bluuebunny/crossref_metadata_2025 huggingface dataset:
EXTREMAL ALMOST-KÄHLER METRICS
Authors: LEJMI MEHDI
Published: July 2010

We generalize the notions of the Futaki invariant and extremal vector field of a compact Kähler manifold to the general almost-Kähler case and show the periodicity of the extremal vector field when the symplectic form represents an integral cohomology class modulo torsion. We also give an explicit formula of the Hermitian scalar curvature in Darboux coordinates which allows us to obtain examples of non-integrable extremal almost-Kähler metrics saturating LeBrun's estimates.
${\mathcal N}=8$ GAUGED SUPERGRAVITY THEORY AND ${\mathcal N}=6$ SUPERCONFORMAL CHERN–SIMONS MATTER THEORY
Authors: AHN CHANGHYUN , WOO KYUNGSUNG
Published: July 2010

By studying the previously known holographic [Formula: see text] supersymmetric renormalization group flow (Gowdigere–Warner) in four dimensions, we find the mass deformed Chern–Simons matter theory which has [Formula: see text] supersymmetry by adding the four mass terms among eight adjoint fields. The geometric superpotential from the 11 dimensions is found and provides the M2-brane probe analysis. As second example, we consider known holographic [Formula: see text] supersymmetric renormalization group flow (Pope–Warner) in four dimensions. The eight mass terms are added and similar geometric superpotential is obtained.
LARGE N REDUCTION ON GROUP MANIFOLDS
Authors: KAWAI HIKARU , SHIMASAKI SHINJI , TSUCHIYA ASATO
Published: July 2010

We show that the large N reduction holds on group manifolds. Large N field theories defined on group manifolds are equivalent to some corresponding matrix models. For instance, gauge theories on S3 can be regularized in a gauge invariant and SO(4) invariant manner.
THE CANONICAL STRUCTURE OF THE FIRST-ORDER EINSTEIN–HILBERT ACTION
Authors: MCKEON D. G. C.
Published: July 2010

The Dirac constraint formalism is used to analyze the first-order form of the Einstein–Hilbert action in d > 2 dimensions. Unlike previous treatments, this is done without eliminating fields at the outset by solving equations of motion that are independent of time derivatives when they correspond to first class constraints. As anticipated by the way in which the affine connection transforms under a diffeomorphism, not only primary and secondary but also tertiary first class constraints arise. These leave d(d-3) degrees of freedom in phase space. The gauge invariance of the action is discussed, with special attention being paid to the gauge generators of Henneaux, Teitelboim and Zanelli and of Castellani.
LOCOMOTION OF ARTICULATED BODIES IN AN IDEAL FLUID: 2D MODEL WITH BUOYANCY, CIRCULATION AND COLLISIONS
Authors: MUNNIER ALEXANDRE , PINÇON BRUNO
Published: July 2010

Articulated solid bodies (ASB) is a basic model for the study of shape-changing underwater vehicles made of rigid parts linked together by pivoting joints. In this paper we study the locomotion of such swimming mechanisms in an ideal fluid. Our study ranges over a wide class of problems: several ASBs can be involved (without being hydrodynamically decoupled), the fluid-bodies system can be partially or totally confined and fluid circulation, buoyancy force and possible collisions between bodies are taken into account. We derive the Euler–Lagrange equation governing the dynamics of the system, study its well-posedness and describe a numerical scheme implemented in a Matlab toolbox (Biohydrodynamics Toolbox).
Multibandwidth Kernel-Based Object Tracking
Authors: Dargazany Aras , Soleimani Ali , Ahmadyfard Alireza
Published: July 2010

Object tracking using Mean Shift (MS) has been attracting considerable attention recently. In this paper, we try to deal with one of its shortcoming. Mean shift is designed to find local maxima for tracking objects. Therefore, in large target movement between two consecutive frames, the local and global modes are not the same as previous frames so that Mean Shift tracker may fail in tracking the desired object via localizing the global mode. To overcome this problem, a multibandwidth procedure is proposed to help
conventional MS tracker reach the global mode of the density function using any staring points. This gradually smoothening procedure is called Multi Bandwidth Mean Shift (MBMS) which in fact smoothens the Kernel Function through a multiple kernel-based sampling procedure automatically. Since it is important for us to have less computational complexity for real-time applications, we try to decrease the number of iterations to reach the global mode. Based on our results, this proposed version of MS enables us to track an object with the same initial point much faster than conventional MS tracker.
Synthesis and Fluorescence Property of Mn‐Doped ZnSe Nanowires
Authors: Han Dongmei , Song Chunfeng , Li Xiaoyu
Published: July 2010

Water‐soluble Mn‐doped ZnSe luminescent nanowires were successfully prepared by hydrothermal method without any heavy metal ions and toxic reagents. The morphology, composition, and property of the products were investigated. The experimental results showed that the Mn‐doped ZnSe nanowires were single well crystallized and had a zinc blende structure. The average length of the nanowires was about 2‐3 μm, and the diameter was 80 nm. With the increase of Mn2+‐doped concentration, the absorbance peak showed large difference. The UV‐vis absorbance spectrum showed that the Mn‐doped ZnSe nanowires had a sharp absorption band appearing at 360 nm. The PL spectrum revealed that the nanowires had two distinct emission bands centered at 432 and 580 nm.
Computational Method for Estimating DNA Copy Numbers in Normal Samples, Cancer Cell Lines, and Solid Tumors Using Array Comparative Genomic Hybridization
Authors: Abkevich Victor , Iliev Diana , Timms Kirsten M. , Tran Thanh , Skolnick Mark , Lanchbury Jerry S. , Gutin Alexander
Published: July 2010

