bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1578: Identification of type X collagen as a pan-cancer serum biomarker
Authors: Prendes Maria J. , Chapman Karen B. , Tam Orlena , Wagner Joseph 
Published: August 2015

Abstract
We previously reported elevated expression of Type X Collagen (COL10A1) in solid tumors of diverse origin (Future Oncology 2012 Aug;8(8): 1031-40). This elevated expression in tumors was primarily localized to vasculature, while COL10A1 expression in most adult tissues was negligible. Given this pattern of expression, we hypothesized that COL10A1 might demonstrate utility as a blood-born tumor biomarker. Serum samples from healthy volunteers and from patients with active cancers of the breast, lung, pancreas, colon, kidney, and bladder were obtained from multiple existing bio-banks. COL10A1 serum levels were assessed in over 400 total patient samples using a polyclonal COL10A1 sandwich ELISA. The overall utility of COL10A1 levels in determining presence of cancer was judged by calculating ROC-AUC scores for each individual cancer type. In general, COL10A1 levels were increased in cancer patients, although this increase varied as a function of cancer type as well as by the bio-bank the sera was obtained from. Given the sensitivity and specificity limitations of polyclonal ELISA technology, even greater performance of COL10A1 as a tumor biomarker could be attainable using high-specificity monoclonal antibodies. We are currently characterizing such tests in prospectively collected sera samples from breast cancer patients. These data suggest that COL10A1 is a potential blood-born pan-cancer biomarker that could prove useful in non-invasive cancer screening as well as in monitoring tumor progression and treatment response.
Citation Format: Maria J. Prendes, Karen B. Chapman, Orlena Tam, Joseph Wagner. Identification of type X collagen as a pan-cancer serum biomarker. [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 1578. doi:10.1158/1538-7445.AM2015-1578
Abstract 1579: Circulating cell-free DNA as a diagnostic marker for epithelial ovarian cancer and an association with epithelial-mesenchymal transition
Authors: Koo Yu-Jin , Min Kyung-Jin , Hong Jin-Hwa , Lee Jae-Kwan 
Published: August 2015

Abstract
Objectives: Although technologies continue to develop, there are still many limitations on detecting circulating tumor cells in blood. In addition, the great genetic heterogeneity in ovarian cancer is one of the major concerns. Therefore, we aimed to investigate the cell-free DNA (cfDNA) as a diagnostic marker for epithelial ovarian cancer (EOC) and evaluate the cfDNA level of epithelial-mesenchymal transition markers.
Methods: Blood was preoperatively collected from women who were assigned to surgery for pelvic mass. DNA was extracted using Qiagen DNA Mini kit and quantification of total cfDNA was performed using real-time PCR with TaqMan Assay with primers directed to the following genes:
GAPDH, β-globin, β-actin, E-cadherin, and fibronectin.
Results: A total of 32 patients with EOC and 17 patients of benign ovarian disease (controls) were included. The median cfDNA level of β-globin was 0 (range, 0-0.35)GE/ml in EOC and 0.41 (range, 0-33.5)GE/ml in control (p = 0.04).
The sensitivity of β-globin cfDNA (&gt;0.4 GE/ml) was 51.9%, which was lower than that of CA-125 (96.3%, if CA-125 &gt;35IU/ml). cfDNA was significantly higher in advanced stage of EOC than early stage EOC (p = 0.02). Plasma E-cadherin level was significantly related with β-globin cfDNA (coefficient 0.886, p&lt;0.001). However, there was no significant association with cfDNA amount and survival outcomes.
Conclusions: Circulating cfDNA can be a promising target for early detection of EOC. The levels of epithelial-mesenchymal transition markers showed a different pattern in plasma and were associated with other cfDNA amounts.
Citation Format: Yu-Jin Koo, Kyung-Jin Min, Jin-Hwa Hong, Jae-Kwan Lee. Circulating cell-free DNA as a diagnostic marker for epithelial ovarian cancer and an association with epithelial-mesenchymal transition. [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 1579. doi:10.1158/1538-7445.AM2015-1579
Abstract 1585: Application of a graphene oxide based microfluidic device (GO Chip) to prostate cancer circulating tumor cell capture and analysis
Authors: Kozminsky Molly , Yoon Hyeun Joong , Palanisamy Nallasivam , Cooney Kathleen , Hussain Maha , Alva Ajjai , Morgan Todd , Nagrath Sunitha 
Published: August 2015

