bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 364: Multi-omics approaches revealed the involvement of immune cells in skeletal muscles of lung cancer cachexia mouse model
Authors: Park Se-Young , Kim Bomi , Lee Myunggyo , Lee Haeseung , Song Na-Young 
Published: June 2023

Abstract
Cancer-associated cachexia (CAC) is a multifactorial syndrome characterized by loss of body weight and skeletal muscle mass that cannot be fully recovered by nutritional support. It accounts for approximately 20 % of cancer-related deaths. However, there are no approved treatments for CAC yet. In order to better understand CAC, we wanted to apply the multi-omics approaches to simultaneously assess tumors and skeletal muscles in CAC mouse models. First, we established a lung cancer cachexia mouse model by orthotopic transplantation of KRAS-mutant lung cancer cells. Lung tumor-bearing mice developed cachexia at 7 weeks post injection, showing over 20 % of body weight loss and wasting of skeletal muscles and fats. The histological and immunoblotting analyses revealed degradation of gastrocnemius (GA) and tibialis anterior (TA) muscles in CAC group. Then, we performed the bulk RNA sequencing to assess transcriptomic changes in lung tumors and GA muscles of CAC mice. In lung tumors, genes associated to ATP metabolic process was upregulated. However, skeletal muscles of CAC mice showed upregulation of genes involved in protein degradation and immune responses, while genes related to energy metabolism were downregulated. Notably, the immunohistochemical staining revealed the increased numbers of infiltrating macrophages and CD8+ T cells in skeletal muscles of CAC mice. These data suggest the involvement of immune cells in lung cancer-associated cachexia. To further identify the distinct immune cell populations involved in CAC, the single cell RNA sequencing was conducted using CD45+ immune cells infiltrated into GA muscles of CAC mice. The enrichment of natural killer cells, dendritic cells and T cells was detected in GA of CAC mice. Moreover, we confirmed the roles of the infiltrating immune cells by using the neutralizing antibodies in CAC mice. Taken together, these data suggest the involvement of the immune cells in the skeletal muscle wasting of CAC mice. These multi-omics approaches will shed light on development of therapeutics for cancer-induced cachexia.
Citation Format: Se-Young Park, Bomi Kim, Myunggyo Lee, Haeseung Lee, Na-Young Song. Multi-omics approaches revealed the involvement of immune cells in skeletal muscles of lung cancer cachexia mouse model [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 364.
Abstract 3800: The disruption of miR-125b-SLC1A5 cascade defines the oncogenicity and differential immune profile in oral carcinoma
Authors: Liu Ying-Chieh , Liu So-Yu , Lin Yu-Cheng , Liu Chung-Ji , Chang Kuo-Wei , Lin Shu-Chun 
Published: June 2023

Abstract
Head and neck squamous carcinoma (HNSCC) including oral SCC (OSCC) is a worldwide malignancy that requires vigorous efforts for interception. The metabolic reprogramming sustains malignant tumor cells to overcome stressful microenvironments. As the glutamine is the one of the essential components which helps cells to erase reactive oxygen species and energy production, the increased uptake of glutamine is a common metabolic hallmark in cancers. Bioinformatic analysis of TCGA HNSCC datasets and RNAseq results in our cohort indicated that solute carrier family 1 member 5 (SLC1A5) is the most eminently dysregulated transporter member among the seven glutamate or neutral amino acid transporters in SLC1A family. This work identified that the knockdown of SLC1A5 expression decreased in vitro oncogenicity, xenografic tumorigenesis and glutamine uptake; increased oxidative stress, cell cycle arrest, and sensitivity to cisplatin and ferroptosis inducer in OSCC cells. By way of contrast, the upregulation of endogenous SLC1A5 expression mediated by CRISPR/dCas9 activation system drove the OSCC oncogenesis. The reporter assay and functional analysis demonstrated that suppressor miRNA miR-125b targeted and attenuated SLC1A5, while NEAT1 lncRNA sponged and ablated miR-125b-SLC1A5 axis. The analysis of TCGA and GEO datasets confirmed the concordant upregulation of NEAT1 and downregulation of miR-125b along with the SLC1A5 upregulation in tumors. Besides, SLC1A5 upregulation defined the worse HNSCC patient survival. In our tumor cohort, OSCC harboring higher SLC1A5 expression had lower CD4+ immune score, and higher scores in M0 and M1 macrophage. GSEA algorithm further deciphered that tumors having higher SLC1A5 expression manifested the repression in glycolysis, apoptosis and p53 signaling. This study concludes that the frequent disruption of NEAT1-miR-125b-SLC1A5 cascade modulates the pluripotent oncogenic activities, the treatment efficacy and the immune landscape in oral carcinoma.
Citation Format: Ying-Chieh Liu, So-Yu Liu, Yu-Cheng Lin, Chung-Ji Liu, Kuo-Wei Chang, Shu-Chun Lin. The disruption of miR-125b-SLC1A5 cascade defines the oncogenicity and differential immune profile in oral carcinoma. [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 3800.
Abstract 3810: MicroRNA-483-5p inhibits cell steatosis and fibrosis by targeting PPARa, TIMP2 and HCC cell proliferation by modulating notch signaling
Authors: Niture Suryakant , Gadi Sashi , Qi Qi , Gyamfi Maxwell , Rios-Colon Leslimar , Varghese Rency , Ressom Habtom , Kumar Deepak 
Published: June 2023

