lu Yang
Publications
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3.48Impact points
DAP5 Ameliorates Cisplatin-Induced Apoptosis of Renal Tubular Cells.
American journal of nephrology. 04/2012; 35(5):456-465.
Background: Nephrotoxicity of cisplatin limits its clinical application. Cisplatin-induced acute renal tubular epithelial cell apoptosis is one of the major mechanisms of cisplatin nephrotoxicity. Here, the role and regulation of death-associated protein 5 (DAP5) in cisplatin-induced tubular cell ap... [more] Background: Nephrotoxicity of cisplatin limits its clinical application. Cisplatin-induced acute renal tubular epithelial cell apoptosis is one of the major mechanisms of cisplatin nephrotoxicity. Here, the role and regulation of death-associated protein 5 (DAP5) in cisplatin-induced tubular cell apoptosis were investigated. Methods: After upregulation of DAP5 expression by plasmid transfection and downregulation of DAP5 expression by small interfering RNA in human kidney tubular epithelial cell line (HKC) cells, the degree of cell apoptosis was assessed by flow cytometric analysis. The expression of Bax and Bcl-2 proteins was detected by Western blot analysis. The relationship between the PI3K/Akt/mTOR signaling pathway and DAP5 was also evaluated. Results: During cisplatin-induced apoptosis in HKC cells, DAP5 underwent proteolytic fragmentation, yielding an 86-kDa species, DAP5/p86. Overexpression of DAP5/p97 and DAP5/p86 increased the translation of Bcl-2 and reduced the extent of cisplatin-induced apoptosis. Knockdown of DAP5 expression using small interfering RNA decreased the translation of Bcl-2 and increased the degree of apoptosis. Neither manipulation affected the expression of Bax. DAP5 expression was positively regulated by the PI3K/Akt/mTOR signaling pathway. Conclusion: Collectively, the results from the present study revealed a new role for DAP5 in cisplatin-induced apoptosis: DAP5/p97 and DAP5/p86 enhanced the translation of the anti-apoptotic protein Bcl-2 and inhibited cisplatin-induced apoptosis. The PI3K/Akt/mTOR signaling pathway may positively regulate the expression of DAP5.
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8.98Impact points
A GATA Transcription Factor Recruits Hda1 in Response to Reduced Tor1 Signaling to Establish a Hyphal Chromatin State in Candida albicans.
PLoS pathogens. 04/2012; 8(4):e1002663.
Candida albicans is an important opportunistic fungal pathogen of immunocompromised individuals. One critical virulence attribute is its morphogenetic plasticity. Hyphal development requires two temporally linked changes in promoter chromatin, which is sequentially regulated by temporarily clearing ... [more] Candida albicans is an important opportunistic fungal pathogen of immunocompromised individuals. One critical virulence attribute is its morphogenetic plasticity. Hyphal development requires two temporally linked changes in promoter chromatin, which is sequentially regulated by temporarily clearing the transcription inhibitor Nrg1 upon activation of the cAMP/PKA pathway and promoter recruitment of the histone deacetylase Hda1 under reduced Tor1 signaling. Molecular mechanisms for the temporal connection and the link to Tor1 signaling are not clear. Here, through a forward genetic screen, we report the identification of the GATA family transcription factor Brg1 as the factor that recruits Hda1 to promoters of hypha-specific genes during hyphal elongation. BRG1 expression requires both the removal of Nrg1 and a sub-growth inhibitory level of rapamycin; therefore, it is a sensitive readout of Tor1 signaling. Interestingly, promoters of hypha-specific genes are not accessible to Brg1 in yeast cells. Furthermore, ectopic expression of Brg1 cannot induce hyphae, but can sustain hyphal development. Nucleosome mapping of a hypha-specific promoter shows that Nrg1 binding sites are in nucleosome free regions in yeast cells, whereas Brg1 binding sites are occupied by nucleosomes. Nucleosome disassembly during hyphal initiation exposes the binding sites for both regulators. During hyphal elongation, Brg1-mediated Hda1 recruitment causes nucleosome repositioning and occlusion of Nrg1 binding sites. We suggest that nucleosome repositioning is the underlying mechanism for the yeast-hyphal transition. The hypha-specific regulator Ume6 is a key downstream target of Brg1 and functions after Brg1 as a built-in positive feedback regulator of the hyphal transcriptional program to sustain hyphal development. With the levels of Nrg1 and Brg1 dynamically and sensitively controlled by the two major cellular growth pathways, temporal changes in nucleosome positioning during the yeast-to-hypha transition provide a mechanism for signal integration and cell fate specification. This mechanism is likely used broadly in development.
