bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3813: Uniparental disomy is associated with embryonal rhabdomyosarcoma in Costello Syndrome and nonsyndromic patients.
Authors: Robbins Katherine M. , Stabley Deborah L. , Conard Katrina , Wu David J. , Stitik Hunter , Kolb Edward A. , Napper Andrew , Mason Robert W. , Gripp Karen W. , Sol-Church Katia 
Published: August 2014

Abstract
Embryonal rhabdomyosarcoma (ERMS) is the most prevalent pediatric soft tissue tumor and is characterized at the molecular level by loss of heterozygosity (LOH) at 11p15.5. We aimed to study ERMS in the context of Costello syndrome (CS), a rare syndromic predisposition to ERMS. Because CS arises from a typically paternal germline mutation in the proto-oncogene HRAS, it is considered a rasopathy. CS results in failure to thrive, intellectual disabilities, short stature, coarse facial features, skeletal abnormalities, congenital heart disease, and a predisposition for cancer, most commonly ERMS. We molecularly characterized seven ERMS tumors from six unrelated CS patients, carrying paternally derived HRAS p.G12S (5) or p.G12A (2) mutations. LOH was evaluated in all CS ERMS tumors by microarray and/or using short tandem repeat (STR) markers along both arms of chromosome 11. One patient developed a second primary ERMS tumor showing the ERMS hallmark LOH limited to 11p15.5. The six other CS ERMS tumors displayed paternal uniparental disomy (UPD) of the entire chromosome 11. Paternal UPD was also observed in a pure ERMS cell line, established using fresh tumor sample from one of the patients with a p.G12A germline mutation. This represents, to our knowledge, the first CS ERMS cell line. Additional cell lines derived from non CS patients were used in this study and included two ERMS (RD and RH36), one Alveolar RMS (RH30), and one mixed A/ERMS (RH18). RH36 cells carried an HRAS mutation at position 61 (p.Q61K). Unexpectedly, both ERMS cell lines, RD and RH36, displayed a complete LOH for chromosome 11. The ARMS RH30 cells carried no mutation in HRAS or LOH. RH18 cells derived from an A/ERMS had no HRAS mutation and showed LOH on both, the p and q arm of chromosome 11, except at locus D11S1338. Cytogenetic analysis with fluorescence in situ hybridization (FISH) on three CS tumors revealed multiple copies of chromosome 11 leading to trisomies and tetrasomies in the tumor and cultured cells. Gene expression revealed loss of imprinting in the growth regulating genes H19, IGF2, and CDKN1C on chromosome 11 not only in CS tumors, but also in nonsyndromic ERMS.
Citation Format: Katherine M. Robbins, Deborah L. Stabley, Katrina Conard, David J. Wu, Hunter Stitik, Edward A. Kolb, Andrew Napper, Robert W. Mason, Karen W. Gripp, Katia Sol-Church. Uniparental disomy is associated with embryonal rhabdomyosarcoma in Costello Syndrome and nonsyndromic patients. [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 3813. doi:10.1158/1538-7445.AM2013-3813
Abstract 382: Profiling angiogenic factors, RTK phosphorylation and inhibition events in breast cancer and endothelial cells using antibody arrays.
Authors: Finkel David J. , James Amy E. , Wegner Greta J. 
Published: August 2014

Abstract
Tumor growth and progression in breast cancer is dependent on angiogenesis, the growth of new vasculature from pre-existing vessels. Since invasive and in situ breast cancers express many angiogenic factors, we examined the profiles of angiogenesis-related proteins in the conditioned media from multiple breast cancer cell lines and their effect on activating receptor tyrosine kinases (RTKs) in Human Umbilical Vein Endothelial Cells (HUVEC). Antibody arrays were used to measure the secretion of multiple angiogenic factors including VEGF, TIMP-1, IGFBP-2, IGFBP-3, THSP-1, Angiogenin, and CXCL16. We then tested the capacity of these breast cancer cell line supernatants to induce receptor tyrosine kinase (RTK) phosphorylation in endothelial cells. After treatment with conditioned media, an increase in the tyrosine phosphorylation of VEGF R1 and VEGF R2 was observed using both antibody arrays and ELISA. Select small molecule VEG FR inhibitors were then screened for their effect on tyrosine phosphorylation events. Axitinib, Ki8751, and Sunitib effectively reduced VEGFR phosphorylation induced in endothelial cells by angiogenic factors released from these breast cancer lines.
Citation Format: David J. Finkel, Amy E. James, Greta J. Wegner. Profiling angiogenic factors, RTK phosphorylation and inhibition events in breast cancer and endothelial cells using antibody 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 382. doi:10.1158/1538-7445.AM2013-382
Abstract 3820: Wnt signaling and telomerase activation in hepatoblastoma.
Authors: Hiyama Eiso , Ueda Yuka , Kamimatsuse Arata , Onitake Yoshiuki , Ogura Kaoru , Hiyama Keiko 
Published: August 2014

