bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B59: Bilateral oophorectomy at age 55 or older does not reduce risk of breast cancer
Authors: Hofstatter Erin , Chagpar Anees
Published: May 2019

Introduction: It is widely accepted that premenopausal bilateral oophorectomy (BSO) reduces the risk of breast cancer. However, recently published data suggest that BSO done after menopause may also reduce risk of breast cancer. We sought to determine the impact of postmenopausal BSO on subsequent breast cancer diagnosis in a nationally representative sample.

Methods: The National Health Interview Survey (NHIS) is a population-based survey conducted annually by the CDC and is designed to be representative of the non-institutionalized civilian population in the United States. We utilized data from the 2010 NHIS cancer supplement to compare breast cancer diagnosis rates in women who underwent postmenopausal BSO versus those who did not. We defined our population of interest as those women ages 65 and older who underwent BSO between the ages of 55-64. Statistical analyses were conducted using SUDAAN software.

Results: In 2010, 21707 women ages 65 and older were surveyed, representing 190,813,389 people in the population. Of these, 0.97% underwent BSO between the ages of 55-64. 4.82% of women 65 years of age and older were surveyed reported developing breast cancer after the age of 65. On univariate analysis, 8.08% of women who had undergone a BSO between the ages of 55-64 developed breast cancer after age 65; whereas 24.11% of women who had not undergone a BSO developed breast cancer after age 65 (p=0.0188). The median age at which women undergoing BSO developed cancer was 74 years, on average 14 years after their oophorectomy. Having a BSO after menopause (vs. not having a BSO) was not associated with age of menarche 11 years or younger (13.8% vs. 15.6%, p=0.3701), parity (91.9% vs. 89.2%, p=0.3793), age at first live birth < 20 (22.5% vs. 34.3%, p=0.0125), family history of a first degree relative with breast cancer (p=0.3726), body mass index 30 or above (31.6% vs. 28.2%, p=0.2811), income (p=0.2819), region (p=0.1811) or race/ethnicity (p=0.7611). However, BSO was found to be associated with higher education levels (p=0.0461), Medicare insurance (98.1% vs. 95.4%, p=0.0002) and increased ever use of HRT (50.3% vs. 25.6%, p= 0.0008). Controlling for these potential confounders on multivariate analysis, BSO was no longer associated with breast cancer after age 65 (OR = 0.38; 95% CI: 0.10-1.43, p=0.1522).

Conclusion: Bilateral oophorectomy performed in women after the age of 55 does not appear to reduce the risk of postmenopausal breast cancer. This patient population should continue to be counseled on other methods to reduce breast cancer risk, such as chemoprevention and weight loss.

Citation Format: Erin Hofstatter, Anees Chagpar. Bilateral oophorectomy at age 55 or older does not reduce risk of breast 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 B59.
Abstract B61: Vitamin D-binding protein and pancreatic cancer: A nested case-control study
Authors: Piper Marina R. , Kopp William , Rager Helen , Horst Ronald L. , Stolzenberg-Solomon Rachael Z.
Published: May 2019

Research examining the association between vitamin D and pancreatic cancer is inconsistent, with some studies showing an elevated risk with increased vitamin D (Stolzenberg-Solomon, 2006, 2009, 2010) and another showing an inverse association. (Wolpin, 2012) This counterintuitive finding has led researchers to investigate levels of vitamin D-binding protein (DBP) as a possible explanation. DBP serves several important functions in the body, including acting as the primary carrier of vitamin D in the bloodstream. (Speeckaert, 2006) Previous research in the Alpha-Tocopherol, Beta-Carotene Study found an inverse trend for DBP and pancreatic cancer in male Finnish smokers, with higher compared to lower DBP concentrations showing a protective association with pancreatic cancer. (Weinstein, 2012)

We conducted a nested case-control study in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial cohort of men and women aged 55-74 at baseline. Between 1993 and 2010, 295 incident cases of pancreatic adenocarcinoma were reported (follow-up to 15.1 years). Two controls (n = 590) who were alive at the time the case was diagnosed were selected for each case and were matched by age, race, sex, month of blood draw. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, adjusting for smoking status and diabetes mellitus.

DBP concentration was not significantly associated with pancreatic cancer overall (highest vs. lowest quintile, ≥7149.4 vs.<3670.4 nmol/L: OR=1.75, 95% CI 0.91-3.37, p-trend=0.32). However, we observed a significantly elevated pancreatic cancer risk among cases diagnosed >5 years after baseline (n = 214 cases, highest vs. lowest quintile, OR=2.12, 95% CI 1.01-4.43, p-value=0.047).

We did not confirm the protective association seen previously. Our results do not support the hypothesis that DBP plays a protective role in pancreatic cancer.

Funded by NCI Contract No. HHSN261200800001E.

