Biomedical subjects

Zhiping Zhang

Publications and source records attributed to Zhiping Zhang.

At least 19 recordsLinked to original sources

PubMed2007

Folate-decorated poly(lactide-co-glycolide)-vitamin E TPGS nanoparticles for targeted drug delivery.

Doxorubicin-loaded nanoparticles (NPs) of vitamin E TPGS-folate (TPGS-FOL) conjugate and doxorubicin-poly(lactide-co-glycolide)-vitamin E TPGS (DOX-PLGA-TPGS) conjugate were prepared by the solvent extraction/evaporation method for targeted chemotherapy of folate-receptor rich tumors. X-ray photoelectron spectroscopy demonstrated that folate was distributed on the NP surface while the drug molecules were entrapped in the NP matrix. The NPs were found of approximately 350nm diameter and exhibited a biphasic pattern of in vitro drug release. The cell uptake of the fluorescent NPs and the cell viability of the drug formulated in the NPs were quantitatively investigated, which were found dependent on the content of targeting TPGS-FOL conjugate. The NPs of 50% TPGS-FOL showed cellular uptake by MCF-7 cells 1.5 times higher and by C6 cells 1.7 times higher than the NPs with no TPGS-FOL component after 30min incubation. The MCF-7 cell viability was found decreased significantly from 50.8% for the drug-loaded NPs of no TPGS-FOL to 8.2% for those of 50% TPGS-FOL after incubation at 100microug concentration at 37 degrees C. The latter NPs also exhibited much lower IC(50) value than the DOX after 24h incubation, i.e., 19.4 vs. 43.7micror MCF-7 cells and 3.3 vs. >100micror C6 cells.

Animals↗

PubMed2006

Interplay between estrogen-related receptor alpha (ERRalpha) and gamma (ERRgamma) on the regulation of ERRalpha gene expression.

Estrogen-related receptor alpha (ERRalpha) modulates estrogen receptor (ER)-mediated activity and is participating in the energy homeostasis by regulation of downstream target genes. The ERRalpha gene itself is proposed to be regulated by peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) through an autoregulatory loop under physiological stimulation. We have previously shown that the close family member ERRgamma is a positive regulator of ERRalpha gene expression. ERRalpha and ERRgamma are coexpressed in metabolically active tissues such as heart, kidney and muscle, yet the physiological role of ERRgamma and its relationship with ERRalpha in gene regulation are currently unknown. The present study examined the interplay of ERRgamma and ERRalpha in regulation of ERRalpha gene expression. Using real-time PCR analyses we found that ERRgamma, like the ERRalpha and PGC-1alpha is induced in mouse liver during fasting. Overexpression of ERRgamma in the HEC-1B cells robustly stimulated the multi-hormone response element (MHRE) of the ERRalpha gene promoter and this activity was repressed by increasing expression of ERRalpha. The two ERRs bind MHRE simultaneously in electrophoretic mobility shift assay (EMSA) and they were detected as multimeric complexes in cells by coimmunoprecipitation. Although ERRalpha and ERRgamma share high sequence identity, they differ in biochemical and molecular characteristics as examined by trypsin digestion, reporter activation and coactivator interaction and utilization. Using chromatin immunoprecipitation (ChIP) assay, we showed that ectopic expression of both ERRalpha and ERRgamma modifies chromatin structure at the MHRE region while ectopic expression of PGC-1alpha in HEC-1B cells promotes ERRgamma but not ERRalpha occupancy at the MHRE region of the ERRalpha gene promoter and enhances the recruitment of coactivator SRC1. These data suggested that ERRalpha and ERRgamma regulate ERRalpha gene expression with different molecular mechanisms.

Animals↗

PubMed2006

Knockdown of mutant K-ras expression by adenovirus-mediated siRNA inhibits the in vitro and in vivo growth of lung cancer cells.

