bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5137: A genome wide RNAi screen identify STAT3 activation as essential for ErbB2 mediated transforamtion of breast cancer cells
Authors: Barrueco Ruth Rodriguez 
Published: August 2012

Abstract
The generation of multidimensional datasets characterizing genetic, epigenetic, and functional properties of large normal and tumor-related samples is creating unique opportunities for the systems-level dissection of mechanisms associated with malignant phenotypes. Integrated data sets may lead to more efficient and specific approaches for the elucidation of therapeutic targets and biomarkers and for the identification of specific small molecule inhibitors. However, the power of these computational methods to study human cancer from an unbiased global perspective is severely compromised by the low through-put approaches necessary to functionally validate the in silico predictions. During the last years, RNA interference (RNAi) emerged as a very powerful genetic strategy to functionally interrogate the entire genome by loss-of-function studies. This cellular process can be experimentally controlled to knock down the expression of any specific gene. Our group has pioneered the development of RNAi-based genetic tools to translate RNAi studies to mammalian systems generating a shRNA-mir pooled lentiviral library that allows performing functional studies at genome-wide level. ErbB2 is a receptor tyrosine kinase found overexpressed in 20-40% of breast tumors correlating with a malignant phenotype and worse prognosis. Different targeted therapies have been developed to specifically inhibit its activity such the monoclonal antibody Herceptin, or the small tyrosine kinase inhibitor Lapatinib. Despite of the success of these inhibitors in the treatment of tumors that overexpress ErbB2, about 30% of them become resistant making necessary to look for alternative targets in these cases. The combination of the state-of-the-art computational analysis and RNAi-based technology toward system biology studies must represent a powerful tool to dissect the regulatory networks that govern the homeostasis of breast tumors. Applying this combined approach to an overexpressing ErbB2 breast cancer model we have identified the genes that are critical in those cells.
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 5137. doi:1538-7445.AM2012-5137
Abstract 5139: Therapeutic targets for neuroblastoma by genome scale siRNA screens
Authors: Howie Heather , Toyoshima Masafumi , Annis James E. , Richard Lauren , Park Julie R. , Grandori Carla 
Published: August 2012

Abstract
∼ 30 % of Neuroblastoma harbor amplifications of the MYCN oncogene, which is the strongest molecular marker of poor prognosis. However, a subset of high-risk neuroblastoma does not carry alterations of the MYCN gene and the molecular pathways underlying their aggressive behavior remains to be elucidated. We have utilized a functional genomics approach with both genetically defined cell systems, as well as molecularly defined neuroblastoma cell lines, to identify critical survival pathways that distinguish MYCN-amplified versus non-amplified neuroblastoma. The results of high throughput siRNA screens targeting the druggable genome will be presented and discussed in light of public microarray data and validation experiments carried out in our laboratory. These findings revealed that different chromatin-remodeling genes, DNA-repair and developmental pathways differentiate MYCN amplified neuroblastoma versus non-amplified, thus highlighting specific new therapeutic targets associated with MYCN status as well as other molecular markers. In addition to pinpointing novel therapeutic targets for high-risk neuroblastoma, our study also functional defines signaling pathways activated in high-risk neruoblastoma and could be utilized to guide rational therapeutic choices.
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 5139. doi:1538-7445.AM2012-5139
Abstract 514: Relationship between loss of heterozygosity of HLA-A gene and HLA class I expression in gastric cancer
Authors: Yoshii Mami , Tanaka Hiroaki , Sakurai Katsunobu , Nagahara Hisashi , Kimura Kenjiro , Amano Ryosuke , Noda Eiji , Kubo Naoshi , Muguruma Kazuya , Yamada Nobuya , Yashiro Masakazu , Maeda Kiyoshi , Sawada Tetsuji , Ohira Masaichi , Ishikawa Tetsuro , Hirakawa Kosei 
Published: August 2012

