bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3971: Genome-wide tissue-based microRNA signature in healthy women predicting breast cancer risk
Authors: Taslim Cenny , Weng Daniel Y. , Brasky Theodore M. , Dumitrescu Ramona G. , Huang Kun , Kallakury Bhaskar V. s. , Krishnan Shiva , Llanos Adana A. , Marian Catalin , Schneider Sallie S. , Spear Scott L. , Troester Melissa A. , Freudenheim Jo L. , Geyer Susan , Shields Peter G. 
Published: August 2015

Abstract
Introduction: Small non-coding microRNAs (miRNAs) play important roles in both normal breast development and breast carcinogenesis. The goal of this study is to identify miRNAs in normal breast tissues which are related to breast cancer risk.
Materials and Methods: We used a high-throughput digital counting of miRNAs without amplification (Nanostring®) to examine miRNA expression in 161 reduction mammoplasty (RM) tissues from two independent studies. A multivariate model was used to identify miRNAs associated with breast cancer risk (based upon Gail risk scores) in a training study (n = 90) then the model was validated in a replication study (n = 71). Risk-related microRNAs were then evaluated in serum for associations with real breast cancer cases using publically available prospective cohort (Sister Study, n = 410).
Results: We identified a 41-miRNA signature in healthy women distinguishing high risk from low risk women with a prediction accuracy of 82% (95% CI = 80% to 87%) in the training study. Predictive accuracy was 69% (95% CI = 65% to 73%) in the replication study. 34 of 41 serum miRNAs that mapped to public data predicted women who developed breast cancer within 18 months after blood draw from those who remained cancer free with accuracy of 59% (95% CI = 57% to 61%). We have also shown that these accuracies were significantly higher than random chance (P &lt; 0.0001). IPA canonical pathway analysis revealed that the risk-related microRNAs targets were significantly enriched for HER-2 signaling in breast cancer, and estrogen-dependent breast cancer signaling, and other important cancer pathways such as molecular mechanisms of cancer, PI3K/AKT signaling, PTEN signaling, and TGF-beta signaling.
Conclusion: Our results indicate that miRNA profiling from breast tissue of healthy patients may identify clinically useful predictors of breast cancer risk and these miRNAs may also work as non-invasive biomarker for early breast cancer prediction.
Citation Format: Cenny Taslim, Daniel Y. Weng, Theodore M. Brasky, Ramona G. Dumitrescu, Kun Huang, Bhaskar V. s. Kallakury, Shiva Krishnan, Adana A. Llanos, Catalin Marian, Sallie S. Schneider, Scott L. Spear, Melissa A. Troester, Jo L. Freudenheim, Susan Geyer, Peter G. Shields. Genome-wide tissue-based microRNA signature in healthy women predicting breast cancer risk. [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 3971. doi:10.1158/1538-7445.AM2015-3971
Abstract 3989: MicroRNA-16 and microRNA-193b as serological predictors for chemoradiation response in esophageal squamous cell carcinoma patients
Authors: Lee Nikki P. , Lai Kenneth K. , Chan Kin Tak , Tong Daniel K. , Law Simon 
Published: August 2015

Abstract
Esophageal cancer is one of the most deadly malignancies along the gastrointestinal tract. Esophageal squamous cell carcinoma (ESCC) is the most common cell type occurring at the upper and middle part of the esophagus. Surgery remains the mainstay treatment for this malignancy, however the long-term prognosis is modest with a 5-year overall survival of approximately 30%. To improve the treatment outcome of this cancer, multimodal treatment strategies including neoadjuvant chemoradiation have been implemented. Such pre-surgery treatment indeed leads to better clinical outcome and increases the chance for cure. Unfortunately patients who do not respond may have to undergo prolonged, unnecessary and potentially toxic treatments with no benefits. Currently, there is no reliable method for chemoradiation response prediction. To address this clinical limitation, we have established a non-invasive assay to stratify chemoradiation responders from non-responders. This study is systematically divided into three phases. In the discovery phase (phase I), we found 23 human microRNAs (out of 742 human microRNAs) with more than 2.5-fold elevation in serum from chemoradiation responders when compared to non-responders. In the selection and small-scale validation phase (phase II), small-scale validation in an independent cohort showed that microRNA-16 and microRNA-193b were two most powerful candidates for indicating chemoradiation responders. In the large-scale validation phase (phase III), we have further validated and confirmed the feasibility of microRNA-16 and miroRNA-193b as discriminators for chemoradiation response in a large cohort of more than a hundred patients. Standard curves were also constructed for these two microRNAs for copy number quantitation. In all, we have newly established a highly sensitive and specific blood-based assay with specific cut-offs for discriminating ESCC patients who are responsive to chemoradiation. This assay works by quantitating the serum level of microRNA-16 and microRNA-193b in ESCC patients, such that patients would be advised to receive pre-surgery chemoradiation if they have elevated levels of circulatory microRNA-16 and microRNA-193b. The development of this assay will benefit patient care by formulating individualized treatment plans.
