bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5078: Identification of novel gene fusions by RNA-seq in gastric cancer
Authors: Cho Geun-A , Kim Hwang-Phill , Shin Jong-Yeon , Lee Won-Cheol , Yoon Young-Kwang , Han Sae-Won , Kim Jong-Il , Seo Jeong-Sun , Kim Tae-You 
Published: August 2012

Abstract
The recent discoveries of gene fusions in prostate cancer, lung cancer and gastric cancer suggested that gene fusion could be recurrent and tumorigenic also in carcinoma not only in haematological malignancies. Here, we have found 19 novel fusion genes and fusion transcripts in 12 gastric cancer cell lines. Using the paired-end RNA-seq approach, we obtained a list of 282 fusion genes and fusion transcripts candidates in 12 gastric cancer cell lines. Among these 282 candidates, we selected 25 candidates to examine: 22 candidates whose number of junction read was greater than 10 and 3 additional candidates whose loci are closely related to 22 previously selected candidates. We validated the candidates via Sanger sequencing. As a result, 19 out of 25 candidates were validated: 7 inter-chromosomal fusions and 12 intra-chromosomal fusions including 6 read-through events. We also performed long-range PCR to confirm genomic rearrangements, through which six candidates did not show any evidence of DNA rearrangements. These six candidates were assumed to be fusion transcripts without DNA-level rearrangements while the others are fusion genes that result from chromosomal rearrangements. Furthermore, we investigated the frequencies of all the 19 validated candidates in normal and tumour tissue pairs of 17 gastric cancer patients to determine whether these fusions are recurrent in other tumours and exist in actual cancer patients. Two inter-chromosomal fusion genes, CCDC67-VAV2 and PVT1-ATE1 were detected only in tumour tissues but in low frequencies: 2/17(11.8%) and 1/17(5.9%) respectively. BCAP29-DUS4L, a read-through event, was detected in 12 tumour tissues, 10 of which were only observed in tumour tissues not in the matched normal pairs. Taken together, we have found 13 fusion genes and 6 fusion transcripts in 12 gastric cancer cell lines, some of which are tumour-specific or highly recurrent in tumour tissues. We believe this study might contribute to find oncogenic fusion genes which can be potential biomarkers or therapeutic targets.
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 5078. doi:1538-7445.AM2012-5078
Abstract 510: Identification and characterization of immunogenic epitopes from CD133 and their potential for use to immunologically target cancer stem cells
Authors: Pinilla Clemencia , Judkowski Valeria , Bunying Alcinette , Ji Jianfei , Li Zhenhua , Bender James , Yu John S. 
Published: August 2012

Abstract
CD133 is a marker that identifies cancer stem cells (CSC) on many solid tumors and its expression has been correlated with shortened survival. Although expressed on many normal tissues and stem cells, CD133 is overexpressed on CSC and normal SC are negative or express low levels of MHC making them less sensitive to recognition by CD8+ cytotoxic T lymphocytes (CTL). Potential CTL epitopes were identified by algorithms to predict binding to HLA-A2. Binding studies showed high affinity binding and low off rates for four candidate epitopes. CTL induction studies using IL-12 secreting dendritic cells to stimulate CD8+ T cells evaluated the immunogenicity of the candidate peptides after three or four weekly in vitro stimulations. Multimer and IFNγ responses were observed with CD133-753, 405 and 708 epitopes. Subsequent studies demonstrated killing of T2 cells loaded with peptide. To evaluate the potential for autoimmunity, mouse homolog peptides of the 753 and 405 epitopes that were shown to have high affinity binding to human HLA-A2 were used to immunize HLA-A2 transgenic mice (9CB6F1-Tg (HLA-A*0201/H2-Kb) A*0201). Mice were immunized 3 times at 3 week intervals in IFA + HBV helper peptide and spleens were harvested 2 weeks after the last immunization and stimulated in vitro for one week with peptide pulsed LPS stimulated- APC. An additional group was sacrificed 6 weeks after the last immunization and studied. IFNγ ELISpot assays showed immune responses to the 753 and 405 peptides in 35% and 40% of mice. Organs, including heart, lung, liver, kidney, stomach, intestine, brain, bone marrow, gonads, and eyes from mice with immune responses were found to be negative for lymphocytic infiltrations supporting a lack of autoimmunity related to the immune response to these peptides. Together these studies support the safety and immunogenicity of these peptides as a potential vaccine to target CD133 cancer stem 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 510. doi:1538-7445.AM2012-510
Abstract 5120: Functional genetic screens identify a rare isoform of RABL3 as a modulator of paclitaxel resistance in ovarian cancer
Authors: Zhang Qing , Ota Takayo , Ohta Tsuyoshi , Shridhar Viji , Chien Jeremy R. 
Published: August 2012