Abstract
Purpose: The abnormal Wnt/β-catenin signaling plays a key role in hepatoblastoma (HBL) development. In HBL, CTNNB1 coding ß-catenin protein with mutated or deleted at hot-spot regions involving exon 3 stimulates this pathway. Previously we reported that the levels of telomerase reverse transcriptase (TERT) mRNA and telomerase activities were correlated with outcomes of the patients with HBL. In this study, we examined the correlation between Wnt/β-catenin signaling and telomerase activation in HBL. And, we investigated the location of β-catenin and TERT in HBL and the expression levels of the Wnt signal genes downstream of ß -catenin.
Methods: Tumors derived from 212 HBL cases treated with the JPLT-2 protocol were analyzed for oncogenic mutations (missense mutations and interstitial deletions in the third exon) of the CTNNB1 gene encoding β-catenin and mutations of Wnt signal genes including APC, AXIN1, and 2. Moreover, these tumors were analyzed for the expression levels of TERT (telomerase reverse transcriptase) and the Wnt signal genes downstream of ß -catenin (MYC, cyclin D1 and MMP7) using Real time RT-PCR and immunohistochemistry.
Results: Oncogenic mutations of CTNNB1 were detected in 163 cases (76.4%) and more than 80% showed abnormalities of Wnt signal genes. The expression levels of TERT were significantly higher in 49 cases without mutation (P &lt; 0.05). Interestingly, Wnt/β-catenin target genes including MYC, cyclin D1 and MMP7 were significantly activated in the tumors with telomerase activation (P = 0.01). ß -catenin staining distinguished the CTNNB1 mutated tumors from others but cyclin D1 and MMP-7 did not. In advanced HBLs, double stain analysis of TERT and β-catenin showed that both were located in the same site in nucleus, suggesting that both proteins were co-localized in nucleus in hepatoblastoma.Conclusions: Wnt/β-catenin signaling in the HBLs without CNNB1 mutations was activated by telomerase activation. The clinical courses in HBLs with mutated Wnt signal gens and high TERT expression seemed to be unfavorable due to highly activated Wnt/β-catenin signaling. This correlated pathway might become molecular targets for advanced hepatoblastoma.
Citation Format: Eiso Hiyama, Yuka Ueda, Arata Kamimatsuse, Yoshiuki Onitake, Kaoru Ogura, Keiko Hiyama. Wnt signaling and telomerase activation in hepatoblastoma. [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 3820. doi:10.1158/1538-7445.AM2013-3820
Abstract 3824: Integrated analysis of array-CGH and gene expression profiling identifies HSPA5 as a prognostic marker in SHH pathway-actived Medulloblastoma.
Authors: Lo Angela Kwok-Fung , Wang Jian , Shen Jianhe , Yu Alexander , Chow Wing-Yuk , Su Jack , Adesina Adekunle , Dauser Robert , Whitehead William , Chintagumpala Murali , Guerra Rudy , Man Tsz-Kwong , Lau Ching C. 
Published: August 2014

