bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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 &gt;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&lt;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&lt;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

Abstract
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&lt;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

Abstract
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.