bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3279: All-trans-retinoic acid (ATRA) markedly augments anti-tumor immunity
Authors: Huang Lu , Chen Zibo , Williams Leila , Chen Yulong , Wang Yunfei , Kawakami Masanori , Roszik Jason , Hwu Patrick , Dmitrovsky Ethan , Peng Weiyi , Liu Xi 
Published: August 2019

Abstract
All-trans-retinoic acid (ATRA) engages diverse actions on populations of immune cells. These include effects on regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), Th17 and other immune cells. Prior work found that ATRA can induce anti-tumor immunity through MDSCs and CD8+ T cells and pro-tumor immunity by increasing Treg cells. In this study, we explored how ATRA modulated anti-tumor immunity in solid tumors. To do this, syngeneic lung cancer and colon cancer models were independently developed by optimizing subcutaneous injections of ED1SQ4 lung cancer and MC38 colon cancer cells into immune-competent mice. ATRA-treatment markedly repressed both syngeneic lung cancer and colon cancer growth as compared to vehicle-treated mice. To exclude the possibility that ATRA directly suppressed growth of cancer cells, ED1SQ4 and MC38 cells were independently implanted subcutaneously into athymic mice in order to allow these lung and colon cancer xenografts to grow. Notably, ATRA-treatment did not reduce the growth of these respective xenograft tumors. Intriguingly, ATRA did not suppress in vitro proliferation of either ED1SQ4 or MC38 cells. This implicated ATRA as engaging mechanisms that affect the tumor microenvironment. To learn if the observed anti-tumorigenic activity was mediated by regulation of T cell immunity, CD4+ or CD8+ T cell populations were depleted in syngeneic mice before in vivo ATRA-treatment. CD4+ and CD8+ T cell depletion from syngeneic mice at least partially reversed the tumor suppressive activity of ATRA. Flow cytometry assays conducted on intratumoral immune cells revealed that ATRA-treatment decreased the CD8+ T to Treg cellular ratios while increasing the ratios of CD8+ T to Treg cells. Cytokine and chemokine assays were performed on these syngeneic cancers as well as on peripheral blood harvested from ATRA or vehicle-treated syngeneic mice in order to identify mediators of the observed anti-tumorigenic effects. Findings will be presented. Taken together, this study uncovered a previously unrecognized role for ATRA in augmenting immunotherapy. These preclinical immunotherapy findings can be translated into the cancer clinic.
Citation Format: Lu Huang, Zibo Chen, Leila Williams, Yulong Chen, Yunfei Wang, Masanori Kawakami, Jason Roszik, Patrick Hwu, Ethan Dmitrovsky, Weiyi Peng, Xi Liu. All-trans-retinoic acid (ATRA) markedly augments anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3279.
Abstract 3281: The association between body mass index (BMI) and risk of pancreatic cancer depends on age at BMI assessment
Authors: Jacobs Eric J. , Newton Christina C. , Patel Alpa V. , Stevens Victoria L. , Islami Farhad , Flanders W. Dana , Gapstur Susan M. 
Published: August 2019

Abstract
Importance: Pancreatic cancer rates in the United States have steadily increased since the early 2000’s despite declines in smoking. This increase is not easily explained by population increases in body mass index (BMI) given the relatively weak association between BMI and pancreatic cancer risk typically observed in epidemiologic studies. Most of these studies, however, assessed BMI in older adulthood, which may be less strongly associated with pancreatic cancer than BMI earlier in adult life.
Objective: To examine the association between BMI and pancreatic cancer mortality by age at BMI assessment.
Design: Prospective cohort study.
Setting: Cancer Prevention Study II (CPS-II), a nationwide study of cancer mortality enrolled in 1982 and followed through 2014.
Participants: 963,317 US adults aged 30 to 89 years at enrollment.
Exposure: BMI calculated from height and weight reported at enrollment.
