bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4848: Effects of cinnamon extracted under acidic conditions on proliferation of MCF7 cells
Authors: Anderson Madison , Stockert Amy 
Published: April 2023

Abstract
Recent evidence suggests that MCF7 cells utilize free fatty acids as a primary energy source by increasing lipase activity in neighboring adipocytes. Research in our lab suggests that lipase activity is increased by cinnamon extract in differentiated 3T3-L1 adipocytes. We hypothesized that since co-cultures between adipocytes and MCF7 cells demonstrated an increase in lipase activity and increased proliferation, cinnamon extract may increase proliferation of MCF7 cells, making cinnamon an important ingredient to avoid in patients with breast cancer. Cells were plated and treated with varying amounts of cinnamon and monitored for proliferation using the MTT assay. Cells consistently, albeit not significantly, showed an increase in proliferation when treated with cinnamon. Additional studies need to be completed in order to confirm these effects and look for significance, although the importance of this finding warrants rapid reporting. Our lab will examine the effects of cinnamon extract at varying concentrations on MCF7 cell proliferation under variable media conditions as well as monitoring the lipase activity in the MCF7 cells.
Citation Format: Madison Anderson, Amy Stockert. Effects of cinnamon extracted under acidic conditions on proliferation of MCF7 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 4848.
Abstract 4850: High salt diet induced tumor initiating stem cells mediate breast cancer progression
Authors: Tucker Lisa , Reid Sonya , Rathmell Jeffrey C. , Tiriveedhi Venkataswarup 
Published: April 2023

Abstract
High-salt (sodium chloride) diets have been associated with several chronic inflammatory diseases. While the role of chronic inflammation in cancer is well established, the specific role of high salt diet in carcinogenesis is unknown. Previous studies with syngeneic murine breast cancer models, both in our laboratory and others, have shown that high salt (HS) diet induced tumor regression through inflammatory activation of anti-tumor adaptive immune responses. We tested this counter-intuitive and suspiciously beneficial role of HS diet by performing sequential passage studies in preclinical murine models. Six week old mice were placed on high salt diet for 2 weeks prior to injection with syngeneic 4T1 and Py230 triple negative breast cancer cells (into BALB/c and C57Bl/6J mice, respectively, referred to as passage-1). Tumors were harvested after four weeks of injection. The cancer cells depleted of immune cells were collected from these harvested tumors and reinjected into new non-tumor bearing mice. This cycle was repeated three times. In passage-1 cohort, by day 28, HS diet induced reduced tumor progression in both 4T1-BALB/c (267 ± 59 mm3) and Py230-C57Bl/6J (238 ± 54 mm3) as compared to regular salt (RS) diet cohort (611 ± 94 mm3 and 473 ± 69 mm3, respectively; p&lt;0.05 for both). However, in passage-4 cohort, by day 28, HS diet induced significantly higher tumor progression in both 4T1-BALB/c (806 ± 91 mm3) and Py230-C57Bl/6J (743 ± 81 mm3) models, as compared to regular salt (RS) diet cohort (577 ± 83 mm3 and 462 ± 77 mm3, respectively; p&lt;0.05 for both). Cellular analysis by flow cytometry revealed that there was a 12-19 fold increase in tumor initiating stems cells (TISCs) in passage-4 HS diet cohort compared to RS diet cohort. Mechanistic studies have demonstrated that there was increased TGFβ expression on TISCs obtained from passage-4 HS diet cohort which correlated with enhanced exhaustion phenotype (CTLA4+) of tumor infiltrating adaptive immune cells (CD4 and CD8 T cells) in this cohort. Co-treatment with anti-TGFβ and anti-CTLA4 monoclonal antibodies (mAb) in passage-4 HS diet cohort, significantly reduced tumor progression (p&lt;0.05), as compared to treatment with either mAb alone. Taken together, these data demonstrated that chronic HS diet leads to expansion of TGFβ expressing TISCs leading to host immune exhaustion and tumorigenesis. Importantly, anti-TGFβ mAb exerted a favorable synergistic effect to enhance the anti-tumor efficacy of immune check-point inhibitors.
Citation Format: Lisa Tucker, Sonya Reid, Jeffrey C. Rathmell, Venkataswarup Tiriveedhi. High salt diet induced tumor initiating stem cells mediate breast cancer progression. [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 4850.
Abstract 4874: Hyperforin induces apoptosis and inhibits invasion via inhibiting AKT/NF-ΚB signaling pathway in colorectal cancer cells
Authors: Chen Ying-Tzu , Chiang I-Tsang , Chang Yuan , Hsu Fei-Ting 
Published: April 2023

