bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2229: Targeted locus amplification based sequencing for mapping viral integration sites in human papillomavirus positive head and neck squamous cell carcinomas
Authors: Demers Imke , Balaji Harini , Feitsma Harma , Sergeeva Irinia , Swennenhuis Joost , Wuerdemann Nora , Wagner Steffen , Kremer Bernd , Huebbers Christian , Klussmann Jens Peter , Speel Ernst-Jan 
Published: June 2022

Abstract
Background: Human papillomavirus (HPV) infections are the principal cause of cervical cancers, subsets of anogenital and head and neck cancers (HNC). During persistent infection, viral DNA integration into the host genome may occur, which is suggested to affect carcinogenesis. One of the most critical limitations of currently used HPV integration detection techniques (PCR-based or NGS-based) is their application to FFPE material, because of DNA fragmentation. The aim of this study was to assess HPV integration in HPV-positive HNSCC cell lines and FFPE tissue comparing the new Targeted Locus Amplification (TLA) technology with previously used PCR technology (APOT/DIPS).
Methods: Seven HPV-positive cell lines and FFPE material of 10 HPV-positive HNSCC were used for HPV integration detection by TLA, a proximity ligation-based next-generation sequencing technique. Crosslinked DNA is digested with restriction enzymes, and re-ligated into chimeric DNA molecules. For cell lines, a PCR based HPV16 target enrichment is performed, and for FFPE material a capture-based target enrichment is performed for HPV16 and HPV18 sequences, both followed by Illumina sequencing.
Results: TLA was able to sequence up to 100 kb around the target, detecting exact HPV integration loci, structural variants, and chromosomal rearrangements. In all cell lines, one or more integration sites were identified, in accordance with APOT/DIPS PCR data and the literature. In the FFPE tissue samples, TLA identified integrated HPV in 6 out of 10 tumors, with simple and complex integration patterns. In general, TLA confirmed PCR data and detected additional integration sites.
Conclusion: TLA provides the opportunity for reliable and robust detection of HPV integration in HNSCC cell lines and FFPE tissue. This new sequencing technology could be a useful tool for further research on HPV integration in disease and patient outcome and eventually in clinical diagnostics.
Citation Format: Imke Demers, Harini Balaji, Harma Feitsma, Irinia Sergeeva, Joost Swennenhuis, Nora Wuerdemann, Steffen Wagner, Bernd Kremer, Christian Huebbers, Jens Peter Klussmann, Ernst-Jan Speel. Targeted locus amplification based sequencing for mapping viral integration sites in human papillomavirus positive head and neck squamous cell carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2229.
Abstract 2235: Identifying populations at elevated risk of cancer outside those traditionally targeted for screening and prevention
Authors: Patel Alpa V. , Deubler Emily , Teras Lauren R. , Colditz Graham A. , Lichtman Cari J. , Cance William G. , Clarke Christina A. 
Published: June 2022

Abstract
Introduction: Currently, populations are identified for cancer screening interventions one cancer type at a time. With new developments in cancer screening, including multi-cancer early detection tests, it is important and timely to understand the overall cancer burden in populations outside those traditionally targeted for single-cancer screenings. Thus, we sought to identify the most important risk factors for developing any invasive cancer, and to calculate associated 5-year absolute risks, with a particular focus on persons under age 50 years.
Methods: Two large American Cancer Society cohorts followed prospectively for cancer, the Cancer Prevention Study-II Nutrition Cohort (CPS-IINC) enrolled from 1992-1993 and Cancer Prevention Study 3 (CPS-3) enrolled from 2006-2013, were used to examine a broad range of cancer risk factors. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for associations between potential risk factors and subsequent overall risk of any invasive cancer. The Individualized Coherent Absolute Risk Estimation tool used these HRs to estimate absolute risk in 5-year age groups.