Abstract
One in seven men in the United States will be diagnosed with prostate cancer in his life time, in part because of the prevalence of screening for serum levels of prostate specific antigen (PSA). However, this has led to the overtreatment of the disease, leading to recommendations against frequent PSA testing and establishing the need for a more informative biomarker in prostate cancer. Circulating tumor cells (CTCs) are rare cells present in the blood stream of cancer patients at the low frequency on the order of one CTC in one billion normal blood cells. The graphene oxide chip (GO Chip) is a microfluidic CTC capture device with increased sensitivity and purity due to its use of the nanomaterial graphene oxide to present a capture antibody against the epithelial cellular adhesion molecule (EpCAM). In this study, whole blood was collected from 50 prostate cancer patients, including those with metastatic, localized, castrate resistant, and castrate sensitive disease, and analyzed using the GO Chip. Captured cells were stained for cytokeratin, CD45, and DAPI, with nucleated cytokeratin positive cells being denoted as CTCs. CTCs were detected in 47 out of 50 patients, and an average of 5.94 CTCs/mL was recovered from each sample. Correlation of CTCs with surrogate endpoints could improve the utility of CTCs as a liquid biopsy, potentially advancing their application in translational research.
Citation Format: Molly Kozminsky, Hyeun Joong Yoon, Nallasivam Palanisamy, Kathleen Cooney, Maha Hussain, Ajjai Alva, Todd Morgan, Sunitha Nagrath. Application of a graphene oxide based microfluidic device (GO Chip) to prostate cancer circulating tumor cell capture and analysis. [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 1585. doi:10.1158/1538-7445.AM2015-1585
Abstract 1591: Comprehensive molecular profiling of circulating tumor cells from metastatic breast cancer patients
Authors: Magbanua Mark Jesus Mendoza , Hauranieh Louai , Roy Ritu , Pendyala Praveen , Sosa Eduardo , Scott Janet , Rugo Hope , Park John 
Published: August 2015

Abstract
Background: Recent enumeration studies on CTCs have demonstrated the clinical value of these cells. The molecular biology of CTCs, however, remains poorly understood.
Methods: We performed RNA and DNA profiling of CTCs from metastatic breast cancer (MBC) patients. 244 blood samples from 162 MBC patients were subjected to immunomagnetic enrichment and fluorescence activated cell sorting (IE/FACS) to isolate highly pure CTCs. Microfluidic-based multiplex QPCR analysis was utilized to determine the expression levels of 64 cancer-related genes. Parallel genome-wide copy number analysis by array comparative genomic hybridization was also performed on CTCs isolated from the same enriched blood samples.
Results: Transcriptional analysis of CTCs was successfully performed in 151 samples from 105 patients. We observed the up-regulation of several genes including CCND1, EPCAM, KRT7 and MUC1 and the down-regulation of hematopoietic-related genes including PTPRC (CD45) and CD68 (adjusted p &lt;0.001) in CTCs. Clustering analysis of expression profiles revealed three CTC clusters, one containing both subtypes basal (ESR1-low) and normal-like (ESR1-low, CAV1/VIM-high) and two other clusters containing luminal subtype (ESR1-high). A subset of CTCs expressed epithelial-mesenchymal transition genes, however, genes for stem cellness were not generally expressed. Serial CTC expression profiling in 28 patients demonstrated changes in expression over time. Exploratory single CTC expression analysis revealed cell-to-cell heterogeneity. Parallel genome-wide copy number analysis in matched CTCs from 49 patients revealed gains (e.g. 1q and 8q), losses (e.g., 8p and 16q), and focal amplifications (e.g. on 8q and 11q including CCND1) that are frequently observed in primary breast cancers. We also observed three copy number clusters with varying levels of genomic aberrations. Up-regulation of CCND1 and ERBB2 in CTCs was associated with increased level of genomic instability.
Conclusions: Parallel gene expression and copy number profiling provided novel insights on the biology of CTCs. Molecular characterization of CTCs may shed further light on the biology of metastasis and disease progression.
Citation Format: Mark Jesus Mendoza Magbanua, Louai Hauranieh, Ritu Roy, Praveen Pendyala, Eduardo Sosa, Janet Scott, Hope Rugo, John Park. Comprehensive molecular profiling of circulating tumor cells from metastatic breast cancer patients. [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 1591. doi:10.1158/1538-7445.AM2015-1591
Abstract 1595: Analysis of circulating epithelial and EMT-like CTCs in pancreatic cancer using a sensitive microfluidic CTC capture device
Authors: Zeinali Mina , Murlidhar Vasudha , Fouladdel Shamileh , Hafner Mathius , Shao Shimeng , Azizi Ebrahim , Wicha Max S. , Cuneo Kyle , Simeone Diane M. , Nagrath Sunitha 
Published: August 2015

