bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4915: Global epigenomic modification platform
Authors: Lin Yi-Shiuan , Leu Yu-Wei , Hou Pei-Chi Peggy , Teng I-Wen , Wang Shi-Gang , Shaw Yeng-Jeng , Lee Kuan-Der , Hsu Chia-Chen , Hung Joyce Yu-Hung , Lin Shih-Cheih , Sun H. Sunny , Chang Yu-Sun , Huang Tim H.-M. , Tsai Shaw-Jenq , Hsiao Shu-Huei 
Published: February 2011

Abstract
DNA methylation is an epigenetic mechanism that governs gene silencing and this silencing could be reversed. Pre-deposited global DNA methylation during differentiation is associated with cell fate determination and abnormal DNA methylation could lead to tumorigenesis. A global DNA methylation manipulation system is thus hypothesized to control the differentiation and tumorigenesis more efficiently. Two platforms were established to loss or gain of DNA methylation genome-wide. For the loss of DNA methylation, an in vivo methylation monitoring system was employed to screen 169 procainamide derivatives and identified three distinct classes of these compounds based on their cytotoxicity and demethylation potency. For the gain of DNA methylation, a global DNA methylation subtraction method was developed to identify and methylate target loci genome-wide. After targeted methylation globally, the drug resistance of cancer cells was reverted to become drug sensitive. The same method was used to identify and methylate the hypomethylated loci within somatic stem cells when compared with the differentiated neuronal cells. The targeted methylation accelerated the differentiation of the somatic stem cell to become neuron-like. With both platforms, we wish to evaluate if global DNA methylation changes is sufficient to steer the cell fate. (Supported in part by NSC 97-2320-B-194-003-MY3, NSC 98-3112-B-194-001 and NSC 97-2627-B-006-003)
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 4915.
Abstract 4921: Selective promoter methylation of the cell differentiation marker, intestinal alkaline phosphatase (iALP), in microsatellite unstable colon cancer
Authors: Shin Joongho , Azarbayejani Azadeh , Lai Victoria , Ahmed Naseem , Hodin Richard , Malo Madhu , Arango Diego , Weber Thomas , Mariadason John M. 
Published: February 2011

Abstract
Tumorigenesis is characterized by excessive cell growth, resistance to apoptosis and aberrant cellular differentiation. In particular, MSI colorectal cancer is frequently characterized by poorly differentiated histology. Histone Deacetylase inhibitors (HDACi) are a novel class of cancer therapeutics that induce growth arrest, apoptosis and differentiation of a variety of tumour types, including colon cancer cells. Differentiation inducing agents have been used effectively to treat hematopoietic malignancies, prompting us to examine the effects of HDACi treatment on differentiation of colon cancer cells, and to compare the effects induced in MSS and MSI colon cancers. Remarkably, while HDACi treatment robustly and consistently induced differentiation induction as measured by alkaline phosphatise activity and iALP gene expression in multiple MSS colon cancer cell lines, approximately 70% of MSI colon cancer cell lines were highly resistant to HDACi-induced ALP induction. Examination of the coding sequence of the iALP gene failed to identify any significant repeat elements suggesting mutation is unlikely to be responsible for lack of iALP induction. Furthermore, transient transfection of an iALP promoter reporter construct demonstrated robust induction in response to butyrate treatment in both MSS and MSI lines, suggesting loss of a key regulatory factor in MSI cell lines is not likely to be responsible. Conversely, examination of iALP promoter methylation by bisulphite conversion and direct sequencing demonstrated multiple CpG sites, including a Sp1/Sp3 binding site, to be methylated in 4 of 5 MSI lines examined, while no methylation was observed in MSS lines. These findings were confirmed using the sequenom assay. ALP promoter methylation was independent of CIMP status. The importance of Sp1/Sp3 in butyrate-induced iALP induction was demonstrated by the ability of the Sp1/Sp3 inhibitor, mithramycin, to attenuate butyrate-induced ALP activity. Finally, consistent with methylation being a key determinant of iALP expression in MSI lines, azacytidine treatment was able to re-induce iALP expression, and butyrate-induction of ALP expression was markedly enhanced in isogenic HCT116 cells lacking the DNA methyltransferases Dnmt1 and Dnmt3b (DKO), compared to parental cells. These findings demonstrate selective promoter methylation of iALP in MSI colon cancer cell lines.
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 4921.
Abstract 4929: Hypermethylation of tumor suppressor gene promoters in basal cell carcinoma
Authors: Brinkhuizen Tjinta , van Engeland Manon , van Marion Ariënne , van Steensel Maurice 
Published: February 2011

