bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 580: Detailed analysis of immune responses induced against patient-specific neoantigens using the ex-vivo induction protocol, NEO-STIM™
Authors: Lenkala Divya , Kohler Jessica , McCarthy Brian , Nelson Michael , DeBarge Rachel , Ware Yvonne , Huang Yuting , Sridar Janani , Nasrullah Yusuf , Hartjano Dewi , Poran Asaf , Sengupta Sejuti , Berg Joost H. van den , Goldstein Matt , Gaynor Richard B. , Buuren Marit M. van 
Published: August 2019

Abstract
Background: Neoantigens are tumor-specific antigens that have been shown to be critical in the anti-tumor immune response. These antigens are not subject to central immune tolerance and are therefore potentially more immunogenic than tumor-associated antigens. The goal of our studies is to assess the immunogenic potential of high-quality neoantigen targets, as defined through our bioinformatic engine RECON®, as well as perform detailed characterization of the induced T cell responses towards these neoantigen targets.
Methods: Patient-specific neoantigens were predicted using our bioinformatic engine RECON. The predicted high quality neoantigens were utilized in our proprietary ex-vivo stimulation protocol NEO-STIM to assess immunogenicity. NEO-STIM is used to prime, activate and expand memory and de novo T cell responses from both the CD4+ as well as the CD8+ compartment. In-depth analysis was performed to characterize the specificity, functionality (cytokine production and cytolytic capacity) and diversity of the induced T cell responses.
Results: Here we present the successful induction of memory and de novo CD8+ T cell responses in PBMCs isolated by leukapheresis from three patients using NEO-STIM (2 with melanoma & 1 with NSCLC). We then deeply characterize the induced CD8+ T cell responses of one of the melanoma patients and show that these responses are functional, specific and have cytolytic capacity. Furthermore, we use paired single cell RNA and TCR sequencing to assess the diversity and gene expression profile of these responses.
Conclusions: NEO-STIM is a novel platform to understand the immunogenic potential of high-quality neoantigen-targets in detail. Moreover, this platform can be utilized to generate T cell products for adoptive cell therapy for patients with a variety of solid and liquid tumors.
Citation Format: Divya Lenkala, Jessica Kohler, Brian McCarthy, Michael Nelson, Rachel DeBarge, Yvonne Ware, Yuting Huang, Janani Sridar, Yusuf Nasrullah, Dewi Hartjano, Asaf Poran, Sejuti Sengupta, Joost H. van den Berg, Matt Goldstein, Richard B. Gaynor, Marit M. van Buuren. Detailed analysis of immune responses induced against patient-specific neoantigens using the ex-vivo induction protocol, NEO-STIM™ [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 580.
Abstract 582: Tumor immunoediting in a lung cancer mouse model harboring EGFR mutations
Authors: Nishii Kazuya , Ohashi Kadoaki , Ninomiya Kiichiro , Makimoto Go , Watanabe Hiromi , Kano Hirohisa , Hara Naofumi , Udono Heiichiro , Kiura Katsuyuki 
Published: August 2019

