bluuebunny/crossref_metadata_2025_split huggingface dataset:
Poly-
N
-Acetylglucosamine Is Not a Major Component of the Extracellular Matrix in Biofilms Formed by
icaADBC
-Positive
Staphylococcus lugdunensis
Isolates
Authors: Frank Kristi L. , Patel Robin 
Published: July 2007

ABSTRACT

Staphylococcus lugdunensis
is a pathogen of heightened virulence that causes infections resembling those caused by
Staphylococcus aureus
rather than those caused by its coagulase-negative staphylococcal counterparts. Many types of
S. lugdunensis
infection, including native valve endocarditis, prosthetic joint infection, and intravascular catheter-related infection, are associated with biofilm etiology. Poly-
N
-acetylglucosamine (PNAG), a polysaccharide synthesized by products of the
icaADBC
locus, is a common mechanism of intercellular adhesion in staphylococcal biofilms. Here we report the characterization of
ica
homologues and the in vitro biofilm formation properties of a collection of
S. lugdunensis
clinical isolates. Isolates formed biofilms in microtiter wells to various degrees. Biofilm formation by most isolates was enhanced with glucose but diminished by sodium chloride or ethanol.
icaADBC
homologues were found in all
S. lugdunensis
isolates tested, although the locus organization differed substantially from that of other staphylococcal
ica
loci.
icaR
was not detected in
S. lugdunensis
, but a novel open reading frame with putative glycosyl hydrolase function is located upstream of the
ica
locus.
icaADBC
sequence heterogeneity did not explain the variability in biofilm formation among isolates. PNAG was not detected in
S. lugdunensis
extracts by immunoblotting with an anti-deacetylated PNAG antibody or wheat germ agglutinin. Confocal microscopy with fluorescently labeled wheat germ agglutinin showed a paucity of PNAG in
S. lugdunensis
biofilms, but abundant extracellular protein was visualized with SYPRO Ruby staining. Biofilms were resistant to detachment by dispersin B and sodium metaperiodate but were susceptible to detachment by proteases. Despite the genetic presence of
icaADBC
homologues in
S. lugdunensis
isolates, PNAG is not a major component of the extracellular matrix of in vitro biofilms formed by this species. Our data suggest that the
S. lugdunensis
biofilm matrix contains proteinaceous factors.
Target Sequence Accessibility Limits Activation-Induced Cytidine Deaminase Activity in Primary Mediastinal B-Cell Lymphoma
Authors: Popov Sergey W. , Moldenhauer Gerhard , Wotschke Beate , Brüderlein Silke , Barth Thomas F. , Dorsch Karola , Ritz Olga , Möller Peter , Leithäuser Frank 
Published: July 2007

Abstract
Activation-induced cytidine deaminase (AID) initiates somatic hypermutation (SHM) and class switch recombination (CSR) in activated B lymphocytes and is potentially implicated in genomic instability of B-cell malignancies. For unknown reasons, B-cell neoplasms often lack SHM and CSR in spite of high AID expression. Here, we show that primary mediastinal B-cell lymphoma (PMBL), an immunoglobulin (Ig)–negative lymphoma that possesses hypermutated, class-switched Ig genes, expresses high levels of AID with an intact primary structure but does not do CSR in 14 of 16 cases analyzed. Absence of CSR coincided with low Ig germ-line transcription, whereas high level germ-line transcription was observed only in those two cases with active CSR. Interleukin-4/CD40L costimulation induced CSR and a marked up-regulation of germ-line transcription in the PMBL-derived cell line MedB-1. In the PMBL cell line Karpas 1106P, CSR was not inducible and germ-line transcription remained low on stimulation. However, Karpas 1106P, but not MedB-1, had ongoing SHM of the Ig gene and BCL6. These genes were transcribed in Karpas 1106P, whereas transcription was undetectable or low in MedB-1 cells. Thus, accessibility of the target sequences seems to be a major limiting factor for AID-dependent somatic gene diversification in PMBL. [Cancer Res 2007;67(14):6555–64]
Lipid Rafts and Nonrafts Mediate Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptotic and Nonapoptotic Signals in Non–Small Cell Lung Carcinoma Cells
Authors: Song Jin H. , Tse Margaret C.L. , Bellail Anita , Phuphanich Surasak , Khuri Fadlo , Kneteman Norman M. , Hao Chunhai 
Published: July 2007

