bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 172: A role for the demethylation of microRNA-496 in MBD2-mediated repression
Authors: Alvarado Sebastian G. , Andrews Stephen D. , Chik Flora , Szyf Moshe 
Published: February 2011

Abstract
BACKGROUND: MicroRNAs are small RNA molecules that have the ability to repress target mRNAs through binding in their 3’ UTR. Prior work has shown that the expression of methyl binding domain protein 2 (MBD2) induces a variety of prometastatic genes through direct demethylation.
HYPOTHESIS: MBD2 turns on microRNA expression through promoter demethylation that in turn suppress other genes.
RESULTS: Methylated DNA Immunoprecipitation (mDIP) and MBD2 ChIP arrays identified a subset of microRNAs that change with the overexpression and transient knockdown of MBD2 in MCF10A and MCF7 cell lines, respectively. Methylation of these microRNAs with bisulfite sequencing and validation of MBD2 binding with quantitative PCR (qPCR) revealed the possible induction of hsa-mir-496 by MBD2. Expression of mir-496 was shown to be induced in MBD2 transfected MCF10A cells and repressed in MCF7 and MDA-231 cells with qPCR. Luciferase promoter assays revealed hsa-mir-496 promoter to be regulated by methylation and driven forward by co-transfection with MBD2. In silico scans of possible targets of hsa-mir-496 identified CPEB3 as a putative target. Expression of CPEB3 was shown to be inversely proportional to MBD2 in MBD2 transfected MCF10A cell lines and transient knockdowns of MBD2 in MCF7 and MDA-231 cell lines with qPCR.
CONCLUSIONS: The discovery of microRNAs has shed a whole new light on transcriptional regulation and with it has raised several questions about specific cell states. Considering that MBD2 causes complete transformation of a cell and plays a large role in tumorigenicity it is essential to characterize the roles of microRNA action with regards to MBD2 and its respective network of action. More importantly to show MBD2 as a key regulator of microRNA expression can further reinforce its role as a DNA demethylase and a key regulator of cancer.
FUTURE DIRECTIONS: Future work will involve testing mir-496 action in the cell with its putative target CPEB3 using 2-O-methyl primer assays in conjunction with luciferase reporter assays in order to probe the functionality of the CPEB3 3′UTR. The aforementioned results and directions will give us a refined picture of our model as well as attempt to define a system of MBD2-microRNA action.
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 172.
Abstract 1722: c-Met overexpression contributes to the acquired apoptotic resistance of non-adherent ovarian cancer cells through a cross-talk mediated by phosphatidylinositol 3-kinase and extracellular signal-regulated kinase 1/2
Authors: Tang Maggie K. S. , Zhou Hong Y. , Yam Judy W. P. , Wong Alice S. T. 
Published: February 2011

Abstract
Ovarian cancer is the most lethal gynecological cancer mainly due to widespread peritoneal dissemination and malignant ascites. Key to this is the capacity of tumor cells to escape suspension-induced apoptosis (anoikis), which also underlies their resistance to chemotherapy. Here we utilized a non-adherent cell culture model to investigate molecular mechanisms of apoptotic resistance of ovarian cancer cells that may mimic the chemoresistance found in solid tumors. We found that ovarian cancer cells acquired a remarkable resistance to anoikis and apoptosis induced by exposure to clinically relevant doses of two front-line chemotherapeutic drugs cisplatin and paclitaxel when grown in three-dimensional (3D) than monolayer cultures. Inhibition of the hepatocyte growth factor (HGF) receptor c-Met, which is frequently overexpressed in ovarian cancer, by a specific inhibitor or small interfering RNA blocked the acquired anoikis resistance and restored chemosensitivity in 3D, not in 2D cultures. These effects were found to be dependent on both phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular-signal regulated kinase (ERK) 1/2 signaling pathways. Inhibitors of PI3K/Akt abrogated ERK1/2 activation and its associated anoikis resistance in response to HGF, suggesting a signaling relay between these two pathways. Furthermore, we identified, as a mechanism of this cross-talk, a central role of Ras. Interestingly, Ras did not lie upstream of PI3K/Akt, whereas PI3K/Akt signaling to ERK1/2 involved Ras. These findings shed new light on the apoptotic resistance mechanism of non-adherent ovarian cancer ascites cells (This study was supported by Hong Kong Research Grants Council 7599/05M and Committee on Research and Conference Grant HKU200807176203 to A.S.T.W.).
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 1722.
Abstract 1728: Membrane androgen receptor ligands: a novel therapeutic approach for the treatment of cancer
Authors: Alevizopoulos Konstantinos , Bacopoulos Nicholas G. , Stournaras Christos 
Published: February 2011

