bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B39: The Health of Women (HOW) Study: A novel approach to the cohort study
Authors: Love Susan , Fischetti Christine , Sullivan-Halley Jane , Clague Jessica , Bernstein Leslie
Published: May 2019

Purpose: The purpose of the Health of Women (HOW) Study is to examine risk factors for breast cancer and factors that may contribute to long-term survivorship through an innovative online system that allows for participant engagement and data sharing with the research community.

Methods: The HOW Study is conducted through online and mobile phone platforms. Questionnaires are developed in our custom built survey tool and are available for completion on the study's website. The system allows for automated skip patterns within questionnaires and collection of data directly into a SQL database. The cohort is open to anyone 18 years or older; recruitment sources include the Love Army of Women and the general public. Participants will be given the opportunity to pose questions they would like to see answered. The HOW Study is also a novel resource allowing outside researchers to submit questions to be incorporated into HOW questionnaires and creating a data sharing platform that facilitates researcher access to HOW data after an application process.

Results: The HOW Study launched October 2012 and currently has 42,600 participants from across the nation and the globe. We have released 1 baseline questionnaire and 4 breast cancer-specific questionnaires to capture diagnosis and treatment with greater than 90% completion rate for each.

Conclusion: We have shown that we can recruit and engage participants in an online cohort study. We believe that this study has the potential to transform epidemiologic research by engaging both participants and the research community. Our second baseline questionnaire will launch in the summer of 2013, which will give us the opportunity to increase enrollment and assess retention.

Citation Format: Susan Love, Christine Fischetti, Jane Sullivan-Halley, Jessica Clague, Leslie Bernstein. The Health of Women (HOW) Study: A novel approach to the cohort study. [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 B39.
Abstract B53: Time to first cigarette and lung cancer risk in Japan
Authors: Ito Hidemi , Gallus Silvano , Hosono Satoyo , Oze Isao , Fukumoto Koichi , Yatabe Yasushi , Hida Toyoaki , Mitsudomi Tetsuya , Negri Eva , Vecchia Calro La , Tanaka Hideo , Matsuo Keitaro
Published: May 2019

Background: Cigarette smoking is the major cause of lung cancer. Although the time to first cigarette (TTFC) of the day is a distinct indicator of nicotine dependence, little information is available on its possible relation to LC.

Methods: This case-control study includes a total of 1,572 incident lung cancer cases and 1,572 non-cancer controls visiting for the first time the Aichi Cancer Center Hospital between 2001 and 2005. We estimated odds ratio (OR) and 95% confidence interval (CI) for TTFC using logistic regression model after adjustment for several potential confounders.

Results: TTFC was inversely associated with the risk of lung cancer. This association was consistent across histological subtypes of lung cancer. For all lung cancers considered among ever smokers and after accurate allowance for smoking quantity and duration, besides other relevant covariates, compared with TTFC more than 60 min, the adjusted ORs were 1.08 (95% CI, 0.73-1.61) for TTFC of 31-60 min, 1.40 (0.98-2.01) for 6-30 min and 1.86 (1.28-2.71) for within 5 min (ptrend, <0.001). Statistically significant heterogeneity by histological subtype was observed (pheterogeneity, 0.002 for former smokers and 0.033 for current smokers).

Conclusions: Nicotine dependence, as indicated by the TTFC, is associated with increased risk of lung cancer and is therefore an independent marker of exposure to tobacco smoking.

Citation Format: Hidemi Ito, Silvano Gallus, Satoyo Hosono, Isao Oze, Koichi Fukumoto, Yasushi Yatabe, Toyoaki Hida, Tetsuya Mitsudomi, Eva Negri, Calro La Vecchia, Hideo Tanaka, Keitaro Matsuo. Time to first cigarette and lung cancer risk in Japan. [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 B53.
Abstract B60: Contraceptive methods and ovarian cancer risk among Chinese women: A report from the Shanghai Women Health Study
Authors: Huang Zhezhou , Beeghly-Fadiel Alicia , Li Honglan , Wen Wanqing , Gao Yutang , Zheng Wei , Shu Xiao-Ou
Published: May 2019

Background: Oral contraceptive (OC) use is known to be associated with reduced ovarian cancer risk; associations with other contraceptive methods, such as intrauterine devices (IUD) and tubal ligation (TL), are less clear. The majority of studies conducted to date have used case-control designs; fewer cohort studies have been conducted, especially among Asian women. As contraception use is popular among Chinese women, and the use of different contraceptive methods differs from Western countries, differences in associations with ovarian cancer risk may exist.

Methods: Data from the prospective Shanghai Women's Health Study (SWHS) was used to evaluate associations between different contraceptive methods and risk of ovarian cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression; models included adjustment for age, education, years of ovulation, body mass index (BMI), first-degree family history of cancer (yes/no), and regular physical activity within 5 years (yes/no).

Results: A total of 164 ovarian cancer cases occurred among 70,349 women after an average follow-up time of 11.74 years. The majority of women had ever used any contraception (77.0%), including OC use (20.4%), contraceptive shots (2.6%), IUD use (55.6%) and TL (14.7%). Ever use of any contraception method was associated with a non-significant reduction in ovarian cancer risk (HR: 0.83, 95% CI: 0.58-1.19). Similarly, among users of contraception, women with durations of OC use longer than the median (≥2 years) tended to have lower ovarian cancer risk (HR: 0.60, 95% CI: 0.26-1.39), while women with durations of IUD use longer than the median (≥23 years) had significantly decreased ovarian cancer risk (HR: 0.48, 95% CI: 0.30-0.75).

