bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PO-011: Role of tumor heterogeneity, tumor microenvironment and tumor initiating cell in gastric carcinogenesis from the perspective of development of hypothesis for its clinical application
Authors: Mukherjee Kalyan Kusum , Mukherjee Dattatreya
Published: December 2020

Gastric Cancer (GC) is one of the most malignant type of cancer due to its rapid progression, distant metastasis and resistant to conventional chemotherapy. This study is to search the development towards specific therapy to overcome conventional chemotherapy resistance and probable hypothesis to develop it. It is known that tumor heterogeneity plays a fundamental essential role in cancer development and chemo resistance. Gastric Carcinoma Tumor initiating cell (GATIC) controls high tumerogenicity, maintenance of self renewal potential, formation of cancer and non cancer cells and chemotherapy resistance. Identifying the putative specific cell marker for purification and functional validation of GATIC, tracing the origin of GATIC, decoding the regulatory mechanism of GATIC, pave the way for the development of GATIC targeted therapy which is in phase of preclinical study and clinical trial. Alteration of tumor microenvironment is deeply implicated in tumor progression and metastasis in gastric cancer patient. Interaction between tumor cell and their microenvironment with cytokines and miRNA in extracellular vesicles such as exosome can have a substantial impact on tumor characteristics. Interaction and its clinical impact of alteration of GC microenvironment will be discussed. In the possible treatment hypothesis the level IL6, M1, CXCl12/CXCR may be blocked and the level of M2, C8+T cell and CCK2R may be amplified to develop TEM directed targeted therapy. After uncovering the mechanism of chemo resistance the differentiation therapy and elimination therapy of gastric carcinoma may be a sustainable targeted therapy. In this context over expression of ATOH1 in GATICS and Lentiviral vector based knockdown of PGK1 may be a treatment method to overcome Chemo resistance of GC. In the way of elimination therapy Cyclopamine and Vismodegib may be a feasible targeted therapy in GC. molecules which is specific suppressor of Wnt/B catenin may be used as a selective therapy for GATIC.

Citation Format: Kalyan Kusum Mukherjee, Dattatreya Mukherjee. Role of tumor heterogeneity, tumor microenvironment and tumor initiating cell in gastric carcinogenesis from the perspective of development of hypothesis for its clinical application [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-011.
Abstract PO-030: Characterizing mechanisms for inhibiting metastasis in triple negative breast cancer
Authors: Yang Dongbo , Dann Christopher , Pott Sebastian , Rosner Marsha
Published: December 2020

Tumor cell heterogeneity has been strongly implicated in metastatic progression of solid tumors such as breast cancer, leading to resistance and recurrence. We hypothesize that inhibiting metastasis will reduce tumor cell heterogeneity and thereby increase therapeutic sensitivity. To test this hypothesis, we expressed the metastasis suppressor Raf Kinase Inhibitory Protein (RKIP or PEBP1) in triple-negative breast cancer (TNBC) cells as a means of comparing the variation in gene expression between individual cells in metastatic versus non-metastatic tumors. Xenograft tumors with or without exogenous RKIP expression were dissociated into single cell suspensions. We removed mouse as well as dead cells, and the remaining cells were loaded onto a Fluidigm C1 high-throughput chip for separation and library preparation. For each condition we performed three independent experiments yielding a total of 1569 cells. We performed controls to ensure that differences were not due to batch effects, cell cycle stage or sample quality. Clustering of single cells across all samples indicated that gene expression profiles are similar, confirming reproducibility. Gene ontology analysis of differentially expressed genes between cells with and without RKIP overexpression reveals gene sets that are important in tumor cell transitions from metastatic to non-metastatic states. These data will allow us to specifically test whether metastatic tumors are more heterogeneous than non-metastatic tumors in TNBC.

Citation Format: Dongbo Yang, Christopher Dann, Sebastian Pott, Marsha Rosner. Characterizing mechanisms for inhibiting metastasis in triple negative breast cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-030.
Abstract PO-031: Innate immune genes distinguish the immune microenvironment of early onset colorectal cancer
Authors: Gardner Ivy H. , Siddarthan Ragavan , Watson Katherine , Dewey Elizabeth , Ruhl Rebecca , Guan Xiangnan , Xia Zheng , Tsikitis Liana V. , Anand Sudarshan
Published: December 2020

Despite a decrease in the incidence of colorectal cancer (CRC) over the last 40 years, the incidence of CRC in people under 50 years old is increasing around the globe. Early onset (≤50 years old) and late onset (≥65 years old) CRC appear to have differences in their clinicopathological and genetic features, but it is unclear if there are differences in the tumor microenvironment. We hypothesized that the immune microenvironment of early onset CRC is distinct from late onset CRC and promotes tumor progression. We used Nanostring immune profiling to analyze mRNA expression of immune genes in FFPE surgical specimens from patients with early (N=40) and late onset (N=39) CRC. We found three genes, SAA1, C7, and CFD, have increased expression in early onset colorectal cancer and distinct immune signatures based on the tumor location. After adjusting for clinicopathological features, increased expression of CFD and SAA1 were associated with worse progression free survival and increased expression of C7 was associated with worse overall survival. Our data demonstrate that the immune microenvironment in early onset CRC is unique, location dependent, and associated with worse outcomes. We propose that age specific immune signatures in the colorectal immune microenvironment can be used as biomarkers for prognosis as well as the development of targeted immune modulatory agents.

