bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B83: Sulfiredoxin is an AP-1 target gene that is required for transformation and shows elevated expression in human skin tumors
Authors: Wei Qiou , Jiang Hong , Matthews Connie , Colburn Nancy 
Published: May 2012

Abstract
B83
Previous studies from others and our lab have shown that activator protein 1 (AP-1) plays a pivotal role in tumorigenesis in vitro and in vivo. Expression of a dominant negative form c-Jun, TAM67, dramatically inhibits tumor promoter induced skin carcinogenesis. In this study, our goals are to identify target genes that are specifically induced by tumor promoter and inhibited by TAM67, and to investigate their functional significances in tumor promotion and progression. First, we demonstrated that Sulfiredoxin (Srx) is a novel target of AP-1 activation and TAM67 inhibition. In mouse epidermis, expression of Srx was upregulated by tumor promoter and inhibited by TAM67 as revealed by DNA microarray. This was further confirmed in mouse epithelial-derived JB6 cells by RT-PCR, Western blotting, luciferase reporter and chromatin immunoprecipitation assays at transcript and protein levels. Next, we demonstrated that Srx is important for maintaining of cellular redox homeostasis through reduction of overoxidized Peroxiredoxins (Prxs). Knockdown of Srx led to a much slower reduction rate of overoxidized Prxs, whereas overexpression of Srx resulted in an increased reduction rate of overoxidized Prxs. Then we found that knockdown of Srx dramatically inhibited tumor promoter induced neoplastic transformation as indicated by anchorage-independent growth in soft agar. This effect was not due to the inhibition of cell proliferation as depletion of Srx stimulated cell proliferation under adherent conditions. Depletion of Srx also led to impaired AP-1 activation and increased cell death under oxidative conditions, which indicated that Srx might be involved in the regulation of AP-1 activity through a novel positive feedback loop. Finally, we examined the expression profiling of Srx in normal skin and tissues from patients with various skin diseases by tissue microarray. We found strong positive expression of Srx in skin malignant tumors. In summary, we identified Srx as a novel target of tumor promoter induced AP-1 activation and is inhibited by TAM67. We demonstrated that Srx is important for maintaining of cellular redox balance and is required for tumor promoter induced neoplastic transformation. We also found strong expression of Srx in human skin malignant tumors. Therefore, we propose that Srx can be used as a marker for skin malignancy, and manipulation of Srx expression may be of interest in cancer prevention and treatment.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B83.
Abstract B88: Plasma carotenoids, tocopherols, retinol and breast cancer risk: Results from the Shanghai Women's Health Study
Authors: Dorjgochoo Tsogzolmaa , Yu-Tang Gao , Chow Wong-Ho , Shu Xiao-ou , Li Honglan , Yang Gong , Cai Qiuyin , Rothman Nathaniel , Cai Hui , Franke Adrian , Zheng Wei , Dai Qi 
Published: May 2012

Abstract
B88

Objective
Studies conducted in Western countries have suggested that lipophilic antioxidants, particularly carotenoids, may have preventive effects on the risk of breast cancer. We prospectively investigated the associations of serum levels of tocopherols, total retinol, total and specific types of carotenoids with the risk of developing breast cancer among Chinese women; a population with low risk of breast cancer and low prevalence of vitamin supplement use.

Methods
A nested case-control study was conducted within the cohort of the Shanghai Women’s Health Study including 365 newly-diagnosed cases and 726 individually-matched controls 40-70 years of age who provided a blood sample at baseline. Multivariate conditional logistic regression analyses were used to assess associations between breast cancer risk and antioxidants.

Results
Overall, we did not observe significant associations between any of the tocopherols, retinol and most carotenoids, and breast cancer risk. Plasma levels of lycopene other than trans, 5-cis and 7-cis were associated with a reduced risk with an OR of 0.56 (95% CI: 0.32-0.97) for the highest quartile versus the lowest after adjusting for plasma levels of other antioxidants. This inverse association was seen predominantly among premenopausal women with a corresponding OR (95% CI) of 0.36 (0.16-0.80). We also found that trans α-cryptoxanthin was associated with a reduced risk of breast cancer in a dose-response manner, with a corresponding OR of 0.59 (95% CI: 0.34-1.01) (P trend, 0.02) and the inverse association for trans α-cryptoxanthin appeared in both pre- and post-menopausal women.