Conclusion: Longer durations of IUD use had beneficial effects on ovarian cancer risk among Chinese women. Due to the high prevalence and long duration of IUD use among Chinese women, and the protective association seen in this study, we estimate that approximately 20 ovarian cancer cases (12.0%) were prevented in this study population. Therefore, patterns of use of different contraceptive methods in China may contribute to the lower incidence of ovarian cancer observed in this country.

Citation Format: Zhezhou Huang, Alicia Beeghly-Fadiel, Honglan Li, Wanqing Wen, Yutang Gao, Wei Zheng, Xiao-Ou Shu. Contraceptive methods and ovarian cancer risk among Chinese women: A report from the Shanghai Women Health Study. [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 B60.
Abstract C19: Prospective association between blood leukocyte telomere length and cancer incidence and mortality
Authors: Gao Tao , Chu Junjie , Zheng Yinan , Zhang Xiao , Baccarelli Andrea A. , Schwartz Joel , Hou Lifang
Published: May 2019

Background and Objective: Telomeres play a critical role in maintaining the structural integrity of chromosomes. Short telomeres may lead to chromosomal instability and increase cancer risk and related death. In this longitudinal study we examined prospective associations between blood leukocyte telomere length (TL) and cancer incidence and mortality.

Methods: Our study population included a total of 791 participants in the prospective Normative Aging Study (NAS), a 1963-established study devoted to determining the health effects of aging. Between January 1999 and December 2012, the participants underwent blood drawing during the NAS visits every 3-5 years. We examined leukocyte TL using quantitative real-time PCR on blood samples collected at each NAS visit, including 1-4 examinations before cancer diagnosis. We used mixed models and Cox models to evaluate the association between TL with cancer incidence and mortality individually. Both models were adjusted for age, race, body mass index, education, and smoking status.

Results: In 579 participants free of baseline cancers, telomeres were significantly shorter in association with aging (P < 0.001) and lower levels of education (P = 0.02). 137(23.7%) new cancer cases (47 prostate, 15 gastrointestinal, and 75 other cancers) occurred throughout the 14-year follow-up. Shorter TL was associated with higher incidence of all cancers combined (OR=1.54, 95%CI 1.02-2.33, P=0.04). Totally, 75 (9.5%) deaths occurred due to cancers (12 prostate, 18 gastrointestinal, 45 other cancers). Subjects with shorter TL (less than median) had increased mortality from all cancer combined (HR= 1.68, 95%CI 0.99-2.87, P=0.05). Relative to subjects in the fourth quartile (longest) of TL, subjects in the first quartile (shortest) had almost twice mortality risk from all cancer combined (HR= 1.90, 95% CI 0.92-3.93, P-trend=0.02). For the cancer subgroups, subjects with shorter TL (less than median) had increased mortality from other cancers (mostly lung and blood cancers)(HR= 2.01, 95%CI 1.07-3.75, P=0.03).

Conclusion: Shorter TL is associated with higher risk of cancer incidence and cancer mortality independent of age, race, body mass index, education, and smoking. More studies are needed to determine the predictive value of blood leukocyte TL in specific cancers, as well as their underlying mechanisms.

Citation Format: Tao Gao, Junjie Chu, Yinan Zheng, Xiao Zhang, Andrea A. Baccarelli, Joel Schwartz, Lifang Hou. Prospective association between blood leukocyte telomere length and cancer incidence and mortality. [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 C19.
Abstract C45: Effects of low-fat and low-carbohydrate dietary patterns combined with physical activity on serum adipokine concentrations among premenopausal women: A randomized trial
Authors: Llanos Adana A.M. , Krok Jessica L. , Peng Juan , Pennell Michael L. , Olivo-Marston Susan E. , Vitolins Mara Z. , Degraffinreid Cecilia R. , Paskett Electra D.
Published: May 2019

Background: There is an ongoing debate regarding what dietary pattern is the most effective for breast cancer prevention. Several studies have examined hypocaloric diets with an emphasis on various macronutrient compositions, yielding inconclusive data regarding their effects on weight loss and breast cancer risk reduction. This study examined the effects of a 1-year intervention of 2 calorie-restricted diets (low-fat or low-carbohydrate [LFD and LCD, respectively]), in combination with increased physical activity (PA), on circulating adipokine concentrations among premenopausal women at increased risk of developing breast cancer.

Methods: Seventy nine overweight/obese premenopausal women were randomized to a LFD or LCD with PA for 52 weeks. Serum adiponectin, leptin and the adiponectin to leptin ratio (A/L) were measured at baseline, and weeks 25 and 52. Linear mixed models, which included fixed effects of treatment arm, time, and a treatment-by-time interaction, were used to assess intervention effects on serum adipokine concentrations.