Citation Format: Ivy H. Gardner, Ragavan Siddarthan, Katherine Watson, Elizabeth Dewey, Rebecca Ruhl, Xiangnan Guan, Zheng Xia, Liana V. Tsikitis, Sudarshan Anand. Innate immune genes distinguish the immune microenvironment of early onset colorectal cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-031.
Abstract PO-057: Host cell-derived TXA2-mediated Gq signaling in tumor cells promotes tumor immune evasion
Authors: Terai Kenta , Konishi Yoshinobu , Ichise Hiroshi , Watabe Tetsuya , Sando Yukari , Kondo Takefumi , Oki Choji , Tsukiji Shinya , Hamazaki Yoko , Murakawa Yasuhiro , Takaori-Kondo Akifumi , Matsuda Michiyuki
Published: December 2020

Tumor-derived prostaglandin E2 (PGE2) promotes tumor progression through evasion of anti-tumor immunity. However, little is known about how PGE2 secretion is regulated within tumor tissues. Here, we show that host cell-derived thromboxane A2 (TXA2) triggers tumor cells to secrete PGE2, resulting in the evasion of anti-tumor immunity. An induction of Ca2+ transients in BrafV600E mouse melanoma cells is sufficient to trigger PGE2 secretion. The frequency of Ca2+ transients is markedly higher in melanoma cells implanted into mice than those in vitro. We show that t he melanoma cells deficient in TXA2 receptor or Gq subunit α do not exhibit Ca2+ transients in vivo nor evade anti-tumor immunity, as do not melanoma cells deficient in cyclooxygenases (COX). Motesanib, a VEGF receptor antagonist, suppresses Ca2+ transients, suggesting the involvement of tumor endothelial cells in the TXA2 production within tumor tissue. These resultsresults identifyresults identifyidentify TXA2 as a critical promotertargetof PGE2-dependent tumorigenesis.

Citation Format: Kenta Terai, Yoshinobu Konishi, Hiroshi Ichise, Tetsuya Watabe, Yukari Sando, Takefumi Kondo, Choji Oki, Shinya Tsukiji, Yoko Hamazaki, Yasuhiro Murakawa, Akifumi Takaori-Kondo, Michiyuki Matsuda. Host cell-derived TXA2-mediated Gq signaling in tumor cells promotes tumor immune evasion [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-057.
Abstract PO-069: Characterizing cell-to-cell heterogeneity and chromosome instability induced by USP22 deficiency in colorectal cancer
Authors: Jeusset Lucile M. , Lichtensztejn Zelda D. , McManus Kirk J.
Published: December 2020

Chromosome instability (CIN) is an aberrant phenotype characterized by an increased rate of gains and losses of chromosomes. CIN is observed in most cancer types, including 85% of colorectal cancer (CRC) cases. Although CIN is a driver of tumor heterogeneity and associated with drug resistance and poor patient prognosis, the genetic defects underlying CIN remain poorly understood. Ubiquitin Specific Peptidase 22 (USP22) is a deubiquitinating enzyme that targets mono-ubiquitin on lysine 120 of histone H2B (H2Bub1). H2Bub1 is a dynamic post-translational modification that modulates chromatin compaction. Importantly, homozygous or heterozygous USP22 deletion is observed in 45% of CRC cases, suggesting this may be a pathogenic event promoting CRC progression. Accordingly, we sought to characterize the impact reduced USP22 expression has on CIN. To reduce USP22 expression in karyotypically stable CRC (HCT116) and immortalized fibroblast (hTERT) cell lines, we employed transient siRNA silencing and stable CRISPR-Cas9 knockout (KO) models. Single-cell quantitative image-based analyses were utilized to monitor CIN-associated phenotypes, including changes in nuclear areas, micronucleus formation and chromosome numbers. In HCT116, USP22 silencing induced CIN phenotypes and an increase in H2Bub1 abundance in mitotic chromosomes. Subsequent mechanistic studies determined that this is accompanied by an increase in the recruitment of the spindle assembly checkpoint kinase BUB1 at metaphase centromeres and an increased frequency of lagging chromosomes in anaphase. Collectively, these data suggest that reduced USP22 expression alters H2Bub1 regulation in mitosis, which impairs mitotic fidelity, thereby inducing CIN. In addition, to assess the relevance of reduced USP22 expression in a distinct cellular context, the impact of USP22 silencing was assessed in hTERT, revealing similar CIN phenotypes, including changes in nuclear area and chromosome numbers. To assess the long-term impact USP22 deletions have on CIN, novel homozygous and heterozygous USP22-KO HCT116 clones were generated and monitored for three months, which revealed dynamic CIN phenotypes and ongoing changes in chromosome complements relative to controls. Collectively, these data identify USP22 as a novel CIN gene and indicate that USP22 deletions in cancer may drive intra-tumor genetic heterogeneity and thereby promote oncogenesis.

