bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-417: Identification of calreticulin as an invasion-associated protein in ovarian cancer by proteomic approach.
Authors: Chiang Fan-Ying , Shih Ho-Jun , Chow Lu-Ping , Torng Pao-Ling , Lin Chin-Tarng 
Published: August 2012

Abstract
Ovarian cancer is the most lethal gynecological cancer among women worldwide. The majority of malignant ovarian tumors are epithelial ovarian cancer and metastasis has occurred in most patients at the time of diagnosis with worse outcome. In our previous study, we have established an ovarian endometrioid carcinoma cell line OVTW59. The original lines were designated as P0, and the highly invasive subline P4 was isolated from 4 rounds of invasion selection. By cDNA microarray analysis and further functional analysis, we have reported insulin-like growth factor binding protein-3 (IGFBP-3) as an invasion suppressor gene that correlated with poor patient survival outcome. In this study, we compared the protein profiles between OVTW59 P0 and P4 using 2D-electrophoresis to select metastasis-associated proteins. The potential candidates were subsequently analyzed by LC-MS/MS. We identified 49 positive invasion-associated proteins and 20 negative invasion-associated proteins. Gene-Ontology analysis showed that more than 50% of these proteins were invasion-related proteins. We then built up a potential network involving these differentially expressed proteins by Ingenuity Pathway Analysis. From these data, we selected Calreticulin for further analysis. Calreticulin has been reported in associated with cell adhesion, apoptosis, wound healing, removal of cancer cells, and autoimmune. By q-RT-PCR, Western blot and scratch test, we found Calreticulin positively associated with cancer invasion in our in-vitro system. In addition, higher Calreticulin expression was found in SCID mice with higher metastasitc capability. Clinically, immunohistochemical staining in 58 cases of ovarian endometiroid cancer will be performed. The result will be further correlated with patient outcome. In this study, we found Calreticulin a novel invasion-associated protein in ovarian endometrioid 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 LB-417. doi:1538-7445.AM2012-LB-417
Abstract LB-7: Protein crosstalk in tumor microenvironment: direct identification of intercellular protein transfer in retinoblastoma after topotecan or radiation treatment
Authors: Lee Susan , Fanter Robert , Harutyunyan Narine , Murphree A Linn 
Published: August 2012

Abstract
Current work on the tumor microenvironment has shown that crosstalk between cancer and normal cells can be of significant importance. Here we show direct intercellular communication between different cancer cell populations can provide insights into the tumor microenvironment and the bystander effect. Retinoblastoma is the primary intraocular cancer in childhood and resistance to current treatments such as chemotherapy or radiation often results in enucleation. We seek to improve retinoblastoma treatments by elucidating the diversity of and communication between retinoblastoma tumors. Here we provide the first direct evidence of intercellular protein transfer between retinoblastoma cells after topotecan or radiation treatment using stable isotope labeling and tandem mass spectrometry-based protein identification. Retinoblastoma Y79 cells were grown in media containing 13C, 15N lysine and arginine analogues (Y79S) so that all the proteins had full incorporation of these stable isotopes. The Y79S cells were untreated, treated with 0.02 micromolar topotecan, or treated with 4 Gy of radiation before being co-cultured with either Y79 or CHLA215 retinoblastoma cells for 48 hr. Protein populations within each cell type and the concentrated media were identified using mass spectrometry-based sequencing. Direct intercellular transfer was monitored using the unique 13C, 15N protein tags. Changes in the tumor microenvironment and the protein communication between retinoblastoma cells with chemotherapy and radiation treatment were monitored using a transwell co-culture system. As expected, irradiation resulted in a significant decrease in Y79S cell number and viability. Additionally, irradiated Y79S cells caused a significant decrease in the viability of the non-irradiated Y79 bystander cells. Studies of the proteins directly transferred from Y79S to the other retinoblastoma cells identified heat shock protein 90 (HSP90) in both the topotecan and radiation studies. Significantly, time point data provided insights into the protein transfer dynamics. We show significant protein transfer by 24 hours with a decrease in isotopically labeled proteins by 48 hours. We are currently working on elucidating the functional roles of HSP90 and the other proteins transferred during chemotherapy and radiation treatment. In summary, we have shown the first evidence for direct protein crosstalk between retinoblastoma cell populations in response to chemotherapy and radiation. We anticipate that this work will lead to greater insights into how tumor heterogeneity contributes to treatment response.
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 LB-7. doi:1538-7445.AM2012-LB-7
Abstract LB-72: A20 ubiquitin ligase-mediated RIP1 polyubiquitin chains inhibits TRAIL-induced apoptosis in glioblastoma
Authors: Bellail Anita C. , Olson Jeffrey J. , Yang Xiaolu , Chen Zhijian J. , Hao Chunhai 
Published: August 2012