Results: Compared to baseline, at week 25, adiponectin decreased 4.1% and 2.3%, leptin decreased 30.0% and 35.3%, and the A/L ratio increased 10.5% and 19.4%, among LFD and LCD participants, respectively. Compared to baseline, at week 52, adiponectin decreased 8.5% and 5.0%, leptin decreased 23.0% and 19.7%, and the A/L ratio increased 23.7% and 44.4%, among LFD and LCD participants, respectively. No differences in adipokine changes by diet were observed. Notably, we observed favorable improvement of adipokine concentrations (adiponectin increased 4.4% and 9.5%, leptin decreased 13.0% and 30.1%, and the A/L ratio increased 21.0% and 52.6%, at weeks 25 and 52, respectively) among women who were adherent to the LCD.

Conclusion: These findings suggest that long-term caloric-restriction with increased PA can effectively modify the obesity-related adipokines and thus, may prove useful as cancer preventive strategies for premenopausal women. Future studies of larger samples are required to confirm the beneficial effects of these interventions among high-risk women.

Citation Format: Adana A.M. Llanos, Jessica L. Krok, Juan Peng, Michael L. Pennell, Susan E. Olivo-Marston, Mara Z. Vitolins, Cecilia R. Degraffinreid, Electra D. Paskett. Effects of low-fat and low-carbohydrate dietary patterns combined with physical activity on serum adipokine concentrations among premenopausal women: A randomized trial. [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 C45.
Abstract C47: microRNA expression profiling in normal breast epithelium of BRCA1 and BRCA2 carriers as prevention targets
Authors: Pruthi Sandhya , Buckmeier Julie , Preese Christina , Suman Vera J. , Hurley Rachel M. , Thompson Patricia
Published: May 2019

Background: MicroRNAs (miRNA) are small, noncoding RNAs with important regulatory roles in tissue development, differentiation, proliferation, and when deregulated tumor formation. The goal of this study was to characterize the miRNA profile of normal breast tissue from carriers of either BRCA1 or BRCA2 mutations, with and without a prior history of cancer, for biomarker discovery for future prevention studies in high risk patient populations.

Methods: MicroRNA profiling was conducted using a panel of breast candidate miRNAs and normal ‘non-cancerous’ tissue biopsy from 15 BRCA1 mutation carriers, 15 BRCA2 mutation carriers and 15 BRCA screened mutation negative subjects from high risk families.

Results: While small differences were observed for any individual miRNA between groups, the most striking observation was the presence of a clear BRCA1 miRNA signature that was distinct from that in BRCA2 subjects or in the high-risk, non-mutation carriers. The BRCA1 pattern was present in normal appearing tissue biopsy independent of previous history of cancer, treatment for cancer, age, menopausal status or oophorectomy. BRCA2 carriers and high risk, mutation negative subjects showed an overall shared miRNA expression pattern. MicroRNA species that distinguished the groups included differences in the expressed levels of let-7a, let-7b, miR-125b, miR-145, miR-15b and members of the miR-181 family. Ongoing efforts include pathway modeling to gain insight on novel targets for prevention along with RT-PCR confirmation of differentiating microRNA species as well the potential downstream targets for example of miR-181b target genes including HOXA7, HOXA9, HOXA11 and PBX3.

Conclusion: The presence of a distinctive miRNA profile in normal appearing tissue of BRCA1 mutation carriers suggest a major role of BRCA1 mutation status on the normal tissue not previously reported. If corroborated, miRNA profiling studies of normal breast tissue may prove useful in both risk assessment as well as providing insight on deregulated pathways for pharmacologic intervention for risk reduction in the BRCA carrier population.

Citation Format: Sandhya Pruthi, Julie Buckmeier, Christina Preese, Vera J. Suman, Rachel M. Hurley, Patricia Thompson. microRNA expression profiling in normal breast epithelium of BRCA1 and BRCA2 carriers as prevention targets. [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 C47.
Abstract C50: Results of a phase II randomized, double-blind, placebo controlled trial of Polyphenon E in women with persistent high-risk HPV infection and low-grade cervical intraepithelial neoplasia
Authors: Nuno Tomas , Garcia Francisco A.R. , Cornelison Terri , Mitchell Amy L. , Greenspan David L. , Byron John W. , Hsu Chiu-Hsieh , Alberts David S. , Chow Sherry
Published: May 2019

In vitro data and pilot clinical trial data suggest that green tea catechins may possess chemopreventive activity for cervical cancer and its precursor lesions. We conducted a randomized, double-blind, placebo controlled trial of Polyphenon E (decaffeinated and enriched green tea catechin extract) in women with persistent human papillomavirus (HPV) infection and low grade cervical intraepithelial neoplasia (CIN1) to evaluate the potentials of Polyphenon E for cervical cancer prevention. Ninety-eight eligible women were randomized to receive either Polyphenon E (containing 800 mg epigallocatechin gallate) or placebo once daily for 4 months. The primary study outcome was oncogenic HPV clearance and clearance of CIN1. Polyphenon E was shown to be acceptable, safe and well tolerated. There was no difference in the response rate by treatment allocation. Complete response, defined as negative for high risk HPV and normal histopathology, was noted in 7 (17.1%) and 6 (14.6%) women in the Polyphenon E and placebo arms, respectively. Partial response, defined as clearance of oncogenic HPV with evidence of CIN1, occurred more frequently in the placebo group 6 (14.6%) vs. 1 (2.4%) in the Polyphenon E arm. Progression, defined as persistent oncogenic HPV with histopathologic evidence of progression, was more common in the Polyphenon E group [3 (7.7%) vs. 6 (14.6%) in the placebo arm, although neither of these observations were statistically significant. Based on the largest randomized placebo-controlled trial of a green tea extract for HPV related cervical disease, we conclude that four months of Polyphenon E intervention did not promote the clearance of persistent high risk HPV and related CIN 1. Further studies may be necessary to better delineate the risk factors for persistent HPV infection and biology of the disease to facilitate the evaluation of chemopreventive strategies.