Abstract
Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is capable of inducing apoptosis in non–small cell lung carcinoma (NSCLC). However, many of the human NSCLC cell lines are resistant to TRAIL, and TRAIL treatment of the resistant cells leads to the activation of nuclear factor-κB (NF-κB) and extracellular signal–regulated kinase 1/2 (ERK1/2). TRAIL can induce apoptosis in TRAIL-sensitive NSCLC cells through the induction of death-inducing signaling complex (DISC) assembly in lipid rafts of plasma membrane. In the DISC, caspase-8 is cleaved and initiates TRAIL-induced apoptosis. In contrast, TRAIL-DISC assembly in the nonraft phase of the plasma membrane leads to the inhibition of caspase-8 cleavage and NF-κB and ERK1/2 activation in TRAIL-resistant NSCLC cells. Receptor-interacting protein (RIP) and cellular Fas-associated death domain–like interleukin-1β–converting enzyme-inhibitory protein (c-FLIP) mediates the DISC assembly in nonrafts and selective knockdown of either RIP or c-FLIP with interfering RNA redistributes the DISC from nonrafts to lipid rafts, thereby switching the DISC signals from NF-κB and ERK1/2 activation to caspase-8–initiated apoptosis. Chemotherapeutic agents inhibit c-FLIP expression, thereby enhancing the DISC assembly in lipid rafts for caspase-8–initiated apoptosis. These studies indicate that RIP and c-FLIP–mediated assembly of the DISC in nonrafts is a critical upstream event in TRAIL resistance and thus targeting of either RIP or c-FLIP may lead to the development of novel therapeutic strategies that can overcome TRAIL resistance in human NSCLC. [Cancer Res 2007;67(14):6946–55]
BEX2 Is Overexpressed in a Subset of Primary Breast Cancers and Mediates Nerve Growth Factor/Nuclear Factor-κB Inhibition of Apoptosis in Breast Cancer Cell Lines
Authors: Naderi Ali , Teschendorff Andrew E. , Beigel Juergen , Cariati Massimiliano , Ellis Ian O. , Brenton James D. , Caldas Carlos 
Published: July 2007

Abstract
We have identified a novel subtype of estrogen receptor (ER)-positive breast cancers with improved outcome after tamoxifen treatment and characterized by overexpression of the gene BEX2. BEX2 and its homologue BEX1 have highly correlated expression and are part of a cluster enriched for ER response and apoptosis genes. BEX2 expression is induced after estradiol (E2) treatment with a peak at 3 h, suggesting BEX2 is an estrogen-regulated gene. BEX2 belongs to a family of genes, including BEX1, NGFRAP1 (alias BEX3), BEXL1 (alias BEX4), and NGFRAP1L1 (alias BEX5). Both BEX1 and NGFRAP1 interact with p75NTR and modulate nerve growth factor (NGF) signaling through nuclear factor-κB (NF-κB) to regulate cell cycle, apoptosis, and differentiation in neural tissues. In breast cancer cells, NGF inhibits C2-induced apoptosis through binding of p75NTR and NF-κB activation. Here, we show that BEX2 expression is necessary and sufficient for the NGF-mediated inhibition (through NF-κB activation) of C2-induced apoptosis. We also show that BEX2 modulates apoptosis of breast cancer cells in response to E2 (50 nmol/L) and tamoxifen (5 and 10 μmol/L). Furthermore, BEX2 overexpression enhances the antiproliferative effect of tamoxifen at pharmacologic dose (1 μmol/L). These data suggest that a NGF/BEX2/NF-κB pathway is involved in regulating apoptosis in breast ancer cells and in modulating response to tamoxifen in primary tumors. [Cancer es 2007;67(14):6725–36]
Dual Specificity Phosphatase 1/CL100 Is a Direct Transcriptional Target of E2F-1 in the Apoptotic Response to Oxidative Stress
Authors: Wang Jianli , Yin David P. , Liu Yu-Xin , Baer Richard , Yin Yuxin 
Published: July 2007

