bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of Renal Allografts Secondary to Candida Vascular Complications in Two Recipients from the Same Donor
Authors: Yannam Govardhana Rao , Wrenshall Lucile , Stevens R. Brian
Published: March 2012

Infections remain a major cause of morbidity and mortality in transplant patients. Organ recipients are also susceptible to donor-derived pathogens and the majority of donor infections are easily treatable. Rarely, some pathogens have produced life-threatening complications by compromising the vascular anastomosis. In this case series we report loss of two kidney allografts secondary to vascular complications due to Candida albicans. Both recipients received grafts from a common donor, in whom Candida bacteremia in the donor was not apparent at the time of organ acceptance but became apparent on delayed cultures.
The Stochastic Evolution of a Protocell: The Gillespie Algorithm in a Dynamically Varying Volume
Authors: Carletti T. , Filisetti A.
Published: March 2012

We propose an improvement of the Gillespie algorithm allowing us to study the time evolution of an ensemble of chemical reactions occurring in a varying volume, whose growth is directly related to the amount of some specific molecules, belonging to the reactions set. This allows us to study the stochastic evolution of a protocell, whose volume increases because of the production of container molecules. Several protocell models are considered and compared with the deterministic models.
Quarry Waste: Chances of a Possible Economic and Environmental Valorisation of the Montorfano and Baveno Granite Disposal Sites
Authors: Dino G. A. , Fornaro M. , Trentin A.
Published: March 2012

The Montorfano and Baveno granite ore bodies are located in the Lake District (VCO-NE Piedmont). They were and are still quarried as dimension stones, with a consequent production of a huge volume of “waste.” In 1995, an Italian company (GMM S.p.A) decided to invest in the valorisation of granite quarry waste as a secondary raw material. An in situ geological prospecting was carried out in order to evaluate the characteristics of the material and the thickness and volume of the useful disposal sites that could be used (by means of geophysical surveys). As a consequence of the field work, the amount of quarry waste was estimated as nearly 2 Mm3. Chemical analysis was carried out on 75 granite samples, in order to individuate the Fe2O3 grade: from 1.321–2.593% of the original waste to 0.160–0.228% after the “dry process” treatment. Three different detailed maps that show the typology, the locations, and the quality distribution of the material in the dumping areas have been drawn up.
Combination Therapy for Diabetic Macular Edema
Authors: Zur Dinah , Loewenstein Anat
Published: March 2012

Diabetic macular edema is a main reason for visual loss in diabetic patients. Until recent years, macular laser photocoagulation was the only available therapy. The awareness that inflammation is an important factor in the pathogenetic process of DME gave reason for intravitreal treatment with corticosteroids. The introduction of anti-VEGF drugs brought a revolutionary change in the treatment of DME. This paper will review the important clinical trials with an emphasis on combination therapies.
Digital Heterodyne Holography Reveals the Non-Quasi-Static Scattering Behaviour of Transversally Coupled Nanodisk Pairs
Authors: Suck Sarah Y. , Bidault Sébastien , Bonod Nicolas , Collin Stéphane , Bardou Nathalie , De Wilde Yannick , Tessier Gilles
Published: March 2012

We reconstruct the full three-dimensional scattering pattern of longitudinal and transverse modes in pairs of coupled gold nanodisks using digital heterodyne holography. Near-field simulations prove that, in our experimental conditions, the induced dipoles in the longitudinal mode are in phase while they are nearly in opposite phase for the transverse mode. The scattering efficiency of the two modes is of the same order of magnitude, which goes against the common belief that antisymmetric transverse modes are “dark.” The analysis of the reconstructed hologram in the Fourier plane allows us to estimate the angular scattering pattern for both excited modes. In particular, the antisymmetric transverse mode scatters light mostly into one half-plane, demonstrating that the quasi-static approximation breaks down in nanodisk pairs even for an interparticle distance lower thanλ/4.
One-Time Broadcast Encryption Schemes in Distributed Sensor Networks
Authors: Szalachowski Pawel , Kotulski Zbigniew
Published: March 2012

Broadcasting is a message-transferring method characteristic for majority of sensor networks. Broadcast encryption (BE) is broadcasting encrypted messages in such a way that only legitimate nodes of a network can decrypt them. It has many potential applications in distributed wireless sensor networks (WSNs) but perfect deploying of that method is very difficult. This is because of a WSN is a very dynamic network which includes nodes with limited computational, storage, and communication capabilities. Furthermore, an attacker in this environment is powerful. He can eavesdrop, modify, and inject messages or even capture a large number of nodes, so the solutions must be both secure and efficient. This paper describes several BE schemes from the point of view of WSNs. We present in details the schemes called onetime, and we show how these methods can be applied in distributed sensor networks. We mainly focus on data origin authentication and rekeying processes, crucial for security in such a hostile environment. An analysis and evaluations of proposed schemes are also provided.
Productivity of Nations: A Stochastic Frontier Approach to TFP Decomposition
Authors: Pires Jorge Oliveira , Garcia Fernando
Published: March 2012

This paper tackles the problem of aggregate TFP measurement using stochastic frontier analysis. We estimate a world production frontier for a sample of 75 countries over a long period. The “Bauer-Kumbhakar” decomposition of TFP is applied to a smaller sample in order to evaluate the effects of changes in efficiency (technical and allocative), scale effects, and technical change. Estimated technical efficiency scores are compared to productivity indexes offered by nonfrontier studies. We conclude that differences in productivity are responsible for virtually all the differences of growth performance between developed and developing nations and that a large part of this is due to allocative efficiency.
Deep Hypothermic Circulatory Arrest with Lung Perfusion/Ventilation in a Patient with Acute Type A Aortic Dissection
Authors: Rodriguez-Blanco Yiliam F. , Garcia Lester , Brice Tania , Ricci Marco , Salerno Tomas A.
Published: March 2012

