bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1913: Role of glypican 1 in regulating fibroblast activation in the prostate cancer tumor microenvironment
Authors: Kaur Sukhneeraj P. , Lee Hee K. , Arnold Robert D. , Cummings Brian S. 
Published: August 2019

Abstract
Cancer is a heterogeneous collection of neoplastic cells, surrounded by non-malignant, stromal cells, and extracellular matrix (ECM), among other constituents. Cross-talk between tumor and stromal cells forms a dynamic tumor microenvironment (TME) that mediates cell growth, proliferation, and metastasis. The TME can inhibit cancer growth and proliferation during the initial stages of carcinogenesis; however, cancer cells can evade these inhibitory signals, and reshape the TME, making it more amenable to their own growth. This gives rise to cancer-associated stromal cells, including cancer-associated fibroblasts (CAFs). CAFs further modulate the TME by regulating the release of growth signals, cell death, ECM remodeling, angiogenesis, and epithelial-mesenchymal transition. Glypican-1 (GPC1) is a cell surface heparan sulfate proteoglycan (HSPG) that has both pro-mitogenic and pro-metastatic activity. GPC1’s role in regulating fibroblasts and their transformation into CAFs has not been investigated. We studied the ability of prostate cancer cells to alter the TME in vitro by exposing human bone fibroblasts (HS-5 cells) to tumor conditioned media (TCM) isolated from a human neuroendocrine (DU-145) and bone (PC-3) metastatic prostate cancer cell lines and assessed changes in cell morphology and cytotoxicity (using MTT). Exposure of HS-5 cells to TCM from DU-145 and PC-3 cells altered cellular morphology to a more mesenchymal phenotype similar to that seen in active myofibroblasts. TCM also decreased MTT staining in a time-dependent manner. We also determined the effect of GPC1 knockdown (KD) in HS-5 cells on cell morphology, migration and cytotoxicity. Interestingly, we saw phenotypic switching of GPC1 KD HS-5 cells to a myofibroblast like morphology akin to that when treated with TCM. There was no change in cytotoxicity in GPC1 KD HS-5 cells as compared to control cells. However, GPC1 KD enhanced the migration of HS-5 cells in wound healing assay. Migration was also increased in GPC1 KD HS-5 cells upon treatment with TCM. GPC1 KD also increased HS-5 cell contractility significantly. Collectively, these data support the hypothesis that GPC1 plays an inhibitory role in the TME of prostate cancer by regulating the activation of fibroblasts.
Citation Format: Sukhneeraj P. Kaur, Hee K. Lee, Robert D. Arnold, Brian S. Cummings. Role of glypican 1 in regulating fibroblast activation in the prostate cancer tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1913.
Abstract 1918: InnoPanelTM -a well characterized panel of 1000 cancer cell lines for anticancer drug development
Authors: Hao Feng , Liu Changpeng , Peng Hao , Zhou Xiaolin , Fu Yunhui , Hou Qiang , Ning Jinying 
Published: August 2019

