bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4433: Fbxw11 promotes leukemia development by activating the NF-κB signaling pathway
Authors: Wang Lina , Liao Jinfeng , Yang Xiao , Feng Wenli , Chen Shayan , Zheng Guoguang 
Published: May 2015

Abstract
F-box proteins serve as the substrate recognition subunit for the SCF E3 ubiquitin ligases. These ligases ubiquitinate specifically phosphorylated substrates and play a pivotal role in the regulation of various signal transduction pathways, which, in turn, are essential for many aspects of tumorigenesis. However the role of Fbxw11 in the development of leukemia and the underlying mechanisms remain largely unknown. Here, we found two transcript variants (Fbxw11c and Fbxw11d) expressed in mouse bone marrow. More importantly, the expression of Fbxw11 in normal hematopoietic stem cells (HSCs) from Notch1-induced leukemia mice was higher than that from control mice. In order to investigate the role of Fbxw11 in leukemia, we established L1210 cell lines over-expressing Fbxw11c or Fbxw11d respectively using the lentivirus system. Over-expression of both Fbxw11 variants stimulated the proliferation of L1210 cells in vitro by cell counting and MTT assay. The tumor xenografts model with over-expression of Fbxw11c or Fbxw11d in DBA/2 mice was further established. Over-expression of both variants resulted in the increased tumor growth in vivo. Investigation of the molecular mechanism revealed that the increased cell proliferation was not due to decrease in cell apoptosis but due to increase in cell cycle. Further studies showed that overexpression of both Fbxw11c and Fbxw11d caused the activation of NF-κB signaling pathway. These findings suggest the important role of Fbxw11 in regulating the development of leukemia and indicate a potent rationale for developing Fbxw11 as a potential therapeutic target against leukemia.
Citation Format: Lina Wang, Jinfeng Liao, Xiao Yang, Wenli Feng, Shayan Chen, Guoguang Zheng. Fbxw11 promotes leukemia development by activating the NF-κB signaling pathway. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4433. doi:10.1158/1538-7445.AM2014-4433
Abstract 4450: Comparison of structural elements in RasGRP3 and RasGRP1 controlling membrane interaction
Authors: Czikora Agnes , Kedei Noemi , Blumberg Peter M. 
Published: May 2015

Abstract
RasGRP comprises a family of guanine nucleotide exchange factors that activate small GTPases, regulating the dissociation of GDP from Ras GTPases to enhance the formation of the active GTP-bound form. RasGRP3 has a region homologous to the phosphoinositide binding region of RasGRP1. The objective of this study was to explore the hypothesis that this region of RasGRP3, like that of RasGRP1, indeed contributes to phosphoinositide binding. For these studies, we prepared full length RasGRP1/3, RasGRP1/3 C1 domain, and truncated (C1-SuPT-PT) RasGRP1 and RasGRP3 green fluorescent protein labeled constructs to transfect human prostate adenocarcinoma (LNCaP) and human cervical carcinoma (HeLa) cells. In HeLa cells, both RasGRP1 and RasGRP3 translocated to the endonuclear membranes, most probably to the Gogli in response to phorbol ester (PMA) and other agents. In the LNCaP cells, which are a PTEN mutant cell line with markedly elevated phosphoinositide levels, RasGRP1 translocates to the plasma membrane. In contrast, the full length RasGRP3 does not translocate to the plasma membrane even though it has a PT (plasma membrane-targeting) domain with a basic/hydrophobic cluster of amino acids (BHC) similar to that of RasGRP1. In parallel, we examined the translocation of the C1 domains of RasGRP1/3 and of the truncated RasGRP1/3 constructs, as well as the corresponding constructs with amino acid substitutions in the predicted phosphoinositide binding domain of RasGRP3. The RasGRP1 translocated to the plasma membrane in response to PMA. The C1 domain of RasGRP3 was insufficient for targeting RasGRP3 to the plasma membrane. However, truncated RasGRP3, which contains the PT domain, showed stronger translocation. Substituting amino acids (Asp647, Lys648 and Ala651) in the PT domain of full length RasGRP3 triggered the plasma membrane translocation in the LNCaP cells. We conclude that the differences in the BHC section of the PT domain of RasGRP3 play an important role in the membrane translocation of RasGRP3 and will reduce its sensitivity to membrane phosphoinositide levels.
Citation Format: Agnes Czikora, Noemi Kedei, Peter M. Blumberg. Comparison of structural elements in RasGRP3 and RasGRP1 controlling membrane interaction. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4450. doi:10.1158/1538-7445.AM2014-4450
Abstract 4451: Novel orphan G-protein-coupled receptor is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma
Authors: Lee Yu Jin , Shin Kyeong Jin , Park Soo-Ah , Ryu Sung H. , Suh Pann-Ghill 
Published: May 2015

