bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep/Wake Firing Patterns of Human Genioglossus Motor Units
Authors: Bailey E. Fiona , Fridel Keith W. , Rice Amber D.
Published: October 2007

Although studies of the principal tongue protrudor muscle genioglossus (GG) suggest that whole muscle GG electromyographic (EMG) activities are preserved in nonrapid eye movement (NREM) sleep, it is unclear what influence sleep exerts on individual GG motor unit (MU) activities. We characterized the firing patterns of human GG MUs in wakefulness and NREM sleep with the aim of determining 1) whether the range of MU discharge patterns evident in wakefulness is preserved in sleep and 2) what effect the removal of the “wakefulness” input has on the magnitude of the respiratory modulation of MU activities. Microelectrodes inserted into the extrinsic tongue protrudor muscle, the genioglossus, were used to follow the discharge of single MUs. We categorized MU activities on the basis of the temporal relationship between the spike train and the respiration cycle and quantified the magnitude of the respiratory modulation of each MU using the eta (η2) index, in wakefulness and sleep. The majority of MUs exhibited subtle increases or decreases in respiratory modulation but were otherwise unaffected by NREM sleep. In contrast, 30% of MUs exhibited marked sleep-associated changes in discharge frequency and respiratory modulation. We suggest that GG MUs should not be considered exclusively tonic or phasic; rather, the discharge pattern appears to be a flexible feature of GG activities in healthy young adults. Whether such flexibility is important in the response to changes in the chemical and/or mechanical environment and whether it is preserved as a function of aging or in individuals with obstructive sleep apnea are critical questions for future research.
Optical Polarizability of Zigzag Single-Walled Carbon Nanotubes Fullerene-Capped at One End and Covalently Bonded with Benzene Rings at the Other End
Authors: Ogloblya O. V. , Hui D. , Strzhemechny Y. M. , Prylutskyy Yu. I.
Published: October 2007

We report on the results of numerical simulations for the linear optical polarizability of single-walled zigzag (9,0) carbon nanotubes with modified ends. The nanotubes of a variable length are fullerene-capped at one end and covalently bonded to a hydrophobic cluster of nine benzene rings at the other end. We investigate electronic and optical properties of such structures within a framework of the Su-Schrieffer-Heeger model. We demonstrated that the localized states in this system exhibit nonlinear characteristics of excited states. The nanotubes have a strongly oscillating dependence of their optical polarizability on the energy of incident light. Spectral features of the optical polarizability drop in intensity and shift towards higher energies with a decrease in the length of a nanotube or upon fullerene-uncapping. The length dependence is similar for the nanotubes without benzene rings, capped either at one or both ends. Potential applications are suggested for hydrophobic pollutant control in liquid-purification systems.
Surface Adsorption and Replacement of Acid-Oxidized Single-Walled Carbon Nanotubes and Poly(vinyl pyrrolidone) Chains
Authors: Chen Wei , Li Xiaojun , Dai Liming
Published: October 2007

Quartz crystal microbalance (QCM) was used to investigate the adsorption of acid-oxidized single-walled carbon nanotubes (Ox-SWNTs) and poly(vinyl pyrrolidone), PVP. It was found for the first time that Ox-SWNTs adsorbed onto the QCM electrode can be effectively replaced by PVP chains in an aqueous solution. This replacement process was also investigated by atomic force miscroscopic (AFM) imaging, which shows good agreement with the QCM measurements. This study provides powerful tools for fundamental investigation of polymer-nanotube interactions and for controlled design/fabrication of functional polymer-nanotube surfaces for potential applications.
Pricing Exotic Options under a High-Order Markovian Regime Switching Model
Authors: Ching Wai-Ki , Siu Tak-Kuen , Li Li-Min
Published: October 2007

We consider the pricing of exotic options when the price dynamics of the underlying
risky asset are governed
by a discrete-time Markovian regime-switching process driven by an observable, high-order
Markov model (HOMM). We assume that the market interest rate, the drift, and the volatility
of the underlying risky asset's return switch over time according to the states of the
HOMM, which are interpreted as the states of an economy. We will then employ the well-known
tool in actuarial science, namely, the Esscher transform to determine an equivalent martingale
measure for option valuation. Moreover, we will also investigate the impact of the high-order
effect of the states of the economy on the prices of some path-dependent exotic options, such
as Asian options, lookback options, and barrier options.
Antimicrobial Activity Does Not Predict Cytokine Response to Adrenomedullin or Its Shortened Derivatives
Authors: Hussain Quratul Ann , Sheehan Barry E. , McKay Ian J. , Allaker Robert P.
Published: October 2007

The aim of this study was to investigate cytokine release from oral keratinocytes and fibroblasts in response to AM and shortened derivatives previously characterised in terms of their antimicrobial activities. Cells were incubated with AM or its fragments (residues 1-12, 1-21, 13-52, 16-21, 16-52, 22-52, 26-52, and 34-52), and culture supernatants collected after 1, 2, 4, 8, and 24 hours. A time-dependant increase in production of interleukin1-αand interleukin 1-βfrom keratinocytes in response to all peptides was demonstrated. However, exposure to fragments compared to whole AM resulted in reduced production of these cytokines (60% mean reduction at 24 hours,P<.001). No consistent differences were shown between the cytokine response elicited by antimicrobial and nonantimicrobial fragments. The production of interleukin-6 and interleukin-8 did not change significantly with time or peptide used. Fibroblast cells were relatively unresponsive to all treatments. This study demonstrates that antimicrobial activity does not predict cytokine response to adrenomedullin or its shortened derivatives.
Simple Orbit Determination Using GPS Based on a Least-Squares Algorithm Employing Sequential Givens Rotations
Authors: de Moraes Rodolpho Vilhena , da Silva Aurea Aparecida , Kuga Helio Koiti
Published: October 2007