Conclusions
Our study did not show strong evidence for an overall protective effect of plasma lipophilic antioxidants on breast cancer risk. The few significant inverse associations for subtype carotenoids need to be confirmed in future studies.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B88.
Abstract B93: Concatenated multitype L2 fusion proteins as prophylactic human papillomavirus vaccines
Authors: Jagu Subhashini , Karanam Balasubramanyam , Gambhira Ratish , Chivukula Sudha , Chaganti Revathi , Lowy Douglas , Schiller John , Roden Richard 
Published: May 2012

Abstract
B93
Vaccination with minor capsid protein L2, is known to induce antibodies that cross-neutralize diverse papillomavirus types.However, neutralizing titers against the homologous type are generally much higher than the titers against heterologous types. We hypothesized that vaccination with concatenated multi-type L2 fusion proteins derived from known cross-protective epitopes of several divergent HPV types might increase immunity across medically significant HPV genotypes. Here, the antibody responses of mice and rabbits to vaccination with HPV16 L2 polypeptides comprising residues 1-88 or 11-200, was compared with multi-type L2 fusion proteins, namely 11-200x3 types (HPV6, 16, 18), 11-88x5 types (HPV1, 5, 6,16, 18), or 17-36x22 types (5 cutaneous, 2 mucosal low risk and 15 oncogenic types), and with a licensed quadrivalent HPV L1 virus-like particle (VLP) vaccine, Gardasil. The monotype L2 polypeptides generated robust neutralization titers against HPV16 but lower titers against other HPV types. In contrast, the antisera to the multi-type L2 fusion proteins, notably 11-200x3 and 11-88x5, induced high neutralizing titers against all heterologous HPVs tested. However, in mice, these neutralizing titers were consistently lower than those to L1 VLP. The in vitro neutralization titers elicited by vaccination with 11-200x3 in different adjuvant combinations tested were not significantly different at two weeks after immunization. However, the vaccines formulated in GPI-0100 adjuvant or alum and ISS 1018 protected mice against HPV16 challenge at four months after immunization in the same manner as HPV16 L1 VLP, whereas 11-200x3 alone or formulated with either alum or ISS 1018 alone was significantly less effective.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B93.
Abstract CN15-01: Aspirin, COX-2, and colorectal cancer
Authors: Chan Andrew 
Published: May 2012

Abstract
CN15-01
Considerable experimental, epidemiological, and clinical data has provided strong evidence for a causative link between chronic inflammation and colorectal cancer, including the well-described association between inflammatory bowel disease and colonic dysplasia. However, beyond inflammatory bowel disease, the precise role of inflammation in sporadic colorectal cancer remains undefined. Inflammation may predispose to cancer through enhanced cellular proliferation and mutagenesis, inability to adapt to oxidative stresses, promotion of angiogenesis, inhibition of apoptosis, and secretion of mediators that may promote tumorigenesis. A specific mechanism through which inflammation promotes carcinogenesis is the pro-inflammatory cyclooxygenase-2 pathway (COX-2). A role for COX-2 in neoplasia is supported by several lines of evidence: 1) “knock-out” of the COX-2 gene inhibits development of polyps in the APC mutant mice; 2) host expression of COX-2, but not COX-1, is required for survival of mouse tumor xenografts; 3) COX-2, but not COX-1, is progressively overexpressed in human colorectal adenomas and cancers; 4) COX-2 gene expression is highly upregulated even in morphologically normal mucosa of APC mutant mice and human colorectal cancer patients; 5) agents with COX-2 activity are effective in inhibiting neoplasia in both animals and humans. In fact, at least six randomized trials have demonstrate that anti-inflammatory drugs such as aspirin and COX-2 selective inhibitors reduce the risk of colorectal adenoma among patients with a prior history of colorectal neoplasia. Recently, in two large prospective cohorts, we observed that aspirin reduces risk of COX-2 positive colorectal cancer but not risk of COX-2 negative colorectal cancer. This data suggest that the anti-cancer benefit of aspirin is primarily mediated through COX-2 inhibition. However, the optimal use of aspirin in light of its associated toxicities remains uncertain. Nonetheless, these results support the importance of continued investigation into COX-2 and related inflammatory pathways to both define markers of susceptibility to colorectal cancer as well as spur development of new preventive interventions.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):CN15-01.
Abstract PR-5: A pooled analysis of 14 cohort studies of body mass index and pancreatic cancer risk
Authors: Genkinger Jeanine , Smith-Warner Stephanie , Prospective Studies of Diet & Cancer Investigators for the Pooling Project of 
Published: May 2012

Abstract
PR-5

Background
Overweight and obesity have been hypothesized to promote pancreatic carcinogenesis by increasing insulin and IGF-1 levels. These factors may stimulate cell division, promote tumor development and increase local blood flow. Studies have reported inconsistent results between overweight and obesity and pancreatic cancer risk.

