bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective Effect of an Extract fromAscaris suumin Experimental Arthritis Models
Authors: Rocha Francisco Airton Castro , Leite Ana Karine Rocha Melo , Pompeu Margarida Maria Lima , Cunha Thiago Mattar , Verri Waldiceu A. , Soares Fernanda Macedo , Castro Rondinelle Ribeiro , Cunha Fernando Queiroz 
Published: April 2008

ABSTRACTWe investigated the effect of an extract from a helminth (Ascaris suum) in zymosan-induced arthritis (ZYA) or collagen-induced arthritis (CIA). Rats and mice, respectively, received 1 mg and 0.1 mg zymosan intra-articularly (i.a.). Test groups received anA. suumextract either per os (p.o.) or intraperitoneally (i.p.) 30 min prior to i.a. zymosan. Controls received saline. Hypernociception was measured using the articular incapacitation test. Cell influx, nitrite, and cytokine levels were assessed in joint exudates. The synovia and distal femoral extremities were used for histopathology. Cartilage damage was assessed through determining glycosaminoglycan (GAG) content. DBA/1J mice were subjected to CIA. The test group receivedA. suumextract i.p. 1 day after CIA became clinically detectable. Clinical severity and hypernociception were assessed daily. Neutrophil influx was determined using myeloperoxidase activity. TheA. suumextract, either i.p. or p.o., significantly and dose-dependently inhibited cell influx and hypernociception in ZYA in addition to reducing GAG loss and ameliorating synovitis. TheA. suumextract reduced i.a. levels of NO, interleukin-1β (IL-1β), and IL-10 but not tumor necrosis factor alpha (TNF-α) in rats subjected to ZYA while reducing i.a. IL-10, but not IL-1β or TNF-α, levels in mice. Clinically, mice subjected to CIA treated with theA. suumextract had less severe arthritis. Hypernociception, myeloperoxidase activity, and synovitis severity were significantly reduced. These data show that a helminth extract given p.o. protects from arthritis severity in two classical arthritis models. ThisA. suumeffect is species independent and functions orally and parenterally. The results show clinical and structural benefits whenA. suumextract is given either prophylactically or therapeutically.
RANDOM MATRICES: THE CIRCULAR LAW
Authors: TAO TERENCE , VU VAN 
Published: April 2008

Let x be a complex random variable with mean zero and bounded variance σ2. Let Nn be a random matrix of order n with entries being i.i.d. copies of x. Let λ1, …, λn be the eigenvalues of [Formula: see text]. Define the empirical spectral distributionμn of Nn by the formula [Formula: see text] The following well-known conjecture has been open since the 1950's: Circular Law Conjecture: μn converges to the uniform distribution μ∞ over the unit disk as n tends to infinity. We prove this conjecture, with strong convergence, under the slightly stronger assumption that the (2 + η)th-moment of x is bounded, for any η > 0. Our method builds and improves upon earlier work of Girko, Bai, Götze–Tikhomirov, and Pan–Zhou, and also applies for sparse random matrices. The new key ingredient in the paper is a general result about the least singular value of random matrices, which was obtained using tools and ideas from additive combinatorics.
Intel Mash Maker
Authors: Ennals Rob , Brewer Eric , Garofalakis Minos , Shadle Michael , Gandhi Prashant 
Published: April 2008

Intel® Mash Maker is an interactive tool that tracks what the user is doing and tries to infer what information and visualizations they might find useful for their current task. Mash Maker uses structured data from existing web sites to create new "mashed up" interfaces combining information from many sources.
The Intel® Mash Maker client is currently implemented as an extension to the FireFox web browser. Mash Maker adds a toolbar to the browser that shows buttons representing enhancements that Mash Maker believes the user might want to apply to the current page. An enhancement might combine the data on the page with data from another source, or visualize data in a new way. Mash Maker is intended to be an integral part of the way the user browses information, rather than being a special tool that a user uses when they want to create mashups.