Abstract
Background: Anti-Programed cell death 1 (PD-1) antibodies such as nivolumab or pembrolizumab show promising treatment effects in smoking-related lung cancer. However, anti-PD-1 antibodies have very little effect on epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). EGFR mutations are the most frequent oncogenic drivers in non-smoking related NSCLC. Therefore, we aimed to explore the mechanism underlying tumor immunoediting in a lung cancer mouse model harboring EGFR mutations.
Methods: We previously established two strains of transgenic lung cancer mouse (C57BL/6) harboring a mouse Egfr exon 19-deletion (mDEL) or a human EGFR L858R (hLR) mutation, driven by a surfactant protein (SP)-C promoter (Ohashi, Cancer Sci. 2008; Ohashi, Cancer Res. 2009). These mice developed EGFR-dependent multifocal lung adenocarcinomas from type II pneumocytes. We modified the two models by transplanting lung tumors subcutaneously into C57BL/6 (Ohashi, AACR. 2018). Evaluation of mice tumor lymphocyte profile was done through flow cytometry or immunohistochemistry (IHC). Effects of T cell depletion or anti-mouse PD-1 antibody (4H2) in vivo were also assessed. Comprehensive analysis of mRNA expression of immuno-checkpoint molecules in the tumors was performed using PanCancer Immune Profiling Panel (NanoString Technologies).
Results: CD4+ T cells and/or CD8+ T cells were depleted in the subcutaneously transplanted tumor model followed by treatment with gefitinib (50 mg/kg/day, 5 days/week) for 2 weeks. As a result, after gefitinib discontinuation, rapid regrowth was seen in the tumors from groups with depletion of CD8+ T cells; depletion of CD4+ T cells had little effect on tumor regrowth, and tumor inhibition continued for 2 weeks after cessation of gefitinib. IHC showed relatively increased numbers of CD4+ T cells in the mice tumors whereas a decrease in the number of CD8+ T cells or Foxp3 positive cells was noted. PD-L1 expression was not observed in the tumors. Consistently, 4H2 showed little effect on tumor growth in vivo. The cancer immune panel showed increased expression of immune mediators such as Ccl6, Clec4n, and Lcn2.
Conclusions: Our results suggest that CD8+ T cells can recognize mice tumors in vivo. New immuno-checkpoint molecules regulating CD8+ T cells from PanCancer Immune Profiling Panel were evaluated. Further, we plan to evaluate the efficacy of various immuno-checkpoint inhibitors in vivo.
Citation Format: Kazuya Nishii, Kadoaki Ohashi, Kiichiro Ninomiya, Go Makimoto, Hiromi Watanabe, Hirohisa Kano, Naofumi Hara, Heiichiro Udono, Katsuyuki Kiura. Tumor immunoediting in a lung cancer mouse model harboring EGFR mutations [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 582.
Abstract 592: Associations of mammographic breast density with breast stem cell marker-defined breast cancer subtypes
Authors: Yaghjyan Lusine , Esnakula Ashwini , Scott Christopher , Wijayabahu Akemi , Jensen Matthew , Vachon Celine 
Published: August 2019

Abstract
Background: High mammographic breast density is a strong, well-established breast cancer risk factor. A recent study found increased expression of stem cell markers in the areas of high breast density, but, whether stem cells may explain high breast cancer risk due to high breast density is unknown. We investigated the association between breast density and the risk of breast cancer by the status of stem cell markers CD44, CD24, and ALDH1A1 in the tumor.
Methods: We included 223 postmenopausal women with primary invasive or in-situ breast cancer and 399 age-matched controls from Mayo Clinic Mammography Study. Percent breast density, absolute dense area and non-dense area were assessed using computer-assisted thresholding technique. Immunohistochemical analysis of the markers was performed on tumor tissue microarrays according to a standard protocol with commercial antibodies. Cases with positive staining (≥1% positively stained cells) on one or more cores were considered marker-positive. We used polychotomous logistic regression to quantify the associations of breast density measures with breast cancer risk by the status of each of the markers. Heterogeneity tests were conducted to compare the differences in associations by marker-defined tumor subtypes.
Results: Of the 223 cancers in the study, 182 (82%) were positive for CD44, 83 (37%) for CD24 and 52 (23%) for ALDH1A1. Associations of percent density were not significantly different across any of the marker-defined subtypes (density 51%+ vs. 11-25%: OR=2.83, 95% CI 1.49-5.37 for CD44+ vs. OR=1.87, 95% CI 0.47-7.51 for CD44-, p-heterogeneity=0.66; OR=2.80, 95% CI 1.27-6.18 for CD24+ vs. OR=2.44, 95% CI 1.14-5.22 for CD24-, p-heterogeneity=0.61; OR=3.04, 95% CI 1.14-8.10 for ALDH1A1+ vs. OR=2.57. 95% CI 1.30-5.08 for ALDH1A1-, p-heterogeneity=0.94). Positive associations of absolute dense area and inverse associations of non-dense area with breast cancer risk were similar across marker-defined subtypes. Similar associations of breast density measures with breast cancer were seen when cancer subtypes were defined using combined marker expression status (none, one positive marker, or two and more positive markers).
Conclusions: We found no evidence of differential associations of breast density measures with breast cancer risk by the status of stem cell markers. However, our power was limited and further studies in larger study populations are warranted to confirm these associations in a larger sample.
Citation Format: Lusine Yaghjyan, Ashwini Esnakula, Christopher Scott, Akemi Wijayabahu, Matthew Jensen, Celine Vachon. Associations of mammographic breast density with breast stem cell marker-defined breast cancer subtypes [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 592.
Abstract 602: Biological monitoring to clarify potential causes of colorectal cancer in Korean diet
Authors: Yang Mihi , Lee Myungah , Kim Jeongseon Kim , Park Jong , Om Aeson , Damonte Jennifer 
Published: August 2019