Citation Format: Lucile M. Jeusset, Zelda D. Lichtensztejn, Kirk J. McManus. Characterizing cell-to-cell heterogeneity and chromosome instability induced by USP22 deficiency in colorectal cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-069.
Abstract PO-089: Spatial profiling of the tumour microenvironment using digital spatial profiling
Authors: Kulasinghe Arutha
Published: December 2020

Immune checkpoint inhibitors (ICI) have shown durable and long-term benefits in a subset of head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC). To identify patient-responders from non-responders, biomarkers are needed which are predictive of outcome to ICI therapy. Cues in the tumour microenvironment (TME) have been informative in understanding the tumour-immune contexture. Methods: In this study, the NanoString GemoMx™ Digital Spatial Profiling (DSP) technology was used to determine the immune marker and compartment specific measurements in a cohort of HNSCC and NSCLC tumours from patients receiving ICI therapy. Results: Our data revealed that markers involved with immune cell infiltration (CD8 T-cells) were not predictive of outcome to ICI therapy. A number of immune cell types (CD4, CD68, CD45, CD44, CD66b) were found to correlate with progressive disease. Conclusions: Our data shows proof of principle for use of digital spatial profiling for the identification of predictive biomarkers for ICI therapy in HNSCC and NSCLC.

Citation Format: Arutha Kulasinghe. Spatial profiling of the tumour microenvironment using digital spatial profiling [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-089.
Abstract PO-092: Immune profiling of the tumor microenvironment using multiplexed ion beam imaging (MIBI)
Authors: Ptacek Jason , Ghosh Srimoyee , Pablo Lourdes , Feng Bin , Zhang Hailei , Sigal Yari , Tarolli Jay G. , Aksoy Murat , Zhang Yi , Finck Rachel , Finn Jessica
Published: December 2020

The growing application of immunotherapy and its ability, or inability, to modulate the tumor microenvironment (TME) has exposed a need for techniques capable of simultaneously tracking large numbers of biomarkers in complex tissue at sub-cellular resolution. To address this, MIBI uses tissue processed similar to standard immunohistochemistry (IHC) methods but with the advantage of being able to stain the tissue simultaneously with a panel of up to 40 metal labeled antibodies. The expression of proteins is imaged by MIBI in a single scan at subcellular spatial resolution by combining the high resolution of an ion beam and the sensitivity of time-of-flight secondary ion mass spectrometry (ToF-SIMS). To characterize the immune infiltrates present in a set of 10 non-small-cell lung carcinoma (NSCLC) samples, a panel of 22 metal labeled antibodies was used to stain the tissue. The stained tissue was then analyzed by MIBI and the masses of detected species were assigned to target biomolecules given the unique label of each antibody. Multi-step processing and segmentation utilizing highly expressed nuclear, membrane, and cytoplasmic markers were performed to accurately determine cell boundaries and enable quantitative analyses of marker expression, cell classification, and the spatial relationships between cell types. Results comparing the abundance of tumor cells, vascular cells, and immune cell subsets between samples identified “cold” tumors with few immune cells and inflamed samples that varied in the type of immune populations present. Immune checkpoint markers (LAG3, PD-1, PD-L1, TIM-3) were also quantified at single cell resolution. In conclusion, this study shows that MIBI offers high-parameter capability necessary to (1) identify the wide range of cell types present within the complex tumor immune landscape, (2) the spatial relationships between these different cell populations, and (3) the expression status of key immunoregulatory proteins.

Citation Format: Jason Ptacek, Srimoyee Ghosh, Lourdes Pablo, Bin Feng, Hailei Zhang, Yari Sigal, Jay G. Tarolli, Murat Aksoy, Yi Zhang, Rachel Finck, Jessica Finn. Immune profiling of the tumor microenvironment using multiplexed ion beam imaging (MIBI) [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-092.
Abstract PO-104: Phenotypic mapping of pathological crosstalk between glioblastoma and innate immune cells by synthetic genetic tracing
Authors: Schmitt Matthias Jürgen , Company Carlos , Dramaretska Yuliia , Barozzi Iros , Göhrig Andreas , Kertalli Sonia , Großmann Melanie , Naumann Heike , Wierikx Jikke , Hulsman Danielle , Glass Rainer , Squatrito Massimo , Serresi Michela , Gargiulo Gaetano
Published: December 2020

Glioblastoma is a lethal brain tumor with a high degree of heterogeneity and resistance to therapy. The lack of genetic tracing approaches to selectively identify tumor states and fate transitions limited our understanding of tumor homeostasis. By translating glioblastoma subtype signatures into synthetic genetic tracing cassettes, we investigated tumor heterogeneity at cellular and molecular level, in vitro and in vivo. Synthetic genetic tracing demonstrated that proneural glioblastoma is a hardwired identity, whereas the mesenchymal glioblastoma is an adaptive and metastable state downstream pro-inflammatory and differentiation cues, similarly wired in breast and lung tumors. Importantly, we discovered that innate immune cells divert glioblastoma cells into a proneural-to-mesenchymal transition causal to therapeutic resistance. Systematic phenotypic mapping using synthetic locus control regions (sLCRs) is a simple, automated, and scalable strategy for genetic tracing, generally applicable to study developmental and disease homeostasis. In glioblastoma, it uncovered causality between various (micro)environmental, genetic and pharmacological perturbations and mesenchymal commitment.

