bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4914: Methylation profiling of CpG islands in multiple drug resistant cell line
Authors: Hung Tsai-Hsien , Shen Chih-Jie , Chen Chuan-Mu , Chong Kowit Yu 
Published: February 2011

Abstract
Multiple drug resistance (MDR) is a major issue to attenuate the effectiveness of chemotherapy to many human malignancies. Despite extensively investigation, MDR inhibitors have been discovered serve side effect. Recently, scientists have reported that proteasome inhibitor, Bertezomib (PS-341), induced apoptosis in a variety of cancer cells and recognized as a novel anticancer therapy approach. Previous study revealed that bertezomib inhibits DNA methyltransferase and led to DNA hypomethylation in myeloid leukemia. Despite its success, some patients are resistant to ongoing proteasome inhibitor treatment. These reports suggested that chemoresistant cell line may develop a novel mechanism to against proteasome inhibitor. To verify the hypothesis, we used human CpG island microarray to indentify epigenetic change and genes expression profile in parental human uterus sarcoma cell line (MES-SA) and MES-SA variant drug resistant cell line (Dx5-C5) Our data has shown that the global genes were hypomethylated in both PS-341 treated MES-SA and Dx5-C5 cell line. Furthermore, the Wnt signalling pathway and cell cycle related gene have significant altered in DNA methylation pattern of Dx5-C5. In summary, our study demonstrated that the cell cycle related gene(s) and upstream gene(s) of Wnt pathway altered its DNA methylation pattern and mRNA expression level in MDR cell line. These data may help us to develop a new strategy for treatment of multiple drug resistance cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4914.
Abstract 4918: Quality assessment of DNA derived from up to 30 year old archival tissues from lung cancer patients for PCR-based methylation analysis using SMART-MSP and MS-HRM
Authors: Kristensen Lasse S. , Wojdacz Tomasz K. , Thestrup Britta B. , Hager Henrik , Hansen Lise Lotte 
Published: February 2011

Abstract
Background: The High-Resolution Melting (HRM) technology has recently been introduced as a rapid and robust analysis tool for the detection of DNA methylation. The methylation status of multiple tumor suppressor genes may serve as biomarkers for early cancer diagnostics, for prediction of prognosis and for prediction of response to treatment. Therefore, it is important that methodologies for detection of DNA methylation continue to evolve. Sensitive Melting Analysis after Real Time - Methylation Specific PCR (SMART-MSP) and Methylation Sensitive - High Resolution Melting (MS-HRM) are two methods for single locus DNA methylation detection based on HRM.
Methods: Here, we have assessed the quality of DNA extracted from 30-years-old Formalin Fixed Paraffin Embedded (FFPE) tissue for DNA methylation analysis using SMART-MSP and MS-HRM. The quality assessment was performed on DNA extracted from 54 Non-Small Cell Lung Cancer (NSCLC) samples derived from FFPE tissue, collected over 30 years and grouped into five-years-intervals. For each sample, the methylation level of the CDKN2A (p16) and RARB promoters were estimated using SMART-MSP and MS-HRM assays designed to assess the methylation status of the same CpG positions. This allowed for a direct comparison of the methylation level estimated by the two methods for each sample.
Results: The methylation level of the CDKN2A promoter was successfully determined by SMART-MSP and MS-HRM in all of the 54 samples. The same methylation estimates were obtained by the two methods in 46 of samples. The methylation level of the RARB promoter was successfully determined by SMART-MSP in all of samples. When using MS-HRM to assess RARB methylation five samples failed to amplify and 15 samples showed a melting profile characteristic for heterogeneous methylation. Out of the remainder 34 samples, for which the methylation level could be estimated, 27 gave the same result as observed when using SMART-MSP.
Conclusion: MS-HRM and SMART-MSP can be successfully used for single locus methylation studies of DNA derived from up to 30-years-old FFPE tissue samples. Furthermore, it can be expected that MS-HRM and SMART-MSP will provide similar methylation estimates when assays are designed to analyze the same CpG positions.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4918.
Abstract 4925: Promoter methylation of RASSF1A Tumor Suppressor Gene Modulates the Effect of Microtubule-Targeting Agent, docetaxl, in Breast Cancer
Authors: Eun-Young Gil , Jo Uk Hyun , Jung Hae Yun , Woo Ok Hee , Seo Jae Hong , Kim Aeree , Lee Eun-Sook , Cho Kyu-Ran , Kim Yeul Hong , Kim Jun Suk , Kim In Sun , Park Kyong Hwa 
Published: February 2011

