bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 331: C-MYC gene amplification in endometrial cancer is associated with aggressive tumors
Authors: Birkeland Even , Krohn Antje , Trovik Jone , Holst Frederik , Werner Henrica M.J. , Krakstad Camilla K. , Wik Elisabeth , Akslen Lars , Simon Ronald , Salvesen Helga B. 
Published: June 2012

Abstract
Endometrial cancer is among the most common gynaecological malignancies in industrialized countries. Although 75% of cancers are treated at an early stage, 15% to 20% recur. Due to these recurrences the demand for systemic therapies and better prognostic markers are vital. Our recent study of global genetic characterisation has identified that C-MYC amplifications associate with aggressive phenotype in uterine cancers (Salvesen et al., PNAS 2009).
The present study was conducted to validate the phenotype associated with C-MYC amplification in a large population based prospectively collected sample series from primary tumours and corresponding metastatic lesions from patients with endometrial cancer. Primary tumours from 399 patients and 80 corresponding metastatic lesions were analysed for amplification of the C-MYC gene using fluorescence in situ hybridization (FISH).
We found that 5% of primary endometrial cancer tumors have C-MYC amplifications or gains. C-MYC amplification is correlated with high FIGO stage (P = 0.003), non-endometroid subtype (P = 0.002), and high grade (P &lt;0.001). Patients with C-MYC amplifications had a significantly poorer recurrence free- (P = 0.002) and disease specific survival (P = &lt;0.001). These data suggest that C-MYC amplification might be one important mechanism involved in endometrial cancer tumourigenesis. Further characterization of C-MYC amplifications in corresponding metastatic lesions are in progress.
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 331. doi:10.1158/1538-7445.AM2011-331
Abstract 3356: Loss of breast epithelial hCLCA2 promotes EMT and increases risk of metastasis
Authors: Elble Randolph C. , Walia Vijay , Yu Yang , Cao Deshou , Sun Miao , Premkumar Louis 
Published: June 2012

Abstract
Transition between epithelial and mesenchymal states is a feature of both normal development and tumor progression. We report that expression of chloride channel accessory protein hCLCA2 is a characteristic of epithelial differentiation in the immortalized MCF10A and HMLE models, while induction of EMT by cell dilution, TGFbeta, or mesenchymal transcription factor Snail sharply reduces hCLCA2 levels. Attenuation of hCLCA2 expression by lentiviral shRNA caused cell overgrowth and focus formation, enhanced migration and invasion, and increased mammosphere formation in methylcellulose. These changes were accompanied by downregulation of E-cadherin and upregulation of mesenchymal markers such as vimentin and fibronectin. Moreover, hCLCA2 expression is greatly downregulated in breast cancer cells with a mesenchymal or claudin-low profile. These observations suggest that loss of hCLCA2 may promote metastasis. We find that higher-than-median expression of hCLCA2 is associated with a one-third lower rate of metastasis over an 18 year period among breast cancer patients compared to lower-than-median (n=344, unfiltered for subtype). Thus, hCLCA2 is required for epithelial differentiation, and its loss during tumor progression contributes to metastasis. Overexpression of hCLCA2 has been reported to inhibit cell proliferation and is accompanied by increases in chloride current at the plasma membrane and reduced intracellular pH (pHi). We found that knockdown cells have sharply reduced chloride current and higher pHi, both characteristics of tumor cells. These results suggest a mechanism for the effects on differentiation. Loss of hCLCA2 may allow escape from pHi homeostatic mechanisms, permitting the higher intracellular and lower extracellular pH that are characteristic of aggressive tumor cells.
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 3356. doi:10.1158/1538-7445.AM2011-3356
Abstract 3357: Partial mesenchymal to epithelial reverting transition in breast and prostate cancer metastases
Authors: Chao Yvonne , Wu Qian , Acquafondata Marie , Dhir Rajiv , Wells Alan 
Published: June 2012

