bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 713: Three-dimensional in vivo blood flow mapping in tumors using optical frequency domain imaging.
Authors: Blauvelt David , Mohan Nishant , Bouma Brett , Jain Rakesh , Padera Timothy , Vakoc Benjamin 
Published: August 2014

Abstract
Angiogenesis in the tumor microenvironment is a chaotic process that results in a dysfunctional vascular network. Unlike normal blood vessels, tumor vessels are dense, tortuous, and leaky. The disorganized nature of the tumor vascular network often leads to unequal perfusion in different parts of the tumor. While some vessels see high blood flow rates, others can be virtually stagnant. This heterogeneity in blood flow can affect oxygen distribution, and, as a result, the efficacy of radiation and chemotherapy. Furthermore, knowing how blood flow varies as a tumor develops is critical for our comprehension of tumor angiogenesis. Finally, our understanding of how anti-angiogenic and chemotherapeutic treatments affect tumor vessels depends on our ability to monitor blood flow. Unfortunately, existing strategies for measuring blood flow are limited by low spatial resolution, long imaging times, or an inability to measure flow over whole tumor volumes. Here, we use optical frequency domain imaging (OFDI) to measure blood flow in individual vessels over an entire tumor volume growing in a mouse. Previously, we have used OFDI to obtain high-resolution images of tumor vasculature. Our new technique is based on an association between the speed of moving blood and the dynamics of optical speckle patterns that are intrinsically generated in OFDI. By employing novel methods to measure these speckle patterns and then relate them to an underlying flow velocity, we are able to generate high-resolution three-dimensional maps of blood flow within tumors. Our results expand the potential of OFDI to characterize the tumor microvasculature by adding wide-field blood flow measurements to its demonstrated ability to characterize microvascular morphology, tumor anatomy, tissue viability, and lymphatic vessel morphology.
Citation Format: David Blauvelt, Nishant Mohan, Brett Bouma, Rakesh Jain, Timothy Padera, Benjamin Vakoc. Three-dimensional in vivo blood flow mapping in tumors using optical frequency domain imaging. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 713. doi:10.1158/1538-7445.AM2013-713
Abstract 717: Detection of premalignancy of esophageal mucosa by multispectral imaging of autofluorescence from protoporphyrin IX.
Authors: Horiuchi Toshikatsu , Morimoto Yuji , Taniguchi Hiroaki , Umetsu Araya , Ogura Shun-ichiro , Iwaya Keiichi , Shinomiya Nariyoshi 
Published: August 2014

Abstract
Background: We have recently found that chemically induced esophageal carcinoma emitted a strong fluorescence originating from protoporphyrin IX (PpIX). The aim of this study was to detect early changes in the esophageal mucosa for clarifying the mechanism of carcinogenesis. For this purpose, we established a novel method for detection of premalignancy based on multispectral fluorescence imaging (MFI) of autofluorescence (AF) from tissue. Methods: We made an N-nitroso-methylbutylamine (NMBA)-induced rat esophageal tumor model (15 mg/L in daily drinking water) and extracted the esophagus. The mucosal side was illuminated by an excitation blue light (405 nm) and the emitted light was captured on an EM-CCD detector (512 x 512 pixels), of which each pixel collected a spectrum ranging from 450 nm to 800 nm. The extracted tissues were further analyzed to measure porphyrins by high-performance lipid chromatography (HPLC). Results: When the mucosa was illuminated by the excitation light, AF with a peak at 630 nm was observed in preneoplastic lesions and HPLC revealed that the origin of AF was PpIX. MFI based on the spectral difference clearly visualized preneoplastic lesions: the spectral pattern of the AF from preneoplastic lesions was different from that from normal mucosa, and the spectral difference became greater with increase in the duration of NMBA administration and the concentration of PpIX also increased with the time course. Conclusion: The results showed that MFI of tissue AF has a potential for cancer screening.
Citation Format: Toshikatsu Horiuchi, Yuji Morimoto, Hiroaki Taniguchi, Araya Umetsu, Shun-ichiro Ogura, Keiichi Iwaya, Nariyoshi Shinomiya. Detection of premalignancy of esophageal mucosa by multispectral imaging of autofluorescence from protoporphyrin IX. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 717. doi:10.1158/1538-7445.AM2013-717
Abstract 728: Fluorescence-guided surgery for human-patient colon cancer tumorgrafts using a fluorophore-conjugated anti-CEA antibody.
Authors: Hiroshima Yukihiko , Maawy Ali , Zhang Yong , Chishima Takashi , Tanaka Kuniya , Bouvet Michael , Endo Itaru , Hoffman Robert M. 
Published: August 2014