Note: This abstract was not presented at the meeting.
Citation Format: Nikki P. Lee, Kenneth K. Lai, Kin Tak Chan, Daniel K. Tong, Simon Law. MicroRNA-16 and microRNA-193b as serological predictors for chemoradiation response in esophageal squamous cell carcinoma patients. [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 3989. doi:10.1158/1538-7445.AM2015-3989
Abstract 3990: Identification of microRNAs from exosomes of bulk and stem cells from prostate cancer by next generation sequencing
Authors: Sanchez Catherine A. , Andahur Eliana , Valenzuela Rodrigo , Castellon Enrique , Ramos Christian , Triviño Juan Carlos 
Published: August 2015

Abstract
Cancer stem cells (CSCs) are related with cancer initiation, metastasis, resistance and recurrence, by regulating their environment in different ways, including the release of exosomes that modify surrounding and distant cells. Exosomes contain, among other molecules, miRNAs. By identifying the entire spectrum of miRNAs included in exosomes from prostate cancer (PCa) cells by next generation sequencing (NGS), is possible to identify miRNAs specifically released by CSCs, and those related with microenvironment regulation.
We stablished adherent primary cell cultures (bulk cells) from PCa tissue from 5 patients. Later, from these cells we obtained CSCs enriched prostatospheres. From bulk and CSCs cultures we purified exosomes by precipitation (ExoQuick-TC, SBI) for miRNAs extraction (mirVana, Ambion). Quality of miRNAs was assessed by Bioanalizer (Agilent Technologies). NGS was performed in the Illumina platform (MiSeq, Illumina) according to manufacturer instructions. Bioinformatic analyses were carried out by Sistemas Genómicos. Overexpressed miRNAs were detected in plasma exosomes by TaqMan miRNA Assays (Lifetechnologies).
We identified 1839 miRNAs in exosomes, and 223 species were differentially expressed between bulk and CSCs, but only 26 significantly. Nineteen of them were known species including 6 that were overexpressed in CSCs respect to bulk cells. These miRNAs target genes related with cell differentiation, matrix remodeling and genic expression. From all miRNA detected, 3 were highly overexpressed among all, and were detected in exosomes isolated from plasma of men with prostatic disease.
Our study extensively characterizes the miRNA from exosomes of PCa cells. Exosomes contain high diversity of miRNAs, different in CSCs and bulk cells, suggesting differential regulation of their microenvironment. From these, CSCs exosome-related miRNAs could be released to bloodstream and play a role in PCa progression and metastasis (FONDECYT 11121525/1140417).