Abstract
Medulloblastoma (MB) is the most malignant brain tumor in children and is characterized by marked biological and clinical heterogeneity. It includes four distinct molecular subtypes [wingless (WNT), sonic hedgehog (SHH), Group 3 and Group 4]. Previous attempts to identify prognostic markers applicable to all MBs were unsuccessful and we therefore hypothesize that each molecular subtype of MB may be associated with its unique prognostic markers. The aim of this study is to identify prognostic markers specific for SHH-active MB tumors. We analyzed SNP-array CGH data and gene expression profiling for 60 pediatric MBs and compared the molecular results with clinical outcome data. Using unsupervised hierarchical clustering, we identified 18 MBs that have activated SHH signaling. This subtype of SHH-active tumors also have frequent chromosome 9q loss which are associated with more favorable outcome. In an attempt to identify candidate genes on chromosome 9q with survival impact, we found that low expression of Heat Shock 70kDa Protein 5 (HSPA5) was significantly associated with better event free survival (EFS) in SHH MB patients independent of other clinical variables. This finding had been validated in two other independent MB cohorts. By immuohistochemistry and western blotting, we confirmed the negative correlation between patient survival and HSPA5 protein expression in SHH tumors. Furthermore, in vitro study indicated that knockdown of HSPA5 by siRNA caused dramatic growth suppression in SHH active MB cells. These findings suggest that HSPA5 is a potential prognostic marker in predicting survival of SHH active MB patients and this protein may also be exploited as therapeutic target for SHH MBs that do not harbor chromosome 9q loss.
Citation Format: Angela Kwok-Fung Lo, Jian Wang, Jianhe Shen, Alexander Yu, Wing-Yuk Chow, Jack Su, Adekunle Adesina, Robert Dauser, William Whitehead, Murali Chintagumpala, Rudy Guerra, Tsz-Kwong Man, Ching C. Lau. Integrated analysis of array-CGH and gene expression profiling identifies HSPA5 as a prognostic marker in SHH pathway-actived Medulloblastoma. [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 3824. doi:10.1158/1538-7445.AM2013-3824
Abstract 3825: Inhibitory effect of PID1 in medulloblastomas, gliomas and ATRT.
Authors: Erdreich-Epstein Anat , Ren Xiuhai , Zhou Hong , Sposto Richard , Ji Lingyun , Pfister Stefan , Kool Marcel , Asgharzadeh Shahab 
Published: August 2014

Abstract
The recently identified PID1 (Phosphotyrosine Interaction Domain containing 1) is a modulator of insulin signaling in adipocytes and muscle cells. Using a number of independent datasets we show that mean PID1 mRNA was lower in unfavorable medulloblastomas (subgroups 3 and 4) and in glioblastomas compared with favorable medulloblastomas (SHH and WNT subgroups) or normal brain, respectively. Higher PID1 mRNA correlated with longer progression-free survival and overall survival in medulloblastoma patients and with longer overall survival in glioma patients. Ectopic expression of PID1 in medulloblastoma, glioblastoma and ATRT (atypical teratoid rhabdoid tumor) cell lines inhibited colony formation by 68% ± 3.5 (p&lt;0.0001 in total of 24 experiments in triplicates) compared with controls. PID1 effects on apoptosis and proliferation were demonstrated by increased sub-G0/G1 and annexinV staining, decreased S-phase. Additionally, PID1 induced mitochondrial depolarization in the medulloblastoma, glioblastoma, and ATRT cell lines. In keeping with PID1 having a PTB (phosphotyrosine binding) domain, endogenous PID1 co-immunoprecipitated with the low density lipoprotein receptor-related protein-1 (LRP1, which is a potential binding partner for PID1 via its C-terminal NPXY motif). However, PID1 with mutated PTB domain retained its inhibitory effects on colony formation, suggesting that other domains of PID1 mediated (or contributed to) PID1’s inhibitory effect. Analysis of PID1 domains comprising its N-terminal region (D1), C-terminal region (D3) and middle region (D2), each comprising approximately 1/3 of the protein, revealed that indeed, each 1/3 of PID1 inhibited colony formation at least as efficiently as full length PID1. Interestingly, although by itself D2 was more inhibitory than full length PID1, when it was combined with D3, which was also inhibitory by itself, we observed marked mitigation of the inhibitory effect of the combined D2+D5 fragment on colony formation, suggesting functional intramolecular interactions in PID1. These data suggest for the first time that PID1 has a tumor suppressor-like effect in brain tumors and shed light on the molecular mechanism of its inhibitory action.
Citation Format: Anat Erdreich-Epstein, Xiuhai Ren, Hong Zhou, Richard Sposto, Lingyun Ji, Stefan Pfister, Marcel Kool, Shahab Asgharzadeh. Inhibitory effect of PID1 in medulloblastomas, gliomas and ATRT. [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 3825. doi:10.1158/1538-7445.AM2013-3825
Abstract 3827: Caveolin-1 acts as a tumor suppressor promoting muscular differentiation in alveolar rhabdomyosarcomas.
Authors: Huertas-Martinez Juan , Barrau Ignasi , Sáinz-Jaspeado Miguel , Lagares-Tena Laura , Mateo-Lozano Silvia , Mora Jaume , Roma Josep , Gallego Soledad , Moran Sebastian , Esteller Manel , Garcia del Muro Xavier , Tirado Oscar M. 
Published: August 2014

