bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4936: MicroRNAs located on 13q and 20q are differentially expressed between normal mucosa, adenomas and carcinomas of the large intestine
Authors: Timmer Lisette M. , Bolijn Anne S. , Carvalho Beatriz , Mulder Chris J.J. , Cuppen Edwin , Meijer Gerrit A. , Diosdado Begoña 
Published: June 2012

Abstract
Background: In colorectal cancer (CRC) miRNA expression profiling studies have reported differences in expression between colorectal carcinomas and controls, microsatellite stable, microsatellite instable and chromosomal instable tumors, and demonstrated prognostic value for some miRNAs. However, the role of miRNAs in CRC pathogenesis has been only partially investigated. CRC results from the gradual accumulation of multiple genetic and epigenetic changes in the colorectal epithelial cells. The majority of CRCs (85%) shows an accumulation of chromosomal abnormalities. In CRC, up to 15% of the annotated miRNAs are located at regions of chromosomal instability implicated in colorectal adenoma to carcinoma progression. Two of the most frequent chromosomal aberrations in CRC are gain of 13q (&gt;50%) and gain of 20q (&gt;65%). A total of 36 miRNAs are located on these chromosomal arms. However, the leading cause of the miRNA's aberrant expression and the pathways through which they contribute to CRC have not been elucidated.
Aim: To investigate the expression of miRNAs located on 13q and 20q in normal colon mucosa, adenomas and CRC.
Materials & Methods: DNA and total RNA was isolated from 48 colorectal adenomas, 51 CRCs and 10 normal mucosa samples. Multiplex Ligation-dependent Probe Amplification (MLPA) was used to determine DNA copy number gain of 13q and/or 20q. Expression levels of 17 miRNAs located on 13q and 19 miRNAs on 20q (miRBase release 15) were measured by TaqMan miRNA assays.
Results: 11 Of the miRNAs located on 13q and 8 of the miRNAs located on 20q were detected in colon tissue. 15 Of these miRNAs were significantly differentially expressed between colorectal tumors compared to controls and 13 were differentially expressed between carcinomas and adenomas (p&lt;0.05). In addition, 11 miRNAs were significantly differentially expressed between tumors with or without a 13q and/or 20q gain (p&lt;0.05).
Conclusion: Gene dosage effects of miRNAs located on chromosomes 13q and 20q play an important role in CRC progression, and taking this into account is essential to achieve a comprehensive understanding of the pathogenesis of this malignancy.
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 4936. doi:10.1158/1538-7445.AM2011-4936
Abstract 4940: Microrna expression profiling in adrenocortical neoplasia: Implications on tumor size and functionality
Authors: Velázquez-Fernández David , Caramuta Stefano , Özata Deniz M , Akcakaya Pinar , Höög Anders , Hamberger Bertil , Bäckdahl Martin , Larsson Catharina , Zedenius Jan , Lui Weng-Onn 
Published: June 2012

Abstract
Background: Tumors arising from the adrenal cortex (ACT) can be hormonally hyperfunctioning or silent. This functional phenotype, as well as their size, is of clinical importance. MicroRNAs are a class of small non-coding RNAs that negatively regulates gene expression. There is increasing evidence for their significant role in tumorigenesis. Their relevance on the functional phenotype and size of these tumors has not been previously documented.
Aim: To characterize differential expression patterns of microRNAs regarding the increasing size and the functional phenotypes of ACT.
Methods: Seventy frozen tissue samples were included: 16 aldosterone-producing adenomas (APA), 14 cortisol producing adenomas (CPA), 14 non-hyperfunctioning adenomas (NhFA), 19 adrenocortical carcinomas (ACC) and 7 normal adrenal cortices as controls. Global microRNA expression profiles were determined using the Agilent Human microRNA microarray, and the results were verified by quantitative real-time PCR.
Results: We observed distinct microRNA expression patterns among different ACT phenotypes: majority of the APA was clustered separately from NhFA and CPA, and the ACC was independently clustered apart from all benign tumors. A larger number of miRNAs were differentially expressed between APA and CPA, while a smaller subset of differently expressed microRNAs was found between functional and non-hyperfunctional adenomas. Among the benign tumors, we found miR-21 expression was significantly correlated with increasing tumor size.
Conclusion: Deregulation of microRNA expression is associated with the functional phenotype and size in ACT, and these microRNAs may have implication related to the development of adrenocortical tumors.
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 4940. doi:10.1158/1538-7445.AM2011-4940
Abstract 4943: microRNAs as clinical biomarkers for lung cancer classification
Authors: Edmonston Tina , Kushnir Michal , Yanai Gila Lithwick , Benjamin Hila , Bibbo Marluce , Thurm Craig , Horowitz Laurie , Huang Yajue , Feinmesser Meora , Barshack Iris , Gilad Shlomit , Chajut Ayelet 
Published: June 2012