Citation Format: Tomas Nuno, Francisco A.R. Garcia, Terri Cornelison, Amy L. Mitchell, David L. Greenspan, John W. Byron, Chiu-Hsieh Hsu, David S. Alberts, Sherry Chow. Results of a phase II randomized, double-blind, placebo controlled trial of Polyphenon E in women with persistent high-risk HPV infection and low-grade cervical intraepithelial neoplasia. [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 C50.
Abstract CN04-01: Reducing lung cancer mortality by 50% in the next decade: Is it feasible?
Authors: Cummings K. Michael
Published: May 2019

Lung cancer deaths are finally declining in the United States after a nearly century long rise. After a steep increase in cigarette use rates over the first half of the 20th century, smoking prevalence rates started declining from their peak in 1964 and the number of lung cancer deaths followed about 30 years later. Today, less than 20% of adults are current smokers, although there is significant variation from state to state and smoking behavior today, in contrast to 50 years ago, is largely concentrated among the poor and less educated members of society and also among individuals with mental health and substance abuse diagnoses. While some predictions have cigarette consumption dropping to near trivial levels in the US over the next 50 years, others have suggested the rate of decline might be much slower than predicted as the ratio of former to ever smokers has stalled. In other words, while fewer young people are taking up smoking, smoking cessation rates among adult smokers have not changed much in the past decade. While having fewer young people take up smoking means less lung cancer in the long run, in the next decade it means that lung cancer mortality rates will be higher than they might otherwise have to be. This presentation asks the question: Is it feasible to lower lung cancer mortality by 50% in the next decade? The answer to this question is yes, if we want it to make it happen. This presentation describes two complimentary strategies to more rapidly reduce lung cancer mortality in the United States over the next decade. The first strategy includes policies that could realistically be implemented in the next few years to dramatically accelerate a reduction in cigarette consumption. The second strategy focuses on ways to promote lung cancer screening among high risk current and former smokers to change the typical prognosis of lung cancer from one of death sentence to one where lung cancer is detected early enough for cure and improved management. Quite simply, maximizing these two intervention strategies will almost assuredly do more to reduce deaths from lung cancer over the next decade than could possibly be hoped for by investing in high risk biomedical research to try to improve current treatment outcomes, and most likely at a small fraction of the cost.

Citation Format: K. Michael Cummings. Reducing lung cancer mortality by 50% in the next decade: Is it feasible? [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 CN04-01.
Abstract CN08-01: Expediting clinical translation of optical molecular imaging techniques in oncology and its role in preventive medicine
Authors: Dam Gooitzen M. van
Published: May 2019

In recent years, significant progress has been made in both optical imaging systems and fluorescent contrast agents for clinical applications. NIRF imaging with a free-floating imaging device mounted on the ceiling of the operating theatre or on a microscope articulating arm during surgery for cancer will enable visualization of tumor delineation, locoregional metastases, remnant disease as well as e.g. tumor-containing lymph nodes. Hereby, the surgeon can both detect (diagnostic) and excise (therapeutic) malignant tissue and possible residual disease at the same time. The use of NIRF optical imaging has a range of advantages. Most prominent among these is the fact that it is very safe technology, simple to operate, fast, high resolution (as low as 1 mm), relatively inexpensive and makes use of non-ionizing radiation. Based on the above, it is clear that intra-operative imaging is on the verge of entering standard clinical practice for surgery. Not only the imaging system but also the availability of clinical grade tumor-targeted probes is of the utmost importance for a successful introduction into clinical practice. This talk will give an overview of the current concepts and future perspectives of intraoperative fluorescence image-guided surgery using non-targeted and targeted optical contrast agents for the first-time ever used in patients with ovarian cancer and the anticipated developments within the next 5 years. It will become clear that agencies like the FDA and EMA will play a major role in bringing this technology into the clinic and the necessity of standardization of methodology when applied in multinational multicenter studies. Moreover, the role of optical molecular imaging as a screening instrument in preventive medicine will be outlined.