The ras mutation, which is observed in 20-30% of human nonsmall cell lung cancers (NSCLCs), is one of common genetic alterations and has been proposed to be a prognostic factor in lung cancer. Oncogene ras appears to be essential for tumor progression and maintenance. Several therapeutic agents have been developed to inhibit ras, such as FTIs and antisense oligonucleotides. A new tool for blocking oncogenes in cancer cells has emerged with the discovery that RNA interference can specifically silence expression of endogenous human genes. In the current study, we used small interfering RNA (siRNA) directed against mutant K-ras to determine the anti-tumor effects of decreasing the levels of this protein in lung cancer cell lines. Adenovirus-mediated siRNA (AdH1/siK-ras(V12)) against K-ras(V12) markedly decreased K-ras(V12) gene expression and inhibited cellular proliferation of NSCLC H441 cells that express the relevant mutation (K-ras codon 12 GGT --> GTT), but produced minimal growth inhibition on NSCLC H1650 cells that lack the relevant mutation. Pretreatment with AdH1/siK-ras(V12) completely abrogated subcutaneous engraftment of H441 cells, as compared with a 100% tumor take in animals that received control vector-treated tumor cells. The in vivo effect of AdH1/siK-ras(V12) treatment was further examined by intratumoral injections after tumor induction. Pre-existing tumor growth was reduced by 45% by a single intratumoral injection. Three or five repeat injections resulted in complete tumor regression in eight of ten nude mice. Further, 23.12% of AdH1/siK-ras(V12) treated H441 cells underwent apoptosis, as compared with 6.13%, and 8.27% in untreated and control vector-treated cells, respectively. These results indicate that adenovirus-mediated siRNA can specifically and efficiently target factors whose expression is altered in malignancy and may have the potential as a therapeutic modality to treat human lung cancer.

Adenocarcinoma↗

PubMed2006

Temperature- and pH-dependent morphology and FT-IR analysis of magnesium carbonate hydrates.

Various morphologies of magnesium carbonate hydrates have been synthesized by carefully adjusting the reaction temperature and pH value of the initial reaction solution in the precipitation process. At lower temperatures (from room temperature to 328 K) and lower pH values (variation with the reaction temperature), magnesium carbonate hydrates are prone to display needlelike morphology, and the axis diameter of the particles decreases with the increase of reaction temperature and pH value. With the further increase of the reaction temperature (333-368 K) and pH value, the sheetlike crystallites become the preferred morphology, and at higher temperatures and pH values, these crystallites tend to assemble into layerlike structures with diverse morphologies, such as spherical-like particles with rosette-like structure and cakelike particles built from sheetlike structure. Fourier transform infrared (FT-IR) spectra show that these various morphologies are closely related to their compositions. The needlelike magnesium carbonate hydrate has a formula of MgCO3.xH2O, in which the value x is greatly affected by the experimental conditions, whereas with the morphological transformation from needlelike to sheetlike structure, their corresponding compositions also change from MgCO3.xH2O to Mg5(CO3)4(OH)2.4H2O in the interval of 328-333 K.

Hydrogen-Ion Concentration↗

PubMed2006

Self-adaptive optical systems for long-distance flying optics.

The focusing characteristics of long-distance flying optics were studied systemically for TEM(mn) Gaussian beams. The results show that the ABCD law of parameter q can be extended to Gaussian modes of any order when waist radius w in the imaginary part of parameter q is replaced by Rayleigh range Z(R) of a certain resonator in the equation. The difference between the real focal length and the geometric focal length, defined as Df, was calculated for laser applications. A novel self-adaptive optical system was demonstrated for precisely controlling the focusing characteristics of long-distance flying optics. Theoretical analyses and experimental results were consistent.

Journal Article↗

PubMed2006

Self-assembled nanoparticles of poly(lactide)--Vitamin E TPGS copolymers for oral chemotherapy.

Nanoparticles (NPs) of poly(lactide)-Vitamin E TPGS (PLA-TPGS) copolymers were synthesized by a dialysis method in the present study to formulate paclitaxel for oral chemotherapy with Caco-2 cells as an in vitro model of the gastrointestinal (GI) drug barrier. The PLA-TPGS NPs were of size 340nm in diameter with 5.2% drug loading. The drug release kinetics showed a 31% initial burst in the first day, followed by 80% accumulative drug release after 30 days in the PBS buffer at pH 7.4, and the release rate was found lower in simulated gastric and intestinal conditions. The internalization of fluorescent PLA-TPGS NPs by Caco-2 cells was visualized by confocal laser scanning microscopy (CLSM). PLA-TPGS NPs showed significant increase in the cellular uptake by 1.8- and 1.4-fold in comparison with poly(lactide-co-glycolide) (PLGA) NPs cultured with HT-29 and Caco-2 cells, respectively, and the cellular uptake efficiency was found affected by the incubation time and the particle concentration in the culture medium. Investigation on HT-29 and Caco-2 cytotoxicity showed advantages of the PLA-TPGS NP formulation versus Taxol. The IC(50) of the PLA-TPGS NP formulation with HT-29 cells was found 40% lower than of Taxol at the same dose of paclitaxel. The results obtained in this research demonstrated feasibility for the PLA-TPGS NPs to be applied for oral delivery of paclitaxel as well as other anticancer drugs.

