Biomedical subjects

Kui Wang

Publications and source records attributed to Kui Wang.

At least 19 recordsLinked to original sources

PubMed2026

Adjuvant apatinib therapy following concurrent chemoradiotherapy in patients with high-risk nasopharyngeal carcinoma: A multicenter, prospective phase 2 study.

PURPOSE: To assess the efficacy and safety of concurrent chemoradiotherapy (CCRT) combined with apatinib in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: This multicenter, prospective, phase II study enrolled patients with newly histologically confirmed LA-NPC, who were randomly assigned to receive CCRT followed by adjuvant apatinib (investigational arm) or CCRT alone (control arm). The investigational arm received 250 mg/day of oral apatinib administered every 28 days for up to six cycles after CCRT. The primary endpoint was 3-year progression-free survival (PFS) and secondary endpoints of overall survival (OS), distant metastasis-free survival (DMFS) and local recurrence-free survival (LRFS) of 3-year, and safety. RESULTS: From July 2018 to September 2020, 44 and 44 patients were randomized into the CCRT-alone and CCRT and apatinib groups, respectively. The median follow-up duration 56 (range: 40.0-58.6) months. The survival outcomes were the 3-year PFS, OS, and DMFS rates in the adjuvant apatinib following CCRT group were significantly higher than those observed in the CCRT-alone group((PFS, 78.6%vs. 54.5%, p = 0.027; OS, 88.1% vs. 75.0%, p = 0.029; DMFS, 85.4%vs. 59.1%, p = 0.009). The 3-year LRFS was similar between the groups. The grade 3-4 treatment-related adverse events(TRAEs) were higher in the former group than in the latter. The most common grade 3-4 non-hematology-related adverse events were hypertension (14.3%), hand-foot syndrome (9.5%), increased transaminase levels (7.1%), and headache (7.1%). CONCLUSION: Apatinib significantly improved the treatment effects of CCRT for high-risk LA-NPC patients. Therefore, CCRT and adjuvant apatinib may represent a promising option for this patient population.

Adjuvant therapy↗

PubMed2006

Fibronectin enhances in vitro vascular calcification by promoting osteoblastic differentiation of vascular smooth muscle cells via ERK pathway.

The process of vascular calcification presents several features similar to osteogenesis in which fibronectin (FN) acts as a regulator of osteoblastic differentiation and the ERK signal pathway is involved. In order to find whether FN promotes the osteoblastic differentiation of vascular smooth muscle cells (VSMCs) through the ERK signal pathway, we investigated the effect of FN on the calcification of VSMCs by using an in vitro cell model. VSMCs cultured in plates with FN (0-20 microg/cm2) coating were induced to calcify by 10 mM sodium beta-glycerophosphate (beta-GP). FN exacerbated VSMC calcification in a dose- and time-dependent manner, as indicated by the number of calcifying nodules per slide and the amount of calcium in the deposition. Data from RT-PCR and immunoblotting assay revealed that FN also enhanced the expression of several phenotypic markers of osteoblasts, including alkaline phosphatase (ALP) activity, osteocalcin (OC), and Osf2/Cbfa1, a key transcription factor in osteoblastic differentiation. Furthermore, a specific inhibitor for ERK, PD98059 (10 microM), significantly suppressed the effect of FN on calcification and phenotypic marker expression. These findings seem to suggest that FN enhanced vascular calcification by promoting the osteoblastic differentiation of VSMCs via ERK signal pathway.

Animals↗

PubMed2006

Multilevel logistic regression modelling with correlated random effects: application to the Smoking Cessation for Youth study.

A multilevel logistic regression model is presented for the analysis of clustered and repeated binary response data. At the subject level, serial dependence is expected between repeated measures recorded on the same individual. At the cluster level, correlations of observations within the same subgroup are present due to the inherent hierarchical setting. Two random components are therefore incorporated explicitly within the linear predictor to account for the simultaneous heterogeneity and autoregressive structure. Application to analyse a set of longitudinal data from an adolescent smoking cessation intervention that motivated this study is illustrated.