A low-cost computer procedure to determine the orbit of an artificial satellite by using short arc data from an onboard GPS receiver is proposed. Pseudoranges are used as measurements to estimate the orbit via recursive least squares method. The algorithm applies orthogonal Givens rotations for solving recursive and sequential orbit determination problems. To assess the procedure, it was applied to the TOPEX/POSEIDON satellite for data batches of one orbital period (approximately two hours), and force modelling, due to the full JGM-2 gravity field model, was considered. When compared with the reference Precision Orbit Ephemeris (POE) of JPL/NASA, the results have indicated that precision better than 9 m is easily obtained, even when short batches of data are used.
On Classical Quotient Rings of Skew Armendariz Rings
Authors: Nasr-Isfahani A. R. , Moussavi A.
Published: October 2007

LetRbe a ring,αan automorphism, andδanα-derivation ofR. If the classical quotient ringQofRexists, thenRis weakα-skew Armendariz if and only ifQis weakα˜-skew Armendariz.
Recovery of Time-Dependent Parameters of a Black-Scholes-Type Equation: An Inverse Stieltjes Moment Approach
Authors: Rodrigo Marianito R. , Mamon Rogemar S.
Published: October 2007

We show that the problem of recovering the time-dependent parameters of an equation of Black-Scholes type can be formulated as an inverse Stieltjes moment problem. An application to the problem of implied volatility calculation in the case when the model parameters are time varying is provided and results of numerical simulations are presented.
Analysis of an SIR Epidemic Model with Pulse Vaccination and Distributed Time Delay
Authors: Gao Shujing , Teng Zhidong , Nieto Juan J. , Torres Angela
Published: October 2007

Pulse vaccination, the repeated application of vaccine over a defined age range, is gaining prominence as an effective strategy for the elimination of infectious diseases. An SIR epidemic model with pulse vaccination and distributed time delay is proposed in this paper. Using the discrete dynamical system determined by the stroboscopic map, we obtain the exact infection-free periodic solution of the impulsive epidemic system and prove that the infection-free periodic solution is globally attractive if the vaccination rate is larger enough. Moreover, we show that the disease is uniformly persistent if the vaccination rate is less than some critical value. The permanence of the model is investigated analytically. Our results indicate that a large pulse vaccination rate is sufficient for the eradication of the disease.
Monotonicity of a Key Function Arised in Studies of Nematic Liquid Crystal Polymers
Authors: Wang Hongyun , Zhou Hong
Published: October 2007

We revisit a key function arised in studies of nematic liquid crystal polymers. Previously, it was conjectured that the function is strictly decreasing and the conjecture was numerically confirmed. Here we prove the conjecture analytically. More specifically, we write the derivative of the function into two parts and prove that each part is strictly negative.
Towards Development of a 3-State Self-Paced Brain-Computer Interface
Authors: Bashashati Ali , Ward Rabab K. , Birch Gary E.
Published: October 2007

Most existing brain-computer interfaces (BCIs) detect specific mental activity in a so-called synchronous paradigm. Unlike synchronous systems which are operational at specific system-defined periods, self-paced (asynchronous) interfaces have the advantage of being operational at all times. The low-frequency asynchronous switch design (LF-ASD) is a 2-state self-paced BCI that detects the presence of a specific finger movement in the ongoing EEG. Recent evaluations of the 2-state LF-ASD show an average true positive rate of 41% at the fixed false positive rate of 1%. This paper proposes two designs for a 3-state self-paced BCI that is capable of handling idle brain state. The two proposed designs aim at detecting right- and left-hand extensions from the ongoing EEG. They are formed of two consecutive detectors. The first detects the presence of a right- or a left-hand movement and the second classifies the detected movement as a right or a left one. In an offline analysis of the EEG data collected from four able-bodied individuals, the 3-state brain-computer interface shows a comparable performance with a 2-state system and significant performance improvement if used as a 2-state BCI, that is, in detecting the presence of a right- or a left-hand movement (regardless of the type of movement). It has an average true positive rate of 37.5% and 42.8% (at false positives rate of 1%) in detecting right- and left-hand extensions, respectively, in the context of a 3-state self-paced BCI and average detection rate of 58.1% (at false positive rate of 1%) in the context of a 2-state self-paced BCI.
Some New Bounds for Mathieu's Series
Authors: Hoorfar Abdolhossein , Qi Feng
Published: October 2007

Two upper and lower bounds for Mathieu's series are established, which refine to a certain extent a sharp double inequality obtained by Alzer-Brenner-Ruehr in 1998. Moreover, the very closer lower and upper bounds forζ(3)are deduced.
Blood Markers for Early Detection of Colorectal Cancer: A Systematic Review
Authors: Hundt Sabrina , Haug Ulrike , Brenner Hermann
Published: October 2007

Background: Despite different available methods for colorectal cancer (CRC) screening and their proven benefits, morbidity, and mortality of this malignancy are still high, partly due to low compliance with screening. Minimally invasive tests based on the analysis of blood specimens may overcome this problem. The purpose of this review was to give an overview of published studies on blood markers aimed at the early detection of CRC and to summarize their performance characteristics.

