bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A143: Vaccination of a concatenated L2 fusion protein with L1 VLP or capsomeres for broad protection against HPV infection
Authors: Jagu Subhashini , Kwak Kihyuck , Garcea Robert L. , Roden Richard B.S. 
Published: May 2012

Abstract
Background: Immunization with L1 major capsid protein in the form of the pentavalent capsomeres or 360mer virus-like particles (VLPs) generates high and long-lived titers of neutralizing antibodies and protection primarily against the human papillomavirus (HPV) type from which the vaccine was derived. Consequently, multivalent L1 VLP vaccines have been developed to expand the breadth of coverage, e.g. Cervarix which contains L1 VLPs that are derived from HPV16 and HPV18 and formulated in alum and monophosphoryl lipid A (MPL) adjuvant. Vaccination with L2 minor capsid protein induces lower titer, but more broadly neutralizing and protective antibody responses in animals. To enhance cross-protection we generated multi-type L2 proteins by fusing cross-neutralizing epitopes of divergent HPV types, e.g. 11-88×5 that is a concatamer of L2 residues 11–88 of HPV1, HPV5, HPV6, HPV16 and HPV18.
Objectives: A low cost HPV vaccine that yields cross-protective antibodies and broad protection against more than a dozen oncogenic HPV types is urgently needed. We sought to combine the advantages of each protective antigen by immunization with titrated doses of multi-type L2 11-88×5 in alum+MPL, or with either HPV16 L1 capsomeres or Cervarix and to assess the importance of adjuvant for L2 dose sparing.
Methods: Mice were vaccinated three times every alternate week and bled two weeks later. Serum antibody titers were determined by ELISA using HPV16 L1 VLP or L2 11-88×5antigen, as well as in vitro HPV pseudovirion neutralization assays.
Results: The absolute titers and dose response to 11-88×5 were similar in mice vaccinated with 11-88×5 alone or in combination with either L1 capsomeres or VLPs. HPV16 L1 VLP generated significantly higher HPV16 neutralization titers than L1 capsomeres, and the capsomeres induce higher titers than 11-88×5. Importantly, the serum IgG titers specific to HPV16 L1 VLP were not influenced by vaccination with L1 capsomeres or VLP in the presence of L2 11-88×5. The in vitro neutralization titers elicited by vaccination with 11-88×5 in the combinations tested were not significantly different at two weeks after immunization but there was a trend at four months for reduced cross-neutralization when 11-88×5 was combined with L1 VLP but not capsomeres.
Conclusions: There is no evidence of interference between the L1 and L2 serum antibody response to co-administration of L1 capsomeres, but not VLP, with multi-type L2 vaccines based on neutralization titers.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A143.
Abstract A20: Random periareolar fine-needle aspiration is highly reproducible in a CALGB multi-institutional cross-sectional study
Authors: Seewaldt Victoria L. , Ibarra Catherine , Yee Lisa D. , Wilke Lee G. , Kulkarni Swati , Wood Marie , Garber Judy , Ford Anne 
Published: May 2012

Abstract
Background: Biomarkers that vary with risk and response to prevention interventions are referred to as “surrogate endpoint biomarkers”. As outlined by Fabian et al., surrogate endpoint biomarkers should be 1) biologically and statistically significantly associated with cancer development, 2) present in a reasonable proportion of at-risk individuals, 3) obtainable by minimally invasive procedures, and 4) reversible with prevention interventions that have been validated to decrease cancer incidence. Many modalities have been suggested as potential surrogate endpoint biomarkers for breast cancer, including mammographic density, serum biomarkers, and breast tissue biomarkers. Currently, there is no consensus as to the optimal surrogate endpoint biomarker.
Random Periareolar Fine Needle Aspiration (RPFNA) is a research technique developed to assess short-term breast cancer risk in women at increased risk for breast cancer. While there is increasing acceptance of RPFNA, neither the reproducibility nor the inter-institutional compatibility of RPFNA has been established. To address these key limitations, the Cancer and Leukemia Group B (CALGB) Prevention Group tested the reproducibility of RPFNA in a multi-institutional cross-sectional study.
Methods: Sixty-three high-risk women from five CALGB institutions (Duke, Ohio State, Roswell Park, Dana-Farber, and Vermont) underwent RPFNA from July 1, 2007 to June 30, 2008. Duplicate bilateral RPFNA was performed on each woman by a single investigator on a single day. Masood Cytology Index score was assessed by a single blinded cytopathologist.
Results: There was a high degree of statistical agreement in the Masood Cytology Index scores of duplicate RPFNA samples from the same breast, with a Spearman correlation coefficient of 0.8312 (p&lt;0.0001). Importantly, while there was agreement in duplicate samples from the same breast, there was lack of agreement between duplicate samples from the opposite breast.
Conclusions: This multi-institutional study demonstrates that RPFNA is a highly reproducible measure of breast cytology in a cooperative group cross-sectional trial. RPFNA did not demonstrate a high degree of agreement between breasts, suggesting that breast cancer risk and progression may occur at different rates in individual breasts from a single woman.
These data provide important validation of the reproducibility of RPFNA in a multi-institutional cross-sectional study that included cohorts that varied in demographic composition. Important future directions will include a larger RPFNA cohort study and testing for the reproducibility of RPFNA samples with atypia before and after administration of chemoprevention agents.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A20.
Abstract A34: Nonmelanoma skin cancer and the risk of second primary cancers: A systematic review
Authors: Wheless Lee , Black Joshua , Alberg Anthony J. 
Published: May 2012

