bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4287: Ets-related gene (Erg) expression in developing and adult mouse tissues
Authors: Sreenath Taduru , Tan Shyh-Han , Mikhalkevich Natallia , Ponniah Sathibalan , Vasioukhin Valeri , Bieberich Charles J. , Sesterhenn Isabell A. , Dobi Albert , Srivastava Shiv , Mohamed Ahmed 
Published: July 2012

Abstract
Oncogenic activation of the ETS Related Gene (ERG) in human neoplasms was originally identified in subsets of Ewing sarcomas, myeloid leukemias and, recently, in the majority of prostate cancers. Expression of human ERG protein and consequently its functions in normal and disease states needs to be better understood in light of its suggested role in cell differentiation and proliferation.
In this study, we analyzed temporal and spatial expression of the Erg protein by immunohistochemical analysis during mouse embryonic and adult organogenesis using a highly specific ERG monoclonal antibody (CPDR ERG-MAb) developed by our group. Initially, we evaluated the specificity of three recently available ERG monoclonal antibodies (Epitomics EPR 3864 and EPR 3863, and CPDR ERG-MAb) using ERG expressing MOLT4, KG1, COLO 320, VCaP tumor cell lines and LNCaP, MCF7, Jurkat cell lines that do not express ERG. Unlike, rabbit monoclonal antibodies to ERG obtained from Epitomics, the ERG MAb did not show cross reactivity to FLI-1 or to the other ETS related proteins. Our comprehensive evaluation of mouse tissues established a widespread immunolocalization of Erg protein in endothelial cells and restricted expression in precartilage and hematopoietic tissues. Intriguingly, Erg is not expressed in any epithelial tissue including prostate epithelium, a common site of tumors with ERG rearrangements and unscheduled ERG expression. Further, use of two different monoclonal antibodies revealed that infiltrating lymphocytes that are occasionally seen in the prostate environment were positive for Fli-1, did not exhibit any Erg expression.
These findings will further aid in investigations of Erg functions in normal and disease conditions.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4287. doi:10.1158/1538-7445.AM2011-4287
Abstract 4291: Functional p38 mitoge-activated protein kinase activity restrains pancreatic cancer growth in vitro and correlates with improved eurvival of pancreatic cancer patients
Authors: Zhong Yi , Naito Yoshiki , Iacobuzio-Donahue Christine A. 
Published: July 2012

Abstract
Introduction: Mammalian p38 mitogen-activated protein kinases (MAPKs) are activated by a wide range of cellular stresses as well as in response to inflammatory cytokines. However, depending on the cell type, p38 MAPK family members and their isoforms may either suppress or promote growth. Because we recently identified p38 as a differentially expressed protein in pancreatic duct adenocarcinoma (PDAC), our goal was to clarify its role in this tumor type.
Methods: Immunolabeling for phospho-p38 was performed using a rabbit PAb (Cell Signaling). Kaplan Meier survival plots were determined based on p38 labeling intensity. Total protein was extracted from PDAC cell lines and used for Western blot analysis of p38 expression. Functional kinase activity was also determined by the p38 kinase assay. Growth of PDAC cell lines in vitro was determined in the presence or absence of the p38 inhibitors SB202190, SB203580 and SB239063 by MTT assay.
Results: Immunolabeling for phospho-p38 in PDAC tissues indicated strong positive expression in 65.06% (54/83) of analyzed cases. p38 overexpression was significantly correlated with prolonged overall survival of these same patients by Kaplan Meier analysis (p=0.0155). By Western blot, phospho-p38 expression was confirmed in a subset of PDAC cell lines, and correlated with functional p38 kinase activity in these same cell lines. Inhibition of p38 MAPK activity using the selective p38 inhibitors SB202190 and SB203580 inhibited starvation and gemcitabine-induced cell death in PDAC cells with high p38 activity compared with vehicle control. By contrast, there was no significant difference in cell growth in PDAC cells without p38 activity when treated with these same p38 inhibitors compared with untreated control cells.
Conclusions: Functional p38 MAPK expression restrains cell growth in vitro, and phospho-p38 overexpression in vivo correlates with improved survival of PDAC patients. These studies support the notion that p38 has anti-proliferative or tumor suppressive functions, and that loss of p38 expression prevents cell stress induced sensitization to cell death.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4291. doi:10.1158/1538-7445.AM2011-4291
Abstract 4293: Notch expression expands the pre-malignant pool of T-cell acute lymphoblastic leukemia clones without affecting self-renewal
Authors: Blackburn Jessica S. , Liu Sali , Langenau David M. 
Published: July 2012