In order to create mashups from normal websites, Mash Maker must first extract structured data from them. If the web site does not provide RDF data, then Mash Maker extracts structured data from the raw HTML using a community-maintained database of
extractors
, where each extractor describes how to extract structured data from a particular kind of web site.
Targeting Endoplasmic Reticulum Stress and Akt with OSU-03012 and Gefitinib or Erlotinib to Overcome Resistance to Epidermal Growth Factor Receptor Inhibitors
Authors: Wang Yu-Chieh , Kulp Samuel K. , Wang Dasheng , Yang Chih-Cheng , Sargeant Aaron M. , Hung Jui-Hsiang , Kashida Yoko , Yamaguchi Mamoru , Chang Geen-Dong , Chen Ching-Shih 
Published: April 2008

Abstract
Preexisting and acquired resistance to epidermal growth factor receptor (EGFR) inhibitors limits their clinical usefulness in patients with advanced non–small cell lung cancer (NSCLC). This study characterizes the efficacy and mechanisms of the combination of gefitinib or erlotinib with OSU-03012, a celecoxib-derived antitumor agent, to overcome EGFR inhibitor resistance in three NSCLC cell lines, H1155, H23, and A549. The OSU-03012/EGFR inhibitor combination induced pronounced apoptosis in H1155 and H23 cells, but not in A549 cells, suggesting a correlation between drug sensitivity and basal phospho-Akt levels independently of EGFR expression status. Evidence indicates that this combination facilitates apoptosis through both Akt signaling inhibition and up-regulation of endoplasmic reticulum (ER) stress–induced, GADD153-mediated pathways. For example, ectopic expression of constitutively active Akt significantly attenuated the inhibitory effect on cell survival, and small interfering RNA–mediated knockdown of GADD153 protected cells from undergoing apoptosis in response to drug cotreatments. Furthermore, the OSU-03012/EGFR inhibitor combination induced GADD153-mediated up-regulation of death receptor 5 expression and subsequent activation of the extrinsic apoptosis pathway. It is noteworthy that the ER stress response induced by this combination was atypical in that the cytoprotective pathway was not engaged. In addition, in vivo suppression of tumor growth and modulation of intratumoral biomarkers were observed in a H1155 tumor xenograft model in nude mice. These data suggest that the concomitant modulation of Akt and ER stress pathways with the OSU-03012/EGFR inhibitor combination represents a unique approach to overcoming EGFR inhibitor resistance in NSCLC and perhaps other types of cancer with elevated basal Akt activities. [Cancer Res 2008;68(8):2820–30]
Genistein Induces the p21WAF1/CIP1 and p16INK4a Tumor Suppressor Genes in Prostate Cancer Cells by Epigenetic Mechanisms Involving Active Chromatin Modification
Authors: Majid Shahana , Kikuno Nobuyuki , Nelles Jason , Noonan Emily , Tanaka Yuichiro , Kawamoto Ken , Hirata Hiroshi , Li Long C. , Zhao Hong , Okino Steve T. , Place Robert F. , Pookot Deepa , Dahiya Rajvir 
Published: April 2008