Abstract
Background: Lung cancers have traditionally been subdivided into two main groups: Small Cell Lung Cancer (SCLC) and Non Small Cell Lung Cancer (NSCLC). Due to limited tumor sample amounts and an abundance of poor quality samples, accurate subclassification of primary lung cancer using small pre-operative biopsies presents a diagnostic challenge using current tools (H&E and immunohistochemical stains). For patients with primary lung cancer, accurate determination of the tumor type significantly influences treatment decisions. Our previous studies have shown that microRNAs are differentially expressed in different subtypes of lung cancer; hence microRNA expression profiling holds a promising new strategy for the precise subclassification of lung cancers. Based on these findings, we present here the development of a microRNA-based qRT-PCR diagnostic assay that uses pathology and cytology samples in order to classify primary lung cancers into four subtypes: squamous, non-squamous, SCLC and carcinoid.
Methods: FFPE tissue blocks and cell blocks from different histological subtypes of lung cancer, taken from primary lung cancer resection or pre-operative diagnostic procedures, were collected. High-quality RNA, including the well-preserved microRNA fraction, was extracted from the samples using proprietary protocols. Expression levels of potential microRNA biomarkers were profiled using a sensitive and specific qRT-PCR platform.
Results: We find that combinations of a few microRNAs can successfully differentiate between different histological types of lung tumors. A classification algorithm was developed that reached high accuracy in the identification of the four main subtypes of lung tumors.
Conclusion:
We developed a highly accurate microRNA-based diagnostic assay that classifies primary lung cancer types with very high sensitivity and specificity. This assay is a simple and reliable diagnostic assay which will offer an accurate and standardized tool for primary lung cancer cytological samples, including those that presently fail pathological evaluation.
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 4943. doi:10.1158/1538-7445.AM2011-4943
Abstract 495: Overexpression of the cold-inducible RNA binding protein RBM3 attenuates the stem cell-like features of PC-3 cells
Authors: Zeng Yu , Kim John , Li Youqiang , Mooney Steven , Shiraishi Takumi , Kulkarni Prakash , Getzenberg Robert 
Published: June 2012