Abstract
MicroRNAs (miRNAs) are small non-coding RNA molecules that bind with 3’ untranslated regions (UTRs) of genes and regulate expression. Downregulation of miR-483-5p (miR-483), is associated with the progression of hepatocellular carcinoma (HCC). However, the molecular and mechanistic role of miR-483 in nonalcoholic fatty liver disease (NAFLD), alcoholic fatty liver diseases (AFLD), and HCC remain elusive. In the current study, we investigated the biological significance of miR-483-5p in NAFLD, AFLD, and HCC in vitro and in vivo. Our data show that the expression of miR-483 was downregulated in tumor samples from HCC patients. Overexpression of miR-483 in HCC cells dysregulated Notch signaling, inhibited cell proliferation/migration, induced apoptosis, and increased sensitivity towards sorafenib/regorafenib; anti-HCC drugs. Interestingly, miR-483 overexpression downregulated cell steatosis and fibrogenic signaling in HCC cells. Mechanistically, miR-483 targets peroxisome proliferator-activated receptor α (PPARα) and tissue inhibitor of metalloproteinases 2 (TIMP2) gene expression by binding to 3’-UTR and suppress cell steatosis and fibrosis. Down-regulation of miR-483 was observed in mice fed with a high-fat diet (HFD) or alcohol which lead to increased hepatic steatosis/fibrosis. Our data suggest that miR-483 inhibits cell steatosis and fibrogenic signaling, and functions as a tumor suppressor in HCC. Therefore, miR-483 may be used as a novel therapeutic target for NAFLD/AFLD/HCC management in patients with fatty live diseases/HCC.
Citation Format: Suryakant Niture, Sashi Gadi, Qi Qi, Maxwell Gyamfi, Leslimar Rios-Colon, Rency Varghese, Habtom Ressom, Deepak Kumar. MicroRNA-483-5p inhibits cell steatosis and fibrosis by targeting PPARa, TIMP2 and HCC cell proliferation by modulating notch signaling. [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 3810.
Abstract 3812: Circular RNAs from the PAX5 oncogene are overexpressed in B-cell malignancies and modulate cancer processes
Authors: Martin Danick M. , Hannay Brandon , Martin Alexis , Veilleux Vanessa , Finn Nicholas , Robichaud Gilles A. 
Published: June 2023

