bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 770: Association of YAP expression with colorectal cancer progression.
Authors: Xie Daxing , Wang Xiangyang , Min Jiang , Li Xiaolan , Hu Jubo , Gong Jianping 
Published: August 2014

Abstract
YAP, a crucial transcriptional coactivator in the Hippo signaling pathway, is upregulated in several human tumors and suggested to promote tumor progression. However, its expression level and role in colorectal cancer (CRC) remain unknown. In this study, YAP expression and the correlation between YAP expression and CRC clinical features were investigated. Quantitative real-time polymerase chain reaction and Western blotting were performed on 30 matched pairs of fresh CRC tissues and adjacent normal mucosae from 30 CRC patients. Immunohistochemical analysis was performed on 116 matched pairs of paraffin-embedded CRC tissues and adjacent normal mucosae, as well as in 73 cases of metastatic lymph nodes. Our results showed YAP expression level in CRC or lymphatic metastatic tissues was clearly higher than that in normal mucosae (P&lt;0.01), whereas that in CRC tissues with lymphatic metastasis was higher than that in tissues without lymphatic metastasis (P&lt;0.05). YAP expression is associated with serosal invasion, lymphatic metastasis, lymph node ratio, remote metastasis, Dukes stage, and the carcinoembryonic antigen level (P&lt;0.05). It is also an independent predictor of the survival of CRC patients (P&lt;0.05). Patients with high YAP expression level exhibited lower overall survival rates than those with low expression (P=0.001). Further analysis showed that YAP predicted CRC prognosis primarily for patients with late-clinical-stage CRC (P=0.002). These findings suggest that YAP is a potential marker for predicting CRC progression and prognosis. YAP upregulation is associated with poor overall survival time in CRC patients, particularly in those with late stage of the disease. Therefore, YAP may be an effective therapeutic target for late-stage tumors.
Citation Format: Daxing Xie, Xiangyang Wang, Jiang Min, Xiaolan Li, Jubo Hu, Jianping Gong. Association of YAP expression with colorectal cancer progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 770. doi:10.1158/1538-7445.AM2013-770
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 780: Knockdown of p53 increases tumorigenicity of human breast cancer cells.
Authors: Liu Fang , Roy Tanima , So Jae Young , Smolarek Amanda , Lu You-Rong , Suh Nanjoo 
Published: August 2014

Abstract
The tumor suppressor p53 is mutated or functionally inactivated in ∼ 70% cancer. p53 causes cell cycle arrest, cellular senescence, or induces apoptosis in response to stress. Although knockdown of p53 has been shown to increase tumorigenicity of human colon and lung cancer cells, it is not known whether knockdown of p53 in human breast cancer cells can indeed lead to increased tumorigenicity. We show that knockdown of p53 in human breast cancer cells significantly increases tumorigenicity in vivo and colony formation on soft agar in vitro. Our ongoing studies are elucidating the underlying mechanisms. To the best of our knowledge, this is the first study demonstrating that knockdown of p53 increases tumorigenicity of human breast cancer cells. Our results highlight the importance of the tumor suppressor p53 in human breast cancer.
Citation Format: Fang Liu, Tanima Roy, Jae Young So, Amanda Smolarek, You-Rong Lu, Nanjoo Suh. Knockdown of p53 increases tumorigenicity of human breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 780. doi:10.1158/1538-7445.AM2013-780
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 794: RNA-Seq and whole transcriptome analyses in ependymomas.
Authors: Costa Fabricio F. , Bischof Jared M. , Hamm Chris , Vanin Elio F. , Bonaldo Maria F. , Iannaccone Stephen , Rajaram Veena , Tomita Tadanori , Goldman Stewart , Soares Marcelo B. 
Published: August 2014

