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Lei Xu

Publications and source records attributed to Lei Xu.

At least 55 records · Page 3Linked to original sources
PubMed2005

Robust prostate cancer marker genes emerge from direct integration of inter-study microarray data.

MOTIVATION: DNA microarray data analysis has been used previously to identify marker genes which discriminate cancer from normal samples. However, due to the limited sample size of each study, there are few common markers among different studies of the same cancer. With the rapid accumulation of microarray data, it is of great interest to integrate inter-study microarray data to increase sample size, which could lead to the discovery of more reliable markers. RESULTS: We present a novel, simple method of integrating different microarray datasets to identify marker genes and apply the method to prostate cancer datasets. In this study, by applying a new statistical method, referred to as the top-scoring pair (TSP) classifier, we have identified a pair of robust marker genes (HPN and STAT6) by integrating microarray datasets from three different prostate cancer studies. Cross-platform validation shows that the TSP classifier built from the marker gene pair, which simply compares relative expression values, achieves high accuracy, sensitivity and specificity on independent datasets generated using various array platforms. Our findings suggest a new model for the discovery of marker genes from accumulated microarray data and demonstrate how the great wealth of microarray data can be exploited to increase the power of statistical analysis. CONTACT: leixu@jhu.edu.

Algorithms↗
PubMed2005

Simple decision rules for classifying human cancers from gene expression profiles.

MOTIVATION: Various studies have shown that cancer tissue samples can be successfully detected and classified by their gene expression patterns using machine learning approaches. One of the challenges in applying these techniques for classifying gene expression data is to extract accurate, readily interpretable rules providing biological insight as to how classification is performed. Current methods generate classifiers that are accurate but difficult to interpret. This is the trade-off between credibility and comprehensibility of the classifiers. Here, we introduce a new classifier in order to address these problems. It is referred to as k-TSP (k-Top Scoring Pairs) and is based on the concept of 'relative expression reversals'. This method generates simple and accurate decision rules that only involve a small number of gene-to-gene expression comparisons, thereby facilitating follow-up studies. RESULTS: In this study, we have compared our approach to other machine learning techniques for class prediction in 19 binary and multi-class gene expression datasets involving human cancers. The k-TSP classifier performs as efficiently as Prediction Analysis of Microarray and support vector machine, and outperforms other learning methods (decision trees, k-nearest neighbour and naïve Bayes). Our approach is easy to interpret as the classifier involves only a small number of informative genes. For these reasons, we consider the k-TSP method to be a useful tool for cancer classification from microarray gene expression data. AVAILABILITY: The software and datasets are available at http://www.ccbm.jhu.edu CONTACT: actan@jhu.edu.

Algorithms↗
PubMed2005

Blocking platelet-derived growth factor-D/platelet-derived growth factor receptor beta signaling inhibits human renal cell carcinoma progression in an orthotopic mouse model.

Renal cell carcinoma is a highly malignant and often fatal disease of the kidney. It is difficult to treat, often because metastases are common at the time of presentation. Platelet-derived growth factor-D (PDGF-D) is a newly discovered member of the PDGF family; its function in tumor progression is largely unknown. Here, we examined the expression level of PDGF-D in human renal cell carcinoma by immunohistochemical staining using tissue arrays. We showed that human renal cell carcinoma expresses high levels of PDGF-D protein. The human renal cell carcinoma cell line SN12-C was stably transfected with pdgf-d cDNA. Overexpression of PDGF-D in SN12-C cells promoted tumor growth, angiogenesis, and metastasis of human renal cell carcinoma in an orthotopic severe combined immunodeficient (SCID) mouse model. PDGF-D overproduction in SN12-C cells increased the proliferation and migration of mural cells in vitro and improved perivascular cell coverage in vivo. Overexpression of PDGF-D led to increased expression of angiopoietin-1 and matrix metalloproteinase-9 in tumor tissues. ShRNAi and Gleevec were used to block PDGF-D expression and PDGF receptor beta (PDGFRbeta) signaling. Inhibition of PDGF-D expression by short hairpin RNA interference (shRNAi) and blockage of PDGFRbeta signaling by Gleevec inhibited the growth and lung metastasis of SN12-C cells grown orthotopically in SCID mice. Thus, PDGF-D is a potential candidate for controlling the progression of metastatic renal cell carcinoma. This opens up an avenue of investigation into novel therapeutic strategies for the treatment of renal cell carcinoma, including the use of recently developed tyrosine kinase inhibitors, such as Gleevec, which inhibit PDGF activity through inhibition of its receptor tyrosine kinase.

