bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1472: The differential expression of miRNAs in breast cancer cell lines
Authors: Rorie Checo J. , Arrington Brianna L. , Godfrey Sherette S. , McCoy Armeshia S. , Gurley Kashenya M. 
Published: May 2015

Abstract
Breast cancer is a heterogenous disease that is the second leading cause of death amongst women in the United States. Triple negative breast cancer (TNBC) is a very aggressive subtype of breast cancer characterized by its loss of estrogen, progesterone and HER2 receptor expression which limits its targets for effective drug therapies. Micro Ribonucleic Acids (miRNAs) are a class of small, endogenous non-coding ribonucleic acids that seem to play an essential role in gene regulation. Changes in the patterns of miRNA expression profiles are serving as potential biomarkers for tumor diagnosis, prognosis of disease-specific outcomes, and the prediction of therapeutic responses in cancer. We analyzed miRNA array (Agilent) expression profiles in triple negative breast cancer cell lines (HCC70, HCC1806, MDA-MB-157) and non-cancerous (AG11132) African American women breast cell lines. We revealed that the TNBC cells exhibited a different miRNA expression pattern when compared to the normal breast cancer cell line. We analyzed the hybridization data files using standard Microsoft Excel techniques and verified our findings using PARTEK Genomics Suite. We combined the data sets from the TNBC cell lines and compared the miRNA array expression profiles to the normal control cell line AG11132. We revealed that there were significant dysregulation of miRNAs including those of the let-7 family, miR-16, miR-31, and miR-25b-1, miR34a, and miR-95 in the triple negative cells as compared to the normal cells. These miRNAs have been described in previous scientific studies to be associated with tumorigenesis in breast cancer. These studies are initial observations that we will follow up with molecular techniques such as real-time PCR and siRNA to validate the results in order to establish more direct correlations to miRNAs and their roles in triple negative breast cancer.
Citation Format: Checo J. Rorie, Brianna L. Arrington, Sherette S. Godfrey, Armeshia S. McCoy, Kashenya M. Gurley. The differential expression of miRNAs in breast cancer cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1472. doi:10.1158/1538-7445.AM2014-1472
Abstract 1487: Identification of oral carcinoma miRNA signature and control OSCC tumorigenesis through Wnt/β-catenin signaling
Authors: Chang Wei-Min , Hsu Yuan-Ming , Chou Sung-Tau , Shieh Yi-Shing , Hsiao Michael , Hsiao Jenn-Ren , Chang Jang-Yang , Shiah Shine-Gwo 
Published: May 2015

Abstract
Aberrant microRNAs (miRNAs) expressions are often happened in cancer. In order to identify miRNAs altered in oral carcinogenesis, we investigated miRNAs and cDNA expression profiles in 40 pair-wise oral squamous cell carcinoma (OSCC) specimens. Eighty-four miRNAs were differentially expressed in the OSCC specimens compared to the matched tissue. Interestingly, 19 down-regulated miRNAs are clustered in DLK-1/Meg3 imprinted domain of chromosome 14q32.2 region. Loss of 14q32.2-miRNAs expression also raised the 14q32.2-miRNA targets expression in OSCC. We identified one target protein, Wnt-7b, was highly expressed in OSCC and regulated by miR-329 and -410. Wnt-7b increased the Wnt/β-catenin signaling activity and promoted OSCC tumor progression. Furthermore we also identify the regulation mechanism that down-regulated 14q32.2 miRNAs. Hyper-methylation in meg-3 differential methylated region (DMR) was confirmed by bisulfate sequencing. The hyper-methylation of meg-3 DMR was also induced by betel nuts extract exposure. In summary, we identified the expression signature of aberrant miRNAs in OSCC and provide a novel molecular insight how betel quid contribute to oral carcinogenesis through the epigenetic silencing of tumor suppressor miRNAs targeting the Wnt/β-catenin signaling pathway.
Note: This abstract was not presented at the meeting.
Citation Format: Wei-Min Chang, Yuan-Ming Hsu, Sung-Tau Chou, Yi-Shing Shieh, Michael Hsiao, Jenn-Ren Hsiao, Jang-Yang Chang, Shine-Gwo Shiah. Identification of oral carcinoma miRNA signature and control OSCC tumorigenesis through Wnt/β-catenin signaling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1487. doi:10.1158/1538-7445.AM2014-1487
Abstract 1489: Pri-let-7a-2 rs629367 associated with increased risk and poor survival of gastric cancer in Chinese by up-regulated let-7a expression
Authors: Xu Qian , Yuan Yuan 
Published: May 2015