Abstract
Ependymoma is a common pediatric central nervous system (CNS) tumor that is believed to originate from ependymal cells located in the lining of ventricular surfaces in the brain. This type of pediatric tumor presents great challenges in treatment despite the advances in neurosurgical techniques and adjuvant therapy. In order to identify possible molecular markers that could improve clinical management and better treatment, we have used RNA-Seq to profile the transcriptome of ependymoma samples with different outcomes. In this study, the ABI SOLiD WT (Whole Transcriptome) technology was utilized to sequence three different ependymoma tumor samples and one normal control brain tissue (enriched for ependymal cells). Whole Transcriptome sequencing produced approximately 10-30 million reads per sample and an average of 30-40% were mapped to the human reference sequence (NCBI Build 36.1) using Novoalign software. After obtaining these mapped locations, Perl scripts were written to overlap these intervals with other annotations and Genespring was used to visualize the reads. Different protein-coding, non-coding and microRNA gene databases were searched for known genes and to calculate the RPKM (Reads Per Kilobase of transcript per Million mapped reads) for each clustered gene. Multiple gene lists were generated corresponding to different RPKM-based comparisons between tumor and control tissues, ultimately enabling the identification of protein-coding genes, non-coding RNAs and microRNAs that are differentially expressed in ependymomas. Protein interaction networks were then built with these genes using the software GeneGo (Thomson Reuters). Thirty genes that are present in these networks are being selected for validation of differential expression in a larger cohort by Real-Time PCR TaqMan customized arrays. In conclusion, we have been able to identify genes differentially expressed in ependymomas, some of which of potential clinical importance.
Financial Support: Ann & Robert H Lurie Children's Hospital of Chicago, The Falk Brain Tumor Foundation and The Maeve McNicholas Memorial Foundation.
[FF Costa, JM Bischof, and C Hamm contributed equally to this work.]
Citation Format: Fabricio F. Costa, Jared M. Bischof, Chris Hamm, Elio F. Vanin, Maria F. Bonaldo, Stephen Iannaccone, Veena Rajaram, Tadanori Tomita, Stewart Goldman, Marcelo B. Soares. RNA-Seq and whole transcriptome analyses in ependymomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 794. doi:10.1158/1538-7445.AM2013-794
Abstract 795: Transcriptome instability as a common characteristic of solid cancers.
Authors: Sveen Anita , Johannessen Bjarne , Teixeira Manuel R. , Lothe Ragnhild A. , Skotheim Rolf I. 
Published: August 2014

Abstract
Analogous to the genomic types of instability describing cancer genomes, we recently proposed transcriptome instability as a genome-wide, pre-mRNA splicing related characteristic of colorectal cancer (Sveen et al., Genome Medicine, 2011). Here, we explore transcriptome instability in several major solid cancer types.
We have analyzed exon microarray data from ten cancer datasets (555 samples; seven cancer types) and four normal tissue types (93 samples; paired samples from colonic mucosa, lung, prostate and the stomach) for variation in relative amounts of aberrant exon usage, based on alternative splicing scores calculated by the FIRMA algorithm. Most major solid cancer types (breast, cervical, colorectal (two datasets), lung, and prostate (two datasets) cancer) showed large variations in aberrant exon usage amounts among the samples, and these amounts were strongly associated with splicing factor expression levels. Thus, we consider these cancer types to exhibit transcriptome instability. Non-random associations with splicing factor (n = 280) expression levels were shown by separation of samples according to aberrant exon usage amounts upon unsupervised hierarchical clustering analyses, and by stronger correlations between aberrant exon usage amounts and splicing factor expression levels than expected by chance (compared with random gene sets and permutations of the aberrant exon usage amounts; P &lt; 0.001).
In comparisons across healthy tissue types and paired cancer and normal datasets, we observed tissue- and cancer-specific patterns in splicing factor correlations. Interestingly, in comparisons across cancer types with transcriptome instability (but not across cancer datasets that did not show transcriptome instability; gastric cancer, a second lung cancer dataset, and neuroblastoma), the non-random associations between aberrant exon usage amounts and splicing factor expression remained intact, indicating a failure to adhere to tissue specificity. Thus, we consider transcriptome instability to be a common feature of most major solid cancer types, and this deviant splicing pattern is associated with splicing factor expression levels.
Citation Format: Anita Sveen, Bjarne Johannessen, Manuel R. Teixeira, Ragnhild A. Lothe, Rolf I. Skotheim. Transcriptome instability as a common characteristic of solid cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 795. doi:10.1158/1538-7445.AM2013-795
Abstract 8: A role for lumican as a biomarker of disease progression in human prostate adenocarcinoma.
Authors: De Velasco Marco A. , Hatanaka Yuji , Kura Yurie , Ando Naomi , Fukushima Emiko , Yamamoto Yutaka , Shimizu Nobutaka , Nozawa Masahiro , Yoshimura Kazuhiro , Yoshikawa Kazuhiro , Nishio Kazuto , Uemura Hirotsugu 
Published: August 2014