Main outcomes and measures: A total of 8,354 participants died of pancreatic cancer during follow-up. Hazard ratios (HRs) for BMI were calculated using multivariable proportional hazards regression models. Population attributable fractions by birth cohort were calculated using HRs from CPS-II and BMI distributions from nationally representative National Health and Examination Surveys (NHANES).
Results: HRs declined with increasing age at BMI assessment. HRs per 5 BMI units among those aged 30-49, 50-59, 60-69, and 70-89 years at assessment were 1.25 (95% confidence interval (CI) 1.18-1.33), 1.19 (95% CI 1.14-1.23), 1.14 (95% CI 1.08-1.21) and 1.13 (95% CI 1.02-1.26), respectively (p-trend = 0.005). The prevalence of obesity in early middle age is substantially higher in more recent US birth cohorts than in earlier ones. Therefore, based on a HR of 1.25 per 5 BMI units at age 45 years, we estimate that 28% of pancreatic cancer deaths in the US among those born from 1970-74 will be attributable to BMI levels &gt; 25 kg/m2, nearly twice the equivalent percentage in those born in the 1930s.
Conclusions and Relevance: BMI before age 50 may be more strongly associated with pancreatic cancer risk than BMI at older ages. These results underscore the importance of preventing excess weight gain before middle age for reducing rates of this highly fatal cancer.
Citation Format: Eric J. Jacobs, Christina C. Newton, Alpa V. Patel, Victoria L. Stevens, Farhad Islami, W. Dana Flanders, Susan M. Gapstur. The association between body mass index (BMI) and risk of pancreatic cancer depends on age at BMI assessment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3281.
Abstract 3283: Associations of change in BMI before surgery with disease-free and overall survival in colorectal cancer patients: Results from the ColoCare Cohort
Authors: Ose Jennifer , Gigic Biljana , Lin Tengda , Boehm Juergen , Schrotz-King Petra , Schrotz-King Petra , Hardikar Sheetal , Himbert Caroline , Schneider Martin , Ulrich Alexis , Ulrich Cornelia M. 
Published: August 2019

Abstract
BACKGROUND Body weight in colorectal cancer patients may change substantially before and after diagnosis and treatment. The prognostic significance of pre-surgery weight loss is still unclear. We investigated the association of pre-surgery weight loss with clinical outcomes in colorectal cancer patients.
METHODS We used prospectively collected data from n=148 newly diagnosed colorectal cancer patients (stage I-IV) from the ColoCare Cohort. Data on body mass index (BMI; (kg)/ m2) 1 year before surgery and at the time of surgery were collected. We calculated BMI differences between these time points. We applied Cox proportional hazard models to investigate associations of BMI change (continuous), biological sex (male, female) and tumor stage (I, II, III, IV) and neoadjuvant chemo- and/or radiotherapy (no/yes).
RESULTS After 24 months of follow-up n=22 patients were deceased and n=19 patients had a recurrence. Pre-surgery change in BMI was associated with poorer overall and disease-free survival: for every loss in one unit in BMI patients had a 47% increase in risk of overall death: Hazard Ratio (HR): 1.47; 95% confidence interval (CI) (1.21-1.76), p=0.0001 and a 44% increase in risk for either death or recurrence: HR: 1.44; 95% CI (1.19-1.73), p=0.0002.
CONCLUSIONS Pre-surgery weight change is, independently of tumor stage, age, biological sex and neoadjuvant therapy, associated with long-term clinical outcomes in colorectal cancer survivors.
Citation Format: Jennifer Ose, Biljana Gigic, Tengda Lin, Juergen Boehm, Petra Schrotz-King, Petra Schrotz-King, Sheetal Hardikar, Caroline Himbert, Martin Schneider, Alexis Ulrich, Cornelia M. Ulrich. Associations of change in BMI before surgery with disease-free and overall survival in colorectal cancer patients: Results from the ColoCare Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3283.