A 50-year-old black male presented with acute type A aortic dissection. Surgical repair was performed under deep hypothermic circulatory arrest (DHCA) with lung perfusion/ventilation throughout the procedure. Details of the lung perfusion technique and its potential benefits and drawbacks are discussed.
Efficacy of the New Double-Layer Stent for Unresectable Distal Malignant Biliary Obstruction: A Single-Center Retrospective Study
Authors: Ito Ken , Igarashi Yoshinori , Mimura Takahiko , Kishimoto Yui , Kikuchi Yoshinori , Okano Naoki
Published: March 2012

Background and Aims. For distal malignant biliary obstruction in cases with short life expectancy, occlusion of plastic stents (PSs) does not usually occur before death, and the application of such a procedure is considered adequate from the viewpoint of cost-effectiveness. Methods and Setting. A new commercially available DLS with side holes, a conventional DLS, and, uncovered self-expanding metal stents (SEMSs) were retrospectively evaluated in patients with jaundice due to unresectable distal malignant biliary obstruction. Results. A total of 64 patients received endoscopic biliary stenting (23 patients with the new DLS, 24 patients with conventional DLS, and 17 patients with uncovered SEMS) from December 2002 to August 2009. Median patency time was found to be 198 days for the new DLS group and 99 days for the conventional DLS group, revealing a significant difference between devices. There was, however, no significant difference in median patency time between the new DLS and the uncovered SEMS (198 days versus 344 days). Conclusion. The new DLS is efficient and safe and may be considered the first choice for unresectable distal malignant obstruction in cases with short life expectancy.
Casein Kinase Iγ2 Impairs Fibroblasts Actin Stress Fibers Formation and Delays Cell Cycle Progression in G1
Authors: Latreille Mathieu , Abu-Thuraia Afnan , Oliva Rossella , Zuo Dongmei , Larose Louise
Published: March 2012

Actin cytoskeleton remodeling is under the regulation of multiple proteins with various activities. Here, we demonstrate that theγ2 isoform of Casein Kinase I (CKIγ2) is part of a novel molecular path regulating the formation of actin stress fibers. We show that overexpression of CKIγ2 in fibroblasts alters cell morphology by impairing actin stress fibers formation. We demonstrate that this is concomitant with increased phosphorylation of the CDK inhibitorp27Kipand lower levels of activated RhoA, and is dependent on CKIγ2 catalytic activity. Moreover, we report that roscovitine, a potent inhibitor of cyclin-dependent kinases, including Cdk5, decreasesp27Kipprotein levels and restores actin stress fibers formation in CKIγ2 overexpressing cells, suggesting the existence of a CKIγ2-Cdk5-p27Kip-RhoA pathway in regulating actin remodeling. On the other hand, we also show that in a manner independent of its catalytic activity, CKIγ2 delays cell cycle progression through G1. Collectively our findings reveal that CKIγ2 is a novel player in the control of actin cytoskeleton dynamics and cell proliferation.
Averting Behavior Framework for Perceived Risk ofYersinia enterocoliticaInfections
Authors: Aziz Sonia N. , Aziz Khwaja M. S.
Published: March 2012

The focus of this research is to present a theoretical model of averting actions that households take to avoid exposure toYersinia enterocoliticain contaminated food. The cost of illness approach only takes into account the value of a cure, while the averting behavior approach can estimate the value of preventing the illness. The household, rather than the individual, is the unit of analysis in this model, where one household member is primarily responsible for procuring uncontaminated food for their family. Since children are particularly susceptible and live with parents who are primary decision makers for sustenance, the designated household head makes the choices that are investigated in this paper. This model uses constrained optimization to characterize activities that may offer protection from exposure toYersinia enterocoliticacontaminated food. A representative household decision maker is assumed to allocate family resources to maximize utility of an altruistic parent, an assumption used in most research involving economics of the family.
Paraoxonase 1 in Chronic Kidney Failure
Authors: Gugliucci Alejandro , Kotani Kazuhiko , Kimura Satoshi
Published: March 2012

In this review we summarize the findings from the literature and our own laboratory on the decreased PON1 activity in renal failure, the mechanisms proposed and the effect of interventions. In addition to profound alterations in lipoproteins, reduced serum PON1 activity has been clearly established in the past decade and could contribute to accelerated development of atherosclerosis in ESRD and in HD. PON1 lactonase activity is lower in ESRD patients. Hemodialysis partially restores PON1 lactonase and the other activities. PON1 activity recovery after dialysis suggests that uremic toxins may play a mechanistic role in PON1 inactivation. Lower PON1 activity in CRF patients is associated with low thiol concentration, high CRP, and is beneficially enhanced with vitamin C and flavonoids. Changes in HDL subclasses, namely lower HDL3in these patients may also play a role in PON1 lower activity. Future research should focus on: (1) mechanistic studies on causes for low PON1 activity and mass; (2) prospective studies focusing on whether there is an added predictive value in measuring PON1 activity (and PON1 activity in HDL3) in this patient population; (3) intervention studies attempting to increase PON1 activity.
Investigation of Multicritical Phenomena in ANNNI Model by Monte Carlo Methods
Authors: Murtazaev A. K. , Ibaev J. G.
Published: March 2012

