bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 147: Identification of cell sub-populations in Neuroblastoma cell lines with single-cell-sequencing analysis
Authors: Tomanelli Michele , Ceresa Davide , Bajetto Adriana , Modesto Paola , Malatesta Paolo , Florio Tullio , Pagano Aldo 
Published: March 2024

Abstract
Neuroblastoma is the most frequent extracranial tumor in neonatal patients. Engineering SKNBE2 Myc-N amplified Neuroblastoma cell lines we generated individual clones expressing NDM29 non-coding-RNA at different levels. Using these cell models we documented a specific role of NDM29 in tumor cell differentiation leading to the identification of novel genes to be pharmacologically targeted for an efficient control of tumor malignancy (CA9 and MCM2 genes). Further studies taking advantage of the same models suggested the possible co-existence of different cell sub-populations in the apparently homogeneous cell culture with possible different roles in tumor maintenance and growth. Here we test this hypothesis by performing single-cell sequencing analysis and identified different sub-populations on the base of their gene expression patterns. The characterization of their specific profiles of membrane markers allowed an efficient separation of the individual populations by FACS analysis. Our preliminary results show the co-existance of cells with a marked neural phenotype with other two populations one VEGF secreting and the other VEGF recipient/responder. These preliminary findings suggest further detailed investigations of possible paracrine loops that might be at the base of tumor cell nodule growth and maintenance.
Citation Format: Michele Tomanelli, Davide Ceresa, Adriana Bajetto, Paola Modesto, Paolo Malatesta, Tullio Florio, Aldo Pagano. Identification of cell sub-populations in Neuroblastoma cell lines with single-cell-sequencing analysis [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 147.
Abstract 1482: FKBP52 drives diverse HCC phenotypes through context-dependent targeting of p53
Authors: Wang Xing , Wu Jingfeng , Tang Chengyan , Li Xiang , Zhu Li , Liu Yaoyu 
Published: March 2024

Abstract
p53 is notably the most frequently mutated protein in hepatocellular carcinoma (HCC), one of the major causes of cancer-related fatalities globally. These mutations often result in some of the most adverse outcomes in HCC, making p53 a prime target for therapeutic intervention. The concept of “hyperstability”of p53 is essential in understanding its gain-of-function and dominant-negative effects in tumorigenesis. However, the mechanisms driving this hyperstability are not completely understood. In this study, we have identified FKBP52, a member of the FK506-binding protein family, as a crucial factor in stabilizing and accumulating p53, irrespective of the type of mutation. Furthermore, our study suggests that FKBP52 could be a valuable biomarker for predicting HCC outcomes. We observed a notable link between FKBP52 levels and the histological differentiation in HCC samples. To corroborate these observations, we performed a series of in vitro and in vivo experiments using liver cancer models. These experiments highlighted the dual nature of FKBP52’s impact on hepatocytes, which varies according to cell type. Given its connection to HCC severity, FKBP52 seems to contribute negatively to the disease’s progression. The insights gained from this study on how FKBP52 influences p53 stabilization are critical. We suggest that targeting the processes upstream of FKBP52 could lead to more effective HCC treatments. These findings emphasize the importance of further investigating this pathway, potentially paving the way for new strategies in liver cancer therapy.
Citation Format: Xing Wang, Jingfeng Wu, Chengyan Tang, Xiang Li, Li Zhu, Yaoyu Liu. FKBP52 drives diverse HCC phenotypes through context-dependent targeting of p53 [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 1482.
Abstract 1527: Exploring the role of tertiary lymphoid structure in the tumor microenvironment of cholangiocarcinoma
Authors: Chung Shin-Yi , Chen Ming-Huang , Yeh Yi-Chen , Chang Yu-Chan , Wang Yu-Cha 
Published: March 2024

