bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4469: S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), and colorectal adenoma risk
Authors: Shrubsole Martha J. , Wagner Conrad , Zhu Xiangzhu , Loukachevitch Lioudmila , Ness Reid M. , Zheng Wei 
Published: August 2012

Abstract
Introduction: Methionine and its metabolic derivatives regulate activity of most methyltransferases and activity of several enzymes involved in one-carbon metabolism. S-adenosylmethionine (SAM), the direct metabolite of methionine, is the methyl donor for nearly all methylation reactions in the body. SAM is irreversibly converted to S-adenosylhomocysteine (SAH), the metabolic precursor of homocysteine. SAH is a potent inhibitor of all methyltransferases. Very few studies have evaluated biological measures of methionine and its metabolites with colorectal cancer. Recently, a large cross-sectional study found plasma methionine was associated with a reduced risk of distal colorectal adenoma. To our best knowledge, no study has evaluated SAM or SAH with colorectal cancer or adenoma. Methods: In this study, we evaluated plasma levels of these markers with risk for colorectal adenoma using a colonoscopy-based matched case-control design. Participants were part of a large case-control study of colorectal adenoma. A subset of cases were individually matched to polyp-free controls in a 1:1 ratio on age, sex, race, study site and date of sample collection. Included in the analysis were 220 pairs of adenoma cases and polyp-free controls. SAM and SAH were measured in a single assay by high-performance liquid chromatography. Sex-specific quantile cutpoints were derived using the distributions among controls. Conditional logistic regression models were used to derive odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations with colorectal adenoma risk after adjusting for age, and other potential confounders. All of the reported P values were two-tailed, and statistical significance was set at 0.05. Result: A statistically significant interaction between sex, SAH or SAM, and adenoma risk was observed. Among women, high SAH was associated with a borderline statistically significant increased risk of adenoma (p for trend=0.08). Among men, both high SAH (OR=0.36, 95% CI: 0.16-0.78, p for trend=0.009) and high SAM (OR=0.41, 95% CI: 0.19-0.88, p for trend=0.02) were associated with decreased risks of adenoma. The joint association of SAM and SAH was also evaluated among men. In comparison to men with low SAH and low SAM, men with high SAM and high SAH had a reduced risk of colorectal adenoma. Conclusion: The findings reported in this study are new, suggesting SAH and SAM may be involved in the development of colorectal adenoma. Further studies are warranted.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4469. doi:1538-7445.AM2012-4469
Abstract 4536: Identification of new prognostic biomarker of gastric cancer by systems analysis
Authors: Seol So-Young , Lim Jae Yun , Yoon Sun Och , Hong Soon Won , Kim Jong Won , Choi Seung Ho , Cho Jae Yong 
Published: August 2012

Abstract
Gastric cancer is one of the most common and cancer-related deaths worldwide and accounts for an estimated 800,000 deaths annually. Prognosis depends on the stage of disease. Even though within same stage, gastric cancer patients present diverse clinical manifestations and prognosis. To differentiate the malignant potential appropriately, many efforts have been made to select prognostic markers. Molecular markers will be important in predicting patients’ outcomes and personalized treatments according to individual biology. In this study, we analyzed the gene expression profile of human gastric cancer (published on CCR) to identify potential biomarkers which could be used to classify patients according to prognosis and also become new therapeutic targets. We found that TXN family genes and ERO1L were significantly overexpressed and related to prognosis. qRT-PCR and tissue microarray validated TXN overexpression and ERO1L have poor prognosis in gastric cancer. Finally, systems analysis revealed TXN family genes are highly correlated with many oncogene and tumor suppressor functional genes and shown relationship on energy and protein synthesis. Survival analysis based on Hierarchical-clustering of TXN family correlated mRNA expression genes revealed that TXN and TXNIP are significantly influenced the patient survival. We evaluated ERO1L and find out also significantly overexpressed in gastric tumor and suggest TXN family members are actively involved in gastric cancer. In vitro hypoxic experiment ERO1L was very highly expressed in hypoxic condition and this also supports TXN high expressed cancer cells are in hypoxic condition. In conclusion, our findings show that a prognostic molecular signature that can predict the poor progression of gastric cancer tumors. Furthermore, unequal distribution of expression patterns reflecting activation of TXN family and ERO1L with different survival rates supports a personalized target therapy in gastric cancer with biomarker gene signature driven patient selection. While further work is needed to elucidate the biological contributions of these markers, the results presented here provide a basis for future investigations of the functional and clinical effect of new target genes in gastric cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4536. doi:1538-7445.AM2012-4536
Abstract 4537: Tumoral expression on peroxisome proliferator-activated receptor ≤ is an independent prognostic marker in intestinal type of gastric cancer
Authors: Cho Soo-Jeong , Lee Jun Ho , Kook Myoung-Cheorl , Choi Il Ju , Ryu Keun Won , Kim Young-Woo 
Published: August 2012

