bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3979: Ethnic polymorphisms in the GGAA microsatellite response element of key Ewing's sarcoma EWS/FLI-target genes
Authors: Monument Michael J. , Beck Robert , Watkins W. Scott , Jorde Lynn B. , Randall R. Lor , Lessnick Stephen L. 
Published: August 2012

Abstract
Study Rationale: Unlike other cancer models, the risk factors predisposing patients to the development of Ewing's sarcoma and predicting subsequent disease behavior are largely unknown. Interestingly, the incidence of Ewing's sarcoma is highest in populations of European descent, which is 10X higher than the incidence observed in those of African descent. Furthermore, cure rates and overall survival are significantly worse in patients of African descent. Recently, it has been shown that the EWS/FLI fusion product selectively binds to a (GGAA)n microsatellite response element embedded within the promoter region of key EWS/FLI-target oncogenes. An increasing number of these repeats also appears to positively affect DNA binding and gene activation. We hypothesize that differences in polymorphic GGAA microsatellites within the promoter regions of key EWS/FLI-target genes may exist in African and European populations, contributing to observed differences in Ewing's sarcoma incidence and outcomes. Methods: Genomic DNA samples were obtained from 100 subjects each of African and European descent. The microsatellite regions within the promoter elements of two key EWS/FLI target genes (NR0B1 and CAV1) were PCR amplified, cloned and sequenced. Microsatellite sequences were analyzed and the overall length of the microsatellite, the total number of GGAA repeats and the maximal number of consecutive repeats were quantified. Data was statistically interpreted using a comparative two-tailed t-test. Results: Measurements of the CAV1 microsatellite response element were quite similar for both African and European subjects. In sharp contrast, marked inter-ethnic variation was observed for the NR0B1 GGAA microsatellite response element. African samples had a significantly longer GGAA microsatellite, a greater number of total (GGAA)n repeats and longer consecutive (GGAA)n repeats (p&lt;0.0001). Conclusions: These data demonstrate a marked inter-ethnic variation in the genetic constitution of the Ewing's sarcoma EWS/FLI-response element within the NR0B1 promoter. Given the epidemiological differences of Ewing's sarcoma susceptibility and disease outcome in these divergent populations and the importance of NR0B1 dysregulation in Ewing's sarcoma oncogenesis, this novel finding warrants further functional investigation.
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 3979. doi:1538-7445.AM2012-3979
Abstract 398: Tumor microenvironment imposes major alterations and profoundly shapes functional status of macrophages: peritoneal and tumor-associated macrophages from tumor hosts are two very different subpopulations
Authors: Torroella-Kouri Marta , Rodriguez Dayron , Silvera Risset , Nadji Mehrjad , Caso Raul , Rodriguez Gracielena , Gonzalez-Perez Ruben R. , Iragavarapu-Charyulu Vijaya , Carrio Roberto 
Published: August 2012

Abstract
Macrophages are key players in the inflammatory response and exhibit significant roles in the different stages of tumor progression. We have previously reported deficient functions of peritoneal macrophages of D1-DMBA3 mammary tumors bearers (T-PEMs). We showed that T-PEMs are impaired in inflammatory activity due to diminished expression of transcription factors NFκB and C/EBP. We have also demonstrated that T-PEMs display neither M1 nor M2 phenotypes, exhibit deficiencies in the production of several inflammatory cytokines, are less differentiated and show increased apoptosis. Importantly, we showed for the first time that their apoptosis in periphery contributes to increased myelopoiesis. We examined the blood monocytes from these tumor mice and demonstrated that these cells are neither inflammatory nor suppressive and are less differentiated, similar to the T-PEMs they later become. In the present study we investigate tumor-associated macrophages (TAMs) from the same tumor model and compare them with T-PEMs and with peritoneal macrophages from normal mice (N-PEMs). Our results show that TAMs downregulate IL-12p70, but upregulate IL-12p40, IL-23, IL-6 and IL-10 and chemokines and their receptors are very differently expressed in these two macrophages subpopulations. NFκB and C/EBP family members are decreased in TAMs as compared with T-PEMs, however NFκBp50 homodimers, STAT1/pSTAT1 and STAT3/pSTAT3 are all overexpressed. Moreover TAMs block T-cell proliferation and are more prone to apoptosis than T-PEMs due to a higher expression of activated caspase-3 and downregulation of Bcl-X. Our results show that T-PEMs and TAMs have equally impaired phagocytic capacity compared with fully-phagocytic N-PEMs. Moreover, TAMs constitutively express iNOS, produce nitric oxide but no arginase and are Gr-1high and CD11blow, thus are not classic myeloid-derived suppressor cells. Collectively, our results show that the exposure to different locations and tumor factor gradients determine macrophage phenotypes and functions. The tumor microenvironment, as the setting in most intimate contact with tumor cells is the one that most alters macrophage activity. Targeting tumor factors and other cells in the tumor microenvironment may allow reversion of macrophage dysfunction.
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 398. doi:1538-7445.AM2012-398
Abstract 3987: Merlin is a negative regulator of human melanoma
Authors: Murray Lucas B. , Lau Ingar , Yu Qin 
Published: August 2012