Results: 15,226 cancers were identified among 429,991 participants within 5 years of follow-up. Several risk factors including smoking history, obesity, alcohol, family history of cancer, and various chronic medical conditions (e.g., diabetes, hypertension) were associated with a higher risk of cancer. Persons above age 50 years, regardless of other risk factors considered, had at least 2% absolute risk per 5 years. Among persons under age 50 years, smoking status was the most important factor differentiating risk. For men under age 50, absolute risk of any cancer did not exceed 2% except for men ages 45-49 years who currently smoke or recently quit (within 30 years). For women under age 50, absolute risk exceeded 2% starting at age 35-39 years for current or recent former smokers, and all women, even long-term nonsmokers, at age 45-49 had over 2% absolute risk.
Conclusions: Smoking history is important in differentiating absolute risk of any cancer in adults under age 50 years. More research to understand the extent to which other cancer risk factors influence risk for specific populations aged &lt;50 years should be carried out.
Citation Format: Alpa V. Patel, Emily Deubler, Lauren R. Teras, Graham A. Colditz, Cari J. Lichtman, William G. Cance, Christina A. Clarke. Identifying populations at elevated risk of cancer outside those traditionally targeted for screening and prevention [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2235.
Abstract 2262: Associations of plasma carotenes with lung cancer risk in a low-income population in the southeastern united states
Authors: Sun Yan , Wu Jie , Yoon Hyung-Suk , Zheng Wei , Cai Hui , Buchowski Maciej S. , Franke Adrian A. , Blot William J. , Shu Xiao-ou , Cai Qiuyin 
Published: June 2022

Abstract
Lung cancer is the second most common cancer and the leading cause of death from cancer in the U.S. Carotenes, with the properties of antioxidation and immunoregulation, have been demonstrated to have anti-carcinogenic effects. Previous prospective studies showed inverse associations of circulating α-carotene and β-carotene with lung cancer risk among European descendants and Asians. The associations of α-carotene and β-carotene isomers with lung cancer risk have not been investigated, particularly among African Americans (AAs) and low-income populations. We conducted a case-control study including 225 incident lung cancer cases and 429 controls, individually matched on age, race, and sex, nested in the Southern Community Cohort Study, including ~86,000 participants, two-thirds of whom are AAs. Carotene plasma concentrations were determined by a validated assay using high-pressure liquid chromatography with photo-diode array detection. Plasma trans-β-carotene (ORT3 VS. T1=0.54; 95% CI: 0.32-0.90; Ptrend=0.03), cis-β-carotene (ORT3 VS. T1=0.55; 95% CI: 0.32-0.93; Ptrend=0.03), and total β-carotene (ORT3 VS. T1=0.50; 95% CI: 0.30-0.84; Ptrend=0.01) were inversely associated with lung cancer risk. The associations remained significant after excluding cases diagnosed within the first year of follow-up. The inverse associations of plasma cis-β-carotene and total β-carotene with lung cancer risk were only observed among AAs and males. Plasma trans-α-carotene, trans-β-carotene, cis-β-carotene, and total β-carotene were inversely associated with lung cancer risk among those with lower body mass index (&lt;median). In summary, plasma levels of β-carotenes were inversely associated with lung cancer risk in AA and low-income populations. Further studies with a larger sample size are warranted to confirm our findings.
Citation Format: Yan Sun, Jie Wu, Hyung-Suk Yoon, Wei Zheng, Hui Cai, Maciej S. Buchowski, Adrian A. Franke, William J. Blot, Xiao-ou Shu, Qiuyin Cai. Associations of plasma carotenes with lung cancer risk in a low-income population in the southeastern united states [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2262.
Abstract 2274: Identification of predisposition and progression gastric cancer biomarkers in Latinos
Authors: Estrada-Florez Ana Patricia , Lott Paul , Toal Ted , Halmai Nicole , Quino Elizabeth , Poceros-Coba Alma , Guevara Alix , Castro Fabian , Suarez Jhon , Mcpherson John , Venkatesh Rasika , Zhang Hongyong , Vang Apri , Polanco Guadalupe , Guerra Joana , Molina Graciela , Parra Carol , Valle Adriana Della , Castelao Esteban , Teixeira Manuel , Bohorquez Mabel , Torres Javier , Corvalan Alejandro Carvajal , Carvajal-Carmona Luis G. 
