bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5185: Identification of a new candidate therapeutic target for gastric cancer by in silico analysis
Authors: Kohmoto Tomohiro , Masuda Kiyoshi , Shoda Katsutoshi , Fujita Yuji , Tange Shoichiro , Ichikawa Daisuke , Otsuji Eigo , Imoto Issei 
Published: August 2018

Abstract
Gastric Cancer (GC) is a leading cause of global cancer mortality, with high incidence rates in Asia including Japan. Although recent studies have provided valuable insights into identification of major driver genes, there are still little therapeutic targets and prognostic markers of GC. Here, we report that a novel driver gene, OverExpressed in Gastric Cancer 1 (OEGC1), would induce cell proliferation and migration of GC.Analyzing gene expression profiles by RNA-Seq and relevant clinical data in TCGA dataset, we identified candidate genes whose mRNA expression was higher in tumor tissues than in non-tumorous and associated with poor prognosis. Through further expression analysis and Cox proportional hazards regression analysis of those candidates, we identified OEGC1 as the most prominent candidate for driver gene. OEGC1 mRNA was expressed highly especially in intestinal type GC. The prognosis of the OEGC1 high-expressed intestinal type GC patients was as poor as that of diffuse type GC patients. Immunohistochemical analysis showed that overexpression of OEGC1 was ectopically found in the tumor cell junctions located in the infiltrated region of tumor. By silencing endogenous OEGC1 using siRNAs, cell proliferation was significantly suppressed and G0/G1 arrest was induced in NUGC3, AGS and MKN7 cells with relatively higher OEGC1 expression. Transwell assay showed that the number of migrated cells was significantly lower for siRNA-OEGC1-transfected cells than for control cells. Our findings suggested that aberrant expression of OEGC1 might play an important role in tumorigenesis of GC, and that OEGC1 might be a possible therapeutic target in GC.
Citation Format: Tomohiro Kohmoto, Kiyoshi Masuda, Katsutoshi Shoda, Yuji Fujita, Shoichiro Tange, Daisuke Ichikawa, Eigo Otsuji, Issei Imoto. Identification of a new candidate therapeutic target for gastric cancer by in silico analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5185.
Abstract 5193: A subpopulation of circulating epithelial tumor cells positive for fatty acid receptor CD36 is linked to aggressiveness of breast cancer disease
Authors: Pizon Monika , Schott Dorothea , Pachmann Ulrich , Pachmann Katharina 
Published: August 2018

Abstract
Background: Breast cancer is one of the leading causes of cancer death for women worldwide. Major hurdles for a successful treatment are cancer metastases, resistance to therapy and disease recurrence. The presence of circulating epithelial tumor cells (CETCs) is closely related to metastasis formation, but the mechanisms through which CETCs promote recurrence of disease are still unclear. CD36 is found in the cell membrane of tumor cells and responsible for taking up fatty acid. It is known that CD36 is a general marker of metastatic cells and its amplification specifically correlated with metastasis in a large number of human tumors. Therefore, the aim of this study was to determine the metastatic marker CD36 on CETCs and to correlate it's frequency with clinicopathological features in breast cancer patients.
Methods: CETCs were determined from blood of 42 patients suffering from breast cancer. The number of vital CETCs and their expression of CD 36 was investigated using the maintrac® method.
Results: CD36 expressing CETCs were detected in 95 % of breast cancer patients. Breast cancer patients with metastatic disease had significantly more CD36 positive CETCs as compared to patients without metastases (median 72% vs. 48%; p&lt;0.05). The fraction of CD36 positive CETCs was significantly higher in patients with HER2 positive primary tumor (69% vs. 54%; p&lt;0.05). Furthermore, triple negative breast cancer patients had significantly more CD36 positive CETCs as compared to hormone receptor positive tissue (median 62% vs. 52%; p&lt;0.05). Interestingly, frequency of CD36 positive CETCs correlated significantly with a blinded determination of Ki-67 proliferation index in tumor tissue (r=0.75; p&lt;0.01). We observed a significant heterogeneity in CD36 immunostaining intensity across CETCs from the same patients.
Conclusion: We showed for the first time that breast cancer patients have detectable CETCs with a high frequency of CD36 which highly correlated with progression of cancer disease. Our findings suggest that using a CD36 antibody treatment may be an effective strategy to fight cancer.
Citation Format: Monika Pizon, Dorothea Schott, Ulrich Pachmann, Katharina Pachmann. A subpopulation of circulating epithelial tumor cells positive for fatty acid receptor CD36 is linked to aggressiveness of breast cancer disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5193.
Abstract 5194: In vivo capture of early metastatic cells through a CXCL12 loaded-dermal filler
Authors: Ieranò Caterina , D'Alterio Crescenzo , Giarra Simona , Napolitano Maria , Santagata Assunta , Barbieri Antonio , Campani Virginia , Luciano Antonio , Arra Claudio , Anniciello Annamaria , Botti Gerardo , Mayol Laura , Rosa Giuseppe De , Pacelli Roberto , Scala Stefania 
Published: August 2018