Adolescent↗

PubMed2006

La(3+)-induced extracellular signal-regulated kinase (ERK) signaling via a metal-sensing mechanism linking proliferation and apoptosis in NIH 3T3 cells.

The effects of La(3+) on the extracellular signal-regulated kinase (ERK) signaling were investigated to explore the mechanism by which La(3+) results in cell proliferation associated with apoptosis in mouse embryo fibroblast NIH 3T3 cells. Our data showed that La(3+) ions could induce a pulse of phosphorylation of ERK mainly through an unknown metal-sensing mechanism, which is different from the Ca(2+)-sensing receptor . The putative sensor protein showed one binding site for La(3+) with a dissociation constant of approximately 8 nM. Inductions of c-fos, c-myc, and cyclin D1 and phosphorylation of retinoblastoma protein (pRb) were observed after activation of ERK. These results are consistent with our previous observation that La(3+) promotes proliferation by helping the cells pass through the G1/S restriction point and enter S phase. This La(3+)-induced signaling cascade exhibited abnormally sustained c-myc induction and pRb phosphorylation. Furthermore, a continual increase of the p53 level was observed along with the signal transduction, and a significant decrease of B-cell lymphoma/leukemia-2 gene was observed after approximately 18 h of incubation. All of the results were highly correlated with the increase of S-phase population and apoptotic cells. Therefore, the experimental results suggested that La(3+) induced cell proliferation and apoptosis compatible to a p53-related mechanism in NIH 3T3 cells via an ERK-signaling cascade induced by a metal-sensing mechanism.

Animals↗

PubMed2006

Induction of human promyelocytic leukemia HL-60 cell differentiation into monocytes by arsenic sulphide: involvement of serine/threonine protein phosphatases.

The clinical efficacy of arsenic sulfide (As(4)S(4)), also known as realgar, in the treatment of leukemia in China is prompting people to explore the underlying mechanism. We examined the realgar-induced differentiation in human promyelocytic leukemia cell line HL-60. Cells exhibited proliferation inhibition when treated with 0.10-1.5 microM of realgar, and underwent monocytic differentiation as indicated by morphological changes, NBT reduction assay, and cytofluorometric analyses of the cell surface antigens, CD11b and CD14. Accompanying the differentiation, the activity of serine/threonine protein phosphatase type 1 (PP1) and type 2A (PP2A) were enhanced, whereas the activity of PP2B remained virtually the same compared to the control. When cells were treated with realgar in the presence of an inhibitor of PP1 and 2A or an inhibitor of PP2B, the differentiation of the cells was partially suppressed as revealed by NBT reduction assay and the expression of CD14. Our data demonstrate that realgar induces monocytic differentiation in HL-60 cells and that some serine/threonine protein phosphatases may be involved in the process.

Arsenicals↗

PubMed2006

Metal ions induced heat shock protein response by elevating superoxide anion level in HeLa cells transformed by HSE-SEAP reporter gene.

The aim of this work is to define the relationship between heat shock protein (HSP) and reactive oxygen species (ROS) in the cells exposed to different concentrations of metal ions, and to evaluate a new method for tracing the dynamic levels of cellular reactive oxygen species using a HSE-SEAP reporter gene. The expression of heat shock protein was measured using a secreted alkaline phosphatase (SEAP) reporter gene transformed into HeLa cell strain, the levels of superoxide anion (O(2)(-)) and hydrogen peroxide (H(2)O(2)) were determined by NBT reduction assay and DCFH staining flow cytometry (FCM), respectively. The experimental results demonstrated that the expression of heat shock protein induced by metal ions was linearly related to the cellular superoxide anion level before cytotoxic effects were observed, but not related to the cellular hydrogen peroxide level. The experimental results suggested that metal ions might induce heat shock protein by elevating cellular superoxide anion level, and thus the expression of heat shock protein indicated by the HSE-SEAP reporter gene can be an effective model for monitoring the dynamic level of superoxide anion and early metal-induced oxidative stress/cytotoxicity.