Abstract
Introduction: It has long been thought that the stem cell-like features of cancer cells contribute to their evolutionary capability to escape therapeutic strategies, such as chemotherapy, radiotherapy, or hormone deprivation in prostate cancer (PCa). At the same time, temperature is perhaps one of the most important elements of the environment. One of the most clinically relevant examples of the effect of temperature on stem-like cells is cryptorchidism, in which germ cells maintained at body temperature that is several degrees higher than in the scrotum do not function to form sperm. In contrast, these pluripotential cells have a high likelihood to develop cancer if they are not rescued by relocating them to the scrotum and therefore a lower environmental temperature, in very early childhood. RNA binding motif 3 (RBM3) belongs to a cold-inducible RNA binding protein family and has been shown to be highly expressed in normal testis tissue but is decreased in cryptorchid mouse. We previously reported that RBM3 was decreased by heat treatment in PCa cell lines. The goal of this study is to investigate the effect of RBM3 over-expression on stem cell-like features of PC-3 cells. Methods: RBM3 mRNA expression was detected by RT-PCR in fetal and adult human tissues, as well as in PCa samples. The normal prostate cell line, PrEc, was sorted with the stem cell surface marker CD133 using flow cytometry. PC-3 cells were transfected with pCMV6-RBM3-GFP vector. The soft agar clonogenic assay was performed with RBM3- or control vector-transfected cells. The expression of stem cell-related genes and miRNAs was determined using PCR array. Results: The RBM3 mRNA level is decreased in fetal tissues and CD133 (+) PrEc cells in comparison to adult tissues and CD133 (−) cells, respectively. Metastatic PCa expresses lower RBM3 mRNA than primary tumors. Moreover, RBM3 expression was decreased upon treatment of chemotherapy and maintained at a low level in the surviving clones after intensive chemo- or heat treatment in both PC-3 and DU-145 cells. PC-3 cells that over-express RBM3 demonstrated less heterogenic morphology than those with a control vector. Importantly, RBM3 over-expression greatly attenuates the anchorage-independent clonogenic ability of PC-3 cells. Additionally, a panel of genes and miRNAs that are involved in neural cell differentiation and self-renew are altered upon RBM3 expression. Conclusion: Taken together, these data suggest that lowering RBM3 may play an important role in maintaining the stem cell-like features of cancer cells during development and progression under environmental stress.
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 495. doi:10.1158/1538-7445.AM2011-495
Abstract 4951: 2-Methoxyestradiol (2-ME2) induces microRNA alterations in prostate cancer cells: Role for miRs in 2-ME2-induced biological effects
Authors: Xie Jianping , Ghosh Rita , Kumar Addanki P. 
Published: June 2012

Abstract
Prostate cancer is the second most common cause of death related to cancer in Western societies. 2-Methoxyestradiol (2-ME2), an endogenous metabolite of 17-β estradiol inhibits tumor cell proliferation in various cancer cells, including the prostate. Previous studies from our laboratory showed that 2-ME2 (i) inhibits proliferation of both androgen responsive and independent cells through induction of apoptosis involving G2/M check point block; (ii) prevents the development of prostate tumors in transgenic adenocarcinoma of mouse prostate (TRAMP) model. Although various molecular targets have been proposed, the mechanism of action behind its antiproliferative activity is still uncertain. Here we investigated the possible role for 2-ME2 induced antiproliferative activity by examining the altered regulation of microRNA (miRNAs). MicroRNAs are small non-coding RNAs that down regulate gene expression during cellular processes including proliferation and apoptosis. We compared the microRNA profile in non-tumorigenic (RWPE-1), androgen responsive (LNCaP) and androgen independent (PC-3) cells in response to 2-ME2 treatment in the presence and absence of androgen-stimulation (only in LNCaP cells) using the stem-loop RT-PCR based Taqman® Array Human MicroRNA Cards (Array A and B) representing 754 unique assays specific to human mature miRNAs (Applied Biosystems, Foster City, CA). Analysis of these data identified expression of only 50% of miRs in prostate cancer cells. About 26% and 12% of these are upregulated; 20.5% and 26% were down regulated in LNCaP and PC-3 cells respectively. However androgen stimulation of LNCaP cells resulted in upregulation of 34.2% and 15% down regulation of miRs whereas 2-ME2 treatment down regulated 28.7% of miRs. Target transcripts for these miRs have been identified. To the best of our knowledge this is the first study to report in-depth investigation of global miR changes in response to 2-ME2 induced biological effects. These data demonstrate that 2-ME2 suppresses proliferation and induces apoptosis in prostate cancer cells through modulation of microRNA signature. Supported by NIH CA 135451 (APK).
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 4951. doi:10.1158/1538-7445.AM2011-4951
Abstract 4956: Identification of microRNAs differentially expressed between lung squamous cell carcinoma and lung adenocarcinoma
Authors: Hamamoto Junko , Yoda Satoshi , Naoki Katsuhiko , Nakayama Sohei , Satomi Ryosuke , Terai Hideki , Ikemura Shinnosuke , Sato Takashi , Hayashi Yuichiro , Soejima Kenzo 
Published: June 2012

