bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3041: GPR56 promotes the adhesion of glioma stem-like cells to the perivascular niche and regulates cell fate
Authors: Moreno Marta , Giera Stefanie , Piao Xianhua , Iglesia Nuria de la 
Published: May 2015

Abstract
INTRODUCTION
Gliobastomas (GBM) are the most aggressive and frequent human malignancies in the central nervous system. A small population of cells within the bulk of these tumors displays properties of normal neural stem cells (NSC). Accordingly, these cells are referred to as glioma stem-like initiating cells (GIC). Thus, deregulation of mechanisms that control NSC biology might contribute to the pathogenesis of GBM. NSC and GIC are localized to the perivascular space where they reside in close apposition to blood vessels (BV), which promote self-renewal and keep these cells in an undifferentiated state. GPR56 is an adhesion G-protein coupled receptor expressed in neural progenitors in the embryonic and adult brain and plays an indispensable role in cortical development. Knockout mice studies show that GPR56 mediates the attachment of radial glial endfeet to pial basement membrane (BM). Some of the components of the pial BM are also present in the extracellular matrix surrounding BV, such as laminin and collagen. Therefore, we hypothesized that GPR56 might mediate NSC/GIC localization to the perivascular niche thus contributing to their stem-related properties.
EXPERIMENTAL PROCEDURES
Here, we have compared the expression of GPR56 in neural progenitors versus more differentiated progeny. In addition, we have assessed the role of GPR56 in the neural stem-like properties of GIC, including their differentiation into more mesenchymal cell types such as endothelial cells or pericytes, by gain- and loss-of-function studies.
RESULTS
We have found that GPR56 is highly expressed in NSC and its expression is downregulated during differentiation. We have also observed that GPR56 is expressed in cells that reside in the perivascular niche. GPR56-knockdown GIC display impaired adhesion to endothelial cells (EC), whereas GPR56 overexpression increases their adhesion to EC. Furthermore, loss of GPR56 increases the ability of GIC to express endothelial/pericyte markers when co-cultured with EC and increases the CD44+ population, suggesting that GPR56 inhibits the acquisition of a mesenchymal-like phenotype.
CONCLUSIONS
Taken together, our findings indicate that GPR56 mediates the adhesion of GIC to EC. Moreover, GPR56 inhibits the acquisition of mesenchymal features. Therefore, we suggest that GPR56 might mediate the attachment of GIC to the perivascular niche while preserving their neural stem-like properties by preventing the acquisition of a mesenchymal-like phenotype.
Citation Format: Marta Moreno, Stefanie Giera, Xianhua Piao, Nuria de la Iglesia. GPR56 promotes the adhesion of glioma stem-like cells to the perivascular niche and regulates cell fate. [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 3041. doi:10.1158/1538-7445.AM2014-3041
Abstract 3067: PIK3CA hotspot mutations are present at a relatively high frequency in CTCs of operable and metastatic breast cancer patients
Authors: Markou Athina N. , Farkona Sofia , Schiza Christina , Eftathiou Antonia , Malamos Nikolaos , Georgoulias Vassilis , Lianidou Evi 
Published: May 2015

Abstract
Introduction: Molecular characterization of CTC is crucial for the investigation of molecular targeted therapies. PIK3CA somatic mutations play a crucial role in response to molecular targeted therapies. We detected PIK3CA mutations at a high frequency in CTC after developing and validating an ultra-sensitive methodology, based on a combination of allele-specific, asymmetric rapid PCR and melting analysis.
Patient and Methods: After optimizing and validating our assay in terms of sensitivity, specificity and robustness, we detected PIK3CA hotspot mutations in EpCAM positive CTCs from 57 metastatic and 118 early breast cancer patients, 26 healthy individuals and 76 corresponding primary tumors. Rapid Real-PCR and melting were performed in triplicate for all samples in the LightScanner32 (Idaho USA), in the presence of LC-Green Plus saturating dye.
Results: The assay could detect 0.05% of mutated dsDNA in the presence of 99.95% wtDNA for both exons and was highly specific (0/26 healthy). We identified PIK3CA mutations in EpCAM positive CTC in 20/57(35.1%) metastatic and in 23/118(19.5%) operable breast cancer patients. In corresponding primary tumors, 45/76(59.2%) samples were positive. Patients with verified metastasis carrying PIK3CA mutations on CTC had significant shorter OS than those without.
Conclusions: We report for the first time that PIK3CA hotspot mutations are present at a relatively high frequency in CTC both in metastatic and operable breast cancer. The presence of PIK3CA mutations in CTC is associated with worse survival in patients with verified metastasis. Evaluation of PIK3CA mutational status on CTCs is a strategy with potential clinical application.
Citation Format: Athina N. Markou, Sofia Farkona, Christina Schiza, Antonia Eftathiou, Nikolaos Malamos, Vassilis Georgoulias, Evi Lianidou. PIK3CA hotspot mutations are present at a relatively high frequency in CTCs of operable and metastatic breast cancer patients. [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 3067. doi:10.1158/1538-7445.AM2014-3067
Abstract 307: The use of biospecimens in cancer population science research
Authors: Carrick Danielle M. , Mette Eliza , Hoyle Brittany , Rogers Scott D. , Gillanders Elizabeth M. , Schully Sheri D. , Mechanic Leah E. 
Published: May 2015