Abstract
Abstract:Aim:Variant in pri-miRNA could affect miRNA expression and mature process or splicing efficiency, thus altering the hereditary susceptibility and prognosis of cancer. We aimed to assess miRNA-let-7 single nucleotide polymorphisms (SNP) associated with the risk and prognosis of gastric cancer (GC) as predicting biomarkers, and furthermore, its possible mechanisms. Method:We designed a two-stage case-control study to screen four miRNA SNPs (pri-let-7a-2 rs629367 and rs1143770, pri-let-7a-1 rs10739971, pri-let-7f-2 rs17276588) in 107 GC patients, 107 atrophic gastritis (AG), and matched 124 controls using PCR-RFLP. Two promising SNPs (pri-let-7a-2 rs629367 and pri-let-7a-1 rs10739971) were validated in another independent 1949 samples (including 579 GC patients, 649 AG and 721 controls) using Sequenom MassARRAY platform and sequencing. Results: We found that pri-let-7a-2 rs629367 CC variant genotype was associated with increased risks of GC and AG by 1.83-fold and 1.86-fold, respectively. For GC prognosis, patients with rs629367 CC genotype had significantly poorer survival than patients with AA genotype (log-rank P=0.004). We further investigated the let-7a expression levels in serum and found that let-7a expression elevated gradually for rs629367 AA, CA, CC genotype in the AG group (P=0.043). Furthermore, we confirmed these findings in vitro study by overexpressing let-7a carrying pri-let-7a-2 wild-type A or polymorphic-type C allele (P&lt;0.001). Conclusion: pri-let-7a-2 rs629367 CC genotype could increase the risks of GC as well as AG and was also associated with poor survival of GC, which possibly by affecting the mature let-7a expression, and could serve as a predicting biomarker for high-risk and poor prognosis of GC.
Note: This abstract was not presented at the meeting.
Citation Format: Qian Xu, Yuan Yuan. Pri-let-7a-2 rs629367 associated with increased risk and poor survival of gastric cancer in Chinese by up-regulated let-7a expression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1489. doi:10.1158/1538-7445.AM2014-1489
Abstract 150: Role of reactive oxygen species in doxorubicin-induced apoptosis of myeloid-derived suppressor cells
Authors: Alizadeh Darya , Katsanis Emmanuel , Larmonier Nicolas 
Published: May 2015

