bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5037: Identifying differentially expressed microRNAs in retinoblastoma
Authors: Martin Joshua , Bryar Paul , Mets Marilyn , Weinstein Joanna , Vanin Elio F. , Costa Fabricio F. , Soares Marcelo B. , Laurie Nikia A. 
Published: August 2012

Abstract
Retinoblastoma, the most common pediatric cancer of the eye, is a devastating and sometimes fatal pediatric cancer. Within the United States, the majority of retinoblastoma patients are diagnosed before their 2nd birthday, and many lose their sight due to this disease. Approximately 75% of the retinoblastoma patients in the United States have unilateral disease, and treatment for many unilateral patients with advanced disease involves enucleation (removal of the eye). Therefore, new more effective targeted therapies for retinoblastoma could save a child's quality of life by preserving their sight. Outside of the United States, advanced retinoblastoma is an even greater clinical challenge in low-income countries, where the mortality rate among children diagnosed with advanced retinoblastoma is as high as 70%. Currently, the chemotherapeutic treatments for retinoblastoma involve the use of broad-based drugs. However, therapies targeted directly to aberrant signaling pathways may provide more effective therapy for this disease. MicroRNAs, short noncoding RNA transcripts that can regulate the expression of target genes, are known to affect the progression of many different tumor types. MicroRNAs (miRNAs) are also ideal therapeutic targets because they are amenable to therapeutic manipulation. To identify miRNAs associated with retinoblastoma progression, we have conducted miRNA profiling studies on 12 late-stage human retinoblastoma tumors. Our analysis has led to the identification of 19 differentially expressed miRNAs (p&lt;0.05) in retinoblastoma as compared to normal human retina. From those 19 miRNAs, 15 miRNAs are newly associated as being differentially expressed in retinoblastoma. These miRNAs could serve as potential therapeutic targets for retinoblastoma due to their known involvement in viability, proliferation, cell cycle regulation, and apoptosis in other tumor types. This is an essential step in the discovery of miRNAs associated with retinoblastoma progression, and in the identification of potential therapeutic targets for this disease.
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 5037. doi:1538-7445.AM2012-5037
Abstract 5182: Real-time molecular imaging of αv-integrin GFP-expression in osteosarcoma cells in vitro and in vivo
Authors: Tome Yasunori , Sugimoto Naotoshi , Yano Shuya , Momiyama Masashi , Maehara Hiroki , Tomita Katsuro , Tsuchiya Hiroyuki , Kanaya Fuminori , Hoffman Robert M. 
Published: August 2012

Abstract
We describe here real-time imaging of αv integrin-GFP expression in osteosarcoma cells (143B) in vitro and in vivo. 143B cells were stably transfected with an αv integrin-GFP vector. Confocal microscopy demonstrated that αv integrin immunofluorescent staining colocalized with αv integrin-GFP fluorescence. In vitro, when αv integrin-GFP osteosarcoma cells were seeded on a dish coated with fibronectin, which bonds αv integrin. αv integrin adhesion plaques were observed by confocal microscopy using the Olympus FV1000. When αv integrin-GFP-expressing 143B cells (1×106) were transplanted in the tibia or injected subcutaneously in nude mice, the cells aligned along collagen orthotopic fibers. In the orthotopic model, osteosarcoma cells punctate expression of αv integrin-GFP was imaged in the osteosarcoma cells as they invaded muscular tissue. In the subcutaneous model, osteosarcoma cells, strongly expressing αv integrin-GFP, were observed around the blood vessels in the tumor. These results show that αv integrin-GFP allows the real-time imaging of the role of αv integrin during cancer cell invasion allowing the further understanding of its role in the process.
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 5182. doi:1538-7445.AM2012-5182
Abstract 5183: Raster-image-correlation spectroscopy of paxillin-GFP-expressing breast cancer cell in vitro and in vivo
Authors: Suetsugu Atsushi , Digman Michelle , Sabatini Federica , Moriwaki Hisataka , Saji Shigetoyo , Gratton Enrico , Hoffman Robert M. 
Published: August 2012