Abstract
[Introduction]Human leukocyte antigen (HLA), located on 6p21.3, encodes for genes involved in antigen processing and presentation. Loss of heterozygosity (LOH) at 6p21.3 may cause downregulation of HLA class I, and may provide tumor cells with an immune-escape tumor phenotype. The aim of this study is to examine HLA class I expression in gastric cancer tissues and cell lines, to clarify the clinical impact of HLA-A dawnregulation on progression of gastric cancer. [Materials and methods]We examined HLA class I expression in clinical samples from 206 patients by immunohistochemical staining. By flow cytometric analysis, we analyzed the expression of HLA class I antigen in gastric cancer cell lines. Furthermore, we performed HLA-A typing in gastric cancer cell lines by PCR-SBT method. [Results]We observed that HLA class I expression was downregulated in metastatic lymph node compared with in primary lesion. HLA class I expression in primary lesion was associated with ly factors and histological types. Furthermore, patients with negative expression of HLA class I showed significantly poorer prognosis. In vitro, we observed the downregulation of HLA class I antigen in OCUM-2MLN cells which have a high potential for lymph node metastasis. By PCR-SBT method, we detected loss of heterozigosity of HLA-A gene in OCUM-2MLN. [Conclusion]We observed that HLA class I expression was associated with poor prognosis of gastric cancer and LOH of HLA-A was recognized in cancer cell line which has potential to develop lymph node metastasis. Our findings suggested that LOH of HLA-A gene would result in provide cancer cells with capacity to metastasize into lymph nodes.
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 514. doi:1538-7445.AM2012-514
Abstract 5150: Oncogene amplification in glioblastomas associates specifically with the increased expression of multiple glycolytic mediators
Authors: Beckner Marie E. , Kant Jeffrey A. , Pollack Ian F. , Nordberg Mary L. , Hamilton Ronald L. 
Published: August 2012

Abstract
Although aberrant enhancement of glycolytic potential is a defining attribute of malignancy, the underlying mechanisms are complex and difficult to ascertain. A network of contributing factors is suspected to permit multiple inputs and redundancy. In this study, 79 oncogenes in glioblastomas were examined by multiplex ligation-dependent amplification (MLPA) for copy number changes to test for associations with real-time quantitative PCR expression levels of genes encoding lactate dehydrogenases (LDHA, LDHC), ATP citrate lyase (ACLY), glycogen synthase (GYS1), carbonic anhydrases (CA3, CA12), a monocarboxylate transporter (SLC16A3), hypoxia inducible factor-1A (HIF1A), and growth factors (VEGFA, PDGFA, & EGF). All were normalized to housekeeping genes and then adjusted to the level of glycolysis by division with concurrent expression of (ENO1) that encodes enolase, a key glycolytic enzyme. Tumors were separated into two groups by a cut-off of 1.10 times ENO1 to define increased and non-increased gene expression relative to glycolysis. Except for CA12 (increased in almost all tumors), expression levels yielded two groups to quantify differences in regard to the percent of tumors with amplified oncogenes. Copy numbers of oncogenes determined by MLPA to be at least 3-fold greater than normal brain DNA (tested concurrently) defined increased levels of amplification for each gene. Of the 17 amplified oncogenes (0-6 per tumor), EGFR was most frequent (11/22 tumors). The greatest difference (52%, p = 0.01) occurred between increased versus non-increased LDHC groups for tumors with amplified oncogenes. The table lists differences for each gene. Thus, amplified oncogenes associate specifically with enhanced expression levels of genes for glycolytic mediators in glioblastomas. Identification of the amplified oncogenes (EGFR &/or others) in individual tumors provides potential targets for down-regulating aberrant glycolysis in brain tumors.

