bluuebunny/crossref_metadata_2025 huggingface dataset:
Compact Dual-Band Planar Inverted-e-Shaped Antenna Using Defected Ground Structure
Authors: Lin Wen Piao , Yang Dong-Hua , Lin Zong-De
Published: January 2014

This paper presents a novel dual-band planar inverted-e-shaped antenna (PIEA) using defected ground structure (DGS) for Bluetooth and wireless local area network (WLAN) applications. The PIEA can reduce electromagnetic interferences (EMIs) and it is constructed on a compact printed circuit board (PCB) size of 10 × 5 × 4 mm3. Experimental results indicate that the antenna with a compact meandered slit can improve the operating impedance matching and bandwidths at 2.4 and 5.5 GHz. The measured power gains at 2.4 and 5.5 GHz band are 1.99 and 3.71 dBi; antenna efficiencies are about 49.33% and 55.23%, respectively. Finally, the good performances of the proposed antenna can highly promote for mobile device applications.
Hierarchical Artificial Bee Colony Algorithm for RFID Network Planning Optimization
Authors: Ma Lianbo , Chen Hanning , Hu Kunyuan , Zhu Yunlong
Published: January 2014

This paper presents a novel optimization algorithm, namely, hierarchical artificial bee colony optimization, called HABC, to tackle the radio frequency identification network planning (RNP) problem. In the proposed multilevel model, the higher-level species can be aggregated by the subpopulations from lower level. In the bottom level, each subpopulation employing the canonical ABC method searches the part-dimensional optimum in parallel, which can be constructed into a complete solution for the upper level. At the same time, the comprehensive learning method with crossover and mutation operators is applied to enhance the global search ability between species. Experiments are conducted on a set of 10 benchmark optimization problems. The results demonstrate that the proposed HABC obtains remarkable performance on most chosen benchmark functions when compared to several successful swarm intelligence and evolutionary algorithms. Then HABC is used for solving the real-world RNP problem on two instances with different scales. Simulation results show that the proposed algorithm is superior for solving RNP, in terms of optimization accuracy and computation robustness.
Discovery of Novel Inhibitors for Nek6 Protein through Homology Model Assisted Structure Based Virtual Screening and Molecular Docking Approaches
Authors: Srinivasan P. , Chella Perumal P. , Sudha A.
Published: January 2014

Nek6 is a member of the NIMA (never in mitosis, gene A)-related serine/threonine kinase family that plays an important role in the initiation of mitotic cell cycle progression. This work is an attempt to emphasize the structural and functional relationship of Nek6 protein based on homology modeling and binding pocket analysis. The three-dimensional structure of Nek6 was constructed by molecular modeling studies and the best model was further assessed by PROCHECK, ProSA, and ERRAT plot in order to analyze the quality and consistency of generated model. The overall quality of computed model showed 87.4% amino acid residues under the favored region. A 3 ns molecular dynamics simulation confirmed that the structure was reliable and stable. Two lead compounds (Binding database ID: 15666, 18602) were retrieved through structure-based virtual screening and induced fit docking approaches as novel Nek6 inhibitors. Hence, we concluded that the potential compounds may act as new leads for Nek6 inhibitors designing.
Diamond-Like Carbon Film Deposition Using DC Ion Source with Cold Hollow Cathode
Authors: Shevchenko E. F. , Tarala V. A. , Shevchenko M. Yu. , Titarenko A. A.
Published: January 2014

Carbon diamond-like thin films on a silicon substrate were deposited by direct reactive ion beam method with an ion source based on Penning direct-current discharge system with cold hollow cathode. Deposition was performed under various conditions. The pressure (12–200 mPa) and the plasma-forming gas composition consisting of different organic compounds and hydrogen (C3H8, CH4, Si(CH3)2Cl2, H2), the voltage of accelerating gap in the range 0.5–5 kV, and the substrate temperature in the range 20–850°C were varied. Synthesized films were researched using nanoindentation, Raman, and FTIR spectroscopy methods. Analysis of the experimental results was made in accordance with a developed model describing processes of growth of the amorphous and crystalline carbon materials.
Comparative Analysis of Linear and Nonlinear Pattern Synthesis of Hemispherical Antenna Array Using Adaptive Evolutionary Techniques
Authors: Subhashini K. R. , Kumar A. T. Praveen
Published: January 2014

Hemispherical antenna arrays are subjected to linear and nonlinear synthesis and are optimized using adaptive based differential evolution (ADE) and fire fly (AFA) algorithm. The hemispherical shaped array with isotropic elements is considered. Antenna element parameters that are used for synthesis are excitation amplitude and angular position. Linear synthesis is termed as the variation in the element excitation amplitude and nonlinear synthesis is process of variation in element angular position. Both ADE and AFA are a high-performance stochastic evolutionary algorithm used to solveN-dimensional problems. These methods are used to determine a set of parameters of antenna elements that provide the desired radiation pattern. The effectiveness of the algorithms for the design of conformal antenna array is shown by means of numerical results. Comparison with other methods is made whenever possible. The results reveal that nonlinear synthesis, aided by the discussed techniques, provides considerable enhancements compared to linear synthesis.
Cancer-Associated Mutations in Healthy Individuals: Assessing the Risk of Carcinogenesis
Authors: Rodriguez-Brenes Ignacio A. , Komarova Natalia L. , Wodarz Dominik
Published: January 2014

