bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3408: Gene expression profiling of MCF10A series of Ha-Ras transformed human breast epithelial cells: Gene expression involved in EMT pathway
Authors: Yang Sihyung , Cho April E. , Lee Eunhye , Lim Soojeong , Novak Raymond F. , Kim So Hee 
Published: August 2012

Abstract
MCF10A series (10A, 10AT, 10ATG3B, 10CA1h and 10CA1a) of breast epithelial cells were examined for gene expression involved in epithelial-mesenchymal transition (EMT) process. This model represents a unique system for examining early and progressive alterations that occur in cells. Microarray analysis showed more than 720 genes are highly expressed (&gt;2 fold, P&lt;0.05) but over 870 genes significantly decreased (&lt;0.5 fold, P&lt;0.05) compared to control 10A. Ontology analysis of 759 highly expressed genes in malignant 10CA1a showed genes involved in metabolism were the greatest. 72 genes progressively increased and 392 genes gradually decreased with the tumorigenicity. 12 genes in EMT were significantly reduced (&lt;0.5 fold, P&lt;0.05) and 24 genes significantly increased (&gt;2 fold, P&lt;0.05) from microarray and 12 genes significantly decreased (P&lt;0.01) and 18 genes were highly expressed (P&lt;0.01) from PCR array. Based on two analyses, BMP7, COL5A2, DSC2, GSK3B, RGS2, TSPAN13 and VIM were highly expressed but MAP1B, TIMP1 and WNT5A significantly decreased. Collectively, altered gene levels in EMT process may correlate with increasing risk of tumorigenicity and these genes may serve as an early prognostic indicator of tumorigenic potential. Supported by grant from NRF (R-2009-006-6765).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3408. doi:1538-7445.AM2012-3408
Abstract 3425: Prognostic significance of BRMS1 promoter methylation in operable breast cancer
Authors: Chimonidou Maria , Stathopoulos Efstathios , Georgoulias Vasilis , Lianidou Evi S. 
Published: August 2012

Abstract
Backround: Breast Cancer Metastasis Suppressor gene-1 (BRMS1) suppresses breast cancer metastasis in multiple experimental models by reducing solitary cell survival and inhibiting growth initiation. Loss of BRMS1 expression has been shown to predict reduced disease-free survival in subsets of breast cancer patients. The BRMS1 promoter region contains a promoter-associated CpG island (CGI) that encompasses the transcriptional start site.The aim of our study was to investigate the methylation status of BRMS1 in breast tumors (FFPES) of operable breast cancer patients and evaluate its prognostic significance. Patients and methods: Using methylation-specific PCR (MSP), we examined BRMS1 promoter methylation in 116 fixed paraffin-embedded tissues (FFPEs): 5 pairs of breast tumors and their surrounding non-cancerous tissues, 4 non-cancerous tissues, 10 benign breast tumors (fibroadenomas), 10 normal breast tissues and 82 breast tumors. All breast tumors were isolated from patients with operable breast cancer. Results: Methylation of BRMS1 promoter was observed in 0/19 (0%) noncancerous breast tissues, in 0/10 (0%) benign breast tumors (fibroadenomas) and in 31/82 (37.8 %) breast cancer tumors. During the follow-up period 22/82 (26.8%) patients relapsed and 20 (24.4%) patients died. BRMS1 methylation was detected in 13/22 (59.1%) patients that relapsed and in 12/20 (60.0%) of patients who died. Disease-free interval (DFI) and overall survival (OS) were significantly associated with BRMS1 promoter methylation (P=0.007). Conclusion: We show for the first time that BRMS1 promoter methylation status in FFPEs from operable breast cancer patients provides important prognostic information and merits to be further evaluated and validated in a larger cohort of patients. This finding is consistent with other studies that showed significant down-regulation of BRMS1 in some breast tumors, especially in metastatic disease, because of epigenetic silencing.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3425. doi:1538-7445.AM2012-3425
Abstract 343: Inhibitory effect of oncolytic adenovirus on transforming growth factor- β-induced epithelial-mesenchymal transition in human cancer cells
Authors: Hashimoto Yuuri , Tazawa Hiroshi , Urata Yasuo , Kagawa Shunsuke , Fujiwara Toshiyoshi 
Published: August 2012