Genomic copy number variations are a typical feature of cancer. These variations may influence cancer outcomes as well as effectiveness of treatment. There are many computational methods developed to detect regions with deletions and amplifications without estimating actual copy numbers (CN) in these regions. We have developed a computational method capable of detecting regions with deletions and amplifications as well as estimating actual copy numbers in these regions. The method is based on determining how signal intensity from different probes is related to CN, taking into account changes in the total genome size, and incorporating into analysis contamination of the solid tumors with benign tissue. Hidden Markov Model is used to obtain the most likely CN solution. The method has been implemented for Affymetrix 500K GeneChip arrays and Agilent 244K oligonucleotide arrays. The results of CN analysis for normal cell lines, cancer cell lines, and tumor samples are presented. The method is capable of detecting copy number alterations in tumor samples with up to 80% contamination with benign tissue. Analysis of 178 cancer cell lines reveals multiple regions of common homozygous deletions and strong amplifications encompassing known tumor suppressor genes and oncogenes as well as novel cancer related genes.
Dual Effect of Neutrophils on pIgR/Secretory Component in Human Bronchial Epithelial Cells: Role of TGF-
Authors: Ratajczak Céline , Guisset Amélie , Detry Bruno , Sibille Yves , Pilette Charles
Published: July 2010

Neutrophils have a dual affect on epithelial pIgR/SC, the critical receptor for transcellular routing of mucosal IgA, but mechanisms of pIgR/SC upregulation remain elusive. Requirements of cytokine, redox, and signalling pathways for pIgR/SC production were assessed in human bronchial epithelial (Calu-3) cells cocultured with increasing numbers of blood neutrophils. Increased SC production was observed after incubation for 48 hrs with intermediate neutrophil numbers (1.25 to ), was favoured by the elastase inhibitor SLPI, and correlated with increased TGF- production. Exogenous TGF- stimulated SC production with a maximal effect at 48 hrs and both TGF-- and neutrophil-driven SC upregulation were dependent on redox balance and p38 MAP-kinase activation. This paper shows that activated neutrophils could upregulate epithelial pIgR/SC production through TGF--mediated activation of a redox-sensitive and p38 MAPK-dependent pathway. An imbalance between the two neutrophil-driven opposite mechanisms (SC upregulation and SC degradation) could lead to downregulation of pIgR/SC, as observed in severe COPD.
The Passage of S100B from Brain to Blood Is Not Specifically
Related to the Blood-Brain Barrier Integrity
Authors: Kleindienst Andrea , Schmidt Christian , Parsch Hans , Emtmann Irene , Xu Yu , Buchfelder Michael
Published: July 2010

Following brain injury, S100B is released from damaged astrocytes but also yields repair mechanisms. We measured S100B in the cerebrospinal fluid (CSF) and serum (Cobas e411 electrochemiluminescence assay, Roche) longitudinally in a large cohort of patients treated with a ventricular drainage following traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH). Statistical analysis was performed with SPSS software applying the Mann-Whitney rank sum test or chi-test where appropriate. S100B in CSF and serum was significantly increased following TBI (n=71) and SAH (n=185) for at least one week following injury. High S100B levels in CSF and serum were inconsistent associated with outcome. The passage of S100B from CSF to blood (100∗serumS100B/CSFS100B) was significantly decreased although the albumin quotient suggested an “open” blood-CSF barrier. Events possibly interfering with the BBB did not affect the S100B passage (P=.591). In conclusion, we could not confirm S100B measurements to reliably predict outcome, and a compromised blood-CSF barrier did not affect the passage of S100B from CSF to serum.
Towards Direct Simulation of Future Tropical Cyclone Statistics in a High‐Resolution Global Atmospheric Model
Authors: Wehner Michael F. , Bala G. , Duffy Phillip , Mirin Arthur A. , Romano Raquel
Published: July 2010

We present a set of high‐resolution global atmospheric general circulation model (AGCM) simulations focusing on the model′s ability to represent tropical storms and their statistics. We find that the model produces storms of hurricane strength with realistic dynamical features. We also find that tropical storm statistics are reasonable, both globally and in the north Atlantic, when compared to recent observations. The sensitivity of simulated tropical storm statistics to increases in sea surface temperature (SST) is also investigated, revealing that a credible late 21st century SST increase produced increases in simulated tropical storm numbers and intensities in all ocean basins. While this paper supports previous high‐resolution model and theoretical findings that the frequency of very intense storms will increase in a warmer climate, it differs notably from previous medium and high‐resolution model studies that show a global reduction in total tropical storm frequency. However, we are quick to point out that this particular model finding remains speculative due to a lack of radiative forcing changes in our time‐slice experiments as well as a focus on the Northern hemisphere tropical storm seasons.
Active Optimal Control of the KdV Equation Using the Variational Iteration Method
Authors: Kucuk Ismail
Published: July 2010

The optimal pointwise control of the KdV equation is investigated with an objective of minimizing a given performance measure. The performance measure is specified as a quadratic functional of the final state and velocity functions along with the energy due to open‐ and closed‐loop controls. The minimization of the performance measure over the controls is subjected to the KdV equation with periodic boundary conditions and appropriate initial condition. In contrast to standard optimal control or variational methods, a direct control parameterization is used in this study which presents a distinct approach toward the solution of optimal control problems. The method is based on finite terms of Fourier series approximation of each time control variable with unknown Fourier coefficients and frequencies. He′s variational iteration method for the nonlinear partial differential equations is applied to the problem and thus converting the optimal control of lumped parameter systems into a mathematical programming. A numerical simulation is provided to exemplify the proposed method.
The Mitogen-Activated Protein Kinase Kinase 4 Has a Pro-Oncogenic Role in Skin Cancer
Authors: Finegan Katherine G. , Tournier Cathy
Published: July 2010