Abstract
Epithelial to mesenchymal transition (EMT) is an oft-studied mechanism for the initiation of metastasis. We have recently shown that once cancer cells disseminate to a secondary organ, a mesenchymal to epithelial reverting transition (MErT) can occur, which we postulate is to enable metastatic colonization. Despite a wealth of in vitro and in vivo studies, evidence of MErT in human specimens is rare and difficult to document because clinically detectable metastases are typically past the micrometastatic stage at which this transition is most likely evident. We obtained specimens of primary and metastatic tumors from breast and prostate cancer patients and evaluated expression of various epithelial and mesenchymal markers by immunohistochemistry. Breast cancer metastases exhibited increased expression of membranous E-cadherin and β-catenin compared to primary tumors, consistent with EMT at the primary site and MErT at the metastatic site. Expression of epithelial markers connexins 26 and 43 was also increased, particularly in brain metastases. Despite the upregulation of epithelial markers in metastases, expression of mesenchymal markers vimentin and FSP1 was mostly unchanged or only slightly decreased. Furthermore, the switch in expression of E-cadherin to N-cadherin that is sometimes detected in EMT, was not found by our immunostaining. N-cadherin detection did not reveal a consistent pattern of expression in primary or metastastic tumors. We observed similar results in prostate cancer metastases; not only was E-cadherin expression increased but also expression inversely correlated with size of the metastasis, suggesting that a second EMT may occur in the ectopic site for tumor growth or to seed further metastases. In summary, we have observed an increased expression of epithelial markers and persistence of mesenchymal markers consistent with a partial MErT that may enable a second EMT at the metastatic site. Our results suggest that cancer cells continue to display phenotypic plasticity beyond the EMT that initiates metastasis.
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 3357. doi:10.1158/1538-7445.AM2011-3357
Abstract 3381: AhR shRNA effectively suppresses B(a)P-mediated induction of slug modulating tumor invasion and cell migration in non small cell lung cancer cell line
Authors: Ahn Kwang-Sung , Park Juwon , Kim Kyungsun , Chae Yang Seok , Won Nam Hee 
Published: June 2012

Abstract
Exposure of B(a)P on lung tissue have been implicated in cancer development and its progression. Even though increasing evidences have been reported adversely effects of B(a)P in tumor progression, mechanism by which exposure of Bap on lung cancer cells increases the metastatic potentials still remains unknown. Here, we show that B(a)P triggers a marked morphological changes of Non Small Cell Lung Cancer (NSCLC) cells. These B(a)P-mediated effects are mimicked by decreasing E-cadherin resulting in loosening cell-cell contacts and by increasing Slug expression resulting in inducing epithelial mesenchymal transition (EMT). In case that NCSCLC cell was prolonged exposed to B(a)P, B(a)P-exposed cells showed increasing cell motility and invasion. They correlate with B(a)P-mediated phosphorylations of JNK and p38. And they are reverted by treatment with their inhibitors. In transient transfection analysis, H1299-snail2, constitutively expressing snail2, increased the cell motility and invasion. AhR shRNA effectively suppresses either B(a)P-mediated tumor invasion and induction of snail2. And suppression of E-caherin was found in H1299-snail2. Results of immunohistochemical stain revealed that Slug strongly expressed in invasive foci of Non Small Cell Lung Cancer tissue. Our results suggested that NSCLC cells prolonged exposed to B(a)P increased cell motility and invasiveness via regulation of expression of Sanil2 by exposure of B(a)P on NSCLC cells.
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 3381. doi:10.1158/1538-7445.AM2011-3381
Abstract 3411: Analysis of gene profile and identification of molecular targets in endometrial cancer stem cells
Authors: Nakamura Mitsuhiro , Kyo Satoru , Zhang Xivzhi , Takakura Masahiro , Maida Yoshiko , Mizumoto Yasunari , Mori Noriko , Bono Yukiko , Sasagawa Toshiyuki , Inoue Masaki 
Published: June 2012

