bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3456: RNA and microRNA analysis of diffused intrinsic pontine glioma specimens
Authors: Sandza Annie E. , Hill Ashley , MacDonald Tobey , Nazarian Javad 
Published: June 2012

Abstract
Diffused intrinsic pontine glioma (DIPG) is one of the most difficult pediatric cancers to treat. To date, there is only limited information on the molecular characteristics of this tumor because of the paucity of adequate tissue for investigation due to its inoperable location within the brainstem. In an attempt to uncover the pathogenesis of DIPG, we have generated comprehensive molecular profiles of coding and non-coding RNA species obtained from pediatric DIPG autopsy specimens. Coding and non-coding RNA species play an important role in oncogenesis. Micro RNAs (miRNAs or miRs) are the more recent non-coding RNA species that have been shown to play an essential role in cancer development and cancer biology. Our aim was to gain insight into the molecular underpinnings of DIPG by generating the complete miRNA and mRNA profiles of the tumor.
Autopsy DIPG specimens were analyzed (n=3). Adjacent non-tumor areas were identified by a neuropathologist and used as controls. Total RNA was extracted and coding and non-coding small RNA were profiled using the Affymetrix platform. A total of 60 miRNA species were found to be dysregulated in DIPG tumor compared to adjacent normal section. Of these, 12 were known human micro RNAs. RNA species that showed to be dysregulated were further validated by RT-PCR (ABI platform). Furthermore, correlation analyses were done to assess expression levels of mRNAs and their corresponding miRs. Our preliminary data indicates specific dysregulation of micro RNA and RNA species that control cellular proliferation and tumorigenesis.
Although preliminary, this is to our best knowledge, the first report of comprehensive RNA profiling of DIPG. Correlation of coding and non-coding RNA species observed here will require further validation. Understanding the molecular makeup of DIPG will provide insight into its pathogenesis and perhaps lead to the development of targeted therapeutics for this disease.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3456. doi:10.1158/1538-7445.AM2011-3456
Abstract 3469: EphrinB2 promotes endothelial cell survival and vascular integrity
Authors: Salvucci Ombretta , Maric Dragan , Zhang Fan , Li Xuri , Basik Mark , Buchanan Marguerite , Tosato Giovanna 
Published: June 2012

Abstract
EphrinB transmembrane ligands and their cognate EphB receptors critically contribute to vascular development through cell-to-cell signaling by the EphB receptor (forward signaling) and by the EphrinB ligand (reverse signaling). Previous studies demonstrated that mutant mice lacking ephrinB2 or EphB4 and a proportion of mice lacking EphB2 and EphB3 display severe defects in the embryonic vascular system and die at the embryo stage likely due to these vascular defects. Previously, we showed that EphB2, EphB4 and EphrinB2 are required for mature endothelial cell assembly into capillary structures. In the currently studies, we observed that silencing EphrinB2 expression in different types of primary human endothelial cells causes significant and time-dependent apoptotic cell death, as measured by cleavage of Poly(ADP-ribose) Polymerase (PARP), caspase-3 and caspase-8. VEGF, bFGF and SDF-1 variously modulated apoptosis induced by loss of EphrinB2 expression in endothelial cells. Gene expression profiling revealed that EphrinB2 silencing is associated with reduced expression of genes linked to regulation of the cell cycle progression and cytoskeleton organization, and with increased expression of pro-apoptotic genes. Breast cancer tissue from a patient treated with bevacizumab, a humanized monoclonal antibody that neutralizes VEGF, displayed evidence of endothelial cell apoptosis, which was associated with selectively reduced EphrinB2 expression, suggesting a link between VEGF signaling, EphrinB2 expression and cell death. These studies show that EphrinB2 expression is critical to endothelial cell survival in vitro and suggest that EphrinB2 contributes to blood vessel integrity in vivo. Thus, in addition to its well-characterized function as a regulator of cell-to-cell adhesion and repulsion, EphrinB2 is an endothelial pro-survival molecule, which may serve as a novel target for anti-angiogenic therapies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3469. doi:10.1158/1538-7445.AM2011-3469
Abstract 3484: Murine and human lymphatic endothelial cells show similar marker profiles and migratory properties
Authors: Coso Sanja , Williams Elizabeth D. 
Published: June 2012