The mitogen-activated protein kinase (MAPK) kinase 4 (MKK4) is a nonredundant component of stress-activated MAPK signaling modules. Its function in tumorigenesis remains highly controversial with some studies indicating that MKK4 is a tumor suppressor, whereas others have reported a pro-oncogenic role. To clarify the role of MKK4 in cancer, we have created a novel mouse model to test the effect of the specific loss of MKK4 in the epidermis on the formation of papillomas caused by activated ras mutation. We have discovered that skin-specific MKK4-deficient mice are resistant to carcinogen-induced tumorigenesis. One mechanism by which MKK4 promotes cell proliferation and the formation of tumors is by increasing epidermal growth factor receptor expression through the c-Jun NH2-terminal protein kinase/c-Jun signaling pathway. Together, our results provide the first genetic demonstration that MKK4 is essential to mediate the oncogenic effect of Ras in vivo, thereby validating MKK4 as a potential drug target for cancer therapy. Cancer Res; 70(14); 5797–806. ©2010 AACR.
Transiently Entrapped Circulating Tumor Cells Interact with Neutrophils to Facilitate Lung Metastasis Development
Authors: Huh Sung Jin , Liang Shile , Sharma Arati , Dong Cheng , Robertson Gavin P.
Published: July 2010

It is unknown why only a minority of circulating tumor cells trapped in lung capillaries form metastases and involvement of immune cells remains uncertain. A novel model has been developed in this study showing that neutrophils regulate lung metastasis development through physical interaction and anchoring of circulating tumor cells to endothelium. Human melanoma cells were i.v. injected into nude mice leading to the entrapment of many cancer cells; however, 24 hours later, very few remained in the lungs. In contrast, injection of human neutrophils an hour after tumor cell injection increased cancer cell retention by ∼3-fold. Entrapped melanoma cells produced and secreted high levels of a cytokine called interleukin-8 (IL-8), attracting neutrophils and increasing tethering β2 integrin expression by 75% to 100%. Intercellular adhesion molecule-1 on melanoma cells and β2 integrin on neutrophils interacted, promoting anchoring to vascular endothelium. Decreasing IL-8 secretion from melanoma cells lowered extracellular levels by 20% to 50%, decreased β2 integrin on neutrophils by ∼50%, and reduced neutrophil-mediated extravasation by 25% to 60%, resulting in ∼50% fewer melanoma cells being tethered to endothelium and retained in lungs. Thus, transendothelial migration and lung metastasis development decreased by ∼50%, showing that targeting IL-8 in melanoma cells has the potential to decrease metastasis development by disrupting interaction with neutrophils. Cancer Res; 70(14); 6071–82. ©2010 AACR.
A Novel Imaging Approach for Early Detection of Prostate Cancer Based on Endogenous Zinc Sensing
Authors: Ghosh Subrata K. , Kim Pilhan , Zhang Xiao-an , Yun Seok-Hyun , Moore Anna , Lippard Stephen J. , Medarova Zdravka
Published: July 2010

The early detection of prostate cancer is a life-saving event in patients harboring potentially aggressive disease. With the development of malignancy, there is a dramatic reduction in the zinc content of prostate tissue associated with the inability of cancer cells to accumulate the ion. In the current study, we used endogenous zinc as an imaging biomarker for prostate cancer detection and progression monitoring. We employed a novel fluorescent sensor for mobile zinc (ZPP1) to detect and monitor the development of prostate cancer in a transgenic mouse model of prostate adenocarcinoma, using in vivo optical imaging correlated with biological fluid-based methods. We showed that the progression of prostate cancer could be monitored in vivo judging by the decreasing zinc content in the prostates of tumor-bearing mice in an age-dependent manner. In a novel quantitative assay, we determined the concentration of mobile zinc in both prostate cell lysates and mouse prostate extracts through simple titration of the ZPP1 sensor. Our findings fulfill the promise of zinc-based prostate cancer diagnostics with the prospect for immediate clinical translation. Cancer Res; 70(15); 6119–27. ©2010 AACR.
AACR Centennial Series: The Biology of Cancer Metastasis: Historical Perspective
Authors: Talmadge James E. , Fidler Isaiah J.
Published: July 2010

Metastasis resistant to therapy is the major cause of death from cancer. Despite almost 200 years of study, the process of tumor metastasis remains controversial. Stephen Paget initially identified the role of host-tumor interactions on the basis of a review of autopsy records. His “seed and soil” hypothesis was substantiated a century later with experimental studies, and numerous reports have confirmed these seminal observations. An improved understanding of the metastatic process and the attributes of the cells selected by this process is critical for the treatment of patients with systemic disease. In many patients, metastasis has occurred by the time of diagnosis, so metastasis prevention may not be relevant. Treating systemic disease and identifying patients with early disease should be our goal. Revitalized research in the past three decades has focused on new discoveries in the biology of metastasis. Even though our understanding of molecular events that regulate metastasis has improved, the contributions and timing of molecular lesion(s) involved in metastasis pathogenesis remain unclear. Review of the history of pioneering observations and discussion of current controversies should increase understanding of the complex and multifactorial interactions between the host and selected tumor cells that contribute to fatal metastasis and should lead to the design of successful therapy. Cancer Res; 70(14); 5649–69. ©2010 AACR.
Variation in Blame Attributions across Different Cancer Types
Authors: Marlow Laura A.V. , Waller Jo , Wardle Jane
Published: July 2010

Background: Cancer communication has begun to focus on prevention through lifestyle change. One possible consequence of this is that attitudes towards people with certain types of cancer could become increasingly negative. In this study, we assessed attributions of blame for five common cancers.