Methods
A pooled analysis of the primary data from 14 prospective cohort studies was conducted. The study sample consisted of 786,042 men and women among whom 2,135 pancreatic cases were identified. All studies measured height and weight at baseline; weight in early adulthood was measured in 11 studies. Study-specific multivariate relative risks (MV RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models, and then pooled by a random effects model.

Results
Compared to individuals with a BMI between 21-22.9 kg/m², a 16% (95% CI: 1-34%) and 47% (95% CI: 23-75%) higher pancreatic cancer risk was observed among overweight (BMI between 25-29.9 kg/m²) and obese (BMI≥30 kg/m²) individuals, respectively. Results were similar for men and women. A positive association was observed for BMI in early adulthood (pooled MV RR = 1.29, 95% CI= 1.07-1.55) comparing BMI≥25 kg/m² to a BMI between 21-22.9 kg/m². Pancreatic cancer risk was higher among individuals who were overweight in early adulthood (BMI≥25 kg/m²) and not obese at baseline (BMI&lt;30 kg/m²) (pooled MV RR=1.30, 95% CI=1.08-1.57), among those who were not overweight in early adulthood (BMI&lt;25 kg/m²) and obese at baseline (BMI≥30 kg/m²) (pooled MV RR=1.38, 95% CI=1.13-1.67) and among those who were overweight in early adulthood (BMI≥25 kg/m²) and obese at baseline (BMI≥30 kg/m²) (pooled MV RR=1.55, 95% CI=1.24-1.95) compared to individuals with a BMI in early adulthood&lt;25 kg/m² and BMI at baseline&lt;30kg/m². Although the association with BMI at baseline and BMI in early adulthood and pancreatic cancer risk was not significantly modified by smoking status, statistically significant positive associations were observed in never and past smokers, whereas a non-significant and weaker association was observed in current smokers.

Discussion and Conclusions
Overall, positive associations were observed for overweight and obese individuals and pancreatic cancer risk. As pancreatic tumors are highly fatal, determining preventive factors offers a feasible approach to reducing this disease’s morbidity and mortality. These results are in line with The World Cancer Research Fund recommendation to maintain body weight within the normal range, as overweight and obesity are also linked to other cancers, diabetes and cardiovascular disease.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):PR-5.
Abstract A1: An miR-502 binding site single-nucleotide polymorphism in the 3′-untranslated region of the SET8 gene is associated with early age of breast cancer onset
Authors: Song Fengju , Zheng Hong , Liu Ben , Wei Sheng , Dai Hongji , Zhang Lina , Calin George , Hao Xishan , Wei Qingyi , Zhang Wei , Chen Kexin 
Published: May 2012

Abstract
Purpose: MicroRNAs regulate gene expression by binding to the 3′-untranslated region (UTR) of target genes. Single-nucleotide polymorphisms of critical genes may affect their regulation by microRNAs. We have identified a single nucleotide polymorphism within the miR-502 seed binding region in the 3′-UTR of the SET8 gene. SET8 methylates TP53 and regulates genome stability. We investigated the role of this SET8 single nucleotide polymorphism and in concert with the TP53 codon72 single nucleotide polymorphism in the propensity for onset of breast cancer.
Experimental Design: We measured the SET8 single nucleotide polymorphisms in a case-control study on 1110 breast cancer cases and 1097 controls.
Results: The SET8 CC and TP53 GG genotypes were independently associated with an earlier age of breast cancer onset in an allele-dose-dependent manner (for SET8, 52.2 years for TT, 51.4 for TC, and 49.5 for CC; and for TP53, 53.1 years for CC, 51.5 for GC, 50.7 for GG). Individuals with combined SET8 CC and TP53 GG genotypes developed cancer at a median age of 47.7 years as compared with 54.6 years for individuals with combined SET8 TT and TP53 CC genotypes. In the 51 breast cancer tissue samples tested, the SET8 CC genotype was associated with reduced SET8, but not miR-502, transcript levels.
Conclusions: These data suggest that the miR-502 binding site single nucleotide polymorphism in the 3′-UTR of SET8 modulates SET8 expression and contributes to the early development of breast cancer, either independently or together with the TP53 codon 72 single nucleotide polymorphism. Larger studies with multiethnic groups are warranted to validate our findings.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A1.
Abstract A117: Physical activity and survival after prostate cancer diagnosis
Authors: Kenfield Stacey A. , Stampfer Meir J. , Giovannucci Edward , Chan June M. 
Published: May 2012