Abstract
The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) apoptotic pathway has emerged as a cancer therapeutic target; however, clinical trials have proven that the vast majority of human cancers are resistant to TRAIL apoptotic pathway-targeted therapies. We show here that A20-mediated ubiquitination inhibits caspase-8 cleavage and TRAIL-induced apoptosis in glioblastoma through two signaling complexes. A20 is highly expressed in glioblastomas and, together with the death receptor 5 (DR5) and receptor-interacting protein 1 (RIP1), forms a DR5-associated plasma membrane bound signaling complex that we named the preligand assembly complex (PLAC) under physiologic conditions. TRAIL treatment leads to the recruitment of caspase-8 to the PLAC for the assembly of a death-inducing signaling complex (DISC). In the DISC, the C-terminal Zinc finger domain of the A20 ubiquitin ligase mediates RIP1 ubiquitination through lysine (K)-63-linked polyubiquitin chains, which bind to the protease domain of caspase-8 and inhibits its dimerization, cleavage and the initiation of TRAIL-induced apoptosis in glioblastoma-derived cell lines and tumor-initiating cells. These results identify A20 ubiquitin ligase as a therapeutic target whose inhibition can overcome TRAIL resistance in glioblastoma and thus have an impact on ongoing clinical trials of TRAIL apoptotic pathway-targeted combination cancer therapies (the manuscript was published online first in Cancer Discovery).
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 LB-72. doi:1538-7445.AM2012-LB-72
Abstract LB-76: Mibefradil, a novel therapy for glioblastoma: An interlaced therapy approach
Authors: Keir Stephen T. , Gray Lloyd , Friedman Henry S. 
Published: August 2012

Abstract
INTRODUCTION: Finding new ways to improve the efficacy and/or overcome resistance to conventional chemotherapy for brain tumor patients is an ongoing research paradigm. Interlaced TherapyTM is a synergistic cancer therapy involving sequential administration of a T-type calcium channel blocker and a cytotoxic agent. For the purpose of this study, mibefradil dihyrdochloride (MBFD), a T-type calcium channel blocker was interlaced with the standard of care treatment - temozolomide (TMZ) for GBM. Different dosing strategies were tested to maximize efficacy of combination. METHODS: Intracranial (ic) adult brain tumor xenografts (D-270 MG) were grown in athymic BALB/c mice. Three days after ic implantation groups of 10 mice were randomly treated with either drug vehicle/control, MBFD alone PO, TMZ alone IP, or the interlaced therapy of agents. Tumor responses for ic xenografts were assessed by difference in median survival. Two sets of studies were conducted to determine most efficacious delivery of combination: 1) Extended treatment regimen with TMZ, and 2) Time optimization of interlaced approach. RESULTS: The interlaced therapy of MBFD and TMZ demonstrated statistically significant (p&lt;0.001) increases in median survival of 142%, 168%, 174%, and 163% vs. control animals when TMZ is delivered on a regimen of 3, 5, 10, and 15 days respectively. More importantly, interlaced therapy produced significant (p&lt;0.026) increases in survival of 48%, 65%, 68% and 61% at 3, 5, 10, and 15 day dosing regimens vs. TMZ alone. When the TMZ dosing regimen was held constant (5 days) and delivered 0.5, 12, 24, 36 and 48 hours after MBFD, the combination produced statistically significant (p&lt;0.001) increases in median survival of 168%, 158%, 105%, 84% and 74% respectively vs. control animals. More importantly, interlaced therapy produced significant (p&lt;0.042) increases in survival of 65%, 58% and 26% respectively at 0.5, 12 and 24 hour time points vs. TMZ alone. CONCLUSION: Our results establish the therapeutic efficacy of the delivery of MBFD and TMZ via Interlaced TherapyTM against D-270 MG xenografts grown intracranially. Furthermore, this study clearly demonstrates that the synchronization of MBFD with TMZ can be optimized. As such, the blockade of T type calcium channels may well be a target that produces clinically effective, safe synchronization that can be used in conjunction with conventional chemotherapy to render it more effective. The results from this study will be used to help guide clinicians as they move forward with clinical trial design to produce the most efficacious combination of MBFD + TMZ using Interlaced TherapyTM.
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 LB-76. doi:1538-7445.AM2012-LB-76
Abstract LB-78: Synergistic effect of combination of MEK and phosphatidylinositol 3-kinase inhibitor on cell death in human prostate cancer DU145 cells
Authors: Kim Yunlim , Hwang Jung Jin , Park Hongzoo , Lee Gil Nam , You Dalsan , Jeong In Gab , Kim Choung-Soo 
Published: August 2012

