bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical Absorption Enhancement in Amorphous Silicon Films and Solar Cell Precursors Using the Aluminum-Induced Glass Texturing Method
Authors: Sahraei Nasim , Venkataraj Selvaraj , Vayalakkara Premachandran , Aberle Armin G.
Published: January 2014

One of the key issues of thin-film silicon solar cells is their limited optical absorptance due to the thin absorber layer and the low absorption coefficient for near-infrared wavelengths. Texturing of one or more interfaces in the layered structure of these cells is an important technique to scatter light and enhance the optical pathlength. This in turn enhances the optical absorption of the solar radiation in the absorber layer and improves the solar cell efficiency. In this paper we investigate the effects of textured glass superstrate surfaces on the optical absorptance of intrinsic a-Si:H films and a-Si:Hp-i-nthin-film solar cell precursors deposited onto them. The silicon-facing surface of the glass sheets was textured with the aluminium-induced glass texturing method (AIT method). Absorption in both intrinsic silicon films and solar cell precursor structures is found to increase strongly due to the textured glass superstrate. The increased absorption due to the AIT glass opens up the possibility to reduce the absorber layer thickness of a-Si:H solar cells.
A Hybrid Common Fixed Point Theorem under Certain Recent Properties
Authors: Kadelburg Zoran , Chauhan Sunny , Imdad Mohammad
Published: January 2014

We prove a common fixed point theorem for a hybrid pair of occasionally coincidentally idempotent mappings via common limit range property. Our result improves some results from the existing literature, especially the ones contained in Sintunavarat and Kumam (2009). Some illustrative and interesting examples to highlight the realized improvements are also furnished.
Prevalence of Anti-JC Virus Antibody in Multiple Sclerosis Patients in Kuwait
Authors: Lamdhade S. , Ashkanani A. , Alroughani R.
Published: January 2014

Background. Multiple sclerosis (MS) therapeutics entered a new era after the development of anti-JC virus (anti-JCV) antibody assay that assesses the risk of development of progressive multifocal leukoencephalopathy (PML) in patients treated with natalizumab. Objective. To determine the prevalence of anti-JCV antibody among MS patients in Kuwait. Methods. Using the national MS registry, demographics and disease characteristics of MS patients who were screened for anti-JC virus antibody were collected. The prevalence of anti-JCV antibody seropositivity and its association with demographic and disease characteristics were evaluated. Results. Out of 110 screened MS patients for anti-JCV antibodies, 65.5% were females. Mean age and disease duration were 29.23 ± 8.55 and 5.39 ± 5.04 years, respectively. 47.3% of patients were already on natalizumab and 52.7% of patients were screened for stratification to either natalizumab or a different Disease Modifying Therapy (DMT). The overall prevalence of anti-JC virus antibody was 40%. Gender (P=0.69), disease duration (P=0.11), and number of natalizumab infusions (P=0.64) were not associated with seropositivity. Patients aged ≥30 years were more likely to be seropositive (P=0.01). Conclusion. The prevalence of anti-JCV antibody is slightly lower than what is reported in published studies. Seropositivity was associated with an increasing age of MS patients.
Two-Step Single Slope/SAR ADC with Error Correction for CMOS Image Sensor
Authors: Tang Fang , Bermak Amine , Amira Abbes , Amor Benammar Mohieddine , He Debiao , Zhao Xiaojin
Published: January 2014

Conventional two-step ADC for CMOS image sensor requires full resolution noise performance in the first stage single slope ADC, leading to high power consumption and large chip area. This paper presents an 11-bit two-step single slope/successive approximation register (SAR) ADC scheme for CMOS image sensor applications. The first stage single slope ADC generates a 3-bit data and 1 redundant bit. The redundant bit is combined with the following 8-bit SAR ADC output code using a proposed error correction algorithm. Instead of requiring full resolution noise performance, the first stage single slope circuit of the proposed ADC can tolerate up to 3.125% quantization noise. With the proposed error correction mechanism, the power consumption and chip area of the single slope ADC are significantly reduced. The prototype ADC is fabricated using 0.18 μm CMOS technology. The chip area of the proposed ADC is 7 μm × 500 μm. The measurement results show that the energy efficiency figure-of-merit (FOM) of the proposed ADC core is only 125 pJ/sample under 1.4 V power supply and the chip area efficiency is 84 k μm2·cycles/sample.
Lipophilicity Assessment of Ruthenium(II)-Arene Complexes by the Means of Reversed-Phase Thin-Layer Chromatography and DFT Calculations
Authors: Shweshein Khalil Salem A. M. , Andrić Filip , Radoičić Aleksandra , Zlatar Matija , Gruden-Pavlović Maja , Tešić Živoslav , Milojković-Opsenica Dušanka
Published: January 2014

The lipophilicity of ten ruthenium(II)-arene complexes was assessed by reversed-phase thin-layer chromatography (RP-TLC) on octadecyl silica stationary phase. The binary solvent systems composed of water and acetonitrile were used as mobile phase in order to determine chromatographic descriptors for lipophilicity estimation. Octanol-water partition coefficient,logKOW, of tested complexes was experimentally determined using twenty-eight standard solutes which were analyzed under the same chromatographic conditions as target substances. In addition,ab initiodensity functional theory (DFT) computational approach was employed to calculatelogKOWvalues from the differences in Gibbs’ free solvation energies of the solute transfer fromn-octanol to water. A good overall agreement between DFT calculated and experimentally determinedlogKOWvalues was established (R2= 0.8024–0.9658).
Developmental Immunotoxicity, Perinatal Programming, and Noncommunicable Diseases: Focus on Human Studies
Authors: Dietert Rodney R.
Published: January 2014

