bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4480: Associations between phytanic acid and alpha-methylacyl-CoA racemase (AMACR) expression in the normal human prostate
Authors: Kataria Yachana , Gann Peter , Enk Erika , Moser Ann , Deaton Ryan , Lu Yi , Nonn Larisa , Sharifi Roohollah , Deane Leslie , Ananthanarayanan Vijayalakshmi , Wright-Geise Margaret 
Published: August 2012

Abstract
Alpha-methylacyl-CoA racemase (AMACR) is an enzyme that is overexpressed in prostate cancer, with lower levels present in normal prostatic tissues. AMACR is involved in the metabolism of phytanic acid - a branched chain saturated fatty acid that has been linked with elevated risks of prostate cancer in several epidemiologic studies. Although considerable research has been done on AMACR as a clinical biomarker in prostate cancer, no study has evaluated the possible link between phytanic acid and AMACR gene expression in the normal human prostate, and thus the possibility that AMACR plays a causal role in prostate carcinogenesis. Fasting blood and histologcally benign prostate tissue samples were obtained from 31 men undergoing radical prostatectomy for the treatment of localized disease. Concentrations of phytanic acid in serum and tissues were determined by isotope dilution gas chromatography-mass spectrometry. RNA was extracted from epithelial cells isolated from fresh-frozen prostate tissues by laser capture microdissection, and AMACR mRNA levels were quantified using real time polymerase chain reaction. Tissue phytanic acid concentrations were not significantly correlated with serum levels nor with prostatic AMACR mRNA levels. Notably, AMACR was significantly inversely correlated with body mass index (Spearman correlation coefficient (r)= –0.43, p=0.02) and directly correlated with Gleason score (r=0.35, p=0.05). Stratification by body mass index revealed an unexpected inverse correlation between wAMACR gene expression levels and phytanic acid concentrations in the prostate (r= –0.95, p= 0.001) in obese men. In conclusion, blood and tissue levels of phytanic acid were not correlated, which suggests that blood measures should not be utilized as a surrogate measure of this fatty acid in the target organ. Contrary to expectation, tissue phytanic acid levels were significantly inversely associated with AMACR gene expression levels in the prostate, but only among obese men.These findings require confirmation in other, larger studies.
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 4480. doi:1538-7445.AM2012-4480
Abstract 4484: A novel objective, image-based phenotypic assay reveals higher α-radiation-induced γ-H2AX level in peripheral blood lymphocytes as a risk predictor for lung cancer
Authors: He Yonggang , Gong Yilei , Gu Jian , Lin Jie , Chang David W. , Lippman Scott M. , Roth Jack , Wu Xifeng 
Published: August 2012

Abstract
Intermediate phenotypic biomarker measures the summary results of genetic variations and may enhance predictive power in cancer risk assessment. In this study, we developed a novel objective, image-based phenotypic assay to measure α-radiation induced DNA double strand breaks (DSBs) in peripheral blood lymphocytes (PBLs) and used it as a potential biomarker for lung cancer risk prediction. γ-H2AX formation in the chromatin flanking DNA DSBs is one of the most sensitive DNA damage markers. In an ongoing lung cancer case-control study, the baseline and α-radiation-induced γ-H2AX immunofluorescence intensities in the PBLs from 403 untreated lung cancer patients and 307 controls subjects were assessed, and the ratio of the induced γ-H2AX level to the baseline γ-H2AX level was used as a variable to evaluate the sensitivity to mutagen challenge. The mean γ-H2AX ratio was significantly higher in cases than controls (case vs. control: 1.46±0.14 vs. 1.41±0.12, p &lt; 0.001). A significantly decreasing trend in γ-H2AX ratio with age was observed for both cases (p for trend =0.003) and controls (p for trend =0.011). Dichotomized at the median level of the γ-H2AX ratio in controls, individuals with high ratio exhibited a significantly increased risk of lung cancer (OR=2.33, 95%CI: 1.67-3.23). There was also a dose-response relationship with lung cancer risk in tertile and quartile analysis (p for trend &lt; 0.001 for both). Analysis of the joint effects of risk factors revealed an apparently elevated risk of lung cancer for subjects with a higher γ-H2AX ratio who were ever smokers, compared with subjects with a low ratio who were never smokers (OR=12.68, 95%CI: 6.84-23.51, p &lt; 0.001). This is the first study applying relative quantification of the γ-H2AX level in PBL to assess the risk for developing lung cancer. Susceptibility to DNA DSBs might help to identify individuals at high risk for this cancer. α-radiation-induced DNA damage as determined with the new γ-H2AX assay could be a novel phenotypic risk factor of lung 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 4484. doi:1538-7445.AM2012-4484
Abstract 4494: Preoperative serum levels of matrix metalloproteinase-2 (MMP-2) and survival of breast cancer among Korean women
Authors: Song Nan , Sung Hyuna , Jeon Sujee , Lee Yunhee , Choi Ji-Yeob , Park Sue K. , Lee Kyoung-Mu , Yoo Keun-Young , Noh Dong-Young , Ahn Se-Hyun , Lee Sang-Ah , Kang Daehee 
Published: August 2012

