bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1564: Evaluation and characterization of anti-RalA autoantibody as a potential biomarker in human prostate cancer
Authors: li jitian , Dai Liping , Casiano Carlos A. , Zhang Jianying 
Published: August 2015

Abstract
Autoantibodies against intracellular tumor associated antigens (TAAs) are commonly found in various types of human cancers. Their utility in providing insights into tumor biology and as potential cancer biomarkers is well documented. In this study, serum autoantibodies to the Ras family small GTP binding protein (RalA) were detected by immunofluorescence assay, enzyme-linked immunosorbent assay (ELISA), and immunoblotting in 353 sera from patients with prostate cancer (PCa), benign prostatic hyperplasia (BPH), and normal controls. Expression of RalA in prostate tumor tissues was evaluated by immunohistochemistry. The cumulative positive rate of autoantibodies against RalA in PCa reached 18.4%, higher than that in sera with BPH (14.7%) and normal human sera (NHS) (2.25%, P&lt;0.01). Twenty seven of 32 (84.4%) sera with positive OD values were consistently positive in immunoblots. The sensitivity and specificity of anti-RalA antibody in PCa detection was 18.4% and 97.8%, respectively. Representative PCa sera showed a cytoplasmic immunofluorescence staining pattern, with more intense staining in the perinuclear regions or partial staining in intracellular membrane. This pattern was similar to that produced by monoclonal RalA antibody. Strong expression of RalA was observed in 76.5% of prostate tumor tissues. Anti-RalA and PSA simultaneously used as diagnostic markers improved the sensitivity of PCa detection to 57.4%. In addition, the appearance of autoantibodies to RalA was assessed over time in the serially collected samples after surgery in cases. In all cancer patients with anti-RalA positive, autoantibodies were detected in 6 of 54 serial samples taken after surgery with a median lead time of 121 days (Interquartile Range, IQR 0-360). In conclusion, autoantibody to RalA might be a potential serological biomarker for the immunodiagnosis of early stage PCa. We are currently identifying additional novel TAAs targeted by serum autoantibodies in PCa by using two-dimensional gel electrophoresis (2DE) and liquid chromatography-tandem-mass spectrometry (LC-MS/MS). The combination of RalA with PSA, and with other antigens in PCa-specific TAA arrays has the potential for significantly improving the sensitivity of early PCa detection and management in diverse populations.
Key words: anti-RalA autoantibody; tumor-associated antigens (TAAs); cancer immunodiagnosis; prostate cancer
Citation Format: jitian li, Liping Dai, Carlos A. Casiano, Jianying Zhang. Evaluation and characterization of anti-RalA autoantibody as a potential biomarker in human prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1564. doi:10.1158/1538-7445.AM2015-1564
Abstract 1566: Association of a serum HPV16 IgG signature and risk of oropharyngeal cancer
Authors: Anderson Karen S. , Langseth Hilde , Wallstrom Garrick , Posner Marshall , Cheng Julia N. , Alam Rizwan , Chowell Diego , Mork Jon 
Published: August 2015

Abstract
Introduction: Human papillomavirus type 16 (HPV16) infection is associated with an increasing fraction of oropharyngeal cancer. The aim of our study was to determine the association of HPV16 antibodies (Abs) and oropharyngeal cancer (OPC) risk in sera obtained prior to clinical diagnosis.
Methods: We identified 92 participants with incident oropharyngeal cancers and 460 age-, gender-, region- and year- matched controls from the Janus Serumbank in Norway. Serum samples were collected from cases, on average, 9.2 years before diagnosis (range, -0.6-14.9 years). 11 cases had serum samples from multiple time points. IgG Abs to the HPV16 antigens E1, E4, E5, E6, E7, L1, L2, and the N-terminal and C-terminal fragments of E2 (NE2, CE2) were quantified in blinded fashion using a custom RAPID ELISA assay. Full-length genes were expressed as GST fusion proteins with a mammalian protein expression system, incubated with sera, and bound IgG was measured. The ratio of relative luminescence units (RLU) values for each antigen to control GST protein was determined. Cutoff values were pre-established as 3 SD&gt;median of 247 healthy controls. A logistic regression classifier of a 7-Ab biomarker panel (E1, NE2, CE2, E4, E5, E6, E7) for the predictive diagnosis of OPC was trained on an independent sample set, and applied to these samples. P-values were calculated by Fisher's exact test. Odds ratios (ORs) of cancer and 95% CIs were calculated.
