bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1130: mPGES-1 drives the oncogenic potential of EGFR signaling
Authors: Finetti Federica , Erika Terzuoli , Donnini Sandra , Giachetti Antonio , Ziche Marina 
Published: June 2012

Abstract
Prostaglandins, mostly PGE-2, have assumed an important role in cancer biology. Regarding of PGE-2 production, recent investigations have focused on PGE-2 synthases (mPGEs-1, mPGEs-2 and cPGEs), specifically on mPGEs-1, the only inducible enzyme among those so far identified in cells. Whereas cPGEs and mPGEs-2 are constitutively expressed at relatively low levels, mPGEs-1 is highly inducible by pro-inflammatory stimuli. mPGEs-1 upregulation has been detected in many epithelial tumors, and its silencing has been reported to reduce preneoplastic lesions. Despite the evidence linking mPGEs-1 and tumorigenesis, most studies investigating the inducible nature of the enzyme in cultured cells have been performed using a variety of inflammatory stimuli, while little is known about the behavior of the enzyme in tumor cells challenged with oncogenic stimuli. In this work we investigated mPGES-1 regulation in cultured epithelial tumor cells exposed to epidermal growth factor (EGF), an oncogene product which, through its receptor, EGF-receptor, is responsible for tumorigenisis in a wide array of solid tumors. We used three cell lines, representative of colon (HT-29), epidermoid (A431) and lung (A549) tumors, examining the expression of mPGEs-1 protein following EGF-receptor activation by EGF. We found that cells responded to EGF-receptor stimulation with a transient surge of the transcription factor Egr-1, its translocation from cytosol to necleus, an increase of mPGEs-1 mRNA and protein, as well as, an enhanced PGE-2 formation. These changes were suppressed by silencing Egr-1 and by EGF-receptor blockade or by inhibitors of the EGF-receptor-dependent mediators, such as MAP-kinase, ERK1/2. Moreover, cell activation through EGF-receptor induced a tumorigenic phenotype, detectable by clonogenic assay, which regressed when mPGEs-1 was silenced. We also explored the effect of inhibiting the EGF-receptor in A431 xenografts on mPGEs-1 expression and tumor growth, finding a parallel decline of both.
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 1130. doi:10.1158/1538-7445.AM2011-1130
Abstract 1139: Ras association domain family protein 1, isoform C (RASSF1C) promotes breast tumor growth in vivo
Authors: Reeves Mark E. , Aragon Robert J. , Alfakouri Mariana , Chen Shin-Tai , Amaar Yousef G. 
Published: June 2012

Abstract
Breast cancer will kill more than 40,000 women in the United States this year, second in cancer deaths only to carcinoma of the lung. Therefore, a better understanding of the molecules and pathways that lead to breast cancer development is important because it could lead to specific therapies that interrupt these pathways. Recently, the Ras association domain family 1 (RASSF1) gene was identified as a Ras effector that plays an important role in carcinogenesis. The RASSF1 gene encodes two major isoforms, RASSF1A and RASSF1C, derived by alternative promoter selection and alternative mRNA splicing. While RASSF1A is extensively studied and is an established tumor suppressor, very little is known about RASSF1C function
Our laboratory is interested in determining the role of RASSF1C in human cancer cell growth. We have previously shown that of RASSF1C promotes cell proliferation and migration and attenuates apoptosis of breast cancer cells in vitro. To confirm our hypothesis that RASSF1C may be a growth promoter, we have tested the growth of human breast cancer cells over-expressing RASSF1C in nude mice. Our preliminary studies show that breast cancer cells over-expressing RASSF1C developed significantly larger tumors compared to control cells. We have confirmed the expression of RASSF1C in tumor tissue using both RT-PCR and immune-staining analyses. Together, our previous in vitro and current in vivo findings further support our hypothesis that RASSF1C, unlike RASSF1A, is not a tumor suppressor and rather it appears to play a role in stimulating proliferation and survival of breast cancer cells.
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 1139. doi:10.1158/1538-7445.AM2011-1139
Abstract 1159: Identification of potential miRNA biomarkers for breast cancer using TaqMan® Pri-miRNA assays
Authors: Liang Yu , Markoy Athina , Lianidou Evi 
Published: June 2012