Citation Format: Catherine A. Sanchez, Eliana Andahur, Rodrigo Valenzuela, Enrique Castellon, Christian Ramos, Juan Carlos Triviño. Identification of microRNAs from exosomes of bulk and stem cells from prostate cancer by next generation sequencing. [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 3990. doi:10.1158/1538-7445.AM2015-3990
Abstract 4001: Array profiling identified upregulated miRNAs and target genes and pathways in laryngeal squamous cell carcinoma
Authors: Lian Meng , Liu Xiaoqin , Han Demin , Fang Jugao , Chen Zhong 
Published: August 2015

Abstract
Background: Laryngeal squamous cell carcinoma (LSCC) is prevalent in the Chinese population, where smoking is a major carcinogen. MicroRNAs (miRNAs) and their gene targets potentially contribute to the multistep regulatory processes of LSCC development.
Objective: The purpose of this study is to investigate and validate aberrant expressed miRNAs in LSCC, and analyze the putative target genes of the screened miRNAs.
Methods: Six pairs of primary Stage II-IV LSCC and adjacent non-neoplastic tissues were surgically removed for miRNA array analysis using the Affymetrix GeneChip miRNA Array 3.0, containing probes for 5683 miRNAs, and the significantly altered miRNAs were validated by the qRT-PCR in an independent cohort of 36 LSCC patients. MiRNA gene targets were predicted using TargetScan, PITA and microRNAorg in GeneSpring 12.5 software. The functional categories and pathways of the target genes were analyzed by GO category and KEGG pathway database.
Results: MiRNAs arrays identified seven up-regulated miRNAs, including hsa-miR-224, hsa-miR-183, hsa-miR-23a, hsa-miR-675, hsa-miR-27a, hsa-miR-503 and hsa-miR-4800-3p in LSCC by the SAM method, and qRT-PCR was performed to validate the screened miRNAs. 72 putative target genes were identified by GeneSpring 12.5 software. These putative target genes are involved in biological processes, such as metabolic, biological regulation, membrane, protein binding, ion binding by GO category analysis, and are the molecular components in MAPK signaling, adherence, and junction pathways by KEGG pathway database analysis.
Conclusions: Seven upregulated miRNAs were identified in LSCC tissues by microarrays, and validated by qRT-PCR. The putative target genes were also identified. These up-regulated miRNAs could serve as potential biomarkers for LSCC diagnosis and therapy.
Citation Format: Meng Lian, Xiaoqin Liu, Demin Han, Jugao Fang, Zhong Chen. Array profiling identified upregulated miRNAs and target genes and pathways in laryngeal squamous cell 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 4001. doi:10.1158/1538-7445.AM2015-4001
Abstract 4006: MiRNA profiling in esophageal precancerous for malignancy progression risk assessment
Authors: Srovnal Josef , Slaby Ondrej , Ehrmann Jiri , Gregar Jan , Radova Lenka , Staffova Katerina , Hajduch Marian 
Published: August 2015

Abstract
Background: Barrett's esophagus (BE) is a metaplastic disease with risk to develop esophageal adenocarcinoma (EAC). Current screening method for BE patients (endoscopy and biopsy) is discomfort, expensive and relatively risky for patients. Moreover, the procedure is complicated by subjective histopathology examination and only 2% of BE patients annually progress to adenocarcinoma. The aim of our study was to identify miRNA profiles in order to predict cancer progression in high-risk BE patients.
Methods and patients: FFPE samples were obtained from 113 patients (35 EAC, 21 low-grade dysplasia of esophagus, 33 BE and 24 healthy control). There were 74 males and 39 females; mean age was 55.9 years, range 15 - 94 years. Total RNA was purified from FFPE biopsy samples using proteinase K treatment followed by RNeasy kit (Qiagen). Microarray analysis was performed using the GeneChip miRNA 3.0 Array (Affymetrix). The data were analyzed using “R” software and the Bioconductor package.
