bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1999: Repurposing an antibiotic for breast cancer treatment using liposomes as a delivery system
Authors: Ataide Janaina Artem , Filipczak Nina , Yalamarty Satya Siva Kishan , Mazzola Priscila Gava , Torchilin Vladimir P. 
Published: April 2023

Abstract
Purpose: Scientific community is always searching for alternatives for cancer treatment and promoting drug repurposing is one of the ways. Rifamycin is a well-known antibiotic, that inhibits RNA synthesis and probably can be explored as cytotoxic agent. Thus, our goal was to repurpose rifamycin for breast cancer treatment using liposomes as a delivery system.
Methods: Liposomes were produced by thin-film evaporation method using egg phosphatidylcholine, cholesterol and DOPE-PEG5k (70:25:5, molar ratio). Non-encapsulated drug was removed using dialysis bags and encapsulated drug was directly determined by UV spectrophotometer. Liposomes were characterized regarding size and surface charge by dynamic light scattering. Liposomes were stored at 4°C and 25°C for stability evaluation, monitoring nanoparticles parameters and drug encapsulation. Formulation biocompatibility was evaluated by hemolysis assay. Finally, cytotoxicity of rifamycin SV and liposomes was evaluated in MCF-7 and MDA-MB-231 cell lines.
Results: Blank liposomes (without drug) and rifamycin-loaded liposomes showed size smaller than 100 nm and polydispersity around 0.2, with slightly negative zeta potential. Rifamycin encapsulation in liposomes was 3mg of drug/10mg of lipid films. Both formulations were stable for at least 21 days when stored at 4°C, keeping above 60% of drug encapsulated. In the concentrations tested (0.5mg/mL of drug, 2mg/mL of lipids), liposomes formulation (blank and loaded) and free rifamycin were biocompatible and non-hemolytic, since hemolysis was below 6%. Blank liposomes were not cytotoxic in tested cell lines. Free rifamycin and rifamycin-loaded liposomes demonstrated the IC50 in the same range between 41 and 46 µg/mL in 24h and 48h for both MCF-7 and MDA-MB-231.
Conclusions: Rifamycin was successfully encapsulated in liposomes, leading to a stable, biocompatible, and non-hemolytic formulation. The liposomal rifamycin demonstrated strong cytotoxicity towards cancer cells similar to that of the free drug.
Citation Format: Janaina Artem Ataide, Nina Filipczak, Satya Siva Kishan Yalamarty, Priscila Gava Mazzola, Vladimir P. Torchilin. Repurposing an antibiotic for breast cancer treatment using liposomes as a delivery system [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 1999.
Abstract 20: In vitro and in vivo investigation of tumor treating fields for treatment of spinal metastasis
Authors: Tatsui Claudio Esteves , Ledbetter Daniel , Alvarez-Breckenridge Christopher 
Published: April 2023

Abstract
Introduction: Tumor treating fields (TTF) are used for treatment of glioblastoma. Its utilization for spinal metastasis has never been described. We investigate the anti-mitotic effect of TTF to inhibit the growth of human cancer cells in vitro and in vivo models of spinal metastasis.
Methods: In vitro: human derived osteosarcoma (Krib-luc-1) and lung adenocarcinoma (A549-luc) cells were seeded in 5 × 3mm human demineralized bone grafts kept in culture while treated with 0kHz (control) or 150kHZ of TTF for 14 days. Bioluminescence images (BLI) were obtained at baseline and 14 days. In vivo: Krib-Luc-1 cells were surgically implanted via transperitoneal approach to L3 vertebra in nude mice. Animals were treated with 0kHz or 150kHz for 30 days or until death. BLI were obtained at day 0 and every 7 days. MRI was obtained at day 22. Histological analysis was performed at the end of the experiment. Control and TTF-treated groups were compared with two-tailed t-tests.
Results: In vitro: BLI of the control groups demonstrated 5-fold and 34-fold higher tumor signal (photons/sec) than corresponding 150 kHz TTF treatment groups at 14 days (A549 p=0.0289; KRIB p=0.00895). In vivo: All mice receiving 0 kHz treatment displayed hind limb paralysis by day 30, while mice treated with 150 kHz TTF displayed tail drop or no signs of paralysis. MRI and histology confirmed smaller tumors corroborating to BLI (3.67-fold change in photons/sec) (p=0.0212) when the 150 kHz TTF treatment group was compared to controls.
Conclusions: Application of TTF at 150kHz reduced cellular proliferation in both in vitro and in vivo models of spinal metastasis. This is the first report of utilization of TTF for treatment of bony tumors and represents the first evidence that TTF could become a revolutionary therapy for spinal metastasis.
Citation Format: Claudio Esteves Tatsui, Daniel Ledbetter, Christopher Alvarez-Breckenridge. In vitro and in vivo investigation of tumor treating fields for treatment of spinal metastasis [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 20.
Abstract 2009: Gemcitabine-loaded EGFR aptamer for targeted therapy of lung cancer
Authors: Park Jun Young , Cho Ye Lim , Chae Ju Ri , Kang Won Jun 
Published: April 2023

