bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2485: A novel quantitative proteomics approach to identify proteins that elicit antibody responses in vaccinated pancreatic cancer patients.
Authors: Jhaveri Darshil T. , Kim Min-Sik , Huang Lanqing , Sharma Rajni , Zhang Zhen , Anders Robert A. , Pandey Akhilesh , Jaffee Elizabeth M. 
Published: August 2014

Abstract
Pancreatic cancer is the fourth leading cause of cancer deaths in the US. Less than 4% of patients have an overall survival of more than 5 years. Our lab has developed an allogeneic, granulocyte-macrophage colony-stimulating factor (GM-CSF) secreting pancreatic cancer vaccine that has recently completed phase II clinical trials. The application of proteomic approaches has gained ground in the identification of new cancer biomarkers, which are beneficial for both early detection and determination of new targets for development of biologically relevant therapies. We have developed a novel Serum Antibodies based SILAC-Immunoprecipitation (SASI) approach. The SASI approach utilizes immunoprecipitation by serum antibodies, which is coupled to the quantitative stable isotope labeling by amino acids in cell culture (SILAC) to identify proteins that elicit an increased antibody response post-vaccination. Using mass spectrometric analysis, the SASI approach comprehensively identified &gt;40 proteins that elicited at least a 2-fold increase in antibody response post-vaccination, from each of the three patients’ sera used. The list of identified proteins includes membrane proteins such as MHC class I complex, transferrin receptor (TFRC) and CD9, secreted proteins such as mesencephalic astrocyte-derived neurotrophic factor (MANF), as well as several cytoplasmic proteins such as regulatory subunit 12A of protein phosphatase 1 (PPP1R12A), galectin 3 and regulatory subunit 8 of the 26S proteasome (PSMC5). We further analyzed PSMC5, TFRC and PPP1R12A for tissue expression in normal, pre-malignant and pancreatic tumor specimens and found these proteins to increase in expression with tumor development. In addition, these proteins were shown to be pancreatic cancer associated antigens that are recognized by post-vaccination antibodies in the sera of patients that received the vaccine and have demonstrated a favorable disease free survival. Most significantly, the antibody responses detected against these proteins in patients with an improved disease-free survival suggests an anti-tumor potential of targeting these proteins. Overall, our data demonstrates that the novel SASI approach can enable identification of candidate proteins as possible new biomarkers for screening, and as new targets for therapeutic intervention.
Citation Format: Darshil T. Jhaveri, Min-Sik Kim, Lanqing Huang, Rajni Sharma, Zhen Zhang, Robert A. Anders, Akhilesh Pandey, Elizabeth M. Jaffee. A novel quantitative proteomics approach to identify proteins that elicit antibody responses in vaccinated pancreatic cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2485. doi:10.1158/1538-7445.AM2013-2485
Abstract 25: Pfetin as a risk factor of recurrence in gastrointestinal stromal tumors.
Authors: Orita Hajime , Ito Tomoaki , Sakurada Mutsumi , Kushida Tomoyuki , Maekawa Hiroshi , Wada Ryo , Suehara Yoshiyuki , Kubota Daisuke , Kondo Tadashi , Sato Koichi 
Published: August 2014

Abstract
Background: Despite complete resection, gastrointestinal stromal tumors (GIST) may recur or metastasize, depending on tumor grade. As such, a sensitive and specific marker is sought to select patients at high risk for recurrence. Previously our group reported Pfetin as prognostic predictors by use of proteomics technology. We used microarray of IHC to identify Pfetin as a statistically significant predictor of prognosis in resected GIST. In this project, we evaluated the role of Pfetin expression by IHC, controlled for clinicopathological data, as a predictor for recurrence.
Methods: 45 patients with primary GIST were treated with complete (R0) resection at our institution between 1995 and 2009. Tumors originated in the stomach (38 cases), small intestine (6 cases), and rectum (1 case).