Abstract
The chemokine CXCL12 and its receptor CXCR4 are critical for orienting and seeding cells in metastatic sites. To distract CXCR4 expressing circulating tumor cells (CTCs) a “fake” pre-metastatic niche was built with a hyaluronic acid based dermal filler hydrogel-CXCL12-loaded (CLG). CXCR4 expressing human T leukemia cells, CCRF-CEM, and murine melanoma cells human CXCR4 transduced, B16-hCXCR4-GFP, were evaluated for migration in vitro toward CLG. CLGs and EGs (empty gels) were subcutaneously injected in C57BL/6 mice and five days later B16-hCXCR4-GFP (5x105 cells) were intravenously injected. Twenty two days later mice were euthanized and hydrogels recovered. Gel trapped cells were recovered through ialuronidase digestion of the gels and lungs were analyzed to detect metastases. Circulating tumor cells (CD45neg/hCXCR4 plus/GFP plus) were assessed in the blood at day 10 and 22 from cells injection. In vitro, CEM and B16-hCXCR4-GFP cells more efficiently migrated toward CLG compared with EG. In vivo, a significantly higher number of B16-hCXCR4-GFP tumor cells was detected within the CLGs compared with EGs, indicating that the CXCL12 in hydrogel enabled recruitment of tumor cells. Concomitantly, lung metastases were significantly reduced in mice carrying CLG, but not EG, as assessed by reduced B16-hCXCR4-GFP positive tumor cells in the lung (75% reduction in lung metastases in mice carrying CLG; p&lt;0.05). CLG recovered cells by hydrogel enzymatic digestion recapitulated the features of melanoma cell line B16-hCXCR4-GFP (epithelial, melanin rich, MELAN A/ S100/ c-kit/CXCR4 +; α-SMA -). CTCs, evaluated at 10 and at 22 days post cells injection, significantly increased in CLG carrying mice compared to EG carrying mice. Our study suggests that a hyaluronic acid (HA) hydrogel, commercially used as dermal filler, loaded with CXCL12 can divert CXCR4 positive circulating tumor cells B16-hCXCR4-GFP. The cells trapped in the CLG can be recovered and characterized. As a corollary, a reduction of CXCR4 dependent lung metastasis was detected. It suggests that hydrogel-CXCL12 trap may be a therapeutic and diagnostic tool to recover and analyze the biology of circulating tumor cells.
Citation Format: Caterina Ieranò, Crescenzo D'Alterio, Simona Giarra, Maria Napolitano, Assunta Santagata, Antonio Barbieri, Virginia Campani, Antonio Luciano, Claudio Arra, Annamaria Anniciello, Gerardo Botti, Laura Mayol, Giuseppe De Rosa, Roberto Pacelli, Stefania Scala. In vivo capture of early metastatic cells through a CXCL12 loaded-dermal filler [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5194.
Abstract 5197: Single-cell analysis of the brain metastatic microenvironment in breast cancer
Authors: Evans Katrina , Nguyen Quy , Blake Kerrigan , Lawson Devon 
Published: August 2018

Abstract
Breast cancer brain metastasis affects 10-20% of patients, and there are no effective treatments. Activated infiltrating microglia and astrocytes are a major component of metastatic breast tumors in the brain, but it is not known whether these cells are involved in the promotion or rejection of breast cancer cells. To characterize the brain metastatic microenvironment, we used an FACS-based approach to capture pure and viable microglia and astrocytes from normal and metastatic mouse brains for single-cell mRNA sequencing analysis. Using this approach, we have captured more than 10,000 microglia and astrocytes from normal and metastatic brains. Applying our analysis pipelines to this data revealed distinct pathways and markers associated with microglia and astrocytes in metastatic brains. Future work will aim to identify spatial locations and function of specific microglia and astrocyte subpopulations in the metastatic brain.
Citation Format: Katrina Evans, Quy Nguyen, Kerrigan Blake, Devon Lawson. Single-cell analysis of the brain metastatic microenvironment in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5197.
Abstract 5198: Androgen receptor signaling affects macrophage differentiation in the human prostate cancer microenvironment
Authors: Cioni Bianca , Nevedomskaya Ekatarina , Stelloo Suzan , Melis Monique , Burgsteden Johan van , Jong Jeroen de , Poel Henk van der , Boer Jan Paul de , Zwart Wilbert , Bergman Andries M. 
Published: August 2018

