bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 123: Molecular mechanisms of RNA and DNA editing in leukemic transformation of hemopoietic stem and progenitor cells
Authors: Isquith Jane Marie , Pham Jessica , Whisenant Thomas , Balaian Larisa , Jamieson Catriona 
Published: April 2023

Abstract
Dysregulation of inflammatory cytokine responsive APOBEC3 cytosine deaminases has been shown to be a contributing factor in cancer evolution, presenting as gene expression changes and inclusion of distinct C-to-T mutation patterns. However, the context specificity and mechanisms by which APOBEC3 enzymes promote cancer initiation and progression require further elucidation. Lentiviral overexpression of APOBEC3C and an editase deficient APOBEC3C mutant in healthy cord blood, bone marrow and MPN patient hematopoietic stem/progenitor cells (HSPCs) allows us to study the effects of innate immune deaminase dysregulation in the hematopoietic niche. We are focusing on the upregulation of APOBEC3C and adenosine deaminase acting on RNA1 (ADAR1), as we have previously shown them to be contemporaneously upregulated in the high-risk myelofibrosis (MF) stem cell population compared to normal aged bone marrow. We can compare these novel differential gene expression changes, RNA hyper-editing sites, and DNA mutation signatures induced by APOBEC3 mutagenesis to abnormalities seen in both hematopoietic malignancies and solid tumor cancers. Gene set enrichment analysis (GSEA) performed on this dataset has exposed numerous deregulated pathways brought on by exaggerated levels of APOBEC3, including changes in splicing pathways. To further investigate the complex relationship between splicing and deaminase deregulation, we treated myeloproliferative neoplasm patient samples and normal HPSCs with Rebecsinib (also known as 17S-FD-895), a pharmacologically stable, potent, and selective small molecule splicing modulator, which interestingly caused significant downregulation of APOBEC3C. We will continue to investigate these findings as a potential target to correct the dysregulation seen in MPN progression. Consequently, we aim to use these findings to identify predictive biomarkers and druggable targets of leukemic initiation progression.
Citation Format: Jane Marie Isquith, Jessica Pham, Thomas Whisenant, Larisa Balaian, Catriona Jamieson. Molecular mechanisms of RNA and DNA editing in leukemic transformation of hemopoietic stem and progenitor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 123.
Abstract 1269: Evaluating the effect of metformin on components of extracellular matrix in colorectal cancer
Authors: Kaur Amar Preet , Bhattacharya Aditi , Bhat Muzaffer Ahmed , Bansal Aakriti , Sen Sudip 
Published: April 2023

Abstract
Introduction: Colorectal cancer (CRC) is the third most common cancer worldwide, and is associated with high morbidity and mortality. Approximately 50% of all CRC patients develop metastases. Tumor microenvironment (TME), including extracellular matrix (ECM), plays an important role in tumor progression and metastasis in CRC, indicating an important role of agents targeting ECM in the treatment of CRC. ECM acts as niche to support cancer cells. In this study, the role of metformin as a therapeutic agent in modulating ECM components of CRC has been studied.
Methods: HCT116 (aggressive, poorly differentiated) and HT 29 (less aggressive, moderately differentiated), human CRC cell lines were treated with different doses of metformin (0.1, 2.5 and 5 mM) for 14 days in vitro and subsequently microarray analysis was done to identify differentially expressed genes. To observe the role of metformin in modulating the ECM, ECM-receptor interaction pathway was given primary focus among the list of pathways identified by DAVID (Database for Annotation, Visualization and Integrated Discovery) bioinformatics resources. The seven differentially expressed genes of ECM-receptor interaction pathway (elucidated by microarray) were -COL3A1, COL4A2, COL5A2, VTN, ITGA6, TNXB and LAMC3. These genes were validated using RT-qPCR in both the cell lines. Protein expression was analyzed by Western blotting. Immunohistochemistry (IHC) was done in different histopathological grades of CRC samples to evaluate the expression and localization of ECM proteins.
