bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4136: Development of a new and sensitive detection technology for galectin cancer proteins.
Authors: van Hattum Hilde , Ruijtenbeek Rob , Hilhorst Riet , Pieters Roland 
Published: August 2014

Abstract
The galectin protein family consists of fifteen galactoside-binding proteins that are present in all classes of life where they function as cell-cell and cell-matrix interaction mediators. Galectins are however also highly overexpressed in various processes related to cancer, including apoptosis, angiogenesis and metastasis. Galectins are therefore excellent targets for tumor diagnostics and medical prognostic purposes. Current proteomic tools, e.g. Polymerase Chain Reaction (PCR) and Enzyme-linked Immunosorbent Assay (ELISA), are based on protein abundance rather than protein activity. In contrast, we have developed a galectin detection assay that visualizes galactoside-binding, i.e. functional, galectins using PamChip® microarray technology. Firstly, antibodies directed against different galectins are efficiently immobilized on the microarray surface by the Fc-binding protein A/G. Then galectin-1 was captured from a spiked cell lysate that is added to the microarray and the unbound proteins are washed away. The galectin presence is subsequently quantified with a general fluorescent ligand that is only bound by active galectins. Several ligands based on lactose and lactosamine were designed and tested. With the best ligands it was possible to detect galectin quantities in the low nanogram range using only 1 μg or less of precious anti-galectin antibodies per measurement. These results are truly promising for the use of the newly developed galectin detection technology in a clinical setting.
Citation Format: Hilde van Hattum, Rob Ruijtenbeek, Riet Hilhorst, Roland Pieters. Development of a new and sensitive detection technology for galectin cancer proteins. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4136. doi:10.1158/1538-7445.AM2013-4136
Abstract 4140: Negative enrichment of circulating tumor cells using geometrically activated surface interaction (GASI) chip.
Authors: Jung Hyo-Il , Hyun Kyung-A , Lee Tae Yoon 
Published: August 2014

Abstract
Circulating tumor cells (CTCs), existing extremely rare in peripheral blood (the order of one cell per 1* 106 nucleated cells), have attracted a lot of attention as they can be exploited to investigate metastasis. The isolation of intact CTCs is challenging owing to their rarity and heterogeneous features.
A lot of methodologies for CTCs enrichment in blood were focused using antibodies to epithelial cell adhesion molecule (EpCAM). However, the recent studies found that the CTCs undergo a process of epithelial-mesenchymal transition (EMT) to adapt oneself to new circumstances which is blood stream and down regulated EpCAM expression on their surface. It is thought that the many CTCs may escape detection by conventional detection methods. So, we decided to use the negative enrichment (i.e. capturing WBCs which are non-target cells and eluting CTCs which are target cells) for isolation of intact and heterogeneous CTCs.
To capture a large number of WBCs in the channel, we developed a geometrically activated surface interaction (GASI)-Chip which is based on the asymmetric herringbone that generate the enhanced mixing flows increasing the surface interaction between the WBCs and CD45 antibody-conjugated channel surface. Using the optimized experimental conditions, we isolated 94.67% of MCF-7 cells (breast cancer cell line) and eliminated 98.94% of Jurkat cells (human T cell lymphoblast like cell line) at 20 μL/min flow rate.
Based on these results, we have attempted to isolate CTCs from patients with several kinds of metastatic cancer patients under the same conditions. The blood samples (1ml) were collected from breast, gastric and lung cancer patients, respectively. After blood samples passed through the GASI-Chip, collected cells were fixed on a slide glass and stained with DAPI for DNA content, PE conjugated Cytokeratin for CTC, and FITC conjugated CD45 for WBC. Following imaging the slide glass, captured images were examined carefully with predefined criteria (DAPI positive, Cytokeratin positive, CD45 negative). The number of isolated CTCs varied from 1 to 51 in 1 ml of blood. Although this device was not intended to process full clinical blood draws, which typically yield 7.5 mL, quite a number of CTCs can be detected from only 1ml of blood compared with other approaches based on the characters of CTCs such as size. Furthermore, the intact and heterogeneous CTCs can be isolated regardless of EpCAM expression because our devices do not require any labeling processes (e.g., EpCAM antibody for CTC).
Citation Format: Hyo-Il Jung, Kyung-A Hyun, Tae Yoon Lee. Negative enrichment of circulating tumor cells using geometrically activated surface interaction (GASI) chip. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4140. doi:10.1158/1538-7445.AM2013-4140
Abstract 4176: MicroRNA-193b is growth-inhibitory in Ewing sarcoma, and represses ErbB4.
Authors: Moore Colin , Jedlicka Paul 
Published: August 2014

