bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear Factor-κB–Related Serum Factors as Longitudinal Biomarkers of Response and Survival in Advanced Oropharyngeal Carcinoma
Authors: Allen Clint , Duffy Sonia , Teknos Theodoros , Islam Mozaffarul , Chen Zhong , Albert Paul S. , Wolf Gregory , Van Waes Carter 
Published: June 2007

Abstract
Purpose: Cytokines and growth factors modulated by transcription factor nuclear factor-κB and secreted by tumor and stromal cells are detectable in serum of patients with advanced cancers, including head and neck squamous cell carcinomas (SCC). Longitudinal changes in these serum factors could be early biomarkers of treatment response and survival.
Experimental Design: Interleukin (IL)-6, IL-8, growth-related oncogene-1 (GRO-1), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) concentrations were determined by Luminex multiplex assay using serum obtained at baseline and every 3 months in a prospective study of 30 patients with locally advanced (stage III/IV) oropharyngeal SCC receiving chemoradiation therapy. The relationship between baseline and direction of change in individual and multiple cytokines with cause-specific and disease-free survival was determined by Cox proportional hazards models and Kaplan-Meier survival analysis. Statistical analyses included adjustment for smoking status and response to chemoradiation.
Results: Three-year cause-specific and disease-free survival was 74.4% and 68.9%. Nonsmoking history (P = 0.05) and higher baseline VEGF (P = 0.003) correlated with increased survival. Longitudinal increases in levels of individual factors predicted decreased cause-specific survival when adjusted for smoking history [IL-6: relative risk (RR), 3.8; 95% confidence interval (95% CI), 2.0-7.4; P = 0.004; IL-8: RR, 1.6; 95% CI, 1.2-2.2; P = 0.05; VEGF: RR, 3.0; 95% CI, 1.6-5.6; P = 0.01; HGF: RR, 2.9; 95% CI, 1.9-4.4; P = 0.02; and GRO-1: RR, 1.2; 95% CI, 1.1-1.3; P = 0.02]. For a given individual, large increases in the upper quartile for any three or more factors predicted poorer cause-specific survival compared with patients with two or fewer large increases in factor levels (P = 0.004).
Conclusions: Pretreatment VEGF levels and longitudinal change in IL-6, IL-8, VEGF, HGF, and GRO-1 may be useful as biomarkers for response and survival in patients with locally advanced oropharyngeal and head and neck SCC treated with chemoradiation.
Distinction of Hereditary Nonpolyposis Colorectal Cancer and Sporadic Microsatellite-Unstable Colorectal Cancer through Quantification of MLH1 Methylation by Real-time PCR
Authors: Bettstetter Marcus , Dechant Stephan , Ruemmele Petra , Grabowski Monika , Keller Gisela , Holinski-Feder Elke , Hartmann Arndt , Hofstaedter Ferdinand , Dietmaier Wolfgang 
Published: June 2007

Abstract
Purpose: Promoter hypermethylation occurs frequently in tumors and leads to silencing of tumor-relevant genes like tumor suppressor genes. In a subset of sporadic colorectal cancers (CRC), inactivation of the mismatch repair gene MLH1 due to promoter methylation causes high level of microsatellite instability (MSI-H). MSI-H is also a hallmark of hereditary nonpolyposis colorectal cancer (HNPCC) in which mismatch repair inactivation results from germ-line mutations. For differentiation of sporadic and hereditary MSI-H tumor patients, MLH1 promoter methylation analysis is a promising tool but is not yet used in daily diagnostics because only qualitative techniques without standardization are available. The aim of this study is to establish a reliable and quantitative MLH1 methylation analysis technique and to define valid MLH1 methylation cutoff values for HNPCC diagnostics.
Experimental Design: We developed a new real-time PCR–based technique to detect and quantify methylation of both proximal and distal hMLH1 promoter regions. We established and validated this technique in a cohort of 108 CRCs [94 MSI-H and 16 microsatellite stable (MSS) cases] comprising a reference (n = 58) and a tester tumor group (n = 50).
Results: The reference tumor group contained 28 HNPCC with proven germ-line mutations or positive Amsterdam I criteria (median age, 37 years) and loss of MLH1 expression, 14 sporadic MSI-H CRC tumors with loss of MLH1 expression and BRAF V600E mutation (median age, 80.5 years), and 16 sporadic MSS CRC (median age, 76.5 years). No MLH1 promoter methylation could be found in any MSS tumors. HNPCC patients showed no or low level of MLH1 promoter methylation. A cutoff value of 18% methylation extent could be determined in this study to define MLH1 hypermethylation specific for sporadic MSI-H cases. Methylation could also be verified qualitatively by melting point analysis. BRAF V600E mutations were not detected in any HNPCC patients (n = 22 informative cases).
Conclusion: According to the present data, quantitative MLH1 methylation analysis in MSI-H CRC is a valuable molecular tool to distinguish between HNPCC and sporadic MSI-H CRC. The detection of a BRAF V600E mutation further supports the exclusion of HNPCC.
A Polymorphism in HDM2 (SNP309) Associates with Early Onset in Superficial Tumors, TP53 Mutations, and Poor Outcome in Invasive Bladder Cancer
Authors: Sanchez-Carbayo Marta , Socci Nicholas D. , Kirchoff Thomas , Erill Nadina , Offit Keneth , Bochner Bernard H. , Cordon-Cardo Carlos 
Published: June 2007

