bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory cytokines modulate chemokine production patterns of HepG2 cells toward initially inclined direction
Authors: Ohashi Tomohiko , Tanabe Junichi , Ishikawa Tetsuya , Okumura Akihiko , Sato Ken , Ayada Minoru , Hotta Naoki , Kuzuya Teiji , Ito Hiroyasu , Nakao Haruhisa , Yoneda Masashi , Kakumu Shinichi 
Published: February 2009

Aim:  Human hepatocytes are known to express an array of inflammatory cytokines and chemokines. In this study, we examined the potential roles of hepatocytes in regulating immune responses in the liver, by assessing the induction of Th1‐ or Th2‐specific chemokines in HepG2 cells after various inflammatory stimulations.Methods:  HepG2 cells were stimulated with IL‐1α, IFN‐γ, IL‐4, IL‐10, and/or CCL2, harvested at several time points, and served for the analyses of cytokine/chemokine mRNA expressions by semi‐quantitative RT‐PCR.Results:  (i) IL‐1α up‐regulated mRNA levels of CXCL8, CXCL10, and CCL2. IFN‐γ increased those of CXCL9, CXCL10, and CCL5, while IL‐4 or IL‐10 had no effect. (ii) Addition of IL‐4 to the culture of IFN‐γ‐stimulated cells, down‐regulated CXCL9 and CXCL10 mRNA levels. (iii) Addition of IFN‐γ to the culture of IL‐1α‐stimulated cells, further up‐regulated CXCL9 and CXCL10 mRNA levels. Addition of IL‐4 decreased CXCL8 and CXCL10 levels, and increased CCL2 level in IL‐1α‐stimulated cells. (iv) CCL2 induced IL‐4 mRNA expression.Conclusions:  IFN‐γ augmented mRNA expression of Th1‐specific chemokines (CXCL9 and CXCL10) in HepG2 cells. IL‐4 had no effect on those of Th2‐spesific chemokines (CCL17 and CCL22); however, it was supposed to augment Th2 response indirectly through the induction of CCL2 under the inflammatory condition. The findings suggest that hepatocytes have ability to promote immune responses in the liver toward the direction, initially determined by the cytokine balances in the local inflammatory region.
Precipitous declines in pinto abalone (Haliotis kamtschatkana kamtschatkana) abundance in the San Juan Archipelago, Washington, USA, despite statewide fishery closure
Authors: Rothaus Don P. , Vadopalas Brent , Friedman Carolyn S. 
Published: February 2009

Pinto abalone ( Haliotis kamtschatkana kamtschatkana ) index stations in the San Juan Archipelago were systematically monitored by the Washington Department of Fish and Wildlife from 1992 through 2006. During this period, abalone abundance declined by 77% and the mean shell length (SL) increased 10.4 mm. Abalone densities at all index stations are currently well below the threshold of 0.15 abalone·m–2 required for successful fertilization. From 1992 to 1996, 16% of individuals encountered measured <90 mm SL, while only 6% of the individuals from 2003 to 2006 were in this small size class. Similarly, the number of those >114 mm SL was greater in the 2000s than in the 1990s. The mean SL of all live abalone observed in the 1990s (107.62 ± 0.87 mm) was significantly different from the mean SL of empty shells (114.21 ± 2.1 mm), but no difference was detected between the mean SLs of empty shells and live abalone in the 2000s (114.97 ± 1.42 mm). Taken together, these data suggest recruitment failure from an Allee response to low population densities.
Prevalence and recurrence of escaped farmed Atlantic salmon (Salmo salar) in eastern North American rivers
Authors: Morris Matthew R.J. , Fraser Dylan J. , Heggelin Anthony J. , Whoriskey Frederick G. , Carr Jonathan W. , O’Neil Shane F. , Hutchings Jeffrey A. 
Published: February 2009

Knowledge of the prevalence of escaped farmed fishes in the wild is an essential first step to assessing the risk resulting from interactions between farmed and wild fishes. This is especially important in eastern North America, where Atlantic salmon ( Salmo salar ) aquaculture occurs near wild Atlantic salmon rivers and where many wild salmon populations are severely depressed. Here, we review the literature on the incidence of escaped farmed salmon in eastern North American rivers, for which there has been no comprehensive compilation to date. Escaped farmed salmon have been found in 54 of 62 (87%) rivers investigated within a 300 km radius of the aquaculture industry since 1984, including 11 rivers that contain endangered salmon populations. Averaged among all investigations, the proportional representation of farmed salmon among adults entering the rivers from the sea was 9.2% (range 0% to 100%). Where data were sufficient to examine temporal trends, farmed salmon proportions varied considerably over time, suggesting that escape events are episodic in nature. We conclude that escaped farmed salmon are sufficiently prevalent in eastern North American rivers to pose a potentially serious risk to the persistence of wild salmon populations, especially in those rivers that are adjacent to existing aquaculture sites.
Dynamic and Efficient Key Management for Access Hierarchies
Authors: Atallah Mikhail J. , Blanton Marina , Fazio Nelly , Frikken Keith B. 
Published: February 2009