Results: HPV16 early antigen seropositivity was present in 13% of patients with OPC and 1% of controls (OR, 17.0; 95% CI, 5.0-74.0, p&lt;0.0001). The probability of seropositivity was inversely associated with the time from serum collection and diagnosis (0-2 years, 84.9; &gt;10 years, 5.4). Abs to CE2 were strongly associated with cases 0-2 years pre-diagnosis (OR, 112.0; 95% CI, 15.0-971.2, p&lt;0.0001).
Conclusion: HPV16 Abs to multiple early viral antigens are detectable years prior to diagnosis of oropharyngeal cancer, and the probability of seropositivity increases closer to diagnosis. A model for screening would help identify individuals at risk for whom interventions and surveillance may be evaluated.
Citation Format: Karen S. Anderson, Hilde Langseth, Garrick Wallstrom, Marshall Posner, Julia N. Cheng, Rizwan Alam, Diego Chowell, Jon Mork. Association of a serum HPV16 IgG signature and risk of oropharyngeal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1566. doi:10.1158/1538-7445.AM2015-1566
Abstract 1569: Development of a noninvasive and sensitive urine screening test for liver cancer targeting circulation-derived cancer DNA biomarkers
Authors: Jain Surbhi , Chen Sitong , Lin Selena Y. , Clemens Adam , Hann Hei-won L. , Chang Ting-Tsung , Hu Chi-Tan , Chen Shun-Hua , Song Wei , Su Ying-Hsiu 
Published: August 2015

Abstract
Hepatocellular carcinoma (HCC), or liver cancer, is an aggressive disease and is regarded as one of the fastest growing cancers in the United States in incidence. The 5-year survival rate of HCC patients drops dramatically from a poor 26%, in early-stage cancer, to a mere 2% in late stages of this disease. The only available early detection biomarker is serum alpha-fetoprotein, which can detect only 40-60% of cases. Our goal is to develop a screening test for early detection of liver cancer, in order to meet this urgent need for new and better biomarkers for HCC. Cancer is a disease of the genome and epigenome, and if we can detect these underlying genetic mutations and epigenetic modifications in the periphery, we can effectively detect cancer early. Hence, we chose a panel of both HCC-associated genetic and DNA methylation biomarkers. We have previously shown that urine contains fragmented cell-free DNA derived from the circulation and that we can detect cancer-related DNA, both mutated and methylated DNA, in the urine of such patients. We have also demonstrated that the concentration of tumor-derived DNA in plasma and in urine is similar in patients with tumors. In order to demonstrate the feasibility of detecting HCC DNA biomarkers in the circulation derived urine DNA, we have developed short amplicon (∼50 bp) PCR-based assays targeting HCC-specific mutations in TP53 and CTNNB1 genes and HCC-specific methylation in GSTP1, RASSF1A and CDKN2A genes. Urine DNA isolated from samples of hepatitis, cirrhosis, and HCC patients were tested in each of the assays and analyzed for individual marker and panel performance. The performance of the markers and our approach towards the development of a targeted next generation urine DNA based HCC screening test is discussed.