Abstract
Background: Over the past two decades, researchers have increasingly used human biospecimens to help evaluate hypotheses related to disease risk, outcomes and treatment options. We conducted an analysis of the population science cancer research grants funded by NCI in order to gain a more comprehensive understanding of the biospecimens involved in those studies. Recognizing that there are many pre-existing collections of biospecimens, we investigated the cost and time efficiencies observed with studies involving the use of existing biospecimens versus collecting new specimens. Methods: Data available for 1,018 extramural, peer-reviewed grants (active as of July 2012) supported by the Division of Cancer Control and Population Sciences, (NCI Division that supports cancer control and population science extramural research grants) were analyzed. Results: 455 of the grants were determined to involve biospecimens. The most common specimen types included were DNA (66% of grants involved DNA), whole blood (51%), serum or plasma (40%), and tissue (39%). Grants that involved the use of existing biospecimens resulted in greater cost (serum/plasma studies were 4.2 times less expensive) and time efficiencies (1.4 times more publications per year resulted) than grants that collected new biospecimens. Conclusions: Clearly, there is an opportunity for NCI to promote future sharing. We are currently working to better catalogue our funded resources and make data available to the extramural community. Further work is being done to investigate possible trends based on year of grant award.
Citation Format: Danielle M. Carrick, Eliza Mette, Brittany Hoyle, Scott D. Rogers, Elizabeth M. Gillanders, Sheri D. Schully, Leah E. Mechanic. The use of biospecimens in cancer population science research. [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 307. doi:10.1158/1538-7445.AM2014-307
Abstract 3071: Size-based isolation of circulating tumor cells (CTCs) in mouse tumor models
Authors: Kolostova Katarina , Hoffman Robert M. , Maawy Ali , Zhang Yong , Bobek Vladimir 
Published: May 2015

Abstract
We report here isolation and cultivation of circulating tumor cells (CTCs) in five human epithelial cancers (lung, prostate, colon, pancreatic and breast cancer) implanted in nude mice. All of the cancer cells were labeled with green fluorescent protein (GFP) for detection. CTCs were isolated with an antigen-independent size-based separation device (MetaCell®, Metacell s.r.o., Ostrava, Czech Republic). We were able to capture on average more than 2 cells for each of above cancer types whereby the tumor has been implanted atleast 2 weeks before blood withdrawal. The number of CTC is dependent on the stage of tumor in animals. There was a very high heterogeneity of the CTCs with regard to cell size and cell phenotype including epithelial- and mesenchymal-like type cells in vitro. The development of a facile in vitro isolation and imaging technology for CTCs will enable deeper understanding of CTC biology.
Citation Format: Katarina Kolostova, Robert M. Hoffman, Ali Maawy, Yong Zhang, Vladimir Bobek. Size-based isolation of circulating tumor cells (CTCs) in mouse tumor models. [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 3071. doi:10.1158/1538-7445.AM2014-3071
Abstract 3072: High-recovery multiplex analysis of circulating tumor cells by density-based enrichment, automated platform immunofluorescence staining, and digital microscopy
Authors: Campton Daniel , Ramirez Arturo , Nordberg Joshua , Blau Anthony , Stilwell Jackie , Kaldjian Eric 
Published: May 2015