Angiopoietin-1↗
PubMed2005

NO mediates mural cell recruitment and vessel morphogenesis in murine melanomas and tissue-engineered blood vessels.

NO has been shown to mediate angiogenesis; however, its role in vessel morphogenesis and maturation is not known. Using intravital microscopy, histological analysis, alpha-smooth muscle actin and chondroitin sulfate proteoglycan 4 staining, microsensor NO measurements, and an NO synthase (NOS) inhibitor, we found that NO mediates mural cell coverage as well as vessel branching and longitudinal extension but not the circumferential growth of blood vessels in B16 murine melanomas. NO-sensitive fluorescent probe 4,5-diaminofluorescein imaging, NOS immunostaining, and the use of NOS-deficient mice revealed that eNOS in vascular endothelial cells is the predominant source of NO and induces these effects. To further dissect the role of NO in mural cell recruitment and vascular morphogenesis, we performed a series of independent analyses. Transwell and under-agarose migration assays demonstrated that endothelial cell-derived NO induces directional migration of mural cell precursors toward endothelial cells. An in vivo tissue-engineered blood vessel model revealed that NO mediates endothelial-mural cell interaction prior to vessel perfusion and also induces recruitment of mural cells to angiogenic vessels, vessel branching, and longitudinal extension and subsequent stabilization of the vessels. These data indicate that endothelial cell-derived NO induces mural cell recruitment as well as subsequent morphogenesis and stabilization of angiogenic vessels.

Animals↗
PubMed2005

Relationship between abnormality of FHIT gene and EBV infection in gastric cancer.

AIM: To examine the aberrant expression of fragile histidine triad (FHIT) gene and protein in gastric cancer, and to evaluate the role of FHIT gene and the relationship between FHIT gene and EBV infection in gastric carcinogenesis. METHODS: FHIT transcripts were detected by nested RT-PCR in 30 cases of gastric cancer and their products were sequenced. FHIT protein was detected by Western blot. EBV infection was detected by PCR method in 50 cases of gastric cancer. RESULTS: The wild type transcripts were detected in all 30 matched normal tissues of gastric cancer. Aberrant transcripts were found in 11/30 (36.7%) gastric cancerous tissues. Sequencing analysis of the aberrant fragments found an RT-PCR product missing exons 5-7 in one case of gastric cancer, and another product missing exons 4-7. Four of ten (40.0%) cases of primary gastric cancer showed absent or decreased expression of FHIT protein as compared with their matched normal tissues. EBV was detected in 5/50 (10%) gastric cancers, among which 4/5 (80%) had aberrant transcripts of FHIT gene. CONCLUSION: Loss of FHIT gene or FHIT protein p1ays an important role in carcinogenesis, development and progression of gastric cancer. EBV infection might influence carcinogenesis of gastric cancer by inducing the abnormality of FHIT gene.

Acid Anhydride Hydrolases↗
PubMed2005

Activity assay of His-tagged E. coli DNA photolyase by RP-HPLC and SE-HPLC.

Escherichia coli DNA photolyase was expressed as C-terminal 6x histidine-fused protein. Purification of His-tagged E. coli DNA photolyase was developed using immobilized metal affinity chromatography with Chelating Sepharose Fast Flow. By one-step affinity chromatography, approximate 4.6 mg DNA photolyase was obtained from 400 ml E. coli culture. The purified His-tagged enzyme was combined with two chromophors, FADH and MTHF. Using the oligonucleotide containing cyclobutane pyrimidine dimer as substrate, both reversed-phase high-performance liquid chromatography and size-exclusion high-performance liquid chromatography were developed to measure the enzyme activity. The enzyme was found to be able to repair the cyclobutane pyrimidine dimer with the turnover rate of 2.4 dimers/photolyase molecule/min.

Chromatography, High Pressure Liquid↗
PubMed2005

Drop splashing on a dry smooth surface.