Abstract
RASSF1A has been previously demonstrated to be inactivated by CpG island methylation in breast cancer cell lines and primary tumor tissues. There have been evidences suggesting that methylation of this gene have a significant impact on biological characteristics of breast tumors and have a relationship with prognosis in breast cancer. The tumor suppressive effect of RASSF1A has been reported to be mediated by its 2 important roles in other cells; induction of cell cycle arrest and apoptosis. Therefore, it is possible that expression status of RASSF1A by promoter methylation may alter patient's sensitivity to chemotherapeutic agents affecting cell cycle. However, there is few data regarding the relationship between the methylation status of RASSF1A gene and clinical response to chemotherapeutic agents in breast cancer patients. In this current study, we show that RASSF1A gene expression was suppressed in the human breast cancer cell lines (MCF-7, MDA-MB-231, and ZR75-1) by the mechanism of promoter methylation using methylation -specific PCR. It was confirmed by the results that treatment with the DNA demethylating agent, 5-aza-2′-deoxycytidine, reactivated the expression of RASSF1A at the level of mRNA and protein. Re-expression of RASSF1A gene in breast cancer cell lines could decrease the cell growth and proliferation by both decreasing cyclin D1 expression and inducing cyclin A and B1 accumulation, then resulting in cell cycle arrest at G2/M phase. In addition, re-introduction of RASSF1A further increased docetaxel-induced cell death in breast cancer cells. We next questioned whether the methylation status of RASSF1A gene is associated with clinical response to taxane-based chemotherapy in breast cancer patients. Fresh frozen primary breast cancer tissues were ananlyzed for methylation status of RASSF1A gene using MS-PCR. Thirty three out of 39 patients (84.6%) showed RASSF1A methylation and 6 had un-methylated gene. Patients who had unmethylated or partially methylated RASSF1A gene showed some mRNA in RT-PCR analysis. And, the clinical response to taxane-based chemotherapy was significantly better in the un-, or partially-methylated patient group (100% vs 62.5%). These results suggest that hypermethylation of the CpG island promoter of RASSF1A may play an important role in breast cancer pathogenesis and is a modulating factor for docetaxel activity in breast cancer patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4925.
Abstract 4928: 14-3-3ζ-mediated hypomethylation of c-myc oncogene by downregulation of Dnmts contributes to initiation and progression of breast cancer
Authors: Xu Jia , Yu Dihua 
Published: February 2011

Abstract
The development of breast cancer is a multistep process and the molecular mechanisms underlying this process are still elusive. Previously, we discovered that 14-3-3ζ overexpression not only contribute to breast cancer progression but also play an important role in breast cancer initiation, including an early stage of breast disease-atypical ductal hyperplasia (ADH). However, the underlying mechanisms remain unclear. Recently, 14-3-3ζ has been shown to bind to Histone H3, Methylation Binding Proteins (MBPs) and HDAC family members, suggesting 14-3-3ζ may play a role in epigenetic regulation. As an initial effort to investigate whether 14-3-3ζ has a role in epigenetic regulation and whether epigenetic regulation by 14-3-3ζ plays a role in breast cancer initiation, we established 14-3-3ζ stable overexpressing lines (10A.14-3-3ζ) in non-tumorigenic MCF10A human mammary epithelial cells (HMEC) and analyzed molecular alterations by cDNA microarray in the 10A.14-3-3ζ cells versus the 10A.vec control cells in a 3D culture system. Interestingly, we found that c-myc, a well known oncogene which is overexpressed in many types of cancer, was upregulated at the mRNA level in the 10A.14-3-3ζ cells versus the 10A.vec cells. We further confirmed c-Myc upregulation at both mRNA level by RT-PCR and protein level by Western Blotting. Additionally, we performed Reverse Phase Protein Array (RPPA) analysis with a series of validated antibodies, and we found that Dnmt1, the key DNA methyltransferase in mammals, was downregulated in 10A.14-3-3ζ cells compared to 10A.vec cells. We have confirmed Dnmt1 downregulation by western blotting. Since c-myc oncogene are well known to be upregulated by hypomethylation as a consequence of Dnmt1 downregulation, these data suggest that 14-3-3ζ may contribute to breast cancer initiation and progression by upregulation of oncogene c-myc via promoter hypomethylation. We will continue this study to provide a better understanding on how 14-3-3ζ contributes to breast cancer initiation and progression via epigenetic deregulation (demethylation) of c-myc.
This study will bring insight into how 14-3-3ζ overexpression elicits the phenotypic changes during the development of breast carcinomas through global deregulation of transcriptome as well as specific gene expressions. Our studies could provide a better understanding of the role of 14-3-3ζ in breast cancer initiation and progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4928.
Abstract 4933: Expression of the N-myc downstream-regulated gene 2 (NDRG2) is frequently suppressed by promoter hypermethylation in human gastrointestinal and pancreatic cancers
Authors: Yamamura Akihiro , Miura Koh , Karasawa Hideaki , Abe Keiko , Mizuguchi Yasuhiko , Jin Guo , Gu Zhaodi , Fukushige Shinichi , Kaneko Naoyuki , Kinouchi Makoto , Ando Toshinori , Yazaki Nobuki , Tanaka Naoki , Sase Tomohiko , Shibata Chikashi , Sasaki Iwao , Horii Akira 
Published: February 2011

