bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3457: A possible role for the Hedgehog pathway ligands Desert and Indian in rhabdomyosarcoma
Authors: Roma Josep , Almazán-Moga Anna , Velasco Pablo , Molist Carla , Isaac Vidal , Segura Miguel F. , Soriano Aroa , Luz Jubierre , Laia Paris , Jaume Reventós , Toledo José Sánchez de , Gallego Soledad 
Published: May 2015

Abstract
Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children, is thought to derive from embryonic cells committed to developing into skeletal muscle and is divided into 2 major subtypes: embryonal and alveolar (eRMS and aRMS, respectively). Hedgehog pathway-belonging proteins are considered to be key regulators of development in pluricellular organisms, exerting crucial roles in processes such as tissue patterning, proliferation and differentiation. Likewise, Hedgehog (HH) signaling also plays important roles in adult organisms such as stem cell maintenance or tissue repair. The 3 Hedgehog ligands present in mammals are named Sonic (SHH), Indian (IHH) and Desert (DHH). Upon binding of a Hedgehog ligand to Patched, active SMO is detected in the membrane and prevents GLI proteosomal processing. GLI is then translocated to the nucleus where it binds to and regulates GLI-specific promoters. Despite the knowledge gathered to date, the mechanism that drives activation of the pathway in RMS is not well understood; the relative importance of the 3 HH ligands has not been elucidated and a possible role for Desert or Indian HH in the pathogenesis of RMS has not been studied. Previous works reported undetectable levels of SHH in RMS tumors and cell lines with Hedgehog pathway activation, suggesting a mechanism of GLI1-upregulation independent of autocrine SHH expression. Herein, we report extremely low levels of SHH expression in the majority of RMS patients (approximately 70%). Conversely, we report a prominent expression of Desert and Indian HH ligands - instead of SHH - in RMS, thereby supporting the possible existence of an autocrine ligand-dependent activation of the Hedgehog pathway in this neoplasia. Furthermore, the expression of DHH significantly correlates with GLI1 levels, pointing to a crucial role of this ligand for the activation of the pathway in RMS.
Citation Format: Josep Roma, Anna Almazán-Moga, Pablo Velasco, Carla Molist, Vidal Isaac, Miguel F. Segura, Aroa Soriano, Jubierre Luz, Paris Laia, Reventós Jaume, José Sánchez de Toledo, Soledad Gallego. A possible role for the Hedgehog pathway ligands Desert and Indian in rhabdomyosarcoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3457. doi:10.1158/1538-7445.AM2014-3457
Abstract 3461: Profiling the effects of MEK inhibition on kinase phosphorylation and protease secretion using antibody arrays
Authors: Wegner Greta , Eleria Erin , Liao Wen-Chieh , Finkel Dave , James Amy 
Published: May 2015

Abstract
The frequent deregulation of ERK signaling in tumors has led to the development of MEK inhibitors, which have proven to be clinically relevant to malignancies harboring BRAF mutations. Since proliferation and invasion are intertwined aspects of metastasis, antibody arrays were used to measure the effect of multiple MEK inhibitors on 43 kinases and 34 proteases. Treatment of SK-BR-3 cells with MEK inhibitors resulted in decreased ERK (T202/Y204) and STAT3 (S727) phosphorylation. Increased p38 phosphorylation was observed following treatment with multiple inhibitors, but a decrease was observed in response to PD0325901. These differential effects demonstrate the utility of arrays for parsing out crosstalk between signaling pathways. To assess the effects of inhibitors across multiple cancer cell lines, changes in ERK phosphorylation were examined using ELISA. High ERK activation was observed in both RTK-driven and RAF/RAS mutation-containing cells, but did not correlate with sensitivity to MEK inhibition and was instead determined to be inhibitor dependent. Protease profiles were also impacted by MEK inhibition, with reduced MMP secretion detected by antibody arrays and ELISAs in inhibitor treated cells.
Citation Format: Greta Wegner, Erin Eleria, Wen-Chieh Liao, Dave Finkel, Amy James. Profiling the effects of MEK inhibition on kinase phosphorylation and protease secretion using antibody arrays. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3461. doi:10.1158/1538-7445.AM2014-3461
Abstract 3478: Differential level of L-homocysteic acid and lysophosphatidylcholine (16:0) in sera of patients with ovarian cancer
Authors: Kim Yun Hwan , Ju Woong , Kim Seung Cheol , Yoo Byong Chul 
Published: May 2015