Mutations associated with hematopoietic malignancies have been repeatedly identified in healthy individuals. For certain cases, such as the t(14;18) translocation and monoclonal B-cell lymphocytosis, no clear link between the presence of aberrant cells and the later development of cancer has been established. Intriguingly, longitudinal studies suggest that these abnormalities persist for long periods of time in some individuals, but in others are transient in which they disappear completely. Here, we present a mathematical model, based on cellular replication limits, that provides a possible explanation for these seemingly contradictory findings. It proposes that the transient and persistent nature of the phenotypes depends on the stage in the differentiation pathway of a given lineage in which the mutation originates. Our work suggests that cellular replication limits may not only prevent cancer by aborting clonal expansion of cells, but also by influencing the fate of altered but nonneoplastic cells in healthy tissue. Cancer Res; 74(6); 1661–9. ©2014 AACR.
Molecular Rules Governing De Novo Methylation in Cancer
Authors: Nejman Deborah , Straussman Ravid , Steinfeld Israel , Ruvolo Michael , Roberts Douglas , Yakhini Zohar , Cedar Howard
Published: January 2014

De novo methylation of CpG islands is seen in many cancers, but the general rules governing this process are not known. By analyzing DNA from tumors, as well as normal tissues, and by utilizing a range of published data, we have identified a universal set of tumor targets, each with its own “coefficient” of methylation that is largely correlated with its inherent relative ability to recruit polycomb. This pattern is initially formed by a slow process of de novo methylation that occurs during aging and then undergoes expansion early in tumorigenesis, where we hypothesize that it may act as an inhibitor of development-associated gene activation. Cancer Res; 74(5); 1475–83. ©2014 AACR.
Abstract A03: Understanding cervical cancer screening among lesbians: a national survey
Authors: Tracy J. Kathleen
Published: January 2014

Objectives: The aim of this study was to examine cervical cancer screening behaviors among lesbians in the US, a population who has documented low rates of cervical cancer screening, despite their risk of contracting the disease.

Procedures: A standardized internet survey was sent to 3,000 self-identified lesbians across the US. The survey assessed the participants' recent cervical cancer screening behaviors and perceived barriers to screening.

Results: The sample consisted of 1,006 respondents, representing every region of the US. Sixty-two percent of the weighted sample were routine screeners. Lack of a physician referral (17.5%) and lack of a physician (17.3%) were the most commonly-cited top reasons for lack of screening. Adjusting for age, education, relationship status, employments status, and insurance status, women who had disclosed their sexual orientation to their primary care physician (adjusted odds ratio [OR] 2.84 [95% confidence interval 1.82-4.45]) or gynecologist (OR 2.30 [1.33-3.96]) had greater odds of routine screening than those who did not. Those who knew that lack of Pap testing is a risk factor for cervical cancer were also more likely to be routine screeners (OR 1.95 [1.30-2.91]), although no association with screening was apparent for women who had more knowledge of general cervical cancer risk factors. Physician recommendation appeared to be a potent determinant of regular screening behavior. Routine screeners perceived more benefits and fewer barriers to screening, and higher susceptibility to cervical cancer, than did women who did not routinely screen.

Conclusions: Women who identify as lesbian are at potentially elevated risk of cervical cancer because they are not routinely screened. Evidence-based interventions should be developed that address critical health beliefs that undermine participation in screening. Given the value placed on physician recommendation, patient-provider communication may serve as the optimal mode for intervention delivery.

Citation Format: J. Kathleen Tracy. Understanding cervical cancer screening among lesbians: A national survey. [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 A03.
Abstract A107: Variation in the prolactin and prolactin receptor genes and familial breast cancer
Authors: Hussain Shehnaz K. , Sehl Mary , Conn Daniel , Sinsheimer Janet S. , Dandekar Uma , Papp Jeanette , Zhang Zuo-Feng , Ganz Patricia A.
Published: January 2014

Background: Breast cancer aggregates within some families, accounting for about 25% of incident cases. Known genetic variants, such as BRCA1/BRCA2 mutations, account for less than 10% of these familial breast cancer cases, thus, research into additional risk or protective genetic factors for familial breast cancer may provide valuable information for risk stratification. Serum levels of prolactin have been associated with sporadic breast cancer risk in previous studies. We sought to test the hypothesis that variation in the genes coding for prolactin (PRL) and the prolactin receptor (PRLR) would be associated with increased or decreased risk of familial breast cancer.

Methods: We designed a case-control study of probands recruited between 1998 and 2009 by the UCLA Family Cancer Registry; a population enriched with women having a strong family history of breast cancer and BRCA1/BRCA2 mutation carriers. Genotyping of tagSNPs in PRL (n=11) and PRLR (n=28) was performed in 351 unrelated women who developed breast cancer and 290 unaffected controls with similar family histories to the cases. Multivariate logistic regression models controlling for age, Ashkenazi Jewish heritage, education, and number of affected relatives were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between SNPs and familial breast cancer. Genotype specific ORs as well as per-allele (additive model) ORs were calculated.