Abstract
Context: Based on empirical evidence, the hypothesis has been set forth that a personal history of non-melanoma skin cancer (NMSC) may be a marker of a high cancer-risk phenotype. Others hypothesize that NMSC may be a marker of high vitamin D synthesis and therefore inversely associated with risk of other malignancies.
Objective: To reconcile these divergent views, we carried out a systematic review to determine the overall association between nonmelanoma skin cancer and subsequent risk of other cancers.
Data Sources: PubMed and Ovid/MEDLINE databases were searched through March 2009. The formal search was supplemented by hand searches.
Study selection: Articles were included if sufficient information was presented to estimate the risk of developing other cancers following NMSC.
Data extraction: Articles were reviewed and data abstracted independently in duplicate with disagreements decided by consensus.
Results: Of the 21 included articles, 15 presented on NMSC in relation to risk of all other cancers combined. NMSC was associated with a 17% increased future risk of another malignancy (summary random-effects RR (SRR) 1.17, 95% confidence interval (CI) 1.11–1.22). This association held true for both squamous cell carcinoma (SRR 1.21, 95% CI 1.14–1.28) and basal cell carcinoma (SRR 1.15, 95% CI 1.07–1.24), and both men (SRR 1.15, 95% CI 1.09–1.20) and women (SRR 1.10, 95% CI 1.04–1.15).
Conclusions: Strong, consistent evidence indicates that a personal history of NMSC is associated with an increased risk of developing other malignancies. For reasons that are presently unknown, nonmelanoma skin cancer may be a marker of a high cancer-risk phenotype.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A34.
Abstract A4: SNP-SNP interaction and nongenetic risk factors combine to identify lung cancer susceptibility: Validation in a prospective study
Authors: Young Robert , Hopkins Raewyn , Hay Bryan , Gamble Greg 
Published: May 2012

Abstract
Introduction: Key risk indicators for lung cancer include a smoking history, genetic factors, increasing age, family history and impaired lung function (COPD). In a case-control study, 20 genetic markers associated with lung cancer were combined with non-genetic risks to derive a lung cancer susceptibility score (LCSS). The aim of this prospective follow up study was to compare the LCSS in a cohort of very high risk smokers, with and without lung cancer.
Methods: A cohort of 728 high risk individuals (smoker/ex-smokers, &gt;40 yrs old, &gt;20 pack years, with spirometric confirmed COPD) were recruited and followed for a mean of 5 years. All volunteers underwent spirometry, completed a modified ATS respiratory questionnaire and gave blood for DNA. These volunteers were recruited from the community (N=420) and a COPD outpatient clinic (N=308). To date, we have identified 53 cases of lung cancer (histology confirmed) in this cohort (24 community and 28 clinic). The 20 SNP panel was genotyped using the iPLEX system. Each subjects' genotypes were combined, in a predefined algorithm, to derive the lung cancer susceptibility score.
Results: COPD patients subsequently diagnosed with lung caner were comparable to those with no lung cancer for age, gender, smoking exposure. The mean LCSS, was higher in those who developed lung cancer than those who did not (LCSS 7.0 vs 5.7, P=0.06), and significantly higher than those recruited from the community with mild-moderate COPD (LCSS 7.0 vs 4.7, P&lt;0.001). The performance characteristics of the LCSS reported here, confirms its utility in high risk smokers, to target lung cancer screening and/or diagnostic approaches (using molecular, cytological and/or radiological based tools).
Conclusion: We show, in a prospectively recruited high risk cohort, that our LCSS identifies those with mild-moderate COPD at greatest risk of lung cancer. Such a group might benefit from aggressive screening/diagnostic approaches, so that their lung cancer is diagnosed in stage 1 when survival has been shown to be dramatically improved.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A4.
Abstract A41: Regulation of Nrf2-dependent gene expression in aging
Authors: Ma Quan , Han Zheyi , Yu Rong 
Published: May 2012

