bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5292: MicroRNA signatures predictive of response to chemotherapy in mCRC.
Authors: Molina-Pinelo Sonia , Carnero Amancio , Rivera Fernando , Estevez-Garcia Purificacion , Bozada Jose M. , Limon Maria L. , Gomez Javier , Pastor Maria D. , Suarez Rocio , Paz-Ares Luis G. , de la Portilla Fernando , Carranza Andres , Sevilla Isabel , Vicioso Luis , Garcia Carbonero Rocio 
Published: August 2014

Abstract
MicroRNAs (miRNAs) are post-transcriptional regulators involved in numerous biological and pathological processes including colorectal cancer (CRC). From a clinical perspective, several studies have identified groups of miRNAs with potential utility for early diagnosis or prognostic stratification of CRC patients. However, very few have evaluated the potential ability of miRNA to predict response to selected chemotherapy regimens. The aim of our study was to evaluate the ability of miRNA expression patterns to predict chemotherapy response in a cohort of 78 patients with metastatic CRC (mCRC). We examined tumor expression levels of 667 miRNAs in the training cohort by TaqMan Low Density Arrays (TLDA). In training cohort (N=39), we identified a miRNA molecular signature with significant association in relevant clinical endpoints (objective response, progression-free and overall survival). In validation cohort (N=39), we validated significantly higher expression levels of miR-107, and miR99a* according to objective response to fluoropyrimidine-based regimens. These results support a substantial role for miRNAs in determining drug response, and highlight their potential value as biomarkers for personalized treatment strategies and as a novel class of therapeutic targets.
Citation Format: Sonia Molina-Pinelo, Amancio Carnero, Fernando Rivera, Purificacion Estevez-Garcia, Jose M. Bozada, Maria L. Limon, Javier Gomez, Maria D. Pastor, Rocio Suarez, Luis G. Paz-Ares, Fernando de la Portilla, Andres Carranza, Isabel Sevilla, Luis Vicioso, Rocio Garcia Carbonero. MicroRNA signatures predictive of response to chemotherapy in mCRC. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5292. doi:10.1158/1538-7445.AM2013-5292
Abstract 5294: The difference of serum RNA profile: RNA extraction and detection method.
Authors: Takizawa Satoko , Akiyama Hideo , Kondo Satoshi , Kosaka Nobuyoshi , Ochiya Takahiro 
Published: August 2014

Abstract
Serum miRNA profiles are widely reported by many .research groups, but they do not always coincide well. The reason of this difference is suggested to be, at least in some cases, due to a difference in the RNA extraction or detection method. In this report, we compare the miRNA expression profiles of RNAs extracted from (1) extracellular vesicles precipitated by ultra-centrifuging (2) precipitation of ExoQuick (3) whole serum by QIAGEN miRNeasy (4) whole serum by Toray "3D-Gene" RNA extraction reagent from liquid sample kit.
In addition to this, the comparison of data obtained by different detection tools will be also shown. In these days, the whole miRNA expression profiling can be done by multiple qRT-PCR, microarrays, and Next Generation Sequencing. However, the feature of each method will reflect to the obtained data and it is no surprise that data obtained by different tools do not match perfectly. We will compare the serum miRNA expression profiles detected by (1) “TaqMan” Array MicroRNA Card (2) QIAGEN miScript miRNA PCR Array (3) “3D-Gene” Human miRNA oligo chip, and discuss the base of method for serum miRNA profiling.
Citation Format: Satoko Takizawa, Hideo Akiyama, Satoshi Kondo, Nobuyoshi Kosaka, Takahiro Ochiya. The difference of serum RNA profile: RNA extraction and detection method. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5294. doi:10.1158/1538-7445.AM2013-5294
Abstract 5305: Transcriptionalregulation by microRNAs in NSCLC.
Authors: Molina-Pinelo Sonia , Gutierrez-Pozo Gabriel , Pastor Maria D. , Hergueta Marta , Moreno-Bueno Gema , Garcia-Carbonero Rocio , Nogal Ana BS , Suarez Rocio , Salinas Ana , Pozo-Rodríguez Francisco , Lopez-Rios Fernando , Agulló-Ortuño Teresa , Palacios Jose , Carnero Amancio , Paz-Ares Luis G. 
Published: August 2014