Abstract
Genistein (4′,5,7-trihydroxyisoflavone) is the most abundant isoflavone found in the soybean. The effects of genistein on various cancer cell lines have been extensively studied but the precise molecular mechanisms are not known. We report here the epigenetic mechanism of the action of genistein on androgen-sensitive (LNCaP) and androgen-insensitive (DuPro) human prostate cancer cell lines. Genistein induced the expression of tumor suppressor genes p21 (WAF1/CIP1/KIP1) and p16 (INK4a) with a concomitant decrease in cyclins. There was a G0-G1 cell cycle arrest in LNCaP cells and a G2-M arrest in DuPro cells after genistein treatment. Genistein also induced apoptosis in DuPro cells. DNA methylation analysis revealed the absence of p21 promoter methylation in both cell lines. The effect of genistein on chromatin remodeling has not been previously reported. We found that genistein increased acetylated histones 3, 4, and H3/K4 at the p21 and p16 transcription start sites. Furthermore, we found that genistein treatment also increased the expression of histone acetyl transferases that function in transcriptional activation. This is the first report on epigenetic regulation of various genes by genistein through chromatin remodeling in prostate cancer. Altogether, our data provide new insights into the epigenetic mechanism of the action of genistein that may contribute to the chemopreventive activity of this dietary isoflavone and have important implications for epigenetic therapy. [Cancer Res 2008;68(8):2736–44]
Manganese Superoxide Dismutase Modulates Hypoxia-Inducible Factor-1α Induction via Superoxide
Authors: Kaewpila Suwimol , Venkataraman Sujatha , Buettner Garry R. , Oberley Larry W. 
Published: April 2008

Abstract
Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that plays an important role in O2 homeostasis. Numerous observations suggest that changes in reactive oxygen species affect HIF-1α stabilization and HIF-1α transcriptional activation in many cell types. The antioxidant enzyme manganese superoxide dismutase (MnSOD) modulates the cellular redox environment by converting superoxide (O2•−) to hydrogen peroxide and dioxygen. Previous results from our group have shown that overexpression of MnSOD in MCF-7 cells alters stabilization of HIF-1α under hypoxic conditions; however, the underlying mechanism(s) is not known. Here, we tested the hypothesis that MnSOD regulates the expression of HIF-1α by modulating the steady-state level of O2•−. We found that decreasing MnSOD with small interfering RNA in MCF-7 cells resulted in (a) an associated increase in the hypoxic accumulation of HIF-1α immunoreactive protein, (b) a significant increase in the levels of O2•− (P &lt; 0.01), but (c) no significant change in the steady-state level of H2O2. Removal of O2•− using spin traps (α-4-pyridyl-1-oxide-N-tert-butylnitrone and 5,5-dimethyl-1-pyrroline N-oxide) or the O2•− scavenger Tempol or an SOD mimic (AEOL10113) resulted in a decrease in HIF-1α protein, consistent with the hypothesis that O2•− is an important molecular effector responsible for hypoxic stabilization of HIF-1α. The evidence from both genetic and pharmaceutical manipulation is consistent with our hypothesis that O2•− can contribute to the stabilization of HIF-1α. [Cancer Res 2008;68(8):2781–8]
Enhancement of UVB-Induced Apoptosis by Apigenin in Human Keratinocytes and Organotypic Keratinocyte Cultures
Authors: Abu-Yousif Adnan O. , Smith Kimberly A. , Getsios Spiro , Green Kathleen J. , Van Dross Rukiyah T. , Pelling Jill C. 
Published: April 2008

Abstract
Topical application of the bioflavonoid 4′,5,7-trihydroxyflavone (apigenin) to mouse skin effectively reduces the incidence and size of skin tumors caused by UVB exposure. The ability to act as a chemopreventive compound indicates that apigenin treatment alters the molecular events initiated by UVB exposure; however, the effects of apigenin treatment on UVB-irradiated keratinocytes are not fully understood. In the present study, we have used three models of human keratinocytes to study the effect of apigenin treatment on UVB-induced apoptosis: HaCaT human keratinocyte cells, primary keratinocyte cultures isolated from human neonatal foreskin, and human organotypic keratinocyte cultures. Each keratinocyte model was exposed to a moderate dose of UVB (300–1,000 J/m2), then treated with apigenin (0–50 μmol/L), and harvested to assess apoptosis by Western blot analysis for poly(ADP)ribose polymerase cleavage, annexin-V staining by flow cytometry, and/or the presence of sunburn cells. Apigenin treatment enhanced UVB-induced apoptosis &gt;2-fold in each of the models tested. When keratinocytes were exposed to UVB, apigenin treatment stimulated changes in Bax localization and increased the release of cytochrome c from the mitochondria compared with UVB exposure alone. Overexpression of the antiapoptotic protein Bcl-2 and expression of a dominant-negative form of Fas-associated death domain led to a reduction in the ability of apigenin to enhance UVB-induced apoptosis. These results suggest that enhancement of UVB-induced apoptosis by apigenin treatment involves both the intrinsic and extrinsic apoptotic pathways. The ability of apigenin to enhance UVB-induced apoptosis may explain, in part, the photochemopreventive effects of apigenin. [Cancer Res 2008;68(8):3057–65]
The Helix-Loop-Helix Protein Id1 Requires Cyclin D1 to Promote the Proliferation of Mammary Epithelial Cell Acini
Authors: Caldon C. Elizabeth , Swarbrick Alexander , Lee Christine S.L. , Sutherland Robert L. , Musgrove Elizabeth A. 
Published: April 2008