Abstract
We performed a pilot study (N=30) to look for the Korean specific risk factors, which can explain an increased incidence rate of colorectal cancer (CRC) among Korean population. Based on the promising data from the pilot study, we performed a case-control study (N=218, age: 64.4 ±13.4 years; N of men=116, 53.2%) with biological monitoring to analyze various biomarkers including clinical/hematological indices, oxidative or inflammatory biomarkers, e.g., c-reactive protein (CRP), malondialdehyde (MDA) or homocysteine, the metabolites of polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs), e.g., urinary 1-OHP, MeIQx and PhIP, and their DNA adducts, e.g., dG-C8-MeIQx and -PhIP, with UPLC/MS/MS. We also obtained participants’ epidemiological, clinical, and behavioral information and developed food frequency questionnaires (FFQ) to collect their food information for one year before cancer diagnoses. Total subjects consumed 53.4±74.0g/day of red meat, and 1.1±3.7g/day of processed meat. After adjustment for sex and age, there were no associations between CRC risk and red or processed meat intake, or urinary MeIQx or PhIP levels. However, there were inverse associations between CRC and milk or calcium intake (ps&lt;0.05). In addition, urinary MeIQx levels were positively associated with intake of lipid or coffee (p=0.06, p&lt;0.01, respectively). LDL-C and CRP levels in the cases were higher than ones from controls (ps&lt;0.05). Among biomarkers, MDA levels were positively correlated to urinary levels of 1-OHP, PhIP and MeIQx (ps&lt;0.05). These relations support the fact that PAHs or HCAs indirectly induce oxidative stress. Finally, fruits and milk intake showed protective effects, however, gender (man), CRP, and lipid intake were risk factors to CRC, based on multivariable regression analyses. Therefore, total lipid intake, oxidative stress, or inflammation may increase risks of CRC in Korean population rather than red or processed meat intake.
Citation Format: Mihi Yang, Myungah Lee, Jeongseon Kim Kim, Jong Park, Aeson Om, Jennifer Damonte. Biological monitoring to clarify potential causes of colorectal cancer in Korean diet [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 602.
Abstract 605: Association of blood lipid profile and lung cancer risk: Results from the Southern Community Cohort Study
Authors: Sun Yan , Wu Jie , Yoon Hyung-Suk , Zheng Wei , Blot William J. , Cai Qiuyin 
Published: August 2019

Abstract
Lung cancer is the second most common cancer and the leading cause of cancer death in the U.S. African Americans (AAs) have a higher incidence rate than any other racial group. Lipid metabolism and homeostasis play important roles in the growth of cancer cells and the regulation of membrane proteins. Some previous epidemiological studies have evaluated the association between blood lipid levels and lung cancer risk; however, the results were inconsistent, and few explored patterns among AAs. To investigate the association of blood lipid levels and lung cancer risk, particularly in a low socioeconomic population and AAs, we conducted a nested case-control study using resources from the Southern Community Cohort Study, a well-characterized prospective cohort study of approximately 86,000 adult men and women, two-thirds of whom are AAs. Blood lipid profiles, including total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TRIG), and lipoprotein-a (Lp-a), were measured in 372 lung cancer cases and 721 matched controls. AAs had lower median levels of TRIG, and higher levels of HDL and Lp-a than European Americans (EAs). Conditional logistic regression analysis revealed an inverse association between TC and lung cancer risk, with an adjusted OR for the highest vs. lowest tertiles of 0.67 (95% CI: 0.45-0.99). This association was observed in both AAs and EAs, but was only statistically significant in EAs. Further stratified analysis found that this association was only significant in cases that were diagnosed within 2 years of blood collection. No significant associations of other lipid markers with lung cancer risk were observed. The findings from our study suggest that the inverse associations between TC and lung cancer risk more likely resulted from cancerous occurrence and progression and associated lifestyle changes rather than being indicative of causal markers.
Citation Format: Yan Sun, Jie Wu, Hyung-Suk Yoon, Wei Zheng, William J. Blot, Qiuyin Cai. Association of blood lipid profile and lung cancer risk: Results from the Southern Community Cohort Study [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 605.
Abstract 608: Examining H. pylori core genes for epidemiological typing
Authors: Yu Guoqin 
Published: August 2019