Abstract
Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood and adolescence. Despite advances in therapy, patients with a histological variant of rhabdomyosarcoma known as alveolar rhabdomyosarcoma (ARMS) have a 5-year survival of &lt;30%. Caveolin-1 (CAV-1), encoding the structural component of cellular caveolae, is a suggested tumor suppressor gene involved in cell signaling. We report that CAV1 is expressed in embryonic rhabdomyosarcoma (ERMS) cell lines and tumor samples. However, in 3 out of 4 different ARMS cell lines and 8 out of 9 clinical samples CAV1 expression is either undetectable or very low. The epigenetic silencing of CAV1 by hypermethylation was tested in ARMS cells before and after azacytidine treatment. CAV1 methylation was evaluated by bisulfite genomic sequencing. Re-expression of CAV1 in two of these cell lines is cytostatic and promotes differentiation. In vivo, CAV1-expressing tumor cells showed growth delay and features of muscular differentiation in comparison with untransfected and vector transfected cells. Our results demonstrated that CAV1 could function as a potent tumor suppressor in ARMS tumors. Inhibition of CAV1 function could contribute to aberrant cell proliferation, leading to ARMS development. The use of peptides that mimic CAV1 function may be of therapeutic use for the treatment of ARMS.
Citation Format: Juan Huertas-Martinez, Ignasi Barrau, Miguel Sáinz-Jaspeado, Laura Lagares-Tena, Silvia Mateo-Lozano, Jaume Mora, Josep Roma, Soledad Gallego, Sebastian Moran, Manel Esteller, Xavier Garcia del Muro, Oscar M. Tirado. Caveolin-1 acts as a tumor suppressor promoting muscular differentiation in alveolar rhabdomyosarcomas. [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 3827. doi:10.1158/1538-7445.AM2013-3827
Abstract 3837: Effect of matrix and intercellular interactions on chemotherapeutic efficacy in a high-throughput format.
Authors: O'Day Christine L. , Ejiri Yoko , Hosoda Masaya 
Published: August 2014

Abstract
Many researchers believe that clinical results often do not coincide with two-dimensional in vitro assays, prompting the need for better correlative cellular models. 3D culture has gained much interest in recent years for the effects of matrix and inter-cellular contacts on tumor growth and progression. We have devised a high throughput assay to look at the effects of matrix and intracellular interactions using a standard 384 2D plate, matrigel in 384 well format and 3D Elplasia micro-space plates with a 200 micron grid. We standardized the media between all three platforms but decreased the cell number 3-4 fold in 2D plates to keep growth within the linear range for a 6 day assay. Media was changed once after 3 days. In all cell lines tested, there were at least one doubling of cell number in 6 days and the rate of growth was fairly consistent between 3D and 2D techniques, with 2D growth slightly faster. We examined differences in potency and efficacy of 6 different agents in 10 cell lines comparing 2D and 3D techniques. These agents are directed at PI3K, DR4/5, MEK, EGFR, and BCL2. Effects due to matrix interactions vs. suspension were noted along with potency and efficacy changes of several compounds when compared to 2D but not in all cells lines. Often EC-50 values for various agents were identical between platforms. In a few cell lines, the potency of a PI3K/mTorr inhibitor was increased three fold but the overall efficacy (defined by area under the curve) was decreased in 2D vs. 3D. DR4/5 agonists also had a mixed profile with some cell lines. TRAIL was dramatically more potent in 2D for some lines and conversely, more potent for others in 3D. Ranges of over 10 fold in EC-50 for Trail were observed between 2D and 3D in the same cell line. This interesting variation between 2D and 3D endpoints prompts the need to correlate 3D potency with clinical data and begs insight into the reasons behind the differences in receptor mediated signaling in 3D. If 3D is more correlative, which many studies suggest, there will be a clear benefit to screening multiple cell lines for efficacy and correlating them with gene expression data in 3D culture for biomarker identification.
Citation Format: Christine L. O'Day, Yoko Ejiri, Masaya Hosoda. Effect of matrix and intercellular interactions on chemotherapeutic efficacy in a high-throughput format. [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 3837. doi:10.1158/1538-7445.AM2013-3837
Abstract 384: NADH oxidase, Enox1 activity, is required for vasculogenesis in Zebrafish.
Authors: Venkateswaran Amudhan , Levic Daniel S. , Melville David B. , Sekhar Konjeti R. , Walsh Alexandra J. , Skala Melissa C. , Crooks Peter A. , Knapik Ela W. , Freeman Michael L. 
Published: August 2014

