bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-71: Carcinogenic significance of integrated hepatitis b viral factors and its genotype in hepatocarcinogenesis.
Authors: Banerjee Soma , Datta Somenath , Roychoudhury Shrabasti , Dasgupta Debanjali , Ghosh Amit , Roy Gaurav , Datta Simanti , Chowdhury Abhijit 
Published: August 2014

Abstract
Integration of Hepatitis B Virus (HBV) is one of the major causes underlying Hepatocellular carcinoma (HCC) development. Recent studies revealed that altered expression of multiple cellular genes due to multiple random integration of viral factors lead to development of HCC. The present study aims to identify the carcinogenic significance of integrated HBV genome and its genotype in HCC development.
Host-Viral Junctions were determined in HCC (T) /adjacent tissues (NT) and cirrhotic (-HCC) tissues by sequencing of Alu PCR product followed by sequence blast. Host gene expression was checked by real time PCR. Competition between two coexisting genotypes was studied by replication assay using genotype specific PCR from media and viral core particle isolated from genotype specific plasmid transfected HepG2 cell line. Similarly, each viral genotype mediated DNA damage (γH2aX foci by confocal microscopy), ROS generation (DCFDA quantitation by Facs analysis and ER stress marker GRP78 luciferase assay), homologous recombination efficiency were also compared.
HBV integration was observed in 66.7% of T (8/12), 33.3% (4/12) NT and 75% (6/8) cirrhotic tissue samples in 18, 4 and 8 different locations respectively. These viral integration analysis within or close to several host genes, such as genes involved in differentiation, signaling, stress response, cell cycle, telomere regulations (8/30, 26.7%) etc and most of them showed altered expression. Interestingly, C-terminal truncated HBX which lost its growth suppressive domain were observed more in T (5/8, 62.5%) than NT (2/4, 50%) tissue samples. Most importantly, upon genotype analysis of each five clones in serum and tissue showed genotype C preferentially integrated in coexistence of both C and D genotype as “free virus” in tissue but D genotype observed in circulation. Genotype specific PCR from HBV/C & D cotransfected media showed that in presence of HBV/C, D replicates better than C but HBV/C with high recombination frequency generates more DNA damage and facilitate viral integration.
Thus random integration of HBV in host chromosome causes alterations in oncogenic gene expression and these alterations presumably lead to clonal selection of hepatocyte that acquires a growth advantage and proceeds towards HCC. Genotype of HBV is an important determining factor for HBV integration and liver inury.
Citation Format: Soma Banerjee, Somenath Datta, Shrabasti Roychoudhury, Debanjali Dasgupta, Amit Ghosh, Gaurav Roy, Simanti Datta, Abhijit Chowdhury. Carcinogenic significance of integrated hepatitis b viral factors and its genotype in hepatocarcinogenesis. [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 LB-71. doi:10.1158/1538-7445.AM2013-LB-71
Abstract LB-82: Chromosome 1q gain as genetic marker for risk stratification of pediatric ependymoma patients - validation as an adverse prognostic marker in the German multicenter HIT2000 trial.
Authors: Pietsch Torsten , Doerner Evelyn , zur Muehlen Anja , Velez-Char Natalia , Warmuth-Metz Monika , Kortmann Rolf-Dieter , von Hoff Katja , Friedrich Carsten , Rutkowski Stefan , von Bueren Andre O. 
Published: August 2014

