bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B06: Dissemination and implementation research in health: What it is and opportunities for funding
Authors: Neta Gila , Chambers David , Vinson Cynthia , Glasgow Russ
Published: May 2019

Epidemiologists and public health researchers are increasingly interested in the translational value of their research. However, only a small fraction (estimated at 14 percent) of scientific discoveries are ever translated into public health practice, and the process from discovery to translation is exceedingly slow – approximately 17 years. There is a clear need for greater speed, relevance and application of scientific discoveries into programs and policies. In the past decade, the National Cancer Institute and the National Institutes of Health (NIH) expanded their mission to include practice-based research to best understand how scientific discoveries and evidence-based interventions can best be translated not only into clinical or community applications but to have a broader impact on population health through changes in policy and practice. Through trans-NIH funding announcements, 15 institutes and centers at the NIH currently are soliciting proposals for research in the field of dissemination and implementation research in health. For the purposes of these announcements, dissemination is defined as the targeted distribution of information and intervention materials to a specific public health or clinical practice audience. The intent is to spread (or scale-up) and sustain knowledge and the associated evidence-based interventions. Implementation is the use of strategies to adopt and integrate evidence-based health interventions and change practice patterns within specific settings. In this presentation we will describe in more detail the emerging field of dissemination and implementation research in health, identify priority research areas that are highlighted in the program announcements, and provide advice on how to prepare an application. We also will provide additional information on training opportunities in dissemination and implementation science, and we will describe resources that are available for cancer researchers. Finally, we will discuss emerging areas including issues such as sustainability, reach and representativeness, cost-effectiveness, and de-implementation (particularly in regard to overtreatment and overdiagnosis in cancer.)

Citation Format: Gila Neta, David Chambers, Cynthia Vinson, Russ Glasgow. Dissemination and implementation research in health: What it is and opportunities for funding. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B06.
Abstract B13: Modeling childhood versus adolescent HPV vaccination in Mali, West Africa
Authors: Schluterman Nicholas H. , Tracy J Kathleen
Published: May 2019

Objectives: Several regions in the developing world, including West Africa, bear a disproportionately high burden of cervical cancer. Incorporating the human papillomavirus (HPV) vaccine into existing childhood vaccination programs may be a practical way to combat cervical cancer in these settings.

Procedures: A compartmental mathematical model compared the occurrence of HPV and cervical cancer outcomes in childhood (age: 1 year) and adolescent (age: 10-14 years) vaccination scenarios over 75 years in Mali, West Africa. The model contained three prominent novel features: adjustable age of vaccination, waning vaccine-induced immunity at a rate of 1% annually, and moderate cross-protection against non-vaccine high-risk HPV (HR-HPV) types.

Results: Compared to a scenario with no vaccination, childhood vaccination resulted in a 53.8% (at 50% vaccine coverage) reduction in combined prevalence of all modeled HPV types in Year 75, whereas adolescent vaccination resulted in a prevalence reduction of 52.7%. After 50 years, childhood and adolescent vaccination produced 15.4% and 22.8% reductions, respectively, in the total number of life-years lost to cervical cancer. From Year 51 to Year 75, childhood vaccination reduced the total number of life-years lost by 42.9%, compared to 45.7% for adolescent vaccination.

Conclusion: Adolescent vaccination will produce a more immediate impact on cervical cancer outcomes than will childhood vaccination, but the effects of the two approaches become similar once the vaccinated cohorts span all living generations. Childhood HPV vaccination could be a practical long-term option for resource-limited countries with existing childhood vaccination programs.

Citation Format: Nicholas H. Schluterman, J Kathleen Tracy. Modeling childhood versus adolescent HPV vaccination in Mali, West Africa. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B13.
Abstract B14: Trends in academic publications on oncology in East Asia: A 10-year survey of the English literature in China, Japan and Korea
Authors: Yu Zhiqi , Xing Junjie , Du Yan , Wang Hantao , Cao Guangwen , Fu Chuangang
Published: May 2019

Background: The incidence and mortality of malignant diseases keep increasing in East Asia, especially in China. The research status on oncology in East Asia is largely unknown. The quality and quantity of academic publications can reflect the research activity. Here, we analyzed contributions of Japan, Korea and China in this field. Methods: We searched PubMed and Web of Science databases for articles published in oncology journals between 2003 and 2012. The total number of articles, citations, impact factors, and the number of articles published in high Impact Factor and the most popular oncology journals were compared among the contributing authors from Japan, Korea and China. Results: During the past decade from 2003 to 2012, 31,338 related articles were published in 96 oncology journals selected. The number of articles from China increased significantly, while there was a notable decline in Japan, and a modest increase in Korea, with an annual incremental rate of 24.97%, -1.69% and 12.66%, respectively. However, the accumulative IF of articles from Japan was higher than that from China (6298.8 vs. 3970.5, p = 0.059) and Korea (6298.8 vs. 2017.2, p = 0.005). Japanese oncologists contributed more publications to international oncology societies with respect to clinical trials, randomized controlled trials and case reports, and published more articles in top oncology journals as compared with China (1212 vs. 524, p = 0.015) and Korea (1212 vs. 344, p = 0.008). Conclusions: Although oncology research in China has been greatly improved over the past 10 years, there is still a significant gap between China and Japan with respect to high-level research on oncology. It is therefore an unshakable responsibility for Chinese oncologists to conduct high level original research and clinical trials on oncology, given China's big population and high cancer incidences.