Administration, Oral↗

PubMed2006

Study of a dual-frequency laser interferometer with unique optical subdivision techniques.

A dual-frequency laser interferometer has been developed based on a low-performance commercial interferometer. An optical resolution of 1.24 nm and a nanometer-scale accuracy have been achieved by using unique techniques to obtain an optical subdivision factor of 1/8. A method for reducing static positioning errors was also shown. The measurement of a free-falling body was performed to test the maximum achievable target velocity of the device. The experimental setup for measuring the static positioning errors was also given. The new interferometer could be widely used in nanometer-scale fabrications and measurements.

Journal Article↗

PubMed2006

The drug encapsulation efficiency, in vitro drug release, cellular uptake and cytotoxicity of paclitaxel-loaded poly(lactide)-tocopheryl polyethylene glycol succinate nanoparticles.

Paclitaxel is one of the most effective antineoplastic drugs. Its current clinical administration is formulated in Cremophor EL, which causes serious side effects. Nanoparticle (NP) technology may provide a solution for such poisonous adjuvant problems and promote a sustained chemotherapy, in which biodegradable polymers play a key role. Our group has successfully synthesized novel poly(lactide)-tocopheryl polyethylene glycol succinate (TPGS) (PLA-TPGS) copolymers of desired hydrophobic-hydrophilic balance for NP formulation of anticancer drugs. The present work is focused on effects of the PLA:TPGS composition ratio on drug encapsulation efficiency, in vitro drug release, in vitro cellular uptake and viability of the PLA-TPGS NP formulation of paclitaxel. The PLA-TPGS copolymers of various PLA:TPGS ratios were synthesized by the ring-opening polymerization method and characterized by GPC and (1)H NMR for their molecular structure. Paclitaxel-loaded PLA-TPGS NPs were prepared by a modified solvent extraction/evaporation method and characterized by laser light scattering for size and size distribution, scanning electron microscopy for surface morphology and zeta potential for surface charge. High performance liquid chromatography was used to measure the drug encapsulation efficiency and in vitro drug release profile. Cancer cell lines HT-29 and Caco-2 were used to image and measure the cellular uptake of fluorescent PLA-TPGS NPs. Cancer cell viability of the drug-loaded PLA-TPGS was measured by MTT assay. It was found that the PLA:TPGS composition ratio has little effects on the particle size and size distribution. However, the PLA-TPGS NPs of 89:11 PLA:TPGS ratio achieved the best effects on the drug encapsulation efficiency, the cellular uptake and the cancer cell mortality of the drug-loaded PLA-TPGS NPs. This research was also carried out in close comparison with the drug-loaded PLGA NPs.

Antineoplastic Agents↗

PubMed2006

Characterization of the surface properties of Mg/Al oxides by the solvation parameter model.

The oxides of different Mg/Al ratios (Mg/Al = 0, 0.1, 5, 10 and infinity) were prepared, and the characterization of these oxides was attempted by estimating characteristic interaction parameters based on the solvation parameter model. The magnitudes of the regression coefficients varied with the increase of Mg/Al ratio. For the oxide of Mg/Al = 0.1 and Al2O3, the contribution of these characteristic interactions for solutes' retention was similar to that of the common silica, and the dipolarity/polarizability (pi*), the solute hydrogen bond donating (alpha2(H)) and accepting (beta2(H)) abilities played an important role. Yet, the retention behavior at a higher Mg/Al ratio (Mg/Al = 5, 10 and MgO) drastically changes, and V(i)/100 (the intrinsic molar volume), pi*, alpha2(H) and beta2(H) all favored the solutes retention. By comparison of the regression coefficients on various normal-phase (NP) and reversed-phase (RP) columns, a new model was developed to correlate the solute retention factors on Mg/Al = 5, 10 and MgO columns with the data of NP and RP columns.

Aluminum Oxide↗

PubMed2006

Estrogen-related receptors-stimulated monoamine oxidase B promoter activity is down-regulated by estrogen receptors.