Methods: Data were collected as part of a population-based survey of women's attitudes to cancer. A sample of 1,620 women rated how much they would blame someone who had a diagnosis of breast cancer, cervical cancer, bowel cancer, lung cancer, and leukemia, as well as chlamydia and obesity.

Results: Few women attributed any blame for someone with leukemia or breast cancer (9% and 15%). The proportions attributing some blame for bowel cancer and cervical cancer were slightly higher (23% and 37%). Patients with lung cancer were considered at least partly to blame by 70% of respondents, approaching chlamydia (87%) and obesity (96%). Attributions of blame for bowel, cervical, and lung cancer were most common among those with more qualifications, and women who knew that cervical cancer was linked to sexual activity were more likely to attribute blame to it (48% versus 32%).

Conclusions: Cancers are not generally seen as a matter of personal responsibility, but lung cancer, and to a lesser extent, cervical and bowel cancer do attract blame attributions. Knowledge of the preventability of cancer seems to be associated with perceived responsibility.

Impact: Increasing awareness of the preventable nature of some cancers might affect blame attributions. Additional research is needed to explore the implications of these findings. Cancer Epidemiol Biomarkers Prev; 19(7); 1799–805. ©2010 AACR.
Fecal MicroRNAs as Novel Biomarkers for Colon Cancer Screening
Authors: Link Alexander , Balaguer Francesc , Shen Yan , Nagasaka Takeshi , Lozano Juan José , Boland C. Richard , Goel Ajay
Published: July 2010

Introduction: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths, but currently available noninvasive screening programs have achieved only a modest decrease in mortality. MicroRNAs (miRNA) play an important role in a wide array of biological processes and are commonly dysregulated in neoplasia. We aimed to evaluate the feasibility of fecal miRNAs as biomarkers for colorectal neoplasia screening.

Materials and Methods: Total RNA was extracted from freshly collected stool samples from 8 healthy volunteers and 29 samples collected via fecal occult blood testing from subjects with normal colonoscopies, colon adenomas, and CRCs. miRNA expression analyses were done with TaqMan quantitative reverse transcription-PCR for a subset of miRNAs. Illumina miRNA microarray profiling was done to evaluate the differences in expression patterns between normal colonic mucosa tissues and stool samples from healthy subjects.

Results: We efficiently extracted miRNAs from stool specimens using our developed protocol. Data from independent experiments showed high reproducibility for miRNA extraction and expression. miRNA expression patterns were similar in stool specimens among healthy volunteers, and reproducible in stool samples that were collected serially in time from the same individuals. miRNA expression profiles from 29 patients showed higher expression of miR-21 and miR-106a in patients with adenomas and CRCs compared with individuals free of colorectal neoplasia.

Conclusion: Our data indicate that miRNAs could be extracted from stool easily and reproducibly. The stools of patients with colorectal neoplasms have unique and identifiable patterns of miRNA expression.

Impact: Fecal miRNAs may be an excellent candidate for the development of a noninvasive screening test for colorectal neoplasms. Cancer Epidemiol Biomarkers Prev; 19(7); 1766–74. ©2010 AACR.
Comparative Biomarker Expression and RNA Integrity in Biospecimens Derived from Radical Retropubic and Robot-Assisted Laparoscopic Prostatectomies
Authors: Ricciardelli Carmela , Bianco-Miotto Tina , Jindal Shalini , Dodd Thomas J. , Cohen Penelope A. , Marshall Villis R. , Sutherland Peter D. , Samaratunga Hemamali , Kench James G. , Dong Ying , Wang Hong , Clements Judith A. , Risbridger Gail P. , Sutherland Robert L. , Tilley Wayne D. , Horsfall David J.
Published: July 2010

Background: Knowledge of preanalytic conditions that biospecimens are subjected to is critically important because novel surgical procedures, tissue sampling, handling, and storage might affect biomarker expression or invalidate tissue samples as analytes for some technologies.

Methods: We investigated differences in RNA quality, gene expression by quantitative real-time PCR, and immunoreactive protein expression of selected prostate cancer biomarkers between tissues from retropubic radical prostatectomy (RRP) and robot-assisted laparoscopic prostatectomy (RALP). Sections of tissue microarray of 23 RALP and 22 RRP samples were stained with antibodies to androgen receptor (AR) and prostate-specific antigen (PSA) as intersite controls, and 14 other candidate biomarkers of research interest to three laboratories within the Australian Prostate Cancer BioResource tissue banking network. Quantitative real-time PCR was done for AR, PSA (KLK3), KLK2, KLK4, and HIF1A on RNA extracted from five RALP and five RRP frozen tissue cores.

Results: No histologic differences were observed between RALP and RRP tissue. Biomarker staining grouped these samples into those with increased (PSA, CK8/18, CKHMW, KLK4), decreased (KLK2, KLK14), or no change in expression (AR, ghrelin, Ki67, PCNA, VEGF-C, PAR2, YB1, p63, versican, and chondroitin 0-sulfate) in RALP compared with RRP tissue. No difference in RNA quality or gene expression was detected between RALP and RRP tissue.

Conclusions: Changes in biomarker expression between RALP and RRP tissue exist at the immunoreactive protein level, but the etiology is unclear.