Citation Format: Matthias Jürgen Schmitt, Carlos Company, Yuliia Dramaretska, Iros Barozzi, Andreas Göhrig, Sonia Kertalli, Melanie Großmann, Heike Naumann, Jikke Wierikx, Danielle Hulsman, Rainer Glass, Massimo Squatrito, Michela Serresi, Gaetano Gargiulo. Phenotypic mapping of pathological crosstalk between glioblastoma and innate immune cells by synthetic genetic tracing [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-104.
Abstract IA17: Lung cancer screening: a public health benefit that may deepen the divide
Authors: Tanner Nichole T.
Published: December 2020

The National Lung Screening Trial (NLST) and most recently the Dutch–Belgian lung-cancer screening trial (NELSON) were transformative, demonstrating the efficacy of low-dose computed tomoagraphy (LDCT), and thus providing the evidence to support the implementation of screening for lung cancer, a cancer for which no efficacious screening strategy was previously available, into medical care. In a population at high risk for lung cancer as defined by age and smoking history, LDCT was associated with a 20-25% reduction on lung cancer mortality. In the absence of screening, only 16% of patients are diagnosed with a disease stage that has potential for cure by surgical resection. Lung cancer screening identifies cancer at an earlier, more treatable stage. Despite these results, a Grade B recommendation from the US Preventive Services Task Force and coverage by the Centers for Medicare and Medicaid Services, only 14.4% of those eligible underwent screening in 2017. The reasons for this reduction in access and utilization of lung cancer screening are multifactorial and include lack of provider time, limited patient and provider knowledge, and insufficient clinical and technological infrastructure. Further, there is an inverse relationship between the location of those at highest risk for lung cancer (e.g., individuals living in rural settings) and the access to lung cancer screening centers. While lung cancer screening has the potential to reduce mortality there is evidence to suggest that disparities in implementation will further widen existing gaps in lung cancer treatment and mortality among those of lower socioeconomic status, minorities, and un/underinsured populations. This presentation will highlight the challenges and suggest possible solutions.

Citation Format: Nichole T. Tanner. Lung cancer screening: a public health benefit that may deepen the divide [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA17.
Abstract IA48: Engagement with Native American communities
Authors: Godfrey Maurice
Published: December 2020

Increasing the numbers of underrepresented minorities (URM) in biomedical research, including cancer, is more than a laudable goal. It is an important priority because it will likely lead to better disease outcomes for people from within these communities. Therefore, we must build capacities to provide pathways for URM students to succeed. Over the past 15 years we have worked with both urban and reservation Native American communities to bring health and science education to their teachers and students. There are some salient and universal principals that must be acknowledged. First and foremost is trust. One does not alter decades of neglect, suspicion, and distrust without serious and open dialogue. Moreover, while one does find many stories of success, they are often anecdotal and, while no less powerful, a foundation must be laid to make these stories much more common. Among the first things that we learned was that the starting point needs to moved back. We had heard that there were programs and partnerships, past and present, within the University of Nebraska Medical Center (UNMC) with an area tribal college. These programs seemingly included collaborations to increase student enrollment in allied health professions or experience research opportunities. Unfortunately, neither had much, if any, success. Thus, we learned that post-secondary engagement was not sufficient to garner positive results. Our first program, even though UNMC is primarily a graduate institution, was a K-8 program for students and teachers. It is there that a foundation of learning, STEM engagement, tapping the natural curiosity of young learners, and providing resources to teachers, especially those in severely under-sourced areas, would have to be set. In addition, spending time within the schools and communities, at times hundreds of miles from campus, was essential to build the necessary trust for this work to continue and become impactful. We have not changed the world, but we have established trust with many communities. Our middle school summer programs have become practically standing room only. We have had many students, high school and undergraduates, engage in research, both bench and community based. We have students who have explored pathways to health careers, and now some are graduating college with their eyes on medical school and research careers. Clearly, decades of neglect will not be alleviated in just a few grant cycles, but significant steps have been made and continued concerted efforts will, in time, bridge gaps that seemed to be chasms not long before.