Note:This abstract was not presented at the conference.

Citation Format: Zhiqi Yu, Junjie Xing, Yan Du, Hantao Wang, Guangwen Cao, Chuangang Fu. Trends in academic publications on oncology in East Asia: A 10-year survey of the English literature in China, Japan and Korea. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B14.
Abstract B18: Breast health promotion among African immigrant women: Intervention recommendations
Authors: Odeneye Ebun O.
Published: May 2019

Breast cancer is now the most common cancer both in developed and developing countries. It is also the leading cause of cancer-related deaths among females in economically developing countries. Additionally, breast cancer among African women is quite aggressive and progressive in nature, and often occurs earlier in life. This, coupled with the fact that African women make up one of the fastest growing immigrant population in the United States and immigrants have been shown to have lower rates of mammogram uptake, warrants scientific inquiry about how to effectively promote awareness and support breast cancer early detection and prevention practices in this population. Using Intervention Mapping (IM), a systematic approach to intervention development, recommendations for a program to promote breast health among African immigrant women in the United States will be presented. Final program recommendations are grounded in current scientific literature on breast health promotion strategies, qualitative formative research through semi-structured interviews with women, and theoretical considerations. The resultant program is a comprehensive, multilevel, evidence-based, culturally-appropriate and theory-driven educational curriculum for African immigrant women. Performance objectives (e.g., “obtain an annual mammogram”) will be specified, and behavioral determinants (e.g. knowledge, attitude and self-efficacy) will be discussed as part of a detailed matrix of change objectives for African immigrant women and community leaders. Innovative approaches, theoretical methods and practical strategies, in addition to program materials and activities, will also be described.

Citation Format: Ebun O. Odeneye. Breast health promotion among African immigrant women: Intervention recommendations. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B18.
Abstract B20: Self-reported memory problems in adult-onset cancer survivors in the United States: Effects of cardiac complications, short sleep duration, and general health
Authors: Jean-Pierre Pascal , Grandner Michael , Henry Elizabeth
Published: May 2019

Background: Memory impairments are debilitating adverse effects of malignant tumors and their various treatments. Factors such as cardiac complications and sleep loss/impairment can exacerbate memory problems for cancer patients and survivors. We examined the relationships among history of cardiac complications, short sleep duration, and self-reported memory problems (SRMP) in adult-onset cancer survivors.

Methods: We included data from middle-aged (41 to 64 years) participants who completed the 2007-2008 National Health and Nutrition Examination Survey (NHANES), a nationally representative, stratified, multistage probability sample of the civilian, non-institutionalized population of the United States. We excluded participants with a history of brain cancer or stroke since these conditions are expected to cause cognitive problems because of direct insults to the brain. Using binary a logistic regression, we determined the prevalence of SRMP in cancer survivors relative to cardiac complications and short sleep duration (< 5 hours/night) by weighting our results proportionally. We controlled for demographic predictors of memory problems: age, sex, race, education and general health.

Results: The sample included 2,289 adults (49% female). There were 46% Whites, 20% Blacks, 29% Hispanics, and 4% Asian/other. A total of 9% of the sample were cancer survivors. Cardiac complications (Odds ratio (OR), 6.97, p < 0.029; 95%CI, 1.21 to 40.05) and short sleep duration (OR, 25.30, p < 0.002; 95%CI, 3.35 to 191.28) statistically significantly predicted SRMP that interfere with activities of daily functioning. Short sleep duration partially mediated the relationship between cardiac complications and SRMP to the order of 9.18% (p < 0.0001). Among participants without a cancer history, neither cardiac complications nor short sleep were associated with SRMP (p > 0.05).

Conclusion: The likelihood of SRMP is higher in cancer survivors with a history of cardiac complications or short sleep duration. Future studies are needed to systematically delineate the cardiac-sleep-memory relationships, which could inform the development of reliable assessment and intervention to mitigate memory impairments and sleep problems for cancer survivors.