Abstract
Identification of cancer biomarkers depends on measuring the differential genotypes and phenotypes between normal and disease tissues. However, cancer is characterized by accumulation of genetic lesions and heterogeneity, and hence great efforts need to be invested to distinguish driver versus passenger abnormalities. Several strategies have been employed to achieve the distinction, including conservation of genetic lesions between mouse models and human diseases, gain of copy number/amplification, deletion/loss of heterogeneity, and epigenetic alterations. Redundancy of some microRNA (miRNA) genes has been an interesting finding and its biological significance is not clear. These redundant miRNA loci have different genomic locations and are transcribed independently, and yet are processed into identical mature miRNA, and these loci are annotated as -1, -2, -3, etc, following the miRNA gene name. Selective expression of these loci could be a regulatory strategy to control expression of other genomically associated genetic elements that are critical to the disease processes, while the required level of mature miRNA can still be maintained by leveraging the redundancy. The proof-of-principle of this rationale was to compare between normal breast and breast cancer cell lines the expression of miRNA genes that have multiple loci and are associated with other genetic elements such as other miRNA genes within the same clusters or their host protein-coding/non-coding genes. This investigation narrowed down to mir-100 gene that is clustered with let-7a-2 gene, both of which lost expression completely in three luminal-type breast cancer cell lines but not in one basal-type cell line and normal breast, whereas expression from let-7a-1 and let-7a-3 remains unchanged between normal breast and cell lines tested. Loss of mir-100 and let-7a-2 expression appears to be caused at least by loss of one copy or both copies of these two loci. Deletion of mir-100 locus can also be detected in clinical specimens. These results suggest that this method might effectively distinguish driver versus passenger differentially expressed genes.
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 1159. doi:10.1158/1538-7445.AM2011-1159
Abstract 1172: The impact of siRNA targeting Colon Cancer Associated Transcript 1 (CCAT-1) on proliferation of HT-29 cells
Authors: Tsivin Victoria , Halle David , Gure Ali O. , Pavlov Vera , Roistacher Marina , Ilyiayev Nadia , Mitrani-Rosenbaum Stella , Stojadinovic Alexander , Trink Barry , Rubinstein Abraham , Nissan Aviram 
Published: June 2012

