bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3793: Effects of DCA and metformin on murine colon cancer growth
Authors: Sticca Robert P. , Murphy Tonya C. 
Published: May 2015

Abstract
Background: Dichloroacetate (DCA) and metformin (M) have been reported to have many effects on cancer cells including alterations in pH homeostasis and glucose metabolism, cell cycle arrest, induction of autophagy and modulation of the tumor microenvironment. These effects have been shown to increase tumor apoptosis, inhibit neoplastic cell proliferation, improve the immune response against tumor cells and decrease the protective inflammatory response in tumors, which has led to the investigation of these drugs as anticancer agents. This study examines the effects of DCA and metformin in a murine colon cancer model both in vivo and in vitro.
Methods: Murine colon cancer cell lines (ATCC CT26-CL25, CT26-WT) and cells isolated from subcutaneous metastatic colon cancer tumors (CT71911) were grown in the presence of DCA (serial concentrations from 12 mM to 192mM) and M (serial concentrations from 8 mM to 48 mM). Viable cells were counted and averaged for 3 separate assays. Balb/c mice in triplicate were injected IP with serial concentrations of DCA and M (8,24,48 mM) beginning one day prior to tail vein administration of 7.5 x 103 colon cancer cells (CT26-WT, CT71911). Daily IP injections of DCA and M were continued for 6 weeks or until the mice succumbed to metastatic cancer. All mice were autopsied and cause of death was recorded.
Results: All three cell lines demonstrated a linear reduction in growth and increased apoptosis with increasing concentrations of DCA. All tumor cells were killed at concentrations above 96 mM. M was cytostatic but not cytotoxic for all three cell lines with minimal growth at 8 mM and no growth at higher concentrations. In vivo, administration of IP DCA prolonged survival by 80 - 89% (days after tumor challenge), while IP metformin prolonged survival by 35 - 38%. Increased survival with both DCA and M was not dose dependent with variation between concentrations less than 10%. All mice died of lung metastases.
Conclusion: Both DCA and M demonstrated beneficial effects on murine colon cancer cells with reductions in cell growth and increased apoptosis in vitro and increased survival in vivo. M exhibited cytostatic activity and a lower improvement in survival while DCA exhibited cytotoxic activity and a longer survival benefit. Further investigation in the use of these agents as adjunct therapies for colon cancer is warranted.
Citation Format: Robert P. Sticca, Tonya C. Murphy. Effects of DCA and metformin on murine colon cancer growth. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3793. doi:10.1158/1538-7445.AM2014-3793
Abstract 380: Discovery of new epigenetic drugs among FDA-approved drug libraries
Authors: Raynal Noël J. , Lee Justin T. , Wang Youjun , Garriga Judith , Malouf Gabriel , Dumont Sarah , Dettman Elisha J. , Gharibyan Vazganush , Ahmed Saira , Chung Woonbok , Childers Wayne E. , Abou-Gharbia Magid , Henry Ryan A. , Andrews Andrew , Jelinek Jaroslav , Cui Ying , Baylin Stephen B. , Gill Donald L. , Issa Jean-Pierre J. 
Published: May 2015

Abstract
Targeting epigenetic pathways to induce tumor suppressor gene reactivation is a promising approach for cancer therapy. Epigenetic drugs produce impressive responses in some patients; however, treatment options are limited to a small number of drugs. We screened drug libraries for epigenetic activity using a live cell-based assay. We found that around 1% of US-FDA approved drugs have significant epigenetic activity detected by GFP reactivation of a DNA methylated and silenced promoter in colon cancer cells. Newly identified drugs, most prominently cardiac glycosides, induced tumor suppressor gene reactivation and showed selective anticancer apoptosis induction. These drugs did not change DNA methylation or histone acetylation globally but induced gene reactivation and cancer cell killing through calcium signaling leading to nuclear exclusion of chromatin repressors. Our data identify new epigenetic drugs that can be rapidly repurposed for cancer clinical trials and raise questions about the safety of commonly used medications.
Citation Format: Noël J. Raynal, Justin T. Lee, Youjun Wang, Judith Garriga, Gabriel Malouf, Sarah Dumont, Elisha J. Dettman, Vazganush Gharibyan, Saira Ahmed, Woonbok Chung, Wayne E. Childers, Magid Abou-Gharbia, Ryan A. Henry, Andrew Andrews, Jaroslav Jelinek, Ying Cui, Stephen B. Baylin, Donald L. Gill, Jean-Pierre J. Issa. Discovery of new epigenetic drugs among FDA-approved drug libraries. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 380. doi:10.1158/1538-7445.AM2014-380
Abstract 3802: Withacnistin blocks binding of STAT3 and STAT5 to growth factor and cytokine receptors and induces regression of breast tumors in vivo
Authors: Zhang Xiaolei , Blaskovich Michelle A. , Forinash Kara D. , Sebti Said M. 
Published: May 2015