Abstract
Increasing evidence from epidemiologic and pathologic studies suggests a role of macrophages in the initiation and progression of prostate cancer (PCa). During PCa development, macrophages (CD68+) are recruited into the human prostate cancer microenvironment, including inflammation-associated M1 and cancer-promoting M2 macrophages. Like other prostate cancer-associated stromal cells, macrophages express the androgen receptor (AR); however, its functionality is not known. CD68+ cells generated in vitro from peripheral white blood cells and PMA activated and IFN and LPS polarized human acute monocytic leukemia THP-1 cells also expressed AR. In these cells AR is an 80KD splice variant, lacking parts of exon 1 and exon 2. AR translocated to the nucleus upon testosterone stimulation, which was counteracted by the AR signaling inhibitor RD162. In vitro generated M1 macrophages expressed the M2 markers CD163 and CD206 upon testosterone stimulation, which was reversed by RD162. AR-ChIP sequencing suggested AR regulated Macrophage Triggering Receptor 1 (TREM1) signaling. Expression of key cytokines (e.g., CCL2, CXCL8, CCL7, IL10, IL1B) involved in TREM1 signaling was upregulated upon testosterone stimulation. Actions of these cytokines is generally associated with a protumor phenotype of macrophages. Conditioned medium from macrophages stimulated with testosterone for 8 hrs resulted in enhanced proliferation and migration of human prostate LNCap and CWRR1 cells. In conclusion, AR signaling might affect differentiation of prostate cancer-associated macrophages into cancer-promoting M2, which affects prostate cancer cell proliferation and migration. Maintaining macrophages in M1 might be a novel mechanism of action of androgen receptor inhibitors.
Citation Format: Bianca Cioni, Ekatarina Nevedomskaya, Suzan Stelloo, Monique Melis, Johan van Burgsteden, Jeroen de Jong, Henk van der Poel, Jan Paul de Boer, Wilbert Zwart, Andries M. Bergman. Androgen receptor signaling affects macrophage differentiation in the human prostate cancer microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5198.
Abstract 5200: Extracellular vesicles in the ascites from gastric cancer patients play critical roles to promote peritoneal dissemination in the intraperitoneal cancer microenvironment
Authors: Ito Atene , kagawa shunsuke , Sakamoto Shuichi , Kuwada Kazuya , Kikuchi Satoru , Kuroda Shinji , Yoshida Ryuichi , Tazawa Hiroshi , Fujiwara Toshiyoshi 
Published: August 2018

Abstract
Although gastric cancer often develops peritoneal dissemination, the underlying mechanism of peritoneal metastasis is still unclear. Extracellular vesicles (EVs) are known to play roles in cell-cell communication. Here, we investigated the existence of EVs in peritoneal ascites of gastric cancer patients and explored their roles in the intraperitoneal cancer microenvironment. We found that EVs actually existed in peritoneal ascites of advanced gastric cancer patients. On the other hand, immune-fluorescent assay of the ascites by using antibodies against CD14 (Monocytes) and CD45 (Leukocytes) revealed that many macrophages existed along with the cancer cells in the peritoneal cavity. EVs purified from peritoneal ascites with cancer dissemination made peripheral blood mononuclear cells-derived macrophages M2-like phenotype which was confirmed by their morphology and expression of CD163/206 (M2 marker). Next, we purified EVs from the culture medium of gastric cancer cell lines. Gastric cancer-derived EVs induced the M2- differentiation in macrophages and the differentiated macrophages promoted migration ability of gastric cancer cells. Finally, we observed that gastric cancer-derived EVs induced apoptosis of cultured mesothelial cells in vitro. These results suggested that EVs in the ascites of gastric cancer patients are possibly derived from gastric cancer and play critical roles in the intraperitoneal cancer microenvironment by affecting the macrophages phenotype and inducing apoptosis in the mesothelial cells, which would be in part the underlying mechanism of peritoneal metastasis.
Citation Format: Atene Ito, shunsuke kagawa, Shuichi Sakamoto, Kazuya Kuwada, Satoru Kikuchi, Shinji Kuroda, Ryuichi Yoshida, Hiroshi Tazawa, Toshiyoshi Fujiwara. Extracellular vesicles in the ascites from gastric cancer patients play critical roles to promote peritoneal dissemination in the intraperitoneal cancer microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5200.
Abstract 5207: HIF-1α regulates the Tie2 receptor on Tie2-expressing monocytes in PyMT breast tumors and augments angiogenic function and metastatic potential
Authors: Steinberger Kayla J. , Forget Mary , Mo Xiaokui , Evans Randall , Gross Amy , Moldovan Leni , Bobko Andrey , Khramstov Valery , Marsh Clay B. , Eubank Timothy D. 
Published: August 2018

