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Jian Zhang

Publications and source records attributed to Jian Zhang.

At least 91 records · Page 5Linked to original sources
PubMed2006

Inhibition of interleukin-6 with CNTO328, an anti-interleukin-6 monoclonal antibody, inhibits conversion of androgen-dependent prostate cancer to an androgen-independent phenotype in orchiectomized mice.

Initially, prostate cancer is androgen dependent. However, most cases progress to an androgen-independent state through unknown mechanisms. Interleukin-6 (IL-6) has been associated with prostate cancer progression including activation of the androgen receptor (AR). To determine if IL-6 plays a role in the conversion of prostate cancer from androgen dependent to androgen independent, we established androgen-dependent LuCaP 35 human prostate cancer xenografts in nude mice, castrated the mice, and blocked IL-6 activity using a neutralizing antibody (CNT0328) for a period of 18 weeks. IL-6 inhibition increased survival of mice and inhibited tumor growth, as reflected by decreased tumor volume and prostate-specific antigen levels, compared with that in mice receiving isotype control antibody. To test the effect of IL-6 inhibition on the conversion from androgen dependent to androgen independent, tumor cells from the treated mice were assessed for their androgen dependence both in vitro and by implanting them into sham-operated or orchiectomized mice. Tumor cells derived from the isotype-treated animals converted to androgen-independent state, whereas tumor cells from the anti-IL-6 antibody-treated mice were still androgen dependent in vitro and in vivo. Although there was no difference in AR levels between the androgen-independent and androgen-dependent tumors, IL-6 inhibition promoted both apoptosis and inhibited cell proliferation in tumors and blocked the orchiectomy-induced expression of histone acetylases, p300 and CBP, which are AR cofactors. These data show that IL-6 contributes to the development of androgen independence in prostate cancer and suggest that it mediates this effect, in part, through modulation of p300 and CBP.

Animals↗
PubMed2006

Neuraminidase pharmacophore model derived from diverse classes of inhibitors.

A three-dimensional pharmacophore model was developed based on 22 currently available inhibitors, which were carefully selected with great diversity in both molecular structure and bioactivity, for discovering new potent neuraminidase (NA) inhibitors to fight against avian influenza virus. The best hypothesis (Hypo1), consisting of five features, namely, one positive ionizable group, one negative ionizable group, one hydrophobic point, and two hydrogen-bond donors, has a correlation coefficient of 0.902, a root mean square deviation of 1.392, and a cost difference of 72.88, suggesting that a highly predictive pharmacophore model was successfully obtained. The application of the model shows great success in predicting the activities of 88 known NA inhibitors in our test set with a correlation coefficient of 0.818 with a cross-validation of 98% confidence level. Accordingly, our model should be reliable in identifying structurally diverse compounds with desired biological activity.

Enzyme Inhibitors↗
PubMed2006

Expression analysis of the NDRG2 gene in mouse embryonic and adult tissues.

N-myc downstream-regulated gene 2 (NDRG2) is believed to be involved in cell growth events. However, its exact function is still unknown. To elucidate the role of this gene, we used an anti-Ndrg2 monoclonal antibody in immunohistochemistry and immunofluorescence assays to analyze the expression pattern of Ndrg2 protein in mouse embryos at various gestational ages and in a variety of adult mouse tissues. Ndrg2 immunoreactivity was generally localized to the cytoplasm. During mouse development, Ndrg2 expression was observed in many developing tissues and organs including the heart, brain, lung, gut, liver, kidney, skeletal muscle, cartilage, chorion, epidermis, and whisker follicles. Ndrg2 expression was developmentally dynamic, being generally lower in the early stages of development and markedly increasing during later stages. Ndrg2 expression was also observed in a variety of adult mouse tissues, particularly in the heart and brain. This is the first demonstration of Ndrg2 protein expression in both embryonic and adult mouse tissues. Our results suggest that NDRG2 plays important roles in histogenesis and organogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Sterilizing Bacillus pumilus spores using supercritical carbon dioxide.

