bluuebunny/crossref_metadata_2025_split huggingface dataset:
Common Cancer Biomarkers
Authors: Basil Christopher F. , Zhao Yingdong , Zavaglia Katia , Jin Ping , Panelli Monica C. , Voiculescu Sonia , Mandruzzato Susanna , Lee Hueling M. , Seliger Barbara , Freedman Ralph S. , Taylor Phil R. , Hu Nan , Zanovello Paola , Marincola Francesco M. , Wang Ena 
Published: March 2006

AbstractThere is an increasing interest in complementing conventional histopathologic evaluation with molecular tools that could increase the sensitivity and specificity of cancer staging for diagnostic and prognostic purposes. This study strove to identify cancer-specific markers for the molecular detection of a broad range of cancer types. We used 373 archival samples inclusive of normal tissues of various lineages and benign or malignant tumors (predominantly colon, melanoma, ovarian, and esophageal cancers). All samples were processed identically and cohybridized with an identical reference RNA source to a custom-made cDNA array platform. The database was split into training (n = 201) and comparable prediction (n = 172) sets. Leave-one-out cross-validation and gene pairing analysis identified putative cancer biomarkers overexpressed by malignant lesions independent of tissue of derivation. In particular, seven gene pairs were identified with high predictive power (87%) in segregating malignant from benign lesions. Receiver operator characteristic curves based on the same genes could segregate malignant from benign tissues with 94% accuracy. The relevance of this study rests on the identification of a restricted number of biomarkers ubiquitously expressed by cancers of distinct histology. This has not been done before. These biomarkers could be used broadly to increase the sensitivity and accuracy of cancer staging and early detection of locoregional or systemic recurrence. Their selective expression by cancerous compared with paired normal tissues suggests an association with the oncogenic process resulting in stable expression during disease progression when the presently used differentiation markers are unreliable. (Cancer Res 2006; 66(6): 2953-61)
DNA Damage–Induced Protein 14-3-3 σ Inhibits Protein Kinase B/Akt Activation and Suppresses Akt-Activated Cancer
Authors: Yang Huiling , Wen Yu-Ye , Zhao Ruiying , Lin Yu-Li , Fournier Keith , Yang Heng-Yin , Qiu Yun , Diaz Jose , Laronga Christine , Lee Mong-Hong 
Published: March 2006

Abstract
14-3-3 σ is induced by tumor suppressor protein p53 in response to DNA damage. p53 can directly transactivate the expression of 14-3-3 σ to cause a G2 cell cycle arrest when cell DNA is damaged. The expression of 14-3-3 σ protein is down-regulated in various tumors, but its function has not been fully established. Protein kinase B/Akt, a crucial regulator of oncogenic signal involved in cell survival and proliferation, is deregulated in many types of cancer. Akt activation can enhance p53 degradation, but its role in DNA damage response is not clear. Here, we show that Akt activation is diminished when p53 and 14-3-3 σ is up-regulated in response to DNA damage. Evidence is provided that 14-3-3 σ binds and inhibits Akt. In keeping with this concept, Akt-mediated cell survival is inhibited by 14-3-3 σ. Significantly, we show that 14-3-3 σ inhibits Akt-mediated cell growth, transformation, and tumorigenesis. Low expression of 14-3-3 σ in human primary breast cancers correlates with Akt activation. These data provide an insight into Akt regulation and rational cancer gene therapy by identifying 14-3-3 σ as a molecular regulator of Akt and as a potential anticancer agent for Akt-activated cancers. (Cancer Res 2006; (66)6: 3096-105)
Increased EP4 Receptor Expression in Colorectal Cancer Progression Promotes Cell Growth and Anchorage Independence
Authors: Chell Simon D. , Witherden Ian R. , Dobson Richard R. , Moorghen Morganaden , Herman Andrew A. , Qualtrough David , Williams Ann C. , Paraskeva Christos 
Published: March 2006