Abstract
Introduction: Peroxisome proliferator-activated receptor ≤ (PPARδ) is a member of the nuclear hormone receptor family that regulates the expression of mediators of the inflammatory response. Metaplastic change secondary to chronic inflammation of gastric mucosa is regarded as a premalignant condition of intestinal-type gastric cancer (IGC). We aimed to evaluate the prognostic significance of PPARδ in IGC patients. Methods: The clinical significance of PPARδ was explored using tissue microarray methods and immunohistochemical staining of specimens from 306 IGC patients. The Kaplan-Meier method was used to calculate survival curves, and differences between the survival curves were assessed using the log-rank test. Cox proportional hazards regression was used to assess the effect of PPARδ expression on survival while controlling for other confounding covariates. Results: Among 306 patients with IGC (stage I-IV), PPARδ expression was detected by immunohistochemistry in the tumors of 209 (68.3%). The patients with PPARδ-positive tumors had significantly lower overall and gastric cancer-specific mortalities (P = 0.0010 and 0.0016, respectively, by the log-rank test) than did those with PPARδ-negative tumors. A positive PPARδ expression was a significant independent prognostic factor for gastric cancer-specific mortality by the Cox regression analysis in patients with IGC (adjusted hazard ratio, 0.42; 95% confidence interval, 0.22-0.81). The relationship between PPARδ and lower mortality was not modified by other clinical variables including tumor stage (all Pinteraction &gt; 0.05). Conclusions: tumor expression of PPARδ was independently associated with lower mortality of patients with IGC. Keywords: Gastric cancer, Intestinal-type gastric cancer, Peroxisome proliferator-activated receptor ≤ (PPARδ), Prognostic marker, Survival
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4537. doi:1538-7445.AM2012-4537
Abstract 4539: Vascular endothelial growth factor gene polymorphisms and clinical outcome in advanced gastric cancer treated with FOLFOX
Authors: Kwon Hyuk-Chan , Kim Sung-Hyun , Oh Sung Yong , Lee Suee , Lee Ji Hyun , Graves Christian A. , Hwang Jung-Ah , Hong Seung Hyun , Kim Hyo-Jin , Camphausen Kevin , Lee Yeon-Su 
Published: August 2012

Abstract
Background: Single-nucleotide polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) gene may have an impact on tumor progression, and response to chemotherapy. The aim of this study is to evaluate the associations between VEGF SNPs and clinical outcome in advanced gastric cancer patients treated with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX). Methods: One hundred ninety recurrent or metastatic gastric cancer patients were enrolled in this study and treated with FOLFOX regimen. Genomic DNA was isolated from whole blood, and six VEGF (-2578C/A, –2489C/T, –1498T/C, –634G/C, 936C/T, and 1612G/A) gene polymorphisms were analyzed by PCR. Results: Patients genotyped G/G for –634G/C gene polymorphism had lower response rate (22.2%) than those G/C or C/C (32.3%, 51.1%; p = 0.034). The median serum levels of VEGF was higher in G/G genotypes than G/C + C/C (724.1 pg/ml vs. 462.4 pg/ml, p = 0.041). Patients with the VEGF –634CG/C polymorphism G/C + C/C genotype had a longer time to progression (TTP) of 4.9 months, compared with the TTP of 3.5 months for those with the G/G (p = 0.012, log-rank test). By multivariate analysis, this G/G genotype of –634G/C polymorphism was identified as an independent prognostic factor (Hazard ratio 1.497, p = 0.017). No significant influence on overall survival (OS) was observed by the –634 G/C. However, other SNPs were not related to response rate, TTP, or OS. Conclusion: Our data suggest that G/G genotype of –634G/C polymorphism is related to the higher serum levels of VEGF, and poor clinical outcome in advanced gastric cancer patients. It may help to identify patients who are more sensitive to FOLFOX regimen.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4539. doi:1538-7445.AM2012-4539
Abstract 4543: Uptake of 18F-FDOPA analogue 3H-L-DOPA is mediated by large neutral amino acid transporter LAT1 in human glioblastoma
Authors: Youland Ryan S. , Kitange Gaspar J. , Pokorny Jenny L. , Sarkaria Jann N. 
Published: August 2012

