bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1365: Visualizing the effect of BIBF1120 in lung cancer cells by imaging-massspectrometry (MS)
Authors: Arai Daisuke , Soejima Kenzo , Yasuda Hiroyuki , Ishioka Kota , Kagawa Shizuko , Hamamoto Junko , Naoki Katsuhiko , Emoto Katsura , Sugiura Yuki , Suematsu Makoto , Betsuyaku Tomoko 
Published: August 2015

Abstract
Background: Angiogenesis plays an important role for tumor maintenance, progression, and metastasis. BIBF1120 is a multiple tyrosine kinase inhibitor, targeting VEGFR, FGFR and PDGFR, and is known as an anti-angiogenic agent. The mechanism by which anti-angiogenic agents suppress the growth of tumors is supposed to be induction of under-nutrition. However, no study has demonstrated the regional differences in the nutrition status of tumors treated by anti-angiogenic agents. Imaging MS is a novel technology that quantitatively visualizes the distribution of hundreds of metabolites in the selected area of tissues.
Aim: The aim of this study is to evaluate the efficacy of BIBF1120 in lung cancer cells, and to examine whether BIBF1120 induces under-nutrition status in association with suppressed angiogenesis in xenograft models of lung cancer using Imaging MS.
Method: We used lung cancer cell lines driven by several types of histology, PC9, H1975, H3122, A549, H69, and H520. The efficacy of BIBF1120 was evaluated by MTS assay and mouse xenograft model. We treated the xenografted mice with BIBF1120 or vehicle for 4 weeks and harvested xenograft tumors. Micro vessel density and percentage of apoptosis cells in the tumors was evaluated by immunohistochemistry using anti-Ki-67 antibody and anti-cleaved caspase 3 antibody, respectively. The effect of BIBF1120 on metabolic status in xenograft tumors was evaluated by imaging MS.
Result: BIBF1120 inhibited the growth of all of the xenograft tumors tested, although it did not directly affect the proliferation rate of those cells in vitro. BIBF1120-treated tumors exhibited significantly lower micro vessel density compared to the vehicle-treated tumors (p&lt;0.05), but BIBF1120 didn't increased the percentage of apoptosis cells. Imaging MS revealed that BIBF1120 treatment reduced 2-3 DPG (a maker of blood flow), glucose intake, and amount of ATP, whereas activated glycolysis via anaerobic metabolic pathway rather than oxidative phosphorylation in peripheral area of tumors.
Conclusion: To our knowledge, this is the first report to demonstrate the effect of BIBF1120 on the nutrition status of tumor cells in a site-specific manner.
Citation Format: Daisuke Arai, Kenzo Soejima, Hiroyuki Yasuda, Kota Ishioka, Shizuko Kagawa, Junko Hamamoto, Katsuhiko Naoki, Katsura Emoto, Yuki Sugiura, Makoto Suematsu, Tomoko Betsuyaku. Visualizing the effect of BIBF1120 in lung cancer cells by imaging-massspectrometry (MS). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1365. doi:10.1158/1538-7445.AM2015-1365
Abstract 1367: Anti-angiogenesis promotes venous thromboembolism through inducing PAI-1 in a mouse xenograft model of human lung carcinoma
Authors: Chen Ni , Ren Meiping , Li Rong , Deng Xin , Li Yongjie , Yan Kai , Xiao Lamei , Yang Yan , Wang Liqun , Luo Mao , Wu Jianbo 
Published: August 2015