Citation Format: Marina R. Piper, William Kopp, Helen Rager, Ronald L. Horst, Rachael Z. Stolzenberg-Solomon. Vitamin D-binding protein and pancreatic cancer: A nested case-control 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 B61.
Abstract B62: Circulating vitamin D binding protein, 25-hydroxyvitamin D, and advanced and lethal prostate cancer risk
Authors: Shui Irene , Wilson Kathryn , Stampfer Meir , Mucci Lorelei , Giovannucci Ed
Published: May 2019

Introduction: Circulating 25-hydroxyvitamin D (25(OH)D) is the most commonly accepted blood biomarker for vitamin D status in epidemiologic studies. We have previously shown that higher circulating 25(OH)D was related to a reduced risk of advanced and lethal prostate cancer (PCa). However, 85-90% of circulating 25(OH)D is bound to vitamin D-binding protein (DBP) and current laboratory assays do not differentiate between bound and unbound forms of 25(OH)D. The role of DBP on PCa remains unclear. DBP extends the half-life of circulating 25(OH)D, but it is not known whether DBP-bound vitamin D activity on prostate cells is less than in the unbound form. DBP circulates at much higher levels than 25(OH)D and may also have independent effects on prostate carcinogenesis. Using prospectively measured circulating DBP and 25(OH)D, we assessed whether DBP was related to advanced/lethal PCa and whether the relationship between 25(OH)D and advanced/lethal PCa was modified by DBP levels.

Methods: We included 164 men diagnosed with advanced (Stage T3b or higher) and lethal (distant metastases or PCa specific cause of death) PCa and 164 matched controls nested in the Health Professionals Follow-up Study. We used unconditional logistic regression, adjusted for matching factors, to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between DBP, 25(OH)D, and advanced/lethal PCa. We assessed effect modification by high and low 25(OH)D or DBP levels using the median value as the cut point.

Results: Circulating DBP and 25(OH)D were modestly correlated in controls (Spearman correlation=0.17; p=0.04). Consistent with our previous study, higher plasma 25(OH)D was associated with a reduced risk of advanced/lethal PCa (OR (95% CI) for highest vs. lowest quartile of 25(OH)D: 0.28 (0.14-0.57); p-trend <0.0001); adjusting for circulating DBP did not change these results. The association between 25(OH)D and advanced/lethal PCa was not modified by DBP level (p-interaction=0.34). Plasma DBP was inversely associated with advanced and lethal PCa risk in those with high 25(OH)D levels (OR (95% CI) for highest vs. lowest quartile of DBP: 0.29(0.08-0.99); p-trend=0.03), but not in those with low 25(OH)D levels (OR (95% CI): 1.32(0.52-3.36); p-trend=0.73). The p-interaction was 0.0003.

Conclusions: Adjusting for circulating DBP did not influence the association between 25(OH)D and advanced/lethal PCa in our study. However, the role of DBP in prostate carcinogenesis warrants future investigation.

Citation Format: Irene Shui, Kathryn Wilson, Meir Stampfer, Lorelei Mucci, Ed Giovannucci. Circulating vitamin D binding protein, 25-hydroxyvitamin D, and advanced and lethal prostate cancer risk. [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 B62.
Abstract C01: Assessment of interest for breast cancer prevention trial participation among BRCA mutation carriers
Authors: Hurley Rachel M. , Suman Vera J. , Daly Mary , Olopade Funmi , Limburg Paul J. , Pruthi Sandhya
Published: May 2019

Purpose: BRCA1 and BRCA2 mutation carriers develop breast cancers with a tumor phenotype unique from spontaneous tumors. We surveyed documented BRCA mutation carriers to determine willingness to be contacted about participation in future breast cancer prevention research studies directed to their unique phenotype that may or may not require breast biopsies.

Methods: At each of the 3 participating institutions, women at least 20 years of age with a documented germline deleterious mutation in BRCA1 or BRCA2 and no prior history of breast cancer were contacted to participate in a survey to ascertain their willingness to be contacted to participate in future prevention trials. Survey results were summarized using descriptive statistics.

Results: Among 56 BRCA1 and BRCA2 mutation carriers who responded, 55.4% of women reported high or very high interest in participating in randomized control study of chemoprevention agent vs. placebo. Within this population, post-menopausal women demonstrated a higher interested in study participation (64.5%) versus pre-menopausal women (38.9%). When examining willingness to undergo breast biopsy for a chemoprevention study, women expressed near equal willingness (42.9%) and unwillingness (44.6%) for biopsy.

Conclusions: BRCA1 and BRCA2 mutation carriers demonstrated significant interest in breast cancer prevention study participation involving trial agent versus placebo, and an equal expression of willingness and unwillingness to undergo breast biopsy, establishing the feasibility for future research elucidating targeted chemoprevention agents.

Citation Format: Rachel M. Hurley, Vera J. Suman, Mary Daly, Funmi Olopade, Paul J. Limburg, Sandhya Pruthi. Assessment of interest for breast cancer prevention trial participation among BRCA mutation carriers. [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 C01.
Abstract C09: Trends in colorectal cancer mortality and screening activities in European countries
Authors: Ouakrim Driss , Negri Eva , Malvezzi Matteo , Bleiberg Harry , Jenkins Mark , Boniol Mathieu , Autier Philippe
Published: May 2019

Background: Randomized trials have shown that fecal-occult-blood-test (FOBT) and endoscopic exterminations of the large bowel were able to decrease the risk of CRC death. We examined whether changes in CRC mortality in Europe were associated with a history of screening.

Methods: We used data collected as part of the Survey of Health, Aging, and Retirement in Europe (SHARE) project to extract information on exposure to CRC screening in subjects 50 years old or more living in 11 European countries. Distinct data were collected for endoscopy (colonoscopy or sigmoidoscopy) and FOBT. Using the WHO mortality database on causes of deaths, we fitted linear regressions from 1989 to 2010 and calculated changes in mortality for men and women living in each of the 11 countries. We used least square regression and computed R-square statistics (expressed in %) to provide estimates of the association between screening history and changes in CRC mortality.