Cations↗

PubMed2006

The mechanism of kinetic inhibition of Cu(II)-induced oxidation of low density lipoprotein by lanthanide ions.

Oral administration of lanthanum chloride (LaCl(3)) was reported to inhibit atherosclerosis in experimental animals, but the mechanism was not clear. In the present work, the effects of La(III) and other lanthanide ions (Ln(III)) on Cu(II)-induced oxidation of isolated low-density lipoprotein (LDL) and the related mechanism were investigated. By monitoring the formation of conjugated dienes (CD), low concentrations of La(III), Gd(III) and Y(III) were found to inhibit Cu(II)-induced LDL oxidation kinetically, as characterized by the prolongation of the lag time, the decrease of the maximal accumulation of CD, and the maximal rate of CD accumulation. Using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) as spin trapping agents, the electron spin resonance (ESR) results showed that La(III) and Gd(III) at low concentrations significantly decreased the level of free radicals, including alkoxyl radical (LO*), alkyl radical (L*), and a transient radical, alkylperoxyl radical (LOO*), generated during LDL oxidation induced by Cu(II). In addition, Fourier-transform infrared spectroscopy (FT-IR) study revealed that La(III) might cause the conformational change and the less aggregation of apolipoprotein B-100 (apoB) in LDL, as demonstrated by the decreasing contents of alpha-helix, intermolecular beta-sheet, unordered structure and beta-turns, and the increasing contents of intramolecular beta-sheet and beta-strands. The inhibitory effect of Ln(III) on Cu(II)-induced LDL oxidation was discussed on the basis of the decreased free radical level and the second structural changes of apoB in LDL.

Apolipoprotein B-100↗

PubMed2006

Lanthanum induces extracellular signal-regulated kinase phosphorylation through different mechanisms in HeLa cells and NIH 3T3 cells.

Lanthanum ion (La3+) was generally regarded as calcium antagonist and was used as calcium channel blocker. However, its potential biological effects on cells were poorly understood. In the present work, it was found that La3+ could induce rapid extracellular signal-regulated kinase (ERK) phosphorylation in both HeLa cells and NIH 3T3 cells, but different mechanisms were involved. At a concentration of 30 microM or higher, La3+ enters the cells and activates ERK through a mechanism involving calmodulin activation inside the cells, which is similar to the action of intracellular Ca2+. However, at lower concentration, free La3+ promoted ERK phosphorylation in NIH 3T3 cells outside the cells through an unknown La3+ sensing mechanism, while Ca2+ exerted much weaker effect. The present results suggested that the biological effects of La3+ on cells maybe involve mechanisms beyond calcium antagonist.

Animals↗

PubMed2006

The efflux of flavonoids morin, isorhamnetin-3-O-rutinoside and diosmetin-7-O-beta-D-xylopyranosyl-(1-6) -beta-D-glucopyranoside in the human intestinal cell line caco-2.

PURPOSE: In this study, we chose three of the flavonoids isorhamnetin-3-O-rutinoside(IRR) diosmetin-7-O-beta-D-xylopyranosyl-(1-6)-beta-D-glucopyranoside(DXG) and morin, which showed obvious efflux, to test the hypothesis that a specific efflux transporter is responsible for their transportation. METHODS: The intestinal epithelial membrane transport of the flavonoids were examined using the monolayer of the human Caco-2 cell line grown in Transwells, a common model of intestinal absorption. The flavonoids were measured by high performance liquid chromatography with UV detector. RESULT: The efflux of morin, IRR and DXG, across Caco-2 cell monolayers was examined over the concentration range from 2 to 200 microM and showed a saturable process. The depletion of the cellular ATP stores with 5 mM iodoacetamide led to a significant inhibition of the efflux. Fifty micromolar verapamil, a chemical inhibitor of P-glycoprotein, had no effect on the transport of the three flavonoids, while the presence of 50 microM MK-571 and 1 mM probenecid, MRP inhibitors, resulted in an obvious reduction in the efflux. Moreover, inhibition of morin transport by MK-571 demonstrated concentration dependence. The transportation of the three flavonoids was compared with apigenin. CONCLUSION: These data support a role for MRPs in the intestinal transcellular efflux of morin, IRR, DXG and possibly other hydrophilic flavonoid aglycons and glycosides.

