bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 801: Clinical application of genomic signature including ALK mutation to the new tumor risk classification for neuroblastoma
Authors: (-Ichikawa) Miki Ohira , Kojima Toshio , Niwa Takafumi , Oba Shigeyuki , Ishii Shin , Takita Junko , Kato Motohiro , Ogawa Seishi , Nakamura Yohko , Kamijo Takehiko , Nakagawara Akira 
Published: February 2011

Abstract
Neuroblastoma (NBL) is one of the most common pediatric tumor arising from developing sympathetic nervous system. Its clinical and biological behavior is markedly heterogenous ranging from aggressive progression despite of intensive therapy to spontanous regression. NBL DNA shows complex patterns of genomic aberrations including MYCN amplification, deletion of chromosome 1p or 11q, and gain of chromosome 17q. We previously constructed the genomic subgrouping system of NBL based on the array CGH analysis for new tumor risk classification of NBL (Tomioka et al, Oncogene 2008). Analysis of 234 tumors by using 2,464 clones-BAC arrays demonstrated there exist three genomic groups (GG) of chromosomal aberrations in NBL: silent (S), partial gains and/or losses (P) and whole gains and/or losses (W). Each GG was further segregated into subgroups with different clinical outcomes clearly defined by MYCN amplification (MYCN-amp), 1p loss, 11q loss and 17q gain. Importantly, high-resolution array CGH analysis also led us to identify a novel genomic alteration in NBL, the activating mutation and amplification of anaplastic lymphoma kinase (ALK) oncogene on chromosome 2p23. In this study, to conduct the clinical validation of our GG risk classification system, array CGH and mutation analysis of ALK gene of 343 sporadic NBLs (stage 1: 48; stage2: 29; stage 4s: 27; stage 3: 60; stage 4: 179; median follow-up period is 78 months) were performed and the clinical impact of the genomic signatures was assessed. The results were fairly reproducible with our previous data, showing that GG-S or GG-W without MYCN-amp exhibited good prognosis (Ss and Ws, 8-year survival rates: &gt;80%), while GG-P or GG-S accompanying MYCN-amp were very poor (Pa and Sa, 8-year survival rates: &lt;35%). ALK gene abnormalities including mutations and amplification were found in 21 tumors in our dataset (6.1%), which caused fatal outcomes of the patients (p&lt;0.01) especially those with MYCN-amp (ALKmut-/MYCNamp+, n=73 vs. ALKmut+/MYCNamp+, n=10, p=0.16). Interestingly, ALK abnormalities were frequently found in the certain genomic subgroups of the tumors, namely, GG-Pa with 1p loss, GG-Ps with 11q loss and GG-Ws with no partial 1p and 11q losses. These results suggested that the combination of genomic signatures with ALK abnormalities will further improve the potential of our tumor risk classification system of NBL.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 801.
