bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3191: The Akt-mTOR axis determines cell fate through the regulation of eIF2α phosphorylation pathway.
Authors: Tenkerian Clara , Mounir Zineb , Krishnamoorthy Jothi , Koromilas Antonis E. 
Published: August 2014

Abstract
Metazoans respond to environmental stress by inducing the phosphorylation of the α subunit of translation initiation factor eIF2 at S51 (eIF2αP), a modification that leads to protein synthesis inhibition. We demonstrate that eIF2αP is induced by pharmacological inhibition or genetic ablation of the PI3K-Akt-mTOR pathway (1). Increased eIF2αP is an evolutionary conserved process that involves the endoplasmic reticulum (ER)-resident protein kinase PERK, which is negatively regulated by Akt dependent phosphorylation at T799. The PERK-eIF2αP arm is downregulated by Akt in cells exposed to ER stress or oxidative stress leading to the induction of cell survival or death respectively. In unstressed cells, the PERK-eIF2αP pathway guards survival and facilitates adaptation to the deleterious effects of PI3K, Akt or mTOR inactivation. Inactivation of the PERK-eIF2αP arm sensitizes tumor death from pharmacological inhibition of the PI3K-Akt-mTOR pathway. The PERK-eIF2αP pathway links Akt and mTOR signaling to translational control with implications in tumor treatment with pharmacological inhibitors of PI3K-Akt-mTOR pathway.
Citation Format: Clara Tenkerian, Zineb Mounir, Jothi Krishnamoorthy, Antonis E. Koromilas. The Akt-mTOR axis determines cell fate through the regulation of eIF2α phosphorylation pathway. [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 3191. doi:10.1158/1538-7445.AM2013-3191
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 3200: Spliced variant of T-cell intercellular antigen 1 (TIA-1) in colorectal cancer.
Authors: Hamdollah-Zadeh Maryam , Ye Xi , Domingo Enric , Kerr David J. , Ladomery Mike R. , Harpar Steve J. , Bates Dave O. 
Published: August 2014

Abstract
Alternative splicing regulates many cancer-associated genes. Splice isoforms that are found in tumors could have diagnostic value and may provide potential drug targets. We identified an endogenous splice variant of TIA-1 (T-cell intercellular antigen-1), short TIA-1 (shTIA-1), expressed in invasive colon cancer cells, which was not expressed in non-invasive adenoma cell lines. In this study we investigated the frequency of shTIA-1 expression in human normal and cancer tissue and if it correlates with advanced-stage of colon cancer.
RNA was extracted from 25μm thick scrolls of formalin fixed paraffin embedded sections of 40 colorectal carcinoma (20 Duke's, 20 Duke's C stage) and normal samples. RT-PCR was carried out to detect full length (flTIA-1) and shTIA-1. Immunohistochemical CD31 staining of microvessels in the same samples was used to assess microvessel density (MVD) and correlate the shTIA isoform expression and stages of the tumors. The results showed that flTIA-1 was less frequently found in tumour than in normal tissues (p=0.002). shTIA-1 was more highly expressed than flTIA-1 and in significantly higher portion of tumors than normal samples (p=0.0106). There was a significantly lower proportion of Duke's B than Duke's C grade tumours with detectable shTIA-1 expression (p=0.018). CD31 staining showed samples with shTIA-1 associated with increased MVD. We did not find any association between stages and MVD, as there was no statistically significant difference in MVD between Duke's B and Duke's C. However tumours had higher MVD than normal tissues from the same patients. These results indicate that a splice variant of TIA-1 is expressed in human colorectal carcinoma and is associated with increased angiogenesis.
Citation Format: Maryam Hamdollah-Zadeh, Xi Ye, Enric Domingo, David J. Kerr, Mike R. Ladomery, Steve J. Harpar, Dave O. Bates. Spliced variant of T-cell intercellular antigen 1 (TIA-1) in colorectal cancer. [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 3200. doi:10.1158/1538-7445.AM2013-3200
Abstract 3206: Multistage vectored siRNA targeting ataxia-telangiectasia mutated for breast cancer therapy.
Authors: Xu Rong , Huang Yi , Mai Jun Hua , Zhang Guo Dong , Guo Xiao Jing , Xia Xiao Jun , Koay Eugene J , Liu Xue Wu , Ferrari Mauro , Shen Hai Fa 
Published: August 2014