Supercritical carbon dioxide (SC CO(2)) has been evaluated as a new sterilization technology. Results are presented on killing of B. pumilus spores using SC CO(2) containing trace levels of additives. Complete killing was achieved with 200 part per million (ppm) hydrogen peroxide in SC CO(2) at 60 degrees C, 27.5 MPa. Addition of water to SC CO(2) resulted in greater than three-log killing, but this is insufficient to claim sterilization. Neither ethanol nor isopropanol when added to SC CO(2) affected killing.

2-Propanol↗
PubMed2006

Acquired tolerance in cadmium-adapted lung epithelial cells: roles of the c-Jun N-terminal kinase signaling pathway and basal level of metallothionein.

Cadmium-resistant cells were developed in our laboratory with rat lung epithelial cells (LECs) by stepwise exposure of LECs to cadmium chloride from 1 microM to 20 microM after 20 passages. To investigate the Cd-resistant phenotype in a long-term perspective, cadmium-resistant cells adapted to 20 microM cadmium (Cd(R)) were then cultured in the absence of cadmium for various passages [Cd(R)(-n)]. All these adapted cells were significantly protected from cadmium toxicity as compared to parental cadmium-sensitive LECs (Cd(S)). The cadmium-resistant phenotype of adapted cells was relatively stable in the absence of cadmium for as long as 40 passages. Basal mRNA level of metallothionein-1 (MT-1) was dramatically higher in Cd(R) than in Cd(R)(-), which may account for the higher Cd-resistance of Cd(R) than Cd(R)(-). MT-1 mRNA level decreased drastically in Cd(R) after cadmium removal, suggesting that the high basal level of MT-1 in Cd(R) may be only partially responsible for cadmium-resistance. Treatment of cells with high levels of cadmium resulted in decreased phosphorylation of c-Jun N-terminal kinase (JNK1/2) in adapted cells than in sensitive cells and this cadmium-induced JNK activity was blocked by JNK inhibitor II, SP600125. Ro318220, a strong activator of JNK, reverted cadmium-sensitive phenotype in adapted cells. Taken together, our results suggest that during cadmium adaptation, cells develop tolerance to cell death, generally due to perturbation of the JNK signaling pathway and the nonresponsiveness of JNK phosphorylation is critical for the Cd-tolerance in these cells.

Adaptation, Physiological↗
PubMed2006

High-affinity glutamate transporter GLAST/EAAT1 regulates cell surface expression of glutamine/neutral amino acid transporter ASCT2 in human fetal astrocytes.

Neutral amino acid transporter ASCT2, together with high-affinity glutamate transporters, belongs to the SLC1 gene family of Na(+)-dependent solute carriers and is one of the major transporters of glutamine in cultured astrocytes. Besides glutamine and other high-affinity substrates--alanine, serine, cysteine or threonine, ASCT2 can also translocate protonated glutamate. The present study elucidated substrate-dependent trafficking of ASCT2 in differentiated primary cultures of human fetal astrocytes. The differentiation induced by 8-bromo-cAMP caused dramatic up-regulation of two co-localized and functionally linked astroglial proteins--glutamate transporter GLAST, that is the only high-affinity router of glutamate into cultured astrocytes, and glutamine synthetase (GS), a cytosolic enzyme that converts at least a part of the arriving glutamate into glutamine. In order to distinguish individual intracellular effects of these two substrates on ASCT2, in some cultures glutamine synthetase was effectively knocked down using siRNA silencing technique. In control conditions, regardless of GS levels, almost the entire ASCT2 immunoreactivity was restricted to the cytosol. Both glutamine and alanine, though to different extents, induced partial redistribution of ASCT2 from the cytosolic compartment to the plasma membrane. However, in cultures with high GS expression, micromolar concentrations of glutamate exhibited more pronounced effect on ASCT2 trafficking than the preferred substrates of this carrier. In contrast, glutamate had no effect on ASCT2 distribution in cultures devoid of GS. D-Aspartate, a metabolically inert substrate effectively transported by GLAST, had no effect in any cell culture utilized. It seems that intracellular glutamine produced by GS from glutamate that, in turn, is supplied by GLAST, is a more potent inducer of ASCT2 trafficking to the cell surface than the ASCT2-mediated translocation of extracellular substrates. At lower pH values (6.2-6.7), the cell surface pool of ASCT2 was significantly larger than at physiological pH. In addition, high concentrations of glutamate, independently from GLAST or glutamate receptor activation, induced further arrival of ASCT2 to the plasma membrane. The pH-dependent functional activation of ASCT2 and the ASCT2-mediated glutamate uptake may play important roles during ischemic acidosis or synaptic activity-induced local acidification.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2006

