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Articles by X Lu
Total Records ( 12 ) for X Lu
  D Zheng , X Li , H Xu , X Lu , Y Hu and W. Fan
 

Docetaxel (Doc) has extraordinary activities against a variety of solid tumors. However, the clinical efficacy of Doc is limited due to its poor solubility, low selective distribution, fast elimination in vivo, etc. In the present study, Doc was incorporated into the core-shell structure of nanoparticles prepared based on our previous work. The obtained docetaxel-loaded nanoparticles (DOCNP) were characterized with various biophysical methodologies, and its antitumor efficacy against malignant melanoma was evaluated both in vitro and in vivo. Our results indicated that Doc could be incorporated into the nanoparticles with high encapsulation efficiency (>90%). The incorporated Doc can be released from DOCNP in a sustained manner. In vitro cytotoxicity studies indicated that DOCNP could effectively kill B16 cells and show a dose- and time-dependent efficacy. Furthermore, intratumoral administration revealed that DOCNP has significantly higher antitumor effect and lower toxicity to normal cells and tissues than free Doc. These results suggest that DOCNP may be a promising drug delivery system in therapy for malignant melanoma.

  X Jin , H Mei , X Li , Y Ma , A. h Zeng , Y Wang , X Lu , F Chu , Q Wu and J. Zhu
 

We studied the apoptosis-inducing properties of the antimicrobial peptide cecropin of Musca domestica in human hepatocellular carcinoma cell line BEL-7402 and its underlying mechanism. Proliferation inhibition of the human hepatocellular carcinoma BEL-7402 cells and the human normal liver cells were determined by the MTT assay, and the cell viability was determined by trypan blue dye exclusion assay. The apoptotic tumor cells treated with cecropin were examined by transmission electron microscopy and terminal-deoxynucleotidyl transferase mediated nick end labeling. The apoptosis rate was measured by flow cytometry (FCM) with PI/Annexin-V double staining. Western blot analysis and RT-PCR were used to determine the expression levels of proteins involved in apoptosis, such as Fas, Fas-L, caspase-8, and caspase-3. The experimental results showed that Musca domestica cecropin inhibited the proliferation of human hepatocellular carcinoma BEL-7402 cells in dose-dependent and time-dependent manners, without affecting the proliferation of normal liver cells. FCM showed that the cell apoptosis rates were 5.1 ± 0.11%, 8.1 ± 0.04%, and 10.9 ± 0.15% after the treating with 100 µM cecropin for 24, 48, and 72 h, respectively. The rates of apoptosis were 5.4 ± 0.14% and 8.0 ± 0.13% after the treating with 25 and 50 µM cecropin for 72 h, respectively. Western blot analysis and RT-PCR showed that the apoptosis-related molecules including Fas, Fas-L, caspase-8 and caspase-3 were activated. This study showed that the antimicrobial peptide cecropin-inducing apoptosis in human hepatocellular carcinoma BEL-7402 cells, which might be associated with upregulation of Fas, Fas-L, and caspase-8 and caspase-3 and triggering extrinsic apoptotic pathway.

  H Bao , H Guo , J Wang , R Zhou , X Lu and S. Shi
 

Summary: We introduce a new visual analytics tool named MapView to facilitate the representation of large-scale short reads alignment data and genetic variation analysis. MapView can handle hundreds of millions of short reads on a desktop computer with limited memory. It supports a compact alignment view for both single-end and paired end short reads, multiple navigation and zoom modes and multi-thread processing. Moreover, MapView offers automated genetic variation detection. MapView has been used in our lab and by over 10 research labs worldwide.

Availability: http://evolution.sysu.edu.cn/mapview/.

Contact: baohua100@hotmail.com; lssssh@mail.sysu.edu.cn

Supplementary information: Supplementary data are available at http://evolution.sysu.edu.cn/mapview/MVF.pdf

  F. L Xiang , X Lu , L Hammoud , P Zhu , P Chidiac , J Robbins and Q. Feng
 

Background— Soluble stem cell factor (SCF) has been shown to mobilize bone marrow stem cells and improve cardiac repair after myocardial infarction (MI). However, the effect of membrane-associated SCF on cardiac remodeling after MI is not known. The present study investigated the effects of cardiomyocyte-specific overexpression of the membrane-associated isoform of human SCF (hSCF) on cardiac function after MI.

