bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1981: M2-macrophage derived exosomes mediates tumor progression via GATA3-IL-4-IL-13 axis in ovarian cancer
Authors: Kanlikilicer Pinar , El-Arabey Amr Ahmed , Denizli Merve , Bayraktar Recep , Ozpolat Bulent , Lopez-Berestein Gabriel , Salama Salama Abdu , Abd-Allah Adel Rashad 
Published: August 2019

Abstract
Tumor microenvironment is the key factor for tumor progression. Stromal cells which consist of, tumor associated macrophages(TAMs), tumor associated fibroblast as well as cancer stem cells has been implicated in the acquisition of oncogenic phenotype via cell-cell communication. Exosomes are the major players in tumor microenvironment that contributes to tumorigenesis. Exosomes carry genetic information from host cells to another cell to reprogram the recipient cell. Exosomes from TAMS has emerged as important mediators of tumor growth. Here, we report that GATA3 is released abundantly from TAM cells via exosomes and promote oncogenesis. GATA3 acts as an oncogenic protein and silencing GATA3 by siRNA led to decrease in tumor cell viability. Our data showed that silencing GATA3 increased the release of IL-4 and IL-13 from EOC cells, which leads to M2 cell polarization from M0 cells. Our results suggest that GATA3 released from macrophage exosomes contributes to tumor growth by affecting intracellular processes as well as tumor microenvironment. P.K. and A. El-A. contributed equally.
Citation Format: Pinar Kanlikilicer, Amr Ahmed El-Arabey, Merve Denizli, Recep Bayraktar, Bulent Ozpolat, Gabriel Lopez-Berestein, Salama Abdu Salama, Adel Rashad Abd-Allah. M2-macrophage derived exosomes mediates tumor progression via GATA3-IL-4-IL-13 axis in ovarian cancer [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 1981.
Abstract 1991: Exploring the potential of exosomes for cancer diagnosis and management: Comparative analysis of isolation methods for optimum yield purity and downstream applications
Authors: Patel Girijesh K. , Khan Mohammad Aslam , Zubair Haseeb , Srivastava Sanjeev Kumar , Khushman Moh’d , Singh Seema , Singh Ajay Pratap 
Published: August 2019

Abstract
Exosomes have received significant attention due to their involvement in several diseases, including cancer, and are being explored as a tool for disease diagnosis and management. As a result, several kits based on different principles are now available in the market for exosome isolation. In this study, we have compared the relative efficacy of four commercial kits from Invitrogen, 101Bio, Wako and iZON along with conventional ultracentrifugation-based method for exosome yield, purity and quality for downstream applications. Cancer cell culture supernatant was used as an abundant and uniform source of exosomes for all methods and exosome quantity, size distribution, zeta potential, marker expression, RNA (qRT-PCR) and protein (mass spectrometry) quality was determined. The Invitrogen method showed the highest yield but the preparation showed broader size distribution likely due to co-precipitation of microvesicles and had the least magnitude of zeta potential (dispersion stability). Exosome preparations from other methods showed accepted size range (&lt;150 nm) with a variable zeta potential (-12mV to -29mV) with good purity. The gel filtration method; however, showed a broader size distribution in the lower size range, which could be due contamination of aggregates of proteins and vitamins molecules. Quality of RNA isolated from all preparations was comparable; however, proteins isolated from Invitrogen method-based exosomal preparation showed contamination of polyethylene glycol (PEG) in mass spectrometry analyses. Similarly, other chemical impurities coming from the precipitant in Invitrogen kit could also be the reason for toxicity of resultant exosomal preparation in biological growth measurement assay. Together, these findings from comparative analyses should serve as a guide for choice and further optimization of exosome isolation methods for their desired downstream applications in cancer biology, therapy and/or biomarker discovery.
Citation Format: Girijesh K. Patel, Mohammad Aslam Khan, Haseeb Zubair, Sanjeev Kumar Srivastava, Moh’d Khushman, Seema Singh, Ajay Pratap Singh. Exploring the potential of exosomes for cancer diagnosis and management: Comparative analysis of isolation methods for optimum yield purity and downstream applications [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 1991.
Abstract 1996: Epigenetic reactivation of BAI1/ADGRB1 suppresses tumor invasion by preventing TGFβ1-induced mesenchymal switch in glioblastoma
Authors: Osuka Satoru , Yang Liquan , Zhu Dan , Hashimoto Hideharu , Devi Narra S. , Meir Erwin G. Van 
Published: August 2019