Gene expression profiling of ovarian tissues for determination of molecular pathways reflective of tumorigenesis.

Ovarian cancer is the fourth leading cause of gynecological cancer death among women in the United States. Early detection is a critical prerequisite to initiating effective cancer therapy. Gene microarray technology and proteomics have provided much of the biomarkers with potential use for diagnosis. However, more research is needed to fully understand disease onset and progression. To this end, we have performed microarray analysis with the goal of identifying molecular interaction networks defining tumor growth. Microarray analysis was performed on a limited set of ovarian tissues with various pathological diagnoses using Human Genome Focus Array (HGFA) for the detection of approximately 8500 human transcripts. Hierarchical clustering identified groups of ovarian tissues reflective of low malignant potential/early cancer onset and possible pre-cancerous stages involving small molecule, cytokine and/or hormone-dependent feed-back responses specific to the pelvic reproductive system and a priori initiated tumor suppression mechanisms. ANOVA followed by post hoc Scheffe confirmed our hypotheses. Moreover, we established a protein/protein interaction database associated with HGFA probe sets. This database was used to build and visualize molecular networks integrating small but significant changes in gene expression. In conclusion, we were able for the first time to delineate an intersecting genetic pattern linking ovarian tissues reflective of low potential malignancy/early cancer onset stages via long distance signaling between tissues of gynecological origin.

Case-Control Studies↗
PubMed2006

A model for DNA detection by metal-enhanced fluorescence from immobilized silver nanoparticles on solid substrate.

N-(2-Mercaptopropionyl)glycine (tiopronin)-coated silver nanoparticles (average diameter of metal core=5 nm) were prepared by a modified Brust method. Tiopronin ligands were partially displaced by thiolate single-stranded oligonucleotides via ligand exchange. These particles were immobilized onto a solid substrate through hybridization with target oligonucleotides in a layer-by-layer approach. The dye-labeled complementary oligonucleotides were bound to the particle layers through hybridization. Fluorescence intensity was enhanced with a simultaneous increase of plasmon absorbance from accumulated particles. A steady state was shown at the 10th particle layer and then the fluorescence enhancement showed a plateau. This result reveals that increasing the particle layer contributes to fluorescence enhancement. This novel method was used to detect DNA hybridization through both absorbance and emission spectral changes.

DNA↗
PubMed2006

Gene conversion is a frequent mechanism of inactivation of the wild-type allele in cancers from MLH1/MSH2 deletion carriers.