Abstract
In vitro cell line assays are broadly used in drug screening to assess drug efficacy, probe drug mechanism, discover and validate predictive biomarkers. High-throughput screen can be performed on cell line collections such as the well-known NCI-60 panel that is consisted of 60 human cancer cell lines developed by the National Cancer Institute (NCI).1Cell lines in such panels are usually well annotated for basic information such as cancer type and subtype, histopathology, and marker gene expression; many experimental parameters are also measured such as doubling time and inoculation density. The utility of cell panels is greatly enhanced with more cell lines that are thoroughly characterized for their genomics by next generation sequencing2-3. To this end, we have developed InnoPanelTM—a panel of 1000 cancer cell lines, including 800 commonly used cancer cell lines, 100 primary cell lines, and 100 engineered cell lines. These cell lines cover all major cancers and majority are genomically characterized with gene expression, mutation and copy number data. Flow cytometry data were also available for engineered cell lines to validate and characterize designed modifications, for example, Siglec-15 overexpression in the CHO-K1 human Siglec-15 cell line. All data are openly available to researchers at our online database InnopediaTM.To make InnoPanelTM-based screening more valuable and accessible to biologists, we developed a bioinformatics pipeline to automate analysis that combines genomics and efficacy data. The utility of such analysis is demonstrated by case studies. InnoPanelTMcan also be customized for a subset of the 1000 cell lines. Subpanel for selected cancer types or cell lines bearing certain features can be constructed. In summary, we developed a well characterized 1000-cell line panel as a valuable resource for researchers working on anticancer drug development.
References1. Shoemaker RH. The NCI60 human tumour cell line anticancer drug screen. Nat Rev Cancer 2006; 6: 813-23.2. Barretina J, Caponigro G, Stransky N, et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature, 2012, 483(7391):603.3. Consortium CCLE. Pharmacogenomic agreement between two cancer cell line data sets. Nature, 2015, 528(7580):84-7.
Citation Format: Feng Hao, Changpeng Liu, Hao Peng, Xiaolin Zhou, Yunhui Fu, Qiang Hou, Jinying Ning. InnoPanelTM -a well characterized panel of 1000 cancer cell lines for anticancer drug development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1918.
Abstract 1924: Rapid screening of anti-OX40 antibodies for cancer immunotherapy
Authors: Gan Tian , Li Yanan , Ni Jian , Yang Benny(Yi) 
Published: August 2019

Abstract
OX40, also known as CD134 or TNFRSF4, is a member of the TNFR superfamily. OX40 is a co-stimulatory receptor, and it interacts with its ligand to provide positive signal for T cell activation. OX40 is not expressed on naïve T cells, however its expression goes up after 24 to 72 hours following activation. Disruption of the OX40 pathway led to defective T cell responses, and overexpression of OX40 caused massive immune activation. Due to its importance in keeping immune homeostasis, strategies modulating the OX40 pathway hold great promise in efforts against cancer and autoimmune diseases.
Based on the promising nature of this target, we focused on developing novel OX40 agonists that would effectively stimulate anti-tumor activity. Dozens of high-affinity candidate antibodies were generated using classic hybridoma technology. In order to directly screen for antibodies for anti-tumor effects in animals, we ranked these antibodies in vivo using the drug screening platform based on humanized mouse models. Specifically, we used B-hOX40 mice and implanted syngeneic tumors subcutaneously, followed by treating mice with purified candidate antibodies. We quickly identified several lead antibodies that effectively inhibited tumor growth using this approach, without prior knowledge of their in vitro activities. Their ability to stimulate T cells was confirmed by an engineered reporter line of Jurkat T cells in vitro. Furthermore, we showed that one clone works in concert with Keytruda in a double humanized model of h-OX40 and h-PD-1. We are currently investigating the mechanisms of action underlying these potentially valuable antibodies and carrying out more combination evaluation studies using other available humanized immune-checkpoint mouse models.
Citation Format: Tian Gan, Yanan Li, Jian Ni, Benny(Yi) Yang. Rapid screening of anti-OX40 antibodies for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1924.
Abstract 1949: Mouse model of metastatic colorectal cancer by orthotopic transplantation of patient derived organoids
Authors: Okamoto Takuya , Yaginuma Katsuyuki , Nagayama Satoshi , Yao Ryoji 
Published: August 2019