Abstract
Over 60% of human T-cell acute lymphoblastic leukemias (T-ALL) harbor NOTCH1 activating mutations, and the cMYC pathway is also commonly activated in this disease. Notch and cMyc have been shown to collaborate in mouse transgenic models of T-ALL, suggesting that these oncogenes function in parallel pathways to enhance tumor growth; however, the exact role of each in T-ALL is unknown. Here, we show that co-expression of Notch and cMyc in zebrafish T cells significantly enhances T-ALL progression compared to cMyc or Notch alone (p&lt;0.001). However, Notch co-expression with cMyc does not enhance proliferation, alter cell cycle kinetics, or modify apoptosis in leukemic cells when compared to T-ALLs expressing cMyc alone. Clonality assays using RT-PCR analyses for T-cell receptor-beta rearrangements indicate that Notch increases the number of T-ALL clones contained within the primary tumor when compared to cMyc expressing leukemais. A large portion of T-ALL clones present in primary Notch and Notch/cMyc leukemias cannot transfer disease into transplanted animals, while all cMyc-alone expressing T-ALLs clones are capable of engraftment and reinitiation of leukemia. Large scale limiting dilution cell transplantation analyses using syngeneic zebrafish demonstrated that primary T-ALLs expressing either Notch or Notch/cMyc have 10-fold less leukemia-initiating frequency when compared to T-ALLs that express only cMyc; however, following serial passaging, both the Notch and Notch/cMyc leukemias exhibit similar leukemia-initiating frequency as cMyc-induced T-ALLs, indicating that Notch signaling does not enhance self-renewal of T-ALL initiating cells. Taken together, our data supports a model where Notch expands a pool of pre-malignant T-ALL clones within the primary tumor, a subset of which acquire additional mutations to confer a fully transformed phenotype. By contrast, cMyc alone is insufficient to increase the overall pool of pre-malignant clones but confers a fully-transformed phenotype to leukemic cells, accounting for the longer latency that likely reflects the acquisition of additional genetic changes in clones. Our data may explain why a subset of relapsed human T-ALLs develop from an underrepresented clone found in the primary leukemia, in that primary human T-ALLs likely have a large pool of pre-malignant clones resulting from NOTCH-pathway activation that are unable to self-renew and thus, cannot give rise to relapsed T-ALL.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4293. doi:10.1158/1538-7445.AM2011-4293
Abstract 4294: Using the zebrafish model to determine the role of the HACE1 tumor suppressor in apoptosis, cell proliferation and development
Authors: McDonald Lindsay A. , Da'as Sahar , D'Alessandro Paul , Sorensen Poul H. , Berman Jason N. 
Published: July 2012

Abstract
HACE1 is a novel tumor suppressor gene located at human chromosome 6q21. HACE1 possesses both ankyrin repeats and a catalytically active HECT domain. HACE1 is downregulated in a variety of human cancers including Wilms’ tumor, melanoma, breast cancer, lung cancer, lymphoma, and colon cancer, thus representing a potentially broadly applicable genetic target. While HACE1 is widely expressed in human tissues, its role in normal development remains unknown. The zebrafish has established itself as a robust model for studying vertebrate development and modeling human cancers by virtue of conserved genetics and direct evaluation of gene expression through imaging afforded by transparent embryos. A zebrafish hace1 homologue has been identified. Whole mount in situ hybridization (WISH) assays with probes to the ankyrin repeats and HECT domains demonstrate expression of zebrafish hace1 in heart, brain and kidney at early developmental time points (24 hours post-fertilization (hpf) – 7 days post-fertilization (dpf)), consistent with human expression. WISH studies in wild type embryos, employing probes to the zebrafish hace1 HECT domain and cmcl2 (heart) or cdh17 (kidney), show co-localization at early developmental time points. Moreover, morpholino knockdown of hace1 in cmcl2-GFP transgenic embryos reveals severely perturbed cardiac development and function beginning at 48 hpf, further implicating this gene in normal vertebrate cardiac development. We have also generated two transgenic zebrafish lines harboring either wild type or dominant negative mutated C876S (C876S DN) human HACE1 genes with a green fluorescent protein (GFP) tag under the control of the ubiquitous β-actin promoter. Compared to wild type embryos, we observed increased apoptosis in 28 hpf C876S DN by acridine orange and caspase 3 assays, both untreated and following irradiation-induced cellular damage. There was no statistically significant difference in cellular proliferation between wild type embryos and C876S DN by 5-bromo-2-deoxyuridine (BrdU) incorporation (p=0.18). These results suggest that loss of HACE1 function alone is not sufficient to lead to a dysregulated cellular proliferation and implicate additional genetic lesions, such as p53 in tumor formation. C876S DN transgenic zebrafish are being crossed with p53 mutated zebrafish in order to determine the combined effect of both mutations on apoptosis, cell proliferation, and tumor formation. Further characterization of the HACE1 transgenic zebrafish model will serve to better our understanding of the role of human HACE1 in normal development and tumorigenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4294. doi:10.1158/1538-7445.AM2011-4294
Abstract 4295: High-throughput screening of osteosarcoma progression: A zebrafish model
Authors: Mohseny Alexander B. , Xiao Wei , Carvalho Ralph , Spaink Herman P. , Hogendoorn Pancras CW , Cleton-Jansen Anne-Marie 
Published: July 2012