Abstract
Although chemotherapy has been used in castration-resistant prostate cancers (CRPCs) for a number of years, only limited improvement in survival is observed. Therefore, novel targeted therapeutic approaches must be developed for the treatment of CRPC. Currently, a wide range of small-molecular kinase inhibitors have been developed that target signaling pathways for survival, and inhibitors for MEK and PI3 kinase are currently being evaluated in clinical trials. To evaluate whether the combination treatment with MEK and PI3 kinase inhibitors is synergistic in prostate cancers, we used AZD6244 and a compound of GlaxoSmithkline (Smithkline) that inhibit MEK and PI3 kinase respectively. The combination of AZD6244-Smithkline showed synergistic anti-proliferative effect on growth of prostate cancer cells compared with the single treatment. In addition, a combination treatment induced apoptotic cell death, cleavage of caspase-9, caspase-3, and PARP synergistically. A significant increase in apoptosis was detected by annexin V-PI staining in DU145 cells after combined treatment compared with the single treatment. This study suggests that the combination with AZD6244 and Smithkline has a significant synergistic effect on cell growth in CRPC DU145 cells via apoptotic pathway.
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 LB-78. doi:1538-7445.AM2012-LB-78
Abstract LB-83: Reduced expression of DRAM2 in tumor cells interferes with both apoptosis and autophagy
Authors: Park Junsoo , Lee Eun-Ju , Jang Ik-Soon 
Published: August 2012

Abstract
Although the role of autophagy in tumorigenesis remains controversial, recent reports support the notion that inhibition of autophagy promotes tumor formation. Damage-regulated autophagy regulator (DRAM) has been identified as an effector molecule that is critical for p53-mediated apoptosis, and we investigated whether there might be other DRAM-like molecules linking autophagy and apoptosis. In this study, we cloned a novel DRAM-homologous protein, DRAM2, and showed that the expression of DRAM2 is down-regulated in ovarian tumors. DRAM2 is mainly localized in the lysosome, and co-localizes with DRAM. While expression of DRAM or DRAM2 individually did not induce cell death, co-expression of DRAM2 with DRAM significantly induced cell death, while the silencing of endogenous DRAM2 attenuated cell death. In addition, overexpression of DRAM2 induces cytoplasmic GFP-LC3 punctuates, and increases the level of endogenous LC3-II. Moreover, the silencing of endogenous DRAM2 interferes with starvation-induced autophagy. Thus, we propose that DRAM2 as well as DRAM is involved in both apoptosis and autophagy.
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 LB-83. doi:1538-7445.AM2012-LB-83
Abstract LB-96: Exploring personalized pathways enriched with putative cancer genes identified by next generation sequencing
Authors: Jia Peilin , Zhao Zhongming 
Published: August 2012

Abstract
Keywords: pathway enrichment test; pathway crosstalk; co-mutation; lung adenocarcinomas; glioblastoma; gene length; cancer mutation genes Contact information of the corresponding author: Zhongming Zhao, Ph.D. Department of Biomedical Informatics Vanderbilt University School of Medicine 2525 West End Avenue, Suite 600 Nashville, TN 37203, USA Phone: (615) 343-9158 FAX: (615) 936-8545 Email: zhongming.zhao@vanderbilt.edu List of abbreviations: GBM, Glioblastoma multiforme; NGS, next generation sequencing. Financial support: None. Abstract Pathway analysis of a set of genes represents an important area in large-scale omic data analysis. However, the application of traditional pathway enrichment methods to next-generation sequencing (NGS) data is prone to several potential biases including genomic/genetic factors (e.g., the particular disease and gene length) and environmental factors (e.g., personal life-style and frequency and dosage of exposure to mutagens). We proposed a novel method for the pathway analysis of NGS mutation data by explicitly taking into account the gene-wise mutation rate. We estimated the gene-wise mutation rate based on the individual-specific background mutation rate, which makes different samples comparable, along with the gene length, which makes different genes comparable. The mutation rate was then utilized as the weight for each gene in our weighted resampling strategy, which builds the null distribution for each pathway while matching the gene length patterns. The empirical P value obtained then provides an adjusted statistical evaluation. We demonstrated our weighted resampling method to a lung adenocarcinomas dataset and a glioblastoma (GBM) dataset, and compared it to other widely applied methods. By explicitly adjusting gene-length, the weighted resampling method effectively reject many marginally significant pathways detected by standard methods, including several long gene based, cancer unrelated pathways. We further demonstrated that by reducing such biases, pathway crosstalk for each individual and pathway co-mutation map across multiple individuals can be objectively explored and evaluated. This method performs pathway analysis in a sample-centered fashion, providing an alternative way for accurate analysis of cancer personalized genomic data.
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 LB-96. doi:1538-7445.AM2012-LB-96
Abstract LB-97: Optimizing SELEX with high-throughput sequencing
Authors: White Brian S. , Ozer Abdullah , Lis John T. , Shalloway David 
Published: August 2012