Hierarchies arise in the context of access control whenever the user population can be modeled as a set of partially ordered classes (represented as a directed graph). A user with access privileges for a class obtains access to objects stored at that class and all descendant classes in the hierarchy. The problem of key management for such hierarchies then consists of assigning a key to each class in the hierarchy so that keys for descendant classes can be obtained via efficient key derivation.We propose a solution to this problem with the following properties: (1) the space complexity of the public information is the same as that of storing the hierarchy; (2) the private information at a class consists of a single key associated with that class; (3) updates (i.e., revocations and additions) are handledlocallyin the hierarchy; (4) the scheme is provably secure against collusion; and (5) each node can derive the key of any of its descendant with a number of symmetric-key operations bounded by the length of the path between the nodes. Whereas many previous schemes had some of these properties, ours is the first that satisfies all of them. The security of our scheme is based on pseudorandom functions, without reliance on the Random Oracle Model.Another substantial contribution of this work is that we are able to lower the key derivation time at the expense of modestly increasing the public storage associated with the hierarchy. Insertion of additional, so-called shortcut, edges, allows to lower the key derivation to a small constant number of steps for graphs that are total orders and trees by increasing the total number of edges by a small asymptotic factor such asO(log*n) for ann-node hierarchy. For more general access hierarchies of dimensiond, we use a technique that consists of adding dummy nodes and dimension reduction. The key derivation work for such graphs is then linear indand the increase in the number of edges is by the factorO(logd − 1n) compared to the one-dimensional case.Finally, by making simple modifications to our scheme, we show how to handle extensions proposed by Crampton [2003] of the standard hierarchies to “limited depth” and reverse inheritance.
Run-Time Enforcement of Nonsafety Policies
Authors: Ligatti Jay , Bauer Lujo , Walker David 
Published: February 2009

A common mechanism for ensuring that software behaves securely is to monitor programs at run time and check that they dynamically adhere to constraints specified by a security policy. Whenever a program monitor detects that untrusted software is attempting to execute a dangerous action, it takes remedial steps to ensure that only safe code actually gets executed.
This article improves our understanding of the space of policies enforceable by monitoring the run-time behaviors of programs. We begin by building a formal framework for analyzing policy enforcement: we precisely define policies, monitors, and enforcement. This framework allows us to prove that monitors enforce an interesting set of policies that we call the infinite renewal properties. We show how to construct a program monitor that provably enforces any reasonable infinite renewal property. We also show that the set of infinite renewal properties includes some nonsafety policies, that is, that monitors can enforce some nonsafety (including some purely liveness) policies. Finally, we demonstrate concrete examples of nonsafety policies enforceable by practical run-time monitors.
The complexity of online memory checking
Authors: Naor Moni , Rothblum Guy N. 
Published: February 2009

We consider the problem of storing a large file on a remote and unreliable server. To verify that the file has not been corrupted, a user could store a small private (randomized) “fingerprint” on his own computer. This is the setting for the well-studied authentication problem in cryptography, and the required fingerprint size is well understood. We study the problem of sublinear authentication: suppose the user would like to encode and store the file in a way that allows him to verify that it has not been corrupted, but without reading the entire file. If the user only wants to readqbits of the file, how large does the sizesof the private fingerprint need to be? We define this problem formally, and show a tight lower bound on the relationship betweensandqwhen the adversary is not computationally bounded, namely:s×q= Ω(n), wherenis the file size. This is an easier case of the online memory checking problem, introduced by Blum et al. [1991], and hence the same (tight) lower bound applies also to that problem.It was previously shown that, when the adversary is computationally bounded, under the assumption that one-way functions exist, it is possible to construct much better online memory checkers. The same is also true for sublinear authentication schemes. We show that the existence of one-way functions is also a necessary condition: even slightly breaking thes×q= Ω(n) lower bound in a computational setting implies the existence of one-way functions.
Trastuzumab Reverses Letrozole Resistance and Amplifies the Sensitivity of Breast Cancer Cells to Estrogen
Authors: Sabnis Gauri , Schayowitz Adam , Goloubeva Olga , Macedo Luciana , Brodie Angela 
Published: February 2009

