bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5218: Development of Anti-CD47 therapy for pediatric brain tumors.
Authors: Gholamin Sharareh , Mitra Siddhartha S. , Richard Chase Elliott , Achrol Achal , Kong Doosik , Shin Jun Jae , Monje-Deisseroth Michelle , Cho Yoon-Jae , Weissman Irving , Cheshier Samuel H. 
Published: August 2014

Abstract
Introduction: Extensive molecular characterization of Brain tumors done in recent years has proven valuable for tumor classification, risk stratification and outcome prediction for current treatment modalities. However the current standard of care has not improved the prognosis and carries an increased risk of cognitive impairments for children with brain tumors. A characteristic feature of tumor progression and recurrence is its ability to evade the immune system. Our hypothesis is that by modulating the innate immune system we can enhance the ability of macrophages to ‘eat and kill’ brain cancer cells. Recent data suggests that the interaction between the cell surface antigen CD47 and its binding partner SIRPα is a mechanism by which non-solid and solid tumors can evade the innate immune system. To see if anti-CD47 therapy is a potential therapy in malignant pediatric brain tumors we first looked at CD47 expression in freshly isolated patient and postmortem samples from 4 different tumor types; Diffused Intrinsic Pontine Glioma, Medulloblastoma, Ependymoma and ATRTs. We tested the hypothesis that blocking CD47- SIRPα interaction induced phagocytosis in an in-vitro phagocytosis assay. We next established orthotopic xenografts models in immune compromised mice and treated them with anti-CD47 humanized antibody, which is currently being developed for clinical trials in hematopoietic and non-CNS malignancies.
Result: CD47 expression was upregulated in all tumor types and was present in &gt;90% of the cells in high grade tumors. Increased CD47 expression was observed in CD15+ and CD133+ putative cancer stem cell population. Blocking the CD47- SIRPα interaction increases tumor phagocytosis by macrophages in-vitro. Systemic treatment with anti-CD47 antibody significantly reduced tumor burden in an orthotopic xenograft setting.
Conclusion: Anti-CD47 therapy is a viable and effective treatment modality for pediatric high grade brain tumors.
Citation Format: Sharareh Gholamin, Siddhartha S. Mitra, Chase Elliott Richard, Achal Achrol, Doosik Kong, Jun Jae Shin, Michelle Monje-Deisseroth, Yoon-Jae Cho, Irving Weissman, Samuel H. Cheshier. Development of Anti-CD47 therapy for pediatric brain tumors. [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 5218. doi:10.1158/1538-7445.AM2013-5218
Abstract 5282: The role of T3-regulated microRNAs in human hepatoma cells.
Authors: Huang Ya-Hui , Lin Yang-Hsiang , Chen Ching-Ying , Lin Kwang-Huei 
Published: August 2014

Abstract
Thyroid hormone (T3)/thyroid hormone receptor (TR) signaling regulates cellular growth, development and differentiation, which play important roles in vivo. T3/TR signaling promotes invasion while suppressing proliferation of hepatoma cells. MicroRNAs (miRNA) are small, short, endogenously expressed non-coding RNAs that negatively regulate gene expression. Aberrant miRNA expression has been observed in various tumor types, including hepatocellular carcinoma. At present, it is unclear whether T3/TR signaling regulates miRNAs in hepatoma cells. In our laboratory, miRNA profiling analysis using the high-throughput stem-loop RT-qPCR method revealed upregulation of miR-21 by T3/TR. A native thyroid hormone response element was identified in the primary miR-21 promoter region using promoter and chromatin immunoprecipitation assays. Overexpression of miR-21 promoted hepatoma cell migration and invasion, similar to that observed with T3 stimulation in hepatoma cells. In addition, anti-miR-21-induced suppression of cell migration was rescued by T3. T-cell lymphoma invasion and metastasis 1 (Tiam1), involved in cell migration and invasion, was identified as a miR-21 target, and downregulated by T3. Tiam1 was upregulated upon knockdown of miR-21, and conversely, downregulated upon miR-21 overexpression. Further, knockdown of Tiam1 enhanced migration and invasion may through increase of vimentin and MMP2 expression in hepatoma cells. The correlation among T3/TR, miR-21 and Tiam1 was observed in vivo is similar with in vitro. These findings indicate that miR-21 is directly upregulated by T3. Moreover, T3-mediated enhancement of hepatoma cell migration and invasion may through miR-21-targeted downregulation of Tiam1.
Citation Format: Ya-Hui Huang, Yang-Hsiang Lin, Ching-Ying Chen, Kwang-Huei Lin. The role of T3-regulated microRNAs in human hepatoma cells. [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 5282. doi:10.1158/1538-7445.AM2013-5282
Abstract 5289: Identification of basal-like subtype-specific MicroRNAs in lymph node negative breast cancer .
Authors: Shi Wei , Bruce Jeff , Yan Rui , Liu Fei-Fei 
Published: August 2014