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited cancer predisposition syndrome caused by germ line mutations in DNA mismatch repair genes, predominantly MLH1 and MSH2, with large genomic rearrangements accounting for 5% to 20% of all mutations. Although crucial to the understanding of cancer initiation, little is known about the second, somatic hit in HNPCC tumorigenesis, commonly referred to as loss of heterozygosity. Here, we applied a recently developed method, multiplex ligation-dependent probe amplification, to study MLH1/MSH2 copy number changes in 16 unrelated Swiss HNPCC patients, whose cancers displayed microsatellite instability and loss of MLH1 or MSH2 expression, but in whom no germ line mutation could be detected by conventional screening. The aims of the study were (a) to determine the proportion of large genomic rearrangements among Swiss MLH1/MSH2 mutation carriers and (b) to investigate the frequency and nature of loss of heterozygosity as a second, somatic event, in tumors from MLH1/MSH2 germ line deletion carriers. Large genomic deletions were found to account for 4.3% and 10.7% of MLH1 and MSH2 mutations, respectively. Multiplex ligation-dependent probe amplification analysis of 18 cancer specimens from two independent sets of Swiss and Finnish MLH1/MSH2 deletion carriers revealed that somatic mutations identical to the ones in the germ line occur frequently in colorectal cancers (6 of 11; 55%) and are also present in extracolonic HNPCC-associated tumors. Chromosome-specific marker analysis implies that loss of the wild-type allele predominantly occurs through locus-restricted recombinational events, i.e., gene conversion, rather than mitotic recombination or deletion of the respective gene locus. (Cancer Res 2006; (66)2: 659-64).

Adaptor Proteins, Signal Transducing↗
PubMed2006

[Challenges in management of cerebral ischemia due to Takayasu's arteritis].

OBJECTIVE: To explore the management of cerebral ischemia caused by Takayasu's arteritis. METHODS: One hundred and three cases treated from 1984 to 2003 were reviewed including 92 females. Seven cases underwent ascending aorta to bilateral internal carotid artery (ICA) bypass, 38 cases to the axillary artery with graft to single ICA bypass. Six cases underwent ascending aorta to axillary bypass with 3 graft to single ICA bypasses as the second stage surgery. Three cases underwent ascending aorta to right ICA bypass with 2 graft to left ICA bypasses as well as 6 subclavian to carotid bypass, PTA in 5 and stenting in 3 cases, etc. RESULTS: Twenty-seven patients with less clinical severity received conservative therapy, 9 of them had mostly temporarily improvement, 15 had slight improvement or basically no change, 1 had hemiplegia and 2 died of stroke and myocardial infarction respectively. Surgically, the short-term effective rate was 87% and operative death 7.8%. Fifty-five patients were followed up, a mean follow-up time was 48 months, and the follow-up rate was 80.9%. The excellently, good, fair, no change and death rate were 36.4%, 38.2%, 20.0%, 3.6% and 1.8% respectively. All patients with PTA or stent had an immediate good response and all recurred within 3 to 5 months. CONCLUSIONS: For treating severe cerebral ischemia caused by Takayasu's arteritis, the ascending aorta to axillary and single ICA reconstruction or the ascending aorta-bilateral axillary bypass for patients with subclavian steal syndrome is advocated; second stage operation from graft to contralateral ICA can be carried out if necessary.

Adolescent↗
PubMed2006

A de novo MLH1 germ line mutation in a 31-year-old colorectal cancer patient.

Hereditary nonpolyposis colorectal cancer is an autosomal dominant cancer predisposition syndrome caused by inherited germ line mutations in DNA mismatch repair genes, predominantly MSH2 and MLH1. Here we report the first proven de novo germ line mutation in MLH1 (c.666dupA) identified in a 31-year-old colorectal cancer patient with the alteration being present in a heterozygous state in all three germ layers and homozygously in his colon cancer. The mutation was absent in both biological parents and all sibs available. Despite extensive polymorphic marker analysis, the parental origin of c.666dupA could not be conclusively determined, representing either a single mutational event in a parental germ cell or (maternal) gonadal mosaicism. Although rare, consequential application of the Bethesda guidelines for genetic testing should allow the clinician to readily identify colorectal cancer patients below age 50 years who carry de novo mismatch repair gene mutations.

Adaptor Proteins, Signal Transducing↗
PubMed2006

DNA degradation in nuclei of muscle cells followed by ischemic injury in a rabbit amputation model.