Adenosine Triphosphate↗

PubMed2006

The permeability and cytotoxicity of insulin-mimetic vanadium (III,IV,V)-dipicolinate complexes.

Vanadium (III,IV,V)-dipicolinate complexes with different redox properties were selected to investigate the structure-property relationship of insulin-mimetic vanadium complexes for membrane permeability and gastrointestinal (GI) stress-related toxicity using the Caco-2 cell monolayer model. The cytotoxicity of the vanadium complexes was assayed with 3-(4,5-dimethylthiazoyl-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assays and the effect on monolayer integrity was measured by the trans-epithelial electric resistance (TEER). The three vanadium complexes exhibited intermediate membrane permeability (P(app) = 1.4-3.6x10(-6) cm/s) with low cellular accumulation level (<1%). The permeability of all compounds was independent of the concentration of vanadium complexes and excess picolinate ligands. Both V(III) and V(V)-dipicolinate complexes induced 3-4-fold greater reactive oxygen and nitrogen species (RONS) production than the V(IV)-dipicolinate complex; while the vanadium (III)-dipicolinate was 3-fold less damaging to tight junction of the Caco-2 cell monolayer. Despite the differences in apparent permeability, cellular accumulation, and capacity to induce reactive oxygen and nitrogen species (RONS) levels, the three vanadium complexes exhibited similar cytotoxicity (IC50 = 1.7-1.9 mM). An ion pair reagent, tetrabutylammonium, increased the membrane apparent permeability by 4-fold for vanadium (III and IV)-dipicolinate complexes and 16-fold for vanadium (V)-dipicolinate as measured by decrease in TEER values. In addition, the ion pair reagent prevented damage to monolayer integrity. The three vanadium (III,IV,V)-dipicolinate complexes may pass through caco-2 monolayer via a passive diffusion mechanism. Our results suggest that formation of ion pairs may influence compound permeation and significantly reduce the required dose, and hence the GI toxicity of vanadium-dipicolinate complexes.

Caco-2 Cells↗

PubMed2006

Expression of aspartyl beta-hydroxylase and its clinicopathological significance in hepatocellular carcinoma.

The human aspartyl beta-hydroxylase is a highly conserved enzyme that hydroxylates epidermal growth factor-like domains in transformation-associated proteins. The aspartyl beta-hydroxylase gene is upregulated in many human malignancies. The purpose of this study was to investigate the expression of aspartyl beta-hydroxylase in hepatocellular carcinoma. Aspartyl beta-hydroxylase mRNA levels were measured in 161 hepatocellular carcinomas and paired nontumorous liver tissues by conventional and real-time RT-PCR. Immunohistochemical staining of aspartyl beta-hydroxylase was performed using EnVision Plus system. The results showed that aspartyl beta-hydroxylase was overexpressed in 150 of 161 hepatocellular carcinomas (93%), including 45 of 48 unifocal small hepatocellular carcinomas (94%). Aspartyl beta-hydroxylase was highly expressed in hepatocellular carcinoma cells in contrast to its low level of expression in non-neoplastic liver cells. The protein expression level of aspartyl beta-hydroxylase in the hepatocellular carcinoma was parallel with the mRNA expression level (r=0.6594, P<0.0001). A significantly higher tumor aspartyl beta-hydroxylase overexpression level was associated with the presence of intrahepatic metastasis and the progression of histological grades. In conclusion, aspartyl beta-hydroxylase is overexpressed frequently in hepatocellular carcinoma, including early-stage small hepatocellular carcinoma, indicating that overexpression of aspartyl beta-hydroxylase plays a role in the development and progression of hepatocellular carcinoma.

