bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3944: High incidence of somatic BAP1 alterations in sporadic malignant mesothelioma
Authors: Nasu Masaki , Pastorino Sandra , Luk Hugh , Flores Erin , Baumann Francine , Powers Amy , Kanodia Shreya , Gaudino Giovanni , Zhang Yu-an , Gazdar Adi , Yang Haining , Pass Harvey I. , Emi Mitsuru , Carbone Michele 
Published: August 2015

Abstract
Background: Malignant mesothelioma (MM) is a lethal tumor whose pathogenesis results from complex interactions between host genetics and environmental carcinogens. BAP1 mutations were reported in 22% and 23% of sporadic MM in two US Caucasian studies whereas BAP1 mutations were found in 61% of sporadic MM in a Japanese study. The significant discrepancy in frequency of BAP1 mutations suggested either a possible influence of ethnicity or differences related to the methodological approaches. Methods: To investigate this apparent discrepancy, we carried out comprehensive genomic analyses using multiple techniques in order to detect somatic alterations of the BAP1 gene in tumors of 22 US Caucasian MM patients. Results: Six mutations were detected by Sanger sequencing, gross gene alterations were found in 7 MM specimens by Multiplex Ligation-Dependent Probe Amplification and copy number analysis, and a new splice variant was identified by cDNA sequencing. Changes in methylation were not observed in our study. Immunohistochemistry (IHC) revealed nuclear BAP1 staining in the 8 MM tumors containing wild-type BAP1 while tumor cells in the 14 biopsies with mutated BAP1 did not show any nuclear staining. We extended our BAP1 IHC analysis to an independent cohort of MM samples from the National Virtual Mesothelioma Bank and we found loss of BAP1 nuclear staining in 46 out of 67 biopsies. Moreover we found similar frequency of BAP1 loss across different MM histological subtypes. Conclusions: We identified somatic alterations of the BAP1 gene in 73.7% of Caucasian MM tumors in two independent cohorts of somatic MMs, underscoring the need to apply integrated genomic analyses to scrutinize the BAP1 gene for its alterations. Immunohistochemistry was the most reliable technique to detect BAP1 mutations in MM biopsies. The high incidence of alterations establishes BAP1 as the most commonly mutated gene in MM, regardless of ethnic background or histological subtype.
Citation Format: Masaki Nasu, Sandra Pastorino, Hugh Luk, Erin Flores, Francine Baumann, Amy Powers, Shreya Kanodia, Giovanni Gaudino, Yu-an Zhang, Adi Gazdar, Haining Yang, Harvey I. Pass, Mitsuru Emi, Michele Carbone. High incidence of somatic BAP1 alterations in sporadic malignant mesothelioma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3944. doi:10.1158/1538-7445.AM2015-3944
Abstract 3947: BP1 protein, a transcription factor, is secreted by breast cancer cells
Authors: Rheey Jinguen , Yakovleva Anna , Yamane Kellie-Ann , Berg Patricia E. 
Published: August 2015

Abstract
Background. BP1 is a homeobox gene which is normally expressed during early hematopoiesis. Homeotic proteins regulate the expression of multiple genes involved in development and differentiation. We have previously shown that BP1 mRNA and protein levels are elevated in 80% of women with invasive ductal breast cancer. Furthermore, BP1 protein (pBP1) overexpression is associated with larger and more aggressive breast tumors. In cultured breast cancer cell lines overexpressing pBP1, we observe decreased cell death and increased proliferation. BP1 overexpression has also been found to stimulate known oncogenes including BCL2 and c-MYC. Methods. Levels of pBP1 were detected in cell extracts (CE) and conditioned media (CM) using Western Blot analysis. Depleted media (DM), in which the pBP1 was removed, and recombinant BP1 protein (rpBP1) were used as controls. Cell viability was assessed using MTT assays. Real-time qPCR was used to measure expression of selected oncogenes.
Results. Our results show that: (a) pBP1 is secreted from three breast cancer cell lines but not from two normal breast epithelial cell lines. (b) pBP1 exhibits mitogenic activity towards breast cancer cells and normal breast cells, whether cells are grown in media containing 10x conditioned medium (CM) from cells secreting pBP1 or in media containing purified recombinant pBP1 (rpBP1). (c) Growth of breast cancer cells or normal breast epithelial cells in CM or rpBP1 leads to up-regulation of selected oncogenes known to be targets of BP1. These oncogenes include BCL2 and MET. BP1 itself was stimulated, but only in normal breast epithelial cells. The mechanism of secretion is under investigation.
Conclusions. Our data suggest that secreted pBP1 can stimulate cell proliferation and gene expression in tumor cells as well as in nearby normal cells.
Citation Format: Jinguen Rheey, Anna Yakovleva, Kellie-Ann Yamane, Patricia E. Berg. BP1 protein, a transcription factor, is secreted by breast cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3947. doi:10.1158/1538-7445.AM2015-3947
Abstract 3951: Functional analysis of the 11q23.3 glioma susceptibility locus
Authors: Baskin Rebekah , Woods Nicholas , Mendoza-Fandino Gustavo , Forsyth Peter , Egan Kathleen , Monteiro Alvaro 
Published: August 2015