Abstract
Background & Aims: A critical factor in the poor outcomes in pancreatic cancer is due to it's silent nature until late in the disease process, so early detection has remained a major issue in this type of cancer. Detection, quantification, and molecular characterization of Epithelial circulating tumor cells (CTCs) as well as Epithelial-to-Mesenchymal Transition (EMT)-like CTCs in peripheral blood have been recognized as a means of “liquid biopsy” technique in the diagnosis of cancer and metastasis.
Methods: A modified version of CTC chip, CTC Carpet chip was used to investigate the inextricable relationship between circulating epithelial and EMT-like CTCs in 40 pancreatic cancer patients at both protein and RNA levels.
Results: The recovery from whole blood spiked with different cancer cell line was validated, achieving a mean efficiency of ∼100% for both HT-29 and Panc-1 cell lines compared to &lt;80% for PC-3 cell line. Out of 40 patients, 38 patients had ≥5 CK+ CTCs with a mean of 21.84 per mL and all 40 samples had ≥ 15 Vim+ CTCs with mean of 89.77 per mL of whole blood. Up to 67 CK+ epithelial and 257 Vim+ EMT like CTCs were detected in these set of samples. The results indicated the significant differences between the numbers of Epithelial CTCs vs. EMT-like CTCs in both stage I-II and IV of these 40 pancreatic cancer patients’ samples.
Conclusion: Although the isolation of CTCs from pancretic cancer is possible nowadays, investigation of their clinical utility has proven less successful than the other cancer types, due to poor sensitivity of many CTC assays for patients with PDAC. Herein, we present an integrated microfluidic technology- and biology-based translational approach using bioengineering tools to identify and study the biological relevance of rare CTCs including both circulating epithelial and EMT-like tumor cells simultaneously from the peripheral blood of pancreatic cancer patients by using multiple markers of interest.
Citation Format: Mina Zeinali, Vasudha Murlidhar, Shamileh Fouladdel, Mathius Hafner, Shimeng Shao, Ebrahim Azizi, Max S. Wicha, Kyle Cuneo, Diane M. Simeone, Sunitha Nagrath. Analysis of circulating epithelial and EMT-like CTCs in pancreatic cancer using a sensitive microfluidic CTC capture device. [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 1595. doi:10.1158/1538-7445.AM2015-1595
Abstract 163: Investigation of molecular mechanisms by which PCA3 modulates prostate cancer cell survival
Authors: Goulart Ana Emilia , Ferreira Luciana B. , de Freitas Paula Priscilla , Batoreu Nadia , BONAMINO MARTIN H. , Gimba Etel Rodrigues Pereira 
Published: August 2015