Abstract
In contrast to histopathological grading which varied in respect to its prognostic value between different clinical trials, extent of resection was found to be consistently associated to the clinical outcome. In retrospective series, gain of genetic material of chromosome arm 1q was identified to predict worse outcome. This marker was mainly assessed by FISH analysis which typically showed failure rates of 15-20 % in archival material.
To validate this marker in a homogenously treated patient cohort, we analysed chromosome 1qin 209 consecutive cases enrolled into the multicenter trial HIT2000 (postoperative chemotherapy and irradiation, in a sequence depending on age and extent of resection) in which formalin-fixed, paraffin embedded material was available for DNA extraction. By using multiplex ligation-dependent probe amplification (MLPA) for 5 markers located on chromosome 1q and control markers, we were able to analyse 206/209 samples (&gt; 98 %) and found a gain of chromosome 1q in 35 cases (17 %). 135/206 ependymomas were located in the infratentorial region. 35 cases were diagnosed as WHO grade II ependymoma, 171 as anaplastic ependymoma (WHO grade III). Interestingly, only 2 of the 35 WHO grade II ependymomas had 1q gain (5.7%).
At a median follow-up of 3.9 years for survivors, patients with tumors showing 1q gain had a significantly lower 4-year overall survival (OS) (±SE) of 58% +/- 9% compared to patients lacking this marker (89% +/- 3%, p=0.002). The distribution of this marker was similar when comparing patients with supra- and infratentorial tumors. Multivariable analysis demonstrated that residual tumor and infratentorial localization were independent risk factors for event-free survival, and gain of chromosome 1q for OS, respectively.
In conclusion, we validated chromosomal 1q gain to be a useful independent genetic marker for risk stratification of pediatric ependymoma patients which can be evaluated by MLPA representing a robust, reliable and cost-efficient method.
Citation Format: Torsten Pietsch, Evelyn Doerner, Anja zur Muehlen, Natalia Velez-Char, Monika Warmuth-Metz, Rolf-Dieter Kortmann, Katja von Hoff, Carsten Friedrich, Stefan Rutkowski, Andre O. von Bueren. Chromosome 1q gain as genetic marker for risk stratification of pediatric ependymoma patients - validation as an adverse prognostic marker in the German multicenter HIT2000 trial. [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 LB-82. doi:10.1158/1538-7445.AM2013-LB-82
Abstract LB-9: Mountain ginseng extract exhibits anti-lung cancer activity by inhibiting the nuclear translocation of NF-κB.
Authors: Jang Ik Soon , Park Junsoo , Lee Seung Hoon , Choi JongSoon 
Published: August 2014

Abstract
Administration of mountain ginseng (MG) extract can restore advanced cancer to a normal state. To elucidate the mechanism by which MG extract prevents the progression of lung cancer, the processes of proliferation and death of lung cancer cells (A549) were examined after treatment with MG extract. Butanol-extracted MG (BX-MG) showed a high inhibitory effect (IC(50) = 2 mg/ml) by attenuating proliferation and inducing apoptosis in lung cancer cells. By HPLC-UV analysis of BX-MG, ginsenosides, Rb1 was identified as the most abundant ginsenoside, followed by Rg1, Re, Rc and Rb2. BX-MG induced caspase-3 dependent apoptosis by inhibiting NF-κB. In addition, BX-MG activated p53 and p21, resulting in the attenuated proliferation of A549 cells. Reduced activity of the NF-κB promoter and increased activity of the p53 promoter indicate that BX-MG regulates apoptosis at the level of transcription in lung cancer cells. Furthermore, BX-MG blocked the nuclear translocation of RelA and the associated reduction in surviving. These results suggest that BX-MG inhibits lung cancer cell growth by activating tumor suppressors and inhibiting nuclear translocation of NF-κB.
Citation Format: Ik Soon Jang, Junsoo Park, Seung Hoon Lee, JongSoon Choi. Mountain ginseng extract exhibits anti-lung cancer activity by inhibiting the nuclear translocation of NF-κB. [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 LB-9. doi:10.1158/1538-7445.AM2013-LB-9
Abstract SY15-01: Merkel cell polyomavirus: its role in pathogenesis and its potential as a molecular target.
Authors: Chang Yuan 
Published: August 2014