Abstract
Background: Epithelial-mesenchymal transition (EMT) is a tumor progression-related process by which epithelial cells lose their epithelial characteristics and acquire mesenchymal properties. EMT promotes the malignant phenotypes including invasion, metastasis and drug resistance, resulting in tumor recurrence and poor prognosis. Therefore, to prevent tumor progression, EMT targeted therapy is required. Oncolytic virotherapy is a promising strategy for anticancer therapy. Although a variety of oncolytic adenoviruses have been developed to induce tumor-selective cell death, the effect of oncolytic adenovirus on the EMT-induced tumor progression remains unclear. In this study, we investigated the biological effect of oncolytic adenovirus on EMT in human cancer cells. Methods: We previously generated a telomerase-specific replication-selective oncolytic adenovirus (OBP-301; Telomelysin), in which the human telomerase reverse transcriptase promoter drives the expression of E1A and E1B for virus replication. Transforming growth factor-β (TGF-β) was used to induce EMT in human lung (A549) and pancreatic (Panc-1) cancer cells. To investigate whether OBP-301 infection affects TGF-β-induced EMT in these cells, western blot and real-time PCR analysis for EMT-related markers were performed. We also examined cell mobility using transwell migration and invasion assays. In vitro antitumor effect of OBP-301 and chemotherapeutic agents in TGF-β-treated cancer cells were assessed by trypan blue exclusion assay. Results: Administration of TGF-β induced mesenchymal characteristics, including spindle-like cell morphology, down-regulation of E-cadherin, up-regulation of vimentin and high motility, in A549 and Panc-1 cells. When TGF-β-treated cancer cells were infected with OBP-301, suppression of E-cadherin expression was attenuated. Conversely, the expression levels of mesenchymal markers, vimentin and N-cadherin, and EMT-inducing transcription factors, Snail, Slug and ZEB1, were reduced. OBP-301 infection also inhibited TGF-β-induced enhancement of migration and invasion in cancer cells. Moreover, OBP-301 efficiently killed TGF-β-treated cancer cells, whereas TGF-β-treated cancer cells were resistant to cisplatin and docetaxel. Conclusion: Our results suggest that telomerase-specific oncolytic adenovirus OBP-301 inhibits TGF-β-induced EMT in human cancer cells. OBP-301 has therapeutic potential against cancer cells that have undergone EMT. Therefore, OBP-301 might be a promising anticancer agent to suppress EMT-mediated cancer progression and metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 343. doi:1538-7445.AM2012-343
Abstract 3434: EphB3 mediates kinase-dependent suppression of non-small cell lung cancer metastasis
Authors: Li Guo , Ji Xiao-dan , Xie Dong 
Published: August 2012

Abstract
Eph family is one of the largest subfamily of receptor tyrosine kinases. Their important but controversial roles in cancer development have drawn growing attentions in recent years. We have recently reported that EphB3 acts as a tumor promoter in human non-small-cell lung cancer (NSCLC) independent of its kinase activity (Cancer Research. 71(3):1156, 2011). In the present study, we find that despite overexpression of EphB3 in NSCLC, the expression of its cognate ligands, ephrin-B1 and ephrin-B2, is significantly down-regulated, leading to reduced tyrosine phosphorylation of EphB3. Activation of EphB3 kinase with either ligand stimulation or genomic engineering (Y608/614E) in EphB3-overexpressing NSCLC cells inhibits cell migratory capability in vitro as well as in vivo metastatic seeding. Furthermore, we have identified a novel EphB3-binding protein, the receptor for activated C-kinase 1 (RACK1), which mediates the assembly of a ternary signal complex comprising protein phosphatase 2A (PP2A), Akt and itself in response to EphB3 activation, leading to reduced Akt phosphorylation and subsequent inhibition of cell migration. Our study reveals a novel tumor-suppressing signaling pathway associated with kinase-activated EphB3 in NSCLC, and provides a potential therapeutic strategy by activating EphB3 signaling, thus inhibiting tumor metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3434. doi:1538-7445.AM2012-3434
Abstract 3440: Effect of neoadjuvant therapy for the number of lymph node micrometastasis in esophageal squamous cell carcinoma
Authors: Lee Tomohiro , Tanaka Hiroaki , Yoshii Mami , Sakurai Katsunobu , Nagahara Hisashi , Kimura Kenjirou , Amano Ryousuke , Noda Eiji , Kubo Naoshi , Muguruma Kazuya , Yamada Nobuya , Yashiro Masakazu , Maeda Kiyoshi , Onoda Naoyoshi , Sawada Tetsuji , Nakata Bunzo , Ohira Masaichi , Ishikawa Tetsurou , Hirakawa Kosei 
Published: August 2012