Abstract
Squamous cell lung cancer and adenocarcinoma are the most common subtypes of the lung tumours.
The search for cancer-directed treatments has increased the need for understanding molecular features of either histological subtypes. The aim of this study was to identify the transcriptional regulation differences due to miRNA expression profiles between SCC and adenocarcinoma. In this work, a total of 44 patients were evaluated to assess the correlation between the miRNA and messenger
RNA expression levels. We detected changes in 56 mRNAs as well as in 9 miRNAs between SCC and adenocarcinoma. Nearly 20% of overall deregulated genes were targeted by at least one of the 9 miRNAs (miR-149, miR-205, miR-375, miR-378, miR-422a, miR-483-5p, miR-494, miR-601 and miR-708) differentially expressed between SCC and adenocarcinoma (table 1). Genes predicted (CEACAM6, CGN, CLDN3, ABCC3, MLPH, ACSL5,
TMEM45B, MUC1) to be targeted by several miRNAs were individually validated by qRT-PCR. We found genes involved in tight junctions and others involved in resistance to anticancer agents. These genes were reliable biomarkers to detect differences between the two most common histological subtypes of lung cancer. Therefore, transcriptional regulation differences through miRNA expression play an important role in key hallmarks of non-small cell lung cancer.
Citation Format: Sonia Molina-Pinelo, Gabriel Gutierrez-Pozo, Maria D. Pastor, Marta Hergueta, Gema Moreno-Bueno, Rocio Garcia-Carbonero, Ana BS Nogal, Rocio Suarez, Ana Salinas, Francisco Pozo-Rodríguez, Fernando Lopez-Rios, Teresa Agulló-Ortuño, Jose Palacios, Amancio Carnero, Luis G. Paz-Ares. Transcriptionalregulation by microRNAs in NSCLC. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5305. doi:10.1158/1538-7445.AM2013-5305
Abstract 5311: The tumorigenic fusion FGFR3-TACC3 escapes miR-99a regulation in glioblastoma .
Authors: Zhang Wei , Parker Brittany C. , Annala Matti J. , Cogdell David , Granberg Kirsi , Sun Yan , Ji Ping , Li Xia , Gumin Joy , Zheng Hong , Hu Limei , Sawaya Raymond , Fuller Gregory , Chen Kexin , Lang Frederick L. , Nykter Matti 
Published: August 2014

Abstract
Fusion genes are common chromosomal aberrations in many cancers, and can be used as prognostic markers and drug targets in clinical practice. We used whole transcriptome sequencing to search for fusion genes in glioma and discovered FGFR3-TACC3 fusions in 4 / 48 glioblastoma but not in any of 43 low- grade glioma samples. The fusion, caused by tandem duplication on 4p16.3, was found in patients of both Caucasian and Asian origin, and was mutually exclusive with EGFR/PDGFR/MET amplification. The 3’-untranslated region (3’-UTR) of FGFR3 is lost in the fusion, and we show that this leads to elevated fusion gene expression through loss of miR-99a regulation. The fusion protein promoted cell proliferation in vitro and tumor progression in vivo, while WT FGFR3 was not tumorigenic even under forced overexpression.
Citation Format: Wei Zhang, Brittany C. Parker, Matti J. Annala, David Cogdell, Kirsi Granberg, Yan Sun, Ping Ji, Xia Li, Joy Gumin, Hong Zheng, Limei Hu, Raymond Sawaya, Gregory Fuller, Kexin Chen, Frederick L. Lang, Matti Nykter. The tumorigenic fusion FGFR3-TACC3 escapes miR-99a regulation in glioblastoma . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5311. doi:10.1158/1538-7445.AM2013-5311
Abstract 5326: MicroRNA profiles discriminate among colon cancer metastasis.
Authors: Acunzo Mario , Nuovo Jerry G. , Zanesi Nicola , Di Leva Giampiero , Pichiorri Flavia , Volinia Stefano , Fernandez Cecilia , Costinenan Stefan , Bottoni Arianna , Burch Aaron , Alder Hansjuerg , Conti Laura , Antenucci Anna , Rosito Immacolata A. , Ciardi Antonio , Liu Chang G. , Drusco Alessandra , Croce Carlo M. 
Published: August 2014