Citation Format: Maurice Godfrey. Engagement with Native American communities [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA48.
Abstract PO-003: Multidisciplinary cancer care among breast, colorectal, and lung cancer patients: A SEER-Medicare analysis
Authors: Sanchez Janeth I. , Doose Michelle , Chollette Veronica , Weaver Sallie J.
Published: December 2020

Background: Multidisciplinary care (MDC) is an essential component of quality cancer care and includes the coordination of treatment provided by a team of 2+ multidisciplinary healthcare professionals. Although MDC is associated with improved health outcomes, it is still unclear if MDC is standard clinical practice among cancer patients or if disparities exist. This study assesses the multilevel (i.e., patient, provider, health system level, and neighborhood) factors associated with receipt of MDC. Methods: We used the Surveillance, Epidemiology and End Results (SEER)–Medicare data (2006-2016) to identify beneficiaries >65 years of age diagnosed with breast, colorectal, or lung cancer. We used multivariate analyses with random effects at the provider- and health system-level to assess the effect of multilevel factors on receipt of MDC. Results: From 2007 to 2015, receipt of MDC increased by 26.2%. Overall, 56.3% of patients received MDC within 2-months of a cancer diagnosis. Unadjusted analyses indicate that the odds of receiving MDC were 27% lower among Blacks compared to non-Hispanic Whites. Female, married, and dual Medicare-Medicaid coverage were significantly more likely to receive MDC (p<0.001). Among patients who received surgery, the odds of receipt of MDC were 40% higher among patients who saw a surgical oncologist compared to patients who saw a general surgeon. Patients whose surgery was performed at a hospital with Rural Primary Status were 53% less likely to receive MDC. Patients residing in more disadvantaged neighborhoods, based on the Area Deprivation Index, and in rural areas were also significantly less likely to receive MDC (p<0.01). Conclusion: Although receipt of MDC has steadily increased over the last decade, the prevalence of MDC among cancer patients remains strikingly low, especially among populations at-risk for health disparities. Future research should identify strategies that work synergistically at multiple levels to improve equitable access to and receipt of MDC for all cancer patients.

Citation Format: Janeth I. Sanchez, Michelle Doose, Veronica Chollette, Sallie J. Weaver. Multidisciplinary cancer care among breast, colorectal, and lung cancer patients: A SEER-Medicare analysis [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-003.
Abstract PO-044: A pilot concept for cancer education outreach to community K-8 schools
Authors: Ondrey Juliana M. , Ondrey Frank
Published: December 2020

Introduction: The authors examined feasible mechanisms for a cancer research lab at a university to improve racial/cultural cancer disparities issues in Minneapolis/St. Paul, Minnesota. The goal was to find tangible mechanisms to preliminarily and proactively attend to racial disparities issues based on recent events in our community. Materials and Methods: The authors identified four domains of activity that could potentially be deployed to the local Black community. These consisted of improved community education, improved health care access, improved researcher education about racism/cultural bias, and education on the concept of trauma informed care. Community cancer education outreach was judged most feasible program’s researchers. In the past, education outreach had been performed at K-8 school science fairs and a community cancer education program where we have been instructors (an entity called Mini-medical school). Demographics for past interactions were analyzed to gauge directing further outreach. Results: In the Twin cities proper 16-19% of the residents are Black (Primarily African American and Somali); in the larger metropolitan area 8-9%, and 6-7% overall in Minnesota. We found that our research program outreach had occurred at a school with only 4.4% Black/African American students. At the larger Cancer education program (Mini medical school), approximately 3.5% of attendees were African American. Both of these outreach activities occurred in communities with much lower percentage than the 16-19% Black community demographic (P<0.001). Discussion: We plan to contact primary schools in local communities of color where we can participate at science or technology fairs as educators/judges based on our scientific expertise. Further, through these local schools and their communities, Cancer disparities education (such as the mini-medical school) could be tailored to neighborhood school communities as part of this outreach. The authors felt participation in this activity by Black physicians/scientists/students, inexpensive access, and maximizing student/family availability for the program would be necessary to optimize the experience. We conclude that such a grass root pilot would provide useful education for the community, perhaps improve cancer research interests in primary grade students, and could feasibly be extended to additional cancer research labs at our university, based on the results of a 1-2 school pilot effort.

Citation Format: Juliana M. Ondrey, Frank Ondrey. A pilot concept for cancer education outreach to community K-8 schools [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-044.
Abstract PO-124: Mutational profiling of DNA repair and mismatch repair genes in the Egyptian colorectal cancer patients using targeted DNA sequencing
Authors: El-Din Youssef Amira Salah , Lotfy Mai M. , Nassar Auhood , Zekri Abdel-Rahman N.
Published: December 2020

Background: Colorectal cancer (CRC) remains one of the most prevalent and deadly tumor worldwide. DNA repair and mismatch repair (MMR) genes play an important role in the occurrence and development of colorectal cancer; however, there is insufficient knowledge of DNA repair and MMR mutational profile in the Egyptian Colorectal cancer (CRC) patients which limit our understanding of its progression.