Citation Format: Gooitzen M. van Dam. Expediting clinical translation of optical molecular imaging techniques in oncology and its role in preventive medicine. [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 CN08-01.
Abstract ED02-03: DNA methylation as a target in cancer prevention
Authors: Belinsky Steven A.
Published: May 2019

Epigenetic silencing of genes and microRNAs (miRs) via chromatin remodeling and cytosine methylation has emerged as a major mechanism in cancer etiology. The reversal of gene and miR silencing by affecting cytosine-DNA methyltransferases (DNMTs), histone methyltransferases (HMTs), or histone deacetylases (HDACs) offers new strategies for cancer prevention and intervention for lung cancer. This presentation will provide an overview of studies using natural chemopreventive agents (e.g., lycopenes, isoflavones, omega-3 fatty acids) that reprogram the epigenome for affecting lung, colon, breast and prostate cancer either through generalized effects or targeting the expression of specific microRNAs to modulate genes involved in cancer. Focused studies from our laboratory using an in vitro model of hTERT/cdk4 immortalized human bronchial epithelial cell lines (HBECs) will describe the sequence of events driving gene and microRNA silencing for lung pre-malignancy and novel preventive strategies to reverse transformation. New concepts that incorporate tissue surrogates and biomarkers to assess in humans the efficacy of chemopreventives for lung cancer will be presented.

Citation Format: Steven A. Belinsky. DNA methylation as a target in 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 ED02-03.
Abstract ED05-02: Targeting estrogen receptors for breast cancer prevention
Authors: Ford Leslie G. , Dunn Barbara K.
Published: May 2019

Before “targeted” therapy was part of the oncology lexicon, the estrogen receptor (ER) was already a much touted target of drug development for breast cancer treatment and prevention. Selective estrogen receptor modulators (SERMs) were developed for the purpose of binding to the ER. Tamoxifen, the first SERM studied for breast cancer treatment and prevention, inhibits the action of the ER in the breast. In the 1980s it elicited improvements in overall and disease-free survival in women with breast cancer and was subsequently tested with a primary endpoint of breast cancer prevention in high-risk women. The Breast Cancer Prevention Trial demonstrated a 49% reduction in new breast cancers in high-risk women, leading to FDA approval of tamoxifen for this purpose in 1998. The was the first FDA approval of an agent for a cancer prevention indication. Subsequently a series of SERMs have been developed for osteoporosis, most notably raloxifene. The Study of Tamoxifen and Raloxifene showed the two SERMs to be equivalent in terms of their ability to target the ER and prevent ER-positive breast cancer, with raloxifene exhibiting overall less toxicity. This agent, already approved for osteoporosis treatment and prevention, was approved for breast cancer prevention in postmenopausal women in 2007. More recently, meta-analyses of these and other studies comparing SERMs to placebo in a variety of disease settings have consistently shown benefits for breast cancer prevention in the SERM arm. The latest approach to targeting the estrogenic effect on breast cancer development involves inhibition of estrogen production, as opposed to estrogen action. The aromatase inhibitors (AIs) prevent the enzyme, aromatase, from converting androgens to estrogens. In postmenopausal women, in whom the majority of AI studies have been carried out, the inhibition of estrogen production is almost complete. The Mammary Prevention 3 trial showed that the AI exemestane decreased the incidence of breast cancer by up to 70% compared to placebo, with different toxicities than tamoxifen. The International Breast Cancer Intervention Study II, which is comparing the AI anastrozole to placebo in high-risk postmenopausal women, is still ongoing. Both the SERM and AI classes of targeted breast cancer prevention agents are effective in preventing ER-positive breast cancers, leaving an urgent need to develop drugs to prevent ER-negative breast cancers.

Citation Format: Leslie G. Ford, Barbara K. Dunn. Targeting estrogen receptors 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 ED05-02.
Abstract PL02-03: Changing landscape of environmental carcinogenesis in Qidong, China: Lessons for prevention
Authors: Kensler Thomas W. , Chen Jian-Guo , Chen Tao-Yang , Egner Patricia , Ng Derek , Munoz Alvaro , Groopman John
Published: May 2019

Residents of Qidong, China, located at the mouth of the Yangtze River, are undergoing a rapid fluctuation in cancer incidence rates at many organ sites, reflecting a dynamic interplay of socio-behavioral, economic and environmental factors. As tracked by their cancer registry, there are extraordinary changes in the China age-standardized incidence rates for the two leading cancer killers in the Qidong region: one going down and the other one up, liver and lung cancer respectively. In endemic areas such as Qidong, liver cancer arises from chronic infection with hepatitis B virus (HBV) and ingestion of aflatoxins. Agricultural and economic reforms in the 1980s promoted a switch from maize to rice as the dietary staple, with concomitant >40-fold decreases in aflatoxin exposure over this period as measured by aflatoxin-albumin adducts in archived serum samples. Universal, subsidized vaccination against HBV was initiated in the early 2000s and likely does not account for the 45% drop in liver cancer incidence over the past quarter century, but augurs well for the future. Age standardized incidence rates for lung cancer, by contrast, have tripled in men over this period, reflecting the high prevalence of smoking (~60%) in adult males and increasing numbers of cigarettes smoked. Women in Qidong, on the other hand rarely smoke. Nonetheless, their rates of lung cancer incidence have doubled over the past decade only, perhaps related to changing patterns of exposures to indoor and outdoor air pollution. Approaches to modulate the impact of these exposures through chemopreventive interventions will be presented. Both primary and secondary prevention strategies appear to offer opportunities for risk reduction in this shifting landscape of exposures to environmental carcinogens.