Developmental immunotoxicity (DIT) is a term given to encompass the environmentally induced disruption of normal immune development resulting in adverse outcomes. A myriad of chemical, physical, and psychological factors can all contribute to DIT. As a core component of the developmental origins of adult disease, DIT is interlinked with three important concepts surrounding health risks across a lifetime: (1) the Barker Hypothesis, which connects prenatal development to later-life diseases, (2) the hygiene hypothesis, which connects newborns and infants to risk of later-life diseases and, (3) fetal programming and epigenetic alterations, which may exert effects both in later life and across future generations. This review of DIT considers: (1) the history and context of DIT research, (2) the fundamental features of DIT, (3) the emerging role of DIT in risk of noncommunicable diseases (NCDs) and (4) the range of risk factors that have been investigated through human research. The emphasis on the human DIT-related literature is significant since most prior reviews of DIT have largely focused on animal research and considerations of specific categories of risk factors (e.g., heavy metals). Risk factors considered in this review include air pollution, aluminum, antibiotics, arsenic, bisphenol A, ethanol, lead (Pb), maternal smoking and environmental tobacco smoke, paracetamol (acetaminophen), pesticides, polychlorinated biphenyls, and polyfluorinated compounds.
Surgical Approaches to Supradiaphragmatic Segment of IVC and Right Atrium through Abdominal Cavity during Intravenous Tumor Thrombus Removal
Authors: Shchukin Dmytro , Lesovoy Vladimir , Garagatiy Igor , Khareba Gennadiy , Hsaine Redouane
Published: January 2014

Objective. The purpose of this study was to investigate safety and feasibility of some surgical approaches to the supradiaphragmatic inferior vena cava (IVC) and the right atrium through the diaphragm from the abdominal cavity.Materials and Methods. The material of the anatomical study included 35 fresh cadavers. Several options of surgical access to the supradiaphragmatic IVC were successively performed. Feasibility and risk level of each of the approaches were evaluated with the use of a special scale.Results. The isolation of the supradiaphragmatic IVC and cavoatrial junction was most easily performed via T-shaped or circular diaphragmotomy (grade “easy” was registered in 74.3% and 80% of patients, resp., compared to 31.4% for transverse diaphragmotomy and 40% for isolation of the IVC in the pericardial cavity). The risk analysis has demonstrated the highest safety level for T-shaped diaphragmotomy (grade “safe” was registered in 60% of cases). The intervention via transverse diaphragmotomy, circular diaphragmotomy, and IVC isolation in the pericardial cavity was graded as “risky” in 80%, 62.9%, and 82.9% of cases, respectively.Conclusions. In our opinion, T-shaped diaphragmotomy is the most safe and easy-to-perform access for mobilization of the supradiaphragmatic IVC through the abdominal cavity.
Contrast Media: Are There Differences in Nephrotoxicity among Contrast Media?
Authors: Solomon Richard
Published: January 2014

Iodinated contrast agents are usually classified based upon their osmolality—high, low, and isosmolar. Iodinated contrast agents are also nephrotoxic in some but not all patients resulting in loss of glomerular filtration rate. Over the past 30 years, nephrotoxicity has been linked to osmolality although the precise mechanism underlying such a link has been elusive. Improvements in our understanding of the pathogenesis of nephrotoxicity and prospective randomized clinical trials have attempted to further explore the relationship between osmolality and nephrotoxicity. In this review, the basis for our current understanding that there are little if any differences in nephrotoxic potential between low and isosmolar contrast media will be detailed using data from clinical studies.
Daytime Sleepiness in Parkinson's Disease: Perception, Influence of Drugs, and Mood Disorder
Authors: Ataide M. , Franco C. M. R. , Lins O. G.
Published: January 2014

Parkinson's disease (PD) is associated with sleep complaints as excessive daytime sleepiness (EDS) and several factors have been implicated in the genesis of these complaints.Objective. To correlate the subjective perception of EDS with variables as the severity of the motor symptoms, medications, and the presence of depressive symptoms.Materials and Methods. A cross-sectional study, using specific scales as Epworth sleepiness scale (ESS), Beck depression inventory (iBeck) and Hoehn and Yahr (HY), in 42 patients with PD.Results. The patients had a mean age of61.2±11.3years and mean disease duration of4.96±3.3years. The mean ESS was7.5±4.7and 28.6% of patients reached a score of abnormally high value (>10). There was no association with gender, disease duration, and dopamine agonists. Patients with EDS used larger amounts of levodopa (366.7±228.0versus460.4±332.25 mg,P=0.038), but those who had an iBeck>20reached lower values of ESS than the others (5.9±4.1versus9.3±4.8,P=0.03).Conclusions. EDS was common in PD patients, being related to levodopa intake. Presence of depressed mood may influence the final results of self-assessment scales for sleep disorders.
Multiple Solutions for a Class ofN-Laplacian Equations with Critical Growth and Indefinite Weight
Authors: Zhang Guoqing , Yao Ziyan
Published: January 2014