Abstract
Glioma is the most common malignant primary brain tumor and is associated with poor prognosis. Single nucleotide polymorphisms (SNPs) associated with glioma risk have recently been investigated through genome-wide association studies (GWAS). Results of these studies have implicated seven independent glioma risk loci in six chromosomal regions. However, the mechanisms by which these SNPs contribute to cancer risk are still unknown. Here, we performed an in-depth functional analysis of one of these risk loci located near the PHLDB1 gene on 11q23.3. We began by retrieving all SNPs in linkage disequilibrium (LD; r2 ≥ 0.2) with the glioma-associated SNP (rs498872). 61 genes contained in the region defined by a boundary of 1Mb from each end of the LD SNPs were considered candidate targets. A subset of 10 candidate functional enhancer/promoter SNPs was defined by overlap with ENCODE biofeatures and allele specific activity in luciferase and EMSA assays in astrocytes and GBM cells. Functional SNPs in the promoter of PHLDB1 implicated its transcriptional regulation in glioma risk. Chromatin conformation capture (3C) identified a physical interaction between one enhancer SNP and the promoter of the DDX6 gene. We also conducted neurosphere formation assays to evaluate the functional role of two top candidate genes, PHLDB1 and DDX6. We found that knockdown of either gene caused a significant reduction in U87MG neurosphere number and size. Taken together, these studies revealed the functional landscape of the 11q23.3 glioma susceptibility locus and implicated the transcriptional regulatory network of PHLDB1 and DDX6 in the mechanism of increased glioma risk.
Citation Format: Rebekah Baskin, Nicholas Woods, Gustavo Mendoza-Fandino, Peter Forsyth, Kathleen Egan, Alvaro Monteiro. Functional analysis of the 11q23.3 glioma susceptibility locus. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3951. doi:10.1158/1538-7445.AM2015-3951
Abstract 3954: lincRNA-UFC1 facilitates cell proliferation and tumor growth in hepatocellular carcinoma by upregulating HuR/β-catenin expression
Authors: LIU LI , Wu Dehua , Cao Chuanhui 
Published: August 2015

Abstract
BACKGROUND & AIMS: Long noncoding RNAs (lncRNAs) have been identified as novel regulators of biologic behaviors in various cancers. However, the oncogenic mechanisms of lincRNA-UFC1 associated with hepatocellular carcinoma (HCC) growth and progression are still unknown. Here, we delved into the mechanistic aspects of lincRNA-UFC1in HCC progression.
METHODS: LncRNA expression profiles are assessed by microarray analysis. Expression of lincRNA-UFC1 was examined in 2 HCC cohorts (cohort 1, n = 49; cohort 2, n = 131) by quantitative real-time PCR or by in situ hybridization. The functions of lincRNA-UFC1 in HCC cells were elucidated by in vitro and in vivo gain- and loss-of-function experiments. The mechanism by which lincRNA-UFC1 contributes to HCC progression was explored through luciferase reporter assays, RNA immunoprecipitation and RNA pull-down assays.
RESULTS: LincRNA-UFC1 was strongly upregulated in HCC tissues, compared with corresponding non-tumor tissues in patients from 2 cohorts. LincRNA-UFC1 expression is associated with tumor size, Barcelona Clinic Liver Cancer (BCLC) stage and poor prognosis. Enhanced lincRNA-UFC1 expression promotes cell proliferation and tumor growth, inhibits apoptosis, and induces cell cycle progression, whereas decreased lincRNA-UFC1 expression represented the opposite effects. Furthermore, lincRNA-UFC1 directly interacts with HuR and regulates β-catenin expression. The level of lincRNA-UFC1 is positively correlated with that of β-catenin in HCC tissues.
CONCLUSIONS: These findings indicate that lincRNA-UFC1 promotes HCC development and progression, indicating its role as a potential therapeutic target for HCC.
Citation Format: LI LIU, Dehua Wu, Chuanhui Cao. lincRNA-UFC1 facilitates cell proliferation and tumor growth in hepatocellular carcinoma by upregulating HuR/β-catenin expression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3954. doi:10.1158/1538-7445.AM2015-3954
Abstract 3959: microRNA as a potential biomarker for hepatitis C virus mediated end-stage liver disease progression
Authors: Ray Ratna B. 
Published: August 2015