Abstract
Background; Cancer stem cells (CSCs) have been known to be the major source of tumor propagation and might be an attractive therapeutic target. Our previous study showed that CD133+ Ishikawa and MFE 280 endometrial cancer cells have the ability of tumorigenicity, self-renewal and differentiation capacity in vitro and in vivo, while CD133- cells did not. Furthermore, CD133+ cells showed more resistance to cisplatin- or paclitaxel-induced cytotoxicity than CD133- cells. These results indicate that CD133 is the CSC maker in endometrial cancer cells. In the present study, we sought to analyze gene profile and identify molecular targets in endometrial cancer stem cells. Methods; We examined microarray analysis to investigate the molecules essential for the CSCs characteristics by 3D-Gene chip (TORAY). Results; Microarray analysis of total 25,000 genes showed that about 500 genes were highly expressed in CD133+ cells, compared to CD133- cells. The ALDH1 gene was up-regulated in CD133+ cells, in accordance with the previous reported expression of ALDH1 on breast and colorectal CSCs. We also found out the elevated expression of ABC transporter genes, ABCG2, ABCG3, ABCG4, ABCG8, ABCC8 and ABCC9. It is well known that cells expressing those genes are resistant to chemotherapeutic agents and associated with side population (SP). Fluorescence activated cell sorter analysis demonstrated that the ratio of SP fraction in CD133+ Ishikawa cells is slightly higher than in CD133- Ishikawa cells (0.8% vs 0.6%). Isolated SP/CD133+ cells ells showed more extensive proliferation and tumorigenicity, compared with non-SP/CD133+, SP/CD133- and non-SP/CD133- cells. Finally, we focused on high expression of MMP14 (MT1-MMP) gene in CD133+ cells. Invasion assay revealed that CD133+ Ishikawa and MFE 280 cells have more invasive property than CD133- Ishikawa and MFE 280 cells. The inhibition of MT1-MMP gene by siRNA significantly reduced the invasive ability of CD133+ cells. These results suggest that MT1-MMP is one of the critical molecules that generate biological features of CSC and may be a potential therapeutic target in endometrial cancer. Conclusions; We demonstrated that SP/CD133+ cells might be more defined CSCs in endometrial cancer and identified important molecules essential for characterizing endometrial CSCs in which MT1-MMP plays critical roles in generating biological features of CSCs in this tumor type. These findings shed light on establishment of molecular target therapy in endometrial cancer.
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 3411. doi:10.1158/1538-7445.AM2011-3411
Abstract 3427: A core invasiveness gene signature reveals reduced EMT in samples from patients with IBC, potentially regulated by decreased EGFR- and TGFb-signaling
Authors: Marsan Melike , Limame Ridha , François Katrien , Bertucci François , Ueno Nato , Lardon Filip , Pauwels Patrick , Van Dam Peter , Vermeulen Peter B. , Dirix Luc Y. , Van Laere Steven J. 
Published: June 2012

Abstract
Introduction. We identified a core invasiveness gene (CIG) signature that predicts the invasive properties of breast cancer cell lines. In the current study, we investigate the translational utility of the current gene signature in human breast cancer, including inflammatory breast cancer (IBC). The latter is a highly invasive and metastatic breast cancer subtype.
Materials and methods. Six publicly available gene expression data sets and a data set on 137 IBC and 252 non-IBC samples were analyzed. Each sample was classified according to sets of stromal (N=2), prognostic (N=2), stem cell (N=3), epithelial-to-mesenchymal transition (EMT) (N=3) and pathway (N=20) gene signatures. In addition, the cell-of-origin subtype classifier and our own CIG-signature were applied. Associations between the CIG-signature and clinicopathological or molecular features were searched for using univariate and multivariate analysis.
Results. We identified associations of the CIG signature (FDR&lt;0.01) with a mammosphere-derived classifier (median Rs=0.49) and with two EMT-signatures (Core-EMT: median Rs=0.52; EMT/stromal classifier: median Rs=0.59). In addition EGFR, STAT3 and TGFb were found to be hyperactivated in CIG-positive tumors (median Rs=0.45; 0.33 and 0.60 respectively). No relations between CIG-expression and stromal gene expression, molecular subtypes or any of the clinicopathological variables were observed. Compared to non-IBC, decreased CIG-expression, TGFb- and EGFR-activation were observed in IBC (respectively P&lt;0.0001, P&lt;0.0001 and P=0.036). As for other EMT-associated gene signatures, both positive (Claudin-low and LYN-signatures: P=0.004 and P=0.015) and negative (EMT/stromal classifier: P=0.015) associations with IBC have been observed. When testing the core-EMT signature, no difference was found (P=0.166).
Discussion. We show that the CIG signature in breast cancer is correlated with EMT, stem cell biology and EGFR-, TGFb- and STAT3-activation. Samples from patients with IBC demonstrate ambiguous EMT-patterns, suggest that tumor cells from patients with IBC are in a specific state of cell plasticity and EMT as such is not the main mode of invasion in IBC. On the contrary, lowered TGFb signaling in IBC suggest a form of collective invasion.
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 3427. doi:10.1158/1538-7445.AM2011-3427
Abstract 3444: Enforced expression of MycN and C-Myc induces different medulloblastoma subtypes
Authors: Kawauchi Daisuke , Robinson Giles , Uziel Tamar , Rehg Jerold , Zindy Frederique , Qu Chunxu , Gajjar Amar , Gilbertson Richard J. , Roussel Martine F. 
Published: June 2012