Abstract
Background:
Breast cancer is a heterogeneous disease both clinically and biologically. With the recent recognition of the many different molecular subtypes, a desire to more specifically categorize tumors to allow tailoring of treatment to individual patients has developed. One particularly aggressive and treatment-resistant group is the “basal-like” subtype. However, the molecular events driving this subtype of breast cancer are largely unknown. Here, we propose to examine whether MicroRNAs specifically expressed in basal-like breast cancers contribute to their development and progression.
Materials and Methods:
Fifty-four formalin fixed paraffin embedded primary tumour samples from lymph-node negative breast cancer patients who were participants in a phase III randomized trial of tamoxifen (Tam) +/- whole breast radiation were collected. Intrinsic molecular subtyping was determined using semi-quantitative analysis of ER, PR, Ki-67, HER2, EGFR and cytokeratin (CK) 5/6 on tissue microarrays (TMAs) constructed from the tumor blocks. Patients were classified into the following categories: luminal A, luminal B, luminal-HER2, HER2 enriched or basal-like phenotypes. The median follow-up for this cohort was 10 years. The expression of 365 miRNAs was measured in these samples using the qRT-PCR based Taqman low density array human miRNA panel (Applied Biosystems). Data were validated in cell line models and further analyzed using level 3 TCGA breast cancer data.
Results:
Twenty-three miRNAs were identified at a significantly different expressed level in basal-like breast cancers (n = 6) compared with other subtypes (n = 48). This differential expression was validated in publically available RNA-Seq data generated by the TCGA for 20 of the 23 miRNAs. Eight of these twenty miRNAs were found to correlate with corresponding copy-number alterations at their genomic loci using the data generated by TCGA. Further analysis is currently underway to determine the potential contribution of methylation to the expression differences observed. The putative target genes and pathways involved will also be analyzed.
Conclusions:
MiRNAs are known to play numerous roles in cancer development and progression. In the current study we report several miRNAs with distinct expression patterns in basal-like breast cancers. Further characterization of the phenotypic impact of this deregulation may lead to a better understanding of this aggressive subtype and provide valuable insight needed to develop novel targeted therapies to treat these tumours.
Citation Format: Wei Shi, Jeff Bruce, Rui Yan, Fei-Fei Liu. Identification of basal-like subtype-specific MicroRNAs in lymph node negative breast cancer . [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 5289. doi:10.1158/1538-7445.AM2013-5289
Abstract 5299: Evaluation of apolipoprotein E polymorphism on the aggressive potential of prostate cancer cell lines.
Authors: Ifere Godwin O. , Demark-Wahnefried Wendy , Desmond Renee , Nagy Tim R. 
Published: August 2014

Abstract
Introduction: Defective cholesterol-modulating apolipoprotein E (ApoE) isoforms could exacerbate prostatic neoplasia. Recent evidence strongly suggests that specific genetic variants of ApoE control peripheral tissue cholesterol efflux. Defects in ApoE may result in reduced prostate cancer cell cholesterol efflux and enriched concentrations of cholesterol in membranes by reducing clearance. Membrane-rich cholesterol could potentially activate cancer-driven signaling processes.
Objective: To determine the relevance of specific ApoE phenotypes as risk factors of aggressive prostate cancer based on their influence on reverse cholesterol transport.
Methods: We evaluated ApoE genotypes of the weakly tumorigenic or nonaggressive prostate cancer cell lines (LNCaP and MDA PCA 2b), and the moderate and highly tumorigenic or aggressive prostate cancer cell lines (PC-3 and DU-145). We examined whether ApoE2/E4 variants were associated with tumor aggressiveness via the expression of caveolin-1(cav-1), a cholesterol-regulated pro-carcinogenic gene.
Results: We observed that the nonaggressive prostate cancer cell lines carried either the Apo ε3/ε3 or ε3/ε4 alleles, while the aggressive prostate cancer cell lines carried the Apo ε2/ε4 alleles. Our results showed a two-fold increase in the expression of cav-1 in the aggressive cell lines, as opposed to the nonaggressive ones. There was a significantly (p&lt;0.01) greater cholesterol efflux from the nonaggressive cells lines compared to the aggressive cells. Also, the aggressive cell lines retained and localized more cholesterol in their membranes as opposed to the less aggressive cell lines.
Conclusions: These results suggest an association between cholesterol status and the aggressive potential of prostate cancer cells. It also highlights the need for further investigation into whether ApoE2/E4 is the dysfunctional phenotype, and whether it has the potential as a biomarker of aggressive prostate cancer.
GRANT SUPPORT: NIH R25CA047888
Citation Format: Godwin O. Ifere, Wendy Demark-Wahnefried, Renee Desmond, Tim R. Nagy. Evaluation of apolipoprotein E polymorphism on the aggressive potential of prostate cancer cell lines. [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 5299. doi:10.1158/1538-7445.AM2013-5299
Abstract 5316: Significant changes in D2-like dopamine gene receptors expression associated with non- small -cell lung cancer: A case control study.
Authors: Sheikhpour Mojhgan , Ahangari Ghasem , Sadeghizadeh Majid , khodadad Kian 
Published: August 2014