Abstract
Purpose: The HDM2 gene represents one of the central nodes in the p53 pathway. A recent study reported the association of a single nucleotide polymorphism (SNP309) in the HDM2 promoter region with accelerated tumor formation in both hereditary and sporadic cancers. In this study, we aim to evaluate the SNP309 in bladder cancer and to link it to TP53 status.
Experimental Design: SNP309 genotyping and TP53 mutation status were done on 141 bladder tumors and 8 bladder cancer cell lines using a RFLP strategy and TP53 genotyping arrays, respectively. Transcript profiling of a subset of cases (n = 41) was done using oligonucleotide arrays to identify genes differentially expressed regarding their SNP309 status.
Results: Of 141 bladder tumors analyzed, 36.9% displayed the SNP309 wild-type (WT; T/T) genotype, whereas 11.3% were homozygous (G/G) and 51.8% were heterozygous (T/G) cases. Patients with superficial disease and the G/G genotype had an earlier age on onset than those with the T/G or T/T genotypes (P = 0.029). Tumors with SNP309 WT genotype significantly displayed TP53 mutations when compared with tumors harboring G/G or T/G genotypes (P &lt; 0.05). SNP309 WT cases had a poorer overall survival than cases with G/G and T/G genotypes (P &lt; 0.05). TP53 mutation status provided enhanced prognostic value (P &lt; 0.001). Transcript profiling identified TP53 targets among those differentially expressed between tumors displaying G/G or T/G SNP309 versus WT cases.
Conclusions: SNP309 is a frequent event in bladder cancer, related to earlier onset of superficial disease and TP53 mutation status. SNP309 genotypes were found to be associated with clinical outcome.
KIF14 Messenger RNA Expression Is Independently Prognostic for Outcome in Lung Cancer
Authors: Corson Timothy W. , Zhu Chang Qi , Lau Suzanne K. , Shepherd Frances A. , Tsao Ming-Sound , Gallie Brenda L. 
Published: June 2007

Abstract
Purpose: The mitotic kinesin KIF14 is overexpressed in multiple cancers including lung cancer. Therefore, we investigated KIF14 expression in association with clinical variables and the effect of KIF14 on in vitro colony formation in non–small-cell lung carcinoma.
Experimental Design: RNA was extracted from 129 untreated, resected tumors and KIF14 expression was quantified by real-time reverse transcription-PCR. Associations with clinical variables were determined by standard statistical methods. KIF14 expression was knocked down by small interfering RNA in H1299 and HeLa cells; proliferation and growth in soft agar were assayed.
Results: Squamous cell carcinoma had the highest KIF14 level, followed by large-cell undifferentiated carcinoma, then adenocarcinoma (P = 0.002). KIF14 level decreased with differentiation (P = 0.01) but was not associated with pathologic stage, T or N stage, or sex. When dichotomized about the median, KIF14 overexpression significantly decreased disease-free survival (Kaplan-Meier log-rank, P = 0.01) and trended toward decreasing overall survival (P = 0.08). In a univariate Cox proportional hazard regression, increasing KIF14 expression decreased disease-free survival [P = 0.01; hazard ratio, 1.44 (95% confidence interval, 1.09-1.91)]. In a multivariate Cox regression, including stage, differentiation, histology, and tumor purity as covariates, KIF14 overexpression remained an independent prognostic factor for disease-free survival [P = 0.01; hazard ratio, 1.45 (95% confidence interval, 1.09-1.94)]. Knockdown of KIF14 in non–small-cell lung carcinoma and cervical carcinoma cell lines decreased proliferation and colony formation in soft agar.
Conclusions: KIF14 expression is independently prognostic for disease-free survival in lung cancer and knockdown decreases tumorigenicity in vitro, showing that it is a clinically relevant oncogene and an exciting therapeutic target for further study.
The Archaeological Framework of the Upper Paleolithic Revolution
Authors: Bar-Yosef Ofer 
Published: June 2007