Abstract
Medulloblastoma (MB), a tumor of the cerebellum, is the most common malignant brain tumor of childhood. MBs are classified histologically and molecularly into four distinct major subgroups, two of which correspond to the deregulation of major developmental pathways, Sonic Hedgehog (SHH) and WNT. Among the two other subgroups, one correlates with high levels of C-MYC expression. Using orthotopic transplantation in the cerebellum or cortex of naïve recipient mice, we showed that enforced expression of MycN in cerebellar granule neuron progenitors (CGNPs) isolated from the cerebellum of postnatal (P) day 6-7 Cdkn2c-/-, Trp53-/-, Atoh1-GFP mice induced MBs with a SHH “signature”. Interestingly, overexpression of C-Myc in the same CGNPs induced MBs with Large Cell Anaplastic (LCA) features and mRNA and microRNA profiles distinct from the SHH subgroup. In vitro analysis revealed that tumor cells were resistant to Shh antagonists, such as cyclopamine and BMP4. Ongoing experiments are focusing on understanding the differences between MycN and C-Myc function in CGNPs.
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 3444. doi:10.1158/1538-7445.AM2011-3444
Abstract 3446: Inhibition of EZH2 suppresses medulloblastoma cell growth
Authors: Alimova Irina N. , Venkataraman Sujatha , Harris Peter , Vibhakar Rajeev 
Published: June 2012

Abstract
EZH2 (enhancer of zeste homologue2) is a polycomb group protein that mediates repression of gene transcription through its Histone 3 Lysine 27methyltransferase activity. EZH2 is highly expressed in many cancers including metastatic prostate cancer, breast cancer, and glioblastoma multiform. EZH2 expression is associated with tumor cell proliferation, invasive growth and aggressive cancer phenotypes. The fact that EZH2 increases tumor cell proliferation and aggressive subgroups in several cancers may be of practical interest because the polycomb proteins have been suggested as candidates for targeted therapy.
We found EZH2 expression to be increased in medulloblastoma when compared to normal cerebellum. Inhibition of EZH2 by RNAi in medulloblastoma cells resulted in suppression of cell growth. To further examine this phenotype we used a global histone methylation inhibitor, 3-Deazaneplanocin A (DZNep). DZNep preferentially inhibits H3 Lys27me via EZH2.
DZNep showed a dose dependent, anti-proliferative and anti-clonogenic activity in medulloblastoma cells. Synergetic effect was shown in cells transfected with shEZH2 and treated with DZNEP. Furthermore DZNep treatment decreased EZH2 protein levels. We found that DZNep induced differentiation of mouse neural stem cells even when they are grown in proliferation medium. Most critically transformation of these neural stem cells was significantly attenuated by shEZH2 and DZNep. Our results suggest that EZH2 is a target for medulloblastoma treatment and that DZNep is an excellent candidate for further testing as a therapeutic candidate.
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 3446. doi:10.1158/1538-7445.AM2011-3446
Abstract 3480: TNFα accelerates tumor vascular leukocyte formation through the induction of integrin α5 expression and adhesion to fibronectin
Authors: Li Bin , Young Pampee 
Published: June 2012