Abstract
Membrane Androgen Receptor (mAR) is a novel, yet of unknown identity, membrane receptor frequently over-expressed in aggressive prostate cancer. mAR is not related to the classical intracellular androgen receptor (AR), a well known therapeutic target for prostate cancer treatment. Consequently, mAR induces tumour cell death by apoptosis in both AR-positive and AR-negative cell lines or in the presence of anti-androgens (e.g. flutamide). Early experimental results with membrane-targeted steroids (androgen-albumin conjugates) have proved the validity of mAR as a novel target of cancer therapy, as based on the anti-cancer action observed in prostate xenograft models (reviewed in IUBMB Life. 2009 Jan;61(1):56-61).
In this study, we describe novel small molecule steroidal mAR ligands that exhibit in vitro anti-cancer activity in the nanomolar range in prostate cancer cell lines. Furthermore, and as based on the identification of functional membrane androgen receptors in non-prostate cancer cells by immuno-fluorescence analysis, we show that selective novel mAR ligands exert broad anti-cancer action in additional cell line panels including colon, non-small cell lung cancer, central nervous system, breast or multi drug resistant cells. Notably, our compounds are selective for mAR binding since control displacement assays failed to identify significant interactions with recombinant Androgen Receptors.
To assess the anti-cancer of our compounds in vivo, we measured the ability of a prototype mAR ligand, MDX-146, to inhibit tumour growth of human PC-3 prostate cancer xenografts. Our results show clear tumour growth inhibition effects of MDX-146 in animals and propose a potential therapeutic role of specific mAR ligands for the treatment of prostate and other cancers.
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 1728.
Abstract 173: Frequent concomitant epigenetic silencing of the SFRPs and SOX1, Wnt/β-catenin regulators, in human hepatocellular carcinoma
Authors: Lin Ya-Wen , Hsieh Chung-Bao , Shih Yu-Lueng , Hsieh Tsai-Yuan , Tsao Chun-Ming , Yan Ming-De 
Published: February 2011

Abstract
Oncogenic activation of the Wnt/β-catenin signaling pathway is common in hepatocellular carcinoma (HCC). The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and have important implications for carcinogenesis. Recently, we have shown that SFRPs are frequently downregulated through promoter hypermethylation in HCC cell lines and clinical HCC tissues. Furthermore, we have demonstrated that restoration of SFRPs could attenuate Wnt signaling in HCC cells with β-catenin point mutation, decrease abnormal accumulation of free β-catenin in the nucleus, and then suppress cell growth. Sox1 encodes a transcription factor involved in the regulation of embryonic development and cell fate determination. Structurally related to TCF/LEFs, several members of the Sox family, including Sox17, Sox3, Sox7, and Sox9, have also been implicated in repressing β-catenin activity by a mechanism that is not well understood. In this study, we found that the Sox1 was severely down-regulated by quantitative reverse transcription polymerase chain reaction (QRT-PCR). Next, we employed bisulfite modification and methylation-specific PCR (MS-PCR) to analyze the feature of Sox1 promoter methylation in the HCC cell lines and found that the majority of the tested cell lines exhibited hypermethylation. Meanwhile, we also examined sixty primary HCC surgical samples and adjacent nonturmorous liver tissues from Taiwan Liver Cancer Network (TLCN). These results showed that aberrant promoter methylation of SOX1 were found in 32 of 60 HCCs (53.3%), in 13 of 50 cirrhotic livers (26%), and in one of 30 normal control tissues (3.3%). Concomitantly, SFRPs was epigenetically inactivated in HCC cell lines and most of all the tumors with methylated SOX1. A significant correlation between the methylation of both genes was found (p &gt;0.05). Furthermore, overexpression of SOX-1 in HCC cells could suppress TCF-dependent transcriptional activity and suppress colony formation. Taken together, our data suggest that SOX1 is a negative modulator of Wnt/β-catenin signaling, and that SOX1 silencing due to promoter hypermethylation is an early event during tumorigenesis and may contribute to aberrant activation of Wnt signaling in HCC.
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 173.
Abstract 1732: Elevated expression of YKL-40, a cancer biomarker, is associated with tumor angiogenesis
Authors: Yan Wei , Cao Jackie Qing , Arenas Richard B. , Bentley Brook , Shao Rong 
Published: February 2011

