bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2976: The potential use of butyrate and propionate to inhibit oncogenic phenotypes in oral squamous cell carcinoma and triple negative breast cancer
Authors: Maisonet Angel J. Amaral 
Published: March 2024

Abstract
Background
Oral squamous cell carcinoma (OSCC) and triple-negative breast cancer (TNBC) are aggressive cancers with low survival rates, particularly in Hispanics. Since the underpinning mechanisms of oncogenesis for both OSCC and TNBC are multifactorial, the development of novel targeted therapies is limited. The tumor microbiome has been shown to modulate the microenvironment. The microbial product short-chain fatty acids (SCFA) may represent a putative target for treatment as they can potentially inhibit cell growth, proliferation, migration, and induce morphologic changes in cancer cells. We evaluated the impact of the SCFAs butyrate, acetate, and propionate on the oncogenic phenotypes of OECM-1 and MDA-231 cell line models for OSCC and TNBC respectively.
Methods
OECM-1 and MDA-231 cell lines were cultured in RPMI-1640 medium supplemented with 10% FBS. Cytotoxicity was determined using an alamarBlue assay by treating the cells with SCFA in a series of 7 concentrations starting at 125 mM (1:2 dilution factor) for 24, 48, and 72 hours (h). Proliferation quantification was performed using trypan blue dye after treatment with SCFA for 24h, 48h and 72h. Migration and invasion were measured after treatment for 24h with SCFAs. Comparative analysis of our results was performed using GraphPad Prism v10.
Results
Higher concentrations of all SCFA decreased cell viability in OSCC and TNBC at all time points. In OECM-1 cells, the average inhibitory concentration of 50% (IC50) was 3mM for butyrate, 382mM for acetate, and 64mM for propionate while in MDA-MB-231 cells, the average IC50 was 4.3mM for butyrate, 462mM for acetate, and 20mM for propionate. Both OECM-1 and MDA-MB-231 cells treated with butyrate and propionate at 5mM resulted in a slower migration after 24h of treatment. Additionally, there was a significant reduction of cell number and proliferation rate after 48h and 72h of butyrate treatment at the concentrations 1mM (p=0.0425) and 5mM (p=0.0007) in OSCC.
Conclusions
Our results show that butyrate and propionate can reduce oncogenic phenotypes in OSCC and TNBC and may represent a potential target for the development of alternative treatment strategies for both cancers. Future work includes measuring the impact of these SCFA in epithelial-mesenchymal transition, loss of adhesion, and cell death.
Citation Format: Angel J. Amaral Maisonet. The potential use of butyrate and propionate to inhibit oncogenic phenotypes in oral squamous cell carcinoma and triple negative 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 2976.
Abstract 2992: miR-200-mediated inactivation of cancer-associated fibroblasts attenuates lung cancer invasion and metastasis
Authors: Cheon Inyoung , Lee Sieun , Ahn Young-Ho 
Published: March 2024

Abstract
Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment and contribute to the development and progression of lung cancer. We aimed to elucidate whether miRNA-200 (miR-200), which is recognized for its ability to suppress EMT, prevents CAFs from promoting cancer progression. Inactivation of CAFs mediated by miR-200 suppressed lung cancer cell invasion, migration, tumorigenesis, and metastasis. Additionally, miR-200 attenuated the ability of CAFs to facilitate the aggressiveness of lung cancer cells, encourage M2 polarization of macrophages, and increase the angiogenic sprouting of vascular endothelial cells. NRP2, known as a co-receptor of VEGFR, was identified as a target of miR-200, mediating the functional activity of miR-200 in CAFs. NRP2-VEGFR signaling promoted the secretion of VEGFD and PTN from CAFs to activate cancer cell migration and invasion. Based on these findings, we suggest that miR-200 impedes cancer progression and metastasis by remodeling CAFs, and that miR-200 and NRP2 are potential therapeutic targets in the treatment of lung cancer.
Citation Format: Inyoung Cheon, Sieun Lee, Young-Ho Ahn. miR-200-mediated inactivation of cancer-associated fibroblasts attenuates lung cancer invasion and metastasis [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 2992.
Abstract 303: Revealing molecular mechanism of G protein-coupled receptor kinase 2 (GRK2)-mediated extracellular matrix remodeling in ovarian cancer
Authors: Lei Weng I , Yu Shan , Lei Chi Teng , Zhang Zhiming , Liu Tzu Ming , Chang Wakam , Lee Leo Tsz On 
Published: March 2024