Adult↗

PubMed2006

Induction of multiple prophages from a marine bacterium: a genomic approach.

Approximately 70% of sequenced bacterial genomes contain prophage-like structures, yet little effort has been made to use this information to determine the functions of these elements. The recent genomic sequencing of the marine bacterium Silicibacter sp. strain TM1040 revealed five prophage-like elements in its genome. The genomes of these prophages (named prophages 1 to 5) are approximately 74, 30, 39, 36, and 15 kb long, respectively. To understand the function of these prophages, cultures of TM1040 were treated with mitomycin C to induce the production of viral particles. A significant increase in viral counts and a decrease in bacterial counts when treated with mitomycin C suggested that prophages were induced from TM1040. Transmission electron microscopy revealed one dominant type of siphovirus, while pulsed-field gel electrophoresis demonstrated two major DNA bands, equivalent to 35 and 75 kb, in the lysate. PCR amplification with primer sets specific to each prophage detected the presence of prophages 1, 3, and 4 in the viral lysate, suggesting that these prophages are inducible, but not necessarily to the same level, while prophages 2 and 5 are likely defective or non-mitomycin C-inducible phages. The combination of traditional phage assays and modern microbial genomics provides a quick and efficient way to investigate the functions and inducibility of prophages, particularly for a host harboring multiple prophages with similar sizes and morphological features.

Bacteriophages↗

PubMed2006

Diverse and unique picocyanobacteria in Chesapeake Bay, revealed by 16S-23S rRNA internal transcribed spacer sequences.

rRNA internal transcribed spacer phylogeny showed that Chesapeake Bay is populated with diverse Synechococcus strains, including members of the poorly studied marine cluster B. Marine cluster B prevailed in the upper bay, while marine cluster A was common in the lower bay. Interestingly, marine cluster B Synechococcus included phycocyanin- and phycoerythrin-rich strains.

Cyanobacteria↗

PubMed2006

Multi-level zero-inflated poisson regression modelling of correlated count data with excess zeros.

Count data with excess zeros relative to a Poisson distribution are common in many biomedical applications. A popular approach to the analysis of such data is to use a zero-inflated Poisson (ZIP) regression model. Often, because of the hierarchical study design or the data collection procedure, zero-inflation and lack of independence may occur simultaneously, which render the standard ZIP model inadequate. To account for the preponderance of zero counts and the inherent correlation of observations, a class of multi-level ZIP regression model with random effects is presented. Model fitting is facilitated using an expectation-maximization algorithm, whereas variance components are estimated via residual maximum likelihood estimating equations. A score test for zero-inflation is also presented. The multi-level ZIP model is then generalized to cope with a more complex correlation structure. Application to the analysis of correlated count data from a longitudinal infant feeding study illustrates the usefulness of the approach.

Adult↗

PubMed2006

Under-nutrition affects time to recurrence of gastroenteritis among Aboriginal and non-Aboriginal children.

This study investigated whether under-nutrition affected time to hospitalization for recurrence of gastroenteritis in Australian children. Linked hospitalization records of all infants, born in 1995 and 1996 in Western Australia, who were admitted for gastroenteritis during their first year of life (n=1001), were retrieved. A survival frailty model was used for determining the factors influencing the recurrent times over the subsequent seven years. Aboriginality and under-nutrition were significantly associated with an increased risk of recurrence (hazard ratios of 2.59 and 1.28). Hospitalizations due to gastroenteritis were common among Aboriginal children who had a higher mean re-admission rate and much shorter intervals between re-admissions than other patients. The proportion of patients with recurrence was also significantly higher for Aboriginals (38.5%) than for other patients (14.2%). Gastroenteritis remains a serious problem in Aboriginal children. This presents a complex challenge to be addressed with public-health principles, political determination and commitment, and adequate resources.

