bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4785: Comparative proteomic analysis of MCF7 and SKBR3 breast cancer cell lines
Authors: Mojtahedi Zahra , Erfani Nasrollah , Ghaderi Abbas 
Published: August 2012

Abstract
Differentially expressed proteins among cancer cell lines fit each cell line as a model for gaining knowledge of heterogeneity in cancer. The aim of our study was to identify differentially expressed proteins between MCF7 (ER+, low HER2 expression) and SKBR3 (ER-, high HER2 expression) cell lines by a proteomic approach. Moreover, a number of proteins in MCF7 cell line were randomly selected and identified. MCF7 and SKBR3 cell lysates were subjected to two dimensional gel electrophoresis and spots of interest were identified by MALDI-TOF/TOF mass spectrometry. Upregulated proteins (≥2 fold and p value &lt;0.05) in MCF7 cells were cellular retinoic acid binding-protein 2, Hsp27, nucleophosmin, electron transfer flavoprotein ≤ subunit, and profilin, and in SKBR3 cells were Rho GDP dissociation inhibitor-α (RhoGDI-α), voltage-dependent anion channel 2, aldehyde dehydrogeanase-2 (ALDH2), LDH- A, LDH-B, pyrophosphates 1, GAPDH, cathepsin D preprotein, and apolipoprotein A-I binding. Most of the identified proteins have been a candidate marker for cancer aggressiveness or drug resistance, but their differential expressions between SKBr3 and MCF7 cells were not known. Apo-lipoprotein binding-protein has not been described in cancer so far. Differential expression of RhoGDI-α was further validated by using western blotting with specific antibody. Further studies are required to clarify the importance of differential expressions of the identified proteins in SKBr3 and MCF7 breast cancer cell line models.
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 4785. doi:1538-7445.AM2012-4785
Abstract 479: The effects of sarcophine-diol (SD) on melanoma B16F10 cell line
Authors: Szymanski Pawel T. , Kuppast Bhimanna , Muley Pratik , Fahmy Hesham 
Published: August 2012

Abstract
Sarcophine diol (SD) is a non-toxic semi-synthetic derivative of sarcophine, a marine natural product. Previously, we studied the chemopreventive effects of SD on non-melanoma tumor development using both animal and cellular models. In this current study, we used the mouse melanoma B16F10 cell line to investigate the possible effects of SD on melanoma cell development. We found that SD at a 250 µM concentrations inhibits cell duplication. Melanoma cells treated with SD do not form the contractile ring, a multi-protein complex involved in cell division. As a result of cytoskeleton modification, cells treated with SD do not show the ability to carry out de novo synthesis of DNA, and their DNA show a high degree of fragmentation compared to untreated controls. To explore the molecular mechanism(s) involved in the disassembly of the contractile machinery, our studies show that SD treatment inhibits cell membrane permeability for small molecular mass compounds (e.g. ethidium bromide which is used as an indicator for cell permeability to Ca2+ ions). These findings are consistent with the observation that SD increases cleavage of phospholipase A2 (PLA2), resulting in low PLA2 enzymatic activity. These findings are also consistent with the observation that SD, in a time- and concentration-dependent manner, inhibits the expression level of the cyclooxygenase-2 (Cox-2). As a result of the decline in membrane permeability in SD treated cells and the negative effect of SD on the protein level of phospholipase C (PLC), which both affect the activity of contractile machinery, the non-dividing cells undergo apoptosis. The latter notion is supported by findings that SD inhibits the expression of STAT-3 (signal transducer and activator of transcription protein), and cyclin D1 (an activator of cyclin-dependent kinase 4, Cdk4). SD treatment also enhances the cellular level of the tumor suppressing protein 53 (p53) and stimulates cleavage of the nuclear poly(ADP-ribose) polymerase (cleaved-PARP). SD also enhances the cellular level of cleaved-Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. All these findings, in addition to inhibition of cell viability, suggest that SD most likely inhibits melanoma cell growth by arresting the cell-division cycle in a Go quiescent phase and simultaneously activates apoptosis via extrinsic and intrinsic pathways.
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 479. doi:1538-7445.AM2012-479
Abstract 4795: Metabolic biomarkers of hepatocellular carcinoma
Authors: Ressom Habtom W. , Xiao Jun Feng , Tuli Leepika , Varghese Rency S. , Zhou Bin , Tsai Tsung-Heng , Ranjbar Mohammad R. Nezami , Wang Jinlian , Cheema Amrita K. , Tadesse Mahlet G. , Goldman Radoslav , Shetty Kirti 
Published: August 2012