AbstractIn this study, we investigated adaptive mechanisms associated with aromatase inhibitor (AI) resistance in breast cancer cells and show that sensitivity to AIs can be extended through dual inhibition of estrogen receptor (ER) and human epidermal receptor-2 (Her-2) signaling. We used human ER-positive breast cancer cells stably transfected with the aromatase gene (MCF-7Ca). These cells grow as tumors in nude mice and are inhibited by AIs. Despite continued treatment, tumors eventually become insensitive to AI letrozole. The cells isolated from these long-term letrozole-treated tumors (LTLT-Ca) were found to have decreased ERα levels. Our results suggest that LTLT-Ca cells survive estrogen deprivation by activation of Her-2/mitogen-activated protein kinase (MAPK) pathway. Here, we show that trastuzumab (antibody against Her-2; IC50 = 0.4 mg/mL) was very effective in restoring the ERα levels and sensitivity of LTLT-Ca cells to endocrine therapy by down-regulation of Her-2/MAPK pathway and up-regulation of ERα. In contrast, trastuzumab was ineffective in the parental hormone-responsive MCF-7Ca cells (IC50 = 4.28 mg/mL) and xenografts. By blocking Her-2, trastuzumab also up-regulates ERα and aromatase expression and hypersensitized MCF-7Ca cells to E2. We show that trastuzumab is beneficial in hormone-refractory cells and xenografts by restoring ER, implicating Her-2 as a negative regulator of ERα. In xenograft studies, the combination of trastuzumab plus letrozole is equally effective in inhibiting growth of MCF-7Ca tumors as letrozole alone. However, on the acquisition of resistance and increased Her-2 expression, the combination of letrozole plus trastuzumab provided superior benefit over letrozole or trastuzumab alone. [Cancer Res 2009;69(4):1416–28]
Association of Variants in Two Vitamin E Transport Genes with Circulating Vitamin E Concentrations and Prostate Cancer Risk
Authors: Wright Margaret E. , Peters Ulrike , Gunter Marc J. , Moore Steven C. , Lawson Karla A. , Yeager Meredith , Weinstein Stephanie J. , Snyder Kirk , Virtamo Jarmo , Albanes Demetrius 
Published: February 2009

Abstract
Significant reductions in prostate cancer incidence and mortality were observed in men randomized to receive 50 mg supplemental vitamin E (α-tocopherol) per day in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We hypothesized that variation in key vitamin E transport genes might directly affect prostate cancer risk or modify the effects of vitamin E supplementation. Associations between prostate cancer risk and 13 polymorphisms in two genes, TTPA and SEC14L2, were examined in 982 incident prostate cancer cases and 851 controls drawn from the ATBC Study. There was no association between the genetic variants and prostate cancer risk. Significant interactions were observed, however, between two variants in SEC14L2 (IVS11+931A&gt;G and IVS11−896A&gt;T) and the trial α-tocopherol supplement such that vitamin E supplementation reduced prostate cancer risk among men who were homozygous for either common allele [odds ratios (OR) and 95% confidence intervals (95% CI), 0.52 (0.30–0.90) and 0.64 (0.46–0.88), respectively] and nonsignificantly increased risk among those who carried one or two copies of either variant allele [ORs and 95% CIs, 1.27 (0.90–1.79) and 1.21 (0.96–1.52), respectively; both P for interaction &lt; 0.05]. Genotype-phenotype analyses revealed significant but modest differences in baseline circulating concentrations of α-tocopherol and serum responses to the vitamin E supplementation for several polymorphisms. This study shows that genetic variation in TTPA and SEC14L2 is associated with serum α-tocopherol but does not have a direct effect on prostate cancer. Our results do, however, suggest that polymorphisms in SEC14L2 may modify the effect of vitamin supplementation regimens on prostate cancer risk. [Cancer Res 2009;69(4):1429–38]
Breast Cancer Cell Lines Contain Functional Cancer Stem Cells with Metastatic Capacity and a Distinct Molecular Signature
Authors: Charafe-Jauffret Emmanuelle , Ginestier Christophe , Iovino Flora , Wicinski Julien , Cervera Nathalie , Finetti Pascal , Hur Min-Hee , Diebel Mark E. , Monville Florence , Dutcher Julie , Brown Marty , Viens Patrice , Xerri Luc , Bertucci François , Stassi Giorgio , Dontu Gabriela , Birnbaum Daniel , Wicha Max S. 
Published: February 2009