Abstract
Merkel cell carcinoma (MCC) was first described as a pathologic entity in 1972, and is an uncommon but aggressive skin cancer with a high propensity for metastasis and recurrence. In 2008, a new human polyomavirus, Merkel cell polyomavirus (MCV) was discovered by digital transcriptome subtraction in an MCC lesion and is now one of eight new human polyomaviruses described in the past five years. MCV is part of the normal, healthy skin flora but causes cancer after viral genome mutations eliminate its replication capacity. Further, MCV is clonally integrated in 70-80% of MCC tumors suggesting a primary role for its involvement in MCV infected MCCs.
The MCV genome is ~5400bp and has features including early, late, and non-coding regulatory regions conserved with other polyomaviruses. The MCV early region encodes for two potential viral oncoproteins: large T antigen (LT) and small T antigen (ST). Experiments show these proteins are expressed in MCC tumor cells from patient biopsies, and that MCV-positive MCC cell lines undergo growth arrest and/or cell death upon T antigen knockdown by short hairpin RNA (shRNA). These experiments provide direct experimental evidence that T antigen expression is necessary for the maintenance of MCV-positive MCC and that MCV is the infectious cause of MCV-positive MCC.
While similar to known polyomaviruses, MCV oncogenes act in new ways, such as activation of the survivin oncoprotein and PP2A-independent targeting of cap-dependent translation. In five years, the diagnosis and treatment potential for an intractable and enigmatic cancer has dramatically changed through the discovery of a viral cause of MCC.
Citation Format: Yuan Chang. Merkel cell polyomavirus: its role in pathogenesis and its potential as a molecular target. [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 SY15-01. doi:10.1158/1538-7445.AM2013-SY15-01
Abstract SY16-02: Embracing complexity: A drosophila approach to cancer therapeutics.
Authors: Cagan Ross L. 
Published: August 2014

Abstract
Cancer's complexity is a key difficulty in identifying useful therapeutics. In place of simplifying the disease, I will describe our use of Drosophila to develop complex, multigenic cancer models that directly reflect current human tumor sequencing data. These include colorectal, pancreatic, and thyroid tumor models. Further, I will discuss our approach– in collaboration with Kevan Shokat's laboratory– that combines fly genetics with medicinal chemistry to develop novel drugs through "rational polypharmacology," emphasizing a balance of "targets" and "anti-targets" that are designed to optimize therapeutic index.
Citation Format: Ross L. Cagan. Embracing complexity: A drosophila approach to cancer therapeutics. [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 SY16-02. doi:10.1158/1538-7445.AM2013-SY16-02
Abstract SY18-04: Next-generation screens for cancer genes.
Authors: Adams David J. 
Published: August 2014

Abstract
In humans diverse mutagenic processes contribute to tumor development and drive tumor evolution. We have been performing genetic screens in mouse models of cancer engineered to carry known driver mutations. Using exome sequencing, whole genome sequencing, and transposons in these models we have identified genes that can promote tumorigenesis and regulate response to therapy. I will talk about our latest progress with these screens and the genes we have discovered.
Citation Format: David J. Adams. Next-generation screens for cancer genes. [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 SY18-04. doi:10.1158/1538-7445.AM2013-SY18-04
Abstract SY30-03: Monitoring tumor evolution by clonal tracking in ctDNA.
Authors: Caldas Carlos 
Published: August 2014

Abstract
Clonal evolution and the resulting tumor heterogeneity presents challenges for molecular diagnostics, tumor burden monitoring and studying mechanisms of drug resistance. In breast cancer circulating mutant cell free DNA (ctDNA) can be used as a ‘liquid biopsy’ to tackle all of these challenges. I will present our data that provides proof of principle for the use of ctDNA to track clonal evolution/clonal selection in both metastatic breast cancer and localized breast cancer treated with neo-adjuvant therapy.
Citation Format: Carlos Caldas. Monitoring tumor evolution by clonal tracking in ctDNA. [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 SY30-03. doi:10.1158/1538-7445.AM2013-SY30-03
Abstract A12: Alkylation of histones by 4-oxo-2-nonenal as a novel modification linked to oxidative stress
Authors: Galligan J J. , Rose K L. , Beavers W N. , Aluise C D. , Shuck S C. , Marnett L J. 
Published: August 2014

