bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular identification of prey in the stomach contents of Harp Seals (Pagophilus groenlandicus) using species‐specific oligonucleotides
Authors: MARSHALL H. D. , HART K. A. , YASKOWIAK E. S. , STENSON G. B. , McKINNON D. , PERRY E. A. 
Published: May 2009

AbstractAll methods of diet analysis in marine mammals, including hard part analysis (HPA), have biases affecting the accuracy of prey‐species identification and frequency in the estimated diet due to differential consumption, digestion and retention. Using PCR amplification of specific prey DNA with species‐specific primers, we developed a DNA‐based method that complements HPA and provides an alternative means to detect prey from stomach contents of Harp Seals (Pagophilus groenlandicus). The target size that could be reliably amplified was determined using a digestion time‐series of Atlantic Cod (Gadus morhua) tissue in simulated seal stomachs. Various target lengths were trialed using general teleost primers; amplicons of approximately 800 bp or less were consistently obtained. Prey species‐specific PCR primers for Atlantic Cod, Arctic Cod (Boreogadus saida) and Capelin (Mallotus villosus) were designed and tested with DNA from the stomach contents of 31 Harp Seals. Amplicons were obtained for all three species‐specific primer sets. Amplification results compared with HPA revealed: (i) Atlantic Cod hard parts were found in five stomachs where no Atlantic Cod DNA amplified, suggesting that Atlantic Cod may be over‐represented in the estimated diet, (ii) amplification of Arctic Cod DNA occurred for 17 stomachs, including all 12 stomachs with, and five stomachs without, Arctic Cod hard parts, and (iii) Capelin DNA amplified for four of five stomachs with Capelin hard parts and for one stomach without Capelin hard parts. We conclude that PCR amplification of specific prey DNA provides a viable means to complement Harp Seal diet analysis by HPA, but suggest that valuable information for quantitative diet analysis rests in a quantitative PCR approach.
Corneal flap thickness with the Moria M2™ microkeratome and Med‐Logics calibrated LASIK blades
Authors: Pietilä Juhani , Huhtala Anne , Mäkinen Petri , Seppänen Matti , Jääskeläinen Markus , Uusitalo Hannu 
Published: May 2009

Abstract.Purpose:  This study aimed to compare and study potential factors that affect the accuracy of corneal flap thickness created in laser‐assisted in situ keratomileusis (LASIK) using the Moria model 2 (M2™) head 130 microkeratome with the Med‐Logics calibrated LASIK blades Minus 20 (ML –20) and Minus 30 (ML –30).Methods:  Corneal thickness in 200 (164 myopic and 36 hyperopic) eyes (100 patients) was measured by ultrasonic pachymetry preoperatively and intraoperatively after flap cutting. A total of 100 eyes were treated with the ML –20 and 100 with the ML –30. The right eye was operated before the left eye in each patient, using the same blade. In an additional group of 40 eyes, the left eye was operated first.Results:  Mean corneal flap thickness using the ML –20 blade for an intended flap thickness of 140 μm was 129.1 μm (standard deviation [SD] 15.6, range 104–165 μm) in right eyes and 111.5 μm (SD 14.5, range 78–144 μm) in left eyes. Mean corneal flap thickness using the ML –30 blade for an intended flap thickness of 130 μm was 127.1 μm (SD 16.6, range 90–168 μm) in right eyes and 109.9 μm (SD 16.8, range 72–149 μm) in left eyes.Conclusions:  Both microkeratome blade types cut thinner flaps than were intended. There was substantial variation in flap thickness. The first flap to be cut with a particular blade was considerably thicker than the second flap cut with the same blade. Based on these data, we recommend the use of disposable single‐use microkeratomes rather than these ML blades.
A Pilot Assessment of a School‐Based Youth Court in a Resource‐Poor African‐American Urban School District: Lessons Learned From Youth Court Volunteers
Authors: Hirschinger‐Blank Nancy , Simons Lori , Volz Gregory L. , Thompson Raymond , Finely Laura , Cleary Joseph 
Published: May 2009