Abstract
HCV accounts for the most frequent cause of end stage liver disease–including hepatocellular carcinoma (HCC), and liver transplantation in the western world. Since HCV-mediated end stage liver diseases are diagnosed much later after infection, identifying the HCV infected individuals at high risk for developing HCC will permit surveillance, early detection and chemoprevention. Liver biopsy or Fibroscan (often used now) has major limitations. Moreover, neither liver biopsy nor fibroscan can predict who will progress to more severe disease. The relationship between HCV infection and microRNA (miRNA) expression is of considerable interest in understanding liver disease progression to HCC. In this present study, we performed a systematic screening approach to identify upregulated miRNAs in the plasma/serum of HCV infected patients with different stages of hepatic histological disease severity. We initially screened serum samples of HCV infected patients with fibrosis and compared with sera of healthy volunteers using serum miRNA array profiling, and identified a group of modulated miRNAs. Subsequent study demonstrated that miR-20a in HCV infected fibrosis and HCC patients sera were significantly upregulated when compared with that of healthy volunteers or non-HCV associated liver disease. However, there was no correlation between the serum levels of miR-20a with HCV viral loads. We next investigated longitudinal plasma samples from HCV-infected patients. Our results suggested that miR-20a remained unaltered in HCV-infected patients who progressed from acute to chronic infection. These data provide evidence that plasma/serum level of miR-20a has potential as sensitive and cost-effective biomarkers for early detection of HCV mediated liver disease. Conclusion: The circulating miR-20a may serve as a potential for predictive biomarker in HCV mediated end stage liver disease.
Citation Format: Ratna B. Ray. microRNA as a potential biomarker for hepatitis C virus mediated end-stage liver disease progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3959. doi:10.1158/1538-7445.AM2015-3959
Abstract 3961: Utility of mir-21 detection by rapid chromogenic in-situ hybridization in the diagnosis of well and moderately differentiated hepatocellular carcinoma
Authors: Kolhe Ravindra , Rojiani Amyn , Mondal Ashis , Mangaonkar Abhishek A. 
Published: August 2015

