bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A08: Analysis of MRGBP and PPIL1 genes in colon cancer
Authors: Akisik Ebru , Dalay Nejat , Yamaner Sumer , Bugra Dursun 
Published: August 2014

Abstract
Colorectal cancer is one of the most common causes of cancer death throughout the world. Colorectal carcinogenesis is a multi-step process and in addition to genetic changes significant changes in DNA methylation and epigenetic events such as histone modifications can also lead to deregulation of gene expression. The histone proteins play a dynamic role in the chromatin structure and transcription. Aberrant protein acetylation, particularly on histones, has been related to cancer while abnormal expression of histone deacetlytransferases (HDACs) are observed in a broad range of cancer types. Therefore, HDACs have emerged as promising targets in cancer therapeutics.
The MRG-binding protein (MRGBP / C20orf20) is a component of the NuA4 histone acetyltransferase (HAT) complex and is involved in the transcriptional activation of specific genes. The MRGBP gene is frequently upregulated in tumors and is thought to play a role in cancer development. On the other hand removal of introns from pre-mRNA is carried out by a large macromolecular spliceosome complex. PPIL1 (Peptidyl-prolylisomerase-like 1) is a component of the human spliceosome and plays a primary role in pre-mRNA splicing for catalyzing isomerization of the peptide bonds. Overexpression of the PPIL1 protein in cancer suggest a potential role of PPIL1 in the in the development and promotion of colon cancer. In the present study we analyzed MRGBP and PPIL1 gene expression levels in matched tumor and normal tissue samples from patients with colorectal cancer.
Tissue samples were collected from 51 patients with colorectal cancer who underwent surgery for tumor resection. The normal tissue specimens used in the study were histologically confirmed to be free of cancer. The HPRT (hypoxanthine-Guanine phosphoribosyltransferase) gene was used as reference. The target and reference genes were amplified in the same multiplex PCR using the LightCycler 480 System. 8-9 nucleotide long UPL probes were labeled with fluorescein (FAM) and TAMRA at the 5′ and 3′ ends, respectively. Expression levels were determined using the Basic Relative Quantification analysis software and the results were evaluated by the Mann-Whitney U test.
Although the median MRGBP expression levels in the tumor tissue were higher than normal tissue (1,72 vs.1,41) the difference was not significant. The median expression levels of PPIL1 in the tumors and normal tissue samples (1,97 vs 1,86) were also similar. Our results indicate that neither MRGBP nor PPIL1 gene expression levels are upregulated in colon cancer cells indicating that these are not directly associated with colorectal cancer.
Citation Format: Ebru Akisik, Nejat Dalay, Sumer Yamaner, Dursun Bugra. Analysis of MRGBP and PPIL1 genes in colon cancer. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A08.
Abstract A16: Role of Hsp90alpha-1, a splice variant of Hsp90alpha, in cancer
Authors: Ghosh Suman , Peterson Laura B. , Vielhauer George , Blagg Brian S. J 
Published: August 2014

Abstract
Molecular chaperone complexes, such as heat shock proteins 90 (Hsp90) and its co-chaperones, are essential for folding nascent polypeptides into their biologically active structures and for the refolding of aggregated and denatured proteins that occur upon cellular stress including cancer. Hsp90 exists as four isoforms in humans. Among them, Hsp90alpha is induced under stressful conditions, detected in the cytoplasm, nucleus and is secreted into extracellular space under metastatic conditions. Hsp90alpha is phosphorylated by DNA-PK at the nucleus under apoptotic conditions and localizes at the edge of the nucleus. Intrigued by the fact that Hsp90alpha might play a role in metastasis as well as in stress resistance, the mechanism of action of Hsp90alpha was investigated. Here we report that Hsp90alpha-1, a splice variant of Hsp90alpha, is up-regulated in cancer cells, predominantly associates with co-chaperone Aha1 in-vivo at the filopodia like extrusion of cell. The Hsp90alpha-1/Aha1 complex was partially disrupted by C- terminal inhibitors in-vivo conditions; and Hsp90alpha-1 and Aha1 redistributed to the cytoplasm from the filopodia following the treatment with the C- terminal inhibitors. Gene knock down analysis reveals that several P-Akt pathway and MAP Kinase pathway proteins were Hsp90alpha-1 dependent. P-Akt also co-localized with the Hsp90alpha-1/Aha1 complex at the filopodia region and suggests that Hsp90alpha-1 plays critical role in maturing/folding proteins that are important for establishing and maintaining cell polarity which is perturbed by the C- terminal inhibitors. Under apoptotic conditions the Hsp90alpha-1/Aha1 complex is present in the cytoplasm and nucleus and Hsp90alpha-1 is phosphorylated. Survivin, being a Hsp90alpha-1 dependent client protein, binds with the Hsp90alpha-1/Aha1 complex at normal and apoptotic conditions confirms that Survivin play dual role in mediating metastases as well as an Inhibitor of Apoptotic Protein (IAP).
Citation Format: Suman Ghosh, Laura B. Peterson, George Vielhauer, Brian S. J Blagg. Role of Hsp90alpha-1, a splice variant of Hsp90alpha, in cancer. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A16.
Abstract A29: Mdm2 E3 ubiquitin ligase function is dispensable for the degradation of Mdm2 itself
Authors: Kim Tae-Hyung , Zhang Yanping 
Published: August 2014