ABSTRACTThis study assesses the benefits of youth court participation for volunteers (N = 14) serving as jurors in an urban school‐based youth court. Focus group and questionnaire data indicate that volunteers are capable of providing more effective sanctioning decisions than adults. Volunteers reported developing citizenship skills including learning about the law and decision‐making skills. The youth court leaders developed self‐confidence and maturity while learning the conflict resolution skills necessary for rendering dispositions and conducting trials. We interpret our findings within the context of the youth court literature, the issue of the school‐to‐prison pipeline, and Elijah Anderson's analysis of the Code of the Street.
Independence of points on elliptic curves arising from special points on modular and Shimura curves, II: local results
Authors: Buium Alexandru , Poonen Bjorn 
Published: May 2009

AbstractIn the predecessor to this article, we used global equidistribution theorems to prove that given a correspondence between a modular curve and an elliptic curveA, the intersection of any finite-rank subgroup ofAwith the set of CM-points ofAis finite. In this article we apply local methods, involving the theory of arithmetic differential equations, to provequantitativeversions of a similar statement. The new methods apply also to certain infinite-rank subgroups, as well as to the situation where the set of CM-points is replaced by certain isogeny classes of points on the modular curve. Finally, we prove Shimura-curve analogues of these results.
Methylation ofTFPI2in Stool DNA: A Potential Novel Biomarker for the Detection of Colorectal Cancer
Authors: Glöckner Sabine C. , Dhir Mashaal , Yi Joo Mi , McGarvey Kelly E. , Van Neste Leander , Louwagie Joost , Chan Timothy A. , Kleeberger Wolfram , de Bruïne Adriaan P. , Smits Kim M. , Khalid-de Bakker Carolina A.J. , Jonkers Daisy M.A.E. , Stockbrügger Reinhold W. , Meijer Gerrit A. , Oort Frank A. , Iacobuzio-Donahue Christine , Bierau Katja , Herman James G. , Baylin Stephen B. , Van Engeland Manon , Schuebel Kornel E. , Ahuja Nita 
Published: May 2009

AbstractWe have used a gene expression array–based strategy to identify the methylation of tissue factor pathway inhibitor 2 (TFPI2), a potential tumor suppressor gene, as a frequent event in human colorectal cancers (CRC). TFPI2 belongs to the recently described group of embryonic cell Polycomb group (PcG)–marked genes that may be predisposed to aberrant DNA methylation in early stages of colorectal carcinogenesis. Aberrant methylation of TFPI2 was detected in almost all CRC adenomas (97%, n = 56) and stages I to IV CRCs (99%, n = 115). We further explored the potential of TFPI2 as a biomarker for the early detection of CRC using stool DNA–based assays in patients with nonmetastatic CRC and average-risk noncancer controls who were candidates for screening. TFPI2 methylation was detected in stool DNA from stage I to III CRC patients with a sensitivity of 76% to 89% and a specificity of 79% to 93%. Detection of TFPI2 methylation in stool DNA may act as a useful adjunct to the noninvasive strategies for screening of CRCs in the future. [Cancer Res 2009;69(11):4691–9]
Chemical Genomics Identifies the Unfolded Protein Response as a Target for Selective Cancer Cell Killing during Glucose Deprivation
Authors: Saito Sakae , Furuno Aki , Sakurai Junko , Sakamoto Asami , Park Hae-Ryong , Shin-ya Kazuo , Tsuruo Takashi , Tomida Akihiro 
Published: May 2009