Using the suitable Trudinger-Moser inequality and the Mountain Pass Theorem, we prove the existence of multiple solutions for a class ofN-Laplacian equations with critical growth and indefinite weight-div∇uN-2∇u+VxuN-2u=λuN-2u/xβ+fx,u/xβ+ɛhx,x∈ℝN,u≠0,x∈ℝN, where0<β<N,V(x)is an indefinite weight,f:ℝN×ℝ→ℝbehaves likeexp⁡αuN/N-1and does not satisfy the Ambrosetti-Rabinowitz condition, andh∈(W1,N(ℝN))*.
Assessment of Renewable Energy Technology and a Case of Sustainable Energy in Mobile Telecommunication Sector
Authors: Okundamiya Michael S. , Emagbetere Joy O. , Ogujor Emmanuel A.
Published: January 2014

The rapid growth of the mobile telecommunication sectors of many emerging countries creates a number of problems such as network congestion and poor service delivery for network operators. This results primarily from the lack of a reliable and cost-effective power solution within such regions. This study presents a comprehensive review of the underlying principles of the renewable energy technology (RET) with the objective of ensuring a reliable and cost-effective energy solution for a sustainable development in the emerging world. The grid-connected hybrid renewable energy system incorporating a power conversion and battery storage unit has been proposed based on the availability, dynamism, and technoeconomic viability of energy resources within the region. The proposed system’s performance validation applied a simulation model developed in MATLAB, using a practical load data for different locations with varying climatic conditions in Nigeria. Results indicate that, apart from being environmentally friendly, the increase in the overall energy throughput of about 4 kWh/$ of the proposed system would not only improve the quality of mobile services, by making the operations of GSM base stations more reliable and cost effective, but also better the living standards of the host communities.
Optimal Sharpening of Compensated Comb Decimation Filters: Analysis and Design
Authors: Troncoso Romero David Ernesto , Laddomada Massimiliano , Jovanovic Dolecek Gordana
Published: January 2014

Comb filters are a class of low-complexity filters especially useful for multistage decimation processes. However, the magnitude response of comb filters presents a droop in the passband region and low stopband attenuation, which is undesirable in many applications. In this work, it is shown that, for stringent magnitude specifications, sharpening compensated comb filters requires a lower-degree sharpening polynomial compared to sharpening comb filters without compensation, resulting in a solution with lower computational complexity. Using a simple three-addition compensator and an optimization-based derivation of sharpening polynomials, we introduce an effective low-complexity filtering scheme. Design examples are presented in order to show the performance improvement in terms of passband distortion and selectivity compared to other methods based on the traditional Kaiser-Hamming sharpening and the Chebyshev sharpening techniques recently introduced in the literature.
Verification and Optimal Control of Context-Sensitive Probabilistic Boolean Networks Using Model Checking and Polynomial Optimization
Authors: Kobayashi Koichi , Hiraishi Kunihiko
Published: January 2014

One of the significant topics in systems biology is to develop control theory of gene regulatory networks (GRNs). In typical control of GRNs, expression of some genes is inhibited (activated) by manipulating external stimuli and expression of other genes. It is expected to apply control theory of GRNs to gene therapy technologies in the future. In this paper, a control method using a Boolean network (BN) is studied. A BN is widely used as a model of GRNs, and gene expression is expressed by a binary value (ON or OFF). In particular, a context-sensitive probabilistic Boolean network (CS-PBN), which is one of the extended models of BNs, is used. For CS-PBNs, the verification problem and the optimal control problem are considered. For the verification problem, a solution method using the probabilistic model checker PRISM is proposed. For the optimal control problem, a solution method using polynomial optimization is proposed. Finally, a numerical example on the WNT5A network, which is related to melanoma, is presented. The proposed methods provide us useful tools in control theory of GRNs.
Adiponectin as a Biomarker of Osteoporosis in Postmenopausal Women: Controversies
Authors: Lubkowska Anna , Dobek Aleksandra , Mieszkowski Jan , Garczynski Wojciech , Chlubek Dariusz
Published: January 2014

The literature reports indicating a link between plasma levels of adiponectin and body fat, bone mineral density, sex hormones, and peri- and postmenopausal changes, draw attention to the possible use of adiponectin as an indicator of osteoporotic changes, suggesting that adiponectin may also modulate bone metabolism. In this study, we attempted to analyze the availablein vitroandin vivoresults which could verify this hypothesis. Although several studies have shown that adiponectin has an adverse effect on bone mass, mainly by intensifying resorption, this peptide has also been demonstrated to increase the proliferation and differentiation of osteoblasts, inhibit the activity of osteoclasts, and reduce bone resorption. There are still many ambiguities; for example, it can be assumed that concentrations of adiponectin in plasma do not satisfactorily reflect its production by adipose tissue, as well as conflictingin vitroandin vivoresults. It seems that the potential benefit in the treatment of patients with osteoporosis associated with the pharmacological regulation of adiponectin is controversial.
On the Periodicity of Some Classes of Systems of Nonlinear Difference Equations
Authors: Stević Stevo , Alghamdi Mohammed A. , Maturi Dalal A. , Shahzad Naseer
Published: January 2014

Some classes of systems of difference equations whose all well-defined solutions are periodic are presented in this note.
Mesenchymal Stem Cells Use IDO to Regulate Immunity in Tumor Microenvironment
Authors: Ling Weifang , Zhang Jimin , Yuan Zengrong , Ren Guangwen , Zhang Liying , Chen Xiaodong , Rabson Arnold B. , Roberts Arthur I. , Wang Ying , Shi Yufang
Published: January 2014