Citation Format: Pascal Jean-Pierre, Michael Grandner, Elizabeth Henry. Self-reported memory problems in adult-onset cancer survivors in the United States: Effects of cardiac complications, short sleep duration, and general health. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B20.
Abstract B35: Aberrant expression of ABCC3 in rectal cancer predicts poor prognosis and pathological response to neoadjuvant chemoradiotherapy via activating the caspase-3 dependent apoptotic pathway
Authors: Yu Zhiqi , Zhang Chang , Gao Xianhua , Xing Junjie , Wang Hao , Yu Enda , Zhang Wei , Zhang Xiaoqing , Cao Guangwen , Fu Chuangang
Published: May 2019

Objective: To clarify the role of ATP binding cassette subfamily C member 3 (ABCC3) on prognosis and pathological response to neoadjuvant chemoradiotherapy in rectal cancer, and further explore the potential molecular mechanism. Design: Retrospective analysis of clinicopathologic factors and detection of ABCC3 expression in pretreatment biopsy specimens from 144 cases of stage II–III rectal cancer who received neoadjuvant chemoradiotherapy and radical surgery. Pathological response according to tumor regression grade and long-term survival curve were further determined. ABCC3 expression was down-regulated using short interfering RNA in colorectal carcinoma cells HT-29 and SW-480. Cell proliferation and apoptosis in response to 5-fluorouracil or irradiation were examined using colony formation assay, single-hit multi-target model, flow cytometry and Hoechst 33342 staining, respectively. Tumor growth following fractional irradiation was measured in xenograft mouse model. Change of intracellular reactive oxygen species contents and activation of cleaved caspase-3 expression were further explored. Results: Aberrant expression of ABCC3 was an independent factor significantly predicting poor pathological response to neoadjuvant chemoradiotherapy (P=0.002) and prognosis (3-year Overall Survival: P=0.011; 3-year Disease-free Survival: P=0.003). Down-regulation of ABCC3 expression significantly increased 5-fluorouracil or irradiation induced cell apoptosis in vitro, and tumor growth was significantly suppressed following irradiations in vivo. Furthermore, inhibition of ABCC3 expression obviously activated caspase-3 dependent apoptotic pathway and decreased intracellular reactive oxygen species exporting from cells after being exposed to irradiations. Conclusion: ABCC3 is an attractive target for improving sensitivity to neoadjuvant chemoradiotherapy and of potential value for a clinical breakthrough in the comprehensive treatment of rectal cancer patients.

Note:This abstract was not presented at the conference.

Citation Format: Zhiqi Yu, Chang Zhang, Xianhua Gao, Junjie Xing, Hao Wang, Enda Yu, Wei Zhang, Xiaoqing Zhang, Guangwen Cao, Chuangang Fu. Aberrant expression of ABCC3 in rectal cancer predicts poor prognosis and pathological response to neoadjuvant chemoradiotherapy via activating the caspase-3 dependent apoptotic pathway. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B35.
Abstract B49: Prediagnostic body-mass index, smoking, and prostate cancer survival
Authors: Yuan Changzheng , Chavarro Jorge , Lindström Sara , Kraft Peter , Ma Jing
Published: May 2019

Background: Few prospective studies have sufficient power to investigate the relationship between obesity and lethal prostate cancer (PC) in detail or within population subgroups, such as by smoking status. This study aimed to investigate the associations of pre-diagnostic body mass index (BMI) with risk of progression from time of PC diagnosis to fatal outcome, to assess effect modification by smoking status and to evaluate the joint effect of BMI and smoking on PC survival.

Methods: We conducted a survival analysis of 10,206 PC patients from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). BMI and smoking status were estimated before PC diagnosis. Deaths among PC patients were categorized into deaths from PC and other causes. We conducted the analysis in 3 parts according to exposures: BMI (18-22.9 kg/m2, 23-24.9 kg/m2. 25-27.9 kg/m2, 28-29.9 kg/m2, 30-34.9 kg/m2, 35 kg/m2+), smoking (Never, former, current) and their joint effect, respectively. Each analysis was performed on prostate cancer specific mortality and other mortality separately. Competing-risks regression model was used to take into account of other causes of death. For the above analyses, two models were used. Model 1 controlled for age at diagnosis, drinking status, diabetes status, cohort, duration between baseline and PC diagnosis; Model 2 further adjusted for PC stage and Gleason score at diagnosis in addition to model 1.

Results: There were 1028 deaths from PC and 1919 other deaths among all PC patients during an average follow up of eight years. Higher BMI was associated with higher risk of death from PC and other causes; compared to BMI (23-24.9 kg/m2) group, men with BMI 35+ kg/m2 had HR=1.83, 1.16-2.91 for PC death and HR=1.49, 1.04-2.14 for other deaths. The positive trend was apparent only among never and former smokers but not current smokers. Similar effect was found among men whose BMI measured >5 years but for men whose BMI was measured <=5 years before PC diagnosis, only those in the highest category (BMI 35+ kg/m2) was associated with higher risk of dying from PC. Former smokers as well as current smokers have significant higher risk of progressing to death after PC diagnosis regardless BMI with significant interaction between BMI and smoking.

Conclusions: Higher BMI and smoking history (former and current smokers) are possible risk factors for dying from PC among all PC cases in the BPC3 cohort. The effect of BMI on PC survival is modified by smoking status.