Results: Over the 22-year period, changes in age-adjusted CRC mortality rates among males/females were -39/-47% in Austria, -34/-32% in France, -30/-44% in Germany, -26/-35% in Switzerland, -17/-23% in Italy, -14/-18% in Denmark, -10/-8% in Sweden, -4/-10% in the Netherlands, +29/-6% in Spain, and +30/+2% in Greece. In males, reports of ever having had an endoscopic examination of the large bowel ranged from 8% in Greece to 35% in Austria. For females, proportions of ever having undergone endoscopic examinations ranged from 8% in Greece to 36% in Austria. FOBT screening over the last 10 years, ranged from 4% in the Netherlands to 61% in Austria for both sexes. In males, a history of one or more endoscopic examination of the large bowel explained 73% of the decrease in CRC mortality. Having had at least one endoscopy or FOBT over the past 10 years explained 54 and 53% of the observed decrease in CRC mortality, respectively. In females, a history of one or more endoscopic examination of the large bowel explained 82% of the decrease in CRC mortality. Having had at least one endoscopy or FOBT over the past 10 years explained 89 and 72% of the decrease, respectively. All R-squares had an associated p value < 0.001.

Conclusions: Changes in CRC mortality are correlated with the level of screening uptake. This provides “real world” evidence of the effectiveness of screening to prevent CRC mortality in the general population and a strong rational for current national CRC screening programs.

Citation Format: Driss Ouakrim, Eva Negri, Matteo Malvezzi, Harry Bleiberg, Mark Jenkins, Mathieu Boniol, Philippe Autier. Trends in colorectal cancer mortality and screening activities in European countries. [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 C09.
Abstract C64: SNPs in genes of the glucose-metabolism pathway and prostate cancer: Interplay with metformin
Authors: Murtola Teemu J. , Wahlfors Tiina , Tammela Teuvo LJ , Mååttånen Liisa , Schleutker Johanna
Published: May 2019

Background: Energy metabolism is important for cancer progression. Energy-producing mitochondria also regulate cell growth and survival. Type II diabetes affects systemic energy metabolism, while both diabetes and antidiabetic treatment likely affect prostate cancer. We studied whether SNPs in genes of the energy-metabolism pathways associate with prostate cancer risk and prognosis, and whether the associations are modified by antidiabetic treatment.

Materials and methods: As part of an international PRACTICAL Consortium, 397 SNPs were genotyped on Illumina's custom array (iCOGS) among 3,719 participants of the Finnish Prostate Cancer Screening Trial and 1,528 hospital-based cases. The study population was linked to Finnish national prescription database for information on medication use.

After correction for multiple testing using adaptive permutation, SNPs showing an association with prostate cancer incidence or mortality at p < 5 x 10-3 significance level were further explored in multivariable-adjusted Cox regression analyses. Analyses on prostate cancer risk and mortality were adjusted for age and screening trial arm. Analyses on prostate cancer case-fatality were additionally adjusted for tumor stage and grade at diagnosis.

Results: After permutation, a total of 30 and 10 SNPs were associated with prostate cancer risk or mortality, respectively. Of these, SNPs in genes PDK1, PGM1 and ENO1 showed consistent associations with prostate cancer risk, disease grade/stage and prostate cancer mortality/case fatality in both study cohorts.

The associations with prostate cancer were stronger among antidiabetic drug users in general, although the interaction terms were not significant. Higher cumulative amount of metformin use attenuated the risk increase among antidiabetic drug users.

Conclusions: Polymorphisms in genes of the energy-metabolism pathways associate with prostate cancer risk, disease severity and prognosis. This association may be modified by diabetes and antidiabetic drug usage. If validated in further studies, these polymorphisms could be used in risk stratification of prostate cancer patients.

Citation Format: Teemu J. Murtola, Tiina Wahlfors, Teuvo LJ Tammela, Liisa Mååttånen, Johanna Schleutker. SNPs in genes of the glucose-metabolism pathway and prostate cancer: Interplay with metformin. [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 C64.
Abstract CN02-02: Elucidating mechanisms of environmentally induced kidney cancers
Authors: Threadgill David
Published: May 2019

Epidemiology data suggests that exposure to trichloroethylene (TCE) is associated with increased susceptibility to a variety of diseases including elevated incidence of kidney cancer. Molecular analysis of kidney cancers from workers in Germany revealed a TCE-specific hotspot mutation in the von Hippel-Lindau (VHL) gene. We used a mouse embryonic stem cell assay to demonstrate that the TCE-associated VHL mutation is highly transforming and confers apoptotic and DNA damage resistance. To investigate genetic susceptibility to TCE, we exposed a genetically diverse mouse population to TCE with or without inorganic arsenic (iAS), a toxicant naturally found in the environment in many locations. We observed cooperation between TCE and iAS in the induction of a gene expression signature in kidneys identical to that caused by the TCE-associated VHL mutation. After one year of exposure, subsets of mice developed kidney cancers, some of which became metastatic to the lung. A systems analysis revealed complex patterns of genetic susceptibility. The results demonstrate that chemical combinations can elicit additive and synergistic toxicities in genetically susceptible individuals.