Abstract
INTRODUCTION: The L-Type amino acid transporter 1 (LAT1) transports large neutral amino acids across the plasma membrane in a variety of cells. Positron emission tomography (PET) imaging with the amino acid tracer 6-18F-fluoro-L-dopa (18F-FDOPA) provides useful histological information in human gliomas in addition to providing better localizing information then CT or MRI alone. This study is the first to correlate LAT1 expression with uptake of the 18F-FDOPA analog, 3H-L-DOPA in human glioblastomas. METHODS: Endogenous expression of LAT1 was evaluated in two established glioblastoma multiforme (GBM) cell lines and three primary GBM xenografts using Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Uptake of FDOPA was assessed in vitro using 3H-L-DOPA as an analog to 18F-FDOPA. Knockdown of LAT1 expression was achieved by lentiviral expression of anti-LAT1 shRNA in GBM lines with high LAT1 expression. The effect of LAT1 knockdown on 3H-L-DOPA uptake was then quantified. RESULTS: Results from Western blotting and qRT-PCR demonstrate that LAT1 is variably expressed in GBM. Levels of 3H-L-DOPA uptake were directly related to LAT1 expression (p&lt;0.001) across the 5 lines. Knockdown of LAT1 was achieved in T98 cells (knockdown efficiency = 82.8%) and xenograft GBM 28 (knockdown efficiency = 73.7%) as confirmed by qRT-PCR and Western blotting. Knockdown of LAT1 reduced 3H-L-DOPA uptake by 57.2% (p&lt;0.0001) in T98 and 52.1% in GBM 28 (p&lt;0.001). CONCLUSIONS: This is the first report of 3H-L-DOPA uptake being driven by LAT1 in human GBM. Our findings suggest LAT1 as a transporter of 18F-FDOPA in GBM. Additional studies are underway to correlate LAT1 expression with PET 18F-FDOPA uptake in patients with GBM.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4543. doi:1538-7445.AM2012-4543
Abstract 4547: Clinical relevance of circulating tumor cells in esophageal cancer
Authors: Effenberger Katharina E. , Reeh Matthias , Riethdorf Sabine , Eichstaedt Dominique , Izbicki Jakob R. , Bockhorn Maximilian , Pantel Klaus 
Published: August 2012

Abstract
Background: Current modalities to predict tumor recurrence and survival in esophageal cancer are insufficient. Locoregional and distant relapse is even common in lymph node-negative patients and more precise staging methods are therefore needed. Little is known about the utility of circulating tumor cells (CTC) as staging tool in esophageal cancer. Methods: In a prospective study we identified CTC in peripheral blood of esophageal cancer patients by two separate methods. We enrolled 85 consecutive esophageal cancer patients (03/2010-10/2011) who were surgically resected (R0) and patients received neither neoadjuvant nor adjuvant therapy. Peripheral blood was taken at the time of primary surgery and CTC were detected by either manual MACS enrichment (anti-cytokeratin plus anti-EpCam) with subsequent anti-cytokeratin staining or the automated CellSearch system (cleared by the FDA for CTC detection in metastatic breast, colon and prostate cancer) in parallel. CTC detection rates and correlation with clinicopathologic parameters were evaluated. The median clinical follow-up time is 11 months ranging from 1 to 19 months. Results: So far, 67 patients have been analysed of which 21 (31.3%) had CTCs using MACS, and 10 (14.9%) using CellSearch. CTCs detected with MACS significantly correlated with tumor size (p=0.040) and aggressive tumor biology as indicated by presence of regional lymph node (p=0.040) and distant metastases (p=0.019). CTCs detected with CellSearch correlated significantly with lymph node (p=0.044) and distant metastases (p=0.045), while no correlation was observed for tumor size or grading. CTC-positive patients had a worse overall survival than CTC-negative patients when tested with the CellSearch system (p=0.009). Conclusion: The presence of CTCs in patients with resectable esophageal cancer correlates with clinicopathologic risk factors.and predicts an unfavorable prognosis. Thus, our pilot study suggests that CTC detection may contribute to an improved staging in esophageal cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4547. doi:1538-7445.AM2012-4547
Abstract 4554: QPCR and sequence analysis of DNA template from a microfluidic CTC isolation platform
Authors: Strauss William , Parker Alex , Juhn Frank , Cronin Maureen , White Emily , Vahidi Behrad , Fang Cong , Klem Erich , Vasko Robert , Romero Juan , Tabchy Adel , Dempsey Paul 
Published: August 2012