Abstract
Tissue oxygenation in the tumor microenvironment serves as a significant parameter in tumor pathophysiology. In fact, normalization of tumor oxygen is associated with inhibition of tumor growth and metastatic capacity. Irregular tumor vessels produced during tumor angiogenesis have low blood perfusion; thus, oxygen transport is decreased in tumors. Tie2-expressing monocytes (TEMs) are a distinct subset of proangiogenic monocytes selectively recruited to tumors in breast cancer patients. Due to the hypoxic nature of the tumor microenvironment, we investigated if oxygen regulates the trafficking of these cells into tumors or if oxygen regulates monocyte differentiation into TEMs once inside the tumor proper. To understand the differentiation of F4/80+/Tie2- cells to Tie2-positivity, we orthotopically implanted PyMT breast tumor cells containing particulate lithium octa-n-butoxy-naphthalocyanine (LiNcBuO) into the mammary fat pads of LysM-Cre control and HIF-1αfl/fl/LysM-Cre mice and evaluated tissue oxygenation by electron paramagnetic resonance (EPR), TEM infiltration, tumor angiogenesis, and metastatic potential. Longitudinal monitoring of physiologic oxygen in tumors using EPR demonstrates the significant role of oxygen-driven TEM regulation in tumor angiogenesis and progression.
Citation Format: Kayla J. Steinberger, Mary Forget, Xiaokui Mo, Randall Evans, Amy Gross, Leni Moldovan, Andrey Bobko, Valery Khramstov, Clay B. Marsh, Timothy D. Eubank. HIF-1α regulates the Tie2 receptor on Tie2-expressing monocytes in PyMT breast tumors and augments angiogenic function and metastatic potential [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5207.
Abstract 5210: Liver prometastatic genes in patients with and without colorectal cancer
Authors: Vidal-Vanaclocha Fernando 
Published: August 2018

Abstract
Metastasis-related hepatic genes were investigated in the tumor-unaffected hepatic tissue from patients with hepatic colorectal cancer (CRC) metastases. In addition, the contribution of CRC and patient's clinical parameters and comorbidities to hepatic expression of CRC prometastatic genes was also studied in new hepatic biopsies from metastasis-free CRC patients and from CRC-free patients used as controls. The expression level of 58% metastasis-associated hepatic genes significantly changed between patients with and without CRC. Principal component and Linear discriminant statistical analyses, and a hierarchical cluster analysis based on Pearson's correlation indices uncovered a subset of 37 CRC-dependent liver prometastatic genes able to segregate patients with and without CRC. Functionally, they belonged to immune regulation, inflammation, metabolic bioprotection, hepatokines and regeneration factors. More importantly, a multivariate canonical correlation analysis showed the additional contribution of patient's pathophysiology and comorbidities to hepatic gene expression and metastasis risk. The liver prometastatic gene expression pattern represented a patient-specific and heterogeneous hepatic reaction to CRC-specific factors, which developed prior to metastatic recurrence and varied according to location of such CRC in the left and right-sided colonic area and rectum.
Citation Format: Fernando Vidal-Vanaclocha. Liver prometastatic genes in patients with and without colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5210.
Abstract 5213: HRH1 inhibition enhances antitumor therapeutic responses through ERK activation in breast cancer
Authors: Fernandez-Nogueira Patricia , Castells Aleix Noguera , Orellana Gemma Fuster , Percaz Leire Recalde , Garcia Nuria Moragas , Plana Anna Lopez , Jimenez Patricia Jauregui , Carbó Maria Neus Carbó , Villaplana Pedro Gascon , Domingo Paloma Bragado , Mancino Mario 
Published: August 2018