Citation Format: David Threadgill. Elucidating mechanisms of environmentally induced kidney cancers. [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 CN02-02.
Abstract CN03-01: The role of NCI's Cancer Intervention and Surveillance Modeling Network (CISNET) in guiding cancer control planning and priorities
Authors: Feuer Eric J.
Published: May 2019

CISNET is a consortium of NCI-sponsored investigators that use simulation modeling to understand past trends in cancer incidence and mortality, and to guide public health research and priorities. In this talk we describe the role of simulation modeling in understanding the population impact of interventions (i.e. screening, treatment and prevention). We review some of the unique aspects of modeling as carried out by CISNET, i.e. the development of flexible broad-based disease models, the ability to model multiple birth cohorts, comparative modeling, transparency in model structure and assumptions, and outreach to partners to make the modeling relevant. Finally, we summarize some of the major accomplishments of CISNET.

Citation Format: Eric J. Feuer. The role of NCI's Cancer Intervention and Surveillance Modeling Network (CISNET) in guiding cancer control planning and priorities. [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 CN03-01.
Abstract CN03-02: Modeling past and future smoking patterns in the U.S
Authors: Holford Theodore R.
Published: May 2019

To evaluate the impact of tobacco control interventions on smoking-related mortality it is essential to develop smoking histories over the life course of different birth cohorts. Analyses that extend the detail beyond prevalence in order to also include initiation, cessation and intensity has received limited attention. US National Health Interview Surveys conducted from 1965-2009 provided cross-sectional information on current smoking behavior. Some of these surveys also provided additional detail on age at initiation and cessation, and smoking intensity. Age-period-cohort models with constrained natural splines were adjusted for survival differences by smoking status to obtain estimates of the prevalence of current, former and never smokers for ages 35-99 in cohorts beginning in 1890. This approach also yielded yearly estimates of initiation, cessation and smoking intensity for each birth cohort which were projected forward through 2050 based on recent trends. These summaries show clear trends by gender, cohort and age over time. If current patterns persist, a slow decline in smoking prevalence is projected from 2010 through 2040. This new method of generating smoking histories has been included in the National Cancer Institute's Smoking History Generator which can be used in micro-simulation models to assess the impact of alternative tobacco control strategies.

Citation Format: Theodore R. Holford. Modeling past and future smoking patterns in the U.S. [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 CN03-02.
Abstract CN04-02: Pancreatic cancer: Deriving a model of prevention
Authors: Rhim Andrew D.
Published: May 2019

Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of cancer-related deaths in the United States. However, PDAC is only the ninth most prevalent cancer, underscoring the grim prognosis in this disease. Indeed, early diagnosis in this disease has been an abject failure, as more than 80% of all patients are diagnosed with either locally advanced or distant metastatic disease, precluding surgical resection. In this brief discussion, the problem of early diagnosis will be contextualized with attention to factors specific to the biology of PDAC that have made this particularly challenging. Finally, strategies utilizing novel bench-to-bedside approaches to identify novel biomarkers and diagnostic strategies, including the measured use of genetically engineered mouse models, will be highlighted.

Citation Format: Andrew D. Rhim. Pancreatic cancer: Deriving a model of 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 CN04-02.
Abstract CN07-01: A phase IIa randomized, double-blind trial of erlotinib in inhibiting EGF receptor signaling in aberrant crypt foci of the colon
Authors: Lipkin Steven , Bhattacharya Asmita , Morgan Timothy , Zell Jason , Gillen Daniel , Wong Vanessa , Chung Jinah , Chen Wen Pin , Gonzalez Rachel , Meyskens Frank , Rodriguez Luz , Szabo Eva , Carroll Robert , Benya Richard
Published: May 2019

Colorectal cancer (CRC) progresses through multiple distinct stages that are potentially amenable to chemopreventative intervention. Epidermal Growth Factor Receptor (EGFR) inhibitors can shrink advanced tumors including CRC. There is significant evidence that EGFR also plays important roles in CRC initiation, and that EGFR inhibitors block tumorigenesis. We therefore performed a double-blind randomized trial (N=45) to test whether the EGFR inhibitor erlotinib (25mg, 50mg and 100mg doses) given for up to 28 days had an acceptable safety and efficacy profile to reduce EGFR signaling biomarkers in colorectal aberrant crypt foci (ACF), a subset of which progress to CRC, and normal rectal tissue. Participants were stratified by NSAID dose. Erlotinib was well tolerated and there were no unanticipated adverse events. Colorectal ACF and normal tissue EGFR signaling changes with erlotinib were modest and there was no clear dose response. However, individuals with high baseline EGFR signaling may potentially constitute a subset that could benefit from this strategy. Overall, our results support the safety of erlotinib in the chemoprevention setting, but efficacy in colorectal EGFR signaling inhibition is likely insufficient to merit further studies without additional pre-screening stratification.

Citation Format: Steven Lipkin, Asmita Bhattacharya, Timothy Morgan, Jason Zell, Daniel Gillen, Vanessa Wong, Jinah Chung, Wen Pin Chen, Rachel Gonzalez, Frank Meyskens, Luz Rodriguez, Eva Szabo, Robert Carroll, Richard Benya. A phase IIa randomized, double-blind trial of erlotinib in inhibiting EGF receptor signaling in aberrant crypt foci of the colon. [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 CN07-01.
Abstract ED01-02: Inflammatory responses in gastrointestinal cancer development and malignant progression
Authors: Oshima Masanobu
Published: May 2019