Abstract 802: Minimal deleted regions and their clinical significances in oral squamous cell cacinomas
Authors: Hsieh Ling-Ling , Chien Huei-Tzu , Huang Shiang-Fu , Chen I-How , Liao Chun-Ta , Wang Hung-Ming 
Published: February 2011

Abstract
With improvements in technologies, DNA alterations on a genome-wide scale have been successfully evaluated in several human cancers. To determine frequently novel deletion regions in oral squamous cell carcinomas (OSCCs) in Taiwan and regions specifically associated with clinicopathologic parameters and prognoses, the 400 polymorphic microsatellite markers from Applied Biosystems PRISM Linkage Mapping Set-MD10 (PE Biosystems, Foster City, CA) were used to examine 63 male primary tumors. To make sure that tumor tissue samples for genome-wide LOH screening consisted &gt;90% tumor cells, LCM was performed on immunostaining slide using a PixCell laser capture microscope (Arcturus Engineering, Mountain View, CA). For increasing reliability of statistical analysis, only when a microsatellite marker was able to provide LOH information in more than 30% (&gt; 19 cases) of the DNA samples was considered to be a successful allelotyping. Based on this criterion, 276 markers were included for the present study. The mean heterozygosity rate in these 276 microsatellite markers was 70.04%. The percentage of LOH among the markers was ranged from 3.85% (marker D20S171) to 65.52% (marker D18S478) with a mean of 33.63% (SD, 12.28%). Twenty-four markers displayed &gt;50% LOH and chromosome regions at 2p21, 2p11.2, 5p15.1, 5q35.1 and 7q21.13 were novel frequent LOH regions not reported previously in OSCC. In this study, we found that markers with a LOH frequency &gt;35% are likely to show LOHs associated with cancer-specific phenotypes. Therefore, only markers with a LOH frequency &gt;35% (121 markers) were used to examine whether there were associations between LOH and the clinicopathologic parameters, including age, anatomic site, tumor stage and risk factors of oral cancer (cigarette smoking, alcohol drinking and AQ chewing) and construct minimal deleted region (MDR). Thirty-two MDRs were defined and 10 novel MDRs were noted. A loss of MDR c19r2 (19q13.42-19q13.43) was correlated significantly with cigarette smoking and a loss of MDR c14r1 (14q24.2-14q32.12) and c11r1 (11q13.4-11q25) was associated with disease-free survival. A loss of MDR c14r1 and c11r1 was associated with the magnitude of genomic instability estimated by the proportion of loci showing LOH (PLOH) and the degree of chromosomal derangement estimated by the mean fractional allelic loss (FAL) in a tumor. In conclusion, our comprehensive allelotype analyses have unveiled a few MDRs involved in the development of OSCC in Taiwan. These results provide useful clues for identification of putative tumor suppressor genes by fine mapping of the suspected MDRs.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 802.
Abstract 81: Differential metabolic and viability responses of the A549 and MRC-5 cell lines upon exposure to selective organic inhibitors of glycolysis
Authors: Farah Ibrahim O. , Lewis Veshell L. 
Published: February 2011

Abstract
Lung cancer is a one of the most prevalent and deadly cancers in United States. Research has shown that cancer cells exhibit higher glycolytic rates than normal cells. Studies on the differential role of the interference with glycolysis/energy generation by cancer cells through the use natural glycolytic inhibitors were limited in the literature. Therefore, we hypothesize that exposure of lung cancer cells to natural inhibitors of glycolysis will negatively influence their metabolic activities as well as their cell viabilities due to the inhibition of substrate-level ATP generation, while differentially not affecting the normal lung phenotype. The human lung fibroblast cell line (MRC-5) was selected to represent the normal human lung and the human alveolar epithelial cell line A549 was selected to represent lung cancer in vitro. These cells were maintained and exposed to eleven different organic reagents including fructose diphosphate (FDP), sodium citrate, ascorbic acid, crude honey, sodium bicarbonate, D-glucose, oxalic acid, glycerol, zinc acetate, pyruvic acid, and sodium ascorbate at concentration levels ranging from 31.3-2,000 ug/ml for 24-72 hours in 5% CO2 and 96 well plates using MTT, Alamar blue and the T4 cellometer assays as well as phase-contrast photo-imaging. Our results indicate that exposure of A549 cells to these organics resulted in concentration dependent differential cell destruction of the A549 cell line. Nine of the eleven organics used showed statistically significant (p&lt;0.05) differential negative effects (impaired metabolic activity and cell death) on the A549 cell line in comparison to its control as well as to their effects on the MRC-5 cell line using MTT, Alamar blue and T4 cell viability assays. Data from the MTT assay showed limitations in detecting the true cell viability in comparison to the T4 data. Viability using the T4 cellometer ranged between 60-76% for the A549 compared to 96-100% for its control as well as the exposed MRC-5 cell line. LC50 using MTT and Alamar blue assays ranged between 161-1041 ug/ml. None of the eleven chemicals used allowed for cell proliferation of the A549 cell line while showing no or minor effects on the MRC-5 cell line. We conclude that nine of the tested organics impaired glycolysis, which is crucial to the generation of cellular energy and survival of the A549 cell line. Supported by NIH-RCMI grant# G12RR13459 and NIH-RISE grant # 63228.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 81.