Citation Format: Changzheng Yuan, Jorge Chavarro, Sara Lindström, Peter Kraft, Jing Ma. Prediagnostic body-mass index, smoking, and prostate cancer survival. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B49.
Abstract B54: A candidate gene study of smoking cessation
Authors: Stevens Victoria L. , Gapstur Susan M. , Sun Juzhong , Jacobs Eric J. , Gaudet Mia M. , Westmaas J. Lee , Patel Alpa V.
Published: May 2019

Background: Efforts to identify genes that influence smoking cessation have been largely unsuccessful to date. However, SNPs in the chromosome 15q25 region that encodes the nicotinic receptor subunits CHRNA5, CHRNA3, and CHRNB4 have been consistently and strongly associated with nicotine dependence as measured directly through dependence surveys or indirectly with smoking quantity (cigarettes per day, cpd). These SNPs have been found to either be modestly or not at all associated with smoking cessation as defined by a variety of different phenotypes. Despite the fact that nicotine dependence influences smoking cessation, these results suggest that cessation may be influenced by a wider range of genetic variants than just those that influence measures of nicotine dependence.

Methods: To identify genes important for smoking cessation, we defined a smoking cessation phenotype based on number of quit attempts; easy quitters achieved successful, long-term (> 1 year) abstinence after their first quit attempt and difficult quitters reported ≥10 attempts before either continuing to smoke or quitting. We identified 1,500 easy quitters and 1,500 difficult quitters who were participants in the Cancer Prevention Study-3 (CPS-3), a large prospective study of cancer incidence and mortality conducted by the American Cancer Society. The association of 83 SNPs from 25 nicotine signaling and metabolism genes that had previously been associated with some aspect of smoking behavior with difficulty quitting was determined using logistic regression.

Results: Three SNPs in three separate genes were significantly associated with difficult quitting (p<0.05). These were SLC6A3 rs2652511 [per allele odds ratio (OR)=0.89, 95% confidence intervals (CI): 0.80-0.99, p-trend=0.040], HTR1B rs6298 (per allele OR=0.88, 95% CI: 0.80-0.99, p-trend=0.034), and CHRNA5 rs16969968 (per allele OR=1.12, 95% CI: 1.00-1.22, p-trend=0.045). A genetic risk score based on number of risk alleles from these three SNPs was also associated with difficult quitting (OR=1.62, 95% CI:1.26-2.08, p=1.9 x 10-4 for score of 5-6 versus 0-2). None of the associations remained statistically significant after correction for multiple comparisons.

Conclusions: Although none of the SNPs investigated were statistically significantly associated with the number of quit attempts, these results suggest that examining this phenotype in future genome-wide association studies would be useful for the discovery of genes that could be targeted for the development of novel smoking cessation aids.

Citation Format: Victoria L. Stevens, Susan M. Gapstur, Juzhong Sun, Eric J. Jacobs, Mia M. Gaudet, J. Lee Westmaas, Alpa V. Patel. A candidate gene study of smoking cessation. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B54.
Abstract B57: Premenopausal plasma ferritin levels, HFE polymorphisms, and risk of breast cancer in the Nurses' Health Study II
Authors: Graff Rebecca E. , Eunyoung Cho , Lindström Sara , Kraft Peter , Willett Walter C. , Eliassen A Heather
Published: May 2019

Background: Evidence from the Nurses' Health Study II (NHSII) suggests that red meat consumption is associated with increased breast cancer risk in premenopausal women. Iron may be responsible by contributing to oxidative stress or effects on immune function.

Methods: We conducted a case-control study nested within the NHSII examining prediagnostic plasma ferritin (n=795 cases, 795 controls), 15 hemochromatosis gene (HFE) SNPs (n=772 cases, 1,368 controls), and breast cancer risk. Cases were diagnosed with cancer after providing blood samples between 1996 and 1999. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for ferritin levels by conditional logistic regression and for HFE SNPs by unconditional logistic regression.

Results: We did not observe a significant association between ferritin levels and breast cancer (top vs. bottom quartile multivariate OR: 1.05, 95% CI: 0.77-1.45, P-value for trend: 0.77). Results did not change when restricted to women who were premenopausal at blood draw, and were similar when cases were examined by hormone receptor status and menopausal status at diagnosis. No HFE SNPs were significantly associated with breast cancer in a log-additive manner. Among controls, ferritin levels were nominally associated with SNPs rs9366637 (P-value for trend: 0.04), rs6918586 (P-value for trend: 0.06) and rs13161 (P-value for trend: 0.07), but results did not remain significant after adjusting for multiple testing.

Conclusions: Ferritin levels and HFE SNPs were not associated with breast cancer risk in this population. Components of red meat other than iron are likely responsible for its positive association with breast cancer in premenopausal women.