Abstract
The binding of STAT3 and STAT5 to growth factor and cytokine receptors such as EGFR and the IL-6 receptor gp130 is critical to their activation and ability to contribute to malignant transformation. Therefore, interfering with these biochemical processes could lead to the discovery of novel anti-cancer agents. In this manuscript, we show that the natural product, Withacnistin (Wit) blocks EGF- and IL-6-stimulated binding of STAT3 and STAT5 to EGFR and gp130. Furthermore, Wit inhibits EGF-, PDGF-, IL-6-, IFNβ- and GM-CSF-stimulation of tyrosine phosphorylation of STAT3 and STAT5 but not of EGFR or PDGFR. The inhibition of P-STAT3 and P-STAT5 occurred very rapidly, within minutes of Wit treatment and growth factor stimulation. Wit also inhibits STAT3 nuclear translocation, DNA binding, promoter transcriptional activation, and it suppresses the expression levels of STAT3 target genes such as Bcl-xL and Mcl-1. Finally, Wit induces apoptosis, inhibits anchorage-independent growth and invasion, and causes breast tumor regression in an ErbB2-driven transgenic mouse model. These data warrant further development of Wit as a novel anti-cancer drug for targeting tumors that harbor hyperactivated STAT3 and STAT5.
Citation Format: Xiaolei Zhang, Michelle A. Blaskovich, Kara D. Forinash, Said M. Sebti. Withacnistin blocks binding of STAT3 and STAT5 to growth factor and cytokine receptors and induces regression of breast tumors in vivo. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3802. doi:10.1158/1538-7445.AM2014-3802
Abstract 3807: A novel imidazole derivate inhibits STAT3 activation via induction of SHP-1 hepatocellular carcinoma
Authors: Su Jung-Chen , Wu Szu-Hsien , Chen Kuen-Feng , Tai Wei-Tien , Huang Jui-Wen , Shiau Chung-Wai 
Published: May 2015

Abstract
The activation of STAT3 signaling cascade has been linked with cell survival, proliferation, and angiogenesis in HCC. Literature have shown that overexpression of SHP-1 suppressed cell proliferation in varies cancer cells. Compounds that can activate SHP-1 and further repress STAT3 activity pathway have potential for treatment of HCC. We investigated whether imidazole derivates can modulate the SHP-1/STAT3 pathway. The result showed that imidazole derivate inhibited both constitutive and interleukin 6-inducible STAT3 phosphorylation in HCC cells and induced cell apoptosis. In addition, we explored protein tyrosine phosphatases (SHP-1 and SHP-2) expression level in HCC cells with the treatment of the imidazole derivate. Interestingly, the imidazole derivate significantly induced the expression of SHP1 and subsequently inhibited the phosphorylation of Src , Jak2 and STAT3. This agent also repressed the expression of STAT3-regulated target genes, including cyclin D1, Mcl-1, and survivin. Overall, our results suggest that the imidazole derivate blocks STAT3 activation through up-regulation of SHP-1, and this may have potential for combination with other chemotherapeutic agents.
Citation Format: Jung-Chen Su, Szu-Hsien Wu, Kuen-Feng Chen, Wei-Tien Tai, Jui-Wen Huang, Chung-Wai Shiau. A novel imidazole derivate inhibits STAT3 activation via induction of SHP-1 hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3807. doi:10.1158/1538-7445.AM2014-3807
Abstract 3819: Clinical potential of the Eph/ephrin profile in breast cancer
Authors: Perez-Tenorio Gizeh , Husa Anna-Maria , Stål Olle 
Published: May 2015