Abstract
Cholangiocarcinoma is the second most common hepatobiliary malignant tumor besides liver cancer, grows from bile duct epithelial cells. However, surgery is the only hope for most patients with cholangiocarcinoma, but the effectiveness of treatment is not outstanding. Even though other methods of treatment, such as chemotherapy and radiation therapy, have limited effects. The immunotherapy and precision treatment have become the latest expectations of patients. Here, we analyzed the TCGA and GEO database to classify the cold and hot tumor using hierarchical clustering. The MCP counter results demonstrated that two genes, MS4A1 and CD79A, could identify the hot and cold tumor subgroups after TCGA data training and similar results show in GEO database. We also performed the tissue array for 105 cholangiocarcinoma tissue samples and found patients with high expression levels of MS4A1 or CD79A have better disease free survival (DFS) and progression free survival (PFS) (p value =0.0131 and 0.0017). In addition, we tested the tertiary lymphoid structures (TLS) signatures in tissue array sections, which is associated with the present of MS4A1 and CD79A. The results shows that patients who received the immunotherapy with TLS signatures have longer overall survival (OS) and PFS (p value =0.017 and 0.006). Collectively, B cell lineages or TLS could be an ideal biomarker to lead the clinical treatment and wish can broader applications in other diseases.
Citation Format: Shin-Yi Chung, Ming-Huang Chen, Yi-Chen Yeh, Yu-Chan Chang, Yu-Cha Wang. Exploring the role of tertiary lymphoid structure in the tumor microenvironment of cholangiocarcinoma [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 1527.
Abstract 1532: Improved reproducibility in multiplex immunofluorescence analysis of the tumor microenvironment using a novel quenching solution
Authors: Levin Matt , Heath Jack , Schrank-Hacker April , Dunn Shelby , Vu Minh-Chau , Hamza Imane , Schwartz David 
Published: March 2024

Abstract
Formalin-fixed, paraffin-embedded (FFPE) tissues are commonly used in histopathology because the fixed tissues are stable and easy to store. In the context of immunofluorescence detection, however, endogenous autofluorescence of FFPE tissues can significantly reduce or mask immunofluorescent signals. The autofluorescence of FFPE tissues is caused by a variety of factors, including the presence of endogenous fluorophores, tissue fixation, and processing. While there are several methods that can be used to quench autofluorescence in FFPE tissues, chemical quenchers, which absorb or scatter light, are most frequently used for multiplex IF. Examples of chemical quenchers commonly used in manual multiplex staining include Sudan Black B and TrueBlack; however, these are not chemically compatible for use on automated platforms such as the Leica Biosystems BOND RX. Due to the need for increased throughput and decreased hands-on time, automation has risen in popularity versus manual staining, leading to a need for a versatile quenching solution compatible with automation. Here we demonstrate that NovaPlex Quenching Solution (NPQS), a novel proprietary quenching agent, reduces the background caused by autofluorescence and enhances the signal of the Cell IDx UltraPlex multiplex immunofluorescent (mxIF) assay across tissue types. Qualitative studies showed a decrease in autofluorescent signal in FFPE mouse spleen stained with antibodies against B220/Foxp3/CD3e, suggesting the utility of NPQS in mouse models of cancer and immunity. Similarly, nonspecific background was decreased across FFPE human tissue types, including lung adenocarcinoma stained for CD8/Foxp3/CD3e/CD4 and tonsil stained for CD8/Foxp3/PD-1/CD4. Further statistical studies in FFPE human tonsil tissue stained with CD8/Foxp3/PD-1/CD4 showed there was no significant decrease in dye intensity across all four markers and channels, resulting in a significant increase in signal-to-noise ratio for both CD8 at 490nm and PD-1 at 650nm (p&lt;0.05). These experiments using Cell IDx/LBS UltraPlex mxIF technology demonstrate an effective method to improve the signal-to-noise ratios of fluorophores without reducing signal intensity from any of the target proteins in these parallel multiplex immunofluorescent assays.
Citation Format: Matt Levin, Jack Heath, April Schrank-Hacker, Shelby Dunn, Minh-Chau Vu, Imane Hamza, David Schwartz. Improved reproducibility in multiplex immunofluorescence analysis of the tumor microenvironment using a novel quenching solution [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 1532.
Abstract 1559: IKZF1 plays a crucial role in the spread of melanoma
Authors: Oh Jongwook , Lee Dong Ki , Lee Soyeon , Park Hyun Woo , Gee Heon Yung 
Published: March 2024