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 5150. doi:1538-7445.AM2012-5150
Abstract 5161: Role of glutamine in cancer growth, invasion and progression: Therapeutic modulation of glutamine pathway
Authors: Yang Lifeng , Nagrath Deepak 
Published: August 2012

Abstract
Glutamine, an alternative carbon source to glucose, has recently been shown to be important for the cancer cell survival, growth and progression. The link between glycolysis, glutaminolysis and fatty acid oxidation is not known. Thus, there is a strong motivation to study metabolic alternations caused by glutamine and uncover links between various fuel sources for highly and less invasive cancer cells. Here, we postulate that glutamine will increase glutamine uptake through up-regulating ASCT2 expression, while decreasing the glucose uptake by down-regulating GLUT1 expression for aggressive cancer cells. However, for non-aggressive cancer cells, glutamine will have no effect on glutamine and glucose uptake. Our findings indicate that NAD+/NADH ratio regulates the glutamine's direct effect on the lactate production irrespective of the bioenergetic substrate requirement for different kinds of cancer cells. Our findings using quantification of metabolites pertaining to central carbon and nitrogen metabolism provided clues as to which pathways relevant to glycolysis, the pentose phosphate pathway, the TCA and urea cycles, lipid cycle, and amino acid and nucleotide metabolisms, may be altered by glutamine in cancer cells, resulting in identification of dominant factors which control cancer metabolism. Through this study, we clearly demonstrate the exact of glutamine's effect on cancer metabolism. Our results set the stage for the development of glutaminolysis inhibitors based therapeutics for reprogramming of cancer metabolism. We believe that development of our oncosecretomics based metabolic strategy provides an unprecedented opportunity for the development of nutritional supplementation that can deregulate the adaptations and alterations induced by various nutrients in cancer metabolism.
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 5161. doi:1538-7445.AM2012-5161
Abstract 517: Anti-glycan IgM and IgG antibodies as new biomarkers for serous ovarian cancers
Authors: Tse Brian WC , Jacob Francis , Pochechueva Tatiana , Nixdorf Sheri , Fedier Andre , Huflejt Margaret , Bovin Nicolai , Fink Daniel A. , Hacker Neville F. , Heinzelmann-Schwarz Viola A. 
Published: August 2012

Abstract
Introduction: Patients with advanced-stage serous cancers (ovarian, peritoneal and tubal) often develop ascites, a protein-rich fluid within the peritoneal cavity which causes significant morbidity and is associated with a poor prognosis. Aberrant glycosylation is a common feature of these cancers and this may impact on the humoral immune response. We hypothesized that serous cancer patients and healthy women have different profiles of anti-glycan antibodies in plasma and ascites. Method: Matched pairs of plasma and ascites were collected from 11 patients with advanced stage disease. A custom-made printed glycan array (PGA) allowed the simultaneous detection of anti-glycan antibodies (AGAs) to 203 chemically synthesised glycans, including some tumour-associated carbohydrate antigens. Identified candidate AGAs were additionally detected using a suspension array in an independent patient cohort of 230 patients. Candidates were selected by their discriminatory power between cancer and healthy controls. One top candidate was further analyzed for its biological behavior using ovarian cancer cell lines. Results: Using PGA, we detected a multitude of AGAs in both plasma and ascites. Levels of AGAs in serum and ascites correlated independent of ascites volume. Serous cancer patients had significantly different levels of plasma IgM to 31 glycans when compared to plasma of 14 healthy control patients, with IgM levels being lower in the cancer group. Significant differences in IgG plasma levels were found for 4 glycans. The trisaccharide P1, part of the P blood group system, was selected for further analyses. Plasma expression of P1 was found independent of cohort and method used. The human serous ovarian cancer cell line, IGROV1, was shown to express P1 and was subsequently sorted into P1-high, P1-low, and P1-negative subpopulations. We found that IGROV1/P1-expressing cells correlated with faster tumor cell migration and invasion. Treatment with a human anti-P1 IgM (clone P3NIL100) inhibited the proliferation of these tumour cells in vitro. Conclusion: P1 expression can be detected in ovarian cancer patients in independent of cohorts. P1 seems to be involved in cancer migration and invasion, and is therefore a potential target for ovarian cancer diagnosis and therapy.
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 517. doi:1538-7445.AM2012-517
Abstract 518: Immunogenicity of cancer/testis antigen XAGE-1d in patients with non-small cell lung cancer (NSCLC)
Authors: Matsumoto Hirofumi , Ohue Yoshihiro , Eikawa Shingo , Mizote Yu , Kurose Koji , Isobe Midori , Uenaka Akiko , Nagayasu Takeshi , Oka Mikio , Nakayama Eiichi 
Published: August 2012