The corona splash due to the impact of a liquid drop on a smooth dry substrate is investigated with high-speed photography. A striking phenomenon is observed: splashing can be completely suppressed by decreasing the pressure of the surrounding gas. The threshold pressure where a splash first occurs is measured as a function of the impact velocity and found to scale with the molecular weight of the gas and the viscosity of the liquid. Both experimental scaling relations support a model in which compressible effects in the gas are responsible for splashing in liquid solid impacts.

Journal Article↗
PubMed2005

An efficient approach for theoretical study on the low-energy isomers of large fullerenes C90-C140.

An approach that consists of a molecular mechanics method based on the second generation reactive empirical bond order (REBO) potential and the more accurate semiempirical method PM3 (Parametric Method No. 3) was proposed to predict the energetically favored isomers of the fullerenes from C90 to C140 at the semiempirical level. All the 578,701 isolated-pentagon-rule isomers of fullerenes from C90 to C140 were enumerated from topological structures and systematically searched using an energy minimization method to select the best 100 low-energy isomers based on the REBO potential for each fullerene. Then these candidate isomers were further optimized by PM3 and ranked again to determine the top low-energy isomers. This approach was applied to calculate the energetically favored isomers of C90-C140. The results of C90-C120 are in good agreement with the published results by quantum-chemical methods. Furthermore, the top five low-energy isomers of C90-C120, as well as C122-C140 which have scarcely been systematically studied before, are also predicted with the approach. The analysis of the structures showed that the hexagon-neighbor rule is an important factor to the stability of C90-C140. The time cost for the systematical search based on the REBO potential was also discussed. It indicates that the approach proposed is efficient for predicting the energetically favored isomers of large fullerenes at the semiempirical level.

Journal Article↗
PubMed2005

High-power efficient continuous-wave TEM00 intracavity frequency-doubled diode-pumped Nd:YLF laser.

We describe experimental results with a diode-pumped, intracavity-doubled cw Nd:YLF laser in multilongitudinal mode and TEM00 spatial transverse mode with a critical phase-matched lithium triborate crystal. Taking into account the thermal effects of Nd:YLF, energy-transfer upconversion, and the thermal fracture limit, we set up a power-scaling model to optimize and design a fundamental diode-pumped Nd:YLF laser. A highly efficient second-harmonic laser was achieved, based on the optimized cavity design. A second-harmonic-generation output power of 20.5 W at a wavelength of 527 nm was obtained at an incident pump power of 60 W, corresponding to an optical-to-optical efficiency of 34.2%. The TEM00 mode green laser operates at a measured M2 parameter of 1.2. The instability of the green laser power is less than +/- 1% RMS.

Journal Article↗
PubMed2005

Effect of glutamate on inflammatory responses of intestine and brain after focal cerebral ischemia.

AIM: To study the modulation of glutamate on post-ischemic intestinal and cerebral inflammatory responses in a ischemic and excitotoxic rat model. METHODS: Adult male rats were subjected to bilateral carotid artery occlusion for 15 min and injection of monosodium glutamate intraperitoneally, to decapitate them at selected time points. Tumor necrosis factor alpha (TNF-alpha) level and nuclear factor kappa B (NF-kappaB) activity were determined by enzyme-linked immunosorbant assay (ELISA) and electrophoretic mobility shift assay (EMSA), respectively. Hemodynamic parameters were monitored continuously during the whole process of cerebral ischemia and reperfusion. RESULTS: Monosodium glutamate (MSG) treated rats displayed statistically significant high levels of TNF-alpha in cerebral and intestinal tissues within the first 6 h of ischemia. The rats with cerebral ischemia showed a minor decrease of TNF-alpha production in cerebral and intestinal tissues. The rats with cerebral ischemia and treated with MSG displayed statistically significant low levels of TNF-alpha in cerebral and intestinal tissues. These results correlated significantly with NF-kappaB production calculated at the same intervals. During experiment, the mean blood pressure and heart rates in all groups were stable. CONCLUSION: Glutamate is involved in the mechanism of intestinal and cerebral inflammation responses. The effects of glutamate on cerebral and intestinal inflammatory responses after ischemia are up-regulated at the transcriptional level, through the NF-kappaB signal transduction pathway.

Animals↗
PubMed2005

Protein abnormality in denervated skeletal muscles from patients with brachial injury.