Abstract
Sequence analysis and quantitative allele specific PCR (QPCR) methods permit genetic profiling of cancer for targeted therapeutic selection; such personalized treatments have been associated with improved outcomes in cancer. Circulating tumor cells (CTC) offer a minimally-invasive opportunity for serial patient sampling, and potentially a means of tracking the molecular evolution that underlies the behavior and response phenotype of the disease including potential therapeutic response markers. Acquiring these types of patient profiles requires a platform and workflow providing reliable detection and recovery of small numbers of mutation-bearing CTC from a blood sample. Availability of such an enabling platform is a necessary prerequisite to the clinical correlation studies needed to demonstrate the utility of mutation-bearing CTC to patient care. We have successfully purified CTCs and converted them into DNA template of sufficient purity and quality to support multiple non-overlapping advanced molecular characterizations. Beginning with whole human blood spiked with defined numbers of cultured cancer cells as surrogates for CTCs, cells were successfully fluid-phase labeled using an anti-EpCAM antibody ferrofluid. Using a proprietary microfluidic sheath flow technology, EpCAM positive, cytokeratin staining cells were selected from 2 to 4 ml of labeled blood. This method produced sufficient DNA template for multiple analyses per patient sample. QPCR analysis of these templates demonstrated reproducible detection of fewer than 1% target cells in a background of non-target cells, allowing detection of the KRAS G12S mutation from as few as 5 recaptured cancer cells. The same DNA templates were then used for hybrid capture and next-generation sequencing of a panel of more than 200 cancer-related genes. This sequencing platform was able to detect multiple somatic mutations in genomic DNA templates produced from samples containing as few as 10 cancer cells per milliliter of blood. Together these data provide initial proof-of-concept for a system capable of detecting and characterizing mutations across any specified set of genes within purified CTC populations.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4554. doi:1538-7445.AM2012-4554
Abstract 4555: Protein and glycan biomarkers of malignant potential in pancreatic cyst fluid
Authors: Maupin Kevin , Curnutte Bryan , Cao Zheng , Partyka Katie , McDonald Mitch , Kwon Richard , Allen Peter , Brand Randall , Simeone Diane , Haab Brian B. 
Published: August 2012

Abstract
The early detection of a portion of pancreatic cancer precursors_cystic neoplasms of the pancreas_is possible through high-resolution abdominal imaging, providing an opportunity to successfully treat these lesions before they become invasive. The increased use of abdominal imaging has led to a higher rate of identifying pancreatic cysts, but currently it is not possible to accurately determine which cysts have high malignant potential and should be removed. Our previous work showed that the glycosylation and abundance of specific proteins in the cyst fluid was significantly different between potentially malignant cysts and benign cysts, providing leads for biomarkers to guide patient management. In this work we tested the hypothesis that a panel of specific protein glycoforms forms an accurate biomarker for pancreatic cysts with high malignant potential. Using antibody-lectin sandwich arrays, screens of nearly 100 different candidate markers and multiple glycoforms of each marker confirmed previous results and also showed that two distinct glycan structures are present on several proteins at high levels in the cyst fluid of cancer precursors (intraductal pancreatic mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN)) but not in benign cysts (serous cystadenomas (SC) and pseudocysts (PC)). The glycans, N-acetyl glucosamine and the blood group H structure, previously have not been recognized as cancer biomarkers. A six-marker panel comprising the measurement of one of these glycans on MUC5AC, MUC16, endorepellin, and fibronectin correctly detected 37 of 39 (95%) potential cancer precursors and 16 of 18 (89%) of the benign cysts. This performance significantly surpasses current diagnostic accuracy. The validation of this biomarker panel could lead to more accurate treatment decisions for patients with potentially malignant cysts while sparing patients with benign cysts from unnecessary procedures.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4555. doi:1538-7445.AM2012-4555
Abstract 456: The Alpha9 nicotinic acetylcholine receptor is the key mediator In nicotine-enhanced cancer metastasis in breast cancer cells
Authors: Wei Po-Li , Hung Chin-Sheng , Chang Yu-Jia 
Published: August 2012

Abstract
Background/purpose: The tobacco-specific mitogen nicotine was reported to correlate with cancer progression and tumorigenesis in breast cancer. Metastasis is a major cause of cancer death, so the influence of nicotine on breast cancer cell migration is also of interest. Our aim is to elucidate the mechanisms of nicotine-enhanced migration of breast cancer cells and thereby achieve better control of metastasis. Methods: The influence of nicotine on breast cancer cell migration was evaluated by trans-well and wound-healing migration assays. Receptor-mediated migration was studied with both a small molecule. inhibitor and small interfering RNA (siRNA). Results: The alpha9 nicotinic acetylcholine receptor, a9nAChR, was identified in breast cancer cell lines MCF-7 and MDA-MB-231. Nicotine enhanced cell migration in both trans-well and wound-healing migration assays. We used a specific inhibitor and siRNA to demonstrate that a9nAChR is the key modulator in mediating nicotine-enhanced breast cancer cell migration through up-regulation of fibronectin and vimentin. Conclusion: Nicotine treatment enhanced breast cancer metastasis through a9nAChR signaling via enhanced fibronectin and vimentin expression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 456. doi:1538-7445.AM2012-456