Abstract
Lung cancer is the leading cause of cancer-related death in the world and non-small cell lung cancer (NSCLC) is the most common types of the lung cancer. Epidermal growth factor receptor (EGFR) is an attractive therapeutic target due to its high expression in NSCLC. Gemcitabine (Gem) has shown antitumor activity against many kinds of solid tumors, including NSCLC. Aptamers emerged as promising drug delivery vehicles because of their high binding affinity for the target molecules. The objective of this study was to develop the aptamer-drug conjugates using the EGFR-specific aptamer. EGFR aptamers selected by the SELEX process and gemcitabine was internally incorporated into the EGFR aptamer. In vitro binding affinity of EGFR and Gem-loaded EGFR aptamer was evaluated on EGFR-positive A549, H460, H1299 cell lines, as well as EGFR-negative H522 cells using confocal microscopy. To determine whether the Gem-loaded EGFR aptamer was effectively internalized, Z-stack images were acquired after 1 hr incubation of Cy5-conjugated EGFR aptamer at 37°C. The ex vivo biodistribution of Cy7-conjugated EGFR aptamer was investigated in NSCLC xenograft nude mice. To confirm the antiproliferative effects of Gem-loaded EGFR aptamer, the MTT cell proliferation assay was carried out in NSCLC cells. In the confocal image of EGFR-positive cells, Gem-loaded EGFR aptamers were selectively bound to the cell surface, while no aptamer binding was observed in H522 cells. Z-stack imaging showed that internalized Gem-loaded EGFR aptamer accumulated in EGFR-positive cells. The ex vivo biodistribution data showed that the Gem-loaded EGFR aptamer exhibited higher binding in EGFR-positive A549 tumors than scramble EGFR aptamer. A549 cells showed significant reduction in proliferation following treatment with Gem-loaded EGFR aptamer. Our results indicated that Gem-loaded EGFR aptamer has a potential therapeutic agent in EGFR-positive NSCLC therapy.
Citation Format: Jun Young Park, Ye Lim Cho, Ju Ri Chae, Won Jun Kang. Gemcitabine-loaded EGFR aptamer for targeted therapy of lung 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 2009.
Abstract 2123: Glycine decarboxylase regulates renal carcinoma progression via interferon stimulated gene factor 3-mediated pathway
Authors: Kim Jin Young , Pham Mai Thi Tuyet , Kim Byung Hoon , Seo Ji Hae , Shin Sojin , Ha Eunyoung 
Published: April 2023

Abstract
Glycine decarboxylase (GLDC) is a mitochondrial enzyme that mediates the degradation of glycine as part of the glycine cleavage system; it is implicated as a tumor suppressor in hepatocellular carcinoma but as an oncogene in the lung cancer. Although GLDC expression in the kidney is second highest next to the liver, very little is known as to the role of GLDC in the kidney. Thus, this study was designed to determine the role of GLDC in the renal carcinoma. We found markedly increased expressions of GLDC in patients with renal cell carcinoma (RCC) classified as poor-risk group based on the Memorial Sloan Kettering Cancer Center prognostic model. In vitro studies revealed that cellular proliferation, colony formation, and migration were decreased in GLDC-deficient renal carcinoma cells while those were increased in GLDC-overexpressing renal carcinoma cells. In vivo xenograft studies with GLDC-deficient and -overexpressing cells also revealed that tumor sizes were noticeably decreased in GLDC-deficient cell-injected mice while those were increased in GLDC-overexpressing cell-injected mice. Mechanistically, we found GLDC regulates renal carcinoma progression via interferon (IFN) stimulated gene factor 3 (ISGF3)-mediated pathway. Poly-IC induced mRNA expression of IFN-α more strongly in GLDC-deficient cells. Expressions of IRF9 and STAT2 were increased in GLDC-deficient cells while those were decreased in GLDC-overexpressing cells. Interferon-responsive genes (IFIT1, IFI44, IFI44L, and IFI27) were also regulated by GLDC as evidenced by increased mRNA expressions in GLDC-deficient cells and increased mRNA expressions in GLDC-overexpressing cells. Knock-down of IRF9 and STAT2 in GLDC-deficient cells reversed decreased cellular proliferation, colony formation, and migration. In summary, the data in this study indicates that GLDC regulates renal carcinoma progression via ISFG3-medated pathway and lay a scientific foundation that could support a therapeutic strategy that targets GLDC for the treatment of renal carcinoma.
Citation Format: Jin Young Kim, Mai Thi Tuyet Pham, Byung Hoon Kim, Ji Hae Seo, Sojin Shin, Eunyoung Ha. Glycine decarboxylase regulates renal carcinoma progression via interferon stimulated gene factor 3-mediated pathway [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 2123.
Abstract 2148: Robust detection of somatic genetic alterations in pancreatic cancer ascites
Authors: Kappagantula Rajya L. , Makohon-Moore Alvin P. , Umeda Shigeaki , Karnoub Elias-Ramzey R. , Melchor Jerry P. , Wood Laura D. , Iacobuzio-Donahue Christine A. 
Published: April 2023