Abstract
Characterizing the metabolic changes pertaining to hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC) is believed to contribute towards early detection, treatment, and our understanding of the molecular mechanisms of HCC. Prospectively evaluated adult patients with LC were recruited from our hepatology practice. All patients were diagnosed to have LC on the basis of established clinical, laboratory and imaging criteria. Cases were diagnosed to have HCC based on either histology or characteristic imaging features. The LC controls were required to be HCC free for at least 6 months from the time of study entry. We compared metabolite levels in sera of 78 HCC cases with 184 LC controls by using ultra performance liquid chromatography coupled with a hybrid quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS). Following data preprocessing, the most relevant ions in distinguishing HCC cases from LC controls were selected by statistical methods. Putative metabolite identifications for these ions were obtained through mass-based database search. Pathway analysis of these putative identifications reveals significant enrichment of metabolites involved in bile acid biosynthesis, porphyrin and chlorophyll metabolism, and arachidonic acid metabolism. Verification of the identities of selected metabolites was conducted by comparing their MS/MS fragmentation patterns and retention time with those from authentic compounds. Quantitation of these metabolites was performed in a subset of the serum samples (10 HCC and 10 LC) using isotope dilution by selected reaction monitoring (SRM) on triple quadrupole linear ion trap (QqQLIT) mass spectrometer. The results of this analysis confirms that metabolites involved in phospholipid catabolism such as sphingosine-1-phosphate (S-1-P) and lysophosphatidylcholine are up-regulated in sera of HCC vs. those with LC. Down-regulated metabolites include those involved in cholesterol metabolism such as glycochenodeoxycholic acid 3-sulfate (3-sulfo-GCDCA), glycocholic acid (GCA), glycodeoxycholic acid (GDCA), taurocholic acid (TCA), taurochenodeoxycholate (TCDCA), as well as those involved in heme catabolism including billuribin, I-Urobili, and bilirubin glucuronide. The preliminary results obtained in this study provide useful insights into our understanding of metabolic differences between HCC and LC.
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 4795. doi:1538-7445.AM2012-4795
Abstract 4861: Triple-negative breast cancers establish a systemic environment that drives malignant progression of otherwise indolent disseminated tumors via EGF and IGF
Authors: Castano Zafira , Marsh Timothy , Tadipatri Ramya , Kuznetsov Hanna , Al-Sahour Fatima , Paktinaz Mahnaz , McAllister Sandra S. 
Published: August 2012

