bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3364: Upregulation of sonic hedgehog contributes to TGF-β1-induced epithelial to mesenchymal transition in NSCLC cells
Authors: Maitah Ma'in Y. , Ali Shadan , Ahmad Aamir , Gadgeel Shirish , Sarkar Fazlul H. 
Published: June 2012

Abstract
Background: Lung cancer especially non-small cell lung cancer (NSCLC) is the major cause of cancer-related deaths in the United States, and the aggressiveness of NSCLC has been shown to be associated with the acquisition of epithelial-to-mesenchymal transition (EMT). The acquisition of EMT phenotype induced by TGF-β1 in several cancer cells has been implicated with tumor aggressiveness and resistance to conventional therapeutics; however, the molecular mechanism of EMT and tumor aggressiveness in NSCLC remains unknown.
Methodology/Principal Findings: In this study, we found, for the first time, that the induction of EMT by chronic exposure of A549 NSCLC cells to TGF-β1 (A549-M cells) led to the up-regulation of sonic hedgehog (Shh) both at the mRNA and protein levels causing activation of hedgehog signaling. Induction of EMT was found to be consistent with aggressive characteristics such as increased clonogenic growth, cell motility and invasion. The aggressiveness of these cells was attenuated by treatment of A549-M cells with pharmacological inhibitors of Hh signaling in addition to Shh knock-down by siRNA. The inhibition of Hh signaling by pharmacological inhibitors led to the reversal of EMT phenotype as confirmed by the reduction of mesenchymal markers such as ZEB1 and Fibronectin, and induction of epithelial marker E-cadherin.
Conclusions/Significance: These results suggest that transcriptional up-regulation of Shh signaling is mechanistically associated with TGF-β1 induced EMT phenotype, and thus the inhibitors of Shh signaling could be useful for the reversal of EMT phenotype, which would inhibit the metastatic potential of NSCLC cells and also make these tumors more sensitive to conventional therapeutics.
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 3364. doi:10.1158/1538-7445.AM2011-3364
Abstract 3383: Hepatocyte growth factor upregulation and signaling is associated with carcinogenesis and mesenchymal characteristics in hepatocellular carcinoma
Authors: Ogunwobi Olorunseun O. , Liu Chen 
Published: June 2012

Abstract
Advanced hepatocellular carcinoma (HCC) is an important cause of cancer mortality worldwide. Epithelial-mesenchymal transition (EMT) has been shown to be an important biological process in cancer progression and metastasis. We have focused on elucidating factors that may induce EMT to promote carcinogenesis and subsequent metastasis in HCC using the BNL CL.2 (BNL) and BNL 1ME A. 7R.1 (1MEA) cell lines. BNL cells are normal hepatocytes whereas the 1MEA cells are HCC cells derived from transformation of the BNL cells. Their morphological characteristics were examined. Expression levels of hepatocyte growth factor (HGF), markers of EMT and mediators of HGF signaling were determined in the cell lines and their functional characteristics were compared. BNL cells were treated with HGF and effects on EMT-marker and mediators of HGF signaling were analyzed. BNL cells display characteristic epithelial morphology whereas 1MEA cells display mesenchymal characteristics when examined following H&E staining. qPCR revealed that 1MEA cells express more HGF (200-fold) than BNL cells and confirmed by immunoblotting. There was associated decreased expression of E-cadherin, albumin, AAT and increased expression of fibronectin, collagen-1 and vimentin. There was also increased expression of COX-2, ERK, Akt, phosphorylated ERK and Akt and 1MEA cells formed numerous colonies in soft agar unlike BNL cells. Treatment of BNL cells with HGF led to decreased expression of E-cadherin and increased expression of fibronectin, vimentin, increased migration and increased expression of COX-2, ERK and Akt. We conclude that development of HCC is associated with upregulation of HGF which promotes the acquisition of morphological and molecular mesenchymal characteristics, carcinogenesis and upregulation of COX-2, ERK, Akt and phosphorylated ERK and Akt. Consequently, HGF signaling may be targeted for therapy in advanced and metastatic HCC.
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 3383. doi:10.1158/1538-7445.AM2011-3383
Abstract 3388: DDX5 modulates Notch signaling via interaction with the MAML1 co-activator and is required to optimal Notch signaling in leukemic cells
Authors: Tian Liang , Lin Shuibin , Gu Yumei , Chen Zirong , Shen Huangxuan , Wu Lizi 
Published: June 2012