Citation Format: Rebecca E. Graff, Cho Eunyoung, Sara Lindström, Peter Kraft, Walter C. Willett, A Heather Eliassen. Premenopausal plasma ferritin levels, HFE polymorphisms, and risk of breast cancer in the Nurses' Health Study II. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B57.
Abstract C13: Population-based evaluation of serum pepsinogen, anti-H. pylori IgG antibody and gastrin-17 tests for gastric cancer screening
Authors: Tu Huakang , Sun Liping , Gong Yuehua , Xu Qian , Long Qi , Bostick Roberd , Yuan Yuan
Published: May 2019

Objective: This study evaluated the role of multiple serological tests (including serum pepsinogen I (PGI), PGII, PGI/II ratio, anti-H. pylori IgG antibody, and gastrin-17 tests) individually and in combination in gastric cancer (GC) screening.

Design: Data were from the Zhuanghe Gastric Cancer Study, a 15-year, population-based endoscopic, gastric diseases screening program in northern China. From 1997 to 2011, esophagogastroduodenoscopies with gastric mucosal biopsies were conducted on 10,693 participants. All serum biomarkers were measured using ELISA, and gastric biopsies were evaluated using standardized criteria. Logistic regression was used to calculate odds ratios (OR) with 95 percent confidence intervals (95% CI) and produce receiver operator characteristic (ROC) curves with corresponding c statistics. In addition, results were replicated in an independent hospital-based population.

Results: PGI/II ratio monotonically decreased as gastric mucosa progresses from normal mucosa to precancerous conditions, and to GC, and a low PGI/II ratio (≥ 6.6) was associated with an increased risk of prevalent GC (OR = 2.34, 95% CI: 1.62, 3.39). PGI/II ratio individually or in combination with PGI, PGII, anti-H. pylori IgG antibody and gastrin-17 provided the same c statistic of 0.62 for screening for GC. PGI, PGII, anti-H. pylori IgG antibody or gastrin-17 tests individually provided c statistics less than or equal to 0.55. For identifying abnormal gastric conditions including GC, the five serological tests in combination provided adequate discriminatory performance (c = 0.77), and yielded a sensitivity of 84.0% and specificity of 50.0%. The results from the independent hospital-based population were similar.

Conclusion: Our results suggest that serum PGI, PGII, PGI/II ratio, anti-H. pylori IgG and gastrin-17 tests can be used as prescreening tests for patients at high risk for GC.

Citation Format: Huakang Tu, Liping Sun, Yuehua Gong, Qian Xu, Qi Long, Roberd Bostick, Yuan Yuan. Population-based evaluation of serum pepsinogen, anti-H. pylori IgG antibody and gastrin-17 tests for gastric cancer screening. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C13.
Abstract C29: Combination of SP17 with CA125 serologic measurement for detection of ovarian cancer
Authors: Chiriva-Internati Maurizio , Mirandola Leonardo , Yu Yuefei , Jenkins Marjorie R. , Cobos Everardo , Figueroa Jose A. , Nijman Hans W. , Kast W. Martin
Published: May 2019

Ovarian cancer (OC) is a serious healthy issue for women worldwide, ranking second for mortality rates among gynecological malignancies. CA125 (MUC16) is the only available biomarker to monitor disease and treatment response in OC but it suffers from poor performance for diagnostic purposes. As a consequence, increasing efforts are being made for the identification of novel tumor biomarkers to improve CA125 test specificity and sensitivity. More than 30 serum biomarkers have been studied alone or in combination with CA125. We have previously shown that SP17, a member of the cancer/testis antigen (CTA) family, is a potential biomarker that allows for the discrimination of the normal ovary from OC cells and for the tracking of OC disease in a xenograft mouse model. Here we hypothesized that SP17 serum levels could be exploited as a diagnostic test to detect early lesions of OC and to discriminate between malignant and benign lesions. We analyzed SP17 expression in primary ovarian tissues from ovarian cancer patients, benign ovarian lesions and healthy subjects through RT-PCR and immunohistochemistry. SP17 and CA125 levels were measured in the sera of the same subjects by ELISA. We found that SP17 expression was restricted to OC cells at the transcriptional and translational levels, and that the measurement of SP17 concentration in the serum afforded accurate discrimination between subjects with different prognoses allowing for predicting overall survival time. SP17 assay alone was superior to CA125 in discriminating between ovarian cancer and benign ovarian tumors: combining SP17 and CA125 assays, we obtained 96% sensitivity, 89% specificity and 97% PPV. SP17 is a novel serum biomarker for ovarian cancer. SP17 serum measurement in combination with CA125 affords improved positive predictive value for diagnostic purposes.