Abstract
Background: Analysis of circulating tumor cells (CTC) is an intense area of diagnostic research that is rapidly evolving from prognostic to therapeutic applications. We applied three sequential technologies - density-based enrichment, automated immunofluorescence staining, and digital microscopy with image analysis to the investigation of recovery rates from blood containing spiked-in tumor cells as a model of CTC.
Materials and Methods: Cultured MCF7, PC3, A549 and LNCaP cells were counted using Vitrotube visualization. ∼100 cells per line were spiked into normal blood samples in two experiments. Density-based enrichment was performed using the AccuCyte tube, float and collector system in a single-tube, two-spin process. Collected cells were processed with an adherence solution and applied to charged microscopic slides with a simple spreading device. After drying, slides were placed onto the Ventana Discovery Ultra automated platform and fluorescently stained with antibodies to cytokeratin, CD45, and EpCAM or EGFR, as well as a nuclear dye. Slides were scanned on a CyteFinder digital microscope and candidate CTCs were identified using CyteMapper image analysis software. CTCs were verified by a reviewer by appropriate morphology and expression of both epithelial and nuclear stains without CD45 expression.
Results: In a total of seven samples the recovery of spiked-in CTCs ranged from 88 to 98% and averaged 91%. This method was successfully applied to samples of blood from patients with triple-negative breast cancer.
Conclusions: Density-based enrichment combined with automated immunofluorescence staining, digital microscopy and confirmation of candidate cells by a trained reviewer, produces exceptional recovery of CTCs and can be used to assess clinical samples.
Recovery of spiked-in CTCsCell line - exptSpiked-in cellsCTCs countedRecoveryLNCaP - 112711691%LNCaP - 212310989%A549 - 1868498%A549 - 212411593%MCF7 - 11099688%MCF7 - 21049288%PC3 - 2888192%
Citation Format: Daniel Campton, Arturo Ramirez, Joshua Nordberg, Anthony Blau, Jackie Stilwell, Eric Kaldjian. High-recovery multiplex analysis of circulating tumor cells by density-based enrichment, automated platform immunofluorescence staining, and digital microscopy. [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 3072. doi:10.1158/1538-7445.AM2014-3072
Abstract 3073: Detection and isolation of circulating tumor cells in ovarian cancer: Principles and methods
Authors: Lee Shin-Wha , Lee Ha-Young , Mo Jin-Young , Kim Byung Chul , Kim Eun Hye , Kim Yong-Man 
Published: May 2015

Abstract
Objective:
The quantitative and qualitative analysis of circulating tumor cells (CTCs) aids in diagnosis of disease, prognosis, disease recurrence, and therapeutic response in several cancers. However, detection and isolation of CTCs from the blood circulation is a difficult task because of their scarcity and the lack of reliable markers to identify these cells. Especially, in epithelial ovarian cancer, there is a little reported data for CTCs and their CTCs has been defined to the EpCAM+ cells, even though EpCAM+ cells are just a few in ovarian cancer. The aim of this study is to investigate the effective principles and methods to detect and isolate CTCs through novel markers in ovarian cancer.
Methods:
CTC analysis was performed in the spiking test to find cancer cells in the human serum mixed with WBCs. Four cell lines including OVCAR3, SKOV3, SNU8 and SNU251 were used and primary cancer cells from 4 patients were analyzed. Cancer cells were isolated on the basis of cell size by filtration through CytoGen capture device, followed by identification according to validated immunocytochemistry based on the expression of DAPI, CD45, EpCAM, CK, CA-125 and HE4.
Results:
We obtained cancer cells more than 90% based on the cell size by filtration. Immunocytochemistry confirmed the epithelial origin through the expression of CK and EpCAM in cancer cell lines. The rate of expression was 35-99 % for CK and 1-99 % for EpCAM. A small number of cancer cell lines expressed CD45 that is the marker of WBC. The expression of CA-125 and HE4 showed their ovarian origin. The rate of expression was 7-98 % for CA-125 and 40-99 % for HE4 in cancer cell lines. Primary cancer cells were detected most effectively as the method of combination with 4 markers, including DAPI, CD45, EpCAM and HE4.
Conclusion:
Our findings provide the first evidence for effective methods to detect and isolate CTCs in ovarian cancer. Combination of DAPI, CD45, EpCAM and HE4 could be a useful marker to support CTCs research in epithelial ovarian cancer.
Citation Format: Shin-Wha Lee, Ha-Young Lee, Jin-Young Mo, Byung Chul Kim, Eun Hye Kim, Yong-Man Kim. Detection and isolation of circulating tumor cells in ovarian cancer: Principles and methods. [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 3073. doi:10.1158/1538-7445.AM2014-3073
Abstract 3074: Detection and enumeration of circulating tumor cells using imaging flow cytometery
Authors: Vaidyanathan Shobana , Weldon Don , Basiji David , Morrissey Philip 
Published: May 2015