Abstract
Breast cancer recurrence rates are variable, suggesting that tumor cells disseminate from primary sites at an early stage but remain indolent for extended periods of time before progressing to symptomatic disease. Little is known about mechanisms that cause otherwise dormant tumors to become overt cancers, making it difficult to predict which breast cancer patients are likely to relapse and therefore likely to benefit from preemptive therapy. To address these challenges, we use a human breast tumor xenograft model in which aggressively growing breast cancers (“instigators”) promote the growth of otherwise indolent breast cancers (“responders”) that have disseminated to distant sites. These pro-tumorigenic systemic effects are established by instigating tumors, in large part, through their mobilization of bone marrow cells (BMCs) that are subsequently recruited to the responding breast tumors, where they create a tumor-supportive microenvironment. We report here that the mechanisms of establishing tumor-supportive systemic environments depend upon the molecular-histopathological subtype of the instigating breast cancer. Instigating cell lines and primary tumor surgical specimens, derived from patients with either triple-negative breast cancer (TNBC) or luminal breast cancer (LBC), established different subtype-specific systemic environments that impinged in different ways upon the malignant features of responding tumor cells and their microenvironment. In particular, the TNBC-induced responding tumor microenvironment was characterized by elevated levels of epidermal growth factor (EGF) and insulin-like growth factor 1 (IGF1). EGF and IGF acted on responding tumor cells in a paracrine manner to induce expression of factors that play a role in tumor-initiation, embryonic stem cell maintenance, and epithelial-mesenchymal transition. Pharmacological administration of EGFR and IGF1R inhibitors prevented responding tumors from acquiring the TNBC-induced malignant features, thus maintaining them in an indolent state. Our results demonstrate that microenvironmental composition, as well as tumor cell phenotypic plasticity and molecular properties, are strongly influenced by the host systemic macroenvironment. Our work suggests that the crosstalk between disseminated tumor cells and their microenvironment can be exploited therapeutically to improve outcomes for patients with TNBC.
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 4861. doi:1538-7445.AM2012-4861
Abstract 4888: Decitabine and vorinostat cooperate to sensitize metastatic human colon carcinoma cells to Fas-mediated apoptosis
Authors: Torres Christina M. , Yang Dafeng , Zimmerman Mary , Bardhan Kankana , Liu Kebin 
Published: August 2012

Abstract
The death receptor Fas and its physiological ligand, FasL, which is expressed on the surface of cytotoxic T-cells (CTLs), regulate apoptosis of cancerous cells. While normal colon epithelial cells express high levels of Fas, Fas expression is diminished in colon carcinomas. Metastatic colon cancers acquire an apopotosis-resistant phenotype often due to the loss of Fas expression and function. Previous studies have implicated Fas-mediated apoptosis as an important contributor of tumor regression. Therefore, targeting Fas resistance is of critical importance in treating colon cancer through Fas-based cancer therapy and immunotherapy. In this study, we explore whether epigenetic pharmacological agents can restore Fas expression and re-establish sensitivity to Fas-mediated apoptosis in metastatic human colon carcinoma cells. First we determined that the epigenetic drugs Decitabine, a DNA methyltransferase inhibitor, and Vorinostat, a HDAC inhibitor, each are capable of up-regulating Fas expression. When combined, these two inhibitors cooperate to increase Fas expression to an even greater extent than each agent alone. Pre-treatment with decitabine, vorinostat, or both drugs followed by incubation with FasL, was able to overcome resistance to FasL-induced apoptosis. Analysis of bisulfite-modified genomic DNA, isolated from human metastatic colon carcinoma cells revealed that the Fas promoter is sporadically methylated; therefore sensitization of Fas receptor expression on the cell surface by decitabine was unlikely through direct inhibition of Fas promoter meythlation. Although the Fas promoter was not heavily methylated, the promoters for BNIP3 and Bik, which are downstream of Fas signaling, were methylated. After treatment with these pharmacological epigenetic inhibitors, alone or in combination, protein levels of both BNIP3 and Bik were increased. Our data suggest that combined modalities of chemotherapy and Fas-based immunotherapy may be an effective approach for the suppression of colon cancer metastasis.
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 4888. doi:1538-7445.AM2012-4888
Abstract 4897: Involvement of Akt isoforms in chemoresistance of carcinoma endometrial cells
Authors: Girouard Julie , Lafleur Marie-Judith , Leblanc Valérie , Asselin Eric 
Published: August 2012