Abstract
Histamine receptor 1 (HRH1) belongs to the rhodopsin-like G-protein-coupled receptor family. Its activation by histamine, a ubiquitous messenger molecule released mostly from mast cells, has been demonstrated to be involved in cell proliferation, embryonic development, and tumor growth. In particular, high levels of HRH1 have been associated with dual behavior in the regulation of several tumors. Most of the physiological and pathological actions of HRH1 have been shown to depend strictly on its level of expression and the tumor cell type under study. We recently established that HRH1 is upregulated in patients with basal and HER2-enriched breast tumors and that its expression correlates with a worse prognosis. Despite this, the functional role of HRH1 basal and HER2 targeted therapies for resistant breast cancer (BC) progression has not so far been addressed. We assessed HRH1 expression in a wide panel of breast cancer cell lines and found HRH1 overexpressed in basal and HER2-targeted therapy resistant to BC cell lines at the protein and mRNA levels, corroborating data previously published using patient databases. Using terfenadine, a selective chemical inhibitor of HRH1, we showed that inhibition of HRH1 activity in basal BC cells leads to sub-G0 accumulation, suppresses proliferation, promotes cell motility and triggers the activation of ERK signaling, initiating the mitochondrial pathway of caspase cascade activation, inducing apoptosis. Moreover, in vivo experiments showed that terfenadine therapy reduced basal and HER2-targeted therapies for resistant BC cell tumor growth but does not affect luminal and parental tumor growth. In conclusion, our results suggest that targeting HRH1 might be an effective therapeutic treatment in patients with basal and HER2-targeted resistant BC tumors.
Citation Format: Patricia Fernandez-Nogueira, Aleix Noguera Castells, Gemma Fuster Orellana, Leire Recalde Percaz, Nuria Moragas Garcia, Anna Lopez Plana, Patricia Jauregui Jimenez, Maria Neus Carbó Carbó, Pedro Gascon Villaplana, Paloma Bragado Domingo, Mario Mancino. HRH1 inhibition enhances antitumor therapeutic responses through ERK activation in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5213.
Abstract 5223: IL-6 regulates the OCT4 expression by epigenetic modulation in hepatocellular carcinoma
Authors: Lai Ssu-Chuan , Chang Te-Sheng , Su Yu-Ting , Wu Yu-Chih , Kuo Yung-Che , Lan Pei-Chi , Huang Yen-Hua 
Published: August 2018

Abstract
Purpose: Chronic hepatic inflammatory cytokine interleukin 6 (IL-6) appears important role in pluripotent transcription factor OCT4 expression particularly in HBV-related hepatocellular carcinomas (HBV-HCC). However, the underlying mechanism still remains largely unknown. Experimental Design: Serum levels of IL-6 were detected using ELISA assays (n = 120). The effects of IL-6 on DNMT/OCT4 expression in HCC were examined using real-time QPCR analysis, RNA interference, and xenograft animal models. The DMNT/OCT4 protein and phospho-STAT (p-STAT) were detected by western blotting. OCT4, and DNMT expression levels in tissues (n = 144) were analyzed by real-time Q-PCR and was correlated with early tumor recurrence using Kaplan-Meier survival analysis. Results: A high positive correlation between the expression levels of OCT4 and epigenetic DNMT family in human HCC tissues was observed. High serum levels of IL-6 were significantly correlated with high OCT4 and DNMT expression. IL-6 stimulated the DNMT expression STAT3-dependently, which stimulated the OCT4 expression in both the cell lines and the xenografted mouse tumors. The inhibition STAT phosphorylation/DNMT expression by dominant negative STAT-Y705F plasmid transfection or DNMT RNA interference significantly suppressed the IL-6-induced OCT4 expression in vitro. Conclusions: The expression of pluripotency-related OCT4 is associated with early tumor recurrence and is regulated by IL-6-induced epigenetic DNMTs in HCC.
Citation Format: Ssu-Chuan Lai, Te-Sheng Chang, Yu-Ting Su, Yu-Chih Wu, Yung-Che Kuo, Pei-Chi Lan, Yen-Hua Huang. IL-6 regulates the OCT4 expression by epigenetic modulation in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5223.