bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 201: The expression of survivin in human oral squamous cell carcinoma and its relationship with clinical factors
Authors: Tamatani Tetsuya , Takamaru Natsumi , Ferdous Tarannum , Uchida Daisuke , Fujisawa Kenji , Nagai Hirokazu , Miyamoto Youji 
Published: July 2012

Abstract
[Background] Survivin is a member of the inhibitor of apoptosis protein family, which is a bifunctional protein that suppresses apoptosis and regulates cell division. Survivin is expressed in various malignant tumors. The overexpression of survivin has been reported to be a poorer prognostic factor in various malignancies. However, the prognostic value of survivin expression in patients with oral cancer is still controversial. Moreover, there are few comparative studies of survivin expression between the cytoplasm and nucleus of individual cells.
[Purpose] The aims of present study were to evaluate the expression of survivin protein in oral squamous cell carcinoma (OSCC) and to elucidate the relationships among the survivin expression, clinical stages, histological differentiation and YK classification.
[Materials and Methods] Four human OSCC cell lines, B88, CAL27, HNt, and HSC3 cells were used in this study. Normal gingival epithelial cells served as control. Survivin expression of cultured cells was detected by western blot. Tissue specimens were obtains from 57 patients with OSCC after surgery or biopsy. Survivin expression was detected by an immunohistochemical method.
[Results] The expression of survivin was detected in cancer cells, but not in normal cells. Immunohistochemical analysis of 57 cases of OSCC showed that 50 (88%) cases expressed survivin. Moreover, analysis of 50 positive cases revealed 28 cases with survivin-positive staining both in the cytoplasm and the nucleus, and 22 cases with survivin expression in cytoplasm only. There was no relationship between survivin expression and clinical stages, or histological differentiation. There were significant differences between survivin expression of nucleus and YK classification, implicated invasion mode of cancer.
[Conclusions] These findings suggested that the expression of survivin in OSCC could be related to invasion mode.
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 201. doi:10.1158/1538-7445.AM2011-201
Abstract 2011: Epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A against non-small cell lung cancer cells
Authors: Kikuchi Junko , Kinoshita Ichiro , Kikuchi Eiki , Shimizu Yasushi , Sakakibara-Konishi Jun , Oizumi Satoshi , Nishimura Masaharu , Dosaka-Akita Hirotoshi 
Published: July 2012

Abstract
Background: The polycomb group gene, EZH2, mediates the histone methyltransferase activity, and functions as transcriptional repressor involved in gene silencing. It is involved in the malignant transformation and biological aggressiveness of several human cancers. We have previously shown that high EZH2 expression is correlated with tumor aggressiveness and is an independent unfavorable prognostic factor in non-small cell lung cancers (NSCLCs). However, the role of EZH2 in lung cancer cells has not been fully determined.
Methods: In the present study, we evaluated the effect of a histone methyltransferase EZH2 inhibitor, 3-Deazaneplanocin A (DZNep), in NSCLC cell lines.
Results: DZNep depleted cellular levels of EZH2 and SUZ12, and inhibited histone H3 lysine 27 trimethylation. DZNep inhibited proliferation of NSCLC cells dose- dependently through apoptosis and G1 cell cycle arrest which was partially associated with cyclin A decrease and p27Kip1 accumulation.
Conclusion: Epigenetic therapy with the histone methyltransferase EZH2 inhibitor DZNep may constitute a novel approach for NSCLCs.
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 2011. doi:10.1158/1538-7445.AM2011-2011
Abstract 2012: Changes in gene expression and global histone marks in a human population exposed to nickel compounds
Authors: Arita Adriana G. , Wu Fen , Sun Hong , Kiok Kathrin , Kluz Thomas , Qu Qingshan , Zhao Najuan , Ruan Ye , Niu Jingping , Hayes Richard , Costa Max 
Published: July 2012