Results: The gene expression of COL4A2, COL5A2, ITGA6, VTN and TNXB by RT-qPCR was decreased with metformin treatment and these results were consistent with microarray data. However, discrepancy was observed in the gene expression of COL3A1 and LAMC3 between microarray and RT-qPCR. Expression of COL3A1, VTN was found to be increased whereas a decrease in expression of ITGA6 was observed in different histopathological grades of CRC samples with IHC. The expression of PI3K and AKT proteins were decreased in HCT116 cells with metformin treatment justifying its anticancer properties.
Conclusions: Anticancer role of metformin via mTOR and PI3K-AKT signaling has been studied before, but this study identifies the novel ECM proteins in CRC that can be modulated by metformin. The results from this study indicates the promising role of metformin in CRC as it is associated with very less side effects and can influence various aspects of cancer biology.
Citation Format: Amar Preet Kaur, Aditi Bhattacharya, Muzaffer Ahmed Bhat, Aakriti Bansal, Sudip Sen. Evaluating the effect of metformin on components of extracellular matrix in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1269.
Abstract 1357: Alpha-synuclein may promote melanoma progression by modulating the levels of tetraspanin proteins
Authors: Aloy Nirjhar Mandal , Graner Michael W. , Witt Stephan N. 
Published: April 2023

Abstract
Alpha-synuclein (α-syn; encoded by gene SNCA), which is an intrinsically disordered protein belonging to the synuclein family, is a common biological factor in Parkinson’s disease and melanoma. Aggressive melanomas express high levels of α-syn, but the precise biological role of this protein in melanoma progression is not known. Our group has previously reported that α-syn promotes the release of extracellular vesicles (EVs) and regulates the trafficking of transferrin receptor in melanoma cells. During our studies of exosomal/EV markers, we found that CD81 and CD9, two key members of the tetraspanin family, were significantly downregulated in SK-MEL-28 SNCA-knock out clones compared to control cells. In contrast, a robust upregulation of CD63, another tetraspanin protein, was observed in SNCA-KO cells, which might be due to a compensatory mechanism for the downregulation of CD81 and CD9. CD81 and CD9 have been proposed as potential therapeutic targets, and CD63 was proposed as a positive prognostic marker in melanoma in numerous studies. Our group has previously shown that knocking out α-syn causes decreased tumor growth in vivo and in vitro. We hypothesize that α-syn regulates the levels of these tetraspanins, possibly by sorting into heterogeneous multivesicular bodies and modulating the exosomal secretion and lysosomal degradation of these proteins. This might be one of the principal mechanisms by which α-syn promotes progression of melanoma. We also have initial evidence from transmission electron microscopy (TEM) that depletion of α-syn causes the morphological alterations of plasma-membrane structure in melanoma cells, and it is known that CD9, CD81 and CD63 are important transmembrane proteins involved in membrane organization. This is the very first report of α-syn as a regulator of cellular homeostasis of CD9, CD81 and CD63, and further work is needed to understand the underlying mechanism.
Citation Format: Nirjhar Mandal Aloy, Michael W. Graner, Stephan N. Witt. Alpha-synuclein may promote melanoma progression by modulating the levels of tetraspanin proteins [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1357.
Abstract 143: A platform for deep evolutionary profiling of cancer resistance
Authors: Ravi Arvind , Sontha Sainikhil , Chowdhury Maisha , Smigiel Jacob , Rees Matthew , Danysh Brian , Roth Jennifer , Parida Laxmi , Lander Eric , Getz Gad 
Published: April 2023

Abstract
Despite the introduction of a number of new therapeutic classes including targeted inhibitors, immunotherapy, and antibody-drug conjugates, the ability to achieve long-term disease control in the majority of patients with advanced cancer remains elusive due to the emergence of resistance. While our understanding of resistance mechanisms continues to expand through preclinical and clinical sequencing efforts, comprehensive approaches to map the distribution of potential resistance mechanisms in a given cell line and drug context require the development of novel approaches.