This study evaluated DNA degradation in nuclei of muscle cells during ischemia in a rabbit limb amputation model. Seven New Zealand rabbits were used. The left rear limb of the animal was amputated. The quadriceps femoris muscle was biopsied, as well as the rabbit carotid arteries. Half of the tissue samples were preserved at a cold temperature (2-4 degrees C), and the other half were kept at room temperature (25 degrees C, global ischemia). Immediately and 4, 8, 12, 16, and 24 h after amputation, muscle tissue samples were stained with the Feulgen reaction and analyzed by an image-analysis system to detect DNA contents in muscle cell nuclei. Samples from carotid arteries were examined with a transmission electron microscope. The results showed that the DNA content in muscle cell nuclei was slightly decreased at 4 and 8 h of global ischemia. At 12 h after global ischemia, the DNA content was found to be significantly decreased (80.03% of baseline). The DNA content dropped to 53.93% of baseline at 16 h of global ischemia. However, in the muscle that was preserved at cold temperature, the DNA contents were only slightly changed along with the ischemia time at 24 h. The DNA changes were confirmed by transmission electron microscopic observations. The present findings could provide evidence for the study of revascularization of ischemic muscle.

Amputation, Surgical↗
PubMed2006

Proteome analysis of combined effects of androgen and estrogen on the mouse mammary gland.

We and other investigators have previously shown that estrogen and androgen have synergistic effects on the growth of mammary epithelial ducts and alveoli in the Noble mouse. However, the molecular mechanisms behind the synergy are unknown. In the present study, we treated female FVB mice with 17-estrodial (E2) and 5-dihydrotestosterone-bezonate (DHT-B) using slow-releasing hormone pellets for 7 months. Dissection showed that hormone treatment caused atypical hyperplasia of mammary ducts and alveoli. A functional proteomic approach was used to study the holistic protein changes in mammary glands. 2-DE was used to separate proteins. Twenty-five protein spots that were differentially expressed in hormone-treated tissues compared to the control were identified by MALDI-TOF-MS, and ESI-quadrupole-TOF-MS, which include some proteins that are correlative with response to estrogen and androgen stimulation, cells differentiation and growth, signal transduction, metabolism, etc. Real-time RT-PCR was carried out to verify the different expression. These results offered some clues to understand the function of E2 and DHT-B.

Androgens↗
PubMed2006

In search of the Chinese self: an fMRI study.

Cultural influences on the concept of self is a very important topic for social cognitive neuroscientific exploration, as yet, little if anything is known about this topic at the neural level. The present study investigates this problem by looking at the Chinese culture's influence on the concept of self, in which the self includes mother. In Western cultures, self-referential processing leads to a memory performance advantage over other forms of semantic processing including mother-referential, other-referential and general semantic processing, and an advantage that is potentially localizable to the medial prefrontal cortex (MPFC). In Chinese culture, however, the behavioral study showed that mother-referential processing was comparable with self-referential processing in both memory performance and autonoetic awareness. The present study attempts to address whether similar neural correlates (e.g. MPFC) are acting to facilitate both types of referencing. Participants judged trait adjectives under three reference conditions of self, other and semantic processing in Experiment I, and a mother-reference condition replaced the other-reference condition in Experiment II. The results showed that when compared to other, self-referential processing yielded activations of MPFC and cingulate areas. However, when compared to mother, the activation of MPFC disappeared in self-referential processing, which suggests that mother and self may have a common brain region in the MPFC and that the Chinese idea of self includes mother.

Awareness↗
PubMed2006

Comparative studies on histological and ultra-structure of the pituitary of different ploidy level fishes.