Abstract
One of the most important prognostic factors for overall survival in colorectal cancer patients is the complete resection of tumor. We have previously demonstrated the effective fluorescence-guided surgery of primary and metastatic cancer with the use of fluorescent probes in mouse models. In this study, we determined the effectiveness of fluorescence-guided surgery using a fluorophore-conjugated anti-CEA antibody for human-patient colon cancer tumorgrafts in nude mouse models. Colon-cancer-patient tumor specimens were initially established subcutaneously in NOD/SCID mice immediately after surgery. The patient tumors were then harvested from NOD/SCID mice and passed orthotopically in nude mice. Eight weeks after orthotopic implantation of human colon cancer tumorgraft, a monoclonal anti-CEA antibody conjugated with Alexa 488 was delivered to tumor-bearing mice as a single intravenous dose 24 hours before laparotomy. Using fluorescence imaging, the primary tumor was clearly visible at laparotomy. The tumor was completely resected under fluorescence navigation. Histologic evaluation of the resected specimen revealed there were no cancer cells in the margin. The cancer cells were strongly stained by anti-CEA antibody conjugated with Alexa488. Fluorescence-guided surgery using a fluorophore-conjugated anti-CEA antibody should improve intraoperative staging and efficacy of resection for CEA-positive colorectal cancer.
Citation Format: Yukihiko Hiroshima, Ali Maawy, Yong Zhang, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman. Fluorescence-guided surgery for human-patient colon cancer tumorgrafts using a fluorophore-conjugated anti-CEA antibody. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 728. doi:10.1158/1538-7445.AM2013-728
Abstract 729: Chimeric antibodies to tumor antigen CEA improve detection of human colon cancer for fluorescence-guided surgery.
Authors: Metildi Cristina A. , Kaushal Sharmeela , Luiken George A. , Hoffman Robert M. , Bouvet Michael 
Published: August 2014

Abstract
Mouse models of human colon cancer were established with fragments of a CEA-expressing patient colon tumor. Mice received tail vein injections of a human-mouse chimeric anti-CEA-Alexa-488 antibody or mouse anti-CEA-Alexa-488 antibody 24 hours prior to fluorescence-guided surgery (FGS). Pre- and post-operative images were obtained to assess for completeness of resection. Mice were subsequently followed for 6 months post-operatively to assess for tumor recurrence and overall survival. At termination, all tumor lesions were harvested and evaluated histologically. Furthermore, the chimeric antibody was tested on frozen tumor and normal tissue arrays comparing it to the mouse antibody. The chimeric antibody demonstrated improved sensitivity and specificity in labeling the CEA-expressing tumor compared to the mouse antibody. The conjugation efficiency of the fluorophore to the chimeric antibody was 2-fold higher than that of the mouse antibody. On frozen tumor tissue arrays, the signal intensity of the chimeric antibody was significantly brighter compared to the mouse antibody indicating improved binding to tumor tissue. The chimeric antibody demonstrated improved specificity as shown by the lower signal intensity in normal human tissue samples compared to the mouse antibody indicating decreased binding of the chimeric antibody. The animals injected with the chimeric antibody had more effective FGS than the animals injected with the mouse antibody indicating improved visualization of tumor margins by the chimeric antibody. The humanized chimeric antibody has greater potential for clinical application for FGS than a mouse antibody.
Citation Format: Cristina A. Metildi, Sharmeela Kaushal, George A. Luiken, Robert M. Hoffman, Michael Bouvet. Chimeric antibodies to tumor antigen CEA improve detection of human colon cancer for fluorescence-guided surgery. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 729. doi:10.1158/1538-7445.AM2013-729
Abstract 760: Fem1b attenuates the transcriptional activity of Gli1 by promoting the ubiquitin mediated degradation of Gli1.
Authors: Gilder Andrew S. , Lu Deyin , Maher Joseph F. 
Published: August 2014