Abstract
Introduction : Lung cancer is the leading cause of cancer-related death and a major health problem worldwide. Approximately 75% of lung tumors are non - small - cell lung cancer (NSCLC) .The alterations of five different Dopamine receptor genes expression (DRD1,DRD2,DRD3,DRD4 and DRD5) in certain diseases of immune and nervous systems have been reported and play multiple role in various disorders such as cancer. Previous controlled studies demonstrated a relationship between changes in dopamine receptor gene expression profiles and clinical improvement. In the present study, it was hypothesized that the dopamine receptor gene expression profile of peripheral blood mononuclear cells in NSCLC patients could be different from those normal individuals which probably increases the risk of NSCLC.
Material and methods: We investigated dopamine receptors gene expression changes in peripheral Blood Mononuclear cells (PBMC) of 30 NSCLC patients compared to normal individuals . The PBMC was separated from normal whole blood by Ficoll-hypaque and then the total cellular RNA was extracted and cDNA was synthesized, Real Time PCR was done By using primer pairs specific for five dopamine receptors mRNA and β-actin as internal control . Finally the specificities of the obtaine PCR products for the respective dopamine receptors fragments were comfirmed by sequencing and expression comparing of two group (patients and normal cases) was done by SPSS analysis .Results: the results show that DRD2, DRD3 and DRD4 expression changes profile were significant change in NSCLC patients compared to normal individuals . but DRD1,DRD5 genes didn't show any significant and changes . Conclusions: We conclude that there is a quantitative significant difference of D2-like dopamine receptor genes expression in non small cell lung cancer . On the other hand these significant differences and profiles could contribute in diagnosis, treatment and survey and monitoring of non small cell lung cancer .In addition it could be a lead for design of future therapeutic strategies
Key words: Dopamine receptors - Non-small cell lung cancer - Gene expression
Citation Format: Mojhgan Sheikhpour, Ghasem Ahangari, Majid Sadeghizadeh, Kian khodadad. Significant changes in D2-like dopamine gene receptors expression associated with non- small -cell lung cancer: A case control study. [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 5316. doi:10.1158/1538-7445.AM2013-5316
Abstract 5356: EZH2-mediated H3K27me3 is involved in epigenetic repression of DLC1 (Deleted in liver cancer 1) in human cancers.
Authors: Au Leung Kuen , Wong Carmen Chak-Lui , Lee Joyce Man-Fong , Wong Chun-Ming , Ng Irene Oi-Lin 
Published: August 2014