The anisotropic Ising model with competing interactions is investigated in wide temperature range and |J1/J| parameters by means of Monte Carlo methods. Static critical exponents of the magnetization, susceptibility, heat capacity, and correlation radius are calculated in the neighborhood of Lifshitz point. According to obtained results, a phase diagram is plotted, the coordinates of Lifshitz point are defined, and a character of multicritical behavior of the system is detected.
Modified MIMO Cube for Enhanced Channel Capacity
Authors: Nagy Lajos
Published: March 2012

This paper deals with the optimization of MIMO antenna elements' position in modified MIMO cube for getting maximal channel capacity in indoor environment. The dependence of the channel capacity on the antenna orientation was analyzed by simulations. We have also examined the effect of the frequency dependence of the antenna system (in case of conjugate matching and nonconjugate matching) for the channel capacity. Based on the simulation results in the created and measured antenna system, the antennas were at a right angle to each other. At the two chosen different structures, we measured the antenna parameters and the channel capacity. In this paper, we present the results of the measurements which clearly confirm our simulations. We will point out the differences between the two antenna structures.
PET/CT in the Staging of the Non-Small-Cell Lung Cancer
Authors: Chao Fangfang , Zhang Hong
Published: March 2012

Lung cancer is a common disease and the leading cause of cancer-related death in many countries. Precise staging of patients with non-small-cell lung cancer plays an important role in determining treatment strategy and prognosis. Positron emission tomography/computed tomography (PET/CT), combining anatomic information of CT and metabolic information of PET, is emerging as a potential diagnosis and staging test in patients with non-small-cell lung cancer (NSCLC). The purpose of this paper is to discuss the value of integrated PET/CT in the staging of the non-small-cell lung cancer and its health economics.
Homotopy Perturbation Method and Variational Iteration Method for Harmonic Waves Propagation in Nonlinear Magneto‐Thermoelasticity with Rotation
Authors: Gepreel Khaled A. , Abo-Dahab S. M. , Nofal T. A.
Published: March 2012

The homotopy perturbation method and variational iteration
method are applied to obtain the approximate solution of the harmonic waves propagation in a
nonlinear magneto‐thermoelasticity under influence of rotation. The problem is solved in one‐dimensional elastic half‐space model subjected initially to a prescribed harmonic displacement and the temperature of the medium. The displacement and temperature are calculated for
the methods with the variations of the magnetic field and the rotation. The results obtained
are displayed graphically to show the influences of the new parameters and the difference between
the methods′ technique. It is obvious that the homotopy perturbation method is more effective and
powerful than the variational iteration method.
Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative Stress
Authors: Daiber Andreas , Oelze Matthias , Wenzel Philip , Bollmann Franziska , Pautz Andrea , Kleinert Hartmut
Published: March 2012

Organic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction, and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which occurs during chronic treatment with these agents, and this phenomenon is largely based on induction of oxidative stress with subsequent endothelial dysfunction. We therefore speculated that induction of heme oxygenase-1 (HO-1) could be an efficient strategy to overcome nitrate tolerance and the associated side effects. Indeed, we found that hemin cotreatment prevented the development of nitrate tolerance and vascular oxidative stress in response to chronic nitroglycerin therapy. Vice versa, pentaerithrityl tetranitrate (PETN), a nitrate that was previously reported to be devoid of adverse side effects, displayed tolerance and oxidative stress when the HO-1 pathway was blocked pharmacologically or genetically by using HO-1+/–mice. Recently, we identified activation of Nrf2 and HuR as a principle mechanism of HO-1 induction by PETN. With the present paper, we present and discuss our recent and previous findings on the role of HO-1 for the prevention of nitroglycerin-induced nitrate tolerance and for the beneficial effects of PETN therapy.
Insulin Resistance Promotes Early Atherosclerosis via Increased Proinflammatory Proteins and Oxidative Stress in Fructose-Fed ApoE-KO Mice
Authors: Cannizzo Beatriz , Luján Agustín , Estrella Natalia , Lembo Carina , Cruzado Montserrat , Castro Claudia
Published: March 2012

High fructose intake induces an insulin resistance state associated with metabolic syndrome (MS). The effect of vascular inflammation in this model is not completely addressed. The aim of this study was to evaluate vascular remodeling, inflammatory and oxidative stress markers, and atheroma development in high-fructose diet-induced insulin resistance of ApoE-deficient mice (ApoE-KO). Mice were fed with either a normal chow or a 10% w/v fructose (HF) in drinking water over a period of 8 weeks. Thereafter, plasma metabolic parameters, vascular remodeling, atheroma lesion size, inflammatory markers, and NAD(P)H oxidase activity in the arteries were determined. HF diet induced a marked increase in plasma glucose, insulin, and triglycerides in ApoE-KO mice, provoked vascular remodeling, enhanced expression of vascular cell-adhesion molecule-1 (VCAM-1) and matrix metalloprotease 9 (MMP-9) and enlarged atherosclerotic lesion in aortic and carotid arteries. NAD(P)H oxidase activity was enhanced by fructose intake, and this effect was attenuated by tempol, a superoxide dismutase mimetic, and losartan, an Angiotensin II receptor antagonist. Our study results show that high-fructose-induced insulin resistance promotes a proinflammatory and prooxidant state which accelerates atherosclerotic plaque formation in ApoE-KO mice.
Renal Protective Effect of Xiao-Chai-Hu-Tang on Diabetic Nephropathy of Type 1-Diabetic Mice
Authors: Lin Chun-Ching , Lin Liang-Tzung , Yen Ming-Hong , Cheng Juei-Tang , Hsing Chung-Hsi , Yeh Ching-Hua
Published: March 2012