Cohort Studies↗

PubMed2006

[Differentiation of HL-60 cells induced by realgar nano-particles].

OBJECTIVE: To investigate the proliferation inhibition and the differentiation effects of realgar (As4S4) nano-particles on human acute myeloid leukemia cell line HL-60. METHOD: Cell viability was determined by MTT and PI-stained cell cycle assays. The realgar induced morphological changes on cells were examined after Wright-Giemsa staining. The cell differentiation was evaluated with NBT and specific cell surface antigen (CD11b and CD14) expression assays. RESULT: HL-60 cells exhibited obvious morphological features of differentiation after the realgar treatment. A 24 h incubation of the cells with 0.25-1.0 micromol x L(-1) realgar caused a great increase in NBT reduction ability. The expressions of CD11b and CD14 were augmented in cells treated with 0.50 micromol x L(-1) realgar for 48 h, and cell cycles were arrested in G1 phase. CONCLUSION: Low dose realgar induces differentiation in human acute myeloid leukemia cell line HL-60.

Antineoplastic Agents↗

PubMed2006

[Monitoring early toxicity of heavy metals including Hg using a HSE-SEAP reporter gene].

OBJECTIVE: To develop a cellular assay based on heat shock signal pathway and secreted alkaline phosphatase (SEAP) reporter gene for investigating/predicting the early toxicity of heavy metals on HeLa cells in Chinese traditional medicine (TCM). METHOD: The pHSE-SEAP plasmid was transfected into HeLa cells to build a HSE-SEAP-HeLa cell model. For validation of the model, the transfected cells were treated by either heating at 42 degrees C for 1 h or incubated with 5 mol x L(-1) CdCl2 for 4 h. Then the cells were covered in complete DMEM culture medium for 48 h and the activity of SEAP (reflecting the cellular level of heat shock protein) in cultural supernatants was measured; meanwhile, cell viability was determined by MTT assays. In addition, the cells were treated by four mercury compounds, HgCl2, merthilate sodium, HgS and cinnabar at the sub-lethal concentrations (determined by MTT assays). Then the heat shock response was detected likewise. RESULT: Significant level of secreted alkaline phosphatase (SEAP) was found in pHSE-SEAP transfected HeLa cells treated either by heating (42 degrees C) or incubating with CdCl2. The heat shock protein was induced by CdCl2 before decrease of cell viability was observed. All four mercury compounds induced heat shock response in both time and concentration-dependant manner. However, there were big differences among the mercury compounds, suggesting potential differences for early-stage toxicity in vivo. CONCLUSION: The pHSE-SEAP transfected HeLa cells respond effectively to heat shock and metal stresses, and therefore provide a practical and repeatable assay for investigating/predicting the early toxicity of heavy metals and mineral-containing drugs in TCM.

Alkaline Phosphatase↗

PubMed2006

[Mechanisms of removing red tide organisms by organo-clays].

We tested the influence of the preparation conditions of the quaternary ammonium compounds (QACs) modified clays on their capacities to remove red tide organisms, then discussed the mechanisms of the organo-clays removing red tide organisms. Hexadecyltrimethylammonium (HDTMA) improved the capacity of clays to flocculate red tide algae, and the HDTMA in metastable state enhanced the toxicity of the clay complexes to algae. The capacities of the organo-clays correlated with the toxicity and the adsorbed amount of the QACs used in clays modification, but as the incubation time was prolonged the stability of the organo-clays was improved and the algal removal efficiencies of the clay complexes decreased. When the adsorbed HDTMA was arranged in different clays in which the spatial resistance was different, there was more HDTMA in metastable state in the three-layer montmorillonite. Because of the homo-ion effect the bivalent or trivalent metal ions induced more HDTMA in metastable state and the corresponding organo-clays had high capacities to remove red tide organisms. When the reaction temperature was 60 degrees C the adsorbed HDTMA was easily arranged on cation exchange sites, if the temperature rose or fell the metastable HDTMA would increase so that the capacity of the clays was improved.

Adsorption↗