Abstract
Circular RNAs (circRNAs) represent a new class of gene products involved in many biological processes. Due to their ability to bind and modulate co-interacting proteins and microRNAs (miRs), circRNAs represent new signaling mediators in cell biology and cancer processes. Recently, we identified circRNAs from the PAX5 oncogene (circPAX5) in B-cells. Given that PAX5 gene products are well established as potent oncogenic regulators of B-cell cancer lesions, we hypothesized that circPAX5 may also be potentially involved in pathogenic processes of B-cell malignancies. In this study, we wanted to understand the role of circPAX5 in B-cell cancer processes and elucidate new potential targets for diagnostic and therapeutic avenues. Using a series of B-cell cancer models and clinical samples, we sequenced, mapped, and profiled circPAX5 expression profiles and found that circPAX5 products are indeed overexpressed in various cancer cell types where the predominant expressed isoform consisted of exons 2 to 5 (circPAX5_2-5) of the PAX5 locus. In addition, we isolated circPAX5 complexes from cancer cells and identified co-interacting small non-coding RNAs, notably microARNs (miRs) by deep sequencing. To further elucidate the functional role of circPAX5 and miR co-interactions, selected miRs from the list were then conditionally overexpressed in B-cells followed by cellular phenotypic assays. Altogether, our results characterize new signaling products and pathways in B-cells. Our data also suggests that circPAX5 products are involved in B-cell cancer processes and could potentially represent new cancer pathways targeted for strategic therapeutic and/or diagnostic strategies in B-cell cancer lesions
Citation Format: Danick M. Martin, Brandon Hannay, Alexis Martin, Vanessa Veilleux, Nicholas Finn, Gilles A. Robichaud. Circular RNAs from the PAX5 oncogene are overexpressed in B-cell malignancies and modulate cancer processes. [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 3812.
Abstract 3863: Aminoflavone confers activity against aromatase inhibitor-resistant breast cancer cells in part via miR125b2-3p restoration
Authors: Brantley Eileen J. , Mavingire Nicole , Khan Salma , Nagaraj Gayathri , Angeloni Shawnee , Wang Charles , Soto Ubaldo 
Published: June 2023

Abstract
Aromatase inhibitor therapy is the most crucial adjuvant treatment option for postmenopausal women with hormone receptor-positive (HR+) non-metastatic breast cancer. However, up to 30% of these patients will experience relapse due in part to aromatase inhibitor resistance. We recently identified miR125b2-3p as a putative tumor suppressor in HR+ breast cancer. We also found that small molecule Aminoflavone (AF) induces miR125b2-3p expression in HR+ breast cancer cells. In the current study, we hypothesized that AF confers anticancer actions in breast cancer cells resistant to aromatase inhibitors via miR125b2-3p reactivation. Using the Alamar Blue and colony forming assays, we discovered that AF demonstrated anticancer activity in estrogen-deprived resistant (EDR) cells designed to mimic aromatase inhibitor resistance. AntagomiR125b2-3p enhanced, while miR125b2-3p mimics diminished colony formation of EDR cells. AF-mediated suppression of colony formation in EDR cells was attenuated during co-treatment with antagomiR125b2-3p and was enhanced during co-treatment with miR125b2-3p mimics. Both miR125b2-3p mimics and AF suppressed EDR cell migration. AntagomiR125b2-3p counteracted AF-mediated suppression of cell migration. Our in silico profiling studies identified the alpha6-integrin, a mediator of breast cancer stem cell activity and metastasis, as one miR-125b2-3p target. Immunohistochemistry of patient tumor samples revealed that alpha 6-integrin protein expression intensified following relapse on the aromatase inhibitor anastrozole. MCF-7 cells transfected to overexpress the alpha 6-integrin were less responsive to anastrozole than those transfected with empty vector. These data suggest that AF restores the tumor suppressor function of miR125b2-3p to inhibit the alpha 6-integrin and confer activity against aromatase inhibitor-resistant breast cancer.
Citation Format: Eileen J. Brantley, Nicole Mavingire, Salma Khan, Gayathri Nagaraj, Shawnee Angeloni, Charles Wang, Ubaldo Soto. Aminoflavone confers activity against aromatase inhibitor-resistant breast cancer cells in part via miR125b2-3p restoration. [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 3863.
Abstract 488: New therapeutic strategies suppressing NAD+ and ATP production in cancer metabolism specific to 3D cultured ovarian cancer cells
Authors: Kudo Kei , Harrington Brittney S. , Ning Franklin , Kamdar Rahul , Shibuya Yusuke , Korrapati Soumya , Fergusson Maria , Kucera Calen , Massimo Fantini , Annunziata Christina M. 
Published: June 2023