Abstract
Introduction: Lymphangiogenesis (growth of nascent lymphatic vessels in vivo and proliferation, migration and tube formation of lymphatic endothelial cells (LECs) in vitro) plays a key role in lymph node metastasis in a number of tumour types (1), including prostate cancer. Mechanisms underlying tumor cell-lymphatic vessel interactions are critical to understand. Thus determining the molecular basis of LEC motility and its relationship to lymphangiogenesis and subsequent metastasis will play an important part in developing novel strategies to prevent metastasis.
We have previously shown that members of the vascular endothelial growth factor (VEGF) family regulate migration of human LECs (2). As the effect of stimulation with VEGF family ligands has not been reported in murine LECs, this study aims to isolate and characterize murine LECs and to compare their migratory profiles to human LECs. This data will be important in determining the relevance of experiments utilizing LECs derived from transgenic and/or human tumor-bearing mice to the study of lymphangiogenesis in human cancers.
Results: Murine LECs were successfully isolated from prostate and skin using a CD34 depletion, CD31 positive selection strategy. Murine LECs expressed lymphatic endothelial cell markers Prox-1 and LYVE-1. The migratory profile of murine LECs was compared to human LECs using a panel of extracellular substrates and VEGF family ligands. VEGF-C and VEGF-D potently stimulated murine LEC migration in vitro. Stimulation of murine LECs with VEGF-C caused activation of pAKT(Ser347), Erk1/2 and JNK signalling pathways, consistent with observations in human LECs.
Conclusions: This study describes a successful, robust protocol for isolation of murine LECs. Murine LECs derived from transgenic and knock-out mouse models will provide important insights into the molecular mechanisms of lymphangiogenesis and allow the study of LECs in the context of cancer metastasis and other disease associated with altered lymphatic vessel architecture or function.
(1) Mumprecht V, Detmar M (2009) J Cell Mol Med, 13: 1405-16
(2) Zeng Y, Opeskin K, Goad J, Williams ED (2006) Cancer Res, 66: 9566-75
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3484. doi:10.1158/1538-7445.AM2011-3484
Abstract 3489: In silico analysis of angiogenesis pathway as a prognostic tool in breast cancer
Authors: Mehta Rutika J. , Jain Rohit K. , Gökmen-Polar Yesim , Badve Sunil 
Published: June 2012

Abstract
Gene expression profiling studies have enabled us to study breast cancer biology at a molecular level. Studies have been geared at identifying better and comprehensive prognostic markers for the development of targeted therapeutics. With the growing use of anti-angiogenic agents as second line agents, we aim to study the prognostic role of angiogenesis related genes through retrospective analyses of publicly available breast cancer gene expression datasets.
Three gene expression datasets from studies by van't Veer et al, Sorlie et al., and Sotiriou et al were analyzed. The data was downloaded from the BRB Array Tools archives and analyzed using BRB Array Tools. Since, we were particularly interested in genes related to angiogenesis; we selected the (CGAP) angiogenesis subset for the purpose of survival analyses. Two endpoints, overall survival (OS) and relapse free survival (RFS), were analyzed. Data for OS was not available for van't Veer et al. A subset analysis for estrogen receptor positive cases was performed.
HIF1A was prognostic for OS and RFS in all datasets. VEGF was associated with survival only in ER+ cases. EGFR is prognostic for RFS but not OS. Several other angiogenesis genes were noted to affect prognosis in terms of OS and RFS (Table 1). Analysis of other publically available datasets will be undertaken to further validate these findings in ER+ and negative subgroups of breast cancer.
These analyses highlight the importance of VEGF as an important marker among ER+ breast cancer patients. Thus, anti-angiogenic agents targeting VEGF may appear to play an important therapeutic role in this subset of patients. The analysis provides additional evidence of the importance of HIF1A in breast cancer. This may help identifying sub-populations of breast cancer that are most likely to respond to targeted therapies. Further immunohistochemical validation in in-vitro models will be performed.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3489. doi:10.1158/1538-7445.AM2011-3489
Abstract 3492: NET as a repressor on transcriptional regulation of MT1-MMP in endothelial cells
Authors: Heo Sun-Hee , Choi Young-Jin , Ryoo Hyun-Mo , Cho Je-Yoel 
Published: June 2012

Abstract
In mice deficient for the Ets family genes, disrupted angiogenesis and malformed vascular system inform critical role of Ets factors in vasculogenesis and angiogenesis. NET is a member of ETS transcription factors and acts as a repressor of transcription. To find role of NET in angiogenesis, angiogenesis related assay were carried out using NET specific siRNA. In addition, it was confirmed regulation of NET on transcription of angiogenesis-regulated genes. Our results showed that suppression of NET expression result in buildup of VEGF-induced tube formation. In addition, suppressed expression of NET induced expression of MT1-MMP. Induction of MT1-MMP expression by knock down of NET expression was not result direct effect of NET on transcription of MT1-MMP in endothelial cells. In endothelial cell, NET suppressed ETS-1 induced-transcriptional activity of MT1-MMP. Our results suggest that NET is a negative regulator of angiogenesis on indirect regulation of MT1-MMP and induction of tube formation by its expressional suppression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3492. doi:10.1158/1538-7445.AM2011-3492
Abstract 3506: γ-secretase inhibitor enhances anti-cancer effects of 5-FU in gastric cancer
Authors: Shin Ji-Young , Lee Kang-Duck , Shin Young-Ho , Chun Kyung-Hee 
Published: June 2012