Mesenchymal stem cells (MSC) are present in most, if not all, tissues and are believed to contribute to tissue regeneration and the tissue immune microenvironment. Murine MSCs exert immunosuppressive effects through production of inducible nitric oxide synthase (iNOS), whereas human MSCs use indoleamine 2,3-dioxygenase (IDO). Thus, studies of MSC-mediated immunomodulation in mice may not be informative in the setting of human disease, although this critical difference has been mainly ignored. To address this issue, we established a novel humanized system to model human MSCs, using murine iNOS−/− MSCs that constitutively or inducibly express an ectopic human IDO gene. In this system, inducible IDO expression is driven by a mouse iNOS promoter that can be activated by inflammatory cytokine stimulation in a similar fashion as the human IDO promoter. These IDO-expressing humanized MSCs (MSC-IDO) were capable of suppressing T-lymphocyte proliferation in vitro. In melanoma and lymphoma tumor models, MSC-IDO promoted tumor growth in vivo, an effect that was reversed by the IDO inhibitor 1-methyl-tryptophan. We found that MSC-IDO dramatically reduced both tumor-infiltrating CD8+ T cells and B cells. Our findings offer an important new line of evidence that interventional targeting of IDO activity could be used to restore tumor immunity in humans, by relieving IDO-mediated immune suppression of MSCs in the tumor microenvironment as well as in tumor cells themselves. Cancer Res; 74(5); 1576–87. ©2014 AACR.
Abstract A110: Associations between genetic variations in inflammation and innate immunity pathways and colorectal cancer
Authors: Wang Hansong , Taverna Darin , Stram Daniel O. , Cheng Iona , Wilkens Lynne R. , Burnett Terrilea , Newcomb Polly A. , Kolonel Laurence N. , Henderson Brian E. , Duggan David , Ulrich Cornelia M. , Marchand Loic Le
Published: January 2014

A strong association between chronic inflammation and colorectal cancer (CRC) risk has been observed. We postulated that common variation in genes involved in the inflammation and innate immunity pathways may result in a chronic pro-inflammatory state that may lead to increased CRC risk. We comprehensively examined the associations of 724 tagSNPs in 37 key genes in these pathways with CRC in two large well-characterized studies. The screening phase included 2,322 discordant sibships (2,535 cases, 3,915 unaffected sibling controls) from the Colon Cancer Family Registry. Nineteen gene regions spanned by 99 top hits from main-effect or interaction-effect analyses in phase 1 were followed up by genotyping 351 well-chosen tagSNPs in 4,783 subjects (2,153 cases, 2,630 controls) in five ethnic groups in the Multiethnic Cohort Study. One SNP rs9858822 in PPAR gamma gene was statistically significantly associated with CRC in the replication phase (p=1.5 × 10-4, odds ratio per allele = 1.36), based on a conservative Bonferroni-corrected significance level 0.05 adjusted for the “effective” number of markers (n=306). The risk allele C was common (frequency 0.3) in African Americans but was rare (frequency < 0.05) in Whites, Japanese Americans, Latinos and Native Hawaiians. We did not detect effect modification by race/ethnicity, BMI, or use of aspirin. Strong, although not statistically significant, associations were also observed for SNPs in the neighborhood region of rs9858822 (p-values as low as 2.5 × 10-4). Further replication is needed.

Citation Format: Hansong Wang, Darin Taverna, Daniel O. Stram, Iona Cheng, Lynne R. Wilkens, Terrilea Burnett, Polly A. Newcomb, Laurence N. Kolonel, Brian E. Henderson, David Duggan, Cornelia M. Ulrich, Loic Le Marchand. Associations between genetic variations in inflammation and innate immunity pathways and colorectal cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A110.
Abstract A111: The Awareness on Loop Electrosurgical Excision Procedure as a strategy for reducing the Incidence and Mortality of Cervical Cancer among Nigerian Market Women
Authors: Adetule Olubunmi Olabisi
Published: January 2014

This paper highlights the level of awareness of Loop Electrosurgical Excision Procedure (LEEP) as a strategy for reducing the incidence and mortality of cervical cancer among the reproductive women in Ibadan North Government of Oyo state, Nigeria. A non-experimental descriptive design was used to find out the level of awareness of LEEP among the market women in Ibadan North Local Government of Oyo State. The sampling technique adopted in the study was the simple random sampling. The sample consisted of young adults, adults and aged women including literate and illiterate. The respondents were reassured of the confidentiality of the data. The instrument used basically was self-structured questionnaire. These questionnaires were administered in four major markets which are Bodija, Sango, Gate, and Gbagi markets in Ibadan North Local Government area of Oyo State, Nigeria. On the respondent awareness of LEEP before this study, only 26 (26%) of the respondents strongly agreed that they have heard about LEEP while 15 (15%) were undecided and 59 (59%) said they have never heard about it, which means that majority of the respondents were not aware of LEEP. The women were asked if LEEP is curative and prevent reoccurrence of cervical cancer; 40 (40%) agreed while 33 (33%) were undecided about this question and 27 (27%) disagreed that it is not curative and cervical cancer can still occur. Regarding the necessity for all women to be aware of the LEEP, 84 (84%) agreed that it is important and necessary for all reproductive and menopausal women to be aware of LEEP which will help to reduce the maternal mortality and morbidity rate, while 15 (15%) were undecided and 1 (1%) disagreed. The women were asked if the awareness of LEEP will decrease the maternal mortality rate of cervical cancer. 85 (85%) agreed that awareness of LEEP will decrease the maternal mortality rate which means that if women are aware of LEEP, it will help them to come to the nearby health center for prompt treatment on time,14 (14%) are undecided and only 1(1%) disagreed. The study shows that most Nigerian market women are not aware of LEEP. There is a need for governments and policy makers to increase publicity on the benefits of LEEP so as to reduce the incidence and mortality rate of cervical cancer in Nigeria.