Abstract
Cyclooxygenase-2 and prostaglandin E2 (PGE2) levels are increased in colorectal cancers and a subset of adenomas. PGE2 signaling through the EP4 receptor has previously been associated with colorectal tumorigenesis. However, changes in EP4 expression during adenoma to carcinoma progression have not been investigated, neither has whether levels of EP4 influence important markers of malignant potential, such as anchorage-independent growth or the tumors growth response to PGE2. We report using immunohistochemistry that in vivo EP4 receptor protein expression was increased in colorectal cancers (100%) as well as adenomas (36%) when compared with normal colonic epithelium. EP4 expression was also higher in colorectal carcinoma compared with adenoma cell lines and increased with in vitro models of tumor progression. Adenoma (PC/AA/C1 and RG/C2) and carcinoma cell lines (HT29) were growth stimulated by PGE2 up to 0.5 μmol/L. However, although carcinoma and transformed adenoma (PC/AA/C1SB10C, a transformed derivative of PC/AA/C1) cells remain stimulated by higher doses of PGE2 (10 μmol/L), the adenoma cell lines were inhibited. Interestingly, enforced expression of EP4 in the adenoma cell line, RG/C2, resulted in stimulation of growth by 10 μmol/L PGE2 and promoted anchorage-independent growth. Both in vivo and in vitro data from this study suggest that increased EP4 receptor expression is important during colorectal carcinogenesis. We propose that high levels of PGE2 in a tumor microenvironment would select for cells with increased EP4 expression, and that the EP4 receptor may therefore represent an important target for colorectal cancer prevention and treatment. (Cancer Res 2006; 66(6): 3106-13)
Global Gene Expression Profiling of Pleural Mesotheliomas: Overexpression of Aurora Kinases and P16/CDKN2A Deletion as Prognostic Factors and Critical Evaluation of Microarray-Based Prognostic Prediction
Authors: López-Ríos Fernando , Chuai Shannon , Flores Raja , Shimizu Shigeki , Ohno Takatoshi , Wakahara Kazuhiko , Illei Peter B. , Hussain Sanaa , Krug Lee , Zakowski Maureen F. , Rusch Valerie , Olshen Adam B. , Ladanyi Marc 
Published: March 2006

Abstract
Most gene expression profiling studies of mesothelioma have been based on relatively small sample numbers, limiting their statistical power. We did Affymetrix U133A microarray analysis on 99 pleural mesotheliomas, in which multivariate analysis showed advanced-stage, sarcomatous histology and P16/CDKN2A homozygous deletion to be significant independent adverse prognostic factors. Comparison of the expression profiles of epithelioid versus sarcomatous mesotheliomas identified many genes significantly overexpressed among the former, including previously unrecognized ones, such as uroplakins and kallikrein 11, both confirmed by immunohistochemistry. Examination of the gene expression correlates of survival showed that more aggressive mesotheliomas expressed higher levels of Aurora kinases A and B and functionally related genes involved in mitosis and cell cycle control. Independent confirmation of the negative effect of Aurora kinase B was obtained by immunohistochemistry in a separate patient cohort. A role for Aurora kinases in the aggressive behavior of mesotheliomas is of potential clinical interest because of the recent development of small-molecule inhibitors. We then used our data to develop microarray-based predictors of 1 year survival; these achieved a maximal accuracy of 68% in cross-validation. However, this was inferior to prognostic prediction based on standard clinicopathologic variables and P16/CDNK2A status (accuracy, 73%), and adding the microarray model to the latter did not improve overall accuracy. Finally, we evaluated three recently published microarray-based outcome prediction models, but their accuracies ranged from 63% to 67%, consistently lower than reported. Gene expression profiling of mesotheliomas is an important discovery tool, but its power in clinical prognostication has been overestimated. (Cancer Res 2006; 66(6): 2970-9)
Antibody-Drug Conjugates Designed to Eradicate Tumors with Homogeneous and Heterogeneous Expression of the Target Antigen
Authors: Kovtun Yelena V. , Audette Charlene A. , Ye Yumei , Xie Hongsheng , Ruberti Mary F. , Phinney Sara J. , Leece Barbara A. , Chittenden Thomas , Blättler Walter A. , Goldmacher Victor S. 
Published: March 2006