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5.21Impact points
Nonlinear Signal Response in Electrospray Mass Spectrometry: Implications for Quantitation of Arsenobetaine Using Stable Isotope Labeling by Liquid Chromatography and Electrospray Orbitrap Mass Spectrometry.
Analytical chemistry. 03/2012;
Isotope amount ratio measurements by electrospray ionization mass spectrometry show large systematic biases. Moreover, the signal ratio response can vary nonlinearly with respect to the amount ratio depending on the concentration of the analyte or coeluting matrix components, among other things. Sin... [more] Isotope amount ratio measurements by electrospray ionization mass spectrometry show large systematic biases. Moreover, the signal ratio response can vary nonlinearly with respect to the amount ratio depending on the concentration of the analyte or coeluting matrix components, among other things. Since isotope dilution relies inherently on the linearity of response, accurate quantitation is then more difficult to achieve. In this study, we outline a method to eliminate the quantitation errors due to the effects of the nonlinear signal response. The proposed approach is a hybrid of the method of standard additions and isotope dilution allowing correction for nonlinear trend. As a proof of concept, determination of arsenobetaine content in fish tissue was performed using liquid chromatography coupled with a linear quadrupole ion trap (LTQ) Orbitrap mass spectrometer. The nonlinear isotope dilution method could, in principle, be applied to correct isotope ratio measurement biases in popular relative quantitation methods of biomolecules such as stable isotope labeling by amino acids in cell culture (SILAC), isotope-coded affinity tag (ICAT), or isobaric tags for relative and absolute quantification (iTRAQ).
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5.38Impact points
Monodisperse Mesocrystals of YF(3) and Ce(3+) /Ln(3+) (Ln=Tb, Eu) Co-Activated YF(3) : Shape Control Synthesis, Luminescent Properties, and Biocompatibility.
Chemistry (Weinheim an der Bergstrasse, Germany). 03/2012;
A family of monodisperse YF(3) , YF(3) :Ce(3+) and YF(3) :Ce(3+) /Ln(3+) (Ln=Tb, Eu) mesocrystals with a morphology of a hollow spindle can be synthesized by a solvothermal process using yttrium nitrate and NH(4) F as precursors. The effects of reaction time, fluorine source, solvents, and reaction ... [more] A family of monodisperse YF(3) , YF(3) :Ce(3+) and YF(3) :Ce(3+) /Ln(3+) (Ln=Tb, Eu) mesocrystals with a morphology of a hollow spindle can be synthesized by a solvothermal process using yttrium nitrate and NH(4) F as precursors. The effects of reaction time, fluorine source, solvents, and reaction temperature on the synthesis of these mesocrystals have been studied in detail. The results demonstrate that the formation of a hollow spindle-like YF(3) can be ascribed to a nonclassical crystallization process by means of a particle-based reaction route in ethanol. It has been shown that the fluorine sources selected have a remarkable effect on the morphologies and crystalline phases of the final products. Moreover, the luminescent properties of Ln(3+) -doped and Ce(3+) /Ln(3+) -co-doped spindle-like YF(3) mesocrystals were also investigated. It turns out that Ce(3+) is an efficient sensitizer for Ln(3+) in the spindle-like YF(3) mesocrystals. Remarkable fluorescence enhancement was observed in Ce(3+) /Ln(3+) -co-doped YF(3) mesocrystals. The mechanism of the energy transfer and electronic transition between Ce(3+) and Ln(3+) in the host material of YF(3) mesocrystals was also explored. The cytotoxicity study revealed that these YF(3) -based nanocrystals are biocompatible for applications, such as cellular imaging.
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5.21Impact points
Determination of the atomic weight of (28)si-enriched silicon for a revised estimate of the avogadro constant.
Analytical chemistry. 03/2012; 84(5):2321-7.