Abstract
H. pylori is the major causative risk factor of a serious of diseases including gastric cancer. It is highly diverse. Conventional method of typing H. pylori has been based on seven MLST loci, which however are not sufficient to distinguish closely-related strains. High diverse core genes that are present in all H. pylori strains are potential good candidates for investigating genomic variation within closely-related strains, therefore improving our understanding of H. pylori -related disease epidemiology. In this study, we investigated the variation of the H. pylori genome, especially its core genes. We downloaded 80 H. pylori whole genome from National Center for Biotechnology Information (NCBI), and identified core genes (99% &lt;= strains &lt;= 100%: 840 genes), Soft core genes (95% &lt;= strains &lt; 99%: 185), Shell genes (15% &lt;= strains &lt; 95%: 933), Cloud genes (0% &lt;= strains &lt; 15%: 2313). Compared with other gene groups, we found that core genes have higher proportion of polymorphic sites, similar level of nucleotide diversity per site, higher recombination events per site, and lower number of gaps per site. In addition, core genes evolve slower than other gene groups with lower Tajima’s D value and nonsynonymous to synonymous ratio. Among the core and soft-core genes, we found that majority have low genetic diversity while a few showed higher diversity. We evaluated these high diverse core genes further in terms of their evolution, function and potential to serve as candidates to distinguish closely related H. pylori strains.
Note: This abstract was not presented at the meeting.
Citation Format: Guoqin Yu. Examining H. pylori core genes for epidemiological typing [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 608.
Abstract 610: A longitudinal investigation of hematologic perturbations among permethrin-exposed pesticide applicators in the Biomarkers of Exposure and Effect in Agriculture Study
Authors: Shearer Joe , Freeman Laura Beane , Liu Danping , Andreotti Gabriella , Hamilton Jennifer , Happel Julie , Lynch Charles , Alavanja Michael , Hofmann Jonathan 
Published: August 2019

Abstract
Background: In the Agricultural Health Study, a large prospective cohort of pesticide applicators, high lifetime use of the insecticide permethrin was associated with an increased risk of multiple myeloma. However, the biological mechanisms through which this association occurs remain to be fully understood.
Methods: Hematologic perturbations were assessed among 33 permethrin-exposed male pesticide applicators enrolled in the Biomarkers of Exposure and Effect in Agriculture study, a molecular substudy within the Agricultural Health Study. Serial blood samples were collected from each participant coinciding with permethrin use including visits during the offseason, an exposure visit the day after use, and for 27 participants a follow-up visit approximately three weeks after use. Complete blood count with white blood cell differential and lymphocyte subsets were collected at each visit. Linear mixed models were used to assess the relationship between permethrin exposure and hematologic parameters, controlling for potential confounders including season of blood draw, age, body mass index, recent cold/infection, and use of other pesticides.
Results: A statistically significant increase in the adjusted mean immature granulocyte count (37%, 95% CI=6%, 76%) was observed the day after permethrin use compared to an offseason visit. Statistically significant (P&lt;0.05) alterations in several red blood cell (RBC) parameters were also observed on the day after permethrin use, including decreased RBC count and hemoglobin and increased mean corpuscular volume and RBC distribution width-SD. Decreases in RBC count and hemoglobin, and increased levels of RBC distribution width-SD persisted approximately three weeks after permethrin use.
Conclusions: Altered hematologic parameters could be indicative of disrupted hematopoiesis, providing insights into the potential biologic plausibility of the observed association between permethrin use and multiple myeloma risk among pesticide applicators.
Impact/Significance: Given the widespread use of permethrin in both residential and commercial settings, our findings may have public health implications beyond occupationally exposed pesticide applicators.
Citation Format: Joe Shearer, Laura Beane Freeman, Danping Liu, Gabriella Andreotti, Jennifer Hamilton, Julie Happel, Charles Lynch, Michael Alavanja, Jonathan Hofmann. A longitudinal investigation of hematologic perturbations among permethrin-exposed pesticide applicators in the Biomarkers of Exposure and Effect in Agriculture Study [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 610.
Abstract 612: Overexpression of PCDHB9 is correlated with tumor progression in esophageal cancer
Authors: Oue Naohide , Yamamoto Yuji , Asai Ryuichi , Sakamoto Naoya , Sentani Kazuhiro , Yasui Wataru 
Published: August 2019