Abstract
Enhancer of zeste homolog 2 (EZH2), the histone methyltransferase of the Polycomb Repressive Complex 2 catalyzing histone H3 lysine 27 tri-methylation (H3K27me3), is frequently up-regulated in human cancers, including hepatocellular carcinoma (HCC). In this study, we identified the tumor suppressor Deleted in liver cancer 1 (DLC1) as a target of repression by EZH2-mediated H3K27me3. DLC1 is a GTPase-activating protein for Rho family proteins. Inactivation of DLC1 results in hyper-activated Rho/ROCK signaling and is implicated in actin cytoskeleton reorganization to promote cancer metastasis. By chromatin immunoprecipitation assay, we demonstrated that H3K27me3 was significantly enriched at the DLC1 promoter region of a DLC1-nonexpressing HCC cell line, MHCC97L. Depletion of EZH2 in MHCC97L by short hairpin RNA reduced H3K27me3 level at DLC1 promoter and induced DLC1 gene re-expression. Conversely, transient overexpression of GFP-EZH2 in DLC1-expressing Huh7 cells reduced DLC1 mRNA level with a concomitant enrichment of EZH2 on DLC1 promoter. An inverse relation in the expression pattern between EZH2 and DLC1 was observed in the liver, lung, breast, prostate, and ovarian cancer tissues. Treating cancer cells with the EZH2 small molecular inhibitor, 3-Deazaneplanocin A (DZNep), restored DLC1 expression in different cancer cell lines, indicating that EZH2-mediated H3K27me3 epigenetic regulation of DLC1 was a common mechanism in human cancers. Importantly, we found that DZNep treatment inhibited HCC cell migration through disrupting actin cytoskeleton network, suggesting the therapeutic potential of DZNep in targeting cancer metastasis. Taken together, our study has shed mechanistic insight into EZH2-H3K27me3 epigenetic repression of DLC1 and advocated the significant pro-metastatic role of EZH2 via repressing tumor and metastasis suppressors.
Citation Format: Leung Kuen Au, Carmen Chak-Lui Wong, Joyce Man-Fong Lee, Chun-Ming Wong, Irene Oi-Lin Ng. EZH2-mediated H3K27me3 is involved in epigenetic repression of DLC1 (Deleted in liver cancer 1) in human cancers. [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 5356. doi:10.1158/1538-7445.AM2013-5356
Abstract 5371: Epigenetic regulation in skin cancer: global DNA methylation profiling in DMBA/TPA induced mice.
Authors: Lee Jong Hun , Shu Limin , Huang Mou-Tuan , Conney Allan H. , Kong Ah-Ng Tony 
Published: August 2014

Abstract
Hypermethylation of CpG islands in the promoter regions of tumor suppressor genes is postulated to be the most relevant epigenetic changes resulting in gene silencing of tumor suppressor gene in cancer. Transcriptionally repressed genes by epigenetic regulation can be reactivated by epigenetic modifications because these silenced genes are still genetically intact. Thus, it is relevant to profile global DNA methylation changes that occur in early stages of carcinogenesis (Jones & Baylin, 2002). To begin addressing this issue, we conducted global profiling of DNA methylation changes in a well-established multistage skin carcinogenesis model using methylated DNA immunoprecipitation (Medip) coupled with CpG island microarray. Tumorigenesis was induced by sequential topical application of mutagen 7,12-Dimethylbenz(a)anthracene (DMBA), and promoting agent 12-O-tetra-decanoylphorbol-13-acetate (TPA), on the dorsal skin of normal CD-1 mice. After 12 weeks, animals were sacrificed and DNA extracted from papillomas. Methylation enriched DNA fragments were pulled down and hybridized to CpG microarray covering 16,030 CpG islands (Agilent, Santa Clara, CA) The results show that significant changes in DNA methylation profile between normal skin and DMBA/TPA induced papilloma, analyzed by Genespring and Bioconductor. After normalization of probe with the gene, 186 genes from 9,867 of up-regulated methylation genes showed at least average 2-fold changes and these include some DNA damage and repair, oxidative stress and inflammatory genes such as Gadd45b and Arnt2. In summary, DMBA/TPA induced mouse skin papilloma undergo extensive aberrant CpG island hypermethylation. Genes detected from Medip-chip assay may be utilized as a potential epigenetic tool to study skin cancer.
Jones, P. A., & Baylin, S. B. (2002). The fundamental role of epigenetic events in cancer. Nature Reviews Genetics, 3, 415-428.
Citation Format: Jong Hun Lee, Limin Shu, Mou-Tuan Huang, Allan H. Conney, Ah-Ng Tony Kong. Epigenetic regulation in skin cancer: global DNA methylation profiling in DMBA/TPA induced mice. [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 5371. doi:10.1158/1538-7445.AM2013-5371
Abstract 5429: Robust in vitro cancer metabolism in non-tumorigenic microglial cells.
Authors: Flores Roberto , Kami Kenjiro , Seyfried Thomas 
Published: August 2014