Impact: Future studies should account for changes in biomarker expression when using RALP tissues, and mixed cohorts of RALP and RRP tissue should be avoided. Cancer Epidemiol Biomarkers Prev; 19(7); 1755–65. ©2010 AACR.
Knowledge and Attitudes about Vitamin D and Impact on Sun Protection Practices among Urban Office Workers in Brisbane, Australia
Authors: Vu Lan H. , van der Pols Jolieke C. , Whiteman David C. , Kimlin Michael G. , Neale Rachel E.
Published: July 2010

Background: Sun exposure is the main source of vitamin D. Increasing scientific and media attention to the potential health benefits of sun exposure may lead to changes in sun exposure behaviors.

Methods: To provide data that might help frame public health messages, we conducted an online survey among office workers in Brisbane, Australia, to determine knowledge and attitudes about vitamin D and associations of these with sun protection practices. Of the 4,709 people invited to participate, 2,867 (61%) completed the questionnaire. This analysis included 1,971 (69%) participants who indicated that they had heard about vitamin D.

Results: Lack of knowledge about vitamin D was apparent. Eighteen percent of people were unaware of the bone benefits of vitamin D but 40% listed currently unconfirmed benefits. Over half of the participants indicated that more than 10 minutes in the sun was needed to attain enough vitamin D in summer, and 28% indicated more than 20 minutes in winter. This was significantly associated with increased time outdoors and decreased sunscreen use. People believing sun protection might cause vitamin D deficiency (11%) were less likely to be frequent sunscreen users (summer odds ratio, 0.63; 95% confidence interval, 0.52-0.75).

Conclusions: Our findings suggest that there is some confusion about sun exposure and vitamin D, and that this may result in reduced sun-protective behavior.

Impact: More information is needed about vitamin D production in the skin. In the interim, education campaigns need to specifically address the vitamin D issue to ensure that skin cancer incidence does not increase. Cancer Epidemiol Biomarkers Prev; 19(7); 1784–9. ©2010 AACR.
A Candidate Gene Study of Folate-Associated One Carbon Metabolism Genes and Colorectal Cancer Risk
Authors: Levine A. Joan , Figueiredo Jane C. , Lee Won , Conti David V. , Kennedy Kathleen , Duggan David J. , Poynter Jenny N. , Campbell Peter T. , Newcomb Polly , Martinez Maria Elena , Hopper John L. , Le Marchand Loic , Baron John A. , Limburg Paul J. , Ulrich Cornelia M. , Haile Robert W.
Published: July 2010

Background: Folate-associated one-carbon metabolism (FOCM) may play an important role in colorectal carcinogenesis. Variation in FOCM genes may explain some of the underlying risk of colorectal cancer.

Methods: This study utilized data from 1,805 population-based colorectal cancer cases and 2,878 matched sibling controls from the Colon Cancer Family Registry. We used a comprehensive haplotype tagging single nucleotide polymorphism (tagSNP) approach to select 395 tagSNPs in 15 genes involved in folate and vitamin B12 metabolism. Genotyping was done using the Illumina GoldenGate or Sequenom platforms. Risk factor and dietary data were collected using self-completed questionnaires. Microsatellite instability (MSI) status was determined using standard techniques, and tumor subsite was obtained from pathology reports. The association between SNPs and colorectal cancer was assessed using conditional logistic regression with sibships as the matching factor and assuming a log additive or codominant model.

Results: In the log additive model, two linked (r2 = 0.99) tagSNPs in the DHFR gene (rs1677693 and rs1643659) were associated with a significant decrease in colorectal cancer risk after correction for multiple testing (odds ratio, 0.87; 95% confidence interval, 0.71-0.94; P = 0.029; and odds ratio, 0.87; 95% confidence interval, 0.71-0.95; P = 0.034 for rs1677693 and rs1643659, respectively). These two linked (r2 = 0.99) tagSNPs and one tagSNP in the MTR gene (rs4659744) were significantly associated with reduced colorectal cancer risk only among individuals not using multivitamin supplements.

Conclusions: Overall, we found only moderate evidence that genetic variation in 15 folate pathway genes may affect colorectal cancer risk except in non–multivitamin users.

Impact: This study suggests that multivitamin supplement use may modify the association between folate pathway genes and colorectal cancer risk in a post-folic-acid-supplemented population. Cancer Epidemiol Biomarkers Prev; 19(7); 1812–21. ©2010 AACR.
Coffee and Tea Intake and Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium
Authors: Galeone Carlotta , Tavani Alessandra , Pelucchi Claudio , Turati Federica , Winn Deborah M. , Levi Fabio , Yu Guo-Pei , Morgenstern Hal , Kelsey Karl , Dal Maso Luigino , Purdue Mark P. , McClean Michael , Talamini Renato , Hayes Richard B. , Franceschi Silvia , Schantz Stimson , Zhang Zuo-Feng , Ferro Gilles , Chuang Shu-Chun , Boffetta Paolo , La Vecchia Carlo , Hashibe Mia
Published: July 2010

Background: Only a few studies have explored the relation between coffee and tea intake and head and neck cancers, with inconsistent results.

Methods: We pooled individual-level data from nine case-control studies of head and neck cancers, including 5,139 cases and 9,028 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI), adjusting for potential confounders.