Abstract
Recently, the incidence of colorectal cancer (CRC) has been increasing year by year and has become the first incidence cancer in Taiwan. Epidermal growth factor receptor inhibitor (EGFR inhibitor) has been recognized as an important target of CRC. Therefore, targeting EGFR and its related signaling could be a potential strategy to overcome this disease. Hyperforin is a natural prenylated phloroglucinol and has been identified as the major molecule responsible for the antidepressant effects. Previous studies indicated that hyperforin has other potentially pharmacologically meaningful biological properties, including antibacterial ability and inhibition of inflammatory mediators. Numerous studies have also pointed out the anti-tumor potential of hyperforin is associated with the induction of apoptosis signaling. However, whether hyperforin may regulate CRC progression and its underlying mechanism is unclear. In our study, we used the MTT assay to prove the cytotoxicity of CRC cells (HT29 and HCT116 cells) was induced by hyperforin. We then used the flow cytometry to confirmed that hyperforin may induce both extrinsic/intrinsic apoptotic pathways in CRC cells. We further demonstrated hyperforin-induced apoptosis pathways is associated with mitochondrial-dependent apoptosis and death receptor dependent apoptosis. Then, transwell invasion, migration, and wound healing assay results proved the inhibition effect by hyperforin in HT29 and HCT116 cells. Additionally, we suggested that hyperforin can effectively inhibit EGFR downstream genes MEK-ERK and AKT signaling, as well as inhibit the phosphorylation of NF-ΚB and the nuclear translocation in CRC cells. In sum, our results show that hyperforin can inhibit the apoptosis and metastasis ability of CRC cells by inhibiting both AKT/NF- ΚB and ERK/NF-ΚB signaling pathway.
Citation Format: Ying-Tzu Chen, I-Tsang Chiang, Yuan Chang, Fei-Ting Hsu. Hyperforin induces apoptosis and inhibits invasion via inhibiting AKT/NF-ΚB signaling pathway in colorectal cancer 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 4874.
Abstract 4913: Enhancer RNA profiles predict sensitivity to a novel GPX4 inhibitor
Authors: Read Timothy , Simpson David , Rimel Jenna , Rhine Christy , Pham Casey , Liechty Cole , Martin Eric , Azofeifa Joey 
Published: April 2023

Abstract
Inhibition of the GPX4 enzyme leads to the rapid accumulation of toxic lipid peroxides and cell death through a process known as ferroptosis. This mechanism has recently garnered significant attention in the field of oncology because many difficult-to-treat tumor types are particularly susceptible to this non-canonical form of cell death. However, robust biomarkers that predict sensitivity to ferroptosis are needed to help select well-defined tumor subtypes and patient segments that are likely to respond to GPX4-targeting. Our nascent RNA platform measures the active transcription of not only protein-coding transcripts, but also transcripts initiating from enhancer regions (enhancer RNAs) critical for defining cell type. We reasoned that these data could afford the unique opportunity to identify non-coding transcripts that could serve as novel biomarkers of sensitivity to ferroptosis. We recently discovered a potent and selective GPX4 inhibitor and profiled the compound for its ability to induce ferroptosis across a diverse group of cancer cell types. We chose several of the most sensitive and resistant cell lines for further examination using our nascent RNA platform and identified novel relationships between sensitivity to ferroptosis and cell-specific enhancer RNA profiles. Importantly, enhancer RNA profiles were more effective at stratifying sensitive and resistant cell lines than protein-coding gene expression. Using enhancer RNA expression profiles as biomarkers of drug sensitivity represents a novel strategy that could ultimately improve our ability to select patient cohorts more likely to benefit from emerging drug candidates and established therapeutics.
Citation Format: Timothy Read, David Simpson, Jenna Rimel, Christy Rhine, Casey Pham, Cole Liechty, Eric Martin, Joey Azofeifa. Enhancer RNA profiles predict sensitivity to a novel GPX4 inhibitor. [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 4913.
Abstract 4931: Novel cancer suppressing role of REIC/DKK3 protein through a downregulation of cell surface PD-L1 in breast cancer cells
Authors: Gohara Yuma , Tomonobu Nahoko , Kinoshata Rie , Audebert Lena , Chen Youyi , Komalasari Ni Luh Gede Yoni , Jiang Fan , Yoshizawa Chikako , Murata Hitoshi , Yamamoto Ken-ichi , Sakaguchi Masakiyo 
Published: April 2023