Method: The PUBMED database was searched for relevant studies published until June 2006. Only studies with more than 20 cases and more than 20 controls were included. Information on the markers under study, on the underlying study populations, and on performance characteristics was extracted. Special attention was given to performance characteristics by tumor stage.

Results: Overall, 93 studies evaluating 70 different markers were included. Most studies were done on protein markers, but DNA markers and RNA markers were also investigated. Performance characteristics varied widely between different markers, but also between different studies using the same marker. Promising results were reported for some novel assays, e.g., assays based on SELDI-TOF MS or MALDI-TOF MS, for some proteins (e.g., soluble CD26 and bone sialoprotein) and also for some genetic assays (e.g., L6 mRNA), but evidence thus far is restricted to single studies with limited sample size and without further external validation.

Conclusions: Larger prospective studies using study populations representing a screening population are needed to verify promising results. In addition, future studies should pay increased attention to the potential of detecting precursor lesions. (Cancer Epidemiol Biomarkers Prev 2007;16(10):1935–53)
Erythropoietin and Its Receptor in Breast Cancer: Correlation with Steroid Receptors and Outcome
Authors: Pelekanou Vassiliki , Kampa Marilena , Kafousi Maria , Dambaki Konstantina , Darivianaki Katerina , Vrekoussis Thomas , Sanidas Elias , Tsiftsis Dimitrios D. , Stathopoulos Efstathios N. , Castanas Elias
Published: October 2007

Autocrine/paracrine erythropoietin (EPO) action, promoting cell survival and mediated by its receptor (EPOR) in various solid tumors, including breast carcinoma, questions about the prognostic and therapeutic interest of this system. The expression of EPO/EPOR is steroid dependent in some tissues; however, a clear relationship of EPO/EPOR and steroid receptors in breast cancer has not been established thus far. Recently, the field of steroid receptors has expanded, including rapid effects mediated by membrane-associated receptors, regulating cell survival or apoptosis. The aim of this study was to evaluate EPO/EPOR and membrane-associated steroid receptor expression in breast carcinoma, in view of their prognostic significance, compared with other established markers [estrogen receptor (ER)-progesterone receptor (PR) status and Her2 expression] and hypoxia-induced factor 1 nuclear localization in 61 breast cancer specimens followed for ≤90 months. We report that EPO-EPOR were expressed in 80% and 84% of samples, although 8% and 2% of nontumoral fields expressed EPO/EPOR too. Membrane-associated receptors for estrogen (mER), progesterone (mPR), and androgen (mAR) were expressed in 96%, 94%, and 93% of cases. Significant correlations between EPO-hypoxia-induced factor 1α, mER-ER, mER-EPO, mAR-EPOR, and mER-mPR-Her2 were found. Finally, EPO, EPOR, and mAR are inversely related to disease-free and overall survival. However, in view of the above correlations, we conclude that EPO/EPOR and membrane steroid receptors are not independent prognostic markers as they are closely related to other established markers. In contrast, they may represent possible new therapeutic targets. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2016–23)
Endogenous Optical Biomarkers of Ovarian Cancer Evaluated with Multiphoton Microscopy
Authors: Kirkpatrick Nathaniel D. , Brewer Molly A. , Utzinger Urs
Published: October 2007

Purpose: Among gynecologic cancers, ovarian cancer is the second most common and has the highest mortality. Currently, there is no accurate early diagnostic technique for ovarian cancer. Furthermore, little is understood regarding the early progression of this disease. We have imaged multiphoton interactions of endogenous tissue constituents from normal and abnormal ovarian biopsies that were kept viable during transport from the operating room and microscopy.

Experimental Design: The ovarian surface and underlying stroma were assessed with two-photon excited fluorescence (2PEF) and second harmonic generation (SHG). High-resolution, optically sectioned images were analyzed for epithelial morphology based on 2PEF and collagen density and structural integrity based on SHG. Additionally, multiwavelength 2PEF provided an estimation of the cellular redox ratio of epithelial cells.

Results: Normal tissue exhibited a uniform epithelial layer with highly structured collagen in the stroma, whereas abnormal tissue exhibited varied epithelium with large cells and substantial quantitative changes to the collagen structure. Samples from patients at high risk for developing ovarian cancer (based on their personal/family history of cancer) exhibited highly variable cellular redox ratios and changes in collagen structure that trended toward cancer samples.

Conclusion: This study highlights differences in endogenous signals in viable ovarian biopsies based on quantitative collagen structural changes and redox ratio estimates that may lead to improved detection and further insights in ovarian cancer, particularly in the early stages of the disease. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2048–55)
Association of Physical Activity with Reproductive Hormones: The Penn Ovarian Aging Study
Authors: Schmitz Kathryn H. , Lin Hui , Sammel Mary D. , Gracia Clarissa R. , Nelson Deborah B. , Kapoor Shiv , DeBlasis Tracey L. , Freeman Ellen W.
Published: October 2007

Background: Physical activity is associated with reduced risk for breast cancer, perhaps through reductions in circulating reproductive hormones (estrogens and androgens). There may also be a role for physical activity in regulating menopausal symptoms. Few studies have examined associations of physical activity on hormone levels. None have examined the potential effect of the menopausal transition on the associations between physical activity and reproductive hormone levels.