Abstract
All of the studies on the global and selective gene promoter changes in epigenetic marks induced by carcinogenic Nickel compounds have been mostly done in tissue culture model systems. Here we report the results of the first study to evaluate the global changes in epigenetic marks and changes in gene expression that occur in the peripheral blood lymphocytes of a human population occupationally exposed to Nickel compounds. Nickel (II) is a toxic nonessential transition metal used in modern industry with other metals to form alloys to produce coins, jewelry, stainless steel, Ni-Cd batteries, and carbon nanoparticles. Nickel is of great environmental concern because occupational exposure to Ni compounds has been associated with an increased risk for lung and nasal cancers. Using an ELISA method, a decrease in both H3K4me3 and H3K9me2 histone marks were found with increasing levels of Nickel in the urine of subjects recruited to the study from a nickel refinery in Jinchang, China. Changes in global levels of other epigenetic marks are also being measured in the samples of subjects recruited to the study. Inter- and intra-individual variability of H3K4me3 and H3K9me2 and other epigenetic marks will also be evaluated in primary lymphocytes of this particular Chinese population. Additionally, changes in gene expression patterns between individuals with low exposure to Ni and those with higher exposure will be compared in order to identify a possible biomarker of Ni exposure. Studies on the effect of Ni compounds to human health are very important since Nickel is a classified human carcinogen. Here we are studying for the first time the mechanisms of nickel-associated changes in gene regulation and global histone epigenetic marks found in the primary lymphocytes of a human population occupationally exposed to Nickel compounds.
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 2012. doi:10.1158/1538-7445.AM2011-2012
Abstract 2014: Modulation of DNA methyltransferases in leukemia cells by curcumin and its associated anti-leukemia activities
Authors: Liu Zhongfa , Wang Hongyan , Wu Lai-chu , Xie Zhiliang , Du Liping , Mo Xiaokui , Chiu Ming , Perrotti Danilo , Grever Michael , Byrd John C. , Liu Shujun , Marcucci Guido , Chan Kenneth K. 
Published: July 2012

Abstract
Purpose: Curcumin, a natural product of curcuma longa and a safe and widely consumed spice, has been shown to exhibit strong in-vitro and in-vivo anti-tumor activity through the inhibition of NF-κB activity, increase of reactive oxygen species (ROS) levels and decrease of the global DNA methylation levels in leukemia cells. We investigated here the molecular mechanisms of down-regulation of DNA Methyltransferases in leukemia cells by curcumin and its associated anti-leukemia activities.
Method: Leukemia cell lines MV4-11, Kasumi-1 and K562 cells and primary leukemia cells from patient with AML were treated with 1-30 μM of curcumin and MV4-11 xenografted nu/nu athymic mice was given i.p. curcumin at 100 mg/kg, and the transcription and protein levels of DNMT1, DNMT3a, DNMT3b, Sp1, p15INK4B and p21 were assessed by either RT-PCR or western blot. The inhibition of NF-κB was determined using Electrophoretic Mobility Shift Assays and the disruption of Sp1-NF-κB/DNMTs promoter complex was investigated by anti-body gel supershifts. The hypomethylating activity of curcumin on the promoter of p15INK4B in MV4-11 cells in-vitro was assessed by a LC-MS/MS method for regional DNA methylation. The anti-proliferative activity of curcumin and cell cycle distribution and apoptosis were evaluated using MTS assay and flow cytometry.
Results: In addition to the pre-defined direct inhibition of the enzymatic activity of DNA methyltransferase 1 (DNMT1), curcumin disrupts Sp1/NF-κB complex on DNMT1, DNMT3a and DNMT3b promoter thereby decreasing the transactivation activity of these complexes and down-regulating their mRNA and protein expression levels in AML cells in vitro and in vivo. Consistent with these findings, we showed that promoter hypermethylation of silenced TSGs i.e., p15INK4B decreased while their expression was up-regulated. This results in the increase of protein function, as we showed that in association with p15INK4B re-expression, curcumin induced cell cycle arrest in the S-phase and increase in SubG1 cell fraction, thereby resulting in significant anti-leukemia activity.
Conclusion: Different from nucleoside analogs (e.g., azanucleosides), curcumin is an effective S-phase independent DNA methylation inhibitor. Further evaluation of curcumin as a single agent and in combination with other epigenetic targeting compounds in human disease is warranted. Supported by NIH-NCI-R21 CA135478 [ZL], NIH-NCI-RO1 CA102031 [GM], and the BioMedical Mass Spectrometry Laboratory [KC & ZL].
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 2014. doi:10.1158/1538-7445.AM2011-2014
Abstract 2017: Demethylation of HIC1 gene sensitizes thyroid cancer cells to TRAIL-induced apoptosis
Authors: Siraj Abdul K. , Al-Rasheed Maha , Husain Azhar , Bavi Prashant , Nuaim Abdul Rahman Al , Alsobhi Saif Al-Deen S. , Al-Dayel Fouad Al-Dayel Fouad , Uddin Shahab , Al-Kuraya Khawla S. 
Published: July 2012