Abstract
Objective: We evaluated whether preoperative serum levels of matrix metalloproteinase-2 (MMP-2) work as a prognostic biomarker in breast cancer prognosis. Methods: Three hundred and three women with histologically confirmed breast cancer were recruited. The follow-up time for all patients was 4.24 years. The MMP-2 levels were quantitatively measured by enzyme-linked immunosorbent assay (ELISA) using the preoperative serum. The relationship of MMP-2 to survival was investigated using Cox's proportional hazard model adjusted for the TNM stage and estrogen receptor (ER) status. Results: In the multivariate analysis, disease-free survival (DFS) was worse among patients with the third tertile of MMP-2 compared to the first tertile of MMP-2 (hazard ratio (HR)=1.80, 95% confidence interval (CI)=1.04-3.11, P=0.04). Furthermore, when the patients were stratified by histological grade and nuclear grade, the worse DFS was predicted by high levels of MMP-2 (HR=2.90 and 95% CI=1.42-5.92 in histological grade III vs. I-II and HR=2.61 and 95% CI=1.26-5.39 in nuclear grade III vs. I-II). In ER negative patients, high levels of MMP-2 also tended to have a worse prognosis (HR=2.75 and 95% CI=1.32-5.73). Conclusions: Our results suggest that the preoperative serum levels of MMP-2 were associated with the survival of breast cancer as a potential prognostic biomarker.
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 4494. doi:1538-7445.AM2012-4494
Abstract 4495: Clinical implications of family history of prostate cancer in an active surveillance cohort
Authors: Goh Chee L. , Saunders Edward , Leongamornlert Daniel , Tymrakiewicz Malgorzata , Thomas Karen , Selvadurai Elizabeth , Woode-Amissah Ruth , Dadaev Tokhir , Mahmud Nadiya , Castro Elena , Olmos David , Guy Michelle , Govindasami Koveela , O'Brien Lynne , Hall Amanda , Wilkinson Rosemary , Sawyer Emma , Olama Ali Amin Al , Easton Douglas , Kote-Jarai Zsofia , Parker Christopher , Eeles Rosalind 
Published: August 2012

Abstract
Background Prostate cancer (PCa) is one of the most heritable cancers and a positive family history (FH) of PCa increases risk to 1st degree relatives by over 2 fold. The search for causative genetic variants has led to genome-wide association studies, which have so far identified over 45 susceptibility loci associated with PCa. However, the clinical utility of FH status or PCa risk SNP profiles to predict disease progression or aggression is yet undefined. We explore their potential prognostic role in patients undergoing Active Surveillance (AS). Methods Those enrolled in the Royal Marsden Hospital AS study were eligible. FH was obtained using questionnaires. For those with missing/incomplete data, hospital records were used. Patients with positive FH were further stratified according to the involvement of 1st and/or 2nd degree relatives. For risk score analyses, DNA was genotyped using the Sequenom MassARRAY iPLEX platform and Taqman assays. The cumulative risk scores for each patient were calculated by summing risk alleles for each loci using the weighted effect as estimated in previous studies. FH status and the SNP risk scores were analysed separately against defined adverse outcomes in AS, including adverse histology on repeat biopsy and time to treatment, to determine their prognostic value. Results 439 patients were eligible for FH analyses. 31% of those have since undergone treatment and 13% have histological upgrade on repeat biopsies. On univariate analysis, there was no significant relationship between FH of PCa in any degree of relation, and biopsy upgrade or time to treatment. For risk score analyses, 391 patients’ DNA were studied. There was also no relationship between the calculated genetic risk scores and biopsy upgrade or time to treatment (p=0.57 and p=0.83 respectively). When analysing differences between the higher and lower genetic risk groups (defined as the top 25% and lowest 25% of the genetic risk distribution), there was again no relationship (p=0.85 and p=0.91 respectively). Conclusion FH status or currently known PCa SNP profile risk scores have not been shown to be prognostic factors and should not be used to influence decisions in AS. This is the first study analysing the implications of PCa risk SNPs in AS.
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 4495. doi:1538-7445.AM2012-4495
Abstract 4504: Retrospective study of clinicopathologic factors associated with ALK rearrangement and survival outcome in Chinese patients with NSCLC
Authors: Zhang Xu-chao , Blanckmeister Carolyn A. , Yang Jinji , Tian Hong-Xia , Chen Jie , Xuan Jian-wei , Xie Zhi , Su Jian , Luo Xin-lan , Yan Hong-hong , Liu Yan-hui , Wu Yi-Long 
Published: August 2012