Abstract
Overexpression of the helix-loop-helix (HLH) protein Id1 has been associated with metastasis in breast cancer, but its role in models of early breast tumorigenesis is not well characterized. We show that the down-regulation of endogenous Id1 via proteosomal degradation and relocalization from the nucleus to the cytoplasm is an early event in the formation of mammary epithelial acini. Overexpression of Id1 in both human MCF-10A and primary mouse mammary epithelial cells disrupted normal acinar development by increasing acinar volume. This occurred in an HLH domain–dependent fashion via an increase in S phase. Id1 overexpression also increased apoptosis leading to accelerated luminal clearance, and this was reversed by coexpression of the proto-oncogene Bcl2, leading to large, disorganized structures with filled lumina. Id1 overexpression was unable to increase the volume of cyclin D1−/− acini, indicating that Id1 is dependent on cyclin D1 for its proliferative effects. In summary, Id1 may contribute to early breast cancer by promoting excessive proliferation through cyclin D1. [Cancer Res 2008;68(8):3026–36]
Analysis of the Mechanisms Mediating Tumor-Specific Changes in Gene Expression in Human Liver Tumors
Authors: Acevedo Luis G. , Bieda Mark , Green Roland , Farnham Peggy J. 
Published: April 2008

Abstract
There is widespread interest in efficient characterization of differences between tumor and normal samples. Here, we show an effective methodology for genome-scale characterization of tumors. Using matched normal and tumor samples from liver cancer patients, as well as non–cancer-related normal liver tissue, we first determined changes in gene expression as monitored on RNA expression arrays. We identified several hundred mRNAs that were consistently changed in the tumor samples. To characterize the mechanisms responsible for creation of the tumor-specific transcriptome, we performed chromatin immunoprecipitation on microarray experiments to assay binding of RNA polymerase II, H3me3K27, and H3me3K9 and DNA methylation in 25,000 promoter regions. These experiments identified changes in active and silenced regions of the genome in the tumor cells. Finally, we used a “virtual comparative genomic hybridization” method to identify copy number alterations in the tumor samples. Through comparison of RNA polymerase II binding, chromatin structure, DNA methylation, and copy number changes, we suggest that the major contributor to creation of the liver tumor transcriptome was changes in gene copy number. [Cancer Res 2008;68(8):2641–51]
Effect of Low-Fat Diet on Development of Prostate Cancer and Akt Phosphorylation in the Hi-Myc Transgenic Mouse Model
Authors: Kobayashi Naoko , Barnard R. James , Said Jonathan , Hong-Gonzalez Jenny , Corman Dan M. , Ku Melvin , Doan Ngan Bao , Gui Dorina , Elashoff David , Cohen Pinchas , Aronson William J. 
Published: April 2008