Abstract
Notch receptor-mediated signaling is essential for embryonic development and adult tissue homeostasis by regulating cell proliferation, differentiation and survival. Aberrant Notch signaling is linked to many epithelial cancers and hematological malignancies. For example, activated NOTCH1 mutations are detected in more than 50% of T cell acute lymphoblastic leukemia (T-ALL) patients. Since the constitutive activation of Notch signaling results in leukemic cell transformation and is required for the maintenance of the leukemic phenotype, the Notch pathway is a promising and highly specific molecular therapeutic target for T-ALL.
We have previously identified the family of the MAML transcriptional co-activators as essential components of the core Notch transcription activation complex. The prototypic member MAML1 was found to be the major co-activator that regulates NOTCH1 oncogenic activities in leukemic cells. Hence, the modulation of MAML1 expression levels or functional activities is expected to affect Notch-induced leukemic initiation and progression. However, it remains unclear how MAML1 function is regulated. To gain insights into the molecular basis underlying MAML1 function, we undertook the task of identifying cellular factors that interact with MAML1 and characterizing their roles in regulating Notch signaling and Notch-mediated T cell leukemia. Through proteomic studies, we identified DDX5, an ATP-dependent DEAD-box RNA helicase, as a component in the MAML1 protein complex. Given the role of DDX5 as a transcriptional modulator, we reasoned that DDX5 might be a critical regulator of MAML1-mediated Notch target genes transcription. We showed that DDX5 interacts with MAML1 in vitro and in vivo, and is associated with the endogenous Notch1 transcription activation complex through interaction with MAML1. Lentiviral-mediated shRNA knockdown of DDX5 resulted in decreased expression of Notch target signature, along with reduced cell proliferation and survival in leukemic cells that carry activated NOTCH1 mutations. Our findings thus revealed an essential role of DDX5 in promoting efficient Notch-mediated transcription in leukemic cells where the Notch pathway is constitutively activated, suggesting that DDX5 might be critical for Notch-mediated T-ALL pathogenesis and could be a potential new target for modulating the Notch signaling in leukemia.
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 3388. doi:10.1158/1538-7445.AM2011-3388
Abstract 3402: Up-regulation and invasive role of MUC18/MCAM in glioma sphere culture
Authors: Shimizu Keiji , Ishida Eri , Kawanishi Yu , Tamura Masakazu , Yawata Toshio 
Published: June 2012

Abstract
Glioblastomas are characterized by aggressive invasion into normal brain tissues, thus limiting complete removal by surgical resection resulting in recurrence. Our identified molecule involved in glioma invasion is important for developing targeted effective therapies in the malignant glioma. Cancer stem cells are capable for self-renewing and are thought to be responsible for tumor metastasis and dissemination. However, the invasive activities of cancer stem cells have not been fully understood. To investigate a role of glioma stem cells in the tumor invasion, tumor sphere culture was established from mouse glioma RSV-M cells. The high tumorigeneity and aggressive migration of RSV-M tumor sphere were observed in intracranial transplantation. Quantitative RT-PCR analysis showed the enhanced expression of metastasis-related genes in RSV-M tumor sphere. Of these, MUC18/MCAM also highly expressed in tumor sphere derived from human glioma cell lines. Importantly, CD133-positive fraction of glioma sphere culture isolated from glioblastoma patients contained a cell population expressing MUC18 but CD133-negative fraction not. To examine a function of MUC18 in glioma cells, the expression or knockdown construct for the gene were introduced into human glioma cells. Over-expression of MUC18 in the glioma cells increased their invasive capacity and clonogenicity in comparison to the parent or knockdown cells. In addition, expression of some metastasis-related genes was up-regulated in MUC18-over-expressing cells. These results suggest that enhanced MUC18 expression of glioma stem cells may contribute to the aggressive invasion of this tumor.
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 3402. doi:10.1158/1538-7445.AM2011-3402
Abstract 3435: Proteomic analysis of changes to the cellular kinome in the epithelial to mesenchymal transition
Authors: Tanowitz Michael , Bean James , Haley John D. , Garton Andrew 
Published: June 2012