Published: June 2022

Abstract
Gastric cancer (GC) disproportionally affects people of Latino ancestry and represent a leading cause of incidence and mortality disparities in this minority populations. When compared to Non-Latino Whites, Latinos are ~2-fold more likely to be diagnosed with and to die of GC. The goal of our research program is to contribute to GC research in patients of Latino ancestry and advance cancer health disparity research. One of the research projects aims at identifying germline variants associated with GC risk. To do so, we are identifying novel gastric cancer genes and detecting mutations in previously reported GC genes, using whole-exome sequencing, in 500 patients who have been diagnosed with early-onset GC and/or who had GC and family history of cancer. Whole exome sequence data collection was recently completed and is being analyzed with the primary goals of estimating the prevalence and penetrance in known cancer genes as well as the identification of new GC genes. Using in-house exome data and publicly available genetic data, we will identify variants with predicted impact in the phenotype to design a panel that will be used for their detection in gastric preneoplasia biopsies. These variants will be tested using duplex sequencing, a highly sensitive method that can detect very rare mutations with ultra-depth sequencing. We will then select the variants with likely functional consequences for tumor initiation and/or progression to generate isogenic gastric organoids to investigate their effect in proliferation, differentiation, and gene expression. We aim to generate a body of work that can be used for risk assessment, prevention, early diagnostic, and that will lead to better outcomes for GC in this important U.S. minority. Dr. Ana Estrada-Florez is the recipient of the AACR Cancer Health Disparities Fellowship.
Citation Format: Ana Patricia Estrada-Florez, Paul Lott, Ted Toal, Nicole Halmai, Elizabeth Quino, Alma Poceros-Coba, Alix Guevara, Fabian Castro, Jhon Suarez, John Mcpherson, Rasika Venkatesh, Hongyong Zhang, Apri Vang, Guadalupe Polanco, Joana Guerra, Graciela Molina, Carol Parra, Adriana Della Valle, Esteban Castelao, Manuel Teixeira, Mabel Bohorquez, Javier Torres, Alejandro Carvajal Corvalan, Luis G. Carvajal-Carmona. Identification of predisposition and progression gastric cancer biomarkers in Latinos [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2274.
Abstract 2282: Efficient sample preparation with Covaris AFA® technology enhances confidence in Illumina® TruSight™Oncology 500 Assay
Authors: Bhattacharyya Debadeep , Pal Kasturi , Daviso Eugenio , Thomann Ulrich 
Published: June 2022

Abstract
High throughput and robust DNA fragmentation is a critical step in Next Generation Sequencing (NGS) for clinical genomics, ultimately ensuring higher quality for the final sequencing data. The typical requirements in NGS workflow (nucleic acid fragmentation, library preparation, sequencing, etc) comprise scalability, efficiency, reliability, and robustness. Failures to achieve confidence in any of the steps can negatively impact sequence data, rendering them unusable for diagnosis. Covaris’ Adaptive Focused Acoustics® (AFA®) technology enables efficient DNA fragmentation regardless of DNA concentration and starting molecular weight, ensuring a tight fragment size distribution, minimal sample loss, and most importantly, desired reliability and reproducibility.Illumina®’s TruSight™ Oncology 500 (TSO 500) protocol describes an enrichment-based approach to convert DNA and RNA extracted from formalin-fixed paraffin embedded (FFPE) tissue samples into libraries enriched for cancer-related genes that can be sequenced on Illumina® sequencing systems. The TSO 500 assay is optimized to prepare libraries from genomic DNA (gDNA) that is sheared to optimized fragment sizes and offers high fidelity determination of DNA variants across 523 cancer relevant genes. The TSO 500 assay is the assay of choice across most cancer centers using a standardized pipeline and therefore is suitable for routine use in precision oncology as a comprehensive genomic profiling solution. This study focuses on demonstrating the optimized DNA fragmentation protocol for TSO 500 assay with parallel 8-sample processing with an ML230 Focused-ultrasonicator.