Abstract
It is well documented that energy metabolism differs between cancerous tissue and normal tissue for a large variety of human and animal tumors. The murine J2 retrovirus contributes to oncogenesis in macrophage cells. The BV-2 microglia cells were immortalized using the v-raf/v-myc carrying J2 retrovirus. These cells, however, do not form tumors when grown in vivo in the natural C57BL/6 host. Consistent with v-raf/v-myc expression, the in vitro metabolic and proliferation rate of the BV-2 cells greatly exceeded that of the tumorigenic and metastatic VM-M3 microglia cells when grown in DMEM containing 25 mM glucose. When controlling for proliferation and ATP production, the BV-2 cells produced more lactate than did the VM-M3 cells under aerobic conditions, thus demonstrating a robust Warburg effect in the BV-2 cells. The Warburg effect is associated with HIF stabilization under aerobic conditions. Mutations in the IDH1 gene produce 2-hydroxyglutarate (2HG), a recognized “onco-metabolite” that also contributes to HIF stabilization under aerobic conditions. Mass spectrometry analysis showed that the non-tumorigenic BV-2 cells made 2-HG only under anoxic conditions. 2-HG was not detected under anoxia or normoxia in VM-M3LM cells, a less malignant clonal variant of VM-M3. It appears that the BV-2 cells have a more robust cancer metabolism than either the high malignant VM-M3 cells or the low malignant VM-M3LM cells. The VM-M3LM cells consumed more oxygen and produced less lactate per ATP than did either the BV-2 cells or the VM-M3 cells, thus displaying a reduced Warburg effect. In other words, the Warburg effect was greatest in the non-tumorigenic BV-2 cells, was lowest in the low malignant VM-M3LM cells, but was intermediate in the high malignant VM-M3 cells. The results suggest that over expression of the v-raf/v-myc oncogenes, production of the IDH1 onco-metabolite, and a robust Warburg effect are not sufficient to drive tumorigenesis in the BV-2 cells. Supported in part from Boston College Res. Expense Fund.
Citation Format: Roberto Flores, Kenjiro Kami, Thomas Seyfried. Robust in vitro cancer metabolism in non-tumorigenic microglial cells. [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 5429. doi:10.1158/1538-7445.AM2013-5429
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 5462: MEDI3185, a potent anti-CXCR4 antibody, inhibits tumor cell migration, signaling and tumor growth in preclinical models.
Authors: Kamal Adeela , Wang Youzhen , Steiner Philipp , Mazzola Anne-Marie , Wetzel Leslie , Passino Melissa , McDermott Brenda , Huang Keven , Bedian Vahe , Greenberg Norman 
Published: August 2014

Abstract
The chemokine receptor CXCR4 is a seven-transmembrane G-protein coupled receptor that mediates chemotaxis and cell migration upon stimulation via its ligand, stromal-derived factor 1 (SDF-1), also called CXCL12. CXCR4 is normally expressed on bone marrow stem and progenitor cells, various circulating lymphocytes, endothelial precursor cells, tissue macrophages and fibroblasts but the aberrant overexpression of CXCR4 is linked to various hematological malignancies, solid tumors and metastatic neoplasms. Moreover, CXCR4 overexpression is correlated with poor prognosis in many types of cancer, including breast, ovarian, colon, pancreatic, AML and glioblastomas. CXCR4 inhibition using siRNA, small-molecule and peptide inhibitors has demonstrated that it can inhibit tumor growth by blocking tumor cell survival/proliferation, metastasis, angiogenesis and tumor immune infiltrates. Here we describe a novel, fully human, antagonistic antibody to CXCR4, MEDI3185, which blocks SDF-1 binding to CXCR4. MEDI3185 has picomolar binding affinity to human CXCR4 and exhibits no significant binding to other chemokine receptors such as CCR4 or CXCR3. In vitro studies demonstrated that MEDI3185 inhibited tumor cell migration, blocked SDF-1 induced tumor cell signaling and induced apoptosis of tumor cells. In preclinical human tumor xenograft models in mouse, MEDI3185 showed single-agent tumor growth inhibition in multiple myeloma and B-cell Burkitt's lymphoma models and had combination activity in ovarian models. In addition, MEDI3185 extended survival as combination therapy in mouse models of CLL and also blocked lung tumor burden in a disseminated ovarian model. Combined, these data suggest that MEDI3185 is a potent CXCR4 antibody for the treatment of both hematological and solid tumors because it has pleiotropic effects on tumor biology that may enhance the efficacy of the current standard of care.
Citation Format: Adeela Kamal, Youzhen Wang, Philipp Steiner, Anne-Marie Mazzola, Leslie Wetzel, Melissa Passino, Brenda McDermott, Keven Huang, Vahe Bedian, Norman Greenberg. MEDI3185, a potent anti-CXCR4 antibody, inhibits tumor cell migration, signaling and tumor growth in preclinical models. [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 5462. doi:10.1158/1538-7445.AM2013-5462