Citation Format: Olubunmi Olabisi Adetule. The awareness on loop electrosurgical excision procedure as a strategy for reducing the incidence and mortality of cervical cancer among Nigerian market women. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A111.
Abstract A116: Inter-scan reproducibility of mammographic density measurements
Authors: Lokate Mariëtte , Emaus Marleen , Kallenberg Michiel , Bakker Marije , Karssemeijer Nico , Veldhuis Wouter , Peeters Petra , Gils Carla van
Published: January 2014

Introduction: A decrease in mammographic density is increasingly used as an intermediate marker to evaluate the effect of interventions for reducing breast cancer risk. Technical aspects, such as a different amount of compression, could influence density measurements. We investigated the inter-scan reproducibility of mammographic density measurements to see whether this may influence measurements of true changes in density.

Methods: We included women with two mammograms made closely after one another (median 12 days), with no true changes in breast density expected to happen: 106 had two Full-Field Digital Mammograms (FFDM), 12 had two Film-Screen Mammograms (FSM) and 52 had one FFDM and one FSM. We estimated intraclass correlation coefficients, and mean absolute density differences between both mammograms.

Results: The intraclass correlation between percent density measurements on two FFDMs was 0.93 (95%CI 0.91-0.95), between two FSMs 0.94 (95%CI 0.84-0.98), and between FFDM and FSM 0.72 (95%CI 0.61-0.80). The mean absolute difference in percent density between two FFDMs was 4.3% (95%CI 3.8-4.9) and between two FSMs 6.5% (95%CI 3.4-9.6). On average, percent density in the same woman was higher on FFDM than on FSM (difference 12.9% (95%CI 11.0-14.8)).

Conclusion: When studying changes in mammographic density, it is important to compare two mammograms of the same type (FSM or FFDM). Even then, although intraclass correlation coefficients are high, the absolute differences in percent density are still of a magnitude that may influence detectability of true changes in mammographic density.

Citation Format: Mariëtte Lokate, Marleen Emaus, Michiel Kallenberg, Marije Bakker, Nico Karssemeijer, Wouter Veldhuis, Petra Peeters, Carla van Gils. Inter-scan reproducibility of mammographic density measurements. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A116.
Abstract A19: miR-19a modulates chemoradiotherapy resistance in human cervical cancer
Authors: Liu Mei , Wu Lingying , Xu Ningzhi , An Jusheng , Hu Jinlong , Huang Manni , Tu Binbin , Hu Chenfei , Wang Zaozao , Zhu Hongxia
Published: January 2014

Cervical cancer is one of the most common cancers in women worldwide. Advanced uterine cervical squamous cell carcinomasuterine (UCSCC) patients in FIGO stage IIb or IIIb treated with platinum based concomitant chemoradiotherapy. However, clinical outcomes vary significantly and are difficult to predict. Tumor intrinsic chemoradiotherapy sensitivity is one of the crucial reasons for concomitant chemoradiotherapy failure in UCSCC. In this study, we identified the relationship between miR-19a and sensitivity to concomitant chemoradiotherapy. The UCSCC patients in FIGO stage IIb or IIIb treated with platinum based concurrent chemoradiotherapy at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences. Patients with progressive disease during first line platinum based chemotherapy or those who suffered recurrent disease within 6 months of completing first line therapy were termed resistant. Patients without recurrence or with recurrences beyond 6 months were termed sensitive. We examined the expression level of miR-19a in 30 cervix biopsies samples, including 10 resistant and 20 sensitive samples. We found miR-19a was significantly up-regulated in resistant group compared with sensitive group (p <0.05). Our study indicated that miR-19a might be a marker to identify cervical cancer patients who are likely to fail concomitant chemoradiotherapy. To verify role of miR-19ain cervical cancer cells is worthy of further investigation.

Citation Format: Mei Liu, Lingying Wu, Ningzhi Xu, Jusheng An, Jinlong Hu, Manni Huang, Binbin Tu, Chenfei Hu, Zaozao Wang, Hongxia Zhu. miR-19a modulates chemoradiotherapy resistance in human cervical cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A19.
Abstract A23: Gene set enrichment analysis of renal cell carcinoma genome-wide association data identifies the JAK-STAT pathway mediating susceptibility
Authors: Shu Xiang , Chen Meng , Ye Yuanqing , Huang Maosheng , Gu Jian , Wood Christopher G. , Wu Xifeng
Published: January 2014