Citation Format: Debadeep Bhattacharyya, Kasturi Pal, Eugenio Daviso, Ulrich Thomann. Efficient sample preparation with Covaris AFA® technology enhances confidence in Illumina® TruSight™Oncology 500 Assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2282.
Abstract 2307: Sequential treatment with abemaciclib plus endocrine therapy inhibits cell proliferation and triggers apoptosis in cell lines resistant to CDK4/6i
Authors: Zapatero-Solana Elisabet , Ganado Maria P. , Ortiz-Ruiz Maria J. , Mur Cecilia , Litchfield Lacey , Merzoug Farhana , Puig Oscar , Lallena Maria Jsoe 
Published: June 2022

Abstract
CDK4/6 inhibitors combined with endocrine therapy (ET) have shown clinical benefit in HR+, HER2- breast cancer. However, development of resistance highlights the need for treatment strategies to improve outcomes. To study resistance mechanisms, breast cancer cell lines were treated with CDK4/6i (abemaciclib or palbociclib) in combination with 4-OH-tamoxifen (tamoxifen) for 120-144h and sorted for resistant cells defined as geminin positive (GEM+), a marker of S/G2/M cell cycle accumulation. To confirm the resistant phenotype, cell lines were treated with tamoxifen plus the CDK4/6 inhibitor used to drive resistance. To understand if sequential CDK4/6i treatment is effective in controlling cell proliferation, resistant cells generated through treatment with palbociclib + tamoxifen or abemaciclib + tamoxifen were treated with abemaciclib + ET (fulvestrant or tamoxifen) or palbociclib + ET, respectively. Geminin/Ki67, annexin V and colony formation assays were performed to evaluate cell proliferation and viability. Molecular characterization by western blot and RNAseq analysis were utilized to provide insights into mechanisms of resistance and the effects of sequential treatment with CDK4/6i + ET. Cell lines resistant to palbociclib + tamoxifen subsequently treated with abemaciclib + ET showed decreased %GEM+ and colony formation ability, decreased Ki67 levels, and increased apoptosis. These effects were not observed in cell lines resistant to abemaciclib + tamoxifen following subsequent treatment with palbociclib + ET. Western blot analysis showed that palbociclib and abemaciclib-resistant cells had increased CDK6 and pERK levels, compared to control. Importantly, treatment of palbociclib-resistant cells with abemaciclib + ET decreased FOXM1, a key regulator of senescence and apoptosis. Cyclin A, a marker of mitosis, was also decreased, consistent with decreased %GEM+ subpopulation in palbociclib + ET resistant cells. These effects were not observed in abemaciclib-resistant cells treated with palbociclib + ET.In summary, our in vitro data provides mechanistic insights into resistance to combination CDK4/6i + tamoxifen and suggests the potential benefit of sequential treatment with abemaciclib + ET to overcome resistance in breast cancer.
Citation Format: Elisabet Zapatero-Solana, Maria P. Ganado, Maria J. Ortiz-Ruiz, Cecilia Mur, Lacey Litchfield, Farhana Merzoug, Oscar Puig, Maria Jsoe Lallena. Sequential treatment with abemaciclib plus endocrine therapy inhibits cell proliferation and triggers apoptosis in cell lines resistant to CDK4/6i [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2307.