Abstract
Glioblastoma (GBM) is the most common and lethal type of malignant brain tumor in adults. GBM cells are highly invasive and diffusely infiltrate throughout the brain, which strongly restricts multimodal therapies. Acquiring a better knowledge of molecular defects underlying GBM invasion is essential for the development of effective therapies.
Brain-specific Angiogenesis Inhibitor 1 (BAI1/ADGRB1) is a transmembrane receptor of the adhesion GPCR family widely expressed in normal brain, but its expression is lost in the majority of glioblastoma through epigenetic silencing and restoration of its expression can inhibit glioma growth (Zhu D. et al, Cancer Res, 2012). Recently, we reported that BAI1 protects p53 from Mdm2-mediated degradation and regulate tumor growth in medulloblastoma (Zhu D. et al, Cancer Cell, 2018). However, it is unclear whether BAI1 loss is important for tumor invasion and the mesenchymal phenotype in GBM.
Microarray analysis of the GBM TCGA dataset revealed that low BAI1 mRNA expression correlates with poor outcome and with expression of many key mesenchymal genes, including Fibronectin1, SLUG, and TWIST1. Restoration of BAI1 expression in human GBM cells suppresses mesenchymal gene expression in culture, and dramatically decreases brain tumor invasion in mice xenografts. Mechanistically, we found that the N-terminal thrombospondin type 1 repeat (TSR#1) of BAI1 inhibits the maturation process of TGFβ1, a key growth factor involved in EMT. BAI1 is silenced epigenetically in GBM cells by methylated CpG-binding protein MBD2, and its expression can be reactivated by KCC-07, a blood-brain barrier permeable MBD2 inhibitor. We found that restoration of BAI1 expression by KCC-07 treatment dramatically reduced tumor cell invasion in orthotopic xenografts model of GBM cells.
These experiments demonstrate that epigenetic silencing of BAI1 is important for activation of the GBM invasive phenotype through TGFβ1 pathway activation. Epigenetic targeting of this process by KCC-07 can reduce GBM invasion and improve patient survival.
Citation Format: Satoru Osuka, Liquan Yang, Dan Zhu, Hideharu Hashimoto, Narra S. Devi, Erwin G. Van Meir. Epigenetic reactivation of BAI1/ADGRB1 suppresses tumor invasion by preventing TGFβ1-induced mesenchymal switch in glioblastoma [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 1996.
Abstract 200: The MCP-1/CCR2 axis enhances VEGF-A-dependent angiogenesis by directly downregulating miR-29c expression in oral squamous cell carcinoma
Authors: Lien Ming-Yu , Tang Chih-Hsin 
Published: August 2019