Citation Format: Thomas W. Kensler, Jian-Guo Chen, Tao-Yang Chen, Patricia Egner, Derek Ng, Alvaro Munoz, John Groopman. Changing landscape of environmental carcinogenesis in Qidong, China: Lessons for 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 PL02-03.
Abstract PL04-03: Working in innovative settings to enhance reach and improve population-based physical activity levels
Authors: Linnan Laura
Published: May 2019

Physically active individuals accrue a wide range of health benefits including reduced risk of cardiovascular disease, stroke, diabetes and metabolic syndrome, certain types of cancer; as well as improving mental health, mood, bone and muscular strength, and reduced risk of falls. However, less than half of US adults (age 18+) meet the national Surgeon General recommendations of at least 150 minutes of moderate physical activity, including 2 days of strength training, each week. Certain subgroups of the population, Blacks, Hispanics, lower education and income levels, and those living in rural locations, are more likely to not meet the guidelines. In addition, 33.9% of the US population are considered “inactive” (e.g. less than 10 minutes of activity/week)….and inactive subgroups are also quite similar to those who do not meet physical activity guidelines. To address key health and cancer disparities, we must consider intervention strategies that improve reach and effectiveness within these subgroups. This presentation will share examples of working within innovative settings to improve physical activity levels, as well as decrease inactivity. We will introduce constructs of the RE-AIM framework to guide this discussion.

Citation Format: Laura Linnan. Working in innovative settings to enhance reach and improve population-based physical activity levels. [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 PL04-03.
Abstract PL05-01: Inflammatory mediators, tumor microenvironment, and progression of colorectal cancer
Authors: DuBois Raymond N.
Published: May 2019

Population studies and experimental observations indicate that chronic inflammation and diet are risk factors for colorectal cancer (CRC). The mechanisms by which these factors contribute to the development of cancer are poorly understood. A large body of work has shown that use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the relative risk for developing colorectal cancer (CRC) by up to 40-50%. NSAIDs exert some of their anti-inflammatory and anti-tumor effects by targeting cyclooxygenase enzymes (COX-1 and COX-2). Prostaglandin E2 (PGE2) is a pro-inflammatory mediator that promotes colorectal cancer progression. The aim of our present study was to determine the underlying mechanisms by which PGE2 affects progression of CRC.

We have found a novel function of pro-inflammatory PGE2 in regulating DNA methylation in colorectal cancer. Our in vitro and in vivo studies demonstrated that PGE2 treatment silenced certain tumor suppressors and DNA repair genes such as CDKN2B (p15), CNR1, MGMT, and MLH1 by enhancing CpG island methylation of their promoter via inducing DNMT1 and DNMT3B expression. We also found that a demethylating agent inhibited the effect of PGE2 on promoting tumor growth in a mouse model of colorectal cancer, indicating that PGE2 accelerates tumor growth via regulating DNA methylation. Furthermore, combined treatment of Apcmin/+ mice with inhibitors of COX-2 and DNA methylation has more effectively anti-tumor effects than either single agent alone. To further determine the clinical relevance of our in vitro and in vivo results, we examine the relationship between COX-2 expression, PGE2 levels, DNMT1/3b expression, CpG island methylation status and expression of these tumor suppressors and DNA repair genes in human colorectal carcinomas. The levels of COX-2 and PGE2 positively correlated with DNMT1 and DNMT3B expression in these human colorectal cancer specimens. Importantly, the PGE2 levels as well as COX-2, DNMT1, and DNMT3B expression are also positively associated with the CpG island methylation in the promoters of these tumor suppressors and DNA repair genes. We also observed a specific type of immune cells (MDSCs) attracted to the tumor microenvironment by the presence of PGE2.

Citation Format: Raymond N. DuBois. Inflammatory mediators, tumor microenvironment, and progression of colorectal 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 PL05-01.
Abstract PP01-01: Chemoprevention of Cancer: Past, Present, and Future
Authors: Sporn Michael B.
Published: May 2019

We will summarize highlights of new concepts relating to chemoprevention of cancer during a long career of research on this topic. Particular emphasis will be placed on the following topics: carcinogenesis as a chronic disease process, the question of whether asymptomatic people are truly healthy, the use of drugs both singly and in combination for chemoprevention of cancer, tumor cell heterogeneity, the importance of the use of multifunctional drugs for chemoprevention, and the application of drugs developed in cancer studies for diseases other than cancer.

Citation Format: Michael B. Sporn. Chemoprevention of Cancer: Past, Present, and Future. [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 PP01-01.
Imaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review
Authors: Woodcock Eric A. , Hillmer Ansel T. , Mason Graeme F. , Cosgrove Kelly P.
Published: May 2019

There is tremendous interest in the role of the neuroimmune system and inflammatory processes in substance use disorders (SUDs). Imaging biomarkers of the neuroimmune system in vivo provide a vital translational bridge between preclinical and clinical research. Herein, we examine two imaging techniques that measure putative indices of the neuroimmune system and review their application among SUDs. Positron emission tomography (PET) imaging of 18 kDa translocator protein availability is a marker associated with microglia. Proton magnetic resonance spectroscopy quantification of myo-inositol levels is a putative glial marker found in astrocytes. Neuroinflammatory responses are initiated and maintained by microglia and astrocytes, and thus represent important imaging markers. The goal of this review is to summarize neuroimaging findings from the substance use literature that report data using these markers and discuss possible mechanisms of action. The extant literature indicates abused substances exert diverse and complex neuroimmune effects. Moreover, drug effects may change across addiction stages, i.e. the neuroimmune effects of acute drug administration may differ from chronic use. This burgeoning field has considerable potential to improve our understanding and treatment of SUDs. Future research is needed to determine how targeting the neuroimmune system may improve treatment outcomes.
Letras e literatura
Authors: Lachat Marcelo
Published: May 2019