Abstract
Melanoma is one of the most fatal type of skin cancer. If melanoma has spread to distant sites, it is refractory to existing therapies with the 5-year survival rate declining to 17%. Metastasis remains as the main barrier to successful therapy, persisting as the main cause of cancer-related death. Thus, understanding metastasis mechanism is vital.
First, we confirmed that IKZF1 gene was more increased in circulating tumor cells than primary tumor cells. Using GFP+ B16F10, we generated an orthotopic melanoma mouse model and isolated GFP+ tumor cells of primary footpad, blood, and lung. In single cell RNA sequencing, IKZF1, IRF8, NFE2 genes were more upregulated in circulating tumor cells than primary tumor cells. We also found these correlations in human melanoma cell line orthotopic mouse model and Braf/Pten mouse model.
Next, we conduct intervention study to find causality in IKZF1 and metastasis. IKZF1 KO led to fewer CTCs and IKZF1 inhibitor, lenalidomide, reduced metastasis in mice.
Collectively, we demonstrate that IKZF1 could contribute the formation of CTC and IKZF1 could be a target for metastasis treatment.
Citation Format: Jongwook Oh, Dong Ki Lee, Soyeon Lee, Hyun Woo Park, Heon Yung Gee. IKZF1 plays a crucial role in the spread of melanoma [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 1559.
Abstract 1571: Upregulation of phosphoglyceric acid mutase (PGAM)-1 is related to lymph node metastasis in gastric cancer
Authors: Wang Helei , Liu Zhicheng , Wang Lei , Wang Zitian , Jamieson Christina , Cacalano Nicholas A. 
Published: March 2024

Abstract
Gastric cancer (GC) is the most common malignancy of the digestive system, causing over 750,000 deaths worldwide. Gastric cancer mortality is largely due to its high level of invasiveness and metastasis to distal organs. Thus, it is an urgent priority to identify mechanisms underlying GC metastasis to improve cancer diagnosis develop of effective biological targeting agents. In this study, we demonstrate that phosphoglyceric acid mutase-1 (PGAM1) was preferentially over-expressed in lymph node metastasis (LNM) tissues of GC patients and correlated with poor prognosis. PGAM1 knock down in two human GC cell lines resulted in impaired cell proliferation and increased cell cycle arrest. Further, PGAM knockdown inhibited migration of both GC cell lines, which correlated with decreased expression of MMP2, MMP9 and ICAM-1. In a murine xenograft model, GC cells with a PGAM1 knockdown displayed decreased growth capacity in vivo. Western blot analysis showed that PGAM1 knockdown in SGC7901 and BGC823 decreased the phosphorylation of Src, FAK and Paxillin relative to the parental cell lines. These results indicate that PGAM1 may play an important role in promoting GC lymph node metastasis by driving cell proliferation and activating cytoskeletal reorganization and cell migration through the regulating Src/FAK/Paxillin pathway.
Citation Format: Helei Wang, Zhicheng Liu, Lei Wang, Zitian Wang, Christina Jamieson, Nicholas A. Cacalano. Upregulation of phosphoglyceric acid mutase (PGAM)-1 is related to lymph node metastasis in gastric 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 1571.
Abstract 1601: The role of complement in pancreatic cancer cachexia
Authors: D'Lugos Andrew C. , Callaway Chandler , Judge Sarah M. , Judge Andrew R. 
Published: March 2024

