bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1481: miR-296 as prognostic and predictive molecular marker for recurrence in early-stage laryngeal carcinoma treated with definitive radiotherapy
Authors: Maia Danielle C C , Carvalho Ana Carolina de , Horst Maria Aderuza , Neto Cristovam Scapulatempo , Carvalho Andre Lopes , Vettore Andre L. 
Published: May 2015

Abstract
Early-stage laryngeal cancer has cure rates above 80% with exclusive radiotherapy. However, when salvage treatment is needed, surgery is the main option and despite efforts to conservative procedures to preserve laryngeal function, up to 50% will require total laryngectomy at diagnosis of recurrence or future. So, the use of microRNAs as molecular markers is a method to be tested with the aim of predicting the chances of success with radiotherapy, lowering tumor relapses and turning possible to reduce the need for salvage procedures that would affect speech and impact in quality of life. Objectives: To identify microRNAs capable of segregating radioresistant from radiosensitive tumors, to determine prognosis in pre-treatment tumors and to predict failure with radiotherapy. Methods: Molecular Screening of 667 microRNAs using taqman low density array (TLDA) for target selection and then validation in 34 patients, being 20 radioresistant and 14 radiosensitive by RT-PCR with individual assays. Statistical analysis was performed by Chi-square and Fisher exact test for associations between variables, and log-rank method of Kaplan-Meier for recurrence free survival between molecular, clinical, demographic and treatment variables. Also to verify differences in distribution between the expression levels in radioresistant and radiosensitive the Mann-Whitney test was performed. Results: Four microRNAs were selected for validation, miR-296, miR-452, miR-183*, miR-200c based on fold-change and literature review and those were analyzed with respect to age, gender, TNM, laryngeal subsite, radiation dose and treatment interval. Among clinical, demographic, treatment and molecular variables, only miR-296 was shown to present different distribution with statistical significance between radioresistant and radiosensitive (p = 0.002), also demonstrated association with recurrence (p = 0.01) with an odds ratio (OR) of 8.6, confidence interval (CI) between 1.7 and 42.2. Conclusions: In our study, only miR-296 demonstrated the ability to predict patients most likely to fail radiotherapy, also showing a worse prognosis for tumors with high expression level. miR-296 is a molecular predictive and prognostic marker to be considered prior to treatment selection for early-stage laryngeal tumors.
Citation Format: Danielle C C Maia, Ana Carolina de Carvalho, Maria Aderuza Horst, Cristovam Scapulatempo Neto, Andre Lopes Carvalho, Andre L. Vettore. miR-296 as prognostic and predictive molecular marker for recurrence in early-stage laryngeal carcinoma treated with definitive radiotherapy. [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 1481. doi:10.1158/1538-7445.AM2014-1481
Abstract 1484: CD57 defines a novel maker of glioblastoma stem cells that have greater invasive potential than CD133+ tumor cells
Authors: Qi Lin , Huang Yu-lun , Kogiso Mari , Mao Hua , Baxter Patricia , Su Jack MF , Perlaky Laszlo , Lau Ching C. , Chintagumpala Murali , Li Xiao-Nan 
Published: May 2015