Abstract
This study evaluated the effect of dietary fat on prostate cancer development by using the Hi-Myc mouse transgenic prostate cancer model. Hi-Myc mice develop murine prostatic intraepithelial neoplasia (mPIN) as early as 2 to 4 weeks and invasive adenocarcinoma between 6 and 9 months due to the overexpression of human c-Myc in the mouse prostate. Three-week-old male Hi-Myc mice were placed on high-fat (HF; 42% Kcal) or low-fat (LF; 12% Kcal) diets, and equal caloric intake was maintained until euthanasia at 7 months. The number of mice that developed invasive adenocarcinoma at 7 months was 27% less in the LF diet group (12/28) compared with the HF diet group (23/33, P &lt; 0.05). Epithelial cells in mPIN lesions in the LF group had a significantly lower proliferative index compared with epithelial cells in the HF group (21.7% versus 28.9%, P &lt; 0.05). During the mPIN phase of carcinogenesis (4 months), the LF group had higher serum insulin-like growth factor (IGF) binding protein-1 levels (21.0 ± 8.9 ng/mL versus 3.2 ± 0.8 ng/mL, P &lt; 0.05) relative to the HF group. Akt (Ser473) phosphorylation, Akt kinase activity, and phosphorylation of downstream targets of Akt in prostates were significantly reduced in the LF diet group compared with the HF group. We conclude that dietary fat reduction delays transition from mPIN to invasive cancer in this Myc-driven transgenic mouse model, possibly through suppression of the IGF-Akt pathway and decreased proliferation of mPIN epithelial cells. [Cancer Res 2008;68(8):3066–73]
Bone Marrow X Kinase–Mediated Signal Transduction in Irradiated Vascular Endothelium
Authors: Tu Tianxiang , Thotala Dinesh , Geng Ling , Hallahan Dennis E. , Willey Christopher D. 
Published: April 2008

Abstract
Radiation-induced activation of the phosphatidyl inositol-3 kinase/Akt signal transduction pathway requires Akt binding to phosphatidyl-inositol phosphates (PIP) on the cell membrane. The tyrosine kinase bone marrow X kinase (Bmx) binds to membrane-associated PIPs in a manner similar to Akt. Because Bmx is involved in cell growth and survival pathways, it could contribute to the radiation response within the vascular endothelium. We therefore studied Bmx signaling within the vascular endothelium. Bmx was activated rapidly in response to clinically relevant doses of ionizing radiation. Bmx inhibition enhanced the efficacy of radiotherapy in endothelial cells as well as tumor vascular endothelium in lung cancer tumors in mice. Retroviral shRNA knockdown of Bmx protein enhanced human umbilical vascular endothelial cell (HUVEC) radiosensitization. Furthermore, pretreatment of HUVEC with a pharmacologic inhibitor of Bmx, LFM-A13, produced significant radiosensitization of endothelial cells as measured by clonogenic survival analysis and apoptosis as well as functional assays including cell migration and tubule formation. In vivo, LFM-A13, when combined with radiation, resulted in significant tumor microvascular destruction as well as enhanced tumor growth delay. Bmx therefore represents a molecular target for the development of novel radiosensitizing agents. [Cancer Res 2008;68(8):2861–9]
Imaging Transgene Activity In vivo
Authors: Gade Terence P.F. , Koutcher Jason A. , Spees William M. , Beattie Bradley J. , Ponomarev Vladimir , Doubrovin Michael , Buchanan Ian M. , Beresten Tatiana , Zakian Kristen L. , Le H. Carl , Tong William P. , Mayer-Kuckuk Philipp , Blasberg Ronald G. , Gelovani Juri G. 
Published: April 2008