Xiao-Chai-Hu-Tang (XCHT), a traditional Chinese medicine formula consisting of seven medicinal plants, is used in the treatment of various diseases. We show here that XCHT could protect type-1 diabetic mice against diabetic nephropathy, using streptozotocin (STZ)-induced diabetic mice and high-glucose (HG)-exposed rat mesangial cell (RMC) as models. Following 4 weeks of oral administration with XCHT, renal functions and renal hypertrophy significantly improved in the STZ-diabetic mice, while serum glucose was only moderately reduced compared to vehicle treatment. Treatment with XCHT in the STZ-diabetic mice and HG-exposed RMC resulted in a decrease in expression levels of TGF-β1, fibronectin, and collagen IV, with concomitant increase in BMP-7 expression. Data from DPPH assay, DHE stain, and CM-H2DCFDA analysis indicated that XCHT could scavenge free radicals and inhibit high-glucose-induced ROS in RMCs. Taken together, these results suggest that treatment with XCHT can improve renal functions in STZ-diabetic mice, an effect that is potentially mediated through decreasing oxidative stress and production of TGF-β1, fibronectin, and collagen IV in the kidney during development of diabetic nephropathy. XCHT, therefore merits further investigation for application to improve renal functions in diabetic disorders.
Genetic Ablation of Cav1 Differentially Affects Melanoma Tumor Growth and Metastasis in Mice: Role of Cav1 in Shh Heterotypic Signaling and Transendothelial Migration
Authors: Capozza Franco , Trimmer Casey , Castello-Cros Remedios , Katiyar Sanjay , Whitaker-Menezes Diana , Follenzi Antonia , Crosariol Marco , Llaverias Gemma , Sotgia Federica , Pestell Richard G. , Lisanti Michael P.
Published: March 2012

Both cell-autonomous and non–cell-autonomous factors contribute to tumor growth and metastasis of melanoma. The function of caveolin-1 (Cav1), a multifunctional scaffold protein known to modulate several biologic processes in both normal tissue and cancer, has been recently investigated in melanoma cancer cells, but its role in the melanoma microenvironment remains largely unexplored. Here, we show that orthotopic implantation of B16F10 melanoma cells in the skin of Cav1KO mice increases tumor growth, and co-injection of Cav1-deficient dermal fibroblasts with melanoma cells is sufficient to recapitulate the tumor phenotype observed in Cav1KO mice. Using indirect coculture experiments with fibroblasts and melanoma cells combined with cytokine analysis, we found that Cav1-deficient fibroblasts promoted the growth of melanoma cells via enhanced paracrine cytokine signaling. Specifically, Cav1-deficient fibroblasts displayed increased ShhN expression, which heterotypically enhanced the Shh signaling pathway in melanoma cells. In contrast to primary tumor growth, the ability of B16F10 melanoma cells to form lung metastases was significantly reduced in Cav1KO mice. This phenotype was associated mechanistically with the inability of melanoma cells to adhere to and to transmigrate through a monolayer of endothelial cells lacking Cav1. Together, our findings show that Cav1 may regulate different mechanisms during primary melanoma tumor growth and metastatic dissemination. Cancer Res; 72(9); 2262–74. ©2012 AACR.
Immune Response Is an Important Aspect of the Antitumor Effect Produced by a CD40L-Encoding Oncolytic Adenovirus
Authors: Diaconu Iulia , Cerullo Vincenzo , Hirvinen Mari L.M. , Escutenaire Sophie , Ugolini Matteo , Pesonen Saila K. , Bramante Simona , Parviainen Suvi , Kanerva Anna , Loskog Angelica S.I. , Eliopoulos Aristides G. , Pesonen Sari , Hemminki Akseli
Published: March 2012

Oncolytic adenovirus is an attractive platform for immunotherapy because virus replication is highly immunogenic and not subject to tolerance. Although oncolysis releases tumor epitopes and provides costimulatory danger signals, arming the virus with immunostimulatory molecules can further improve efficacy. CD40 ligand (CD40L, CD154) induces apoptosis of tumor cells and triggers several immune mechanisms, including a T-helper type 1 (TH1) response, which leads to activation of cytotoxic T cells and reduction of immunosuppression. In this study, we constructed a novel oncolytic adenovirus, Ad5/3-hTERT-E1A-hCD40L, which features a chimeric Ad5/3 capsid for enhanced tumor transduction, a human telomerase reverse transcriptase (hTERT) promoter for tumor selectivity, and human CD40L for increased efficacy. Ad5/3-hTERT-E1A-hCD40L significantly inhibited tumor growth in vivo via oncolytic and apoptotic effects, and (Ad5/3-hTERT-E1A-hCD40L)–mediated oncolysis resulted in enhanced calreticulin exposure and HMGB1 and ATP release, which were suggestive of immunogenicity. In two syngeneic mouse models, murine CD40L induced recruitment and activation of antigen-presenting cells, leading to increased interleukin-12 production in splenocytes. This effect was associated with induction of the TH1 cytokines IFN-γ, RANTES, and TNF-α. Tumors treated with Ad5/3-CMV-mCD40L also displayed an enhanced presence of macrophages and cytotoxic CD8+ T cells but not B cells. Together, our findings show that adenoviruses coding for CD40L mediate multiple antitumor effects including oncolysis, apoptosis, induction of T-cell responses, and upregulation of TH1 cytokines. Cancer Res; 72(9); 2327–38. ©2012 AACR.
Vasoactive Peptides with Angiogenesis-Regulating Activity Predict Cancer Risk in Males
Authors: Belting Mattias , Almgren Peter , Manjer Jonas , Hedblad Bo , Struck Joachim , Wang Thomas J. , Bergmann Andreas , Melander Olle
Published: March 2012

Background: Tumor development requires angiogenesis, and antiangiogenesis has been introduced in the treatment of cancer patients; however, how the cardiovascular phenotype correlates with cancer risk remains ill-defined. Here, we hypothesized that vasoactive peptides previously implicated in angiogenesis regulation predict long-term cancer risk.