Abstract
Mdm2 has long been considered the major negative regulator of both p53 stability and activity. The RING finger domain of Mdm2 confers its E3 ubiquitin ligase activity, and through this function Mdm2 controls p53 stability, additionally, auto-ubiquitination of Mdm2 is believed to be the primary mechanism of Mdm2 degradation. In vitro, mutation or truncation of the RING domain in Mdm2 resulted in loss of ubiquitin ligase activity towards both Mdm2 and its substrate p53. In contrast, recent knock-in mouse models indicate that under physiological conditions the Mdm2 RING-mediated E3 ubiquitin ligase function is dispensable for Mdm2 degradation. To investigate the in vivo significance of Mdm2 auto-ubiquitination, we compared two Mdm2 knock-in mouse strains each harboring a single amino acid substitution in RING domain (C462A) or C-terminus (Y487A). Both knock-in mutants disrupt Mdm2 E3 ligase activity for p53. We observed that (1) mutant Mdm2 protein (C462A or Y487A) fails to degrade p53 protein. (2) Wild type and mutant Mdm2 are degraded similarly. Despite efficient disruption of p53 degradation, half-life assays demonstrated that neither of the Mdm2 mutants affected the rate of degradation of Mdm2 itself indicating not only that Mdm2 auto-ubiquitination is not the primary mechanism for Mdm2 degradation in vivo, but also that an additional mechanism is in action to regulate Mdm2. (3) Inhibition of proteasomal degradation by MG-132 resulted in similar levels of accumulation of both wild type and mutant Mdm2s suggesting Mdm2 degradation is mediated via the proteasome. In vivo ubiquitination assay reconfirmed that Mdm2 RING domain mutation does not affect degradation and accumulation of Mdm2 itself, further implicating the possibility of an outside E3 ligase activity. In conclusion, auto-ubiquitination of Mdm2 is not necessary for Mdm2 degradation in vivo. The identification of E3 ubiquitin ligases with specificity for Mdm2 is an important next step to gain mechanistic insight into the regulation of Mdm2 regulation, and with that, p53.
Citation Format: Tae-Hyung Kim, Yanping Zhang. Mdm2 E3 ubiquitin ligase function is dispensable for the degradation of Mdm2 itself. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A29.
Abstract A32: In vivo imaging of ERK activity of mouse breast cancer cells reveals heterogeneity in response to anti-cancer drugs and tumor forming capacity
Authors: Kumagai Yuka , Matsuda Michiyuki 
Published: August 2014