Abstract
Tumors may be initiated and maintained by a cellular subcomponent that displays stem cell properties. We have used the expression of aldehyde dehydrogenase as assessed by the ALDEFLUOR assay to isolate and characterize cancer stem cell (CSC) populations in 33 cell lines derived from normal and malignant mammary tissue. Twenty-three of the 33 cell lines contained an ALDEFLUOR-positive population that displayed stem cell properties in vitro and in NOD/SCID xenografts. Gene expression profiling identified a 413-gene CSC profile that included genes known to play a role in stem cell function, as well as genes such as CXCR1/IL-8RA not previously known to play such a role. Recombinant interleukin-8 (IL-8) increased mammosphere formation and the ALDEFLUOR-positive population in breast cancer cell lines. Finally, we show that ALDEFLUOR-positive cells are responsible for mediating metastasis. These studies confirm the hierarchical organization of immortalized cell lines, establish techniques that can facilitate the characterization of regulatory pathways of CSCs, and identify potential stem cell markers and therapeutic targets. [Cancer Res 2009;69(4):1302–13]
Human Renal Cancer Cells Express a Novel Membrane-Bound Interleukin-15 that Induces, in Response to the Soluble Interleukin-15 Receptor α Chain, Epithelial-to-Mesenchymal Transition
Authors: Khawam Krystel , Giron-Michel Julien , Gu Yanhong , Perier Aurélie , Giuliani Massimo , Caignard Anne , Devocelle Aurore , Ferrini Silvano , Fabbi Marina , Charpentier Bernard , Ludwig Andreas , Chouaib Salem , Azzarone Bruno , Eid Pierre 
Published: February 2009

Abstract
Although interleukin-15 (IL-15) is a powerful immunomodulatory factor that has been proposed for cancer immunotherapy, its intratumoral expression may be correlated with tumor progression and/or poor clinical outcome. Therefore, neoplasias potentially sensitive to immunotherapy should be checked for their IL-15 expression and function before choosing immunotherapy protocols. Primary human renal cancer cells (RCC) express a novel form of membrane-bound IL-15 (mb-IL-15), which displays three major original properties: (a) It is expressed as a functional membrane homodimer of 27 kDa, (b) it is shed in the extracellular environment by the metalloproteases ADAM17 and ADAM10, and (c) its stimulation by soluble IL-15 receptor α (s-IL-15Rα) chain triggers a complex reverse signal (mitogen-activated protein kinases, FAK, pMLC) necessary and sufficient to ~induce epithelial-mesenchymal transdifferentiation (EMT), a crucial process in tumor progression whose induction is unprecedented for IL-15. In these cells, complete EMT is characterized by a dynamic reorganization of the cytoskeleton with the subsequent generation of a mesenchymal/contractile phenotype (α-SMA and vimentin networks) and the loss of the epithelial markers E-cadherin and ZO-1. The retrosignaling functions are, however, hindered through an unprecedented cytokine/receptor interaction of mb-IL-15 with membrane-associated IL-15Rα subunit that tunes its signaling potential competing with low concentrations of the s-IL-15Rα chain. Thus, human RCC express an IL-15/IL-15R system, which displays unique biochemical and functional properties that seem to be directly involved in renal tumoral progression. [Cancer Res 2009;69(4):1561–9]
Whole Genome Comparison of Allelic Imbalance between Noninvasive and Invasive Small-Sized Lung Adenocarcinomas
Authors: Nakanishi Hirofumi , Matsumoto Shingo , Iwakawa Reika , Kohno Takashi , Suzuki Kenji , Tsuta Koji , Matsuno Yoshihiro , Noguchi Masayuki , Shimizu Eiji , Yokota Jun 
Published: February 2009