Results: Familial breast cancer risk was inversely associated with carriership of the minor alleles for three PRLR SNPs in the additive models, rs9292573 (OR=0.7, 95% CI=0.5-0.9), rs10805603 (OR=0.6, 95% CI=0.4-0.9), and rs1587607 (OR=0.7, 95% CI=0.5-1.0). PRLR SNP rs249522 was associated with increased risk of cancer in the additive model (OR=1.8, 95% CI =1.2-2.7). Minor allele carriers of the PRL SNP rs12210179, located in a putative transcription factor binding site, had a decreased risk of cancer in the additive model (OR=0.7, 95% CI=0.5-0.9).

Conclusion: These data suggest that genetic variation in PRL and PRLR are associated with breast cancer in a population with a strong family history of breast cancer.

Citation Format: Shehnaz K. Hussain, Mary Sehl, Daniel Conn, Janet S. Sinsheimer, Uma Dandekar, Jeanette Papp, Zuo-Feng Zhang, Patricia A. Ganz. Variation in the prolactin and prolactin receptor genes and familial 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 A107.
Abstract A16: Genetic polymorphisms in the carcinogen metabolism pathway and lung cancer risk
Authors: Dalay Nejat , Buyru Nur , Yalniz Zubeyde
Published: January 2014

Alterations affecting genes involved in the carcinogen metabolism are associated with cancer susceptibility since these can affect the detoxification capacity of the gene product. Genes regulating the carcinogen metabolism are also highly effective in the pathways involved in lung cancer development. The microsomal epoxide hydroxylase gene EPHX1 participates in the detoxification and activation of the carcinogenic compounds in the cigarette smoke. Two polymorphic changes in the EPHX1 gene result in slow and fast alleles with low and high enzyme activity. This differential effect suggests that these polymorphisms may affect individual lung cancer risk.

Myeloperoxidase (MPO) is an oxidative enzyme released in response to cigarette smoke from the lung tissue. A G>A polymorphism located in the 5' untranslated region of the MPO gene that may be responsible for reduced transcriptional activity due to the decreased binding affinity for the SP1 transcription factor. In individuals carrying the A allele metabolic procarcinogen compounds are not effectively activated. Therefore, this variant is thought to play a protective role in lung cancer.

The NAD(P)H dehydrogenase (NQO1) gene is an important mediator of lung cancer and codes for a cytoplasmic electron reductase which prevents the production of reactive radical species by detoxification of the quinones and their derivatives. Mutations in the NQO1 gene have been associated with susceptibility to various forms of cancer. A C to T substitution at codon 187 of the gene results in almost undetectable enzyme activity in the homozygote individuals carrying the variant allele. In this study we investigated the association of the EPHX1, MPO and NQO1 gene variants with lung cancer in 126 patients and 64 healthy individuals.

Gene expression analysis was performed using the LightCycler 480 Real Time PCR system and hybridization probes. To analyze the genotypes the EPHX1, MPO and NQO1 genes were amplified by polymerase chain reaction and the presence of the gene variants was investigated by restriction fragment length polymorphism after digestion with specific restriction enzymes.

No significant differences in the distribution of the genotypes and allele frequencies were observed between the patients and the control group for the MPO gene and the two different polymorphic variants of the EPHX1 gene. The NQO1 expression levels were higher in the patients when compared to the controls but the difference was not significant. On the other hand, a significant association was observed between the CC genotype and NQO1 expression.

Citation Format: Nejat Dalay, Nur Buyru, Zubeyde Yalniz. Genetic polymorphisms in the carcinogen metabolism pathway and lung cancer risk. [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 A16.
Abstract A18: Pre-diagnostic serum antioxidant levels and prediction of TMPRSS2:ERG fusion status in prostate cancer
Authors: Judson Gregory , Pettersson Andreas , Meisner Allison , Mucci Lorelei
Published: January 2014

Background: The TMPRSS2:ERG gene fusion is a distinct molecular subtype of prostate cancer characterized by chromosomal rearrangements joining the androgen responsive TMPRSS gene with ERG, an oncogenic member of the ETS gene family. TMPRSS2:ERG is thought to be an early pathologic event occurring in 50% of prostate tumors and resulting in more than 100,000 fusion positive cancer cases each year in the US. No studies to date have examined underlying risk factors associated with development of the fusion. Oxidative stress and the production of free radicals may result in chromosomal instability and predispose to the formation of TMPRSS2:ERG positive prostate cancer. Higher levels of serum antioxidants prior to prostate cancer diagnosis may therefore be protective against later development of fusion positive cancer.

Methods: We undertook a case-control analysis nested within the prospective Physicians' Health Study and the Health Professionals Follow-up Study among men with prostate cancer (n=331) and age-matched controls (n=2139). The cohorts include pre-diagnostic bloods with antioxidant levels at baseline as well as tumor tissue to characterize TMPRSS2:ERG status among prostate cancer cases. We used multivariate logistic regression analysis to determine if plasma antioxidant levels influenced the development of the TMPRSS2:ERG fusion.