Abstract
Nrf2 is a transcription factor which controls induction of antioxidant and detoxification enzymes, and, therefore, plays an essential role in protection against chemical carcinogens. Here, we reported that expression of Nrf2 and its dependent genes was affected by age and became compromised in aged mouse livers. Detail analysis revealed that age-dependent Nrf2 expression was regulated primarily at transcriptional level. Accordingly, we cloned and characterized the promoter region of mouse Nrf2 gene. We identified multiple Sp1 binding sites and confirmed their binding activity by gel-shift and chromatin immunoprecipitation assay. We also showed that the identified Sp1 sites were functional since knockdown of Sp1 expression impaired Nrf2 promoter activity as well as expression of Nrf2-dependent genes. We then compared Sp1 expression and its binding activity to Nrf2 promoter in young and aged mouse liver tissues. While no significant change in Sp1 expression was found, Sp1 binding activity was severely impaired in aged tissues. Given that Sp1-binding sites are GC rich elements, we analyzed their methylation status in Nrf2 promoter, and found that Sp1 sites were highly methylated in aged tissues. In support of the role of methylation, treatment of a mouse hepatoma cell line with demethylase inhibitors indeed reduced Sp1 binding to Nrf2 promoter. We also cloned and analyzed human Nrf2 promoter. Multiple Sp1 binding sites were identified and shown to be equally functional as in mouse Nrf2 promoter. Thus, we propose that age-dependent expression of Nrf2 and its downstream genes is regulated by methylation. A strategy that targets methylation would help to restore Nrf2-mediated protection against oxidative stress or chemical carcinogens in aged tissues.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A41.
Abstract A59: Xanthohumol from hops (Humulus lupulus L.) generates superoxide anion radicals via a mitochondria-mediated mechanism
Authors: Strathmann Julia , Klimo Karin , Sauer Sven , Okun Juergen , Prehn Jochen , Gerhauser Clarissa 
Published: May 2012

Abstract
Xanthohumol (XN), a polyphenol from hops (Humulus lupulus L.), exerts a broad spectrum of cancer chemopreventive activities, including the induction of apoptosis in human cancer cell lines. We speculated that apoptosis induction involved pro-oxidant effects at the mitochondrial membrane, leading to uncoupling of the respiratory chain and subsequent membrane collapse. Here, we investigated whether XN has potential to induce reactive oxygen species (ROS). By co-treatment of benign prostate hyperplasia cells (BPH-1) with XN and dihydroethidium (DHE), specifically oxidized by superoxide anion radicals (O2-*), we measured an immediate dose- and time-dependent increase in fluorescence, whereas Amplex Red, specific for hydrogen peroxide (H2O2), was not oxidized, indicating the formation of O2-*. O2-* formation was significantly inhibited by co-treatment with the anti-oxidants ascorbic acid and N-acetyl cysteine or the superoxide dismutase mimetic MnTMPyP. Fluorescence microscopy images of BPH-1 stained with MitoSOX Red, specific for mitochondrial O2-*, suggested a mitochodrial origin of O2-* formation, which was confirmed by XN-mediated induction of O2-* in isolated mitochondria. Furthermore, in BPH-1-ρ0 (rho-zero) cells, harboring non-functional mitochondria, XN-treatment did not induce O2-*. As one mechanism of XN-mediated O2-* formation, we hypothesize that XN is oxidized to its respective phenoxylradical by intracellular oxidases in the presence of glutathione (GSH) and traces of H2O2, which produces O2-* as side poduct. This was supported by the finding that inhibition of oxidases with diphenylene iodonium (DPI) significantly inhibited XN-induced O2-* formation. Additionally, we demonstrated a time- and dose-dependent increase in oxidized glutathione (GSSG) and global GSH depletion upon XN-treatment. Strikingly, within 15min after XN treatment, intracellular ATP production was reduced by 94% and we observed direct inhibition of complexes I – III of the respiratory chain in submitochondrial particles from bovine heart, as well as in BPH-1. In parallel, the mitochondrial membrane potential broke down already after 10min of XN-treatment and as a consequence, release of cytochrome c was observed, leading to the induction of apoptosis.
In this study, we demonstrate cancer chemopreventive activity of XN by the induction of O2-*, which disrupts the cellular redox balance and mitochondrial integrity and subsequently triggers cancer cells into apoptosis.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A59.
Abstract A68: Aromatase inhibition and chemopreventive potential of novel resveratrol derivatives
Authors: Marler Laura E. , Cushman Mark , Sun Bin , Mesecar Andrew D. , Jermihov Katie , van Breemen Richard B. , Pezzuto John M. 
Published: May 2012

