bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 6078: Circulating tumor cell-based early detection of breast cancer
Authors: Drake Justin M. , Kamalanathan Kaylee J. , Galeano-Garces Catalina , Bristow Nathaniel , Heller Nicholas , Ahmadi Mahdi , Hedeen Olivia , Hesch Alexa , Schaap Grant , Hapke Joel , Miller Jeff , Babris Ivo , Le Tuan , Clacko Tony , Hong Jiarong , Konety Badri , Parthasarathy Jayant 
Published: March 2024

Abstract
Although mammograms have been a useful tool since the first half of the 20th century and have an acceptable sensitivity (87%) in the general population, that drops to &lt;50% in women with dense breasts making it an ineffective screening tool in this population. Cell free DNA (cfDNA) has proven to be an inadequate alternative in this population, and while MRI is acceptable, it is expensive. Astrin Biosciences has developed a blood-based assay that detects circulating tumor cells (CTCs) at a high sensitivity to serve as an alternative screening method to mammography in breast cancer early detection, specifically in women with high-density breasts.
Astrin’s technology integrates holographic imaging, machine learning, and microfluidics to identify CTCs in the blood stream. Omics analysis can then be performed on the collected cells to further differentiate patients with cancer from matched healthy controls. Astrin has initiated a small cohort study to investigate the sensitivity and specificity of CTC detection in women with early-stage breast cancer. Astrin’s small cohort study, including patients with ductal carcinoma in situ, stage 1, and stage 2 breast cancer patients, demonstrated &gt; 85% sensitivity and specificity. A large cohort study is being conducted to validate these preliminary results.
The small cohort study demonstrates the ability of Astrin Bioscience’s platform to detect cancer cells at an early stage, particularly in breast cancer. This technology will drastically increase the effectiveness of breast cancer screening modalities available to patients. Additionally, since it is a blood-based assay, it can be performed at shorter intervals in high-risk populations than mammograms which require a full patient appointment.
Citation Format: Justin M. Drake, Kaylee J. Kamalanathan, Catalina Galeano-Garces, Nathaniel Bristow, Nicholas Heller, Mahdi Ahmadi, Olivia Hedeen, Alexa Hesch, Grant Schaap, Joel Hapke, Jeff Miller, Ivo Babris, Tuan Le, Tony Clacko, Jiarong Hong, Badri Konety, Jayant Parthasarathy. Circulating tumor cell-based early detection of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6078.
Abstract 6085: Leveraging targeted epigenetic and genetic detection for cost-effective cancer classification
Authors: Crawford Robert , Krajacich Ben , Lleshi Ermira , Negrea Aurel , Andreasen Lisabet , Fullgrabe Jens , Monahan Jack , Morley David , Puddu Fabio , Walker Donna McDade , Kruglyak Semyon , Creed Páidí 
Published: March 2024

Abstract
The combinatorial power of genetics and epigenetics is vital to understanding biology in healthy and cancerous states. Utilizing a recent novel approach, we enable the simultaneous identification of modified cytosine and the canonical bases A, C, T & G in an enzymatic single-workflow solution. Generating this information across the whole genome provides a much-improved understanding of genetic and epigenetic changes, but can require a large amount of sequencing, particularly when exploring at depth. Enrichment protocols such as target enrichment enable deep interrogation of target areas whilst maintaining cost effectiveness.
Target enrichment panels enable the selective isolation of sequences of interest through target hybridization. Using commercially available panels combined with the novel enzymatic single-workflow solution we show uniform performance across a range of input amounts with reduced sequencing requirements. Samples used were cell free DNA (cfDNA) from patient samples with either Stage I or IV Colorectal Cancer and reportedly healthy controls and were targeted using pan-cancer and methylome panels. Widespread differences such as hypermethylation are clearly observed in late-stage cancer vs early-stage or healthy controls demonstrating utility of the approach for applications such as liquid biopsy.
Refining genetic and epigenetic investigations to a narrower region of interest can improve detection of low prevalence disease associated biomarkers at significant sequencing depth and lower sequencing costs.
Citation Format: Robert Crawford, Ben Krajacich, Ermira Lleshi, Aurel Negrea, Lisabet Andreasen, Jens Fullgrabe, Jack Monahan, David Morley, Fabio Puddu, Donna McDade Walker, Semyon Kruglyak, Páidí Creed. Leveraging targeted epigenetic and genetic detection for cost-effective cancer classification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6085.
Abstract 6131: Increasing self efficacy, self confidence, and genetic knowledge via the Community Genetic Navigation Engagement Specialist Train-the-Trainer program
Authors: Rodriguez Janet , Mendez Joel Sanchez , Rodriguez Yaneth L. , Baezconde-Garbanati Lourdes , Ricker Charité , Barahona Rosa , Rosales Bianca , Hernandez Daisy , Gutierrez Natalia , Culver Julie , Stern Mariana 
Published: March 2024