Genome-wide association studies (GWAS) have successfully discovered novel loci associated with renal cell carcinoma (RCC) risk. However, a portion of genetic variation contributing to RCC susceptibility remains uncovered by traditional individual SNP analysis in GWAS. Several pathway-based analytical tools have been developed to complement individual SNP analysis. In this study, we performed gene set enrichment analysis using our RCC GWAS dataset comprised of 894 cases and 1,516 controls with three different tools: GenGen, SNP ratio test, and ALIGATOR. Seven pathways defined by KEGG, GO, and REACTOME were significantly associated with RCC susceptibility in all the three algorithms, with JAK-STAT-signaling (155 genes, PGenGen=0.033, PSNP ratio=0.002, and PALIGATOR=0.002) and Glycine-Serine-Threonine-metabolism (31 genes, PGenGen=0.04, PSNP ratio=0.043, and PALIGATOR<0.001) being the most significant. Gene-based analysis identified 13 genes in the JAK-STAT signaling pathway as being significantly associated with RCC risk, with OSM (oncostatin M) reaching the highest significance (p=0.003). Similar analysis in the Glycine -Serine-Threonine-metabolism pathway identified GLYCTK (glycerate kinase) as the most significant (p=0.003) among seven significant genes identified. We further validated the top significant variants from these two pathways in a replication GWAS dataset of 1,311 cases and 3,423 controls from NCI. One SNP (rs757903) located in PIK3CG (catalytic subunit of PI3K) in the JAK-STAT-signaling pathway was successfully validated with another three reaching borderline significance. Meta-analyses confirmed that these four SNPs were significantly associated with RCC risk, and increased the risk up to 20%. Individuals who carry three to four risk genotypes were at a 2-fold increase in RCC risk, compared to reference group with at most one risk genotype (OR: 1.73, 95% CI: 1.38–2.16, p= 1.47×10−6). Our results suggest that JAK-STAT-signaling may play an important role in RCC tumorigenesis and identify several new avenues for future investigation into the genetic factors mediating susceptibility to RCC.

Citation Format: Xiang Shu, Meng Chen, Yuanqing Ye, Maosheng Huang, Jian Gu, Christopher G. Wood, Xifeng Wu. Gene set enrichment analysis of renal cell carcinoma genome-wide association data identifies the JAK-STAT pathway mediating susceptibility. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A23.
Abstract A24: IGF2/H19 and PEG1/MEST DNA methylation in CIN1, CIN2, CIN3 and cervical cancer in Tanzanian women: In search of disease progression biomarkers
Authors: Vidal Adriana C. , Nye Monica , Murphy Susan K. , Overcash Francine , Oneko Olola , Bartlett John A. , Huang Zhiqing , Mlay Pendo , Obure Joseph , Smith Jennifer S. , Hernandez Brenda , Hoyo Cathrine
Published: January 2014

Background: Epigenetic mechanisms have been hypothesized to be etiologically involved in progression of cervical intraepithelial neoplasia (CIN) to invasive cervical cancer (ICC), although empirical data are lacking.

Methods: We enrolled 148 controls, 38 CIN and 48 ICC cases at Kilimanjaro Christian Medical Centre from 2008-2009. HPV was genotyped by HPV linear array and HIV-1 serostatus was tested by two rapid HIV tests. DNA methylation was measured at differentially methylated regions (DMRs) regulating genomic imprinting of IGF2/H19 and PEG1/MEST imprinted domains, using pyrosequencing. Logistic regression models were used to estimate odd ratios (ORs).

Results: After adjusting for age, HPV infection, parity, hormonal contraceptive use, and HIV-1 serostatus, a 10% decrease in methylation at the IGF2 CTCF3 DMR was associated with a significantly higher risk of ICC (OR=2.00, 95% CI 1.14-3.44) and CIN (OR=1.51, 95% CI 1.00-2.50). We observed similar, albeit weaker pattern of associations between the H19 DMR and ICC and PEG1/MEST (OR= 1.51, 95% CI 0.90-2.53, and OR= 1.44, 95% CI 0.90-2.35, respectively). Restricting analyses to older women (>30 years old) further strengthened these associations.

Conclusions: Aberrant DNA methylation at regulatory regions of imprinted genes may increase susceptibility to CIN and ICC and this association appears independent of HPV infection. While the small sample size limits inference, these findings support the hypothesis that DNA methylation at imprinted domains, including IGF2/H19 and PEG1/MEST, may represent susceptibility loci that can be exploited to identify, from among a large number of CIN, those likely to progress.

Citation Format: Adriana C. Vidal, Monica Nye, Susan K. Murphy, Francine Overcash, Olola Oneko, John A. Bartlett, Zhiqing Huang, Pendo Mlay, Joseph Obure, Jennifer S. Smith, Brenda Hernandez, Cathrine Hoyo. IGF2/H19 and PEG1/MEST DNA methylation in CIN1, CIN2, CIN3 and cervical cancer in Tanzanian women: In search of disease progression biomarkers. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A24.
Abstract A36: Resveratrol decreases DNMTs in a human relevant animal model of breast cancer
Authors: Qin Wenyi , Zhu Weizhu , Zhang Ke , Clarke Kaitlin , Sauter Edward R.
Published: January 2014

Background: We previously reported that trans-resveratrol (resveratrol) downregulates the expression DNA methyltransferases (DNMTs) 1 and 3b in vitro and demethylates the tumor suppressor gene RASSF-1a in the breasts of women who are at increased breast cancer risk. Effects increased with increasing dose/circulating level of the agent, respectively. In the current report, we evaluated the effect of increasing doses of resveratrol on mammary tumor formation in the ACI rat, which develops estrogen dependent mammary carcinoma.

