bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epstein-Barr Virus Latent Membrane Protein 1 (CAO) Up-regulates VEGF and TGFα Concomitant with Hyperlasia, with Subsequent Up-regulation of p16 and MMP9
Authors: Stevenson David , Charalambous Chrystalla , Wilson Joanna B. 
Published: October 2005

Abstract
EBV latent membrane protein 1 (LMP1) is an oncoprotein frequently expressed in nasopharyngeal carcinoma. We have generated transgenic mice expressing the nasopharyngeal carcinoma–derived CAO strain of LMP1 and LMP1 of the B95-8 strain, using the viral ED-L2 promoter for epithelial expression. LMP1CAO and LMP1B95-8 induce transforming growth factor α expression and epidermal hyperplasia. However, levels of total epidermal growth factor receptor (EGFR) decline with the appearance of phosphorylated EGFR products, suggesting that the negative feedback loop upon EGFR expression is intact or that there is faster turnover at these early stages of carcinogenesis. In the L2LMP1CAO mice, increased levels of vascular endothelial growth factor are also seen at an early stage in the skin. As the phenotype worsens, with increasing hyperplasia and vascularization leading to keratoacanthoma, p16INK4a and matrix metalloproteinase 9 expression is induced. The lesions can progress spontaneously to carcinoma. Carcinoma cell lines developed from these mice show high levels of total and phosphorylated EGFR. These data show that the induction of signaling through EGFR by LMP1 is an early event in carcinogenesis and that any inhibition upon EGFR expression is lifted during progression. Furthermore, expression of LMP1 is not sufficient to inhibit induction of p16INK4a in response to abnormal proliferation. These data are consistent with the cooperative effects seen between LMP1 and loss of the INK4a locus in transgenic mice and with the frequency of loss of this locus in EBV-associated nasopharyngeal carcinoma.
Overlapping Gene Expression in Fetal Mouse Intestine Development and Human Colorectal Cancer
Authors: Hu Michael , Shivdasani Ramesh A. 
Published: October 2005

Abstract
Pathways relevant to cancer are well known to overlap with fetal development, as reflected in reactivation of embryonic genes in tumors. However, molecular evidence for this notion has gathered in piecemeal fashion, and systematic approaches have rarely been applied to gauge the extent and global characteristics of the overlap in gene expression between developing tissues and cancer. The fraction of genes that is expressed aberrantly in a given cancer and also developmental in primary function is unknown, and the tissue specificity of recapitulated gene expression remains unexplored. We developed a statistical method to relate expression profiles from human colon cancer and diverse nonintestinal tumors to transcripts that decline in expression with epithelial differentiation in the fetal mouse gut. For genes that are overexpressed in colon cancer, we computed 8% to 19% likelihood that they were expressed transiently during epithelial morphogenesis in intestine development. Among genes dysregulated in other tumors, the corresponding likelihood fell between 1% and 6%. Similarly, low probabilities were obtained when we compared genes not overexpressed in colon cancer with transcriptional profiles in intestine organogenesis. Genes that increase after fetal gut epithelial differentiation were not differentially represented between cancerous and normal colon. Our findings systematically characterize the global extent and tissue specificity of developmental expression programs in colorectal cancer and illustrate the use of such an approach to identify candidate biomarkers and therapeutic targets.
Targeted Disruption of Smad4 in Mouse Epidermis Results in Failure of Hair Follicle Cycling and Formation of Skin Tumors
Authors: Yang Leilei , Mao Chunming , Teng Yan , Li Wenlong , Zhang Jishuai , Cheng Xuan , Li Xiaobing , Han Xinghai , Xia Zhaofan , Deng Hongkui , Yang Xiao 
Published: October 2005