Abstract
The Ras-Raf-MEK-ERK pathway is critical for normal physiological development and for carcinogenesis. However, the activity of this signaling cascade has never been examined in living cancer tissues due to technical difficulty. We have recently developed transgenic mice expressing a Förster resonance energy transfer (FRET) biosensor for ERK, which allows us to monitor cellular ERK activity in living tissues under two-photon (2P) microscopes.
To study the role of ERK in mammary tumors, we crossed MMTV-Neu mice with the mice expressing the ERK FRET biosensor and observed in vivo under 2P. In the primary mammary tumors, the ERK activity exhibited significant divergence among the tumor cells. Such heterogeneity was significantly diminished in the secondary tumor cells. A MEK inhibitor PD0325901 and an EGFR/HER2 inhibitor Lapatinib suppressed ERK in both the primary mammary tumor cells and the secondary mammary tumor cells. Interestingly, we found that a small number of cells with low ERK activity in primary tumors that did not respond to Lapatinib. We sorted cells depending on ERK activity and obtained ERKlow and ERKhigh population.The ERKlow population exhibited higher tumorsphere formation in nonadherent culture condition and tumor formation in syngeneic mice. Notably, the tumors developed from ERKlow cells exhibited heterogeneous ERK activity similar to primary tumors. Taken together, our results suggest that the heterogeneous ERK activity might be related to cancer stem cell in tumors.
Citation Format: Yuka Kumagai, Michiyuki Matsuda. In vivo imaging of ERK activity of mouse breast cancer cells reveals heterogeneity in response to anti-cancer drugs and tumor forming capacity. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A32.
Abstract A44: The role of ultraconserved noncoding RNAs in oncogenic transformation
Authors: Nguyen Hung Thanh , Chan Lifang , Voorhoeve Mathijs 
Published: August 2014

Abstract
Ultra conserved regions are stretches of DNA in the genome of &gt;200bp that are 100% conserved between human, mouse and rat. Their overall conservation in a wide variety of vertebrates is often &gt;95%. There are ~ 500 such regions in the human genome. Their function and the reason for their extreme sequence conservation are unknown. A majority of these ultraconserved genes (UCG) is expressed as non-coding RNAs, and many of the UCGs are differentially expressed in tumors and locate to cancer-associated regions in the genome. Some UCGs show small sequence variants between cancer patients and control cohorts, further suggesting that they may be causally involved in tumorigenesis. We have employed a genetically defined model of carcinogenesis to screen a limited set of cancer-associated UCGs and found that expression of two of these UCGs can directly affect the p16-pRb tumor suppressor pathway and contribute to the transformation of primary human cells.
Citation Format: Hung Thanh Nguyen, Lifang Chan, Mathijs Voorhoeve. The role of ultraconserved noncoding RNAs in oncogenic transformation. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A44.
Abstract A51: p53 and p21 mRNA and protein expression in treated synthetic estrogen in mouse transgenic animal model
Authors: Salleh Mohd Nazil , Cheng Tan Mei , Hashim Thuaibah , Lai Henkie Isahwan Ahamd Mulyadi , Ramli Wan Khairuzzaman Wan 
Published: August 2014

Abstract
Studies with Diethylstilbestrol (DES) in humans and rodents have resulted in a spectrum of toxic and carcinogenic effects. Previous findings on gene expression profiles following DES treatment showed that p53, p21 and bax was transcriptionally regulated in this model. In the present studies,Reverse Transcriptase in situ Polymerase Chain Reaction and immunohistochemistry techniques for localization and expression of p53, p21 and bax at cellular levels was applied. Animal were housed individually and treated with 500μmole/kg b.w of DES, (ip) once daily up to 4 days. Our results have shown, the expression of p53, p21 and bax mRNA were greater in wild-type compared to p53+/- knockout mice. In addition, p53, p21 and bax mRNA were significantly higher in DES-treated compared to control-vehicle animals. Collectively, similar patterns of expression also were seen in p53 and p21 proteins and scored according to the percentage of positive nuclear staining. Therefore, the combination of p53 and p21 were concluded to be a valuable markers and prognostic for carcinogenesis and progression of endometrial cancer.
Citation Format: Mohd Nazil Salleh, Tan Mei Cheng, Thuaibah Hashim, Henkie Isahwan Ahamd Mulyadi Lai, Wan Khairuzzaman Wan Ramli. p53 and p21 mRNA and protein expression in treated synthetic estrogen in mouse transgenic animal model. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A51.
Abstract A56: Spontaneous aggregation and novel signalosome organization of BENTA-associated gain-of-function CARD11 mutants in lymphocytes
Authors: Stinson Jeffrey Richard , Snow Andrew L. 
Published: August 2014