Results: There were 8 recurrences, with the following characteristics. (1) Pfetin negative cases were significantly related to recurrence (p=0.002). (2) By univariate analysis, tumor size, mitoses, dissemination (tumor explosion), invasion (other organ) as well as Pfetin were significant predictors. According to multivariate analysis using these 5 factors, tumor mitosis and Pfetin were the most significant risks (p=0.059). (3) All 8 cases of recurrence were grouped as high risk according to Fletcher's classification. This demonstrated high accuracy.
Conclusions: We determined that tumor mitoses and Pfetin under-expression correlate with recurrence. These markers may have utility in selecting patients for adjuvant therapy.
Citation Format: Hajime Orita, Tomoaki Ito, Mutsumi Sakurada, Tomoyuki Kushida, Hiroshi Maekawa, Ryo Wada, Yoshiyuki Suehara, Daisuke Kubota, Tadashi Kondo, Koichi Sato. Pfetin as a risk factor of recurrence in gastrointestinal stromal tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 25. doi:10.1158/1538-7445.AM2013-25
Abstract 2508: Mass spectrometric immunoassay for insulin-like growth factor 1.
Authors: Nedelkov Dobrin , Niederkofler Eric , Phillips David , Krastins Bryan , Kiernan Urban , Tubbs Kemmons , Lopez Mary 
Published: August 2014

Abstract
Mass Spectrometric Immunoassays (MSIA) are protein quantification methods that utilize mass spectrometric detection for quantification of targeted protein analytes affinity retrieved by surface-immobilized antibodies. This rather straightforward concept is realized through affinity pipette devices (MSIA-Tips) that enable high-throughput assaying of hundreds of samples per day. Described here is the development and validation of mass spectrometric immunoassay for insulin-like growth factor 1 (IGF1).
MSIA-Tips derivatized with anti-IGF-1 antibody were used for affinity isolation of IGF1 from human samples. Long R3 (LR3) IGF1, spiked into samples prior to the affinity isolation, served as internal reference standard for signal normalization and IGF1 quantification. Following capture and elution, both the intact proteins and their surrogate tryptic peptides were analyzed via LC/MS. Linear standard curves were built that spanned the range of 1 to 1,500 ng/mL. The assay exhibited intra- and inter-assay precisions of &lt;10%, and linearity and spiking-recovery in the 90 - 110% range. Data was compared to that obtained with a commercially available ELISA, yielding good correlation. The data correlation between intact IGF1 and peptide-based IGF1 MS analyses was good, demonstrating the applicability of the IGF1 MSIA across MS platforms.
Citation Format: Dobrin Nedelkov, Eric Niederkofler, David Phillips, Bryan Krastins, Urban Kiernan, Kemmons Tubbs, Mary Lopez. Mass spectrometric immunoassay for insulin-like growth factor 1. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2508. doi:10.1158/1538-7445.AM2013-2508
Abstract 2514: The association between personal sun exposure, serum vitamin D and global methylation in human lymphocytes, in a population of healthy adults in South Australia.
Authors: Nair-Shalliker Visalini , Dhillon Varinderpal , Clements Mark , Armstrong Bruce K. , Fenech Michael 
Published: August 2014

Abstract
A positive association between solar UV exposure and micronuclei (MN) frequency (biomarker of chromosome breakage or loss) was previously reported with the effect of solar UV exposure on DNA damage greater when serum vitamin D (25(OH)D) levels were insufficient (&lt;50nmol/L). MN formation can result from global hypomethylation of the DNA repeat sequence, which is suggested to be a significant factor in driving oncogenesis. Therefore the aim was to evaluate the relationship between lymphocytic DNA methylation pattern in LINE-1 repetitive elements and solar UV exposure in 208 male and female participants from South Australia. Possible modifying effects of serum 25(OH)D levels were examined. Personal solar UV exposure was estimated from hours of outdoor exposure over 16 weeks recalled at the time of blood collection. DNA methylation pattern in LINE-1 repetitive elements was assessed in peripheral blood lymphocytes using pyrosequencing. DNA methylation in LINE-1 repetitive elements decreased with increasing sun exposure (% decrease=0.5% per doubling of sun exposure; 95%CI: -0.7-0.2 pvalue=0.00003). There was no correlation between LINE-1 methylation and MN frequency, however for every 1% increase in LINE-1 methylation there was a corresponding 4.3% (95% CI:0.6-8.1 p-value=0.02) increase in nucleoplasmic bridges (biomarker of dicentric chromosome formation) and a 4.3% increase in necrosis (CI:1.9-6.8 p-value=0.0005). This suggests that the reduction in LINE-1 methylation with increased solar exposure may be too small to explain increases in MN frequency and therefore other mechanisms must be considered. There was no clear relationship between 25(OH)D and DNA methylation. In conclusion, the inverse relationship between solar UV radiation and LINE-1 DNA methylation status suggests a role for solar UV exposure in influencing genomic methylation patterns, which in turn appears to be associated with specific biomarkers of cell death (necrosis) and chromosomal stability (NPBs). If this holds true, then the use of LINE-1 hypomethylation, and possibly methylation of other sequences such as Alu repeats, as a biomarker for studying the role of UV in inducing both skin and internal cancers (and other diseases) might deserve further consideration.