Abstract
Background: Osteosarcoma is the most common primary malignant bone tumour of non-hematologic origin. The survival of the patients has reached a plateau phase partly due to a poor understanding of osteosarcoma tumorigenesis. Previously we identified murine mesenchymal stem cells (mMSCs) that formed aggressive osteosarcoma-like lesions after injection in mice (Mohseny et al. J Pathol. 2009 Nov;219(3):294-305). In the current study we aimed to set up a high-throughput model to confirm the mMSCs transformation and to investigate further progression of these cells in vivo.
Methods: The mMSCs were isolated from the bone marrow of C57BL/6 as well as BALB/c mice and cultured for 8 months. Cells of early and late passages were labeled with a fluorescent dye (CM- Dil) and injected into the yolk sacs of 2-days old transgenic zebrafish embryos with GFP labeled vascular system. The embryos were subjected to live imaging for 3 days to screen for cell homing, proliferation, migration and angiogenesis. Subsequently genome wide mRNA expression analysis for both zebrafish and mouse transcripts was performed.
Results: The mMSCs were confirmed to transform in vitro after a period of crisis. High passage mMSCs, i.e. after the transformation, could proliferate, migrate into the fish body and induce angiogenesis whereas low passage MSCs, i.e. prior to transformation, did not. The microarray expression study was technically feasible as mouse transcripts from injected cells were detectable among the more abundant zebrafish RNA.
Conclusions: The present study corroborates mMSCs transformation during long-term in vitro culturing. Furthermore it provides an efficient zebrafish model for studying mMSCs tumourigenic progression to characterize clinical relevant processes like migration and angiogenesis. After analyzing both mMSCs and zebrafish embryos on gene-expression level, the differential behavior of normal and transformed mMSCs as well as the host response can provide new insights into osteosarcoma progression.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4295. doi:10.1158/1538-7445.AM2011-4295
Abstract 4299: CD150, A predictor for xenotransplantation of acute lymphoblastic leukemia to NOD/SCID mice
Authors: Huang Liang , Wang Na , Ma Shuyan , Liu Jingping , Wang Min , Song Xiaoming , Chen Shi , Chen Taiping , Chen Yiyou , Zhou Jianfeng 
Published: July 2012

Abstract
CD150 is a member of the SLAM family that recently has been reported to be differentially expressed among primitive progenitors in the bone marrow of adult mouse. It was utilized to purify hematopoietic stem cells using a simple combination of SLAM family members. To elucidate the presence of this family on acute lymphoblastic leukemia (ALL), we analyzed the expression of this family member on human B-ALL progenitor cells, as well as its relationship with the engraftment of leukemic blasts in serial xenotransplantation assay. Expression analysis was carried out by flow cytometry. We combined the expression pattern of human CD150, CD244 and CD48 with serial xenotransplantation of B-ALL progenitor cells to indicate their relationship. Our data showed that CD48 and CD244 were expressed on most B-ALL progenitor cells, and interestingly only blast cells with low percentage of CD150+ population were able to reconstitute leukemia into primary, secondary and tertiary NOD/SCID mice. In conclusion, SLAM family members are present on B-ALL progenitor cells and the engraftment potential of leukemic blasts is correlated negatively with the proportion of CD150+ cells, the percentage of which can serve as a useful predictor for graft success of B-ALL to immune deficient mice. The mechanism of CD150 as a predictor is under further investigation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4299. doi:10.1158/1538-7445.AM2011-4299
Abstract 430: 4F2hc mediates renal cancer cell (RCC) behavior
Authors: Poettler Marina , Kalinowska Waclawa , Novotny Rene , Braemswig Kira H. , Haitel Andrea , Susani Martin , Zielinski Christoph C. , Prager Gerald W. 
Published: July 2012