Methods: 91 female rats were treated with a slow release estradiol (E2) pellet plus one of the following: 5 mg/kg/day (low dose) resveratrol (n=23), 25 mg/kg/day (high dose) resveratrol (n=22), 0.1mg/kg/week 5-azacytadine (aza) (n=22), an inhibitor of DNMTs which is used clinically, or control (n=24). The animals were examined weekly to assess for the presence of tumor formation. After 5.5 months of treatment, the animals were sacrificed and the mammary glands harvested, with half of each gland snap frozen and the other half formalin fixed. Specimens were evaluated by a board certified pathologist to confirm histology as benign or malignant. DNMT1 and 3b were measured by qRT-PCR.

Results: Tumor formation was lowest (18% of rats) in the high dose resveratrol and 5-aza groups, intermediate in the low dose resveratrol group (26%) and highest in control (33%). DMNT1 expression was significantly (p<0.0001) influenced by treatment, while DNMT3b was not. On the other hand, DNMT3b expression was significantly (p<0.0001) influenced by histology (benign vs. malignant), whereas DNMT1 was not.

Conclusion: Treatment with resveratrol and 5-aza significantly influence DNMT expression, which may be important in the prevention/delay of mammary tumor formation. This mechanism of action of resveratrol warrants further investigation.

Citation Format: Wenyi Qin, Weizhu Zhu, Ke Zhang, Kaitlin Clarke, Edward R. Sauter. Resveratrol decreases DNMTs in a human relevant animal model of breast cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A36.
Abstract A48: Mevalonate pathway inhibitors as chemopreventive agents on lung cancer cell lines: p53 might be a potent regulator
Authors: Lee Hwa Young , Kim In Kyoung , Lee Hye In , Kang Hye Sun , Park Chan Kwon , Ha Jick Hwan , Kim Seung Joon , Lee Sang Haak
Published: January 2014

Objectives: The mevalonate pathway has a crucial role in maintaining cellular homeostasis by cholesterol synthesis and protein prenylation. The mevalonate pathway inhibitors, statins and bisphosphonates have long been tested as anticancer agents, but because of the tumor-selective mechanisms, effects of the drugs on lung cancer cells are not clear. P53, a central regulator of stress responses, can induce cell cycle arrest, cell death or senescence depending on the level of cellular stresses. The current study investigated the effects of simvastatin and zolendronic acid on non-small-cell lung cancer (NSCLC) cells and whether the anti-tumor effects are related to p53 mutation status.

Material and Methods: We treated 3 NSCLC cells, A549 (p53 wild type), H522 (mutant) and H358 (null), with simvastatin and zolendronic acid to investigate cellular proliferation, cell cycle activity, intracellular reactive oxygen species (ROS) and expression of p53 target genes.

Results: In light microscopy, simvastatin (1 uM) caused morphologic changes in all 3 NSCLC cells. The cytotoxicity assay revealed that the synergistic impact with simvastatin (1 uM) and zolendronic acid (50 uM) existed on 72 hour cell survival, which was shown only in p53-wt cells. Expression of cyclin D1, which is important regulator of G1 to S phase progression, was decreased in p53-null and mutant cells but increased in p53-wt cells. Intracellular ROS levels after 24 hour treatment with blends of simvastatin and zolendronic acid was increased more than 2-fold in p53-wt cells, not in p53-null or mutant cells. Regulation of oxidative stress by p53 was shown with the increased expression of p53 target genes, cytochrome c oxidase 2 and TP53-induced glycolysis and apoptosis regulator quantified by real-time polymerase chain reaction.

Conclusions: Our data indicate that taken together, combination of simvastatin and zolendronic acid may have synergistic anti-proliferative effects in lung cancer cells which have functional p53, and those are mediated by increased cellular oxidative stress leading to apoptosis rather than cell cycle arrest. Targeting mevalonate pathway has the potential for lung cancer prevention, by inducing cellular metabolic stress responses mediated by p53.

Citation Format: Hwa Young Lee, In Kyoung Kim, Hye In Lee, Hye Sun Kang, Chan Kwon Park, Jick Hwan Ha, Seung Joon Kim, Sang Haak Lee. Mevalonate pathway inhibitors as chemopreventive agents on lung cancer cell lines: p53 might be a potent regulator. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A48.
Abstract A63: Combination aspirin and/or calcium chemoprevention with colonoscopy in colorectal cancer prevention: Cost-effectiveness analyses
Authors: Pence Barbara C. , Belasco Eric J. , Lyford Conrad P.
Published: January 2014

Background: Evidence from large-scale studies has shown that low dose aspirin and calcium are effective low risk strategies for primary prevention of colorectal cancer (CRC). We analyzed the cost-effectiveness of combination aspirin and calcium chemoprevention used with colonoscopy for primary prevention of CRC, using population-based compliance rates.

Methods: Cost-effectiveness of prevention strategies was compared using Markov chain Monte Carlo simulations of a hypothetical population with 100,000 persons starting at 50 years of age with a colonoscopy compliance rate of 50%. Once adenomas were detected, colonoscopy was repeated every 4 years until no adenomas recurred. Our data sources included state transition rates, CRC incidence, and treatment complication rates determined from existing literature. Age-adjusted US standard population mortality rates were used and costs were estimated from Medicare reimbursement data. The target population was US adults, ages 50 to 75, for whom primary CRC prevention methods are recommended within the general population.