Abstract
Background: ALK rearrangement and EGFR mutation are significant molecular subtypes of non-small cell lung cancer (NSCLC) that are targets for different tyrosine kinase inhibitors (TKIs). We tested a large cohort of NSCLC patients for ALK, EGFR and KRAS abnormalities and correlated clinical factors with the ALK fusion gene and overall survival (OS). Methods: ALK status was detected by RACE sequencing; EGFR and KRAS status were also detected by direct DNA sequencing. OS was estimated by the Kaplan-Meier method. Results: 294 consecutive, unselected, banked NSCLC cases were tested; 27 (9.2%), 79 (29.2%) and 26 (9.6%) patients were ALK-, EGFR- and KRAS-positive, respectively. ALK rearrangement and EGFR mutation were largely exclusive (r=−0.15, P=0.007) although two cases were both ALK- and EGFR-positive. In non-parametric tests, ALK-positivity was associated with female gender (χ2=5.189; P=0.023), non/light-smoking (χ2=6.067; P=0.014) and adenocarcinoma (χ2=4.301; P=0.038). The ALK fusion partner was EML4 in all 27 cases; EML4-ALK fusion variants V1, V2 and V3 (V3a/V3b/V3c) made up the majority (24/27) of EML4-ALK fusions. There were no significant OS differences between ALK-positive, EGFR-mutant, KRAS-mutant and triple-negative groups, between ALK-positive and -negative patients, or when ALK-positive cases were matched 1:2 or 1:1 with (non-TKI-treated) controls balancing for disease stage, gender, histology and EGFR/KRAS status. In ALK-positive patients, bivariate analysis found that non- or light-smoking status (P=0.016) and prior surgery (P=0.024) were associated with increased OS and a multivariate Cox regression model found that disease stage and surgical treatment were prognostic for OS. In a multivariate logistic regression model, female gender (HR=2.793; P=0.041), wild type EGFR (HR=15.147; P=0.001), non/light-smoking (HR=3.572; P=0.020) and adenocarcinoma (HR=5.713; P=0.024) were significantly associated with ALK-rearrangement. Conclusion: Overall, the ALK fusion gene occurred in 9.2% of NSCLC patients, and was associated with non/light-smoking history, adenocarcinoma histology and female gender. ALK fusion variants were mostly V1-3, which may inform ALK screening by RT-PCR. ALK rearrangement was not a favorable prognostic factor in NSCLC, although smoking history may influence OS in ALK-positive patients. A TKI (crizotinib) now exists for ALK-positive NSCLC and may improve OS in these patients.
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 4504. doi:1538-7445.AM2012-4504
Abstract 4520: Elevated serum antibodies against insulin-like growth factor-binding protein-2 allow detecting early stage cancers: Evidences from glioma and colorectal carcinoma studies
Authors: Song Sonya W. , Li Yuchen , Zhang Jing , Zhang Bin , Yang Wei , You Gan , Xu Kaiyu , Wu Jing , Luo Chenghua , Jiang Tao 
Published: August 2012

