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C L Wu

Publications and source records attributed to C L Wu.

At least 19 recordsLinked to original sources

Alpha-methylacyl-CoA racemase: a multi-institutional study of a new prostate cancer marker.

AIM: To test whether alpha-methylacyl-CoA racemase (AMACR) is a sensitive and specific marker of prostate cancer. METHODS AND RESULTS: The expression levels of AMACR mRNA were measured by real-time polymerase chain reaction. A total of 807 prostatic specimens were further examined by immunohistochemistry specific for AMACR. Quantitative immunostaining analyses were carried out by using the ChromaVision Automated Cellular Imaging System and the Ariol SL-50 Imaging System, respectively. AMACR mRNA levels measured in prostatic adenocarcinoma were 55 times higher than those in benign prostate tissue. Of 454 cases of prostatic adenocarcinoma, 441 were positive for AMACR, while 254 of 277 cases of benign prostate were negative for AMACR. The sensitivity and specificity of AMACR immunodetection of prostatic adenocarcinomas were 97% and 92%, respectively. Both positive and negative predictive values were 95%. By automatic imaging analyses, the AMACR immunostaining intensity and percentage in prostatic adenocarcinomas were also significantly higher than those in benign prostatic tissue (105.9 versus 16.1 for intensity, 45.7% versus 0.02% and 35.03% versus 4.64% for percentage, respectively). CONCLUSIONS: We have demonstrated the promising features of AMACR as a biomarker for prostate cancer in this large series and the potential to develop automated quantitative diagnostic tests.

Adenocarcinoma↗

Loss of p16 expression is of prognostic significance in locally advanced prostate cancer: an analysis from the Radiation Therapy Oncology Group protocol 86-10.

PURPOSE: The retinoblastoma (RB) cell cycle regulatory pathway is known to be deregulated in virtually all known human tumors. The protein product of the RB gene, pRB, and its upstream regulator, p16, are among the most commonly affected members of this pathway. We investigated the prognostic significance of both pRB and p16 expression in locally advanced prostate cancers, from patients treated on the Radiation Therapy Oncology Group (RTOG) protocol 86-10. MATERIALS AND METHODS: Sixty-seven cases from RTOG 86-10 had immunohistochemically stained slides, judged interpretable for both p16 and pRB, available for analysis. Median follow-up was 8.9 years (range, 6.0 to 11.8 years) for surviving patients. Staining for each marker was then correlated with overall survival, local progression, distant metastasis, and disease-specific survival. RESULTS: Loss of p16 expression, as defined by expression was significantly associated with reduced overall survival (P =.039), disease-specific survival (P =.006), and higher risk of local progression (P =.0007) and distant metastasis (P =.026) in the univariate analysis. In the multivariate analysis, loss of p16 was significantly associated with reduced disease-specific survival (P =.0078) and increased risk of local failure (P =.0035) and distant metastasis (P =.026). A borderline association with reduced overall survival (P =.07) was also evident. Loss of pRB was associated with improved disease-specific survival on univariate (P =.028) and multivariate analysis (P =.043), but carried no other significant outcome associations. CONCLUSION: Loss of p16 is significantly associated with adverse clinical outcome in cases of locally advanced prostate cancer.

Adult↗

Involvement of cholecystokinin receptor in the inhibition of gastrointestinal motility by estradiol in ovariectomized rats.

BACKGROUND: The effects of estradiol benzoate (EB) on gastric emptying, gastrointestinal transit and plasma levels of cholecystokinin (CCK) were studied in ovariectomized rats. METHODS: Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na2 51CrO4. Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radiolabeled marker. Blood samples were collected for E2 and CCK radioimmunoassay. RESULTS: After treatment of EB (4-25 microg/kg), gastric emptying and gastrointestinal transit were inhibited, whereas plasma concentrations of E2 and CCK were increased in a dose-dependent manner. The selective CCK(A) receptor antagonists, devazepide and lorglumide, effectively attenuated the EB-induced inhibition of gastric emptying and gastrointestinal transit. L-365,260, a selective CCK(B) receptor antagonist, did not alter the EB-induced inhibition of gastric emptying and gastrointestinal transit. CONCLUSIONS: The results suggest that EB inhibits gastric emptying and gastrointestinal transit in ovariectomized rats via a mechanism involving CCK stimulation and CCK(A) receptor activation.

Animals↗

Molecular genetic analysis of the NF2 gene in young patients with unilateral vestibular schwannomas.