Citation Format: Visalini Nair-Shalliker, Varinderpal Dhillon, Mark Clements, Bruce K. Armstrong, Michael Fenech. The association between personal sun exposure, serum vitamin D and global methylation in human lymphocytes, in a population of healthy adults in South Australia. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2514. doi:10.1158/1538-7445.AM2013-2514
Abstract 2521: Associations between changes in circulating inflammatory biomarkers and reduced BMI achieved in SMART and PREFER behavioral weight loss interventions.
Authors: Linkov Faina Y. , Komaroff Marina , Edwards Robert , Lokshin Anna , Styn Mindi , Bovbjerg Dana , Burke Lora 
Published: August 2014

Abstract
OBJECTIVE
Obesity, increasingly recognized to be associated with low-grade systemic inflammation, is a global pandemic that has been linked to several forms of malignancies, including breast, colon, and endometrial cancer (EC). The goal of this study was to explore longitudinal inflammatory biomarker changes in overweight and obese participants of the SMART and PREFER behavioral weight loss trials, focusing on participants who were most successful in reducing body mass index (BMI) by the 12th month of the intervention. We hypothesized that overweight and obese individuals undergoing intentional weight loss would experience changes in the levels of proinflammatory cytokines and several other biomarkers associated with the development of EC and other malignancies.
METHODS
Participants were selected on the basis of weight loss over a period of 12 months in two major behavioral weight loss trials ― SMART and PREFER ― conducted at the University of Pittsburgh. Serum samples were obtained at baseline, 6 and 12 months from 68 participants (baseline mean body mass index (BMI) was 33.62 ± 4.1 kg/m2). Twenty-six bead based xMAP immunoassays were used for this study, including cytokines, chemokines, and hormones. These biomarkers were chosen on the basis of their link to inflammation and cancer development in previous research. Repeated measures mixed models were used to evaluate the association between changes in biomarkers and BMI from baseline with and without adjustment for covariates, including age, gender, and race.
RESULTS
Participants lost an average of 16.83 kg from baseline to 12 months, with the largest change occurring in the first 6 months of the intervention. Both repeated measures ANOVA models (with and without covariates) demonstrated that among 26 biomarkers, changes in adiponectin, CRP, C-Peptide, IGFBP-1, insulin, leptin, PAI-1 (total), resistin, sE-selectin were significantly associated with BMI change.
CONCLUSIONS
This study contributes to an emerging literature beginning to explore biological mechanisms that may contribute to health benefits of even moderate weight loss. Results also emphasize the importance of further studies of biomarkers that showed significant changes after weight loss to determine the molecular pathways involved.
Citation Format: Faina Y. Linkov, Marina Komaroff, Robert Edwards, Anna Lokshin, Mindi Styn, Dana Bovbjerg, Lora Burke. Associations between changes in circulating inflammatory biomarkers and reduced BMI achieved in SMART and PREFER behavioral weight loss interventions. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2521. doi:10.1158/1538-7445.AM2013-2521
Abstract 2545: Genome-wide association study identifies a novel susceptibility locus at 12q23.1 for lung squamous cell carcinoma in Chinese.