Abstract
The epithelial to mesenchymal transition (EMT) is a developmental program characterized by loss of cell-cell contacts, loss of cell polarity, and acquisition of a migratory phenotype. Many of the hallmarks of EMT correspond to aspects of carcinogenesis, particularly with regard to metastasis and invasion, and EMT is associated with the development of tumor cell resistance to EGFR inhibitors. We have applied proteomic approaches to examine changes to the cellular kinome in response to various EMT-inducing ligand treatments. For our studies we chose the H358 NSCLC line after week-long single or combination treatments with Hepatocyte Growth Factor (HGF), Transforming Growth Factor Beta (TGFβ) and Oncostatin M (OSM). We used several approaches to probe for changes following EMT using mass spectroscopy: whole cell lysate fractionation to provide an unbiased overview of cellular proteins, affinity isolation of cellular phospho-proteins, and targeted analysis of ATP binding proteins (KinativTM). Using these methods we have identified a host of protein changes that are clustered across several signaling pathways and cellular functions. Among these are changes in receptor tyrosine kinases centered around phylogenetically related groupings such as Tyro3/Mer/Axl and Ron/Met, concerted changes in actin-dependent motor proteins consistent with changes in migratory behavior, and changes indicative of reorganization of calcium signaling networks. Functional consequences of these changes and their potential to inform therapeutic interventions will be discussed.
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 3435. doi:10.1158/1538-7445.AM2011-3435
Abstract 3439: Sarcomatoid renal cell carcinoma as a biological example of epithelial to mesenchymal transition (EMT)
Authors: Boström Anna-Karin , Möller Christina , Nilsson Elise , Axelson Håkan , Johansson Martin E. 
Published: June 2012

Abstract
About 8% of clear cell renal cell carcinoma (CCRCC) cases contain areas of a radically different morphology, demonstrating spindle shaped cells and a histological resemblance to sarcomas. These biphasic neoplasms are called sarcomatoid CCRCC (sCCRCC). Patients diagnosed with sCCRCC face a considerably worse prognosis due to an increased propensity for metastasis. Using a set of biphasic CCRCC cases, we showed that sCCRCC has a higher proliferative index and more prononced vimentin expression as compared to the CCRCC counterpart. We selected a CCRCC/sCCRCC case demonstrating overgrowth as well as metastatic spread for extended immunohistochemical characterization. Using mouse xenografts we evaluated a $$$$CCRCC cell-line and put forward the hypothesis that some CCRCC cell-lines may be derived from the sarcomatoid component rather than from the clear cell part, with obvious implications for the validity of in vitro models of CCRCC. We confirm that sCCRCC is derived from the clear cell component and show that sCCRCC morphologically and immunohistochemically may represent a completed epithelial mesenchymal transition (EMT). Furthermore we suggest that TGF-β1 may be the driving force behind sarcomatoid transdifferentiation i.e. EMT in CCRCC.
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 3439. doi:10.1158/1538-7445.AM2011-3439
Abstract 345: The intratumoral Wnt2B expression affects tumor progression in malignant pleural mesotheliomas
Authors: Kobayashi Masashi , Huang Cheng-long , Miyahara Ryo , Sonobe Makoto , Menju Toshi , Kikuchi Ryutao , Ishikawa Masashi , Kitamura Jiro , Iwakiri Shotaro , Itoi Kazumi , Date Hiroshi 
Published: June 2012

Abstract
Introduction: Malignant pleural mesotheliomas are aggressive tumors with a poor prognosis. It is considered to be important to identify the molecular targets for the treatment against malignant pleural mesotheliomas. We have recently found the Wnt1 expression to affect tumor progression in non-small cell lung cancers, through the induction of various Wnt-targets (Huang et al, Eur J Cancer 2008). Therefore, we performed a clinical study on the intratumoral expressions of the canonical Wnts, such as Wnt1 and Wnt2B, in relation to their targets, including c-Myc and survivin. Methods: Sixty-five cases with malignant pleural mesotheliomas were investigated. Immunohistochemical assays were performed to evaluate the intratumoral expressions of Wnt1, Wnt2B, c-Myc and survivin. In addition, the Ki-67 proliferation index was evaluated by immunohistochemistry, and the apoptotic index was evaluated by the TUNEL method. Results: The Ki-67 proliferation index was significantly higher in c-Myc-high tumors than in c-Myc-low tumors (P=0.008). In addition, the Ki-67 proliferation index was also significantly higher nuclear-survivin-high tumors than in nuclear-survivin-low tumors (P=0.004). Regarding the intratumoral expressions of canonical Wnts, 18 tumors (27.7%) were Wnt1-high tumors, and 36 tumors (55.4%) were Wnt2B-high tumors. The rate of Wnt2B-high tumors was significantly higher than the rate of Wnt1-high tumors (P=0.024). Regarding tumor histology, the Wnt2B expression was the significantly highest in epithelial type (P&lt;0.001). On the other hand, there was no significant difference in the Wnt1 expression according to the tumor histology (P=0.163). Furthermore, the Wnt 2B expression significantly correlated with expressions of c-Myc and survivin (P&lt;0.001 and P&lt;0.001, respectively). The c-Myc expression was significantly higher in Wnt2B-high tumors than in Wnt2B-low tumors (P&lt;0.001), and the survivin expression was also significantly higher in Wnt2B-high tumors than in Wnt2B-low tumors (P=0.007). In contrast, there was no significant difference in c-Myc or survivin expressions according to the Wnt1 expression (P=0.218 and P=0.688, respectively). Conclusions: The intratumoral Wnt2B expression affects tumor progression of malignant pleural mesothelioma through the induction of c-Myc and survivin. The Wnt2B could be a candidate of targets of the molecular therapy against malignant pleural mesotheliomas.
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 345. doi:10.1158/1538-7445.AM2011-345
Abstract 3455: Comparison of expression profiles of pediatric high and low grade brainstem gliomas to pediatric supratentorial high grade astrocytomas
Authors: Buczkowicz Pawel , Bartels Ute , Morrison Andrew , Bouffet Eric , Tabori Uri , Hawkins Cynthia 
Published: June 2012