Abstract
Background: Colorectal cancer (CRC) is the second and third leading cause of cancer deaths in US Hispanic/Latino (H/L) men and women, respectively. The Community Genetic Navigation Specialists (CoGENES) train-the-trainer program created a workforce of community health workers (CHWs) to educate H/L individuals about genetic testing, counseling, and research.
Methods: The CoGENES three-week program, consisted of six in-person sessions, with a curriculum in both Spanish/English developed and delivered by experts, in Spanish, using presentations and hands-on activities. Acculturation, Latino values, self-efficacy, genetics and tumor testing knowledge, and self-confidence were assessed via pre- and post-training. Differences in scores were analyzed via Wilcoxon matched-pairs signed-rank tests with exact p-values.
Results: Median age of the 12 participants was 50 (IQR = 12), 9 were female, 92% were Mexican-born, half completed 1-2 years of college, and 67% were very hispanic oriented. Self-efficacy increased after training, with pre- training median-score = 38.5 (IQR = 3) and post-training score = 39.5 (IQR =2.5) (p = 0.0547). Certainty about understanding tumor testing increased after training (p = 0.0039). The median number of correct answers on the 16-item genetic knowledge scale increased from 6.5 to 9.5 and the median number of “don’t know” responses decreased from 5 to 0 after training. Finally, self-confidence to train future CoGENES was significantly higher (p = 0.0098) at post-test.
Conclusion: The CoGENES culturally tailored program led to improved self-efficacy, increased genetic knowledge, and self-confidence in a cohort of Hispanic community health educators. Findings will be shared within COPECC, and other NCI funded programs.
Citation Format: Janet Rodriguez, Joel Sanchez Mendez, Yaneth L. Rodriguez, Lourdes Baezconde-Garbanati, Charité Ricker, Rosa Barahona, Bianca Rosales, Daisy Hernandez, Natalia Gutierrez, Julie Culver, Mariana Stern. Increasing self efficacy, self confidence, and genetic knowledge via the Community Genetic Navigation Engagement Specialist Train-the-Trainer program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6131.
Abstract 6168: Sex-distinct patterns of molecular pathways associated with brain tumor edema
Authors: Jackson Pamela R. , Curtin Lee , Ranjbar Sara , Singleton Kyle W. , Mrugala Maciej M. , Zimmerman Richard S. , Bendok Bernard R. , Canoll Peter , Swanson Kristin R. 
Published: March 2024