Abstract
Gene silencing associated with aberrant methylation of promoter region CpG islands is an acquired epigenetic alteration. It serves as an alternative to genetic defects in the inactivation of tumor suppressor and other genes in human cancers. Several genes have been shown to be epigenetically inactivated in a wide range of tumors and most neoplasms show hypermethylation of one or more genes. Concurrent methylation status of the CpG islands of 24 genes were determined in 40 PTC cases and in a panel of PTC cell lines, using methylation specific PCR. Seven genes demonstrated a relatively high frequency of aberrant methylation: RASF1 (95%), HIC1 (55%), GSTP1 (26%), P14 (25%), TMS1 (24%), DCR1 (17%) and SERF (15%). Five genes (BRACA1, P15INK4B, MGMT, BLU and APC) showed a low frequency (2-6%) of methylation, and no methylation was detected for the remaining twelve genes (P16INK4A, APAF1, FANCF, FAS, MINT25, P73, MLH1, DAPK, RARB, CASP8, E-Cadherin and SOC1.
Statistical analysis demonstrated that frequency of methylated and unmethylated HIC1 was significant (p &lt;0.05). Further clinical analysis demonstrated significant association of only HIC1 methylation with: age of patients, stage of disease and expression of HIC1 IHC data (p = &lt;0.0001, &lt;0.0173 and &lt; 0.0448; respectively). HIC1 has been shown to be hypermethylated in different cancers and confers bad prognosis. HIC1 is a tumor suppressor gene which encodes a transcriptional repressor with five Kruppel-like Cys2-His2 zinc fingers in the C terminus and a protein-protein interaction domain called the BTB/POZ domain at the N terminus.
Analysis of BCPAP-1 and TPC1 (papillary thyroid cell lines) revealed that they are completely methylated for HIC1 gene. Treatment of methylated thyroid cell line with the methyltransferase inhibitor, 5-aza-2’deoxy-cytidine, resulted in partial demethylation and re-expression of HIC1 gene, suggesting the role of methylation in silencing of the gene. We further evaluated the role of HIC1 gene after demethylation for apoptosis. After demethylation of HIC1 gene with 5-aza-2’deoxy-cytidine we treated our PTC cell lines with increasing doses of TRAIL and evaluated its response by Annexin/PI dual staining. We found that after demethylation of HIC1 there was increase in percentage apoptosis following increasing doses of TRAIL suggesting that HIC1 gene plays a major role in inducing apoptosis in PTC.
In conclusion, HIC1 methylation may be a promising molecular marker to predict patient outcome in PTC, and may be used as therapeutic demethylating target.
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 2017. doi:10.1158/1538-7445.AM2011-2017
Abstract 2019: An epigenetic reactivation screen identifies pathways important in pleomorphic liposarcomas
Authors: Pascarelli Kara , Plantinga Matthew , Doyle Katherine , Roberts Chad , Zhou Yan , von Mehren Margaret , Lev Dina , Broccoli Dominique 
Published: July 2012