Although there are studies published about the neuroprotective effect of estrogen, little is known about the mechanisms and cellular targets of the hormone. Recent reports demonstrate that estrogen down-regulates the expression of monoamine oxidase A and B (MAO-A and MAO-B) in the hypothalamus of the Macaques monkey, both of which are key isoenzymes in the neurotransmitter degradation pathway. Additionally, estrogen-related receptor alpha (ERRalpha) up-regulates MAO-B gene expression in breast cancer cells. ERRalpha recognizes a variety of estrogen response elements and shares many target genes and coactivators with estrogen receptor alpha (ERalpha). In this study, we investigate the interplay of ERs and ERRs in the regulation of MAO-B promoter activity. We demonstrate that ERRalpha and ERRgamma up-regulate MAO-B gene activity, whereas ERalpha and ERbeta decrease stimulation in both a ligand-dependent and -independent manner. Ectopically expressed ERRalpha and ERRgamma stimulate the expression of MAO-B mRNA and protein as well as increase the MAO-B enzymatic activity in ER-negative HeLa cells. The ability of ERRs to stimulate MAO-B promoter activity was reduced in ER-positive MCF-7 and T47D cells. Several AGGTCA motifs of the MAO-B promoter are responsible for up-regulation by ERRs. Interestingly, ERalpha or ERbeta alone have no effect on MAO-B promoter activity but can down-regulate the activation function of ERRs, whereas glucocorticoid receptor does not. By using chromatin immunoprecipitation assay, we demonstrate that ERs compete with ERRs for binding to the MAO-B promoter at selective AGGTCA motifs, thereby changing the chromatin status and cofactor recruitment to a repressed state. These studies provide new insight into the relationship between ERalpha, ERbeta, ERRalpha, and ERRgamma in modulation of MAO-B gene activity.

Chromatin↗

PubMed2006

Nanoparticles of poly(lactide)/vitamin E TPGS copolymer for cancer chemotherapy: synthesis, formulation, characterization and in vitro drug release.

Paclitaxel is one of the best anticancer drugs, which has excellent therapeutic effects against a wide spectrum of cancers. The formulation of paclitaxel used in its currently clinical administration includes Cremophor EL, which has been found to cause serious side effects. Nanoparticle formulation of paclitaxel may provide an ideal solution for this problem and achieve a sustained chemotherapy. A novel copolymer, poly(lactide)-vitamin E TPGS (PLA-TPGS), was synthesized from lactide and d-alpha-tocopheryl polyethylene glycol 1000 succinate by bulk polymerization for nanoparticle formulation of anticancer drugs. 1H NMR, FTIR and GPC were used to detect molecular structure of the copolymer. Paclitaxel-loaded PLA-TPGS nanoparticles were fabricated by a modified solvent extraction/evaporation technique with or without emulsifier involved, which were characterized by laser light scattering for size and size distribution; field emission scanning electron microscopy for surface morphology; zeta potential for surface charge; X-ray photoelectron spectroscopy for surface chemistry. The drug encapsulation efficiency and the in vitro drug release kinetics were measured by high-performance liquid chromatography. Formulation optimization was pursued. The particles were found of around 300 nm in size and narrow size distribution. Of all, 89% drug encapsulation efficiency has been achieved for nanoparticles of 5% drug loading. The drug release from PLA-TPGS nanoparticles was found to be biphasic with an initial burst of 17% in the first day, followed by a sustained pattern with 51% release after 31 days.

Antineoplastic Agents, Phytogenic↗

PubMed2006

In vitro investigation on poly(lactide)-Tween 80 copolymer nanoparticles fabricated by dialysis method for chemotherapy.