Abstract
Recent RNA-sequencing studies have identified variant transcripts, fusion transcripts and novel transcripts in cancer. However, little is known about the role of these variant transcripts in tumor development. To identify a specific role of these variant transcripts in tumor development toward chemotherapy resistance, we generated a custom retroviral cDNA expression library from 10 ovarian tumors with resistance to chemotherapy. Retrovirues were generated from the custom library, and they were used to transduced exogenous genes into ovarian cancer cell line A1847, a cell line chosen for its sensitivity to paclitaxel. A1847 cells transduced with retroviruses carrying alkaline phosphatase was used as a control. Transuced cells were selected with 25 nM paclitaxel. 87 clones survived the selection in library-tranduced cells whereas none survived the selection in alkaline phosphatase-tranduced control cells. Forty seven clones survive the secondary screens. Sequence analysis of transduced genes in these surviving clones indicate that 4 paclitaxel-resistant clones contain RABL3 splice variant. Although 195 accessions corresponding to wildtype transcripts are reported in AceView, there is a single accession corresponding to RABL splice variant that we identified in this screen. RNAi-mediated downregulation of RABL3 resulted in enhance sensitivity toward paclitaxel in these resistant clones. Ectopic expression of RABL3 splice variant resulted in increased resistant to paclitaxel. Collectively, these results demonstrate the feasibility of performing functional genetic screens to identify novel splice variants involved in tumor development.
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 5120. doi:1538-7445.AM2012-5120
Abstract 5125: Functional genomic strategies to identify oncogenes in breast cancer
Authors: Guest Stephen , Haddad Ramsi , Gray Joe , Ethier Stephen 
Published: August 2012

Abstract
During the process of tumorigenesis and tumor progression cancer cells acquire an array of genetic alterations. The theory of oncogene addiction proposes that a small portion of these alterations generate driver oncogenes that are critical for maintaining the transformed phenotype. Strong support for this theory comes from the identification and subsequent therapeutic targeting of individual driver oncogenes that has resulted in significant clinical responses. However, in solid tumors that contain multiple driver oncogenes, these responses are not durable and it is therefore likely that multiple oncogenes will need to be identified and targeted in these tumors in order to reverse the transformed phenotype and effect durable clinical responses. Identifying multiple driver oncogenes among the large number of mutated/amplified genes that are present in most solid tumors is a nontrivial task that will require novel approaches. In this study, we have developed an approach that combines exome sequencing, array comparative genomic hybridization, expression analysis and genome-wide, RNAi-based functional screening to identify driver oncogenes that are functioning in individual cell lines derived from human tumors. In a pilot study using this approach we have shown that of the 583 amplified genes in the SUM225 breast cancer cell line only 45 are hits in the RNAi-based functional screen. Similarly, of the 806 genes that are mutated in this cell line only 26 are hits in the RNAi-based functional screen. Interestingly, the SMPD3 gene that was both amplified and a hit in the functional screen also contained a point mutation and this point mutation was present in another HER2 positive breast cancer cell line, SUM190. The identification of SMPD3 as a likely driver oncogene in the SUM225 and SUM190 cell lines highlights the power of an approach that combines sequence and copy number data with functional screening to identify driver oncogenes. Future analysis will incorporate expression data to further refine this approach.
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 5125. doi:1538-7445.AM2012-5125
Abstract 5129: Identification of therapeutic targets for HPV-positive and HPV-negative head and neck cancers using high throughput RNAi screening
Authors: Azorsa David O. , Gonzales Irma M. , Henderson Meredith C. , Sima Chao , Arora Shilpi 
Published: August 2012

Abstract
Cancers of the head and neck account for three percent of all malignancies in the United States and is the sixth most common type of cancer worldwide. Historically, the two most common risk factors for head and neck squamous cell carcinomas (HNSCC) were tobacco use and/or heavy alcohol consumption. Recent growing evidence strongly supports a role for human papillomavirus (HPV) in a subset (15-30%) of HNSCC and there is currently a rise in HPV-related head and neck cancers. In order to improve treatment of head and neck cancers and identify etiology-specific therapeutic targets, we applied a functional genomics based approach utilizing high-throughput RNAi (HT-RNAi) to identify genes specifically involved in growth of either HPV-positive or HPV-negative HNSCC cells. A HT-RNAi assay was developed to quantify the effects of gene specific siRNA on growth inhibition of two HPV-positive (SCC-090 and UMSCC-047) and two HPV-negative (SCC-25 and CAL-27) HNSCC cell lines. For HT-RNAi screening, the four cell lines were reverse-transfected with siRNA from a library targeting 7000 druggable genes with four siRNA per gene and assessed for growth modulation at 96 hours post transfection. The data was normalized using Z-score analysis and statistical cut-offs were set. Following data analysis, we generated a hit list of gene targets that are involved in growth of HPV-positive or HPV-negative HNSCC cells. Validation of these genes will identify potential therapeutic targets for head and neck tumors depending on their HPV status. Furthermore, these findings demonstrate the effectiveness of using HT-RNAi as a tool for the identification of etiologic-specific targets.
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 5129. doi:1538-7445.AM2012-5129
Abstract 5160: Global metabolomic profiles distinguish malignant from non-malignant human mammary epithelial cell responses to endogenous p53 upregulation by MDM2 antagonism
Authors: Yau Christina , Gabriel Bianca , Scott Gary , Brand Martin , Benz Christopher C. 
Published: August 2012