Authors: Shen Hongbing , Dong Jing , Jin Guangfu , Chu Minjie , Lin Dongxin , Hu Zhinbin 
Published: August 2014

Abstract
Adenocarcinoma (AC) and squamous cell carcinoma (SqCC) are two major histological subtypes of lung cancer. Genome-wide association studies (GWAS) have made considerable advances in the understanding of lung cancer susceptibility. Obvious heterogeneity has been observed between different histological subtypes of lung cancer, but genetic determinants in specific to lung SqCC have not been systematically investigated. Here, we performed the GWAS analysis specifically for lung SqCC in 833 SqCC cases and 3,094 controls followed by a two-stage replication in additional 2,223 lung SqCC cases and 6,409 controls from Chinese populations. We found that rs12296850 in SLC17A8-NR1H4 gene region at12q23.1 was significantly associated with risk of lung SqCC at genome-wide significance level [additive model: odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.72-0.84, P= 1.19×10-10]. Subjects carrying AG or GG genotype had a 26% (OR = 0.74, 95% CI = 0.67-0.81) or 32% (OR = 0.68, 95%CI = 0.56-0.83) decreased risk of lung SqCC, respectively, as compared with AA genotype. However, we did not observe significant association between rs12296850 and risk of lung AC in a total of 4,368 cases with lung AC and 9,486 controls (OR= 0.96, 95%CI = 0.90-1.02, P=0.173). These results indicate that genetic variations on chromosome 12q23.1 may specifically contribute to lung SqCC susceptibility in Chinese population.
Citation Format: Hongbing Shen, Jing Dong, Guangfu Jin, Minjie Chu, Dongxin Lin, Zhinbin Hu. Genome-wide association study identifies a novel susceptibility locus at 12q23.1 for lung squamous cell carcinoma in Chinese. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2545. doi:10.1158/1538-7445.AM2013-2545
Abstract 2550: A genome-wide association study of breast cancer survival according to molecular subtype in Korean women.
Authors: Song Nan , Choi Ji-Yeob , Sung Hyuna , Yoo Keun-Young , Han Wonshik , Noh Dong-Young , Ahn Sei-Hyun , Kang Daehee 
Published: August 2014

Abstract
Background: Breast cancer is heterogeneous disease according to ethnicity and molecular subtype. In this study, we conducted a genome-wide association study (GWAS) to evaluate the association between susceptibility loci and breast cancer survival by the molecular subtypes which were classified into four subtypes based on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in Korean women.
Methods: Analyses included 2,023 invasive breast cancer patients, comprised of ER/PR+ and HER2- (N=1,006), ER/PR+ and HER2+ (N=245), ER/PR- and HER2+ (N=226), ER/PR- and HER2- (N=279), and unknown subtype (N=267), from Seoul Breast Cancer Study (SeBCS). For analyses, 555,117 SNPs were genotyped using Affymetrix SNP Array 6.0 and 2,416,663 SNPs were imputated based on HapMap Phase II (release 22). Cox proportional hazard models adjusted for age, recruited centers, and TNM stage were used to test the association of these SNPs with disease-free survival (DFS) and overall survival (OS) by molecular subtype.
Results: With median follow-up periods of 3.8 years in DFS and 4.0 years in OS, there was significant difference in survival between molecular subtypes tested by log-rank (P&lt;0.0001, Log-rank test). Compared to ‘ER/PR+ and HER2-‘, ‘ER/PR- and HER2+’ and ‘ER/PR- and HER2-’ were associated with a poorer prognosis (HRER/PR- and HER2+ (95% CI)=2.00 (1.35-2.97), HRER/PR- and HER2-=2.37 (1.70-3.29) in DFS and HRER/PR- and HER2+=2.54 (1.50-4.30), HRER/PR- and HER2-=2.59 (1.65-4.08) in OS). By molecular subtypes, we identified 5 SNPs associated with DFS (HRrs161041(PPP2R2B)=2.35 (1.68-3.30) in ER/PR+ and HER2-, HRrs1896346(TBX3)=8.19 (3.52-19.08) in ER/PR+ and HER2+, HRrs1278329(ADAM12)=3.96 (2.23-7.02) in ER/PR- and HER2+, HRrs10894375(NTM)=3.10 (2.02-4.74), HRrs10825036(PCDH15)=2.87 (1.90-4.34) in ER/PR- and HER2-) and 3 SNPs associated with OS (HRrs7659008(LYPLA1P2)=0.20 (0.09-0.39) in ER/PR+ and HER2-, HRrs4750561(CDNF)=0.12 (0.05-0.29), and HRrs4807216(SF3A2)=11.51 (4.30-30.81) in ER/PR- and HER2+) in breast cancer with the level of P-value&lt;1×10−5.