Abstract 3295: GPRASP1:A novel potential biomarker for neuroendocrine carcinoma
Authors: Xiong Minggang , Wang Fuhao , Zhau Haiyen E. , Huang Xin , Chung Leland , Zhang Jian , Lu Yi 
Published: August 2019

Abstract
Neuroendocrine differentiation has been observed to correlate with the progression and prognosis of prostate cancer (PCa), gastric cancer and pancreatic cancer, but the mechanisms remain unclear. GPRASP-1, a G protein coupled receptor-associated sorting protein 1, is known as a significant modulator of lysosomal sorting, and functional down-regulation of G- protein coupled receptors by interacting with Beclin2. The GPRASP-1 was originally considered as a serum tumor biomarker for breast cancer and later it was confirmed as a ubiquitous tumor marker among lung, liver and brain cancers. Based on its function as a tumor biomarker, we conducted serum ELISA analysis of GPRASP-1, and correlated results with RNAseq and gene copy numbers among a large cohort of PCa patients. We found overexpression and gene amplification of GPRASP-1 in 24 of 77 patients (31%) with neuroendocrine PCa (NEPCa). The patients with elevated serum GPRASP-1 level had a higher risk of metastasis to liver, lung and lymph nodes. Furthermore, immunohistochemical analysis for GPRASP-1 showed a strong staining of the pathological section from pancreatic neuroendocrine carcinoma patients and their liver metastases. Knocking down of the GPRASP-1 in a NEPCa PC3 cell line showed dramatic downregulation of TACR family, Tachykinin Receptor, which is known to be involved in the neuroinflammation and neurotransmitter transport and cancer proliferation. Our results offer a novel link among GPRASP-1, neuroendocrine differentiation and castration resistance in human PCa. We proposed serum GPRASP-1 can serve as a novel biomarker differentiating cancers with and without neuroendocrine differentiation. (Supported by NSFC projects 81773146; Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, 2017B030301018); JCYJ20170412152943794, JCYJ20170412154619484, JCYJ20170307105128101, JCYJ2017030711041760)
Note: This abstract was not presented at the meeting.
Citation Format: Minggang Xiong, Fuhao Wang, Haiyen E. Zhau, Xin Huang, Leland Chung, Jian Zhang, Yi Lu. GPRASP1:A novel potential biomarker for neuroendocrine carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3295.
Abstract 3297: Prediagnostic circulating concentrations of vitamin D binding protein and survival among colorectal cancer patients
Authors: Yuan Chen , Song Mingyang , Wolpin Brian M. , Meyerhardt Jeffrey A. , Ogino Shuji , Hollis Bruce W. , Chan Andrew T. , Fuchs Charles S. , Wu Kana , Wang Molin , Smith-Warner Stephanie A. , Giovannucci Edward L. , Ng Kimmie 
Published: August 2019

Abstract
Higher total 25-hydroxyvitamin D [25(OH)D] levels are associated with an improvement in survival among colorectal cancer (CRC) patients, but the relationships between plasma vitamin D binding protein (VDBP), bioavailable or free 25(OH)D, and CRC survival remain unknown. In two prospective cohort studies, the Health Professionals Follow-Up Study and the Nurses’ Health Study, we examined the association between prediagnostic plasma levels of VDBP, bioavailable 25(OH)D, and free 25(OH)D and survival among 604 participants diagnosed with CRC between 1991 and 2011. Plasma 25(OH)D and VDBP were directly measured, while bioavailable and free 25(OH)D were calculated using a validated formula based on total 25(OH)D, VDBP, and albumin levels. Cox proportional hazards models were used to estimate hazard ratios (HRs) for overall and CRC-specific mortality, adjusted for other prognostic markers and potential confounders. During the follow-up, there were 279 deaths, 177 of which were due to CRC (63%). Higher VDBP levels were associated with a significant improvement in overall and CRC-specific survival (Ptrend=0.005 and 0.02, respectively). Compared to patients in the lowest quartile, those in the highest quartile of VDBP had a multivariable-adjusted HR of 0.61 (95% confidence interval [CI], 0.42-0.89) for overall mortality and 0.56 (95% CI, 0.35-0.92) for CRC-specific mortality. The results remained similar after further adjustment for total 25(OH)D levels. In contrast, no association with overall or CRC-specific mortality was observed for bioavailable or free 25(OH)D levels. In conclusion, higher prediagnostic plasma VDBP levels were associated with improved survival among CRC patients. The clinical utility of VDBP as a prognostic marker warrants further exploration, as well as research into underlying mechanisms of action.