Abstract
We previously identified altered lumican expression in prostate tumors from genetically modified mice. Lumican is a small leucine-rich extracellular matrix protein that has been shown to modulate cell migration and proliferation during embryonic development, and tissue repair. Expression and distinct glycosylation patterns of lumican in several tumor and stromal tissues has been shown to play important roles in vascular invasion, differentiation, proliferation, and invasion. To determine a possible role for lumican as a prognostic biomarker for prostate cancer, we examined protein expression in normal and tumor specimens from prostatectomy cases. Tissue microarrays were constructed and immunostained for lumican. Slides were digitized and the expression levels of lumican were scored in both the stroma and epithelia. Expression scores were compared with clinicopathological features and disease progression, defined as death or biochemical recurrence. Stromal Lumican expression in tumor was negatively associated with Gleason score, differentiation, node/metastasis status and disease progression. Progression free survival was significantly longer for patients with high expression of stromal lumican (HR=0.25; P=0.005). Based on this set, stromal expression of lumican correlated to good clinical outcome for patients with prostate cancer and thus appears to be a strong prognostic biomarker for disease progression.
Citation Format: Marco A. De Velasco, Yuji Hatanaka, Yurie Kura, Naomi Ando, Emiko Fukushima, Yutaka Yamamoto, Nobutaka Shimizu, Masahiro Nozawa, Kazuhiro Yoshimura, Kazuhiro Yoshikawa, Kazuto Nishio, Hirotsugu Uemura. A role for lumican as a biomarker of disease progression in human prostate adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 8. doi:10.1158/1538-7445.AM2013-8
Abstract 81: Rapamycin increases radiosensitivity of cancer cells by induction of premature senescence.
Authors: Nam Hae Yun , Han Myung Woul , Chang Hyo Won , Lee Yoon Sun , Lee Myungjin , Kim Mi Ra , Lee Hyang Ju , Jeoung Ji Yung , Moon So Young , Kim Hyo Jung , Kim Sang Yoon , Kim Seong Who 
Published: August 2014

Abstract
Autophagy is frequently activated in radioresistant cancer cells. Rapamycin, mammalian target of rapamycin (mTOR) inhibitor, activates autophagy but enhances radiosensitivity. The mechanism of these actions by which such opposing functions coexist was investigated on radiation-resistant cancer cell lines (AMC-HN-9 and U-87) and the antitumor activity was evaluated in mice bearing xenografts of the cancer cells. Enhanced autophagic flux induced by radiation returned to untreated control levels. Treatment of the cancer cells with rapamycin leads to the potentiation and prolongation of radiation-induced autophagy, the increases in senescence-associated β-galactosidase activity, heterochromatin formation, and irreversible growth arrest. Furthermore, rapamycine resulted in a tumor regrowth delay and increased the level of β-galactosidase staining and the expression of heterochromatin markers in irradiated xenografts. These results suggest that even though autophagy is a survival mechanism in radioresistant cells, a persistent activation of autophagy by mTOR inhibitor induces premature senescence in these cells, eventually making the cells radiosensitive. Our data suggest a novel mechanism by which an inhibition of mTOR pathway increases autophagy but paradoxically increases radiosensitivity in radioresistant cancer cells.
Citation Format: Hae Yun Nam, Myung Woul Han, Hyo Won Chang, Yoon Sun Lee, Myungjin Lee, Mi Ra Kim, Hyang Ju Lee, Ji Yung Jeoung, So Young Moon, Hyo Jung Kim, Sang Yoon Kim, Seong Who Kim. Rapamycin increases radiosensitivity of cancer cells by induction of premature senescence. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 81. doi:10.1158/1538-7445.AM2013-81
Abstract 827: Identification of the insulin-like growth factor 2 mRNA binding protein (IGF2BP1) as an important regulator of cIAP1 translation and apoptosis in rhabdomyosarcomas.
Authors: Faye Mame Daro , Graber Tyson , Langlois Stephanie , Cowan Kyle , Holcik Martin 
Published: August 2014