Abstract 815: Relationship between altered expression levels of MIR21, MIR143, MIR145, and MIR205 and clinicopathologic features of esophageal squamous cell carcinoma(ESCC)
Authors: Makino Hiroshi , Ucida Eiji , Akagi Ichiro , Miyashita Masao , Nomura Tsutomu , Hagiwara Nobutoshi , Ishibashi Osamu , Takizawa Toshihiro 
Published: February 2011

Abstract
Background. In spite of the undisputed importance of altered expression patterns of miRNAs in various cancers, there is little information on the clinicopathologic significance of cancer-related miRNAs (i.e., MIR21, MIR143, MIR144, MIR145, and MIR205) in esophageal squamous cell carcinoma (ESCC).
Methods. We examined the expression levels of the precursor and mature miRNA genes in ESCC using Real-Time PCR. Furthermore, we investigated the relationships between the expression levels of these five miRNAs and the clinicopathologic parameters of ESCC patients.
Results. The expression levels of pre-MIR21 and pre-MIR144 were lower in ESCC than in the corresponding normal esophageal epithelium (p &lt; 0.05). The expression levels of mature MIR21 and mature MIR145 were higher in ESCC than those in normal epithelium (p &lt; 0.05). The mature/pre ratio of MIR21 in ESCC was higher than that in normal epithelium (p &lt; 0.05). In the other cancer-related miRNAs, the mature/pre ratio followed a similar tendency to MIR21. Furthermore, altered expression of these miRNAs was related to the clinicopathologic features of ESCC patients. The high expression of mature MIR21 and mature MIR205 was associated with lymph node positivity in ESCC patients (p &lt; 0.05). The high levels of expression of mature MIR143 and mature MIR145 were associated with recurrence of metastasis in ESCC patients (p &lt;0.05).
Conclusions. The findings may imply that the processing of pre-miRNAs into mature miRNA is accelerated in ESCC. Analysis of the expression levels of miRNAs should provide useful information for evaluation of the staging, prognosis, and treatment of ESCC patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 815.
Abstract 817: KRAS and BRAF mutation spectrum in 1,035 FFPE tumor samples submitted for clinical testing
Authors: Bender Ryan P. , McGinniss Matthew J. , Dejesa-Jamanila Liza , Kuslich Christine 
Published: February 2011

Abstract
Activating mutations in both the KRAS and BRAF genes are associated with poor prognosis and non-response to anti-EGFR therapies in patients with advanced cancers. Clinical guidelines have recommended that KRAS mutational status be determined in all patients with metastatic colorectal cancer that are being considered for anti-EGFR therapies. In this study, a pathologist reviewed an H&E slide of each tumor sample and determined the percent tumor nuclei and percent necrosis. Each specimen was macrodissected and DNA was extracted. DNA was then amplified with primers flanking KRAS exon 2 (codons 12 and 13), and KRAS exon 3 (codon 61), and BRAF exon 15. Using the ABI3730 and Mutation Surveyor software, mutations were scored as positive when evident in both the forward and reverse reactions. Following analysis of the 1,035 clinical tumor specimens submitted to our lab for KRAS mutation analysis by direct sequencing, 387 or 37% had a mutation. Codon 61 mutations accounted for 18 of the 387 mutations identified, or 4.6%. Furthermore, four rare KRAS mutations were identified [G12dup, G12L, G13R and G13C]. These 22 mutations would not be detected by the commonly used clinical qPCR KRAS mutational analysis kits, as they are designed to identify only the 7 most common codon 12 and 13 mutations. Colorectal specimens accounted for 684 of the 1,035 samples in the study of which 286 or 41% of these had KRAS mutations. Of the 237 clinical specimens tested for BRAF exon 15 mutations, 28 or 12% had mutations. Of these, 26 were the common V600E mutation, but two were rare [c.1798_1799GT&gt;AA (p.V600K) and c.1798_1799GT&gt;AG (p.V600R)]. Both of the rare mutations were present in skin cancer samples. Colon specimens had a BRAF mutation rate of 10%, while skin specimens had a mutation rate of 61%. Mutational analysis of KRAS in tumor samples by direct DNA sequencing detects a greater variety of mutations in KRAS than kit-based qPCR assays, including mutations that affect codon 61. Based on the data presented omitting rare variants in codons 12 and 13 and omitting codon 61 would decrease the analytical sensitivity of KRAS mutational analysis to 94%.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 817.