Approximately 20% of malignant cancers are associated with chronic infectious disease. Moreover, accumulating evidence has indicated that infection-induced chronic inflammation plays an important role in cancer development. For example, atrophic gastritis and chronic hepatitis caused by H. pylori infection and hepatitis virus infection, respectively, are risk factors for cancer development in the respective organs. Consistently, regular use of non-steroidal anti-inflammatory drugs (NSAIDs) that target cyclooxygenase (COX)-2, reduces a risk of gastrointestinal cancer development. We have constructed gastric cancer mouse model, Gan mice, by transgenic expression of Wnt1, COX-2, and mPGES-1, which activates canonical Wnt signaling and inflammatory COX-2/PGE2 pathway simultaneously in the stomach. Importantly, Gan mice develop inflammation-associated gastric cancer with 100% incidence. Using Gan mouse model, we have found that bacterial infection through TLR/Myd88 signaling as well as proinflammatory cytokine TNF-α pathway are required for gastric tumor development. Both pathways activate NF-κB in cancer cells, and recent results indicate that NF-κB activation induces dedifferentiation of epithelial cells through acquisition of stem-cell-like properties. Moreover, it has been shown that p53 mutation activates NF-κB pathway in cancer tissues. These results indicate that NF-κB activation caused by cytokine signaling or oncogenic activation plays a key role in gastrointestinal cancer development. Moreover, our preliminary results indicate that inflammatory responses are required also for malignant invasion. Accordingly, regulation of chronic inflammation will be an effective preventive strategy against gastrointestinal cancer development and progression.

Citation Format: Masanobu Oshima. Inflammatory responses in gastrointestinal cancer development and malignant progression. [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 ED01-02.
Abstract PL01-03: Tobacco assessment and cessation in cancer patients: An urgent need
Authors: Toll Benjamin A.
Published: May 2019

Tobacco use is associated with poor outcomes (e.g., increased toxicity) in cancer patients, and tobacco cessation is related to several favorable outcomes (e.g., improved response to cancer treatments, decreased risk for a second primary tumor, increased survival). However, tobacco cessation support is not routinely provided to cancer patients. This presentation will cover the current status of tobacco assessment and cessation in clinical practice and in clinical trials. Specifically, national data regarding cancer treatment provider behaviors and preferences with regard to tobacco assessment and cessation support will be discussed. In addition, tobacco use assessment and referral or provision of treatment in national clinical trials will be reviewed. Strategies for implementation of tobacco cessation into standard clinical cancer care will be discussed, with a presentation of a variety of prototypical programs. The ongoing need for additional research in all of these areas will also be discussed.

Citation Format: Benjamin A. Toll. Tobacco assessment and cessation in cancer patients: An urgent need. [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 PL01-03.
Spielt die retinale Nervenfaserschichtdicke bei Migränepatienten eine Rolle?
Authors: Göbel Katja
Published: May 2019

Background: Migraine is a chronic neurological disorder. However, its pathogenesis is still unclear. This study aimed to measure the posterior ocular structure in patients with migraine using enhanced depth imaging (EDI)-optical coherence tomography (OCT) and explore the probable pathogenesis of migraine. Methods: A total of 115 patients diagnosed with migraine and 50 healthy volunteers were recruited. These participants underwent an ocular examination to exclude the ocular diseases. Retinal nerve fiber layer thickness, macular thickness, and choroid thickness were assessed using EDI-OCT. Results: The nasal peripapillary retinal nerve fiber layer (pRNFL) was significantly thinner in the migraine with aura group (p = 0.001) than that in the control group. The inferior inner macular layer was thinner in the migraine with aura group (p = 0.005). The 3 subfields of choroid were significantly thinner in the migraine with aura group (p = 0.044, 0.008, and 0.029). However, there was no difference between the migraine without aura group and the control group. The nasal pRNFL in migraine with aura was negatively correlated with the product of duration (months) and number of attacks/month (p = 0.039). Conclusion: The changes in the ocular posterior structure may serve as evidence of the trigeminovascular system mechanism underlying migraine and transneuronal retrograde degeneration of the primary visual cortex, which reflects the cortical spreading depression.
Komparative Analyse von Sicherheits- und Funktions-Outcomes der anterioren versus retropupillaren Irisklauen-IOL-Implantation
Authors: Mora Paolo , Calzetti Giacomo , Favilla Stefania , Forlini Matteo , Tedesco Salvatore , Date Purva , Tagliavini Viola , Carta Arturo , Frisina Rino , Pedrotti Emilio , Gandolfi Stefano
Published: May 2019