AbstractThe Upper Palaeolithic Revolution, sometimes called ‘the Creative Explosion’, is seen as the period when the forefathers of modern forager societies emerged. Similarly to the Industrial and Neolithic Revolutions, it represents a short time span when numerous inventions appeared and cultural changes occurred. The inventions were in the domain of technology, that is, shaping of new stone tool forms, longdistance exchange of raw materials, the use of bone, antler and ivory as well as rare minerals for the production of domestic and ritual objects. Spatial analysis of ‘living floors’ indicates the presence of a kitchen area, sleeping grounds, storage facilities (in certain regions) and a discard zone. We can also detect a certain increase in social hierarchy and the presence of shamans. Body decorations indicate the appearance of personal individuality. Several hypotheses were offered as an explanation for the initiation of all these cultural changes often grouped under the term ‘modern behaviour’. It stands to reason that attributing the new successful technologies observed in the Eurasian Upper Palaeolithic to intrinsic social processes and economic innovations by local Middle Palaeolithic populations would need a better archaeological demonstration than that available today. For the time being, the emergence of Modern humans in sub-Saharan Africa, their socio-economic dynamism that caused their expansion through the Nile Valley into the Near East, and their migration along the ‘southern route’ of Asia as far as Australia, is the most plausible scenario though it still leaves much to be desired from future archaeological research.
Farnesyltransferase inhibitors inhibit T-cell cytokine production at the posttranscriptional level
Authors: Marks Reinhard E. , Ho Allen W. , Robbel Christian , Kuna Todd , Berk Seth , Gajewski Thomas F. 
Published: June 2007

AbstractSeveral cytoplasmic proteins, such as GTPases of the Ras family, containing a C-terminal CAAX motif are prenylated by farnesyltransferase to facilitate localization to cellular membranes where activation occurs. Farnesyltransferase inhibitors (FTIs) interfere with this farnesylation process, thereby preventing proper membrane localization and rendering the proteins unavailable for activation. Currently, FTIs are being explored as antineoplastic agents for the treatment of several malignancies. However, since farnesylated proteins like Ras are also involved in intracellular signaling in lymphocytes, FTIs might interfere with T-cell activation. Based on this hypothesis we examined the effect of several FTIs on cytokine production in response to anti-CD3 + anti-CD28 monoclonal antibodies or PMA + ionomycin. Murine Th1 and Th2 clones, stimulated in the presence of FTIs, showed a dose-dependent reduction of lineage-specific cytokine secretion (IFN-γ, IL-2, IL-4, IL-5). However, no inhibition of ERK or JNK MAP kinases was observed, nor was induction of cytokine mRNA affected. Rather, intracellular cytokine protein synthesis was blocked. Inhibition of human T-cell INF-γ production also was observed, correlating with reduced phosphorylation of p70S6K. These results indicate that FTIs inhibit T-cell activation at the posttranscriptional level and also suggest that they may have potential as novel immunosuppressive agents.
Macrophages prevent the differentiation of autoreactive B cells by secreting CD40 ligand and interleukin-6
Authors: Kilmon Michelle A. , Wagner Nikki J. , Garland Alaina L. , Lin Li , Aviszus Katja , Wysocki Lawrence J. , Vilen Barbara J. 
Published: June 2007

AbstractActivation of the innate immune system promotes polyclonal antibody secretion to eliminate invading pathogens. Inherent in this process is the potential to activate autoreactive B cells and induce autoimmunity. We showed previously that TLR-stimulated dendritic cells and macrophages regulate B cell tolerance to Smith antigen, in part through the secretion of interleukin-6 (IL-6). In this manuscript, we show that neutralization of IL-6 fails to abrogate macrophage-mediated repression and identify soluble CD40 ligand (CD40L) as a second repressive factor secreted by macrophages. CD40L selectively repressed Ig secretion by chronically antigen-experienced (anergic) immunoglobulin transgenic and nontransgenic B cells but not by transiently stimulated B cells. The importance of macrophages in maintaining B cell tolerance was apparent in lupus-prone MRL/lpr mice. Compared with C57BL/6 mice, macrophages from MRL/lpr mice were significantly less efficient at repressing immunoglobulin secretion coincident with diminished IL-6 and CD40 ligand production. These data indicate that macrophages regulate autoreactive B cells by secreting repressive factors that prohibit terminal differentiation of B cells. The regulation of autoreactive B cells by macrophages is diminished in lupus-prone mice suggesting a role in autoimmunity.
Characteristics of primary and immortalized fibroblast cells derived from the miniature and domestic pigs
Authors: Oh Ho-Yeon , Jin Xun , Kim Jong-Geun , Oh Myung-Joo , Pian Xumin , Kim Jun-Mo , Yoon Moon-Seok , Son Chae-Ik , Lee Young Sik , Hong Ki-Chang , Kim Hyunggee , Choi Yun-Jaie , Whang Kwang Youn 
Published: June 2007