Abstract
Background
Basal-cell carcinoma (BCC) is the most frequent malignancy in Caucasians, with increasing incidence. Overactivity of the Sonic Hedgehog pathway is implicated in BCC etiology, however recent literature suggests that BCC carcinogenesis may be more complex.
Silencing of tumor suppressor genes by promoter hypermethylation, influenced by hypoxia, results in deregulation of cancer-related pathways. Since BCC arises in a hypoxic micro-environment, we assumed that epigenetic modifications may play a major part in BCC tumorigenesis. In this pilot we investigated promoter hypermethylation of tumor suppressor genes selected for their possible involvement in BCC. Eventually, knowledge of epigenetic modifications in BCC may impact diagnosis, classification, and treatment.
Methods
DNA was isolated from 33 formalin fixed paraffin-embedded BCC of 3 different histological subtypes. Marked tumor tissue was macroscopically scraped from slides and collected. CpG island methylation status of 10 promoter regions was analysed by methylation-specific PCR on sodium bisulfite-treated DNA. Data were compared with 36 normal skin tissue samples. All data were analysed with SPSS version 17.0. We used the Pearson Chi-Square test. Statistical significance was defined as a p-value ≤0.05.
Results
DNA methylation levels of the examined candidate gene promoters in tumor tissue compared to normal skin tissue were significantly higher for the following genes: APC 100% vs. 47,1% (p&lt;0,001); sFRP5 93,9% vs. 42,4% (p&lt;0,001); SHH 90,9% vs. 50,0% (p&lt; 0,001) and 81,8% vs. 56,3% (p= 0,029) for CylD. In addition, the PTCH1 promoter showed a tendency to hypermethylation. The remaining promoters of sFRP1, sFRP2, sFRP4, TSC1 and RASSF1A showed no hypermethylation.
Conclusions
From our preliminary data we conclude that in BCC, promoters of several tumor suppressor genes, which may normally inhibit BCC growth, show aberrant methylation resulting in silencing of these genes. As a consequence, signalling pathways implicated in cancerous growth such as the SHH-, WNT- and NFκB- routes may be affected. Our data provide evidence that epigenetic modifications may play a role in BCC tumorigenesis. Genome-wide analyses will be our next step to screen for more relevant genes and to chart the full extent of genomic methylation changes in BCC. This entirely new approach may lead to new insights into development and treatment of BCC.
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 4929.
Abstract 4931: Methylation of the hTERT promoter: a potential cancer biomarker for leptomeningeal metastasis detection in cerebrospinal fluids
Authors: Benhattar Jean , Bougel Stéphanie , Gallagher Gabrielle , de Flaugergues Jeanne-Chantal , Janzer Robert 
Published: February 2011