Abstract
The expansion of myeloid-derived suppressor cells (MDSC) in the blood, secondary lymphoid organs and tumor beds in animal cancer models and in patients with many types of cancers participates to the immunosuppressive environment associated with the development of tumors. MDSC frequency correlates with the disease stage and prognosis. MDSC can not only impair innate and adaptive antitumor immune responses, but these cell also contribute to enhance tumor angiogenesis and metastatic potential. The therapeutic targeting of MDSC (depletion,functional inactivation or differentiation into pro-inflammatory cells) promotes the efficacy of immunotherapeutic interventions. Conventional anticancer agents such as docetaxel, gemcitabine or sunitinib have been used to eliminate tumor-induced MDSC. We have observed that the anthracycline doxorubicin can deplete MDSC that expanded in the murine mammary tumor models 4T1 and EMT6 and in the EL4 thymoma model. Doxorubicin-mediated elimination of MDSC is associated with increased T and NK cell activity and the combination of this drug with adoptive T lymphocyte transfer impairs tumor development and metastatic spreading. We here present results indicating that doxorubicin-mediated apoptosis of MDSC may depend on an increased production of reactive oxygen species (ROS) by these cells. MDSC from gp91-/- mice (lacking the gp91phox glycosylated subunit of the NADPH oxidase flavocytochrome b558, responsible for the production of superoxide ion O2·-) were less sensitive to doxorubicin-induced cell death than their wild-type counterparts. Consistently, the effects of doxorubicin on
MDSC were partially impaired in tumor-bearing gp91-/- animals compared to wild-type mice. Interestingly the level of ROS in CD4+ or CD8+ T and NK cells were low and unchanged by doxorubicin administration. These observations may partly explain the selective effects of this chemotherapeutic agent on immunosuppressive MDSC while effector lymphocytes are spared and the subsequent increased in the effector to suppressor cell ratios, resulting in a mitigated immunosuppressive tumor environment.
Citation Format: Darya Alizadeh, Emmanuel Katsanis, Nicolas Larmonier. Role of reactive oxygen species in doxorubicin-induced apoptosis of myeloid-derived suppressor cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 150. doi:10.1158/1538-7445.AM2014-150
Abstract 1501: Optimizing small RNAseq of archived serum samples from the Janus Serum Bank - a search for cancer biomarkers
Authors: Rounge Trine B. , Lyle Robert , Lauritzen Marianne , Kjaerheim Kristina , Grotmol Tom , Grimsrud Tom K. , Gislefoss Randi E. , Tretli Steinar , Ursin Giske , Langseth Hilde 
Published: May 2015

Abstract
Introduction
miRNAs are a distinct class of small non-coding RNA molecules that regulate the expression of protein coding genes. They are present and stable in the cell-free body fluids such as plasma, serum and urine. The Janus Serum Bank contains 317 000 serum samples and more than 61 000 incident cancer cases diagnosed during follow-up. It is well-suited for studies of miRNAs as early cancer biomarkers since samples are collected pre-diagnostically.
Aim
To establish a high-throughput sequencing approach for obtaining high quality miRNA expression profiles from archived Janus serum samples stored for up to 41 years. Further aims were to assess the quantity and quality of small RNAs in the samples, and establish guidelines for the optimal sequencing depth.
Methods
Total RNA was extracted from eight pilot samples using Trizol and miRNeasy (Qiagen) columns. Sequencing libraries were made using ScriptMiner (EpiCentre) and the samples were sequenced on one HiSeq (Illumina) lane. After adaptor removal the sequences were aligned unguided to the genome. Reads mapping to mirBASE and Ensembl smallRNA features were counted and sequencing saturation curves were calculated. DESeq was used for differential expression analyses.
Results
High-throughput sequencing results from the Janus samples, with storage times ranging from 13 to 39 years, show that miRNAs are preserved in the samples. High quality miRNA expression profiles, including on average 641 miRNAs per sample, were obtained from our pilot samples. Most of the uniquely mapped reads, on average 84%, are miRNA. We can also identify protein coding RNAs and other groups of small RNA, on average respectively 9% and 6% of the uniquely mapped reads. The preliminary results from sequencing saturation curves, tracking miRNA discovery in each sample as a measure of input reads, have identified a guideline for optimal sequencing depth.
Conclusion and future perspectives
Here we have shown that the stability, quantity and quantity of long-term stored sera from the Janus Serum Bank are sufficient for obtaining high-quality miRNA expression profiles. High-throughput sequencing approach will be used in the search for miRNA expression profiles as early cancer biomarkers for early diagnosis, improved therapy and surveillance of cancer.
Citation Format: Trine B. Rounge, Robert Lyle, Marianne Lauritzen, Kristina Kjaerheim, Tom Grotmol, Tom K. Grimsrud, Randi E. Gislefoss, Steinar Tretli, Giske Ursin, Hilde Langseth. Optimizing small RNAseq of archived serum samples from the Janus Serum Bank - a search for cancer biomarkers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1501. doi:10.1158/1538-7445.AM2014-1501
Abstract 1514: An AC electrokinetic microarray device for isolation of cell circulating free nucleic acid from the blood of cancer patients
Authors: Marciniak Jennifer , Sonnenberg Avery , Rassenti Laura , Ghia Emanuela , Widhopf George , Skowronski Elaine , Manouchehri Sareh , Kipps Thomas J. , Heller Michael J. , Charlot David J. , Krishnan Rajaram 
Published: May 2015