Abstract
G protein-independent pathway (β-arrestin dependent signaling cascade) is initiated by activated GPCRs phosphorylated by G protein-coupled receptor kinases (GRKs), triggering multiple signaling pathways. The purpose of this research is to reveal the role of GRK2 on the tumor microenvironment (TME). Through in vitro assays, we showed that GRK2 overexpression led to loss of cell-matrix and cell-cell adhesion. The cell spreading assay further indicated that the loss of focal adhesion (FA) assembly and cell size decreased in GRK2-overexpressing cells. In vivo experiments demonstrated that tumor formation and metastasis were suppressed in xenograft mouse models implanted with GRK2-overexpressing ovarian cancer cells. In addition, label-free imaging detection of the collagen pattern suggested that GRK2 overexpression caused bundle loss but the formation of thicker, twisted collagen fibers in xenograft tumor samples. Together with the transcriptome and proteomic data, we hypothesize that GRK2 suppresses cell motility and metastasis by reducing FA and extracellular matrix (ECM) remodeling in ovarian cancer. This research revised the mechanisms underlying GRK2-mediated ovarian cancer metastasis and suggested the potential to target the GRK2-meditated pathway for cancer suppression.
Citation Format: Weng I Lei, Shan Yu, Chi Teng Lei, Zhiming Zhang, Tzu Ming Liu, Wakam Chang, Leo Tsz On Lee. Revealing molecular mechanism of G protein-coupled receptor kinase 2 (GRK2)-mediated extracellular matrix remodeling 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 303.
Abstract 3032: Generation of a FOXC2-deficient melanoma cell line using CRISPR-Cas9 gene editing
Authors: Clark Devanand M. , Conde Patrick D. , Hargadon Kristian M. 
Published: March 2024

Abstract
Melanoma, a cancer derived from pigment-producing melanocytes of the skin, is a highly aggressive cancer characterized by rapid growth and metastasis. FOXC2 is a forkhead box transcription factor family member that is often dysregulated in various cancers, including melanoma, where its expression correlates with metastatic progression and drug resistance. To gain insight into the oncogenic activity of FOXC2 in melanoma, we have employed CRISPR-Cas9 gene editing technology to generate a novel FOXC2-deficient B16-F10 murine melanoma cell line. This model will be a useful tool for studying the tumor-promoting functions of FOXC2.
Citation Format: Devanand M. Clark, Patrick D. Conde, Kristian M. Hargadon. Generation of a FOXC2-deficient melanoma cell line using CRISPR-Cas9 gene editing [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 3032.
Abstract 3045: PPAR-α antagonist enhances immunotherapy and anti-angiogenic therapy to inhibit murine renal cancer
Authors: Gillespie Michael , Chen Valerie , Howard Isabella , Smith Keira , Freund Dave , Standifer Nathan , Burdette Dara , Dubensky Thomas W. , Whiting Sam , Panigrahy Dipak 
Published: March 2024

Abstract
Peroxisome proliferator activated receptor alpha (PPARα) is a transcription factor and master regulator of fatty acid oxidation. PPARα ligands modulate the switch between co-activator and co-repressor transcription complexes at PPARα-controlled target genes. In addition, PPARα has been shown to transrepress NF-κB signaling and inhibit angiogenesis. Renal cell carcinoma (RCC) expresses high levels of PPAR-α and is a highly angiogenic cancer. Current frontline treatments for RCC include chemotherapy, anti-angiogenics, and immunotherapy but are limited by the immune suppressive state of the tumor microenvironment. TPST-1120 is a novel PPARα antagonist for the treatment of cancer patients that binds in the ligand binding domain, positioning the AF-2 activation helix in an inactive conformation. The inactive conformation has a lower affinity for co-activator motifs and reduces activation of PPARα regulated genes. In a CHO-based reporter cell line, TPST-1120 potently competed against the PPARα-specific agonist GW7647 (IC50 = 36 nM at 20 nM GW7647) and an endogenous PPARα agonist oleoylethanolamide (OEA; IC50 = 15 nM at 30 µM OEA). Furthermore, in an enzyme fragment complementation assay, we demonstrated that TPST-1120 inhibited agonist-induced binding of PPARα to MED1 by destabilizing the co-activator complex thereby stabilizing the inactive conformation of PPAR-α. In a murine model of renal cell adenocarcinoma (RENCA), TPST-1120 treatment for 12 days (30 mg/kg qd) reduced tumor growth by 52% as a monotherapy (p&lt;0.0001). Consistent with these findings, TPST-1120 inhibited tumor angiogenesis and proliferation as quantified by Ki67 levels. Combination treatment with current frontline therapeutics resulted in synergistic tumor inhibition of 74% with anti-PD1 (200 ug Q3D for 12 days) and 81% with cabozantinib (15 mg/kg QD for 15 days) (p&lt;.0001). Flow cytometry-based analysis of tumors demonstrated increased CD8+ T cell infiltration in the TME as well as decreases in M2 and elevations in M1 macrophages. Importantly, we demonstrate that TPST-1120 can reverse an immunosuppressive class of immune cells to promote anti-tumor immunity and anti-angiogenesis in kidney cancer in the absence of overt toxicity. These data support advancement of TPST-1120 into RCC.
Citation Format: Michael Gillespie, Valerie Chen, Isabella Howard, Keira Smith, Dave Freund, Nathan Standifer, Dara Burdette, Thomas W. Dubensky, Sam Whiting, Dipak Panigrahy. PPAR-α antagonist enhances immunotherapy and anti-angiogenic therapy to inhibit murine renal 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 3045.
Abstract 3051: JunAP, a peptide antagonist against the activator protein 1 transcription factor complex, demonstrates cancer cell cytotoxicity and reduced invasion in vitro and tumor regression in vivo in TNBC models
Authors: Mendelson Karen , Mattes Zachary F. , Leong Siok , Ramirez Ricardo , Koester Mark , Scuoppo Claudio , Diehl Julia , Gallagher Erin , Gonzales Jerel , Abbate Franco , Ghamsari Lila , Merutka Gene , Kappel Barry J. , Vainstein-Haras Abi , Rotolo Jim A. 
Published: March 2024