Abstract
Raster-image-correlation spectroscopy (RICS) is a noninvasive technique to detect and quantify events in the living cell, including concentrations of molecules and their diffusion coefficients. Any cell containing a fluorophore that can be imaged with a laser scanning microscope can be analyzed with RICS. We obtained RICS images with an Olympus FluoView FV1000 confocal microscope using Olympus FluoView software to acquire data and SimFCS software to perform RICS analysis. Paxillin is involved in the assembly of focal adhesions, which was linked to green fluorescent protein (GFP) for the current study. In this study, we describe RICS of paxillin-GFP expression in breast cancer cells (MDA-MB-231) in vitro and in vivo. Slow-moving membrane-bound paxillin proteins were measured in live breast cancer cells in vitro. Paxillin-GFP-expressing breast cancer cells (1×106) were injected in the epigastric cranials vein of the nude mouse. Paxillin-GFP-expressing breast cancer cells became attached to the inner vessel wall within 3 hours after injection. Rapidly-moving cytosolic paxillin-GFP molecules were imaged with RICS. With the ability to measure the molecular dynamics of paxillin in cancer cells in vitro and in vivo by RICS, we are now capable of studying the role of both slow-moving paxillin in the cell membrane and rapidly-moving cytosolic paxillin in cancer-cell behavior.
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 5183. doi:1538-7445.AM2012-5183
Abstract 5186: A new mode of integrin–Ecadherin cross talk that modulates invasion and metastasis
Authors: Danen Erik H. 
Published: August 2012

Abstract
Cellular interactions with the extracellular matrix (ECM) are mediated by transmembrane receptors of the integrin family. These interactions coordinate signal transduction cascades impinging on cell survival, proliferation, and migration. Ablation of the β1 integrin gene attenuates initiation and growth of breast and skin cancers and β1 antibodies sensitize breast tumors in mice to radiotherapy. However, the role of β1 integrins in breast cancer progression from a localized tumor to metastatic disease is unknown. We show that peptide blocking or gene silencing of β1 integrins can cause a shift from cohesive multicellular strand invasion to individual cell migration, which acts pro-metastatic in breast cancer cells. While tumor growth of β1 integrin-depleted breast cancer cells is reduced, intravasation and lung metastasis of cells from these small tumors in an orthotopic mouse model is dramatically enhanced, as is migration in a zebrafish xenograft model. Depletion of β1 integrins alters the balance between miR-200 miRNAs and ZEB transcriptional repressors leading to a transcriptional downregulation of E-cadherin, which is essential for the induction of individual cell migration and enhanced metastasis. These findings demonstrate that disturbed integrin-mediated interactions with the ECM in cancer cells can alter cell migration strategies and metastatic potential through a miRNA-transcription factor network that controls cell-cell adhesion.
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 5186. doi:1538-7445.AM2012-5186
Abstract 5187: Urokinase plasminogen activator receptor (uPAR) and integrin α5β1 regulate plasminogen activator inhibitor-1 (PAI-1) activity in medulloblastoma cells
Authors: Nalla Arun Kumar , Asuthkar Swapna , Gujrati Meena , Dinh Dzung H. , Rao Jasti S. 
Published: August 2012