Abstract
Context: Higher levels of physical activity have been linked with a lower risk of advanced prostate cancer (PCa), but no studies have examined whether activity post-diagnosis is beneficial for PCa survivors.
Objective: To assess the relationship between physical activity, and duration and pace of walking, with total and PCa-specific mortality.
Design, Setting, and Participants: Prospective study of 2,686 men in the Health Professionals Follow-up Study diagnosed with PCa, and with follow-up from 1986 through 2008. Physical activity was assessed repeatedly both before and after diagnosis. To generate the total activity score, we summed activity-specific metabolic equivalent (MET)-hours per week. To reduce the potential influence of disease on activity level, we excluded from the analysis men with diagnosed metastases at diagnosis, and we only utilized activity information from four to six years before death. We used multivariable Cox proportional hazard models adjusted for risk factors for PCa mortality. We calculated hazard ratios for total mortality and PCa-specific mortality.
Results: Of the men who were alive for at least 4 years after their post-diagnosis physical activity assessments, we documented 554 deaths, with 22% due to prostate cancer. Men who were physically active, especially those engaging in 3 or more MET-hours of total activity, had a 35% lower risk of death from any cause (hazard ratio, 0.65 [95% CI, 0.52, 0.82]) and a modest non-significant reduction in risk of prostate cancer death (hazard ratio, 0.88 [95% CI, 0.52, 1.49]), after adjustment for other risk factors for PCa mortality and pre-diagnosis physical activity. While no benefit from walking was observed for PCa mortality, men who walked 4 or more hours per week versus those who walked less than 20 minutes per week had a 23% lower risk of all-cause mortality (95% CI, 0.61, 0.97; p-trend=0.01). In addition, compared to men who walked less than 90 minutes at an easy walking pace, those who walked 90 or more minutes at a normal to very brisk pace had a 51% lower risk of all-cause mortality (95% CI, 0.37, 0.64). More vigorous activity, and longer duration of activity, was associated with significant further reductions in risk for all-cause mortality. More vigorous activity was associated with a borderline-significant reduction in risk for PCa mortality.
Conclusions: In a cohort of men with PCa, physical activity was associated with a lower risk of overall mortality. Regular vigorous activity may reduce mortality from prostate cancer.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A117.
Abstract A12: Increased urinary 8-hydroxy-2′-deoxyguanosine excretion in long-distance bus drivers in Taiwan
Authors: Han Yueh-Ying , Donovan Maryann , Sung Fung-Chang 
Published: May 2012

Abstract
Objective: Professional bus drivers are exposed to environments containing air pollution and reactive oxygen species (ROS) that can induce cellular oxidative stress and DNA damage. This study investigated environmental factors associated with oxidative DNA damage in a cohort of long distance bus drivers.
Methods: In a comparison study, urinary 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage, was examined in 120 male long distance bus drivers and 58 male office workers in Taiwan. Multivariate logistic regression was used to analyze association between urinary 8-OHdG levels and environmental factors.
Results: Bus drivers had higher urinary 8-OHdG levels (adjusted odds ratio (aOR) = 9.4, 95% confidence interval (CI) = 3.5–28.2) compared with office workers. Increased urinary 8-OHdG level was significantly related to cigarette smoking (aOR = 18.0, 95% CI = 7.1–52.1), consumption of energy drinks (aOR = 5.0, 95% CI = 2.1–12.6), and regular exercise (aOR = 3.8, 95% CI = 1.5–10.2). A strong exposure-response relationship was found between urinary 8-OHdG and urinary cotinine (p &lt; 0.0001). Among nonsmokers, bus drivers (aOR = 3.9, 95% CI = 1.0–17.7) had higher urinary 8-OHdG than office workers. Among both bus drivers and office workers, those who drank energy drinks (aOR = 3.7, 95% CI = 1.2–12.2) had higher 8-OHdG levels than those who did not drink energy drinks.
Conclusion: Adjusted for smoking, levels of 8-OHdG were increased in long-distance bus drivers exposed to traffic exhaust and ingested energy drinks. Future studies should explore what aspects of energy drinks may contribute to increased urinary 8-OHdG.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A12.
Abstract A133: Racial/ethnic differences in serum sex steroid hormone concentrations in a nationally representative sample of U.S. adolescent males
Authors: Lopez David S. , Rohrmann Sabine , Rifai Nader , Platz Elizabeth 
Published: May 2012