Abstract
The activator protein 1 (AP-1) transcription factor is a dimeric complex consisting of proteins from the JUN, FOS, MAF, and ATF families. AP-1 complexes have been identified as novel therapeutic targets in cancer due to their role in tumor growth, invasion, metastasis, angiogenesis and chemoresistance. Dimerization of components of the AP-1 complex via leucine zipper domain interactions is required for DNA binding and subsequent transcriptional activity. We designed a peptide (Jun antagonizing peptide, JunAP) targeting the basic leucine zipper motif of AP-1 to antagonize AP-1 complex formation and prevent associated activity. Fluorescence polarization and DNA ELISA assays demonstrate target binding and selectivity of JunAP towards AP-1 family members, co-immunoprecipitation experiments reveal that JunAP blocks protein-protein interactions between cJun and its key binding partners, and reporter assays confirm inhibition of AP-1 transcriptional activity in vitro. Pathway analysis of RNA sequencing data confirmed by qPCR analysis shows that JunAP disrupts key pathways required for cell survival and migration. Corresponding functional in vitro assays reveal that JunAP exhibits an inhibitory effect on invasion in Boyden chamber assays and demonstrates potent cytotoxicity in Jun-dependent cells. Further, in a BT549 triple negative breast cancer subcutaneous xenograft model, administration of JunAP results in tumor regression, demonstrating the anti-cancer potential of targeting the AP-1 complex. In summary, these data support JunAP as a potent peptide antagonist of the AP-1 transcription factor family that warrants further development as a potential therapeutic option for AP-1 driven tumors.
Citation Format: Karen Mendelson, Zachary F. Mattes, Siok Leong, Ricardo Ramirez, Mark Koester, Claudio Scuoppo, Julia Diehl, Erin Gallagher, Jerel Gonzales, Franco Abbate, Lila Ghamsari, Gene Merutka, Barry J. Kappel, Abi Vainstein-Haras, Jim A. Rotolo. JunAP, a peptide antagonist against the activator protein 1 transcription factor complex, demonstrates cancer cell cytotoxicity and reduced invasion in vitro and tumor regression in vivo in TNBC models [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 3051.
Abstract 3083: Unveiling the role of chemotherapy-resistant, slow-cycling cancer cells in driving cancer cachexia
Authors: Cho Jaebeom , Lee Ho-Young 
Published: March 2024

Abstract
Cancer cachexia, a systemic disease marked by substantial, involuntary weight loss, predominantly affecting muscle and adipose tissue, manifests in patients with advanced-stage cancer. The emergence of cancer cachexia poses significant challenges to cancer treatment, diminishing the efficacy of anticancer medications, and the resultant muscle loss adversely impacts the daily lives of patients, diminishing the overall quality of life. Notably, cancer cachexia is implicated in 30-40% of cancer-related deaths, underscoring the pivotal need to comprehend its underlying principles and propose apt interventions to enhance both survival rates and the well-being of cancer patients. Based on our previous findings, cancer cells exhibiting a slow cell cycle, resistant to widely employed clinical chemotherapy agents, exhibit the formation of proinflammatory tumor microenvironment. The escalation of systemic inflammatory cytokines has long been suggested as a potential mechanism contributing to cancer cachexia. Building upon these insights, we hypothesized that slow-cycling cancer cells (SCCs) featuring resistance to chemotherapy are pivotal contributors to cancer cachexia. We investigated the impact of drug-resistant SCCs on the loss of differentiated myotubes and lipid droplets in vitro and muscle and fat loss in in vivo conditions. Interestingly, these cells induced more severe muscle and fat losses. Upon scrutinizing this cell population, we found the overexpression of a particular membrane protein, Protein A. The increase of this Protein A enhanced the release of exosomes from the cell through a novel mechanism distinct from its classical functions, consequently amplifying the release of inflammatory substances originating from cancer cells. In summary, our study elucidates that chemotherapy-resistant cancer cells, characterized by a slow cell cycle, intensify the secretion of inflammatory substances in a manner contingent upon the overexpression of a membrane protein A, which leads to the depletion of muscle and fat located in the distal peripheral regions.
Citation Format: Jaebeom Cho, Ho-Young Lee. Unveiling the role of chemotherapy-resistant, slow-cycling cancer cells in driving 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 3083.
Abstract 3092: MICRO-TAG: A novel fluorescence-based real-time cellular target engagement platform for drug discovery
Authors: Babic Ivan , Bryan Nikolas , Cunningham Claire , Sampson Avery , Starczynowski Daniel , Nurmemmedov Elmar 
Published: March 2024