The much anticipated overhaul of the International System of Units (SI) will result in new definitions of base units in terms of fundamental constants. However, redefinition of the kilogram in terms of the Planck constant (h) cannot proceed without consistency between the Avogadro and Planck constan... [more] The much anticipated overhaul of the International System of Units (SI) will result in new definitions of base units in terms of fundamental constants. However, redefinition of the kilogram in terms of the Planck constant (h) cannot proceed without consistency between the Avogadro and Planck constants, which are both related through the Rydberg constant. In this work, an independent assessment of the atomic weight of silicon in a highly enriched (28)Si crystal supplied by the International Avogadro Coordination (IAC) was performed. This recent analytical approach, based on dissolution with NaOH and its isotopic characterization by multicollector inductively coupled plasma mass spectrometry, is critically evaluated. The resultant atomic weight A(r)(Si) = 27.976 968 39(24)(k=1) differs significantly from the most recent value of A(r)(Si) = 27.976 970 27(23)(k=1). Using the results generated herein for A(r)(Si) along with other IAC measurement results for mass, volume, and the lattice spacing, the estimate of the Avogadro constant becomes N(A) = 6.022 140 40(19) × 10(23) mol(-1).
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3.28Impact points
Vaginal Film Drug Delivery of the Pyrimidinedione IQP-0528 for the Prevention of HIV Infection.
Pharmaceutical research. 03/2012;
PURPOSE: Polymeric quick-dissolving films were developed as a solid dosage topical microbicide formulation for the vaginal delivery of the highly potent and non-toxic, dual-acting HIV nonnucleoside reverse transcriptase inhibitor (NNRTI) pyrimidinedione, IQP-0528. METHODS: Formulated from approved e... [more] PURPOSE: Polymeric quick-dissolving films were developed as a solid dosage topical microbicide formulation for the vaginal delivery of the highly potent and non-toxic, dual-acting HIV nonnucleoside reverse transcriptase inhibitor (NNRTI) pyrimidinedione, IQP-0528. METHODS: Formulated from approved excipients, a polyvinyl alcohol (PVA) based film was manufactured via solvent casting methods. The film formulations were evaluated based upon quantitative physicochemical evaluations defined by a Target Product Profile (TPP) RESULTS: Films dosed with 0.1% (w/w) of IQP-0528 disintegrated within 10 min with over 50% of drug released and near 100% total drug released after 30 min. The IQP-0528 films were found to be non-toxic in in vitro CEM-SS and PBMC cell-based assays and biologically active with sub-nanomolar efficacy against HIV-1 infection. In a 12 month stability protocol, the IQP-0528 films demonstrated no significant degradation at International Conference on Harmonization (ICH) recommended standard (25°C/65% relative humidity (R.H.)) and accelerated (40°C/75% R.H.) environmental conditions. CONCLUSIONS: Based on the above evaluations, a vaginal film formulation has been identified as a potential solid dosage form for the vaginal delivery of the topical microbicide candidate IQP-0528.
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5.21Impact points
Protein Quantitation Using Ru-NHS Ester Tagging and Isotope Dilution High-Pressure Liquid Chromatography-Inductively Coupled Plasma Mass Spectrometry Determination.
Analytical chemistry. 03/2012; 84(6):2769-75.
An accurate, simple, and sensitive method for the direct determination of proteins by nonspecies specific isotope dilution and external calibration high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS) is described. The labeling of myoglobin (17 kDa), trans... [more] An accurate, simple, and sensitive method for the direct determination of proteins by nonspecies specific isotope dilution and external calibration high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS) is described. The labeling of myoglobin (17 kDa), transferrin (77 kDa), and thyroglobulin (670 kDa) proteins was accomplished in a single-step reaction with a commercially available bis(2,2'-bipyridine)-4'-methyl-4-carboxybipyridine-ruthenium N-succinimidyl ester-bis(hexafluorophosphate) (Ru-NHS ester). Using excess amounts of Ru-NHS ester compared to the protein concentration at optimized labeling conditions, constant ratios for Ru to proteins were obtained. Bioconjugate solutions containing both labeled and unlabeled proteins as well as excess Ru-NHS ester reagent were injected onto a size exclusion HPLC column for separation and ICPMS detection without any further treatment. A (99)Ru enriched spike was used for nonspecies specific ID calibration. The accuracy of the method was confirmed at various concentration levels. An average recovery of 100% ± 3% (1 standard deviation (SD), n = 9) was obtained with a typical precision of better than 5% RSD at 100 μg mL(-1) for nonspecies specific ID. Detection limits (3SD) of 1.6, 3.2, and 7.0 fmol estimated from three procedure blanks were obtained for myoglobin, transferrin, and thyroglobulin, respectively. These detection limits are suitable for the direct determination of intact proteins at trace levels. For simplicity, external calibration was also tested. Good linear correlation coefficients, 0.9901, 0.9921, and 0.9980 for myoglobin, transferrin, and thyroglobulin, respectively, were obtained. The measured concentrations of proteins in a solution were in good agreement with their volumetrically prepared values. To the best of our knowledge, this is the first application of nonspecies specific ID for the accurate and direct determination of proteins using a Ru-NHS ester labeling reagent.