Abstract
Introduction: Regardless of the stage at diagnosis most patients with pancreatic ductal adenocarcinoma develop peritoneal disease and some malignant ascites (MA) as well. Prior studies have shown that MA negatively affects overall treatment efficacy and survival. Despite the clinical significance of MA it has not been studied to any great extent.
Methods: We collected MA and matched normal tissue samples at autopsy from 20 PDAC patients who were initially diagnosed at stages IIB to IV. Whole exome or targeted sequencing was previously performed on each PDAC. Each MA sample was centrifuged twice at 4000 RPM first and then at 15000 RPM to separate the cell pellet (CP) from the cell-free ascites fluid. We next extracted DNA from the CP, matched normal tissue, and the cell-free DNA (cfDNA) from the ascites fluid, and all were submitted to the Genomics Core for MSK-IMPACT, a targeted cancer gene panel representing 505 genes.
Results: Results of the first five patients are complete and the remaining are in process. Comparison of the CPs and/or cfDNA to the matched tumor samples indicated 100% concordance for detected variants. However, the somatic alterations of the CP specifically versus the matched cfDNA were divergent in all patients analyzed thus far. Virtually all copy number alterations in all patients were deep deletions (range 66 to 187 cancer genes deleted) affecting multiple DNA repair pathways including homologous recombination deficiency and microsatellite repair.
Conclusions: Samples of MA, when both the cell pellet and cfDNA are sequenced, accurately represent the genetic features of the matched PDAC tissue and may serve as an alternative mode of sampling for precision medicine. Differences in the genetics of the CP versus the cfDNA suggest polyclonality in the peritoneal space. Moreover, the finding of deep deletions in targetable DNA repair pathways suggest a therapeutic vulnerability for exploration. Given that paracentesis is often performed in the palliative setting and may be performed multiple times over the course of a patients’ management, it also offers an opportunity to determine how clonal dynamics in the peritoneal space change over time. Patients with MA have poor overall survival compared to patients without MA so these patients may benefit from this type of tracking which could potentially help with their treatment.
Citation Format: Rajya L. Kappagantula, Alvin P. Makohon-Moore, Shigeaki Umeda, Elias-Ramzey R. Karnoub, Jerry P. Melchor, Laura D. Wood, Christine A. Iacobuzio-Donahue. Robust detection of somatic genetic alterations in pancreatic cancer ascites [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 2148.
Abstract 2428: Cancer stem cells maintain stemness via autocrine activation of the IFN/JAK/STAT signaling pathway
Authors: Li Aidan , Bai Xuetao , Li Na , Cai Shurui , Banerjee Ananya , Lavudi Kousalya , Wang Linzhou , Ge Qianyun , Yang Yajing , Wang Qi-En 
Published: April 2023