Abstract
The ataxia-telangiectasia mutated (ATM) protein plays a central role in DNA damage response and cell cycle checkpoints, and may be a promising target for cancer therapy if normal tissue toxicity could be avoided. Our strategy to target ATM for breast cancer therapy involves the use of liposomal-encapsulated, gene-specific ATM small interfering RNA (siRNA) delivered with a well-characterized porous silicon-based multistage vector (MSV) delivery system (MSV/ATM). Here we have shown that biweekly treatment of MSV/ATM suppressed ATM expression in tumor tissues, and consequently inhibited growth of MDA-MB-231 orthotopic tumor in nude mice. At the therapeutic dosage, neither free liposomal ATM siRNA nor MSV/ATM triggered acute immune response in BALB/c mice, including changes in serum cytokines, chemokines or colony-stimulating factors. Weekly treatments of mice with free liposomal ATM siRNA or MSV/ATM for 4 weeks did not cause significant changes in body weight, hematology, blood biochemistry, or major organ histology. These results indicate that MSV/ATM is biocompatible and efficacious in inhibiting tumor growth, and that further preclinical evaluation is warranted for the development of MSV/ATM as a potential therapeutic agent.
Citation Format: Rong Xu, Yi Huang, Jun Hua Mai, Guo Dong Zhang, Xiao Jing Guo, Xiao Jun Xia, Eugene J Koay, Xue Wu Liu, Mauro Ferrari, Hai Fa Shen. Multistage vectored siRNA targeting ataxia-telangiectasia mutated for breast cancer therapy. [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 3206. doi:10.1158/1538-7445.AM2013-3206
Abstract 3212: Capillary electrophoresis for upstream and downstream biopharmaceutical development.
Authors: Nguyen Uyen , Ramirez Francisco , Mack Scott , Darling Susan , Proctor John , Boge Annegret 
Published: August 2014

Abstract
In order to bring an antibody or other biologic drug to market, each step of the process needs to be carefully monitored. Charge heterogeneity and apparent MW via SDS-PAGE are two of the most commonly assessed parameters. Ideally, similar methods should be used from the beginning of development (low expression, complex matrix) to late in production and QC (high concentration, pure material).Capillary techniques such as iCE and CE-SDS are currently heavily used in downstream product development but pose challenges for small scale screening and characterization during cell culture and formulation development. Here we present the Simple Western that combines in one novel instrument, Peggy, capillary electrophoresis with an immunoassay to provide highly reproducible and fully automated analysis of monoclonal antibodies. This sensitive technology measures either size or charge in complex samples and provides critical charge heterogeneity, size, and product titer information without the need for sample purification. Data will be presented demonstrating the application of the Simple Western technique and the iCE technology for the analysis of monoclonal antibodies against VEGF and the ability of the two techniques to provide consistency of data across the whole range of product development. In addition we show examples for the unique capability of this technology to assess affinity information for these anti VEGF antibodies to different charge isoforms of VEGF.
Citation Format: Uyen Nguyen, Francisco Ramirez, Scott Mack, Susan Darling, John Proctor, Annegret Boge. Capillary electrophoresis for upstream and downstream biopharmaceutical development. [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 3212. doi:10.1158/1538-7445.AM2013-3212
Abstract 3215: Detecting low abundance therapeutic targets for ovarian cancer using engineered gold nanoparticles.
Authors: Giri Karuna , Arvizo Rochelle 
Published: August 2014