Abstract
Wildtype (wt) p53 can alter metabolic pathways and mitochondrial function but it is unclear whether these responses are similar in normal and malignant cells, where it is also hypothesized that p53wt can modulate the Warburg effect. Therefore, we used a small molecule inhibitor of MDM2, MI-63 (Ding et al., J. Med. Chem. 2006; Ascenta/Sanofi), to induce ∼5-fold intracellular increases in p53wt protein levels within 24 h of treating malignant (MCF-7) or non-malignant (MCF10A) human mammary epithelial cells, whereupon global biochemical changes were assayed in replicate (x6) extracts using various mass spectrometry platforms (GC/MS, LC/MS/MS; Metabolon, Durham, NC). Extracts from similarly treated p53mut malignant SKBr3 cells were also assessed. Normalized (to total protein) and imputed data from 310 known and detected biochemicals were compared for treatment effects (Wilcoxon rank sum test, p&lt;0.05). Treatment significantly altered levels of 93 biochemicals (58 up, 35 down) in the malignant MCF-7 cells, 62 (39 up, 23 down) in the non-malignant MCF10A cells, and 24 (20 up, 4 down) in the malignant p53mut SKBr3 cells. Common to both MCF-7 and MCF10A, p53wt upregulation increased NAD+ and NADP+ levels, responses not seen in SKBr3 cells. Upregulation of p53wt selectively suppressed polyamines (spermidine, putrescine) in MCF10A, whose response to MI-63 is cytostatic unlike the apoptotic response of MCF-7 or treatment unaffected growth of SKBr3 cells. Relative to MCF10A, MCF-7 cells showed opposing energy-related biochemical responses in glucose, glucose-6-phophosphate, 3-phosphoglycerate and pyruvate pools, along with increases in the glutaminolysis product succinate, suggesting that p53wt upregulation enhances glycolytic and mitochondrial (TCA) production of pyruvate in malignant MCF-7 cells yet decreases glycolysis and pyruvate production in non-malignant MCF10A cells. This conclusion that p53wt upregulation increases glycolysis, pyruvate production and mitochondrial ATP synthesis in MCF-7 was confirmed using live cell extracellular flux analysis of oxygen consumption and acid production (Seahorse XF), which showed opposing treatment responses by MCF10A and no treatment effects in SKBr3. Altogether, these findings point to opposing metabolic and bioenergetic responses induced by p53wt upregulation in malignant and non-malignant mammary epithelial cells, consistent with p53wt induced reversal of the Warburg effect, and offering new insights into pathways associated with different therapeutic and cell fate responses induced by novel small molecule MDM2 antagonists like MI-63.
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 5160. doi:1538-7445.AM2012-5160
Abstract 5163: Differential effects of IGF-2 on epithelial mesenchymal transition (EMT) in African- American and Caucasian breast cancer cell lines
Authors: Hamilton Nalo M. , Amis Louisa , Davis Willie L. , Saldivar April 
Published: August 2012

Abstract
Breast cancer is a multifactorial disease that disproportionately affects women. Breast cancer patients with the worst prognosis tend to be premenopausal, African-American (AA) and present with aggressive, estrogen-independent tumors unresponsive to standard endocrine therapy. Because of these factors, it is important to discover unique biomarkers for screening and treatment of breast cancer. One potential candidate is the insulin-like growth factor-II (IGF-2). Studies indicate that tumors that express high levels of IGF-2 are more aggressive, exhibit a basal-like phenotype and tend to metastasize. Suggesting that enhanced or altered IGF-2-mediated cell signaling pathways may be involved in the pathogenesis and disease progression of metastatic, ER-null breast cancer. We hypothesize that this may be due to the ability of IGF-2 to affect the mesenchymal epithelial transition (EMT) of these cells. To assess the potential effect(s) of proIGF-2 on EMT, we have over-expressed pro- and mature- forms of IGF-2 in human breast cancer cell lines: MCF-7, T47D, Hs578T, CRL-2329, CRL-2335 and Z75D-30. There are phenotypic changes that are characteristic of EMT, cellular morphology was evaluated by phase-contrast and confocal microscopy on days 5, 15, 20, and 30 post-transfection. In cells overexpressing proIGF-2 and mIGF-2, qRT-PCR and Western immunoblot analysis were used to assess expression and activation of E-cadherin, PI3K/AKT, SNAI1/2, RelB, Bcl-2, ERα and ERβ. This project will evaluate proIGF-2 as an initator of EMT and cancer metastisis. [Research support from the Robert Wood Johnson Foundation and Loma Linda University School of Pharmacy]
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 5163. doi:1538-7445.AM2012-5163
Abstract 5279: Over-expression of EGFRviii induces an angiogenic switch in infiltrative human glioblastomas
Authors: Røsland Gro V. , Talasila Krishna , Bjerkvig Rolf , Miletic Hrvoje 
Published: August 2012