Abstract
Rhabdomyosarcoma, a neoplasm characterized by undifferentiated myoblats-like cells, is the most common soft tissue sarcoma of childhood and represents 3-4% of all childhood cancers. IGF2BP1 is an oncofetal protein that was first identified in the rhabdomyosarcoma RD cell line and was shown to be overexpressed in a variety of cancers. Our group has previously identified IGF2BP1 as a potential translation modulator of the cellular inhibitor of apoptosis protein 1 (cIAP1), a key regulator of the NFκB signaling pathway and of caspase-8 mediated cell death in mammalian cells. In this study, we report that IGF2BP1 and cIAP1 expression is upregulated in a panel of rhabdomyosarcoma cell lines. We also show that IGF2BP1 is a positive regulator of cIAP1 translation, specifically through an internal ribosome entry site (IRES) mechanism. Finally, we report that altering the levels of cIAP1 in two rhabdomyosarcoma cell lines, RH36 and RH41, either by IGF2BP1 knock-down or by a Smac mimetic coumpound, sensitizes these cells to TNFα-mediated cell death. Our results identify IGF2BP1 and cIAP1 as important regulators of apoptosis in rhabdomyosarcomas.
Citation Format: Mame Daro Faye, Tyson Graber, Stephanie Langlois, Kyle Cowan, Martin Holcik. Identification of the insulin-like growth factor 2 mRNA binding protein (IGF2BP1) as an important regulator of cIAP1 translation and apoptosis in rhabdomyosarcomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 827. doi:10.1158/1538-7445.AM2013-827
Abstract 847: PIAS3 induction of apoptosis is p53-independent and has STAT3-independent mediators.
Authors: Dabir Snehal , Liu Yu , Wildey Gary , Dowlati Afshin 
Published: August 2014

Abstract
Protein inhibitor of activated STAT3 (PIAS3) is an endogenous inhibitor of STAT3 that negatively regulates STAT3 transcriptional activity and cell growth and demonstrates limited expression in the majority of human squamous cell carcinomas of the lung. In the present study we sought to determine if PIAS3 inhibits cell growth in non-small cell lung cancer (NSCLC) cell lines by induction of apoptosis and further determine the dependence of PIAS3 activity on p53 status by using both wild-type and p53-null cells. Our results demonstrate that over-expression of PIAS3 promotes caspase 3 activation and PARP cleavage. Furthermore, the expression of pro-survival family members BclXL and Bcl-2 is decreased. These effects were observed after both transient and regulated expression of exogenous PIAS3 and were independent of p53 status. PIAS3 inhibition of STAT3 luciferase activity was also p53 independent. Microarray experiments were performed to further investigate the STAT3-dependence of PIAS3-induced apoptosis by comparing its gene expression signature with that of STAT3 siRNA treated cells. IPA pathway analysis showed that a number of genes related to cell death were significantly increased by PIAS3. Furthermore, a subset of apoptotic genes, including CIDEC and DAPK2, were uniquely expressed only after PIAS3 expression and not after STAT3 siRNA. Thus, PIAS3 may represent a promising lung cancer therapeutic target because of its p53-independent efficacy as well as its potential to synergize with direct STAT3 inhibitors.
Citation Format: Snehal Dabir, Yu Liu, Gary Wildey, Afshin Dowlati. PIAS3 induction of apoptosis is p53-independent and has STAT3-independent mediators. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 847. doi:10.1158/1538-7445.AM2013-847
Abstract 849: Reactive oxygen species mediated activation of AMP activated protein kinase and c-Jun N-terminal kinase plays a critical role in beta sitosterol induced apoptosis in multiple myeloma U266 cells.
Authors: Cho Sun-Mi , Kim Ji-Sung , song Hyosook , Sohn Eun-Jung , Kim Ji-Hyun , Jung Ji Hoon , Kim Jung-Hyo , Jeong Soo-Jin , Lee Eun-OK , Lee HyoJeong , Kim Sung Hoon 
Published: August 2014