Abstract
[Introduction] Esophageal squamous cell carcinoma (ESCC) often develops lymph node metastasis. Several study demonstrated that micrometastasis (MM) in lymph nodes was an independent prognostic factor for ESCC. Recently effect of neoadjuvant therapy including chemotherapy and chemoradiontherapy has been reported. The aim of this study was to investigate the affect of on MM in lymph nodes for ESCC. [Materials and methods] We retrospectively reviewed clinical data of consecutive162 patients with ESCC who underwent esophagectomy accompanied with systemic lymphadectomy in our institution from 2000 to 2010. Firstly, we analyzed the relapse free survival of 90 patients who underwent surgical resection without neoadjuvant therapy and assessed the impact of MM in lymph nodes on prognosis of ESCC by immunohistochemistry using anti-cytokeratin antibody. Next we examined MM in lymph nodes of 72 patients who underwent surgical resection with neoadjuvant therapy and evaluate the effect of neoadjuvant therapy on MM in lymph nodes. [Results] Of 5414 lymph nodes from 90 patients with cStage II/III (surgery group), we detected 311(5.1%) of overt metastasis detected by H&E staining and 124(2.3%) of MM in lymph nodes. The clinicopathological factors related to the postoperative relapse included pTNM Stage and number of lymph node metastasis with MM. Otherwise, in neoadjuvant Group, Of 3466 lymph nodes from 72 patients, we detected 154(4.4%) of overt metastasis and 19(0.4%) of MM. In neoadjuvant group, the rate of MM was decreased from 2.3% to 0.4% as compared to that of surgery group. Importantly, the rate of MM in upper mediastinal region was decreased by neoadjuvant therapy. [Conclusion] We demonstrated the significance of micrometastasis in lymph nodes for prognosis of esophageal cancer. Our findings suggested that neoadjuvant therapy may reduce the number of micrometastasis. Neoadjuvant therapy should be estimated as the standard therapy against esophageal squamous cell carcinoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3440. doi:1538-7445.AM2012-3440
Abstract 3455: p53 status determines the radio-sensitizing effect of an Akt kinase inhibitor in malignant gliomas
Authors: Patel Disha R. , Gordon Nicolaus , Chakravarti Arnab , Palanichamy Kamalakannan 
Published: August 2012

Abstract
Purpose: It has been reported that PI3K-Akt pathway, which plays a role in cell survival and apoptosis, is deregulated in many cancer types. In gliomas, amplification and constitutive activation of Akt, which can result from amplifications in TKIs including EGFR, IGFR1α, PDGFRα, etc. and mutations in PI3K, PTEN, etc. are thought to play a role in radiation resistance. Some have tried to modulate the PI3K/Akt pathway by targeting molecules upstream of Akt such as Ras and PI3K, while others have used inhibitors targeting molecules downstream of Akt, such as mTOR. These inhibitors have been shown to reduce cancer cell growth in vitro and in vivo, but have had limited success in clinical settings as single agents. In our study, we have investigated the use of a phosphatidylinositol ether lipid analogue (PIA) that directly inhibits Akt activation as a radiosensitizer for GBM. Materials and Methods: We utilized multiple established (U87, LN18, LN229) and primary (VC3, MGH8, OSU61) cell lines with varying molecular and genetic signatures to determine radiosensitizing effects of PIA. We performed Annexin V, clonogenic survival, and COMET assays on glioma cells treated with PIA, radiation (RT), and a combination of PIA and RT. Western blot was performed using these cell lines to examine the changes in expression of PI3K-Akt pathway, apoptotic, and pro-survival proteins following treatment. Furthermore, we sequenced tumor suppressor genes p53 and PTEN in all cell lines used in this study. Gene silencing of p53 was done in U87 cells via a lentiviral transfection of shRNA. Results and Conclusions: PIA decreases the activation of Akt to a considerable extent (∼80%), induces apoptosis, and reduces clonogenicity of all cell lines tested. A subset of cell lines did show enhanced radiosensitization when PIA is combined with RT. Further detailed investigation of differential radiosensitizing effects led us to discover the link between p53 status, Akt kinase inhibition, and radiosensitization. GBMs with intact p53 had no radiosensitizing effect after Akt kinase inhibition, whereas radiosensitization was observed if either p53 is null or mutated. This observation was further validated using isogenic U87 p53 knockdown cells. Surprisingly, MGMT status, a predictive marker of outcome in GBM, did not determine radiosensitizing effects of PIA in the GBM cells tested. Through this preclinical study, we have identified which subset of GBM patients will derive benefit from Akt kinase inhibition and the investigations conducted justify future clinical trials and lays ground work for phase I study.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3455. doi:1538-7445.AM2012-3455
Abstract 347: The role of the epithelial-mesenchymal transition in the maintenance of stemness in neural and glioma stem cells
Authors: Fernandez Nestor , Wu Megan , Das Sunit 
Published: August 2012