Citation Format: Maurizio Chiriva-Internati, Leonardo Mirandola, Yuefei Yu, Marjorie R. Jenkins, Everardo Cobos, Jose A. Figueroa, Hans W. Nijman, W. Martin Kast. Combination of SP17 with CA125 serologic measurement for detection of ovarian cancer. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C29.
Abstract C36: miR-22 represses Wnt Signaling in human colon cancer cells
Authors: Neha Chetlangia , Rao Srinivasa Rao , Karunagaran Devarajan
Published: May 2019

Background: Wnt signaling is an evolutionarily conserved pathway that plays an important role in processes like development, differentiation and metastasis. Aberrant activation of Wnt signaling has been implicated in various tumors, predominantly of breast and colon. MicroRNAs are short non-coding RNAs that are frequently deregulated in cancer. Expression of the microRNA miR-22 was reported to be significantly lower in colorectal cancer tissues than that in normal adjacent mucosa. Based on bioinformatics predictions, we identified several Wnt signaling intermediates as potential targets for miR-22. As Wnt signalling is constitutively active in colon cancer cell lines SW480 and SW620, we hypothesize that miR-22 might be a potential regulator of Wnt signaling in colon cancer.

Methods: Wnt signaling was stimulated in HEK293 cells by treating them with 25mM Lithium Chloride (LiCl). Wnt signaling activation was assayed using TOPFlash/FOPFlash luciferase activity in HEK293, SW480 and its metastatic derivative SW620, after overexpressing miR-22 using a plasmid construct. CyclinD1 promoter luciferase assay, Western blotting and quantitative RT-PCR were used to study the expression of downstream targets of Wnt signaling. Direct targets of miR-22 were validated by performing 3'-UTR luciferase assays. Plasmid constructs were used to overexpress or knockdown c-Myc.

Results: Overexpression of miR-22 resulted in decreased TOP-Flash luciferase activity in LiCl-treated HEK293 cells and the colon cancer cells SW480 and SW620. miR-22 repressed Wnt signaling target genes CyclinD1, c-Myc and TCF7L2, at both mRNA and protein levels. It also decreased the mesenchymal markers (Snail and Vimentin) at the protein level. Overexpression of miR-22 down-regulated BCL9L protein levels and also targeted the BCL9L 3' UTR, as demonstrated by luciferase reporter assay. In HEK293 cells, overexpression of c-MYC repressed miR-22 levels whereas knockdown of endogenous c-Myc by shRNA up-regulated miR-22 levels.

Conclusions: miR-22 inhibits Wnt signaling and potentially exerts this effect by targeting the Wnt activator BCL9L. The repression of mesenchymal markers by miR-22 suggests a role for it in Epithelial to Mesenchymal Transition. Further, the Wnt target gene c-Myc regulates the expression of miR-22, suggesting the existence of a positive feedback loop involving miR-22/Wnt Signaling/c-Myc by which miR-22 may indirectly regulate its own expression. Our findings therefore demonstrate a novel role for miR-22 in the regulation of Wnt signaling in colon cancer cells.

Citation Format: Chetlangia Neha, Srinivasa Rao Rao, Devarajan Karunagaran. miR-22 represses Wnt Signaling in human colon cancer cells. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C36.
Abstract C61: High fat triggers oncogenic K-Ras activity and a COX2 dependent feed-forward loop to induce pancreatic ductal adenocarcinoma development
Authors: Philip Bincy , Roland Christina L. , Daniluk Jarek , Liu Yan , Chatterjee Deyali , Gomez Sobeyda Berenice , Ji Baoan , Haojie Huang , Wang Huamin , Fleming Jason B. , Logsdon Craig D. , Cruz-Monserrate Zobeida
Published: May 2019

Obesity is a risk factor for Pancreatic Ductal Adenocarcinoma (PDAC), but the molecular mechanisms involved are unclear. Oncogenic mutation of K-Ras occurs early and nearly universally in patients with this disease. However, recent evidence indicates that oncogenic Ras is not fully active and for activity to surpass the threshold required to engage a Ras-inflammation feed-forward loop, it requires a stimulus. We hypothesized that high-fat intake acts as an inflammatory stimulus, increasing K-Ras activity and that cyclooxygenase -2 (COX2) expression is required in the inflammatory loop. LSL-K-Ras mice were crossed with elastase-CreER (acinar cell-specific) or Pdx1-Cre (pancreatic cell-specific) to “knock-in” expression of oncogenic K-Ras. Additionally, acinar cell-specific -Ras mice were crossed with COX2 conditional knockout mice. All mice were fed isocaloric diets with different amounts of fat and a COX2 inhibitor was administered to some acinar cell-specific -Ras mice. Pancreata were analyzed for Ras activity, Phospho-ERK levels, inflammation, fibrosis, PanIN and PDAC development. We observed that consumption of a high fat diet (HFD) led to increased K-Ras activity, PanIN formation, fibrotic stroma and PDAC development compared to a control diet. Additionally, we observed a significant reduction in the survival of mice fed a HFD. Genetic deletion of COX2 in acinar cells and COX2 systemic inhibition prevented the HFD-induced effects in acinar cell-specific -Ras mice. These findings indicated that a HFD stimulates activation of oncogenic K-Ras and initiates an inflammatory feed-forward loop requiring the expression of COX2 leading to pancreatic inflammation, fibrosis, PanINs and PDAC. This mechanism may explain the PDAC risks associated with consumption of a HFD.