Abstract
Thromboembolism is a major source of morbidity and mortality in patients with cancer. Increased incidence of venous thromboembolism (VTE) was associated with anti-vascular endothelial growth factor (VEGF) treatment in cancer. However, the mechanism of VTE initiation remains elusive. In this study, we addressed the effect of bevacizumab, a humanized monoclonal antibody against VEGF-A on either an inferior vena cava stenosis or a saphenous vein model using a xenograft mouse model. We found that treatment of bevacizumab accelerated thrombosis in a saphenous vein model with an increased thrombus weight in an inferior vena cava stenosis model. Administration of bevacizumab inhibited the growth of lung tumor by suppressing angiogenesis. Both intrathrombotic PAI-1 expression and plasma PAI-1 level was significantly increased by the treatment of bevacizumab. Furthermore, pharmacologic inhibition of PAI-1 with PAI-039 blocked the bevacizumab-induced venous thrombosis, but showed no change in tumor growth. Collectively, these findings indicate that PAI-1 plays a role in VET with anti-angiogenesis therapy, and have efficacy as a therapeutic strategy to prevent VET.
Citation Format: Ni Chen, Meiping Ren, Rong Li, Xin Deng, Yongjie Li, Kai Yan, Lamei Xiao, Yan Yang, Liqun Wang, Mao Luo, Jianbo Wu. Anti-angiogenesis promotes venous thromboembolism through inducing PAI-1 in a mouse xenograft model of human lung carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1367. doi:10.1158/1538-7445.AM2015-1367
Abstract 1381: The vascular targeted and antitumor effects of gene electrotransfer of plasmid silencing endoglin with tissue specific and constitutive promoter
Authors: Stimac Monika , Dolinsek Tanja , Lampreht Ursa , Cemazar Maja , Sersa Gregor 
Published: August 2015

Abstract
Endoglin, the transforming growth factor-β (TGF-β) co-receptor, mediates proliferation, differentiation and migration of endothelial cells forming neovasculature. It is promising target for vascular targeted therapies for the treatment of cancer, although its specific, safe and long-lasting targeting remains the challenge. One of the options for targeted and prolonged silencing is gene electrotransfer (GET) of plasmid DNA encoding shRNA against endoglin. In our study we used two plasmid DNAs; one with tissue specific promoter for endothelial cells (TS plasmid) and the other with constitutive promoter (CON promoter). In vitro, we evaluated the transfection efficacy using flow cytometry measurement of transfected cells and determined the vascular targeted effects by tube formation assay. The therapeutic potential of the GET of plasmids and comparison of theirs efficacies in vitro was obtained by measuring tumor growth and by analyzing histological sections for determining area of necrosis and a number of activated blood vessels.
In vitro, we demonstrated the tissue specificity of TS plasmid on several cell lines, and the antiangiogenic efficacy of GET of either of both plasmids, as reduced tube formation of 2H11 endothelial cells. In vivo, on a murine mammary TS/A tumor model, we demonstrated good antitumor effect of GET of either of both plasmids in treatment of smaller tumors in avascular phase of growth, as well as on bigger tumors, already well vascularized, possibly due to both, the antiangiogenic and vascular disrupting effect. In order to support that, the histological analysis has demonstrated an increase in necrosis and a decrease in the number of blood vessels in therapeutic groups. Therefore, using GET of TS plasmid we were able to demonstrate that it is specific, safe and has quite the same efficacy as the GET of CON plasmid. Therefore, our approach can represent a novel alternative to other therapeutic approaches that aim at silencing endoglin, which represents also an alternative target in VEGF resistant (unresponsive) tumors.
Citation Format: Monika Stimac, Tanja Dolinsek, Ursa Lampreht, Maja Cemazar, Gregor Sersa. The vascular targeted and antitumor effects of gene electrotransfer of plasmid silencing endoglin with tissue specific and constitutive promoter. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1381. doi:10.1158/1538-7445.AM2015-1381
Abstract 1389: Study on cancer stem cell marker CD90 in liver cancer
Authors: Chen Wei-Ching , Lai Ming-Derg 
Published: August 2015