Abstract
Ewing sarcoma, the second most common cancer of bone and soft tissue in adolescents and young adults, is an aggressive malignancy with poor long-term outcome. Ewing sarcoma is driven primarily by the EWS/Fli-1 fusion oncoprotein, which arises from the recurrent t(11,22) translocation. Our laboratory has been interested in identifying microRNAs (miRs) with growth-modulating properties in Ewing sarcoma, manipulation of which could potentially be used for novel therapies, as shown in preclinical studies for other cancers. We have previously shown that replacement of select miRs, normally repressed by EWS/Fli1, can inhibit the growth of Ewing sarcoma cells. To identify additional, and more potent, miRs with growth-suppressive properties in EWS, we have performed a phenotype-based, secondary miniscreen in Ewing sarcoma cell lines. This screen, using transfection of miR mimics into the EWS cell lines A673 and SK-ES-1, followed by growth assays as read-out, identified miR-193b as a strong candidate growth suppressive miR in Ewing sarcoma. Subsequent cloning and stable overexpression of endogenous miR-193b verified the growth suppressive phenotype. Examination of candidate targets further identified ErbB4 as potently repressed upon miR-193b overexpression. ErbB4 has recently been shown to play a key role in Ewing sarcoma, specifically as a driver of metastasis and as a mediator of resistance to cytotoxic chemotherapy, key biological parameters that define high-risk disease. With the need for therapy expansion in pediatric EWS, miR-193b replacement, through ErbB4 inhibition, may be a way to help control high-risk disease.
Citation Format: Colin Moore, Paul Jedlicka. MicroRNA-193b is growth-inhibitory in Ewing sarcoma, and represses ErbB4. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4176. doi:10.1158/1538-7445.AM2013-4176
Abstract 4190: miR-30 as a tumor suppressor connects EGF/Src signal to EMT and ERG.
Authors: Kao Chiao-Jung , Martiniez Anthony , Shi Xu-Bao , Dobi Albert , de Vere White Ralph W. , Kung Hsing-Jien 
Published: August 2014

Abstract
Src tyrosine kinase (Src) is implicated in the development of bone metastasis and castration-resistance of prostate cancer. Src inhibitors are currently being tested in clinical trials for such diseases. Understanding the molecular and cellular actions of Src inhibitors holds the key to future improvement of this line of therapy. Here we describe the microRNA expression profiles modulated by two Src inhibitors and demonstrate that the miR-30 family members are the most prominently induced species. Consistent with its tumor suppressor role, miR-30 is downmodulated by oncogenic signals such as epidermal growth factor (EGF) and hepatocyte growth factor (HGF), and is generally underexpressed in prostate cancer specimens. A number of epithelial to mesenchymal transition (EMT)-associated genes are predicted targets of miR-30. Among these genes the Ets Related Gene (ERG) is the most frequently overexpressed-oncogene in prostate cancer activated by genomic fusion events between promoter upstream sequences of the TMPRSS2 and coding sequences of ERG. We showed by ERG 3’UTR-reporter and mutagenesis assays that ERG is a direct target of miR-30. Overexpression of miR-30 in prostate cancer cells suppresses EMT phenotypes and inhibits cell migration and invasion. It also inhibits the in vitro and in vivo growth of VCaP cells, which depends on TMPRSS2-ERG for proliferation. TMPRSS2-ERG is generally regulated by androgen at the transcriptional level. Our finding reveals a new post-transcriptional mechanism of TMPRSS2-ERG regulation by Src and growth signals via miR-30 providing a rationale for targeting ERG positive castration resistant tumors with Src inhibitors.
Citation Format: Chiao-Jung Kao, Anthony Martiniez, Xu-Bao Shi, Albert Dobi, Ralph W. deVere White, Hsing-Jien Kung. miR-30 as a tumor suppressor connects EGF/Src signal to EMT and ERG. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4190. doi:10.1158/1538-7445.AM2013-4190
Abstract 4198: MiR-17-92 cluster promotes human cholangiocarcinoma growth upon the activation of STAT3 signaling pathway.
Authors: Zhu Hanqing , Han Chang , Wu Tong 
Published: August 2014

