bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5341: Clinical relevance of metastasis-related miRNAs in early breast cancer.
Authors: Markou Athina N. , Yousef George M. , Liang Yu , Stathopoulos E , Georgoulias Vassilios , Lianidou Evi S. 
Published: August 2014

Abstract
Introduction
It was recently demonstrated that miRNAs control breast cancer metastasis by influencing multiple metastatic steps. In this study we firstly evaluated the clinical relevance of specific miRNAs -recently shown to correlate with metastasis in breast cancer by exploring their expression profile in FFPEs samples of early breast cancer patients in respect to the clinical outcome of the patients. Finally, we investigated the correlations between the expression of these selected miRNAs and other parameters such as ER and PR expression.
Materials and Methods
One hundred and twelve (112) FFPE blocks were obtained from breast tumors of early breast cancer patients (follow-up period of 11 years) and 13 mammoplasty specimens from healthy tissues which were used as controls. The median overall survival (OS) and disease free interval (DFI) were 84 and 68 months respectively. We have chosen to quantify the expression of six metastasis related miRNAs, namely: miR-10b, miR-2,1 miR-205, miR-210, miR-335 and let-7a by RT-qPCR in the LightCycler (Roche). HER2, ER and PR expression of the primary tumors was detected by immunohistochemistry with the monoclonal antibody CB11 and with monoclonal antibodies to ER and PR, respectively, using the OPTIMAX automated system. For all miRNAs relative expression was determined using the ΔCq approach and expression values were normalized to miR-191 which has been shown to be a suitable reference miRNA.
Results
Kaplan-Meier survival curves demonstrated that patients with high miR-21 expression (n=56) had a significant shorter DFI than those with low miR-21 expression (P=0.043). Moreover, patients with low expression of miR-205 (n=57) had both shorter DFI and OS time than those with high expression levels (P=0.040 and P=0.047 respectively). However, the expression levels of the other four miRNAs were not related with the DFI and OS. We also found that in the ER-negative subgroup (n=46), disease relapse was more common in patients where miR-10b was over-expressed (P=0.019), while in the PR-negative subgroup (n=47), disease relapse was more common in patients with miR-21 overexpression (P&lt;0.001) or miR-10b overexpression (P =0.016). Finally, in the group of PR-negative patients we noticed that patients who overexpressed miR-21 had shorter OS (P=0.021).
Conclusions
Quantification of metastasis related miRNAs expression in primary tumors can give important prognostic information in patients with early breast cancer.
Citation Format: Athina N. Markou, George M. Yousef, Yu Liang, E Stathopoulos, Vassilios Georgoulias, Evi S. Lianidou. Clinical relevance of metastasis-related miRNAs in early 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 5341. doi:10.1158/1538-7445.AM2013-5341
Abstract 5347: MiRNA expression profile of tumor microenvironment in murine liver metastatic model.
Authors: Marquez Joana , Schaub Arianne , Unzurrunzaga Maite , Garcia Patricia , Badiola Iker 
Published: August 2014