Abstract
Ovarian cancer is the gynecological cancer with the highest mortality rate. As resistance to treatment is acquired and many patients relapse, new treatment strategies are needed. A model that strongly reflects the features of recurrent ovarian cancer in the peritoneal cavity is the "cancer stem cells (CSCs)," which are enriched when cells are cultured in three dimensions (3D) on low-attachment plates. The unique metabolic system of the "3D CSCs" is the subject of a novel therapeutic approach. Here, we show that ovarian cancer 3D CSCs have strong NAD+ production capacity, which is particularly dependent on nicotinamide phosphoribosyl transferase (NAMPT), known as the rate-limiting enzyme in the salvage pathway of NAD+ production. We found that NAMPT inhibition blocks NADPH and ATP production as well as NAD+, and subsequently suppresses the synthesis capacity of proteins, fat droplets, and cholesterol in the 3D ovarian cancer cells. In addition, we found that the combination of NAMPT inhibitor and the ALDH inhibitor disulfiram had a pronounced synergistic effect. This synergy inhibits oxidative phosphorylation and ALDH activity and promotes reactive oxygen species and apoptosis via caspase 3/7 cleavage, which leads to death of the 3D cultured cells. Our results demonstrate that high NAMPT expression in ovarian cancer is likely to be a strong poor prognostic factor and that the combination of a NAMPT inhibitor and disulfiram could be a new treatment option to treat or prevent recurrent ovarian cancer. Our novel findings focus on NAMPT addiction as a property of ovarian cancer 3D CSCs, and strongly suggest the combined inhibition of NAMPT and ALDH as a potential therapeutic strategy.
Citation Format: Kei Kudo, Brittney S. Harrington, Franklin Ning, Rahul Kamdar, Yusuke Shibuya, Soumya Korrapati, Maria Fergusson, Calen Kucera, Fantini Massimo, Christina M. Annunziata. New therapeutic strategies suppressing NAD+ and ATP production in cancer metabolism specific to 3D cultured ovarian 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 488.
Abstract 5257: Activation of NRF2-mediated oxidative stress response pathway by curcumin analog FLLL12: Implication for chemoprevention
Authors: Lukmon Raji , Adeluola Adeoluwa A. , Amin A.R.M. Ruhul 
Published: June 2023

Abstract
Purpose: Carcinogenesis is a multi-step complex process initiated with irreversible genetic mutation due to endogenously derived or carcinogen-induced oxidative stress. Activation of the antioxidant pathways ameliorates oxidative stress, protects cells from carcinogenic insults, and plays a pivotal role in chemoprevention. We have previously reported that FLLL12 is a potent curcumin analog, possesses in vitro and in vivo anticancer activity, and has better pharmacokinetic profiles than curcumin. The purpose of the current study is to identify novel pathways activated by FLLL12 using RNASeq analysis.
Methods: MDA686, a head and neck cancer cell line, were treated with 2 µM FLLL12 for 24h. Total RNA was isolated and used for RNASeq analysis. 2-fold differentially expressed genes were used for Ingenuity Pathway Analysis to identify the most significantly affected pathways. Real-time qPCR and western blotting were used to confirm the expression of the genes associated with the most significantly affected pathways and their protein products respectively in normal, premalignant, and malignant cell lines.
Results: Whole transcriptome analysis using RNASeq identified 641 genes that were either upregulated or downregulated by 2-folds after FLLL12 treatment. Enrichment of this gene set with Ingenuity Pathway Analysis identified the ferroptosis signaling pathway, the tumor microenvironment pathway, and the NRF2-mediated oxidative response pathway as the top three most significantly affected pathways by FLLL12. We confirmed the activation of HMOX-1, NQO1, SLC7A11, and GCLC mRNA and proteins in HOK (normal), MSK-LEUK1 (premalignant), and MDA686TU (malignant) cells. Although these genes are common for the ferroptosis signaling pathway and the NRF2-mediated oxidative response pathway, treatment of cells with ferroptosis inhibitors, ferrostatin 1, and deferoxamine, had no effect on FLLL12-induced cell death suggesting that these genes are associated with oxidative stress response pathway.
Conclusions: Our results strongly suggest that FLLL12 activates the oxidative stress response pathway in normal, premalignant, and malignant head and neck cancer cell lines and has strong promise for chemoprevention.
Citation Format: Raji Lukmon, Adeoluwa A. Adeluola, A.R.M. Ruhul Amin. Activation of NRF2-mediated oxidative stress response pathway by curcumin analog FLLL12: Implication for chemoprevention. [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 5257.
Abstract 5264: Cucurbitacin D modulates the Nrf2 signaling pathway and protects against benzo[a]pyrene-induced liver injury
Authors: Malik Shabnam , Rodriguiez Anyssa , Sikander Mohammed , Zubieta Daniel , Halaweish Fathi T. , Chauhan Subhash C. , Jaggi Meena 
Published: June 2023