Abstract
Conjugates of the anti-CanAg humanized monoclonal antibody huC242 with the microtubule-formation inhibitor DM1 (a maytansinoid), or with the DNA alkylator DC1 (a CC1065 analogue), have been evaluated for their ability to eradicate mixed cell populations formed from CanAg-positive and CanAg-negative cells in culture and in xenograft tumors in mice. We found that in culture, conjugates of either drug killed not only the target antigen-positive cells but also the neighboring antigen-negative cells. Furthermore, we showed that, in vivo, these conjugates were effective in eradicating tumors containing both antigen-positive and antigen-negative cells. The presence of antigen-positive cells was required for this killing of bystander cells. This target cell–activated killing of bystander cells was dependent on the nature of the linker between the antibody and the drug. Conjugates linked via a reducible disulfide bond were capable of exerting the bystander effect whereas equally potent conjugates linked via a nonreducible thioether bond were not. Our data offer a rationale for developing optimally constructed antibody-drug conjugates for treating tumors that express the target antigen either in a homogeneous or heterogeneous manner. (Cancer Res 2006; 66(6): 3214-21)
Oncogene-Induced Senescence: Putting the Brakes on Tumor Development
Authors: Braig Melanie , Schmitt Clemens A. 
Published: March 2006

Abstract
Cellular senescence, a permanent cell cycle arrest, is considered a safeguard mechanism that may prevent aged or abnormal cells from further expansion. Although the term “replicative senescence” stands for the widely accepted model of a terminal growth arrest due to telomere attrition, the significance of “oncogene-inducible senescence” remained an issue of debate over the years. A number of recent studies now show the effect of this acute and telomere-independent form of senescence as a tumor-protective, fail-safe mechanism in vivo that shares conceptual and possibly therapeutic similarities with the genetically encoded apoptosis machinery. (Cancer Res 2006; 66(6): 2881-4)
Prostaglandin E Receptor EP4 Antagonism Inhibits Breast Cancer Metastasis
Authors: Ma Xinrong , Kundu Namita , Rifat Salah , Walser Tonya , Fulton Amy M. 
Published: March 2006

Abstract
Cyclooxygenase-2 (COX-2) expression in epithelial tumors is frequently associated with a poor prognosis. In a murine model of metastatic breast cancer, we showed that COX-2 inhibition is associated with decreased metastatic capacity. The COX-2 product, prostaglandin E2 (PGE2), acts through a family of G protein–coupled receptors designated EP1-4 that mediate intracellular signaling by multiple pathways. We characterized EP receptor expression on three murine mammary tumor cell lines and show that all four EP isoforms were detected in each cell. Stimulation of cells with either PGE2 or the selective EP4/EP2 agonist PGE1-OH resulted in increased intracellular cyclic AMP and this response was inhibited with either EP2 or EP4 antagonists. Nothing is known about the function of EP receptors in tumor metastasis. We tested the hypothesis that the prevention of EP receptor signaling would, like inhibition of PGE2 synthesis, inhibit tumor metastasis. Our results show for the first time that antagonism of the EP4 receptor with either AH23848 or ONO-AE3-208 reduced metastasis as compared with vehicle-treated controls. The therapeutic effect was comparable to that observed with the dual COX-1/COX-2 inhibitor indomethacin. EP3 antagonism had no effect on tumor metastasis. Mammary tumor cells migrated in vitro in response to PGE2 and this chemotactic response was blocked by EP receptor antagonists. Likewise, the proliferation of tumor cells was also directly inhibited by antagonists of either EP4 or EP1/EP2. These studies support the hypothesis that EP receptor antagonists may be an alternative approach to the use of COX inhibitors to prevent tumor metastasis. (Cancer Res 2006; 66(6): 2923-7)
Reducing the “Risk” of Chemoprevention: Defining and Targeting High Risk—2005 AACR Cancer Research and Prevention Foundation Award Lecture
Authors: Lippman Scott M. , Lee J. Jack 
Published: March 2006