A proteomic analysis was performed to compare protein expression between normal sternocleidomastoid muscle and denervated muscle. Two-dimensional electrophoresis (2-DE) of muscle proteins showed that 26 proteins among about 800 spots in 2-DE gel displayed a decrease and 6 proteins an increase in expression in muscles with denervation atrophy compared to normal controls; the identified proteins that were abnormally expressed could be generally grouped together as metabolic proteins, chaperone proteins, and contractile-apparatus proteins. The significance of these altered proteins is discussed. In particular, the decrease in hD54 may reduce the activity of transmembrane signaling in atrophied muscle, while the disregulation of DnaJC 1 showed a possible role of molecular chaperones in the functional recovery of atrophied muscles.

Adult↗
PubMed2005

Cystatin C prevents degeneration of rat nigral dopaminergic neurons: in vitro and in vivo studies.

Destruction of nigrostriatal dopaminergic (DA) pathway triggers various persistent responses, such as inflammation and increased synthesis of neural growth factors, both in striatum and in substantia nigra. The pathological processes involved in such responses are poorly characterized and could contribute to secondary damage and/or regeneration in the central nervous system (CNS). Cystatin C was previously implicated in the process of neurodegeneration. However, its biological role during neurodegeneration is not understood and remains controversial. The present study identified an increased cystatin C mRNA level in the DA-depleted rat striatum, starting from the second week following a 6-OHDA-induced lesion. Immunohistochemical analysis confirmed the increase in cystatin C protein level in the striatum following DA depletion. Double-labeled fluorescence immunohistochemistry revealed that nigrostriatal neurons, astrocytes, and microglia contributed to the elevated level of cystatin C. Exposure to 6-hydroxydopamine, a DA-specific neurotoxin, resulted in DA neurons loss in the fetal mesencephalic cultures, an effect which could be partially reversed by treatment with cystatin C. Moreover, in vivo DA neurons survival study showed that administration of cystatin C in rats with 6-OHDA-induced lesion partially rescued the nigral DA neurons. The results indicate that the 6-OHDA lesioning induced a relatively slow but sustained up-regulation of cystatin C expression and suggest that the inhibitor may exert a neuroprotective action on DA neurons. The findings raise the possibility that cysteine proteinase inhibitors may be new candidates for neuroprotective treatment of Parkinson's disease. Cystatin C may be useful therapeutically in limiting neuropathy in Parkinson's disease.

Animals↗
PubMed2005

[Genetic polymorphisms of nucleotide repair gene hMTH1 in southern Chinese Han population].

In order to study the genetic polymorphisms of nucleotide repair gene hMTH1 in southern Chinese Han population, the polymorphisms of the gene's promoter and its five exons among peripheral blood lymphocytes of 172 Chinese Han people were analyzed with polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing. The sequences of the promoter and exon 1 of hMTH1 gene were conserved. A T to C polymorphism was detected at the 73th base in exon 2. The genotype frequencies of TT and TC were 93.02% and 6.98%, respectively. The allelic frequencies of T and C were 96.51% and 3.49%, respectively. A T to C polymorphism was detected at codon 45 in exon 3, which was first reported. The genotype frequencies of TT and TC were 95.35% and 4.65%, respectively. The allelic frequencies of T and C were 97.67% and 2.33%, respectively. A G to A polymorphism was detected at codon 83 in exon 4. The genotype frequencies of GG and GA were 89.53% and 10.47%, respectively. The allelic frequencies of G and A were 94.77% and 5.23%, respectively. A C to T polymorphism was detected at codon 119 in exon 5. The genotype frequencies of CC and CT were 95.93% and 4.07%, respectively. The allelic frequencies of C and T were 97.97% and 2.03%, respectively.

Asian People↗
PubMed2005

[Experimental study of the safety of sustained inflation strategy in acute respiratory distress syndrome in sheep].