Polysorbate 80 (Tween 80) has been widely used as an emulsifier with excellent effects in nanoparticles technology for biomedical applications. This work was thus triggered to synthesize poly(lactide)/Tween 80 copolymers with various copolymer blend ratio, which were synthesized by ring-opening polymerization and characterized by 1H NMR and TGA. Nanoparticles of poly(lactide)/Tween 80 copolymers were prepared by the dialysis method without surfactants/emulsifiers involved. Paclitaxel was chosen as a prototype anticancer drug due to its excellent therapeutic effects against a wide spectrum of cancers. The drug-loaded nanoparticles of poly(lactide)/Tween 80 copolymers were then characterized by various state-of-the-art techniques, including laser light scattering for particles size and size distribution, field emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM) for surface morphology; laser Doppler anemometry for zeta potential; differential scanning calorimetry (DSC) for the physical status of the drug encapsulated in the polymeric matrix; X-ray photoelectron spectrometer (XPS) for surface chemistry; high performance liquid chromatography (HPLC) for drug encapsulation efficiency; and in vitro drug release kinetics. HT-29 cells and Glioma C6 cells were used as an in vitro model of the GI barrier for oral chemotherapy and a brain cancer model to evaluate in vitro cytotoxicity of the paclitaxel-loaded nanoparticles. The viability of C6 cells was decreased from 37.4 +/- 4.0% for poly(D,L-lactide-co-glycolic acid) (PLGA) nanoparticles to 17.8 +/- 4.2% for PLA-Tween 80-10 and 12.0 +/- 5.4% for PLA-Tween 80-20 copolymer nanoparticles, which was comparable with that for Taxol at the same 50 microg/mL drug concentration.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Aldo-keto reductase 1 family B7 is the gene induced in response to oxidative stress in the livers of Long-Evans Cinnamon rats.

The Long-Evans Cinnamon (LEC) rat strain (Atp7b m/m), which accumulates copper in the liver due to mutations in the Atp7b gene, is a useful model for investigating the relationship between oxidative stress and hepatocarcinogenesis. To determine the effect of this mutation on oxidative stress marker genes, we performed oligonucleotide array analysis (Affymetrix), and compared the results in Atp7b m/m rats with those of a sibling line with the Atp7b w/w genotype. We focused our studies on the expression of the aldo-keto reductase 1 family B7 (AKR1B7)-like protein gene, since this gene codes for reductase enzymes involved in the detoxification of oxidizing compounds (e.g., aldehydes) and was differentially expressed in Atp7b m/m and Atp7b w/w rat liver. Akr1B7 mRNA expression was significantly increased in comparison with the expression of 4 other known oxidative stress responsive genes, haem-oxygenase-1 (HO-1), thioredoxin (Trx), aldehyde reductase (AKR1A1), and glucose-6-phosphate dehydrogenase (G6PDH). By searching binding motifs, five nuclear factor kappa B (NF-kappaB) binding sites were located in the 5'-upstream region of the akr1b7 gene. Transient co-transfection with both I-kappaBalpha and the Akr1b7 6 kb promoter (p6.0-AKR-Luc) inhibited luciferase activity of p6.0-AKR-Luc in HepG2 cells. Cuprous ion however did not affect the transcription activity induced by p6.0-AKR-luc. Gel-shift assay showed that the DNA binding activity of NF-kappaB increased in the livers of LEC rats, suggesting that the oxidative stress is mediated through NF-kappaB. The results indicate conclusively that in LEC rat liver, akr1b7 might be up-regulated by oxidative stress mediated through NF-kappaB, but not that mediated directly by copper.

5' Untranslated Regions↗

PubMed2005

Distribution patterns of PCDD/Fs in chlorinated chemicals.

The purpose of this research was to determine polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) in five chlorinated chemicals (phthalocyanine copper, phthalocyanine green, chloranil-1 and 2, and triclosan), and to compare their 2,3,7,8-tetrachlordibenzo-IpI-dioxin equivalents (TEQ). The distribution patterns of total PCDD/Fs and 2,3,7,8-substituted PCDD/Fs were elucidated in detail. The TEQ values of toxic PCDD/Fs in all chemicals were in the range of 5.03-1379.55 ng I-TEQ/kg. The contribution of OCDD and OCDF in phthalocyanine green was 75% of the total TEQ. For chloranils, the maximum contribution of toxic PCDD/Fs was from 2,3,7,8-substituted HxCDF and 2,3,7,8-substituted HpCDF. The TEQ of HxCDF and HpCDF in chloranil-1 was 90% and in chloranil-2 was 71%. And the toxic contribution increased with the degree of chlorination for PCDFs.

Anti-Infective Agents, Local↗

PubMed2003

Estrogen stimulates estrogen-related receptor alpha gene expression through conserved hormone response elements.