Abstract

Background
The pig, Sus scrofa domestica includes both the miniature and commercial domestic breed. These animals have influenced the human life and economies and have been studied throughout history. Although the miniature breeds are more recent and have increasingly been used in a variety of biomedical studies, their cell lines have rarely been established. Therefore, we sought to establish primary and immortal cell lines derived from both the miniature and domestic pig to better enable insight into possible in vivo growth differences.

Results
The in vitro lifespan of primary domestic pig fibroblast (PF) and miniature pig fibroblast (MPF) cells using a standard 3T3 protocol was determined. Both of the primary PF and MPF cells were shown to have a two-step replicative senescence barrier. Primary MPF cells exhibited a relatively shorter lifespan and slower proliferation rate compared to those of primary PF cells. Beyond senescence barriers, lifespan-extended PF and MPF cells were eventually established and indicated spontaneous cellular immortalization. In contrast to the immortalized PF cells, immortal MPF cells showed a transformed phenotype and possessed more frequent chromosomal abnormalities and loss of p53 regulatory function. The lifespan of primary MPF and PF cells was extended by inactivation of the p53 function using transduction by SV40LT without any detectable senescent phenotype.

Conclusion
These results suggest that p53 signaling might be a major determinant for the replicative senescence in the MPF cells that have the shorter lifespan and slower growth rate compared to PF cells in vitro.
New research models and novel signal analysis in studies on preterm labor: a key to progress?
Authors: Pierzynski Piotr , Oczeretko Edward , Laudanski Piotr , Laudanski Tadeusz 
Published: June 2007

AbstractPreterm labor affects up to 20% of pregnancies, is considered a main cause of associated neonatal morbidity and mortality and is responsible for neonatal care costs of multimillion euros. In spite of that, the commercial market for this clinical indication is rather limited, which may be also related to high liability. Consequently, with only a few exceptions, preterm labor is not in the orbit of great interest of the pharmaceutical industry. Coordinated effort of research community may bring the change and help required to reduce the influence of this multifactorial syndrome on society. Between the novel techniques that are being explored in a SAFE (The Special Non-Invasive Advances in Fetal and Neonatal Evaluation Network) group, there are new research models of preterm labor as well as novel methodology of analysis of biological signals. In this article, we briefly describe new clinical and nonclinical human models of preterm labor as well as summarize some novel methods of data processing and analysis that may be used in the context of preterm labor.
Recombinant nucleases CEL I from celery and SP I from spinach for mutation detection
Authors: Pimkin Maxim , Caretti Elena , Canutescu Adrian , Yeung Jeffrey B , Cohn Heather , Chen Yibai , Oleykowski Catherine , Bellacosa Alfonso , Yeung Anthony T 
Published: June 2007

Abstract

Background
The detection of unknown mutations is important in research and medicine. For this purpose, a mismatch-specific endonuclease CEL I from celery has been established as a useful tool in high throughput projects. Previously, CEL I-like activities were described only in a variety of plants and could not be expressed in an active form in bacteria.

Results
We describe expression of active recombinant plant mismatch endonucleases and modification of their activities. We also report the cloning of a CEL I ortholog from Spinacia oleracea (spinach) which we termed SP I nuclease. Active CEL I and SP I nucleases were expressed as C-terminal hexahistidine fusions and affinity purified from the cell culture media. Both recombinant enzymes were active in mutation detection in BRCA1 gene of patient-derived DNA. Native SP nuclease purified from spinach is unable to incise at single-nucleotide substitutions and loops containing a guanine nucleotide, but the recombinant SP I nuclease can cut at these sites.