Here, we describe the design of a platform for profiling cancer resistance at scale. Beginning with a single sensitive parental cancer cell line, the EGFR-mutant lung cancer line PC9, we optimize pre-existing diversity using a combination of single-cell subcloning and alkylator mutagenesis, and generate 50 independently evolved clones resistant to the EGFR inhibitor osimertinib. Profiling of this library via multiplexed whole genome sequencing (WGS) demonstrates convergent mutations in the MAPK pathway. Taking a similar approach, we profile the NTRK1-fusion-driven KM12 colon cancer cell line, yielding convergent, clinically observed, on-target resistance mutations to the NTRK inhibitor larotrectinib.
Taken together, these results provide an initial proof-of-concept for the high-throughput generation of viable drug-resistant cancer clones. Future efforts to increase mutational diversity as well as assess additional drug and disease contexts will broaden the utility of this approach.
Citation Format: Arvind Ravi, Sainikhil Sontha, Maisha Chowdhury, Jacob Smigiel, Matthew Rees, Brian Danysh, Jennifer Roth, Laxmi Parida, Eric Lander, Gad Getz. A platform for deep evolutionary profiling of cancer resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 143.
Abstract 1452: Big data analysis revealed signalling activity and key regulators in human prostate cancer cell lines
Authors: Cheng Siyuan , Li Lin , Yu Xiuping 
Published: April 2023

Abstract
Background: Human prostate cancer (PCa) cell lines are the most used models for research. The commonly used PCa cell lines can be roughly categorized into 3 groups: androgen receptor (AR)+, neuroendocrine (NE)+ and double negative (AR- NE-) cell lines. However, although these cell lines have been extensively used in PCa research since their establishment decades ago, a global molecular characterization of these cell lines is still lacking, especially in the aspect of cell signaling activity and their clinical relevance, which requires a large scale of data mining.
Methods: The RNA-seq, DNA-seq and proteomic datasets were gathered from public cohort and our lab’s collection. From these data, a PCa cell line multi-omics database (PCMD) was established. Single sample gene set enrichment analysis (ssGSEA) was used to reveal the signaling pathways enriched in each PCa cell line. Additionally, human PCa patient single cell RNAseq data-based deconvolution and human PCa patient bulk RNAseq data-based nearest-neighbor (NN) graph analysis were used to evaluate the clinical relevance of each PCa cell line. The DNA-seq, ATAC-seq, DNase HS-seq and Bisulfite-seq datasets were used to annotate the key genes.
Results: The PCMD database was established by compiling more than 1000 RNASeq datasets derived from various PCa cell lines. The important signaling pathways and transcription factors were revealed for each PCa cell line. Further, the cell lines were annotated with relative clinical stages. Additionally, an interactive webApp was established for scientists to explore and visualize PCMD data.
Conclusion: our research characterized PCa cell lines using unbiased strategies and large sample number. It is our hope that this study would aid researchers to develop hypothesis and choose appropriate cell line to use.
Funding: This study is supported by: Feist-Weiller Cancer Center, LSU Health Shreveport.
Citation Format: Siyuan Cheng, Lin Li, Xiuping Yu. Big data analysis revealed signalling activity and key regulators in human prostate cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1452.
Abstract 1918: Reducing human papillomavirus associated cancers and disparities among Hispanics/Latinos through the adapted NCI NON CHE (National Outreach Network Community Health Education) program
Authors: Ramos Alejandra , Aristizabal Carolina , Baezconde-Garbanati Lourdes 
Published: April 2023

Abstract
While HPV vaccination has dramatically reduced HPV-related cancer incidences in certain demographic groups, it continues to disproportionately affect Hispanics/Latinos. The NON CHE program at (USC), (NCCC), aims to understand the gaps in Human Papillomavirus (HPV) knowledge and vaccination uptake, cervical cancer screenings, and addresses the barriers to participating in clinical trials (CT) by conducting culturally-sensitive educational workshops to the community.