Abstract
Smad4 is the common mediator of transforming growth factor-β (TGF-β) superfamily signaling, which functions in diverse developmental processes in mammals. To study the role of Smad4 in skin development, a keratinocyte-specific null mutant of Smad4 (Smad4co/co;K5-Cre) was generated in mice using the Cre-loxP system. The Smad4-mutant mice exhibited progressive alopecia as a result of the mutant hair follicles failing to undergo programmed regression. Sonic hedgehog (Shh) was only detected in Smad4-mutant hair follicles at the catagen stage. Seventy percent of Smad4co/co; K5-Cre mice developed spontaneous tumors within 12 months of birth. c-Myc and cyclin D1 were up-regulated whereas p21 and p27 expressions were decreased, which correlated with the epidermal hyperplasia in Smad4 mutants. Interestingly, coordinated deletion of the Smad4 and PTEN genes resulted in accelerated hair loss and skin tumor formation, suggesting that Smad4 and PTEN act synergistically to regulate epidermal proliferation and differentiation. All of our data indicate that Smad4 is essential for catagen induction and acts as a critical suppressor in skin tumorigenesis.
Effect of p53 Status and STAT1 on Chemotherapy-Induced, Fas-Mediated Apoptosis in Colorectal Cancer
Authors: McDermott Ultan , Longley Daniel B. , Galligan Leeona , Allen Wendy , Wilson Timothy , Johnston Patrick G. 
Published: October 2005

AbstractWe investigated the role of p53 and the signal transducer and activator of transcription 1 (STAT1) in regulating Fas-mediated apoptosis in response to chemotherapies used to treat colorectal cancer. We found that 5-fluorouracil (5-FU) and oxaliplatin only sensitized p53 wild-type (WT) colorectal cancer cell lines to Fas-mediated apoptosis. In contrast, irinotecan (CPT-11) and tomudex sensitized p53 WT, mutant, and null cells to Fas-mediated cell death. Furthermore, CPT-11 and tomudex, but not 5-FU or oxaliplatin, up-regulated Fas cell surface expression in a p53-independent manner. In addition, increased Fas cell surface expression in p53 mutant and null cell lines in response to CPT-11 and tomudex was accompanied by only a slight increase in total Fas mRNA and protein expression, suggesting that these agents trigger p53-independent trafficking of Fas to the plasma membrane. Treatment with CPT-11 or tomudex induced STAT1 phosphorylation (Ser727) in the p53-null HCT116 cell line but not the p53 WT cell line. Furthermore, STAT1-targeted small interfering RNA (siRNA) inhibited up-regulation of Fas cell surface expression in response to CPT-11 and tomudex in these cells. However, we found no evidence of altered Fas gene expression following siRNA-mediated down-regulation of STAT1 in drug-treated cells. This suggests that STAT1 regulates expression of gene(s) involved in cell surface trafficking of Fas in response to CPT-11 or tomudex. We conclude that CPT-11 and tomudex may be more effective than 5-FU and oxaliplatin in the treatment of p53 mutant colorectal cancer tumors by sensitizing them to Fas-mediated apoptosis in a STAT1-dependent manner.
CpG Island Methylation of DNA Damage Response Genes in Advanced Ovarian Cancer
Authors: Teodoridis Jens M. , Hall Jacqueline , Marsh Sharon , Kannall Hilary D. , Smyth Catriona , Curto Jorge , Siddiqui Nadeem , Gabra Hani , McLeod Howard L. , Strathdee Gordon , Brown Robert 
Published: October 2005