Abstract
Growing evidence from clinical investigations has shown that increased serum levels of YKL-40 are correlated with short survival and metastasis in a broad type of human cancers. These data suggest that YKL-40 in the blood may present a powerful tool for cancer diagnosis and prognosis. However, pathological activity of YKL-40 in cancer development is poorly understood. Here, we explored a functional role for YKL-40 in vasculature development of human cancer. In a survey of twenty cases of breast ductal carcinoma in situ (DCIS) and thirty-eight cases of infiltrating ductal carcinoma (IDC), we found that expression levels of YKL-40 in specimens from DCIS were barely detectable, but different levels of YKL-40 were present in IDC. Nine out of thirty-eight IDC cases showed high levels of YKL-40 and nine cases displayed medium levels of YKL-40, whereas the rest twenty cases were low or negative. Interestingly, in an analysis of vasculature formation in these IDC samples, we found that different blood vessel densities significantly correlated with different degrees of YKL-40 expression. To test this possible angiogenic activity of YKL-40 in tumor development, we utilized angiogenic xenograft models by subcutaneous injection of SCID/Beige mice with a brain tumor line U87 cells which express strong endogenous YKL-40 and U87 cells with siRNA knockdown of YKL-40. siRNA knockdown of YKL-40 notably suppressed tumor angiogenesis and tumor development relative to high levels of YKL-40 expressed in control U87 cells. Further, to dissect cellular and molecular mechanisms underlying YKL-40-induced tumor angiogenesis, we treated human microvascular endothelial cells with YKL-40 and found that YKL-40 was capable of binding to heparan sulfate on ectodomain of membrane receptor syndecan-1 (S1). The activated S1 prompted its interaction with adjacent receptor integrin αvβ3, leading to activation of intracellular cascades including phosphorylation of focal adhesion kinase and MAP kinase. A series of individual signaling inhibitors blocked YKL-40-induced angiogenesis in vitro. Collectively, these data strongly suggest that YKL-40 expressed in cancer activates vascular endothelial cell angiogenesis to promote tumor development. These findings may hold promise for developing novel therapeutic agents targeting YKL-40, a cancer biomarker that is overexpressed in a wide range of human cancers.
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 1732.
Abstract 1735: Expression of circadian genes correlate with liver metastasis and prognosis in colorectal cancer
Authors: Oshima Takashi , Kunisaki Chikara , Sato Tsutomu , Yamada Roppei , Fujii Shoich , Yamamoto Naoto , Shiozawa Manabu , Akaike Makoto , Rino Yasushi , Masuda Munetaka , Imada Toshio 
Published: February 2011