Methods: We measured midregional proatrial natriuretic peptide (MR-proANP), proadrenomedullin (MR-proADM), and C-terminal preprovasopressin (copeptin) in fasting plasma from participants of the Malmö Diet and Cancer Study that were free from cancer prior to the baseline exam in 1991 to 1994 (1,768 males and 2,293 females). We used Cox proportional hazards models to determine the time to first cancer event in relation to baseline levels of vasoactive peptides during a median follow-up of 15 years.

Results: First cancer events occurred in 366 males and in 368 females. In males, one SD increase of MR-proANP, copeptin, and MR-proADM was independently related to incident cancer [HR (95% CI)] by 0.85 (0.74–0.96), P = 0.012; 1.17 (1.04–1.32), P = 0.009; and 1.12 (0.99–1.26), P = 0.065, respectively, and a summed biomarker score identified an almost 2-fold difference in cancer risk between the top and bottom quartile (P < 0.001). In younger males, the biomarker score identified a more than 3-fold increase in risk between the top and bottom quartile (P < 0.001). Among females, we found no relationship between biomarkers and cancer incidence.

Conclusions: Our data suggest that vasoactive peptide biomarkers predict cancer risk in males, particularly in younger males.

Impact: Our findings may have implications for cancer risk prediction and present novel, potentially drug modifiable, mechanisms underlying cancer development. Cancer Epidemiol Biomarkers Prev; 21(3); 513–22. ©2012 AACR.
Telomere Length and Genetic Variation in Telomere Maintenance Genes in Relation to Ovarian Cancer Risk
Authors: Terry Kathryn L. , Tworoger Shelley S. , Vitonis Allison F. , Wong Jason , Titus-Ernstoff Linda , De Vivo Immaculata , Cramer Daniel W.
Published: March 2012

Background: Telomeres protect chromosomal ends, shorten with cellular division, and signal cellular senescence, but unchecked telomere attrition can lead to telomere dysfunction, upregulation of telomerase, and carcinogenesis. Shorter telomeres in peripheral blood leukocytes (PBL) have been associated with elevated cancer risk. Furthermore, genetic variants in and around the TERT gene have been implicated in carcinogenesis.

Methods: We measured relative telomere length (RTL) in PBLs of 911 cases and 948 controls from the New England case–control (NECC) study, a population-based study of ovarian cancer. In addition, we assessed germ line genetic variation in five telomere maintenance genes among 2,112 cases and 2,456 controls from the NECC study and the Nurses' Health Study, a prospective cohort study. ORs and 95% CIs were estimated by logistic regression.

Results: Overall, we observed no differences in telomere length between cases and controls. Compared with women with RTL in the longest tertile, women with RTL in the shortest tertile had no increase in risk (OR = 1.01, 95% CI: 0.80–1.28). However, several SNPs in the TERT gene, including rs2736122, rs4246742, rs4975605, rs10069690, rs2736100, rs2853676, and rs7726159, were significantly associated with ovarian cancer risk. We observed a significant gene-level association between TERT and ovarian cancer risk (P = 0.00008).

Conclusion: Our observations suggest that genetic variation in the TERT gene may influence ovarian cancer risk, but the association between average telomere length in PBLs and ovarian cancer remains unclear.

Impact: The role of telomeres in ovarian carcinogenesis remains unsettled and warrants further investigation. Cancer Epidemiol Biomarkers Prev; 21(3); 504–12. ©2012 AACR.
Tumor Suppressor Function of PGP9.5 Is Associated with Epigenetic Regulation in Prostate Cancer—Novel Predictor of Biochemical Recurrence after Radical Surgery
Authors: Mitsui Yozo , Shiina Hiroaki , Hiraki Miho , Arichi Naoko , Hiraoka Takeo , Sumura Masahiro , Honda Satoshi , Yasumoto Hiroaki , Igawa Mikio
Published: March 2012

Background: The expression level of protein G product 9.5 (PGP9.5) is downregulated because of promoter CpG hypermethylation in several tumors. We speculated that impaired regulation of PGP9.5 through epigenetic pathways is associated with the pathogenesis of prostate cancer.

Methods: CpG methylation of the PGP9.5 gene was analyzed in cultured prostate cancer cell lines, 226 localized prostate cancer samples from radical prostatectomy cases, and 80 benign prostate hyperplasia (BPH) tissues.

Results: Following 5-aza-2′-deoxycytidune treatment, increased PGP9.5 mRNA transcript expression was found in the LNCaP and PC3 cell lines. With bisulfite DNA sequencing, partial methylation of the PGP9.5 promoter was shown in LNCaP whereas complete methylation was found in PC3 cells. After transfection of PGP9.5 siRNA, cell viability was significantly accelerated in LNCaP but not in PC3 cells as compared with control siRNA transfection. Promoter methylation of PGP9.5 was extremely low in only one of 80 BPH tissues, whereas it was found in 37 of 226 prostate cancer tissues. Expression of the mRNA transcript of PGP9.5 was significantly lower in methylation (+) than methylation (−) prostate cancer tissues. Multivariate analysis of biochemical recurrence (BCR) after an radical prostatectomy revealed pT category and PGP9.5 methylation as prognostically relevant. Further stratification with the pT category in addition to methylation status identified a stepwise reduction of BCR-free probability.