Neurofibromatosis type 2 (NF2) must be suspected in patients presenting with a unilateral vestibular schwannoma at a young age who are therefore at theoretical risk of developing bilateral disease. We identified 45 patients aged 30 years or less at the onset of symptoms of a unilateral vestibular schwannoma. Molecular genetic analysis of the NF2 gene was completed on peripheral blood samples in all 45 and on 28 tumour samples. No pathogenic NF2 mutations were identified in any of the blood samples. NF2 point mutations were identified in 21/28 (75%) tumour samples and loss of heterozygosity (LOH) in 21/28 (75%) tumour samples. Both mutational hits were identified in 18/28 (65%) tumour samples. In one multilobular tumour, one (presumably first hit) mutation was confirmed which was common to different foci of the tumour, while the second mutational event differed between foci. The molecular findings in this patient were consistent with somatic mosaicism for NF2 and the clinical diagnosis was confirmed with the presence of two meningiomas on a follow up MRI scan. A further patient developed a contralateral vestibular schwannoma on a follow up MRI scan in whom neither of the truncating mutations in the vestibular schwannoma were present in blood. It is important when counselling patients with unilateral vestibular schwannomas to identify (1) those at risk of bilateral disease, (2) those at risk of developing other tumours, and (3) other family members at risk of developing NF2. Comparing tumour and blood DNA cannot exclude mosaicism in the index case and cannot, therefore, be used to predict those at risk of developing further tumours. However, identification of both mutations or one mutation plus LOH in the tumour and exclusion of those mutations in the blood samples of the sibs or offspring of the affected case may be sufficient to render further screening unnecessary in these relatives.

Adolescent↗

Lithium-pilocarpine-induced status epilepticus in immature rats result in long-term deficits in spatial learning and hippocampal cell loss.

Rat pups age of 14 postnatal day (P14) were subjected to lithium-pilocarpine (Li-PC) model of status epilepticus (SE). Control rats (n=6) were given an equivalent volume of saline intraperitoneally. Behavioral testing began on P60 including the Morris water maze, the radial arm maze, and the rotarod test. Brain were then analyzed with cresyl violet stain for histological lesions and evaluated for mossy fiber sprouting with the Timm stain. We observed spatial memory deficits both in the Morris water maze and radial arm maze in Li-PC-treated rat. There was no motor impairment in Li-PC-treated rat by the rotarod test. Two of six Li-PC-treated rats showed cell loss in hippocampal CA1 subfield. The Timm staining pattern was similar in both control and Li-PC-treated rats. Result of this study suggests that Li-PC-induced SE in immature rats cause long-term cognitive deficit and permanent cell loss in hippocampal CA1, but spare motor impairment.

Aging↗

Cables enhances cdk2 tyrosine 15 phosphorylation by Wee1, inhibits cell growth, and is lost in many human colon and squamous cancers.

Cyclin-dependent kinase 2 (cdk2) is a small serine/threonine kinase that regulates cell cycle progression. Cdk2 activity is tightly controlled by several mechanisms, including phosphorylation and dephosphorylation events. Cables is a recently described novel cdk-interacting protein. In proliferating cells, Cables was predominantly localized in the nucleus by cell fractionation and immunostaining. Expression of Cables in HeLa cells inhibited cell growth and colony formation. Cables enhanced cdk2 tyrosine 15 phosphorylation by the Wee1 protein kinase, an inhibitory phosphorylation, which led to decreased cdk2 kinase activity. The gene encoding Cables is located on human chromosome 18q11-12, a site that is frequently lost in squamous, colon, and pancreas cancers. We found that Cables was strongly expressed in normal human epithelial cells including squamous and glandular mucosa. Breast and pancreatic cancers show strong Cables expression; however, loss of Cables expression was found in approximately 50-60% of primary colon and head and neck cancer specimens. Lack of Cables expression was associated with loss of heterozygosity on chromosome 18q11. The data provide evidence for a Cables-mediated interplay between cdk2 and Wee1 that leads to inhibition of cell growth. Conversely, loss of Cables may cause uncontrolled cell growth and enhance tumor formation.

Animals↗

Prothymosin alpha enhances protective immune responses induced by oral DNA vaccination against pseudorabies delivered by Salmonella choleraesuis.