Abstract
The Eph receptors belong to a large family of receptors tyrosine kinase. The Ephs and their ligands ephrins are aberrantly expressed in cancer. However, due their complex signaling and promiscuous interactions, a wide screening of the entire family will be important to determine their clinical value. Purpose: The Eph receptor tyrosine kinase family has been implicated in breast cancer but their role in tumor progression remains elusive. Therefore we aimed to profile the Eph receptors and their ligands ephrins in breast cancer samples to define them as potential clinical markers or therapeutic targets.
Experimental design: Gene expression of Eph/ephrins was quantified by RT-PCR using a TaqMan® Micro Fluidics Cards Microarray custom designed for 21 Eph/ephrin family members: EphA1-A8, EphB1-B4 and EphB6, ephrinA1-A5, ephrinB1-B3 and 2 endogenous controls: GAPDH and HPRT1 in 70 breast cancer tumors.
Results: We found that high expression of EphBs, and particularly EphB2, was associated to worse outcome among postmenopausal patients with lymph node infiltration. Additionally high EphB2 expression correlated with HER2 positive status.
Conclusions: Our results suggest that the EphB receptor family may have prognostic value for postmenopausal breast cancer patients with lymph nodal infiltration. We will continue this study in a larger patient material in order to better evaluate the therapeutic impact of this family.
Citation Format: Gizeh Perez-Tenorio, Anna-Maria Husa, Olle Stål. Clinical potential of the Eph/ephrin profile in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3819. doi:10.1158/1538-7445.AM2014-3819
Abstract 382: Inhibition of BET bromodomain proteins as a therapeutic approach in prostate cancer
Authors: Wyce Anastasia , Degenhardt Yan , Bai Yuchen , Le BaoChau , Korenchuk Susan , Crouthamel Ming-Chih , McHugh Charles F. , Vessella Robert , Creasy Caretha L. , Tummino Peter J. , Barbash Olena 
Published: May 2015

Abstract
BET (bromodomain and extra-terminal) family proteins are epigenetic regulators known to control expression of genes involved in cell growth and oncogenesis. Selective small molecule BET inhibitors prevent binding of BET proteins to acetylated histones and inhibit transcriptional activation of BET target genes. BET inhibitors attenuate cell growth and survival in a number of hematologic cancer models, partially through down-regulation of the critical oncogene, MYC. We hypothesized that BET inhibitors will similarly regulate expression of MYC family genes (MYC, MYCN, MYCL1) in solid tumor models characterized by MYC family amplification or over-expression. We and others have recently shown activity for BET inhibitors in MYCN-amplified neuroblastoma models, with concomitant down-regulation of MYCN expression. Here we describe the effects of the highly specific BET inhibitor, I-BET762, on MYC expression and cell growth in prostate cancer models. I-BET762 treatment inhibited MYC expression accompanied by growth inhibition and decreased survival in prostate cancer cell lines that over-express MYC. In addition to MYC signatures, gene expression profiling in cell lines identified numerous cell cycle-associated genes as being significantly down-regulated by I-BET762. Importantly, our data suggests that I-BET762 effects are partially driven by MYC down-regulation and underlines the critical importance of additional mechanisms of I-BET762 induced phenotypes. Consistent with our in vitro observations, BET inhibition reduces MYC expression and tumor burden in a primary model of castration resistant prostate cancer that expresses high levels of MYC. Taken together, our data highlight the potential of BET inhibitors as a novel therapeutic approach to treat prostate tumors driven by MYC over-expression.
Citation Format: Anastasia Wyce, Yan Degenhardt, Yuchen Bai, BaoChau Le, Susan Korenchuk, Ming-Chih Crouthamel, Charles F. McHugh, Robert Vessella, Caretha L. Creasy, Peter J. Tummino, Olena Barbash. Inhibition of BET bromodomain proteins as a therapeutic approach in prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 382. doi:10.1158/1538-7445.AM2014-382
Abstract 3822: Correlation between worse prognosis and lower expression of the TPPP gene in patients with hepatocellular carcinoma, detected by multiarray analysis
Authors: Inokawa Yoshikuni , Nomoto Shuji , Hishida Mitsuhiro , Takano Nao , Kanda Mitsuro , Fujiwara Michitaka , Koike Masahiko , Sugimoto Hiroyuki , Fujii Tsutomu , Nakayama Goro , Yamada Suguru , Tanaka Chie , Kobayashi Daisuke , Iwata Naoki , Kodera Yasuhiro 
Published: May 2015