Abstract
Diffuse intrinsic pontine gliomas (DIPG) are one of the most devastating pediatric malignancies and currently the number one cause of brain tumor related death in children with a 10-12 month median survival. Despite this very little is understood about the biology of these tumors. We have already shown potential novel therapeutic targets for DIPG using high-resolution SNP-based analysis. We performed high resolution genetic analysis using whole-genome single-nucleotide polymorphism (SNP) arrays (Affymetrix 500K and 6.0) on post mortem tumor with matched normal brain samples (n=9) and surgical samples (n=2) for a series of DIPG patients as well as pediatric supratentorial high grade astrocytomas (sHGA, n=20). Here we extend our initial study to include expression array analysis, amalgamating the datasets to generate a more complete understanding of the genetic alterations underlying brainstem gliomas. Expression profiling using Illumina HumanHT-12 arrays was conducted on 26 high grade brainstem gliomas, including 23 DIPGs, 51 low grade brainstem gliomas and 30 supratentorial high grade astrocytomas. Expression profiles highlighted the distinctiveness of DIPGs when compared to high grade supratentorial astrocytomas. Analysis resulted in two groups of DIPGs when clustering based on most significant differentially expressed genes (p &lt; 0.005) with one group being more similar to pediatric low grade brainstem gliomas and the other distinct from both the supratentorial high grade tumors and other brainstem gliomas. This data will increase our understanding of brainstem glioma biology, information crucial to the development of agents targeted more specifically towards this devastating 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 3455. doi:10.1158/1538-7445.AM2011-3455
Abstract 3460: Genome-wide copy number analysis reveals novel somatic mutations associated with choroid plexus tumorigenesis
Authors: Merino Diana M. , Shlien Adam , Pienkowska Malgorzata , Tabori Uri , Malkin David 
Published: June 2012

Abstract
Choroid plexus carcinomas (CPCs) are aggressive pediatric neoplasms accounting for less than 1% of brain tumors, but representing more than 10% of brain tumors in children under 1 year of age. CPCs are frequently observed in the context of the Li-Fraumeni Syndrome (LFS), yet this association has not been fully elucidated. The genetic mechanisms leading to this disease are poorly understood; however, we have recently demonstrated that TP53 status and total structural variation are correlated with tumor subtype and clinical outcome in choroid plexus tumor (CPT) patients, distinguishing between individuals with CPC and choroid plexus papilloma (CPP), a benign tumor with a more favorable prognosis. We set out to characterize genomic regions in which copy number variation and gene expression changes are uniquely associated with CPC tumors in order to identify genes that may serve as markers in tumor diagnosis and prognosis.
DNA and RNA from 59 choroid plexus tumors (CPC, n=29 and CPP, n=30) and two samples of normal choroid plexus tissue were obtained from a multi-institutional tissue and clinical database. We conducted high-resolution copy number alteration (CNA) and gene expression analysis for each tumor sample using highly dense microarrays (Affymetrix SNP 6.0 and Exon 1.0 ST array, respectively). DNA microarray data was segmented using a Hidden Markov Model (HMM) approach. Statistical analysis was carried out using Partek Genomics Suite in which CNAs and gene expression changes between CPC, CPP, and normal choroid plexus samples were contrasted. We identified 14 CPC-unique loci harboring CNAs with corresponding gene expression changes (p&gt;0.05). We observed that CNAs were found at loci where cancer genes with well-characterized oncogenic functions have been previously identified (1p13.2, 1p13.3, 1p21.3, 1p22.1 and 5q13.3). Furthermore, more than 90% of tumors with copy number alterations and expression changes at these five loci also harbored mutant TP53.
These observations suggest involvement of several genes in the malignant progression of CPCs, which may help elucidate the aggressiveness and poor clinical outcome of this tumor subtype compared to the more favorable CPP. Further analysis of CNAs and expression at these loci in the context of TP53 mutations, will provide a more refined genetic profile that will facilitate diagnosis of CPTs and aid in predicting patient outcome.
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 3460. doi:10.1158/1538-7445.AM2011-3460