Abstract
Glucose deprivation, a cell condition that occurs in solid tumors, activates the unfolded protein response (UPR). A key feature of the UPR is the transcription program activation, which allows the cell to survive under stress conditions. Here, we show that the UPR transcription program is disrupted by the antidiabetic biguanides metformin, buformin, and phenformin depending on cellular glucose availability. These drugs inhibit production of the UPR transcription activators XBP1 and ATF4 and induce massive cell death during glucose deprivation as did the antitumor macrocyclic compound versipelostatin. Gene expression profiling shows remarkable similarity in the modes of action of biguanides and versipelostatin determined by the broad range of glucose deprivation-inducible genes. Importantly, during glucose deprivation, most of the biguanide suppression genes overlap with the genes induced by tunicamycin, a chemical UPR inducer. Gene expression profiling also identifies drug-driven signatures as a tool for discovering pharmacologic UPR modulators. Our findings show that disrupting the UPR during glucose deprivation could be an attractive approach for selective cancer cell killing and could provide a chemical genomic basis for developing UPR-targeting drugs against solid tumors. [Cancer Res 2009;69(10):4225–34]
A Genetic Screen Identifies Topoisomerase 1 as a Regulator of Senescence
Authors: Humbert Nicolas , Martien Sébastien , Augert Arnaud , Da Costa Marco , Mauen Sébastien , Abbadie Corinne , de Launoit Yvan , Gil Jesús , Bernard David 
Published: May 2009

Abstract
Normal cell growth can be permanently blocked when cells enter a state known as senescence. This phenomenon can be triggered by various stresses, such as replicative exhaustion, oncogenic stimulation, or oxidative stress. Senescence prevents transmission of aberrant signals to daughter cells and thus prevents irreversible damage that could favor cancer development. To identify new genetic events controlling senescence, we have performed a loss-of-function genetic screen on normal human cells. We report that knockdown of topoisomerase I (Top1) results in an increased replicative potential associated with a decrease in senescence markers and a diminished DNA damage response. In addition, Top1 depletion also favors a bypass of oncogene-induced senescence. Conversely, Top1 constitutive expression induces growth arrest, the appearance of a senescence marker, and an activation of the DNA damage response. Altogether, these results reveal an unanticipated function of Top1 in regulating senescence. [Cancer Res 2009;69(10):4101–6]
Comparison of Primary Neuroblastoma Tumors and Derivative Early-Passage Cell Lines Using Genome-Wide Single Nucleotide Polymorphism Array Analysis
Authors: Volchenboum Samuel L. , Li Cheng , Li Shuli , Attiyeh Edward F. , Reynolds C. Patrick , Maris John M. , Look A. Thomas , George Rani E. 
Published: May 2009

Abstract
Stromal contamination is one of the major confounding factors in the analysis of solid tumor samples by single nucleotide polymorphism (SNP) arrays. As we propose to use genome-wide SNP microarray analysis as a diagnostic platform for neuroblastoma, the sensitivity, specificity, and accuracy of these studies must be optimized. To investigate the effects of stromal contamination, we derived early-passage cell lines from nine primary tumors and compared their genomic signature with that of the primary tumors using 100K SNP arrays. The average concordance between tumor and cell line for raw loss of heterozygosity (LOH) calls was 96% (range, 91–99%) and for raw copy number alterations, 71% (range, 43–87%). In general, there were a larger number of LOH events identified in the cell lines compared with the matched tumor samples (mean increase, 3.2% ± 1.9%). We have developed an algorithm that shows that the presence of stroma contributes to under-reporting of LOH and copy number loss. Notable findings in this sample set were uniparental disomy of chromosome arms 11p, 1q, 14q, and 15q and a novel area of amplification on chromosome band 11p15. Our analysis shows that LOH was identified significantly more often in derived cell lines compared with the original tumor samples. Although these may in part be due to clonal selection during adaptation to tissue culture, our study indicates that stromal contamination may be a major contributing factor in underestimation of LOH and copy number loss events. [Cancer Res 2009;69(10):4143–9]
Characterization of a Naturally Occurring Breast Cancer Subset Enriched in Epithelial-to-Mesenchymal Transition and Stem Cell Characteristics
Authors: Hennessy Bryan T. , Gonzalez-Angulo Ana-Maria , Stemke-Hale Katherine , Gilcrease Michael Z. , Krishnamurthy Savitri , Lee Ju-Seog , Fridlyand Jane , Sahin Aysegul , Agarwal Roshan , Joy Corwin , Liu Wenbin , Stivers David , Baggerly Keith , Carey Mark , Lluch Ana , Monteagudo Carlos , He Xiaping , Weigman Victor , Fan Cheng , Palazzo Juan , Hortobagyi Gabriel N. , Nolden Laura K. , Wang Nicholas J. , Valero Vicente , Gray Joe W. , Perou Charles M. , Mills Gordon B. 
Published: May 2009