Abstract
E2F-1 mediates apoptosis through transcriptional regulation of its targets. We report here that E2F-1 acts as a direct transcriptional regulator of dual specificity phosphatase 1 (DUSP1; CL100), a threonine and tyrosine phosphatase that inhibits mitogen-activated protein (MAP) kinases. We found that DUSP1 is transcriptionally induced by ectopic E2F-1 expression and that extracellular signal–regulated kinase 1/2 are dephosphorylated in the presence of E2F-1 and DUSP1. E2F-1 mediates apoptosis in the cellular response to oxidative stress. DUSP1 levels are significantly increased in an E2F-1–dependent manner following oxidative stress but not other stresses examined. DUSP1 mediates the cellular response to oxidative stress. We found that E2F-1 binds to chromatin encompassing the DUSP1 promoter and greatly stimulates the promoter activity of the DUSP1 gene. In particular, E2F-1 physically binds to an E2F-1 consensus sequence and a palindromic motif in the DUSP1 promoter. Interestingly, E2F-1 is acetylated following oxidative stress. Our findings show that E2F-1 is a transcriptional activator of DUSP1 and that DUSP1 is a link between E2F-1 and MAP kinases. [Cancer Res 2007;67(14):6737–44]
Control of Her-2 Tumor Immunity and Thyroid Autoimmunity by MHC and Regulatory T Cells
Authors: Jacob Jennifer B. , Kong Yi-chi M. , Meroueh Chady , Snower Daniel P. , David Chella S. , Ho Ye-Shih , Wei Wei-Zen 
Published: July 2007

AbstractImmune reactivity to self-antigens in both cancer and autoimmune diseases can be enhanced by systemic immune modulation, posing a challenge in cancer immunotherapy. To distinguish the genetic and immune regulation of tumor immunity versus autoimmunity, immune responses to human ErbB-2 (Her-2) and mouse thyroglobulin (mTg) were tested in transgenic mice expressing Her-2 that is overexpressed in several cancers, and HLA-DRB1*0301 (DR3) that is associated with susceptibility to several human autoimmune diseases, as well as experimental autoimmune thyroiditis (EAT). To induce Her-2 response, mice were electrovaccinated with pE2TM and pGM-CSF encoding the extracellular and transmembrane domains of Her-2 and the murine granulocyte macrophage colony-stimulating factor, respectively. To induce EAT, mice received mTg i.v. with or without lipopolysaccharide. Depletion of regulatory T cells (Treg) with anti-CD25 monoclonal antibody enhanced immune reactivity to Her-2 as well as mTg, showing control of both Her-2 and mTg responses by Treg. When immunized with, Her-2xDR3 and B6xDR3 mice expressing H2bxDR3 haplotype developed more profound mTg response and thyroid pathology than Her-2 or B6 mice that expressed the EAT-resistant H2b haplotype. In Her-2xDR3 mice, the response to mTg was further amplified when mice were also immunized with pE2TM and pGM-CSF. On the contrary, Her-2 reactivity was comparable whether mice expressed DR3 or not. Therefore, induction of Her-2 immunity was independent of DR3 but development of EAT was dictated by this allele, whereas Tregs control the responses to both self-antigens. These results warrant close monitoring of autoimmunity during cancer immunotherapy, particularly in patients with susceptible MHC class II alleles. [Cancer Res 2007;67(14):7020–7]
A Galactolipid Possesses Novel Cancer Chemopreventive Effects by Suppressing Inflammatory Mediators and Mouse B16 Melanoma
Authors: Hou Chia-Chung , Chen Yi-Ping , Wu Jyh-Horng , Huang Chi-Chang , Wang Sheng-Yang , Yang Ning-Sun , Shyur Lie-Fen 
Published: July 2007