Este trabalho consiste em uma discussão acerca das noções de “letras” e de “literatura”, construídas historicamente sobre continuidades letradas e descontinuidades literárias. Pretendese, assim, compreender melhor as especificidades das práticas letradas dos séculos XVI, XVII e XVIII em Portugal e na América portuguesa, a fim de que esses textos não sejam lidos fora do tempo ou apenas a partir de uma única concepção temporal: a da modernidade literária com seus anseios de ruptura.
Uma preceptiva do Oitocentos
Authors: Chauvin Jean Pierre
Published: May 2019

Durante o final do século XIX, circularam diversos manuais de cunho pragmático no Brasil. Concebidos como obras a orientar práticas profissionais, elas também poderiam ser lidas à luz de determinados preceitos retóricos, que se supunham extintos com o advento do Romantismo. Neste trabalho, examina-se o Novo manual epistolar ou Arte de escrever, de Machado Coelho, publicado em 1882.
Rapid Successful Reperfusion of Basilar Artery Occlusion Strokes With Pretreatment Diffusion‐Weighted Imaging Posterior‐Circulation ASPECTS <8 Is Associated With Good Outcome
Authors: Guillaume Morgan , Lapergue Bertrand , Gory Benjamin , Labreuche Julien , Consoli Arturo , Mione Gioia , Humbertjean Lisa , Lacour Jean‐Christophe , Mazighi Mikael , Piotin Michel , Blanc Raphaël , Richard Sébastien ,   the Endovascular Treatment in Ischemic Stroke (ETIS) Investigators, Decroix Jean‐Pierre , Wang Adrien , Evrard Serge , Tchikviladzé Maya , Bourdain Frederic , Rodesh Georges , Coskun Oguzhan , Di Maria Federico , Pico Fernando , Rakotoharinandrasana Haja , Tassan Philippe , Poll Roxanna , Corabianu Ovide , de Broucker Thomas , Smadja Didier , Redjem Hocine , Ciccio Gabriele , Smadja Stanislas , Alamowitch Sonia , Fahed Robert , Desilles Jean‐Philippe , Obadia Mickael , Fisselier Matthieu , Sabben Candice , Ille Olivier , Manchon Eric , Garcia Pierre‐Yves , Turjman Francis , Riva Roberto , Labeyrie Paul‐Emile , Bracard Serge , Anxionnat René , Braun Marc , Schmitt Emmanuelle , Planel Sophie , Derelle Anne‐Laure , Tonnelet Romain , Liao Liang
Published: May 2019

Background

The association between time to reperfusion and clinical outcome is well known in anterior circulation strokes, whereas the impact of main time metrics remains unknown in posterior circulation strokes. We investigated the clinical effect of different time intervals from symptom onset to reperfusion on the 90‐day clinical outcome in acute ischemic stroke patients with basilar artery occlusion, and especially in the subset population presenting a low stroke volume on baseline diffusion‐weighted imaging.

Methods and Results

We studied patients included in the prospective, multicenter, observational
ETIS
(Endovascular Treatment in Ischemic Stroke) registry who had had basal artery occlusion and had achieved successful reperfusion (modified Thrombolysis In Cerebral Infarction 2b‐3). Three time intervals (onset to reperfusion, onset to imaging, and imaging to reperfusion) were considered in all patients and separately in patients with pc‐
ASPECTS
(posterior‐circulation Alberta Stroke Program Early Computed Tomography Score) <8 and ≥8 on baseline diffusion‐weighted imaging. The primary end point was good outcome defined as 90‐day modified Rankin Scale scores of 0 to 2. Among the 95 included patients, 38 (40%) achieved a good outcome. In all patients, no significant association was found between the different time intervals and outcome. In patients evaluated with diffusion‐weighted imaging (n=61) at baseline, a significant negative association was found between imaging‐to‐reperfusion time for patients with pc‐
ASPECTS
<8 (adjusted odds ratio=0.4 per 30‐minute increase; 95% CI 0.18‐0.85;
P
=0.02) compared with those with pc‐
ASPECTS
≥8.

Conclusions

In patients with basilar artery occlusion and pc‐
ASPECTS
<8 at baseline diffusion‐weighted imaging, clinical outcome is highly dependent on the time from imaging to reperfusion, which suggests that rapid endovascular reperfusion should be performed after imaging in these patients.
Increased Complement 3 With Suppression of miR‐145 Induces the Synthetic Phenotype in Vascular Smooth Muscle Cells From Spontaneously Hypertensive Rats
Authors: Chen Lan , Fukuda Noboru , Otsuki Tomoyasu , Tanaka Sho , Nakamura Yoshihiro , Kobayashi Hiroki , Matsumoto Taro , Abe Masanori
Published: May 2019

Background

We previously reported that vascular smooth muscle cells (
VSMC
s) from spontaneously hypertensive rats (
SHR
s) show the increased expression of complement 3 (C3) and the synthetic phenotype. We targeted the
SHR
C3 gene (C3 knockout [C3
KO] SHRs
) by the zinc finger gene editing method. In the current study, we investigated the mechanisms underlying the increased expression of C3 and the role of endogenous C3 in the synthetic phenotype of
SHR VSMC
s in comparison to cells from Wistar‐Kyoto (
WKY)
rats and C3
KO SHR
s.