Abstract
Sustained oxidative stress leads to the generation of toxic concentrations of the lipid aldehydes 4-hydroxy-2-nonenal (4-HNE) and 4-oxononenal (4-ONE), which are capable of covalently modifying the side-chains of Cys, His, and Lys residues. These protein modifications have been identified as a contributing factor in numerous disease states, including cancer, cardiovascular disease, neurodegeneration and diabetes. Here, we describe a novel class of histone modifications resulting from lipid electrophile adduction of His and Lys residues. Utilizing click chemistry with ω-alkynyl-4-ONE (a4-ONE), we have identified all-four core histones as targets for modification in RKO cells treated with physiologically relevant concentrations of electrophile. Isolation of chromatin from these cells reveals H2B as a highly susceptible target to modification by 4-ONE, while H2A, H3 and H4 show minimal reactivity. Interestingly, similar experiments with a4-HNE failed to identify any of the core histones as targets for modification. 4-HNE reacts heavily with Cys residues, which histones lack, whereas 4-ONE reacts primarily with the ϵ-amine of Lys residues. A proteomic investigation of site-specific modifications in RKO cells treated with 4-ONE reveals H2B Lys117 as a major target for modification. The predominant stable species detected on H2BK117 results from a 1,2-addition and net acylation analogous to Lys acetylation. H2BK117 is a surface exposed Lys residing on the face of the nucleosome core particle. Treatment of RKO cells with physiologically relevant doses of 4-ONE results in the altered expression of 40 genes. Electrophile adduction of histones provides a previously unexplored link between oxidative stress and gene regulation.
Citation Format: J J. Galligan, K L. Rose, W N. Beavers, C D. Aluise, S C. Shuck, L J. Marnett. Alkylation of histones by 4-oxo-2-nonenal as a novel modification linked to oxidative stress. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr A12.
Abstract A14: Understanding the role of ATRX in the development and progression of glioma
Authors: Goldberg Hannah E. , Kernohan Kristin D. , Berube Nathalie G. 
Published: August 2014

Abstract
Gliomas are tumors that arise from glial cells within the brain and spinal cord and account for approximately 30% of all central nervous system neoplasms. Emerging evidence indicates that unique molecular and genetic footprints define glioma subtypes. The Atrx gene is commonly mutated in a subset of gliomas across all tumor grades and within both the pediatric and adult populations. ATRX is a chromatin remodeling protein that is necessary for proper neural development. Loss of ATRX conditionally in the forebrain of the mouse starting at embryonic day 8.5 leads to an increase in replication stress and p53-mediated cortical cell death. Microarray analysis of control and Atrx-null neonatal forebrains indicates a significant increase in the expression of many cancer-related genes. Many of these overexpressed genes are involved in cellular migration, invasion, and epithelial-mesenchymal transition — important cellular phenotypes known to contribute to glioma development. Our data highlight oncogenic signaling pathways that become activated in the absence of the ATRX protein in the brain that may promote tumorigenesis when combined with additional genetic mutations, such as p53 mutations.
Citation Format: Hannah E. Goldberg, Kristin D. Kernohan, Nathalie G. Berube. Understanding the role of ATRX in the development and progression of glioma. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr A14.
Abstract A30: Inhibiting histone methylation as an epigenetic therapeutic approach for pancreatic cancer
Authors: Govindarajan Rajgopal 
Published: August 2014

Abstract
We evaluated the potential of an investigational histone methylation reversal agent, 3-deazaneplanocin A (DZNep), in improving the chemosensitivity of pancreatic cancer to nucleoside analogs (i.e., gemcitabine). DZNep brought delayed but selective cytotoxicity to pancreatic cancer cells without affecting normal human pancreatic ductal epithelial (HPDE) cells. Co-exposure of DZNep and gemcitabine induced cytotoxic additivity or synergism in both well- and poorly-differentiated pancreatic cell lines. In contrast, DZNep exerted antagonism with gemcitabine against HPDE cells with significant reduction in cytotoxicity compared with the gemcitabine-alone regimen. DZNep marginally depended on purine nucleoside transporters for its cytotoxicity, but the transport dependence was circumvented by acyl derivatization. Drug exposure studies revealed that a short priming with DZNep followed by gemcitabine treatment rather than co-treatment of both agents to produce a maximal chemosensitization response in both gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer cells. DZNep rapidly and reversibly decreased trimethylation of histone H3 lysine 27 but increased trimethylation of lysine 9 in an EZH2- and JMJD1A/2C-dependent manner, respectively. However, DZNep potentiation of nucleoside analog chemosensitization was found to be temporally coupled to trimethylation changes in lysine 27 and not lysine 9. Polymeric nanoparticles engineered to chronologically release DZNep followed by gemcitabine produced pronounced chemosensitization and dose-lowering effects. Together, our results identify that an optimized DZNep exposure can presensitize pancreatic cancer cells to anticancer nucleoside analogs through the reversal of histone methylation, emphasizing the promising clinical utilities of epigenetic reversal agents in future pancreatic cancer combination therapies.
Citation Format: Rajgopal Govindarajan. Inhibiting histone methylation as an epigenetic therapeutic approach for pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr A30.
Abstract A46: LSD1 globally mediates epigenetic modifications on androgen receptor-dependent enhancers
Authors: Cai Changmeng , He Housheng Hansen , Brown Myles , Balk Steven P. 
Published: August 2014