Abstract
Alterations in cellular pathways related to both endocrine and angiogenic factors may contribute to breast cancer progression. Inhibition of the elevated levels of these pathways is associated with clinical benefits. However, underlying mechanisms by which endocrine-related pathways and angiogenic factor signaling cooperatively promote breast cancer progression remain unclear. In this study, we report that novel orphan G-protein-coupled receptor (GPCR), GPR YJ, is oncogenic and mediates anti-estrogen resistance in breast cancer. GPR YJ is overexpressed in breast cancer cells and tissues, where elevated expression correlates with high tumor grade. Also, GPR YJ induces the expression of several angiogenic factors (VEGF, bFGF and IL-8), as well as ErbB (amphiregulin, epiregulin and neuregulins), which activate their respective pathways, leading to increased cell proliferation and survival, enhanced anchorage-independent growth, and promoted migration and invasion. In vivo, GPR YJ promotes the formation of large, well-vascularized tumors that metastasize to distant organs such as lymph nodes, lung and liver. Thus, deregulated expression of GPR YJ contributes to breast cancer progression and metastasis by inducing several growth factors that alter tumor-specific cell fates and the tumor stromal microenvironment.
Citation Format: Yu Jin Lee, Kyeong Jin Shin, Soo-Ah Park, Sung Ho Ryu, Pann-Ghill Suh. Novel orphan G-protein-coupled receptor is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4451. doi:10.1158/1538-7445.AM2014-4451
Abstract 4453: Synergistic anticancer effect of combination of AZD6244 and BYL719 targeting KRAS mutant in non-small cell lung cancer
Authors: Jho Eun Hye , Kang Sin I. , Bae Yeon-Hee , Park Young Mee , Sun Jong-Mu , Ahn Jin Seok , Park Keunchil , Ahn Myung-Ju 
Published: May 2015

Abstract
KRAS mutation is found in 10-30% of non-small cell lung cancer (NSCLC) and highly correlated with smokers. So far, targeted agents demonstrating therapeutic activity against K-ras mutation are not available in a clinical setting. In this study, we show that dual agents, MEK inhibitor, AZD6244, and PI3K inhibitor, BYL719, have a synergistic effect on only KRAS mutant NSCLC cells. We defined that the combination of AZD6244 and BYL719 at ratios of IC50 1/2:1/2, 1:1, 2:2 (μM / μM) has ratio-dependent synergistic effect. In vitro, the combination of AZD6244 and BYL719 potently inhibited cell proliferation with cytotoxicity in H2009 and A549 cells more than the same cells treated with single drug. Also, BYL719 enhanced AZD6244-induced apoptosis and the combination treatment induced cleavage-PARP and Bim overexpression. In vivo, the antitumor efficacy was potentiated by co-treatment of AZD6244 and BYL719 in A549 xenografts. These data suggest that the combination of MEK and PI3K inhibitors might be a candidate for clinical development for its synergistic effect against KRAS-driven lung cancer.
Citation Format: Eun Hye Jho, Sin Il Kang, Yeon-Hee Bae, Young Mee Park, Jong-Mu Sun, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn. Synergistic anticancer effect of combination of AZD6244 and BYL719 targeting KRAS mutant in non-small cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4453. doi:10.1158/1538-7445.AM2014-4453
Abstract 4458: PDLIM2 is essential for feedback regulation of the B1 integrin-FAK-RhoA signalling pathway to maintain epithelial cell polarity and suppress transformation
Authors: Kiran-Deevi Ravi , Cox Orla T. , O'Connor Rosemary 
Published: May 2015