Results: Caffeinated coffee intake was inversely related with the risk of cancer of the oral cavity and pharynx: the ORs were 0.96 (95% CI, 0.94–0.98) for an increment of 1 cup per day and 0.61 (95% CI, 0.47–0.80) in drinkers of >4 cups per day versus nondrinkers. This latter estimate was consistent for different anatomic sites (OR, 0.46; 95% CI, 0.30–0.71 for oral cavity; OR, 0.58; 95% CI, 0.41–0.82 for oropharynx/hypopharynx; and OR, 0.61; 95% CI, 0.37–1.01 for oral cavity/pharynx not otherwise specified) and across strata of selected covariates. No association of caffeinated coffee drinking was found with laryngeal cancer (OR, 0.96; 95% CI, 0.64–1.45 in drinkers of >4 cups per day versus nondrinkers). Data on decaffeinated coffee were too sparse for detailed analysis, but indicated no increased risk. Tea intake was not associated with head and neck cancer risk (OR, 0.99; 95% CI, 0.89–1.11 for drinkers versus nondrinkers).

Conclusions: This pooled analysis of case-control studies supports the hypothesis of an inverse association between caffeinated coffee drinking and risk of cancer of the oral cavity and pharynx.

Impact: Given widespread use of coffee and the relatively high incidence and low survival of head and neck cancers, the observed inverse association may have appreciable public health relevance. Cancer Epidemiol Biomarkers Prev; 19(7); 1723–36. ©2010 AACR.
Risk of Genome-Wide Association Study–Identified Genetic Variants for Colorectal Cancer in a Chinese Population
Authors: Xiong Fang , Wu Chen , Bi Xinyu , Yu Dianke , Huang Liming , Xu Jian , Zhang Tongwen , Zhai Kan , Chang Jiang , Tan Wen , Cai Jianqiang , Lin Dongxin
Published: July 2010

Background: Recent genome-wide association studies have identified 10 single nucleotide polymorphisms (SNP) associated with colorectal cancer (CRC) in Caucasians. This study evaluated the effects of these newly identified SNPs in a Chinese population.

Methods: We assessed the associations of these 10 SNPs with CRC in a case-control study that consisted of 2,124 cases and 2,124 controls. Odds ratios (OR) and 95% confidence intervals were computed by logistic regression, and cumulative effect of risk genotypes were also calculated.

Results: We found that only five SNPs (rs6983267, rs4939827, rs10795668, rs3802842, and rs961253) were significantly associated with risk of CRC in our study population in the same direction as reported by previous genome-wide association studies, with the ORs ranging from 1.11 to 2.96. A cumulative effect was observed with the ORs being gradually elevated with increasing number of risk genotypes (Ptrend = 1.32 × 10−21), and patients carrying ≥4 risk genotypes had 3.25-fold increased CRC risk (95% confidence interval, 2.24-4.72) compared with patients carrying no risk genotype. Furthermore, we found that rs10795668 was associated with increased risk only in rectal cancer but not colon cancer, and rs3802842 was also significantly associated with advanced stages of CRC.

Conclusions: These results suggest that rs6983267, rs4939827, rs10795668, rs3802842, and rs961253 SNPs are associated with the risk of CRC in the Chinese population individually and jointly.

Impact: Our results provide new insights into colorectal tumorigenesis and have potential implications in early detection and target treatment of CRC in non-Western populations. Cancer Epidemiol Biomarkers Prev; 19(7); 1855–61. ©2010 AACR.
Metabolic Syndrome and Breast Cancer in the Me-Can (Metabolic Syndrome and Cancer) Project
Authors: Bjørge Tone , Lukanova Annekatrin , Jonsson Håkan , Tretli Steinar , Ulmer Hanno , Manjer Jonas , Stocks Tanja , Selmer Randi , Nagel Gabriele , Almquist Martin , Concin Hans , Hallmans Göran , Häggström Christel , Stattin Pär , Engeland Anders
Published: July 2010

Background: Few studies have assessed the metabolic syndrome (MetS) as an entity in relation to breast cancer risk, and results have been inconsistent. We aimed to examine the association between MetS factors (individually and combined) and risk of breast cancer incidence and mortality.

Methods: Two hundred ninety thousand women from Austria, Norway, and Sweden were enrolled during 1974-2005, with measurements of height, weight, blood pressure, and levels of glucose, cholesterol, and triglycerides. Relative risks (RR) of breast cancer were estimated using Cox proportional hazards regression for each MetS factor in quintiles and for standardized levels (z-scores) and for a composite z-score for the MetS.

Results: There were 4,862 incident cases of breast cancer and 633 deaths from breast cancer identified. In women below age 50, there was a decreased risk of incident cancer for the MetS (per 1-unit increment of z-score; RR, 0.83; 95% confidence interval, 0.76-0.90) as well as for the individual factors (except for glucose). The lowest risks were seen among the heaviest women. In women above age 60, there was an increased risk of breast cancer mortality for the MetS (RR, 1.23; 95% confidence interval, 1.04-1.45) and for blood pressure and glucose. The strongest association with mortality was seen for increased glucose concentrations.

Conclusions: The MetS was associated with a decreased risk of incident breast cancer in women below age 50 with high body mass index, and with an increased risk of breast cancer mortality in women above 60.

Impact: Lifestyle interventions as recommended for cardiovascular disease prevention may be of value to prevent breast cancer mortality in postmenopausal women. Cancer Epidemiol Biomarkers Prev; 19(7); 1737–45. ©2010 AACR.
Well-Done Meat Consumption, NAT1 and NAT2 Acetylator Genotypes and Prostate Cancer Risk: The Multiethnic Cohort study
Authors: Sharma Sangita , Cao Xia , Wilkens Lynne R. , Yamamoto Jennifer , Lum-Jones Annette , Henderson Brian E. , Kolonel Laurence N. , Le Marchand Loïc
Published: July 2010

Background: Prostate cancer (PC) is the most common male malignancy in the United States and disparities in risk exist among ethnic/racial groups. A high intake of well-done meat and the presence of the rapid NAT1 and slow NAT2 acetylator genotypes, as modifiers of the carcinogenic effect of heterocyclic amines, were hypothesized to increase PC risk and possibly explain these ethnic differences in risk.