Abstract
Merlin is a cytoskeletal linker protein encoded by the neurofibromatosis type 2 (NF2) gene. Like the other Band 4.1 protein family members, it serves to connect cell surface proteins to the actin cytoskeleton. Defects in the protein caused by mutations of the NF2 gene give rise to NF2 disease, which is generally characterized by the formation of bilateral vestibular schwannomas and, to a lesser extent, meningiomas and ependymomas. In addition to these tumor types, merlin has been shown to be mutated and/or merlin protein expression lost in other cancers including mesothelioma, thyroid cancers, and melanomas, albeit to a lesser extent. In the current study, we set out to elucidate the role of merlin in the progression of human melanoma. We first show that merlin knockdown enhances melanoma cell migration and invasion in vitro. Furthermore, we show that decreased merlin expression leads to increased subcutaneous melanoma growth in immuno-compromised mice. Tumors derived from merlin knockdown cells display border regions that are generally less well defined, with cases in which tumor cells are visible in the surrounding dermis and adipose tissue, which is consistent with the more invasive phenotype observed in vitro upon merlin knockdown. To compliment these knockdown experiments we overexpressed merlin in a metastatic melanoma cell line. Upon increased merlin expression, the melanoma cells exhibit decreased in vitro migration, invasion, and proliferation. These cells also display a diminished ability to form anchorage independent colonies in soft agar. Additionally, increased merlin expression inhibits in vivo subcutaneous growth of the melanoma cells in our xenograft experiments. Lastly, we surveyed several signaling pathways to identify a mechanism that exerts the negative regulatory effect of merlin on melanoma growth. We found that merlin protein levels in human melanoma cells are correlated with the extent of induced activation of the known tumor suppressors in the Hippo signaling pathway, MST1/2 Ser/Thr kinases, which have been shown to function downstream of merlin in other cell types. Taken together, these results provide evidence for the first time that merlin is a negative regulator of human melanoma progression and that it may exert its inhibitory effects through the activation of the MST1/2 kinases.
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 3987. doi:1538-7445.AM2012-3987
Abstract 399: Deletion of the Mint3 gene in mice abrogates macrophage functions and increases resistance to cancer metastasis
Authors: Hara Toshiro , Sakamoto Takeharu , Seiki Motoharu 
Published: August 2012

Abstract
Hypoxia inducible factor-1 (HIF-1) is the master transcription factor to shift the energy production system from oxidative phosphorylation (OXPHOS) to glycolysis during hypoxia. Although most cells employ OXPHOS for ATP during normoxia, macrophage is unique in using glycolysis constitutively. We have proposed that macrophages use Mint3 to inhibit FIH-1 that suppresses transcriptional activity of HIF-1 during normoxia. To demonstrate physiological function of Mint3 in macrophages, we establish Mint3 deficient mice and analyze macrophage specific functions. The mutant mice have no apparent phenotype but exhibit significant resistance against lipopolysaccaride (LPS)-induced septic shock and cancer metastasis. Macrophages obtained from the mutant mice exhibit 60% levels of ATP content compared to wild type cells, lower levels of glycolysis, cytokine production and motility. Thus, cell type specific role of Mint3 in energy production in macrophages is demonstrated for the first time using genetically manipulated mice. Specific function of Mint3 in macrophages might allow us developing therapeutics to regulate excessive macrophage functions during infection and diseases such as cancer.
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 399. doi:1538-7445.AM2012-399
Abstract 3990: SPANXA1 suppresses tumor metastasis through WNT pathway in lung cancer
Authors: Kang Po-Hsiang , Hsu Chia-Ying , Su Kang-Yi , Chen Hsuan-Yu , Yu Sung-Liang 
Published: August 2012