Abstract
Gli1 is a member of the Gli family of zinc finger transcription factors that functions in stem cell biology, and as an oncogene in malignant transformation. The Hedgehog signaling pathway in flies and mammals shares homology to the sex determination pathway of C. elegans in which the Gli-like transcription factor TRA-1 is regulated by the ubiquitin ligase adapter FEM-1. Here we provide evidence that the mammalian FEM-1 homolog Fem1b regulates Gli1 transcriptional activity. Consistent with this, we demonstrate an interaction between Fem1b and Gli1, and show that Fem1b promotes the ubiquitylation and proteasome-mediated degradation of Gli1. Fem1b mediated ubiquitylation of Gli1 was dependent on the VHL box domain of Fem1b, shown to interact with Elongin B/C-Cul2-box protein ubiquitin ligases. Fem1b reduced Gli1 transcriptional activity in a reporter assay, and this reduction was also dependent on the VHL box of Fem1b. Given that Gli1 up-regulation promotes tumorigenesis in glioblastoma, medulloblastoma, basal cell carcinoma, and a variety of epithelial malignancies, we hypothesize that Fem1b antagonizes the oncogenic capacity of Gli1 by targeting Gli1 for ubiquitin-mediated destruction in the proteasome.
Citation Format: Andrew S. Gilder, Deyin Lu, Joseph F. Maher. Fem1b attenuates the transcriptional activity of Gli1 by promoting the ubiquitin mediated degradation of Gli1. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 760. doi:10.1158/1538-7445.AM2013-760
Abstract 762: Genome-wide mapping of binding sites for the DEK oncoprotein by ChIP-seq.
Authors: Sanden Carl , Järvstråt Linnea , Ullmark Tove , Nilsson Björn , Gullberg Urban 
Published: August 2014

Abstract
The DEK oncogene is overexpressed in a wide range of cancers, including acute myeloid leukemia (AML). While DEK was initially described as a protein binding to certain topological chromatin structures, recent studies implicate DEK in the epigenetic and transcriptional regulation of specific genes. To assess the global gene binding of DEK, we performed chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq). We demonstrate that DEK does not bind evenly throughout the genome, but rather accumulates around transcription start sites, with binding to promoters and initial parts of the coding sequences. Furthermore, gene set enrichment analysis revealed that DEK preferentially binds genes associated with epigenetic regulation of gene expression. Our results represent the first genome-wide characterization of DEK binding, and further establish DEK as a transcriptional regulator with a specific set of target genes.
Citation Format: Carl Sanden, Linnea Järvstråt, Tove Ullmark, Björn Nilsson, Urban Gullberg. Genome-wide mapping of binding sites for the DEK oncoprotein by ChIP-seq. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 762. doi:10.1158/1538-7445.AM2013-762
Abstract 765: DDX31 regulates p53 tumor suppressive activity in renal cell carcinomas.
Authors: Katagiri Toyomasa , Fukawa Tomoya , Matsuo Taisuke , Kanayama Hiro-omi 
Published: August 2014