OBJECTIVE: To evaluate the effects of lung recruitment maneuver (RM) on hemodynamics and lung structure with sustained inflation (SI) in acute respiratory distress syndrome (ARDS) in sheep, to look for a safe range of pressure and time of SI. METHODS: Fourteen anaesthetized sheep were subjected to lung lavage through a broncho-fibroscope to reproduce ARDS, and quasi-static pressure-volume (P-V) curves were obtained with low flow technique. The upper inflection point (UIP) and the lower inflection point (LIP) were found, and then 5 cm H(2)O (1 cm H(2)O=0.098 kPa) below UIP, UIP, 10 cm H(2)O above UIP, 20 cm H(2)O above UIP as the peak pressure of SI were selected as the test pressure. They were randomized to four groups (U-5, U+0, U+10, U+20). The duration of SI was 60 seconds. Hemodynamics and oxygenation indexes were monitored and recorded during and after SI until the study was terminated 2 hours later, then CT and lung tissue biopsy were performed. RESULTS: Pneumothorax was found in U+20 groups, resulting in the death of sheep. Hemodynamics was affected significantly in other groups during SI. In U+10 groups, cardiac output (CO) and cardiac index (CI) were lowered at 15 seconds after RM began, and recovered slowly after RM; in U+0 group and U-5 group, the entire RM could be carried out to the end, and biopsy showed bullous emphysema in U+0 group. CONCLUSION: The impairment of the hemodynamics and damage to the lung structure should be prevented when RM is performed in ARDS patients, and the inflation pressure should be limited within the range of UIP or 5 cm H(2)O under UIP to avoid adverse effect on hemodynamics.

Animals↗
PubMed2005

[Clinical comparative study of airway pressure release ventilation and continuous positive airway pressure ventilation].

OBJECTIVE: To evaluate the effects of airway pressure release ventilation (APRV) and continuous positive airway pressure (CPAP) on hemodynamics, lung mechanics and oxygen metabolism index. METHODS: Fifteen ARDS cases ventilated and monitored by the pulse contour method (PiCCO) were randomized into APRV group and CPAP group, then lung recruitment maneuver (RM) was executed every 4 hours. In APRV group, Phigh was 35 cm H(2)O (1 cm H(2)O=0.098 kPa) and Plow was set at lower inflection point (LIP) of the static pressure-volume (P-V) curve. In CPAP group, CPAP was also 35 cm H(2)O. The duration of RM in both groups was 40 seconds. Before and after RM the parameters of lung mechanics, oxygen metabolism index and hemodynamics were monitored and compared. RESULTS: (1) In APRV group cardiac index (CI) was decreased slightly during RM with shorter duration than CPAP group. (2) The parameters of lung mechanics and oxygenation were improved significantly in both groups, and they were better in APRV group than CPAP group. CONCLUSION: In APRV group sedation can be abstained during RM, and the hemodynamics were hardly disturbed. Improvement of lung mechanics and oxygenation is much better with APRV than CPAP mode.

Aged↗
PubMed2005

[Immunostimulatory effect of human peripheral blood dendritic cells transfected by adeno-associated virus containing Her2/neu gene].

OBJECTIVE: To observe the immunostimulatory effect of human peripheral blood dendritic cells (DCs) transfected by Her2/neu gene delivered by adeno-associated virus. METHODS: The mononuclear cells in healthy donors were isolated by Ficol-Hypaque density gradient separation and divided into transfection group and control group without transfection by the recombinant virus. The cells were initially cultured in RPMI 1640 medium supplemented with 10% AB human serum, followed by addition of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and tumor necrosis factor (TNF)-alpha into the medium. The surface markers of DC were detected by flow cytometry, allogeneic mixed lymphocyte reaction assayed by 3H-TdR incorporation and the specific killing activity of T cells evaluated by MTT assay. RESULTS: The expression rates of CD1a, CD86 and CD83 of the transfected DCs were 98.10%, 99.42%, and 84.59%, and those of the non-transfected DCs were 92.69%, 98.07%, and 82.72%, respectively, showing no obvious differences between the two groups. The rates of CD4 and CD80 expression were 61.02% and 97.61%, respectively, in the transfected DCs, significantly higher than those in the non-transfected cells (36.19% and 55.5%). Both groups of DCs stimulated a strong T cell proferation response. The transfected DCs were capable of inducing specific killing of the target tumor cells, with the highest killing rate of (39.7+/-7.2)%. CONCLUSION: The immunostimulatory effect of human peripheral blood DCs can be enhanced by Her2/neu gene transfection mediated by adeno-associated virus.

Cells, Cultured↗