Abstract
Colorectal cancer (CRC) is the second most recurrent cancer type and one of the most lethal diseases around the worldwide. The lethality of the CRC is due to the metastasis and the principal target is the liver. Although the main responsible of the metastasis is the cancer cell we can not obviate the crucial role of the host organ and how the cells of the host organ support the progression of the disease. The crosstalk of the tumor microenvironment with the tumor has been deeply studied from the cellular point of view but the regulatory pathways of these processes still remain unknown. The epigenetic regulation has been postulated as one important process implicated in the regulation of cellular changes. The microRNA (miRNA) expression is one of the variants of the epigenetic regulation. In this work we study the deregulation of the miRNA expression in the metastasized liver respect to healthy condition using a murine in vivo liver metastasis model.
We inoculated CT26 murine colon carcinoma cell intrasplenically in BALB/c mice and after 15 days we sacrificed the animals to obtain four liver cell types (hepatocytes, liver sinusoidal endothelial cells, Kupffer cells and hepatic stellate cells). Then we isolated the total RNA and performed gene expression and miRNA expression microarrays (Agilent) comparing the tumor received cells with control cells (PBS injected animal's cells). The gene expression microarray helps us finding the biological and cellular sense of the deregulated miRNAs and could be an important data source to elucidate the therapeutic option of each deregulated miRNAs. An in vivo approach is a more realistic model that can show more elements implicated in the crosstalk of the different liver cell types. This fact show us several results in the different cell types with expected and unexpected new miRNA deregulations. For instance downregulation of miR-16 and miR-15b and upregulation of miR-138 has been found in hepatic stellate cells with important role in activation proliferation and apoptosis of this cell type and we also observed deregulation of miR-135 in liver sinusoidal cells. These are some of the examples of a large amount of miRNA identified. Nowadays we are checking the role of each deregulated miRNA in the cellular processes to verify their implication in the metastatic progression and postulate them as therapeutic targets.
Citation Format: Joana Marquez, Arianne Schaub, Maite Unzurrunzaga, Patricia Garcia, Iker Badiola. MiRNA expression profile of tumor microenvironment in murine liver metastatic model. [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 5347. doi:10.1158/1538-7445.AM2013-5347
Abstract 5369: Methylation profile of markers for epithelial-mesenchymal transition and stem cell in tamoxifen-resistant MCF-7 breast cancer cell line.
Authors: Lee Youngseok , Kim Aeree , Kim Han-Kyeom 
Published: August 2014

Abstract
DNA methylation plays a key role in the epigenetic-based regulation of gene expression. Several genes that showed increased hypomethylations of gene promotors in antiestrogen-resistant breast cancer cells were found to be increased in tumor cells and possess oncogenic activity. The purpose of this study is to investigate the differences of methylation profiles, especially EMT markers, between tamoxifen-sensitive breast cancer cell lines and tamoxifen-resistant cell lines using MCF7 and tamoxifen-resistant MCF7 (MCF7-R) cell lines, and then to indentify the presence of the identified markers in the breast tissues of recurred patients with antiestrogen treatments. Bisulphite-converted genomic DNA was assayed on Infinium Human Methylation 450K Beadchips using the Illumina Infinium HD methylation assay kit using four groups of the cells including MCF7, MCF7-R, MCF+E2 and MCF7-R+E2. . In MCF7-R cells, 31023 CpG sites showed altered methylations, with 13617 hypomethylated and 17406 hypermethylated, compared with MCF7. The numbers of hypomethylated and hypermethylated CpG sites in the promoter regions were 4719 and 3347, respectively. Among the well-known EMT markers, the genes meeting the results of methylation status selected were CTNNB1, SNAIL2, TWIST1, LEF1, GSC and ETS1. Although the results of the current study suggest that aberrant DNA methylations of EMT markers are not the main force driving the molecular biology of resistance against antiestrogen therapy, these will contribute and result in to some extent.
Citation Format: Youngseok Lee, Aeree Kim, Han-Kyeom Kim. Methylation profile of markers for epithelial-mesenchymal transition and stem cell in tamoxifen-resistant MCF-7 breast cancer cell line. [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 5369. doi:10.1158/1538-7445.AM2013-5369
Abstract 5372: Cocaine enhances HIV-1 integration by modulating the epigenetic signatures of CD4+ T cells.
Authors: Addai Amma , Dash Chandravanu 
Published: August 2014