Results: Of seven antioxidants examined (alpha-tocopherol, alpha-carotene, beta-carotene, beta-cryptoxanthin, gamma-tocopherol, lutein, and lycopene), levels of beta-carotene above the lowest quartile were protective against fusion positive vs. fusion negative prostate cancer (OR 0.49, 95% CL 0.28-0.86, p = 0.01). This association was driven by a non-significantly decreased risk of fusion positive cancer vs. controls (OR 0.75, 95% CL 0.51-1.09, p = 0.13) and a significantly increased risk of fusion negative cancer vs. controls (OR 1.58, 95% CL 1.03-2.41, p = 0.03). None of the six other antioxidants were associated with fusion status, and none of the antioxidants, including beta-carotene, predicted overall prostate cancer risk.

Discussion: Previous studies examining antioxidant status and overall prostate cancer risk have been inconclusive. This is the first study to examine pre-diagnostic serum antioxidant levels in relationship to fusion status. We find that beta-carotene levels may alter prostate cancer risk based on molecular subtype.

Citation Format: Gregory Judson, Andreas Pettersson, Allison Meisner, Lorelei Mucci. Prediagnostic serum antioxidant levels and prediction of TMPRSS2:ERG fusion status in prostate 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 A18.
Abstract A20: Predictive value of plasma hepatocyte growth factor levels in gastric cancer risk: A Nested Case-Control Study within the Korean Multicenter Cancer Cohort
Authors: Ma Seung Hyun , Yang Jae Jeong , Kwang-Pil Ko , Shin Aesun , Shin Hai-Rim , Kang Daehee , Yoo Keun-Young , Park Sue K.
Published: January 2014

Background: HGF (hepatocyte growth factor) is also known as a scatter factor and is multifunctional cytokine that modulates processes such as growth, adhesion, motility, matrix degradation, invasion, and angiogenesis. We investigated whether serum HGF was a biomarker for the early detection and diagnosis of gastric cancer in a nested case-control study.

Methods: The study population was composed of 282 cases and 282 matched controls within the Korean Multicenter Cancer Cohort. Plasma HGF was measured by enzyme-linked immunosorbent assay (ELISA). Conditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence intervals (CI).

Results: According to stratified analysis on age, sex, H. pylori infection, CagA and smoking, gastric cancer patients which are older, female, H. pylori positive, CagA positive and non-smokers had significantly higher serum HGF concentrations than normal controls. When conducting a logistic regression analysis of a group with the lowest concentration as a reference after dividing them into quartile according to serum HGF concentration, also, a group with the highest serum HGF concentration(≥393.7 pg/mL) showed a significantly increased risk of gastric cancer(OR=2.4 95% CI 1.4-3.9). In addition, higher serum HGF concentrations were associated with an increased risk for gastric cancer and it was statistically significant (p for trend=0.0054).

Conclusions: Our finding suggested the possibility that HGF protein can be a biomarker to predict the risk of gastric cancer.

Citation Format: Seung Hyun Ma, Jae Jeong Yang, Ko Kwang-Pil, Aesun Shin, Hai-Rim Shin, Daehee Kang, Keun-Young Yoo, Sue K. Park. Predictive value of plasma hepatocyte growth factor levels in gastric cancer risk: A nested case-control study within the Korean Multicenter Cancer Cohort. [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 A20.

Note: This abstract was not presented at the conference.
Abstract A25: Genetic Variants in 15q25.1 and age onset of Pancreatic Cancer
Authors: Wei Chongjuan , Huang Yu-jing , Chen Jane , Pande Mala , Amos Chris , Frazier Marsha
Published: January 2014

Background: Genome-wide association studies have demonstrated the association between single-nucleotide polymorphisms (SNPs) in the chromosome 15q25.1 region and an increased lung cancer risk through smoking behavior mediated by nicotine dependence susceptibility. Cigarette smoking is also a major risk factor for development of pancreatic cancer and has been reported to be associated with early onset of this disease. Therefore, we hypothesize that variation in this region may influence the age onset of the pancreatic cancer through smoking behavior.

Methods: In this preliminary study, 3 tagging SNPs in 15q25.1 region were genotyped in 427 newly-diagnosed, non-Hispanic White patients with pancreatic cancer. Two of the SNPs, rs7164594 and rs3841324, are in the CHRNA5 gene and the third SNP rs684513 is in PSMA4 gene, respectively.

Results: Our results showed that the two tagging SNPs rs7164594 and rs3841324 in CHRNA5 were not associated with age-associated risk of pancreatic cancer. However, for the tagging SNP rs684513, the variant homozygotes (CC) had a protective effect on age of onset [adjusted HR=0.69 (0.46-1.03), p=0.070], compared with the wild type and heterozygotes (GG+CG), with a 4-years difference in at age of onset [64.81 ± 2.10 vs. 60.60 ± 0.53; log-rank p= 0.042]. Further stratification analysis showed that a reduced risk associated with the variant homozygous (CC) was more pronounced in the subgroup of non-smokers and former smokers [adjusted HR=0.48 (0.26-0.91), p=0.023].

Conclusion and impact: This observation provided preliminary evidence for the association between genetic variant in the chromosomal region 15q25.1 and the age of onset of pancreatic cancer. However, a comprehensive study of all other tagging SNPs covering 15q25.1 region will be worthwhile to conduct.