Abstract
Cancer metastasis proceeds through multiple steps and metastatic colonization is formed by disseminated tumor cells with proliferative capacity in distant tissues. In the analysis of metastasis, macroscopically completed lesions are often used for subjects, which is attributed to the difficulty to capture the early process occurring in living body and the analysis using human specimen is particularly limited. To capture the metastatic process of colorectal cancer (CRC) and to identify cell population involved in it, we produced the mouse model for CRC by orthotopic transplantation of patient derived organoids (PDOs). Unlike ectopic transplantation models, this model precisely recapitulates the metastasis process in human patients. To evaluate the metastasis potentials, the patient matched organoids from the primary, the synchronous liver metastasis and the post-chemotherapy liver recurrence lesion were established. No significant difference in macroscopic morphology or pathogenic mutations were noted among the organoids. The organoids were marked by fluorescent protein and luciferase fusion gene to be visualized the process over time by in vivo imaging system and injected under rectal mucosa on prolapse. Each graft reflected histopathological feature of the surgical specimen. At the results of observation, the lung metastases were frequently occurred in recurrence organoids mouse models, but little occurred in primary or metastasis ones. The lung metastases were considered to be in the early stage of metastasis, because they spread diffusely in each lung lobes, and could not be confirmed macroscopically. They were forming two state; one appeared to be the embolism in blood vessels around the bronchus and others were the micro-metastases in lung tissue. The orthotropic transplantation of patient-matched PDOs provides unique opportunities to explore the metastasis process of CRC.
Citation Format: Takuya Okamoto, Katsuyuki Yaginuma, Satoshi Nagayama, Ryoji Yao. Mouse model of metastatic colorectal cancer by orthotopic transplantation of patient derived organoids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1949.
Abstract 197: Molecular interactions of Globo H ceramide with translin-associated factor X (TRAX) underlie its proangiogenic activities
Authors: Yu John , Wang Sheng-Hung , Cheng Jing-Yan , Hung Jung-Tung , Lin Chun-Cheng , Lo Fei-Yun , Lee Chien-Wei , Yu Alice L. 
Published: August 2019

Abstract
Glycosphingolipids (GSLs) are ubiquitous glycolipids in eukaryotic plasma membranes that consist of a polar glycan chain and a hydrophobic sphingosine- containing ceramide tail. Although GSLs display various diversities and functions, the mechanistic details of GSL interactions with membranous or intracellular components are poorly understood. Globo H ceramide (GHCer), a tumor-associated GSL overexpressed in most types of epithelial cancers, is a potential target of cancer immunotherapy. Previously, we showed that GHCer is shed by cancer cells to mediate immune suppression and promote angiogenesis in the tumor microenvironment. At the cellular level, GHCer from cancer cells binds to translin-associated factor (TRAX), with consequent release of PLCB1 from TRAX to trigger Ca2+ mobilization. Herein, we found that Gb5-ceramide (Gb5Cer), the pentasaccharide precursor of GHCer, could not promote angiogenesis nor Ca2+ mobilization. At the molecular level, ELISA and biacore analysis revealed that GHCer binds to TRAX with a distinct dissociation constant of 4.09×10-8 M, while its precursors, galactosyl-, lactosyl-, Gb4-, and Gb5Cer- showed negligible binding to TRAX. Molecular docking and molecular dynamics indicated that the fucose residue of Globo H is an important contributor to a favorable glycan conformation for interaction with TRAX, consistent with the finding that Gb5Cer had no proangiogenic activities. In addition, GHCer competed with recombinant C-terminus region of phospholipase C β1 (PLCB1) for binding to TRAX, thus providing a molecular mechanism for the proangiogenic effect of GHCer on tumor microenvironment. This study provides the first evidence for interaction of TRAX with a non-protein GSL, deciphered distinct regions of TRAX for interacting with glycan and lipid portions of GHCer, and illustrated the crucial contribution of fucose moiety on GHCer for its interaction with TRAX and angiogenic activity.
Citation Format: John Yu, Sheng-Hung Wang, Jing-Yan Cheng, Jung-Tung Hung, Chun-Cheng Lin, Fei-Yun Lo, Chien-Wei Lee, Alice L. Yu. Molecular interactions of Globo H ceramide with translin-associated factor X (TRAX) underlie its proangiogenic activities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 197.
Abstract 1970: Melatonin inhibits osteolytic bone metastasis through interrupting cancer cells-derived osteolytic factor and reduce osteoclast differentiation
Authors: Lai Jyun-Lin , Chang An-Chen , Chen Po-Chun , Tang Chih-Hsin 
Published: August 2019