Aim: This study aimed to sequence DNA repair and mismatch repair (MMR) genes frequently associated with colorectal cancer (CRC) progression in order to identify their frequencies in the Egyptian CRC patients which may help in understanding colorectal carcinogenesis and developing personalized therapy. Material and methods: Biopsy samples were collected from 62 CRC Egyptian patients. The libraries were performed using Qiaseq UMI-based targeted panel and sequenced via Ion proton sequencer. The detected genetic variants with an average coverage of 500x were annotated against Cosmic and dbSNP and Clinvar databases using Ingenuity Variant analysis (IVA). Results: Regarding DNA repair genes, our results revealed that ATM & CHEK2 genes harbored 19 and 4 variants, respectively. The most frequently detected pathogenic mutations in the ATM were COSM1350741 (29%), COSM1351020 (26%) & COSM41596 (17%) while those pathogenic mutations detected in the CHEK2 were rs772683219 (2%) & rs587780181 (2%). As per MMR genes, it has been shown that MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 & PMS2 harbored 6, 6, 8, 6, 7, 3 & 4 variants, respectively. The identified pathogenic mutations in the MLH1 were COSM1131469 (32%) & rs63750217 (2%), while those pathogenic mutations detected in the MSH2 were rs63749832 (7%), COSM26124 (5%), rs63750084 (2%). Moreover, the highly frequent detected pathogenic mutations were COSM1438892 (7%) in MSH3, & rs267608093 (10%), COSM13395 (6%), COSM13394 (3%) in MSH6. Regarding PMS1, The most frequently detected pathogenic mutation was COSM1404081 (10%). However, no pathogenic mutations were detected in both PMS2 & MLH3 genes. Conclusion: In this data set, we shed the light on the most frequently identified DNA repair and MMR genetic mutations that are crucial for understanding colorectal carcinogenesis and developing ethnic-based personalized therapies in the Egyptian CRC patients.

Citation Format: Amira Salah El-Din Youssef, Mai M. Lotfy, Auhood Nassar, Abdel-Rahman N. Zekri. Mutational profiling of DNA repair and mismatch repair genes in the Egyptian colorectal cancer patients using targeted DNA sequencing [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-124.
Abstract PO-126: PVT1 exon 9 transcript regulates claudin 4 expression and migration in triple negative breast cancer
Authors: Levine Fayola , Ogunwobi Olorunseun
Published: December 2020

Breast cancer (BC) is a heterogeneous disease that is classically driven by the estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor 2 (EGFR2/HER2) signaling pathways. Triple negative breast cancer (TNBC), is a lethal subtype of invasive BC tumors that are ER-, PR- and HER2-. A subtype of TNBC is claudin low (CL). Dysregulation of claudin proteins disrupts tight junctions, consequently inducing the epithelial-to-mesenchymal transition (EMT) in cancers. This leads to enhanced motility and metastasis. Patients with CL TNBC have worse prognosis than patients with other BC subtypes. PVT1 is a long noncoding RNA (lncRNA) transcribed from the 8q24 genomic locus that has been implicated in multiple cancers including BC. Amplification of the 8q24 gene locus is a common event in many malignant diseases and is associated with poor clinical outcomes.

Although previous research has implicated PVT1 as an important player in BC, the underlying molecular mechanisms of PVT1 in CL TNBC was previously unknown. We assessed PVT1 expression in BC, and we observed that PVT1 exons 4A, 4B, and 9 are significantly upregulated in MDA MB 231 cells (claudin low) and significantly downregulated in MDA MB 468 cells (claudin high), in comparison to T47D (ER+). We have confirmed that claudin expression, specifically claudins 1, 3, 4 and 7, are significantly higher in MDA MB 468 cells and significantly lower in MDA MB 231 cells. Knockdown of PVT1 exon 9 expression in the MDA MB 231 cell line, led to a significant reduction in migration when compared to cells transfected with a control scramble siRNA, indicating that PVT1 exon 9 regulates migration in CL TNBC. Interestingly, we observed that claudin 4 expression, and not claudins 1, 3 and 7, was increased in cells where PVT1 exon 9 was knocked down when compared to the control cells. This indicates that PVT1 exon 9 regulates claudin 4 protein stability in CL TNBC. We also assessed the expression of EMT markers (vimentin, fibronectin, and E-cadherin) in MDA MB 231 cells. We observed no changes in EMT markers when PVT1 exon 9 is knocked down; however, our data suggests that EMT markers are more highly expressed in MDA MB 231 cells in comparison to MDA MB 468 cells. Taken together, our data indicate that PVT1 exon 9 regulates claudin expression and migration in CL TNBC, and may have implications for clinical outcomes in TNBC.