Abstract
Treatment of soft tissue sarcomas with chemotherapy has met with limited success as few agents have demonstrated clinical efficacy, with standard therapies having a 25-30% response rate in large multi-institutional trials with current standard therapy of doxorubicin and ifosfamide. Pleomorphic liposarcomas have complex karyotypes, hindering identification of characteristic genome changes amenable to targeted treatment. Aberrant epigenetic silencing of genes is observed in cancers and is an established mechanism to abrogate tumor suppressor pathways. To gain insight into the biology of pleomorphic liposarcomas, we carried out an epigenetic reactivation screen to identify genes silenced by methylation of CpG dinucleotides. Three cell lines derived from pleomorphic liposarcomas were treated with 5-aza-2-deoxycytidine for 2 cell doublings prior to extraction of RNA. Total RNA from duplicate cultures of treated and untreated cells was hybridized to the Affymetrix U133plus2 expression chip. Initial filtering for only those genes affected in all three cell lines identified 201 genes with altered expression, 59 of which are down regulated and 142 of which are up regulated. We validated candidate genes by sequencing sodium bisulfite modified genomic DNA isolated from the three cell lines used in the reactivation screen. We chose candidates reported as being affected by promoter hypermethylation in other systems, stratifin (SFN); aka 14-3-3-σ, clusterin (CLU) and e-cadherin (CDH1). The data confirm that all candidates exhibit methylation of CpG islands located within 400 bp of the 5’ start site. To further validate candidates we tested the methylation status of SFN, CLU, and CDH1 in DNA isolated from12 pleomorphic liposarcomas, as well as DNA isolated from adipocytes, preadipocytes and adult adipose derived stem cells. Gene interaction networks were generated through the use of Ingenuity Pathway Analysis (Ingenuity® Systems, www.ingenuity.com). Conditional hypergeometric tests were done for testing the association of Gene Ontology using GOstats package in Bioconductor. Top scoring networks identified in this analysis included cancer, lipid metabolism, and cell cycle/death. In conclusion, the pathways identified here may form the basis for future development of targeted therapy against pleomorphic liposarcomas.
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 2019. doi:10.1158/1538-7445.AM2011-2019
Abstract 2021: Mechanism of the coordinate regulation of liver cancer by nuclear receptor CAR and beta catenin
Authors: Dong Bingning , Moore David 
Published: July 2012

Abstract
Aberrant activation of β-catenin is a critical contributor to many different cancers, including up to 34% of human hepatocellular carcinogenesis. Liver-specific activation of β-catenin is not sufficient to drive tumorigenesis in mice. However, nearly all of the tumors produced in the widely used diethylnitrosamine (DEN; carcinogen) plus phenobarbital (PB; promoter) mouse liver cancer model have activating mutations in β-catenin. The nuclear receptor CAR, a primary regulator of drug metabolism and detoxification, is the target of PB in the DEN-PB model, suggesting a synergistic functional interaction of these two transcription factors. Thus, we hypothesize that β-catenin and CAR synergistically induce liver tumorigenesis. We induced CAR and full β-catenin activation by TC treatment (CAR agonist) of liver specific-Cre/catnb lox/lox(ex3) mice (homozygous β-catenin activation by knockout of phosphorylation sites in exon3). Consistent with previous studies, activation of either CAR or β-catenin only induces mild hepatomegaly but not tumorigenesis in one month. However, the combined activation of both CAR and β-catenin causes uncontrolled liver growth (up to 25% liver/body weight ratio). Ki67 staining reveals significant hepatocyte proliferation in the double activation group, but not in any of the single activation groups. This indicates that CAR and β-catenin coordinately regulates liver growth. Uncontrolled liver growth leads to mouse death, which prevents us studying tumorigenesis. Accordingly, we also treated liver specific-Cre/catnb wt/lox(ex3) mice (heterozygous β-catenin activation) with TC. After 8 month, HCC were observed in 13 out of 15 experimental treated mice whereas no tumor was observed in the control mice (either TC treated catnb wt/lox(ex3) mice or CRE treated catnb wt/lox(ex3) mice, suggesting a cooperative and synergistic role of CAR and β-catenin in HCC formation. Bioinformatic gene array analysis shows that tumors generated in our mouse model share similar expression signature with human HCC carrying β-catenin mutation. Thus, the study on the mechanism of our mouse model will provide new therapeutic approaches in liver cancer and its prevention.
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 2021. doi:10.1158/1538-7445.AM2011-2021
Abstract 2023: Isolation of breast tumor initiating cells (TICs) by exogenous delivery of the OCT4 transcription factor
Authors: Beltran Adriana S. , Richarson Bryan , Rivenbark Ashley , Casbas-Hernandez Patricia , Yang Xinni , Blancafort Pilar 
Published: July 2012