Methods and Results

Nonmuscle myosin heavy chain staining of aortas from
SHR
s at 1 day after birth was stronger in comparison to
WKY
rats and C3
KO SHR
s.
DNA
synthesis in
VSMC
s from
SHR
s was significantly higher in comparison to
WKY
rats and C3
KO SHR
s. Immunohistochemical staining of renin and liver X receptor α in
VSMC
s from
SHR
s was stronger in comparison to
WKY
rats and C3
KO SHR
s. The expression of renin, Krüppel‐like factor 5, and liver X receptor α proteins in
VSMC
s from
SHR
s was significantly higher in comparison to
WKY
rats and C3
KO SHR
s. The expression of synthetic phenotype markers osteopontin, matrix gla, and
l
‐caldesmon, growth factors transforming growth factor‐β1 and platelet‐derived growth factor‐A, transcription factors Krüppel‐like factor 5 and liver X receptor α, and angiotensinogen
mRNA
s in
VSMC
s from
SHR
s was significantly higher in comparison to
WKY
rats and C3
KO SHR
s. The expression of miR‐145
mRNA
in
VSMC
s from
SHR
s was suppressed in comparison to cells from
WKY
rats. miR‐145 inhibitor significantly increased the expression of C3 in
VSMC
s from
WKY
rats, but not in cells from
SHR
s.

Conclusions

These findings indicate that the increased C3 with the suppression of miR‐145 induces the synthetic phenotype through Krüppel‐like factor 5 and the activation of the renin‐angiotensin system through liver X receptor α in
VSMC
s from
SHR
s.
Anesthetizing the Fibrillating Heart
Authors: Hanna Peter , Zhu Ching , Rajendran Pradeep S. , Shivkumar Kalyanam
Published: May 2019

See Article
Lee et al
Verruconis heveae, a novel species from Hevea brasiliensis in Thailand
Authors: HUANRALUEK NARUEMON , PHUKHAMSAKDA CHAYANARD , SENWANNA CHANOKNED , HONGSANAN SINANG , JAYAWARDENA RUVISHIKA S. , BHAT DARBHE J. , HYDE KEVIN D.
Published: May 2019

Verruconis heveae, a new species accommodated in Sympoventuriaceae was isolated from dried latex on bark of a rubber tree (Hevea brasiliensis) collected from Phayao Province, Thailand. The comparison of its morphological characters distinguished V. heveae from other Verruconis species by having brown, woolly mycelium on the natural substrate and solitary, ellipsoidal to subglobose, 1–3 septate conidia. Phylogenetic analysis of a combined LSU and ITS dataset revealed a distinct lineage within Sympoventuriaceae.
Limonium dagmarae (Plumbaginaceae), a new species from Namaqualand coast, South Africa
Authors: MUCINA LADISLAV , HAMMER TIMOTHY A.
Published: May 2019

A new species of Limonium from Namaqualand coast, South Africa is here described and named L. dagmarae. Shared morphological characters with related South African species place the new species within L. sect. Circinaria. Evidence is presented to segregate the new species from relatives based on discrete morphological and environmental characters. The holotype of the L. dagmarae is preserved at NBG.
Two novel species of Marasmius (Marasmiaceae, Agaricales) from lower northern Thailand
Authors: WANNATHES NOPPARAT , SUWANNARACH NAKARIN , KUMLA JATURONG , LUMYONG SAISAMORN
Published: May 2019

Two new species of Marasmius secton Sicci are described based on field work conducted in Phu Hin Rong Kla National Park, Thailand. Marasmius thailandicus is characterized by small, thin yellowish white basidiomes, ellipsoid basidiospores and dimorphic caulocystidia. Marasmius rongklaensis is distinguished by a conical, velutinous pileus, ellipsoid basidiospores, dimorphic cheilocytidia and pileipellis a hymeniderm with pileosetae. Comprehensive description along with illustrations, photographs, and a comparison with phenetically similar taxa are provided. The taxonomic position has been confirmed by phylogenetic analyses of the internal transcribed spacer (ITS1-5.8S-ITS2) sequences of the ribosomal DNA.
Milenascopia gen. nov. (Orthoptera: Proscopiidae) from the Brazilian Amazon Basin and a pictorial key to Proscopiini genera
Authors: QUEIROZ LARISSA LIMA DE , RAFAEL JOSÉ ALBERTINO
Published: May 2019

A new genus of Proscopiidae, Milenascopia gen. nov., is described from Brazil, with two included species, namely Milenascopia bilineata gen. nov., sp. nov. (type-species) and Milenascopia tenuis gen. nov., sp. nov. A pictorial key of Proscopiini, based on the male genitalia is provided.