Abstract
MicroRNAs are being exploited for diagnosis, prognosis and monitoring of cancer and other diseases. Their small non immunogenic size, high tissue specificity, and critical role in oncogenesis provide new biomarkers for diagnosing and classifying cancer as well as predicting patients’ outcomes. MicroRNAs signatures have been identified for many human tumors, including colorectal cancer. This tumor affects about one million individuals in developed countries, and about half of them die for recurrences. In most cases, metastatic disease is difficult to predict and to prevent with adequate therapies. The identification of microRNAs signatures for metastatic disease, could aid to define the risk and localization of recurrences in patients with unknown micrometastasis.
In this study, tissues of three different groups of colorectal cancer (CRC) patients were analyzed: microarray and cards analysis were performed on 66 patients with or without lymph nodes and/or liver recurrences; a second group of 16 metastatic patients were selected for RT-PCR; finally, in situ hybridization was carried out on tissue cores arrays belonging to a different set of patients with and without positive lymph nodes and/or liver metastasis.
MicroRNA-31, 21, 93, and 103 up-regulation together with miR-566 down-regulation defined the CRC metastatic signature. Moreover, in situ hybridization data defined metastatic localization: miR-200c up-regulation together with miR-566 down-regulation characterized lynphonodal invasion, while liver recurrences were defined by miR-31, 93 and 103 over-expression.
Citation Format: Mario Acunzo, Jerry G. Nuovo, Nicola Zanesi, Giampiero Di Leva, Flavia Pichiorri, Stefano Volinia, Cecilia Fernandez, Stefan Costinenan, Arianna Bottoni, Aaron Burch, Hansjuerg Alder, Laura Conti, Anna Antenucci, Immacolata A. Rosito, Antonio Ciardi, Chang G. Liu, Alessandra Drusco, Carlo M. Croce. MicroRNA profiles discriminate among colon cancer metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5326. doi:10.1158/1538-7445.AM2013-5326
Abstract 5334: Tumor-associated-macrophage induces CD44 expression through microRNAs suppression promotes cancer progression and chemoresistance.
Authors: Ishimoto Takatsugu , Watanabe Masayuki , Ozaki Nobuyuki , Iwatsuki Masaaki , Baba Yoshifumi , Yoshida Naoya , Baba Hideo 
Published: August 2014

Abstract
Objectives: CD44 has recently been identified as one of the cell surface markers associated with cancer stem cells (CSCs) in several types of tumor. We have reported the functional role of CD44 variant isoform in the maintenance of low reactive oxygen species (ROS) levels in gastrointestinal cancer cells. While, microRNA (miRNA) is involved in the pathogenesis of many cancers and the networks of miRNA regulate CSCs properties. However, the mechanism underlying the miRNA in the regulation of CSC marker is mostly unrevealed. Methods and Results: To investigate the mechanism in the regulation of CD44, we performed 384 miRNA quantitative RT-PCR array analysis in six human gastrointestinal cancer cell lines that differ in CD44 expression status. We found 59 miRNAs which are suppressed in CD44 high expressing cancer cells, and further investigated the predicted 33miRNAs which interact directly with CD44 3’UTR using the online miRNA target database. As a result in these analyses, we identified 2 miRNA candidates, which could regulate CD44 expression in gastrointestinal cancer. In this study, we especially focused on miR-328 and examined the functional relevance of miR-328 implicated in CD44 regulation. We found that gastrointestinal cancer cells transfected with miR-328 mimic decreased CD44 expression and led to inhibition of cancer cell growth and impairing chemo- and ROS- resistance. Furthermore, we investigated the mechanism underlying the regulation of miR-328 by using human macrophage and gastrointestinal cancer cell lines. We found that co-culture with tumor-associated-macrophages (TAMs) triggers the CD44 expression through suppression of miR-328 in gastrointestinal cancer cells and promote stem-like property that possess sphere-forming ability. Finally, we showed that TAMs are closely related with both CD44 over-expression and miR-328 under-expression in human gastric cancer tissue. Conclusions: These findings reveal that TAMs in tumor microenvironment contribute CD44 expression via miR-328 suppression, resulting in tumor progression through enhancing ROS defense.
Citation Format: Takatsugu Ishimoto, Masayuki Watanabe, Nobuyuki Ozaki, Masaaki Iwatsuki, Yoshifumi Baba, Naoya Yoshida, Hideo Baba. Tumor-associated-macrophage induces CD44 expression through microRNAs suppression promotes cancer progression and chemoresistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5334. doi:10.1158/1538-7445.AM2013-5334
Abstract 536: Insulin-like growth factor II (IGF-II) is a potential target for the treatment of triple negative breast cancers (TNBC).
Authors: Radhakrishnan Vinodh Kumar , Tan Qianwei , De León Marino A. , De León Daisy D. 
Published: August 2014