Abstract
Adenovirus vector carrying REIC gene (Ad-REIC) is currently in clinical evaluation. The anti-cancer effect of Ad-REIC is mainly caused by two ways, cancer specific apoptosis via endoplasmic reticulum stress with an abundant REIC protein and indirect immune effects by the secreted REIC protein. The former had been well studied that gave us general comprehension of its mechanisms, however latter has still not been fully elucidated. To clear this, we have aimed to identify putative receptor(s) to the extracellularly secreted REIC protein, and have fortunately succeeded to identify five candidates. Surprisingly, the identified receptors all worked to bind with PD-L1 and hold it to stabilize on the plasma membrane, and the REIC binding to the receptors induced liberation of PD-L1 from the receptors’ lock, resulting in an accelerated degradation of PD-L1. This novel insight may lead to the elucidation in important part of the REIC-mediated indirect anti-cancer role.
Citation Format: Yuma Gohara, Nahoko Tomonobu, Rie Kinoshata, Lena Audebert, Youyi Chen, Ni Luh Gede Yoni Komalasari, Fan Jiang, Chikako Yoshizawa, Hitoshi Murata, Ken-ichi Yamamoto, Masakiyo Sakaguchi. Novel cancer suppressing role of REIC/DKK3 protein through a downregulation of cell surface PD-L1 in breast cancer 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 4931.
Abstract 5015: Wee1 inhibition and its synthetic lethal combination with Chk1 inhibition in mouse model of neuroendocrine prostate cancer
Authors: Chao Yapeng , Chen Yuzhou , Liu Yu , Connelly Jaclyn A. , Wang Hong , Wang Qiming Jane 
Published: April 2023

Abstract
The mitotic regulator Wee1 is a critical regulator of G2/M cell cycle checkpoint and DNA damage response pathways. Wee1-targeted agents are under active clinical investigation in multiple cancer types. However, Wee1 and its inhibitors have not been well studied in prostate cancer, particularly neuroendocrine prostate cancer (NEPC). In this study, we investigated the therapeutic potential of Wee1 inhibitor AZD1775 and its synthetic lethal combination with Chk1 inhibitor in the context of NEPC. Our data demonstrated increased Wee1 expression in NEPC cells and tumors. Treatment of NEPC cells with AZD1775 inhibited NEPC tumor cell survival with greater potency as compared to other prostate cancer cells, demonstrating increased vulnerability of NEPC cells to Wee1 inhibition. We further identified synthetic lethality between the inhibition of Wee1 and several protein kinases, particularly Chk1, another key G2/M checkpoint kinase. Using an autochthonous adenocarcinoma mouse prostate (TRAMP) model that gives rise to NEPC tumors, we assessed the efficacy of AZD1775 and a highly selective Chk1 inhibitor SRA737 as single agents and in combination on the progression, survival, and metastatic spread of NEPC tumors in vivo. AZD1775 and SRA737 when used as single agents significantly suppressed tumor growth, improved overall survival, and incidence of distant metastases of mice with NEPC tumors. The combination of AZD1775 and SRA737 on a sequential 2-wk treatment schedule was more efficacious in suppressing tumor growth and metastasis than each drug alone in castrated TRAMP NEPC tumors. Mechanistically, the combination of Chk1 and Wee1 inhibitors synergized to reduce the inhibitory phosphorylation of CDK1 at Y15 and Cdc25c at S216, resulting in enhanced activation of CDK1/cyclin B complex, abrogation of G2/M checkpoint, and consequent premature mitotic entry, which ultimately led to mitotic catastrophe and apoptosis. Our findings provide promising preclinical evidence supporting the therapeutic values of Wee1 and Chk1 inhibitors as single agents and in combination for the treatment of NEPC.
Citation Format: Yapeng Chao, Yuzhou Chen, Yu Liu, Jaclyn A. Connelly, Hong Wang, Qiming Jane Wang. Wee1 inhibition and its synthetic lethal combination with Chk1 inhibition in mouse model of neuroendocrine prostate 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 5015.
Abstract 5191: Modeling age-related changes in the tumor microenvironment in an orthotopic immunocompetent murine pancreatic cancer model - a novel approach
Authors: Green Morgan M. , Fujimoto Tara , Taniguchi Cullen , Fowlkes Natalie 
Published: April 2023