Citation Format: Fayola Levine, Olorunseun Ogunwobi. PVT1 exon 9 transcript regulates claudin 4 expression and migration in triple negative breast cancer [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-126.
Abstract PO-142: Development of Empirical Dietary Inflammatory Pattern (EDIP) scores with different food groups and biomarkers
Authors: Guyonnet Emma , Amankwah Millicent , Chen Yalei , Martini Rachel , Davis Melissa , Newman Lisa
Published: December 2020

Background: The empirical dietary inflammatory pattern (EDIP) is a hypothesis- driven dietary pattern used to assess the inflammatory potential of diet in the US population. It is usually composed of food groups obtained from a food-frequency questionnaire. Methods: EDIP scores were calculated for 4 models from 24hr recalls reported by 67 women noncancer controls that had signed an informed consent prior to participation. The Luminex Human Chemokine Multiplex Assay was used to measure 11 chemokines and cytokines. As seen in previous studies, we first derived a model, EDIP-Limited (EDIP-L), by entering 18 food groups in reduced rank regression models followed by a multivariable regression analysis to identify a dietary pattern that predicts concentrations of two inflammatory biomarkers: IL-6 and TNF-a. We derived another EDIP score using a new model, EDIP-All Inclusive (EDIP-AI), which included the same 18 food groups to predict all 11 biomarkers. Lastly, we developed two other EDIP models. EDIP-Limited New (EDIP-LN) used 14 new food groups derived from the same 24hr recalls, only predicting IL-6 and TNF-a. EDIP-All New (EDIP-AN) used those 14 food groups with all 11 biomarkers. Results: In this study, we optimize models for EDIP and report the differences in EDIP scores based on the inflammatory biomarkers and food groups used in analysis. Briefly, the components of EDIP-L were not significant. After including all the biomarkers, the components of EDIP-AI were: “fruit juice” (p = 0.0009), “snacks” (p = 0.0008), “leafy green vegetables” (p = 0.0074), “low-energy beverages” (p = 0.0098), “red meat” (p = 0.0038), “fruit” (p = 0.0002) and “whole wheat grains” (p = 0.0138). Similarly, after reorganizing our food items into 14 food groups, the components of EDIP-LN were not significant. However, components of EDIP-AN were: “fruit juice” (p = 0.0107), “snacks” (p = 0.0116) and “fruit” (p = 0.0026). Conclusions: Findings demonstrate the EDIP scores differ based on the inflammatory biomarkers and food groups used in the analysis on the same noncancer controls. Depending on the methods used, an individual’s diet may be considered more pro- or anti-inflammatory. This study provides insight into the inflammatory potential of an individual’s diet and the factors that may affect how we calculate this potential.

Citation Format: Emma Guyonnet, Millicent Amankwah, Yalei Chen, Rachel Martini, Melissa Davis, Lisa Newman. Development of Empirical Dietary Inflammatory Pattern (EDIP) scores with different food groups and biomarkers [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-142.
Abstract PO-175: National trends in younger onset obesity-related cancer incidence
Authors: Begi Talia , Tripathi Osika , Offor Paris , Thompson Caroline A.
Published: December 2020

Obesity is a risk factor for many cancers, and obesity-related cancer incidence in the United States (U.S.) has been rising over the years. In the recent decades, the younger population of the United States has experienced an increase in obesity.

These increases have been the highest among ethnic minorities, and in the Southeast, while they have been less evident in the Northeast. The impact of rising rates of obesity among younger individuals on younger onset cancer incidence is less well understood. We estimated 15-year trends in incidence for 11 obesity-related cancers among adults under the age of 50 stratified by race/ethnicity and geographic region of the United States. Age adjusted incidence rates for cancers of the female breast, colorectal, endometrial, esophageal, hepatocellular carcinoma, kidney, multiple myeloma, non-cardia gastric, ovarian, pancreatic, and thyroid cancers were calculated from 2001-2016 using data obtained from Surveillance, epidemiology, and End Results (SEER-18). Data were stratified by age +/- 50 years old, four racial/ethnic groups: non-Hispanic white (NHW), non-Hispanic black (NHB), Asian American or Pacific Islander (AAPI), and Hispanic, and four geographical regions: West, Midwest, Northeast, and Southeast, and by sex. We used SEER*Stat and JoinPoint software for analysis. We observed statistically significant increasing 15-year trends among younger adults for colorectal cancer in NHWs, NHBs, and Hispanics, kidney cancer in all race groups, multiple myeloma among NHBs, non-cardia gastric cancer in Hispanic males and thyroid cancer in NHW and AAPI males. Stratification by geography revealed increasing trends of younger onset female breast cancer in the Midwest and that increasing trends for younger onset myeloma, non-cardia gastric, and thyroid cancers are steepest in the Northeastern U.S. and steepest for younger onset colorectal cancer in the Southeast U.S. We observed increasing trends in younger onset cancers of the kidney, colorectal, multiple myeloma, non-cardia gastric, thyroid, and female breast. Preventing obesity in ways such as education, better food produce availability and programs, and lower healthcare costs may reduce the impact of these cancers. Reduced age for screening for colorectal cancer may improve opportunity for earlier detection and improved prognoses in younger adults.