Abstract
Magnetic resonance imaging (MRI) is a centerpiece of clinical management of brain tumor patients, yet the biology underlying even commonly interpreted imaging changes is unclear. The purpose of this project was to understand what biology is associated with brain tumor edema abundance and if that association was sex distinct. We have developed a two-compartment model of MRI signal intensity to quantitatively estimate relative edema abundance from T2-weighted MRIs. Multiparametric MRIs were preprocessed with bias field correction and intensity normalization. The images were co-registered and segmented for abnormal regions and normal tissue. The segmentations and preprocessed images were utilized in the edema mathematical model to estimate the fraction of extracellular space (Fecs) and fraction of intracellular space (Fics). Through an ongoing image-localized biopsy collection protocol, we analyzed 179 samples (Female: 75; Male: 104) from 55 patients (Female: 21; Male: 34) for bulk RNA-Seq. Samples were characterized by their edema Fecs scores and underwent differential expression, gene set enrichment analysis using MSigDB hallmarks and cellular deconvolution using CIBERSORTx. Through differential expression and gene set enrichment analyses of these spatial biopsies, we have identified sex-distinct gene expression and pathways corresponding to regions of high vs low edema. Within highly edematous regions, male samples were amplified for respiratory pathways, while female samples were suppressed. Connecting changes on MRIs with molecular markers from image-localized biopsies provides an opportunity to identify the biological drivers of brain tumor associated imageable edema. Specifically, elucidating the sex-distinct patterns connecting changes on MRI with cellular populations and molecular pathways could be used to better interpret imaging of patients and interpreting treatment response.
Citation Format: Pamela R. Jackson, Lee Curtin, Sara Ranjbar, Kyle W. Singleton, Maciej M. Mrugala, Richard S. Zimmerman, Bernard R. Bendok, Peter Canoll, Kristin R. Swanson. Sex-distinct patterns of molecular pathways associated with brain tumor edema [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6168.
Abstract 625: Remodeling of the tumor microenvironment in esophageal squamous cell carcinoma by neoadjuvant immunochemotherapy and its impact on therapeutic efficacy
Authors: Aizemaiti Rusidanmu , Zhang Huifang , Zhu Changbin , Zhou Kun , Hu Tao , Lin Shuang , Teng Xiao , Wang Jin , Li Xing , Ye Peng 
Published: March 2024

Abstract
Background: Patients with local advanced esophageal squamous cell carcinoma (ESCC) benefited from neoadjuvant immunochemotherapy (NAI) with 22%-55% of complete pathological responses (pCR). While unpredicted therapeutic resistance hampered prognosis of these patients. Thus, this study aimed to investigate tumor microenvironment (TME) remodeling pre- and post-NAI identifying predictive biomarkers and potential targets for patients with resistance to NAI.
Methods: 65 patients with locally advanced ESCC, who were treated with neoadjuvant anti-PD-1 antibody and platinum-based chemotherapy at the First Affiliated Hospital of Zhejiang University School of Medicine between November 2019 and June 2020, were included in this study. Genomic DNA and RNA from paired pre-and post-treatment FFPE samples were harvested and subjected to targeted DNA and RNA sequencing. Pre- and post- therapeutic microenvironment and immune cell infiltration were dynamically assessed based on RNA sequencing data.
Results: 37 of 65 patients responded to NAI(TRG0-1), while 28 of 65 patients displayed unfavored response (TRG2-3). Comparative analysis of TME characteristics before and after NAI revealed that, in the TRG2-3 group, LRRC15+ CAFs, and fibroblasts were significantly upregulated, while CD4 T cells and endothelium cells exhibited downregulation. Especially, TIGIT tended to be upregulated after NAI in the TRG 2-3 group. In the TRG0-1 group, significant upregulation of activated B cells, T-cells, myeloid dendritic cells, together with notable downregulations of immune suppressive features like Type 2 T helper cells, Tregs and LRRC15+ CAFs were observed in post-treatment samples.
Conclusions: Our study indicates the dynamic remodeling of TME during-NAI treatment might influence therapeutic efficacy and disclose potentially targetable resistant mechanisms. These preliminary findings pave the way for further validation through prospective clinical studies.
Citation Format: Rusidanmu Aizemaiti, Huifang Zhang, Changbin Zhu, Kun Zhou, Tao Hu, Shuang Lin, Xiao Teng, Jin Wang, Xing Li, Peng Ye. Remodeling of the tumor microenvironment in esophageal squamous cell carcinoma by neoadjuvant immunochemotherapy and its impact on therapeutic efficacy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 625.
Abstract 6250: The RNA editing landscape of lung cancer in never smokers
Authors: Sang Jian , Zhao Wei , Zhang Tongwu , Landi Maria Teresa 
Published: March 2024