Materials and Methods: Data from the Penn Ovarian Aging Study were used for this analysis. Self-reported physical activity was assessed in 391 women up to four times over 10 years and extending across the menopausal transition. Other assessments included reproductive hormones via RIA (estradiol, luteinizing hormone, follicle-stimulating hormone, testosterone, DHEA sulfate), body weight, and height. Multivariate repeated measures regression models were developed to compare reproductive hormone levels within physical activity tertiles, adjusting for age, follow-up time, smoking, and ethnicity.

Results: Activity level was inversely associated with estradiol in the subgroup in the late transition stage. Adjusted means for estradiol were 24.6 and 37.9, a relative difference of 54% in estradiol when comparing highest to lowest activity tertile (P = 0.02). Similarly, in this subgroup, there was an inverse association between physical activity and testosterone levels (means of 11.1 and 15.94 in the highest and lowest tertile, a 47% relative difference; P = 0.01). There were no significant associations of activity with any other reproductive hormone.

Conclusions: These results identify a particular window of the menopausal transition during which physical activity is associated with reduced estradiol and/or testosterone levels. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2042–7)
Polymorphisms in Nucleotide Excision Repair Genes, Polycyclic Aromatic Hydrocarbon-DNA Adducts, and Breast Cancer Risk
Authors: Crew Katherine D. , Gammon Marilie D. , Terry Mary Beth , Zhang Fang Fang , Zablotska Lydia B. , Agrawal Meenakshi , Shen Jing , Long Chang-Min , Eng Sybil M. , Sagiv Sharon K. , Teitelbaum Susan L. , Neugut Alfred I. , Santella Regina M.
Published: October 2007

Genes involved in the nucleotide excision repair (NER) pathway, which removes bulky DNA adducts, are potential low-penetrance cancer susceptibility genes. We recently reported an association between detectable polycyclic aromatic hydrocarbon (PAH)-DNA adducts and breast cancer risk. Using a population-based breast cancer case-control study on Long Island, New York, we examined whether polymorphisms in NER genes modified the association between PAH-DNA adducts and breast cancer risk. We examined polymorphisms in ERCC1 (3′-untranslated region 8092C/A), XPA (5′-untranslated region −4G/A), XPD (Asp312Asn in exon 10), XPF (Arg415Gln in exon 8), and XPG (Asp1104His in exon 15) in 1,053 breast cancer cases and 1,102 population-based controls. The presence of at least one variant allele in XPD was associated with a 25% increase in the odds ratio [OR, 1.25; 95% confidence interval (95% CI), 1.04-1.50] for breast cancer. The increase associated with homozygosity of the variant alleles for XPD and ERCC1 was stronger among those with detectable PAH-DNA adduct levels (OR, 1.83; 95% CI, 1.22-2.76 and OR, 1.92; 95% CI, 1.14-3.25 for detectable versus nondetectable adducts and homozygous wild-type genotype for XPD and ERCC1, respectively). We found no association between XPA, XPF, and XPG genotypes, PAH-DNA adducts, and breast cancer risk. When we combined genotypes for these NER pathway genes, there was a significant trend for increasing breast cancer risk with increasing number of putative high-risk alleles. Overall, this study suggests that the risk of breast cancer may be elevated among women with polymorphisms in NER pathway genes and detectable PAH-DNA adducts. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2033–41)
Breast Cancer Risk Is Associated with the Genes Encoding the DNA Double-Strand Break Repair Mre11/Rad50/Nbs1 Complex
Authors: Hsu Huan-Ming , Wang Hui-Chun , Chen Sou-Tong , Hsu Giu-Cheng , Shen Chen-Yang , Yu Jyh-Cherng
Published: October 2007

The evolutionarily conserved Mre11-Rad50-Nbs1 (MRN) complex, consisting of proteins encoded by the genes Mre11, Rad50, and Nbs1, was recently shown to play a crucial role in DNA double-strand break (DSB) repair by recruiting the nuclear protein kinase ataxia telangiectasia mutated to DSB sites, leading to activation of this DNA repair network. Given the fact that carriers of defective mutation and polymorphic variants of ataxia telangiectasia mutated are at higher risk of developing breast cancer, we hypothesized a role of the MRN genes in determining breast cancer susceptibility. This hypothesis was examined both in a case control study of 559 breast cancer patients and 1,125 healthy women of single-nucleotide polymorphisms in Mre11, Rad50, and Nbs1 and by the in vivo detection of binding between Mre11 and BRCA1, encoded by the breast cancer susceptibility gene BRCA1. We were also interested in defining whether any association between MRN genes and breast cancer was modified by reproductive risk factors reflecting the level of estrogen exposure or susceptibility to estrogen exposure, as estrogen is known to initiate breast cancer development due to its metabolites causing DSB formation. Support for the hypothesis came from the observations that (a) one single-nucleotide polymorphism in Nbs1 was significantly associated with breast cancer risk, and a trend toward an increased risk of developing breast cancer was found in women harboring a greater number of putative high-risk genotypes of MRN genes (an adjusted odds ratio of 1.25 for each additional putative high-risk genotype; 95% confidence interval, 1.10-1.44); (b) this association between risk and the number of putative high-risk genotypes was stronger and more significant in women thought to be more susceptible to estrogen, i.e., those with no history of full-term pregnancy, those older (≥26 years of age) at first full-term pregnancy, or those having had fewer (<2) full-term pregnancies; the risk effect conferred by harboring a higher number of high-risk genotypes of MRN genes was more significant in women without a history of breast feeding; and (c) Mre11 and BRCA1 were shown to form a complex in vivo, and this interaction was increased by irradiation. This study supports the role of the MRN pathway in breast cancer development, further strengthening the suggestion that mechanisms regulating DSB repair may play a mutator role driving breast cancer pathogenesis. (Cancer Epidemiol Biomarkers Prev 2007;6(10):2024–32)
Data Sources for Measuring Colorectal Endoscopy Use Among Medicare Enrollees
Authors: Schenck Anna P. , Klabunde Carrie N. , Warren Joan L. , Peacock Sharon , Davis William W. , Hawley Sarah T. , Pignone Michael , Ransohoff David F.
Published: October 2007