Abstract
The successful translation of gene therapy for clinical application will require the assessment of transgene activity as a measure of the biological function of a therapeutic transgene. Although current imaging permits the noninvasive detection of transgene expression, the critical need for quantitative imaging of the action of the expressed transgene has not been met. In vivo magnetic resonance spectroscopic imaging (MRSI) was applied to quantitatively delineate both the concentration and activity of a cytosine deaminase–uracil phosphoribosyltransferase (CD-UPRT) fusion enzyme expressed from a transgene. MRSI enabled the generation of anatomically accurate maps of the intratumoral heterogeneity in fusion enzyme activity. We observed an excellent association between the CD-UPRT concentration and activity and the percentage of CD-UPRT+ cells. Moreover, the regional levels of UPRT activity, as measured by imaging, correlated well with the biological affect of the enzyme. This study presents a translational imaging paradigm for precise, in vivo measurements of transgene activity with potential applications in both preclinical and clinical settings. [Cancer Res 2008;68(8):2878–84]
Targeting a Tumor-Specific Laminin Domain Critical for Human Carcinogenesis
Authors: Tran Mark , Rousselle Patricia , Nokelainen Pasi , Tallapragada Sruthi , Nguyen Ngon T. , Fincher Edgar F. , Marinkovich M. Peter 
Published: April 2008

Abstract
Laminin-332 is critical for squamous cell carcinoma (SCC) tumorigenesis, but targeting it for cancer therapy has been unachievable due to key role of laminin-332 in promoting tissue integrity. Here, we show that a portion of laminin-332, termed G45, which is proteolytically removed and absent in normal tissues, is prominently expressed in most human SCC tumors and plays an important role in human SCC tumorigenesis. Primary human keratinocytes lacking G45 (ΔG45) showed alterations of basal receptor organization, impaired matrix deposition, and increased migration. After SCC transformation, the absence of G45 domain in ΔG45 cells was associated with deficient extracellular signal-regulated kinase and phosphotidylinositol 3-kinase (PI3K) pathway activation, impaired invasion, deficient metalloproteinase activity, and absent tumorgenicity in vivo. Expression of G45 or activated PI3K subunit in ΔG45 cells reversed these abnormalities. G45 antibody treatment induced SCC tumor apoptosis, decreased SCC tumor proliferation, and markedly impaired human SCC tumorigenesis in vivo without affecting normal tissue adhesion. These results show a remarkable selectivity of expression and function for laminin-332 G45 in human SCC tumorigenesis and implicate it as a specific target for anticancer therapy. [Cancer Res 2008;68(8):2885–94]
Targeting CD24 for Treatment of Colorectal and Pancreatic Cancer by Monoclonal Antibodies or Small Interfering RNA
Authors: Sagiv Eyal , Starr Alex , Rozovski Uri , Khosravi Rami , Altevogt Peter , Wang Timothy , Arber Nadir 
Published: April 2008

AbstractCD24 is a potential oncogene reported to be overexpressed in a large variety of human malignancies. We have shown that CD24 is overexpressed in 90% of colorectal tumors at a fairly early stage in the multistep process of carcinogenesis. Anti-CD24 monoclonal antibodies (mAb) induce a significant growth inhibition in colorectal and pancreatic cancer cell lines that express the protein. This study is designed to investigate further the effects of CD24 down-regulation using mAb or small interfering RNA in vitro and in vivo. Western blot analysis showed that anti-CD24 mAb induced CD24 protein down-regulation through lysosomal degradation. mAb augmented growth inhibition in combination with five classic chemotherapies. Xenograft models in vivo showed that tumor growth was significantly reduced in mAb-treated mice. Similarly, stable growth inhibition of cancer cell lines was achieved by down-regulation of CD24 expression using short hairpin RNA (shRNA). The produced clones proliferated more slowly, reached lower saturation densities, and showed impaired motility. Most importantly, down-regulation of CD24 retarded tumorigenicity of human cancer cell lines in nude mice. Microarray analysis revealed a similar pattern of gene expression alterations when cells were subjected to anti-CD24 mAb or shRNA. Genes in the Ras pathway, mitogen-activated protein kinase, or BCL-2 family and others of oncogenic association were frequently down-regulated. As a putative new oncogene that is overexpressed in gastrointestinal malignancies early in the carcinogenesis process, CD24 is a potential target for early intervention in the prevention and treatment of cancer. [Cancer Res 2008;68(8):2803–12]