Abstract
Glioblastoma multiforme (GBM) is the most common and most aggressive primary brain tumor where local cancer cell invasion into the normal brain represents a major obstacle preventing successful therapeutic interventions. A well known mediator of invasion, proliferation and survival, is the epidermal growth factor receptor (EGFR). Amplification and subsequent over-expression of EGFR protein is the most common genetic alteration in primary GBM, with a frequency of about 40%. Of the GBMs that have an amplification of EGFR, 63-75% also show genetic rearrangements of the gene, resulting in tumors that express both the wild type, as well as mutated forms of EGFR. The most common mutation in EGFR, is the EGFRviii, were the ligand binding part of the protein is missing (del exon 2-7). This mutation leads to a constitutive activation of the protein. In patients with amplified EGFR, 50-60% also express the EGFRviii. In this work we determined a functional role of EGFRviii within invasive human GBM cells in vivo. We cultured human GBM cells, lacking EGFR amplification and EGFRviii expression, in serum-free neuro-basal (NB) medium. By orthotopic transplantation into the brains of immunodeficient rats, tumors developed that showed a highly infiltrative non-angiogenic phenotype. By over-expressing EGFRviii in these tumors, we demonstrate a robust switch towards angiogenesis as shown by dynamic-contrast enhanced MRI and by histologic verification of angiogenic vessels. Molecular analysis confirmed an up-regulation of HIF1A as well as a panel of angiogenic factors. Our results demonstrate a distinct role of EGFRviii as a vital driver of angiogenic tumor growth within human GBMs in vivo. Thus, the presented observations should have important implications for therapeutic strategies targeting EGFRviii in 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 5279. doi:1538-7445.AM2012-5279
Abstract 5285: ADAM12: A novel mediator of tumor angiogenesis
Authors: Roy Roopali , Moses Marsha A. 
Published: August 2012

Abstract
ADAM12 (a disintegrin and metalloprotease) is a member of a family of integral membrane and secreted Zn-dependent metalloproteases that have diverse roles in normal and pathological states. Human ADAM12 is expressed as two alternatively spliced forms, a membrane-anchored long form (ADAM12-L), and a short secreted form (ADAM12-S). Increased levels of ADAM12 mRNA and protein have been reported in a variety of cancers including colon, hepatocellular, lung, gastric and glioblastoma. We have previously reported that urinary ADAM12 is predictive of disease status and stage in breast cancer. We have also demonstrated that expression of ADAM12 isoforms in breast tumor cells results in a higher rate of tumor take, increased tumor size and endocrine resistance. ADAM12-S expression stimulated migration and invasion of breast tumor cells in vitro and local and distant tumor invasion in vivo. In the course of these studies, we observed that ADAM12 is upregulated in the vessels of aggressive breast tumors as compared to normal adjacent breast tissue. ADAM12-overexpressing breast tumors also displayed a higher microvascular density. Furthermore, we found that angiogenic tumors express higher levels of ADAM12 compared to their preangiogenic counterparts. The goal of the present study was to determine whether ADAM12 regulates tumor angiogenesis. Basal levels of ADAM12-L expression in HUVEC and HMVEC are relatively low, however, both ADAM12 protein and mRNA expression is significantly increased when cells are stimulated with growth factors such as VEGF, bFGF or inflammatory cytokines such as TNFα, TGFβ or IL1α. Interestingly, VEGF stimulation of endothelial cells (EC) resulted in ADAM12 protein expression and/or localization specifically along the invadopodia of these cells. Consistent with these results, we found that ADAM12 overexpression in EC resulted in significantly increased rates of migration, capillary tube formation and increased adhesion to fibronectin and type IV collagen but not laminin. In vivo studies demonstrate that ADAM12 significantly increases bFGF-mediated angiogenesis in the mouse corneal pocket assay. Taken together, our data provide evidence supporting a novel role for ADAM12 in the regulation of endothelial cell function and tumor angiogenesis. Studies to investigate the mechanism/s by which ADAM12 may regulate angiogenesis are ongoing. [The authors acknowledge the support of NIH PO1 CA045548, The Breast Cancer Research Foundation and The Simeon J. Fortin Foundation]
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 5285. doi:1538-7445.AM2012-5285