Abstract
Cancer cachexia is a multifactorial condition characterized by skeletal muscle atrophy and dysfunction that impairs longevity and quality of life for the vast majority of cancer patients. Recently, we discovered through unbiased proteomic analyses that the complement system is activated in the skeletal muscle of cachectic pancreatic cancer patients. Therefore, the purpose of this study was to investigate the role of complement in pancreatic cancer cachexia. To accomplish this, we obtained genetically modified, C57Bl6/J congenic mice lacking the central regulator of complement, C3 (C3−/− mice). Wild-type (C57Bl6/J, WT, n=12) and C3−/− mice (n=11) (male, 12 weeks old) received orthotopic injections of mouse pancreatic cancer cells (KPC) into the pancreas, and as non-cancer controls, WT (n=8) and C3−/− (n=4) mice received injections of PBS into the pancreas. Mice were monitored daily and euthanized at IACUC-mandated tumor endpoint (body condition score ≤ 2; range: 14-15 days). In-vivo diaphragm function was assessed immediately prior to euthanasia via M-mode ultrasound. Skeletal muscles (soleus, SOL; tibialis anterior, TA; diaphragm, DIA) were harvested and ex-vivo contractile function was assessed on strips of costal diaphragm. Diaphragmatic excursion and respiratory rate were reduced with KPC tumor burden in WT mice, but preserved in C3−/− mice. Deletion of C3 did not influence the KPC-induced reduction of body mass or KPC tumor growth. Atrophy of limb muscle mass (SOL, TA) and fiber size (TA) during KPC tumor burden was attenuated in C3−/− mice. Maximal specific force of DIA was greater in C3−/− versus WT KPC-bearing mice. KPC tumor burden increased collagen content in the DIA of WT mice, but not C3−/− mice. Diaphragm fiber size was reduced in WT KPC-bearing mice, but preserved in C3−/− mice. KPC tumor burden induced significant increases in immune cell (CD45+) infiltration and fibroadipogenic progenitor cell (PDGFRa+) abundance in the DIA of WT tumor-bearing mice, but to a lesser extent in C3−/− mice. These findings suggest complement activation is causative in pancreatic cancer-induced skeletal muscle wasting and dysfunction. Inhibition of complement during cancer cachexia may possess therapeutic potential for the preservation of skeletal muscle mass and function.
Citation Format: Andrew C. D'Lugos, Chandler Callaway, Sarah M. Judge, Andrew R. Judge. The role of complement in pancreatic cancer cachexia [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 1601.
Abstract 1638: Regulation of spindle pole integrity by the MASTL-ENSA-aurora a pathway during mitosis
Authors: Kim Seul , Jun Kyoungho , Kim Ye-Hyun , Kim Jae Sung 
Published: March 2024

Abstract
The preservation of spindle pole integrity is crucial for proper spindle assembly and chromosome segregation in mitosis, yet the precise mechanisms governing spindle pole integrity remain elusive. During mitosis, phosphorylated Ensa (p-ENSA) localizes to spindle poles, and the inhibition of ENSA leads to a range of mitotic defects, including misaligned chromosomes, multipolar spindles, asymmetric bipolar spindles, and centrosome aberrations, resulting in a delayed mitotic progression. Remarkably, the mitotic delay induced by ENSA inhibition is alleviated upon depletion of PP2A-B55α, but spindle pole defects persist. Significantly, we have observed an interaction between ENSA and Aurora A during mitosis, and the inhibition of ENSA diminishes Aurora A expression at the mitotic spindle poles. Intriguingly, the injection of MKI-2-sensitized tumors is associated with heightened chromosomal instability and downregulation of the MASTL-ENSA-Aurora A pathway in an orthotopic breast cancer mouse model. These findings offer new insights into the regulation of spindle pole integrity through the MASTL-ENSA-Aurora A pathway during mitosis, emphasizing the pivotal role of ENSA in recruiting Aurora A to the spindle pole, independently of PP2A-B55α.
Citation Format: Seul Kim, Kyoungho Jun, Ye-Hyun Kim, Jae Sung Kim. Regulation of spindle pole integrity by the MASTL-ENSA-aurora a pathway during mitosis [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 1638.
Abstract 1665: Investigating Daple-FLT3 gene fusion in leukemia cells and its response to kinase inhibitors
Authors: Nguyen Elena , Ear Jason 
Published: March 2024