Abstract
We have determined the methylation frequencies of 24 CpG islands of genes associated with DNA damage responses or with ovarian cancer in 106 stage III/IV epithelial ovarian tumors. We have analyzed this data for whether there is evidence of a CpG island methylator phenotype or associations of CpG island methylation with response to chemotherapy in advanced ovarian cancer. Frequent methylation was observed for OPCML, DCR1, RASSF1A, HIC1, BRCA1, and MINT25 (33.3%, 30.7%, 26.4%, 17.3%, 12.3%, and 12.0%, respectively), whereas no methylation was observed for APAF-1, DAPK, FANCF, FAS, P14, P21, P73, SOCS-3, and SURVIVIN. The remaining genes showed only a low frequency of methylation, &lt;10%. Unsupervised gene shaving identified a nonrandom pattern of methylation for OPCML, DCR1, RASSF1A, MINT25, HIC1, and SFRP1, supporting the concept of concordant methylation of these genes in ovarian cancer. Methylation of at least one of the group of genes involved in DNA repair/drug detoxification (BRCA1, GSTP1, and MGMT) was associated with improved response to chemotherapy (P = 0.013). We have examined the frequency of a polymorphism in the DNA methyltransferase gene DNMT3b6, which has been previously reported to affect gene transcription and cancer risk. The genetic polymorphism in the DNMT3b6 gene promoter (at position −149) is not significantly associated with the concordant methylation observed, but is weakly associated with the overall frequency of methylation at the genes examined (P = 0.04, n = 56). This supports the hypothesis that genetic factors affecting function of DNMT genes may underlie the propensity of tumors to acquire aberrant CpG island methylation.
Gene Expression Changes and Signaling Events Associated with the Direct Antimelanoma Effect of IFN-γ
Authors: Gollob Jared A. , Sciambi Catherine J. , Huang Zhiqing , Dressman Holly K. 
Published: October 2005

AbstractIFN-γ plays a role in the response to melanoma indirectly through its effect on the immune system and directly through its antiproliferative and proapoptotic effects on melanoma cells. To understand the molecular basis for the direct antimelanoma effect of IFN-γ, we studied IFN-induced changes in gene expression and signaling among three human melanoma cell lines (DM6, DM93, and 501mel). These were resistant to the antimelanoma effect of IFN-α, and only DM6 cells exhibited growth inhibition and apoptosis with IFN-γ. Through DNA microarray analysis, we found that the antimelanoma effect of IFN-γ in DM6 was associated with the down-regulation of multiple genes involved in G-protein signaling and phospholipase C activation (including Rap2B and calpain 3) as well as the down-regulation of genes involved in melanocyte/melanoma survival (MITF and SLUG), apoptosis inhibition (Bcl2A1 and galectin-3), and cell cycling (CDK2). The antimelanoma effect of IFN-γ was also associated with the up-regulation of the proapoptotic dependence receptor UNC5H2 and the Wnt inhibitor Dkk-1. Whereas both IFNs were able to activate Stat1 in all cell lines, the delayed activation of the extracellular signal-regulated kinase, p38, and c-Jun NH2-terminal kinase mitogen-activated protein kinases occurred only in DM6 with IFN-γ, and the effect of IFN-γ on cell growth and survival as well as gene expression in DM6 was dependent on the coordinate activation of MEK1 and p38. These findings provide new insights into the signaling events and gene expression changes associated with growth inhibition and apoptosis in melanoma and may thereby assist in identifying new targets for the treatment of melanoma.
Epimorphin Overexpression in the Mouse Mammary Gland Promotes Alveolar Hyperplasia and Mammary Adenocarcinoma
Authors: Bascom Jamie L. , Fata Jimmie E. , Hirai Yohei , Sternlicht Mark D. , Bissell Mina J. 
Published: October 2005

Abstract
Epimorphin/syntaxin-2 (EPM) is a plasma membrane–anchored protein that has at least two distinct functions depending on its membrane topology: vesicle fusion when localized to the cytoplasmic surface and morphogenic signaling when localized to the extracellular surface. Transgenic mice that express full-length extracellular EPM fused to the NH2-terminal signal sequence of interleukin-2, under the control of the whey acidic protein (WAP) gene promoter, exhibit aberrant mammary gland morphogenesis associated with increased expression of CCAAT enhancer binding protein β (C/EBPβ). Here we report that aged nulliparous and uniparous female WAP-EPM transgenic mice develop alveolar hyperplasias and well-differentiated adenocarcinomas that express high levels of C/EBPβ, keratin-14, matrix metalloproteinase-3, and β-catenin. This study reveals another pathway in which overexpression and alteration of a normal morphogenic process promote the development of cancer in the mammary gland.
The Threshold Level of Adenomatous Polyposis Coli Protein for Mouse Intestinal Tumorigenesis
Authors: Li Qin , Ishikawa Tomo-o , Oshima Masanobu , Taketo Makoto M. 
Published: October 2005