Abstract
In the United States, African American (AA) women have a lower incidence of breast cancer compared to Caucasian (CA) women, but higher overall mortality. Our lab have demonstrated that Breast Cancer from AA patients express significantly higher levels of IGF-II and show a higher activation of the IGF signaling system in African American (AA) when compared to Caucasian (CA) women. We showed that IGF-II promotes breast cancer progression and metastasis by inhibiting tumor cell death and promoting resistance to chemotherapy, thus contributing to increased breast cancer (BC) mortality. This study was designed to determine how IGF-II contributes to the aggressiveness of TNBC, the most deadly of breast tumors, which is highly prevalent among AA. To analyze IGF-II in a TNBC cell model, we chose cell lines established from tumors of AA and CA breast cancer patients. Expression of IGF-II and IGF-II regulated proteins mRNA expression was probed using the CFX96 real time PCR system. Similarly, IGF-II and related proteins expression was analyzed by western blots and chemiluminescence. We also characterized the epigenetic activation of IGF-II in these cell lines since variation in the expression of IGF-II alleles regulates a signature of proteins associated with tumor aggressiveness. Our exciting results demonstrated that higher IGF-II levels in TNBC cells from AA was associated with distinct epigenetic changes that included different promoter activation and higher levels of IGF-II translation which are inheritable traits. In contrast, TNBC from CA had higher IGF-II levels due to different molecular IGF-II regulation. Thus, IGF-II is an important biomarker and can be used as therapeutic target for treatment of TNBC.
Citation Format: Vinodh Kumar Radhakrishnan, Qianwei Tan, Marino A. De León, Daisy D. De León. Insulin-like growth factor II (IGF-II) is a potential target for the treatment of triple negative breast cancers (TNBC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 536. doi:10.1158/1538-7445.AM2013-536
Abstract 5374: Sulforaphane reactivates the expression of Nrf2 through CpGs demethylation in TRAMP C1 cells.
Authors: Zhang Chengyue , Su Zheng-Yuan , Khor Tin Oo , Kong Ah-Ng 
Published: August 2014

Abstract
Prostate cancer is one of the most deadly malignancies among men in the United States. Recent evidence suggests epigenetic alteration is involved during the development and progression of prostate cancer. Previously we have demonstrated that Nrf2, a key regulator of cellular antioxidant defense systems, was epigenetically silenced in TRAMP prostate cancers, as well as tumorigenic TRAMP C1 cells. Sulforaphane (SFN), an isothiocyanate rich in cruciferous vegetables, has been shown to be a potent cancer prevention agent for years. The aim of this study is to investigate the potential of SFN to reactivate the expression of Nrf2 in TRAMP C1 cells via epigenetic modifications. Bisulfite genomic sequencing (BGS) showed that treatment of SFN resulted in demethylation of the first 5 CpGs in the promoter region of Nrf2 gene. Methylation DNA immunoprecipitation (MeDIP) analysis revealed that SFN significantly reduced the anti-mecyt antibody binding to the first 5 CpGs of the Nrf2 promoter, corresponding to the BGS results. Reversion of the methylation status was found to be associated with re-expression of Nrf2 and its downstream NQO-1 at the mRNA and protein levels. Further analysis showed that SFN treatment decreased the expression of DNA methyltransferases (DNMTs), particularly DNMT1 and DNMT3a. Though SFN treatment showed differential effects on the protein expression of various HDACs, it increased the global level of active chromatin marker acetyl-H3. Taken together, our study suggests that SFN may exert its chemoprevention effect through epigenetic regulation modification of Nrf2 gene with subsequent induction of its downstream anti-oxidative stress pathway.
Citation Format: Chengyue Zhang, Zheng-Yuan Su, Tin Oo Khor, Ah-Ng Kong. Sulforaphane reactivates the expression of Nrf2 through CpGs demethylation in TRAMP C1 cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5374. doi:10.1158/1538-7445.AM2013-5374
Abstract 538: IGF2 role in trastuzumab-resistance in JIMT-1 cells.
Authors: Helu Xousaen M. , De Leon Daisy D. 
Published: August 2014