The estrogen-related receptor alpha gene encodes a nuclear receptor protein, ERR alpha, whose structure is closely related to the estrogen receptors. ERR alpha modulates estrogen receptor (ER)-mediated signaling pathways both positively and negatively. It is selectively expressed in a variety of cell types during development and in adult tissues. We have previously shown that estrogen stimulates the expression of the ERR alpha gene in mouse uterus. In this study, we found that the ERR alpha gene is stimulated by estrogen in mouse uterus and heart but not in liver. Estrogen also stimulates the expression of ERR alpha in the human breast and endometrial cell lines. The human ERR alpha gene promoter contains multiple Sp1 binding sites, and the Sp1 protein is required for the promoter activity. The major estrogen response is mediated by a 34-bp DNA element that contains multiple steroid hormone response element half-sites (MHREs) that are conserved between the human and mouse ERR alpha gene promoters. Mutations made at a single or multiple sites of the MHREs abolished the ER-mediated transcription of the element in transient transfection experiments. By chromatin immunoprecipitation assay, we demonstrated the interaction between ER alpha and MHREs of the endogenous ERR alpha gene promoter in MCF-7 cells. Estrogen treatment further enhanced the association of ER alpha and MHREs in vivo. The present study demonstrated that the ERR alpha gene is a downstream target of ER alpha.

Animals↗

PubMed2003

Phosphorylation of Kruppel-like factor 5 (KLF5/IKLF) at the CBP interaction region enhances its transactivation function.

The Kruppel-like factor 5 (KLF5/IKLF) belongs to the Kruppel family of genes which bind GC-rich DNA elements and activate or repress their target genes in a promoter context and/or cellular environment-dependent manner. In the present study, we used the Gal4 fusion assay system to characterize the mechanism of transactivation by KLF5. We demonstrated that the transactivation function of KLF5 was enhanced by CREB-binding protein (CBP) and blocked by wild-type but not mutant E1A. Over expression of CBP reversed the inhibition effect of E1A. With various lengths of KLF5 fusion protein, the transactivation functions were localized to 156 amino acid residues at the N-terminal region and 133 amino acid residues adjacent to the Zn finger motif. We mapped the CBP and KLF5 interaction domain to the N-terminal region of CBP (amino acids 1-232) and the N-terminal region of KLF5 (amino acids 1-238) where one of the activation functions resides. The histone acetyltransferase (HAT) activity of CBP does not play a role in the transactivation function of KLF5 nor does it acetylate KLF5 in vitro. However, phosphorylation is important in KLF5 transactivation activity. Inhibition of protein kinase activity by H7 or calphostin C blocked both full-length and N-terminal fragment (amino acids 1-238) KLF5 activities. Mutation at a potential protein kinase C phosphorylation site within the CBP interaction domain of KLF5 reduces its transactivation function. Furthermore, using the GST pull-down approach, we showed that phosphorylation of KLF5 enhances its interaction with CBP. The results of the present study provide a mechanism for KLF5 transactivation function.

Acetylation↗

PubMed2003

An intronic alternative promoter of the human lactoferrin gene is activated by Ets.

Lactoferrin expresses in a variety of tissues and involves in various aspects of host defense mechanisms. The lactoferrin gene is differentially regulated through multiple signaling pathways. Recently, an alternative form of human lactoferrin mRNA (Delta LF) was found in normal human tissues but absent from the tumor cells. In this study, we identified the transcription start sites of the Delta LF in mammary gland and bone marrow and demonstrated that the Delta LF is the product of an alternative (P2) promoter present in the first intron of the lactoferrin gene. The P2 promoter has high activity in Jurkat and U937 and low activity in RL95-2 and HEC-1B cell lines. Nonetheless, the promoter activity in HEC-1B cells was dramatically enhanced with overexpression of the Ets-1 transcription factor. The GFP-tagged lactoferrin is present in the cytoplasm whereas GFP-tagged Delta LF is found in both nucleus and cytoplasm as examined by fluorescence and confocal microscopy.

Cell Line↗

PubMed2002

CTLA4 dimorphisms and the multiple sclerosis phenotype.

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), expressed on activated T cells, binds to B7 molecules on antigen-presenting cells. Signaling via CTLA-4 results in downregulation of ongoing T-cell clonal expansion. A single-nucleotide polymorphism (SNP) in exon 1 of CTLA4 is associated with susceptibility to several autoimmune diseases, including multiple sclerosis (MS). In this two-stage study, we investigated whether haplotypes composed of exon 1-SNP alleles and alleles of a promoter-region SNP influence age at onset, disease severity and disease course in MS. In stage 1, deviations in CTLA4 haplotype frequencies were observed in patients subgrouped by course; in stage 2, none of these original associations were confirmed.

Abatacept↗