Abstract
Background: Accumulating studies have shown strong correlation of HCC and co-morbidity factors including smoking. Tobacco smoke contains benzo[a]pyrene, which is extremely carcinogenic and contributes to liver damage. Cucurbitacin, a triterpene, has a wide range of biological activities, including antioxidant, anti-inflammatory, and anti-cancer properties. However, their hepatoprotective effects remain poorly understood. In the current study, we examined the hepatoprotective activity of cucurbitacin D, a novel analog of cucurbitacin, against benzo[a]pyrene-induced liver injury in human HepG2 cells.
Method: To investigate the hepatoprotective effect of cucurbitacin D against benzo[a]pyrene-induced liver damage, proliferation, clonogenicity, migration, invasion, Western blotting, and qPCR analyses were performed. The DCFDA assay was performed to determine the level of intracellular reactive oxygen species (ROS) in liver cells.
Results: Functional assays showed that cucurbitacin D exhibited cytoprotective effects against dose-dependent growth inhibition by benzo[a]pyrene in human HepG2 cells. This protective effect was likely associated with antioxidant potential of cucurbitacin D, as evidenced by the attenuation of ROS observed by fluorimeter and fluorescence microscopy. Western blotting analysis demonstrated Cucurbitacin D targets Nrf-2 signaling pathway and associated effector proteins including HO-1 and LC3A in protecting liver cells against benzo[a]pyrene induce oxidative damage. Further studies are underway to understand the underlying molecular mechanism of action.
Conclusion: These findings demonstrate the hepatoprotective effects of cucurbitacin D against benzo[a]pyrene-induced liver damage, making it a promising ingredient for nutritional supplements.
Citation Format: Shabnam Malik, Anyssa Rodriguiez, Mohammed Sikander, Daniel Zubieta, Fathi T. Halaweish, Subhash C. Chauhan, Meena Jaggi. Cucurbitacin D modulates the Nrf2 signaling pathway and protects against benzo[a]pyrene-induced liver injury. [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 5264.
Abstract 5277: Activation of TRPM8 channel suppresses prostate cancer growth and progression
Authors: Asuthkar Swapna 
Published: June 2023

Abstract
Prostate cancer (PC) is one of the most prevalent male malignancies and a leading cause of cancer-related deaths in men. While androgen-deprivation therapy is successful in the early stages of PC, tumor cells eventually become resistant to its effects. With a median survival of 18 months, the shift to androgen-independent prostate cancer (AIPC) has a poor prognosis. Mechanisms causing this change have yet to be explained, however mounting evidence implicates the loss of transient receptor potential melastatin 8 (TRPM8) as a significant contributor. The prostate epithelium normally expresses the ionotropic receptor TRPM8. Our team has recently shown that testosterone-induced activation of TRPM8 enhances Ca2+ absorption and causes apoptosis. This prompted us to propose that increased TRPM8 activity on the plasma membrane is cytotoxic to PC cells and that TRPM8 internalization is a crucial step in the pathogenesis of PC. We examined the amounts of TRPM8 mRNA in benign tumor and metastatic PC patient datasets. TRPM8 mRNA is initially elevated in the early stages of PC but is increasingly lost during the progression to AIPC. In addition, male and female TRPM8−/− mice exhibited increased serum testosterone levels, heightened AR activity, and activation of cell cycle, invasion, and adhesion-related effectors. In both AR+ and AR− xenograft models, our research reveals that TRPM8 possesses potent antitumor properties. Given this, investigating the in vivo role of TRPM8 in PC has the potential to significantly enhance patient outcomes by preventing progression to the androgen-independent state.
Citation Format: Swapna Asuthkar. Activation of TRPM8 channel suppresses prostate cancer growth and 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 5277.