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0.61Impact points
Two new N-acetyldopamine tetrapolymers from Periostracum Cicadae.
Journal of Asian natural products research. 03/2012; 14(3):204-9.
Two new N-acetyldopamine tetrapolymers, cicadamide A (1) and cicadamide B (2), were isolated from Periostracum Cicadae, and their structures were elucidated as 3-acetylamino-7-(3″-acetylamino-7″-(N-acetyl-2‴-aminoethyl)-1″,4″-benzodioxan-2″-yl)-2-(2'-(3″″,4″″-dihydroxyphenyl)-3'-acetylamino-... [more] Two new N-acetyldopamine tetrapolymers, cicadamide A (1) and cicadamide B (2), were isolated from Periostracum Cicadae, and their structures were elucidated as 3-acetylamino-7-(3″-acetylamino-7″-(N-acetyl-2‴-aminoethyl)-1″,4″-benzodioxan-2″-yl)-2-(2'-(3″″,4″″-dihydroxyphenyl)-3'-acetylamino-1',4'-benzodioxan-7'-yl)-1,4-benzodioxane (1) and 3-acetylamino-7-(3″-acetylamino-6″-(N-acetyl-2‴-aminoethyl)-1″,4″-benzodioxan-2″-yl)-2-(2'-(3″″,4″″-dihydroxyphenyl)-3'-acetylamino-1',4'-benzodioxan-7'-yl)-1,4-benzodioxane (2), by the combined analysis of 1D NMR and 2D NMR, and mass spectrometry. Pharmacological investigation on two compounds obtained in this study showed that part of them had anti-inflammatory activities.
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3.74Impact points
The anti-EGFR antibody cetuximab sensitizes human head and neck squamous cell carcinoma cells to radiation in part through inhibiting radiation-induced upregulation of HIF-1α
Cancer letters. 02/2012;
In this study, we investigated the mechanisms underlying cetuximab-mediated radiosensitization of HNSCC. Irradiation of HNSCC cells upregulated hypoxia-inducible factor-1 alpha (HIF-1α) via a mechanism involving de novo synthesis of HIF-1α protein. Radiation-induced upregulation of HIF-1α was comple... [more] In this study, we investigated the mechanisms underlying cetuximab-mediated radiosensitization of HNSCC. Irradiation of HNSCC cells upregulated hypoxia-inducible factor-1 alpha (HIF-1α) via a mechanism involving de novo synthesis of HIF-1α protein. Radiation-induced upregulation of HIF-1α was completely abolished by concurrent treatment of HNSCC cells with cetuximab. Experimental elevation of constitutively expressed HIF-1α abolished cetuximab-mediated radiosensitization in HNSCC cells, whereas downregulation of HIF-1α by siRNA or a small molecule inhibitor enhanced responses of cetuximab-resistant HNSCC cells to cetuximab plus radiation. Our data suggest that cetuximab sensitizes cancer cells to ionizing radiation in part through inhibition of radiation-induced upregulation of HIF-1α.
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8.58Impact points
Chemoaffinity-Mediated Synthesis of NaRES(2)-Based Nanocrystals as Versatile Nano-Building Blocks and Durable Nano-Pigments.
Journal of the American Chemical Society. 02/2012; 134(6):3255-64.
In this article, we present a chemoaffinity-mediated synthetic strategy toward trivalent rare earth (RE) sulfides-based nanocrystals with poor affinity between cation and anion (i.e., RE(3+) and S(2-)). With the affinity mediation among multiple constituents based on hard and soft acid and base theo... [more] In this article, we present a chemoaffinity-mediated synthetic strategy toward trivalent rare earth (RE) sulfides-based nanocrystals with poor affinity between cation and anion (i.e., RE(3+) and S(2-)). With the affinity mediation among multiple constituents based on hard and soft acid and base theory, we synthesized a series of monodisperse NaRES(2) nanocrystals (RE = La to Lu, Y). The revelation of the nanocrystal growth mechanism from both experimental evidence and crystal structure modeling has enabled a robust control over the sizes and morphologies of the nanocrystals. This principle of chemoaffinity has also promised the synthesis of well-defined but even more complex RE-based hetero-nanostructures (i.e. NaLaS(2)-Au, Au@NaLaS(2), NaLaS(2)@Ag(2)S, Au@NaLaS(2)@Ag(2)S) with tunable optical properties. Furthermore, this synthetic method has yielded durable NaCeS(2)-based red nano-pigments under ambient conditions, with superior brightness and permeability in polydimethylsiloxane.