Abstract
Despite advances in treatment, Glioblastoma multiforme (GBM) continues to carry a horrible prognosis with an average overall survival of only 14 months [Stupp et al, 2005]. GBMs are heterogeneous tumors that contain a subpopulation of stem-cell like cells called glioblastoma stem cells (GSCs). GSCs appear to be chemotherapy- and radiation-resistant and are thought to be responsible for GBM progression [Kang et al, 2007; Bao et al, 2006]. More effective GBM therapies must target GSCs, underscoring the importance of understanding GSC biology. Our study examines the epithelial-mesenchymal transition (EMT) and its converse, the mesenchymal-epithelial transition (MET), in the context of GSCs and neural stem cells (NSCs). We hypothesize that the zinc-finger enhancer binding transcription factor (ZEB)/miR-200 feedback loop is relevant in the context of GSCs and is modulated by TGF-β and BMP. We have found that ZEB1 and miR-200 define divergent glioma cell populations: qRT-PCR shows differential expression of ZEB1 and miR-200 in mature human astrocytes, human fetal NSC, and human GSCs (GliNS1). In GSCs, BMP antagonism (noggin) or TGF-β stimulation results in increased ZEB1 expression. Conversely, BMP4 stimulation increases miR-200b/c, while noggin or TGF-β treatment decrease miR-200b/c expression. BrdU proliferation studies show increased proliferation with TGF-β stimulation and decreased proliferation with BMP treatment in three GSC lines. TGF-β signaling also confers an invasive phenotype in GSCs while BMP4 treatment decreases invasion, suggesting a role for TGF-β and BMP parallel to that seen in EMT and MET. Western blot analysis reveals that treatment of GSCs with TGF-β induces phosphorylation of Stat3, which has been shown to be a driver of EMT [Carro MS, 2010]. Interestingly, BMP and TGF-β treatment does not change Sox2 protein expression, suggesting that the GliNS1 GSCs retain their stem cell identity. However, Bmi1 increases with BMP stimulation and decreases with TGF-β treatment, while ID1 increases with BMP treatment, suggesting that the stem-ness in GSCs is modulated by these cytokines. In conclusion, BMP and TGF-β control the ZEB1/miR-200 feedback loop in GSCs and affect cell proliferation and invasive capability. We are continuing studies to determine the relevance of TGF-β and BMP signaling to patients with GBM.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 347. doi:1538-7445.AM2012-347
Abstract 3473: Beta catenin inhibitor ICG-001 attenuates proliferation of hepatic tumor initiating cells in Pten deficient models
Authors: Medina Vivian Galicia , Kassa Anketse D. , Stiles Bangyan L. 
Published: August 2012