Background: Estimates of colorectal cancer test use vary widely by data source. Medicare claims offer one source for monitoring test use, but their utility has not been validated. We compared ascertainment of sigmoidoscopy and colonoscopy between three data sources: self reports, Medicare claims, and medical records.

Materials and Methods: The study population included Medicare enrollees residing in North Carolina (n = 561) who had participated in a telephone survey on colorectal cancer tests. Medicare claims were obtained for the 5 years preceding the survey (January 1, 1998 to December 31, 2002). Information about sigmoidoscopy and colonoscopy procedures conducted in physician offices were abstracted from medical records. Sensitivity, specificity, positive predictive value, negative predictive value, agreement, and κ statistics were calculated using the medical record as the gold standard. Agreement on specific procedure type and purpose was also assessed.

Results: Agreement between claim and medical record regarding whether an endoscopic procedure had been done was high (over 90%). Agreement between self report and medical record and between self report and claim was good (79% and 74%, respectively). All three data sources adequately distinguished the type of procedure done. None of the data sources showed reliable levels of agreement regarding procedure purpose (screening or diagnostic).

Conclusion: Medicare claims can provide accurate information on whether a patient has undergone colorectal endoscopy and may be more complete than physician medical records. Medicare claims cannot be used to distinguish screening from diagnostic tests. Recognizing this limitation, researchers who use Medicare claims to assess rates of colorectal testing should include both screening and diagnostic endoscopy procedures in their analyses. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2118–27)
Low-Fat, Low-Glycemic Load Diet and Gene Expression in Human Prostate Epithelium: A Feasibility Study of Using cDNA Microarrays to Assess the Response to Dietary Intervention in Target Tissues
Authors: Lin Daniel W. , Neuhouser Marian L. , Schenk Jeannette M. , Coleman Ilsa M. , Hawley Sarah , Gifford David , Hung Hau , Knudsen Beatrice S. , Nelson Peter S. , Kristal Alan R.
Published: October 2007

Purpose: We examined the feasibility of using gene expression changes in human prostate epithelium as a measure of response to a dietary intervention.

Materials and Methods: Eight men with newly diagnosed prostate cancer were randomized to a low-fat/low-glycemic load intervention arm (<20% energy from fat and total daily glycemic load <100) or a “standard American” control arm (≈35% energy from fat and total daily glycemic load >200). Prostate tissue was collected before randomization and ∼6 weeks later, at the time of radical prostatectomy. Epithelium was acquired by laser capture microdissection, and transcript abundance levels were measured by cDNA microarray hybridization and confirmed by quantitative reverse transcription-PCR.

Results: Men in the intervention arm consumed 39% less total energy (P = 0.004) and the difference in weight change between intervention and control arms was −6.1 kg (P = 0.02). In the intervention arm, 23 (0.46%) of 5,711 cDNAs with measurable expression were significantly altered (P < 0.05; false discovery rate, ≤10%). In the control arm, there were no significant changes in transcript expression, even when using a false discovery rate as high as 50%.

Conclusions: A 6-week, low-fat/low-glycemic load diet was associated with significant gene expression changes in human prostate epithelium. These results show the feasibility of using prostate tissues collected at diagnosis and at surgery to study the effects of dietary manipulation on prostate tissue, which may give insight into the molecular mechanisms underlying the associations of diet and obesity with the development or progression of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2150–4)
Prediagnostic Plasma C-Peptide and Pancreatic Cancer Risk in Men and Women
Authors: Michaud Dominique S. , Wolpin Brian , Giovannucci Ed , Liu Simin , Cochrane Barbara , Manson JoAnn E. , Pollak Michael N. , Ma Jing , Fuchs Charles S.
Published: October 2007

Background: Hyperinsulinemia and insulin resistance have been proposed as underlying mechanisms for the increase in pancreatic cancer among long-standing diabetics and obese individuals. An association between serum insulin levels and pancreatic cancer risk was reported in a recent study, but the population was composed of heavy smokers and their findings may not be generalizable to nonsmokers.

Methods: Pancreatic cancer cases and matched controls were obtained from four large-scale prospective cohorts to examine the association between prediagnostic plasma levels of C-peptide and insulin and pancreatic cancer. One hundred ninety-seven pancreatic cancer cases were diagnosed during a maximum of 20 years of follow-up, after excluding cases diagnosed within 2 years of blood collection or with baseline diabetes. We estimated OR and confidence intervals (CI) using conditional logistic regression with adjustment for pancreatic cancer risk factors.