Abstract
Metaplastic breast cancers (MBC) are aggressive, chemoresistant tumors characterized by lineage plasticity. To advance understanding of their pathogenesis and relatedness to other breast cancer subtypes, 28 MBCs were compared with common breast cancers using comparative genomic hybridization, transcriptional profiling, and reverse-phase protein arrays and by sequencing for common breast cancer mutations. MBCs showed unique DNA copy number aberrations compared with common breast cancers. PIK3CA mutations were detected in 9 of 19 MBCs (47.4%) versus 80 of 232 hormone receptor–positive cancers (34.5%; P = 0.32), 17 of 75 HER-2–positive samples (22.7%; P = 0.04), 20 of 240 basal-like cancers (8.3%; P &lt; 0.0001), and 0 of 14 claudin-low tumors (P = 0.004). Of 7 phosphatidylinositol 3-kinase/AKT pathway phosphorylation sites, 6 were more highly phosphorylated in MBCs than in other breast tumor subtypes. The majority of MBCs displayed mRNA profiles different from those of the most common, including basal-like cancers. By transcriptional profiling, MBCs and the recently identified claudin-low breast cancer subset constitute related receptor-negative subgroups characterized by low expression of GATA3-regulated genes and of genes responsible for cell-cell adhesion with enrichment for markers linked to stem cell function and epithelial-to-mesenchymal transition (EMT). In contrast to other breast cancers, claudin-low tumors and most MBCs showed a significant similarity to a “tumorigenic” signature defined using CD44+/CD24− breast tumor–initiating stem cell–like cells. MBCs and claudin-low tumors are thus enriched in EMT and stem cell–like features, and may arise from an earlier, more chemoresistant breast epithelial precursor than basal-like or luminal cancers. PIK3CA mutations, EMT, and stem cell-like characteristics likely contribute to the poor outcomes of MBC and suggest novel therapeutic targets. [Cancer Res 2009;69(10):4116–24]
Up-regulation of L1CAM in Pancreatic Duct Cells Is Transforming Growth Factor β1– and Slug-Dependent: Role in Malignant Transformation of Pancreatic Cancer
Authors: Geismann Claudia , Morscheck Mascha , Koch Dorothee , Bergmann Frank , Ungefroren Hendrik , Arlt Alexander , Tsao Ming-Sound , Bachem Max G. , Altevogt Peter , Sipos Bence , Fölsch Ulrich R. , Schäfer Heiner , Müerköster Susanne Sebens 
Published: May 2009