Abstract
Tumor associated myeloid cells are believed to promote tumor development by stimulating tumor growth, angiogenesis, invasion and metastasis. Tumor associated myeloid cells that co-express endothelial and myeloid markers represent a pro-angiogenic subpopulation known as vascular leukocytes. Recently, we and others have demonstrated that tumor-derived TNFα promotes local tumor growth and vascularity. Our data suggest that tumor growth is in part due to TNFα-mediated increased numbers of tumor-associated vascular leukocytes (ie myeloid-endothelial biphenotypic cells). The work detailed herein explored the mechanism by which TNFα mediates endothelial differentiation of myeloid cells. Our studies showed that fibronectin is a robust facilitator of endothelial differentiation of blood mononuclear cells in vitro. We have found that TNFα treatment of monocytes significantly increased expression of α5β1 integrin, a major fibronectin receptor enriched on endothelial cells, leading to a consequent 4-fold increase in fibronectin adhesion. Furthermore, TNFα treated monocytes upregulated expression of endothelial markers, flk-1(VEGFR2/KDR) and VE-cadherin. Integrin α5 subunit inhibitory antibodies blocked adhesion to fibronectin as well as consequent upregulation of flk-1 and VE-cadherin transcripts, implying a role for outside-in signaling by the α5β1 integrin after binding fibronectin. Finally, treatment of mouse tumors with anti-α5 antibodies reduced accumulation of tumor vascular leukocytes in vivo. Our studies suggest that tumor-cell derived TNFα constitutes a tumor microenvironment signal that promotes differentiation of tumor-associated monocytes towards a proangiogenic/provasculogenic myeloid-endothelial phenotype via upregulation of the fibronectin receptor α5β1.
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 3480. doi:10.1158/1538-7445.AM2011-3480
Abstract 349: Fascin expression in colorectal cancer metastases predicts survival after curative-intent surgery
Authors: Sullivan Catherine , Guo Xiaojie , Wang Zuoheng , Theoharis Constantine , Rimm David L. , Boffa Daniel J. 
Published: June 2012

Abstract
Background: Patients with metastatic colorectal cancer that is limited to a few lesions in the lungs or liver may benefit from the complete surgical removal of all deposits of metastatic cancer (referred to as a curative metastasectomy). Although the outcome after this curative-intent surgery is considerably better than patients with more extensive metastatic cancer, only a third of the surgical patients are actually cured. As a result, there is a great need for a mechanism to predict outcome after surgery for limited metastatic cancer, in order to better match patients with effective therapy.
Fascin is an actin bundling protein linked to epithelial to mesenchymal transformation and metastatic progression. Fascin expression has previously demonstrated prognostic potential in patients with extensive metastatic colorectal cancer. We hypothesized that Fascin expression within surgically removed colorectal cancer metastases would correlate with survival after curative-intent surgery.
Methods: 82 paraffin embedded colorectal metastases collected after curative-intent surgery between 1990 and 2008 were incorporated into tissue microarrays (TMAs) in two fold redundancy. Fascin expression within the metastases was determined by quantitative immunofluorescence using Automated Quantitative Analysis (AQUA), and normalized based on a panel of cell lines (AQUA score range 0-72). The median follow up was 2.8 years and thus far 51 patients have died (62%).
Results: The majority of colorectal cancer metastases had been removed from the liver (70 patients), while 12 represented pulmonary metastases. There were no differences in survival by location of metastases (p = .65). Survival was analyzed based on high (top quartile, n = 21) and low (bottom three quartiles, n = 61) expression of Fascin (AQUA score cut point of 3.4). High expression of Fascin correlated with a worse prognosis, HR 1.97; 95% CI 1.07-3.62 p = .009.
Conclusions: Fascin expression within colorectal cancer metastases may be used to predict outcome after curative-intent surgery. Patients with high Fascin expression may be considered for additional therapy or may be advised against particularly high risk procedures. Further study is warranted to validate the role of Fascin expression analysis in this patient cohort.
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 349. doi:10.1158/1538-7445.AM2011-349