Abstract
Glioblastoma multiforme (GBM) is the most aggressive and lethal brain tumor that occurs both in children and adults. Diffuse invasion into normal brain tissue is one of the important biologic features that make GBM refractory to conventional therapies. While existing studies on GBM invasion are primarily conducted using tumor core tissues from surgical resections, it is unclear whether unresectable, infiltrative GBM cells would be more informative for studying their invasive nature compared to those in the resected tumor cores. More importantly, little is known if and which cancer stem cell populations are driving glioma invasion. To address these fundamental issues, we utilized our panel of 7 (6 pediatric and 1 adult) patient tumor-derived orthotopic xenograft mouse models of GBM to isolate invasive GBM cells (infiltrating normal mouse brain parenchyma) and tumor core GBM cells and directly compared their biological differences. Our result showed that the invasive cells have stronger neurosphere forming efficiency in vitro in a serial dilution assay and increased tumorigenic capacity after in vivo transplantation (particularly at 100 cells/mouse) compared to the tumor core cells. A screening of putative cancer stem cell markers (CD133, CD15, CD24/CD44, CD57 and CD117) showed that invasive GBM cells are enriched (&gt;2 folds) with CD57+ cells compared to the tumor core cells, and these infiltrating cells were predominantly CD57+/CD133-. Even the CD133+ cells were frequently dual-positive with CD57 (CD33+CD57+), not only in the xenograft tumors but also in a separate set of patient GBM samples. Mechanistically, we found that CD57+ cells expressed high levels of self-renewal genes and tend to stay in G0/G1 phases. In conclusion, we showed that invasive GBM cells are biologically deferent from the matched tumor core cells and identified CD57 as a novel stem cell marker that is associated with GBM infiltration. Our findings suggest that new anti-invasion therapies should target CD57+ cells in addition to CD133+ cells in GBM.
Citation Format: Lin Qi, Yu-lun Huang, Mari Kogiso, Hua Mao, Patricia Baxter, Jack MF Su, Laszlo Perlaky, Ching C. Lau, Murali Chintagumpala, Xiao-Nan Li. CD57 defines a novel maker of glioblastoma stem cells that have greater invasive potential than CD133+ tumor 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 1484. doi:10.1158/1538-7445.AM2014-1484
Abstract 1492: Prediction of cancer progression in Barrett's esophagus patients using miRNA profiling
Authors: Srovnal Josef , Slaby Ondrej , Ehrmann Jiri , Gregar Jan , Radova Lenka , Sedlackova Michaela , Hajduch Marian 
Published: May 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 histopathological examination. Approximately 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 68 patients (10 EAC, 4 high-grade and 21 low-grade dysplasia of esophagus, and 33 BE). There were 49 males and 19 females; median age was 58 years, range 27 - 97 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, 68 GeneChip miRNA 3.0 Arrays were performed in 68 patients (8 poor quality arrays were excluded). Expression profiles of 1733 human miRNAs, 1658 human pre-miRNAs and 2216 human sno-RNAs and sca-RNAs were analyzed. In supervised clustering analysis we found 29 differentially expressed miRNAs, 7 pre-miRNAs and 9 sno-RNAs (p&lt;0.001 or logFC &lt;-2 or logFC &gt;2) in EAC patients compared to BE patients. One of the dominant findings was decreased expression of miR-22 in EAC samples, which is known to function as a tumor suppressor and histone deacetylase 4 regulator.
Conclusion: We have identified miRNA profiles allowing for better diagnostics of cancer progression in BE patients, which, however, will require further validation.
Acknowledgment: This work was financially supported by IGA MZ CR NT13585-3/202, IGA UP LF 2013_015, 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, Michaela Sedlackova, Marian Hajduch. Prediction of cancer progression in Barrett's esophagus patients using miRNA profiling. [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 1492. doi:10.1158/1538-7445.AM2014-1492
Abstract 1508: A highly sensitive and reliable methodology (ARMS-PM system) for detection of K-ras mutations in FFPE samples
Authors: Duan Wei-Tao , Wang Xiujuan , Hu Lihong , Zhu Feng , Yu Dehua 
Published: May 2015

Abstract
The association between the activating mutations of K-ras gene and poor clinical response to current targeted therapies against epidermal growth factor receptor (EGFR ) such as cetuximab (Erbitux®) and panitumumab (Vectibix®) in colorectal cancer (CRC) has been well documented. Therefore detection of K-ras mutation status will guide effective therapeutical options for patients with CRC. Here we developed a new method for the rapid and reliable detection of K-ras mutations by using a combination of the modified mutation-specific ARMS primers, peptide nucleic acid (PNA) clamping and taqman-MGB probes, named ARMS-PM system. In the ARMS-PM system, the wild-type K-ras DNA is completely blocked by PNA at a higher annealing temperature, and the mutant gene is selectively amplified by the modified ARMS primers and the amplicon extending signals are collected by the taqman-MGB probe at the same time. The ARMS-PM system can detect approximately 10 copies of the mutant gene stably in somatic cells at the background of 10ng genomic DNA. In addition, the premixed reaction was introduced into this system to allow the assay to be completed in only one step of sample loading, which minimizes the potential contamination significantly.
By using this assay, we analyzed the K-ras mutations in 1014 Chinese CRC and 205 Chinese lung cancer FFPE samples in comparison with Sanger sequencing. Our results showed that the positive rates were 38.6% and 10.2% 38.0% in CRC and lung cancer samples respectively, which were higher than that measured by Sanger sequencing (38.0% and 7.1%). The coincidence rates of the two methods were 97.3% for the positive samples and 97.7 for the negative samples. The total coincidence rate was 97.8%. In conclusion, our study provides a basis for the detection of somatic mutations in K-ras in a routine clinical setting. The ARMS-PM assay allows the detection of the activating K-ras mutations in FFPE samples with better sensitivity and feasibility than the current assays used in clinic. &lt;!–EndFragment–&gt;
Citation Format: Wei-Tao Duan, Xiujuan Wang, Lihong Hu, Feng Zhu, Dehua Yu. A highly sensitive and reliable methodology (ARMS-PM system) for detection of K-ras mutations in FFPE samples. [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 1508. doi:10.1158/1538-7445.AM2014-1508
Abstract 1509: A ARMS-PNA PCR assay for detection of EGFR mutations in FFPE tumor samples
Authors: Zhao Shanshan , Guo Xiao , Long Ziwen , Yu Dehua 
Published: May 2015

