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Y Cao

Publications and source records attributed to Y Cao.

At least 55 records · Page 3Linked to original sources
PubMed2001

Fatty acid CoA ligase 4 is up-regulated in colon adenocarcinoma.

Arachidonic acid metabolism plays an important role in colon carcinogenesis. Cyclooxygenase-2 (COX-2), which catalyzes the rate-limiting step in the synthesis of prostaglandins from arachidonic acids, is known to be up-regulated in colon cancer, and multiple lines of evidence indicate that it is a critical early step in colon carcinogenesis. Recently, 15-lipoxygenase-1, the enzyme that converts arachidonic acid to 15(S)-HETE, was also found to be up-regulated in colon carcinoma. In our previous studies, we cloned a gene that encodes another arachidonic acid-using enzyme, fatty acid CoA ligase 4 (FACL4), and showed that overexpression of this enzyme prevents apoptosis. We have also showed that FACL4 and COX-2 synergistically inhibit apoptosis by reducing the intracellular level of free arachidonic acid. Here, we report that expression of FACL4 is significantly increased in colon adenocarcinoma compared with adjacent normal tissue at both the mRNA and protein levels by quantitative RT-PCR (paired t test, P < 0.015), immunoblot, and immunohistochemical staining. We found that the increase in expression level of FACL4 mRNA relative to control ranged between 2.4- and 54.5-fold; the average fold-increase was 13.4. The increase in FACL4 protein expression is between 2.4- and 65.0-fold. In addition, we found that a higher level of increased FACL4 expression was correlated with well and moderately differentiated adenocarcinoma, whereas no similar correlation was observed with COX-2 expression. The in situ hybridization results indicate that expression of FACL4 is localized predominantly in the colon epithelium but not in the stroma. The onset of FACL4 up-regulation appears to occur during the transformation from adenoma to adenocarcinoma because FACL4 expression was not increased above normal in the three colon adenomas examined. Finally, we observed that a tumor promoter significantly induced FACL4 expression. These findings suggest that the FACL4 pathway may be important in colon carcinogenesis, and that the development of selective inhibitors for FACL4 may be a worthy effort in the prevention and treatment of colon cancer.

Adenocarcinoma↗
PubMed2001

Photoinduced conversion of silver nanospheres to nanoprisms.

A photoinduced method for converting large quantities of silver nanospheres into triangular nanoprisms is reported. The photo-process has been characterized by time-dependent ultraviolet-visible spectroscopy and transmission electron microscopy, allowing for the observation of several key intermediates in and characteristics of the conversion process. This light-driven process results in a colloid with distinctive optical properties that directly relate to the nanoprism shape of the particles. Theoretical calculations coupled with experimental observations allow for the assignment of the nanoprism plasmon bands and for the first identification of two distinct quadrupole plasmon resonances for a nanoparticle. Unlike the spherical particles they are derived from that Rayleigh light-scatter in the blue, these nanoprisms exhibit scattering in the red, which could be useful in developing multicolor diagnostic labels on the basis not only of nanoparticle composition and size but also of shape.

Anisotropy↗
PubMed2001

Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression.

Alteration of gene expression is a crucial component of adaptive responses to hypoxia. These responses are mediated by hypoxia-inducible transcription factors (HIFs). Here we describe an inhibitory PAS (Per/Arnt/Sim) domain protein, IPAS, which is a basic helix-loop-helix (bHLH)/PAS protein structurally related to HIFs. IPAS contains no endogenous transactivation function but demonstrates dominant negative regulation of HIF-mediated control of gene expression. Ectopic expression of IPAS in hepatoma cells selectively impairs induction of genes involved in adaptation to a hypoxic environment, notably the vascular endothelial growth factor (VEGF) gene, and results in retarded tumour growth and tumour vascular density in vivo. In mice, IPAS was predominantly expressed in Purkinje cells of the cerebellum and in corneal epithelium of the eye. Expression of IPAS in the cornea correlates with low levels of expression of the VEGF gene under hypoxic conditions. Application of an IPAS antisense oligonucleotide to the mouse cornea induced angiogenesis under normal oxygen conditions, and demonstrated hypoxia-dependent induction of VEGF gene expression in hypoxic corneal cells. These results indicate a previously unknown mechanism for negative regulation of angiogenesis and maintenance of an avascular phenotype.

Amino Acid Sequence↗
PubMed2001

Molecular cloning and characterization of a cDNA encoding soybean nodule IMP dehydrogenase.