Abstract
Oral squamous cell carcinoma (OSCC), the sixth most common malignancy worldwide, has a poor prognosis due to its aggressiveness and potential for metastasis. Activation of monocyte chemoattractant protein-1 (MCP-1) and its receptor, CC chemokine receptor 2 (CCR2), induces angiogenic activation of endothelial cells, inflammatory responses and aberrant MCP-1/CCR2 expression in malignant tissues. However, the effect of MCP-1 and CCR2 in OSCC angiogenesis is unclear. Our study sought to determine how the MCP-1/CCR2 axis mediates VEGF-A expression in OSCC and results in angiogenesis. Immunohistochemistry (IHC) analysis identified higher concentrations of VEGF-A protein expression in tissue obtained from patients with OSCC compared with tissue from healthy controls; the degree of VEGF-A tumor expression was significantly associated with the clinical disease stage. Our in vitro investigations found that MCP-1 dose-dependently regulated VEGF-A expression through the CCR2, ILK and MEK signal transduction pathways. Following MCP-1 application, conditioned medium from the human OSCC cell line SCC4 significantly promoted endothelial progenitor cell (EPC) migration and tube formation; these events were attenuated and VEGF-A production was suppressed when we stimulated the OSCC cells with the pathway inhibitors RS102895, KP392, and PD98059. We also showed that microRNA (miR)-29c expression was negatively regulated by MCP-1 via the CCR2/ILK/MEK cascade, tying in with an analysis of the cancer genome atlas (TCGA) database showing lower levels of miR-29c expression in tissues from patients with oral cancer compared with samples from healthy controls. According to our results, the MCP-1/CCR2 axis promotes VEGF-A expression in OSCC via the ILK and MEK signal transduction pathways and downregulates miR-29c expression. Thus, MCP-1/CCR2 mediation of VEGF-A mobilizes EPCs required for OSCC and is important for tumor angiogenesis. MCP-1/CCR2 may be an appropriate target in the treatment of OSCC angiogenesis.
Citation Format: Ming-Yu Lien, Chih-Hsin Tang. The MCP-1/CCR2 axis enhances VEGF-A-dependent angiogenesis by directly downregulating miR-29c expression in oral squamous cell carcinoma [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 200.
Abstract 2008: CENP-E kinesin facilitates chemokine ligand CCL18 translocation to promote migration in triple negative breast cancer
Authors: Mullen McKay M. 
Published: August 2019

Abstract
Our research is focused on the molecular mechanisms responsible for enhanced cellular proliferation and migration as it relates to triple negative breast cancer (TNBC). Advances in visualization techniques and technologies work to provide an in-depth view of various cellular mechanisms, allowing us to capture molecular level protein-protein interactions previously unknown. There are more than 40 kinesin motor proteins found within the spindle assembly checkpoint, classified into 14 families, which each play essential roles in microtubule-dependent intracellular trafficking. This assembly is a critical component to the cell cycle control complex that acts during mitosis to prevent chromosome missegregation and aneuploidy. Centromere associated protein E (CENP-E) is a kinesin motor protein that shows aberrant overexpression in TNBC which facilitates exponential cell growth and eventual metastasis that occurs in TNBC. Growing awareness through scientific discoveries sheds light on the fact that it is a rare occurrence for biological functions to be attributed to a single mutated macromolecule. Most physiological processes arise from a complex orchestration of cellular events occurring between multiple molecules acting in concert. The nature of protein-protein transactions that drive gene activation appear to be dynamic in TNBC cells thus enabling uncontrolled proliferation. We believe that a pleiotropic network of small molecules may be working cooperatively with CENP-E to facilitate the exponential cell growth and eventual metastasis that occurs in TNBC cells. Currently, we are carrying out spectral imaging and biophysical force measurements to delineate CCL18-elicited cell mechanics and breast cancer metastasis. To address this, we have incorporated syntelin, a small inhibitory molecule targeted to CENP-E in an effort to analyze the resultant effect it has on this network of proteins we believe may be involved in the CENP-E signaling cascade. Taken together, these results indicate that syntelin may comprise a novel targeted chemotherapeutic intervention for TNBC.
Citation Format: McKay M. Mullen. CENP-E kinesin facilitates chemokine ligand CCL18 translocation to promote migration in triple negative breast cancer [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 2008.
Abstract 2009: Leronlimab, a humanized monoclonal antibody to CCR5, blocks breast cancer cellular invasion and enhances cell death induced by DNA damaging chemotherapies
Authors: Jiao Xuanmao , Wang Min , Pestell Richard G. 
Published: August 2019