Abstract
Introduction: Colon cancer Associated Transcript-1 (CCAT-1) is a non-coding RNA transcript highly expressed in colorectal cancer (CRC) but not in normal colonic tissue. The role of CCAT-1 in tumorigenesis is yet to be defined. Small interfering RNAs (siRNA) are a group of sequence-specific posttranscriptional gene silencing molecules. Recent advances in the design and delivery of targeting siRNA molecules allows efficient and highly specific gene silencing in mammalian systems. The most common application of siRNA gene-silencing in oncology is to identify loss-of-function phenotypes in genes that will result in decreased proliferation or death of cancer cells.
Aim: To study the role of colon cancer associated transcript 1 (CCAT-1) in proliferation of human colon cancer cells using RNA interference.
Methods: Small interfering RNAs (siRNA) targeting CCAT-1 were transfected into HT-29 colon cancer cells. At day one, 80×105 HT-29 cells per well were plated and suspended in RPMi 1640 medium. At day two, 50 pmol CCAT-1 siRNA and 0.5 µl lipofectamine 2000 were added to each well. CCAT-1 expression was studied by real-time PCR in order to evaluate gene silencing. Cell proliferation was studied by MTT incorporation assay. Twenty four hrs after transfection, 50 µl of MTT were added to the cells media and incubated for 4 h at 37° C. The purple Formazan product, converted MTT, was dissolved by the addition of 150µl/well DMSO and OD readings were obtained at 550 nm.
Results:By examining AV average OD readings at 550 nm, untreated HT-29 cells (10 wells), cells treated with lipofectamine 2000 (10 wells) and cells silenced by siRNA of CCAT-1 (10 wells) showed a significant decrease in proliferation: 2.4±0.64, 1.54±0.63, 0.8±0.14 respectively (p=0.002). Furthermore, comparing AV OD readings between 24 and 48 h in the silenced cells, showed a decrease of 38% in proliferation. This was compared to untransfected cells and cells treated with lipofectamine 2000 which showed an increase of 39% and 22% respectively. Twenty four hrs after transfection, real time PCR results showed a reduction in CCAT-1 RNA levels of 70% compared to controls and 48 hrs after transfection, CCAT-1 RNA levels were reduced to 55% of baseline.
Conclusions: Our results may support a role for CCAT-1 in the regulation of colon cancer cell proliferation.
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 1172. doi:10.1158/1538-7445.AM2011-1172
Abstract 1175: Persistent upregulation of U6 small RNA in the serum of breast cancer patients
Authors: Appaiah Hitesh , Goswami Chirayu , Mina Lida , Badve Sunil , Sledge George , Liu Yunlong , Nakshatri Harikrishna 
Published: June 2012

Abstract
Serum microRNAs have the potential to be valuable biomarkers of cancer. This investigation addresses two issues that impact their utility: a) appropriate normalization controls and b) whether their altered levels persist in patients who are clinically free of disease. Sera from 40 age-matched healthy women and 39 breast cancer patients without clinical disease at the time of serum collection were analyzed for microRNAs let-7f, miR-16, miR-21, and miR-155 using quantitative real-time PCR. U6 and 5S, which are transcribed by RNA polymerase III (RNAP-III), and the small nucleolar RNA44 (SNORD44), were also analyzed for normalization. Sera from additional 14 healthy and 15 patients with overt metastasis were examined for U6, miR-16, and miR-195 levels. SNORD44 and miR-16 did not vary significantly in the sera of patients and healthy volunteers and thus served as normalization controls. Unexpectedly, we observed upregulation of U6 (2.4 fold, p=0.001) and 5S RNAs (1.7-fold, p=0.02) but not any of the other microRNAs analyzed in the sera of patients without active disease. U6 level was significantly elevated in the sera of patients with overt metastasis compared to healthy women. Elevated serum U6 levels in patients who are clinically cancer-free suggest persistently altered systemic RNAP-III activity in cancer patients and that cancer cells may not be the only primary source of serum U6. Additionally, U6 and 5S, to some extent, are of limited value for normalization.
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 1175. doi:10.1158/1538-7445.AM2011-1175
Abstract 1195: EphA4 is a novel tumor suppressor in lung adenocarcinoma
Authors: Peng Shaohua 
Published: June 2012