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2.28Impact points
A Meta-Analysis of Interleukin-10-1082 Promoter Polymorphism Associated with Gastric Cancer Risk.
DNA and cell biology. 02/2012;
We aimed to explore the role of allele A/G single nucleotide polymorphism (SNP) of gene Interleukin 10 (IL-10) promoter-1082 in the susceptibility to gastric cancer through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. Desirable data were ex... [more] We aimed to explore the role of allele A/G single nucleotide polymorphism (SNP) of gene Interleukin 10 (IL-10) promoter-1082 in the susceptibility to gastric cancer through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. Desirable data were extracted and registered into databases. Twenty studies were ultimately eligible for the meta-analysis of IL-10-1082 A/G SNP. We adopted the most probably appropriate genetic model (dominant model), with the combined group of GG-plus-GA genotypes compared with the AA genotype. Potential sources of heterogeneity were sought out via subgroup analyses and sensitivity analyses, and publication biases were estimated. Between IL-10-1082 GG-plus-GA genotypes with the risk of developing gastric cancer, statistically significant association could be noted with overall gastric cancer, being mainly in Asian subgroup, large sample subgroup, high quality subgroup, intestinal-type subgroup, cardia-type subgroup, and some genotyping method subgroups. Our meta-analysis indicates that IL-10-1082 GG-plus-GA genotypes are associated with the overall risk of developing gastric cancer and seem to be more susceptible to overall gastric cancer in Asian populations. IL-10-1082 GG-plus-GA genotypes are more associated with the pathologically intestinal-type gastric cancer or anatomically cardia-type gastric cancer.
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2.10Impact points
Correlation of aberrant expression of CD133 with FHIT and malignant phenotype of colorectal adenocarcinoma.
International journal of colorectal disease. 02/2012;
BACKGROUND: The relationship between the expression of CD133 and fragile histidine triad (FHIT) or prognosis in Chinese colorectal adenocarcinoma is unknown and needs to be explored. MATERIAL AND METHODS: The samples of colorectal adenocarcinoma from 200 Chinese patients with follow-up were analyzed... [more] BACKGROUND: The relationship between the expression of CD133 and fragile histidine triad (FHIT) or prognosis in Chinese colorectal adenocarcinoma is unknown and needs to be explored. MATERIAL AND METHODS: The samples of colorectal adenocarcinoma from 200 Chinese patients with follow-up were analyzed for the expression of CD133 and FHIT proteins by immunohistochemical method. RESULTS: CD133 was highly expressed in up to 42.0% (84/200) of this group of colorectal adenocarcinomas. The expression of CD133 was significantly higher in carcinoma than in normal (P = 0.0001) and in adenomatous mucosas (P = 0.004). CD133 positively corresponds to histological grade, clinical stage, regional lymphatic metastasis, and distant metastasis (all P < 0.05). The mean overall survival time was shorter in patients with CD133 high expression than in those with CD133 low expression (P = 0.0001). The expression of CD133 was inversely correlative with that of FHIT (r = -0.464, P = 0.0001) in colorectal adenocarcinoma. CD133 was an independent prognostic factor (P = 0.0001). CONCLUSIONS: The expression of CD133 may be inversely correlated with the expression of FHIT. It is suggested that CD133 may play an important role in the evolution of colorectal adenocarcinoma and be considered as a potential marker for the prognosis.
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Acute toxicity of chlorobenzenes in Tetrahymena: Estimated by microcalorimetry and mechanism.
Environmental toxicology and pharmacology. 02/2012; 33(3):377-85.