Abstract
Background: The diagnosis of leptomeningeal metastases is usually based on the finding of malignant cells by cytological examination in the cerebrospinal fluid (CSF). However, cytology is only moderately sensitive, and sensitive and specific cancer biomarkers may improve the detection of tumor cells in the CSF. Expression of telomerase hTERT subunit might be such a marker but its use is hampered by proliferating normal lymphocyte cells. hTERT methylation, characterizing most cancer cells, might be an alternative as proliferating lymphocytes have unmethylated hTERT promoter. The aim of this study was to develop a specific, sensitive, quantitative, and fast method for detection of hTERT methylation and to explore its use as a cancer biomarker in the diagnosis of metastatic tumors in CSF.
Materials and methods: hTERT methylation levels were assayed by several quantitative techniques including methylation-sensitive dot blot assay (MS-DBA), methylation-sensitive high resolution melting (MS-HRM), and a newly developed real-time MS-HRM assay. We used MS-HRM assays for the analysis of 59 CSF specimens from 50 patients including 31 CSFs from 23 patients with a known malignancy suspected for leptomeningeal metastasis.
Results: MS-HRM assays both allowed hTERT methylation quantification in CSF samples. The MS-HRM detected samples containing more than 10% of hTERT methylated alleles whereas real-time MS-HRM detected methylation below 10%. PCR products were obtained from 54 CSF samples (92%). hTERT methylation was only detected in the CSF from patients with a known malignancy.
Conclusion: The real-time MS-HRM analysis is a fast, sensitive, and specific technique for methylation assessment in many diagnostic and research applications. As an adjunct to the traditional examination of CSF, the hTERT MS-HRM approach could be perform as routine diagnosis of leptomeningeal metastases and could become a valuable tool for further management and planning of treatment.
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 4931.
Abstract 4932: Genistein Can Induce Demethylation Of Wnt Negative Regulatory Genes In Prostate Cancer Cells
Authors: Phillip Cornel J. , Moreno Carlos S. 
Published: February 2011

Abstract
Among American men, prostate cancer is a prevalent malignancy that accounts for an estimated 192,280 new cases and 27,360 deaths in 2009. Previous work has determined that the adenomatous polyposis coli (APC) gene that negatively regulates the Wnt pathway is hypermethylated in a high proportion of prostate cancers. We hypothesized that methylation of additional Wnt negative regulatory genes may also play a role in prostate cancer progression such as SRY box 7 (SOX7), Wnt inhibitory factor 1 (WIF1), secreted frizzled-related protein 1 (SFRP1) and dickkopf-related protein 3 (DKK3). To test this hypothesis, the basal level methylation status was tested in several prostate cancer patient tumor and adjacent normal samples by methylation specific PCR. When the methylation status of some of these genes was explored, there was variation in the methylation of some of these genes, particularly DKK3 among different patients. This preliminary finding may suggest that the methylation status of some of these genes may play a role in the progression of prostate cancer. In this study, we propose that demethylation of these Wnt negative regulatory genes may allow for a decrease activity of the Wnt signaling pathway. Genistein is a soy isoflavone that has many potentially therapeutic activities, including demethylation of DNA. We hypothesized that treatment of prostate cancer cells could lead to demethylation and re-expression of these genes. To test our hypothesis, prostate cancer cell lines LNCAP and DU145 were treated with for 6 days with concentrations of 5, 10, and 20 µM genistein. We observed a dose-dependent reduction in methylation of SOX7, DKK3, WIF1, and SFRP1. Taken together, these data indicate that genistein may have therapeutic value for patients with prostate cancer. As a therapeutic agent, genistein treatment has potential solely or in combination with other compounds to demethylate Wnt negative regulatory genes and possibly impact patient outcomes.
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 4932.
Abstract 4936: Promoter methylation in prostate cancer: A pilot study
Authors: Delgado-Cruzata Lissette , Gonzalez Karina , Santella Regina M. , Shen Jing 
Published: February 2011