Results: Prediagnostic plasma C-peptide was positively associated with pancreatic cancer risk (OR, 1.52; 95% CI, 0.87-2.64, highest compared with the lowest quartile, Ptrend = 0.005). The association was not modified by body mass index or physical activity but seemed to be slightly stronger among never smokers than ever smokers. Fasting C-peptide and insulin were not related to pancreatic cancer; however, we observed a strong linear association for nonfasting C-peptide and pancreatic cancer (OR, 4.24; 95% CI, 1.30-13.8, highest versus lowest quartile, Ptrend < 0.001).

Conclusions: Based on our finding of a strong positive association with nonfasting C-peptide levels, we propose that insulin levels in the postprandial state may be the relevant exposure for pancreatic carcinogenesis; however, other studies will need to examine this possibility. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2101–9)
Bulky DNA Adduct Formation and Risk of Bladder Cancer
Authors: Castaño-Vinyals Gemma , Talaska Glenn , Rothman Nathaniel , Alguacil Juan , Garcia-Closas Montserrat , Dosemeci Mustafa , Cantor Kenneth P. , Malats Núria , Real Francisco X. , Silverman Debra , Serra Consol , Carrato Alfredo , Tardon Adonina , Garcia-Closas Reina , Kogevinas Manolis , Vermeulen Roel
Published: October 2007

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with risk of bladder cancer and with increased bulky DNA adduct levels in several studies, mainly in smokers. We investigated the relation between bulky PAH-DNA adducts in peripheral blood mononuclear cells and bladder cancer in nonsmoking subjects from a large hospital-based case-control study in Spain. Additionally, we examined the association between DNA adduct formation and several air pollution proxies. The study comprised 76 nonsmoking cases and 76 individually matched controls by sex, region of residence, age, and smoking status (never, former). To maximize the relevance of the DNA adduct measurement as a proxy of PAH exposure, subjects selected had not changed residence, occupation, and major lifestyle factors during the last 10 years. Bulky DNA adducts were measured using the 32P-postlabeling technique, nuclease P1 treatment. The percentage of detectable adducts was higher in controls (41%) than in cases (32%) with an odds ratio of 0.75 (95% confidence interval, 0.36-1.58). In an analysis limited to controls, a higher percentage of DNA adducts was found among those whose last residence was in a big city (50%) compared with those living in villages (19%; P = 0.04). No consistent associations were found for other markers of air pollution. In this study, among nonsmokers with stable environmental and lifestyle factors, bulky DNA adducts were not associated with bladder cancer risk. Results do not support an association of bladder cancer risk with low-level exposure to PAHs as measured through the formation of bulky DNA adducts in peripheral mononuclear cells. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2155–9)
Responses of Biomarkers of Folate and Riboflavin Status to Folate and Riboflavin Supplementation in Healthy and Colorectal Polyp Patients (The FAB2 Study)
Authors: Powers Hilary J. , Hill Marilyn H. , Welfare Mark , Spiers Alison , Bal Wendy , Russell Jean , Duckworth Yvonne , Gibney Eileen , Williams Elizabeth A. , Mathers John C.
Published: October 2007

Epidemiologic data suggest that increasing folate intake may protect against colorectal cancer. Riboflavin may interact with folate to modulate the effect. A double-blind randomized placebo-controlled intervention study (the FAB2 Study) was carried out in healthy controls and patients with colorectal polyps (adenomatous and hyperplastic) to examine effects of folic acid and riboflavin supplements on biomarkers of nutrient status and on putative biomarkers of colorectal cancer risk (DNA methylation and DNA damage; to be reported elsewhere). Ninety-eight healthy controls and 106 patients with colorectal polyps were stratified for the thermolabile variant of methylene tetrahydrofolate reductase, MTHFR C677T, and were randomized to receive 400 μg of folic acid, 1,200 μg of folic acid, or 400 μg of folic acid plus 5 mg of riboflavin or placebo for 6 to 8 weeks. Blood samples and colon biopsy samples were collected for the measurement of biomarkers of folate and riboflavin status. Supplementation with folic acid elicited a significant increase in mucosal 5-methyl tetrahydrofolate, and a marked increase in RBC and plasma, with a dose-response. Measures of riboflavin status improved in response to riboflavin supplementation. Riboflavin supplement enhanced the response to low-dose folate in people carrying at least one T allele and having polyps. The magnitude of the response in mucosal folate was positively related to the increase in plasma 5-methyl tetrahydrofolate but was not different between the healthy group and polyp patients. Colorectal mucosal folate concentration responds to folic acid supplementation to an extent comparable to that seen in plasma, but with a suggestion of an upper limit. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2128–35)
Relationship between Age Maximum Height Is Attained, Age at Menarche, and Age at First Full-Term Birth and Breast Cancer Risk
Authors: Li Christopher I. , Littman Alyson J. , White Emily
Published: October 2007