Inosine monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting step in de novo purine biosynthesis and is a postulated key enzyme in nitrogen assimilation in ureide-exporting nodules. A 2016 bp cDNA for IMPDH, designated as IMPDH, was cloned from a soybean nodule cDNA library. IMPDH encodes a polypeptide of 502 amino acids with a predicted molecular weight of 53000 and a pI of 5.54. The deduced IMPDH is 70.5% identical to that in Arabidopsis, with a 100% homology in the putative active-site region. Expressing the cloned cDNA in Escherichia coli mutant strain KLC381 (DeltaguaB) restored IMPDH activity, permitting bacterial growth on minimal medium. Southern blot analysis suggested a single copy of IMPDH gene in the soybean genome. Northern blot analysis showed that the expression of IMPDH gene is apparently nodule-specific.

Amino Acid Sequence↗
PubMed2001

Alkyl exchange reactions of organocobalt porphyrins. A bimolecular homolytic substitution reaction.

Reaction of organocobalt(III) porphyrins with a cobalt(II) complex of a distinguishable porphyrin or tetrapyrrole resulted in the reversible exchange of the organic axial ligand. The exchange reaction was facile in such solvents as benzene, toluene, dichloromethane, chloroform, and pyridine; was unaffected by total exclusion of light; was faster than would be expected for a homolytic process given known Co-C bond dissociation energies; and was of broad scope with respect to the organic ligand. Methyl, benzyl, primary alkyl, secondary alkyl, and acyl groups exchanged, but phenyl groups did not. The position of the exchange equilibrium was independent of the direction of approach and was nonstatistical. The relaxation to equilibrium appeared to be consistent with that of a second-order process. The rate of the reaction varied with the identity of the R group in the order Bzl > or = Me > Et approximately n-Pr > i-Pr > i-Bu > acetyl approximately neopentyl approximately 2-adamantyl. However, the total variation in reaction rates was remarkably small. Attempts to find evidence of free-radical intermediates by trapping with TEMPO or CO or by alkyl group interchange with an excess of an alkyl halide of a distinct alkyl group were unsuccessful over a time scale comparable to multiple half-lives of the exchange reaction. In addition, no rearrangement products were detected in exchange reactions of the 5-hexenyl group. Use of cobalt porphyrin reactants that were sterically encumbered on both faces with groups large enough to prevent formation of a bridged, Co-C-Co structure resulted in a 5 or more order of magnitude decrease in the rate of methyl exchange, if not its outright cessation, when run with total exclusion of light. The decrease in the rate of the thermal exchange process revealed the existence a slow photochemical exchange process that was driven by room lights. All evidence was consistent with a bimolecular S(H)2 mechanism for the thermal exchange mechanism.

Cobalt↗
PubMed2001

[Clinical evaluation of frameless stereotaxy in minimally invasive neurosurgery].

OBJECTIVE: To evaluate the utility of frameless stereotaxy in minimally invasive neurosurgery. METHODS: A retrospective review of 200 cases of craniotomy and laminotomy procedures using frameless stereotaxy systems performed from December 1999 to June 2001 was made, including 43 cases of AVM, 39 cases of aneurysm, 30 of meningioma, 27 of cavenous malformation, 19 of glioma, 8 of neuronoma, 5 of pituitary tumor, 4 of angioreticuloma, 3 of metastatic tumor, 14 cases of craniotomy with other causes, and 8 spinal tumors. Data of MRI or CT, conducted one day before the operation, were entered into the neuronavigation systems and analyzed. A 3-D simulation of model of cranium or spinal cord was reestablished and operative approach was designed. During the operation, the lesion can be located accurately. RESULTS: The lesions and important anatomical structures were accurately located and the location errors of lesions were within the limit of 2 mm. Postoperative neurological complications occurred only in 10 cases (5.0%). No operative death occurred. CONCLUSION: The frameless stereotaxy is very helpful for brain and spinal surgery, especially for the cases with lesions located deep in the brain. Its accuracy of location is very important in protecting normal brain tissues. The neuronavigation systems are changing the pattern of traditional neurosurgical procedures and serve as the guarantee of minimally invasive neurosurgery.

Humans↗
PubMed2001

Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway.