Citation Format: Chongjuan Wei, Yu-jing Huang, Jane Chen, Mala Pande, Chris Amos, Marsha Frazier. Genetic variants in 15q25.1 and age onset of pancreatic 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 A25.
Abstract A31: Targeting Oncogenic Ras Activation for Cancer Prevention
Authors: Baoan Ji , Haojie Huang , Yan Liu , Jaroslaw Daniluk , Craig Logsdon
Published: January 2014

Increased Ras activity levels due to active mutations of Ras are critical for tumorigenesis. These oncogenic Ras mutations are considered to be locked in a permanent “On” state and “constitutively active”. Yet, surprisingly, expression of oncogenic Ras at physiologically levels in genetically engineered mice with “knock-in” mutant Ras has little effect on most cells. Here, we demonstrated that oncogenic K-Ras is not at all constitutively active. Rather, oncogenic K-Ras can be readily activated by upstream stimulants such as diet-induced hormones (eg. Cholecystokinin) and inflammatory stimuli (eg. PGE2 or LPS). However, unlike wild-type Ras, oncogenic K-Ras is very slow to inactivate. This effect on oncogenic K-Ras signaling kinetics leads to dramatically amplified levels of Ras activity initiated by physiologic stimuli. Sustained increase of Ras activity involves a feed-forward loop in which increased Ras activity generates more inflammatory mediators which act as Ras stimulants. High Ras activity led to acinar cell senescence and generated inflammation and fibrosis resembling the histological features of chronic inflammation with abundant precancerous lesions that spontaneously progressed to cancer only in animals expressing physiologic levels of oncogenic Ras. In summary, oncogenic Ras is not constitutively active but predisposes cells to pathological alterations dependent upon Ras activity levels. Since a large population of normal healthy humans harbors Ras mutations, in addition to targeting Ras downstream signaling pathways a reduction of factors that can activate Ras signaling may provide an important alternative cancer preventive value. These data also provide a mechanistic explanation for the link between inflammation, Ras and cancer and provide insights for cancer prevention.

Citation Format: Ji Baoan, Huang Haojie, Liu Yan, Daniluk Jaroslaw, Logsdon Craig. Targeting oncogenic Ras activation for cancer prevention. [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 A31.
Abstract A35: Resistant starch inhibition of azoxymethane-induced preneoplastic lesions with and without antibiotic treatment
Authors: Nelson Bridget , Ai Yongfeng , Roberts Carter , Liu Peng , Jane Jay-lin , Birt Diane
Published: January 2014

Colorectal cancer is one of the more prevalent cancers in Western cultures, and previous studies suggest an interaction between diet and colon carcinogenesis. Starches have been modified to be more indigestible. This allows the starch to continue through the digestive tract to the colon where it is fermented by the gut microflora to produce short chain fatty acids (SCFA). SCFA are beneficial to colon health due to their ability to regulate anti-inflammation and apoptotic pathways and inhibit colonic preneoplastic lesions such as aberrant crypt foci (ACF) and mucin depleted foci (MDF), two common lesions associated with colon cancer. By adding an antibiotic regimen, a stronger pressure will be placed on the gut microflora and this added pressure of an altered gut microflora is believed to negate the protective effects of resistant starches. Preneoplastic lesions were induced in rats with azoxymethane (AOM), a known colon cancer carcinogen, with saline used as a control. An antibiotic cocktail of vancomycin and imipenem was administered via drinking water to select groups for three days following AOM treatment. The rats were then fed experimental diets containing either control starch (CS) or high amylose-lipid complexed resistant starch (RS5) for ten weeks. Distal colon sections were collected and stained to observe ACF and MDF. There was no significant difference in ACF numbers between the CS and RS5 diet groups but there was a significant difference between the numbers of MDF observed between the two diets, with the CS rats producing more MDF than RS5 rats. A significant antibiotic effect was also observed between the two diet groups with all RS5 rats producing zero MDF and the CS treatment animals producing between 0.2-1.8 MDF. This result could indicate that RS5 does indeed retain its protective effects with an altered gut microflora. This result could also suggest that MDF may not be a suitable lesion for colon cancer studies as the highest number of MDF were observed in saline treated animals. The deliberate addition of antibiotics was a novel approach in the colon carcinogenesis-diet interaction, but the results suggest that repeated experimentation is needed to confirm the retained protective effects of resistant starch diets.

Citation Format: Bridget Nelson, Yongfeng Ai, Carter Roberts, Peng Liu, Jay-lin Jane, Diane Birt. Resistant starch inhibition of azoxymethane-induced preneoplastic lesions with and without antibiotic treatment. [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 A35.
Abstract A37: Beta-cryptoxanthin restores nicotine-reduced lung SIRT1 to normal levels and inhibits nicotine-promoted lung tumorigenesis and emphysema in A/J mice
Authors: Iskandar Anita , Liu Chun , Smith Donald , Hu Kang-Quan , Choi Sang-Woon , Ausman Lynne , Wang Xiang-Dong
Published: January 2014