Abstract
MiR-17-92 cluster is a potent oncogenic miRNA which has been shown to promote cell proliferation, increase angiogenesis and sustain cell survival in several cancer types. However, the potential role of miR-17-92 cluster in hepatic carcinogenesis has not been investigated. This study was designed to examine the impact of miR-17-92 in hepatic cancer cells. qRT-PCR analysis showed that the expression of miR-17-92 cluster is increased in several human hepatic cancer cell lines compared to the transformed, non-cancerous hepatic cell line, THLE-2. In addition to that, paraffin slides from human hepatic cancer sample also show higher expression of miR-19a as a result of in situ hybridization. The miR-17-92 inhibitors (blocking each individual miRNAs within the cluster) prevented hepatic cancer cell growth. In contrast, stable transfection of pri-miR-17-92 cluster increased cholangiocarcinoma cell (CCLP-1) proliferation. IL-6 treatment greatly upregulates the miR-17-92 cluster mRNA and each individual miRNA level. However, blocking IL-6/STAT3 signaling by STAT3 siRNA or STAT3 phosphorylation inhibitor both inhibit upregulation of miR-17-92 by IL-6 stimulation. Since there is a reported binding site on promoter region of miR-17-92 cluster for STAT3, we used synthesized DNA probe to precipitate STAT3, and found IL-6 treatment increases the STAT3 binding to the promoter of miR-17-92. IL-6 stimulates CCLP-1cell growth, but blocking miR-17-92 will abolish this effect. Targetscan and other prediction tools were used to predict many possible targets of miR-17-92, such as PTEN. Western blot analysis showed decreased PTEN protein level in CCLP-1 cells transfected with the pri-miR-17-92 cluster, suggesting that PTEN may represent one of the miR-17-92 downstream targets. Further experiments are undergoing to show the IL-6 activates STAT3 and thus promote cholangiocarcinoma cell growth through increasing miR-17-92 cluster level.
Citation Format: Hanqing Zhu, Chang Han, Tong Wu. MiR-17-92 cluster promotes human cholangiocarcinoma growth upon the activation of STAT3 signaling pathway. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4198. doi:10.1158/1538-7445.AM2013-4198
Abstract 4203: Overexpression of miR-26a-2 in human liposarcoma is correlated with poor patient survival.
Authors: Lee Dhong Hyun Tony , Amanat Soroosh , Goff Catherine , Weiss Lawrence , Cutter Suzanne , Said Jonathan , Doan Ngan , Ogawa Seishi , Matsubara Aiko , Forscher Charles , Koeffler H.Phillip 
Published: August 2014

Abstract
Approximately 90% of well-differentiated/de-differentiated LPS (WDLPS/DDLPS), the most common LPS subtype, have chromosomal amplification at 12q13-q15. Many protein-coding genes in the region, such as MDM2 and CDK4, have been studied as potential therapeutic targets for LPS treatment with minimal success. Within this amplicon near the MDM2 gene, our SNP array analysis identified frequent amplification of miR-26a-2. Besides being in the amplicon, we found that miR-26a-2 is overexpressed significantly in WDLPS/DDLPS, as well as in myxoid/round cell LPS (MRC). Furthermore, Kaplan-Meier survival analysis showed that overexpression of miR-26a-2 significantly correlated with poor patient survival in both types of LPS.
Based on these findings, we hypothesized that miR-26a-2 plays an important role in LPS tumorigenesis, regardless of LPS subtypes. Overexpression of miR-26a-2 in LPS cells could help the growth and survival of cancer cells in a cell type-specific manner, including faster cell proliferation, faster cell migration, enhanced clonogenicity, suppressed adipocyte differentiation, and/or resistance to apoptosis. Inhibition of miR-26a-2 in LPS cells using anti-miR-26a-2 resulted in the opposite responses.
To explain further the effect of miR-26a-2 overexpression in LPS cells, we performed in sillico analysis and identified 93 candidate targets of miR-26a-2. Among these candidate genes, we found that RCBTB1 (RCC1 and BTB domain containing protein 1) was located at 13q12.3-q14.3, a recurrent region of loss of heterozygosity (LOH) in human LPS. Indeed, overexpression of RCBTB1 made cells more susceptible to apoptosis. Likewise, inhibition of RCBTB1 made cells more resistant to apoptosis.
In conclusion, our study reveals, for the first time, the contribution that miR-26a-2 makes to LPS tumorigenesis, partly through inhibiting RCBTB1. Our study shows that miR-26a-2 is a novel therapeutic target for human LPS.
Citation Format: Dhong Hyun Tony Lee, Soroosh Amanat, Catherine Goff, Lawrence Weiss, Suzanne Cutter, Jonathan Said, Ngan Doan, Seishi Ogawa, Aiko Matsubara, Charles Forscher, H.Phillip Koeffler. Overexpression of miR-26a-2 in human liposarcoma is correlated with poor patient survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4203. doi:10.1158/1538-7445.AM2013-4203
Abstract 4243: Regulation of H3K9 methylation by the demethyltransferase gene JMJD1C in multiple myeloma.
Authors: LoBello Janine , DiPerna Danielle , Gale Moly , Watanabe Aprill , Hostetter Galen , Fonseca Rafael , Salhia Bodour 
Published: August 2014