Abstract
PDLIM2 is a PDZ-LIM domain protein that regulates the stability of transcription factors (NFkB and STATs) in the nucleus. It is also associated with the cytoskeleton at cell adhesions and cell junctions and is required for polarized cell migration. PDLIM2 expression is suppressed by methylation in different cancers, but is strongly expressed in invasive breast cancer cells that have undergone an Epithelial Mesenchymal Transition (EMT). Moreover, PDLIM2 expression is associated with poor outcome in basal breast cancers and its expression can be enhanced by vitamin D-induced differentiation of breast cancer cells.
Since PDLIM2 expression repression may facilitate oncogenic transformation and its expression is modulated by the differentiation status of breast cancer cells we asked whether it is essential for maintaining a non-transformed epithelial phenotype. To address this we suppressed PDLIM2 in MCF10A cells and assessed the phenotype and mechanism in 3D Matrigel cultures. We found that PDLIM2 suppression is sufficient to disrupt cell polarization and acinar formation in Matrigel cultures. MCF10A cells with suppressed PDLIM2 formed spheres of proliferating cells that exhibited reduced apoptosis in the luminal space, compared to control acini with hollow or apoptotic lumina. Spheroids with suppressed PDLIM2 had increased expression of cell-cell adhesion proteins including E cadherin and β-catenin. Proteins associated with cell-matrix adhesion were also up-regulated, including activated beta 1 (β1) integrin, laminin, and fibronectin production. Interestingly, both the IGF-1 Receptor and RACK1, which scaffolds IGF-1R to β1 integrin, were increased, indicating a transformed phenotype. FAK and cofilin phosphorylation, and RhoA activity were also enhanced in spheroids with PDLIM2 suppressed compared to controls. Importantly, pharmacological inhibition of either FAK or Rho Kinase (ROCK) was sufficient to rescue the polarity defect and abrogate all the phenotypic changes in MCF10A cell spheroids caused by PDLIM2 suppression.
We conclude that PDLIM2 mediates feedback regulation of the β1-integrin signalling pathway through FAK and RhoA that is essential for maintenance of polarized breast epithelial acinar structures, and for suppression of uncontrolled proliferation and cellular transformation.
Citation Format: Ravi Kiran-Deevi, Orla T. Cox, Rosemary O'Connor. PDLIM2 is essential for feedback regulation of the B1 integrin-FAK-RhoA signalling pathway to maintain epithelial cell polarity and suppress transformation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4458. doi:10.1158/1538-7445.AM2014-4458
Abstract 4468: Tumor vasculature targeting using cell-specific thioaptamer decorated chitosan nanoparticle
Authors: Jiang Dahai , Mangala Lingegowda S. , Wang Hongyu , Wu Sherry , Rao Lokesh G. , Rodriguez-Aguayo Cristian , Pradeep Sunila , Volk David E. , Lopez-Berestein Gabriel , Sood Anil K. 
Published: May 2015

Abstract
Anti-angiogenesis targeted therapy using RNA interference is a powerful tool to inhibit tumor growth and metastasis Here, we developed chitosan/thioaptamer nanoparticles that are capable of cell-type specific binding and delivery of siRNA into tumor-associated endothelial cells Thioaptamer (TA) was created by partial substitution of oxygen with sulfur on the aptamer phosphate backbone at the 5′dA position to enhance binding affinity and stability A combinatorial DNA aptamer library was established for cell-based selection method known as SELEX (systematic evolution of ligands by exponential enrichment) Endothelial cells isolated from both human ovarian tumors and normal human ovarian tissues were used to screen for selective thioaptamers After 10 cycles of cell-SELEX, two candidates, Endo28 and Endo31 showed highly specific binding to both human microvascular endothelial cells (HMVEC) and vasculature of human ovarian cancer tissue Endo28 decorated chitosan nanoparticles (CH/TA-siRNA) were ∼200 nm, positively charged (22mV), and spherical in shape The incorporation of thioaptamer Endo28 and siRNA to chitosan was confirmed using 1HNMR and PCR CH/TA-siRNA nanoparticles were intact and stable in the presence of serum at 37° C Intravenous administration of CH/TA nanoparticles into mice with HeyA8 ovarian tumors resulted in successful binding of aptamer to endothelial cells as well as delivery of siRNA into tumors TEM7 is a tumor biomarker found on the surface of endothelial cells TEM7 silencing using siRNA reduced endothelial tube formation and migration In orthotopic mouse models of ovarian cancer, murine TEM7 siRNA loaded nanoparticles showed substantial reduction in tumor growth as well as reduced angiogenesis These data have implications for new anti-angiogenesis approaches
Citation Format: Dahai Jiang, Lingegowda S. Mangala, Hongyu Wang, Sherry Wu, Lokesh G. Rao, Cristian Rodriguez-Aguayo, Sunila Pradeep, David E. Volk, Gabriel Lopez-Berestein, Anil K. Sood. Tumor vasculature targeting using cell-specific thioaptamer decorated chitosan nanoparticle. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4468. doi:10.1158/1538-7445.AM2014-4468
Abstract 4480: Double targeting nanoscale drug delivery system for treatment and imaging of metastatic solid cancers
Authors: Ahmed Md Shakir U. , Abdalla Mohamed O. , Turner Timothy 
Published: May 2015