Abstract
Androgen receptor (AR) belongs to nuclear receptor superfamily and plays pivotal roles in development of prostate and prostate cancer. The lignded AR binds to AR responsive elements (ARE) on the enhancers and mediates the transcription activity. AR binding on chromatin appears to depend on the binding of pioneer factor FOXA1, which recognizes the active sites marked with high level of mono- or di-methylation of Histon 3 lysine 4 (H3K4me1-2) and then make the site accessible for AR binding. However, the in depth mechanism how FOXA1 opens the enhancer and whether this results in further chromatin modification remains unclear. Through ChIP-seq studies coupled with gene expression array, we have found LSD1 (lysine specific demethylase 1) together with its binding partner CoRest were recruited by FOXA1 to the AR-dependent enhancer and its histone demethylation functions were then activated by liganded AR. This results in the loss of methylation marks and activation of gene transcription but not affecting AR binding or AR-mediated nucleosome dynamics. In contrast to this activator function, LSD1 can also formed corepressor complex to suppress the transcription of a subset of genes. This comprehensive study clearly suggested distinct roles of LSD1 as a coactivator versus a corepressor in different protein complexes therefore to mediate different cell functions.
Citation Format: Changmeng Cai, Housheng Hansen He, Myles Brown, Steven P. Balk. LSD1 globally mediates epigenetic modifications on androgen receptor-dependent enhancers. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr A46.
Abstract A55: Histone deacetylase inhibitors as differentiation agents in breast cancer cells
Authors: Ismail Houssam , Bail Martine , Laperrière David , Hilmi Khalid , Mader Sylvie 
Published: August 2014

Abstract
FOXA1 and GATA3 are two luminal lineage transcription factors that form a cross-regulatory transcriptional network that controls the morphogenesis of the mammary gland and regulates estrogen receptor (ER) signaling. Approximately two thirds of breast tumors overexpress ER at the time of diagnosis. Antiestrogen therapy has been effective in blocking the proliferative effects of ER, but unfortunately a significant proportion of patients will relapse due to resistance. Histone deacetylase inhibitors (HDACis) have been shown to suppress ER expression in ER+ breast cancer cells and are currently being tested in clinical trials in combination with antiestrogens for treatment of ER+ breast tumors. Here, we report that the HDACi Trichostatin A (TSA) abrogates the expression of FOXA1 and GATA3, as well as that of ER in MCF-7 breast cancer cells. Using gene expression microarrays, we observed that several markers of lactogenic differentiation including the cholesterol biosynthesis pathway were induced by TSA treatment. Moreover, expression of ER, FOXA1 and GATA3 is reduced during lactation in the mouse mammary gland. Finally, overexpression of GATA3 in MCF-7 cells reduced the TSA-mediated induction of lactogenic markers, suggesting that GATA3 may act as a repressor of lactogenic differentiation. Altogether, our studies suggest that HDACi treatment partially mimics differentiation events taking place in ER+ cells during lactogenesis. Future experiments will examine the mechanisms and clinical relevance of the differentiation properties of HDACis.
Citation Format: Houssam Ismail, Martine Bail, David Laperrière, Khalid Hilmi, Sylvie Mader. Histone deacetylase inhibitors as differentiation agents in breast cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr A55.