Abstract
Renal cell carcinoma (RCC) is the most common cancer of the kidney, and up to 30% of patients with RCC present with metastatic disease, yet its oncogenic origins are poorly understood. At an early stage, RCC can be cured by surgical resection, which is the most effective treatment for localized RCC tumors .Moreover, cytokine therapies, such as interleukin-2 or IFN-a, are widely used as a first-line treatment for metastatic disease. Therefore, it is highly important to develop a new molecular target agent(s) against RCC. However, these treatments can be associated with severe toxicity. Therefore, it is highly important to develop a new molecular target agent(s) against RCC. To identify therapeutic targets for cancer and understand the detailed molecular mechanism of carcinogenesis, we analyzed the expression profiling of clear cell RCC (ccRCC), which is a major histologic type of RCC, and identified DEAD (Asp-Glu-Ala-Asp) box polypeptide 31 (DDX31), a novel member of the DEAD box protein family, which is frequently up-regulated in the vast majority of human RCCs. Immunohistochemistry analysis indicated that DDX31 positivity was an independent prognostic factor for RCC patients. RNAi-mediated knockdown of DDX31 significantly suppressed RCC cell growth. Concordantly, expressing exogenous DDX31 promoted the growth of HEK293 cells. We also found that endogenous DDX31 interacted and colocalized with nucleophosmin (NPM1), involved in ribosome biogenesis and regulation of p53–HDM2 pathway, in nucleoli. Knockdown of DDX31 or NPM1 decreased pre-ribosome RNA biogenesis. Interestingly, in DDX31-knockdown cells, NPM1 was translocated from nucleoli to the nucleoplasm or cytoplasm, and then bound to HDM2, which prevented HDM2 from interacting with the p53 protein, resulting in p53 stabilization by inhibiting p53 ubiquitination. Our findings suggest that the DDX31–NPM1 complex plays critical roles in cell proliferation of RCC.
Citation Format: Toyomasa Katagiri, Tomoya Fukawa, Taisuke Matsuo, Hiro-omi Kanayama. DDX31 regulates p53 tumor suppressive activity in renal cell carcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 765. doi:10.1158/1538-7445.AM2013-765
Abstract 778: Suppression of lung adenocarcinoma progression by NKX2-1 is dependent on p53 Status.
Authors: Lee Huei , Chen Po-Ming , Wu Tzu-Chin , Cheng Yawen , Chen Chih-Yi 
Published: August 2014

Abstract
This article investigates the mechanistic aspects of NKX2-1 as a tumour suppressor and its oncogenic properties in lung adenocarcinoma. We show that NKX2-1 is a transcriptional factor that directly regulates p53 transcription. In p53 wild-type cells, NKX2-1 interacts with SP1 to down-regulate IKKβ transcription. In p53 mutated cells, NKX2-1 elevates the mutant p53/NF-Y complex to up-regulate IKKβ transcription. NKX2-1-mediated IKKβ expression is responsible for the efficacy of soft agar growth, invasion, and xenograft lung tumour nodule formation. Moreover, tumour aggressiveness attenuated by NKX2-1-mediated IKKβ is predominately through the shuffling of Foxo3a between the cytosol and nucleus of lung cancer cells to modulate E-cadherin expression. A consistent association of NKX2-1 with IKKβ and E-cadherin expression was observed in tumours from lung adenocarcinoma patients. P53 mutated tumours with high NKX2-1 expression have poorer overall survival (OS) and relapse-free survival (RFS) rates than those with low-NKX2-1 expression. Conversely, p53 wild-type tumours with high-NKX2-1 tumours have more favourable OS and RFS rates than those with low-NKX2-1 expression. As such, we demonstrate that aberrant transcription of IKKβ underlines the ability of NKX2-1 to act as a tumour suppressor or to display oncogenic properties in lung adenocarcinoma.
Citation Format: Huei Lee, Po-Ming Chen, Tzu-Chin Wu, Yawen Cheng, Chih-Yi Chen. Suppression of lung adenocarcinoma progression by NKX2-1 is dependent on p53 Status. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 778. doi:10.1158/1538-7445.AM2013-778
Abstract 797: Targeted next generation sequencing of FFPE lung cancer tissue.
Authors: Endris Volker , Stenzinger Albrecht , Penzel Roland , Warth Arne , Schirmacher Peter , Weichert Wilko 
Published: August 2014