Abstract
Crassocephalum rabens (Asteraceae) is a popular anti-inflammatory folk medicine and food supplement. We investigated the cancer chemopreventive bioactivity of C. rabens phytocompounds in vitro and in vivo using cell- and gene-based bioassays and a mouse B16 melanoma model. The bioactive glyceroglycolipid 1,2-di-O-α-linolenoyl-3-O-β-galactopyranosyl-sn-glycerol (dLGG) that was identified from C. rabens was found in vitro and in vivo to be a potent nitric oxide (NO) scavenger. dLGG treatment inhibited both mRNA and protein expression of inducible NO synthase and cyclooxygenase-2 (COX-2) in murine macrophages and inhibited COX-2 gene transcription in 12-O-tetradecanoylphorbol-13-acetate (TPA)–treated B16 cells. In immunohistochemical studies, dLGG inhibited TPA-induced expression of COX-2 and nitration of proteins in mouse skin. dLGG could also significantly inhibit lipopolysaccharide-induced prostaglandin E2 production in murine macrophages. Furthermore, dLGG prevented nuclear translocation of cytoplasmic nuclear factor-κB (NF-κB) by suppressing IκBα phosphorylation and degradation. Structure-activity relationship study by electrophoretic mobility shift assay indicated that the dilinolenoylglycerol moiety in dLGG is the essential structural feature preventing NF-κB·DNA complex formation. A dLGG-enriched extract from C. rabens (10 mg/kg) markedly suppressed B16 melanoma growth in C57BL/6J mice following i.p. administration, an effect comparable with that of cisplatin, a cancer chemotherapeutic drug. This study shows the detailed molecular mechanism(s) underlying the anti-inflammatory and tumor-suppressive effects of a natural galactolipid. [Cancer Res 2007;67(14):6907–15]
MFG-E8/Lactadherin Promotes Tumor Growth in an Angiogenesis-Dependent Transgenic Mouse Model of Multistage Carcinogenesis
Authors: Neutzner Melanie , Lopez Theresa , Feng Xu , Bergmann-Leitner Elke S. , Leitner Wolfgang W. , Udey Mark C. 
Published: July 2007

Abstract
The relevance of angiogenesis in tumor biology and as a therapeutic target is well established. MFG-E8 (also termed lactadherin) and developmental endothelial locus 1 (Del1) constitute a two-gene family of αvβ3/β5 ligands that regulate angiogenesis. After detecting MFG-E8 mRNA in murine tumor cell lines, we sought to determine if MFG-E8 influenced tumorigenesis in Rip1-Tag2 transgenic mice, a cancer model in which angiogenesis is critical. MFG-E8 mRNA and protein were increased in angiogenic islets and tumors in Rip1-Tag2 mice compared with normal pancreas. Frequencies of angiogenic islets and tumor burdens were decreased in MFG-E8–deficient Rip1-Tag2 mice compared with those in control Rip1-Tag2 mice. Invasive carcinomas were modestly underrepresented in MFG-E8–deficient mice, but tumor frequencies and survivals were comparable in these two strains. Absence of MFG-E8 also led to decreases in tumor vascular permeability without obvious changes in vascular morphology. Decreased proliferation was noted in angiogenic islets and increases in apoptotic cells were detected in islets and tumors. Compensatory increases in mRNA encoding proangiogenic proteins, including FGF2, in angiogenic islets, and Del1, in angiogenic islets and tumors, were also detected in MFG-E8–deficient mice. MFG-E8 and its homologue Del1 may represent relevant targets in cancer and other diseases in which angiogenesis is prominent. [Cancer Res 2007;67(14):6777–84]
Therapeutic Vaccination against Murine Lymphoma by Intratumoral Injection of Recombinant Fowlpox Virus Encoding CD40 Ligand
Authors: Liu Aichun , Guardino Alice , Chinsangaram Lek , Goldstein Matthew J. , Panicali Dennis , Levy Ronald 
Published: July 2007