Abstract
Background: An estimated 80-90% of all hepatocellular carcinomas (HCC) arise from cirrhotic liver in chronic hepatitis B or C infection. Identifying well-differentiated HCC arising in the background of cirrhosis is a challenging task relying solely on morphology of core biopsies. In addition, presence of dysplasia (micro/macro) in cirrhotic nodules makes the task more difficult. In HCC, microRNAs (miRNAs) have an aberrant expression profile with possible applications in diagnosis, especially for early, symptomatic disease. Sub-cellular and tissue localization of miRNAs may help us understand their biological roles and contribution to disease along with aiding diagnosis.
Design: The aim of this study was to evaluate the utility of mir-21 detection by rapid chromogenic in-situ hybridization (CISH) as a diagnostic tool in the setting of well and moderately differentiated HCCs. Archival blocks and slides were retrieved and reviewed after obtaining IRB approval (table 1). Manufacturers guidelines were followed for CISH (NAR-1, FAM-labeled Has-miR-21 probe) on a total of 202 cases. Nuclear mir-21 CISH stain was graded as: negative (-), weak (1+), moderate (2+) or strong (3+) and distribution was graded as: focal (&lt;10%), multifocal (10-50%) or diffuse (&gt;50%).
Table 1.Table showing cases considered for mir-21 detection by CISH.HistologyNumber of casesHCC150Intrahepatic cholangiocarcinoma12Metastases from colonic adenocarcinoma23Metastases from gallbladder adenocarcinoma5Normal liver tissue12
Results: Neoplastic cells in HCC showed a strong (2-3) multifocal to diffuse nuclear staining for mir-21 in 100% of the cases of whole tissue slides and 91% of HCC cases in tissue microarray slides when compared to the staining pattern seen in normal liver cells (0%). As expected, 85% of cases with liver metastases from colonic and gallbladder adenocarcinoma showed strong nuclear staining for mir-21.
Conclusion: Rapid CISH technique can clearly identify increased nuclear expression of mir-21 and aid in diagnosis of well and moderately differentiated HCC.
Citation Format: Ravindra Kolhe, Amyn Rojiani, Ashis Mondal, Abhishek A. Mangaonkar. Utility of mir-21 detection by rapid chromogenic in-situ hybridization in the diagnosis of well and moderately differentiated hepatocellular carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3961. doi:10.1158/1538-7445.AM2015-3961
Abstract 3964: How to fish a good micro-marker out from a worthless lake: The case of cell-free miR-181a-5p and breast cancer
Authors: Ferracin Manuela , Lupini Laura , Salamon Irene , Saccenti Elena , Zagatti Barabara , Mangolini Alessandra , Zanzi Maria Vittoria , Carcoforo Paolo , Rocchi Andrea , Cavallesco Giorgio , Frassoldati Antonio , Hollingsworth Alan B. , Negrini Massimo 
Published: August 2015

Abstract
The hypothesis to use microRNAs (miRNAs) circulating in blood as cancer biomarkers was formulated some years ago based on promising initial results. After some exiting discoveries, however, it became evident that the accurate quantification of cell-free miRNAs (i.e. that retrieved in serum or plasma) was more challenging than expected. Difficulties were linked to the strong impact that many, if not all, pre- and post- analytical variables (i.e. tissue preparation, storage condition, extraction method, quantification technique, normalization approach) have on the final result.
In this study, we used currently available high-throughput technologies to identify miRNAs present in plasma and serum of patients with breast, colorectal, lung and melanoma tumors, and healthy controls. Then, we used droplet digital PCR (ddPCR) technology to get an accurate absolute quantification of specific cell-free miRNAs. We assessed the level of 8 different miRNAs (miR-320a, miR-21-5p, miR-378a-3p, miR-181a-5p, miR-3156-5p, miR-2110, miR-125a-5p, miR-425-5p, miR-766-3p) in 180 samples from healthy controls and cancer patients. We identified miRNAs specifically modulated in one or more cancer types. Plasma and serum from the same patient provided different results in terms of absolute miRNA amount and modulation. The significant reduction of miR-181a-5p levels in serum of breast cancer patients was further validated using two independent cohorts, one from Italy (n = 70) and one from US (n = 90). This study finally powers the use miR-181a-5p as a breast cancer biomarker.
Citation Format: Manuela Ferracin, Laura Lupini, Irene Salamon, Elena Saccenti, Barabara Zagatti, Alessandra Mangolini, Maria Vittoria Zanzi, Paolo Carcoforo, Andrea Rocchi, Giorgio Cavallesco, Antonio Frassoldati, Alan B. Hollingsworth, Massimo Negrini. How to fish a good micro-marker out from a worthless lake: The case of cell-free miR-181a-5p and breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3964. doi:10.1158/1538-7445.AM2015-3964
Abstract 3965: MicroRNA markers for the diagnosis of pancreatic cancer
Authors: Kojima Motohiro , Sudo Hiroko , Kawauchi Junpei , Takizawa Satoko , Kondou Satoshi , Nobumasa Hitoshi , Ochiai Atsushi 
Published: August 2015