Abstract
Ovarian cancer (OVC) is one of the most difficult cancers to detection in the early periods of its development. Therefore there have been numerous attempts to find a biomarker for OVC, but an accurate diagnostic marker is yet to be discovered. In this study, we profiled OVC candidate metabolites from serum to find potential diagnostic marker for OVC. Information of low-mass-ions (LMIs) in serum was obtained by using MALDI-TOF. MALDI-MS analysis of each serum sample was repeated six times in order to reduce experimental errors. Intensity of LMI mass peak was normalized using total peak area sums. Normalized intensity of LMI was used in principal component analysis-discriminant analysis (PCA-DA) to discriminate 142 OVC from 100 controls. LC-MS/MS was used to identify the selected LMIs. Extracted ion chromatogram (EIC) analysis was used to measure the relative quantity of candidate metabolite from the LMI mass peak areas. The concentration of common metabolite in serum was determined by ELISA. Top 20 LMI mass peaks with weigh factor over 0.05 were selected to separate OVC from controls. Among them two LMIs with 184.05 m/z and 496.30 m/z were identified as L-homocysteic acid (HCA) and lysophosphatidylcholine (LPC) (16:0), respectively. Relative quantity of LPC (16:0) was decreased in OVC serum (P=0.05), whereas the amount of HCA was significantly higher in OVC serum (P&lt;0.001). HCA was not detected in 59 cases out of 63 controls, but most cases of OVC (16 out of 25) showed significantly higher amount of HCA. When the cutoff was 10 nmol/ml, sensitivity and specificity of HCA were 64.0% and 96.9%, respectively. Level of LPC (16:0) was significantly correlated with tumor grade (P=0.045). Both HCA and LPC (16:0) showed correlation with stage and tumor histology, but limited sample number could not assign the statistical significance. HCA alone showed a potential power of biomarker for OVC. Even the stratified screening including LPC (16:0) did not significantly increase the power for OVC screening, our present study showed that a good example of profiling of LMIs in serum can be useful to select and identify candidate metabolites for OVC screening.
Citation Format: Yun Hwan Kim, Woong Ju, Seung Cheol Kim, Byong Chul Yoo. Differential level of L-homocysteic acid and lysophosphatidylcholine (16:0) in sera of patients with ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3478. doi:10.1158/1538-7445.AM2014-3478
Abstract 348: JMJD3 promotes the survival of diffuse large B-cell lymphoma subtypes via distinct mechanisms
Authors: Zhang Yan 
Published: May 2015

Abstract
Diffuse large B-cell lymphoma (DLBCL), the most common form of non-Hodgkin's lymphoma, comprises multiple biologically and clinically distinct subtypes including germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL. Dysreguation of genes related with B cell differentiation contributes to the tumorigenesis of DLBCL; the. Jumonji domain containing-3 (JMJD3), a histone 3 Lys27 (H3K27) demethylase, plays a known role in antigen-driven B-cell differentiation in GCB cells. But the mechanism of JMJD3 in DLBCL progression remains poorly uncerstood. Here we show that JMJD3 exerts an anti-apoptotic effect in both ABC and GCB subtypes of DLBCL. The downregulation of JMJD3 increased apoptosis among DLBCL cells. In the ABC subtype, JMJD3 regulates the interferon regulatory factor 4 (IRF4) in a demethylase activity-dependent fashion. Interestingly, IRF4 could reciprocally regulate the expression of JMJD3, forming a positive feedback regulation loop. The expression of IRF4 was sufficient to rescue survival induced by the JMJD3 suppression selectively in the ABC type. In the GCB subtype, JMJD3-mediated survival was dependent upon increased expression of the anti-apoptotic protein BCL2. Treatment with JMJD3 siRNA could also reduce tumor volume concordant with increased apoptosis of DLBCL cells. Our results demonstrate a previously unrecognized role of JMJD3 in the survival of both the ABC and GCB subtype of DLBCL and provide molecular insight into the mechanisms by which the JMJD3-IRF4 or JMJD3-BCL2 axis controls this process.
Key words:
DLBCL, apoptosis, JMJD3, IRF4, BCL2
Citation Format: Yan Zhang. JMJD3 promotes the survival of diffuse large B-cell lymphoma subtypes via distinct mechanisms. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 348. doi:10.1158/1538-7445.AM2014-348
Abstract 3489: A novel investigation into chemotherapy-induced peripheral neuropathy using iPSC-derived human neurons
Authors: Komatsu Masaaki , Wheeler Heather E. , Wing Claudia , Delaney Shannon , Dolan M Eileen 
Published: May 2015

Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is the major dose-limiting side effect of many anti-cancer drugs including taxanes, vinca alkaloids and platinating agents. These drugs represent standard of care for common cancers, however there are no effective treatments and no means to identify patients at risk for CIPN. The mechanisms underlying CIPN have not been precisely determined and few human neuronal models to study CIPN exist. Recent technology has allowed for the differentiation of induced pluripotent stem cells (iPSC) to human neurons. We have utilized genetically diverse human neurons as a model to study the effects on chemotherapy on neuronal health and on neurite morphology including neurite outgrowth, processes and branching. Upon treatment of human neurons with paclitaxel, vincristine or cisplatin (1 nM to 100 µM) for 72 hours, we identified reproducible decreases in cell median neurite process length per magnitude of drug concentration of 12-14%, 6-18% and 2-4%, respectively. No decrease in neurite length was observed with hydroxyurea, an agent that does not cause neuropathy. The morphological changes differed across drugs, with vincristine treatment showing the most dramatic effect on neurite outgrowth, paclitaxel showing an intermediate effect, and cisplatin showing no effect up to 1 µM of drug. To determine whether the model could be used for evaluation of genes important in CIPN, we used siRNA to decrease expression of TUBB2A, a gene known to be associated with paclitaxel-induced neuropathy. Transient knockdown of TUBB2A caused decreases of mean neurite process length (interaction P = 2.2 x 10-8) and total neurite outgrowth (interaction P = 1.8 x 10-10) of neurons 48 hours post-paclitaxel treatment. We are using this novel approach to screen agents that may be used to prevent or treat CIPN.
Citation Format: Masaaki Komatsu, Heather E. Wheeler, Claudia Wing, Shannon Delaney, M Eileen Dolan. A novel investigation into chemotherapy-induced peripheral neuropathy using iPSC-derived human neurons. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3489. doi:10.1158/1538-7445.AM2014-3489
Abstract 3498: A systematic approach to evaluate and select preclinical study workflow software applications for oncology
Authors: Ibsen Eric M. , Kumer Jeffrey 
Published: May 2015