Abstract
Background: Contrary to the hypothesis that the racial/ethnic disparity in prostate cancer (PCa) has a hormonal basis, we did not observe a statistically significant difference in serum testosterone concentration between non-Hispanic black (NHB) and non-Hispanic white (NHW) adult men in the nationally-representative Third National Health and Nutrition Examination Survey (NHANES III), although NHB men had a higher estradiol level. Unexpectedly Mexican-American men (MA) had the highest testosterone level. In this study, we evaluated racial/ethnic differences in hormone concentrations during puberty, the time of prostate maturation.
Methods: We measured serum testosterone, estradiol, and sex hormone binding globulin (SHBG) concentrations by immunoassay for 161 adolescent males aged 12–19 who participated in the morning examination of Phase I of NHANES III. Free testosterone and free estradiol were estimated. Geometric mean concentrations were compared by race/ethnicity using linear regression adjusting for age, Tanner (puberty) stage, percent body fat (%BF), waist circumference (WC), physical activity, smoking, and the other hormones.
Results: In 12–15 year olds, MA males had the highest total and free testosterone concentration (MA vs NHB: P&lt;0.05). In 16–19 year olds, the pattern for total testosterone was similar to that for younger adolescents, whereas free testosterone did not differ by race/ethnicity. In 12–15 year olds, MAs had the lowest total (MA vs NHW: P&lt;0.05) and free estradiol. In 16–19 year olds, NHBs had the highest and MAs the lowest total and free estradiol levels (NHB vs MA: P&lt;0.05).
Conclusion: MA male adolescents had the highest testosterone and older NHB male adolescents had the highest estradiol levels, patterns similar to adult males in NHANES III.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A133.
Abstract A17: Using high-throughput imaging cytometry to unmask the true nature of oral lesions in a high-risk community
Authors: Poh Catherine F.Y. , Guillaud Martial , Zhang Lewei , MacAulay Calum , Rosin Miriam 
Published: May 2012

Abstract
Vancouver's Downtown Eastside is a high-risk community for oral cancer. Previous study has shown its prevalence of tobacco and alcohol consumption and high incidence of oral cancer (one cancer identified in 150 residents screened). Additionally, oral infection and inflammation are commonly seen in this community. In British Columbia, we are evaluating several technologies and their interactions for the screening and early detection. Direct fluorescence visualization (FV) has shown its high sensitivity for the detection of oral cancer or precancer, but can also highlight other oral conditions which are commonly seen within community setting. We start to look at the utility of imaging cytometry as an adjunct tool in oral cancer screening. There is an urgent need to develop an effective strategy for oral cancer screening in such a high risk community.
Objectives: 1) To using imaging cytometry to measure the altered nuclear phenotype (cNPS) and 2) To see if cNPS can increase the accuracy of using FV only for oral screening.
Methods: From 2004/11–2009/2, we have collected 355 exfoliative cell samples using a small curved interdental tooth brush from this high-risk community. Samples were spun down onto slides, the DNA quantitatively labeled and automatically scanned by the cyto-savant®. For each object (nucleus/debris) imaged ∼110 features were calculated and used by a cell recognition decision tree to differentiate cells from debris.
Results: Among 355 brushings, 4 from cancerous sites, 90 from non cancerous common oral lesions (60, trauma; 28, inflammation; 12, infection), and from tongue with no lesion under clinical white light and FV examinations. Using previously trained algorithm with 84% sensitivity and 97% specificity to examine these samples, there was no difference between gender, age groups, smoking habit, and immune status (presence of HIV infection). This algorithm can correctly identified 3 out of 4 high-grade lesions and 89% normal cases. For those non-cancerous common oral lesions, using FV followed with the examination of cNPS at the FV loss area can drastically increase the accuracy from 10% to 83% (trauma, 13% to 90%; inflammation, 6% to 78%; infection 0% to 75% respectively).
Conclusion: The pilot results indicate support the potential usage of the combination of direct FV and imaging cytometry in oral cancer screening in a high-risk community.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A17.