Abstract
Gold nanoparticles (AuNPs) have been widely studied for use in disease therapeutics as targeting and imaging agents, drug delivery vehicles and as self-therapeutics. When AuNPs interact with the biological milieu they form a corona layer, which is predominantly composed of proteins. The outer “soft” layer is dynamic and here proteins are free to exchange over time. The inner “hard” layer on the other hand consists of proteins firmly bound to the NP surface. The Vromans effect predicts that given a limited surface area, low affinity, high abundance proteins, that first attach to the surface, are over time replaced by high affinity, low abundance proteins. Our aim was to enrich low abundance proteins on the AuNP surface to probe for differentially expressed proteins that are not detected by traditional methods of protein identification. We studied the binding of ovarian cell lysates (cancerous and non cancerous) to 10 nm sized positively and negatively charged AuNPs. The formation of corona around the AuNPs was characterized by dynamic light scattering and zeta potential measurements. The composition of the protein corona was identified using mass spectrometry. Proteins were also identified from the cell lysate pool to serve as a control to assess protein enrichment on NP surface. Using this approach, Hepatoma Derived Growth Factor (HDGF) was identified as a low abundance protein that was detected by mass spectrometry in cancer cells only after enrichment on the surface of positively charged AuNPs. HDGF is overexpressed in multiple ovarian cancer cells lines and knock down using siRNA shows decrease in cell proliferation, G2/M arrest and apoptosis. This suggests an important role of HDGF in the tumorigenicity of ovarian cancer, which could serve as an important therapeutic target for the disease.
Citation Format: Karuna Giri, Rochelle Arvizo. Detecting low abundance therapeutic targets for ovarian cancer using engineered gold nanoparticles. [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 3215. doi:10.1158/1538-7445.AM2013-3215
Abstract 3220: A microfluidic, multi-analyte, high sensitivity, immunoassay platform for rapid biomarker detection.
Authors: Pande Rajiv , Leamon John H. , Putnam Marty , Pitta M , Svancara D , Tu J 
Published: August 2014

Abstract
Traditionally, protein analytes or biomarkers have been measured individually in ELISAs. However, it is becoming increasingly clear that multiple markers are associated with multivariate diseases like cancer. Despite demand, the adoption of multi-analyte biomarker tests in clinical research has been severely limited for many reasons including technical concerns regarding assay reproducibility, time and the labor-intensive nature of assay panel development, and reported non-correlation with conventional ELISA data. To address this issue, we have developed a novel fully automated desktop immunoassay platform that enables simultaneous interrogation of four analytes in eight individual samples on a single disposable microfluidic cartridge in under an hour. We have devised a unique approach to immobilize antibodies that results in assays with high sensitivities (femtomolar) and broad dynamic ranges (&gt;4 logs). Twenty microliters of patient sample are split into parallel channels containing individual immunoassays. By segregating each assay to a discrete location, the multi-analyte assay mimics single-analyte ELISAs, thus enabling each assay to operate under its optimal conditions. This methodology combines the specificity of a traditional ELISA immunoassay, where the sample is assayed by a singular pair of capture and detect antibodies eliminating cross-reactivity and other negative interactions from other antibody pairs while offering the benefits of a multiplexed antigen analysis. We describe the system's design, speed, sensitivity and reproducibility using data generated with a custom-built 4-analyte pro-inflammatory panel cartridge (IL-1β, IL-6, IL-10 and TNFα) on clinical samples. We demonstrate that our assay system is ideal for quantitative analysis of soluble protein markers in clinical research and in clinical trials.
Citation Format: Rajiv Pande, John H. Leamon, Marty Putnam, M Pitta, D Svancara, J Tu. A microfluidic, multi-analyte, high sensitivity, immunoassay platform for rapid biomarker detection. [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 3220. doi:10.1158/1538-7445.AM2013-3220
Abstract 3222: Broad spectrum metabolite profiling reveals metabolic finger and footprinting which correlate to gene expression signatures of triple-negative breast cancer (TNBC).
Authors: Beatty Alexander , Fink Lauren , Strigun Alexander , Rennefahrt Ulrike , Schmitz Oliver , Schiewe Hajo , Moeller Niels , Noppinger Patricia R. , Reszka Regina , Peterson Jeffrey R. 
Published: August 2014