Abstract
The use of software applications to automate the workflow specific to preclinical oncology trials can significantly improve labor efficiency, data quality & security while preserving both methodology and results in a searchable database in perpetuity. The typically daunting and complex selection process can be simplified, facilitated and expedited by applying a systematic approach derived from those developed and used by oncology departments in some large pharmaceutical companies. Criteria common across these companies have been identified and combined into a single codified evaluation method. The first step is to identify and define a detailed set of system requirements based on the needs for each user level: technicians, scientists, statisticians, analytical labs, management and other stakeholders involved with animal studies. Some requirements are specific to specific animal models and must be considered for inclusion. Requirements may include functions such as staff intercommunications, protocol development, ACUC restrictions, tumor induction methods, treatments, group composition, tasks, measurements, schedules, analysis, graphing and reporting methods, etc. Each requirement is then assigned a weight based on its’ relative importance to the users. Frequency of use is also taken into consideration when developing a requirement weight. Software applications under consideration are evaluated by scoring the extent to which each requirement is met. To determine the top applications for in-house evaluation on actual studies, a preliminary evaluation of Requirement Scores may be performed by referencing user manuals. Requirement Scores are multiplied by their predetermined weight to derive a Net Requirement Score (NRS). NRSs are summed to achieve a Total Score. The applications selected with the highest NRS are usually evaluated in the lab on actual studies. Requirements are then scored by a small team of users in regular lab use. The Total Score is used to identify which software best meets the needs of the research organization as a whole. The implementation of a systematic approach to evaluate software for animal study workflow automation can save time and help ensure the objective selection of the best system available for a lab.
Citation Format: Eric M. Ibsen, Jeffrey Kumer. A systematic approach to evaluate and select preclinical study workflow software applications for oncology. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3498. doi:10.1158/1538-7445.AM2014-3498
Abstract 3503: Somatic mutations and aberrant expression of RNF43 are recurrently found in intraductal papillary mucinous neoplasms of the pancreas
Authors: Sakamoto Hitomi , Kuboki Yuko , Hatori Takashi , Yamamoto Masakazu , Sugiyama Masanori , Shibata Noriyuki , Shimizu Kyoko , Shiratori Keiko , Furukawa Toru 
Published: May 2015

Abstract
Background: RNF43 encodes ring finger protein 43, an ubiquitin ligase, and is recently uncovered as mutated in intraductal papillary mucinous neoplasms of the pancreas (IPMNs). We studied mutations and aberrant expressions of RNF43 and their associations with molecular and clinicopathological features in IPMNs. Materials and methods: Studied were 178 IPMNs operated upon between 2001 and 2010 at Tokyo Women's Medical University Hospital. Formalin-fixed and paraffin-embedded tissues of the 178 cases and frozen tisssues of 56 of the cases were subjected for immunohistochemical and the next generation semiconducter sequencing analyses, respectively. Detected mutations were validated by Sanger sequencing. Results: Expression of RNF43 was reduced in 60 (33.7%) of the 178 IPMNs. Somatic mutations in RNF43 were found in 10 (17.9%) of the 56 examined cases, in which frameshift mutations, a nonsense mutation, and missense mutations were found in 5, 1, and 4 cases, respectively. These mutations were significantly associated with RNF43 expression (p = 0.008) and GNAS mutation (p = 0.012), however, not associated with tumor grade, histological subtype or prognosis. Conclusion: These results indicate that RNF43 may function as a tumor suppressor and play a role in development of IPMN.
Citation Format: Hitomi Sakamoto, Yuko Kuboki, Takashi Hatori, Masakazu Yamamoto, Masanori Sugiyama, Noriyuki Shibata, Kyoko Shimizu, Keiko Shiratori, Toru Furukawa. Somatic mutations and aberrant expression of RNF43 are recurrently found in intraductal papillary mucinous neoplasms of the pancreas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3503. doi:10.1158/1538-7445.AM2014-3503
Abstract 3504: Regulation of cell cycle progression by Ikaros in leukemia
Authors: Dovat Elanora , Payne Jonathon , Casiano Carlos M. , Sloane Justin , Gowda Chandrika , Payne Kimberly J. , Dovat Sinisa , Song Chunhua 
Published: May 2015