Abstract
Interferons (IFNs) and Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling are best known for their roles in immunity. However, recent work has suggested that both IFNs and the JAK/STAT pathways are associated with tumor growth and progression, as well as the maintenance of cancer stem cell (CSC) populations. To better understand the regulation of the CSC population maintenance by the IFN/JAK/STAT signaling pathway, we enriched CSCs from a panel of non-small cell lung cancer (NSCLC) cell lines by using spheroid culture and determined the phosphorylation of STAT1. We found that sphere cells exhibit increased level of pSTAT1-Y701 compared to their corresponding bulk cells. We further determined the expression level of a few interferon-stimulated genes (ISGs) and found that sphere cells possess enhanced expression of ISG54 and ISG56 genes, which are normally induced by type I IFN (IFN-I), as well as IFNA and IFNB. These results indicate that the IFN-I/STAT1 signaling is highly activated in CSCs, which produce and secrete increased amount of IFN-I. To directly show the effect of IFN-I on the stemness of NSCLC cells, we treated NSCLC cells with IFNβ, and found that IFNβ can significantly enhance the expression of SOX2, a stem cell-specific transcription factor; Inhibition of the JAK signaling blocked both basal and IFNβ-induced SOX2 expression. In addition, knockdown of STAT1 also reduced SOX2 expression, indicating that STAT1 activation plays an important role in mediating IFN-induced enhancement of stemness. Finally, the ChIP assay demonstrated that STAT1 protein can bind to the promoter region of the SOX2 gene to serve as a transcription factor. In summary, our results indicate that CSCs produce and secrete IFN-I via their enhanced JAK/STAT1 signaling. The secreted IFN-I can bind to the receptor on the CSCs, further activate their JAK/STAT1 signaling, promoting the expression of SOX2 and maintenance of stemness of CSCs via an autocrine manner.
Citation Format: Aidan Li, Xuetao Bai, Na Li, Shurui Cai, Ananya Banerjee, Kousalya Lavudi, Linzhou Wang, Qianyun Ge, Yajing Yang, Qi-En Wang. Cancer stem cells maintain stemness via autocrine activation of the IFN/JAK/STAT signaling pathway [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 2428.
Abstract 2433: SERPINA12 promotes the tumorigenic capacity of hepatocellular carcinoma stem cells through hyperactivation of AKT/β-catenin signaling
Authors: Yu Huajian , Zhou Lei , Loong Jane Ho-Chun , Lam Ka-Hei , Wong Tin-Lok , Ng Kai-Yu , Tong Man , Ma Victor WS , Wang Yanyan , Zhang Xiang , Lee Terence K , Yun Jing-Ping , Yu Jun , Ma Stephanie 
Published: April 2023

Abstract
Hepatocellular carcinoma (HCC) is an aggressive disease with a poor clinical outcome. Understanding the mechanisms that drive cancer stemness, which we now know is the root cause of therapy failure and tumor recurrence, is fundamental for designing improved therapeutic strategies. The aim of this study is to identify molecular players specific to CD133+ HCC to better design drugs that can precisely interfere with cancer stem cells (CSCs) but not normal stem cell function. Transcriptome profiling of epithelial-specific ‘normal’ CD133+ cells isolated from fetal and regenerating liver against ‘HCC’ CD133+ cells isolated from proto-oncogene driven and inflammation-associated HCC revealed preferential overexpression of SERPINA12 in HCC but not fetal and regenerating liver cells. SERPINA12 upregulation in HCC is tightly associated with aggressive clinical and stemness features, including survival, tumor stage, cirrhosis, and stemness signatures related to embryonic stem cells, oncogenic dedifferentiation and undifferentiated HCC status. Enrichment of SERPINA12 in HCC is mediated by promoter binding of the well-recognized β-catenin effector TCF7L2 to drive SERPINA12 transcriptional activity. Functional characterization identified a unique and novel role of endogenous SERPINA12 in promoting self-renewal, therapy resistance and metastatic abilities. Mechanistically, SERPINA12 functioned through binding to GRP78, resulting in a hyperactivated AKT/GSK3β/β-catenin signaling cascade, forming a positive feed-forward loop. Intravenous administration of rAVV8-shSERPINA12 sensitized HCC cells to sorafenib and impeded the CSC subset in an immunocompetent HCC mouse model. Collectively, our findings revealed that SERPINA12 is preferentially overexpressed in epithelial HCC CD133+ cells and is a key contributor to HCC initiation and progression by driving an AKT/β-catenin feed-forward loop.
Citation Format: Huajian Yu, Lei Zhou, Jane Ho-Chun Loong, Ka-Hei Lam, Tin-Lok Wong, Kai-Yu Ng, Man Tong, Victor WS Ma, Yanyan Wang, Xiang Zhang, Terence K Lee, Jing-Ping Yun, Jun Yu, Stephanie Ma. SERPINA12 promotes the tumorigenic capacity of hepatocellular carcinoma stem cells through hyperactivation of AKT/β-catenin 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 2433.
Abstract 2435: Single cell spatial analysis identifies regulators of brain tumor initiating cells
Authors: Mirzaei Reza , D’Mello Charlotte , Liu Marina , Nikolic Ana , Kumar Mehul , Visser Frank , Bose Pinaki , Gallo Marco , Yong Wee 
Published: April 2023