Results: In total, 113 GeneChip miRNA 3.0 Arrays were performed in 113 patients. Expression profiles of 1733 human miRNAs were analyzed. In supervised clustering analysis we found 8 differentially expressed miRNAs (p&lt;0.001 or logFC 2) in BE patients compared to EAC patients and 10 differentially expressed miRNAs (p&lt;0.001 or logFC 2) in LGD patients compared to EAC patients. One of the dominant findings was decreased expression of miR-223 in EAC and LGD samples, which is known to function as a tumor suppressor blocking E2F1. Using LOOCV classifier with 13 miRNAs signature we were able to correctly classify 86 from 113 samples (AUC = 0.840). Prediction model fails mostly in LGD prediction (18/21), probably due to incorrect pathological classification.
Conclusion: We have identified miRNA profiles and signature allowing for better diagnostics of cancer progression in BE and LGD patients, which, however, will require further validation.
Acknowledgment: This work was financially supported by IGA UP LF 2014_019, NPU LO1304, CZ.1.05/2.1.00/01.0030 and CZ.1.07/2.3.00/30.0004.
Citation Format: Josef Srovnal, Ondrej Slaby, Jiri Ehrmann, Jan Gregar, Lenka Radova, Katerina Staffova, Marian Hajduch. MiRNA profiling in esophageal precancerous for malignancy progression risk assessment. [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 4006. doi:10.1158/1538-7445.AM2015-4006
Abstract 4014: Whole-genome microRNA profiling identifies prognostic serum biomarkers of esophageal adenocarcinoma
Authors: Wei Yongyue , Su Li , Christiani David C. 
Published: August 2015

Abstract
Background: Cell free circulating microRNAs (cfmiRNAs) have been recognized as robust and stable biomarkers of cancers. However, little is known about the prognostic significance of cfmiRNAs in esophageal adenocarcinoma (EA). In this study, we explored whether specific cfmiRNA profiles could predict EA prognosis and whether H. pylori (HP) infection status could influence the association between cfmiRNAs and EA survival outcomes.
Methods: At discovery stage, we profiled 1075 cfmiRNAs in 6 pooled serum samples from 30 EA patients and 30 cancer-free control subjects. After filtration, a total of 589 cfmiRNAs were stably detectable in the serum samples. The most significantly differential expressed cfmiRNAs were then validated the association with overall survival (OS) in an independent cohort of 82 patients, using Log-Rank test and multivariate Cox regression models in overall samples or stratified by HP infection status. qRT-PCR was used for cfmiRNA profiling in validation. HP infection status was determined by immunoblotting assay.
Results: We identified a 21-cfmiRNA panel that could distinguish EA patients from cancer-free subjects (multiple response analysis by Hotelling T test, P = 3.0E-12). In validation, the OS analysis among HP-positive subtype patients showed that no cfmiRNA was significantly associated with EA prognosis. In HP-negative patients, however, 9 cfmiRNAs were significantly associated with OS (minimal P = 1.9E-4, all FDR adjusted q-value &lt; 0.05). A risk-score analysis by combining the 9 cfmiRNA biomarkers showed a worse outcome in high-risk group (HR = 12.82, P = 0.0075) that showed better prediction of prognosis than individual cfmiRNA alone.
Conclusions: Our findings suggest that deregulated cfmiRNAs may contribute to EA prognosis and HP infection status may modify the association between cfmiRNAs and EA survival.
Citation Format: Yongyue Wei, Li Su, David C. Christiani. Whole-genome microRNA profiling identifies prognostic serum biomarkers of esophageal adenocarcinoma. [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 4014. doi:10.1158/1538-7445.AM2015-4014
Abstract 4046: Interleukin-10 and programmed death-1 cooperate to regulate tumor antigen-specific CD8+ T cells in melanoma patients
Authors: Sun Zhaojun , Fourcade Julien , Pagliano Ornella , Chauvin Joe-Marc , Sander Cindy , Kirkwood John M. , Zarour Hassane M. 