AbstractPancreatic ductal adenocarcinoma (PDAC) is thought to originate from ductal structures, exhibiting strong desmoplastic reaction with stromal pancreatic myofibroblasts (PMF), which are supposed to drive PDAC tumorigenesis. Previously, we observed high expression of the adhesion molecule L1CAM (CD171) in PDAC cells accounting for chemoresistance. Thus, this study aimed to investigate whether PMFs are involved in the induction of tumoral L1CAM and whether this contributes to malignant transformation of pancreatic ductal cells and PDAC tumorigenesis. Immunohistochemistry of tissues from chronic pancreatitis specimens revealed considerable L1CAM expression in ductal structures surrounded by dense fibrotic tissue, whereas no L1CAM staining was seen in normal pancreatic tissues. Using the human pancreatic duct cell line H6c7, we show that coculture with PMFs led to a transforming growth factor-β1 (TGF-β1)–dependent up-regulation of L1CAM expression. Similarly, L1CAM expression increased in monocultured H6c7 cells after administration of exogenous TGF-β1. Both TGF-β1– and PMF-induced L1CAM expression were independent of Smad proteins but required c-Jun NH2-terminal kinase activation leading to the induction of the transcription factor Slug. Moreover, Slug interacted with the L1CAM promoter, and its knockdown abrogated the TGF-β1– and PMF-induced L1CAM expression. As a result of L1CAM expression, H6c7 cells acquired a chemoresistant and migratory phenotype. This mechanism of TGF-β1–induced L1CAM expression and the resulting phenotype could be verified in the TGF-β1–responsive PDAC cell lines Colo357 and Panc1. Our data provide new insights into the mechanisms of tumoral L1CAM induction and how PMFs contribute to malignant transformation of pancreatic duct cells early in PDAC tumorigenesis. [Cancer Res 2009;69(10):4517–26]
Cancer Vaccine Enhanced, Non–Tumor-Reactive CD8+ T Cells Exhibit a Distinct Molecular Program Associated with “Division Arrest Anergy”
Authors: Beyer Marc , Karbach Julia , Mallmann Michael R. , Zander Thomas , Eggle Daniela , Classen Sabine , Debey-Pascher Svenja , Famulok Michael , Jäger Elke , Schultze Joachim L. 
Published: May 2009

AbstractImmune-mediated tumor rejection relies on fully functional T-cell responses and neutralization of an adverse tumor microenvironment. In clinical trials, we detected peptide-specific but non–tumor-reactive and therefore not fully functional CD8+ T cells post-vaccination against tumor antigens. Understanding the molecular mechanisms behind nontumor reactivity will be a prerequisite to overcome this CD8+ T-cell deviation. We report that these non–tumor-reactive CD8+ T cells are characterized by a molecular program associated with hallmarks of “division arrest anergy.” Non–tumor-reactive CD8+ T cells are characterized by coexpression of CD7, CD25, and CD69 as well as elevated levels of lckp505 and p27kip1. In vivo quantification revealed high prevalence of non–tumor-reactive CD8+ T cells with increased levels during cancer vaccination. Furthermore, their presence was associated with a trend toward shorter survival. Dynamics and frequencies of non–target-reactive CD8+ T cells need to be further addressed in context of therapeutic vaccine development in cancer, chronic infections, and autoimmune diseases. [Cancer Res 2009;69(10):4346–54]
3,3′-Diindolylmethane Enhances Taxotere-Induced Apoptosis in Hormone-Refractory Prostate Cancer Cells through Survivin Down-regulation
Authors: Rahman KM Wahidur , Banerjee Sanjeev , Ali Shadan , Ahmad Aamir , Wang Zhiwei , Kong Dejuan , Sakr Wael A. 
Published: May 2009

Abstract
Survivin, a member of inhibitor of apoptosis family, is associated with both prostate cancer progression and drug resistance. Therefore, we hypothesized that survivin may play a potentially important role in hormone-refractory prostate cancer (HRPC) and bone metastatic disease; thus, targeting of survivin signaling could enhance therapeutic efficacy in prostate cancer. 3,3′-Diindolylmethane (DIM) has been known to have cancer chemoprevention activity. However, no information is available regarding the down-regulation of survivin by DIM, which could result in the chemosensitization of HRPC cells to Taxotere-induced killing. We investigated the effect of DIM alone or in combination with Taxotere using LNCaP and C4-2B prostate cancer cells. We observed that DIM enhanced Taxotere-induced apoptotic death in both cell lines. These enhancing effects were related to a decrease in survivin expression as well as androgen receptor and nuclear factor-κB (NF-κB) DNA-binding activity. We also found that knockdown of survivin expression by small interfering RNA transfection increased DIM-induced cell growth inhibition and apoptosis, whereas overexpression of survivin by cDNA transfection abrogated DIM-induced cell growth inhibition and apoptosis in both prostate cancer cells. Importantly, luciferase assays showed a significant reduction of survivin-Luc and NF-κB-Luc activity in prostate cancer cells exposed to DIM and Taxotere. Furthermore, combination treatment significantly inhibited C4-2B bone tumor growth, and the results were correlated with the down-regulation of survivin. From these results, we conclude that inactivation of survivin by DIM enhanced the therapeutic efficacy of Taxotere in prostate cancer in general, which could be useful for the treatment of HRPC and metastatic prostate cancer. [Cancer Res 2009;69(10):4468–75]
A Three-Dimensional Osteogenic Tissue Model for the Study of Metastatic Tumor Cell Interactions with Bone
Authors: Mastro Andrea M. , Vogler Erwin A. 
Published: May 2009