Abstract
Progenitor or tumor initiating cells (TICs) are “altered” stem cells with the capacity to form solid tumors. Tumor suppressor PTEN (phosphatase and tensin homologue deleted on chromosome ten) is aberrantly expressed in liver cancers. Liver specific Pten (Pm) mice develop liver cancer following an extensive phase of chronic lipid accumulation and demonstrate escalating levels of hepatic injury markers from 6-12M, prior to hepatic progenitor cell proliferation. In addition, TUNEL analysis revealed that hepatocytes from Pm mice undergo extensive apoptosis relative to control mice. We hypothesize that hepatocyte cell death induced by hepatic injury presents an opportunity for TICs to proliferate and consequently form mixed lineage tumors. Attenuation of hepatic injury by Akt2 deletion reduces progenitor cell proliferation and delays tumor development. Our analyses also revealed that the Wnt/β-Catenin signaling pathway is the likely molecular mediator of TIC proliferation in our Pm model. Wnt ligands including 7a and 10a as well as Wnt signaling receptor Fzd 2 are induced. In this study, we investigate the role of the Wnt/β-Catenin pathway in the activation of hepatic progenitor cells in the Pten deletion liver cancer model using novel Wnt/β-catenin inhibitor ICG-001. ICG-001 is a small molecule which specifically inhibits β-Catenin/CBP interaction. Coactivator CBP/β-Catenin/T cell factor (TCF) mediated transcription has been reported as critical for stem cell/progenitor cell proliferation. Here we demonstrate that ICG-001 significantly attenuates proliferation of hepatic cancer stem cell line P0 in vitro and also inhibits hepatotoxin induced proliferation of hepatic TICs in vivo in liver Pten null mice. Our preliminary results indicate that targeting the cancer stem cell niche may prove to be a viable approach to inhibit liver tumorigenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3473. doi:1538-7445.AM2012-3473
Abstract 3478: CD44+CD24low+ progenitors in ER negative breast cancer have higher Notch1 activation, self-renewal, and chemo resistance and generate CD44+CD24neg cells and tumors that metastasize
Authors: Azzam Diana J. , Elger Katherine Drews , Zhao Dekuang , Ranganathan Prathibha , Capobianco Tony , Minn Andy J. , Creighton Chad , Picon Manuel , Sun Jun , Pan Chendong , Wander Seth A. , Ashry Dorraya El , Slingerland Joyce M. 
Published: August 2012

Abstract
CD44 surface expression is associated with self renewal in several cancers. While CD44+/CD24neg/low/ESA+ breast cancer subpopulations are enriched for cancer stem cells (CSC), the relative contributions of CD24 negative versus low subpopulations to stemness and metastasis is poorly defined. Here we show that CD44+/CD24low+ CSC give rise to CD44+/CD24neg progeny with reduced tumorigenicity and altered drug sensitivities. CD44+/CD24low+ subpopulations in MDA-MB-231 and in primary dissociated ER negative breast cancers show greater sphere and soft agar colony formation, Notch1 activation, Sox2 and Nanog expression and chemo resistance compared to CD44+/CD24neg. CD44+/CD24low+ can self-renew and give rise to CD44+/CD24neg cells, while CD44+/CD24neg progeny are exclusively CD44+/CD24neg. Tumorigenicity was increased and metastasis arose exclusively from orthotopic CD44+CD24low+ xenografts. CD44+/CD24low+ had greater expression of metastasis- and embryonic stem cell- associated and Notch pathway activated genes than CD44+/CD24neg cells. Moreover, MDA-MB-231 cells overexpressing Notch1 intracellular domain (N1-ICD) had higher Sox2 expression, and higher indices of CSC self-renewal (higher % CD44+/CD24low+, ALDH1 activity, sphere and soft agar colony formation), all of which were abrogated by Sox2 knockdown. Gamma secretase inhibition reduced ES-TFs and self-renewal in CD44+CD24low+ progenitors, but had no effect on proliferation or survival of CD44+CD24neg cells supporting further clinical development of Notch targeting drugs for cancer treatment in humans. Thus, CD44+CD24low+ and CD44+CD24neg CSC in ER negative breast cancer have distinct properties. CD44+CD24low+ can self-renew and generate CD44+CD24neg progeny. Orthotopic xenograft CD44+CD24low+ tumors arose with reduced latency with higher frequent, were larger, and the sole source of metastasis. Notch1 activation of Sox2 drives CD44+CD24low+ self-renewal and is blocked by GSI providing a strong rationale for use of GSI as CSC targeting agents in ER negative breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3478. doi:1538-7445.AM2012-3478