Ziel: Vergleich der funktionellen und klinischen Outcomes von Intraokularlinsen (IOL) bei Fixation mit Irisklauen an der Vorder- versus Hinterfläche der Iris. Patienten und Methoden: Multizentrische retrospektive Studie. Analysiert wurden Daten zu Augen, denen ab Januar 2015 eine anteriore oder retropupillare Irisklauen-IOL implantiert wurde, wenn der Kapselsack infolge einer vorhergehenden Kataraktoperation, Verletzung oder IOL-Dislozierung oder -Trübung keinen ausreichenden Halt bot. Für den Einschluss in die Studie mussten die Patientenakten Daten sowohl zur präoperativen Lage als auch zu den Zeitpunkten 1 und 12 Monate nach der Implantation enthalten. Die beiden Gruppen wurden hinsichtlich folgender Parameter verglichen: beste korrigierte Sehschärfe in der Ferne (Fernvisus c. c.), sphärischer und zylindrischer Refraktionsfehler, Endothelzelldichte (EZD), zentrale Netzhautdicke (ZND) sowie prozentualer Anteil und Art der postoperativen Komplikationen. Ergebnisse: Insgesamt 60 Augen von 60 Patienten im Alter von 73 ± 13 Jahren wurden in die Studie eingeschlossen: 28 Augen (47%) mit anterior und 32 Augen (53%) mit retropupillar fixierter Irisklauen-IOL. Präoperativ waren die Gruppen in allen Aspekten vergleichbar, außer dass die Gruppe mit retropupillar fixierter IOL einen signifikant höheren Anteil an Patienten mit geschlossener Bulbusverletzung in der Vorgeschichte aufwies (p = 0,03). Nach dem Eingriff zeigten beide Gruppen vergleichbare Verbesserungen des Fernvisus c. c. (finaler Fernvisus c. c.: 0,34 ± 0,45 vs. 0,37 ± 0,50 logMAR in der Gruppe mit anterior vs. retropupillar platzierter IOL). Auch bei den Refraktionsfehlern und der ZND waren in der Nachbeobachtung keine Gruppenunterschiede festzustellen. Bei beiden Gruppen traten ein vergleichbares Maß an EZD-Verlust und eine vergleichbare Inzidenz postoperativer Komplikationen ein; die häufigste Komplikation war hierbei das zystoide Makulaödem. Multivariate lineare Regressionsanalysen ergaben, dass der Fernvisus c. c. nach 1 Monat der beste Prädiktor für den finalen Fernvisus c. c. war. Schlussfolgerungen: Zur Korrektur der Aphakie in Augen mit inadäquatem Kapselsack-Halteapparat ist die Irisklauen-Fixation einer IOL in der Vorderkammer und Hinterkammer gleichermaßen wirksam und sicher.
Implantation einer torischen IOL bei einem Patienten mit Keratokonus und vorhergehender perforierender Keratoplastik: Fallbericht und Literaturübersicht
Authors: Allard Karin , Zetterberg Madeleine
Published: May 2019

Hintergrund: Eine Kataraktoperation bei Patienten mit Keratokonus mit oder ohne vorherige perforierende Keratoplastik (pKP) kann problematisch sein, weil die Auswahl der Intraokularlinse (IOL) und die Vorhersage des refraktiven Ergebnisses schwierig sind. Wir berichten hier über die Versorgung eines Patienten mit Keratokonus und früherer pKP auf einem Auge. Fallbericht: Ein 71-jähriger Patient hat bilateral eine Katarakt und einen fortgeschrittenen Keratokonus; im linken Auge wurde zuvor eine pKP vorgenommen. Präoperativ betrug die beste korrigierte Sehschärfe (Visus c. c.) im rechten Auge 20/150 bei -5,75 sph -9,75 cyl 72° und im linken Auge 20/40 bei -0,25 sph -5,0 cyl 50°. Am rechten Auge wurde eine Phakoemulsifikation mit Implantation einer sphärischen IOL vorgenommen, im linken Auge wurde eine torische IOL implantiert. Der postoperative Visus c. c. betrug im rechten Auge 20/80 bei +1,25 sph -3 cyl 65° und im linken Auge 20/25 bei -0,5 sph -3,25 cyl 80°. Schlussfolgerungen: Die Korrektur von Post-pKP-Astigmatismus und Katarakt mittels Phakoemulsifikation und Implantation einer torischen IOL kann eine effektive und sichere Behandlungsoption sein. Das refraktive Outcome nach einer Kataraktchirurgie bei Patienten mit fortgeschrittenem Keratokonus ist schon bei Verwendung von nichttorischen IOL schwierig vorherzusagen; Operateure sollten sich hier stets der verschiedenen Quellen biometrischer Fehler und deren möglicher Folgen bewusst sein.
O que a “primeira novela brasileira” pode nos dizer sobre o papel das letras coloniais no estudo de literatura?
Authors: De Martini Marcus
Published: May 2019

Neste artigo, discute-se a posição lateral das letras coloniais, no âmbito das escolas e universidades, atrelada ao questionamento do papel da literatura e dos métodos de ensino. A discussão concentra-se na análise da História do Predestinado Peregrino e de seu irmão Precito, composta segundo as preceptivas retórico-poéticas, em chave teológicopolítica pelo jesuíta Alexandre de Gusmão, em 1682.
Intussusceptive Vascular Remodeling Precedes Pathological Neovascularization
Authors: Ali Zaheer , Mukwaya Anthony , Biesemeier Antje , Ntzouni Maria , Ramsköld Daniel , Giatrellis Sarantis , Mammadzada Parviz , Cao Renhai , Lennikov Anton , Marass Michele , Gerri Claudia , Hildesjö Camilla , Taylor Michael , Deng Qiaolin , Peebo Beatrice , del Peso Luis , Kvanta Anders , Sandberg Rickard , Schraermeyer Ulrich , Andre Helder , Steffensen John F. , Lagali Neil , Cao Yihai , Kele Julianna , Jensen Lasse Dahl
Published: May 2019

Objective—

Pathological neovascularization is crucial for progression and morbidity of serious diseases such as cancer, diabetic retinopathy, and age-related macular degeneration. While mechanisms of ongoing pathological neovascularization have been extensively studied, the initiating pathological vascular remodeling (PVR) events, which precede neovascularization remains poorly understood. Here, we identify novel molecular and cellular mechanisms of preneovascular PVR, by using the adult choriocapillaris as a model.