Citation Format: Talia Begi, Osika Tripathi, Paris Offor, Caroline A. Thompson. National trends in younger onset obesity-related cancer incidence [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-175.
Abstract PO-184: Air pollution in relation to risk of pancreatic cancer in the Multiethnic Cohort Study
Authors: Bogumil David , Wu Anna H. , Stram Daniel , Tseng Chiu-Chen , Cheng Iona , Setiawan Veronica Wendy
Published: December 2020

Background: There are limited studies that have investigated the association between ambient gaseous and particulate matter (PM) air pollutants and risk of pancreatic cancer. Results from published studies are inconsistent, the strongest evidence was a significant, 16% increase in risk of pancreatic cancer mortality per 10 µg/m3 increase in PM <2.5 µm (PM2.5) in China. We used data from the Multiethnic Cohort Study to examine prospectively associations between ambient air pollutants and incident pancreatic cancer, while adjusting for a comprehensive list of confounding factors. Methods: Kriging Interpolation was used to estimate individual, time varying, monthly, air pollutant exposure levels of nitrogen oxides (NOX, NO2) and PM (PM2.5, PM10) pollutants for 100,527 men and women, who resided largely in Los Angeles County at the time of enrollment (1993-1996) through 2014. We observed 844 incident cases of pancreatic cancer among cohort members during the 18-years of follow up. Cox proportional hazard models were used to estimate the association between each air pollutant and risk of pancreatic cancer. All models adjusted for age, sex, race/ethnicity, neighborhood socioeconomic status, body mass index, diabetes mellitus, and smoking history. Results: PM2.5 was non-significantly positively associated with risk of pancreatic cancer (hazard ratio [HR]=1.33; 95% CI: 0.91, 1.95 per 10 µg/m3). No associations were observed with other pollutants (PM10 [HR=0.99; 95% CI=0.96, 1.07 per 10 ppb], NO2 [HR=0.99, 95% CI 0.93; 1.17], NOx [HR=1.01 95% CI=0.96, 1.07]). In stratified analyses, we did not observe heterogeneity by race/ethnicity (PM2.5 p=0.17, PM10 p=0.16, NO2 p=0.30, NOx p=0.27) or smoking status (PM2.5 p=0.72, PM10 p=0.85, NO2 p=0.53, NOx p=0.28). Conclusions: In this prospective cohort study of air pollution and risk of pancreatic cancer, we did not observe an increase in risk associated with PM2.5, PM10, NO2, or NOx. These results add to the scarce data on the association between air pollution and pancreatic cancer risk.

Citation Format: David Bogumil, Anna H. Wu, Daniel Stram, Chiu-Chen Tseng, Iona Cheng, Veronica Wendy Setiawan. Air pollution in relation to risk of pancreatic cancer in the Multiethnic Cohort Study [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-184.
Abstract PO-192: Exploring the contribution of introgressed ancient DNA to prostate cancer racial disparity
Authors: Useh Evi O. , Venugopal Suresh , Molokwu Chidi N.
Published: December 2020

Introduction Prostate cancer is the most common cancer in men and there is racial disparity in prostate cancer incidence and mortality globally, with greater disease burden in men of African ancestry, followed by European ancestry and least in men of Asian ancestry. The etiology of prostate cancer is not fully understood but includes genetic and environmental factors. Present day non-Africans are reported to have introgressed DNA from Neanderthal and Denisovan ancestors. Over 170 prostate cancer associated single nucleotide polymorphisms (SNPs) have been identified from several genome-wide association studies (GWAS), with SNPS on chromosomes 2, 8 and 22 reported as showing variation between African and non-African men with prostate cancer. We performed analysis of prostate cancer associated SNPs on chromosomes 2, 8 and 22 to determine if DNA introgression could explain the racial variation. Methods We obtained data on prostate cancer associated SNPs from the GWAS catalog (https://www.ebi.ac.uk/gwas) and from reports that were not included in the catalog. Using an Ancient Genome Browser provided by the Max Plank Institute (https://www.eva.mpg.de/genetics/genome-projects/neandertal/index.html), we determined whether SNPs on chromosomes 2, 8 and 22 were present in African, Neanderthal or Denisovan genomes. Based on the results, we inferred that SNPs were introgressed if they were present in Neanderthal or Denisovan genomes but absent from African genomes. Results 49, 59 and 17 prostate cancer SNPs were reported in chromosomes 2, 8 and 22 respectively. 23/49 in ch2, 25/59 in c 8 and 9/17 in ch22 were present in in Neanderthal and or Denisovan genomes. SNPs in ch2 (rs13403657, rs12621278) and ch8 (rs7825414) were present in Neanderthal or Denisovan genomes but absent in African genomes. These SNPs lie in regions that have previously been reported to harbour introgressd DNA. Conclusion Our analyses identified prostate cancer associated SNPs that are likely to have been introgressed into present day non-Africans by extinct Neanderthal and Denisovan ancestors. Phenotypic changes caused by introgressed DNA could be contributing to racial disparities in prostate cancer in present day humans.

Citation Format: Evi O. Useh, Suresh Venugopal, Chidi N. Molokwu. Exploring the contribution of introgressed ancient DNA to prostate cancer racial disparity [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-192.