Conclusion
The insect cell-expressed CEL I orthologs may not be identical to their native counterparts purified from plant tissues. The present expression system should facilitate further development of CEL I-based mutation detection technologies.
Differential regulation of CD11b on γδ T cells and monocytes in response to unripe apple polyphenols
Authors: Graff Jill C , Jutila Mark A 
Published: June 2007

AbstractLeukocyte adhesion and migration are mediated partially by CD11b/CD18 (membrane-activated complex-1, CR3). Earlier studies have demonstrated a role for green tea polyphenols in down-regulating CD11b on CD8+ T cells and monocytes. We have shown recently a stimulatory effect of unripe apple polyphenols (APP) on γδ T cells. Thus, we compared the effect of APP on bovine γδ T cell and monocyte CD11b expression. Purified bovine monocytes and monocyte-depleted PBLs were cultured with APP. CD11b levels decreased on monocytes in response to APP. In contrast, a γδ T cell subset responded to APP by up-regulating CD11b. The CD11b regulation was not seen on γδ T cells or monocytes treated with APP fractions depleted of tannins. The APP-induced down-regulation of CD11b on monocytes was inhibited by an anti-CD11b mAb, consistent with previous studies showing that polyphenols bind CD11b. As expected, the anti-CD11b mAb had no effect on the APP response in resting γδ T cells, as these cells lacked CD11b. Consistent with the changes in surface CD11b expression, APP-treated γδ T cells showed increased adherence to pastic, whereas monocyte adhesion was reduced. APP also induced cytokine gene expression in γδ T cells. Some polyphenols are thought of as anti-inflammatory agents; however, these data, as well as other ongoing studies, indicate they have a proinflammatory effect on γδ T cells. In vivo, plant polyphenols may enhance γδ T cell migration and function at sites of inflammation, where they could induce rapid, immune-regulatory and innate-like immune responses.
Age-Related Changes in Heritability of Behavioral Phenotypes Over Adolescence and Young Adulthood: A Meta-Analysis
Authors: Bergen Sarah E. , Gardner Charles O. , Kendler Kenneth S. 
Published: June 2007

AbstractThe relative proportions of genetic and environmental variance in behavioral measures have been studied extensively. A growing body of literature has examined changes in heritability measures over time, but we are unaware of any prior efforts to assess developmental heritability changes for multiple behavioral phenotypes using multiple data sources. We have chosen to explore the proportional genetic influences on a variety of behaviors during the genetically and environmentally labile adolescent and young adult years. This meta-analysis examined 8 behavioral domains and incorporated only primary research articles reporting two or more heritability time points in order to minimize the age-to-age error variability. Linear regression analyses revealed significant cross-time heritability increases for externalizing behaviors, anxiety symptoms, depressive symptoms, IQ, and social attitudes and nonsignificant increases for alcohol consumption, and nicotine initiation, but no evidence of heritability changes for attention-deficit/hyperactivity disorder. A variety of mechanisms may underlie these findings including the rising importance of active genotype-environment correlation, an increase in gene expression, or proportional reductions in environmental variance. Additional longitudinal studies and the inclusion of measures of total variance in primary research reports will aid in distinguishing between these possibilities. Further studies exploring heritability changes beyond young adulthood would also benefit our understanding of factors influencing heritability of behavioral traits over the lifespan.
Etiology of the Stability of Reading Difficulties: The Longitudinal Twin Study of Reading Disabilities
Authors: Astrom Raven L. , Wadsworth Sally J. , DeFries John C. 
Published: June 2007

AbstractResults obtained from previous longitudinal studies of reading difficulties indicate that reading deficits are generally stable. However, little is known about the etiology of this stability. Thus, the primary objective of this first longitudinal twin study of reading difficulties is to provide an initial assessment of genetic and environmental influences on the stability of reading deficits. Data were analyzed from a sample of 56 twin pairs, 18 identical (monozygotic, MZ) and 38 fraternal (dizygotic, DZ), in which at least one member of each pair was classified as reading-disabled in the Colorado Learning Disabilities Research Center, and on whom follow-up data were available. The twins were tested at two time points (average age of 10.3 years at initial assessment and 16.1 years at follow-up). A composite measure of reading performance (PIAT Reading Recognition, Reading Comprehension and Spelling) was highly stable, with a stability correlation of .84. Data from the initial time point were first subjected to univariate DeFries-Fulker multiple regression analysis and the resulting estimate of the heritability of the group deficit (h2g) was .84 (± .26). When the initial and follow-up data were then fitted to a bivariate extension of the basic DF model, bivariate heritability was estimated at .65, indicating that common genetic influences account for approximately 75% of the stability between reading measures at the two time points.