Abstract
A specialized bioreactor based on the principle of simultaneous growth and dialysis permits growth of three-dimensional (3D), multiple-cell-layer osteogenic tissue from isolated osteoblasts over long, continuous-culture intervals (tested up to 10 months with no sign of necrosis). The resulting tissue recapitulates the stages of bone development observed in vivo, including phenotypic maturation of cobblestone-shaped osteoblasts into stellate-shaped osteocytes interconnected by many intercellular processes. Gene expression profiles parallel cell-morphologic changes with time, ultimately leading to increased expression of osteocyte-associated molecules such as E11, DMP1, and sclerostin. Contiguous, cm2-scale macroscopic mineral deposits that form within the bioreactor are consistent with bone hydroxyapatite. The simple to use bioreactor system provides an in vitro model that permits the study and manipulation of cancer cell interactions with bone tissue in real time. Metastatic human breast cancer cells, MDA-MB-231GFP, introduced into the model grow and colonize osteoblastic tissue in a manner reflecting various characteristics of pathologic tissue observed in the clinic. Specifically, MDA-MB-231GFP cells are observed to penetrate the thick extracellular matrix in which osteoblasts are embedded and to form chains reminiscent of "Indian files," described for infiltrating lobular or metaplastic breast carcinomas. Osteoblasts appear to be marshaled into a parallel alignment with cancer cells, followed by erosion of extracellular matrix structural integrity. Tissue degradation appears to be accompanied by increased expression of osteoblast inflammatory cytokines. [Cancer Res 2009;69(10):4097–100]
Complex Oncogenic Translocations with Gene Amplification Are Initiated by Specific DNA Breaks in Lymphocytes
Authors: Wright Sarah M. , Woo Yong H. , Alley Travis L. , Shirley Bobbi-Jo , Akeson Ellen C. , Snow Kathy J. , Maas Sarah A. , Elwell Rachel L. , Foreman Oded , Mills Kevin D. 
Published: May 2009

AbstractChromosomal instability is a hallmark of many tumor types. Complex chromosomal rearrangements with associated gene amplification, known as complicons, characterize many hematologic and solid cancers. Whereas chromosomal aberrations, including complicons, are useful diagnostic and prognostic cancer markers, their molecular origins are not known. Although accumulating evidence has implicated DNA double-strand break repair in suppression of oncogenic genome instability, the genomic elements required for chromosome rearrangements, especially complex lesions, have not been elucidated. Using a mouse model of B-lineage lymphoma, characterized by complicon formation involving the immunoglobulin heavy chain (Igh) locus and the c-myc oncogene, we have now investigated the requirement for specific genomic segments as donors for complex rearrangements. We now show that specific DNA double-strand breaks, occurring within a narrow segment of Igh, are necessary to initiate complicon formation. By contrast, neither specific DNA breaks nor the powerful intronic enhancer Eμ are required for complicon-independent oncogenesis. This study is the first to delineate mechanisms of complex versus simple instability and the first to identify specific chromosomal elements required for complex chromosomal aberrations. These findings will illuminate genomic cancer susceptibility and risk factors. [Cancer Res 2009;69(10):4454–60]