Abstract
Circulating cell-free (ccf) DNA is becoming a biomarker of interest for cancer diagnosis and monitoring. The isolation of ccf-DNA from plasma may be used as a “liquid biopsy” and could replace more invasive tissue biopsies for analysis of cancer-related mutations. Conventional methods for isolation of ccf-DNA from plasma are costly, time-consuming, and require a significant amount of sample processing, which could result in loss of important biomarkers.
An AC electrokinetic microarray device has been developed to reduce the time and cost needed for sample processing. In an earlier study, this microarray device was used to rapidly (15 minutes) isolate ccf-DNA from 25 μL of unprocessed blood from 15 chronic lymphocytic leukemia (CLL) patients to compare PCR and sequencing results with classical ccf-DNA isolation processes and gold standard isolation of DNA directly from lymphocytes. Our objective now is to determine if there is a correlation between the on-chip fluorescence imaging data of the ccf-DNA with the lymphocyte cell counts.
Blood was collected from CLL patients in lithium heparin collection tubes. SYBR Green was added to the CLL blood sample to label the ds-DNA. A 25 μL aliquot of the CLL blood was inserted into the AC electrokinetic microarray device. A 10 kHz sinusoidal waveform was applied at 11 volts peak-to-peak for three minutes without fluid flow. With the field still on, the chip was washed for five minutes with 1x TE at a rate of 100 µL/min to remove other blood components. Once the wash was complete, a fluorescence image was taken for analysis. The white blood cell counts and % lymphocyte data were used to calculate the concentration of lymphocytes in each patient sample, and the fluorescence images were analyzed for average fluorescence in a defined region of interest. The preliminary data shows some correlation between the number of lymphocytes in the patient blood and the fluorescence calculated from the images. It is important to note that while the sample size was small, the data shows promise and calls for a larger study.
Citation Format: Jennifer Marciniak, Avery Sonnenberg, Laura Rassenti, Emanuela Ghia, George Widhopf, Elaine Skowronski, Sareh Manouchehri, Thomas J. Kipps, Michael J. Heller, David J. Charlot, Rajaram Krishnan. An AC electrokinetic microarray device for isolation of cell circulating free nucleic acid from the blood of cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1514. doi:10.1158/1538-7445.AM2014-1514
Abstract 1516: Automated circulating DNA purification from large volumes of plasma
Authors: Withers Sydnor T. , Dressler Mary , Cowan Cristopher A. 
Published: May 2015

Abstract
The circulating DNA found in human plasma is enriched for genomic DNA from minority tissues such as tumors, fetuses, and transplanted tissue. This sub fraction of blood has become an area of interest for development and disease as the nucleic acid recovered may represent a source of biomarkers for study. One milliliter of plasma typically yields between 1 ng and 50 ng of DNA. The current commercial DNA purification methods limit researchers' ability to scale their samples in both volume and number. Automated solutions are not available to process large numbers of samples with volumes greater than 1 ml, and manual methods can process up to 5 ml of plasma. Here we present a fully automated solution to extract DNA from 1-64 samples up to 8 ml in volume. The system provides an intuitive user interface to select run options and enter barcodes for reagents and samples. Any combination of sample volumes may be processed together in a single run. Samples are eluted in 50 µl of nuclease-free water in either plates or tubes. We have found that the performance of our system meets or exceeds common commercial alternatives over their common sample input volume.
Citation Format: Sydnor T. Withers, Mary Dressler, Cristopher A. Cowan. Automated circulating DNA purification from large volumes of plasma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1516. doi:10.1158/1538-7445.AM2014-1516
Abstract 1521: Quantitation of HER2 gene amplification using digital PCR
Authors: Li Kelly , Do Devin , Hegerich Patricia , Ping Bruno , Keys David , Majumdar Nivedita , Jackson Stephen , Cifuentes Francisco , Chen Caifu 
Published: May 2015