Nicotine, a large constituent of cigarette smoke, is associated with an increased risk of lung cancer but the data remains inconsistent. Here, we found that nicotine treatment not only induced emphysema, but also increased both lung tumor multiplicity and volume, in 4-nitrosamino-1-(3-pyridyl)-1-butanone (NNK)-initiated lung cancer in A/J mice. This tumor-promoting effect of nicotine was accompanied with significant reductions of survival probability and lung Sirtuin 1 (SIRT1), which has been proposed as a tumor suppressor. The decreased SIRT1 was associated with increased levels of AKT phosphorylation and interleukin (il)-6 mRNA, but decreased tumor suppressor p53 and retinoic acid receptor (rar)-beta mRNA levels in the lungs. Using this mouse model, we then determine whether a xanthophyll beta-cryptoxanthin (BCX), which is associated with a reduced risk of lung cancer from a pooled analysis of seven prospective cohort studies, can inhibit the nicotine-induced emphysema and lung tumorigenesis. We found that BCX supplementation at two different doses reduced the nicotine-promoted lung tumor multiplicity and volume, as well as emphysema in mice treated with both NNK and nicotine. Moreover, BCX supplementation restored the nicotine-suppressed lung SIRT1, p53, and rar-beta to the levels of the control group, increased the survival probability, and decreased the lung il-6 mRNA and AKT phosphorylation levels. The present study indicates that the SIRT1 is a potential target for the action of BCX against emphysema and lung cancer. In addition, our study established a relevant animal lung cancer model for studying tumor growth within emphysemateous microenvironments.

Citation Format: Anita Iskandar, Chun Liu, Donald Smith, Kang-Quan Hu, Sang-Woon Choi, Lynne Ausman, Xiang-Dong Wang. Beta-cryptoxanthin restores nicotine-reduced lung SIRT1 to normal levels and inhibits nicotine-promoted lung tumorigenesis and emphysema in A/J mice. [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 A37.
Abstract A39: Dietary supplementation with curcumin enhances metastatic growth of Lewis lung carcinoma in mice
Authors: Yan Lin
Published: January 2014

The present study investigated the effects of dietary supplementation with curcumin (the principal curcuminoid of the popular Indian spice turmeric) on spontaneous metastasis of Lewis lung carcinoma (LLC) in female C57/BL6 mice. Mice were fed the AIN93G control diet or that diet supplemented with 2% or 4% curcumin for 5 weeks at which time they were injected subcutaneously with 2.5 x 105 viable LLC cells. The subcutaneous primary tumor was surgically removed when it reached approximately 8 mm in diameter, and the experiment was terminated 10 days after the surgery. There was no difference in pulmonary metastatic yield among the groups. Curcumin supplementation at either dietary level did not significantly affect tumor growth. However, the combine data from both curcumin groups showed that curcumin treatment increased tumor cross-sectional area by 46% (p < 0.05) and tumor volume by 70% (p < 0.05) compared with the controls. Curcumin supplementation increased plasma concentrations of the angiogenic factors fibroblast growth factor-basic (p < 0.05) and vascular endothelial growth factor (p < 0.05), as well as the inflammatory cytokines interleukin-1β (p < 0.05) and monocyte chemotactic protein-1 (p < 0.05) compared with the controls. These results demonstrate that curcumin does not prevent metastasis, and indicate that it can enhance metastatic growth of LLC in mice, perhaps through up-regulation of angiogenesis and inflammation.

Citation Format: Lin Yan. Dietary supplementation with curcumin enhances metastatic growth of Lewis lung carcinoma in mice. [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 A39.
Abstract A41: Butyl benzyl phthalate induces metastasis and angiogenesis of hepatocellular carcinoma through a nongenomic AhR/G protein signaling
Authors: Tsai Eing-Mei , Tsai Cheng-Fang
Published: January 2014

The widespread use of phthalates as plasticizers particularly in polyvinylchloride (PVC) products has raised public health concerns recently due to their adverse health effects, including cancer. Although sufficient evidences of animal investigations suggested the association of phthalates exposure and hepatoma, the mechanisms remain unclear. This study of the effects of phthalates on hepatoma cells progression through AhR shows that butyl benzyl phthalate (BBP) stimulates AhR at the cell surface, interacts with G protein, and triggers the downstream signaling cascade. The experimental results suggest that BBP activates AhR through a nongenomic action, involving G protein signaling other than the classical genomic AhR action. Further experiments have shown that BBP induces both in vitro and in vivo angiogenesis through the AhR/ERK/VEGF pathway. Moreover, the study also reveals that BBP treatment promotes migration, invasion in vitro and metastasis in vivo via AhR/Gβ/PI3K/Akt/NF-κB pathway. Collectively, the findings suggest a novel nongenomic AhR mechanism of phthalates that contributes to tumor progression in hepatoma. The finding will be useful when developing approaches for preventing and treating liver cancer.