Abstract
Akt (also known as PKB) is a crucial survival kinase that is normally activated by growth factors, but in tumors, it is constitutively activated at a high frequency through oncogenic events affecting its upstream regulation. Since studies have demonstrated that the three Akt isoforms exhibit distinct physiological functions, we propose that Akt isoforms may contribute differently in chemoresistance of endometrial carcinoma cells. In order to determine the specific role of each Akt isoform, we have stably produced transfectants in which the expression of Akt is downregulated by specific shRNAs for Akt1, Akt2 and Akt3 using the KLE endometrial carcinoma cell line. This endometrial cell line is known to constitutively express the three Akt isoforms and to highly resist to chemotherapeutic treatment. In this study, we have demonstrated that the downregulation of Akt1 and Akt2 by RNA interference strongly sensitizes KLE cells to cisplatin, doxorubicin and taxol and affects cell proliferation. Moreover, cisplatin treatment of these cells induced the activation of pro-apoptotic factors such as the cleavage of caspase -3, -6, -9 and PARP and it also inhibited the expression of anti-apoptotic factors such as XIAP and Bcl-2. Alternatively, we used constitutively active Akt expression vectors for each isoform to produce stable transfectants using the chemosensitive Hec 1A endometrial cancer cell line, in which no Akt activity is detected. Constitutive Akt1 and Akt2 expression leads to an increase in cell proliferation, as well as resistance to apoptosis after chemotherapeutic treatment in these stable transfectants. Moreover, Akt isoforms contribute differently in other cancer cell processes, such as migration. We showed that Akt2 blocks cell motility, while the activation of Akt1 or Akt3 does not show any effect on our endometrial cancer cell model. Our findings highlight the contribution of Akt1 and Akt2 isoforms in the molecular mechanisms that govern chemoresistance of endometrial carcinoma. Furthermore, Akt isoform-specific transfectants will provide a solid model to determine the involvement of each Akt isoform in tumor progression and metastasis.
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 4897. doi:1538-7445.AM2012-4897
Abstract 49: Targeting the TNF network in human ovarian cancer - A systems biology approach
Authors: Kulbe Hagen , Chakravarty Probir , Moore Robert , Iorio Francesco , Montoya Alexander , Saez-Rodriguez Julio , Cutillas Pedro , Balkwill Frances 
Published: August 2012

Abstract
In a recent publication (Kulbe et al Cancer Res 2011 epub ahead of print), we have shown how key pathways in cancer-related inflammation and Notch signaling are part of an autocrine malignant cell network in high-grade serous ovarian cancer, HGSOC. This network, that we have named the TNF network, has paracrine actions on angiogenesis, the stromal signature and the immune cell infiltrate in HGSOC. We have now used a systems biology approach, combining data from phospho-proteomic mass spectrometry and gene expression array analysis, to define the best therapeutic targets within the network and to identify drugs that may synergise with cytokine and chemokine inhibitors. First, we established a hierarchy of kinases involved in the TNF network and analyzed the constitutively active kinases in one of the high TNF network cell lines. Of 45 constitutively active kinases, 33 of these kinases showed direct interactions with each other. Next, we mapped gene expression microarray data onto the Connectivity Map of drugs in order to identify compounds having an effect on transcription similar to that of the TNF network. Among the identified candidate drugs were luteolin, apigenin and resveratrol. One of the known targets of this class of drugs is the protein kinase Casein kinase II (CSNK2A1), a kinase activated in association with the TNF network. In conclusion, we have identified kinases, particularly CK2, associated with the TNF network that may play a central role in sustaining the cytokine network and/or mediating its effects in ovarian cancer. We believe our findings have implications for our understanding of ovarian cancer biology and the development of new and more effective treatments for this disease.
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 49. doi:1538-7445.AM2012-49
Abstract 50: Abrogation of stromal TGF-β signaling induces DNA damage and genetic/epigenetic alterations in neighboring epithelia
Authors: Achyut B. , Bader David A. , Pang Yanli , Harris Curtis C. , Yang Li 
Published: August 2012