Abstract
Background: Tumor-specific immunity of insulin-like growth factor binding protein-2 (IGFBP-2) has been reported in several cancers. We aimed to assess the role of serum IGFBP-2 antibodies (IGFBP-2-Abs) in early cancer detection. Patients and Methods: Glioma and colorectal carcinoma (CRC) were used as models. Serum IGFBP-2 and IGFBP-2-Abs were measured in 260 tumor patients (145 gliomas, 45 colorectal polyps, and 70 CRCs) and 141 controls. Receiver operating characteristic curves were applied. Results: Serum IGFBP-2-Ab levels were significantly elevated in tumors (mean: 82.1 ng/ml, median: 17 ng/ml, range: 0-1,387 ng/ml) compared with controls (10.6 ng/ml, 0 ng/ml, 0-212 ng/ml) (P &lt; 0.0001), and higher in early than advanced cancers opposite of serum IGFBP-2 levels. IGFBP-2-Abs effectively discriminated between controls and grade II and III gliomas [area under the curve (AUC): 0.821-0.864; 95% confidence interval (CI) = 0.762-0.936; P &lt; 0.0001], and CRC I-II (AUC: 0.668; 95% CI = 0.566-0.770; P = 0.002) as well as indicative of advanced polyps at high risk of CRC (AUC: 0.72; 95% CI = 0.630-0.811; P &lt; 0.0001). The sensitivity and specificity for diagnosing grade II-III gliomas reached 66.2% - 83.8% and 81%. Combined serum IGFBP-2 and IGFBP-2-Abs augmented the discriminative power of all stage tumors (AUC: 0.823), gliomas (AUC: 0.800), and CRCs (AUC = 0.917). Conclusions: Our results first demonstrate IGFBP-2-Abs for early cancer detection, and in combination of serum IGFBP-2 for improved cancer diagnosis.
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 4520. doi:1538-7445.AM2012-4520
Abstract 4529: Prognostic implications of TSPO in human colorectal cancer
Authors: McKinley Eliot T. , Ayers Gregory D. , Smith Ralph A. , Zhao Ping , Washington Mary K. , Manning Henry C. 
Published: August 2012

Abstract
Translocator protein (TSPO), previously referred to as peripheral benzodiazepine receptor, is an 18kDa outer mitochondrial membrane protein involved in a number of cellular processes including steroid synthesis, cholesterol metabolism, proliferation, and apoptosis. Elevated TSPO expression has been linked with disease progression, diminished survival, and aggressiveness in a number of cancers. Studies conducted in our laboratory have demonstrated that positron emission tomography (PET) imaging with TSPO targeted probes can be used to non-invasively quantify TSPO levels in tumors. These imaging studies suggest that TSPO ligand PET may be a valuable clinical cancer imaging biomarker. In the current studies, TSPO expression in human colon cancer and paired liver metastases was evaluated using tissue microarrays. These arrays were constructed using 99 primary colon cancers and 95 matched primary colon cancers and liver metastases from Vanderbilt patients with known clinical outcomes. Among these, we found that nearly 2/3 of the colon cancers were positive for TSPO expression (64%). Similar to previous studies in other organ sites, elevated TSPO expression was significantly associated with higher tumor grade in the Vanderbilt cohort of CRC patients. Among patients with grade 2 or grade 3 tumors, an individual with elevated TSPO expression was 3 times more likely to have a grade 3 tumor than a grade 2 tumor. In comparing matched primary colon cancers and associated liver metastases, we found a strong concordance between TSPO levels and localization across matched specimens. No correlation was observed between TSPO expression and Ki67 or pEGFR levels suggesting the potentially unique information provided by the measurement of TSPO levels. In conclusion, clinically relevant prognostic information can be obtained by the measurement of TSPO expression in colorectal cancer. Thus, TSPO targeted PET may be a promising-non invasive biomarker in this setting.
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 4529. doi:1538-7445.AM2012-4529
Abstract 4574: FGFR1 amplification in high grade, estrogene receptor positive and metastasized breast cancers
Authors: Pfaltz Katrin , Schneider Sandra , Güth Uwe , Kilic Ergin , Eppenberger-Castori Serenella , Tapia Coya F. 
Published: August 2012