Abstract
Tumor Initiating cells (TICs) are being extensively studied for their role in tumor etiology, maintenance and resistance to treatment. Herein, we describe a novel approach to generate TICs by transduction of human primary breast cell preparations with exogenous expression of the OCT4 transcription factor. The OCT4 transduced breast colonies (OTBCs) underwent an immortalization process, as reflected by loss of p16 and enhanced telomerase expression. OTBCs exhibited cancer stem cell antigens, such as CD44high/CD24low/-. Consistently, these cells generated subcutaneous tumors in nude mice with colonization capabilities. As little as 1-50 cells were sufficient to induce tumor formation and thereby these cells had TIC properties. Histological analysis of these tumors revealed poorly differentiated breast carcinomas. RNAi-mediated knock-down of OCT4 and downstream embryonic targets of OCT4, resulted in suppression of the self-renewal ability, suggesting that this phenotype was dependent on OCT4. Genome-wide microarray analysis supported the finding that OCT4 over-expression in these clones was molecularly associated with Epithelial-to-Mesenchymal Transition (EMT) gene signatures and strongly correlated with the claudin-low intrinsic subtype of breast cancer. Our experimental approach provides a novel model system to dissect genes, small RNAs and small molecules that could be used to effectively target breast cancer self-renewal and tumor initiation.
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 2023. doi:10.1158/1538-7445.AM2011-2023
Abstract 2027: CBX7 protein, whose expression is decreased in human carcinomas, positively regulates E-cadherin expression by interacting with the HDAC2 protein
Authors: Federico Antonella , Pallante Pierlorenzo , Bianco Mimma , Monti Maria , Cozzolino Marianna , Leone Vincenza , Pucci Pietro 
Published: July 2012

Abstract
CBX7 is a chromobox family protein encoding a novel Polycomb protein whose expression shows a progressive reduction, well related with the malignant grade of the thyroid neoplasias. Indeed, CBX7 protein levels decreased in an increasing percentage of cases going from benign adenomas to papillary, follicular and anaplastic thyroid carcinomas. To elucidate the function of CBX7 in carcinogenesis, we searched for CBX7 interacting proteins by a proteomic analysis. By this approach, we identified several proteins among which we selected Histone deacetylase 2 that is well known to play a key role in neoplastic cell transformation and to downregulate E-cadherin expression, whose loss is a critical event in the Epithelial-Mesenchymal Transition (EMT). We confirmed by co-immunoprecipitation that CBX7 physically interacts with the Histone deacetylase 2 protein and is able to inhibit its activity. Then, we showed that both these proteins bind the E-cadherin promoter, and that CBX7 is able to upregulate E-cadherin expression. Consistent with these data we found a positive statistical correlation between CBX7 and E-cadherin expression in human thyroid carcinomas. Finally, we demonstrated that the expression of CBX7 increases the acetylation status of the histones H3 and H4 on the E-cadherin promoter. Therefore, the ability of CBX7 to positively regulate E-cadherin expression by interacting with Histone deacetylase 2 and inhibiting its activity on the E-cadherin promoter would account for the correlation between the loss of CBX7 expression and a highly malignant phenotype in thyroid cancer patients.
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 2027. doi:10.1158/1538-7445.AM2011-2027