Several pubertal and reproductive events are well established risk factors for breast cancer. Age maximum height attained is an understudied potential breast cancer risk factor that may affect risk through mechanisms different from those of other pubertal and reproductive events. We assessed the relationships between different pubertal/reproductive events and risk of different types of breast cancer in a prospective cohort of 27,536 women. Women were recruited between 2000 and 2002 and completed a mailed questionnaire. As of 2005, 585 women were diagnosed with breast cancer. Using a Cox proportional hazards model, women who reached their maximum height at ≤12 years of age had a 1.4-fold [95% confidence interval (95% CI), 1.0-1.8] increased risk of breast cancer compared with women who reached their maximum height at ≥17 years of age (Ptrend = 0.04). This association was primarily limited to more aggressive tumors, specifically those that were estrogen receptor–negative (hazard ratio, 1.9; 95% CI, 1.0-3.9) and diagnosed at a regional or distant stage (hazard ratio, 1.8; 95% CI, 1.0-3.1). There was no difference in the relation of age at menarche with breast cancer by tumor stage, whereas late age at first full-term pregnancy primarily increased risks of less-aggressive disease, including lobular, estrogen receptor–positive, and localized stage tumors. Age at maximum height seems to be an independent risk factor for breast cancer that is more strongly associated with relatively aggressive tumors that have a poorer prognosis compared with the types of tumors that are associated with ages at menarche and first full-term birth. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2144–9)
Polymorphisms in Apoptosis- and Proliferation-Related Genes, Ionizing Radiation Exposure, and Risk of Breast Cancer among U.S. Radiologic Technologists
Authors: Sigurdson Alice J. , Bhatti Parveen , Doody Michele M. , Hauptmann Michael , Bowen Laura , Simon Steven L. , Weinstock Robert M. , Linet Martha S. , Rosenstein Marvin , Stovall Marilyn , Alexander Bruce H. , Preston Dale L. , Struewing Jeffrey P. , Rajaraman Preetha
Published: October 2007

Background: Although genes involved in apoptosis pathways and DNA repair pathways are both essential for maintaining genomic integrity, genetic variants in DNA repair have been thought to increase susceptibility to radiation carcinogenesis, but similar hypotheses have not generally been raised about apoptosis genes. For this reason, potential modification of the relationship between ionizing radiation exposure and breast cancer risk by polymorphic apoptosis gene variants have not been investigated among radiation-exposed women.

Methods: In a case-control study of 859 cases and 1,083 controls within the U.S. Radiologic Technologists cohort, we assessed breast cancer risk with respect to 16 candidate variants in eight genes involved in apoptosis, inflammation, and proliferation. Using carefully reconstructed cumulative breast dose estimates from occupational and personal diagnostic ionizing radiation, we also investigated the joint effects of these polymorphisms on the risk of breast cancer.

Results: In multivariate analyses, we observed a significantly decreased risk of breast cancer associated with the homozygous minor allele of CASP8 D302H [rs1045485, odds ratio (OR), 0.3; 95% confidence interval (95% CI), 0.1-0.8]. We found a significantly increased breast cancer risk with increasing minor alleles for IL1A A114S (rs17561); heterozygote OR 1.2 (95% CI, 1.0-1.4) and homozygote OR 1.5 (95% CI, 1.1-2.0), Ptrend = 0.008. Assuming a dominant genetic model, IL1A A114S significantly modified the dose-response relationship between cumulative personal diagnostic radiation and breast cancer risk, adjusted for occupational dose (Pinteraction = 0.004).

Conclusion: The U.S. Radiologic Technologists breast cancer study provided a unique opportunity to examine the joint effects of common genetic variation and ionizing radiation exposure to the breast using detailed occupational and personal diagnostic dose data. We found evidence of effect modification of the radiation and breast cancer dose-response relationship that should be confirmed in studies with more cases and controls and quantified radiation breast doses in the low-to-moderate range. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2000–7)
Assessment of 54 Biomarkers for Biopsy-Detectable Prostate Cancer
Authors: Parekh Dipen J. , Ankerst Donna Pauler , Baillargeon Jacques , Higgins Betsy , Platz Elizabeth A. , Troyer Dean , Hernandez Javier , Leach Robin J. , Lokshin Anna , Thompson Ian M.
Published: October 2007

Objective: We analyzed the association of 54 biomarkers from seven classes including adipokines, immune response metalloproteinases, adhesion molecules, and growth factors with prostate cancer risk adjusting for the Prostate Cancer Prevention Trial (PCPT) risk score.

Methods: A total of 123 incident prostate cancer cases and 127 age-matched controls were selected from subjects in the San Antonio Center for Biomarkers of Risk of Prostate Cancer cohort study. Prediagnostic serum concentrations were measured in the sample collected at baseline using LabMAP technology. The odds ratios (OR) of prostate cancer risk associated with serum concentrations of 54 markers were estimated using univariate conditional logistic regression before and after adjustment for the PCPT risk score. Two-way hierarchical unsupervised clustering techniques were used to evaluate whether the 54-marker panel distinguished cases from controls.

Results: Vascular endothelial growth factor, resistin, interleukin 1Ra (IL-1Ra), granulocyte colony-stimulating factor, matrix metalloproteinase-3, plasminogen activator inhibitor, and kallikrein-8 were statistically significantly (P < 0.05) underexpressed in prostate cancer cases, and α-fetoprotein was statistically significantly overexpressed in prostate cancer cases, but all had area underneath the receiver-operating characteristic curve <60%; none were statistically significant adjusting for multiple comparisons (P < 0.0008) or after adjustment for the PCPT risk score. Statistical clustering of patients by the marker panel did not distinguish a separate group of cases from controls.