Abstract
SPANX (Sperm protein associated with the nucleus, X-linked) gene family has been found higher expression in many cancers, such as testicular germ tumor, melanoma, glioblastoma and hematologic malignancies. However, in our previous study, the gene expression array analysis showed that the expression of SPANX family member A1 (SPANXA1) was higher in lower invasive lung cancer cells, CL 1-0, than in higher invasive cells, CL 1-5. Real-time PCR was used to confirm that mRNA expression of SPANXA1 was 8 times higher in CL 1-0 than CL 1-5. In vitro assays showed that migration and invasion abilities of CL 1-5 stable transfectants were decreased in a dose-depended manner. Interestingly, cell morphology dramatically changed from mesenchymal-like to epithelial-like in CL 1-5 SPANXA1 stable transfectants, which was consistent to its decreased invasive ability in vitro. Therefore, we demonstrated metastasis ability of CL 1-5 SPANXA1 stable transfectants would be down-regulated in vivo, which was performed in mouse metastasis model by tail-vein injection. Next, we set up CL 1-0 lentiviral-base shRNA knockdown clones, and the cell mobility and invasion ability were increased. Because SPANXA1 could induce the cell morphology change, we evaluate the effect of SPANXA1 on the expression of EMT markers. We found up-regulation of E-cadherin, an epithelial marker, and down-regulation of vimentin and N-cadherin, which were known as mesenchymal markers in presence of SPANXA1. Finally, to identify the underlying mechanism of SPANXA1, we carried out gene expression array and 3 of top 10 pathways are EMT-related. Furthermore, quantitative RT-PCR validation showed WNT pathway is involved in SPANXA1-repressed metastasis indicated that SPANXA1 might provide a new treatment in lung cancer.
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 3990. doi:1538-7445.AM2012-3990
Abstract 3992: Tid1, a tumor suppressor, regulating the cancer initiation properties of HNSCC
Authors: Chen Yu-Hsuan , Lo Jeng-Fan 
Published: August 2012

Abstract
Background: Tid1, a DNAJ/Hsp40 family protein, functions as a tumor suppressor in different types of cancer including HNSCC and influences many signaling pathway in cancer cells. Expression of Tid1 protein is negatively associated with the malignancy of HNSCC cells and tumor tissues. In addition, it has been shown that Tid1 interacts with P53, which exerts negative regulation of Nanog, one of the transcriptional factors to maintain the cellular stemness properties. Epithelial-mesenchymal transition (EMT), a process by which epithelial cells lose their polarity and later acquire a migratory mesenchymal phenotype, is one of the crucial processes that induce tumor invasion and metastasis. Further, gain of EMT could promote stem cells (SCs) properties. Accumulating data support the hierarchical model of cancer initiating cells (CICs) or cancer stem cells (CSCs) in that each tumor formation is governed by a rare subpopulation of cells with self-renewal capacity. CICs have been demonstrated to have capacities of promoting tumor growth, tumor regeneration and metastatic progression. Methods: Cancer cells with Tid1 knockdown or overexpression were generated to evaluate the different properties of stemness and tumorigenicity in vitro and in vivo. Further, the differential gene expression profile of EMT signature and stemness of cancer cell with Tid1 upregulation or downregulation were examined. Results: We observed that Tid1 knockdown enhanced expression of EMT-activator, Snail, and stemness marker Grp78, Nanog, and also exhibited higher ability of migration, invasion, anchorage-independent and sphere formation. In addition, Tid1 overexpression cells decreased cell mobility, sphere formation ability and displayed loss of EMT-activator and stemness marker. Conclusion: Overall, we proved that expression of Tid1 is negatively correlated with EMT and cancer initiation properties in HNSCC. Tid1 potentially could be a key regulator involved in differentiation of cancer cell. Further, therapeutic strategies on target Tid1 mediated malignant properties will be an alternative treatment on for HNSCC.
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 3992. doi:1538-7445.AM2012-3992
Abstract 3993: MiRNA-141 and methylation regulation of WNT signal pathway by suppressing SOX17 in esophageal cancer
Authors: Guo Mingzhou , Jia Yan , Yang Yunsheng , Zhan Qimin , Herman James G. 
Published: August 2012