Abstract
Circulating tumor cells (CTCs), released into the bloodstream from primary and metastatic cancers, are valuable tools for understanding tumor biology. However, since they are rare, their detection is hampered by low efficiency and a lack of standardization in current technologies. To overcome these problems, we used Imaging Flow Cytometery along with fluorescent RNA detection probes to collect imagery from large number of cells to assess the number of CTCs. In this study, we spiked peripheral blood mononucleated cells (PBMCs) with SKBR-3 human breast cancer cells and added probes for relevant RNA targets such as EPCAM and Her-2. Taking advantage of the probes’ ability to detect RNA in live cells, combined with the capacity to acquire multi-spectral images of large numbers of cells, we demonstrate image based parameters that can be used to assess the frequency of CTCs in an objective and statistically significant manner.
Citation Format: Shobana Vaidyanathan, Don Weldon, David Basiji, Philip Morrissey. Detection and enumeration of circulating tumor cells using imaging flow cytometery. [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 3074. doi:10.1158/1538-7445.AM2014-3074
Abstract 3086: The genetic landscape of the childhood liver cancer hepatoblastoma
Authors: Kappler Roland , Eichenmüller Melanie , Trippel Franziska , Strom Tim M. , Schweinitz Dietrich von 
Published: May 2015

Abstract
Hepatoblastoma (HB) is the most common malignant liver tumor in children with a histology that resembles various stages of the developing liver. To explore the genetic origin of this cancer, we performed whole-exome sequencing of 8 tumors and matched germline tissue. In average, we detected only three sequence variants per tumor, which is the lowest mutation rate ever reported for any cancer. Mutations of ß-catenin (CTNNB1) displayed the only recurrent event occurring in all tumors, thereby underscoring the significance of activated Wnt signaling in the genesis of HB. Gene ontology analysis revealed a predominance of candidate genes involved in the regulation of gene expression and transcription, including the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2). Targeted resequencing of a cohort of 50 HB cases and cell lines revealed NFE2L2 mutations in 10% of all tumors. Interestingly, all mutations were located in or adjacent to the DLG and ETGE motifs of the NFE2L2 protein that are known to be recognized from the KEAP1/CUL3 complex for proteasomal degradation. In line with this, cells transfected with mutant NFE2L2 were insensitive to KEAP1-mediated downregulation of NFE2L2 signaling. Clinically, overexpression of the NFE2L2 target gene NQO1 in tumor tissues was significantly associated with high tumor stage, metastasis, and poor outcome. These data suggest that activation of NFE2L2-KEAP1 signaling through mutations in NFE2L2 is a prominent characteristic in pediatric liver tumors, thereby advocating inhibition of aberrant NFE2L2 activity as a therapeutic option, especially in high-risk patients with advanced disease.
Citation Format: Roland Kappler, Melanie Eichenmüller, Franziska Trippel, Tim M. Strom, Dietrich von Schweinitz. The genetic landscape of the childhood liver cancer hepatoblastoma. [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 3086. doi:10.1158/1538-7445.AM2014-3086
Abstract 31: Phosphatidylserine-specific phospholipase A1 (PSPLA1) expression in colorectal cancer correlates with tumor invasion and hematogenous metastasis
Authors: Iida Yuuki , Sunami Eiji , Ishihara Soichiro , Yamaguchi Hironori , Tsuno Nelson H. , Kitayama Joji , Watanabe Toshiaki 
Published: May 2015