Abstract
Human Immunodeficiency Virus (HIV-1) has claimed the lives of over 25 million people. Illicit drug use serves as a co-factor for HIV/AIDS. Cocaine, a commonly used drug among HIV-1 positive individuals, serves as a cofactor for HIV-1 infection and progression to acquired immunodeficiency syndrome (AIDS). Previous studies suggest that cocaine increases HIV-1 replication in cell cultures, peripheral blood mononuclear cells (PBMCs) and animal models. However, the mechanism by which cocaine enhances HIV-1 replication in CD4+ T cells remains largely unknown. During HIV-1 replication, the viral genome is reverse transcribed into a double stranded DNA (dsDNA) by HIV-1 reverse transcriptase (RT). This viral dsDNA is transported into the nucleus in the form of a pre-integration complex (PICs) that contains the viral integrase (IN) and other viral and cellular proteins. Integration is a critical step in the HIV-1 life cycle. The main objective of this study is to examine the effects of cocaine on HIV-1 integration by its modulation of epigenetic signatures of CD4+ T cells. However, there are no studies on cocaine-induced integration in CD4+ T cells which serves as the main targets for HIV-1 replication in vivo. A correlation between DNA methylation and HIV-1 integration is yet to be demonstrated biochemically and mechanistic information is limited. Experimental strategy for in vitro study involves the production of infectious HIV-1 NL4.3 virus, isolation of HIV-1 PICs from SupT1 lymphoma infected cells and carrying out integration assay. Our preliminary data demonstrates cocaine and DNA demethylating agent (5-aza-2′-deoxycytidine) both enhance HIV-1 integration. The isolated PICs are active in integrating viral DNA into target DNA and integration was more efficient in unmethylated DNA than methylated DNA. To confirm integration activity, we performed quantitative nested PCR analysis using primers specific to the target and viral DNA. We propose that results from this project will help us better understand the role of cocaine in HIV-integration by modulating the epigenetic signatures of CD4+ T cells. Furthermore, understanding the molecular details of HIV-1 integration will aid in the discovery of novel targets that can synergize with integrase inhibitors as part of an approach to cure HIV/AIDS.
*Amma Addai is supported by T32 grant #2T32H007735-17 from
NIH/NHLBI to Dr. S. E. Adunyah
Citation Format: Amma Addai, Chandravanu Dash. Cocaine enhances HIV-1 integration by modulating the epigenetic signatures of CD4+ T 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 5372. doi:10.1158/1538-7445.AM2013-5372
Abstract 5380: Detection of OvCa1 in human malignancies.
Authors: Jackson Jessica L. , Grothaus Kristen A. , Temm Connie J. , Mayo Lindsey D. , Sanduksy George E. 
Published: August 2014

Abstract
Immunohistochemistry biomarkers are currently being developed to target specific proteins found in cancer cells, which could contribute to a better understanding of specific types of cancers and provide information to develop better treatments for cancer patients. The biomarker and putative tumor suppressor, OvCa1, has a function that is not well characterized. Due to a lack of staining reagents, we developed monoclonal antibodies of OvCa1 to examine multiple human malignancies. The goal of this project was to gain a better understanding of OvCa1 and its role in cancer. Primary cancers with different histological grades as well as metastatic lesions were examined with the monoclonal antibodies. Ovarian cancer tissue samples from the Indiana University Simon Cancer Center Tissue Bank were used for this study. The samples were fixed in neutral buffered formalin and processed into paraffin blocks. The tissues were cut using a microtome and placed on slides. Staining of the OvCa1 antibody was completed using immunohistochemistry (IHC) techniques. Thirty-one samples were evaluated including low grade tumors, medium grade tumors, high grade tumors, and metastatic ovarian carcinomas. All cases revealed a range of staining intensity with the OvCa1 antibody. The results indicated that OvCa1 for the high grade, stage 3/4, ovarian carcinomas had the highest staining intensity. Medium grade tumors had less OvCa1 expression. The metastatic tumors had less staining than any of the other three grades. Immunostaining was observed primarily in the cytoplasm and nucleus of the tumor cells. In addition, we evaluated approximately 20 tumors from various different organs. These included prostate, breast, spleen, lung, colon, stomach, and kidney tumors, which were positive for immunostaining with the OvCa1 antibody. In summary, the results indicated that all histological grades expressed the biomarker, OvCa1, and the staining intensity was highest in the high grade, stage 3/4, tumors. Our preliminary studies demonstrated a further need to delineate OvCa1 as a potential biomarker, which could be used for early detection and diagnosis of ovarian cancer.
Citation Format: Jessica L. Jackson, Kristen A. Grothaus, Connie J. Temm, Lindsey D. Mayo, George E. Sanduksy. Detection of OvCa1 in human malignancies. [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 5380. doi:10.1158/1538-7445.AM2013-5380
Abstract 5385: Gene expression changes downstream of APC loss predict tumor phenotype.
Authors: Pehar Andjela , Cole Jennifer M. , Prosperi Jenifer R. 
Published: August 2014