Methods: This study examined the associations between well-done (red) meat consumption, NAT1 and NAT2 acetylator genotypes, and PC risk among five ethnicities (African American, Native Hawaiian, Japanese American, Latino, and Caucasian) in a case-control study of PC nested within the Multiethnic Cohort study. Cases (n = 2,106) and controls (n = 2,063) were genotyped for eight single nucleotide polymorphisms in NAT1 and seven single nucleotide polymorphisms in NAT2 that characterized all common alleles for these genes. Well-done meat intake was computed based on responses to a detailed food frequency questionnaire including a question on meat preference. Conditional logistic regression was used in the analysis.

Results: There was no evidence of an increased risk associated with preference for well-done meat, intake of well-done meat, and NAT1 or NAT2 genotypes (jointly or separately).

Conclusions: These results do not support the hypothesis that exposure to heterocyclic amines is associated with risk of PC. However, additional studies with more precise exposure measures are needed. Cancer Epidemiol Biomarkers Prev; 19(7); 1866–70. ©2010 AACR.
Nonmelanoma Skin Cancer and the Risk of Second Primary Cancers: a Systematic Review
Authors: Wheless Lee , Black Joshua , Alberg Anthony J.
Published: July 2010

Background: Based on empirical evidence, a personal history of nonmelanoma skin cancer (NMSC) has been hypothesized to be a risk factor for other cancers. Others hypothesize that NMSC may be a marker of high cutaneous vitamin D synthesis and therefore inversely associated with risk of other malignancies. To reconcile these divergent views, we carried out a systematic review to determine the association between NMSC and subsequent risk of other cancers.

Methods: Bibliographic databases were searched through March 2009. Studies were included if sufficient information was presented to estimate the risk of developing other cancers following NMSC. Studies were reviewed and data were abstracted independently in duplicate with disagreements resolved by consensus.

Results: Of the 21 included studies, 15 reported the association between NMSC and risk of all other cancers combined. NMSC was significantly associated with increased risk of another malignancy among cohort studies based on cancer registries [summary random-effects relative risk (SRR), 1.12; 95% confidence interval (CI), 1.07-1.17; n = 12 studies) and those with individual-level data (SRR, 1.49; 95% CI, 1.12-1.98; n = 3). In stratified analyses of registry studies, this association held true for both squamous (SRR, 1.17; 95% CI, 1.12-1.23; n = 7) and basal cell carcinoma (SRR, 1.09; 95% CI, 1.01-1.17; n = 7), and both men (SRR, 1.14; 95% CI, 1.09-1.20; n = 12) and women (SRR, 1.10; 95% CI, 1.04-1.15; n = 12).

Conclusions: Strong, consistent evidence indicates that a personal history of NMSC is associated with increased risk of developing other malignancies.

Impact: For unknown reasons, NMSC may be a risk factor for other cancers. Cancer Epidemiol Biomarkers Prev; 19(7); 1686–95. ©2010 AACR.
Timing of Menarche and First Birth in Relation to Risk of Breast Cancer in A-Bomb Survivors
Authors: McDougall Jean A. , Sakata Ritsu , Sugiyama Hiromi , Grant Eric , Davis Scott , Nishi Nobuo , Soda Midori , Shimizu Yukiko , Tatsukawa Yoshimi , Kasagi Fumiyoshi , Suyama Akihiko , Ross Phillip , Kopecky Kenneth J. , Li Christopher I.
Published: July 2010

Background: The length of the interval between age at menarche and age at first birth is positively associated with breast cancer risk. We examined the risk of breast cancer in atomic bomb survivors to investigate whether women exposed to radiation between menarche and first birth had a higher risk of radiogenic breast cancer than women exposed at the same age but outside this interval.

Methods: Women (n = 30,113) were classified into three reproductive status at the time of the bombings (ATB) categories (premenarche, between menarche and first birth, or after first birth). Poisson regression was used to test the primary hypothesis.

Results: When the background rate of breast cancer was taken to depend on city, age ATB, and attained age only, the radiation-related excess relative risk (ERR) varied significantly among the three categories (P = 0.049). However, after controlling for significant heterogeneity in the baseline risk of breast cancer between reproductive status ATB groups (P < 0.001), no significant heterogeneity (P = 0.88) was observed in the ERR, with an ERR per Gy of 1.36 [95% confidence interval (CI), 0.54-2.75] for women exposed between menarche and first birth ATB, and 1.07 (95% CI, 0.22-3.62) and 1.53 (95% CI, 0.63-2.90) for those exposed premenarche or after first birth, respectively.

Conclusions: The radiation-associated risk of breast cancer does not vary significantly by reproductive status ATB.