Abstract
Prostate cancer is a leading cause of cancer death among men in the United States. The current method used for the screening for prostate cancer, the prostate-specific antigen (PSA) test, has poor specificity and sensitivity. This has lead to the search for new biomarkers that can improve the prostate cancer screening, either by themselves or in combination with established markers. Epigenetic modifications, believed to occur early during tumorgenesis are one of the new measurements that could aid in improving prostate cancer screening. We conducted a case-control study to determine the association of promoter methylation of p16 INK4a and GSTP1 and prostate cancer risk. Twenty seven histologically confirmed prostate cancer patients were matched by age and ethnicity to twenty four controls. DNA was extracted from plasma, and percentage of DNA methylation was determined by pyrosequencing. We found that methylation levels were consistently higher in cases than in controls, but this difference was not statistically significant (p16 INK4a OR (95%CI)=2.38 (0.75-7.50); GSTP1 OR (95%CI)=2.57 (0.79-8.40). Methylation levels in these regions were also investigated in tumor and normal adjacent tissue samples from cases. Promoter regions of these genes are hypermethylated in prostatic tumors (7.2% for p16INK4a and 95.8% for GSTP1). Hypermethylation of both regions is statistically significantly associated with tumor status with OR p16INK4a =5.0, 95%CI: 1.3-19.1 and ORGSTP1=22.9, 95%CI: 2.7-198.6, respectively. The correlations of GSTP1 and p16INK4a methylation levels in matched tissue and plasma samples were also determined. Pearson's correlation coefficient was 0.46 for GSTP1 methylation when comparing tumor tissue and plasma (p=0.037). However, the tissue-plasma correlation for p16INK4a methylation levels was not statistically significant. Our samples size is small, but our results are encouraging suggesting that plasma DNA methylation levels at the promoter regions of p16INK4a and GSTP1 are relevant in the etiology of prostate cancer and may be useful as markers of the onset of prostate 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 4936.
Abstract 4945: Epigenetic silencing of microRNA-34b/c in human gastric cancer
Authors: Suzuki Hiromu , Yamamoto Eiichiro , Nojima Masanori , Tokino Takashi , Imai Kohzoh , Toyota Minoru , Shinomura Yasuhisa 
Published: February 2011

Abstract
Altered expression of microRNA (miRNA) is strongly implicated in cancer, and recent studies have shown that some miRNAs are silenced in association with CpG island hypermethylation in cancer. To identify epigenetically silenced miRNAs in gastric cancer (GC), we screened for miRNAs induced by 5-aza-2′-deoxycytidine (DAC) and 4-phenylburtyrate (PBA) treatment in GC cell lines. By using miRNA microarray (Agilent technologies), we analyzed a panel of 470 miRNAs in MKN74 and AGS cells treated with or without DAC and PBA, and found that 172 and 151 of the miRNAs were significantly upregulated (&gt;5-fold) by the drug treatment, respectively. Among them, we noted miR-34b and miR-34c, which are direct targets of p53, and are frequently silenced in colorectal cancer. Here, we show that miR-34b and -c are frequently downregulated in GC in association with DNA hypermethylation. Reporter assay revealed strong promoter activity in the upstream CpG island of miR-34b/c. Methylation of the CpG island was frequently observed in GC cell lines (13/13, 100%) and primary GC specimens (83/118, 70%), but not in normal gastric mucosa. By in situ hybridization analysis, we observed downregulated expression of miR-34b in primary GC specimens. Methylation of the CpG island was also detected in the non-tumorous gastric mucosa of the GC patients. Notably, quantitative methylation analysis by bisulfite-pyrosequencing revealed higher methylation levels in gastric mucosa with multiple GCs than those with single GCs. Transfection of precursor molecules of miR-34b or miR-34c into GC cells suppressed cellular growth. Gene expression microarray analysis revealed that miR-34b or miR-34c induced dramatic changes in the gene expression profile in GC cells. Particularly, “cell cycle” and “M phase” genes are significantly enriched among the genes downregulated by miR-34b/c. Our results suggest that miR-34b/c are novel tumor suppressors in GC, and that methylation of miR-34b/c CpG island might be a useful marker to predict GC risk.
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 4945.
Abstract 4949: Epigenetic silence of ASPP1 and ASPP2 genes promotes tumor growth in HBV-positive hepatocellular carcinoma
Authors: Zhao Jian , Guo Yajun 
Published: February 2011