Abstract
The activating mutations of Epidermal growth factor receptor (EGFR) are the predictive markers for response to tyrosine kinase inhibitors gefitinib and erlotinib in non-small cell lung cancer(NSCLC). Therefore detection of EGFR mutations will guide effective therapeutical options for patients with NSCLC. Here we developed a new method for the rapid and reliable detection of EGFR mutations by using a combination of modified mutation-specific ARMS primers and peptide nucleic acid (PNA) clamping system, named ARMS-PNA assay. In this real-time PCR system, the wild-type EGFR DNA is completely blocked by PNA with a higher annealing temperature, and the mutant gene is selectively amplified by the modified ARMS primers and the amplicon extending signals are collected by the taqman-probe at the same time. The ARMS-PNA assay could detect 29 mutations on EGFR gene with a sensitivity of 0.5% under the background of a total of 10ng wild-type genomic DNA. By using this assay, we analyzed the EGFR mutations in 1033 Chinese NSCLC FFPE samples in comparison with Sanger sequencing. Our results showed that the positive rates were 50.1%, which were higher than that measured by Sanger sequencing (48.3%). The coincidence rates of the two methods were 99.0% for the positive samples and 95.5% for the negative samples. The total coincidence rate was 97.2%. In conclusion, our study provides a basis for the detection of somatic mutations in EGFR in a routine clinical setting. The ARMS-PNA PCR assay allows the detection of the activating EGFR mutations in FFPE samples with better sensitivity and feasibility than the current assays used in clinic.&lt;!–EndFragment–&gt;
Citation Format: Shanshan Zhao, Xiao Guo, Ziwen Long, Dehua Yu. A ARMS-PNA PCR assay for detection of EGFR mutations in FFPE tumor samples. [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 1509. doi:10.1158/1538-7445.AM2014-1509
Abstract 1512: Detection of somatic alterations in plasma from lung cancer patients
Authors: Costa Jose L. , Justino Ana , Barroso Ana , Parente Barbara , Machado Jose C. 
Published: May 2015

Abstract
Tumor-specific (somatic) mutations in plasma can serve as biomarkers for tumor detection, monitor tumor response to specific therapies, detect residual disease after surgery, and long-term follow-up. The intrinsic low abundance of circulating cell-free tumor DNA (cfDNA) makes the detection and quantification of such mutations in plasma a challenging task. This small scale study aims to establish a comprehensive strategy to be used in the detection of clinical relevant somatic alterations in plasma of lung cancer patients.
Plasma samples obtained at different stages of disease progression and/or treatment were collected from a group of 11 lung cancer patients and used to isolate cfDNA. Genetic alterations in the EGFR gene (p.E746_A750del and p.L858R) identified at diagnosis in tumor biopsies were used as surrogate markers to optimize and validate the next generation sequencing strategy and data analysis workflow. The Ion AmpliSeq Colon and Lung cancer panel was used to analyze hotspot and targeted regions of 22 genes implicated in colon and lung cancers, including the EGFR gene mutations mentioned. The amplified products were used to prepare libraries and were sequenced using the Ion PGM system. Quantitative real time PCR and digital PCR assays were used to confirm selected results.
Tumor derived genetic alterations could be identified in as little as 10ng of cfDNA. EGFR alterations identified in cfDNA mirrored the alterations identified in all tumor biopsies. EGFR alterations with allelic frequencies as low as 3% could be detected in cfDNA. Additionally, in case of samples collected after therapy, a clear decrease in the cfDNA allelic frequency of the EGFR mutation, that made the patient eligible for therapy, was observed. Furthermore, the screening of a larger panel of genes allowed the identification in two cases of additional gene mutations (e.g. MET and KRAS) that may have impact in the clinical management of patients.
In this study, we demonstrate the capacity to identify clinically relevant somatic EGFR mutations in plasma. The possibility to assess information from a larger panel of genes makes this strategy attractive for further optimization of treatment options. The strategy is now being extended to a larger cohort of patients to push forward the concept of liquid biopsy in the clinical management of cancer patients.
Citation Format: Jose L. Costa, Ana Justino, Ana Barroso, Barbara Parente, Jose C. Machado. Detection of somatic alterations in plasma from lung 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 1512. doi:10.1158/1538-7445.AM2014-1512
Abstract 1515: Simultaneous detection of KRAS and TP53 mutations in human cancer cell lines using multiplex qPCR
Authors: Patel Sunali , Woo Cora , Wilde Joyce , Phanse Sundiep 
Published: May 2015