Conclusion: This is the first clinical and comprehensive study of inactivation of the PGP9.5 gene via epigenetic pathways in primary prostate cancer.

Impact: CpG methylation of PGP9.5 in primary prostate cancer might become useful as a molecular marker for early clinical prediction of BCR after radical prostatectomy. Cancer Epidemiol Biomarkers Prev; 21(3); 487–96. ©2012 AACR.
Genetic Susceptibility to Type 2 Diabetes and Breast Cancer Risk in Women of European and African Ancestry
Authors: Hou Ningqi , Zheng Yonglan , Gamazon Eric R. , Ogundiran Temidayo O. , Adebamowo Clement , Nathanson Katherine L. , Domchek Susan M. , Rebbeck Timothy R. , Simon Michael S. , John Esther M. , Hennis Anselm , Nemesure Barbara , Wu Suh-Yuh , Leske M. Cristina , Ambs Stefan , Niu Qun , Zhang Jing , Pierce Brandon , Cox Nancy J. , Olopade Olufunmilayo I. , Huo Dezheng
Published: March 2012

Background: Epidemiologic studies have reported a positive association between type 2 diabetes (T2D) and breast cancer risk, independent of body weight.

Methods: We investigated 40 genetic variants known to be associated with T2D in relation to breast cancer risk among 2,651 breast cancer cases and 2,520 controls of African or European ancestry that were pooled from seven studies.

Results: We found that two T2D risk alleles in Caucasian women (rs5945326-G, rs12518099-C) and one in women of African ancestry (rs7578597-T) were positively associated with breast cancer risk at a nominal significance level of 0.05, whereas two T2D risk alleles were inversely associated with breast cancer risk in Caucasian women (rs1111875-C, rs10923931-T). The composite T2D susceptibility score (the number of risk allele) was not significantly associated with breast cancer risk.

Conclusion: The association between established T2D genetic susceptibility variants and breast cancer risk in women of African or European ancestry is likely weak, if it does exist.

Impact: The pleiotropic effects of known T2D risk alleles cannot explain the association between T2D and breast cancer risk. Cancer Epidemiol Biomarkers Prev; 21(3); 552–6. ©2012 AACR.
Tissue and Serum Mesothelin Are Potential Markers of Neoplastic Progression in Barrett's Associated Esophageal Adenocarcinoma
Authors: Rizk Nabil P. , Servais Elliot L. , Tang Laura H. , Sima Camelia S. , Gerdes Hans , Fleisher Martin , Rusch Valerie W. , Adusumilli Prasad S.
Published: March 2012

Background: Mesothelin is overexpressed in several malignancies and is purportedly a specific marker of malignant transformation. In this pilot study, we investigated whether tissue and serum mesothelin are potential markers of neoplastic progression in Barrett's esophagus (BE) and in esophageal adenocarcinoma (EAC).

Methods: Mesothelin expression was retrospectively evaluated in normal, BE, and EAC tissue from surgically resected esophageal specimens (n = 125). In addition, soluble mesothelin-related peptide (SMRP) levels were measured in serum.

Results: Normal esophageal mucosa did not express mesothelin. BE tissue with high-grade dysplasia specifically expressed mesothelin, whereas BE tissue with low-grade or without dysplasia did not. Fifty-seven (46%) EAC tumors were positive for mesothelin. EAC tumors with BE expressed mesothelin more often than those without BE (58% vs. 35%, P = 0.01). SMRP levels were elevated in 70% of EAC patients (mean = 0.89 nmol/L; range: 0.03–3.77 nmol/L), but not in patients with acid reflux and/or BE.

Conclusions: Mesothelin is commonly expressed in BE-associated EAC. On the basis of this pilot study, a prospective study is under way to evaluate tissue and serum mesothelin which are potential markers of neoplastic progression in BE and in EAC (NCT01393483).

Impact: Current surveillance methods in Barrett's esophagus are invasive and neither cost-effective nor sensitive. This pilot study suggests that serum mesothelin is a marker of neoplastic transformation in BE and may provide a noninvasive method to improve identification of malignant transformation. Cancer Epidemiol Biomarkers Prev; 21(3); 482–6. ©2012 AACR.
Milk and Dairy Consumption among Men with Prostate Cancer and Risk of Metastases and Prostate Cancer Death
Authors: Pettersson Andreas , Kasperzyk Julie L. , Kenfield Stacey A. , Richman Erin L. , Chan June M. , Willett Walter C. , Stampfer Meir J. , Mucci Lorelei A. , Giovannucci Edward L.
Published: March 2012

Background: Whether milk and dairy intake after a prostate cancer diagnosis is associated with a poorer prognosis is unknown. We investigated postdiagnostic milk and dairy intake in relation to risk of lethal prostate cancer (metastases and prostate cancer death) among participants in the Health Professionals Follow-Up Study.

Methods: The cohort consisted of 3,918 men diagnosed with apparently localized prostate cancer between 1986 and 2006, and followed to 2008. Data on milk and dairy intake were available from repeated questionnaires. We used Cox proportional hazards models to calculate HRs and 95% CIs of the association between postdiagnostic milk and dairy intake and prostate cancer outcomes.