Abstract
Surgery is the most effective therapy for early gastric cancers. In advanced gastric cancer (AGC), achievement of loco-regional control after tumor resection is less successful because of frequent recurrences after surgical and medical therapies. Combinations of 5-fluorouracil (5-FU) and platinum analogues or cytotoxic agents, such as capecitabine, cisplastin, oxaliplatin and S-1, are currently widely accepted as standard treatment for AGC. However, survival of AGC patients following sedative chemotherapy is poor. Therefore, the development of novel therapies has been needed, and some clinical studies already have been performed using novel molecular targeting agents have shown hopeful activity, particularly in combination with cytotoxic agents. Recently, the importance of Notch signal pathway has been reported in gastric cancer. Gamma-secretase inhibitors (GSI), a notch proteolytic activation blocker, can be considered as a novel target agent for gastric cancer.
In this study, the anti-proliferation effects of GSI combined with 5-FU on gastric cancer cells in vitro and in vivo were studied. GSI combined with 5-FU was treated on gastric cancer cells, and then cell-proliferation by MTT assay, apoptosis by annexin V and expressions of protein level were determined by western blotting. Effects of GSI combined with 5-FU on tumor growth in vivo was assessed in an experimental model with orthotopically grown tumors. In gastric cancer cells, GSI combined with 5FU significantly inhibited cell proliferation and induced apoptosis. It was confirmed by expression changes of apoptosis related protein, such as caspase-3, caspase-8, caspase-9, PARP, BCL2, BID and BAX. GSI is also known to regulate PI3K/PTEN/AKT signaling pathway. After treatment with GSI plus 5-FU, this pathway was significantly down-regulated, and more, over-expression of constitutively activated AKT could prevent the apoptosis induction by combination treatment. This is suggested that the combination treatment with GSI plus 5-FU decreases the gastric cancer cell growth through inhibition of PI3K/PTEN/AKT signaling pathway. Moreover, administration of GSI in combination with 5-FU drastically reduced gastric tumor burdens in orthografted mice without prominent gastrointestinal toxicity. In conclusion, we present here that the combination treatment with GSI plus 5-FU has a potential for therapeutic activity in advanced gastric cancer patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3506. doi:10.1158/1538-7445.AM2011-3506
Abstract 3507: Sulforaphane facilitates mitotic cell death triggered by arsenic trioxide
Authors: Yih Ling-Huei , Kuo Hsiao-Hui , Wu Yi-Chen 
Published: June 2012

Abstract
Arsenic trioxide (ATO) is an important antileukemic drug, but its use as a single agent in clinical trials against solid tumors was found to be mostly not effective or too toxic. Given the toxicity of chemotherapeutic agents, there is a considerable interest in the use of natural compounds with anti-tumorigenic properties for cancer treatment. In this study, we demonstrate that the cytotoxicity of ATO is significantly increased by cotreatment with non-toxic concentration of sulforaphane, an isothiocyanate found in cruciferous vegetables. The increased cytotoxicity was preceded by enhanced generation of reactive oxygen species and ATO-induced mitotic abnormalities and mitotic arrest. Consequently, sulforaphane facilitated mitotic cell death caused by ATO. However, neither zVADfmk (a pan caspase inhibitor) nor necrostatin (a necrosis inhibitor) prevented the cell death induced by the combined treatment indicating that caspase-dependent apoptosis or nercrosis is not involved in the enhanced cytotoxicity. In addition, no significant change on NF-κB-dependent transcription was observed at the non-toxic concentration used in this study indicating that sulforaphane did not exert the enhanced killing effect by inhibition of NF-κB. Since induction of mitotic arrest and mitotic cell death selectively kills highly proliferating cells, the enhanced mitotic cell death induced by cotreatment of ATO and sulforaphane provides a strategy to selectively kill cancer cells and to enhance the therapeutic efficacy of ATO.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3507. doi:10.1158/1538-7445.AM2011-3507
Abstract 351: Tumor kinome profiling of early systemic disease dissemination in rectal cancer
Authors: Saelen Marie G. , Flatmark Kjersti , Folkvord Sigurd , de Wijn Rik , Rasmussen Heidi , Fodstad Oystein , Ree Anne H. 
Published: June 2012