In mammals, the canonical nuclear factor kappaB (NF-kappaB) signaling pathway activated in response to infections is based on degradation of IkappaB inhibitors. This pathway depends on the IkappaB kinase (IKK), which contains two catalytic subunits, IKKalpha and IKKbeta. IKKbeta is essential for inducible IkappaB phosphorylation and degradation, whereas IKKalpha is not. Here we show that IKKalpha is required for B cell maturation, formation of secondary lymphoid organs, increased expression of certain NF-kappaB target genes, and processing of the NF-kappaB2 (p100) precursor. IKKalpha preferentially phosphorylates NF-kappaB2, and this activity requires its phosphorylation by upstream kinases, one of which may be NF-kappaB-inducing kinase (NIK). IKKalpha is therefore a pivotal component of a second NF-kappaB activation pathway based on regulated NF-kappaB2 processing rather than IkappaB degradation.

Animals↗
PubMed2001

The metastasis-associated Mts1(S100A4) protein could act as an angiogenic factor.

The involvement of Mts1(S100A4), a small Ca(2+)-binding protein in tumor progression and metastasis had been demonstrated. However, the mechanism by which mts1(S100A4) promoted metastasis had not been identified. Here we demonstrated that Mts1(S100A4) had significant stimulatory effect on the angiogenesis. We detected high incidence of hemangiomas--benign tumors of vascular origin in aged transgenic mice ubiquitously expressing the mts1(S100A4) gene. Furthermore, the serum level of the Mts1(S100A4) protein increased with ageing. Tumors developed in Mts1-transgenic mice revealed an enhanced vascular density. We showed that an oligomeric, but not a dimeric form of the Mts1(S100A4) protein was capable of enhancing the endothelial cell motility in vitro and stimulate the corneal neovascularization in vivo. An oligomeric fraction of the protein was detected in the conditioned media as well as in human serum. The data obtained allowed us to conclude that mts1(S100A4) might induce tumor progression via stimulation of angiogenesis.

Angiogenesis Inducing Agents↗
PubMed2001

Vascular endothelial growth factor-B-deficient mice display an atrial conduction defect.

BACKGROUND: Vascular endothelial growth factors (VEGFs) and their receptors are essential regulators of vasculogenesis and angiogenesis in both embryos and adults. One of the factors with a still unknown physiological function is VEGF-B, which is expressed in many tissues, including the heart. METHODS AND RESULTS: Mice carrying a targeted deletion in the VEGF-B gene were developed. In VEGF-B(-/-) animals, no gross abnormalities were observed in organs that normally show high expression of VEGF-B, such as the heart, muscle, and kidney. Analysis of heart function by ECG showed that adult VEGF-B(-/-) mice have an atrial conduction abnormality characterized by a prolonged PQ interval. VEGF- or basic fibroblast growth factor-induced corneal angiogenesis was similar in normal and VEGF-B(-/-) mice. CONCLUSIONS: VEGF-B seems to be required for normal heart function in adult animals but is not required for proper development of the cardiovascular system either during development or for angiogenesis in adults.

Animals↗
PubMed2001

Metalloprotease-disintegrin ADAM 12 interacts with alpha-actinin-1.

ADAM 12, a member of the ADAM family of proteins (containing A Disintegrin And Metalloprotease domain), has been implicated in differentiation and fusion of myoblasts. While the extracellular domain of ADAM 12 contains an active metalloprotease and a region involved in cell adhesion, the function of the cytoplasmic tail of ADAM 12 has been less clear. Here we show that the cytoplasmic domain of ADAM 12 interacts in vitro and in vivo with alpha-actinin-1, an actin-binding and cross-linking protein. Green fluorescent protein fused to ADAM 12 cytoplasmic domain co-localizes with alpha-actinin-1-containing actin stress fibres in C2C12 cells. The interaction between ADAM 12 and alpha-actinin-1 is direct and involves the 58-amino acid C-terminal fragment of ADAM 12 and the 27 kDa N-terminal domain of alpha-actinin-1. Consistently, expression of the 27 kDa fragment of alpha-actinin-1 in C2C12 cells using a mitochondrial targeting system results in recruitment of the co-expressed ADAM 12 cytoplasmic domain to the mitochondrial surface. Moreover, alpha-actinin-1 co-purifies with a transmembrane, His6-tagged form of ADAM 12 expressed in C2C12 myoblasts, indicating that the transmembrane ADAM 12 forms a complex with alpha-actinin-1 in vivo. These results indicate that the actin cytoskeleton may play a critical role in ADAM 12-mediated cell-cell adhesion or cell signalling during myoblast differentiation and fusion.

ADAM Proteins↗
PubMed2001

Effects of angiostatin gene transfer on functional properties and in vivo growth of Kaposi's sarcoma cells.