Abstract
Success of drug discovery programs can be amplified by adopting emerging technologies that can interrogate drug targets within their physiological context. Cell target engagement (CTE) presents a combined biological & biophysical method, which provides quantitative evaluation of target-drug interaction within the native environment of the cell. The currently available luminescence-based CTE methods are limited to measurement of end-point signal and poor resolution, thereby limiting their mechanistic and stoichiometric insight. We have developed MICRO-TAG, a novel fluorescence-based CTE platform, which relies on complementation of split-RNAse A. It enables interrogation of target engagement without interfering with folding, localization and function of target proteins - all within the physiological milieu of the cell. Uniquely, this new platform allows for quantitation and monitoring of CTE in real- time in the cell. It enables extraction of important parameters from target-drug interaction: target thermal profile and temperature of aggregation (Tagg), time required to reach equilibrium (teq), apparent association rate (Kon) and physiologically relevant drug:target binding affinity (KD). We provide data demonstrating potential and utility of MICRO-TAG platform on drug targets, such as KRAS, MTH1, EGFR, and UBE2N. The platform demonstrates relevance for discovery of novel drug candidates targeting challenging drug targets such as transcription factors. This highly scalable and quantitative novel method for assessing drug-target interaction within cells can enhance drug discovery programs, and offers potential to rapidly identify clinically relevant hit compounds for challenging drug targets.
Citation Format: Ivan Babic, Nikolas Bryan, Claire Cunningham, Avery Sampson, Daniel Starczynowski, Elmar Nurmemmedov. MICRO-TAG: A novel fluorescence-based real-time cellular target engagement platform for drug discovery [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 3092.
Abstract 3100: Interactive analysis of drug testing data for functional precision oncology with Breeze 2.0
Authors: Potdar Swapnil , Ianevski Filipp , Ianevski Aleksandr , Tanoli Ziaurrehman , Wennerberg Krister , Seashore-Ludlow Brinton , Kallioniemi Olli , Östling Päivi , Aittokallio Tero , Saarela Jani 
Published: March 2024

Abstract
High throughput screening (HTS) is used to screen large numbers of small molecules in cell-based assays to predicting their potential therapeutic response and when applying approved drug libraries using HTS it becomes drug repurposing. The Drug Sensitivity and Resistance Testing (DSRT) platform established at FIMM has been extensively used in testing panels of approved and investigational drugs on cells, both conventional cell lines and primary cell models derived from cancer patient samples. The results help in deepen our understanding of drug efficacy in individual patients and across specific disease to guide future patient stratification.
Breeze 2.0 is an open access, web-based platform for interactive analysis of drug screening data in real time. Breeze accepts raw data in a simple tabular format and generates detailed quality control metrics, plots, dose-response curve fits, drug response quantification in form of IC50/EC50/AUC and Drug Sensitivity Scores (DSS). Besides tabular results, Breeze generates interactive, informative, and intuitive visualizations, such as plate heatmaps, scatterplots, barplots, clustered heatmaps, circular plots, for further analysis. Based on manually-curated published datasets available through Breeze 2.0, users can instantly compare their drug response patterns with the existing DSRT profiles from patient samples, as well as cell lines. Importantly, Breeze 2.0 has integrated curated reference DSRT data tested on bone marrow samples from healthy control individuals, which plays a crucial role in understanding cancer-selective drug response by de-prioritizing generally toxic compounds. The end-users can select multiple healthy controls or relevant patient/cell line samples and choose the drugs of interest to visualize the overlaid dose responses, as well as response quantification metrics. Breeze 2.0 is built in R, PHP, MySQL and is freely accessible at https://breeze.fimm.fi/v2
Citation Format: Swapnil Potdar, Filipp Ianevski, Aleksandr Ianevski, Ziaurrehman Tanoli, Krister Wennerberg, Brinton Seashore-Ludlow, Olli Kallioniemi, Päivi Östling, Tero Aittokallio, Jani Saarela. Interactive analysis of drug testing data for functional precision oncology with Breeze 2.0 [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 3100.