AbstractThe interaction between CD40 ligand (CD40L, CD154) and its receptor CD40 on antigen-presenting cells is essential for the initiation of cell-mediated and humoral immune responses. Malignant B cells also express CD40 and respond to CD40L by enhancing expression of costimulatory molecules. In this study, we investigated the therapeutic antitumor effect of intratumoral administration of recombinant fowlpox virus encoding murine CD40L (rF-mCD40L) in a murine B-cell lymphoma model. BALB/c mice with established s.c. and widely metastatic A20 lymphoma tumors were treated with intratumoral injections of rF-mCD40L together with systemic chemotherapy. This combined chemoimmunotherapy resulted in complete tumor regression and long-term survival of the mice. Some tumor cells in the injected sites expressed the CD40L transgene and had increased expression of the CD80 and CD86 costimulatory molecules. The therapeutic effect was dependent on CD8 but not on CD4 T cells. Moreover, there was a requirement that the recombinant CD40L virus be injected directly into the tumor, as opposed to peritumoral or distant sites. Thus, rF-mCD40L injected directly into the tumor microenvironment enhances the immunogenicity of tumor B cells. The results support future plans for intratumoral injection of rF-mCD40L in patients with lymphoma. [Cancer Res 2007;67(14):7037–44]
Nongenomic β Estrogen Receptors Enhance β1 Adrenergic Signaling Induced by the Nicotine-Derived Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone in Human Small Airway Epithelial Cells
Authors: Majidi Mourad , Al-Wadei Hussein A. , Takahashi Takashi , Schuller Hildegard M. 
Published: July 2007

Abstract
Women are at higher risk for the development of lung adenocarcinoma than men; however, the mechanisms responsible for this are poorly understood. In lung adenocarcinoma cells, the estrogen receptor β (ERβ) is the predominating form. We found that 17β-estradiol enhanced proliferation of the putative cells of origin of lung adenocarcinoma, small airway epithelial cells (HPLD1), in response to the nicotine-derived nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Reverse-phase protein microarrays combined with Western blotting revealed that NNK induced phosphorylation of ERβ, an effect that involved stimulation of the adrenergic receptors β1 (β1AR). In transiently transfected cells, β1AR coprecipitated with ERβ, which increased with NNK treatment. ERβ enhanced NNK-induced cyclic AMP accumulation as well as Gαi-mediated mitogen-activated protein kinase/extracellular signal–regulated kinase (ERK) 1/2 activation. Coexpression of β1AR and ERβ activated NNK-mediated ERK1/2 cooperatively. ERβ gene knockdown, as well as coexpression of the dominant negative Ras and Raf, reduced stimulation of ERK1/2 by NNK. Whereas NNK phosphorylated Akt at Thr308 and Ser473, ERβ had no effect on this activity. Luciferase reporter assays showed that, in response to NNK, ERβ stimulated transcription of serum responsive element (SRE) but had a very small effect on the activity of estrogen responsive element (ERE). Together, the phosphorylation of ERβ, the dependence on Gαi proteins, the activation of ERK1/2, and the preferential targeting of SRE over the classic ERE pathway support a role for nongenomic ERβ in the development of smoking-associated lung cancer. This novel cooperation between β1AR and ERβ signaling may contribute to the prominence of lung adenocarcinoma in women. [Cancer Res 2007;67(14):6863–71]
Small Interfering RNA–Directed Reversal of Urokinase Plasminogen Activator Demethylation Inhibits Prostate Tumor Growth and Metastasis
Authors: Pulukuri Sai Murali Krishna , Rao Jasti S. 
Published: July 2007

Abstract
Recent studies have shown that small interfering RNA (siRNA) silences genes at the transcriptional level in human cells. However, the therapeutic potential of siRNA-mediated transcriptional gene silencing remains unclear. Here, we show that siRNA targeted to the urokinase plasminogen activator (uPA) promoter induced epigenetic transcriptional silencing in human prostate cancer cells. This silencing resulted in a dramatic reduction of tumor cell invasion and angiogenesis in vitro. Furthermore, the results from a bioluminescence tumor/metastasis model showed that the silencing of uPA significantly inhibits prostate tumor growth and the incidence of lung metastasis. Our findings represent a potentially powerful new approach to not only epigenetic silencing of metastasis or growth-promoting genes as a cancer therapy, but also as a means to shed light on how aberrant de novo methylation during cancer progression might be targeted to specific sequences. [Cancer Res 2007;67(14):6637–46]
Histone Deacetylase Inhibitors Enhance Lexatumumab-Induced Apoptosis via a p21Cip1-Dependent Decrease in Survivin Levels
Authors: Nawrocki Steffan T. , Carew Jennifer S. , Douglas Leslie , Cleveland John L. , Humphreys Robin , Houghton Janet A. 
Published: July 2007