Abstract
Pancreatic cancer is the third leading cause of cancer-related deaths in the U.S. and is most frequently diagnosed between the ages of 65-74 years. Only 11.5% of patients are expected to survive 5 years after diagnosis. There is extensive evidence that tumor microenvironment (TME) plays a critical role in cancer progression and metastasis. Despite the fact that most patients are diagnosed over the age of 60, most preclinical murine tumor models utilize young, healthy, adolescent mice, failing to account for structural and/or functional changes in stroma and immune cells that occur in tissues over time and contribute to tumor progression. Marked differences in lifespan between mice and humans preclude natural development of many age-related physiologic changes in mice that occur in humans over the course of decades. We performed a pilot study to test our hypothesis that KPC pancreatic tumors grown orthotopically in the pancreas of genetically engineered, C57BL/6-Tg (LMNA*G608G) HClns/J mice, a model of Hutchinson-Gilford progeria syndrome with features of accelerated aging, would have altered tumor growth in comparison to tumors in age-matched wild type controls. We found that tumor growth in LMNA mice outpaced that of WT mice. Quantitative digital image analysis showed significantly reduced intratumoral infiltration of CD45+ leukocytes in LMNA mice in comparison to WT (p=0.0098). There was a significant reduction in tumor-infiltrating CD3+ T cells (p=0.038) and F4/80+ macrophages (p=0.0102). Our data supports the hypothesis that functional, age-related, immune and/or stromal changes in the TME impact pancreatic tumor growth and progression. Innovative strategies that better model age-related changes in the TME may better recapitulate the aggressive course of pancreatic cancer in aged patients.
Citation Format: Morgan M. Green, Tara Fujimoto, Cullen Taniguchi, Natalie Fowlkes. Modeling age-related changes in the tumor microenvironment in an orthotopic immunocompetent murine pancreatic cancer model - a novel approach. [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 5191.
Abstract 5197: NCG-hIL2 mice: a novel model to support the development of T regulatory and NK cells
Authors: Zhang Xinxin , Wu Meirong , Wang Huiyi , Yu Weiwei , Zhu Fang , Xu Jianming , Sun Hongyan , Wang Hongyu , Ju Cunxiang , Chen Santi Suryani , Li Zhiying , Moore Mark Wade , Zhao Jing , Gao Xiang 
Published: April 2023