Abstract
BACKGROUND: Cancer/testis (CT) antigens expresses in various cancers and normal testis. Because of no expression of HLA class-I antigen in normal testis, CT antigens are promising molecular target for specific cancer immunotherapy. XAGE-1 gene has been identified as a CT-like antigen, and XAGE-1 gene has four alternative splice variants: XAGE-1a, XAGE-1b, XAGE-1c, and XAGE-1d. We previously reported that the transcript of XAGE-1a and XAGE-1b coded the same protein (GAGED2, isoform a, 81 amino acids) and the transcript of XAGE-1d coded another protein (GAGED2, isoform b, 69 amino acids). The first half of XAGE-1b and 1d protein (1-32 amino acids) is same sequence. On the other hand, XAGE-1c transcript codes some peptides but not a protein. Previously, immunogenic analyses of XAGE-1b have been performed because of its dominant expression, however, few analysis of XAGE-1d was performed. In this study, we investigated the immunogenicity of XAGE-1d in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Tumor tissue samples for extracting mRNA were obtained from NSCLC patients treated surgical resection at Nagasaki University Hospital during the period from 2005 to 2010. Sera and PBMCs were obtained from NSCLC patients who visited Kawasaki Medical School Hospital during the period from 2005 to 2010. Splising variants of XAGE-1 gene were analyzed by quantitative real-time PCR with specific TaqMan probe-primer sets. Antibody responses to XAGE-1d were analyzed by ELISA using synthesized XAGE-1b protein. In antibody-positive patients, CD4+ T-cell responses against XAGE-1d were examined by IFN-γ ELISA. Epitope-peptides recognized by XAGE-1d specific T-cells were determined by ELISA using XAGE-1d-overlapping peptides (OLPs). RESULTS: In quantitative real-time PCR, expression of XAGE-1d mRNA was observed in 16/38 specimens (42.1%) that were also positive with XAGE-1b mRNA. The correlation coefficiency of the expression was 0.8047. Protein expression of XAGE-1d was observed in cytoplasm, being different from that of XAGE-1b in the nucleus in lung cancer cell lines by immunohistochemical staining. Antibody against XAGE-1d was detected in lung cancer patients who were also positive with XAGE-1b antibody. By a limiting dilution, a CD4+ T-cell clone was obtained from PBMCs in a seropositive patient. HLA class II restricted recognition of XAGE-1d was confirmed using various allogeneic EBV-B cells as APC. 14-mer minimal epitope peptide was determined. CONCLUSION: The findings indicate that XAGE-1d co-expresses with XAGE-1b and is immunogenic in NSCLC patients.
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 518. doi:1538-7445.AM2012-518
Abstract 5181: Dynamic cellular adhesivity of breast cancer cells conferred by CD44 varies with mesenchymal or epithelial phenotype
Authors: Delgadillo Luis F. , Shirure Venktesh S. , Liu Tiantian , Goetz Douglas J. , Benencia Fabian , Burdick Monica M. 
Published: August 2012