Abstract
Purpose: As an alternative to the drawbacks of current advanced cancer treatments such as conventional chemotherapy, we propose a multifunctional double targeting drug delivery system that utilizes the combination of cancer-targeting peptides fused to amphiphilic polymer coated iron oxide nanoparticles (IONPs) and loaded with suitable anticancer drugs as the payload.
Methods: PC3 human prostate cancer cell line will be used initially to test the efficiency of the proposed drug delivery system. Our target sites of choice are the luteinizing hormone releasing hormone receptor (LHRH-R) and the urokinase-type plasminogen activator receptor (uPAR), and docetaxel was selected as the payload. A modified LHRH (ligand for LHRH-R) and AE105 (ligand for uPAR) were conjugated to polymer coated IONPs according to the manufacturer's protocol.
Results: Conjugated IONPs were characterized by gel electrophoresis and Dynamic Light Scattering (DLS). IONPs showed expected narrow size distribution after conjugation with peptide ligand. The average hydrodynamic size of non targeted IONPs (36.84 nm) was increased upon conjugation of double peptide to their surface (44.06 nm). Conjugation of peptides to carboxylic groups of polymer coating on IONPs resulted in a decrease of zeta potential from -70.43 mV to -58.06 mV. Prussian blue staining demonstrated that LHRH and AE105 conjugated IONPs were internalized efficiently by the PC3 cells. The drug loading and release capability of conjugated IONPs will be evaluated by HPLC. In addition the internalization of conjugated IONPs will also be examined utilizing Magnetic Resonance Imaging (MRI), and tumor eradication will be determined by MTT assay.
Conclusions: We expect a significant enhancement in the binding efficiency of the LHRH-IONPs-AE105 to the prostate cancer cells, increased efficiency in tumor eradication, and better imaging and monitoring capabilities because IONPs can be visualized by MRI during molecular imaging of the prostate cancer cells. Therefore, we believe the optimization of the proposed system will enhance targeted nanomedicine and significantly improve the health outcomes and quality of life for cancer patients because of the following reasons: 1) its ability to deliver anticancer drugs specifically to cancer cells while sparing the surrounding normal tissues, and 2) the capability of in situ monitoring of the therapeutics.
Citation Format: Md Shakir U. Ahmed, Mohamed O. Abdalla, Timothy Turner. Double targeting nanoscale drug delivery system for treatment and imaging of metastatic solid cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4480. doi:10.1158/1538-7445.AM2014-4480
Abstract 4489: Targeting cancer cells and antitumor effects of brucine immunonanoparticles on hepatocellular carcinoma in vivo
Authors: Qin Jianmin 
Published: May 2015