Abstract
Osteolytic bone metastasis is seen in lung, breast, and prostate cancer and is associated with severe complications such as bone pain, fractures and hypercalcemia. In the bone microenvironment, osteoclasts play an important role in bone remodeling and bone resorption. Metastatic cancer cells may increase osteoclast differentiation and activity by releasing inflammatory cytokines including receptor activator of nuclear factor kappa-B ligand (RANKL), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and IL-8, leading to bone resorption and osteolytic lesions. The endogenous hormone melatonin is known to modulate bone resorption. Increasing evidence suggests that melatonin inhibits cancer cell proliferation, angiogenesis and metastasis. Up until now, the inhibitory role of melatonin in osteolytic bone metastasis has remained unclear. In In vitro study, we observed that melatonin inhibits the differentiation of precursor osteoclasts and promotes apoptosis in mature osteoclasts. We injected mice tibia with luciferase-labeled osteolytic cancer cell lines (lung cancer: A549, prostate cancer: PC-3) to establish bone metastasis. After 4 weeks of intraperitoneal injection with melatonin, IVIS fluorescence signaling indicated that melatonin inhibited tumor growth. X-ray imaging of the bone revealed an improvement in bone resorption after melatonin treatment. In In vitro melatonin also reduced RANKL protein and mRNA expression in the A549 and PC-3 cell lines. Our data indicate that melatonin improves bone mass by inhibiting the expression of cancer-derived osteolytic factors and by promoting apoptosis in mature osteoclasts. Our future investigations will seek to determine the signaling pathway involved in melatonin-regulated RANKL expression in cancer cells. In summary, our findings provide insight into the benefits of melatonin treatment in osteolytic bone metastasis.
Citation Format: Jyun-Lin Lai, An-Chen Chang, Po-Chun Chen, Chih-Hsin Tang. Melatonin inhibits osteolytic bone metastasis through interrupting cancer cells-derived osteolytic factor and reduce osteoclast differentiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1970.
Abstract 1974: Autocrine TIMP-1-mediated chemoresistance via induction of IL-6 in NSCLC
Authors: Xiao Wei , Rojiani Amyn M. , Gupta Sampa Ghoshal , Rojiani Mumtaz V. 
Published: August 2019

Abstract
Our previous studies have confirmed the well-defined antiapoptotic functions of TIMP-1. We have shown that overexpressing TIMP-1 in NSCLC cells increases cell survival with activation of the ERK pathway via phosphorylation of BAD at serine 112. Knocking down TIMP-1 in NSCLC cells increased the levels of miR-125a-5p with concomitant upregulation in apoptosis. These studies beg the question- does modulation of TIMP-1 affect chemotherapy in NSCLC? To address this question we examined two cell lines, A549 and H460, and their specific shRNA-mediated TIMP-1 gene knockdown clones. We found that TIMP-1 mediated chemoresistance against two front line chemotherapeutic agents (Gemcitabine and Cisplatin) as determined by increased apoptosis in the KD clones. In order to determine any contribution of cytokine activity towards this antiapoptotic function of TIMP-1, we carried out a cytometric bead array assay. The results of this screening assay which included potential inflammatory cytokines and growth factors, indicated that IL-6 plays a role in mediating the chemoresistance in TIMP-1 expressing NSCLCs. We then determined endogenous IL-6 levels in our array of NSCLC cell lines and found a direct correlation of IL-6 levels with TIMP-1 levels. It is important to note that IL-6 expression is precisely regulated with TIMP-1 production at both protein and mRNA levels. The effect of TIMP-1 on IL-6 levels is more pronounced under hypoxic versus normoxic conditions. Importantly, IL-6 expression is upregulated by addition of exogenous human recombinant TIMP-1 in a time- and dose- dependent manner. Blocking of TIMP-1 signaling with specific neutralizing antibodies delayed the IL-6 upregulation. Moreover, addition of rhTIMP-1 or rhIL-6 rescued apoptosis induced by chemotherapeutic agents albeit to a limited extent. Although early in the investigation, our studies suggest that interventions impacting the TIMP-1/IL-6 axis in NSCLCs may provide an efficient target to boost effects of clinical chemotherapy.
Citation Format: Wei Xiao, Amyn M. Rojiani, Sampa Ghoshal Gupta, Mumtaz V. Rojiani. Autocrine TIMP-1-mediated chemoresistance via induction of IL-6 in NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1974.
Abstract 1975: Multivariate exome analysis identifies CXCR5-CXCL13 signaling as a key driver in early breast cancer development and prognosis
Authors: Dill Courtney D. , Griffen Tiara , Young Corey , Carey Kaylin , Lillard James W. 
Published: August 2019