Abstract 820: Molecular markers for head and neck cancer detection
Authors: Pereira Lutecia , Reis Isildinha , Duncan Robert , Goodwin Jarrard , Franzmann Elizabeth 
Published: February 2011

Abstract
Introduction: Fifty thousand new cases of HNSCC are diagnosed in the United States each year. Unfortunately, most of these cases are advanced and only cured about 40% of the time. Cure rates could reach over 80% if diagnosed in earlier stages. We are developing a simple and inexpensive molecular screening test for the early detection of HNSCC. The markers under investigation are detectable in oral rinses and include soluble CD44 (solCD44), hyaluronic acid (HA) and total protein.
Materials and Methods: To study the population most likely to benefit from this early detection test, high-risk controls were identified by their smoking and/or drinking behavior from primary care clinics. They received a complete head and neck exam and had no clinical evidence of malignancy or premalignancy. Low-risk controls were normal volunteers. All subjects completed a detailed questionnaire including demographic, socioeconomic, risk factor and general health information. Oral samples were collected using a previously described swish and gargle method. We performed the solCD44, HA and protein assays in blinded fashion on oral rinses from 18 HNSCC cases, 18 frequency-matched high-risk controls and 21 low-risk controls using previously reported ELISA and ELISA-like assays.
Results: We statistically assessed the adequacy of matching between the cases and high-risk controls with respect to age, gender, race, socioeconomic status, tobacco and alcohol exposure and oral health. There were no significant differences between cases and controls for any of these variables except for a borderline significant difference in race. Log2solCD44 levels were significantly higher in cancer cases (2.42 ng/ml) and high-risk controls (2.12 ng/ml) compared to low risk controls (0.64 ng/ml, p&lt;0.05). Log2protein levels were also higher in cancer cases (0.88 mg/ml) and high-risk controls (0.97 mg/ml) compared to low-risk controls (0.52, p&lt;0.05). Following receiver operating curve analysis, the AUC for distinguishing high-risk controls from low-risk controls was 0.94 for solCD44 and 0.82 for protein. The AUC for distinguishing cancer from low-risk controls was 0.95 for solCD44 and 0.77 for protein. After adjusting for race, the AUC for distinguishing cancer from high-risk controls was 0.76 for solCD44 and 0.68 for protein. Both of these were better for the nonwhite group (0.84 for solCD44 and 0.83 for protein).
Conclusions: In this preliminary data set, the solCD44 and protein test appear to effectively distinguish HNSCC cases from high and low-risk controls. Race may have an impact on results. Further work including more subjects with longer follow-up must be done to confirm or refute these findings.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 820.