Abstract
The urokinase plasminogen activator (uPA) system is a dynamic extracellular protease system that regulates both proteolytic and non-proteolytic events associated with cancer progression. In earlier studies, we have demonstrated that radiation-induced cell adhesion was associated with uPAR expression and downregulation of uPAR effectively inhibited radiation-induced cell adhesion of medulloblastoma cells. Herein, we further investigated the impact of uPAR downregulation on plasminogen activator inhibitor (PAI-1), a key regulator component of the uPA system, and its role in cell adhesion. With radiation treatment, the levels of uPAR and PAI-1 increased in D283 and UW228 cells. Surprisingly, knockdown of uPAR elevated the levels of PAI-1. The increase in PAI-1 levels in uPAR-knocked down cells was regulated by activation of cJUN/CREB signaling molecules. Moreover, studies show that the reduced interaction between uPAR and integrin α5β1 plays a critical role in PAI-1 release into the extracellular matrix, thereby enhancing the cell detachment process. Incubation of medulloblastoma cells with Tiplaxtinin-PAI-039, a potent PAI-1 activity inhibitor, increased the association of uPAR with integrin α5β1 and cell adhesion. Interestingly, prolonged inhibition of PAI-1 activity adversely affected cell viability; we were able to revert this effect by exogenously supplementing cells with recombinant PAI-1. Moreover r-PAI-1 showed no significant effect on cell adhesion whereas it increased the association of uPAR with integrin α5β1. Expression of full-length (FL) uPAR elevated uPA and PAI-1 levels both at the transcriptional and the translational levels. These increased PAI-1 levels play a pivotal role in regulating uPA activity by binding and translocating integrin α5β1 towards the uPA/uPAR complex. Taken together, the results of the present study lead us to conclude that levels of uPAR and integrin α5β1, and their association on the cell surface dictate the function of PAI-1 to maintain extracellular homeostasis.
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 5187. doi:1538-7445.AM2012-5187
Abstract 5189: N-cadherin promotes metastasis by enhancing motility through Akt3 suppression
Authors: Yao Jiahong , Hazan Rachel 
Published: August 2012

Abstract
Here we show that in vivo mammary expression of N-cadherin in the PyMT model which enhances breast tumor metastasis results in selective inhibition of Akt3 expression and phosphorylation. Similarly, exogenous expression of N-cadherin in PyMT tumor cells which enhances motility caused a dramatic reduction in Akt3 expression and activation. Moreover, knockdown of Akt3 in PyMT cells enhanced cell motility, disrupted mammary morphogenesis but had no effect on cell proliferation. Conversely, overexpression of constitutively active Akt3 inhibited cell motility, suggesting signaling through Akt3 relays motility suppression by N-cadherin. Taken altogether, these findings demonstrate that N-cadherin suppresses Akt3 to promote cell motility and highlight the intricate regulation of the AKT pathway by N-cadherin during metastasis.
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 5189. doi:1538-7445.AM2012-5189
Abstract 519: Identification of a novel target for antibody therapy of breast cancer
Authors: Okano Fumiyoshi , Saito Takanori , Ido Takayoshi , Kurihara Akira , Kobayashi Shinichi , Narita Yoshinori , Minamida Yoshitaka , Sato Masahiro , Toriyama Yuko , Yonehara Tetsu 
Published: August 2012

Abstract
Identification of breast cancer-specific antigens may promote development of safe and successful immunotherapy of breast cancer. Caprin-1 has been known to be an intracellular protein related to cell proliferation as a function, but it has not been reported to be a target for the treatment of cancer. Here we report that this molecule is a novel breast cancer antigen which can be targeted for antibody therapy. Caprin-1 is highly expressed in at least 70% of breast cancers based on the results of immunohistochemical staining of human several breast cancer tissues, but hardly expressed in human normal tissues. Importantly, a part of this molecule is highly expressed in extracellular region of many breast cancer cells. A mouse monoclonal antibody raised against the extracellular domain of Caprin-1 showed anti-tumor effects in all tumor-bearing mouse models in which various cancer cells expressing Caprin-1 were implanted. The monoclonal antibody induced complete regression in one of the tumor-bearing models. Humanized antibody has been prepared and preclinical studies are currently underway.
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 519. doi:1538-7445.AM2012-519
Abstract 5190: DNA aptamer-targeted periostin inhibits adhesion and migration of breast cancer
Authors: Lee Yu Jin , Kim Il Shin , Kim Yoon Dong , Lee Kyung Min , Noh Dong-Young , Kim Kyong-Tai , Ryu Sung-Ho , Suh Pann-Ghill 
Published: August 2012