Approach and Results—

Using hypoxia or forced overexpression of VEGF (vascular endothelial growth factor) in the subretinal space to induce PVR in zebrafish and rats respectively, and by analyzing choriocapillaris membranes adjacent to choroidal neovascular lesions from age-related macular degeneration patients, we show that the choriocapillaris undergo robust induction of vascular intussusception and permeability at preneovascular stages of PVR. This PVR response included endothelial cell proliferation, formation of endothelial luminal processes, extensive vesiculation and thickening of the endothelium, degradation of collagen fibers, and splitting of existing extravascular columns. RNA-sequencing established a role for endothelial tight junction disruption, cytoskeletal remodeling, vesicle- and cilium biogenesis in this process. Mechanistically, using genetic gain- and loss-of-function zebrafish models and analysis of primary human choriocapillaris endothelial cells, we determined that HIF (hypoxia-induced factor)-1α-VEGF-A-VEGFR2 signaling was important for hypoxia-induced PVR.

Conclusions—

Our findings reveal that PVR involving intussusception and splitting of extravascular columns, endothelial proliferation, vesiculation, fenestration, and thickening is induced before neovascularization, suggesting that identifying and targeting these processes may prevent development of advanced neovascular disease in the future.

Visual Overview—

An online visual overview is available for this article.
Genetic Determinants of Circulating Glycine Levels and Risk of Coronary Artery Disease
Authors: Jia Qiong , Han Yi , Huang Pin , Woodward Nicholas C. , Gukasyan Janet , Kettunen Johannes , Ala‐Korpela Mika , Anufrieva Olga , Wang Qin , Perola Markus , Raitakari Olli , Lehtimäki Terho , Viikari Jorma , Järvelin Marjo‐Riitta , Boehnke Michael , Laakso Markku , Mohlke Karen L. , Fiehn Oliver , Wang Zeneng , Tang W.H. Wilson , Hazen Stanley L. , Hartiala Jaana A. , Allayee Hooman
Published: May 2019

Background

Recent studies have revealed sexually dimorphic associations between the carbamoyl‐phosphate synthase 1 locus, intermediates of the metabolic pathway leading from choline to urea, and risk of coronary artery disease (
CAD
) in women. Based on evidence from the literature, the atheroprotective association with carbamoyl‐phosphate synthase 1 could be mediated by the strong genetic effect of this locus on increased circulating glycine levels.

Methods and Results

We sought to identify additional genetic determinants of circulating glycine levels by carrying out a meta‐analysis of genome‐wide association study data in up to 30 118 subjects of European ancestry. Mendelian randomization and other analytical approaches were used to determine whether glycine‐associated variants were associated with
CAD
and traditional risk factors. Twelve loci were significantly associated with circulating glycine levels, 7 of which were not previously known to be involved in glycine metabolism (

ACADM

,

PHGDH

,

COX
18‐
ADAMTS
3

,

PSPH

,

TRIB
1

,

PTPRD

, and

ABO

). Glycine‐raising alleles at several loci individually exhibited directionally consistent associations with decreased risk of
CAD
. However, these effects could not be attributed directly to glycine because of associations with other
CAD
‐related traits. By comparison, genetic models that only included the 2 variants directly involved in glycine degradation and for which there were no other pleiotropic associations were not associated with risk of
CAD
or blood pressure, lipid levels, and obesity‐related traits.

Conclusions

These results provide additional insight into the genetic architecture of glycine metabolism, but do not yield conclusive evidence for a causal relationship between circulating levels of this amino acid and risk of
CAD
in humans.
A new species of Syzygium (Myrtaceae) from the Agasthyamalai Biosphere Reserve, Kerala, India
Authors: SREEKALA A. K. , PILLAI DIVYA S. , AKHIL R. , SURENDRAN ANJANA , RAMASUBBU R.
Published: May 2019

Syzygium ponmudianum, a new tree species from Ponmudi, Agasthyamalai Biosphere Reserve, Kerala, India is described. This species is closely allied to Syzygium benthamianum and S. myhendrae but differs from it by having a reddish brown coloured cylindrical stem, large sized leaves with 22-29 pairs of secondary veins, deltoid and persistent calyx lobes, pyriform hypanthium, variously statured filaments, deep purple berries with ovate seeds.
New species, new record, and key to the species of Rhagovelia in the robusta group (Hemiptera: Heteroptera: Veliidae) from Venezuela
Authors: MAGALHÃES OSÉIAS MARTINS , REDUCIENDO-KLEMENTOVÁ BARBORA , SVITOK MAREK , MOREIRA FELIPE FERRAZ FIGUEIREDO
Published: May 2019

Rhagovelia kmenti Magalhães & Moreira, sp. nov. is described, illustrated, and compared with congeners. The new species belongs to the robusta group and its males can be distinguished from group congeners by the dark-brown general coloration, the armature of the hind trochanter, femur, and tibia, and by the distinctive shape of the paramere. In addition, Rhagovelia brunae Magalhães & Moreira, 2016 is newly recorded from Venezuela and a key to the species of the robusta group from the country is presented.
Marthamea bayae, a new species of stonefly from Algeria (Plecoptera: Perlidae)
Authors: LAMINE SMAIL , LOUNACI ABDELKADER , REDING JEAN-PAUL G. , VINÇON GILLES
Published: May 2019

A new species of the perlid genus Marthamea Klapálek, M. bayae sp. n. from Algeria is described and illustrated based on the morphology of adults and larvae. This is the first known record for the genus from North Africa.
The Effects of Surface Longwave Spectral Emissivity on Atmospheric Circulation and Convection over the Sahara and Sahel
Authors: Chen Yi-Hsuan , Huang Xianglei , Chen Xiuhong , Flanner Mark
Published: May 2019