Abstract
Purpose of the study. To assess binding and functional interaction of the humanized monoclonal antibody to CCR5 (Leronlimab) with human breast cancer cell lines. The G protein coupled receptor CCR5, is normally expressed on a subset of T cells and serves as a co-receptor for HIV infection. During malignant transformation CCR5 expression is known to increase in a number of cancers (breast cancer (BCa), prostate cancer, colon cancer, melanoma). CCR5 targeted cancer clinical trials using small molecular inhibitors opened to accrual in late 2018. CCR5 is expressed in &gt;50% of human BCa, primarily in triple negative BCa. Its expression in human BCa correlates with poor outcome and CCR5+ BCa epithelial cells have characteristics of cancer stem cells, forming mammospheres and initiating tumors with &gt;60-fold greater efficiency in mice. Reintroduction of CCR5 expression into CCR5 negative BCa cells promotes tumor metastases and induces DNA repair gene expression and activity. The CCR5 inhibitor Leronlimab has been used for treatment of &gt;550 patients HIV, including meeting its primary endpoints in a phase III study, without significant adverse events reported.
Results. Leronlimab bound to CCR5 expressed in human breast cancer cell lines with 98% efficiency. Leronlimab abrogated CCL5 induced Ca+2 flux and blocked 3-d matrigel invasion of MDA-MB-231 cells. Leronlimab also augmented cell killing by DNA damage inducing agents Doxorubicin.
Conclusions. Leronlimab binds CCR5 in BCa cells, blocking breast cancer cellular invasion and augmenting cell killing by DNA damage inducing chemotherapies. As CCR5 augments DNA repair and is expressed selectively on cancerous but not normal breast epithelial cells, Leronlimab may enhance the tumor specific activities of DDR-based treatments, allowing a reduction in dose of standard chemotherapy and radiation.
Citation Format: Xuanmao Jiao, Min Wang, Richard G. Pestell. Leronlimab, a humanized monoclonal antibody to CCR5, blocks breast cancer cellular invasion and enhances cell death induced by DNA damaging chemotherapies [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 2009.
Abstract 201: The mechanism of vascular mimicry in clear cell renal cell cancer
Authors: Yang Jun-Ping , Peng Xing-Si , Qian Chao-Nan 
Published: August 2019

Abstract
Although anti-angiogenic drugs were used as first-line treatment in metastatic clear cell renal cell cancer (ccRCC), some patients with metastatic ccRCC still had limited survival benefit from anti-angiogenic therapy. The main reason was resistance to anti-angiogenesis treatment. Tumor blood vessel could be divided into endothelial cell-derived or tumor cell-derived vessels. Tumor cell-derived vascular channel was called as tumor vascular mimicry (VM). PAS-CD34 staining in ccRCC tissues revealed that the expression status of VM was different in ccRCC patients. And the progression-free survival and overall survival were significantly shorter in ccRCC patients with high VM expression level. To explore the effect of VM on the resistance to anti-angiogenesis treatment and the molecular mechanism of VM, we successfully established a three-dimensional culture model for the formation of tumor cell-derived vessel-like structures. We found the formation of blood vessel-like structures in kidney cancer cells was not affected by the anti-angiogenic drug, such as Sunitinib, suggesting that VM was closely associated with resistance to anti-angiogenic therapy. Moreover, we had discovered the “molecular signature of vascular mimicry in renal cancer”. Using this signature, 531 ccRCC patients in TCGA could be divided into two groups with different prognosis. More importantly, we found that HGF/c-MET signaling pathway regulated the expression of Serpinb2 through the downstream AKT pathway, and thus affected the formation of vascular mimicry in SN12C, 786-O cells. In addition, we also had found that HGF could promote the formation of blood vessel-like structure in lung and bladder cancer cells, and the " molecular signature of vascular mimicry in renal cancer " also could differentiate patients with renal papillary carcinoma, bladder cancer, endometrial cancer, lung adenocarcinoma cancer, and pancreatic cancer. These finding suggested that the molecular mechanism of vascular mimicry in renal cancer was universal, to some extent. This project partially elucidated the molecular mechanism of vascular mimicry in renal cancer and its clinical significance, laying a theoretical foundation for the development of more effective anti-angiogenic drugs.
Citation Format: Jun-Ping Yang, Xing-Si Peng, Chao-Nan Qian. The mechanism of vascular mimicry in clear cell renal cell cancer [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 201.
Abstract 2011: Potassium usnate inhibits invasion and metastasis in colorectal cancer: Implication of clinical application of a water-soluble form of usnic acid in anticancer therapy
Authors: Yang Yi , Bae Woo Kyun , Lee Kyung Hwa , Moon Kyung-Sub , Park So-Yeon , Zhou Rui , Taş Isa , Gamage Chathurika , Lee Sueun , Jung Chaeyong , Kim Kyung Keun , Ha Hyung-Ho , Kim Hangun 
Published: August 2019