Abstract 822: KRAS and BRAF mutation analysis using formalin fixed and paraffin embedded colorectal tissue and fine needle aspiration biopsies from thyroid
Authors: Meireles Sibele Inacio , Nakano Fabio E. , Consolin Luciane Choppa do Valle , Stiepcich Mônica Maria Ágata , Hoff Ana O. , Biscolla Rosa Paula Mello , Coudry Renata Almeida 
Published: February 2011

Abstract
Point mutations in codons 12, 13 and 61 of the KRAS gene and in codon 600 of the BRAF gene can be identified in neoplastic tissue from many different organs. KRAS mutations are present in approximately 40% of sporadic colorectal adenocarcinoma and this analysis is important to determine response to anti-EGFR targeted therapies. BRAF mutations are present in approximately 40% of the papillary thyroid carcinoma and 10% sporadic colorectal adenocarcinoma. BRAF mutation V600E is associated with more aggressive thyroid tumors and its detection is important for thyroid cancer prognosis. Detection of BRAF mutation in colorectal cancer is also useful for characterizing sporadic tumors. A method developed in-house to identify mutations in KRAS (codos 12 and 13) was validated using formalin-fixed paraffin-embeded tissue (FFPE) from 31 surgical specimens diagnosed with metastatic colorrectal cancer. Similarly, a method for BRAF mutation analysis (codon 600) was developed and validaded using 39 smears from fine needle aspiration biopsies (FNAB) of the thyroid. Cytology analysis was performed to confirm the presence of neoplastic or suspected lesions. DNA was extract from 1-4 slides containing the FFPE tissue sections or smears from the FNAB. Mutation analyses were performed by Sanger sequencing and results were compared with pyrosequencing. Automatic analysis of nucleotide sequences using the SeqScape software (Applied Biosystems) was also implemented. There was 85.7% and 100% concordance between Sanger sequencing and pyrosequencing for KRAS and BRAF mutation analysis, respectively. Precision intra- and inter-assay analysis were concordant, with the exception of one sample with KRAS mutation. Sensitivity was evaluated using pools containing different proportions of mutated and non-mutated DNA from cell lines. Data analysis by visual inspection resulted in the detection of the mutant allele in samples with at least 10% of mutated DNA. However, KRAS and BRAF mutations analysis using SeqScape software detected the mutant allele in pools containing at least 30% and 25% of mutated DNA, respectively. This is in accordance with the overall sensitivity observed by standard sequencing analysis. In conclusion, KRAS and BRAF mutation analysis can be successfully performed using small amount of tissue sections from FFPE specimens and smears from FNAB. This material has the advantage of requiring small amounts of sample and also allows cytology review of the tissue content prior to molecular analysis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 822.
Abstract 825: Development of RNA quality-control methods to improve tissue archiving and molecular diagnostic testing
Authors: Stanoszek Lauren M. , Crawford Erin L. , Blomquist Thomas , Willey James C. 
Published: February 2011

Abstract
Biospecimen collection and processing methods practiced today yield clinical samples with a wide variation in RNA quality. Efforts to improve these methods are inadequate due to insufficient means to measure RNA quality. Improved RNA quality control (QC) measurement methods will enable establishment of cut-off criteria to determine which biospecimens will yield reliable RT-PCR results. Implementation of such criteria will enable existing banks of samples with variable RNA quality to be used for reverse transcriptase polymerase chain reaction (RT-PCR)-based diagnostic test development. Sources of inter-sample variation in RNA quality include RNA integrity, genomic DNA (gDNA) contamination, and substances that either a) interfere with RT efficiency and/or b) carry over to cDNA and cause gene-specific inhibition of PCR efficiency. An RNA integrity reference model was established by incubating A549 cell line populations at room temperature for different amounts of time following cytolysis. Between 0 and 100 min. post cytolysis, ACTB degradation, as well as the degradation of other major housekeeping genes, was more rapid than decline in RNA Integrity Number (RIN) Score, a measurement based on microcapillary electropheresis. Quantification of single-copy CC10 gene gDNA in RNA controlled for gDNA contamination and measurement of transcript abundance of each gene relative to known number of respective cDNA internal standards controlled for PCR inhibitors. The RT inhibition test uses a Reverse Transcription Standards Mixture (RTSM) that contains a known number of copies of ERCC (External RNA Control Consortium) RNA and cDNA standards. A known quantity of RTSM is added to an RNA sample and measurement of PCR product from the RNA standard relative to its cDNA standard following RT-PCR assesses RT efficiency. These RT-PCR tests have been implemented on an Agilent 2100 Bioanalyzer® and are being developed for implementation on high throughput RT-PCR platforms such as the Biotrove OpenArray® nanoarray and the Gene Express Standardized Expression Measurement (SEM) Center™. Improved methods for biospecimen collection will be selected and will then be used to identify which samples collected according to present methods are suitable for analysis by RT-PCR-based molecular diagnostic tests.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 825.