Abstract
Interleukin 2 is a key molecule that promotes the expansion and activation of lymphocytes, including T regulatory cells (Tregs) and natural killer (NK) cells. Tregs are specialized subpopulation of T cells that suppress the immune response by inhibiting T cell proliferation and cytokine production. NK cells are the predominant innate immune subset that mediates anti-tumor and anti-viral responses. Both Tregs and NK cells are two critical immune cells that play an important role in cancer immunotherapy, however, there is a lack of models that supports the in vivo status of these two immune subsets. To address this, we developed a severe immunodeficient mouse model, NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt (NCG-hIL2), by knocking in the human IL-2 gene on the NCG background. The ability of this model to support Treg and NK cells was then compared to NCG and tested with the reconstitution of human peripheral blood mononuclear cells (PBMC) and human hematopoietic stem cells (HSC).
In the PBMC engrafted mice, the presence of IL-2 supported the development of T cells, especially the Tregs, with 53.74% in Tregs in NCG-IL2 compared to 4.81% in NCG mice (test at 2 weeks of reconstruction). Similarly, the NK cells are also supported with those cohort engrafted with human HSC (91.63% in NK cells in NCG-IL2 compared to 0.53% in NCG mice, test at 10 weeks of reconstruction). Notably, reconstituted NK cells expressed various NK receptors such as NKp30, NKp44, NKp46, NKG2D, and CD94 in NCG-IL2 mice. They produced comparable levels of granzyme when compared with human peripheral blood-derived NK cells, and a considerable amount of perforin protein was detected in the plasma of huHSC-NCG-hIL2 mice.
In conclusion, compared with NCG mice, humanized NCG-hIL2 mice can reconstruct more abundant immune cells and have a wider application in anti-tumor research. It is an ideal model for the preclinical study of anti-tumor therapeutics.
Citation Format: Xinxin Zhang, Meirong Wu, Huiyi Wang, Weiwei Yu, Fang Zhu, Jianming Xu, Hongyan Sun, Hongyu Wang, Cunxiang Ju, Santi Suryani Chen, Zhiying Li, Mark Wade Moore, Jing Zhao, Xiang Gao. NCG-hIL2 mice: a novel model to support the development of T regulatory and NK 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 5197.
Abstract 520: Investigation the function and application of spermine in castration-resistant prostate cancer
Authors: Sun Jingkai , Chiu Peter Ka-Fung , Xie Tingting , Teoh Jeremy Yuen-Chun , Ng Chi-Fai 
Published: April 2023

Abstract
Introduction & Objectives: Spermine (Spm) is a typical metabolite that is highly concentrated in healthy prostate epithelium maintaining cell growth and functions. Our previous studies found that Spm was significantly decreased in PCa tissue than in benign prostate tissue, as was the urinary Spm in PCa. This study aimed to reveal the specific role of Spm in PCa.
Materials & Methods: In this study, Spm was resupplied to castration-resistant prostate cancer (CRPC) cells (PC3 and DU145). Following Spm treatment, MTT (methyl thiazolyl tetrazolium) and EdU (5-ethynyl-2’-deoxyuridine) assay were used to determine the cell proliferation of CRPC cell lines. Cellular apoptosis, cell cycle distribution and mitochondrial membrane potential were analyzed by flow cytometry. Cellular reactive Oxygen species (ROS) level was measured by fluorescence microscope. mRNA and ATAC sequencing in spermine-treated CRPC cells were performed to reveal the related mechanism for Spm effect.
Results: In the in vitro studies, Spm was found to inhibit the cell viability of CRPC cells. Transwell assays demonstrated that Spm impaired migration and invasion ability. And Spm blocked tumor progression by inducing G2/M arrest and cellular apoptosis in CRPC cells dose-dependently. mRNA seq revealed that a series of genes were altered after Spm treatment and indicated the potential functional pathway of Spm might be mitophagy. We integrated mRNA seq data with ATAC seq profiles and accessed those genes regulated by polyamine metabolism and Spm-induced mitophagy. Results showed the sequencing tracks for the HMOX1 locus contain higher ATAC-seq peaks at the promoter under Spm treatment. Spm could affect oxidative phosphorylation which will lead to mitophagy and mitochondrial metabolism by modulating the transcriptional accessibility of genes. After Spm treatment, cellular ROS was upregulated while the mitochondrial membrane potential collapsed. Subsequently, western blot results showed that PINK1-mediated mitophagy related-proteins were significantly regulated.
Conclusion: Our results indicated that Spm treatment led to mitochondrial dysfunction and subsequently degraded through mitophagy in CRPC cells. Our findings could provide a theoretical basis and have preliminary clinical implications in developing Spm as a promising agent against CRPC by inducing cellular mitophagy in CRPC cells.
Citation Format: Jingkai Sun, Peter Ka-Fung Chiu, Tingting Xie, Jeremy Yuen-Chun Teoh, Chi-Fai Ng. Investigation the function and application of spermine in castration-resistant prostate 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 520.