Citation Format: Surbhi Jain, Sitong Chen, Selena Y. Lin, Adam Clemens, Hei-won L. Hann, Ting-Tsung Chang, Chi-Tan Hu, Shun-Hua Chen, Wei Song, Ying-Hsiu Su. Development of a noninvasive and sensitive urine screening test for liver cancer targeting circulation-derived cancer DNA biomarkers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1569. doi:10.1158/1538-7445.AM2015-1569
Abstract 1575: Serum circulating miR–Test application: Standardized protocol for miR–Test clinical application
Authors: Montani Francesca , Marzi Matteo , Dezi Fabio , Dama Elisa , Carletti Rose Mary , Veronesi Giulia , Nicassio Francesco , Di Fiore Pier Paolo , Bianchi Fabrizio 
Published: August 2015

Abstract
Lung cancer is leading cause of cancer death worldwide. Being lung cancer asymptomatic in its early stages, the majority of patients are diagnosed with advanced disease. Therefore, it is vital that screening programs and novel diagnostic tools are developed to increase lung cancer early detection. The development of a minimally invasive blood-based diagnostic tool would be ideal as a first-line screening procedure. An increasing number of studies are demonstrating that fluctuations of circulating miRNAs are associated to lung cancer. Recently, we described a serum circulating miRNA signature (miR-Test) diagnostic for asymptomatic, early stage, lung cancer, that was validated in a large cohort of individuals (N = 1115) enrolled in the lung cancer screening program COSMOS (Continuous Observation of SMOking Subjects). However, the transfer to the clinic of a blood test based on circ-miRNAs requires the establishment of standardized operating procedures (SOPs), working instructions and guidelines for all pre-analytical and analytical procedures.
We identified possible sources of variability affecting circulating miRNAs, analyzed their impact on the miR-Test performance, and defined a standardized protocol to optimize miR-Test application. Analysis of all possible technical and biological variation affecting circ-miRNAs level, revealed two main sources of variability: one related to analytical procedures for miRNAs extraction and quantification, and the other due to pre-analytical conditions, on how samples are prepared. The extraction causes the main source of analytical imprecision.
In conclusion, we identified an optimal protocol for the application of miR-Test for lung cancer early diagnosis.
Citation Format: Francesca Montani, Matteo Marzi, Fabio Dezi, Elisa Dama, Rose Mary Carletti, Giulia Veronesi, Francesco Nicassio, Pier Paolo Di Fiore, Fabrizio Bianchi. Serum circulating miR–Test application: Standardized protocol for miR–Test clinical application. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1575. doi:10.1158/1538-7445.AM2015-1575
Abstract 1581: A study of pulmonary and peripheral vein blood as sources of circulating tumor cells in early lung cancer
Authors: Murlidhar Vasudha , Reddy Rishindra M. , Azizi Ebrahim , Zhao Lili , Grabauskiene Svetlana , Zhang Zhuo , Ramnath Nithya , Lin Jules , Chang Andrew C. , Carrott Philip W. , Lynch William R. , Orringer Mark B. , Wicha Max S. , Palanisamy Nallasivam , Beer David G. , Nagrath Sunitha 
Published: August 2015

Abstract
Lung cancer is one of the most prevalent cancers world-wide. It is usually diagnosed at an advanced stage with low survival rates. Early detection and intervention can have a profound impact in improving survival. Circulating tumor cells (CTCs), or cells shed by the tumor into the blood circulation, offer a less invasive method of tumor biopsy. Surgical lobectomy for early stage lung cancers provides access to the pulmonary vein (PV) draining the affected lobe, and is presumably an enriched source of CTCs shed by the primary lung tumor. Analyzing peripheral (Pe) and pulmonary vein (PV) blood combined could potentially shed light onto optimal markers and disease progression. We hypothesize that blood from the pulmonary vein has a higher abundance of CTCs than peripheral blood, thereby providing a larger yield of CTCs from early lung cancer patients for downstream analysis. A cohort of greater than 30 lung cancer patients was enrolled in a pilot study. PV and Pe blood specimens from these patients were obtained at different time points in the perioperative time period, and were processed through a high-throughput microfluidic device, the OncoBean Chip that isolates CTCs by immuno-affinity based capture. A higher number of PV CTCs were detected than from Pe. In addition, rare CTC clusters were observed in the PV blood in some cases, which were further characterized for protein expression. Gene expression analysis was performed for comparison of CTCs obtained from these two different sources. Evaluating different CTC sources along the venous drainage of a tumor could potentially offer an insight into CTC biology and spread of the disease.
Citation Format: Vasudha Murlidhar, Rishindra M. Reddy, Ebrahim Azizi, Lili Zhao, Svetlana Grabauskiene, Zhuo Zhang, Nithya Ramnath, Jules Lin, Andrew C. Chang, Philip W. Carrott, William R. Lynch, Mark B. Orringer, Max S. Wicha, Nallasivam Palanisamy, David G. Beer, Sunitha Nagrath. A study of pulmonary and peripheral vein blood as sources of circulating tumor cells in early lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1581. doi:10.1158/1538-7445.AM2015-1581
Abstract 1589: Investigation of circulating tumor cells from head and neck cancer patients undergoing radiation therapy: A pilot study
Authors: Eblan Michael J. , Myung Ja Hye , Caster Joseph M. , Chera Bhishamjit S. , Hong Seungpyo , Wang Andrew Z. 