Abstract
Increasing evidence points towards the importance of epigenetic changes in the pathogenesis of multiple myeloma (MM). The biochemical modifications that govern epigenetics are DNA methylation, and post-translational modifications of histone proteins. Histone methylation is catalyzed by histone methyltransferases (HMT) and histone demethylases (HDMT). The purpose of our study was to interrogate genomics data to identify HMT or HDMT genes that are altered in MM. We mined copy number, gene expression and whole genome sequencing data generated as part of the Multiple Myeloma Research Consortium Genomics Initiative. Collectively, the datasets converged on numerous alterations involving histone methylation of lysine 9 (H3K9). One of these genes, the HDMT JMJD1C, was over-expressed in approximately 15% of MM samples examined. We validated over-expression of JMJD1C expression by RT-PCR in over 50 clinical MM samples and 10 human myeloma cell lines (HMCLs). We also confirmed over-expression of JMJD1C by immunohistochemistry (IHC) in a tissue microarray (TMA) consisting of over 60 MM samples. Next we demonstrated a negative correlation between JMJD1C expression and H3K9 methylation by IHC and western blot in 6/10 HMCL and in over 60% of clinical samples examined on the TMA. This validates the H3K9 demethylase activity of JMJD1C. Furthermore, we demonstrated that, in general, H3K9 methylation, a repressive mark associated with heterochromatin, is low in a large percentage of samples. To study the functional significance, we generated a double knockout isogenic cell line pair in U266 cells using zinc finger nuclease technology. We performed ChIP-seq and RNA-seq analyses to identify genes affected by JMJD1C binding to H3K9. Our data indicate that loss of JMJD1C expression alleviates the repression conferred by H3K9 methylation in MM. Studies are ongoing to realize JMJD1C as a potential and novel therapeutic target in MM.
Citation Format: Janine LoBello, Danielle DiPerna, Moly Gale, Aprill Watanabe, Galen Hostetter, Rafael Fonseca, Bodour Salhia. Regulation of H3K9 methylation by the demethyltransferase gene JMJD1C in multiple myeloma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4243. doi:10.1158/1538-7445.AM2013-4243
Abstract 4250: DNA methylation portraits of breast cancer in a population-based cohort.
Authors: Gindin Yevgeniy , Davis Sean , Walker Robert L. , Zhu Yuelin J. , Bilke Sven , Sherman Mark E. , Figueroa Jonine , Meltzer Paul S. 
Published: August 2014