Abstract
SELEX (systematic evolution of ligands by exponential enrichment) identifies oligonucleotide “aptamers” that bind their protein targets with high affinity and specificity. Beyond inhibiting all protein function, aptamers can target specific functional regions (e.g., phosphorylation sites and catalytic domains) leaving other function intact. This selective inhibition is a valuable tool for dissection of signal transduction pathways, such as the growing list implicated in cancer by sequencing efforts interrogating tumor genomes. New technological innovations in aptamer discovery aim to keep pace with this need by improving the efficiency of the traditional SELEX enrichment process wherein oligonucleotides are iteratively bound to target, eluted, and amplified to purify an initial random library to a few high-affinity aptamers. Principal among these advances is the adoption of high-throughput sequencing (HTS-SELEX) to detect enrichment of candidate aptamers within the evolving pool. The improved sensitivity of high-throughput sequencing over the traditional use of cloning and sequencing reduces the number of rounds required to reach detectable enrichment. As with traditional SELEX, enrichment and hence number of rounds and overall efficiency are dependent on the free target and oligonucleotide pool concentrations. Though early theoretical approaches have addressed these issues for traditional SELEX, realizing the potential efficiency gains of the new HTS-SELEX approach requires an analysis and resulting protocol tailored to it specifically. Here we provide such an analysis and also re-examine earlier theoretical approaches to traditional SELEX. We show that HTS-SELEX motivates an optimization condition different from that of traditional SELEX and consider the role of stochastic fluctuations in the relatively low multiplicities of the enriched species resulting from the earlier enrichment detection of HTS-SELEX. Unlike previous approaches seeking to maximize some measure of per-round enrichment, this analysis is a global optimization of the entire SELEX process. It results in a specific recommendation for free target concentration, constant across rounds and simply related to the desired affinity, and for corresponding total ligand concentration. Applying the global analysis to an optimization condition appropriate for traditional SELEX again yields recommendations that are provably optimal and that differ from those previously published.
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 LB-97. doi:1538-7445.AM2012-LB-97
Abstract LB-98: Transcriptomic and genomic landscape of ovarian cancer stem cells
Authors: Zehir Ahmet , Ertem Server A. , Moore Malcolm A.S. 
Published: August 2012

Abstract
Ovarian cancer (OvCa) is the fifth leading cause of death among woman in USA. OvCa remains a fatal disease because of the lack of accurate early diagnostic methods as well as the heterogeneous nature of the disease itself. The cancer stem cell (CSC) hypothesis states the existence of a sub-population of cells in tumors that has the ability to self-renew as well as generating a fully differentiated tumor tissue. CSCs are also postulated to be resistant to conventional therapies, which might explain the recurrent nature of many cancers. We have recently identified a novel cellular structure in the ascites of NOD/SCID mice engrafted intraperitoneally with an OvCa cell line, consisting of free-floating chains of 4-72 cells with an extensive pericellular glycocalyx. We termed these structures “catenae” (Latin for “chains”). Catena develop by symmetric self-renewal and each cell retain tumor initiating function when transplanted in NOD/SCID IL2Rγ null mice. To elucidate the transcriptomic terrain and analyze expression of known and novel biomarkers, we performed RNA sequencing of catena using the SOLiD platform. We obtained more than 110 Million single reads of which ∼ 60% mapped uniquely to the human genome. Using this powerful technology, we detected expression of 15494 genes with RPKM values higher than 0.3 for which there are 42931 alternatively spliced transcripts. Roughly 3.5% of these alternative-splicing events seem to be novel. By using the aligned reads we detected 14361 single nucleotide polymorphisms (SNPs) which, after filtering, lead to 199 genes with novel SNPs. We also used the cancer genome atlas (TCGA) public database to determine whether any of these SNPs might be responsible for fast recurrence of ovarian cancer or shorter life span of patients. Furthermore, we detected novel fusion genes, which might lead to molecular classifications in ovarian CSCs. Once validated, these SNPs and fusion genes might prove to be pharmaceutical targets for eradication of ovarian cancer or improving patients’ lives.
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 LB-98. doi:1538-7445.AM2012-LB-98