Abstract
CD90 is a glycophosphatidylinositol (GPI)-anchored glycoprotein, which is highly expressed in stem cells. CD90 involves in immunological function and nonimmunological functions, including cell adhesion, migration and cell death. The published data show that CD90 is a tumor suppressor gene in ovarian cancer and nasopharyngeal carcinoma. However, several studies indicate that CD90 is a potential marker for liver cancer stem cells (CSCs). It suggests that CD90 leads to different function in different tumors. In order to elucidate the role of CD90 in liver cancer progression, the HepG2 and Hep3B stable transfectants expressing exogenous CD90 were established and the tumorigenic ability was analyzed in vivo and in vitro. We further analyzed the stemness properties of the transfectants and found that CD90 increased the sphere formation ability and ALDH activity. We further analyzed the role of CD90 in ovarian cancer cell and found that there is a controversial phenotype in SKOV3 cell compared to liver cancer cell. Several cell surface markers have been used to identify liver cancer stem cells including CD90, EpCAM, CD133, CD44, and CD13. Among these markers, CD90 is particularly interesting since overexpression of CD90 inhibited the growth of another type of tumor. We analyzed the cross-talk interaction between CD90 and the other CSC markers and found that there was a cause-effect relationship. We further identified the signaling transduction pathway in mediating the processes of CD90-induced tumorigenic ability. Our findings provide a concept to target stemness-associated signaling axis as a strategy to treat cancer.
Citation Format: Wei-Ching Chen, Ming-Derg Lai. Study on cancer stem cell marker CD90 in liver cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1389. doi:10.1158/1538-7445.AM2015-1389
Abstract 1398: Metastatic neuroblastoma cancer stem cells exhibit flexible plasticity and adaptive stemness signaling
Authors: Ramraj Satish Kumar , Khan Faizan H. , Aravindan Sheeja , Natarajan Mohan , Herman Terence S. , Aravindan Natarajan 
Published: August 2015

Abstract
High-risk neuroblastoma (HR-NB) presented with hematogenous metastasis is one of the most difficult cancers to cure with poor patient survival. Aggressive tumors contain populations of rapidly proliferating clonogens that exhibit stem cell properties, cancer stem cells (CSCs). Conceptually, CSCs that evade intensive multimodal therapy dictates tumor progression, relapse/recurrence and poor clinical outcomes. Herein, we investigated the plasticity and stem-cell related molecular response of aggressive metastatic neuroblastoma cells that fits CSC model. Well characterized clones of ‘metastatic site derive aggressive cells’ (MSDACs) from the manifold of metastatic tumors of clinically translatable HR-NB were characterized for their CSC fit. Alternated, yet stabilized (three generations) microenvironment simulation experiments with ‘serum-free stem cell medium’ to ‘growth medium with serum’ and vice versa identified flexible revocable plasticity. Signatures stem-cell related molecular responses consistent with phenotypic conversions are observed. Successive reintroduction to the favorable niche not only regained identical EMT, self-renewal capacity, pluripotency maintenance, and other stem-cell related signaling events, but also instigated additional events depicting the aggressive adaptive plasticity. Together, these results demonstrated the flexible plasticity of HR-NB MSDACs that typically fits in CSC model and further identified the intrinsic adaptivness of the successive phenotype switching that clarify the heterogeneity of HR-NB. Moreover, the continuous ongoing acquisition of stem-cell related molecular rearrangements may hold the key for the switch from favorable disease to HR-NB.
Citation Format: Satish Kumar Ramraj, Faizan H. Khan, Sheeja Aravindan, Mohan Natarajan, Terence S. Herman, Natarajan Aravindan. Metastatic neuroblastoma cancer stem cells exhibit flexible plasticity and adaptive stemness signaling. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1398. doi:10.1158/1538-7445.AM2015-1398
Abstract 1404: A red-shifted fluorescent substrate for aldehyde dehydrogenase, AldeRed 588-A, for labeling viable ALDH-positive cells
Authors: Chu Vi , Taganov Konstantin , Ramesh D , Asbrock Nick , Pomper Martin 
Published: August 2015

Abstract
Normal and cancer stem cells can be isolated based upon the enzymatic activity of aldehyde dehydrogenase I (ALDH1), a detoxifying enzyme responsible for oxidation of hazardous aldehyde byproducts. ALDH1 has been used to isolate cancer stem cells of various human malignancies including bladder, breast, cervical, colon, head and neck, liver, lung, pancreas, prostate and ovary. Currently, the ALDEFLUORTM assay which uses a fluorescent substrate is the only commercially available reagent for ALDH detection. The substrate used in this assay primarily emits in the green region of the electromagnetic spectrum (512nm). For researchers with valuable cell and transgenic animal models in which the target gene of interest has been tagged with eGFP, ALDEFLUOR therefore cannot be used. Selection of cells positive for aldehyde dehydrogenase (ALDH) activity from a green fluorescent background is thus difficult with existing reagents. We now describe a red-shifted fluorescent substrate for ALDH, AldeRed 588-A, that provides additional flexibility for utilizing ALDH as a marker for stem cell and cancer stem cell isolation. The activity of AldRed 588-A was compared with the ALDEFLUOR reagent and demonstrated similar ability to fractionate ALDHpos cells in a number of cell lines tested.
Citation Format: Vi Chu, Konstantin Taganov, D Ramesh, Nick Asbrock, Martin Pomper. A red-shifted fluorescent substrate for aldehyde dehydrogenase, AldeRed 588-A, for labeling viable ALDH-positive cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1404. doi:10.1158/1538-7445.AM2015-1404
Abstract 1414: Molecular and functional characterization of ovarian cancer stem cells
Authors: Lupia Michela , Bertalot Giovanni , Colombo Nicoletta , Confalonieri Stefano , Di Fiore Pier Paolo , Cavallaro Ugo 
Published: August 2015