Abstract
Genome scale molecular profiling methods have had a major impact on the classification, diagnosis, and management of breast cancer. However, the biological basis and fundamental consequences of differential DNA methylation across molecular breast cancer subtypes is incompletely understood. In this study, we used gene expression and DNA methylation data from 208 unselected breast cancer samples obtained from a Polish population-based study. We used a network biology approach to identify gene co-methylation modules - sets of highly correlated DNA methylation probes. We found two gene co-methylation modules strongly correlated with Basal (hypermethylated in Basal) and Luminal B (hypermethylated in Luminal B) breast cancer subtypes. Functional analysis of the Basal gene co-methylation module shows that it significantly overlaps with genes silenced during epithelial to mesenchymal transition. The Luminal B gene co-methylation module significantly overlaps with gene targets of the Polycomb repression complex 2. Kaplan-Meier survival analysis revealed poor prognosis associated with hypermethylation of the Luminal B gene co-methylation module. This study offers new biological perspectives of the vital role of DNA methylation in breast cancer.
Citation Format: Yevgeniy Gindin, Sean Davis, Robert L. Walker, Yuelin J. Zhu, Sven Bilke, Mark E. Sherman, Jonine Figueroa, Paul S. Meltzer. DNA methylation portraits of breast cancer in a population-based cohort. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4250. doi:10.1158/1538-7445.AM2013-4250
Abstract 4251: Genomewide methylation and expression profiles in cervical cancer.
Authors: Yongil Kwon , Lee Nakwoo , Lee Sungjong 
Published: August 2014

Abstract
Cervical carcinoma is one of the most common cancers in females. This cancer begins with precancerous stages and can evolves to carcinoma over 10 years or more. Cervical cancer is a multistep process with accumulation of genetic and epigenetic alterations in regulatory genes, leading to activation of oncogenes and inactivation or loss of tumor suppressor genes. We aimed to identify genetic alterations associated with pre-cancerous stage and also with cervical cancer. For this purpose, microarray comparative genomic hybridization(Illumina 450K and Illumina Expression HT12 Human CGH Whole-Genome Arrays) was performed with 16 cases of cervical intraepithelial neoplasia(CIN) of different stages and 3 cases of carcinoma. We identified epigenetic inactivation of TSGs by hyper- or hypo-methylation which has been recognized as an important and alternative mechanism in tumorigenesis. Here we discuss these epigenetic alterations in cervical intrapeithelial neoplasia and cervical cancer focusing on DNA methylation.
Citation Format: Kwon Yongil, Nakwoo Lee, Sungjong Lee. Genomewide methylation and expression profiles in cervical cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4251. doi:10.1158/1538-7445.AM2013-4251
Abstract 4252: Redefining the DNA methylome of prostate cancer using DNA methylation arrays.
Authors: Ramalho-Carvalho Joao , Henrique Rui , Sayols Sergi , Gomez Antonio , Jerónimo Carmen , Esteller Manel 
Published: August 2014

Abstract
Prostate cancer (PCa) is the most common noncutaneous malignancy and a leading cause of cancer death among men. Clinically localized disease might be successfully treated whereas disseminated disease remains mostly lethal. During prostate cancer development and progression, tumor cells undergo abnormal epigenetic modifications, including DNA methylation alterations. DNA methylation is the most studied epigenetic alteration in human cancer, and is associated with transcriptional repression of both coding and non-coding regions of the genome. Aberrant DNA methylation is gaining force in the fields of cancer risk assessment, diagnosis and therapy monitoring in different cancer types, including prostate cancer. Importantly, aberrant hypermethylation is widespread during neoplastic alteration of prostate cells, suggesting that restoration of a normal prostate epigenome through treatment with demethylating drugs could be clinically beneficial.
The main aim of this work was to identify new epigenetically downregulated CpG's in PCa, using the 450K cytosine microarray-based approach, followed by validation in a larger set of clinical samples.
We used the Infinium HumanMethylation450 BeadChip (Illumina) to consistently and significantly detect CpG methylation changes in prostate cancer tissues in comparison with morphological normal prostate tissue. The selected genomic regions were validated by pyrosequencing. The methylation data were subsequently confirmed at mRNA level using qRT-PCR. To prove the functional role of aberrant DNA methylation, we also performed a treatment with 5-Aza-2′-Deoxycytidine in PCa cell lines.
Our work might provide new translational applications to the clinical management of PCa patients, based on of DNA methylation changes in PCa.
Citation Format: Joao Ramalho-Carvalho, Rui Henrique, Sergi Sayols, Antonio Gomez, Carmen Jerónimo, Manel Esteller. Redefining the DNA methylome of prostate cancer using DNA methylation arrays. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4252. doi:10.1158/1538-7445.AM2013-4252