Abstract
It is well known that inactivation of tumor suppressor gene (TSG) by promoter hypermethylation plays an important role during the development and progression of cancer. NDRG2 (N-myc downstream regulated gene 2) is considered to be one of the candidate TSGs. Significant down-regulation in various human cancers were observed, but the molecular mechanisms of reduced expression and the ways to carcinogenesis are largely not well understood. To elucidate the mechanisms in expressional suppression of NDRG2, we studied the methylation status of the putative promoter region in this gene. NDRG2 has two promoters; we first found that the mRNA transcription predominantly starts from the promoter containing exon 1b in organs of the digestive system. Then the expression level of NDRG2 was analyzed by quantitative real-time RT-PCR using 20 colorectal, 6 gastric, and 5 pancreatic cancer cell lines; many cell lines showed reduced expression. Bisulfite modification followed by nucleotide sequencing analyses in the putative promoter region revealed that the methylation status correlated with the suppressed expression. We extended our analysis to the primary tumors by immunohistochemical examination to elucidate clinical significance of suppressed expression of NDRG2 in tumorigenesis; matched normal and cancerous tissues from cancer patients with digestive system were analyzed and observed suppressed expression of NDRG2 in 19 of 20 colorectal, 8 of 10 gastric, and 85 of 86 pancreatic cancer specimens. We then designed a set of primer pairs for methylation specific PCR and examined the relationship between expression level of NDRG2 and promoter hypermethylation in resected primary tumor specimens. Association between methylation status and clinicopathologic features are now studied and the newly obtained results will be presented.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4933.
Abstract 4935: Hyperemethylation of retinoid X receptors genes in non-small cell lung cancers and its clinical implication
Authors: Lee Su M. , Kim Mi J. , Lee Ji Y. , Park Jae Y. , Kim Dong S. 
Published: February 2011

Abstract
Retinoid X receptors (RXRs) are nuclear receptors for retinoids that play a critical role in the regulation of growth and differentiation in normal and tumor cells. Deregulation of RXR expression has been reported in non-small cell lung cancer (NSCLC); however, the mechanism underlying the impaired expression of RXRs in lung cancer is not known. Aberrant methylation of promoter CpG islands is known to be a major mechanism for inactivation of tumor suppressor genes. We investigated the methylation status of the RXR genes in 139 surgically-resected NSCLCs and correlated the results with the clinicopathologic characteristics of the patients. Methylation in the tumors was detected at RXRα (5.7%), RXRβ (4.3%), and RXRγ (23.7%). RT-PCR analysis showed that RXRγ methylation correlates with mRNA expression. Methylation of the RXRγ gene was not significantly associated with the prognosis of patients; however, when the patients are categorized by smoking status, the effect of RXRγ methylation on prognosis was significantly different between never- and ever-smokers (P = 0.003 [test for homogeneity]); specifically, RXRγ methylation was associated with a significantly worse survival in never-smokers, whereas it exhibited a better survival outcome in ever-smokers, although not statistically significant. This finding suggests that methylation-associated down-regulation of the RXRγ gene may play a differential role in the carcinogenesis of NSCLCs according to smoking status, but further studies are needed to confirm this.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4935.
Abstract 4948: Silencing of Hint1, a novel tumor suppressor gene, by promoter hypermethylation in human breast cancer
Authors: Zhang Yu-jing , Li Haiyang , Joe Andrew K. , Hibshoosh Hanina H. , Weinstein Bernard , Santella Regina M. 
Published: February 2011