Abstract
The adenomatous polyposis coli (APC) gene, whose mutations are responsible for familial adenomatous polyposis, is a major negative controller of the Wnt/β-catenin pathway. To investigate the dose-dependent effects of APC protein in suppressing intestinal tumorigenesis, we constructed mutant mice carrying hypomorphic Apc alleles ApcneoR and ApcneoF whose expression levels were reduced to 20% and 10% of the wild type, respectively. Although both hypomorphic heterozygotes developed intestinal polyps, tumor multiplicities were much lower than that in ApcΔ716 mice, heterozygotes of an Apc null allele. Like in ApcΔ716 mice, loss of the wild-type Apc allele was confirmed for all polyps examined in the ApcneoR and ApcneoF mice. In the embryonic stem cells homozygous for these hypomorphic Apc alleles, the level of the APC protein was inversely correlated with both the β-catenin accumulation and β-catenin/T-cell factor transcriptional activity. These results suggest that the reduced APC protein level increases intestinal polyp multiplicity through quantitative stimulation of the β-catenin/T-cell factor transcription. We further estimated the threshold of APC protein level that forms one polyp per mouse as ∼15% of the wild type. These results also suggest therapeutic implications concerning Wnt signaling inhibitors.
Oncogenomics 2005 Meeting Report: Dissecting Cancer through Genome Research
Authors: Feigal Ellen G. , Dracopoli Nicholas C. , Trent Jeffrey M. 
Published: October 2005

Abstract
The Oncogenomics Conference was held on February 2 to 5, 2005 at the Omni San Diego Hotel, San Diego, CA. The meeting chairpersons were Dr. Jeffrey Trent (Translational Genomics Research Institute, Phoenix, AZ) and Dr. Nicholas Dracopoli (Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ). This fourth conference sponsored by the AACR brought together a diverse group of scientists working in the fields of genome research, cancer biology, and epidemiology, and explored how genomic research can be used most effectively to impact the clinical response to cancer. Advances in the clinical application of pharmacogenomics to predict response to oncology therapeutic modalities led to a dramatic increase in the number of presentations and posters with a clinical focus at this year's meeting. The keynote address was given by Dr. William Evans (St. Jude Children's Hospital, Memphis, TN) who discussed the pharmacogenomics of acute lymphoblastic leukemia as a cancer paradigm.
Oxovanadium(IV)-sulfite compounds: Synthesis and structural and physical studies
Authors: Chilas George I. , Miras Haralampos N. , Manos Manolis J. , Woollins J. Derek , Slawin Alexandra M. Z. , Stylianou Marios , Keramidas Anastasios D. , Kabanos Themistoklis A. 
Published: October 2005

Abstract
Reaction of VIVOCl2 in strongly acidic aqueous solution with either (NH4)2SO3 or Na2SO3 and Bu4NBr at ~70°C in the pH range 2.5-4.5 gives the clusters (NH4)2{[V4
IV(μ
4-O)2(μ
3-OH)2](VIVO)2(μ
3-SO3)4O4(H2O)2} and (n-Bu4N)2{[V4
IV(μ
4-O)2(μ
3-OH)2](VIVO)2(μ
3-SO3)4O4(H2O)2}, respectively. Reaction of NH4VVO3 with (NH4)2SO3 resulted in the isolation of the first compound. When the latter reaction is carried out in the presence of MgO, compound (NH4)[VIVO(SO3)1.5H2O]∞.2.5H2O was isolated instead. Compound (n-Bu4N)2{[V4
IV(μ
4-O)2(μ
3-OH)2](VIVO)2(μ
3-SO3)4O4(H2O)2} and (NH4)[VIVO(SO3)1.5H2O]∞.2.5H2O were characterized by X-ray structure analysis. The crystal structure of species (n-Bu4N)2{[V4
IV(μ
4-O)2(μ
3-OH)2](VIVO)2(μ
3-SO3)4O4(H2O)2} revealed a unprecedented hexanuclear cluster consisting of a cubane core [M4(μ
4-O)2(μ
3-OH)2] connected to two other metal atoms through the core oxo-groups and four μ
3-SO3 bridges. Compound (NH4)[VIVO(SO3)1.5H2O]∞.2.5H2O represents a rare example of an open-framework species prepared under mild conditions. Cyclic voltammetric examination of compound (n-Bu4N)2{[V4
IV(μ
4-O)2(μ
3-OH)2](VIVO)2(μ
3-SO3)4O4(H2O)2} revealed a redox process which was assigned to the oxidation of one core of vanadium(IV) to vanadium(V).
Selective synthetic methods using vanadium-mediated redox reactions
Authors: Hirao Toshikazu 
Published: October 2005