Abstract
Breast cancer (BrCa) is the most frequently diagnosed cancer and the second leading cause of cancer-related death among women worldwide despite new developments in prevention and treatment. More recently, rapid increases in BrCa incidence have been reported in countries of the Asia-Pacific region. Age of diagnosis in Asian BrCa patients is much younger than age of diagnosis in western countries, such as the United States, and Asian early BrCa patients tend to be pre-menopausal, whereas only 15-30% of western BrCas are pre-menopausal. The mechanisms responsible for early BrCa remain unknown. Furthermore, it remains controversial whether early breast cancer has unique tumor biology. The goal of this study was to characterize the molecular phenotype of early BrCa in the context of CXCL13, CXCR5 and associated gene expression. We hypothesized that CXCR5-CXCL13 signaling contributes to the aggressive phenotype of early BrCa. A bioinformatic approach was used to aid in characterizing this condition. Our patient cohort data (50 females of Korean descent, age ≤ 35 years) was obtained from The International Cancer Genome Consortium (ICGC). DESeq analysis was used to identify genes differentially expressed among normal tissue and primary tumor groups. Weighted Gene Network Co-expression (WGCNA) analysis was carried-out to identify gene networks associated with factors influencing BrCa prognosis. Finally, canonical pathway, upstream regulator, and gene interaction analysis was conducted using Ingenuity Pathway Analysis. Our data show CXCL13, CXCR5, and associated genes (LTA, LTB, IL10, IL27RA, TNFRSF13B, TNFRSF17, and TNFRSF9), which have been previously shown to drive tertiary lymphoid structure (TLS) formation, were significantly associated with the molecular phenotype of early BrCa in our patient cohort. Taken together, our findings suggest TLSs contribute to the tumor immune microenvironment and contribute to early BrCa progression.
Citation Format: Courtney D. Dill, Tiara Griffen, Corey Young, Kaylin Carey, James W. Lillard. Multivariate exome analysis identifies CXCR5-CXCL13 signaling as a key driver in early breast cancer development and prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1975.
Abstract 1979: Interaction of atorvastatin and CX3CR1-fractalkine in androgen-dependent prostate cancer cells: Effect on PI3K pathway
Authors: Al-Husein Belal 
Published: August 2019

Abstract
Prostate cancer (PC) management lacks any targeted therapies. Statins have shown anticancer effects against PC in both in vitro and in vivo studies. CX3CR1 is a receptor expressed by many cancer cells, including PC. In this research, we studies the interaction between atorvastatin and CX3CR1/fractalkine on androgen-dependent PC cell line 22Rv1 vs. normal prostatic cells, RWPE1. Experimental settings were based on testing effect of atorvastatin in presence of fractalkine or by removing its effect using fractalkine neutralizing antibodies. MTT proliferation assay and adhesion assay, together with testing the expression of CX3CR1, p-AKT and p-GSK-3 were used. Results showed that fractalkine partially blunts the effect atorvastatin on proliferation and adhesion of PC cells. Similar effects were not noticed on normal prostatic cells. Western blotting showed a dose-dependent reduction in the expression of CX3CR1, p-akt and p-GSK-3 in presence of fractalkine, that was further enhanced when fractalkine was neutralized using specific antibodies. Results suggest the deprivation of fractalkine as a synergistic mechanism to enhance effects of atorvastatin and probably other anticancer agents.
Citation Format: Belal Al-Husein. Interaction of atorvastatin and CX3CR1-fractalkine in androgen-dependent prostate cancer cells: Effect on PI3K pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1979.