Citation Format: Chen Yuan, Mingyang Song, Brian M. Wolpin, Jeffrey A. Meyerhardt, Shuji Ogino, Bruce W. Hollis, Andrew T. Chan, Charles S. Fuchs, Kana Wu, Molin Wang, Stephanie A. Smith-Warner, Edward L. Giovannucci, Kimmie Ng. Prediagnostic circulating concentrations of vitamin D binding protein and survival among colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3297.
Abstract 3309: Healthcare resource utilization in follicular lymphoma patients treated with maintenance rituximab in the Veterans Health Administration
Authors: Halwani Ahmad S. , Li Catherine , Rasmussen Kelli M. , Patil Vikas , Yong Christina , Burningham Zachary , Sauer Brian C. 
Published: August 2019

Abstract
OBJECTIVES: Examine healthcare resource utilization (HCRU) in follicular lymphoma (FL) patients treated with or without maintenance rituximab (MR).
METHODS: FL patients treated in the Veterans Health Administration (VHA) between 2006-2014 were identified by linking information from the VA Cancer Registry System (VACRS) and the Corporate Data Warehouse. HCRU was defined as the total number of outpatient visits (OPV), inpatient visits (IPV), and the number of emergency department visits (EDV) during follow-up time, which was approximately four years. To avoid immortal time bias, a prescription time distribution matching method was performed, followed by an inverse probability weighted regression analysis to account for variation in the follow-up period. The observational period was partitioned into four-yearly intervals. The observed HCRU value was weighted by the inverse of the probability of not being censored by the end of the yearly interval. A generalized linear model with Poisson distribution and log link was performed for each of the four intervals while adjusting for the covariates. Using a 95% bootstrap confidence interval, the change of HCRU was summed across the four-yearly intervals to obtain the cumulative change of HCRU between FL patients who received MR or did not receive MR.
RESULTS: From 2006-2014, 2,290 FL patients were diagnosed at VHA. After excluding patients with a prior cancer, documented grade 3b or stage I disease, 905 MR-eligible patients remained, of which 319 (35%) received MR and 586 (65%) did not receive MR. When compared with non-MR patients, MR patients were slightly more likely to have a mean increase in OPV (0.69%; CI: 0.44%-0.94%) and a mean decrease in IPV (14.83%; CI: 16.09%-13.58%). There was no significant change in the number of EDV between the MR treated and non-MR treated patients.
CONCLUSIONS: This nationwide real-world study suggests that on average FL patients treated with MR have fewer IPV and more OPV than non-MR patients.
Note: This abstract was not presented at the meeting.
Citation Format: Ahmad S. Halwani, Catherine Li, Kelli M. Rasmussen, Vikas Patil, Christina Yong, Zachary Burningham, Brian C. Sauer. Healthcare resource utilization in follicular lymphoma patients treated with maintenance rituximab in the Veterans Health Administration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3309.
Abstract 3336: Changes in prescriptions for breast cancer medications after Medicaid expansion
Authors: Maclean Johanna Catherine , Halpern Michael T. , Hill Steven C. , Pesko Michael F. 
Published: August 2019

Abstract
Introduction: As of summer 2018, 34 states have expanded Medicaid eligibility under the Affordable Care Act. While the Medicaid expansions decreased rates of being uninsured among women with breast cancer and increased early breast cancer detection, it is unknown whether expansions increased receipt of medications used to prevent and treat breast cancer. This study examines differences over time in receipt of two types of breast cancer hormonal therapies (tamoxifen and aromatase inhibitors) and associated payments for these medications in states that did vs. did not expand Medicaid during the period 2011-2017.