Gene transfer delivery of endogenous angiogenesis inhibitors such as angiostatin would circumvent problems associated with long-term administration of proteins. Kaposi's sarcoma (KS), a highly vascular neoplasm, is an excellent model for studying tumor angiogenesis and antiangiogenic agent efficacy. We investigated the effects of angiostatin gene transfer in in vitro and in vivo models of KS-induced neovascularization and tumor growth. A eukaryotic expression plasmid and a Moloney leukemia virus-based retroviral vector for expression of murine angiostatin were generated harboring the angiostatin cDNA with cleavable leader signals under the control of either the strong cytomegalovirus promoter/enhancer or the Moloney leukemia virus long terminal repeat. Angiostatin secretion was confirmed by radioimmunoprecipitation and Western blot analysis. Supernatants of angiostatin-transfected cells inhibited endothelial cell migration in vitro. Stable gene transfer of the angiostatin cDNA by retroviral vectors in KS-IMM cells resulted in sustained angiostatin expression and delayed tumor growth in nude mice, which was associated with reduced vascularization. These findings suggest that gene therapy with angiostatin might be useful for treatment of KS and possibly other highly angiogenic tumors.

Angiostatins↗
PubMed2001

A constitutively active pituitary adenylate cyclase activating polypeptide (PACAP) type I receptor shows enhanced photoaffinity labeling of its highly glycosylated form.

In the present study, we have analyzed a previously identified constitutively active pituitary adenylate cyclase activating polypeptide (PACAP) type I (PAC1) receptor with a deletion of the single amino acid residue Glu(261) (Y.-J. Cao, G. Gimpl, F. Fahrenholz, A mutation of second intracellular loop of pituitary adenylate cyclase activating polypeptide type I receptor confers constitutive receptor activation, FEBS Lett. 469 (2000)). This glutamic acid residue is highly conserved within the second intracellular loop of class II G protein-coupled receptors and may thus be of importance for many members of this receptor class. To explore the molecular characteristics of this mutant receptor, we performed photoaffinity labeling using previously defined photoreactive PACAP analogues. In COS cells, the PAC1 receptor was expressed in two differently glycosylated forms: a M(r) 75,000 and a M(r) 55,000 form. According to partial deglycosylation, at least three carbohydrate chains may exist in the rat PAC1 receptor expressed in COS cells. The constitutively active PAC1 receptor was expressed at the surface of COS-7 cells at the same density as the wild-type receptor. With respect to the different photoreactive PACAP analogues, the labeling specificity was the same for the wild-type versus mutant receptor: (125)I-[Lys(15)(pBz(2))]-PACAP-27 and (125)I-[Bpa(22)]-PACAP-27 were efficiently incorporated into each of the receptors, whereas (125)I-[Bpa(6)]-PACAP-27 labeled each of the receptors only to a negligible extent. This suggests that both receptors have the same or at least a very similar hormone binding site which is in close contact to Tyr(22) and Lys(15) located in the carboxy-terminal alpha-helical region of the PACAP-27 molecule. However, in comparison with the wild-type PAC1 receptor, the constitutively active receptor showed a markedly (approx. 6--8-fold) enhanced photoaffinity labeling efficiency in particular of the high glycosylated form. The enzymatically deglycosylated rat PAC1 receptor was efficiently labeled by photoreactive PACAP analogues. In contrast, nonglycosylated PAC1 receptors produced by tunicamycin treatment of the transfected COS-7 cells showed a 30-fold lower affinity for PACAP-27 and were capable of signal transduction with 30--50-fold lower potency as compared with the glycosylated PAC1 receptors.

Adenylyl Cyclases↗
PubMed2001

Genome-wide gene expression profiles of the developing mouse hippocampus.

We have analyzed the developmental molecular programs of the mouse hippocampus, a cortical structure critical for learning and memory, by means of large-scale DNA microarray techniques. Of 11,000 genes and expressed sequence tags examined, 1,926 showed dynamic changes during hippocampal development from embryonic day 16 to postnatal day 30. Gene-cluster analysis was used to group these genes into 16 distinct clusters with striking patterns that appear to correlate with major developmental hallmarks and cellular events. These include genes involved in neuronal proliferation, differentiation, and synapse formation. A complete list of the transcriptional changes has been compiled into a comprehensive gene profile database (http://BrainGenomics.Princeton.edu), which should prove valuable in advancing our understanding of the molecular and genetic programs underlying both the development and the functions of the mammalian brain.

Animals↗
PubMed2001

A comprehensive review of CT-based dosimetry parameters and biochemical control in patients treated with permanent prostate brachytherapy.