Abstract
Adenosine-to-Inosine (A-to-I) editing represents a crucial RNA modification mechanism, holding the potential to drive carcinogenesis. This sophisticated post-transcriptional process is catalyzed by a series of ADAR (adenosine deaminase acting on RNA) family members, which can profoundly reshape the cellular epitranscriptomic landscape. While previous explorations have illuminated the important role of A-to-I editing in lung cancer tumorigenesis and prognosis, most studies have focused on lung cancer from smokers. To investigate the contribution on RNA-editing in lung cancers in never smokers (LCINS) , we embarked on a rigorous dissection of A-to-I RNA editing events in 603 LCINS. Harnessing transcriptome and whole-genome sequencing technologies, we identified 15,880 A-to-I sites, of which 75% were positively linked to the enzymatic activity of ADAR1. 92.80% of detected editing sites were located at Alu repetitive regions, with the remainder in non_Alu repeat (4.1%) and non-repeat regions (3.1%). The global RNA editing levels, measured as Alu Editing Index (AEI), were found to be significantly associated with ADAR1 expression, Tumor Mutational Burden, and Neoantigens Burden. A subtle correlation between global RNA editing levels and tumor stage was also noted. Delving into cancer-associated editing events, we identified 5,539 differentially edited sites in tumors compared with normal tissues, which were located at 823 genes, including several key tumor suppressors and oncogenes, like MDM2, BRAF, TP53, BRCA2, ATM, and VHL. Subsequent pathway analysis identified TGF-beta, Notch Signaling, and DNA Damage Response as the key pathways for cancer progression. Using the characterized A-to-I editing profiles, we built a prognostic risk stratification model, with high risk scores significantly linked to poor survival outcomes, even after adjusting for other clinical factors. Our study provides a comprehensive A-to-I editing landscape of lung cancer in never smokers, highlighting the potential roles of RNA modifications in the pathogenesis of this lethal disease.
Citation Format: Jian Sang, Wei Zhao, Tongwu Zhang, Maria Teresa Landi. The RNA editing landscape of lung cancer in never smokers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6250.
Abstract 626: EGFL6 induced HER2-HER3 signaling controls accurate centrosome deposition of activated ERK and mitotic spindle formation in ovarian cancer cells
Authors: Bai Shoumei , Gupta Navneet , Jiang Qi , Buckanovich Ronald J. 
Published: March 2024

Abstract
Epidermal growth factor EGF-like domain multiple-6 (EGFL6) is highly expressed in high grade serous ovarian cancer (HGSOC) cells and ovarian tumor vasculature. EGFL6 acts on tumor cells to drive tumor cell proliferation and migration. To better understand EGFL6 signaling and develop therapeutic strategies to target EGFL6 signaling in HGSOC, we evaluated phosphorylation of putative EGFL6 receptors and their downstream signaling. We demonstrated that EGFL6 induced phosphorylation and activation of ERBB/HER family of receptors; EGFL6 treatment of ovarian cancer cells led to rapid and transient phosphorylation of EGFR while inducing prolonged activation of both HER2 and HER3, with subsequent phosphorylation of ERK. Interestingly, we found that in EGFL6 stimulated ovarian cancer cells undergoing mitosis, pERK localized to the centrosome and the contractile ring. EGFL6 neutralizing antibodies reduce ERK phosphorylation and resulted in pERK being aberrantly localized. This resulted in altered mitotic spindle alignment and an increased number of cells undergoing mitotic catastrophe. Furthermore, combination anti-EGFL6 therapy with the pan-EGFR receptor inhibitor neratinib, compared to either therapy alone, led to an increase in aberrant pERK localization and cancer cell death in vitro. Consistent with these findings, dual anti-EGFL6 and neratinib therapy significantly restricted tumor growth in vivo, resulting in increased tumor cell death and a reduction in angiogenesis. Combined our data identify an unexplored role for pERK at the centrosome and suggest that dual targeting of the EGFL6/HER signaling axis maybe an effective therapeutic strategy in ovarian cancer.
Citation Format: Shoumei Bai, Navneet Gupta, Qi Jiang, Ronald J. Buckanovich. EGFL6 induced HER2-HER3 signaling controls accurate centrosome deposition of activated ERK and mitotic spindle formation in ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 626.
Abstract 6266: Neurotensin receptor 1 regulates dimerization of HER2-HER4 and proliferation of non-small cell lung cancer cells
Authors: Moody Terry W. , Ramos-Alvarez Irene , Jensen Robert T. 
Published: March 2024