Methods and Results— A novel mouse model with tetracycline-inducible and cardiac-specific overexpression of membrane-associated hSCF was generated. MI was induced by left coronary artery ligation. Thirty-day mortality after MI was decreased in hSCF/tetracycline transactivator (tTA) compared with wild-type mice. In vivo cardiac function was significantly improved in hSCF/tTA mice at 5 and 30 days after MI compared with wild-type mice. Endothelial progenitor cell recruitment and capillary density were increased and myocardial apoptosis was decreased in the peri-infarct area of hSCF/tTA mice. Myocyte size was decreased in hSCF/tTA mice 30 days after MI compared with WT mice. Furthermore, hSCF overexpression promoted de novo angiogenesis as assessed by matrigel implantation into the left ventricular myocardium.

Conclusions— Cardiomyocyte-specific overexpression of hSCF improves myocardial function and survival after MI. These beneficial effects of hSCF may result from increases in endothelial progenitor cell recruitment and neovascularization and decreases in myocardial apoptosis and cardiac remodeling.

  S Girotra , X Lu , I Popescu , M Vaughan Sarrazin , P. A Horwitz and P. Cram
  Background—

Hospital volume has been widely embraced as a proxy measure for hospital quality; little attention has been focused on an alternative quality measure–hospital specialization. Even though specialization occurs on a continuum, previous studies have only focused on a small number of highly specialized hospitals (single-specialty hospitals). Studies on the broad relationship between hospital specialization and outcomes after coronary artery bypass grafting (CABG) are limited.

Methods and Results—

We conducted a retrospective cohort study of 705 084 Medicare patients (1130 hospitals) who underwent CABG during 2001 to 2005. We stratified hospitals into quintiles, based on their degree of cardiac specialization (proportion of a hospital's Medicare discharges classified as Major Diagnostic Category 5–cardiovascular diseases). We compared patient and hospital characteristics and outcomes across quintiles of cardiac specialization. Patient characteristics were generally similar across quintiles, but mean annual CABG volume increased progressively from quintile 1 (least specialized) to quintile 5 (most specialized). Unadjusted 30-day mortality was similar at hospitals in quintiles 1 to 4 (4.8%), except quintile 5, where mortality was lower (4.3%). A strong inverse association was seen between hospital cardiac specialization and 30-day mortality after adjustment for patient characteristics (Ptrend=0.001). However, this was no longer significant after additional adjustment for CABG volume (Ptrend=0.65). Results were similar for other mortality outcomes and length of stay.

Conclusions—

After accounting for patient characteristics and CABG volume, greater cardiac specialization was not associated with clinically significant improvement in patient outcomes. This study calls into question the benefit of cardiac specialization for the vast majority of CABG-performing US hospitals.

  X Lu , Q Wang , G Hu , C Van Poznak , M Fleisher , M Reiss , J Massague and Y. Kang
 

Bone metastasis is mediated by complex interactions between tumor cells and resident stromal cells in the bone microenvironment. The functions of metalloproteinases in organ-specific metastasis remain poorly defined despite their well-appreciated role in matrix degradation and tumor invasion. Here, we show a mechanism whereby two distinct metalloproteinases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS1) and matrix metalloproteinase-1 (MMP1), orchestrate a paracrine signaling cascade to modulate the bone microenvironment in favor of osteoclastogenesis and bone metastasis. Proteolytic release of membrane-bound epidermal growth factor (EGF)-like growth factors, including Amphiregulin (AREG), heparin-binding EGF (HB-EGF), and transforming growth factor (TGF) from tumor cells suppress the expression of osteoprotegerin (OPG) in osteoblasts and subsequently potentiate osteoclast differentiation. EGF receptor (EGFR) inhibitors block osteolytic bone metastasis by targeting EGFR signaling in bone stromal cells. Furthermore, elevated MMP1 and ADAMTS1 expression is associated with increased risk of bone metastasis in breast cancer patients. This study established MMP1 and ADAMTS1 in tumor cells, as well as EGFR signaling in osteoblasts, as promising therapeutic targets for inhibiting bone metastasis of breast cancer.

  X Lu , J. A Shapiro , C. T Ting , Y Li , C Li , J Xu , H Huang , Y. J Cheng , A. J Greenberg , S. H Li , M. L Wu , Y Shen and C. I. Wu
 

Postmating reproductive isolation is often manifested as hybrid male sterility, for which X-linked genes are overrepresented (the so-called large X effect). In contrast, X-linked genes are significantly under-represented among testis-expressing genes. This seeming contradiction may be germane to the X:autosome imbalance hypothesis on hybrid sterility, in which the X-linked effect is mediated mainly through the misexpression of autosomal genes. In this study, we compared gene expression in fertile and sterile males in the hybrids between two Drosophila species. These hybrid males differ only in a small region of the X chromosome containing the Ods-site homeobox (OdsH) (also known as Odysseus) locus of hybrid sterility. Of genes expressed in the testis, autosomal genes were, indeed, more likely to be misexpressed than X-linked genes under the sterilizing action of OdsH. Since this mechanism of X:autosome interaction is only associated with spermatogenesis, a connection between X:autosome imbalance and the high rate of hybrid male sterility seems plausible.