Abstract
Usnic acid (UA), a lichen secondary substance, has considerable anticancer activity in vitro, whereas its effect in vivo is limited. Here, potassium usnate (KU) was prepared by the salinization of UA to enhance its water solubility. KU showed increased bioavailability compared with UA in the tumor, liver, and plasma of a CT26 syngeneic mouse tumor xenograft model after oral administration, as determined by LC-MS/MS analysis. KU exhibited potent anticancer effects on colorectal cancer cells and inhibited liver metastasis in an orthotopic murine colorectal cancer model. KU treatment downregulated the epithelial-mesenchymal markers Twist, Snail, and Slug and the metastasis-related genes CAPN1, CDC42, CFL1, IGF1, WASF1, and WASL in cells and tumor tissues. The present results suggest the potential application of the water-soluble form of UA, KU, in anticancer therapy.
Citation Format: Yi Yang, Woo Kyun Bae, Kyung Hwa Lee, Kyung-Sub Moon, So-Yeon Park, Rui Zhou, Isa Taş, Chathurika Gamage, Sueun Lee, Chaeyong Jung, Kyung Keun Kim, Hyung-Ho Ha, Hangun Kim. Potassium usnate inhibits invasion and metastasis in colorectal cancer: Implication of clinical application of a water-soluble form of usnic acid in anticancer therapy [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 2011.
Abstract 2018: Cannabinoid receptor 2 agonist JWH-015 inhibits growth and metastasis of triple negative breast cancers through regulation of autophagy mechanism
Authors: Chatterjee Nabanita , Das Subhadip , Ahirwar Dinesh K. , Mishra Sanjay , Ganju Ramesh 
Published: August 2019

Abstract
Metastasis to distant organs is the major cause of mortality associated with breast cancer. Triple-negative breast cancer (TNBC) subtype has been shown to be associated with worst patient survival due to high metastasis rate and lack of targeted therapies. Therefore, there is an utmost need to develop novel therapeutic strategies against TNBC growth and metastasis. Cannabinoids are known to possess anti-cancer activity. However, the associated psychotropic activity limits the therapeutic use of Cannabinoids in breast cancer patients. Here, we used synthetic cannabinoid JWH-015 which activates cannabinoid receptor 2 (CB2) and is devoid of psychotropic activity. In vitro molecular analysis revealed that JWH-015 induces TNBC cell death by activating autophagy associated apoptosis. In addition, we have further shown using in vivo tumor models, that JWH-015 potentially inhibits TNBC growth and metastasis through activation of autophagy mechanisms. Further analysis showed that JWH-015 treated tumors recruited the reduced number of macrophages compared to vehicle control treated tumors. In addition, there were more anti-tumor M1-type macrophages present in JWH-015 treated tumors. Conversely, vehicle control treated tumors possessed a higher number of pro-tumor M2-type macrophages. These observations have established the anti-metastatic potential of JWH-015 in different TNBC pre-clinical mouse models. The mechanistic studies have elaborated the role of JWH-015-induced autophagy in promoting tumor cell death to inhibit TNBC growth and metastasis.
Citation Format: Nabanita Chatterjee, Subhadip Das, Dinesh K. Ahirwar, Sanjay Mishra, Ramesh Ganju. Cannabinoid receptor 2 agonist JWH-015 inhibits growth and metastasis of triple negative breast cancers through regulation of autophagy mechanism [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 2018.