This study quantifies the impact of the inclusion of realistic surface spectral emissivity in the Sahara and Sahel on the simulated local climate and beyond. The surface emissivity in these regions can be as low as 0.6–0.7 over the infrared window band while close to unity in other spectral bands, but such spectral dependence has been ignored in current climate models. Realistic surface spectral emissivities over the Sahara and Sahel are incorporated into the Community Earth System Model (CESM) version 1.1.1, while treatments of surface emissivity for the rest of the globe remain unchanged. Both the modified and standard CESM are then forced with prescribed climatological SSTs and fixed present-day forcings for 35-yr simulations. The outputs from the last 30 years are analyzed. Compared to the standard CESM, the modified CESM has warmer surface air temperature, as well as a warmer and wetter planetary boundary layer over the Sahara and Sahel. The modified CESM thus favors more convection in these regions and has more convective rainfall, especially in the Sahara. The moisture convergence induced by such inclusion of surface spectral emissivity also contributes to the differences in simulated precipitation in the Sahel and the region south to it. Compared to observations, inclusion of surface spectral emissivity reduces surface temperature biases in the Sahara and precipitation biases in the Gulf of Guinea but exacerbates the wet biases in the Sahara. Such realistic representation of surface spectral emissivity can help unmask other factors contributing to regional biases in the original CESM.
Internal Wave Radiation through Surface Mixed Layer Turbulence
Authors: Czeschel Lars , Eden Carsten
Published: May 2019

In a series of large-eddy simulations with different forcing, we study the generation of internal gravity waves at the base of the surface mixed layer. If turbulent eddies act as obstacles and undulate the base of the mixed layer, horizontal velocities associated with inertial oscillations and Ekman dynamics can move the obstacles relative to the stratified interior, exciting internal gravity waves similar to lee waves. We find strong evidence that the “obstacle mechanism” is able to excite large parts of the internal wave spectrum, including near inertial waves. The high-frequency part of the excited wave spectrum is filtered by the increased stratification in the transition layer between the mixed layer and lower stratified interior, but a substantial part of the wave spectrum is able to overcome this barrier, hence contributing to interior mixing. The magnitude of the downward-radiated energy below the transition layer depends on the source of turbulence, but we show that the obstacle mechanism, especially under destabilizing heat fluxes, has the potential to contribute considerably to the internal wave energy in the interior ocean.
What Drives Ethnic Homophily? A Relational Approach on How Ethnic Identification Moderates Preferences for Same-Ethnic Friends
Authors: Leszczensky Lars , Pink Sebastian
Published: May 2019

Individual preferences for same-ethnic friends contribute to persistent segregation of adolescents’ friendship networks. Yet, we know surprisingly little about the mechanisms behind ethnic homophily. Prior research suggests that ethnic homophily is ubiquitous, but a social identity perspective indicates that strong ingroup identification drives ingroup favoritism. Combining a social identity perspective with a relational approach, we ask whether the presumed increased homophily of high identifiers extends to all ingroup members, or whether it is conditional on the strength of same-ethnics’ identification. We propose that the strength of ethnic identification affects not only how much individuals desire same-ethnic friends, but also how attractive they are as potential friends to others. Fitting stochastic actor-oriented models to German adolescent school-based network panel data, we find that ethnic homophily is driven by an interplay of peers’ ethnic identification: high identifiers befriend same-ethnic peers who share their strong ethnic identification, while excluding same-ethnic low identifiers. Low identifiers, in turn, tend to avoid befriending inter-ethnic high identifiers. Our relational approach reveals that ethnic homophily is hardly ubiquitous but requires strong identification of both parties of a (potential) friendship.
Short-Term Risk Factor Profile of Pediatric Choanal Atresia Repair Using ACS-NSQIP National Database
Authors: Marston Alexander P. , Patel Terral , Nguyen Shaun A. , White David R.
Published: May 2019

Objectives:

The goal of this study is to describe the 30-day postoperative sequelae of pediatric choanal atresia repair and identify predictive factors for adverse events.

Study Design:

The American College of Surgeons’ National Surgery Quality Improvement Program-Pediatric (NSQIP-P) database was searched between January 2012 and December 2015 to identify pediatric patients status post choanal atresia repair. Postoperative outcomes included surgical site complications, readmissions, and total length of stay.

Results:

A total of 178 children underwent choanal atresia repair. The overall complication rate was 6.2%, while the 30-day readmission rate was 15%. Patients with CHARGE had a longer mean duration of hospitalization (26.91 days vs 8.05 days, P = .013). Additionally, patients ≤10 days of age had longer duration of hospitalization (17.84 days vs 9.24 days, P ≤ .001) and higher readmission rates (33.30% vs 10.1%, P = .001). Among the nonsyndromic cohort, ventilator dependence was a predictor of postoperative complications (odds ratio [OR] = 16.08, P < .001), higher readmission rates (OR = 5.46, P = .002), and a longer hospital stay (OR = 18.69, P < .001).

Conclusion:

Analysis of the 2012-2015 NSQIP-P data set reveals that patients with a diagnosis of CHARGE and those ≤10 days of age have a longer duration of hospitalization. Increased risk of postoperative complications and longer duration of hospitalization were both influenced by chronic steroid use and ventilator dependence.