Previously, we showed that vaccination with the glycoprotein D (gD) gene of pseudorabies virus (PrV) delivered by Escherichia coli induced protective immune responses. In this study, we report that oral DNA vaccination with attenuated Salmonella choleraesuis carrying the PrV gD gene conferred protective immunity in mice against PrV. Moreover, co-delivery of the prothymosin alpha gene carried by S. choleraesuis enhanced the vaccine efficacy. Our results thus demonstrate for the first time, to our knowledge, the effectiveness of oral DNA vaccination using S. choleraesuis as a delivery vehicle and the potential usefulness of prothymosin alpha as a DNA vaccine adjuvant.

Adjuvants, Immunologic↗

Vaccination with the glycoprotein D gene of pseudorabies virus delivered by nonpathogenic Escherichia coli elicits protective immune responses.

Attenuated intracellular bacteria, such as Salmonella and Shigella, have been exploited to act as gene delivery vectors. In this study, we report that nonpathogenic, live Escherichia coli can be used for the delivery of DNA vaccines in vivo, leading to generation of immune responses against plasmid-encoded foreign antigens. The pseudorabies virus (PrV) DNA vaccine carrying the glycoprotein D (gD) gene delivered by E. coli was able to induce protective immune responses in mice against a lethal PrV challenge. Co-delivery of E. coli carrying plasmid DNA encoding prothymosin alpha enhanced cellular immune responses to the PrV DNA vaccine delivered by E. coli. Our results suggest that nonpathogenic E. coli may be used as a vector for DNA vaccines in veterinary uses.

3T3 Cells↗

Binding of ATP to the fructose-2,6-bisphosphatase domain of chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase leads to activation of its 6-phosphofructo-2-kinase.

To understand the mechanism by which the activity of the 6-phosphofructo-2-kinase (6PF-2K) of chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is stimulated by its substrate ATP, we studied two mutants of the enzyme. Mutation of either Arg-279, the penultimate basic residue within the Walker A nucleotide-binding fold in the bisphosphatase domain, or Arg-359 to Ala eliminated the activation of the chicken 6PF-2K by ATP. Binding analysis by fluorescence spectroscopy using 2'(3')-O-(N-methylanthraniloyl)-ATP revealed that the kinase domains of these two mutants, unlike that of the wild type enzyme, showed no cooperativity in ATP binding and that the mutant enzymes possess only the high affinity ATP binding site, suggesting that the ATP binding site on the bisphosphatase domain represents the low affinity site. This conclusion was supported by the result that the affinity of ATP for the isolated bisphosphatase domain is similar to that for the low affinity site in the wild type enzyme. In addition, we found that the 6PF-2K of a chimeric enzyme, in which the last 25 residues of chicken enzyme were replaced with those of the rat enzyme, could not be activated by ATP, despite the fact that the ATP-binding properties of this chimeric enzyme were not different from those of the wild type chicken enzyme. These results demonstrate that activation of the chicken 6PF-2K by ATP may result from allosteric binding of ATP to the bisphosphatase domain where residues Arg-279 and Arg-359 are critically involved and require specific C-terminal sequences.

Adenosine Triphosphate↗

Structure determination of the Si3N4/Si(111)- (8 x 8) surface: a combined study of Kikuchi electron holography, scanning tunneling microscopy, and ab initio calculations.

A comprehensive atomic model for the reconstructed surface of Si3N4 thin layer grown on Si(111) is presented. Kikuchi electron holography images clearly show the existence of adatoms on the Si3N4(0001)/Si(111)-(8x8) surface. Compared with the ab initio calculations, more than 30 symmetry-inequivalent atomic pairs in the outmost layers are successfully identified. Scanning tunneling microscopy (STM) images show diamond-shaped unit cells and nine adatoms in each cell. High-resolution STM images reveal extra features and are in good agreement with the partial charge density distribution obtained from total-energy calculations.

Journal Article↗

Sesquiterpenoid constituents of the liverworts Lepidozia fauriana and Lepidozia vitrea.

The sesquiterpene constituents of the essential oils of the Taiwanese liverworts Lepidozia fauriana and L. vitrea were investigated. 11,12-Dihydrochiloscyphone and 7,10-anhydro-11,12-dihydrochiloscypholone were isolated from L. fauriana and spectroscopically characterised together with their hydrogenation products. From the same species three amorphane derivatives amorpha-4,9-dien-14-al, amorpha-4,9-dien-2-ol and 7,14-anhydroamorpha-4,9-diene, and from L. vitrea two oxygenated elemanes, namely 7-acetoxy-elema-1,3-dien-8-ol and elema-1,3-dien-7-ol, were isolated and identified. Structure elucidation was carried out by NMR spectroscopy and chemical correlations in conjunction with enantioselective gas chromatography were utilized to establish absolute configurations.