Abstract
Resveratrol, a naturally occurring stilbene found in the human diet, has been shown to mediate a host of biological activities. It has been reported to display both estrogenic and anti-estrogenic activities, depending on cell type and conditions, but inhibition of aromatase activity is weak (IC50 = 25 µM). We have conducted a systematic study in which about 60 substituted stilbenes were synthesized and evaluated for biologic potential. Several of these synthetic derivatives were found to inhibit aromatase activity with IC50 values in the sub-micromolar range. Within the series, structure-activity relationships demonstrated substitution of an amine group produced greater inhibition than a nitro group, and the position of these groups was of greater importance than the number and position of methoxy groups. Compound 1 [(E)-4-(3,5-dimethoxystyryl)aniline] was one of the most potent inhibitors, with an IC50 of 0.31 µM, which is comparable to that of aminoglutethimide (IC50 = 0.2 µM). In addition, crystallographic analysis revealed compound 1 binds to quinone reductase 2 in an orientation similar to that of resveratrol, but demonstrates greater inhibitory potency. Compound 1 has been synthesized on a multigram scale, oral administration with laboratory animals indicates excellent absorption and good metabolic stability, and more advanced testing is underway. (Supported by program project P01 CA48112 awarded by the National Cancer Institute)
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A68.
Abstract A76: Curcumin inhibits head and neck squamous cell carcinoma (HNSCC) migration
Authors: Clark Cheryl A. , Rong Joyce , Nathan Cherie-Ann O. 
Published: May 2012

Abstract
Purpose: Curcumin has been shown to inhibit HNSCC cell proliferation through the AKT/MTOR pathway. We wanted to study the biological effects of curcumin-induced AKT/MTOR inhibition in HNSCC.
Procedures: Soluble proteins (pS6, p4EBP1, FGF2 and MMP-9) extracted from cells treated with or without 20µM curcumin overnight were analyzed by western blot. Cell motility with and without 5, 10, and 20µM curcumin was determined by transwell migration assay and compared using one-way ANOVA in four HNSCC cell lines (FaDu, PCI15A, SCC40 and SCC066).
Results: We used the highly invasive SCC cell line PCI15a to investigate the effects of curcumin on the AKT/MTOR pathway in vitro. Phosphorylated S6 (pS6) and p4EBP1 were inhibited in cells treated with 20µM curcumin for 24 hours. Curcumin inhibited the downstream effector FGF2 by 80% in SCC40 and completely abrogated the downstream effector MMP-9 in the PCI15a cell line. Compared to vehicle, curcumin significantly inhibited migration of the HNSCC cell lines in the transwell migration model. A significant dose-response was found among the four curcumin concentrations for all four cell lines compared to vehicle (p&lt;0.001).
Conclusions: Curcumin inhibits migration of HNSCC cell lines trough the AKT/MTOR pathway and its downstream targets. Cancer cell migration is a highly regulated process that permits dissemination from the primary tumor. Concentrations that inhibited cell proliferation through inhibition of AKT/MTOR and its downstream target MMP-9 were sufficient to inhibit the invasion of a variety of HNSCC cell lines in vitro. This sensitivity of HNSCC cells to retardation of cell migration by curcumin further highlights its chemopreventive properties.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A76.
Abstract B107: The association of soy consumption and lung cancer among Japanese women: Analyses stratified by smoking status and reproductive factors
Authors: Okasaka Toshiki , Matsuo Keitaro , Ito Hidemi , Hosono Satoyo , Kawase Takakazu , Tanaka Hideo , Yokoi Kohei , Tajima Kazuo 
Published: May 2012