Abstract
Lung cancer is the leading cause of death from cancer, but the mechanisms behind its initiation and progression are not completely understood. Receptor tyrosine kinases (RTKs) are important in normal cellular physiology as well as in the pathogenesis of a variety of tumors. In this study, we explored the roles of the human Eph kinase family in lung adenocarcinoma. The Eph fmaily is the largest RTK superfamily with 14 receptors and 8 ligands (ephrins). Eph receptors have been implicated both as tumor suppressors and oncogenes. To explore the effect of Eph receptors and ephrins on lung cancer, we analyzed gene expression and survival data from 432 lung adenocarcinomas from Director's Challenge Consortium by univariate Cox proportional hazards model. Of the 11 Eph receptors and 8 ephrins analyzed, only the expression of EphA4, EphA5, EphB2, ephrinA1, and ephrinB3 correlated with overall survival. Analysis of an independent dataset confirmed that EphA4 and ephrinA1 expression negatively correlated with survival in lung adenocarcinoma. After adjusting for age, gender and stage, low EphA4 expression remained significantly associated with a poor outcome for both overall and relapse-free survival with a hazard ratio of 1.57. To validate the gene expression profile data, we measured EphA4 expression in 9 NSCLC cell lines and found that the expression levels of EphA4 by microarray were well correlated with expression levels measure by qPCR and Western blotting (R2=0.89, R2=0.79 respectively), which indicate that the tissue microarray probesets are of high quality. To investigate the role of EphA4 as a putative tumor suppressor, we overexpressed EphA4 in NSCLC cell lines with low basal expression and found that the cell migration was inhibited by 38% and E-cadherin expression was increased. Likewise, E-cadherin expression was decreased with EphA4 knockdown in NSCLC cell lines with high basal EphA4 expression. These data are consistent with a role for EphA4 as a tumor suppressor via increased expression of the cell surface adhesion protein E-cadherin and concomitant decreased cell migration.
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 1195. doi:10.1158/1538-7445.AM2011-1195
Abstract 12: JAK2V617F drives Mcl-1 expression and sensitizes acute myeloid leukemia cells to dual inhibition of JAK2 and Bcl-XL
Authors: Guo Jun , Roberts Lisa , Kraft Jeffrey B. , Merta Philip J. , Glaser Keith B. , Shah Omar J. 
Published: June 2012

Abstract
Constitutive activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) axis is fundamental to the molecular pathogenesis of a host of hematological disorders, including acute leukemias and myeloproliferative neoplasms (MPN). We demonstrate here that the major JAK2 mutation observed in these diseases (JAK2V617F) enforces Mcl-1 transcription via STAT3 and STAT5 signaling. Targeting this lesion with JAK inhibitor I (JAKi-I), attenuates STAT3 binding to the Mcl-1 promoter and suppresses Mcl-1 transcript and protein expression. The neutralization of Mcl-1 in JAK2V617F-harboring acute leukemia lines sensitizes them to apoptosis induced by the BH3-mimetic and Bcl-XL/Bcl-2 inhibitor, ABT-263. Moreover, simultaneously targeting JAK and Bcl-XL/-2 is synergistic in the presence of the JAK2V617F mutation. These findings suggest that JAK/Bcl-XL/-2 inhibitor combination therapy may have applicability in a range of hematological disorders characterized by activating JAK2 mutations.
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 12. doi:10.1158/1538-7445.AM2011-12
Abstract 1251: Anti-cancer mechanisms of se compounds: A stable isotope-resolved metabolomic (SIRM) approach
Authors: Fan Teresa WM , Lorkiewicz Pawel , Higashi Richard M. , Lane Andrew N. 
Published: June 2012