Abstract
Purpose: WNT/β-catenin gene SOX17 was reported frequently methylated in colonic and hepatic cancer. To explore epigenetic changes of SOX17 as esophageal cancer marker and therapeutic target, epigenetic regulation and tumor suppressor function of SOX17 were analyzed in study. Experimental Design: Methylation specific PCR (MSP) was employed to examine SOX17 methylation in 8 esophageal cancer cell lines and 9 normal mucosa, 60 dysplasia and 169 cancer tissue. Semi-quantitative RT-PCR method was used to examine SOX17 expression before and after 5-aza-2′-deoxycytidine treatment of esophageal cancer cells. Expression of SOX17 and β-catenin were detected by immunohistochemistry (IHC) in esophageal cancer and adjacent tissue. Luciferase reporter assay, colony formation, transfection and western blotting were applied to analyze SOX17 function in WNT signal pathway. Prediction software and miRNAs related detection methods were preformed to evaluate miRNA regulation of SOX17. Results: SOX17 was silenced by promoter region methylation and reactivated by 5-aza-2′-deoxycytidine treatment in esophageal cancer cell lines. Loss of SOX17 expression and accumulation of β-catenin in nuclear and cytoplasm were associated with promoter region hypermethylation in esophageal cancer(test, P=0.0359, P=0.0105). Restoration of SOX17 expression inhibited β-catenin/TCF-dependent transcription and colony formation. The presence of SOX17 methylation correlated significantly with alcohol history in esophageal cancer(test, P=0.0057). MiR-141 was also found to down-regulate SOX17 expression and activated the WNT signal pathway. Conclusions: SOX17 is frequently methylated in esophageal cancer, and SOX17 expression is regulated both by miR-141 and promoter region methylation. Loss of SOX17 removes the normal inhibition of WNT signaling and promotes esophageal tumorigenesis.
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 3993. doi:1538-7445.AM2012-3993
Abstract 3996: Identification of DEC1-interacting protein DNAJB6 and its role in esophageal squamous cell carcinoma
Authors: Yu Zhuoyou , Wong Victor Chun Lam , Chan Kwok Wah , Lung Maria Li 
Published: August 2012

Abstract
Esophageal squamous cell carcinoma (ESCC) has an especially high incidence in China, with five-year survival rates in Hong Kong being of ∼14%. Previously, a critical region at 9q33-34 was narrowed down and identified to be associated with tumor-suppressive function in ESCC. Within this region, Deleted in Esophageal Cancer 1 (DEC1), was identified to suppress anchorage-independent growth and tumorigenesis. In this study, we searched for DEC1-interacting partners by yeast two-hybrid screening. DNAJ (Hsp40) homologue subfamily B member 6 (DNAJB6) was identified as a DEC1-interacting protein and its interaction was further confirmed by the GST pull-down assay and co-localization studies. A putative DEC1-interacting sequence was mapped to the C-terminal end of DNAJB6 coding sequence. Using a tissue microarray constructed with tissues from Hong Kong, significantly higher survival in distant metastasis-free (M0) patients was found to be associated with higher DNAJB6 nuclear staining. DNAJB6 is down-regulated in 12 out of 14 (85.7%) ESCC cell lines, when compared to expression in an immortalized normal esophageal epithelial cell line. The two isoforms of DNAJB6 have distinct cellular localizations. DNAJB6a is mainly localized to the nucleus, while DNAJB6b shows diffuse staining in both the nucleus and cytoplasm. Through migration/invasion assay, we showed that expressions of both isoforms were inversely associated with migration/invasion ability of ESCC cell lines. These results suggest DNAJB6 plays a role in ESCC migration/invasion and metastasis. This gene may play a critical role in ESCC metastasis in an isoform-specific manner, which will be the focus of future studies.
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 3996. doi:1538-7445.AM2012-3996
Abstract 3999: Experimental study of tumor suppressor gene RBM5 in non-small cell lung cancer
Authors: Wang Ke , Shao Chen , Zhao Lijing 
Published: August 2012