Abstract
Genes encoding transmembrane proteins expressed specifically in cancer cell may be ideal biomarkers for diagnosis. Previously, we showed that overexpression of PCDHB9, which was identified as a transmembrane protein, promotes peritoneal metastasis and correlates with poor prognosis in patients with gastric cancer. However, expression of PCDHB9 in esophageal cancer remains unclear. In the present study, we investigated the expression and function of PCDHB9 in esophageal squamous cell carcinoma (ESCC). Immunohistochemical analysis demonstrated that 51 (40%) of 128 GC cases were positive for PCDHB9. PCDHB9 expression was correlated with T classification, N classification and tumor stage. There was no significant correlation between PCDHB9 expression and patient survival. Cell adhesion to fibronectin and invasion activity were significantly reduced by PCDHB9 knockdown. These results suggest that PCDHB9 may be a novel biomarker and therapeutic target for ESCC.
Citation Format: Naohide Oue, Yuji Yamamoto, Ryuichi Asai, Naoya Sakamoto, Kazuhiro Sentani, Wataru Yasui. Overexpression of PCDHB9 is correlated with tumor progression in esophageal 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 612.
Abstract 616: Literature review and meta-analyses of the prevalence of microsatellite instability high (MSI-H) and deficient mismatch repair (dMMR) for colorectal (CRC), gastric (GC), endometrial (EC) and ovarian cancers (OC) in Chinese population
Authors: Liu Xiaoqiao , Fan Jiaqi , Liaw Kai-Li , Xu Mo , Zhou Yu , Amonkar Mayur , Zeng Gefei 
Published: August 2019

Abstract
Purpose Given the high prevalence of MSI-H/dMMR in gastrointestinal and gynecologic cancers we systematically collected published studies and investigated its’ prevalence for Chinese CRC, GC, EC, OC subjects to better understand the size of potential target population available for pembrolizumab treatment in China.
Experimental Design Both Chinese and English literature were searched in WanFang and PubMed database respectively. Studies were included if they assessed prevalence of MSI-H by PCR based method investigating 5 markers from NCI or Promega panel, and/or dMMR by immunohistochemistry (IHC) for all 4 MMR proteins. Studies focusing only on hereditary or sporadic cancer were filtered out. Among eligible studies, meta-analyses (DerSimonian Laird random effect model) were performed on the proportion of MSI-H/dMMR for each tumor type by R metafor package. Prevalence for advanced stage (III/IV) were also extracted if the data were available.
Results For CRC, the prevalence of MSI-H estimated from 11 studies (13.7% [10.2-17.6%]) was similar as that of dMMR from 22 studies (14.6% [12.3-17.1%]). Pooled prevalence of MSI-H/dMMR from 32 studies (12,341 subjects) was estimated at 14.1% (12.2-16.1%), and 9.7% (7.2-12.5%) from 17 studies (3,933 subjects) for advanced stage CRC. The prevalence estimation for GC, EC and OC were 18.5%, 26% and 12.9% respectively. Further, the prevalence in advanced stage cancer, regardless of the cancer type, tended to be numerically lower than the all-stage combined prevalence.
Conclusions This was the first study comprehensively integrating published studies to estimate prevalence of MSI-H/dMMR across 4 main tumor types for Chinese subjects. The meta-analysis indicated the prevalence of MSI-H/dMMR for all or advanced stage Chinese cancer patients might be similar as that for western population.
Citation Format: Xiaoqiao Liu, Jiaqi Fan, Kai-Li Liaw, Mo Xu, Yu Zhou, Mayur Amonkar, Gefei Zeng. Literature review and meta-analyses of the prevalence of microsatellite instability high (MSI-H) and deficient mismatch repair (dMMR) for colorectal (CRC), gastric (GC), endometrial (EC) and ovarian cancers (OC) in Chinese population [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 616.