Abstract
Epithelial Ovarian Cancer (OC) is one of the leading causes of death for women, and no significant therapeutic progress has been made in the last decades.
Recent data suggest that one of the mechanisms accounting for resistant and/or relapsing disease is a subpopulation of cells in human tumors with stem-like characteristics (cancer stem cells, CSCs). CSCs are defined as a small subpopulation of cells within the tumor bulk that possess the capacity, on one hand, to self-renew and, on the other hand, to give rise to all heterogeneous cancer cell lineages that compose the tumor of origin. The CSC hypothesis provides an attractive cellular mechanism to explain the therapeutic refractoriness, dormant behavior, and relapse of the disease.
Our study aims at assessing ovarian cancer stem cells (OCSC) as causal players in OC etiology and progression and at defining their molecular and functional profile. Specifically, we are pursuing the following objectives through the accomplishment of these milestones: 1) collection of normal and pathological samples; 2) identification of OCSC based on functional properties; 3) comparison of gene expression profiles between cancer stem cells and their normal counterpart; 4) characterization of novel genes/pathways involved in OCSC function (clonogenicity, tumorigenicity, quiescence, chemoresistance, etc.).
This workflow is being applied to a series of fresh surgical samples of OC as well as to normal ovarian surface epithelium (OSE) and fallopian tube epithelium (FTE), namely the tissues of origin of OC. Thus, we obtained a collection of primary cells that recapitulate many traits of the original tissue both in vitro and in vivo. The gene expression profiles of sphere-forming SC has been compared to that of adherent, parental cells, aimed at identifying stemness-associated genes. This screening has been extended to OC, OSE, and FTE, resulting in a set of genes that are differentially expressed in OCSC as compared to their normal counterparts.
A subset of such genes has been selected for the subsequent validation, both as OCSC biomarkers that could have clinical applications and as drivers in the biological and pathogenic function of OCSC.
Our study might set the stage for innovative therapeutic approaches aimed at the selective elimination of OCSC, thus preventing tumor recurrence and chemoresistance, namely the two main causes of ovarian cancer lethality.
Citation Format: Michela Lupia, Giovanni Bertalot, Nicoletta Colombo, Stefano Confalonieri, Pier Paolo Di Fiore, Ugo Cavallaro. Molecular and functional characterization of ovarian cancer stem cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1414. doi:10.1158/1538-7445.AM2015-1414
Abstract 1426: Lung epithelial cells induce both phenotype alteration and senescence in breast cancer cells
Authors: Furukawa Masashi , Wells Alan , Wheeler Sarah , Clark Amanda M. 
Published: August 2015