Results: We ascertained 229 prostate cancer deaths and an additional 69 metastases during follow-up. In multivariate analysis, total milk and dairy intakes after diagnosis were not associated with a greater risk of lethal prostate cancer. Men with the highest versus lowest intake of whole milk were at an increased risk of progression (HR = 2.15, 95% CI: 1.28–3.60; Ptrend < 0.01). Men in the highest versus lowest quintile of low-fat dairy intake were at a decreased risk of progression (HR = 0.62; 95% CI: 0.40–0.95; Ptrend = 0.07).

Conclusions: With the exception of whole milk, our results suggest that milk and dairy intake after a prostate cancer diagnosis is not associated with an increased risk of lethal prostate cancer.

Impact: This is the first larger prospective study investigating the relation between postdiagnostic milk and dairy intake and risk of lethal prostate cancer. Cancer Epidemiol Biomarkers Prev; 21(3); 428–36. ©2012 AACR.
Trends in Colorectal Cancer Incidence Rates in the United States by Tumor Location and Stage, 1992–2008
Authors: Siegel Rebecca L. , Ward Elizabeth M. , Jemal Ahmedin
Published: March 2012

Background: Results from case–control studies outside the United States have been conflicted about the efficacy of colonoscopy for reducing cancer risk in the right colon. To contribute to this discourse from an alternative perspective, we analyzed high-quality surveillance data to report on recent trends in population-based colorectal cancer incidence rates by tumor location in the United States.

Methods: Data from cancer registries in the Surveillance, Epidemiology, and End Results Program were analyzed to examine colorectal cancer incidence trends from 1992 through 2008 among individuals aged ≥50 years (n = 267,072). Joinpoint regression analysis was used to quantify annual percent change in age-standardized rates by tumor location and disease stage.

Results: Incidence rates for right-sided colon tumors decreased annually by 2.6% (95% CI: 2.0–3.2) since 1999 in men and 2.3% (CI: 1.6–3.0) since 2000 in women, after remaining stable during the previous seven/eight years. Incidence rates for left-sided tumors were generally decreasing from 1992 to 2008 in both sexes. Beginning in 1999/2000, substantial, almost identical annual declines occurred for late-stage disease in both the right and left colon: 3.9% (CI: 3.1–4.8) and 4.2% (CI: 3.5–4.9), respectively, in men; and 3.3% (CI: 2.5–4.1) and 3.3% (CI: 2.8–3.8) in women.

Conclusion: Large declines in the incidence of right-sided colon tumors among individuals 50 years and older began around 2000.

Impact: Increased colonoscopy utilization during the past decade may have contributed to a reduction in risk for cancers in both the right and left colorectum in the United States. Cancer Epidemiol Biomarkers Prev; 21(3); 411–6. ©2012 AACR.
Nitrosamines and Heme Iron and Risk of Prostate Cancer in the European Prospective Investigation into Cancer and Nutrition
Authors: Jakszyn Paula G. , Allen Naomi E. , Lujan-Barroso Leila , Gonzalez Carlos A. , Key Timothy J. , Fonseca-Nunes Ana , Tjønneland Anne , Føns-Johnsen Nina , Overvad Kim , Teucher Birgit , Li Kuanrong , Boeing Heiner , Trichopoulou Antonia , Oikonomou Eleni , Sarantopoulou Maria , Saieva Calogero , Krogh Vittorio , Tumino Rosario , Ricceri Fulvio , Bueno-de-Mesquita H. Bas , Huerta José M. , Ardanaz Eva , Arguelles Marcial V. , Molina-Montes Esther , Larrañaga Nerea , Wirfält Elisabet , Wallström Peter , Johansson Mattias , Stattin Pär , Khaw Kay-Tee , Jenab Mazda , Fedirko Veronika , Riboli Elio
Published: March 2012

Background: The evidence about nitrosamines and heme iron intake and cancer risk is limited, despite the biologic plausibility of the hypothesis that these factors might increase cancer risk. We investigated the association between dietary nitrosamines and heme iron and the risk of prostate cancer among participants of European Prospective Investigation into Cancer and Nutrition (EPIC).

Methods: Data on food consumption and complete follow-up for cancer occurrence was available for 139,005 men, recruited in 8 European countries. Estimates of HRs were obtained by proportional hazard models, stratified by age at recruitment, and study center, and adjusted for total energy intake, smoking status, marital status, dairy products, educational level, and body mass index.

Results: After a mean follow-up of 10 years, 4,606 participants were diagnosed with first incident prostate cancer. There was no overall association between prostate cancer risk and nitrosamines exposure (preformed and endogenous) or heme iron intake (HR for a doubling of intake: 1.00; 95% CI: 0.98–1.03 for N-Nitrosodimethlyamine, 0.95; 95% CI: 0.88–1.03 for endogenous Nitrosocompounds, and 1.00; 95 CI: 0.97–1.03 for heme iron).

Conclusions and Impact: Our findings do not support an effect of nitrosamines (endogenous and exogenous) and heme iron intake on prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 21(3); 547–51. ©2012 AACR.
Tobacco Addiction and The Risk of Upper Aerodigestive Tract Cancer in A Multicenter Case-Control Study
Authors: YC Lee , M Marron , S Benhamou , C Bouchardy , W Ahrens , H Pohlabeln , P Lagiou , D Trichopoulos , A Agudo , X Castellsague , V Bencko , I Holcatova , K Kjaerheim , F Merletti , L Richiardi , GJ Macfarlane , TV Macfarlane , R Talamini , L Barzan , C Canova , L Simonato , DI Conway , PA McKinney , P Thomson , A Znaor , CM Healy , BE McCartan , P Boffetta , P Brennan , M Hashibe
Published: March 2012

Background: While previous studies on tobacco and alcohol and the risk of upper aerodigestive tract (UADT) cancers have clearly shown dose-response relations with the frequency and duration of tobacco and/or alcohol, studies on addiction to tobacco itself as a risk factor for UADT cancer have not been published, to our knowledge. The aim of this report is to assess whether smoking addiction is a risk factor for UADT SCC risk in the multicenter case-control study (ARCAGE) in Western Europe independent of tobacco smoking or alcohol drinking intensity or duration.