Methods: Materials such as a PowerPoint presentation and Human Papillomavirus Vaccination (HPV) infographics were adapted by the NCI to ensure the message can influence the target audience. Educational workshops were conducted via Zoom. Recruitment of participants were facilitated by partnering with community organizations across Los Angeles County (LAC) which is NCCC’s catchment area. The effectiveness of the workshops was assessed by delivery of pre and post surveys that captured demographics and a series of true and false questions that measured HPV knowledge. 3- and 6-month follow-up surveys are distributed among participants of those of age 18 - 26 and to parents of children 9 - 18 years of age to assess vaccination intake.
Results: A total of 1,515 people have been reached during educational workshops, health fairs, and outreach events from October 2021 to September 2022. Our results demonstrate that the 236 participants, (55.6%) Spanish-speaking and (26.9%) English-speaking had not heard of HPV indicating the sparse availability and accessibility of information contributing to parents’
unfamiliarity of the HPV vaccine (79.5%) between the two groups. However, there was a positive distribution of likely to get vaccine (72.88%) and likely to vaccinate their children (47.88%.) Their lack of awareness stemmed from lack of provider motivation (44.2%) and limited health education (39.5%.)
Conclusion: Conducting culturally tailored educational workshops to disseminate information on Human Papillomavirus (HPV) has helped Hispanics/Latinos understand what HPV is and reduce the stigma. Effective dissemination of HPV education requires it to be inclusive, concise, and engaging to motivate community members to seek preventive care.
Citation Format: Alejandra Ramos, Carolina Aristizabal, Lourdes Baezconde-Garbanati. Reducing human papillomavirus associated cancers and disparities among Hispanics/Latinos through the adapted NCI NON CHE (National Outreach Network Community Health Education) program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1918.
Abstract 1931: Racialized economic segregation and late-stage colorectal cancer in the United States, 2009-2017
Authors: Santiago-Rodriguez Eduardo J. , Shariff-Marco Salma , Bailey Zinzi D. , White Justin S. , Allen Isabel E. , Hiatt Robert A. 
Published: April 2023

Abstract
We examined the association between racialized economic segregation and late-stage colorectal cancer (CRC) in the US. All CRC cases diagnosed during 2009-2017 were identified using the United States Cancer Statistics database. Late-stage CRC was determined according to the presence of distant involvement (node or site) of the tumor at diagnosis. Racialized economic segregation was measured at the county level by the Index of Concentration at the Extremes (ICE) using the 2013-2017 American Community Survey estimates. ICE was calculated to show the extent to which individuals’ residence at diagnosis was located in counties of concentrated advantage or disadvantage. Four ICE metrics were considered, consisting of the difference between the number of households with White individuals reporting incomes in the top quintile of the US distribution, and the number of households with non-White (all people of color (POC), Black, Latino, or Asian American/Pacific Islander) individuals reporting incomes in the lowest quintile, divided by the total of households in the county. ICE metrics were further divided into quintiles based on the distribution of all counties in the US, with Q1 denoting least advantaged counties and Q5 the most advantaged counties. Multilevel logistic regression models accounting for clustering at counties were fit. Models were adjusted for age at diagnosis, sex, race and ethnicity, census region and year of diagnosis. A total of 1,356,053 cases were included in the analysis; mean age at diagnosis was 67 years, 52% were men, and 20% of cases had a late-stage diagnosis. In adjusted analysis for ICE-POC, people residing in less advantaged counties had higher odds of late-stage diagnosis than people residing in the most advantaged counties (OR [95% CI], Q1: 1.08 [1.05-1.11], Q2: 1.06 [1.04-1.09], Q3: 1.04 [1.02-1.07], Q4: 1.03 [1.01-1.05], Q5: reference). Similar results were observed on all four ICE metrics. Racialized economic segregation was associated with higher odds of late-stage CRC. These findings underscore the role of institutionalized racism as a driver of health inequities, with laws and policies that led to residential segregation also impacting the conditions for timely preventive care.