Gas Chromatography-Mass Spectrometry↗

Effect of local anesthetics on patient recovery after transrectal biopsy.

OBJECTIVES: To determine the analgesic efficacy of local anesthetics injected lateral to the seminal vesicles before prostate biopsy, during and immediately after the procedure, because pain is a common side effect of transrectal ultrasound-guided prostate biopsy. METHODS: Patients were randomized to receive 5 mL of either 1% lidocaine or sterile normal saline injected (under ultrasound guidance) lateral to the seminal vesicles bilaterally before performance of the prostate biopsies, with the patient and physician unaware of the treatment group. Five minutes after the injection, a series of 12 prostate biopsies were performed. A visual analog scale (VAS) for pain at rest and with activity was obtained before the biopsy (preprocedure VAS) and immediately (intraprocedure VAS) and 30 minutes (postprocedure VAS) after the biopsy. Surveys examining the patients' expectations for biopsy pain were administered before and immediately after the biopsy. RESULTS: No significant differences were found between the groups with regard to demographic data, VAS pain scores at rest and with activity, and survey results. CONCLUSIONS: Injection of lidocaine lateral to the seminal vesicles before prostate biopsy did not diminish biopsy-associated pain.

Aged↗

Strain compounding: spatial resolution and performance on human images.

Compounding has long been used to reduce speckle brightness variations by incoherently combining partially correlated measurements of the same image object. Conventionally, decorrelation between measurements is introduced by imaging from different spatial positions (i.e., spatial compounding) or within different frequency ranges (i.e., frequency compounding). An alternative compounding approach based on speckle decorrelation of an object under different strain conditions was recently proposed. The new approach was referred to as strain compounding. Speckle correlation of strain compounding was previously analyzed using simulations and radiofrequency (RF) data from a gelatin-based phantom. Results indicated that effective speckle reduction is possible at strains potentially achievable in certain clinical situations. In this paper, performance of strain compounding is further analyzed. Potential degradation in spatial resolution of strain compounding is compared to that of conventional approaches using computer simulations. Results show that strain compounding potentially can achieve the same level of speckle reduction, with less degradation in spatial resolution if a large compression can be applied. Performance of strain compounding is also tested using postdetection human images acquired by a commercial imaging system. Two-dimensional (2-D) speckle tracking is performed to correct for tissue motion resulting from external compression and to ensure that the images to be compounded are spatially matched. Thyroid images show that speckle brightness variations can be effectively reduced without significant degradation in spatial resolution. Speckle reduction in liver imaging is also demonstrated. However, speckle reduction is not as significant as in thyroid imaging, due to the fact that a large compression cannot be achieved.

Humans↗

Regional anesthesia and anticoagulation.

The perioperative use of neuraxial techniques in the presence of anticoagulation is a controversial issue. There are significant pharmacokinetic differences between anticoagulants that will affect the timing of neuraxial needle insertion or catheter removal. The pharmacologic profiles of commonly used anticoagulants in the perioperative period are reviewed. Studies examining the use of neuraxial techniques in the presence of various anticoagulants are reviewed and evaluated in the context of the American Society of Regional Anesthesia consensus statements.

Anesthesia, Conduction↗

Postoperative immuno-gene therapy of murine bladder tumor by in vivo administration of retroviruses expressing mouse interferon-gamma.

The murine MBT-2 bladder tumor model in syngeneic C3H/HeN mice was used to investigate the feasibility of gene therapy based on the delivery of interferon-gamma (IFN-gamma) in vivo by retroviral vectors. We constructed a recombinant retroviral vector pRUFneo/IFN-gamma, which was transfected into a retroviral packaging cell line psiCRE, to produce psiCRE/pRUFneo/IFN-gamma cells. The expressions of the neo and IFN-gamma genes were verified by reverse transcription-polymerase chain reaction and IFN-gamma was detected in the culture supernatant from psiCRE/pRUFneo/IFN-gamma cells. After receiving MBT-2 cells admixed with retroviral pRUFneoIFN-gamma supernatant, C3H/HeN mice exhibited lower tumor incidence, lower tumor mass, and higher survival rate, as well as higher antitumor responses compared to those injected with MBT-2 cells admixed with control retroviral supernatant. Moreover, the retroviral pRUFneoIFN-gamma supernatant was able to suppress the growth of rechallenged tumors in postoperated mice. Although the IFN-gamma protein secreted from psiCRE/pRUFneo/IFN-gamma cells partly contributes to the antitumor effect of retroviral pRUFneoIFN-gamma supernatant, the retroviruses carrying the IFN-gamma gene transduced MBT-2 cells in vivo, which may result in enhancing local IFN-gamma production from tumor cells. Because bladder is suitable for the intravesical instillation of therapeutic agents, in vivo administration of retroviral vectors encoding IFN-gamma may be explored for the treatment of bladder cancer.