Abstract
Recent rapid advances in analytical tools, especially NMR and mass spectrometry, allow an unprecedented range of metabolites and their transformation pathways to be determined, which transcends classical targeted metabolic studies. We have coupled these tools with stable isotopic tracers [1-3] to investigate the anticancer efficacy and mechanism(s) of different selenium forms using lung adenocarcinoma A549 cells as a model. Selenite (SeO3), methylseleninic acid (MSA) and selenomethionine (SeM) induced distinct changes in steady-state concentrations and 13C labeling patterns of various metabolites including amino & organic acids, nucleotides, antioxidants, as well as phospholipids (PL) and PL metabolites. These changes were determined using a combination of multi-nuclear 2-D NMR, GC-MS, and FT-ICR-MS techniques, which enabled perturbations in multiple metabolic pathways to be simultaneously reconstructed for relating to phenotypic changes. At low µM levels, both SeO3 and MSA inhibited growth, caused cytoskeleton disintegration, and reduced the mitochondrial redox potential in A549 cells. SeM was growth-stimulatory at ≤ 10 µM and inhibited growth but only at 40-fold higher concentration and the extent was much less than MSA or SeO3. These phenotypic differences were related to the early inhibition of glutaminolysis, Krebs cycle, and protein biosynthesis by SeO3, rapid inhibition of pyruvate carboxylation by MSA. SeM had few comparable metabolic effects. Subsequent inhibition of PL biosynthesis was also more substantial in MSA and SeO3 than in SeM-treated cells. The protein and gene expression for key enzymes in these pathways were probed to discern altered metabolic regulations. Thus, the anti-cancer action of MSA differed from that of SeO3 while SeM was not effective against lung cancer cells. The SIRM approach facilitated the resolution of the complex, form-specific anticancer mechanism of Se compounds and is generally applicable to other cancer research problems.
1. Fan, T., et al., Metabolomics-edited transcriptomics analysis of Se anticancer action in human lung cancer cells. Metabolomics Journal, 2005. 1(4): p. 325-339
2. Lane, A.N. and T.W.-M. Fan, Quantification and identification of isotopomer distributions of metabolites in crude cell extracts using 1H TOCSY. Metabolomics, 2007. 3: p. 79-86.
3. Lane, A.N., et al., Isotopomer analysis of lipid biosynthesis by high resolution mass spectrometry and NMR. Analytica Chimica Acta, 2009. 651: p. 201-208.
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 1251. doi:10.1158/1538-7445.AM2011-1251
Abstract 1254: Altered lipid and glucose metabolism is a cellular adaptation to tumor acidic microenvironments
Authors: Wojtkowiak Jonathan W. , Barkey Natalie M. , Kumar Virendra , Lloyd Mark C. , Gatenby Robert A. , Gillies Robert J. 
Published: June 2012

Abstract
As a consequence of increased glucose metabolism and poor perfusion, solid tumors are acidic. Tumor cells must overcome this physical microenvironmental barrier in order to progress. To better understand phenotypes associated with extracellular acidosis, MDA-MB-231 human breast carcinoma cells were acutely and chronically exposed to low pH (6.7) growth conditions. In the acute phase, low pH reduced proliferation, induced a G1cell cycle arrest, and increased cytoplasmic vacuolization, with no observable effect on cell viability. Following chronic (3 month) exposure, MDA-MB-231 cells had restored proliferation to control levels with no cell cycle arrest, yet remained highly vacuolated. Our prior work identified a subset of these vacuoles to be autophagic, while the rest appeared to be lipid droplets. Confocal microscopy of MDA-MB 231 cells stained with Nile Red, an intracellular fluorescent lipophilic dye, identified the cytoplasmic vacuoles as lipid aggregates. A significant number of lipid aggregates accumulated in low pH treated MDA-MB-231 cells (p &lt; 0.01), and this was also observed in a series of breast and non-breast cancer cell lines, suggesting that this is a universal response to extracellular acidosis. To investigate the source of the lipid, it has been observed that accumulation is serum dependent; indicating that it is either dependent on growth factors or comes from an exogenous (albumin) source. To investigate a de novo mechanism, high resolution NMR spectroscopy was used to measure 13C enriched lactate isotopomers following metabolism of D-[1,2-13C] glucose. These analyses showed that glucose flux through the pentose phosphate pathway was three-fold higher in low pH cells, compared to controls, representing a major shift in glucose metabolism from Embden Meyerhoff to the Pentose Phosphate pathway, which results in increased production of NADPH, necessary for de novo lipid synthesis. Autofluorescence microscopy showed an altered distribution of NAD(P)H under acidic conditions. Furthermore, C75, a fatty acid synthase inhibitor, induced significant cytotoxicity in low pH treated MDA-MB-231 cells, but not controls. This is further indicative of a de novo mechanism. These data suggest that the cellular survival response to extracellular acidosis depends on lipid accumulation and profound changes in glucose metabolism.
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 1254. doi:10.1158/1538-7445.AM2011-1254