Abstract
The neurotensin receptor 1 (NTSR1) is a 418 amino acid type A G protein-coupled receptor which causes phosphatidylinositol turnover and proliferation of non-small cell lung cancer (NSCLC) cells (Moody et al., Peptides 2021; 137: 710480). Adding the agonist NTS to NSCLC cells increases transactivation of the receptor tyrosine kinases (RTK) EGFR, HER2 and HER3 (Moody et al., Biology 2023 12: 957). The RTK tyrosine phosphorylation and growth caused by NTS is impaired by SR48692, a small molecule NTSR1 antagonist. The effects of NTS were investigated on HER4 using NSCLC cells. By Western blot, cell lines NCI-H522 and H661 had high levels of NTSR1, HER 4 and neuregulin 1 (NRG1), a ligand for HER4 but not NTSR2, HER3 or NRG2. By RT-PCT, high levels of HER4 and its isoforms JM-a, CYT1 and CYT2 were present in NCI-H522 and H661 cells. Adding NTS (0.1 μM) or NRG1 (0.01 μg/ml) to NCI-H522 or H661 cells increased P-Tyr1284-HER4 and P-ERK 3-fold. Using immunoprecipitation techniques, adding NTS to NSCLC cells increased formation of HER4-HER2 heterodimers which leads to cancer proliferation (Lucas et al., Pharmacol Rev 2022; 74:18). The increase in PY1284-HER4 caused by NTS was impaired by SR48692, HER4 siRNA, NRG1 siRNA or ibrutinib (TKI). The NTSR1 regulation of HER4 transactivation is impaired by GM6001 (MMP inhibitor]), PP2 (Src inhibitor) or N-acetylcysteine (antioxidant). The clonal growth of NSCLC cells is increased by NTS or NRG1 but decreased by SR48692 or ibrutinib. The results indicate that NTS increases the formation of HER2/HER4 heterodimers leading to the proliferation of NSCLC cells.
Citation Format: Terry W. Moody, Irene Ramos-Alvarez, Robert T. Jensen. Neurotensin receptor 1 regulates dimerization of HER2-HER4 and proliferation of non-small cell lung cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6266.
Abstract 6267: Evaluating estrogen receptor signaling modifications at bone marrow related stiffnesses in metastatic breast cancer
Authors: Northcutt Logan Alexander , Rafat Marjan , Rhoades Julie 
Published: March 2024

Abstract
Bone metastasis is highly prevalent in breast cancer (BC) patients with metastatic disease and can increase the risk of hypercalcemia and pathological fractures. Several studies have evaluated the mechanisms of metastasized BC cells’ involvement in bone destruction, but how the bone marrow (BM) microenvironment contributes to this process remains ambiguous. Recent studies have shown that as BC cells experience increased stiffnesses outside of the primary microenvironment, there is higher expression of epithelial-to-mesenchymal transition (EMT) markers, increased expression of osteolytic proteins, and decreased drug responses. However, these changes have not been evaluated at stiffnesses relative to the BM. Estrogen receptor (ER) status also plays a pivotal role in BC patient survival. Clinical studies have indicated that the majority of ER+ patients with metastatic disease have more incidences of bone metastases compared to ER- patients. There is some evidence that suggests that the physical properties can also affect estrogen receptor signaling at the primary site, however, there is minimal work to establish how the physical factors of the BM can affect ER sensitivity after metastasis. We hypothesize that higher stiffness ranges of the BM can alter the estrogen receptor sensitivity of metastasized tumor cells and increase osteolysis. To analyze this question, we seeded ER+ BC cell lines (MCF7s and T47Ds) on CytoSoft® Rigidity Plates that mimicked the stiffness of the BM (0.5 - 32 kPa). After 2 days in culture, we probed the expression of downstream estrogen signaling factors, GREB1, PGR, and TIFF1, to evaluate estrogen activity using western blot. Our results show an increase in downstream estrogen signaling at higher stiffnesses (32 kPa) compared to lower stiffnesses (0.5 kPa) at the protein level but not at the transcriptional level. In the future, we will analyze factors associated with osteolysis (ITGB3, TGFB-RII, and PTHLH). Additionally, we plan to conduct RNA sequencing to analyze any larger transcriptional changes at different stiffnesses. Overall, this work gives insight into how estrogen signaling changes in the BM compared to the primary site. It will also give us insight into potential therapeutic targets for ER+ BC after metastasis to the bone.
Citation Format: Logan Alexander Northcutt, Marjan Rafat, Julie Rhoades. Evaluating estrogen receptor signaling modifications at bone marrow related stiffnesses in metastatic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6267.