Abstract
The Ankyrin-repeat-, SH3-domain- and proline-rich-region containing protein (ASPP) family of proteins regulates apoptosis through interaction with p53 and its family members. This study evaluates the epigenetic regulation of ASPP1 and ASPP2 in HBV-positive hepatocellular carcinoma (HCC) and explores the effects of down-regulation of ASPP1 and ASPP2 on the development of HCC. The expression of ASPP1 and ASPP2 was diminished in HCC cells by epigenetic silence owing to hypermethylation of ASPP1 and ASPP2 promoters as detected by methylation-specific PCR (MS-PCR) and 5-Aza-2′-Deoxycytidine treatment. Analyses of 51 paired HCC and surrounding non-tumor tissues revealed that methylation of ASPP1 and ASPP2 was associated with the decreased expression of ASPP1 and ASPP2 in tumor tissues (38.1% vs 6.7% in ASPP1, P = 0.018, and 50% vs 15% in ASPP2, P = 0.012). The correlations of the expression and the methylation of ASPP1 and ASPP2 with p53 gene status were further analyzed. HCCs harboring wild type p53 gene were more frequent to have decreased ASPP2 expression (P = 0.028). Whereas no statistic significance was found between down-regulation of ASPP1 and p53 gene status (P = 0.704). Methylation of ASPP1 and/or ASPP2 in the surrounding non-tumor tissues was closely related with the tumor size (P = 0.031) and the tumor stage (P = 0.010). This result indicates that methylation of ASPP1 and ASPP2 may participate in the early stage of neoplasia. Moreover, ASPP2 became methylated upon HBV X protein (HBx) expression. The expression of HBx enhanced the recruitment of DNMT1 and DNMT3A on ASPP2 promoter to initiate DNA methylation, and subsequent increased the binding of methyl-CpG binding proteins on its promoter to suppress ASPP2 expression. The suppressive effects on tumor growth by ASPP1 and ASPP2 were examined with RNA interference mediated gene silence. Down-regulation of ASPP1 and ASPP2 promoted the growth of HCC cells in soft agar and in nude mice, and decreased the sensitivity of HCC cells to apoptotic stimuli. In conclusion, ASPP1 and ASPP2 genes are frequently down-regulated by DNA methylation in HBV-positive HCC, which may play important roles in the development of HCC. These findings provide a new insight into the molecular mechanisms leading to hepatocarcinogenesis and may have potent therapeutic applications.
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 4949.
Abstract 4955: Advances in gene expression microarray profiling from small amounts of adenocarcinoma and normal total RNA samples
Authors: Lucas Anne Bergstrom , Lin Gary , Mullinax Becky , Jacobs Sharoni , Fulmer-Smentek Stephanie 
Published: February 2011

Abstract
Gene expression profiling by microarray analysis provides an important avenue for understanding biological mechanisms, classifying tissue and tumor types, and identifying signs for diagnosis and prognosis. To address the need for high sensitivity gene expression profiling of low quantities of total RNA, we have developed a modified linear amplification procedure that generates quantities of Cy-labeled cRNA suitable for oligonucleotide microarray experiments from total RNA input amounts as low as 10 nanograms. This new procedure, available in the new Low Input Quick Amp Labeling Kit, employs the AffinityScript Reverse Transcriptase, a mutant MMLV-RT that binds primer-template complexes with 10-fold higher efficiency than wild type MMLV-RT, resulting in increased cDNA yields and improved sensitivity from smaller sample inputs. The protocol uses a single round of IVT amplification without purification of the cDNA product resulting in labeled cRNA in less than one day, enabling gene expression profile comparisons in less than two days. Comparisons of probe signals from technical replicate samples demonstrate high reproducibility with wide dynamic ranges, and generally comparable signals across a broad range of input amounts. This new labeling approach was used to detect differences in gene expression between cancerous and normal cells using new gene expression arrays with updated content resulting in gene expression profiling results consistent with the current literature.
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 4955.