Abstract
Antigen receptor (AgR)-induced NF-κB activation is a critical determinant of lymphocyte growth and survival. However, constitutive NF-κB activity can drive excessive lymphoproliferation and oncogenesis. We recently described a novel human lymphoproliferative disorder designated as BENTA (B cell Expansion with NF-κB and T cell Anergy), caused by germline gain-of-function mutations in the lymphocyte-specific scaffolding protein CARD11. Similar, somatic CARD11 mutations are found in ~10% of activated B cell-type diffuse large B cell lymphomas (ABC-DLBCL). Normally, AgR ligation converts CARD11 into an active conformation that nucleates a large multi-protein signalosome incorporating BCL10, MALT1, and other components that ultimately facilitate activation of IκB kinase (IKK) and nuclear translocation of NF-κB. We have now identified four different heterozygous CARD11 missense mutations (E134G, G123S, G123D, C49Y) in affected patients. Similar to BENTA patient cells and DLBCL tumors, ectopic expression of each mutant triggers constitutive NF-κB activation in B and T cell lines without AgR stimulation. Using confocal microscopy, we now demonstrate that these CARD11 mutants form large, spontaneous perinuclear aggregates with a novel, shell-like substructure. While BCL10 is largely excluded, other signaling components such as MALT1 and phospho-IκB kinase (IKK) are found within or closely colocalized with CARD11 shells, suggesting these aggregates are sites of active signaling. Our results provide the first evidence that gain-of-function CARD11 mutants assemble into a compartmentalized, active signalosome with a distinct structural organization. Further imaging and biochemical analysis of these aggregates will provide new insights into aberrant CARD11 signaling in BENTA patient lymphocytes and DLBCL tumors harboring active CARD11 mutations.
Citation Format: Jeffrey Richard Stinson, Andrew L. Snow. Spontaneous aggregation and novel signalosome organization of BENTA-associated gain-of-function CARD11 mutants in lymphocytes. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A56.
Abstract B23: Cysteine (C)-X-C receptor 4 induces oxidative stress through NADPH oxidase-2 in prostate cancer cells
Authors: Jones Kia J. , Chetram Mahandranauth A. , Bethea Danaya A. , Hinton Cimona V. 
Published: August 2014

Abstract
Reactive oxygen species (ROS), and the coupled oxidative stress, have long been implicated in the onset and progression of many cancers, including prostate cancer (PCa). One of the mechanisms by which ROS contributes to cancer is by acting as a second messenger, relaying signals from the cell surface to important signaling proteins, thereby regulating a variety of cellular processes. We have demonstrated that ROS increased the expression and activity of the chemokine (CXC) receptor, type 4 (CXCR4), which resulted in proliferation, invasion and trans-endothelial migration of PCa cells. Similarly, a study in human hepatoma cells revealed that CXCR4, and its ligand, stromal cell derived factor 1 alpha (SDF-1α), promoted ROS accumulation; however, the source (s) of ROS following growth factor stimulation have not been investigated. Identifying the sources of ROS that leads to oxidative stress in the tumor microenvironment remain areas of intense research. A recent study demonstrated that the increased ROS generation observed in PCa cell lines of varying aggressiveness was largely contributed by the NADPH oxidase family of enzymes. Herein, we observed that SDF-1α promoted ROS accumulation in C4-2 human PCa cells. We also established that NOX, an extramitochondrial ROS-generating system, was the primary source of ROS instead of the mitochondria. Moreover, expression of the isoform, NOX2, was preferentially regulated by CXCR4 at transcriptional and post-transcriptional levels. Finally, NOX2 expression correlated with PCa aggressiveness in microarray datasets. Therefore, we hypothesize that the SDF-1α /CXCR4 signaling axis mediates ROS production in PCa through NADPH-oxidases, resulting in oxidative stress that encourages tumor progression. Results generated from this study will further elucidate the mechanism (s) by which growth factor signaling promotes oxidative stress to enhance tumor development. Understanding the relationship between known cancer promoting elements, such as CXCR4, ROS and NOX, will facilitate the development of more comprehensive therapeutics to enhance current clinical strategies to combat cancer metastasis.
Citation Format: Kia J. Jones, Mahandranauth A. Chetram, Danaya A. Bethea, Cimona V. Hinton. Cysteine (C)-X-C receptor 4 induces oxidative stress through NADPH oxidase-2 in prostate cancer cells. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B23.
Abstract B35: Amentoflavone inhibits angiogenesis and stimulates apoptosis in cells
Authors: Liu Zhihe , Zhang Jinli , Cao Wenjuan 
Published: August 2014