Abstract
The Adenomatous Polyposis Coli (APC) tumor suppressor is mutated or hypermethylated in up to 70% of human breast cancer cases. Our previous studies demonstrated that Apc mutation advances the MMTV-Polyoma Middle T Antigen (PyMT) model of breast cancer, with an increase in signaling downstream of focal adhesion kinase (FAK)/Src/JNK activation in MMTV-PyMT;ApcMin/+ tumors. In addition, the majority of tumors that arose in the MMTV-PyMT;ApcMin/+ animals were classified as adenosquamous carcinoma as compared to tumors from MMTV-PyMT;Apc+/+ animals, which were solid carcinomas. Given the heterogeneous nature of these tumors, laser capture microdissection (LCM) of the adenosquamous carcinoma in MMTV-PyMT;ApcMin/+ tissues followed by quantitative real-time RT-PCR was performed to identify gene expression changes responsible for the altered tumor phenotype. In parallel studies, gene expression microarrays were performed using triplicate samples of the MMTV-PyMT;Apc+/+ and MMTV-PyMT;ApcMin/+ cell lines. RNA samples were subjected submitted to quality control via the Agilent Bioanalyzer and were hybridized to Affymetrix Mouse Genome 430 2.0 microarrays. Data analysis was performed using the Gene-Go software, and significant changes were confirmed using qRT-PCR. Multiple changes consistent with the phenotypic and proliferative changes downstream of APC loss were identified, including changes in expression of cyclooxygenase-2 (COX-2). The findings presented here indicate that APC-mediated gene expression changes can be used to predict tumor phenotype and downstream therapeutic targets.
Citation Format: Andjela Pehar, Jennifer M. Cole, Jenifer R. Prosperi. Gene expression changes downstream of APC loss predict tumor phenotype. [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 5385. doi:10.1158/1538-7445.AM2013-5385
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 5387: Integrative analysis of transcriptomic and metabolomic data reveals a critical role for aminosugar metabolism in prostate cancer.
Authors: Panzitt Katrin , Shojaie Ali , Putluri Nagireddy , Basu Sumanta , Putluri Vasanta , Samanta Susmita , Ittmann Michael , Vergara Ismael , Michailidis George , Palapattu Ganesh , Sreekumar Arun 
Published: August 2014

Abstract
Prostate Cancer is the second most common cause of cancer-related death in men in the US. Like other tumors, prostate cancer development and progression is dictated by multiple molecular events that include changes in levels of genes, transcripts, proteins and metabolites. To better understand the biology of prostate cancer development it is essential to integrate these disparate yet related datasets. Our laboratory has identified matched transcriptomic, proteomic and metabolomic changes in localized prostate cancer relative to adjacent benign tissue as well in metastatic disease compared to organ-confined tumor. To study this using a System's Biology approach we have recently embarked on a pilot study aimed at integrating transcriptomic and metabolomic data to obtain biochemical pathways that key to prostate cancer development. Using an in-house network-based enrichment strategy, amino sugar metabolism was found to be significantly enriched in organ-confined prostate cancer but not in metastatic disease. Amino sugar metabolism describes the utilization of glucose-derived carbon and amino acid (mostly glutamine)-derive nitrogen to produce glucosamines. These amino sugars participate in synthesis of immune modulatory compounds as well as in glycosylation cascades. In this study, we describe the molecular analyses of Glucosamine-6 phosphate-N-acetyl Transferase (GNPNAT1), a key enzyme that converts D-glucosamine 6-phosphate to N-acetyl-D-glucosamine 6-phosphate, in prostate cancer. Our results indicate upregulation of GNPNAT1 in organ-confined prostate cancer as compared to benign adjacent tissue as well as metastatic tissue and regulation of the pathway by androgen. Stable knockdown of GNPNAT1 in androgen dependent LNCap cells leads to diminished cell growth and cell cycle arrest. In contrast, growth and cell cycle are not affected by the knockdown of GNPNAT1 in androgen independent C4-2 cells. Knockdown of GNPNAT1 in C4-2 cells enhances invasiveness which is not observed in LNCap knockdown cells. In this work we show that GNPNAT1 is linked to androgen receptor (AR) action and thus is a critical enzyme for the survival of androgen dependent prostate cancer cells.
Citation Format: Katrin Panzitt, Ali Shojaie, Nagireddy Putluri, Sumanta Basu, Vasanta Putluri, Susmita Samanta, Michael Ittmann, Ismael Vergara, George Michailidis, Ganesh Palapattu, Arun Sreekumar. Integrative analysis of transcriptomic and metabolomic data reveals a critical role for aminosugar metabolism in prostate 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 5387. doi:10.1158/1538-7445.AM2013-5387
Abstract 540: Role of EphB4-EphrinB2 as novel target in Her2 positive breast cancer.
Authors: Duarte A. , Quaresma J. , Trindade A. , Tripathy P. , Liu X. , Krasnoperov V. , Liu R. , Gill P.S. 
Published: August 2014