Abstract
Oxovanadium(V) compounds serve as Lewis acids with oxidation capability and induce one-electron oxidative transformations of organosilicons, organotins, organoaluminums, organoborons, organozincs, and/or their ate complexes. Low-valent vanadium-catalyzed stereoselective reductive transformations, including dehalogenation, pinacol coupling, and the related radical reaction, have been developed by constructing a multicomponent redox system in combination with a coreductant and an additive.
Oral therapy of L-glutamic acid γ-monohydroxamate-vanadium (2:1) complex: Improvement of blood glucose profile in different types of diabetic rodents
Authors: Shechter Y. , Goldwaser I. , Mironchik M. , Tsubery H. , Fridkin M. 
Published: October 2005

Abstract
We report that oral administration of vanadium (+5) combined with L-glutamic acid γ-monohydroxamate at 1:2 stoichiometry [L-Glu(γ)HXM.VO3
-] is highly effective in reducing blood glucose levels (BGLs) in a wide variety of diabetic rodents. In streptozocin-treated rats, a single administration (0.28 mmol/kg body wt) decreased BGL from 490 to 360 mg/dl within 1 h of administration, keeping this reduced level for additional 22 h, and a daily dose of 0.14 mmol/kg was found optimal. In Zucker diabetic fatty (ZDF) rats, a single dose of 0.14 mmol/kg normalized BGL within 8 h of administration, and maintained normal value for additional two days. In db/db mice, a single L-Glu(γ)HXM.VO3
- administration of 0.2 mmol/kg decreased BGL from 500 ± 50 to 240 ± 20 mg/dl at 2 h, but was less effective afterwards. In high-carbohydrate (CHO)-fed Psammomis obesus, a single oral dose (0.14 mmol/kg) normalized BGL over a period of two days, and a daily dose of 0.07 mmol/kg/d, at the time P. obesus was transferred from low- to high-CHO diet, fully arrested the development of hyperglycemia characterizing this diabetic rodent. Finally, we found that the index of toxicity of orally administered L-GLU(γ)HXM-vanadate in rodents is 5-7 times lower than that of free sodium vanadate.
Macehuales and the Corporate Solution: Colonial Secessions in Nahua Central Mexico
Authors: Perkins Stephen M. 
Published: October 2005