Abstract
4F2, a transmembrane protein, has a heteromeric structure, consisting of a heavy subunit (4F2hc, CD98hc, SLC3A2) and a light subunit, extracellular linked together via disulfid bounds. The light chains provide amino acid transport activity, while the heavy chain physically interacts with a conserved motif of integrin beta subunits, thereby mediating adhesion-induced signal transduction. A genetic knockout of 4F2hc in animals is embryonic lethal, overexpression of 4F2hc in somatic cells leads to malignant transformation.
In the present study we aimed to characterize 4F2hc expression in renal cell cancer (RCC) as a diagnostic or prognostic marker, as well as to indentify a potential functional role of 4F2 in tumor cell behavior. By immunohistochemistry and analysis of multi tissue arrays, we found that 4F2hc is highly expressed in papillary, clear cell and chromophobe RCC, while no 4F2hc expression was found in benign tumors, such as oncocytomas. Thereby, 4F2hc expression directly correlated with grade of differentiation suggesting 4F2hc as a novel and reliable marker for the more malignant subtype II papillary renal cell cancer (type II 83.34 %, type I 4.76 % 4F2hc positive, p &lt; 0.00001; n = 51).
To evaluate a potential functional role of 4F2 in renal cancer cell behavior, we generated a stable low 4F2hc clear cell RCC cell line (93% downregulation) and compared the protein expression as well as the tumor cell behavior with a high expressing mock transfected counterpart cell line. We found that tumor cell behavior such as cell proliferation, cell survival and cell migration were significantly impaired, whenever 4F2 expression was downregulated. As 4F2 light chain distribution to cell surface is dependent on 4F2hc, leucine amino acid transport in low 4F2hc/Caki2 cells is impaired, as shown by C14-leucine uptake assays. Transfection of silent mutations either lacking integrin interaction site (delta WALLL) or amino acid transport capabilities (Cys109_330Ser) in low4F2/ Caki2 cells revealed a functional relevance of 4F2hc upon tumor cell behavior.
From these data we conclude that 4F2 (1) represents a promising new diagnostic marker for RCCs, whereby grade of differentiation correlates with amount of 4F2 expression, and (2) 4F2 might play a functional role in renal cancer cell behavior.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 430. doi:10.1158/1538-7445.AM2011-430
Abstract 4300: Selective GFP labeling of cancer with a telomerase-specific adenovirus (OBP-401) to report future recurrence after resection
Authors: Kishimoto Hiroyuki , Aki Ryoichi , Urata Yasuo , Bouvet Michael , Momiyama Masashi , Tanaka Noriaki , Fujiwara Toshiyoshi , Hoffman Robert M. 
Published: July 2012

Abstract
We have previously developed a telomerase-specific replicating adenovirus expressing GFP (OBP-401). Intraperitoneal (i.p.) injection of OBP-401 specifically labeled peritoneal tumors with GFP enabling real-time surgical navigation. However, technical difficulty of removing microscopic tumors still remains, which makes it difficult to eradicate disease completely, even after so-called complete resection. In this study we report an additional advantage of OBP-401. Weeks after surgical navigation with OBP-401, recurrent tumor nodules were observed with GFP imaging, indicating that OBP-401 treatment for peritoneal disseminated disease enabled detection of its subsequent recurrence after surgical navigation. Thus tumor labeling with a genetic reporter has important advantages over antibody and other non-genetic labeling since reminant disease remains labeled and can be further resected.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4300. doi:10.1158/1538-7445.AM2011-4300
Abstract 4301: Deletion-mapping identifies the regions within MN1 that regulates its transforming activity in hematopoietic cells
Authors: Kandilci Ayten , Bonten Jacqueline , Janke Laura , Neal Geoffrey , Terranova Sabrina , Grosveld Gerard 
Published: July 2012

Abstract
The oncogene MN1 is deregulated in human acute myeloid leukemias and its overexpression is known to induce proliferation and repress myeloid differentiation of primitive human and murine hematopoietic cells, which causes myeloid leukemia in mouse models. To study the role of different regions within MN1 in MN1-induced leukemia, we generated in-frame deletion mutants of the protein. Using retroviral transduction assays, we found that the regions between amino acids 12 to 228 and 570 to 1273 are required for its in vivo transforming activity, although the 12-228-mutant was still capable of repressing myeloid differentiation and inducing self-renewal in vitro. Both MN1 and the 12-228-mutant increased the frequency of common myeloid progentiors (CMP) in vitro and microarray comparison of purified CMPs identified Hoxa9, Meis1, Myb, Cebpa, Cebpb and Cebpd among many other differentially expressed transcripts as potential candidates that mediate MN1-induced leukemia.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4301. doi:10.1158/1538-7445.AM2011-4301