Impact: It is possible that radiation exerts similar carcinogenic effects on the breast regardless of its stage of differentiation, or that the differences in radiosensitivity are too small to be detected in this cohort. Cancer Epidemiol Biomarkers Prev; 19(7); 1746–54. ©2010 AACR.
Genomic Alterations and Allelic Imbalances Are Strong Prognostic Predictors in Osteosarcoma
Authors: Smida Jan , Baumhoer Daniel , Rosemann Michael , Walch Axel , Bielack Stefan , Poremba Christopher , Remberger Klaus , Korsching Eberhard , Scheurlen Wolfram , Dierkes Christian , Burdach Stefan , Jundt Gernot , Atkinson Michael J. , Nathrath Michaela
Published: July 2010

Purpose: Osteosarcoma, the most common primary malignant tumor of the bone, is characterized by complex karyotypes with numerous structural and numerical alterations. Despite attempts to establish molecular prognostic markers at the time of diagnosis, the most accepted predictive factor remains the histologic evaluation of necrosis after neoadjuvant chemotherapy. The present approach was carried out to search for genome-wide recurrent loss of heterozygosity and copy number variations that could have prognostic and therapeutic impact for osteosarcoma patients.

Experimental Design: Pretherapeutic biopsy samples of 45 osteosarcoma patients were analyzed using Affymetrix 10K2 high-density single nucleotide polymorphism arrays. Numerical aberrations and allelic imbalances were correlated with the histologically assessed response to therapy and clinical follow-up.

Results: The most frequent genomic alterations included amplifications of chromosome 6p21 (15.6%), 8q24 (15.6%, harboring MYC), and 12q14 (11.1%, harboring CDK4), as well as loss of heterozygosity of 10q21.1 (44.4%). All these aberrations and the total degree of heterozygosity of each tumor were significantly associated with an adverse outcome of patients and were used to define a chromosomal alteration staging system with a superior predictive potential compared with the histologic regression grading.

Conclusions: Structural chromosomal alterations detected by single nucleotide polymorphism analysis provide a simple but robust parameter to anticipate response to chemotherapy. The proposed chromosomal alteration staging system might therefore help to better predict the clinical course of osteosarcoma patients at the time of initial diagnosis and to adapt neoadjuvant treatment in patients resistant to the current protocols. Clin Cancer Res; 16(16); 4256–67. ©2010 AACR.
Differential Diagnoses of Systemic Mastocytosis in Routinely Processed Bone Marrow Biopsy Specimens: A Review
Authors: Horny H.-P. , Sotlar K. , Valent P.
Published: July 2010

Diagnosis of systemic mastocytosis (SM) is mainly based on the morphological demonstration of compact mast cell infiltrates in various tissue sites. In almost all patients such infiltrates are detected in the bone marrow. Reliable immunohistochemical markers for the diagnosis and grading of SM have been established, but various differential diagnoses including myeloproliferative neoplasms, basophilic and eosinophilic leukemias may be very difficult to delineate. Even more challenging is the recognition of hematological neoplasms with signs of mast cell differentiation but not fulfilling diagnostic criteria for SM, especially the rare myelomastocytic leukemia. It is also important to separate the reactive state of mast cell hyperplasia from indolent variants of SM, especially those with a very low degree of bone marrow infiltration and absence of compact mast cell infiltrates. When the lymphocytic component of the SM infiltrate is very prominent, SM may be confused with an indolent lymphoma, especially lymphoplasmacytic lymphoma which almost always shows a marked reactive increase in mast cells. In aggressive and leukemic variants of SM, mast cells may be very atypical and devoid of metachromatic granules. This hypogranulation can be regarded as cellular atypia and may lead to the misdiagnosis aspect of monocytic leukemia or histiocytic neoplasm. Regarding immunohistochemical anomalies, mast cells in aggressive and leukemic SM have been found to express CD30 (Ki1-antigen). Thus, anaplastic large cell lymphoma or Hodgkin’s disease may first be considered rather than SM. There is increasing evidence that most patients with long-standing adult-type urticaria pigmentosa-like skin lesions have in fact indolent SM. Therefore, such skin lesions are an important clue to the correct diagnosis in these patients. However, in aggressive or leukemic SM skin lesions are usually absent and then the correct diagnosis relies on an appropriate investigation of bone marrow biopsy specimens using both SM-related immunohistochemical markers (tryptase, KIT, CD25, CD30) but also markers excluding potential differential diagnoses. Investigation for presence of the activating KIT point mutation D816V is very helpful to establish a correct diagnosis of SM in all the difficult cases exhibiting a low degree of bone marrow infiltration or puzzling morphological findings.
Super-High-Dose Methylprednisolone Does Not Improve Efficacy or Induce Glucocorticoid Resistance in Experimental Allergic Encephalomyelitis
Authors: Wei Zhi-sheng , Hong Ming-fan , Su Quan-xi , Wang Xiao-hui , Yu Qing-yun , Peng Zhong-xing , Zhang Ming-xing , Jie Ao , Wang Rui , Huang Ye-qing
Published: July 2010

Objective: To investigate whether a super-high dose (SHD) of methylprednisolone (MP) improves its efficacy or induces glucocorticoid (GC) resistance, and to explore the potential mechanisms of GC resistance in experimental allergic encephalomyelitis (EAE). Methods: The therapeutic effects of SHD and low-dose MP were evaluated in EAE by analyzing clinical scores, pathological changes and cytokine production. Immunohistochemistry and RT-PCR were used to investigate the expression of GC receptor (GR) isoforms and splicing factor SRp30c. Results: Both MP doses had similar therapeutic effects. The ratio of GRα to GRβ was positively correlated with clinical score changes. However, there was no difference in the GRα/GRβ ratio between SHD and low-dose MP groups. SRp30c mRNA was correlated with GRβ expression. Conclusion: This study indicates that the GRα/GRβ ratio is associated with GC sensitivity, and SRp30c may play an important role in promoting alternative splicing of GR pre-mRNA to generate GRβ in EAE rats. Compared with low-dose MP, SHD MP does not improve efficacy or induce GC resistance.