Abstract
TNBC constitutes ∼20% of all breast cancers and disproportionately affects younger women and African-American women. This genomically heterogeneous disease is defined by the lack of expression of estrogen and progesterone receptors and the lack of amplification of HER2/neu. TNBC is resistant to standard breast cancer therapies. Due to the lack of a predominant genetic lesion associated with the disease, identification of metabolic fingerprints within TNBC is a critical first step for identification of molecular drivers and development of targeted therapies. Metabolite profiling (metabolomics) of a wide range of metabolites can be used to globally profile the metabolic state of cancer cells. Nine widely used TNBC-derived cell lines already characterized by gene expression signatures were analyzed by metabolomics. Two different approaches were combined: (i) untargeted, broad profiling including LC-MS/MS and GC-MS, and (ii) targeted UPLC-MS/MS Energy platform technology which covers polar key metabolites mainly reflecting energy status and nucleotide biosynthesis. Finally, 239 high quality metabolites were statistically evaluated in cell lysates and 128 metabolites in spent media samples collected from all cell lines. Using innovative bioinformatics and data mining tools we identified metabolic alterations in energy utilization, lipid synthesis, and other pathways of importance to highly proliferative cells that differ significantly from an untransformed control cell line (MCF-10A). Major metabolic changes combining results of metabolic fingerprinting and footprinting and their biological relevance will be discussed.
Citation Format: Alexander Beatty, Lauren Fink, Alexander Strigun, Ulrike Rennefahrt, Oliver Schmitz, Hajo Schiewe, Niels Moeller, Patricia R. Noppinger, Regina Reszka, Jeffrey R. Peterson. Broad spectrum metabolite profiling reveals metabolic finger and footprinting which correlate to gene expression signatures of triple-negative breast cancer (TNBC). [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 3222. doi:10.1158/1538-7445.AM2013-3222
Abstract 3224: Metabolite profiling as tool for the identification of differentiating and prognostic markers of prostate carcinoma.
Authors: Kristiansen Glen , Reszka Regina , Kamlage Beate , Bethan Bianca , Lein Michael , Stephan Carsten , Jung Klaus 
Published: August 2014

Abstract
Background and objective: Metabolomic research offers a deeper insight into biochemical changes in cancer metabolism and is a promising tool for identifying novel biomarkers. We aimed to evaluate the diagnostic and prognostic potential of metabolites in prostate cancer (PCa) tissue after radical prostatectomy.
Material and methods: 107 matched-paired tissue samples collected after radical prostatectomy were subjected to the MxPTM Broad Profiling by gas chromatography- mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (Patent WO 2010/139711 A1: "Means and methods for diagnosing prostate carcinomas"). Aminoadipic acid, cerebronic acid, gluconic acid, glycerophosphoethanolamine, 2- hydroxybehenic acid, isopentenyl pyrophosphate, maltotriose, 7-methylguanine, and tricosanoic acid were related to clinicopathological variables like prostate volume, tumor stage, Gleason score, preoperative prostate-specific antigen (PSA), and disease recurrence in the follow-up. Non-parametric statistical tests, receiver- operating characteristics (ROC) and univariate and multivariate analyses (Kaplan- Meier curve; Cox regression) were performed.
Results: All metabolites showed higher concentrations in malignant than in non- malignant samples except for gluconic acid and maltotriose, which had lower levels in tumors. ROC analyses showed a clear differentiation for all metabolites with a maximal area under the curve of 0.86 for tricosanoic acid. However, the metabolites were not related to tumor stage and Gleason grade. "Aminoadipic acid, gluconic acid, and maltotriose levels were associated with tumor recurrence (Kaplan-Meier analysis) and were, together with tumor stage and Gleason score, a successful metabolite combination in the multivariate Cox regression model for the prediction of tumor recurrence."
Conclusions: This exemplary study performed with selected metabolites from a global metabolic profiling investigation proves that metabolites in prostate carcinoma tissue can be used, in combination with traditional pathological and histomorphological parameters, as promising diagnostic and prognostic tools.
Citation Format: Glen Kristiansen, Regina Reszka, Beate Kamlage, Bianca Bethan, Michael Lein, Carsten Stephan, Klaus Jung. Metabolite profiling as tool for the identification of differentiating and prognostic markers of prostate carcinoma. [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 3224. doi:10.1158/1538-7445.AM2013-3224
Abstract 3237: Combination therapy of paclitaxel and EW-7197, a novel ALK5 inhibitor prolonged the life span of breast tumor bearing mice.
Authors: Kim Sol J. , Son Jee Y. , Kim Min J. , Park Sang A. , Lee Seon J. , Park So Y. , Kim Seung W. , Kim Dae-Kee , Nam Jeong S. , Sheen Yhun Y. 
Published: August 2014