Conclusion: This study suggests that associations between SNPs and survival were heterogeneous according to the molecular subtype of breast cancer. Furthermore, Additional larger studies are needed to replicate these findings.
Citation Format: Nan Song, Ji-Yeob Choi, Hyuna Sung, Keun-Young Yoo, Wonshik Han, Dong-Young Noh, Sei-Hyun Ahn, Daehee Kang. A genome-wide association study of breast cancer survival according to molecular subtype in Korean women. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2550. doi:10.1158/1538-7445.AM2013-2550
Abstract 2553: Characterization of rare germline variants in somatically mutated melanoma genes in melanoma-prone families.
Authors: Yang Xiaohong (Rose) , Burke Laura , Jacobs Kevin , Cullen Michael , Boland Joseph , Burdett Laurie , Malasky Michael , Rotunno Melissa , Yeager Meredith , Chanock Stephen , Tucker Margaret , Goldstein Alisa 
Published: August 2014

Abstract
CDKN2A and CDK4 are the two major susceptibility genes for melanoma identified so far. However, these two genes only account for melanoma susceptibility in a small proportion of melanoma-prone families, suggesting the existence of other susceptibility genes. In addition, melanoma is among the tumors with the highest mutation rate and a large number of mutated genes have been identified that affect multiple key biological pathways. The goal of this study is to examine whether rare germline sequence variants and/or copy number variations (CNVs) in these genes may influence melanoma risk in melanoma-prone families without known CDKN2A/CDK4 mutations. Methods: We conducted exome sequencing in blood-derived DNA in 75 melanoma cases from 23 American melanoma families with ≥3 affected members. We evaluated rare non-synonymous variants, defined as allele frequency less than 0.1% reported in public databases (dbSNP, 1000 Genomes, or NHLBI's Exome Variant Server), in 37 genes (including BRAF, NRAS, KIT,PTEN, CDKN2A, GRIN2A, etc.) that are frequently mutated in melanoma. We also screened CNVs in these genes using data from the Nimblegen 3x720k exon-focused CGH tiling arrays, in which blood-derived DNA from 79 melanoma cases and 25 spouses were analyzed in the same mutation-negative families. We used the Nexus Copy Number™ built-in FASST2 algorithm to identify significant CNVs (significant threshold=0.000001; minimal number of probes per segment=5; log2 ratio&gt;0.3 for gains and -0.3 for losses). Results: We identified 10 rare variants in 10 genes that showed partial/complete co-segregation with disease and were absent in our internal controls (N∼400). Four of these variants occurred in all cases within their respective families and 3 of them were novel. We did not identify any disease-related CNVs in these genes except for a deletion in exon 1β of CDKN2A/ p14ARF in 6 out of 7 melanoma cases in one big family. Our findings suggest that rare variants in somatically mutated genes may confer susceptibility to melanoma risk in a subset of families. However, these variants need to be validated, checked for functional relevance, and evaluated in a large number of cases and controls to determine their role in disease susceptibility.
Citation Format: Xiaohong (Rose) Yang, Laura Burke, Kevin Jacobs, Michael Cullen, Joseph Boland, Laurie Burdett, Michael Malasky, Melissa Rotunno, Meredith Yeager, Stephen Chanock, Margaret Tucker, Alisa Goldstein. Characterization of rare germline variants in somatically mutated melanoma genes in melanoma-prone families. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2553. doi:10.1158/1538-7445.AM2013-2553