This investigation of the legal separation, or 'secession,'of indigenous subject villages from municipal governments in the Tepeaca district of Puebla, Mexico finds that early colonial (1521–1650) and late colonial (1651–1821) cases differed in their litigation and consequences. Early Spanish officials decided cases based predominantly on pre-Hispanic tradition, only permitting separations that preserved older indigenous social units. Bourbon officials of the late era, in contrast, enabled an entirely new type of pueblo to develop. Indigenous commoners (macehuales) used secessions to rupture relations with indigenous nobles (caciques) and local Spanish agriculturalists. The corporate organization of new pueblos in Puebla was without pre-Hispanic precedent.En este artículo, investigo la separación legal, o "secesión", de sujetos indígenas de sus municipios en el distrito de Tepeaca, Puebla, en México. Ahí, los trámites coloniales tempranos (1521–1650) contrastaban con los trámites coloniales tardíos (1651–1821) tanto en su litigio como en sus consecuencias. Los funcionarios españoles del primer período resolvían los casos basándose sobre todo en la tradición prehispánica, y permitiendo tan sólo separaciones que preservaban las entidades sociales indígenas previamente existentes. En contraste, los funcionarios borbones permitían el desarollo de un nuevo tipo de pueblo. Los macehuales hacían uso del proceso de secesión para romper sus relaciones con caciques y agricultores españoles locales. La organización corporativa de los pueblos nuevos en Puebla no tuvo precedente en la era prehispánica.
Sensitivity of an indigenous amphipod (Corophium colo) to chemical contaminants in laboratory toxicity tests conducted with sediments from Sydney Harbor, Australia, and vicinity
Authors: McCready Stephanie , Greely Christopher R. , Hyne Ross V. , Birch Gavin F. , Long Edward R. 
Published: October 2005

Abstract
Laboratory survival tests were conducted with an indigenous infaunal amphipod, Corophium colo, on 103 sediment samples from Sydney Harbor (NSW, Australia) and vicinity, containing a wide range of chemicals and concentrations. The present study describes the sensitivity of C. colo to the sediments and compares the results to data for North American amphipods (Rhepoxynius abronius and Ampelisca abdita) previously used to establish and validate sediment-quality guidelines (SQGs). The incidence of toxicity increased with increasing contam ination, as indicated by increasing numbers of SQGs exceeded and increasing mean SQG quotients. The incidence of highly toxic results (p &lt; 0.05 and mean amphipod survival of &lt;80% that of controls) for highly contaminated samples was approximately half (28–40%) that of a large U.S. database (74%). The incidence of highly toxic responses for samples with intermediate levels of contamination also was lower in the present study (5–13%) compared to the results in large U.S. studies (∼30–50%). Corophium colo reburial tests showed greater sensitivity compared to survival tests, with a maximum incidence of statistically significant responses in moderately contaminated sediments of 70%. The present study showed that adult Corophium organisms are suitable for testing lethal responses in highly contaminated sediments (i.e., with mean effects range-median quotients of &gt;1.5). Reburial results provide additional sensitivity.
Weathering and aging of 2,4,6-trinitrotoluene in soil increases toxicity to potworm Enchytraeus crypticus
Authors: Kuperman Roman G. , Checkai Ronald T. , Simini Michael , Phillips Carlton T. , Kolakowski Jan E. , Kurnas Carl W. 
Published: October 2005

Abstract
Energetic materials are employed in a wide range of commercial and military activities and often are released into the environment. Scientifically based ecological soil-screening levels (Eco-SSLs) are needed to identify contaminant explosive levels in soil that present an acceptable ecological risk. Insufficient information for 2,4,6-trinitrotoluene (TNT) to generate Eco-SSLs for soil invertebrates necessitated toxicity testing. We adapted the standardized Enchytraeid Reproduction Test and selected Enchytraeus crypticus for these studies. Tests were conducted in Sassafras sandy loam soil, which supports relatively high bioavailability of TNT. Weathering and aging procedures for TNT amended to test soil were incorporated into the study design to produce toxicity data that better reflect the soil exposure conditions in the field compared with toxicity in freshly amended soils. This included exposing hydrated TNT-amended soils in open glass containers in the greenhouse to alternating wetting and drying cycles. Definitive tests showed that toxicity for E. crypticus adult survival and juvenile production was increased significantly in weathered and aged soil treatments compared with toxicity in freshly amended soil based on 95% confidence intervals. The median effect concentration and 20% effective concentration for reproduction were 98 and 77 mg/kg, respectively, for TNT freshly amended into soil and 48 and 37 mg/kg, respectively, for weathered and aged TNT soil treatments. These findings of increased toxicity to E. crypticus in weathered and aged TNT soil treatments compared with exposures in freshly amended soils show that future investigations should include a weathering and aging component to generate toxicity data that provide more complete information on ecotoxicological effects of energetic contaminants in soil.