Abstract
Inactivation of tumor suppressor genes in stromal fibroblast induces epithelial cancer development, suggesting an important role of stroma in epithelial homoeostasis. We investigated the underlying mechanisms in squamous cell carcinoma (SCC) development due to loss of TGF- signaling in FSP1+ fibroblasts (Tgfbr2fspKO). We found that stroma specific deletion of Tgfbr2 resulted a loss of p15 and p16, the cyclin dependent kinase (CDK) inhibitors in adjacent epithelia. In addition, there was an increased p21 methylation in the promoter region of the p53 binding site. These data suggest that multiple cell cycle checkpoints were compromised in the epithelia of Tgfbr2fspKO mice. Consistent with these observations, there was an increased cell proliferation in the epithelial compartment. The mechanisms mediating the cross talk between the epithelia and the stroma apparently involved inflammation that occurred only in the Tgfbr2fspKO mice but not in Tgfbr2flox/flox mice. This is characterized by an increased CD45+ leukocyte infiltration, increased cytokines expression (IL-10, IFN-γ TNF-α and GM-CSF) and elevated levels of iNOS, COX2 and NFκB. Interestingly, a significant DNA damage, featured by 8-Oxo-dG DNA adduct formation, and elevated expression of γ-H2AX, a histone protein in response to DNA double strand break, was observed in Tgfbr2fspKO mice. Inhibition of inflammation with COX2 inhibitor (Celecoxib) or germ free housing condition, significantly delayed epithelial hyperplasia/dysplasia and reduced DNA damage in Tgfbr2fspKO mice. Examination of human esophageal cancers showed a downregulation of TβR2 in the stromal fibroblast, and an increased inflammation and DNA damage similar to Tgfbr2fspKO mice. Together, our data demonstrate that attenuation of stromal TGF- signaling induces inflammation that in turn causes DNA damage, epigenetic and genetic alterations in epithelia. Therefore, therapeutic targeting of inflammation and tumor microenvironment may be useful in treating cancers with downregulation of TGF- signaling in stroma.
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 50. doi:1538-7445.AM2012-50
Abstract 5000: Epigenomic profiling of oral cancer
Authors: Yoshiba Sayaka 
Published: August 2012

Abstract
Epigenetic aberration, such as dysregulation of DNA mathylation is often associated with human carcinogenesis. To analyze DNA methylation profiles of oral cancers, and to identify the methylation pattern specific to the clinicopathological features, we performed genome-wide methylation analysis using Infinium HumanMethylation27 BeadArray system. We found 2,361 aberrantly methylated CpG sites in 59 oral cancers compared to 3 normal mucosal tissues. By unsupervised clustering analysis, oral cancer was divided into two methylation epigenotypes that are significantly correlated with incidence of lymph node metastasis and differentiation grades. We selected the classifier genes that can predict tumor metastasis in the training set, and demonstrated that they are validated to be predictive in the independent test sample, preoperative biopsy samples. In summary, we identified two methylation epigenotypes correlated with clinical outcome in oral cancer, and candidate classifier genes that would be useful in patient stratification for intensive therapy to overcome the tumor recurrence.
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 5000. doi:1538-7445.AM2012-5000
Abstract 5001: Epigenetic networks in breast cancer
Authors: Liu Chunmei , Dong Shoulian , Stevens Junko 
Published: August 2012

Abstract
Epigenetic mechanisms are essential for normal development and maintenance of normal gene expression patterns in humans. Recent studies suggest that epigenetic alterations may be the key initiating events in some forms of cancers and global changes in the epigenome are a hallmark of cancers. Phospholipase D (PLD) catalyzes the hydrolysis of phophatidylcholine to generate the lipid second messenger phosphatidic acid (PA) and choline and regulates multiple cellular pathways. Elevated expression of PLD1 promoted cell proliferation and has been associated with the progression and metastasis of multiple cancers. In this work, we showcased the applications of our new epigenetic tools by elucidating the changes in chromatin organization (3C), DNA methylation and microRNA expression that underlies the aberrant expression level of PLD1 in breast cancers. Differences in PLD1 expression and the epigenetic network between tamoxifen responsive (MCF-7) and non-responsive (MDA-MB-231) breast cancer cell lines were compared to associate epigenetic changes with their cancer phenotypes. Effects of DNA demethylation and histone acetylation induced by methyltransferase inhibitor (5-aza-2′-deoxycytidine) and histone deacetylase inhibitor (Trichostatin A) were also investigated to provide insights into the molecular mechanisms of epigenetic drugs.
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 5001. doi:1538-7445.AM2012-5001