Citation Format: Bincy Philip, Christina L. Roland, Jarek Daniluk, Yan Liu, Deyali Chatterjee, Sobeyda Berenice Gomez, Baoan Ji, Huang Haojie, Huamin Wang, Jason B. Fleming, Craig D. Logsdon, Zobeida Cruz-Monserrate. High fat triggers oncogenic K-Ras activity and a COX2 dependent feed-forward loop to induce pancreatic ductal adenocarcinoma development. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C61.
Abstract CN03-03: The impact of reduced tobacco smoking on lung cancer mortality in the United States during 1975-2000
Authors: Moolgavkar Suresh
Published: May 2019

A consortium of six groups using common inputs and independent models estimated the number of U.S. lung cancer deaths averted over the period 1975-2000 in the United States as a result of changes in smoking behavior beginning in the mid-fifties, and also the number of deaths that could have been averted had tobacco control been completely effective in eliminating smoking in 1965, following the issuance of the first Surgeon General's report (SGR) on Smoking and Health in 1964. Our results suggest that approximately 795,000 lung cancer deaths were averted, 550,000 among males and 245,000 among females. However, this total number represents only about 30% of the lung cancer deaths that could potentially have been averted during this period. Enhanced tobacco control efforts are necessary to reduce further the burden of lung cancer in the U.S. population.

Citation Format: Suresh Moolgavkar. The impact of reduced tobacco smoking on lung cancer mortality in the United States during 1975-2000. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr CN03-03.
Abstract CN04-03: Stemming the rising tide of liver and esophageal cancer
Authors: Thompson Patricia A.
Published: May 2019

Obesity has been convincingly linked to non-viral/non-alcoholic liver carcinogenesis (HCC) and to esophageal adenocarcinoma (EAC). Both HCC and EAC have five-year survival rates below 50% with little to no advancement in treatment options over the past decade. In obesity-associated HCC and EAC, bile acids and their biology as signaling molecules are emerging as potentially shared mechanistic factors generally in gastrointestinal cancers and in particular in the liver and in the esophagus. Emerging work on the role of bile acid-based therapeutics for the prevention of cancer risk factor intermediates will be presented. This will include status of clinical trials with bile acid based drugs, their molecular targets and novel opportunities for drugs targeting metabolic disturbances in the obese as prevention agents for HCC and EAC.

Citation Format: Patricia A. Thompson. Stemming the rising tide of liver and esophageal cancer. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr CN04-03.
Abstract CN07-02: Local transdermal therapy for DCIS and for breast cancer prevention
Authors: Khan Seema A.
Published: May 2019

Pharmacological breast cancer prevention is efficacious but has had low uptake by high risk women. The breast is a skin appendage, with a well-developed internal lymphatic circulation; preliminary studies have shown that small molecules which penetrate the skin concentrate well in the breast with low systemic exposure. We conducted a Phase II randomized trial comparing oral tamoxifen to 4-OHT gel applied to the breast skin, in women needing surgical resection of core-biopsy proven DCIS. Our goal was to assess relative breast tissue drug concentration and anti-proliferative efficacy in DCIS lesions. Although the study was halted early due to interruption in drug supply, preliminary results demonstrate good skin penetration, low systemic concentrations, and reduction in cell proliferation similar to that achieved with oral tamoxifen. These data support the continued investigation of this mode of drug delivery to the breast, with the potential for decreasing the toxicity of proven prevention agents, and for expanding the prevention drug portfolio to effective drugs that penetrate the skin, but systemic use is constrained by toxicity.

Citation Format: Seema A. Khan. Local transdermal therapy for DCIS and for breast cancer prevention. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr CN07-02.
Abstract CN08-03: 3-D electron microscopy in cellular and molecular imaging: Applications to cancer
Authors: Subramaniam Sriram
Published: May 2019

Emerging methods in 3-D biological electron microscopy provide powerful tools and great promise to bridge a critical gap in imaging in the biomedical size spectrum. This comprises a size range of considerable interest that includes cellular protein machines, giant protein and nucleic acid assemblies, small subcellular organelles and bacteria. These objects are generally too large and/or too heterogeneous to be investigated by high resolution X-ray and NMR methods; yet the level of detail afforded by conventional light and electron microscopy is often not adequate to describe their structures at resolutions high enough to be useful in understanding the chemical basis of biological function. The long-term mission of our research program is to obtain an integrated molecular understanding of cellular architecture by combining novel technologies for 3-D biological imaging with advanced methods for image segmentation and computational analysis. I will review our recent progress in imaging and modeling dynamic biological systems, with particular emphasis on applications to signal transduction, HIV/AIDS and cancer.