Abstract
Two large-scale, phase III cancer prevention trials, the Breast Cancer Prevention Trial (BCPT) of tamoxifen and Prostate Cancer Prevention Trial (PCPT) of finasteride, concluded with strikingly positive and simultaneously problematic results: reduced cancer risks but a major adverse finding with each agent that prevented its widespread use in the community. For most moderate-risk people, such as those studied in the BCPT and PCPT, the benefit of reduced breast or prostate cancer does not outweigh the major risk of tamoxifen (endometrial cancer in the BCPT) or apparent risk of finasteride (high-grade prostate cancer in the PCPT). Promising interventions with biologically active substances are likely to have adverse, perhaps unforeseen effects, especially with long-term preventive use. Acceptance of such agents will depend heavily on the level of cancer risk of the target population. This article outlines research in molecularly identified high-risk oral intraepithelial neoplasia that creates the clinical opportunity for optimizing the risk-benefit ratio of agents to prevent oral cancer. Two other major research efforts focused on improving preventive agent risk-benefit ratios are molecular-targeted research designed to target away from known adverse signaling pathways and multidisciplinary research based on the PCPT that will develop comprehensive models of prostate cancer risk (especially of aggressive prostate cancer) and pharmacoecogenetic models for identifying high-risk men most likely to benefit from (and not be harmed by) finasteride or similar (5α-reductase inhibiting) agents. Defining and targeting high-risk populations, developing molecular-targeted approaches, and developing accurate pharmacoecogenetic models promise to reduce the risk of chemoprevention and ultimately to reduce the risk and burden of major cancers. (Cancer Res 2006; 66(6): 2893-903)
The Archaeology of Bengal: Trading Networks, Cultural Identities
Authors: Ray Himanshu Prabha 
Published: March 2006

AbstractThe objective of this paper is to draw on archaeological data from Bengal to address issues relating to the social and cultural milieu of trade from the 5th-4th centuries BC to the 6th-7th centuries AD. Trading activity by its very nature was mobile, cut across political frontiers and as a result created its own networks of communication and information transfer. Within this extensive trading system, diverse communities in Bengal developed distinctive cultural identities as they interacted with their unique environment as well as with the larger Indic cultural sphere. This cultural identity included religious affiliation and it is important to highlight the vibrancy and dynamism of these cultural identities from the prehistoric period to the 8th-9th centuries AD. L'objectif de cet article est de partir des données archéologiques du Bengale pour en extraire les problématiques en relation avec le milieu social et culturel du monde commercial du 5eme-4eme s. av. J.-C. au 6eme-7eme s. de notre ère. L'activité commerciale fut, par sa nature même, mobile, au-delà des frontières politiques et créa en conséquence ses propres réseaux de communication et de transfert de l'information. Dans le cadre de ce système de commerce extensif, diverses communautés au Bengale ont développé des identités culturelles spécifiques en établissant des relations aussi bien avec leur propre environnement qu'avec la sphère culturelle indienne plus générale. Cette identité culturelle inclut les affiliations religieuses et il est important de mettre en valeur la vivacité et le dynamisme de ces identités culturelles de la période préhistorique au 8eme-9eme siècle de notre ère.
Dynamics of the Upper Oceanic Layers in Terms of Surface Quasigeostrophy Theory
Authors: Lapeyre G. , Klein P. 
Published: March 2006

Abstract
In this study, the relation between the interior and the surface dynamics for nonlinear baroclinically unstable flows is examined using the concepts of potential vorticity. First, it is demonstrated that baroclinic unstable flows present the property that the potential vorticity mesoscale and submesoscale anomalies in the ocean interior are strongly correlated to the surface density anomalies. Then, using the invertibility of potential vorticity, the dynamics are decomposed in terms of a solution forced by the three-dimensional (3D) potential vorticity and a solution forced by the surface boundary condition in density. It is found that, in the upper oceanic layers, the balanced flow induced only by potential vorticity is strongly anticorrelated with that induced only by the surface density with a dominance of the latter. The major consequence is that the 3D balanced motions can be determined from only the surface density and the characteristics of the basin-scale stratification by solving an elliptic equation. These properties allow for the possibility to reconstruct the 3D balanced velocity field of the upper layers from just the knowledge of the surface density by using a simpler model, that is, an “effective” surface quasigeostrophic model. All these results are validated through the examination of a primitive equation simulation reproducing the dynamics of the Antarctic Circumpolar Current.
Wind Stress Dependence on Ocean Surface Velocity: Implications for Mechanical Energy Input to Ocean Circulation
Authors: Duhaut Thomas H. A. , Straub David N. 
Published: March 2006