Animals↗

Retrovirus-mediated transfer of prothymosin gene inhibits tumor growth and prolongs survival in murine bladder cancer.

To explore the potential use of prothymosin alpha(ProT), a putative thymic hormone, in gene therapy for bladder cancer, we generated a replication-defective recombinant retroviral vector encoding ProT and tested its antitumor effect on the MBT-2 murine bladder cancer. C3H/HeN mice injected with MBT-2 cells in conjunction with retroviruses encoding ProT exhibited smaller tumor mass, lower tumor incidence and higher survival rate, as well as higher antitumor cytotoxic activities compared with those injected with control viruses. However, such effects were not observed in severe combined immunodeficiency mice, suggesting that ProT exerts antitumor effects through its immunomodulatory activities. Cell growth in monolayer culture and colony formation in soft agar were enhanced in ProT gene-modified MBT-2 clones, and such growth-promoting activities of ProT could be reversed if its nuclear localization signal (NLS) was deleted. To circumvent the proliferation-promoting effect of ProT on tumor cells, a retroviral vector encoding ProT lacking NLS was constructed. Our results showed that retroviruses encoding NLS-deleted ProT was more efficacious than those encoding wild-type ProT in prolonging survival of tumor-bearing mice. This is the first report indicating that ProT, in particular NLS-deleted ProT, delivered by retroviral vectors may be further explored for the treatment of bladder cancer.

Animals↗

Ascending cholangitis provokes IL-8 and MCP-1 expression and promotes inflammatory cell infiltration in the cholestatic rat liver.

BACKGROUND/PURPOSE: Postoperative cholangitis is one of the most common complications after bile duct reconstruction. The pathogenesis and early consequences of ascending cholangitis still are unidentified. METHODS: Male Sprague-Dawley rats were divided into 5 treatment groups: control (n = 4), blood sampling and liver biopsy only; group I, [BDL/Eschericha coli; n = 6], ligation of common bile duct (BDL) for a week, followed by Roux-en-Y choledochojejunostomy (RYCJ) and injection of E coli (ATCC 25922) into Roux limb after 24 hours; group II, [BDL/NS; n = 5], same procedures as in group I, with injection of normal saline (NS) into Roux limb; group III, [SBDL/E coli; n = 6], primary RYCJ was constructed 1 week after sham ligation of common bile duct (SBDL) followed by the same treatment as group I; Group IV, [SBDL/N.S; n = 6], same procedures as in group III, but injecting NS into Roux limb. All animals were killed after 24 hours of treatment. Blood was sampled for culture and serum cytokine levels. The liver was harvested for quantitative bacterial culture, as well as for MCP-1, interleukin (IL)-8 (CINC in the rat) and transforming growth factor beta1 mRNA expression by reverse transcriptase polymerase chain reaction (RT-PCR) and for immunohistochemistry. The choledochojejunostomy was resected for culture. Serum cytokine levels were detected by ELISA kits. RESULTS: A significant increase of E coli ATCC 25922, occurred in the livers of group I rats, compared with group IV (P =.037). MCP-1 expression increased in all groups, compared with control (P =.000). The IL-8 mRNA expression was significantly higher in group I than in control (P =.021). The expression of TGF-beta1 mRNA was similar among the groups (P =.361), consistent with the immunohistochemistry results. The serum MCP-1 and IL-8 levels were higher in the 4 groups than in the control (P =.000) and were significantly higher in group I than in group IV (P =.001). CONCLUSIONS: This study found that a significant colonization of E coli of the same strain was present in the cholestatic rat liver injected into the Roux limb, which was associated with a higher expression of liver MCP-1 and IL-8 mRNA, a significant increase of serum MCP-1 and IL-8, and a more evident inflammatory cell infiltration into the porta hepatis.

Anastomosis, Roux-en-Y↗