  J. L Espinoza , H Takamatsu , X Lu , Z Qi and S. Nakao
 

Antibodies specific to moesin, which are frequently detectable in the serum of patients with aplastic anemia (AA), can induce tumor necrosis factor- (TNF-) secretion from monocytes and a human monocytic leukemia cell line THP-1. We investigated the mechanisms responsible for TNF- secretion from monocytic cells induced by the auto-antibodies that are purified from the sera of AA patients. TNF- induction by anti-moesin antibodies depended on the amount of cell surface moesin expressed by THP-1 cells. F(ab')2 fragments prepared from the anti-moesin antibodies were able to stimulate THP-1 cells to secrete TNF- and this stimulatory effect was enhanced by cross-linking of moesins with anti-human IgG F(ab')2 fragment antibodies. Anti-moesin antibodies as well as their F(ab')2 fragments induced the phosphorylation of ERK1/2 in monocytic cells and this effect was suppressed by the addition of an ERK1/2 inhibitor. Moreover, anti-moesin antibody treatment induced the phosphorylation of moesin proteins in the monocytes and THP-1 cells within 30 min. These results indicate that anti-moesin antibodies induce TNF- secretion from monocytes through the activation of the ERK1/2 pathway provoked by direct binding to moesin on the cells.

  D. M Zuo , L. Y Zhang , X Lu , Y Liu and Z. L. Chen
 

Mannan-binding lectin (MBL) is a C-type serum lectin, which is believed to play an important role in the innate immunity against a variety of pathogens. MBL can bind to sugar determinants of a wide variety of microorganisms, neutralize them and inhibit infection by complement activation through the lectin pathway and opsonization by collectin receptors. Given that small intestine is a predominant site of extrahepatic expression of MBL, here we addressed the question whether MBL is involved in mucosal innate immunity. The carbohydrate recognition domain (CRD) genes of mouse MBL-C (mMBL-C) were cloned and expressed in Escherichia coli. Recombinant mMBL-C-CRD binds to Shigella flexneri 2a in a calcium-dependent manner and that interaction could be blocked by the anti-mMBL-C-CRD antibody. mMBL-C-CRD protein could inhibit the adhesion of S. flexneri 2a to intestinal mucosa, while administration of anti-mMBL-C-CRD antibody caused an increased level of bacteria adhesion in vitro. Administration of recombinant mMBL-C-CRD protein reduced the secretion of IL-6 and monocyte chemoattractant protein 1 from primary intestinal epithelial cells stimulated with S. flexneri 2a. Furthermore, neutralization of MBL activity by anti-MBL-C-CRD resulted in a significant increase in the number of S. flexneri 2a that colonized the intestines of BALB/c mice and attenuated the severity of inflammation seen in the areas of bacterial invasion. These findings suggest that mMBL-C may protect host intestinal mucosa by directly binding to the bacteria.

  S Lahiri , H Park , E. L Laviad , X Lu , R Bittman and A. H. Futerman
 

FTY720, a sphingosine analog, is in clinical trials as an immunomodulator. The biological effects of FTY720 are believed to occur after its metabolism to FTY720 phosphate. However, very little is known about whether FTY720 can interact with and modulate the activity of other enzymes of sphingolipid metabolism. We examined the ability of FTY720 to modulate de novo ceramide synthesis. In mammals, ceramide is synthesized by a family of six ceramide synthases, each of which utilizes a restricted subset of acyl-CoAs. We show that FTY720 inhibits ceramide synthase activity in vitro by noncompetitive inhibition toward acyl-CoA and uncompetitive inhibition toward sphinganine; surprisingly, the efficacy of inhibition depends on the acyl-CoA chain length. In cultured cells, FTY720 has a more complex effect, with ceramide synthesis inhibited at high (500 nm to 5 µm) but not low (<200 nm) sphinganine concentrations, consistent with FTY720 acting as an uncompetitive inhibitor toward sphinganine. Finally, electrospray ionization-tandem mass spectrometry demonstrated, unexpectedly, elevated levels of ceramide, sphingomyelin, and hexosylceramides after incubation with FTY720. Our data suggest a novel mechanism by which FTY720 might mediate some of its biological effects, which may be of mechanistic significance for understanding its mode of action.

 
 
 
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