Abstract
It is pointed out that accounting for an ocean surface velocity dependence in the wind stress τ can lead to a significant reduction in the rate at which winds input mechanical energy to the geostrophic circulation. Specifically, the wind stress is taken to be a quadratic function of Ua − uo, where Ua and uo are the 10-m wind and ocean surface velocity, respectively. Because |Ua| is typically large relative to |uo|, accounting for a uo dependence leads only to relatively small changes in τ. The change to the basin-averaged wind power source, however, is considerably larger. Scaling arguments and quasigeostrophic simulations in a basin setting are presented. They suggest that the power source (or rate of energy input) is reduced by roughly 20%–35%.
Wave Force on an Ocean Current
Authors: Kenyon Kern E. , Sheres David 
Published: March 2006

Abstract
Linear momentum of surface gravity waves changes with time during refraction by a horizontally variable current, as is predicted by ray theory; the momentum change per unit time requires a force by the current on the waves. According to Newton’s third law, the waves apply an equal but opposite force back on the current. The wave force of linear waves on the current is calculated for a steady horizontal shear current and it is found to be directly proportional to the wave momentum times the shear in the current. For a current like the Gulf Stream it is theoretically possible for the wave force on the current to be as large as the Coriolis force on the current to the depth of wave influence; the effect on equatorial surface currents is likely to be even more significant. Considering the reasonable conjecture that the orbital angular momentum of the waves cannot be exchanged with the current, the growth or decay of the wave amplitude in the shear current is computed as well. An exponential growth or decay of the amplitude is obtained with the e-folding scale being proportional to the current shear. A comparison between the calculated wave force and the Coriolis force for reported data describing the reflection of waves by the Gulf Stream is presented. The potential effects of the wave force on the surface extent of such currents and their observations by remote sensing, including possible bias in estimation of their transport capacity, are discussed. Instances of potential positive and negative feedback acting during the interaction between the waves and the current are outlined.
Optimal Growth of Antarctic Circumpolar Waves
Authors: Aiken Christopher M. , England Matthew H. , Reason Christopher J. C. 
Published: March 2006

Abstract
Generalized stability theory is applied to a simple dynamical model of interannual ocean–atmosphere variability in the southern midlatitudes to determine the perturbations that create the most rapid growth of energy in the system. The model is composed of a barotropic quasigeostrophic atmosphere coupled to a 1.5-layer quasigeostrophic ocean, each linearized about a zonally invariant mean state, and with atmospheric and ocean surface temperature obeying a simple heat balance. Eigenanalysis of the system reveals modes of interannual variability that resemble the so-called Antarctic Circumpolar Wave (ACW), consistent with an earlier analytical study of the system. The optimal excitation of these modes relative to an energy norm is found to be a perturbation almost entirely restricted to the ocean momentum field and is shown to resemble strongly the optimal perturbations in energy for the system. Over interannual time scales most rapid growth is seen in zonal wavenumbers 4–6, despite the fact that the least-damped eigenmodes of the system are of a lower zonal wavenumber. The rapid transient growth in energy occurs by extracting perturbation energy from the mean state through advection of the mean meridional oceanic temperature gradient. This transient growth of high-zonal-wavenumber modes dominates the model’s variability when it is forced by noise that is white in space or time. A dominant low-zonal-wavenumber response, consistent with the observed and modeled ACW, occurs only when the forcing is red in space or time, with decorrelation scales greater than 3 yr or 10 000 km. It is concluded that, if the ACW is a coupled mode analogous to that supported in this simple model, then it is excited by other large-scale phenomena such as ENSO rather than by sources of higher-frequency forcing.