Abstract
Breast cancer is the second leading cause of death in women. Overexpression of Human Epidermal Growth Factor Receptor 2 (HER2) is detected in 20-30% of breast cancers. Overexpression of HER2 is linked to poor prognosis, more aggressive phenotype, and resistance to chemotherapy and hormonal treatment. HER2 is part of a four member family of cell surface receptors that are implicated in transmission of signals controlling cell growth and differentiation. HER2 has an intracellular domain with tyrosine kinase catalytic activity. Dimerization of HER2 activates the MAP kinase and AKT pathways. HER2 receptor also heterodimerizes with the IGF1 receptor in trastuzumab-resistant cell lines. The insulin-like growth factor 2 (IGF2) has an important role in fetal and cancer development signaling through the insulin-like growth factor 1 receptor (IGF1R), the insulin receptor (InsR), and cross-talk with the estrogen receptor alpha and beta (ERα, ERß). We hypothesize that IGF2 mediates trastuzumab-resistance in JIMT-1 cell line. IGF2 mRNA and protein levels were determined in trastuzumab-sensitive cell lines (BT474, SKBR3, and ZR 75-30) and trastuzumab-resistant cell line (JIMT-1) by qPCR and Western blot. We also analyzed the effect of IGF2 inhibition treatment on the phosphorylation levels of HER2. Our study showed that IGF2 increases in trastuzumab-resistant cell line, JIMT-1. Furthermore, inhibition of IGF2 decreases JIMT-1 cell viability compared to control and renders cells sensitive to trastuzumab. These findings provide a potential therapy target for trastuzumab-resistant breast cancers.
Citation Format: Xousaen M. Helu, Daisy D. De Leon. IGF2 role in trastuzumab-resistance in JIMT-1 cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 538. doi:10.1158/1538-7445.AM2013-538
Abstract 5383: Overexpression of the vitamin D catabolizing enzyme CYP24A1 is caused by gene amplification and results in highly proliferative colorectal tumors.
Authors: Höbaus Julia , Aggarwal Abhishek , Hummel Doris M. , Thiem Ursula , Fetahu Irfete , Mesteri Ildiko , Kallay Enikö 
Published: August 2014

Abstract
Vitamin D insufficiency increases risk of colorectal cancer. Vitamin D is produced photochemically in the skin, thus, low sunlight exposure results in vitamin D insufficiency. Vitamin D is further processed in the liver to its storage form calcidiol (25-OH vitamin D3). Calcidiol can be activated by 1α-hydroxylation to the secosteroid hormone calcitriol (1α,25-OH vitamin D3). Although systemic levels of bioactive calcitriol are regulated by the kidneys, almost every tissue can synthesize and degrade calcitriol. Tissue calcitriol acts in an autocrine/paracrine manner and controls proliferation, apoptosis, and differentiation.
In colorectal cancer, the calcidiol and calcitriol-degrading enzyme CYP24A1 is substantially overexpressed both on mRNA and protein level. High CYP24A1 levels markedly reduce the half-life of vitamin D metabolites, likely reducing the anti-tumorigenic effects of calcitriol in the tumor. The causes and consequences of this overexpression are not fully understood.
Here, we investigated gene amplification of the CYP24A1 locus (20q13.2) as a possible cause of CYP24A1 overexpression and increased proliferation as a consequence thereof. Quantitative real time PCR assays showed that approximately 60% of colorectal tumors carry CYP24A1 gene amplification (n=127). This gene amplification correlated with increased mRNA expression (ρ=0.38, p&lt;0.001). Aberrantly high CYP24A1 expression may reduce the anti-proliferative actions of calcitriol and lead to increased proliferation. In our colorectal cancer cohort, CYP24A1 mRNA expression correlated with expression of several proliferation markers (e.g. CDC6 ρ=0.60, p&lt;0.001).
In conclusion, our data suggest that CYP24A1 gene amplification results in increased mRNA expression in colorectal tumors. Further, high CYP24A1 expression correlates with increased proliferation, possibly caused by an inhibition of the anti-proliferative effects of calcitriol. Tumor specific inhibition of CYP24A1 may provide a future strategy to restore local vitamin D levels and its anti-tumorigenic activities.
Citation Format: Julia Höbaus, Abhishek Aggarwal, Doris M. Hummel, Ursula Thiem, Irfete Fetahu, Ildiko Mesteri, Enikö Kallay. Overexpression of the vitamin D catabolizing enzyme CYP24A1 is caused by gene amplification and results in highly proliferative colorectal tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5383. doi:10.1158/1538-7445.AM2013-5383