Abstract
Seventy-two small-sized (≤2 cm in diameter) lung adenocarcinomas consisting of 15 noninvasive and 57 invasive tumors were subjected to whole genome allelic imbalance (AI) scanning and mutational analysis of the EGFR, KRAS, and TP53 genes to elucidate genetic pathways of early-stage lung adenocarcinomas. The chromosome 13q13 region showed the most frequent AI (58%) and was affected at similar frequencies between noninvasive and invasive tumors (53% and 60%, respectively), as EGFR and KRAS mutations were. The number of AI regions as well as the frequency of TP53 mutations in invasive tumors was significantly higher than those in noninvasive ones [9.8 ± 5.6 versus 4.8 ± 2.8 (P = 0.00002) and 61% versus 13% (P = 0.001), respectively]. In particular, AIs at the chromosome 11p11-p12, 17p12-p13, and 18p11 regions in invasive tumors were significantly more frequent than those in noninvasive ones (P &lt; 0.01). The results indicated that noninvasive tumors were developed by EGFR, KRAS, and 13q alterations and progressed to invasive ones by subsequent alterations of several tumor suppressor genes, including those on 11p11-p12, 17p12-p13, and 18p11 and TP53. AI at 8p21 was significantly more frequent in advanced stages (&gt;IA) and associated with worse prognoses (P = 0.04) and, thus, would be involved in invasion and/or metastasis of adenocarcinoma cells and useful for the prediction of prognosis of patients with small-sized lung adenocarcinoma. [Cancer Res 2009;69(4):1615–23]
Functional Analysis of 11q13.5 Amplicon Identifies Rsf-1 (HBXAP) as a Gene Involved in Paclitaxel Resistance in Ovarian Cancer
Authors: Choi Jung Hye , Sheu Jim Jinn-Chyuan , Guan Bin , Jinawath Natini , Markowski Paul , Wang Tian-Li , Shih Ie-Ming 
Published: February 2009

Abstract
The chromosome 11q13.5 locus is frequently amplified in several types of human cancer. We have previously shown that 11q13.5 amplification was associated with significantly shorter overall survival in ovarian cancer patients, but the molecular mechanisms of how amplification of this locus contributes to disease aggressiveness remain unclear. Because ovarian cancer mortality is primarily related to resistance of chemotherapeutic agents, we screened the top six candidate genes within this amplicon for their contribution to drug resistance. Rsf-1 (also known as HBXAP) was found to be the only gene in which gene knockdown sensitized tumor cells to paclitaxel. Rsf-1 has been known to interact with hSNF2H to form an ISWI chromatin remodeling complex. We found that Rsf-1 was up-regulated in paclitaxel-resistant ovarian cancer cell lines, and Rsf-1 immunoreactivity in primary ovarian carcinoma tissues correlated with in vitro paclitaxel resistance. Ectopic expression of Rsf-1 significantly enhanced paclitaxel resistance in ovarian cancer cells. Down-regulation of hSNF2H or disruption of hSNF2H and Rsf-1 interaction enhanced paclitaxel sensitivity in tumor cells with Rsf-1 up-regulation. Rsf-1 expression altered expression in several genes and activated certain signaling pathways that may contribute to drug resistance. In conclusion, our results suggest that Rsf-1 is the major gene within the 11q13.5 amplicon that contributes to paclitaxel resistance, and the formation of the Rsf-1/hSNF2H complex is required for inducing this phenotype. [Cancer Res 2009;69(4):1407–15]
Methylation-Mediated Repression of GADD45α in Prostate Cancer and Its Role as a Potential Therapeutic Target
Authors: Ramachandran Kavitha , Gopisetty Gopal , Gordian Edna , Navarro Loida , Hader Christiane , Reis Isildinha M. , Schulz Wolfgang A. , Singal Rakesh 
Published: February 2009

Abstract
Defects in apoptotic pathway contribute to uncontrolled proliferation of cancer cells and confer resistance to chemotherapy. Growth arrest and DNA damage inducible, alpha (GADD45α) is up-regulated on docetaxel treatment and may contribute to docetaxel-mediated cytotoxicity. We examined the mechanism of regulation of GADD45α in prostate cancer cells and the effect of its up-regulation on sensitivity to docetaxel chemotherapy. Expression of GADD45α in PC3 cells was higher than that in Du145 and LNCaP cells (17- and 12-fold, respectively; P &lt; 0.05). Although the proximal promoter region was unmethylated in all three cell lines, methylation of a 4 CpG region upstream of the proximal promoter correlated inversely with gene expression levels. Methylation was reversed by treatment of Du145 and LNCaP cells with DNA methyltransferase inhibitors, leading to reactivation of GADD45α expression in these cells. The 5′ 4 CpG region was also frequently methylated in prostate cancer tissues. Methylation of this region correlated inversely with gene expression in prostate cancer and benign prostate tissues. The methyl binding protein MeCP2 was associated with the methylated 4 CpGs in Du145 cells, and knockdown of MeCP2 in these cells (Du145 MeCP2−) led to a significantly increased expression of GADD45α (3-fold; P = 0.035) without affecting the methylation status of the gene. Enhanced sensitivity to docetaxel was observed by up-regulation of GADD45α in Du145 cells by recombinant expression of GADD45α or pretreatment with 5-azacytidine. Our results show that GADD45α is epigenetically repressed and is a potential target for treatment of prostate cancer. [Cancer Res 2009;69(4):1527–35]