Abstract
Background: Although the physiological functions of various phospholipases, such as lysophospholipase D (Autotaxin), has been extensively investigated, those of Phosphatidylserine-Specific Phospholipase A1 (PSPLA1), a kind of phospholipase involved in allergic reactions, has not been fully elucidated yet. Here, we evaluated the role of PSPLA1 in oncogenesis and tumor metastasis of colorectal cancer.
Materials and Methods: Surgical specimens of 85 consecutive patients with colorectal cancer who received surgery in our department between January 2005 and December 2005 were immunostained with a monoclonal antibody to PSPLA1. The correlation between PSPLA1 expression and the clinico-pathological variables was analyzed by univariate and multivariate analyses. The impact of PSPLA1 expression on the prognosis of the patients was assessed, in comparison with the other clinico-pathological variables.
Results: PSPLA1 expression significantly correlated with tumor size, tumor depth and hematogenous metastasis in univariate analysis, and tumor depth and hematogenous metastasis were independent variables in multivariate analysis. The disease-free survival (DFS) of patients with high-PSPLA1 expression was significantly shorter compared to those with low expression. The presence of hematogenous metastasis, however, was the only independent factor associated with poor DFS.
Conclusion: PSPLA1 expression in colorectal cancer was associated with tumor invasion and metastasis.
Citation Format: Yuuki Iida, Eiji Sunami, Soichiro Ishihara, Hironori Yamaguchi, Nelson H. Tsuno, Joji Kitayama, Toshiaki Watanabe. Phosphatidylserine-specific phospholipase A1 (PSPLA1) expression in colorectal cancer correlates with tumor invasion and hematogenous metastasis. [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 31. doi:10.1158/1538-7445.AM2014-31
Abstract 3109: ALK as a valid therapeutic target for the treatment of rhabdomyosarcoma
Authors: Wierdl Monika , Tsurkan Lyudmila , Tollemar Viktor , Chi Lying , Stewart Elizabeth , Dyer Michael A. , Potter Philip M. 
Published: May 2015

Abstract
Anaplastic Lymphoma Kinase (ALK) is a transmembrane receptor tyrosine kinase, a member of the insulin receptor family, with a tightly controlled expression pattern. Deregulated ALK expression has been linked to the development of several types of cancers. Typically, chromosomal translocations involving ALK generate constitutively expressed chimeric oncoproteins, such as NPM-ALK in anaplastic large cell lymphoma and EML4-ALK in non-small cell lung carcinoma. However, activating mutations in ALK, and increased copy number that result in aberrant gene expression, have also been observed in neuroblastoma and colorectal cancers. Based on the above observations, several small molecule ALK inhibitors have been developed and are in clinical trials for a variety of tumors expressing this kinase. This has resulted in the use of crizotinib for the treatment of EML4-ALK + lung cancers.
Recently several large scale immunohistochemistry and genome sequencing studies of pediatric rhabdomyosarcoma (RMS) revealed aberrant ALK expression. It was found that ALK mRNA expression was significantly different in alveolar (ARMS) and embryonic RMS (ERMS), the two major histological subtypes in children. Thus, ALK expression might play a role in tumorigenesis for this disease, and this kinase may represent a valid therapeutic target for the treatment of RMS. To answer this question we analyzed ALK expression in a large panel of RMS cell lines, and pediatric tumor samples by quantitative PCR and immunoblotting. We also compared the sensitivity of these cells to a series of ALK inhibitors. Our results indicate that the majority of ARMS cell lines demonstrated significantly higher ALK mRNA expression as compared to ERMS, and to normal human myoblast control cells. This was confirmed by western analysis. Growth inhibition assays confirmed that all RMS lines were more sensitive to crizotinib and LDK-378 than control lines, consistent with the hypothesis that ALK is a driver of cell growth in these tumors.
Based on our in vitro analysis, we suggest that ALK inhibition may represent an effective therapeutic modality for the treatment of ALK+ RMS. Preclinical studies to confirm or disprove this hypothesis are currently underway.
Supported by St. Jude Children's Research Hospital and by the American Lebanese Syrian Associated Charities
Citation Format: Monika Wierdl, Lyudmila Tsurkan, Viktor Tollemar, Lying Chi, Elizabeth Stewart, Michael A. Dyer, Philip M. Potter. ALK as a valid therapeutic target for the treatment of rhabdomyosarcoma. [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 3109. doi:10.1158/1538-7445.AM2014-3109