Abstract
The circadian rhythms are daily oscillations in various biological processes, and generated by the feedback loops of eight core circadian genes. These eight genes are, Clock, casein kinase I ε (CKI ε), cryptochrome1 (Cry1) and cryptochrome2 (Cry2), Period1 (Per1), Period2 (Per2) and Period3 (Per3), Bmal1. Recent studies have suggested that the circadian genes participate in the growth and development of various cancers. This study examined the relations of the circadian genes expression to clinicopathological factors and prognosis in patients with colorectal cancer. We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 202 patients with untreated colorectal cancer. The relative expression levels of the circadian genes in the specimens were measured by quantitative real-time, reverse-transcription polymerase chain reaction. Expressions of Clock and CKI ε in cancer tissue were significantly higher than those in adjacent normal mucosa. Expressions of Per1 and Per3 in cancer tissue were significantly lower than those in adjacent normal mucosa. Analysis of the relations between clinicopathological features and expressions of the eight circadian genes showed that high expression of the Bmal1 and low expression of the Per1 correlated with liver metastasis. In the analysis of the relations between prognosis and expressions of the eight circadian genes, the prognosis of high expression of the Per2 was significantly better than that of low expression of the Per2. Our results suggest that over-expression of the Bmal1 and reduced expression of the Per1 might promote liver metastasis, and reduced expression of Per2 might shorten prognosis in colorectal cancer. Thus over-expression of the Bmal1 gene and reduced expression of the Per1 gene may be a useful predictor of liver metastasis. And reduced expression of Per2 may be useful as prognostic factor in patients with colorectal 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 1735.
Abstract 1737: Lipocalin-2/NGAL expression is associated with poor prognostic variables in human mammary, endometrial and ovarian carcinomas
Authors: Ross Jeffrey S. , Sheehan Christine E. , Kallakury Bhaskar V.S. 
Published: February 2011

Abstract
BACKGROUND: Recent literature has shown that lipocalin-2, a lipophilic ligand transporter member of the lipocalin family has a possible role as a biomarker and a modulator of human cancers. Elevated levels of lipocalin-2 have been demonstrated in several types of human cancer. However, its role as a prognostic biomarker has not been widely reported.
DESIGN: Formalin-fixed, paraffin-embedded tissue sections from 146 invasive mammary, 124 endometrial and 59 ovarian carcinomas were immunostained by automated method (Ventana Medical Systems Inc., Tucson, AZ) using rat monoclonal lipocalin-2/NGAL (R&D Systems, Minneapolis, MN). Cytoplasmic immunoreactivity was semiquantitatively scored based on staining intensity and distribution and the results were correlated with morphologic and prognostic variables.
RESULTS: Cytoplasmic lipocalin-2 overexpression was observed in 78/146 (53%) of invasive mammary carcinomas and correlated with PR positive status [63% PR positive versus 41% PR negative, p=0.012] and disease recurrence [69% recurrent versus 48% non-recurrent, p=0.021). On multivariate analysis, advanced stage, lipocalin-2 overexpression, ER negative status, metastatic disease at diagnosis and positive node status were independent predictors of disease recurrence; while advanced stage, metastatic disease at diagnosis and positive node status were independent predictors of shortened survival. In endometrial carcinomas, cytoplasmic lipocalin-2 overexpression was observed in 47/124 (38%) tumors, and correlated with tumor grade (52% grade 3 vs. 43% grade 2 vs. 21% grade 1, p=0.045) and with ER negative status [52% ER negative vs 28% ER positive, p=0.049]. There was no correlation with disease recurrence or overall survival. In invasive ovarian carcinomas, cytoplasmic lipocalin-2 overexpression correlated with tumor grade (0% grade 1 vs. 40% grade 2 vs. 67% grade 3, p=0.006) and advanced tumor stage (32% stage I vs. 65% stage III vs. 100% stage IV, p=0.018). Lipocalin-2 expression did not correlate with patient survival.
CONCLUSION: Lipocalin-2 overexpression correlates with varying markers of biologic aggressiveness in human mammary, endometrial and ovarian carcinomas warranting further study.
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 1737.
Abstract 1744: αB-crystallin as a novel marker of lymph node metastasis in breast cancer
Authors: Kim Haesung , Lee Younok , Kang Hee Joon , Kim Lee-Su 
Published: February 2011