Abstract
Genetic alterations in KRAS and TP53 genes are common in many cancers and the understanding of their role in progression of cancer is vital for the design of successful treatment approaches. Studies suggest that mutations in KRAS and TP53 genes independently hindered the use of EGFR inhibiting drugs like Cetuximab (Erbitux) for the treatment of colorectal cancer (1). The genetic alterations in these genes are now routinely checked before starting any expensive treatments. Here, we successfully demonstrated use of duplex mutli-color SNP genotyping assays to detect KRAS and TP53 mutation in human colon cancer cell lines. This method can be potentially used to analyze samples with limited quantity and get as much information as possible from a single sample. To study the impact of these mutations, we generated gene expression profiles of 672 genes related to signaling pathways by using the Human signal transduction medium-throughput OpenArray® Panel. Selected cancer genes like BRAC1, BAX, CFLAR, MYC and others were evaluated using multiplexed single-tube PCR simultaneously detecting four different targets in the same sample. These results demonstrate that duplex SNP genotyping and multiplexed gene expression profiling from a single sample increases research capacity in situations when sample is limited.
Reference:
1. A Oden-Gangloff, F Di Fiore, F Bibeau, A Lamy, G Bougeard, F Charbonnier, F Blanchard, D Tougeron, M Ychou, F Boissière, F Le Pessot, J-C Sabourin, J-J Tuech, P Michel and T Frebourg.TP53 mutations predict disease control in metastatic colorectal cancer treated with cetuximab-based chemotherapy. British Journal of Cancer (2009) 100, 1330-1335
Citation Format: Sunali Patel, Cora Woo, Joyce Wilde, Sundiep Phanse. Simultaneous detection of KRAS and TP53 mutations in human cancer cell lines using multiplex qPCR. [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 1515. doi:10.1158/1538-7445.AM2014-1515
Abstract 153: High neuropilin-1 expression on monocytes is positively associated with trastuzumab-mediated antibody-dependent cellular cytotoxicity of the HER2-overexpressing breast cancer cell line
Authors: Kawaguchi Kosuke , Suzuki Eiji , Kawashima Masao , Toi Masakazu 
Published: May 2015

Abstract
Purpose
Neuropilin-1 (Nrp1) was initially characterized as a guide for migrating cells and axons in developing nervous systems and is essential for the precise formation of neurons and vasculature. However, it was recently reported to also play an important role in the immune system. This study aimed to investigate the role of Nrp1 on monocytes in trastuzumab-mediated antibody-dependent cellular cytotoxicity (ADCC) targeting the HER2-positive human breast cancer cell line SKBR3. In addition, we evaluated the gene expression profile of monocytes expressing high and low levels of Nrp1.
Methods
Peripheral blood mononuclear cells from healthy volunteers were prepared using BD Vacutainer CPT Cell Preparation Tubes. The cells were stained with fluorescein isothiocyanate-conjugated anti-CD14 and allophycocyanin-conjugated anti-Nrp1 antibodies, and Nrp1high and Nrp1low monocyte subsets were sorted using FACSAria. These cells were used as effector cells in a conventional ADCC assay with SKBR3 as target cells and trastuzumab as the antibody. Target cell cytotoxicity was measured using the LDH cytotoxic test kit. The effector cell to target cell ratios of 20:1 and 10:1 were used. Gene expression analysis was performed by Affymetrix GeneChip microarrays. All study protocols were approved by the Ethics Committee for Clinical Research, Kyoto University Hospital, Kyoto, Japan (authorization number G424).
Results
The LDH cytotoxic test revealed significantly higher target cancer cell cytotoxicity in sorted Nrp1high monocytes than in Nrp1low monocytes (75% vs. 45%, p&lt;0.01). Trastuzumab-mediated ADCC was significantly suppressed by Nrp1 neutralization antibodies in a dose-dependent manner (Control arm 14.3%, Treatment arm 6%; p&lt;0.01). Gene expression analysis revealed that 308 genes were up-regulated in the Nrp1high population, including monocyte-specific chemokine receptor and hematopoietic transcriptional factor.
Conclusion
These results suggest that determination of Nrp1 expression can be used to classify monocytes as populations with and without cellular cytotoxic activity. Analysis of Nrp1 expression levels in monocytes can therefore be used to identify HER2-positive breast cancer patients for whom trastuzumab therapy will be less effective.
Citation Format: Kosuke Kawaguchi, Eiji Suzuki, Masao Kawashima, Masakazu Toi. High neuropilin-1 expression on monocytes is positively associated with trastuzumab-mediated antibody-dependent cellular cytotoxicity of the HER2-overexpressing breast cancer cell line. [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 153. doi:10.1158/1538-7445.AM2014-153