Abstract
Control of cell cycle progression is achieved by the coordinated function of a large set of genes that are highly conserved in eukaryotic organisms. Malignant cells have impaired regulation of cell cycle progression which results in uncontrolled cellular proliferation. Thus, understanding the regulation of cell cycle progression in malignant cells is essential to advance our knowledge of the process of malignant transformation and for designing novel treatments. Ikaros is a zinc finger protein that acts as a tumor suppressor in leukemia. The loss of Ikaros activity due to deletion or mutation has been associated with the development of high-risk B-cell acute lymphoblastic leukemia (B-ALL), as well as with T-cell ALL and acute myelogenous leukemia (AML). Ikaros binds DNA and regulates transcription of its target genes via chromatin remodeling. The mechanism of Ikaros tumor suppressor activity is largely unknown. Here, we present evidence that Ikaros regulates cell cycle progression in leukemia. Using quantitative Chromatin Immunoprecipitation assay (qChIP), we demonstrate that Ikaros binds in vivo to promoter regions of several genes that regulate cell cycle progression in B-ALL cell lines and in primary cells from patients with B-ALL. To study how Ikaros regulates transcription of these genes, luciferase reporter assays were performed. The promoter regions of three Ikaros target genes were cloned into luciferase reporter constructs. Each of these constructs has been co-transfected with Ikaros or an empty vector (as a negative control) into HEK 293T cells. Results showed that Ikaros represses transcription of the three genes that promote cell cycle progression. Overexpression of Ikaros in leukemia cells by retroviral transduction results in reduced transcription of the cell cycle promoting genes, as evidenced by quantitative real-time PCR (qRT-PCR), as well as cell cycle arrest. These data suggest that Ikaros regulates cell cycle progression in leukemia by direct repression of the transcription of the genes that promote cell cycle progression, and identifies one mechanism of Ikaros function as a tumor suppressor in leukemia.
Citation Format: Elanora Dovat, Jonathon Payne, Carlos M. Casiano, Justin Sloane, Chandrika Gowda, Kimberly J. Payne, Sinisa Dovat, Chunhua Song. Regulation of cell cycle progression by Ikaros in leukemia. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3504. doi:10.1158/1538-7445.AM2014-3504
Abstract 3505: Regulation of Cyclin A1 promoter by the Wilms tumor gene, WT1
Authors: Pandey Sony , Moazam Mustafa , Kuerbitz Steven J. , Fraizer Gail C. 
Published: May 2015

Abstract
Cyclin A1(CCNA1) is a unique type of Cyclin A expressed predominantly in highly proliferative tissues such as the testis and bone marrow. In hematopoietic cells CCNA1 expression has been observed in CD34+ progenitor cells, leukemia stem cells and leukemia cell lines. Similarly, Wilms tumor 1 (WT1) gene expression has been observed in these highly proliferative, undifferentiated cells. Regulation of CCNA1 expression is poorly understood, but the CCNA1 gene promoter is a highly GC-rich TATA-less sequence, containing three potential WT1 binding sites. Chromatin immunoprecipitation analysis of two of the three sites revealed binding of the WT1 protein to chromatin in K562 leukemia cells. To assess the role of WT1 in CCNA1 regulation, activation of the CCNA1 promoter by WT1 was measured using luciferase reporter constructs in K562 cells. The distal construct (-1180/+145 ) contains two potential WT1 sites, and the activity of this reporter construct was up-regulated by WT1 co-transfection. In contrast, the proximal (-454/+145) promoter region contains no canonical WT1 binding sites. Suprisingly, the proximal promoter was also up-regulated by WT1 co-transfection. Transcription factor binding site analysis revealed 6 GC boxes -within the core promoter region of the proximal promoter construct that we predicted could serve as non-canonical WT1 binding sites. To determine the importance of these GC boxes for WT1 binding, we treated K562 cells with Mithramycin A, which blocks binding at GC rich sequences. We found that Mithramycin A treatment decreased the activity of both the distal and proximal promoter constructs. Finally we demonstrated that WT1 mediated activation of CCNA1 promoter required an intact DNA binding domain, as a mutant WT1 expression construct lacking the zinc finger domain failed to activate any of the CCNA1 promoter constructs. Overall these results show that WT1 binding can up-regulate the CCNA1 promoter. This observation supports our previous finding that overexpressing WT1 in K562 cells increased CCNA1 mRNA. These data suggest that elevated WT1 expression could mediate increased CCNA1 expression in leukemia cells and thereby enhance proliferation. Overall, our results are consistent with the hypothesis that both WT1 and CCNA1 behave as oncogenes in leukemia.
Citation Format: Sony Pandey, Mustafa Moazam, Steven J. Kuerbitz, Gail C. Fraizer. Regulation of Cyclin A1 promoter by the Wilms tumor gene, WT1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3505. doi:10.1158/1538-7445.AM2014-3505