Abstract
Introduction: Deletion within the lung cancer tumour suppressor region at 3p21.3 constitutes the earliest premalignant chromosomal aberration in human lung cancers. Nineteen genes map to this region. RNA Binding Motif 5(RBM5) maps to one end of this 19-gene deletion breakpoint, and is not included in a slightly smaller 17-gene deletion that is common to breast and renal tumours. This suggests a critical role of RBM5 in lung cancers. To further explore the role of RBM5 in lung cancer, we examine the RBM5 expression in primary tissues and the associated function in vitro. Method: Paired non-tumor and tumor samples were obtained from 30 adenocarcinomas. The mRNA and protein expression of RBM5 were examined by semi-quantitative reverse transcription-polymerase chain reaction and Western blot. A549 cell line was used to determine the apoptotic function of RBM5 in vitro. A549 cells were transient transfected with RBM5, the AnnexinV, PAPP and cell cycle analysis were performed by flow cytometry and Western blot respectively. Results: We found that RBM5 mRNA and protein expression levels were reduced in tumor tissue compared the non-tumor tissue (P&lt;0.05). Overexpression of RBM5 in A549 cells resulted in an increase of PAPP expression, phosphatidyl serine (PS) flip to the outer cellular membrane and G arrest in cell cycle. Conclusion: Decreased expression of RBM5 in adenocarcinomas suggests that RBM5 may play a crutial role in the carcinogenesis. Enhanced apoptotic activity induced by RBM5 overexpression in A549 cell line might be one of the essential mechanisms by which RBM5 function as a tumour suppressor.
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 3999. doi:1538-7445.AM2012-3999
Abstract 4: Gene amplification of EGFR, HER2, HER3 and HER4 in esophageal squamous cell carcinoma
Authors: Kato Hiroaki , Arao Tokuzo , Matsumoto Kazuko , Fujita Yoshihiko , Kimura Hideharu , Nishiki Kouhei , Shiraishi Osamu , Yasuda Atsushi , Peng Ying-Feng , Shinkai Masayuki , Imano Motohiro , Imamoto Haruhiko , Yasuda Takushi , Okuno Kiyotaka , Shiozaki Hitoshi , Nishio Kazuto 
Published: August 2012

Abstract
Overexpression of epidermal growth factor receptor (EGFR) and its family members HER2, HER3 and HER4 are found in a variety of human malignancies and their roles in cancer development and progression has been widely recognized for long time. Molecular drugs targeting EGFR family, such as small-molecule inhibitors and specific monoclonal antibodies, are now under intensive investigation in clinical setting. In esophageal squamous cell carcinoma (ESCC), EGFR and HER2 are frequently overexpressed and their poor prognostic impacts have been reported to date. However, there is no study evaluating gene amplification of EGFR, HER2, HER3 and HER4 simultaneously in ESCC in a large cohort. We examined gene amplification of EGFR, HER2, HER3 and HER4 using realtime PCR-based copy number assay on 196 surgical specimens of formalin-fixed, paraffin-embedded (FFPE) samples. Gene amplification of EGFR and HER2 (copy number &gt; 4) was observed in 7 % and 11%, respectively. Although the copy numbers were relatively low, we found gene amplification of HER3 and HER4 to be observed in 8% and 7%, respectively. Gene amplification at least one or more genes was observed in 23 % (45/196) of ESCC samples. Overlapping gene amplification was identified in 8 % (15/196) of samples. In relation with clinical characteristics, gene amplification of HER2 and HER4 was significantly involved in shorter relapse-free survivals in stage III ESCC. In conclusion, gene amplification of EGFR family was frequently observed in ESCC and PCR-based copy number assay could be a powerful tool for detecting gene amplification using FFPE samples. Our results strongly encourage the development of EGFR family-targeted therapy for ESCC with gene amplification.
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 4. doi:1538-7445.AM2012-4