Abstract
Introduction: Recent advances in the treatment of non-small-cell lung cancer (NSCLC) with new agents require accurate histological subtyping at diagnosis in order to avoid the higher risk of an adverse response and obtain a maximum therapeutic response. However, interobserver variability, tumor heterogeneity and the degree of differentiation may influence the decision concerning a pathological diagnosis of NSCLC. We therefore in this study attempted to identify specific microRNAs as standardized biomarkers with high sensitivity and specificity for distinguishing between squamous cell carcinoma (SCC) and adenocarcinoma (AC).
Methods: Quantitative real time polymerase chain reaction (qRT-PCR) based microRNA array was performed to identify microRNAs differentially expressed between SCC and AC using 86 resected NSCLC samples as well as adjacent normal tissues. The results were confirmed by independent qRT-PCR assays with the same test samples and an additional 88 validation samples and the usefulness of the identified microRNAs as biomarkers to distinguish between SCC and AC was evaluated.
Results: Three microRNAs (hsa-miR-196b, hsa-miR-205 and hsa-miR-375) were identified. Discriminant analysis combining all 3 microRNAs appeared to distinguish SCC from AC accurately in the test samples and the validation samples, showing sensitivity and specificity of 76% and 80%, and 85% and 83%, respectively.
Conclusions: Hsa-miR-196b, hsa-miR-205 and hsa-miR-375 were identified as biomarkers capable of distinguishing between lung SCC and lung AC. These newly identified microRNAs may prove to be highly valuable molecular markers for the classification of NSCLC histologic subtypes, and could potentially contribute to the pathogenesis of each subtype of NSCLC.
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 4956. doi:10.1158/1538-7445.AM2011-4956
Abstract 4959: Deregulation of microRNA expression patterns during cervical carcinogenesis
Authors: Wilting Saskia M. , Snijders Peter JF , van de Wiel Mark A. , van Wieringen Wessel N. , Meijer Chris JLM , Steenbergen Renske DM 
Published: June 2012

Abstract
At present little is known about the involvement of alterations in microRNA (miRNA) expression patterns during the development of cervical cancer. In this study we investigated genome-wide miRNA expression profiles in normal cervical squamous epithelium, high-grade precancerous lesions (CIN2/3), squamous cell carcinomas (SCC) and adenocarcinomas (AdCAs), all of which were high-risk HPV positive. In addition, miRNA expression profiles were integrated with previously generated genome-wide chromosomal profiles of the same samples.
Unsupervised hierarchical clustering showed that miRNA expression profiling enables the distinction of normal cervical squamous epithelium, CIN2/3 lesions, SCCs and AdCAs. Differential miRNA expression analysis comparing normals, CIN2/3 lesions and SCCs identified early (temporal), late, and continuously differentially expressed miRNAs in cervical carcinogenesis (n=106). Differential expression of selected miRNAs could be validated by qRT-PCR in the same samples as well as in cervical scrapes of women with abnormal cytology and underlying high-grade CIN disease compared to control scrapes. In general, miRNAs located in the same cluster showed similar expression profiles, suggesting common regulatory mechanisms. For 5 of the 106 differentially expressed miRNAs, altered expression could be directly linked to underlying chromosomal alterations. Finally, cell viability assays indicated that ectopic expression of 2 selected miRNAs influenced cell proliferation in vitro, indicating functional relevance of differential miRNA expression during cervical carcinogenesis.
In conclusion, deregulation of miRNA expression patterns occurs during cervical carcinogenesis and has functional relevance for cervical cancer development. Since deregulated miRNA expression in cervical (pre)malignant disease is reflected and detectable in cervical scrapes, miRNAs represent a highly promising class of disease markers for further improvement of the triage of high-risk HPV positive women.
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 4959. doi:10.1158/1538-7445.AM2011-4959
Abstract 4961: MicroRNA profile predicts recurrence after resection in patients with hepatocellular carcinoma within the Milan criteria
Authors: Sato Fumiaki , Hatano Etsuro , Kitamura Koji , Myomoto Akira , Fujiwara Takeshi , Takizawa Satoko , Tsuchiya Soken , Uemoto Shinji , Shimizu Kazuharu 
Published: June 2012