Abstract
Tumor metastasis is multiple step pathological process involved in the final phase of tumor development. During this process, tumor cells obtain invasiveness and metastatic potential. Periostin, a mesenchyme-specific gene, has emerged as critical contributor of tumor metastasis and angiogenesis. Clinical evidence has supported that periostin are highly expressed in several cancers including breast, where it is associated with a poor outcome. Thus, periostin is a potential therapeutic target for the regulation of breast cancer growth and metastasis. In this study, we generated and characterized a DNA aptamer directed against human periostin (PNDAs) through utilization of Advanced-SELEX process. Aptamers have been selected that bind to periostin with nanomolar binding affinity (Kd: 1nM) and specificity. Furthermore, PNDA specifically binds to periostin which is expressed in breast cancer tissues and serum. In addition, PNDA treatment led to a reduction of integrin-mediated breast cancer cell migration and adhesion by 50%. Also, PNDA can significantly decrease activation of various components of integrin signal transduction pathways and their downstream effector molecules. Together, our data suggest that DNA aptamer targeting periostin may have potential as an agent to inhibit breast cancer growth and metastasis.
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 5190. doi:1538-7445.AM2012-5190
Abstract 52: Gene expression profiling of breast cancer associated fibroblasts and their adjacent counterparts
Authors: Al-Rakan Maha A. , Colak Dilek , Al-Bakheet Albandary , Kaya Namik , Aboussekhra Abdelilah 
Published: August 2012

Abstract
Abstract Breast cancer has a major impact on the health of women worldwide including Saudi Arabia, where it is considered the most frequently diagnosed cancer (∼22% of all female cancers) and the leading cause of cancer deaths among women. Breast carcinomas are complex neoplasms that develop by the accumulation of different mutations in the epithelial cells. However, increasing evidence suggests that changes in the cellular microenvironment contribute to tumorgenesis through paracrine effects. Fibroblasts, the predominant cells of the stromal breast carcinomas, play an important role in the development and spread of cancer cells. However, the nature and the mediators of the crosstalk between cancer cells and their stromal fibroblasts are still not well defined. In this study we performed genome wide expression analysis on 5 Carcinoma-Associated Fibroblasts (CAFs) and their corresponding Tumor Counterpart Fibroblasts (TCFs) (from the same breast cancer patients) as compared to 3 normal breast fibroblasts (NBFs) from breast cancer free patients admitted for plastic surgery. To this end, Affymetix's latest Gene Chip® Human Genome U133 Plus 2.0 Array, which has more than 54,000 probe sets, was used. A threshold of ≤2≥ fold was considered as significant difference in the analysis of the microarray data. We performed 3 different comparisons; CAFs with TCFs, CAFs with NBFs and TCFs with NBFs. The analysis of the microarray data showed that the number of genes that were differentially expressed between CAFs and NBFs reached 101, and only 42 genes were differentially expressed between CAFs and TCFs. Interestingly, 77 genes were found to be differentially expressed between TCFs and NBFs. This data was confirmed by quantitative RT-PCR. Next, we used Ray Bio® Human cytokine Antibody Array 5 Map, which has 80 probed cytokines, and showed differential expression profile of different cytokines secreted by TCF, CAF and NBF cells, confirming that TCFs are different than CAFs and NBFs indicating that TCFs are indeed active stromal fibroblasts. Moreover, we examined the expression level of α-SMA, TGF-β and SDF-1 proteins (3 well known markers of active fibroblasts) and found their expression higher in TCFs than NBFs. In addition, we performed ELISA against SDF-1, VEGFA and IL-6 (3 cytokines known to promote breast carcinogenesis) and found their levels higher in TCFs than in NBFs conditioned media. Therefore, despite the fact that TCFs exist in histologically normal breast tissues, they are not physiologically normal, but rather present some features of active fibroblasts and thereby they may participate in breast cancer development / recurrence.
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 52. doi:1538-7445.AM2012-52
Abstract 520: Regulation of natural killer cell development and antitumor immunity by the IL-15 system
Authors: Lee Gilbert A. , Liou Yae-Huei , Wang Szu-Wen , Jiang Si-Tse , Liao Nan-Shih 
Published: August 2012