Abstract
Background: In vitro and in vivo studies have showed that brucine can inhibit the growth of liver cancer cells and animals with bearing cancer , and may be a promising anti-cancer drugs. However, high toxicity, poor water solubility, short half-life, narrow therapeutic window, close therapeutic and toxic dose limit its clinical application in malignant tumor treatment. In this study, we report on the preparation , in vivo distribution and antitumor effect of the brucine immuno-nanoparticles. Methods: Anionic polymerization and chemical modification technology was used to prepare carboxylated polyethylene glycol-poly lactic acid copolymer carrier material, phacoemulsification technology was employed to prepare carboxylated polyethylene glycol-polylactic acid copolymer brucine nanoparticles and chemical coupling technology was utilized to develop anti-human AFP McAb-polyethylene glycol-poly lactic acid copolymer brucine immuno-nanoparticles. The nude mice in situ transplanted liver cancer model was established by surgical technique, and the brucine immuno-nanoparcitles was injected by caudal vein at indicated time. The liver and kidney function and AFP level were assayed , and the anti-tumor effect was observed after intravenous administration of the brucine immuno-nanoparticles.
Results:This results showed that in vivo application of brucine immuno-nanoparticles caused temporary liver and kidney functions damage and significantly reduced AFP secretion. Brucine immuno-nanoparticles had good slow releasing and tumor targeting properties. The brucine immuno-nanoparticles inhibited CD34 expression and angiogenesis of tumor tissues, induced tumor apoptosis, and inhibited tumor growth.
Conclusions: The brucine immuno-nanoparticles has good tumor targeting and obvious anti-tumor effects , and is a promising targeted drug for liver cancer therapy in the future.
Note: This abstract was not presented at the meeting.
Citation Format: Jianmin Qin. Targeting cancer cells and antitumor effects of brucine immunonanoparticles on hepatocellular carcinoma in vivo. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4489. doi:10.1158/1538-7445.AM2014-4489
Abstract 4504: Urokinase plasminogen activator-dependent tumor penetrating peptide
Authors: Teesalu Tambet , Sugahara Kazuki N. , Braun Gary B. , Kotamraju Venkata Ramana , Ruoslahti Erkki 
Published: May 2015

Abstract
Activity of tumor penetrating peptides depends on C-end Rule (CendR) peptide motif (R/KXXR/K) that must be C-terminally exposed for tissue and cell penetration. We describe here a cryptic CendR peptide (uCendR; amino acid sequence: RPARSGR↓SAGGSVA) that is proteolytically activated by urokinase-type plasminogen activator (uPA), a protease overexpressed in human tumors. uPA cleavage unmasks the cryptic CendR element of uCendR peptide and triggers its binding and internalization to the neuropilin-expressing cultured cancer cells. Intradermally injected post-cleavage mimic of uCendR peptide (RPARSGR) increases permeability of skin microvessels to tracer compounds. Phage and silver nanoparticles functionalized with uCendR peptide in combination with angiogenic integrin-recruitment motif (CRGDC) home to tumor blood vessels, extravasate, and trigger vascular exit of co-injected tracer compounds. This study shows that modular tumor penetrating peptides that are specifically activated by a tumor derived protease can be developed for tumor-targeted drug delivery.
Citation Format: Tambet Teesalu, Kazuki N. Sugahara, Gary B. Braun, Venkata Ramana Kotamraju, Erkki Ruoslahti. Urokinase plasminogen activator-dependent tumor penetrating peptide. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4504. doi:10.1158/1538-7445.AM2014-4504
Abstract 4508: Engineering a single ubiquitin ligase for the selective degradation of all activated ErbB receptor tyrosine kinases
Authors: Li Hui 
Published: May 2015

Abstract
Interrogating specific cellular activities often entails the dissection of posttranslational modifications or functional redundancy conferred by protein families, which demands more sophisticated research tools than simply eliminating a specific gene product by gene targeting or RNA interference. We have developed a novel methodology that involves engineering a single SCFbTrCP-based ubiquitin ligase that is capable of not only simultaneously targeting the entire family of ErbB receptor tyrosine kinases for ubiquitination and degradation, but also selectively recruiting only activated ErbBs. The engineered SCFbTrCP ubiquitin ligase effectively blocked ErbB signaling and attenuated oncogenicity in breast cancer cells, yet had little effect on the survival and growth of non-cancerous breast epithelial cells. Therefore, engineering ubiquitin ligases offers a simple research tool to dissect the specific traits of tumorigenic protein families, and provides a rapid and feasible means to expand the dimensionality of drug discovery by assessing protein families or posttranslational modifications as potential drug targets.
Note: This abstract was not presented at the meeting.
Citation Format: Hui Li. Engineering a single ubiquitin ligase for the selective degradation of all activated ErbB receptor tyrosine kinases. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4508. doi:10.1158/1538-7445.AM2014-4508