PURPOSE: The American Brachytherapy Society recommends that postprostate implant dosimetry be performed on all patients undergoing transperineal interstitial permanent prostate brachytherapy (TIPPB) utilizing CT scan clinical target volume reconstructions. This study was undertaken to assess the recommended dosimetry parameters from a large cohort of patients undergoing TIPPB that would predict for PSA relapse-free survival (PSA-RFS). METHODS AND MATERIALS: Seven hundred nineteen consecutive patients with clinical stage T1/T2 adenocarcinoma of the prostate underwent TIPPB using either I-125 or Pd-103. Postimplant dosimetry was performed at 2 to 3 weeks with CT scan 3-dimensional reconstructions obtained on all patients. The D90 and D100 doses (defined as the minimum dose covering 90% and 100% of the prostate volume, respectively) and the V100 (defined as the percent of the prostate receiving 100% of the prescribed dose) were obtained for each patient. Regression analysis was performed on the D90 dose, D100 dose, and V100 to test for cutoff points that would predict for PSA-RFS, defined by a modification of the American Society for Therapeutic Radiology and Oncology consensus panel statement. A cutoff value was found and was subjected to subset analysis to assess for its robustness. Treatment-related factors were tested for their ability to achieve dosimetry at or above the cutoff dose. RESULTS: The median follow-up from this cohort is 30 months (7-71 months) with a 48-month PSA-RFS of 89.5%. A D90 dose-response cutoff value > or =90% of the prescribed dose was identified. Prostate implants with a D90 dose <90% of the prescribed dose had an 80.4% 4-year PSA-RFS, while those with a D90 dose > or =90% of the prescribed dose had a 92.4% 4-year PSA-RFS (p = 0.001). No cutoff value was found for the V100 and D100 dose that predicted for PSA-RFS. Using the cutoff value, the D90 dose at 90% of the prescribed dose, a difference in 4-year PSA-RFS survival was identified for patients treated with I-125 (p = 0.04), Pd-103 (p = 0.01), TIPPB as monotherapy (p = 0.001), the addition of hormone therapy (p = 0.005), and TIPPB without hormone therapy (p = 0.001). The D90 dose was not significant for the group of patients treated with external beam radiotherapy and TIPPB (p = 0.15). The only significant finding from Cox regression analysis to predict for a poor D90 dose (<90% of the prescribed dose) was a CT/TRUS volume ratio >1.5 (p = 0.02). CONCLUSIONS: The American Brachytherapy Society recommends that postimplant CT-based dosimetry be performed for all patients treated with TIPPB. This prospective study identified that the D90 dose > or =90% of the prescribed dose can be used as a factor for predicting PSA-RFS in patients treated with brachytherapy. A dose-response using the D90 dose was observed for several typical clinical treatment variations used in the practice of TIPPB. Using the D90 dose appears to be a satisfactory parameter for predicting outcome in patients treated with TIPPB.

Adenocarcinoma↗
PubMed2001

Retroposon analysis of major cetacean lineages: the monophyly of toothed whales and the paraphyly of river dolphins.

SINE (short interspersed element) insertion analysis elucidates contentious aspects in the phylogeny of toothed whales and dolphins (Odontoceti), especially river dolphins. Here, we characterize 25 informative SINEs inserted into unique genomic loci during evolution of odontocetes to construct a cladogram, and determine a total of 2.8 kb per taxon of the flanking sequences of these SINE loci to estimate divergence times among lineages. We demonstrate that: (i) Odontocetes are monophyletic; (ii) Ganges River dolphins, beaked whales, and ocean dolphins diverged (in this order) after sperm whales; (iii) three other river dolphin taxa, namely the Amazon, La Plata, and Yangtze river dolphins, form a monophyletic group with Yangtze River dolphins being the most basal; and (iv) the rapid radiation of extant cetacean lineages occurred some 28-33 million years B.P., in strong accord with the fossil record. The combination of SINE and flanking sequence analysis suggests a topology and set of divergence times for odontocete relationships, offering alternative explanations for several long-standing problems in cetacean evolution.

Animals↗
PubMed2001

Imaging and spectroscopy of artificial-atom states in core/shell nanocrystal quantum dots.

Current imaging scanning tunneling microscopy is used to observe the electronic wave functions in InAs/ZnSe core/shell nanocrystals. Images taken at a bias corresponding to the s conduction band state show that it is localized in the central core region, while images at higher bias probing the p state reveal that it extends to the shell. This is supported by optical and tunneling spectroscopy data demonstrating that the s-p gap closes upon shell growth. Shapes of the current images resemble atomlike envelope wave functions of the quantum dot calculated within a particle in a box model.

Journal Article↗