Abstract
Background: Her2 amplification drives tumor growth in 20% of breast cancers. Her2 targeted therapies have improved survival, but eventual failure occurs and additional targeted therapies to overcome resistance are needed. EphB4 and EphrinB2 receptor kinase -ligand pair is induced in Her2 positive tumors and is a novel target.
Methods: Her2 positive tumor cell lines and Her2 transgenic mouse lines were studied for expression of EphB4-EphrinB2. The role of EphB4-EphrinB2 was examined by knock down with shRNA. In vivo tumor xenograft studies with Her2 positive cell lines resistant or sensitive to Her2 targeted therapy, and Her2 transgenic mouse were treated with soluble decoy receptor (soluble EphB4-Albumin fusion protein). Tumor response and activation status of Her2 were examined.
Results: EphB4 and EphrinB2 are induced in Her2 positive tumor cell lines with further induction in trastuzumab (Herceptin) resistant tumor lines. Knock down of EphB4 with shRNA reduced the cell viability by nearly 80% compared to control shRNA. In vivo studies with sEphB4-Albumin also reduced the tumor growth by 70-80% accompanied by the reduction in pHer2 and pEGFR. No effect was seen on pHer3. Combination with lapatinib and sEphB4-Albumin was additive. sEphB4-Albumin inhibited tumor growth in Her2 resistant tumor cell lines by 56%.
Conclusion: EphB4 and EphrinB2 are induced by Herceptin sensitive and resistant Her2 positive tumors. EphB4 provides survival advantage to Her2 positive trastuzumab sensitive and resistant tumors. sEphB4-Albumin inhibits tumor growth as single agent in both trastuzumab sensitive and resistant tumors. sEphB4-Albumin is currently in the clinical development and thus worthy of investigation in Her2 positive cancers.
Citation Format: A. Duarte, J. Quaresma, A. Trindade, P. Tripathy, X. Liu, V. Krasnoperov, R. Liu, P.S. Gill. Role of EphB4-EphrinB2 as novel target in Her2 positive 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 540. doi:10.1158/1538-7445.AM2013-540
Abstract 5407: The novel roles of BRCA1/ATM-associated BRAT1 in glucose/mitochondrial metabolism and tumor cell growth.
Authors: So Eui Young , Ouchi Toru 
Published: August 2014

Abstract
BRAT1 (BRCA1-associated ATM activator) was identified as a novel DNA-damage response protein. It physically interacts with both BRCA1 and ATM, and is required for ATM-activation under conditions of cell stress. We have recently discovered that it also binds to DNA-PKs, implicating the broad role of BRAT1 in DNA repair as well as in DNA damage response. By taking advantage of BRAT1 knockdown HeLa and U2OS cells, we found that loss of BRAT1 expression significantly decreased cell proliferation and tumorigenecity both in vitro and in vivo. Cell motility is remarkably lowered when BRAT1 is depleted. These results demonstrate novel function of BRAT1 in cell proliferation, migration, and tumorigenesis of cancer cells. Interestingly, glucose uptake and production of mitochondrial ROS (reactive oxygen species) are highly increased in BRAT1 knockdown. These findings suggest novel functions of BRAT1 in regulating glucose metabolism and mitochondrial function. Functional interaction of BRCA1/ATM pathway and glucose/mitochondria metabolism are discussed.
Citation Format: Eui Young So, Toru Ouchi. The novel roles of BRCA1/ATM-associated BRAT1 in glucose/mitochondrial metabolism and tumor cell growth. [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 5407. doi:10.1158/1538-7445.AM2013-5407