The toxicity of chlorobenzenes to Tetrahymena growth metabolism was studied by microcalorimetry. The growth constant (k), peak time (T) and generation times (T(G)) were calculated. IC(50) of chlorobenzenes was obtained through the kinetic parameters. The results suggested that the order of toxicity ... [more] The toxicity of chlorobenzenes to Tetrahymena growth metabolism was studied by microcalorimetry. The growth constant (k), peak time (T) and generation times (T(G)) were calculated. IC(50) of chlorobenzenes was obtained through the kinetic parameters. The results suggested that the order of toxicity was 1,2,4-trichlorobenzene>o-dichlorobenzene>p-dichlorobenzene>m-dichlorobenzene>chlorobenzene. ATR-FTIR spectra revealed that amide groups and PO(2)(-) of the phospholipid phospho-diester, both in the hydrophobic end exposed to the outer layer, were the easiest to be damaged. The relationship between IC(50) and chemicals structure parameters (E(LUMO), E(HOMO), logK(OW), ∑Q(R), ΔQ(πR) and ΔE), indicated that the more chlorine atoms were substituted, the greater the toxicity was. Chlorobenzenes have toxicity of non-polar narcosis. Their toxicity is proportional to their concentrations at the site of action, and caused by membrane perturbation.
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3.03Impact points
Adherence and associated virulence gene expression in acid treated E. coli O157:H7 in vitro and in ligated pig intestine.
Microbiology (Reading, England). 02/2012;
Escherichia coli O157:H7 that interact with intestinal epithelial cells in animals and humans do so after passage through the low pH in the stomach. This study compared adherence and its associated virulence gene expression in acid-treated (AT) and non-acid treated (NAT) Escherichia coli O157:H7 str... [more] Escherichia coli O157:H7 that interact with intestinal epithelial cells in animals and humans do so after passage through the low pH in the stomach. This study compared adherence and its associated virulence gene expression in acid-treated (AT) and non-acid treated (NAT) Escherichia coli O157:H7 strain 86-24 in vitro and in ligated pig intestine. It was found that AT O157:H7 had a decreased adherence phenotype in vitro, which was accompanied by a significant decrease in expression of stcE and toxB but not of the LEE genes. gadE, a key regulator of acid-resistance, genes involved in in quorum sensing, and global regulators cyaA, hfq, lrp, fis and himA were highly expressed. Notably, expression of ureD was increased 29-fold. AT O157:H7 colonized the pig intestine as effectively as NAT O157:H7 bacteria. Expression of 70 of 73 virulence genes from bacteria recovered from the intestine was similar between AT and NAT O157:H7 except ureD, pagC and bax, whose level of expression was reduced in the AT bacteria. Genes involved in acid response, regulators gadE, cyaA and hfq, and toxin synthesis (stx2A and stx2B) were expressed at significantly reduced levels in the intestine. Expression of the LEE and putative adhesion factors ehaA, cahA, iha and lpf2, as well as ureD was high in the intestine. These data indicate that AT O157:H7 bacteria behave differently in vitro from in vivo and that passage of O157:H7 bacteria through the low pH of the stomach may have little effect on virulence of the bacteria in the intestine.
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[Effect of pemetrexed plus platinum for chemotherapy-naive advanced non-small cell lung cancer].
Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases. 02/2012; 35(2):97-101.
To evaluate the effect of pemetrexed plus platinum for chemotherapy-naive advanced non-small cell lung cancer (NSCLC), and to explore thymidylate synthetase (TS) expression as the predictive and prognostic factor for this treatment. This retrospective study enrolled 51 patients with chemotherapy-nai... [more] To evaluate the effect of pemetrexed plus platinum for chemotherapy-naive advanced non-small cell lung cancer (NSCLC), and to explore thymidylate synthetase (TS) expression as the predictive and prognostic factor for this treatment. This retrospective study enrolled 51 patients with chemotherapy-naive advanced NSCLC (non-squamous) treated at Department of Thoracic Medical Oncology in Beijing Cancer Hospital from Jan 2008 to Oct 2009. All patients received pemetrexed plus platinum as first-line treatment. TS expression was detected in 30 patients who had enough tissue samples by immunohistochemistry. The objective response rate (ORR) was 37.3%. Median progression-free surrival (PFS) was 5.3 months (95%CI: 3.9 - 6.7), and median overall surrival (OS) was 19.0 months (95%CI: 11.6 - 26.4). Univariate analysis showed that gender, pathology, smoking status and response were significantly correlated with OS. Cox-regression analysis showed that pathology was an independent prognostic factor. Rate of Grade 3/4 adverse events was low. In 30 patients with enough tissue samples were available, TS expression positive rate was 33.3% (10/30). Chi-square test showed that TS expression was not associated with ORR. Multivariate analysis showed that pathology, response and TS expression (P = 0.003, 0.005 and 0.001, respectively) were the prognostic factors. The therapeutic effect and tolerance of pemetrexed plus platinum regiment were definite as first-line treatment for chemotherapy-naive advanced NSCLC, and TS expression was an independent prognostic factor.