Abstract
The HINT1 protein, a member of the histidine triad (HIT) family, is highly conserved in diverse species and ubiquitously expressed in mammalian tissues. Hint1 has been proven a haploinsufficient suppressor gene. In previous studies, it was demonstrated that promoter hypermethylation of Hint1 may play a role in the development of colon cancer and hepatocellular carcinoma (HCC). In the present study, we investigated the aberrant methylation of the Hint1 promoter and explored possible relationships between aberrant methylation and clinicopathological features and other parameters in breast cancer. Hypermethylation of Hint1 was evaluated by methylation specific PCR (MSP) in 81 breast cancer samples, of which 17 cases (21%) displayed Hint1 promoter hypermethylation. A statistically significant inverse correlation was found between Hint1 promoter hypermethylation and p27Cip1/Kip1 expression. This is consistent with our previous finding that HINT1 up-regulates cellular levels of p27Cip1/Kip1. No significant correlation was found between the Hint1 promoter methylation status and the expression of p53, p21, estrogen receptor (ER), progesterone receptor (PR) and HER2/neu. Taken together, these results suggest that promoter hypermethylation of Hint1 may contribute to carcinogenesis of breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4948.
Abstract 495: Inhibition of the prolyl isomerase Pin1 reduces CD133 and Sox2 expression and enhances radiosensitivity in glioblastoma cells
Authors: Chen Edmund I. T. , Huang Yu-Wen , Lai Li-Chuan 
Published: February 2011

Abstract
Pin1, a prolyl isomerase, specifically recognizes the phosphorylated Ser/Thr-Pro motifs and induces cis/trans isomerization of its target proteins. Such conformational changes have profound effects on the function of Pin1 substrates. Pin1 has been shown to be overexpressed in many human cancers, and Pin1 over-expression is often associated with up-regulation of cyclin D1 and β-catenin. Here we report that, in cell culture studies, enhanced Pin expression occurs in radiation-resistant glioblastoma cells (GBM-R) or CD133-expressing glioblastma cells (S1) compared with controls. Ectopic expression of Pin1 but not mutated Pin1(K63A) increased the viability of GBM cells to IR.CD133-expressing glioma cells are known to play a key role in tumor recovery after treatment and are resistance to radiotherapy. Here we showed that Pin1 knock-down in GBM-R or GBM-CD133 (+) cells enhanced their sensitivities to radiation or anti-GBM drug TMZ. Moreover, Pin1 knockdown increased apoptopic population in GBM-CD133 (+) cells. It appeared that Pin1 knockdown reduced the ability of S1 cells to repair double-stranded breaks. Interestingly, Pin1 knockdown decreases the expression of stemness genes including CD133, Sox-2, Bmi1 and c-Myc etc., and silencing of Pin1 can interfere with sphere formation in S1 cells. Our results suggest that Pin1 is an important regulator of the resistance of GBM-R or GBM-CD133 (+) to radiotherapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 495.
Abstract 496: Enhance efficacy of photodynamic therapy in combination with selenium in TC-1 animal model
Authors: Oh Eun Kyung , Wen Lanying , Bae Sumi , Lee Sung Ha , Cho Young Lae , Ahn Woong Shick 
Published: February 2011

Abstract
Photodynamic therapy (PDT) is a promising cancer treatment modality that involves the interaction of the photosensitizer, molecular oxygen and light of specific wavelength to destroy tumor cells. To improve efficacy of PDT, the efforts are underway to develop combination protocols. Selenium is an essential trace element and has anticarcinogenic properties on a various human cancer model. The aim of this study was to investigate the synergetic anti-tumor effects of PDT plus selenium in vitro and in vivo.
To compare the anti-proliferative effects by PDT, Selenium, or PDT plus selenium, MTT assay, microscopic observation and FACS analysis were performed. Apoptosis signaling pathways were analyzed using mouse signal transduction pathwayRT profiler PCR array (Superarray). For the vivo study, when tumor size was approximately 8 to 10 mm, Radachlorin (10mg/kg b.w.) was injected in to the tail vein at 3 hrs before irradiation with 100 J/cm2 of light and then selenium (1ug/kg b.w) was administrated daily during 20 days.
Our results demonstrate that combination of selenium with PDT strongly inhibits growth of TC-1 cell and tumor in TC-1 cell implanted mice when compared to the other groups. Moreover, PDT and selenium treatment in TC-1 cells had apoptosis features in microscope and FACS analysis. Increased apoptosis was associated with tumor inhibition in the combination therapy group. In signal transduction pathway Superarray, genes closely relate to NFkB, p53, and phopholipase C pathway such as vcam1, mdm2, and fos were very significantly down-regulated at least 10 fold in TC-1 cell following co-treatment of PDT and selenium. Furthermore, anti-apoptosis related genes and tumor-promoting genes, birc2, birc3, hk2, ccl2, ptgs2, wisp1, mmp10 and wisp1 were also significantly down-regulated. Up-regulated genes by co-treatment of PDT and selenium had relatively low ranges of fold change than fold range of down-regulated genes and were related with cell survival and proliferation mechanism.
These data indicate that combination therapy of selenium and PDT could more effectively induce tumor suppression response compared to PDT or Selenium alone. We suggest that combination therapy using PDT and selenium can be a useful to for inducing synergistic anticancer effect.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 496.