Conclusions: This age-matched case-control study did not support findings of increased diagnostic potential from a 54-marker panel when compared with the conventional risk factors incorporated in the PCPT risk calculator. Future discovery of new biomarkers should always be tested and compared against conventional risk factors before applying them in clinical practice. (Cancer Epidemiol Biomarkers Prev 2007;16(10):1966–72)
Association between Toll-Like Receptor Gene Cluster (TLR6, TLR1, and TLR10) and Prostate Cancer
Authors: Chen Yen-Ching , Giovannucci Edward , Kraft Peter , Lazarus Ross , Hunter David J.
Published: October 2007

Background: Chronic inflammation may be a risk factor for prostate cancer. Previously, we found significant associations between single nucleotide polymorphisms (SNPs) and haplotypes in Toll-like receptor (TLR) 4 and the risk of prostate cancer. TLR6, TLR1, and TLR10 are also involved in the pathogen-mediated inflammation pathway. A Swedish study observed associations between sequence variants in the TLR6-TLR1-TLR10 gene cluster and the risk of prostate cancer. We assessed if genetic polymorphisms of this gene cluster were associated with the risk of prostate cancer in a U.S. population.

Methods: In a nested case-control design within the Health Professionals Follow-Up Study, we identified 700 participants with prostate cancer who were diagnosed after they had provided a blood specimen in 1993 and by January 31, 2000. Controls were 700 age-matched men without prostate cancer who had had a prostate-specific antigen test. We genotyped 19 common (>5%) haplotype-tagging SNPs chosen from the SNPs discovered in a resequencing study spanning TLR6, TLR1, and TLR10 to test for the association between sequence variants cluster and prostate cancer.

Results: Neither individual SNPs nor common haplotypes in the three gene regions were associated with altered risk of prostate cancer or subgroups of aggressive prostate cancer. No effect modification was observed for age, body mass index, or family history of prostate cancer, except that TLR6_3649 showed nominally significant interaction with family history at the P < 0.05 level.

Conclusion: Inherited sequence variants of the innate immune gene cluster TLR6-TLR1-TLR10 were not appreciably associated with the risk of prostate cancer in this cohort. (Cancer Epidemiol Biomarkers Prev 2007;16(10):1982–9)
Plasma and Dietary Carotenoids Are Associated with Reduced Oxidative Stress in Women Previously Treated for Breast Cancer
Authors: Thomson Cynthia A. , Stendell-Hollis Nicole R. , Rock Cheryl L. , Cussler Ellen C. , Flatt Shirley W. , Pierce John P.
Published: October 2007

Dietary carotenoids show numerous biological activities, including antioxidant activity, induction of apoptosis, and inhibition of mammary cell proliferation. Studies examining the role of carotenoid consumption in relation to breast cancer recurrence are limited and report mixed results. We tested the hypothesis that breast cancer survivors with high dietary and plasma carotenoids would show significantly lower levels of oxidative stress than breast cancer survivors with low dietary and plasma carotenoid levels. Two hundred seven postmenopausal breast cancer survivors from the Women's Healthy Eating and Living Study volunteered for this ancillary study. Dietary data were analyzed by the Arizona Food Frequency Questionnaire and plasma carotenoids α-carotene, β-carotene, lutein plus zeaxanthin, lycopene, and β-cryptoxanthin and quantified with high-performance liquid chromatography, and immunoaffinity chromatography-monoclonal antibody–based ELISAs were used to analyze the urine samples for 8-hydroxy-2′-deoxyguanosine (8-OhdG) and 8-iso-prostaglandin-F2α (8-iso-PGF2α). The correlations between dietary and plasma carotenoids were 0.34 for β-carotene, 0.46 for α-carotene, 0.39 for β-cryptoxanthin, 0.27 for lycopene, 0.30 for lutein plus zeaxanthin, and 0.30 for total carotenoids. The 8-OHdG oxidative stress biomarker was significantly reduced at the highest quartile of total plasma carotenoid concentrations (P = 0.001) and 8-iso-PGF2α was moderately reduced (P = 0.088). Dietary carotenoid levels were not significantly associated with oxidative, stress indicators, although dietary lycopene and lutein/zeaxanthin were modestly associated with 8-OHdG levels (P = 0.054 and 0.088, respectively). Key findings include a significant inverse association between total plasma carotenoid concentrations and oxidative stress as measured by urinary 8-OHdG and a moderately significant inverse association with 8-iso-PGF2α, a protective association that was not shown for dietary carotenoid intake. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2008–15)
The Use of FoxP3 as a Biomarker and Prognostic Factor for Malignant Human Tumors
Authors: Schreiber Taylor H.
Published: October 2007

Only since the early 21st century has it been proven that the immune system can actively defend the body against the development of malignant tumors. Escape from this process, termed immunosurveillance, has been shown to be required for the development of many tumors in both mice and humans, and may be a necessary prerequisite for the establishment of many malignancies. Serendipitously, an evolution in the understanding and characterization of immunosuppressor cells, regulatory T cells, has coincided with the establishment of tumor immunosurveillance. These two fields merged when it was found that the recruitment of regulatory T cells within tumors was a dominant mechanism tumors used to escape immunosurveillance. Regulatory T cells are specifically identified with antibodies which recognize the transcription factor, FoxP3. The presence of FoxP3+ cells within tumors has been shown to predict the prognosis, invasiveness, and metastatic ability of some tumors by modulating the ability of the immune system to target tumor cells. Furthermore, depletion of regulatory T cells from tumors could lead to the rejection of both early- and late-stage tumors by the host immune system. These findings suggest that the widespread use of FoxP3 as a biomarker should be explored for human tumors to enable physicians to make better decisions in oncologic care and to prepare the field for novel therapeutic agents directed at the elimination of regulatory T cells within tumors. (Cancer Epidemiol Biomarkers Prev 2007;16(10):1931–4)