Abstract
Background. Hepatocellular carcinoma (HCC) patients who undergo liver resection often suffer multicentric occurrence after surgery. Therefore, understanding carcinogenesis in background liver is important.
Methods. Control liver samples (super normal [SN]), were taken from 11 cases of metastatic liver cancer. We selected corresponding normal tissue from typical cases of HCC with chronic hepatitis C (corresponding normal [CN]) for comparison. Expression profiling and methylation arrays were performed to compare SN and CN. Array data showed that the tubulin polymerization promoting protein (TPPP) gene showed differences in both array analyses. The relationship between clinicopathological factors of 179 HCC patients and TPPP expression was investigated.
Results. The expression array showed that the TPPP gene was decreased by 2.236-fold (log2 ratio) in CN compared with SN. The methylation array showed a higher value of methylation for CN (0.730) than SN (0.384). We studied TPPP gene expression by real-time reverse transcription PCR. When compared expression level of TPPP (TPPP value ×103/GAPDH), among SN (n=11), normal liver tissue of HCC patients (n=179), and tumor tissue of HCC (n=179), there were significant differences (median: 116, 4.60, and 2.63, respectively). The group with lower TPPP expression in tumors compared with normal tissue showed a worse prognosis of overall survival than that in the increased expression group (P=0.0317). Strongly reduced TPPP expression in tumor tissue compared with normal tissue (ratio &lt;0.3, n=57) was detected as an independent prognostic factor by multivariate analysis (P=0.0310).
Conclusions. Expression of the TPPP gene in tumor and non-cancerous liver tissue in HCC patients is significantly lower compared with SN. HCC patients with this low TPPP expression show a poor prognosis. This indicates that this gene is a new candidate of tumor suppressor genes in HCC. Low TPPP expression in liver tissue might be a predictor of HCC.
Citation Format: Yoshikuni Inokawa, Shuji Nomoto, Mitsuhiro Hishida, Nao Takano, Mitsuro Kanda, Michitaka Fujiwara, Masahiko Koike, Hiroyuki Sugimoto, Tsutomu Fujii, Goro Nakayama, Suguru Yamada, Chie Tanaka, Daisuke Kobayashi, Naoki Iwata, Yasuhiro Kodera. Correlation between worse prognosis and lower expression of the TPPP gene in patients with hepatocellular carcinoma, detected by multiarray analysis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3822. doi:10.1158/1538-7445.AM2014-3822
Abstract 3825: High DAPK expression is correlated with worse prognosis in colorectal cancer patients
Authors: Ivanovska Jelena , Zlobec Inti , Diamantis-Karamitopoulou Eva , Dawson Heather , Koelzer Viktor Hendrik , Agaimy Abbas , Garreis Fabian , Laqua William , Lugli Alessandro , Hartmann Arndt , Schneider-Stock Regine 
Published: May 2015

Abstract
Objectives: Death-associated protein kinase (DAPK) is a cytoskeleton-associated serine/threonine kinase. It functions as a potent inhibitor of cell polarization and migration. DAPK loss has been shown to be associated with advanced tumor stages and unfavorable prognosis in many tumor types. However, the prognostic relevance of DAPK in patients with colorectal cancer is only poorly understood. Thus, we aimed to investigate the impact of DAPK protein expression on clinical outcome in patients with colorectal cancer.
Methods: Samples from 220 colorectal cancer patients with a median follow-up of 60 months were analyzed for immunohistochemical DAPK protein expression on tissue microarrays. The effect of endogenous DAPK protein expression on cell migration was analyzed applying the ECIS system (electric cell-substrate impedance sensing) with stable DAPK knockdown (shRNA) and DAPK overexpressing cell lines generated from HCT116 wild type colon cancer cells. Colony formation ability was analyzed using soft agar assay.
Results: In Kaplan-Meier-curve analysis DAPK loss was associated with longer survival time (p&lt; 0.001). The 5-year survival rates were 52.3% and 25.6% in patients with DAPK negative tumors and DAPK positive tumors, respectively. 76.1% of DAPK positive tumors showed evidence of tumor budding. After adjusting for TNM stage in multivariate Cox regression analysis, DAPK retained its strong independent prognostic value. Patients with DAPK overexpressing tumors had a 1.9 times increased risk of death from the tumor than those with DAPK negative tumors. DAPK expression in tumor center showed a loss of expression toward the front (p=0.0126). This was in agreement with ECIS migration results indicating higher migration rate for DAPK shRNA cells. DAPK wild type cells showed an increased number of colonies in soft agar assay in comparison to other cell types. Colony formation ability showed time-dependent effects for DAPK overexpression.
Conclusion: In contrast to the well-known function of DAPK as a tumor suppressor, our data showed DAPK overexpression to be associated with aggressiveness of tumors and an unfavorable outcome. This interesting and new finding has to be further evaluated.
Citation Format: Jelena Ivanovska, Inti Zlobec, Eva Diamantis-Karamitopoulou, Heather Dawson, Viktor Hendrik Koelzer, Abbas Agaimy, Fabian Garreis, William Laqua, Alessandro Lugli, Arndt Hartmann, Regine Schneider-Stock. High DAPK expression is correlated with worse prognosis in colorectal cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3825. doi:10.1158/1538-7445.AM2014-3825
Abstract 3828: An 18-gene signature for vascular invasion is associated with aggressive features and reduced survival in breast cancer
Authors: Mannelqvist Monica , Wik Elisabeth , Stefansson Ingunn M. , Akslen Lars A. 
Published: May 2015