The histological and ultra-structure of the pituitary in diploid red crucian carp (Carassius auratus red var.), triploid crucian carp and allotetraploid hybrids within and after the breeding season were comparatively studied. The result showed that there were six endocrine cell types in the pituitary of these three kinds of fishes, and there was an obvious difference in cell size among different ploidy level fishes. As for the same type of pituitary cells, the cell size was increased gradually with the increasing ploidy level. In the breeding season, the allotetraploid hybrids had higher proportion of gonadotropin cells (GTH) than triploids, and the triploids had higher proportion of GTH than diploids. The results were related to the earlier sexual maturity of allotetraploid hybrids and sterility of triploid crucian carp. On the other hand, among the three kinds of fishes, the proportion of somatotropin (STH) cells in triploids crucian carp was the highest, whereas that in allotetraploid hybrids was the lowest. The results might be connected with the faster growth rate of triploids and slower growth rate of allotetraploid hybrids. In addition, in GTH cells of meso-adenohypophysis after the breeding season, there were many endocrine particles in triploids, while those endocrine particles were released from the cells in allotetraploids and diploids. This result showed that the sterility of triploid crucian carp might be related to the hormone which was not released from the GTH cells. In a word, the present study indicated that the differences in the structure of pituitary among different ploidy level fishes contributed to their difference in the growth rate and gonadal development.

Animals↗
PubMed2006

Cytomegalovirus infection of trophoblast cells elicits an inflammatory response: a possible mechanism of placental dysfunction.

OBJECTIVE: We sought to determine whether cytomegalovirus infection of extravillous trophoblast cells induces inflammatory changes that lead to cell death. STUDY DESIGN: Extravillous trophoblast (HTR-8/SVneo) cells were infected with cytomegalovirus. Cell death assays were performed 8 to 48 hours after infection. The expression and secretion of cytokines (interleukin-6 and -8) preceding cell death was measured by polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Cell viability (lactate dehydrogenase assay) was reduced approximately 20%, and rates of apoptosis (measured by TdT-mediated dUTP-X nick end labeling [TUNEL] assay) were increased approximately 40% at 16 to 48 hours after infection. Significantly elevated levels of caspase-3 mRNA levels were observed before increased cell death. Interleukin-6 and -8 mRNA expression and protein secretion were up-regulated 8 to 16 hours after cytomegalovirus infection. CONCLUSION: Placental exposure to cytomegalovirus induces an inflammatory response that precedes invasive trophoblast cell death. Cytomegalovirus may prevent normal placental invasion, which results in adverse reproductive outcomes that are associated with placental dysfunction.

Apoptosis↗
PubMed2006

Characterization of a specific arabinosyltransferase activity involved in mycobacterial arabinan biosynthesis.

Mycobacterium smegmatis strains that contain inactivated EmbA or EmbB proteins are unable to synthesize terminal Arabeta1-->2Araalpha1-->5(Arabeta1-->2Araalpha1-->3)Araalpha1-->5Araalpha1-->(Ara(6)) motif in the cell wall polysaccharide arabinogalactan. Instead, the mutants contain a linear Arabeta1-->2Araalpha1-->5Araalpha1-->5Araalpha1-->(Ara(4)) motif, suggesting that these proteins are involved in the synthesis or transfer of the disaccharide Arabeta1-->2Araalpha1--> to an internal 5-linked Ara. Therefore, we synthesized a linear Arabeta1-->2Araalpha1-->5Araalpha1-->5Araalpha1-->5Araalpha1--> with an octyl aglycon as an arabinosyl acceptor in cell-free assays. A facile assay was developed using the chemically synthesized glycan, membrane, and particulate cell wall as the enzyme source, and 5-phosphoribose diphosphate pR[(14)C]pp as the arabinose donor. The results unequivocally show that two arabinofuranosyl residues were added at the tertiary -->5Araalpha1--> of the synthetic glycan. This activity was undetectable in strains of M. smegmatis where embB or embA had been genetically disrupted. Normal activity could be restored only in the presence of both EmbA and EmbB proteins.

Carbohydrate Sequence↗