Abstract
Tumor hypoxia as common determinant of resistance to cytotoxic therapies and metastatic behavior is an emerging hypothesis. In baseline tumor biopsy specimens from rectal cancer patients receiving preoperative chemoradiotherapy, using peptide arrays with 144 tyrosine kinase substrates, we have recently shown [Folkvord et al., Int J Radiat Oncol Biol Phys 2010] that phosphopeptide levels generated by tumors with poor response to the chemoradiotherapy were significantly higher than substrate phosphorylation resulting from tumors with good treatment response. The elevated kinase activity in poor-responding tumors was suppressed by the ex vivo addition of the tyrosine kinase inhibitor sunitinib and proved to represent signaling mediated by VEGFR, EGFR, and PI3K/AKT, which is known to be implicated in experimental radiation resistance. Given that these signaling pathways might be involved in adaptive responses to tumor hypoxia, this follow-up study aimed to determine whether the tumor kinase activity signatures might also correlate to systemic disease dissemination. Immunomagnetic detection of tumor cells in bone marrow aspirates was undertaken at the time of diagnosis, and bone marrow micrometastases (BMM) were observed in 33 of 55 (60%) of the patients from whom tumor kinase activity signatures had been obtained. In this new analysis, association between ex vivo sunitinib inhibition of the kinase activity and BMM status was studied, and phosphorylation of 31 tyrosine kinase substrates was significantly more strongly inhibited by sunitinib in the BMM negative patients than in the BMM positive individuals. Interestingly, discriminating phosphopeptides represented proteins derived from signaling pathways implicated in angiogenesis; e.g., signaling mediated by PDGFR, VEGFR, and EPOR, which is a central response to tumor hypoxia and fundamental for metastasis formation. At present, this patient cohort has a median follow-up of 41 months (range 13-58) and has demonstrated significantly poorer metastasis-free survival for the BMM-positive group than for the BMM-negative group (p = 0.008). In conclusion, in this cohort of rectal cancer patients, a tumor phenotype defined by a subset of tyrosine kinase activities insusceptible to the ex vivo inhibitory effect of sunitinib was associated with early systemic dissemination. This project was supported by the EU FP7 grant number 222741 (METOXIA).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 351. doi:10.1158/1538-7445.AM2011-351
Abstract 3525: Targeting Group VIA phospholipase A2 using small molecules for ovarian cancer treatment
Authors: Xu Yan , Li Hui , Zhao Zhenwen , Antalis Caryl , Emerson Robert , Zhang Sheng , Zhang Zhongyin , Zhao Zhanzhong , Gang Wei , Yan Libo , Cai Qingchun 
Published: June 2012

Abstract
Epithelial ovarian cancer (EOC) causes estimated 13,850 deaths in 2010 in the United State. More effective treatment regimens are urgently required for this deadly disease. We and others have obtained ample evidence indicating that lysophosphatidic acid (LPA) plays an important role in EOC development. We have recently shown that the levels of LPA and several other bioactive lipids in the tumor environment of EOC are regulated by Group VIA calcium-independent phospholipase A2 beta (iPLA2β) expressed in tumor microenvironment, suggesting that targeting iPLA2β in both host and tumor cells will likely to be beneficial. To test this idea, we used bromoenol lactone (BEL), a selective inhibitor of iPLA2β in vivo, and found that BEL significantly inhibited EOC tumorigenesis and metastasis in mouse xenograft models using human SKOV3 and HEY ovarian cancer cells. Moreover, the combination of BEL with paclitaxel (PTX), one of the mostly commonly used therapeutics in EOC, almost completely blocked tumor development in the xenograft mouse model. BEL showed very low or no detectable cytotoxic effects in mice. Another iPLA2 inhibitor, FKGK11, also inhibited tumor development in the xenograft mouse model, supporting that the major target of action was iPLA2. The combinational effects of BEL and PTX in vivo likely stem from their distinct cellular effects. BEL and FKGK11 reduced adhesion, migration, and invasion of EOC cells in vitro; the reduced ability appears to increase the vulnerability of tumor cells to PTX. In summary, this is the first attempt to target iPLA2 using a small inhibitor molecule for cancer treatment in vivo. In addition, the work is also rather unique by targeting activity of the same molecule (iPLA2) in both host and tumor cells. These results provide an important basis for development of new treatment modalities for EOC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3525. doi:10.1158/1538-7445.AM2011-3525