Abstract
CD44 is a highly pleiotropic molecule whose many structural variants and glycan modifications determine function, particularly with respect to cell adhesion. In this study, we investigated the E-selectin ligand function of CD44 and its relationship with the mesenchymal versus epithelial cell phenotypes of breast cancer cells. Real time RT-PCR analysis for epithelial and mesenchymal cell markers showed that MDA-MB-231 and Hs-578T breast cancer cells are mesenchymal-like cells, but BT-20 and MDA-MB-468 breast cancer cells are epithelial-like cells. Flow cytometry revealed that all cell lines expressed CD44. Further exploration of the expression of specific CD44 isoforms at the mRNA level (by real time RT-PCR) and at the protein level (by flow cytometry) showed that mesenchymal-like breast cancer cells predominantly expressed CD44s but nearly undetectable levels of CD44v isoforms. On the other hand, epithelial-like cells expressed CD44s as well as CD44v isoforms. These results indicate that there are divergent CD44 isoform expression patterns in mesenchymal-like versus epithelial-like breast cancer cell lines. Further distinctions were observed in CD44 function in cells of the two phenotypes. Western blot analysis demonstrated that CD44 expressed by BT-20 cells were positive for E-selectin ligand activity, whereas CD44 of MDA-MB-231 cells failed to exhibit such functionality. Moreover, CD44v isoforms expressed by BT-20 cells, but not CD44s by MDA-MB-231 cells, mediated E-selectin adhesion under physiological flow conditions. Despite the positive ligand activity, none of the CD44v isoforms expressed by BT20 cells possessed HECA-452 reactivity by Western blot analysis. This finding indicates the absence of conventional sialofucosylated carbohydrates and the presence of potentially novel E-selectin reactive glycans. Collectively, these results show that CD44 expressed by epithelial-like cells, but not mesenchymal-like cells, are functional E-selectin ligands. Our investigation therefore implies an association of breast cancer cell adhesivity with the epithelial phenotype. Thus, future studies mechanistically linking the E-selectin ligand activity of CD44 isoforms with epithelial-to-mesenchymal transition may provide targets for novel breast cancer diagnostics, prognostics, and therapeutics.
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 5181. doi:1538-7445.AM2012-5181
Abstract 5267: Mouse models of cancer at The Jackson Laboratory Repository
Authors: Boswell Deborah M. , Rockwood Stephen F. , Sasner Michael , Lutz Cathleen M. , Davisson Muriel T. , Donahue Leah Rae 
Published: August 2012

Abstract
As one of the largest collections of characterized mouse strains available, The Jackson Laboratory Repository serves the scientific community as a resource to archive and distribute mouse models. Among the hundreds of new strains acquired or developed annually are a transgenic model for prostate hyperplasia that progresses to adenoma/adenocarcinoma, a transgenic model of large B cell lymphoma similar to tumors seen in patients with SLE and Sjogren's syndrome; and a targeted mutation strain of Lats1 (large tumor suppressor) that develops soft tissue sarcomas, ovarian stromal cell tumors and increased sensitivity to carcinogens. Conditional (floxed) strains that are useful in generating tissue-specific mutants have been recently added to the Repository and include mutations of Perp (TP53 apoptosis effector), Msh2 (mutS homolog 2, E. coli), and Irf8 (interferon regulatory factor 8). A transgenic strain that expresses Cre recombinase specifically in the large intestine has applications in colon cancer research. A combination mutant strain (containing targeted mutations of Vhl, von Hippel-Lindau tumor suppressor, and Pten, phosphatase and tensin homolog, and a transgene with Cre recombinase expression driven by Cdh16, cadherin 16) is a model for benign mixed adenosquamous genital tract tumors resembling clear cell cystadenomas observed in patients with Von Hippel-Lindau syndrome. The TEL-AML1 (Etv6-RUNX1, t12;21) translocation/fusion protein associated with childhood acute lymphoblastic leukemia is conditionally expressed by a targeted mutation strain. For transplantation research, a number of “humanized” mouse strains are available. These typically are immune compromised lines and/or lines that provide continuous circulation of human growth factors supporting a platform for a humanized microenvironment. A number of new research tool strains have been added to the Repository, including a fluorescent reporter for carcinoma metastasis, the Cre reporter R26R-Confetti strain which allows individual cell labeling with nuclear-localized membrane-targeted or cytoplasmic fluorescent proteins, and transgenic strains expressing the KikGR flurorescent protein which changes color from green to red upon activation. The Repository maintains a searchable on-line resource (www.jax.org) for each strain. Researchers can submit their strains by using the on-line form available at The Jackson Laboratory website: www.jax.org/donate-a-mouse. Supported by NIH, HHMI, The Ellison Medical Foundation and several private charitable foundations.
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 5267. doi:1538-7445.AM2012-5267