Citation Format: Eduardo J. Santiago-Rodriguez, Salma Shariff-Marco, Zinzi D. Bailey, Justin S. White, Isabel E. Allen, Robert A. Hiatt. Racialized economic segregation and late-stage colorectal cancer in the United States, 2009-2017 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1931.
Abstract 1934: Incidence and survival outcomes of younger adults with colorectal cancers by age group: a SEER analysis
Authors: Aqeel Sheeba Ba , Groman Adrienne , Attwood Kristopher , Iyer Renuka , Mukherjee Sarabjit , Vadehra Deepak 
Published: April 2023

Abstract
Background: The incidence of colorectal cancer (CRC) is increasing in younger adults (&lt;50 years). Most cases occur between 40 and 49 years. Adolescents and young adults (AYA,15-39 years) with CRC have more aggressive disease. We sought to compare the incidence and outcomes of CRC in AYA with patients in the 40-49 age group.
Methods: Surveillance, Epidemiology, and End Result (SEER) was analyzed from 2000-2019. Survival outcomes were analyzed using Kaplan-Meier methods, and comparisons were made using the log-rank test. Cox regression models were used to evaluate univariate and multivariate associations with survival outcomes. SAS v9.4 (Cary, NC) and SEER*Stat v8.4 were used, with a significance level of 0.05.Results: A total of 13,877 AYA patients and 43,771 patients in the age group 40-49 years were identified. The annual incidence rate per 100,000 AYA patients increased from 3.1 in 2000 to 5.3 in 2019. In the 40-49 cohort, the annual incidence rate per 100,000 increased from 21.6 in 2000 to 28.0 in 2019. The annual percent change for incidence for the AYA cohort was higher 3.1% (95% CI 2.8,3.4) than the 40-49 cohort 1.4% (95% CI 1.2,1.6). The 2-year overall survival (OS) rate was not different among the two groups. Disease-specific survival (DSS) was slightly but significantly inferior in the AYA group, 83% (95%CI 0.82,0.83) compared to in the 40-49 cohort, 84% (95%CI 0.83,0.84). Factors associated with inferior DSS in the AYA group were male sex, black race, advanced stage, lack of chemotherapy, and longer time to treatment.
Conclusion: Our study shows that the annual percent change in incidence rate was higher in AYA patients compared to those in the 40-49 age group from 2000-2019. DSS was slightly lower in AYA patients; OS was similar in both groups. Further studies are needed to understand the discrepancies.
Table 1: Baseline characteristics of AYA and 40-49yr patients AYA 13877(24.1%) 40-49yr 43771(75.9%) Overall 57648(100%) P value Age at diagnosis Mean/Standard deviation 34/4.6 45.5/2.8 42.7/5.9 &lt;0.001 Gender Male 51.9% 53.6% 53.2% &lt;0.001 Race Non-Hispanic White 54.2% 59.4% 58.2% &lt;0.001 Non-Hispanic Black 12.1% 13.3% 13% Asian or Pacific Islander 33% 26.7% 28.2% Unknown 0.6% 0.6% 0.6% Stage Localized 22.2% 26.5% 25.5% &lt;0.001 Regional 31.6% 30.2% 30.6% Distant 20% 19.2% 19.4% Unstaged 1.8% 1.7% 1.7% Blank 24.4% 22.3% 22.8% Chemotherapy No/Unknown 33.8% 39.4% 38.1% &lt;0.001
Citation Format: Sheeba Ba Aqeel, Adrienne Groman, Kristopher Attwood, Renuka Iyer, Sarabjit Mukherjee, Deepak Vadehra. Incidence and survival outcomes of younger adults with colorectal cancers by age group: a SEER analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1934.