Abstract
It is recently reported that microRNAs (miRNAs) are stably present in serum and potentially useful in the diagnosis of cancer. Using highly sensitive microarray, 3D-Gene®, we examined comprehensive miRNA expression profiles in serum obtained from 66 pancreatic cancer patients and 100 matched healthy volunteer as the study set, and found that 122 miRNA markers differentiated pancreatic cancer patients from healthy control with a statistical significance. We then validated the diagnostic performance of these markers using serum obtained from 33 pancreatic cancer patients and 50 healthy controls. One of the single miRNA markers for pancreatic cancer yielded more than 90% diagnostic sensitivity and specificity, and combined use of two markers perfectly differentiated cancer and healthy samples. Furthermore, combinations of miRNAs that differentiated pancreatic cancer not only from healthy samples but also from non-malignant pancreatic diseases or other digestive (esophagus, stomach, liver and colon) cancers were also identified, and their diagnostic accuracies were superior to those of CEA or CA19-9. Our results suggest that these miRNA markers have clinical values to screen out pancreatic cancer patients.
Citation Format: Motohiro Kojima, Hiroko Sudo, Junpei Kawauchi, Satoko Takizawa, Satoshi Kondou, Hitoshi Nobumasa, Atsushi Ochiai. MicroRNA markers for the diagnosis of pancreatic cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3965. doi:10.1158/1538-7445.AM2015-3965
Abstract 3974: A preclinical study for miR181b as therapeutic in Eu-TCL1FL-tg mouse model for CLL
Authors: Bresin Antonella , Callegari Elisa , D'Abundo Lucilla , Cattani Caterina , Bassi Cristian , Zagatti Barbara , Narducci Maria Grazia , Caprini Elisabetta , Pekarsky Yuri , Croce Carlo Maria , Sabbioni Silvia , Negrini Massimo , Russo Giandomenico 
Published: August 2015

Abstract
Chronic lymphocytic leukemia (CLL) is a malignancy of B cells with immunophenotype of memory cells. Downstream pathways to BCR, like NFkB, AKT and ERK, and anti-apoptotic proteins such as Bcl2 and Mcl1, are thought to contribute to expansion and survival of the malignant cells. CLL patients show different clinical course: tumor clones having no V-gene mutations, many CD38+ or ZAP-70+ B cells, chromosome 11q deletion and high expression of TCL1, had an aggressive, usually fatal course, whereas patients with mutated clones, few CD38+ or ZAP-70+ B cells and low TCL1 expression, had an indolent course. Recent studies identified a microRNA signature associated with prognosis and progression in B-CLL. Particularly, miR181b is down-regulated in aggressive forms of CLL and its expression is inversely correlated to Tcl1 levels.
An increasing number of studies are considering microRNAs as potentially useful therapeutic agents. Given that MCL-1, BCL-2 and TCL1 are proved targets for miR181b, that Akt activation is enhanced by Tcl1 and a crosstalk between Akt and ERK or NFkB exists, we performed a preclinical evaluation of miR181b therapeutic efficacy in a mouse model of CLL, the Eu-TCL1 transgenic mouse, previously generated by us.
In vitro enforced expression of miR-181b mimics induced a significant apoptotic effect in human B-cell line EHEB, as well as in mouse Eμ-TCL1 leukemic splenocytes. Molecular analyses revealed that miR-181b not only affected the expression of Tcl1, Bcl2 and Mcl1 anti-apoptotic proteins, but also increased the expression level of the NFkB inhibitor protein IkB-alpha and reduced the phosphorylation levels of Akt and Erk1/2. Notably, an anti-TCL1 siRNA could similarly down-modulate Tcl1 but exhibited a reduced or absent activity on other relevant proteins, as well as a reduced effect on cell apoptosis and viability. In vivo studies indicated a significant capability of miR-181b in reducing leukemic cells expansion and increasing survival of treated mice. These data indicate that miR-181b exerts a broad range of actions, affecting proliferative, survival and apoptotic pathways, both in mice and human, and can potentially be employed to reduce expansion of B-CLL leukemic cells.
Citation Format: Antonella Bresin, Elisa Callegari, Lucilla D'Abundo, Caterina Cattani, Cristian Bassi, Barbara Zagatti, Maria Grazia Narducci, Elisabetta Caprini, Yuri Pekarsky, Carlo Maria Croce, Silvia Sabbioni, Massimo Negrini, Giandomenico Russo. A preclinical study for miR181b as therapeutic in Eu-TCL1FL-tg mouse model for CLL. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3974. doi:10.1158/1538-7445.AM2015-3974