Published: August 2015

Abstract
Background: Circulating tumor cell (CTC) enumeration provides prognostic information in patients with metastatic breast, prostate, colorectal and lung cancer. However, the effect of radiation therapy (RT) on CTCs in patients with primary head and neck malignancies has not been explored. The purpose of this exploratory study is to examine how CTCs, as measured by a novel cell capture technique, respond to RT in patients with head and neck cancer. Methods: A total of a 16 patients undergoing definitive radiation for primary, non-metastatic head and neck cancer were enrolled in this pilot study. Peripheral blood was collected at 5 time points, including at baseline prior to starting RT, at the first week, mid-point and final week during treatment, and at least 4 weeks after completion of RT. Quantification of CTCs was performed with a novel device that used a biomimetic combination of three cancer cell-specific antibodies (aEpCAM, aHer-2, and aEGFR) immobilized through poly(amidoamine) dendrimers and E-selectin, which respectively induce concurrent stationary binding and dynamic cell rolling of the tumor cells. Results: CTCs were successfully detected in all patients before the start of radiation (100%), including patients with HPV/p16 positive or negative tumors. The novel CTC device yielded up to a 4-fold enhancement in capture efficiency relative to the aEpCAM-functionalized surface. The average CTC count in patients before RT was 386 CTCs per mL (range, 18 to 1134 CTCs per mL), significantly higher than the average CTC count of 90 CTCs per mL after the completion of radiation (range, 5 to 393 CTCs per mL). All but one patient demonstrated a decrease in measured CTCs at sequential time points during the course of RT. The patient with an elevation in CTCs during RT had residual metastatic carcinoma detected after left level II selective cervical neck dissection, which was performed 12 weeks post-RT due to persistent radiographic lymph nodal abnormality. At a median follow-up of 1.5 months, no patient has had a local or distant failure. Conclusions: We have demonstrated that our novel technology can affectively capture CTCs in head and neck cancer patients. Importantly, our pilot data shows CTCs decrease over the course of RT, suggesting CTCs can be a predicative biomarker for radiotherapy response. Further study will investigate associations between CTC kinetics and clinical outcomes.
Citation Format: Michael J. Eblan, Ja Hye Myung, Joseph M. Caster, Bhishamjit S. Chera, Seungpyo Hong, Andrew Z. Wang. Investigation of circulating tumor cells from head and neck cancer patients undergoing radiation therapy: A pilot study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1589. doi:10.1158/1538-7445.AM2015-1589
Abstract 159: LncRNA RoR enhances the c-Myc mRNA stability in colon cancer
Authors: Huang Jianguo 
Published: August 2015

Abstract
Background: Emerging evidence has implicated long non-coding RNAs (lncRNAs) as master gene regulators; and they are often aberrantly expressed in a variety of human diseases including cancer. One of the mechanisms of lncRNA-mediated gene expression involves modulation of translation or mRNA stability by interacting with RNA binding proteins. We have previously demonstrated that lncRNA-RoR is a strong negative regulator of p53 in response to DNA damage. The present study was to determine whether and how lncRNA-RoR regulates c-Myc in colon cancer.
Methods: MTT assays were used to determine cell growth. Colon cancer tissue array was used to determine the level of lncRNA-RoR in colon cancer tissues by qRT-PCR. Interaction between lncRNA-RoR and RNA binding proteins was confirmed by RNA co-immunoprecipitation and RNA precipitation. LncRNA-RoR knockout in colon cancer cells was through CRISPR/Cas9 system. Dual fluorescent in situ hybridization (FISH) was used to determine the relative levels of lncRNA-RoR and c-Myc mRNA, and their co-localizations in colon cancer specimens. The effect of lncRNA-RoR on tumor growth was determined by a xenograft mouse model.