Abstract
Soybean products intake has been suggested to have protective effects against breast cancer. As for lung cancer, we previously reported that soy consumption showed inverse association with the risk of non-small cell lung cancers (NSCLC) with epidermal growth factor receptor mutations among Japanese. However, other possible heterogeneity of its effect on the etiology of NSCLC by background characteristics is still unclear. In this study, we investigated the impact of soy consumption on the development of NSCLC among larger number of Japanese women, with the association of smoking status, reproductive factors, as well as histology.
We conducted a case-control study with 420 NSCLC women cases and 840 age-sex matched control subjects. Dietary exposures were evaluated based on a semi-quantitative food frequency questionnaire, including items on lifestyles, menstrual and reproductive history. Soy consumption was categorized into two groups: a lower third group, “Low consumption group (LCG)” which intake of soy was less than 30.3 mg/day, and others, “High consumption group (HCG)” which intake of soy were 30.3mg/day or more. We assessed the impact of soy consumption on lung cancer by calculating odds ratios (ORs) and their 95% confidence intervals (CIs) of HCG, relative to LCG with adjustment for potential confounding factors using logistic regression model.
In the overall analysis, we observed inverse association with high consumption of soy products [OR: 0.87, 95%CI: 0.65–1.16]. When stratified by smoking status, HCG in never smokers showed significantly inverse association showed an OR below unity [OR: 0.69, 95%CI: 0.50–0.96] in spite of the increased OR among HCG in ever smokers [OR: 2.02, 95%CI: 1.11–3.68]. As for reproductive factors, ORs of HCG were consistently below unity among women with pre-menopause [OR: 0.55, 95%CI: 0.29–1.04], menopause after 50 years old [OR: 0.57, 95%CI: 0.34–0.94], and no delivery [OR: 0.57, 95%CI: 0.15–1.06]. It is interesting to note that on histology based analysis, we found inverse association between high consumption of soy products and adenocarcinoma [OR: 0.57, 95%CI: 0.34–0.94] among never smokers, despite the increased ORs were seen among ever smokers [OR: 3.35, 95%CI: 0.17–67.7].
In this study, consumption of soybean products generally demonstrated an inverse association with NSCLC. In addition, the results indicated the interaction between soy consumption and smoking status for the impact on the development of NSCLC. We also found associations among soy consumption, reproductive factors and lung cancer, which indicated that female hormonal factors might be involved in the etiology of NSCLC. Further epidemiological evaluation is warranted.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B107.
Abstract B119: Racial variation in umbilical cord blood leptin concentration in male babies
Authors: Lai Gabriel Y. , Rohrmann Sabine , Agurs-Collins Tanya , Sutcliffe Catherine G. , Bradwin Gary , Rifai Nader , Bienstock Jessica , Platz Elizabeth A. 
Published: May 2012

Abstract
Objective: Because studies have reported that higher birth weight is associated with higher prostate cancer risk later in life, we hypothesized that racial differences in utero affecting birth weight contribute to the racial disparity in prostate cancer risk. Leptin is a candidate for evaluating this hypothesis because it may influence fetal development, and levels in adulthood have been associated with prostate cancer risk in some studies.
Methods: Leptin concentration was measured by ELISA in venous cord blood collected from 70 African-American and 37 white male full-term births. Sex steroid hormones and insulin-like growth factor (IGF) axis concentrations were measured previously. Separately by race, we calculated geometric mean leptin concentrations and estimated adjusted geometric means using linear regression.
Results: Leptin was positively correlated with birth (r=0.34) and placental (r=0.25) weights, IGF-1 (r=0.21), and IGF binding protein (BP)-3 (r=0.29) adjusting for race. Mean (± standard error) birth weight was lower (p=0.0011) in African-American (3,237 ± 342 g) than white (3,477 ± 395 g) male babies. Unadjusted geometric mean leptin did not differ (p=0.92) between African Americans (5,280 pg/mL; 95% CI: 4,322–6,451) and whites (5,187 pg/mL; 95% CI: 3,938–6,832). However, adjusted geometric mean leptin was nonstatistically significantly higher (p=0.15) in African Americans (5,954 pg/mL; 95% CI: 4,725–7,502) than whites (4,133 pg/mL; 95% CI: 2,890–5,910).
Conclusion: We observed a non-significantly higher adjusted cord blood leptin concentration in African-American compared with white male babies, although unadjusted levels were similar. If our hypothesis were correct, we would have expected higher unadjusted leptin levels and birth weight among African-American babies. Funding: NCI grants U54 CA091409, U54 CA091431, T32 CA009314; doctoral research fund, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B119.