Abstract
Natural killer (NK) cells are innate immune cells involved in tumor surveillance. The development and effector function of NK cells require IL-15 signal, which is “trans-presented” to IL-15Rβγ on NK cells by IL-15Rα on neighboring cells. Because the IL-15Rα intracellular (IC) domain has the capacity to recruit signaling molecules, we generated knock-in (KI) and transgenic (Tg) mice that lack the IC domain to assess independently the role of the IL-15 trans-presentation level. In this study, we found that the IL-15Rα level on bone marrow-derived dendritic cells (BMDCs) generated by KI and Tg mice determines the level of Stat5 phosphorylation in NK cells, thus offering the opportunity to study quantitative effects of IL-15 trans-presentation on NK cell development and function in vivo. We also found that NK cell homeostasis, mature NK cell differentiation, and acquisition of effector functions require different levels of IL-15 trans-presentation input to achieve full status. In order to investigate the effects of IL-15 trans-presentation level in anti-tumor immunity in vivo, we established the tumor inoculation experiment. Our preliminary data showed that the growth of B16/OVA melanoma increased in Il15−/− mice in comparison to WT mice. We will assess the role of the IL-15 system in anti-tumor immunity.
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 520. doi:1538-7445.AM2012-520
Abstract 5200: Nestin regulates stem cell functions of pancreatic cancer cells
Authors: Matsuda Yoko , Hagio Masahito , Yanagisawa Yuji , Suzuki Taeko , Kawamoto Yoko , Kawahara Kiyoko , Naito Zenya , Ishiwata Toshiyuki 
Published: August 2012

Abstract
Introduction: Nestin, a class VI intermediate filament, is expressed in pancreatic exocrine progenitor cells. Previously, we reported that 30% of PDAC cases expressed nestin in cancer cells, and its expression was correlated with invasion (Kawamoto, et al. Hum Pathol 2009). Knockdown of nestin using shRNA in human PDAC cell lines inhibited cell migration and invasion in vitro and liver metastasis in vivo. Restoring the expression level of nestin returned the inhibition of cell migration and invasion to the previous level (Matsuda, et al. Cancer Biol Ther 2011). In this study we analyzed the expression and roles of nestin in pancreatic cancer stem cells. Methods: Expressions of stem cell markers and nestin were analyzed using immunocytochemistry and real-time PCR. To assess cancer stem cells, a sphere formation assay was performed as follows: cells were grown in an ultra-low attachment surface plate supplemented with epithelial growth factor and fibroblast growth factor 2. Nestin-regulating molecules were clarified by DNA microarray analysis. Results: The expression level of nestin was high in sphere-forming PDAC cells, and its expression levels correlated with sphere-forming ability. In DNA microarray analysis using nestin shRNA-transfected clones and nestin-expression vector transfected-clones, at a 2-fold cut-off, only transcriptional factor 4 (TCF4) showed a compatible change coincident with nestin expression. It has been reported that TCF4 is involved in the Wnt pathway, and negatively regulates the transcription of NANOG. In real-time PCR, expression levels of TCF4 and NANOG correlated with nestin expression level. Conclusion: Nestin expression levels correlated with sphere-forming ability and expression levels of TCF4 and NANOG. These results indicate that nestin regulate stemness via TCF4 and NANOG.The expression of nestin is associated with highly metastatic cancer stem-like cells, and nestin regulates migration, invasion, and metastasis by altering the pancreatic cancer stem cell function.
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 5200. doi:1538-7445.AM2012-5200