/5 prostate cancers compared to benign prostatic hyperplasia.

PURPOSE: Because Gleason grade 4/5 cancer is the primary cause of failure to cure prostate cancer, we examined the molecular profiles of this high grade cancer in search of potentially new therapeutic interventions as well as better serum markers than prostate specific antigen. MATERIALS AND METHODS: We compared the gene expressions in fresh frozen tissues from 9 men with Gleason grade 4/5 cancer to 8 men with benign prostatic hyperplasia (BPH) treated with radical retropubic prostatectomy. Labeled complementary RNA from each of the 17 tissues was applied to HuGeneFL probe arrays representing approximately 6,800 genes (Affymetrix, Inc., Santa Clara, California). After removing all genes undetectable in BPH and grade 4/5 cancers, and transforming the data into a parametric distribution, we chose only those up and down-regulated genes with a p difference in fluorescence between grade 4/5 cancer and BPH of p <0.0005. This value reduced the data set to 40 up-regulated and 111 down-regulated genes. We then eliminated all genes that were not expressed in all 8 BPH and 9 grade 4/5 tissues, which produced a final set of 86 genes, of which 22 were up-regulated and 64 were down-regulated. RESULTS: Cluster analysis cleanly separated men with grade 4/5 cancers from those with BPH. Only 17 of the 86 candidate genes (20%) were known to be prostate cancer related and 42 (49%) were related to other cancers. The most up-regulated gene is Hepsin, a trypsin-like serine protease with its enzyme catalytic domain oriented extracellularly. Prostate specific membrane antigen is the second most up-regulated gene (all other reports on prostate specific membrane antigen have been at the protein level). The genes for prostate specific antigen (hK3) and human glandular kallikrein2 (hK2) showed equivalent expression levels 10 times the average of other genes. Complete lists of all 22 up-regulated genes and 64 down-regulated genes, together with their locus on the chromosome, are presented in rank order. CONCLUSIONS: We characterize for the first time 64 down-regulated and 22 up-regulated genes in Gleason grade 4/5 cancer, using the gene profile from BPH as control tissue. A number of interesting new genes, previously undescribed in prostate cancer, are presented as possibilities for further study.

Aged↗
PubMed2001

[Deletion mapping of chromosome 18q and Smad proteins expression analysis in urinary bladder carcinomas].

OBJECTIVE: To investigate the role of loss of heterozygosity (LOH) on chromosome 18q in the carcinogenesis and progression of urinary bladder cancer and to provide clues for early detection and positional cloning of related genes. METHODS: Deletion mapping was performed on 18q using 12 microsatellite markers. Immunohistochemistry staining was used to evaluate the expression level of two tumor suppressor candidates Smad 2 and Smad 4 in this region. RESULTS: LOH in at least one of the 12 microsatellites on 18q was detected in 84.2% (32/38) of patients with bladder cancer. The minimal deletion region included tumor suppressor candidate Smad 4. Immunohistochemical study revealed that 21.1% (8/38) of the cases had up-regulated Smad 2 protein and 34.2% (13/38) of the cases had down-regulated Smad 2 protein. Smad4 protein expression was down-regulated in 68.4% (26/38) of the cases but up-regulated Smad 4 expression was seen in only one case. CONCLUSIONS: LOH on 18q was closely linked with bladder cancer. The irregular expression of tumor suppressor candidates Smad 2 and Smad 4 may play important role in the initiation and progression of bladder neoplasms.

Adolescent↗
PubMed2001

[Comprehensive evaluation of medical system by using generalized fuzzy set theory].

Based on the theory of generalized fuzzy set, a comprehensive evaluation model has been built, which provides residuals estimate, evaluate function and test methods needed. Verified by the prognosis of 30 patients with myocardial infarction in a motion experiment during rehabilitation, its coincidence rate was found to be above 90%. This model can be developed and applied to medical system and other systems for evaluations as well.

Evaluation Studies as Topic↗
PubMed2001

[Subcloning and sequencing of DNA fragment related to salt tolerance in Sinorhizobium meliloti 042B].

A 4 kb ClaI DNA fragment related to salt tolerance from S. meliloti 042B was digested by HindIII down 2.4 kb fragment, and a 1.6 kb ClaII-HindIII fragment was retained on plasmid pML122. Then, the 2.4 kb DNA fragment was ligated with plasmid pBBR1-MCS2, and the recombinant plasmid was transformed to E. coli DH5 alpha, and transformant GS2 was obtained. Three-parental mating experiments were carried out with transformant GS2 as donor, salt sensitive strains GZ17 as recipient and pRK2013 as helper plasmid, then the transconjugant GG2 was selected on FY plates containing kanamycin and 0.4 mol/L NaCl. The remaining DNA fragment was self ligated with pML122 and then transformed into E. coli S17-1 and transformat GS0 was obtained. Two-parental mating experiment was carried out with transformant GS0 as donor and salt sensitive strain GZ17 as recipient, but no transconjugant was obtained on the FY plates. Then, the 2.4 kb HindIII DNA fragment was ligated into sequencing vector pGEM-7Zf(+) for sequencing. The result of sequencing and analysis showed that the 2.4 kb DNA fragment contained three ORFs. According to the result of sequencing, further subcloning was conducted and 1.9 kb HindIII-Sac II DNA fragment related to salt tolerance was obtained.

Amino Acid Sequence↗
PubMed2001

[Changes of tangent time constant in the transformation of F-V curve configuration in COPD and cor pulmonale patients and clinical implications].

OBJECTIVE: To explore the changes of tangent time constant (tau t) in the transformation of F-V curve configuration in COPD and cor pulmonale patients and clinical implications. METHODS: We determined the F-V curves in 90 COPD patients (43 with chronic bronchitis, 47 with emphysema) and 31 complicated with cor pulmonale; all patients were in the ameliorated period. The tau t at high, mid and low lung volumes, tau t75, tau t50, tau t25, were measured on each F-V curve. RESULTS: 1. Normal ranges: F-V curve configuration with plateau, linear, convex and concave types; |tau t75| > ls or < ls; tau t25 < ls; tau t relationship with "adolescent fashion" or "old fashion". 2. Light and moderate abnormality: With convex type; |tau t75| < ls; tau t25 approximately = ls or > ls; "trumpet fashion" changes. 3. Serious abnormality: With hyperbolic type; |tau t75| < ls; tau t25 = 4s-10s; "tower fashion" changes. CONCLUSION: Hyperbolic type, extreme prolongation of tau t25 and "tower fashion" changes can be assigned as 3 important indices to assess the severity of disease. The convenience and correctness of the method may be available for clinical application.

Adult↗
PubMed2001

[Study on the determination of iodine by inductively coupled plasma atomic emission spectrometry].

A new method for determining iodine had been developed in ICP-AES. An oxidant, NaNO2 and a sample containing iodine ion were mixed in the PHD hydroid generation device, the producing iodine molecules were nebulized in nebulizer and then the iodine gas came into troch directly. The problem that the intensity of iodine decreases with the increase of time was solved. It was found that NaNO2 decreased the effect of Cl- in the low acidity. A detection limit of 14 ng.mL-1 was obtained and the RSD of the measurement for 2 micrograms.mL-1 of iodine was 1.2% (n = 10). The average recoveries of iodine were 99.44%. The method was applied to the determination of salt and seawater.

Iodides↗