Abstract
Background: The FGFR1-gene (fibroblast growth factor receptor 1) is located at chromosome 8p12 encoding for a tyrosine kinase. FGFR1 is involved in cell cycle, differentiation, survival, apoptosis, and angiogenesis. Recently, it was shown that breast cancer cell lines harboring a FGFR1 amplification were more sensitive to treatment with an FGFR inhibitor. To estimate if FGFR inhibitors can be a therapeutic option in human breast cancer we investigated the prevalence and the histological subtypes of FGFR1 amplification in a large cohort of breast cancers. Methods: Tissue micro-arrays with 907 breast cancers were hybridized using the commercially available fluorescent in-situ hybridization probe (FGFR1/CEN8; ZytoVision®). The results were interpreted as following: a normal gene status was considered as a ratio (FGFR1/CEN8): 0.8-1.9, an amplification was defined as a ratio β2.0, a polysomy was defined as more than &gt;4 FGFR1 and CEP8 signals. Results: FGFR1 amplification was observed in 8.9% (n=81), a normal gene status was found in 80.7% (n=732), and a polysomy was detected in 10.2% (n=93) tumors. FGFR1 amplified breast cancers showed the following features: expression of estrogen receptor 85% (67/78), ductal 72.8% (59/81), high grade (G3) 45.5% (35/77), her2 over-expression (score2+/3+) 16% (12/75), and 18% (13/72) recurrence. Comparing T (T1, T2, T3) and N (N0 and &gt;N0)-categories between FGFR1 amplified and non-amplified tumors the following results were seen: T1: 25% (19/77) vs. 34% (245/719), T2: 56% (43/77) vs. 48% (345/719), T3: 9% (7/77) vs. 6% (43/719), N0: 44.5% (28/63) vs 53% (338/641), &gt;N0: 55.5% (35/63) vs 47% (303/641). We could observe a slight better long term overall survival in patients treated with anti-hormonal therapy and FGFR1 amplified breast cancers (p=0.085). Conclusions: FGFR1 amplification is prevalent (8.9%) in breast cancer, especially among the most frequent subtypes such as estrogen receptor positive breast cancers (10%) and ductal type (8%). Further, FGFR1 amplified breast cancer showed often unfavorable/aggressive features such as a high tumor grade (45.5%), larger tumor diameter, and metastasis (55.5%). These patients are a clinically relevant group since they need aggressive adjuvant treatment regimen. The detection of FGFR1 amplification could help in the identification of some patients already at higher risk which might benefit from a new therapeutic option with FGFR1 inhibitors.
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 4574. doi:1538-7445.AM2012-4574
Abstract 4598: Allelic loss of NDST4, a putative tumor suppressor gene, is associated with tumor progression of colorectal cancer
Authors: Tzeng Sheng-Tai , Tsai Ming-Hong , Lee Jing-Xing , Yang Ya-Chien 
Published: August 2012

Abstract
Colorectal cancer (CRC) is one of the most common malignancies in the world. Many molecular abnormalities have been reported in CRC, of which accumulated alterations of tumor suppressor genes (TSGs) and proto-oncogenes are required for the disease development. Genomic deletion is reflected in a genetic mechanism called loss of heterozygosity (LOH). Allelic deletion at tumor suppressor loci is common in all human cancers, and contributes to TSG silencing. By allelotyping with 22 polymorphic microsatellite markers spanning from chromosome 4pter to 4qter, we first defined the most frequent LOH region at 4q27, which occurred allelic imbalance in 32.1% (34/106) of colorectal carcinomas. After fine deletion mapping in these carcinomas, we further identified a minimal region harboring one gene with known functions, named NDST4. By quantitative RT-PCR, NDST4 expression could hardly be detected in 10 of 11 CRC cell lines, and was downregulated in 57.7% (30/52) of CRC tumors. Importantly, NDST4 expression was significantly decreased in tumors compared with matched normal mucosa or adenomas (P&lt;0.01). In addition, immunohistochemistry staining of CRC tissue array also demonstrated decreased protein levels in Dukes’ stages C and D tumors. We further directly determined the genetic loss of NDST4 in colorectal tumors by use of 3 microsatellite markers located upstream of and inside NDST4 gene. Sixty (29.9%) of 201 carcinomas exhibited LOH at one or more microsatellite loci. Allelic loss of NDST4 was increased in patients with late stage of tumor extension (T3 and T4), lymph node involvement and distant metastasis (P=0.011, 0.053 and 0.058, respectively). Notably, LOH at MS5979 locus, a newly identified microsatellite marker within NDST4 gene, was significantly associated with disease progression of Dukes’ stages (P&lt;0.01). Taken together, NDST4 could be a CRC-associated TSG and its genetic loss might be involved in tumor progression. In addition, the LOH assay established in the study could be a potential diagnostic and prognostic test in CRC.
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 4598. doi:1538-7445.AM2012-4598