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5.00Impact points
Gastrin inhibits a novel, pathological colon cancer signaling pathway involving EGR1, AE2, and P-ERK.
Journal of molecular medicine (Berlin, Germany). 01/2012;
Human anion exchanger 2 (AE2) is a plasma membrane protein that regulates intracellular pH and cell volume. AE2 contributes to transepithelial transport of chloride and bicarbonate in normal colon and other epithelial tissues. We now report that AE2 overexpression in colon cancer cells is correlated... [more] Human anion exchanger 2 (AE2) is a plasma membrane protein that regulates intracellular pH and cell volume. AE2 contributes to transepithelial transport of chloride and bicarbonate in normal colon and other epithelial tissues. We now report that AE2 overexpression in colon cancer cells is correlated with expression of the nuclear proliferation marker, Ki67. Survival analysis of 24 patients with colon cancer in early stage or 33 patients with tubular adenocarcinoma demonstrated that expression of AE2 is correlated with poor prognosis. Cellular and molecular experiments indicated that AE2 expression promoted proliferation of colon cancer cells. In addition, we found that transcription factor EGR1 underlies AE2 upregulation and the AE2 sequester p16INK4a (P16) in the cytoplasm of colon cancer cells. Cytoplasmic P16 enhanced ERK phosphorylation and promoted proliferation of colon cancer cells. Gastrin inhibited proliferation of colon cancer cells by suppressing expression of EGR1 and AE2 and by blocking ERK phosphorylation. Taken together, our data describe a novel EGR1/AE2/P16/P-ERK signaling pathway in colon carcinogenesis, with implications for pathologic prognosis and for novel therapeutic approaches.
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2.09Impact points
Comparison of Standard- and Low-Tube Voltage 320-Detector Row Volume CT Angiography in Detection of Intracranial Aneurysms with Digital Subtraction Angiography as Gold Standard.
Academic radiology. 12/2011; 19(3):281-8.
The aim of this study was to prospectively assess the effect of low-tube voltage (80 kVp) 320-detector row volume computed tomographic (CT) angiography (L-VCTA) in the detection of intracranial aneurysms, with three-dimensional (3D) spin digital subtraction angiography (DSA) as the gold standard. Fo... [more] The aim of this study was to prospectively assess the effect of low-tube voltage (80 kVp) 320-detector row volume computed tomographic (CT) angiography (L-VCTA) in the detection of intracranial aneurysms, with three-dimensional (3D) spin digital subtraction angiography (DSA) as the gold standard. Forty-eight patients with clinically suspected subarachnoid hemorrhages were divided into two groups. One group underwent L-VCTA and DSA, while the other group underwent conventional-tube voltage (120 kVp) volume CT angiography (C-VCTA) and DSA. Vascular enhancement, image quality, detection accuracy of aneurysms, and radiation dose were compared between the two groups. For objective image quality, the L-VCTA group had higher mean vessel attenuation, correlated with higher image noise and lower signal-to-noise ratio, than the C-VCTA group. For subjective image quality, there were no significant differences between the two groups regarding scores for arterial enhancement, depiction of small arterial detail, interference of venous structures, and overall image quality scores. The mean effective dose for the L-VCTA group was significantly lower than for the C-VCTA group (0.56 ± 0.25 vs 1.84 ± 0.002 mSv), with a reduction of radiation dose of 69.73%. With 3D DSA as the reference standard, the sensitivity, specificity, and accuracy in the L-VCTA and C-VCTA groups were 94.12%, 100%, 94.4% and 100%, 100%, and 100%, respectively. In both groups, there were significant correlations for maximum aneurysm diameter measurements between volume CT angiography and 3D DSA; no statistical difference in the mean maximum diameter of each aneurysm was measured between volume CT angiography and 3D DSA. L-VCTA is helpful in detecting intracranial aneurysms, with results similar to those of 3D DSA, but at a lower radiation dose than C-VCTA.
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5.38Impact points
Synthesis of Fe3O4@phenol formaldehyde resin core-shell nanospheres loaded with Au nanoparticles as magnetic FRET nanoprobes for detection of thiols in living cells.
Chemistry (Weinheim an der Bergstrasse, Germany). 12/2011; 18(4):1154-60.