Citation Format: Eing-Mei Tsai, Cheng-Fang Tsai. Butyl benzyl phthalate induces metastasis and angiogenesis of hepatocellular carcinoma through a nongenomic AhR/G protein signaling. [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 A41.
Abstract A42: Estradiol induced prostaglandin E2 expression to regulate cell proliferation through MAPK/PI3K/COX2 signal pathway in Her2/neu breast cancer cell
Authors: Tsai Eing-Mei , Hsieh Tsung-Hua
Published: January 2014

Prostaglandin E2 (PGE2), a product of cyclooxygenase-2 (COX-2) enzymatic activity, induced aromatase activity which converts androgens to estrogens and mediates cell biological function. However, the relationship between estradiol (E2), COX-2 and PGE2 signaling pathway in Her-2/neu breast cancer cell was still unclear. In this report, we elucidate the mechanisms that mediate COX-2 expression and define the relationship of E2 and PGE2 with clinicopathological characteristics in breast cancer patients. The results were presented to demonstrate that the high level of PGE2 (P=0.02) and E2 (P=0.09) was significantly correlated with histological grade. To further investigate the signaling pathways mediating COX-2 gene expression, the experiments were performed in human breast cancer cell lines. In vitro study we found that time and dose courses of COX-2 were induced by E2 treatment in human breast adenocarcinoma cell lines Her-18(Her-2/neu stable expression cell lines), but not in MCF-7 cell lines. Furthermore, the effect was eliminated by pretreatment with MAPK, P38, PI3K, Her-2 inhibitor and estrogen antagonist ICI 182,780. Collectively, our data indicate that MAPK/PI3K/COX-2 is the functional signaling pathway intermediates linking Her-2/neu and E2 and suggest that inhibitors of PGE2 synthesis will suppress cancer cell proliferation in human breast cancer cell lines.

Citation Format: Eing-Mei Tsai, Tsung-Hua Hsieh. Estradiol induced prostaglandin E2 expression to regulate cell proliferation through MAPK/PI3K/COX2 signal pathway in Her2/neu breast cancer cell. [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 A42.
Abstract A50: PAR-4 (prostate apoptosis response-4) modulates cell survival and chemosensitivity to docetaxel in MCF-7 breast cancer cells
Authors: Pereira Michelly C. , Bessa-Garcia Simone A. de , Nagai Maria A.
Published: January 2014

PAWR (PKC apoptosis WT1 regulator) also known as prostate apoptosis response-4 (PAR-4) was first identified in prostate cancer cells undergoing apoptosis. It encodes a 332-amino-acid protein that induces cancer cell apoptosis, and causes tumor regression by activating Fas/FasL and inhibiting NF-κB activity. Experimental evidence indicates that PAR-4 is a central actor in cancer cell survival and may be a target for cancer-selective targeted therapeutics, however, little is currently known regarding its role in breast cancer tumorigenesis. In this study, we sought to investigate the effects of PAR-4 over-expression and suppression on cell proliferation, apoptosis, and drug sensitivity in breast cancer cells. MCF-7 cells were stably transfected with expression vectors for PAR-4 over-expression, or transiently transfected with siRNA for PAR-4 knockdown. Proliferation assays were performed using MTT, and apoptosis was evaluated using acridine orange staining, fluorescence microscopy, and flow cytometry. PAR-4 over-expression reduced MCF-7 proliferation rates compared with parental or control cells. Conversely, PAR-4 knockdown led to increased MCF-7 proliferation. Par-4 down-regulation also led to increased BCL-2 and reduced BID transcripts. PAR-4 over-expression did not affect the cell cycle profile. However, MCF-7 cells with increased Par-4 expression showed reduced ERK phosphorylation, suggesting that the inhibition of cell proliferation promoted by Par-4 is mediated by the MAPK/ERK1/2 pathway. MCF-7 cells with increased Par-4 expression showed an increased proportion of early apoptotic cells. Increased Par-4 expression also enhanced the sensitivity of MCF-7 breast cancer cells to docetaxel. PAR-4 has inhibitory effects on breast cancer cell proliferation and survival, and may increase breast cancer cells' chemosensitivity.

Supported by FAPESP and CNPq.

Citation Format: Michelly C. Pereira, Simone A. de Bessa-Garcia, Maria A. Nagai. PAR-4 (prostate apoptosis response-4) modulates cell survival and chemosensitivity to docetaxel in MCF-7 breast 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 A50.
Abstract A70: Ginger phytochemicals exhibit robust synergy to inhibit prostate cancer cell proliferation
Authors: Gundala Sushma Reddy , Brahmbhatt Meera , Aneja Ritu
Published: January 2014

An emerging notion accepts cancer as a preventable lifestyle disease. Fruits and vegetables offer non-toxic therapeutic options for prostate cancer in particular, since its slow growth offers a wide window for chemopreventive intervention. Fruits and vegetables contain various phytochemicals, including polyphenols and flavonoids that are well-known for their anti-inflammatory, and antiproliferative roles. However, the failure of several single-agent clinical trials has fueled a paradigm shift to appreciate that health benefits of fruits and vegetables are not ascribable to individual phytochemicals but rather to synergistic interactions among them. We recently reported the growth-inhibiting and apoptosis-inducing properties of whole ginger extract (GE) in in vitro and in vivo prostate cancer models. Nevertheless, the nature of interactions among the constituent ginger biophenolics, viz. 6-gingerol (6G), 8-gingerol (8G), 10-gingerol (10G), and 6-shogoal (6S), remains elusive. Here we show the antiproliferative efficacy of the most-active biophenolics present in GE as single-agents and in binary combinations, and investigate nature of their interactions using the Chou-Talalay combination-index (CI) method. Our data demonstrate that binary combinations of ginger phytochemicals synergistically inhibit cellular proliferation of human prostate cancer PC-3 cells with CI values ranging from 0.03 to 0.88. To appreciate synergy among ginger phytochemicals present in GE, the natural relative abundance of ginger biophenolics was quantitated using LC-UV/MS methods. Interestingly, combining GE with its constituents (in particular, 6G) resulted in significant augmentation of GE's antiproliferative activity. These data generate compelling grounds for further preclinical evaluation of GE alone and in combination with individual ginger biophenols for prostate cancer management.