Abstract
Gene amplification is a common genetic abnormality in many types of cancers and has been implicated in playing important roles in cancer development. The most common types of amplified genes are oncogenes and drug-resistance genes. For example, Human epidermal growth factor receptor 2 (HER2) gene amplification, occurring in about 10-30% of breast cancer cases, is strongly associated with aggressive tumor progression and poor prognosis. HER2 also presents an effective therapeutic target, and several HER2 targeting agents have been approved for treatment of HER2 positive breast cancer by FDA. Analysis of HER2 gene amplification is important not only in selecting right patients for HER2 targeting agents but also monitoring the response to therapy and predicting clinical outcomes. Currently, fluorescence in situ hybridization (FISH) and immunohistochemical (IHC) analysis are standard testing approaches for HER2 gene amplification. However, the challenge for these methodologies is that HER2 gene amplification is less quantitative, especially with some samples whose HER2/CEP17 ratio fall into equivocal range, and the workflow is labor intensive. We have developed digital PCR (dPCR) technology on the QuantStudio™ 3D Digital PCR System and quantify gene copy numbers from zero to eight with high accuracy and precision. We analyzed FFPE samples for HER2 gene amplification and our data show that dPCR provides a robust and quantitative detection, simple workflow and a quick turn around time. This study demonstrate that dPCR quantitation of gene amplification could potentially be used to study any loci that are amplified in cancer.
Citation Format: Kelly Li, Devin Do, Patricia Hegerich, Bruno Ping, David Keys, Nivedita Majumdar, Stephen Jackson, Francisco Cifuentes, Caifu Chen. Quantitation of HER2 gene amplification using digital PCR. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1521. doi:10.1158/1538-7445.AM2014-1521
Abstract 1522: Direct quantitative PCR of LINE repeats to quantify CFC-DNA in serum
Authors: Charlot David Jean , Bhalla Megha , Krishnan Raj , Tu Gene 
Published: May 2015

Abstract
Background: Cell free circulating (cfc)-HMW DNA is a proposed diagnostic and prognostic biomarker for malignant tumors. Apoptotic DNA (less than 200 bp) is present in the circulation of normal healthy individuals whereas DNA released from dead cancer cells produces HMW DNA (greater than 400 bp). We developed LINE assay for direct serum/plasma quantitation of cfc-DNA concentration and integrity. LINE (Long Interspersed Elements) is highly conserved repetitive element in human genome with ∼500,000 copies/g.e. These large numbers of copies allow cfc DNA quantitation from small sample volume.
Methods: Sera of 15-30 CRC and Lung cancer patients (early and late stage) from retrospective studies, 5 CRC patients (late stage) from prospective studies along with healthy normals were characterized for cfc-DNA quantity and integrity by LINE Assay. All the samples were prescreened for hemolysis by Potassium assay. Quantitative real-time PCR of LINE repeats was performed with 2 sets of primers (less than 200 bp and greater than 400 bp) amplifying different lengths of DNA. We used 10ul serum directly as a template for qPCR without DNA purification. DNA integrity was determined as a ratio of concentration of longer over shorter LINE fragments.
Results: LINE Assay has a detection limit of 0.08 pg of DNA. Both CRC and lung cancer patients from Retrospective studies have significantly high HMW DNA concentration and DNA integrity as compared to healthy normals (statistically significant at p-value less than 0.05). ROC curves of HMW DNA for detecting early and late stage CRC and Lung have areas under the curves of greater than 0.80. High concentration of HMW DNA along with high DNA integrity also follows the trend of treatment of CRC patients from prospective studies.
Conclusions: LINE Assay is a robust, highly sensitive, and high-throughput method to measure different sizes of cfc-DNA. Our experiments demonstrate that this sizing capability helps to calculate DNA integrity which is a strong indicator for treatment monitoring in prospective studies and cancer staging in solid tumors. The high sensitivity of the LINE assay helps in direct DNA quantitation in serum.
Citation Format: David Jean Charlot, Megha Bhalla, Raj Krishnan, Gene Tu. Direct quantitative PCR of LINE repeats to quantify CFC-DNA in serum. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1522. doi:10.1158/1538-7445.AM2014-1522