Abstract
PCA3 is a prostate-specific non coding RNA (ncRNA), involved in the control of prostate cancer (PCa) cell survival, through modulating androgen receptor (AR) signaling. We aimed to investigate whether several cancer related genes, including those involved in epithelial-mesenchymal transition (EMT) and AR co-regulators could modulate LNCaP cell survival in response to PCA3 downregulation. We also aimed to promote PCA3 stable silencing through a lentiviral vector containing a PCA3 short hairpin RNA (shRNA) specific sequence. Small interfering RNA (siRNA) or lentivirus vector-based shRNA were used to downregulate PCA3 expression. Upon PCA3 downregulation, cells were analyzed by qRT-PCR to investigate mRNA expression. Flow cytometry was performed to analyze the percentage of LNCaP GFP + cells and trypan blue staining to analyze the number of viable cells after PCA3 stable silencing. Among 14 AR co-regulators genes investigated, 12 were upregulated in siPCA3-transfected cells in relation to controls. We also found that among 84 cancer-related genes tested, 16 were differentially expressed in LNCaP siPCA3-transfected cells when compared to transfected cells with a scramble sequence. Of these, 30% are genes coding for signal transduction molecules and transcription factors. Gene expression profile of EMT-related genes revealed that E-cadherin, Claudin-3, Cytokeratin-18, Snail, Twist and Slug are upregulated in LNCaP siPCA3-transfected cells compared to control, while Claudin-4, Cytokeratin-8 and Vimentin are downregulated. LNCaP cells transduced with lentiviral vectors carrying the GFP gene and shPCA3 stably dowregulated PCA3 expression, producing a reduction of 60% of LNCaP GFP+ cells compared to shScr transduced or non-transduced LNCaP cells. Our results suggest that the decrease in the number of LNCaP viable cells upon siPCA3 transfection is not modulated by the classical EMT program. Observed upregulation of most tested AR co-regulators upon PCA3 silencing indicates that this non-coding RNA could negatively modulate the transcription of these genes. Our data further suggest that that this ncRNA perform a regulatory role in gene expression, being able to modulate gene expression of several signaling pathways related to cancer. Finally, stable silencing of PCA3 expression using lentivirus vector shows potential as a PCa therapeutic approach by negatively modulating cell survival.
Citation Format: Ana Emilia Goulart, Luciana B. Ferreira, Paula Priscilla de Freitas, Nadia Batoreu, MARTIN H. BONAMINO, Etel Rodrigues Pereira Gimba. Investigation of molecular mechanisms by which PCA3 modulates prostate cancer cell survival. [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 163. doi:10.1158/1538-7445.AM2015-163
Abstract 1630: Effects of rhBMP-2 on osteosarcoma tumorigenesis
Authors: Piperdi Sajida , Geller David , Park Amy , Chung So Hak , Gorlick Richard 
Published: August 2015

Abstract
Introduction: Osteosarcoma (OS) is the most common primary bone malignancy in children and young adults. Complete surgical extirpation of bulk tumor is essential to successful treatment of OS. While historically ablative surgery such as amputations were the mainstay of treatment, wide excision has been shown to provide equivalent survival results, permitting for limb-salvage surgery in over 90% of cases. Following tumor resection, structural allograft bone is often employed to reconstruct the involved extremity. Bone Morphogenetic Protein-2 (BMP-2), a member of the TGF beta superfamily, possesses tremendous osteoinductive potential and could theoretically be used to promote bone healing but has been historically contraindicated due to concern it may stimulate residual tumor. To date, the role of BMP-2 in OS remains unclear and its effect on OS remains controversial. The purpose of this investigation is to evaluate the effect of exogenous recombinant human BMP-2 (rhBMP-2) on osteosarcoma. We hypothesize that exposure of osteosarcoma to rhBMP-2 will not stimulate tumor growth or development.
Methods: Functional assays were performed using five standard osteosarcoma cell lines (143B, MG-63, SaOS-2, U20S, and HOS) and three patient derived xenograft cell lines (OS17, OS31, LM7). The concentration of rhBMP-2 utilized varied between 0.5 to 2 μg/ml. Motility (random migration) was measured by wound healing scratch assay. Migration (both haptotaxis and chemotaxis) was quantitatively measured using Boyden Chamber assay. Invasion was also measured using Boyden chamber over which a thin layer of extracellular matrix is applied. Comparison between different concentrations of rhBMP-2 upon different time points on osteosarcoma cell lines and characterizations are completed and underway.
Results: Preliminary findings suggest that exogenous rhBMP-2 does not increase the ability of osteosarcoma cells to migrate and invade in all tested lines (143B, MG-63, OS17). Quantitative migration decreases with increasing concentration of rhBMP-2 over a 5-hour time course in all tested lines (143B, SaOS-2, MG-63, OS17). Invasion did not increase with increasing rhBMP-2 concentration in any tested line (143B, SaOS-2, OS17).
Conclusions and Future Directions: Preliminary results support the contention that exposure of osteosarcoma to exogenous rhBMP-2 does not increase in vitro tumorigenesis. In fact, findings suggest that rhBMP-2 may have a protective effect in that tumor migration decreases following exposure. Continued characterization using additional tumor lines is ongoing.
Citation Format: Sajida Piperdi, David Geller, Amy Park, So Hak Chung, Richard Gorlick. Effects of rhBMP-2 on osteosarcoma tumorigenesis. [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 1630. doi:10.1158/1538-7445.AM2015-1630
Abstract 1642: Antitumor activity of lurbinectedin toward ovarian clear cell carcinoma
Authors: Takahashi Ryoko , Mabuchi Seiji , Matsumoto Yuri , Kawano Mahiru , Sasano Tomoyuki , Kuroda Hiromasa , Kozasa Katsumi , Sawada Kenjirou , Kimura Tadashi 
Published: August 2015