Abstract
Glioblastomas (GBMs) are aggressive brain tumors with extensive intratumoral heterogeneity. Here, we used spatial transcriptomics and single-cell ATAC-seq to dissect the transcriptome of distinct anatomical regions of the tumor microenvironment. We identified numerous extracellular matrix (ECM) molecules including biglycan elevated in areas infiltrated with brain tumor-initiating cells (BTICs). Single-cell RNA sequencing showed that the ECM molecules were differentially expressed by cells including injury response versus developmental BTICs. Exogeneous biglycan or overexpression of biglycan resulted in a higher proliferation rate of BTICs, and this was associated mechanistically with LDL receptor-related protein 6 (LRP6) binding and activation of the Wnt/β-catenin pathway. Biglycan-overexpressing BTICs grew to a larger tumor mass and higher mesenchymal phenotypes when implanted intracranially in mice. This study points to the spatial heterogeneity of ECM molecules in the GBM microenvironment and suggests biglycan-LRP6 axis as a therapeutic target to curb GBM growth.
Citation Format: Reza Mirzaei, Charlotte D’Mello, Marina Liu, Ana Nikolic, Mehul Kumar, Frank Visser, Pinaki Bose, Marco Gallo, Wee Yong. Single cell spatial analysis identifies regulators of brain tumor initiating 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 2435.
Abstract 2440: HOTAIR functionality and regulation in ovarian cancer stem cells
Authors: Wang Weini , Zhou Yanchi , Wang Ji , Ozes Ali , O’Hagan Heather M. , Mitra Anirban , Nephew Kenneth P. 
Published: April 2023

Abstract
Ovarian cancer (OC) is the fifth leading cause of cancer-related death among American women. Persistence of OC stem cells (OCSCs) is believed to contribute to resistance to platinum-based chemotherapy and disease relapse. We have previously shown that epigenetic changes in OCSCs play a role in post-therapy OCSC persistence and demonstrated the potential to target OCSC using epigenetic therapies. HOXC transcript antisense RNA (HOTAIR) has been shown to be associated with chemoresistance and overexpressed in high-grade serous OC (HGSOC). HOTAIR interacts with Polycomb Repressive Complex 2 (PRC2) and plays a key role in chromatin remodeling. Because HOTAIR is a known epigenetic regulator of differentiation and developmental genes in OC, we hypothesized that HOTAIR regulates OCSCs and epigenetic targeting HOTAIR will prevent tumor relapse. To produce loss-of-function phenotypes of HOTAIR and investigate the function of this gene, we utilized the paired CRISPR guide RNA design to delete the functional sites of HOTAIR in a panel high grade serous OC cell lines (Kuramochi, OVCAR3) without affecting nearby protein-coding gene. Knockout of HOTAIR re-sensitized OC cells to platinum treatment and significantly decreased (P&lt;0.001) the OCSC population and stemness-related phenotypes, including inhibiting stemness-associated gene expression ALDH1A1, Notch3, Sox9, and PROM1 and in vitro spheroid forming ability under low attachment conditions. Integrated analysis of RNA-seq and ATAC-seq on control and HOTAIR knockout cells revealed HOTAIR altered global chromatin dynamics to change downstream gene expression, particularly, the NF-kB pathway. In xenograft assays using HGSOC cells, combining a HOTAIR inhibitor with an EZH2 inhibitor and chemotherapy significantly decreased in vivo tumor formation and increased mouse survival. In summary, depletion of HOTAIR functionally decreased OCSC phenotypes and malignant potential and reprogrammed HGSOC to a less stem-like phenotype. There is an urgent need to develop new therapeutic strategies to target OCSCs and overcome chemoresistant OC, and the results of this study suggest that targeting HOTAIR in combination with epigenetic therapies may represent a novel therapeutic strategy to prevent tumor relapse in OC.
Citation Format: Weini Wang, Yanchi Zhou, Ji Wang, Ali Ozes, Heather M. O’Hagan, Anirban Mitra, Kenneth P. Nephew. HOTAIR functionality and regulation in ovarian cancer stem 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 2440.