Abstract
Amentoflavone (8-[5-(5,7-dihydroxy-4-oxo-chromen-2-yl)-2-hydroxy-phenyl]-5,7-dihydroxy -2-(4-hydroxyphenyl) chromen-4-one, AF) is a biflavonoid derived from the extracts of Selaginella tamariscina. It has been shown that AF has diverse biological effects including anti-inflammatory, anti-viral, inhibition of fatty acid synthesis, and anti-tumor. It is well known that high cell proliferation and angiogenesis are two key factors in tumorigenesis. In this study, we report that AF inhibited proliferation, and stimulated apoptosis in fibroblasts. Incubation of fibroblast with AF showed inhibitory effect on cell viability and exhibited a series of cellular changes that were consistent with apoptosis. By western blot analysis, our date indicated significant increases in the amounts of cleaved-caspase 3, 8, 9 and Bax, several apoptotic promoters, and a significant decrease in TCTP, an apoptotic inhibitor, in fibroblast treated with AF. Furthermore, AF showed significant inhibitions on the proliferation, migration, and tube formation of endothelial cells, which are associated with angiogenesis. In conclusion, this study suggests that AF stimulates apoptosis in fibroblasts and inhibits angiogenesis of endothelial cells. Therefore, AF is a promising molecule which can be used in cancer treatment.
Note: This abstract was not presented at the conference.
Citation Format: Zhihe Liu, Jinli Zhang, Wenjuan Cao. Amentoflavone inhibits angiogenesis and stimulates apoptosis in cells. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B35.
Abstract B40: Cytokines secreted by macrophages isolated from tumor microenvironment of inflammatory breast cancer patients possess chemotactic properties
Authors: Mohamed Mona Mostafa , El-Ghonaimy Eslam A. , Nouh Mohamed A. , Schneider Robert J. , Sloane Bonnie F. , El-Shinawi Mohamed 
Published: August 2014

Abstract
Introduction: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer and is characterized by rapid progression and dismal outcome. Although there is a growing literature describing the role of macrophages in non-IBC, the role of macrophages in IBC is unclear. The aims of the present study were to: 1) assess macrophages infiltration within the tumor tissues of non-IBC and IBC patients; 2) isolate and profile cytokines of macrophages drained from breast tumor axillary tributaries of non-IBC and IBC patients and 3) test whether major cytokines secreted by tumor draining macrophages induce motility of the IBC cell line SUM149.
Methods: Tumor-infiltrating macrophages were measured by immunohistochemical (IHC) techniques using CD14 and CD68 monoclonal antibodies. Blood drained from axillary vein tributaries was collected from non-IBC and IBC patients during breast cancer surgery and total mononuclear cells isolated by density gradient centrifugation using Histopaque. The percentage of monocytes/macrophages (CD14+) in the total isolated leukocytes was calculated by flow cytometry using fluorochrome-labeled monoclonal antibodies (APC-CD14 and PerCP-CD3). CD14+ population was separated from total mononuclear cells using an immuno-magnetic bead separation technique. CD14+ cells were seeded overnight in appropriate culture media at 37°C in a humidified CO2 incubator and conditioned media were collected and cytokines profiled. To test whether cytokines secreted by CD14+ enhances motility and invasion of SUM149 cells, we used wound healing and invasion assays.
Results: Our results revealed that there was an increase in the number of infiltrated macrophages (CD14+ cells) in IBC tumor tissues and axillary tributaries drained blood as compared to non-IBC. Cytokine profiling of IBC-CD14+ cells revealed a significant increase in tumor necrosis factor-alpha (TNF-α); monocyte chemoattractant protein-1 (MCP-1) also known as CC-chemokine ligand 2 (CCL-2); interleukin-10 (IL-10) and interleukin-8 (IL-8) as compared to non-IBC CD14+ cells. TNF-α, IL-8 and IL-10 cytokines significantly increased motility and invasion of SUM149 cells.
Conclusion: IBC cancer tissues are characterized by high infiltration of monocytes/macrophages that secrete cytokines that may contribute to dissemination of IBC cells.
Citation Format: Mona Mostafa Mohamed, Eslam A. El-Ghonaimy, Mohamed A. Nouh, Robert J. Schneider, Bonnie F. Sloane, Mohamed El-Shinawi. Cytokines secreted by macrophages isolated from tumor microenvironment of inflammatory breast cancer patients possess chemotactic properties. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B40.