Abstract
Objectives:Lurbinectedin is a marine-derived covalent DNA minor groove binder and is structurally similar to trabectedin except for the C subunit. Lurbinectedin (PM01183) is a newly developed antitumor agent that is currently being investigated in phase I/II clinical trials in patients with solid tumors including ovarian cancer. The objective of this study is to investigate the effectiveness of lurbinectedin as a single agent or as combination with existing antitumor agent against ovarian clear cell carcinoma which is regarded as an aggressive chemoresistant histological subtype.
Methods:Using human ovarian clear cell carcinoma cell lines, the anti-tumor effects of lurbinectedin, SN38, topotecan, doxorubicin, cisplatin and paclitaxel as single agent were assessed by MTS assay. Then the cytotoxicities of combination treatments involving lurbinectedin and 1 of the 4 agents were evaluated by isobologram analysis to examine which of these combinations displayed synergistic effects. The antitumor activities of the combination treatments were also examined using cisplatin-resistant and paclitaxel-resistant ovarian clear cell carcinoma sublines, which were derived from the parental clear cell carcinoma cells by continuously exposing them to cisplatin or paclitaxel. Finally, using nude mice inoculated with clear cell carcinoma cells, we examined the growth-inhibitory effect of lurbinectedin in vivo.
Results:Lurbinectedin showed significant antitumor activity toward chemosensitive and chemoresistant CCC cells in vitro. Mouse xenografts of CCC cells revealed that lurbinectedin significantly inhibits tumor growth. Concurrent exposure to lurbinectedin and SN-38 resulted in synergistic interactions in CCC cell lines. The combination of lurbinectedin plus SN-38 also had strong synergistic effects on both the cisplatin-resistant and paclitaxel-resistant CCC cell lines. Treatment with everolimus significantly enhanced the antitumor activity of single agent lurbinectedin and combination of lurbinectedin plus SN-38.
Conclusions:Lurbinectedin is a promising agent for CCC as a first-line chemotherapy and as a second-line treatment of recurrent CCC that had previously been treated with cisplatin or paclitaxel. Moreover, lurbinectedin combined with irinotecan may be more efficacious for the management of CCC.
Citation Format: Ryoko Takahashi, Seiji Mabuchi, Yuri Matsumoto, Mahiru Kawano, Tomoyuki Sasano, Hiromasa Kuroda, Katsumi Kozasa, Kenjirou Sawada, Tadashi Kimura. Antitumor activity of lurbinectedin toward ovarian clear cell carcinoma. [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 1642. doi:10.1158/1538-7445.AM2015-1642
Abstract 1655: Targeting RFX-1 as a novel therapeutic strategy in hepatocellular carcinoma
Authors: Su Jung-Chen 
Published: August 2015

Abstract
Regulatory factor X (RFX) 1 is a transcription factor that has been linked to negative regulation of tumor progression; however, its biological function and signaling cascades are unknown. In this study, we identify RFX-1 is a negative regulator of cell proliferation in human HCC. We demonstrated that ectopic expression of RFX-1 suppressed the colony forming ability of HCC cell lines through activating SHP-1 expression. In addition, nude mice bearing RFX-1-overexpressing tumors showed a repression of growth rate compared to the control group. Notably, we demonstrated that mRNA and protein level of RFX-1 is highly correlated with SHP-1 in 101 clinical HCC patients, indicating that RFX-1 might be a tumor suppressor of human HCC. To identify the RFX-1 activator for HCC therapy, we screened in-house small molecule library and found that one of small molecules, SC-2001, targeted RFX-1 and exhibited potent anti-tumor effect on HCC cells. In addition, we proved that SHP-1 activation and STAT3 dephosphorylation induced by SC-2001-activated RFX-1. Furthermore, genetic knockdown of RFX-1 reversed SC-2001-induced cell growth inhibition. Importantly, by a mouse xenograft model, silencing of RFX-1 could rescue the anti-HCC tumor effect caused by SC-2001 in vivo, implying that RFX-1 is a promising target for HCC therapy. Taken together, our results indicated that RFX-1/SHP-1/STAT3 signaling might a potential strategy for HCC therapy, and SC-2001 is a promising lead compound for drug development of HCC target therapy.
Citation Format: Jung-Chen Su. Targeting RFX-1 as a novel therapeutic strategy in hepatocellular carcinoma. [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 1655. doi:10.1158/1538-7445.AM2015-1655