Abstract
Establishment of an adequate vascular network is a crucial event for tumor development. Emerging research has implicated the endothelial redox state as a significant regulator of vascular growth and remodeling. ENOX1 encodes a protein that is expressed in mammalian endothelial cells and exhibits NADH oxidase activity. Recent research suggests that ENOX1 functions as a positive regulator of angiogenesis. However, direct genetic evidence supporting this hypothesis is lacking. We used a zebrafish model to directly examine the role of Enox1 during embryonic vascular development. Whole mount in situ hybridization coupled with immunocytochemistry performed on zebrafish cryosections show that enox1 message and the translated protein are expressed in heart and blood vessels during embryonic development. Furthermore, use of immunocytochemistry demonstrates that Enox1 co-localizes with vascular expression of the ETS-domain transcription factor fli in heart and intersegmental vessels. Using in vivo multiphoton microscopy, we show that morpholino-mediated knockdown of Enox1 in Zebrafish embryos increases NADH fluorescence, an expected consequence of loss of Enox1 oxidase activity. Phenotypic manifestations resulting from loss of Enox1 function in embryos include vascular defects, most notably loss of fli-eGFP and flk-eGFP (receptor kdr, VEGFR2 in mammals) expression in intersegmental vessels and a loss of blood circulation in the intersegmental vessels. Pharmacological inhibition of Enox1 activity using a novel small molecule phenocopies the defects observed following morpholino-mediated functional knockdown. Together, these results show that Enox1-mediated redox regulation is essential for vasculogenesis in vertebrates in vivo. These results, in conjunction with previous work that demonstrated that inhibition of ENOX1 radiosensitized tumor vasculature, support the hypothesis that ENOX1 represents a novel target for impairing tumor angiogenesis.
Citation Format: Amudhan Venkateswaran, Daniel S. Levic, David B. Melville, Konjeti R. Sekhar, Alexandra J. Walsh, Melissa C. Skala, Peter A. Crooks, Ela W. Knapik, Michael L. Freeman. NADH oxidase, Enox1 activity, is required for vasculogenesis in Zebrafish. [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 384. doi:10.1158/1538-7445.AM2013-384
Abstract 3859: Characterization of imaging-enhanced models of disseminated multiple myeloma.
Authors: Baugher Meridith , Baranski Jenifer , Balagurunathan Deepa , Bull Christopher , Winchell Noah , Shaw Darren , Trachet Erin , Lister Deanne , McConville Patrick , Leopold Wilbur R. 
Published: August 2014

Abstract
Multiple myeloma is a cancer of the plasma cells that is characterized by multiple localized lesions in the marrow, particularly of the spine, skull, and pelvis, although soft tissue lesions also occur. It is the second most common blood cancer, affecting approximately 45,000 people in the US. Most preclinical modeling of myeloma employs SC xenografts that mimic the less common plasmacytoma form of the disease. Systemic (IV) implants are also used, but studies typically are based on a single survival endpoint, limiting knowledge about the progression and response of the disease under treatment. In order to more quantitatively monitor disseminated disease progression and response to treatment, we have characterized two human (JJN3 and MM1S) and one murine (5TGM1) myeloma models that have been modified to express luciferase. All models were characterized by 100% tumor take rate and focal dissemination of the disease to the spine and skull that mimic clinical experience. These models showed individual and reproducible patterns of spread to other sites, and differed in their sensitivities to standards of care. Analysis of tumor doubling times, tumor titrations, luminescence-based growth delay, and survival all indicated that the bioluminescence signal was a reliable quantitative indicator of viable tumor burden, even under treatment with clinical standard of care agents. Luciferase labeling and the tight correlation between luminescence signal and viable tumor burden raises the possibility of differential real-time tracking of tumor progression and response at individual sites.
Citation Format: Meridith Baugher, Jenifer Baranski, Deepa Balagurunathan, Christopher Bull, Noah Winchell, Darren Shaw, Erin Trachet, Deanne Lister, Patrick McConville, Wilbur R. Leopold. Characterization of imaging-enhanced models of disseminated 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 3859. doi:10.1158/1538-7445.AM2013-3859