Citation Format: Sushma Reddy Gundala, Meera Brahmbhatt, Ritu Aneja. Ginger phytochemicals exhibit robust synergy to inhibit prostate cancer cell proliferation. [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 A70.
Abstract A71: Curcubitacin B exhibits cytotoxic effects by inhibiting Integrin-HER2 signaling in breast cancer cells
Authors: Gupta Parul Gupta , Srivastava Sanjay K.
Published: January 2014

Integrins have recently been shown to play an important role in promotion of cell motility and survival in various cancers through cooperative signaling with EGFRs. Integrins transmit cell survival signals through ILK-Paxillin complex and further play role in activating AKT signaling. Curcubitacin B (CuB) is a steroidal class of chemical present in the plants belonging to cucurbitaceae family. CuB has shown cytotoxic potential in several cancers by causing G2/M cell cycle arrest and inhibition of JAK/STAT3 pathway. However, the exact mechanism of CuB and its role in metastasis and cell survival is not known. Our results show that CuB significantly suppressed the growth of MDA-MB-231, SKBR3, HCC1806 and MCF-7 breast cancer cells in a concentration and time-dependent manner. CuB also induced apoptosis and down-regulated ILK1 expression. In addition, CuB down-regulated ITGB4 and ITGA6 protein expression and suppressed the phosphorylation of AKT at Ser473, paxillin at Tyr118. Previous studies have shown that TGFβ mediates physical association of ITGB4 and HER2, through Src kinase to enhance cell survival and motility. Interestingly we observed significant downregulation of Src, EGFR and HER2 in different breast cancer cells, suggesting that CuB suppresses cooperative signaling of Integrins and HER2. We also observed that TGFβ pretreatment imparted protection from CuB's cytotoxic effects, indicating that CuB modulates TGFβ mediated Integrin signaling. Taken together our results indicate the anti-cancer effects of CuB in breast cancer cells by targeting ITGB4/ITGA6, Src, ILK and TGFβ. Further detailed mechanistic work is in progress. [Supported in part by R01 grants CA106953 and CA129038 (to S.K.S) awarded by the National Cancer Institute].

Citation Format: Parul Gupta Gupta, Sanjay K. Srivastava. Curcubitacin B exhibits cytotoxic effects by inhibiting integrin-HER2 signaling in breast 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 A71.
Abstract A72: Efficacy and safety of multiple doses of polyphenon E in prostate cancer using TRAMP mice
Authors: Ha Jick Hwan , Kim Seung Joon , Lee Hea Yon , Yeo Chang Dong , Park Chan Kwon , Lee Sang Haak , Park Jong Y.
Published: January 2014

Purpose: The purpose of this study was to assess the efficacy and safety of polyphenon E as a chemopreventive agent against prostate cancer using the transgenic adenocarcinoma of mouse prostate (TRAMP) mice model.

Experimental Design: Seven week old 128 male control C57BL/6 mice and 128 male TRAMP mice were treated with 3 different doses of polyphenon E orally at a human achievable dose. Animals were sacrificed at 12, 22, and 32 weeks of age. For the safety study, complete blood counts with leukocyte differentials and blood chemistry levels for liver and kidney functions were determined. For the efficacy study, weight of the prostate, tumor progression and metastasis, and histopathological evaluation of all organs were assessed. Prostate histology was assessed separately for each lobe of the prostate (i.e., the anterior, dorsal, lateral, and ventral lobes) since lesions progress differently in each lobe of the mouse.

Results: Polyphenon E treatment significantly inhibited prostate cancer progression and metastasis in TRAMP mice model. As expected, metastases were observed in all untreated TRAMP mice (100%, 8 of 8) at 32 weeks of age. However, significant reductions were found in all three polyphenon E treated groups with a dose response manner. 50% (6 of 12), 27% (3 of 11), and 12.5% (2 of 12) of low, intermediate, and high dose treated groups exhibited metastasis of prostate cancer to distant organ sites, respectively. Furthermore, treated TRAMP mice resulted in significant delay in tumor progression from 12 to 32 weeks of age with a dose response manner. No adverse effect in polyphenon E treatment group was found in control C57BL/6 mice up to 32 weeks of age regardless amount of polyphenone E treatment.

Conclusion: Polyphenon E was an effective chemopreventive agent in the progression of prostate cancer in the animal model. Polyphenon E also showed minimal toxicity in the mice model.

Citation Format: Jick Hwan Ha, Seung Joon Kim, Hea Yon Lee, Chang Dong Yeo, Chan Kwon Park, Sang Haak Lee, Jong Y. Park. Efficacy and safety of multiple doses of polyphenon E in prostate cancer using TRAMP mice. [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 A72.