Abstract
Gene fusions are frequently found in leukemia and other cancers. The signaling scaffold protein, Daple (CCDC88C), has been found to undergo gene fusion to the receptor tyrosine kinase, FLT3. Specifically, a fragment of the coiled-coil domain from Daple and tyrosine kinase domain (TKD) of FLT3 are found fused together. How the gene product from this gene fusion functions in rewiring the signaling network in cells and whether this gene product can be targeted though pharmacological inhibitions remain unclear. Cell surface receptors, such as receptor tyrosine kinases (RTKs), activate cell signaling and genetic mutations that lead to constitutive receptor activation can promote unregulated cell proliferation, survival, and migration. Leukemia patients with hyperactive RTKs are treated with tyrosine kinase inhibitors (TKIs), such as Imatinib and Sorafenib. Here we demonstrate how TKIs can directly block the activation of Daple-FLT3 and prevent hyperactivation of its downstream pathways. Our studies unveil a strategy to identify other compounds which may serve as an additive, or alternative, approach to treating patients with Daple gene fusion.
Citation Format: Elena Nguyen, Jason Ear. Investigating Daple-FLT3 gene fusion in leukemia cells and its response to kinase inhibitors [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 1665.
Abstract 1668: Association of stem cell-like phenotype with isoform specific functions of AKTs in hepatocytes
Authors: Slarve Ielyzaveta , Wang Yushan , Alba Mario , He Lina , Stiles Bangyan 
Published: March 2024

Abstract
Introduction: Liver cancer is the sixth most common cancer and the third leading cause of cancer-related deaths worldwide. It is associated with abnormal activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, which is implicated in regulation of cancer stem cells (CSCs). The present study investigated the effects of AKT loss on stem cell-like phenotype in immortalized mouse hepatocytes.
Methods: Immortalized hepatocytes were established from mice with Akt1 (Akt1−/−; Akt1-null) or Akt2 (Akt2−/−; Akt2-null) whole-body deletion. Cell morphology was assessed via microscopy. Cell proliferation was evaluated with hemacytometer count and MTT assay. Cell migration towards a chemoattractant was assessed via transwell assay. Cell viability was evaluated in response to chemotherapy treatment. The ability of cells to
Results: When compared to WT cells, which exhibited cuboidal epithelial-like features, Akt1-null and Akt2-null cells demonstrated elongated mesenchymal-like morphology. Loss of either isoform was associated with a significantly decreased cell growth (p&lt;0.05). Akt1-null cells migrated faster towards a chemoattractant in the transwell assay, were significantly more resistant to sorafenib, and formed a significantly higher number of spheres in the sphere formation assay (p&lt;0.01). Proteomic analysis revealed that both Akt1-null and Akt2-null cells exhibited increased expression of CSC marker CD44, along with other proteins associated with liver cancer, including PDGFRA, CDH2, MMP14, and COX2 (p&lt;0.05). Additionally, Akt1-null cells exhibited elevated levels of ANXA1 and ANXA3 (p&lt;0.01).
Conclusions: Loss of both AKT isoforms resulted in decreased cell proliferation and elevated expression of proteins with a previously reported role in liver cancer invasion, migration, and epithelial-mesenchymal transition. AKT1 loss correlated with an enhanced stem cell-like phenotype, including increased migration towards a chemoattractant, higher resistance to chemotherapy, and enhanced ability to form spheres. These results contribute to the understanding of the role of AKT isoforms in regulating stemness in liver cancer and may serve as a basis for investigation into isoform specific inhibitors. Further investigation into cellular mechanisms governing these phenotypes is required.
Citation Format: Ielyzaveta Slarve, Yushan Wang, Mario Alba, Lina He, Bangyan Stiles. Association of stem cell-like phenotype with isoform specific functions of AKTs in hepatocytes [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 1668.
Abstract 1685: Investigating PAX8 interactions in ovarian cancer
Authors: Sereti Kostianna , Russo Anna , Raisner Ryan , Gascoigne Karen 
Published: March 2024

Abstract
Ovarian cancer is the most lethal gynecological cancer and there is a critical unmet need to develop novel therapies. The transcription factor, PAX8, is upregulated in ~80% of renal, ovarian, endometrial and thyroid tumors and its overexpression correlates with higher risk of death and recurrence. PAX8 represents a promising target because of its high specificity and low expected toxicity, but how it promotes tumorigenesis remains elusive. Using proximity labeling followed by mass spectrometry, we identified a list of PAX8 binding partners and have further confirmed these interactions at the genomic level through ChIP-seq and ATAC-seq. Our findings reveal novel PAX8 interactions and a potential therapeutic approach for ovarian cancer treatment.
Citation Format: Kostianna Sereti, Anna Russo, Ryan Raisner, Karen Gascoigne. Investigating PAX8 interactions in ovarian 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 1685.