Abstract
Introduction: Vascular invasion, i.e. tumor cells entering the vascular system, is considered to be an early step in the metastatic process and important for the progress of malignant tumors. By microarray and qPCR, we previously constructed an 18-gene signature in relation to vascular invasion among endometrial cancer patients. Here, we wanted to investigate the vascular invasion signature (VIS) among breast cancers patients.
Methods: The 18-gene signature was studied in 11 gene expression data sets of breast cancer including information on 2423 patients. The genes in the signature were investigated in the external data sets and related to clinical data and follow-up information. We also wanted to examine if our signature was associated with other published signatures related to tumor progression.
Results and Conclusions: High VIS showed associations with aggressive features of breast cancer such as high tumor grade, hormone receptor negativity, HER2 positive tumors, presence of a basal-like phenotype, reduced patient survival and response to cytostatic treatment. Correlations between VIS and other signatures for tumor progression indicate an involvement in similar biological processes. In conclusion, the vascular invasion signature showed strong and consistent associations with aggressive features of breast cancer.
Citation Format: Monica Mannelqvist, Elisabeth Wik, Ingunn M. Stefansson, Lars A. Akslen. An 18-gene signature for vascular invasion is associated with aggressive features and reduced survival in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3828. doi:10.1158/1538-7445.AM2014-3828
Abstract 3830: E2F1-FOXM1 activation predicts progression of non-muscle invasive bladder cancer
Authors: Kim Seon-Kyu , Lee Se-Ra , Roh Yun-Gil , Song Bicna , Park Kiejung , Leem Sun-Hee , Chu In-Sun 
Published: May 2015

Abstract
Backgrounds: Bladder cancer is a genetic disorder driven by the accumulative changes of the multiple genes, such as E2F1, FOXM1, and EZH2. The objective of this study is to estimate a prognostic value of gene expression signature and identify putative signaling pathway for mediating progression of non-muscle invasive bladder cancer (NMIBC).
Methods: Gene expression profiling was performed using primary NMIBC cohort to identify a signature correlated with disease progression. The signature was validated in three independent cohorts. The association between the signature and prognosis of NMIBC patients was assessed using various statistical methods including a leave-one-out cross-validation and multivariate Cox regression analyses. The upstream regulator analysis of the genes in the signature was performed by Ingenuity Pathway Analysis TM. We also confirmed a prognostic relevance of the signature with experimental assays using bladder cancer cell lines.
Results: Kaplan-Meier analysis in the discovery cohort revealed significant differences in disease progression associated with the expression signature of E2F1-associated genes (p = 0.003), which produced consistent prognostic pattern in the validation cohorts. Multivariate Cox regression analysis revealed that the signature was an independent strong predictor of disease progression (hazard ratio = 6.082, 95% confidence interval = 3.280 to 11.279, p &lt; 0.001). In subset analyses, the signature could identify patients who would benefit from intravesical immunotherapy. Lastly, upstream regulator analyses and experimental assays of the signature revealed that NMIBC progression could be mediated by E2F1-FOXM1 pathways.
Conclusion: The prognostic molecular signature defined by activation of E2F1 and FOXM1 represents a promising diagnostic tool to identify high risk NMIBC patients.
Citation Format: Seon-Kyu Kim, Se-Ra Lee, Yun-Gil Roh, Bicna Song, Kiejung Park, Sun-Hee Leem, In-Sun Chu. E2F1-FOXM1 activation predicts progression of non-muscle invasive bladder cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3830. doi:10.1158/1538-7445.AM2014-3830