Results: Ectopic expression of lncRNA-RoR upregulated, whereas RoR-siRNA inhibited c-Myc mRNA and protein level, which was further confirmed by lncRNA-RoR knockout. Mechanistically, we showed that lncRNA-RoR directly interacted with RNA binding proteins, hnRNP U and hnRNP D, both of which are implicated in stability of c-Myc mRNA. This interaction was further confirmed by RNA immunoprecipitation. In consistent with these findings, ectopic expression of lncRNA-RoR stimulated cell proliferation but knockout of lncRNA-RoR significantly decreased cell proliferation. Moreover, ectopic expression of lncRNA-RoR in HCT-116 cells significantly promoted tumor growth in a xenograft mouse model. Finally, qPCR array showed the significant upregulation of lncRNA-RoR in colon cancer tissues. Similarly dual FISH revealed a strong correlation between lncRNA-RoR and c-Myc mRNA in colon cancer tissues.
Conclusion: It is well known that c-Myc mRNA has a very short half-life and regulation of c-Myc mRNA stability is complex. Our results suggest a novel mechanism of regulation of c-Myc mRNA stability involving lncRNA-RoR, hnRNP U and hnRNP D.
Citation Format: Jianguo Huang. LncRNA RoR enhances the c-Myc mRNA stability in colon cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 159. doi:10.1158/1538-7445.AM2015-159
Abstract 1590: CD133-expressing circulating tumor cells might predict poor prognosis in patients with head and neck cancer
Authors: Hsieh Jason Chia-Hsun , Shiao Harber Hung-Bo , Chao Bill Yuan-Jhih , Lin Ming-Jung , Chang John Wen-Cheng , Wang Hung-Ming , Wu Tyler Min-Hsien 
Published: August 2015

Abstract
PURPOSE: The prognostic value of circulating tumor cells (CTCs) number in patients with head and neck carcinoma (HNSCC) has been reported to be positive. The hypothesis of the additional markers on CTCs might predict clinical outcomes have been proposed. This study aimed to elucidate the prognostic/predictive value of CD133-expressing CTCs in HNSCC patients.
PATIENTS AND METHODS: In a prospective single-center study, CTCs were enumerated in the peripheral blood of 24 subjects, including 14 patients with HNSCC and 10 healthy donors, at baseline and 2 weeks after starting first dose of chemotherapy. CTCs were measured using an immunomagnetic separation technique by combined negative and positive selection strategies. Immunofluorescence staining methods were applied for surface marker identification. Tumor response at 12 weeks after chemotherapy of the whole cohort was performed by computed tomograpgy or magnetic resonance imaging scans following RECIST criteria 1.1.
RESULTS: In the first step of efficacy evaluation phase, an average recovery rate of 85.5% and a R2 value of 0.9932 were found when compared between spiked and recovered blood samples. A CTCs detection rate of 100.0% (14/14) was found by this protocol and the number could successfully differ HNSCC patients from healthy donors (P = 0.001). The mean and median (range) of baseline CTC number were 105.0 and 87.2 (34.5-358.1) cells/mL of blood. The higher baseline CTCs number was associated with higher tumor stage (AJCC 7th edition, P = 0.003). The higher absolute number (&gt;5cells/mL of blood) of baseline CD133-expressing CTCs could predict poor survivals (Kaplan-Meier survival curves, P = 0.013). In all assessable patients, a high correlation rate of 92.9% was found between changes of CTCs (decline or elevation) and CT responses (progressive disease [PD] and partial response [PR]/Stable disease [SD]) with a P value of 0.005 (Fisher exact test).
CONCLUSION: The number of CD133-expressing CTCs might be a useful prognostic for survivals and predictors for imaging response evaluation at 12 weeks in patients with HNSCC. Further investigation in large-scale prospective trials is warranted on the basis of the findings in this study.
Citation Format: Jason Chia-Hsun Hsieh, Harber Hung-Bo Shiao, Bill Yuan-Jhih Chao, Ming-Jung Lin, John Wen-Cheng Chang, Hung-Ming Wang, Tyler Min-Hsien Wu. CD133-expressing circulating tumor cells might predict poor prognosis in patients with head and neck cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1590. doi:10.1158/1538-7445.AM2015-1590