Abstract
Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) preferentially induces apoptosis in malignant cells by binding to the death receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). Several agents that therapeutically exploit this phenomenon are being developed. We investigated the anticancer activity of two novel, highly specific agonistic monoclonal antibodies to TRAIL-R1 (mapatumumab, HGS-ETR1) and TRAIL-R2 (lexatumumab, HGS-ETR2) in colon cancer cell lines. Our analyses revealed that colon cancer cells display significantly higher surface expressions of TRAIL-R2 than TRAIL-R1, and are more sensitive to lexatumumab-induced apoptosis. The proapoptotic effects of lexatumumab in TRAIL-resistant HCT8 and HT29 cells were dramatically augmented by the histone deacetylase inhibitors trichostatin A or suberoylanilide hydroxamic acid. The presence of p21, but not p53, was critical for the synergy between lexatumumab and histone deacetylase inhibitors. The absence of p21 did not interfere with the formation of the death-inducing signaling complex by lexatumumab, suggesting the involvement of other apoptotic and/or cell cycle regulators. Indeed, treatment with suberoylanilide hydroxamic acid greatly reduced the expression of the inhibitor of apoptosis protein survivin and cdc2 activity in HCT116 p21+/+ cells but not in the HCT116 p21−/− cells. Inhibition of cdc2 activity with flavopiridol decreased survivin expression and sensitized the p21-deficient cells to lexatumumab-induced apoptosis. Similarly, small interfering RNA–mediated knockdown of survivin also enhanced lexatumumab-mediated cell death. Therefore, survivin expression plays a key role in lexatumumab resistance, and reducing survivin expression by inhibiting cdc2 activity is a promising strategy to enhance the anticancer activity of lexatumumab. [Cancer Res 2007;67(14):6987–94]
Fascin, a Novel Target of β-Catenin-TCF Signaling, Is Expressed at the Invasive Front of Human Colon Cancer
Authors: Vignjevic Danijela , Schoumacher Marie , Gavert Nancy , Janssen Klaus-Peter , Jih Gloria , Laé Marick , Louvard Daniel , Ben-Ze'ev Avri , Robine Sylvie 
Published: July 2007

AbstractCancer cells become metastatic by acquiring a motile and invasive phenotype. This step requires remodeling of the actin cytoskeleton and the expression of exploratory, sensory organelles known as filopodia. Aberrant β-catenin-TCF target gene activation plays a major role in colorectal cancer development. We identified fascin1, a key component of filopodia, as a target of β-catenin-TCF signaling in colorectal cancer cells. Fascin1 mRNA and protein expression were increased in primary cancers in a stage-dependent manner. Fascin1 was exclusively localized at the invasive front of tumors also displaying nuclear β-catenin. Forced expression of fascin1 in colorectal cancer cells increased their migration and invasion in cell cultures and caused cell dissemination and metastasis in vivo, whereas suppression of fascin1 expression by small interfering RNA reduces cell invasion. Although expression of fascin1 in primary tumors correlated with the presence of metastases, fascin1 was not expressed in metastases. Our studies show that fascin1 expression is tightly regulated during development of colon cancer metastases and is a novel target of β-catenin-TCF signaling. We propose that transient up-regulation of fascin1 in colorectal cancer promotes the acquisition of migratory and invasive phenotypes that lead to metastasis. Moreover, the expression of fascin1 is down-regulated when tumor cells reach their metastatic destination where migration ceases and proliferation is enhanced. Although metastasis to vital organs is often the cause of mortality, only limited success has been attained in developing effective therapeutics against metastatic disease. We propose that genes involved in cell migration and invasion, such as fascin1, could serve as novel targets for metastasis prevention. [Cancer Res 2007;67(14):6844–53]