Methods: The study’s data source is the Medicaid State Drug Utilization Database (SDUD). This data set, compiled by the Centers for Medicaid and Medicare (CMS), is administrative data submitted by state Medicaid programs. The data comprise outpatient prescription medications that are covered under the Medicaid Drug Rebate Program for which Medicaid serves as a third-party payer; this includes aggregate numbers of prescriptions and associated payments for individuals enrolled in both fee for service and managed care Medicaid programs. Both branded and generic prescriptions for three aromatase inhibitors (anastrozole, exemestane, and letrozole) were included in the study’s analyses. Analyses used differences-in-differences and event study models (controlling for state characteristics) to compare changes in Medicaid expansion states to changes in non-expansion states before vs. after expansion.
Results: Initial regression analyses indicate that prescriptions for all hormonal therapy medications increased by 27% (p&lt;0.05) and prescriptions for aromatase inhibitors (branded and generics combined) increased by 29% (p&lt;0.05) in expansion states relative to non-expansion states. Prescriptions for tamoxifen and for generic aromatase inhibitors only also increased significantly. Post-expansion, both total payments and Medicaid payments for all hormonal therapies increased by 13% (p&lt;0.01) in expansion states relative to non-expansion states. The similar increases for total and Medicaid payments suggest that state Medicaid programs, not patients, financed the increased hormonal therapy prescription payments.
Conclusions: Our findings indicate that states that expanded Medicaid with the ACA experienced increased prescriptions for breast cancer hormonal therapies relative to states that did not expand Medicaid; this effect of Medicaid expansion increased over time. The increased prescriptions were financed by Medicaid, not by patients.
Citation Format: Johanna Catherine Maclean, Michael T. Halpern, Steven C. Hill, Michael F. Pesko. Changes in prescriptions for breast cancer medications after Medicaid expansion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3336.
Abstract 3340: Lung cancer stigma: A ten year look at public attitudes about lung cancer
Authors: Rigney Maureen , Rapsomaniki Eleni , King Jennifer C. 
Published: August 2019

Abstract
Background: Lung cancer is the leading cause of cancer death in the United States in both men and women (ACS Facts and Figures, 2018). The presence of lung cancer stigma is well documented (Chapple et al, 2004; Chambers et al, 2012; Marlow et al, 2015) and has been shown to impact the care and treatment of lung cancer survivors (Tod et al. 2008; Carter-Harris et al 2014). In 2008, a large survey of over 1000 members of the general population revealed that most participants felt lung cancer was principally caused by external factors, that it was preventable, and that lung cancer patients were at least partly to blame for their illness (Weiss et al. 2014; 2017). We replicated the survey to understand whether perceptions have changed over the last decade.
Methods: 1001 members of the general public were surveyed with the identical survey instrument from 2008 survey along with three additional questions at the end. The survey was carried out by phone and online between June 6 and July 26, 2018. Statistical analysis was performed comparing 2008 and 2018 datasets using paired t-tests if normally distributed or Mann-Whitney U tests for continuous data and Chi-squared or Fisher’s exact test for categorical data.
Results: General awareness about lung cancer has significantly improved over the last decade with 94% of the public reporting familiarity with lung cancer (p&lt;.001). Sixty five percent of respondents reported increased visibility of lung cancer in the media. Despite the increased visibility of the disease, stigma remains a critical problem. There were no statistically significant changes in the proportion that felt that patients are at least partly to blame for their illness (56% in 2018). Sixty-eight percent of respondents felt that patients experience the same or more stigma than 10 years ago. In addition, despite the increased awareness there was no increase in the proportion of people who donate or volunteer time to lung cancer organizations and no increase in those selecting lung cancer as the type of cancer they believe should receive more research support.
Conclusions: After a decade of research progress in lung cancer, these data show that lung cancer awareness has been considerably elevated. Unfortunately, they also indicate that the stigma surrounding the disease remains pervasive. This work underscores the need to address stigma with proactive multilevel approaches (Hamann, 2018).
Citation Format: Maureen Rigney, Eleni Rapsomaniki, Jennifer C. King. Lung cancer stigma: A ten year look at public attitudes about lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3340.