Methods: The analyses included 1,905 ever smoking UADT SCC cases (871 oral cavity/oropharynx, 814 hypopharynx/larynx, 127 esophagus, and 93 overlapping oral cavity/pharynx) and 1,489 ever smoking controls. The addiction variables included first cigarette after waking up, difficulty refraining from smoking in places where it is forbidden, and cigarettes per day. Odds ratios (OR) and 95% confidence intervals (95% CI) for UADT cancers with addiction variables were estimated with unconditional logistic regression, adjusting for center, age, sex, education level, alcohol consumption, and tobacco smoking.

Results: Among current smokers, 76.47% of cases were categorized in the highest addiction level, whereas 54.69% of controls were in that category. The participants who smoked their first cigarette within 5 minutes of waking up were two times more likely to develop UADT SCC (OR = 2.22, 95% CI 1.57–3.15) than those who smoked 60 minutes after waking up. A higher modified Fagerstram score, reflecting greater tobacco addiction, was associated with an increased risk of UADT SCC among current smokers, but not among former smokers.

Conclusion: We observed that time to first cigarette after waking up was associated with UADT SCC risk, regardless of heavy smoking or alcohol drinking behaviors. These results are consistent with residual effect of smoking that was not captured by the questionnaire responses alone.
An Affective Booster Moderates the Relationship Between Message Frame and Behavioral Intentions
Authors: RA Ferrer , WMP Klein , LE Zajac , SR Land , BS Ling
Published: March 2012

This study examined whether emotion moderates the degree to which framed messages influences colorectal cancer (CRC) screening intentions and self-efficacy for screening. Previous research has demonstrated that loss-framed messages are more effective than gain-framed messages in motivating detection behaviors such as screening. However, overall effects of framing in the context of health messages have been small and heterogeneous, highlighting the pressing need to identify moderators of framed message effectiveness. We paired a standard framing manipulation with an “affective booster” to increase anticipated and anticipatory emotions associated with the framed messages in a 2 × 2 (gain-loss by affective booster-no booster). The loss-framed message was paired with a complementary affective booster intended to facilitate worry and regret; the gain-framed message was paired with a complementary booster intended to facilitate relief. Consistent with previous research, we found that loss-framed messages were more effective in increasing intentions to screen for CRC (Î2 = -.38, t = -2.19, p = .03, d = 0.55). The inclusion of the affective booster had no overall effect on intentions to screen (Î2 = -.06, t = -0.39, p = .70, d = 0.10). However, we found a significant interaction (Î2 = .48, t = 2.13, p = .04, d = 0.53), such that among individuals who received gain-framed messages (but not loss-framed messages), the affective booster increased message persuasiveness. A similar pattern of results was uncovered with respect to self-efficacy for screening, where an affective booster increased self-efficacy among the gain-frame message recipients, bringing their self-efficacy in line with those who had received the loss-framed message. This study indicates that in the presence of affective boosters, loss-framed messages may lose their advantage over gain-framed messages in motivating detection behaviors.
Selective Lymph Node Dissection for Castration-Resistant Prostate Cancer
Authors: Busch Jonas , Hinz Stefan , Kempkensteffen Carsten , Erber Barbara , Klopf Christian , Weikert Steffen , Miller Kurt , Magheli Ahmed
Published: March 2012

Background: No relevant data have been published on the impact of retroperitoneal lymph node dissection (LND) on clinical outcome in patients with castration-resistant prostate cancer. Methods: We retrospectively studied the records of 6 patients with lymph node metastases from castration-resistant prostate cancer who underwent a retroperitoneal LND between 2005 and 2010. Complication rate and clinical outcome were examined. Results: Mean patient age was 69.2 (63–81) years. Primary therapy was radical prostatectomy, radiation therapy, or pelvic LND and androgen deprivation in 3, 2 and 1 cases, respectively. Mean prostate-specific antigen (PSA) at LND was 37.6 (20.3–139) ng/dl. LND was performed as a modified unilateral (n = 3), bilateral (n = 1) and bilateral extended (n = 2) approach with a median lymph node density of 0.739 (0.111–1). Preoperative Charlson index was 0 (n = 3) or 1 (n = 3). No intra- or postoperative complications occurred. The average postoperative decline of PSA was 39.3% (–99.4 to +31.3). Differences between mean pre- and postoperative PSA velocities and densities were 23.9 ng/ml/year and 11.2 months, respectively (p = 0.24 and p = 0.40). Four patients (67%) developed bone metastases after a mean period of 23.5 (5–58) months. Median bone metastases-free survival was 15.5 months and median overall survival after LND was 31.7 months on Kaplan-Meier analysis. Conclusions: A selective LND in castration-resistant prostate cancer patients could be safely performed. A positive effect on the PSA and PSA kinetics was accomplished for the majority of patients. This new surgical approach represents an alternative treatment option in the palliative setting of prostate cancer patients and could delay toxic systemic therapy up to 12 months.