Abstract
TGF-β has multifunctional effects on carcinogenesis. In the early stage tumor, TGF-β acts as a tumor suppressor but in later stage of tumor, TGF-β promotes tumor invasiveness and metastasis. TGF-βRI kinase has been the target of anti-metastatic drugs, so we have synthesized new ALK5 inhibitor (EW-7197) and investigated anti-metastatic effects of EW-7197. The treatment of the EW-7197 also inhibited the luciferase activity in the lung of 4T1-Luc cell-orthotopic implanted mouse compared to that of untreated animal. The levels of MMP2 and MMP9 were decreased in the lung and breast tumor of the EW-7197 treated mice. To determine the inhibitory effect of EW-7197 on TGF-β1-induced transcriptional activation, we performed luciferase reporter gene assay in breast cancer cells. EW-7197 effectively blocked TGF-β1-induced luciferase activity in the cells in a dose-dependent manner. TGFß signaling, the phosphorylation of smad2/3 was decreased by EW-7197. TGFß-stimulated mesenchymal markers of epithelial mesenchymal transition (EMT) were inhibited by ALK5 inhibitor concomitant treatment. And also, EW-7197 showed higher inhibition on cell motility and cell invasion based on wound healing assay or invasion assay. Further, we investigated combination effect of EW-7197 and paclitaxel. To investigate anti-metastatic effect we did experiment on BALB/c-nu/nu MB231-luc cells xenografted mice by treating EW-7197 and paclitaxel. Both EW-7197 alone group and EW-7197 and paclitaxel combination group showed inhibition of metastasis and the expression of lung metastatic markers were inhibited. We experiment on BALB/c-nu/nu MB231 cells xenografted mice for survival analysis. EW-7197 and paclitaxel combination therapy lengthen the life span of mice. In summary, EW-7197 could be effective therapeutic choice for breast cancer metastasis. Also EW-7197 and paclitaxel combination therapy could be more effective than paclitaxel alone therapy for anti-metastatic effect and survival.
Citation Format: Sol J. Kim, Jee Y. Son, Min J. Kim, Sang A. Park, Seon J. Lee, So Y. Park, Seung W. Kim, Dae-Kee Kim, Jeong S. Nam, Yhun Y. Sheen. Combination therapy of paclitaxel and EW-7197, a novel ALK5 inhibitor prolonged the life span of breast tumor bearing mice. [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 3237. doi:10.1158/1538-7445.AM2013-3237
Abstract 3243: DIM inhibits growth of human gastric cancer through modulation of the hippo signaling pathway.
Authors: Li Xiu Juan , Lee Hwan Hee , Kim Soo Mi 
Published: August 2014

Abstract
3, 3-diindolylmethane (DIM) has been reported that it has anti-proliferative effects in many cancer cells. However, the biological functions of DIM in human gastric cancer cells are unknown. Genetic and biological studies have confirmed the importance of the novel hippo tumor suppressor pathway in regulating cell proliferation, apoptosis, organ size, and tumorigenesis in mammals. Thus, the purpose of this study was to investigate the cytotoxic effects of DIM in human gastric cancer cells and to elucidate whether DIM induces cell death by activating the hippo signaling pathway. Four human gastric cancer cell lines (SNU1, SNU16, SNU484, and SNU638) were used to test the response of DIM. MTT, cell cycle and western blot analyses were conducted. DIM significantly inhibited the proliferation of human gastric cancer cells in a dose-dependent manner. The percentage of G1 phase cells increased 24h after being treated by DIM. DIM reduced CDK2, CDK4, CDK6, CyclinD1 protein levels and increased p53 protein levels. DIM also induced cleaved poly (ADP-ribose) polymerase, cleaved-caspase-9 levels, and diminished pro-caspase-3 protein expression levels. Additionally, DIM increased P-LATS1, Mob1, P-Mob1, P-Yap protein levels and reduced Yap protein levels. Moreover, DIM inhibited the growth of human esophageal tumors in an orthotopic mouse model. These results suggest that DIM can sensitize gastric cancers by modulating the hippo signaling pathway linked to tumorigenesis.
Citation Format: Xiu Juan Li, Hwan Hee Lee, Soo Mi Kim. DIM inhibits growth of human gastric cancer through modulation of the hippo signaling pathway. [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 3243. doi:10.1158/1538-7445.AM2013-3243
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.