Results: Outcome measures included incremental cost-effectiveness ratios, life-years saved, and cancer-free years saved. Compared to no screening, colonoscopy with aspirin and colonoscopy with both aspirin and calcium were the most cost-effective strategies based on cancer-free years saved. In terms of overall life-years saved, colonoscopy with and without aspirin were the most cost-effective options.

Conclusion: Given its strong positive effect, an aspirin-calcium regimen should be recommended for use in primary colorectal cancer prevention, especially when colonoscopy is also utilized.

Impact: Cost-effectiveness analysis is a valid tool for comparing multiple chemoprevention/screening strategies in a population.

Citation Format: Barbara C. Pence, Eric J. Belasco, Conrad P. Lyford. Combination aspirin and/or calcium chemoprevention with colonoscopy in colorectal cancer prevention: Cost-effectiveness analyses. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A63.
Abstract A65: Activation of ERK1/2 using combination of aspirin, curcumin and sulforaphane regimen leads to NF-κB inhibition and apoptosis in pancreatic cancer cells
Authors: Thakkar Arvind , Sutaria Dhruvitkumar , Grandhi Karthik , Huang Ying , Wang Jeffrey , Prabhu Sunil
Published: January 2014

Pancreatic cancer ranks as the fourth most deadly form of cancer in the United States with approximately 37,000 deaths each year. Due to poor prognosis, attention has recently focused on the chemoprevention of this disease rather than on diagnosis and treatment. The present study aims to evaluate the combinatorial chemopreventive effects of low doses of aspirin (ASP), curcumin (CUR), sulforaphane (SFN) alone and in combination ACS (ASP+CUR+SFN) on two pancreatic cancer cell lines, MIA PaCa-2 and Panc-1. Results demonstrated that low doses of ASP (1mM), CUR (10μM) and SFN (5μM) alone did not reduce cell viability, whereas combination ACS reduced cell viability by ∼70% (P<0.001). ACS treatment also induced cell apoptosis by ∼60% accompanied by activation of caspase- 3 and Poly (ADP-ribose) polymerase (PARP) proteins. The NF-κB DNA binding activity was inhibited by ∼45% (P<0.01) and ∼75% (P<0.001) in MIA PaCa-2 and Panc-1 cells respectively. The reduction in NF-κB activity was accompanied by down-regulation of phospho IκBα and phospho Akt proteins. Mechanistic studies revealed that ACS promoted reduction in cell viability, associated with increased expression of phospho extracellular signal-regulated kinase 1/2 (ERK1/2), phospho c-Jun, phospho p38 MAPK and phospho p53 proteins. Furthermore, to evaluate the significance of activation of ERK1/2 pathway on ACS induced reduction in cell viability and NF-κB, the cells were pretreated with U0126 (ERK1/2 inhibitor). The inhibition of ERK1/2 by U0126 pretreatment abolished the effect of ACS on cell viability and NF-κB DNA binding activity. Overall, our results for the first time, illustrate that low dose ACS combinations impart synergistic suppressive activity than chemopreventive agents alone thus confirming the importance of novel combination chemoprevention strategies against pancreatic cancer.

Citation Format: Arvind Thakkar, Dhruvitkumar Sutaria, Karthik Grandhi, Ying Huang, Jeffrey Wang, Sunil Prabhu. Activation of ERK1/2 using combination of aspirin, curcumin, and sulforaphane regimen leads to NF-κB inhibition and apoptosis in pancreatic cancer cells. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A65.
Abstract A66: A Comparison of Helical Tomotherapy with Standard Radiotherapy Treatment Planning (AP/PA) in Patients with Wilms' Tumor and Ewing's Sarcoma
Authors: Sarfo-Kantanka Kofi , Crilly Richard , Moll Logan
Published: January 2014

Purpose/Objective: Radiation carries the risk of inducing complications directly linked to the amount absorbed by tissues. In this initial study, we compare the helical tomotherapy with standard(AP/PA) radiotherapy treatment for pediatric patients with lung metastasis associated with Wilms' tumor and Ewing's sarcoma. We hypothesize that helical tomotherapy will allow for more effective tumoricidal irradiation while minimizing harmful radiation to proximate sensitive structures.

Methods/Materials: The full body CT-scans from pediatrics patients were used to compare two radiotherapy techniques. Treatment plans were designed using HiArt- Tomotherapy and Eclipse planning systems for AP/PA traditional external beam radiotherapy with 12Gy/10x to PTV lung. Optimization was pushed for higher avoidance and data extracted for paired t–test analysis.

Results: The volume prescription dose (V12) in both plans showed no significant differences. However, doses of the lung and spinal column were more homogenous in the helical tomotherapy than the AP/PA. There was a statistical significance (p<0.05) at V10 for the esophagus, breast buds, heart, l. kidney, spinal column and thyroid but no significance for r. kidney and spinal cord. At V5 there were no significance for r. kidney, l. kidney and esophagus but all other avoidant structures were statistically significant. The long term effects of these dose volumes is presently little studied.

Conclusion: Overall, it was observed that the helical tomotherapy is better for treating volumes that minimize dose to normal tissues and supply uniform doses when needed. As treatment techniques are refined, there is an increased need to understand the effects of lower doses on pediatric tissue.

Citation Format: Kofi Sarfo-Kantanka, Richard Crilly, Logan Moll. A comparison of helical tomotherapy with standard radiotherapy treatment planning (AP/PA) in patients with Wilms' tumor and Ewing's sarcoma. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A66.