Abstract
Purpose: Breast cancer is the most common cancer in women. The lung is one of the most common sites of breast cancer metastasis. While metastatic seeding is often accompanied by a dormancy-promoting mesenchymal to epithelial reverting transitions (MErT), we aimed to determine whether lung epithelial cells can impart this phenotype on aggressive breast cancer cells.
Methods: Co-culture experiments of normal lung epithelial cell lines (SAEC, NHBE or BEAS-2B) and breast cancer cell lines (MCF-7 or MDA-MB-231) were conducted. Flow cytometry analysis, immunofluorescence staining for E-cadherin or Ki-67 and senescence associated beta-galactosidase assays assessed breast cancer cell outgrowth and phenotype.
Results: Co-culture of the breast cancer cells had different effects on breast cancer cells. The epithelial MCF-7 cells were increased in number but still clustered even if in a slight more mesenchymal spindle morphology. On the other hand, the mesenchymal MDA-MB-231 cells survived but did not progressively grow out in co-culture. These aggressive carcinoma cells underwent an epithelial shift as indicated by cuboidal morphology and increased E-cadherin. Disruption of E-cadherin express in MDA-MB-231 using shRNA prevented this phenotypic reversion in coculture. In addition, we had noted enlarged MDA-MB-231 cells in the co-cultures with SAEC and NHBE but not BEAS-2B cells as suggestion of senescence. A subset of these cells stained with the senescence associated marker β-galactosidase (SA-β-gal). Lung cells limited cancer cell growth kinetics as noted by both (1) some of the cells becoming larger and positive for senescence markers/negative for proliferation marker Ki-67, and (2) Ki-67 positive cells significantly decreasing in MDA-MB-231 and MCF-7 cells after co-culture.
Conclusions: Our data indicate that normal lung epithelial cells can drive an epithelial phenotype and suppress the growth kinetics of breast cancer cells by changing their phenotypes.Similar to the hepatocytes, these normal cells may promote the survival, seeding and even dormancy of aggressive mesenchymal carcinoma cells, with phenotypes similar to MDA-MB-231 cells, but also provide progressive signaling when stressed accounting for the spindle morphology and slightly increased growth rates of the epithelial carcinoma cells, such as those MCF-7 represents. In this latter manner, insults the small airway may provoke an outgrowth from dormant breast cancer cells.
Citation Format: Masashi Furukawa, Alan Wells, Sarah Wheeler, Amanda M. Clark. Lung epithelial cells induce both phenotype alteration and senescence in breast cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1426. doi:10.1158/1538-7445.AM2015-1426
Abstract 1427: Embigin is overexpressed in pancreatic ductal adenocarcinoma and regulates cell motility through epithelial to mesenchymal transition via the TGF-β pathway
Authors: Jung Dawoon E. , Kim Jeong Mi , Kim Chanyang , Song Si Young 
Published: August 2015

Abstract
Embigin is a member of the immunoglobulin superfamily and encodes a transmembrane glycoprotein. Strong expression of Embigin has been observed in the mouse endoderm during early postimplantation embryogenesis and in the gut and visceral endoderm at the somite stage. There have been reports of Embigin involvement in neuromuscular junction formation and plasticity; however, the molecular functions of Embigin in other organs are unknown. Pancreatic cancer is an extremely aggressive malignancy, and it is necessary to understand the biology of pancreatic cancer to better detect and treat this disease. Our aim was to investigate the possible role of Embigin in pancreatic cancer. In pancreatic ductal adenocarcinoma tissues, Embigin expression was higher than that in normal pancreatic tissues. Immunohistochemical analysis revealed expression of Embigin in pancreatic cancer cells, as well as expression of monocarboxylate transporter 2 (MCT2) in cancer tissues. To gain further insight, we transfected BxPC-3 and HPAC pancreatic cancer cells with siRNA or shRNA targeting Embigin and observed reductions in cell proliferation, migration, invasion, wound healing, and reduced levels of matrix metalloproteinases-2 and -9. Silencing of Embigin increased intracellular L-lactate concentration by 1.5-fold and decreased MCT2 levels at the plasma membrane. Furthermore, Embigin silencing led to a reduced expression of PI3K, GSK3-β, and Snail/Slug. Upon treating BxPC-3 cells with transforming growth factor-β (TGF-β), we observed elevated expression of Snail/Slug, Embigin, and Vimentin; meanwhile, when treating cells with SB-216763, a GSK3-β inhibitor, we noted decreases in GSK3-β, Snail/Slug, and Embigin expression, suggesting that the TGF-β signaling cascade, comprising PI3K, GSK3-β, Snail/Slug, and Embigin signals, mediates epithelial to mesenchymal transition (EMT) in pancreatic cancer cells. These findings indicate the involvement of Embigin in EMT in pancreatic cancer progression and suggest Embigin as a putative target for the detection and/or treatment of pancreatic cancer.
Citation Format: Dawoon E. Jung, Jeong Mi Kim, Chanyang Kim, Si Young Song. Embigin is overexpressed in pancreatic ductal adenocarcinoma and regulates cell motility through epithelial to mesenchymal transition via the TGF-β pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1427. doi:10.1158/1538-7445.AM2015-1427