Abstract
αB-crystallin, the member of small heat shock protein, is known as an anti-apoptotic protein and is associated with aggressive tumor behavior. In addition, recent study revealed that αB-crystallin was overexpressed in a metastatic variant of the GI101A human breast carcinoma cell line. The purpose of this study was to investigate whether expression of αB-crystallin was associated with lymph node metastasis. And also we evaluated the relationship of expression of αB-crystallin and other established prognostic factors. Eighty two patients who underwent breast cancer surgery and chemotherapy at Hallym Sacred Heart hospital were enrolled. Expression of αB-crystallin was determined by immunohistochemical staining using monoclonal antibody (SPA-222, Stressgen Biotech.) and graded as negative=0, weakly positive=1, moderately positive=2 and highly positive=3. Estrogen receptor, progesterone receptor, cERB-2, lymphatic tumor emboli, histologic grades and other tumor markers were compared with αB-crystallin expression. Expression of αB-crystallin in breast cancer tissues was associated with lymph node metastasis (p=0.01), lymphatic tumor emboli (p&lt;0.01), high nuclear grade (p=0.02) and triple negative status (p=0.02). Five of 6 visceral metastasis cases showed highly expression of αB-crystallin. Results of this study revealed a strong relationship between αB-crystallin and lymph node metastasis of breast cancer. And also the expression of αB-crystallin significantly correlated with other breast tumor markers. We thought that αB-crystallin could be a novel marker of lymph node metastasis 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 1744.
Abstract 1750: Reduced xpression of Reelin (RELN) gene is associated with high recurrence rate of hepatocellular carcinoma
Authors: Okamura Yukiyasu , Nomoto Shuji , Kanda Mitsuro , Hayashi Masamichi , Fujii Tsutomu , Sugimito Hiroyuki , Takeda Shin , Nakao Akimasa 
Published: February 2011

Abstract
Background and Aims: Hepatocellular carcinoma (HCC) is one of the world's top five causes of cancer-related deaths and has limited treatment options. HCC is one of the few cancers for which the etiology of the underlying disease is known in most cases. However, the molecular pathogenesis of HCC has not been fully elucidated. Recently described genome-wide approaches robustly detect many candidate genes that are regulated in HCC. Here we attempt to identify the novel genes with altered expressions related to clinical factors using a double-combination array, which contains an expression array and a single nucleotide polymorphism (SNP) array. Moreover, we analyzed the identified gene, using quantitative reverse transcription polymerase chain reaction (RT-PCR) and methylation-specific PCR.
Samples and Methods: A 68-year-old woman with chronic hepatitis C was diagnosed with HCC and underwent liver resection. On the same HCC sample, we performed double-combination array analysis. We consequently analyzed the identified gene, using quantitative RT-PCR, methylation-specific PCR, and un-methylated specific PCR in five HCC cell lines, together with 48 pairs of HCC tissues (HTs) and adjacent non-tumorous tissues (NTs) obtained from patients who underwent hepatectomy. The results were compared with the clinico-pathological data.
Results: There was decreased expression of the Reelin (RELN) gene in HT at the level of −3.0. We then used the SNP-Chip array to confirm that the copy number of chromosome 7 where RELN is located did not show any abnormalities. These results suggest that RELN expression was reduced without LOH or deletion. We then examined the sequence of the promoter region of RELN gene and found many CpG islands. Therefore, we hypothesized that hypermethylation of the CpG islands was the mechanism for its decreased expression in HT. Thirty-four of 48 (79.2%) samples had decreased RELN expression level in HTs and the expression level of HTs was clearly reduced compared with that of NTs (P &lt; 0.002). We found that 18 of 48 (37.5%) HTs had promoter hypermethylation of the RELN gene. In regard to clinical data, the patients with reduced expression in HTs have a high recurrence rate (P = 0.028).
Conclusion. The present study suggests that our method is able to detect novel genes with altered expression and that RELN is a novel gene associated with recurrence of HCC.
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 1750.