Lab website: http://electron.nci.nih.gov

Citation Format: Sriram Subramaniam. 3-D electron microscopy in cellular and molecular imaging: Applications to cancer. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr CN08-03.
Abstract DL01-01: Cancer Genomes and their Implications for Early Detection
Authors: Vogelstein Bert , Kinzler Kenneth W.
Published: May 2019

In the past five years, it has become possible to identify all of the mutations contributing to neoplasia in an individual cancer, leading to a deeper understanding of the pathogensis of neoplasia. The challenge now is to exploit this wealth information to reduce cancer deaths. Most current efforts towards this goal are focused on curing patients with advanced disease through “personalized” medicine approaches. However, the barriers to curing such patients are now being recognized, in part through the insights gained from cancer genome sequencing. Alternative strategies to reduce cancer deaths are therefore essential to achieving this goal. Fortunately, it is now clear that there are only ~150 genes, operating through ~12 well-recognized pathways, that drive the initiation and progress of the most common types of human cancers. These genes and pathways provide enormous opportunities for the early detection of neoplasia through sophisticated genomic, proteomic, and imaging-based technologies. Widespread implementation of early detection and prevention methods has the capacity to reduce cancer deaths by more than 75% in the foreseeable future.

Citation Format: Bert Vogelstein, Kenneth W. Kinzler. Cancer Genomes and their Implications for Early Detection. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr DL01-01.
Abstract ED01-03: Forward and backward cell transformation induced by microenvironment factors: A tribute to Allan H. Conney
Authors: Dong Zigang
Published: May 2019

The cancer microenvironment affects cell proliferation and growth. By using JB6 cells and a melanoma cell culture system, we have studied forward and backward cell transformation by microenvironment factors. Embryonic stem (ES)-preconditioned 3-dimensional (3-D) culture of cancer cells induces cancer cell reprogramming and results in a change in cancer cell properties such as differentiation and migration in skin melanoma. Using the ES-preconditioned 3-D microenvironment model, we provided evidence showing that the ES microenvironment inhibits proliferation and anchorage-independent growth of SK-MEL-28 melanoma cells. We also found that the ES microenvironment suppresses telomerase activity and thereby induces senescence in SK-Mel-28 cells. Furthermore, we observed that gremlin, an antagonist of BMP4, is secreted from ES cells and plays an important role in cellular senescence. Knocking down gremlin in the ES microenvironment increases proliferation and anchorage-independent growth of SK-MEL-28 melanoma cells. Taken together, these results demonstrated that gremlin is a crucial factor responsible for abrogating melanoma properties in the ES-preconditioned 3-D microenvironment.

In a collaborative effort, Dr. Allan Conney's group demonstrated that an aqueous extract of the parametrial fat pads from SKH-1 mice enhanced the conversion of JB6 P+ cells from an epithelial-like morphology growing in liquid medium to cells with a fibroblast-like morphology with decreased E-cadherin and increased Twist, and these cells also formed colonies in soft agar. Mechanistic studies indicated that an extract of parametrial fat stimulated the formation of reactive oxygen species in JB6 P+ cells. These studies provide the first in vitro demonstration of a fat tissue-induced transformation of an epithelial cell. We also showed that several microenvironmental factors can induce JB6 cell neoplastic cell transformation.

Citation Format: Zigang Dong. Forward and backward cell transformation induced by microenvironment factors: A tribute to Allan H. Conney. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr ED01-03.
Abstract ED02-01: Epigenetic variation as the missing link between aging and cancer
Authors: Issa Jean-Pierre
Published: May 2019

DNA methylation affects gene expression and genome stability in complex ways depending on the location of the CpG site in question. In humans, methylation patterns are highly regulated and generally conserved between different individuals with R2>0.98 when comparing promoter DNA methylation genome wide among unrelated individuals of similar age. Despite this high degree of regulation, there are quantitative differences in methylation between individuals as well as evidence of methylation drift (increase at some loci, decrease at other loci) associated with aging in mammals. There is also a large degree of methylation drift in cancer cells (compared to normal tissues in the same individual) and a smaller but significant drift in other diseases such as atherosclerosis and neuro-degeneration.

Genome wide methylation drift associated with age in multiple species (humans, mice, monkeys) is tissue specific and affects up to a quarter of the methylome. The consequences of drift are twofold. First, it induces epigenetic diversity within a tissue that can serve as fodder for Darwinian selection to promote the development of proliferative diseases such as cancer and atherosclerosis. Second, given that some genes are affected more prominently due to genomic structural features, enough cells are affected in older tissues to potentially change gene expression and tissue function.

The determinants of age-related methylation drift remain largely unknown. There are diverse observations suggesting that the rate of drift can be modified by diet, chronic inflammation and exposures, and preliminary data suggesting a genetic component to the drift as well. Some of the outstanding questions in the field include the possibilities that methylation drift is modified by germline polymorphisms that influence DNA methylation genome wide, by prenatal exposures including diet and environmental toxins, and by lifestyle factors (including diet, exposures and exercise) that affect low level inflammation systemically. The model whereby methylation drift enables Darwinian selection at the tissue level also implies that possibility of preventing age-related development of pre-neoplasia and neoplasia through interventions targeting epigenetic processes.

Citation Format: Jean-Pierre Issa. Epigenetic variation as the missing link between aging and cancer. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr ED02-01.