Abstract
Objective: Hepatocellular carcinoma (HCC) is difficult to manage due to the high frequency of post-surgical recurrence. Early detection of the HCC recurrence after liver resection is important in making further therapeutic options, such as salvage liver transplantation. In this study, we utilized microRNA expression profiling to assess the risk of HCC recurrence after liver resection.
Methods: We examined microRNA expression profiling in paired tumor and non-tumor liver tissues from 73 HCC patients who satisfied the Milan Criteria. We constructed prediction models of recurrence-free survival using the Cox proportional hazard model and principal component analysis. The prediction efficiency was assessed by the leave-one-out cross-validation method, and the time-averaged area under the ROC curve (ta-AUROC).
Results: The univariate Cox analysis identified 13 and 56 recurrence-related microRNAs in the tumor and non-tumor tissues, such as miR-96. The number of recurrence-related microRNAs was significantly larger in the non-tumor-derived microRNAs (N-miRs) than in the tumor-derived microRNAs (T-miRs, P&lt;0.0001). The best ta-AUROC using the whole dataset, T-miRs, N-miRs, and clinicopathological dataset were 0.8281, 0.7530, 0.7152, and 0.6835, respectively. The recurrence-free survival curve of the low-risk group stratified by the best model was significantly better than that of the high-risk group (Log-rank: P=0.00029). The T-miRs tend to predict early recurrence better than late recurrence, whereas N-miRs tend to predict late recurrence better (P&lt;0.0001). This finding supports the concept of early recurrence by the dissemination of primary tumor cells. and multicentric late recurrence by the ‘field effect’.
Conclusion: microRNA profiling can predict HCC recurrence in Milan criteria cases.
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 4961. doi:10.1158/1538-7445.AM2011-4961
Abstract 4970: Mutational and functional analysis reveals ADAMTS18 metalloproteinase as a novel driver in melanoma
Authors: Prickett Todd D. , Wei Xiaomu , Viloria Cristina G. , Molinolo Alfredo , Lin Jimmy C. , Cruz Pedro , Rosenberg Steven A. , Davies Michael A. , Gershenwald Jeffrey E. , López-Otin Carlos , Samuels Yardena 
Published: June 2012

Abstract
An important feature of cellular signaling and migration involves the proteolytic cleavage of extracellular matrix and/or pro-ligands involved in signal transduction. Proteins called proteases are responsible for this action and include the matrix-metalloproteinase family and the A Disintegrin and Metalloproteinases family to name a few. The A Disintegrin and Metalloproteinases with Thrombospondin domains (ADAMTS) have been suggested to function as tumor suppressors as several have been found to be epigenetically silenced in various cancers. Thus further analysis is warranted in determining if ADAMTS genes/proteins play a role in melanoma genesis.
In the present study we performed a mutational analysis of 19 ADAMTS gene family members in human melanoma and identified a large fraction of melanomas to harbor somatic mutations. To evaluate the functional consequences of the most commonly mutated gene, ADAMTS18, six of its mutations were biologically examined. ADAMTS18 mutations had little effect on melanoma cell growth under standard conditions, but reduced cell dependence on growth factors. ADAMTS18 mutations also reduced adhesion to Laminin-I and increased migration in vitro and metastasis in vivo. Melanoma cells expressing mutant ADAMTS18 had reduced cell migration after shRNA-mediated knockdown of ADAMTS18, suggesting that ADAMTS18 mutations are growth-, migration- and metastasis- promoting in melanoma. These results demonstrate that the ADAMTS18 is a major target for mutational activation in melanoma and may be a useful diagnostic and/or therapeutic 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 4970. doi:10.1158/1538-7445.AM2011-4970