A magnetic, sensitive, and selective fluorescence resonance energy transfer (FRET) probe for detection of thiols in living cells was designed and prepared. The FRET probe consists of an Fe(3)O(4) core, a green-luminescent phenol formaldehyde resin (PFR) shell, and Au nanoparticles (NPs) as FRET quen... [more] A magnetic, sensitive, and selective fluorescence resonance energy transfer (FRET) probe for detection of thiols in living cells was designed and prepared. The FRET probe consists of an Fe(3)O(4) core, a green-luminescent phenol formaldehyde resin (PFR) shell, and Au nanoparticles (NPs) as FRET quenching agent on the surface of the PFR shell. The Fe(3)O(4) NPs were used as the core and coated with green-luminescent PFR nanoshells by a simple hydrothermal approach. Au NPs were then loaded onto the surface of the PFR shell by electric charge absorption between Fe(3)O(4)@PFR and Au NPs after modifying the Fe(3)O(4)@PFR nanocomposites with polymers to alter the charge of the PFR shell. Thus, a FRET probe can be designed on the basis of the quenching effect of Au NPs on the fluorescence of Fe(3)O(4)@PFR nanocomposites. This magnetic and sensitive FRET probe was used to detect three kinds of primary biological thiols (glutathione, homocysteine, and cysteine) in cells. Such a multifunctional fluorescent probe shows advantages of strong magnetism for sample separation, sensitive response for sample detection, and low toxicity without injury to cellular components.
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8.35Impact points
Bioinformatics analysis of proteomic profiles during the process of anti-Thy1 nephritis.
Molecular & cellular proteomics : MCP. 12/2011;
Anti-Thy1 nephritis is a well-established experimental mesangial proliferative nephritis model. Exploring the molecular mechanisms of pathophysiology in anti-Thy1 nephritis may elucidate the pathogeneses of mesangial proliferation. We examined the roles and acting mechanisms of differentially expres... [more] Anti-Thy1 nephritis is a well-established experimental mesangial proliferative nephritis model. Exploring the molecular mechanisms of pathophysiology in anti-Thy1 nephritis may elucidate the pathogeneses of mesangial proliferation. We examined the roles and acting mechanisms of differentially expressed proteins (DEPs) by bioinformatics analysis of glomeruli proteomic profiles during the course of anti-Thy1 nephritis. In total, 108 DEPs were found by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), and 40 DEPs were identified by MALDI-TOF and LC-MS. DEPs were classified into five clusters (Clusters 1-5), according to their expression trends using Cluster 3.0 software, involved in regulating biological processes such as the stress response, cell proliferation, apoptosis, energy metabolism, transport, and the actin cytoskeleton. The expression patterns of ten DEPs, distributed across five clusters, including AKR1A1, AGAT, ATP6V1B2, HIBADH, MDH1, MPST, NIT2, PRDX6, PSMB7, and TPI1, were validated by Western blotting. Based on Western blotting and immunohistochemistry, we also found that the DEP FHL2, which was primarily expressed in the mesangial region, was downregulated on days 3 and 5, and upregulated on day 10. In vitro, we found that FHL2 overexpression induced mesangial cell proliferation by increasing the number of S-phase cells and decreasing G2/M-phase cells, while inhibiting FHL2 had the opposite effect. This study explored novel DEPs and their expression patterns during anti-Thy1 nephritis, and elucidated FHL2's effect on mesangial cell proliferation. These results will contribute to our understanding of the pathogenesis of mesangial proliferation.
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2.07Impact points
Spiro[pyrrolidine-2,3'-oxindole] derivatives synthesized by novel regionselective 1,3-dipolar cycloadditions.
Molecular diversity. 12/2011;
A series of spiro-oxindole derivatives was synthesized by novel regioselective 1,3-dipolar cycloadditions of isatin, α-amino acids, and (E)-β-aryl-nitro-olefins. Regioisomers were produced in each reaction and the major products showed different regioselectivity compared to previously reported spiro... [more] A series of spiro-oxindole derivatives was synthesized by novel regioselective 1,3-dipolar cycloadditions of isatin, α-amino acids, and (E)-β-aryl-nitro-olefins. Regioisomers were produced in each reaction and the major products showed different regioselectivity compared to previously reported spiro-oxindole derivatives.
Following (38)
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Barnabas Abban
Huawei Technologies Co. Ltd. -
Wang Weibing
University of Science and Technology of China -
Jayanta Roy-Chowdhury
Albert Einstein College of Medicine -
Robert I Glazer
Georgetown University -
Topics (244)