Abstract
Although beta sitosterol has been well known to have anti-tumor activity in liver, lung, colon, stomach, breast and prostate cancers via cell cycle arrest and apoptosis induction, the underlying mechanism of anti-cancer effect of beta sitosterol in multiple myeloma cells was never elucidated until now. Thus, in the present study, the role of reactive oxygen species (ROS) in association with AMP-activated protein kinase (AMPK) and c-Jun N-terminal kinase (JNK) pathways was demonstrated in beta sitosterol treated multiple myeloma U266 cells. Beta sitosterol exerted cytotoxicity, increased sub-G1 apoptotic population and activated caspase-9 and -3, cleaved poly (ADP-ribose) polymerase (PARP) followed by decrease in mitochondrial potential in U266 cells. Beta sitosterol promoted ROS production, activated AMPK, acetyl-CoA carboxylase (ACC) and JNK in U266 cells. Also, beta sitosterol attenuated the phosphorylation of AKT, mammalian target of rapamycin (mTOR) and S6K, and the expression of cyclooxygenase (COX)2 and VEGF in U266 cells. Conversely, AMPK inhibitor compound C and JNK nhibitor SP600125 suppressed apoptosis induced by beta sitosterol in U266 cells. Furthermore, ROS scavenger N-acetyl-L-cysteine (NAC) attenuated beta sitosterol mediated sub-G1 accumulation, PARP cleavage, JNK and AMPK activation in U266 cells. Overall, these findings for the first time suggest that ROS mediated activation of cancer metabolism related genes such as AMPK and JNK plays an important role in beta sitosterol induced apoptosis in U266 multiple myeloma cells.
Citation Format: Sun-Mi Cho, Ji-Sung Kim, Hyosook song, Eun-Jung Sohn, Ji-Hyun Kim, Ji Hoon Jung, Jung-Hyo Kim, Soo-Jin Jeong, Eun-OK Lee, HyoJeong Lee, Sung Hoon Kim. Reactive oxygen species mediated activation of AMP activated protein kinase and c-Jun N-terminal kinase plays a critical role in beta sitosterol induced apoptosis in multiple myeloma U266 cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 849. doi:10.1158/1538-7445.AM2013-849
Abstract 861: Analysis of predictive genes in triple negative breast cancer in response to a gamma-secretase inhibitor.
Authors: Olsauskas-Kuprys Roma , Osipo Clodia 
Published: August 2014

Abstract
Defined by the lack of estrogen and progesterone receptors and amplification of human epidermal growth factor receptor-2 (HER-2), triple negative breast cancer (TNBC) is a devastating disease with no approved, targeted therapy to date. Characterized by aggressive behavior which includes high rates of metastasis and very poor prognosis, TNBC is presently treated with DNA-damaging agents such as cisplatin or carboplatin. The overall survival outcomes for women with TNBC is dismal and consequently TNBC research requires identification of biomarkers that specifically mediate signaling pathways that lead to disease progression and metastasis. Notch receptors which are necessary for self-renewal and survival of breast cancer stem cells are excellent candidate biomarkers to investigate in various subtypes of TNBC. Based on the critical need to identify predictive biomarkers, we hypothesized that inhibition of the Notch pathway via γ-secretase inhibition (GSI) will provide an effective blockade of TNBC growth in specific subtypes where predictive Notch gene expression profiles are significantly up or downregulated. A panel of three TNBC cell lines were used in this study: MDA-MB-231 (mesenchymal stem-like), MDA-MB-468 (basal-like 1), and BT549 (luminal). Using real-time PCR, Notch pathway-associated genes were measured which include Notch-1 and Notch-4 receptors, Notch target genes (i.e. Deltex-1, Hes-1, Hes-5, and Hey-1), and genes such as IL-8 and MMP-9 which are associated with aggressive tumor behavior. Both anchorage-dependent and anchorage-independent growth assays were measured in response to MRK-003 GSI, carboplatin, and the combination. We have identified for the first time a TNBC line (MDA-MB-468) that expressed the highest level of Hes-1, a Notch gene target, and is the most sensitive to single agent MRK-003 GSI treatment. We also identified that this cell line with the highest sensitivity to MRK-003 GSI upregulates Notch-4 and IL-8 in response to the GSI to a greater extent than either of the two other TNBC lines. Furthermore, the addition of carboplatin at its IC50 concentration significantly increased the sensitivity of MRK-003 GSI in otherwise insensitive TNBC lines. These results suggest for the first time that: 1) Hes-1 could potentially be a valuable predictive biomarker of Notch activity in TBNC; 2) induction of Notch-4 and/or IL-8 could predict response to MRK-003 GSI; and 3) carboplatin might provide a means to increase sensitivity to MRK-003 GSI in resistant TNBC.
Citation Format: Roma Olsauskas-Kuprys, Clodia Osipo. Analysis of predictive genes in triple negative breast cancer in response to a gamma-secretase inhibitor. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 861. doi:10.1158/1538-7445.AM2013-861