Abstract 2312: Efficacy of targeted osmotic lysis is increased by cell cycle inhibition in M Phase
Authors: Edenfield Samantha , Gould Harry J. , Paul Dennis 
Published: June 2022

Abstract
Voltage-gated sodium channels (VGSCs) are upregulated in aggressive carcinomas, making these channels a target for novel clinical therapies. Targeted Osmotic Lysis (TOL) is a novel cancer therapy that combines pharmacologically blocking Na+,K+, ATPase (sodium pumps) while stimulating VGSCs with a pulsed electric field. The consequent increase in intracellular Na+ causes an osmotic lysis of the cells that overexpress VGSCs. Noncancerous cells, with fewer VGSCs do not lyse. We hypothesized that variability in efficacy of TOL is due to VGSC expression that varies across the cell cycle. We assessed cell surface expression of VGSCs and Na+,K+-ATPase during phases of the cell cycle in which there are single copies of DNA compared with phases in which DNA has doubled. For this, DNA was labeled with either propidium iodide or DAPI and VGSCs were labeled with a pan-specific VGSC antibody while Na+,K+-ATPases were labelled with a pan-specific Na+,K+-ATPase antibody in eight immortalized cancer and non-cancer cell lines. With flow cytometry we showed that VGSC expression doubled during phases of cell division (S-M phases) while Na+,K+-ATPase expression increased by 1.5-fold. To further elucidate the role of VGSCs and Na+,K+-ATPases throughout the cell cycle, S-Trityl-L-cysteine (STLC) was used to suspend the cell cycle in M phase. We hypothesized that treating cancer cells with TOL in the S-M phases would lead to increased cell death, compared to cells that were not suspended in M phase by STLC (G0-G1 phases). Cells were either treated with STLC or media without drug for 24 hours, then exposed to TOL treatment. The efficacy of the treatment was measured using a MTT assay revealing that cell death was greater in STLC-treated cells than control cells. By using cell cycle inhibitors, we may increase the efficacy of TOL for treating advanced carcinomas that overexpress VGSCs.
Citation Format: Samantha Edenfield, Harry J. Gould, Dennis Paul. Efficacy of targeted osmotic lysis is increased by cell cycle inhibition in M Phase [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2312.
Abstract 2334: Inhibition of DHFR modulates anti-tumor immunity
Authors: Boese Austin , Young Isabelle , Kang Jihoon , Malin Courteney , Hwang Jung Seok , Kang Sumin 
Published: June 2022

Abstract
Lung cancer is the second most common type of cancer in both men and women and has the highest mortality rate. Non-small cell lung cancer (NSCLC) makes up most cases. Immune checkpoint inhibitors have significantly improved the clinical management of some NSCLC cases, yet many lung cancer patients still fail to respond to conventional immunotherapy. Therefore, more research is needed to characterize cellular pathways contribute to immune checkpoint inhibitor (ICI) resistance in NSCLC patients. Dysregulated cellular metabolism is a common feature of many cancer types, and metabolites are now known to modulate several functions inside cells such as signaling pathways and epigenetic control of gene expression. Therefore, targeting tumor metabolism may be able to combat NSCLC immunotherapy resistance. To identify potential metabolic pathways involved in the anti-tumor immune response, we employed a metabolic inhibitor-based drug screen in human NSCLC cell lines and tested for expression changes in a panel of known immune regulator genes. Notably, pharmacologic inhibition of dihydrofolate reductase (DHFR) downregulated the mRNA expression of anti-phagocytic surface protein cluster of differentiation 24 (CD24) in lung cancer cells. In line with this, shRNA knockdown and overexpression of DHFR, decreased and increased CD24 RNA and protein levels, respectively. These results show that the metabolic enzyme DHFR is involved in CD24 gene expression. Cancer cells heavily rely on DHFR for enhanced nucleotide biosynthesis to facilitate rapid tumor growth, and DHFR inhibitors are already used in the clinic for cancer therapy. This study highlights a novel interaction between reprogrammed cancer metabolism and the anti-tumor immune response, with possible clinical implications for DHFR inhibitors such as methotrexate in combination with conventional cancer immunotherapy agents.
Citation Format: Austin Boese, Isabelle Young, Jihoon Kang, Courteney Malin, Jung Seok Hwang, Sumin Kang. Inhibition of DHFR modulates anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2334.