Published: August 2015

Abstract
With the recent success of immune checkpoint blockade in the clinic, it is expected that strategies aimed at counteracting the negative immunoregulatory networks in the tumor microenvironment will develop into potent therapy for melanoma. Here, we report that programmed death-1high (PD-1high) tumor antigen (TA)-specific CD8+ T cells present at periphery and at tumor sites in patients with advanced melanoma upregulate IL-10 receptor (IL-10R) expression. IL-10 is produced by multiple PBMC subsets in melanoma patients and acts directly on IL-10R+ TA-specific CD8+ T cells to impede proliferation and increase apoptosis. PD-1 blockade augments IL-10R expression by TA-specific CD8+ T cells, suggesting that PD-1 blockade renders PD-1+ TA-specific CD8+ T cells more sensitive to the immunosuppressive effects of endogenous IL-10. As a result, we show that IL-10 blockade adds to PD-1 blockade to increase the expansion and functions of TA-specific CD8+ T cells. Collectively, our findings support dual IL-10 and PD-1 blockade to counteract melanoma-induced T cell dysfunction and enhance TA-specific CD8+ T cell responses in patients with advanced melanoma.
Citation Format: Zhaojun Sun, Julien Fourcade, Ornella Pagliano, Joe-Marc Chauvin, Cindy Sander, John M. Kirkwood, Hassane M. Zarour. Interleukin-10 and programmed death-1 cooperate to regulate tumor antigen-specific CD8+ T cells in melanoma patients. [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 4046. doi:10.1158/1538-7445.AM2015-4046
Abstract 405: Kindlin-2 regulates integrin function and sensitivity to docetaxel in prostate cancer cells
Authors: Plow Edward F. , Das Mitali , Hirbawi Jamila , Sossey-Alaoui Khalid 
Published: August 2015

Abstract
Over the past decade, many lines of evidence have emerged to implicate the three members of the kindlin family of FERM domain proteins as important regulators of integrin adhesion receptors. Specifically, kindlins appear to cooperate with talin to be essential regulators of the ligand binding function of integrins and thereby enhance the adhesive and migratory responses of cells. Kindlin-2 (FERMT2) is the most broadly distributed of the kindlins. To explore the relationship between integrin activation and kindlin-2, prostate cancer cell lines were screened and LNCaP prostate cancer cells were found to express relatively low levels of kindlin-2 and endogenous levels of beta-1 integrin on their surface. A portion of this integrin was expressed in an activated state as detected with an activation specific antibody, HUTS-4. These cells were transfected with vectors for kindlin-2, with or without talin-head domain, a combination that leads to activation of β3 integrins in model cells. Transfections with kindlin-2 suppressed β1 integrin activation on the surface of the LNCaP cells. This inhibitory effect was abolished by mutation of kindlin-2 that prevented its binding to integrin cytoplasmic tail. This inhibitory response to kindlin-2 on β1 integrin was in stark contract to the effects of kindlin-2 plus talin-head expression on β3 function, where co-expression of the same constructs enhanced integrin activation. A mutation in kindlin-2, deletion of its last 15 amino acids, that blocks activation of β3 integrins without preventing its binding to the integrin, also prevents its inhibition of β1 function. We next looked at the effects of kindlin-2 on docetaxel induced apoptosis as monitored with Annexin V staining and cell death as monitored by propidium iodide staining (both by flow cytometry). Compared to LNCaP cells expressing EGFP alone, cells overexpressing EGFP-kindlin-2 were protected against apoptosis and cell death. This effect was dependent upon binding of kindlin-2 to the cytoplasmic tail of integrins. Hence, the capacity of kindlin-2 to influence integrin function depends upon the integrin subfamily and can range from activation to suppression of function. Kindlin-2, which is often overexpressed in transformed cells, may desensitize cells towards chemotherapeutic agents.
Citation Format: Edward F. Plow, Mitali Das, Jamila Hirbawi, Khalid Sossey-Alaoui. Kindlin-2 regulates integrin function and sensitivity to docetaxel in prostate 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 405. doi:10.1158/1538-7445.AM2015-405