Abstract
In view of a personalized medicine, the screening of somatic mutations in an individual tumor that predict therapeutic outcome has become an increasing need in the clinical and molecular diagnostics. In most laboratories, Sanger sequencing has become an accepted standard, but due to the limited screening throughput and the increasing demand for targeted sequencing, the application of next-generation sequencing in the molecular diagnostic has turned into focus. Whole-genome or whole-exome sequencing approaches provide a comprehensive view of an individual tumor mutation load, but the current high costs and the excess of information without a direct clinical implication limit the routine use of this technology. In this study, we evaluated a targeted resequencing approach that focuses on somatic hotspot cancer mutations based on semiconductor sequencing. We especially took attention on the reliability of the method concerning sample quality, mutation type and reproducibility. We used DNA extracted from formalin-fixed, paraffin embedded (FFPE) tumor tissues (biopsy and resection) of different tumor degree and overall quality that were previously screened for the presence of EGFR mutations (exon 18-21) by Sanger sequencing. 190 amplicons covering hotspot mutations in 46 genes were generated in a multiplex PCR reaction (AmpliSeqTM), barcoded and 8 samples were run on a single IonTorrent 318 chip. We were able to successfully sequence all samples with a mean coverage rate of 670.000 reads (AQ20:560.000) and an average read depth of 2947 AQ20 reads / amplicon. In all but one sample, variant calling identified the EGFR mutation, missing only one low level 9bp insertion in exon 20. Moreover, we identified additional 43 mutations in 17 genes and uncovered three previously unknown EGFR amplifications. Taken together, amplicon-based semiconductor sequencing is a powerful and cost-effective method working with low-quality DNA material, enabling routine diagnostic next-generation sequencing.
Citation Format: Volker Endris, Albrecht Stenzinger, Roland Penzel, Arne Warth, Peter Schirmacher, Wilko Weichert. Targeted next generation sequencing of FFPE lung cancer tissue. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 797. doi:10.1158/1538-7445.AM2013-797
Abstract 809: High-resolution genomic profiling reveals gains of CCND1 and EGFR associated with disease progression in Taiwanese oral cavity squamous cell carcinomas.
Authors: Chien Huei-Tzu , Huang Shiang-Fu , Chen I-How , Liao Chun-Ta , Wang Hung-Ming , Cheng Sou-De , Hsieh Ling-Ling 
Published: August 2014

Abstract
The genetic mechanisms underlying Taiwanese oral cavity squamous cell carcinoma (OSCC) are still largely unknown. We used high-resolution single nucleotide polymorphism microarrays (Affymetrix 500K) to detect copy number alterations (CNAs) in 26 OSCC tumor tissues. Genomic copy number was determined by calculating the intensity ratio between the OSCC and a set of 270 normal DNAs from HapMap project. Segmented copy numbers for each tumor were inferred with the hidden markov model (HMM) using the Partek GS software. Genomic Identification of Significant Targets in Cancer (GISTIC) analysis (version 2.0) was used to identify significant CNAs using a residual Q-value cutoff of 0.25. A total of 25 significant regions (2 focal amplifications and 23 deletions) were identified. The well known oncogene EGFR and CCND1 are resided in these two focal amplification regions (7p11.2 and 11q13.3), respectively. Several candidate cancer related genes such as FHIT (3p14.2), FAT (4q35.1), SH3GL2 (9p22.2) and ARHGAP21 (10p12.1) are known to locate in the identified 23 deletion regions. Furthermore, we found that 7p11.2 amplification and 4q35.2 deletion was mutually exclusive by ‘inter-target relationships’ (ITR) analysis using dimension reduction permutation (DRP) methods. Copy number gains of EGFR and CCND1 were also confirmed along with fluorescence in situ hybridization (FISH) and TaqMan CN assay (Hs01818912_cn and Hs00655630_cn), respectively. We found that the concordance rate was 70.59% for EGFR and 75.00% for CCND1. To further explore the clinical value of copy number gains of EGFR and CCND1 in OSCC, 182 OSCC cases were analyzed. Preliminary results indicated that gains of CCND1 were associated with tumor differentiation, lymph node metastasis and lymph node extracapsular spread (LNECS); while amplification of EGFR gene was significantly associated with tumor stage and lymph node metastasis but not LNECS. Furthermore, gains of CCND1 were significantly associated with poor disease-free and overall survival. On the other hand, amplification of EGFR was not associated with either disease-free or overall survival. Taken together, we have identified that gains of CCND1 and EGFR gene were significantly associated with disease progression in Taiwanese oral cavity squamous cell carcinomas.
Citation Format: Huei-Tzu Chien, Shiang-Fu Huang, I-How Chen, Chun-Ta Liao, Hung-Ming Wang, Sou-De Cheng, Ling-Ling Hsieh. High-resolution genomic profiling reveals gains of CCND1 and EGFR associated with disease progression in Taiwanese oral cavity squamous cell carcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 809. doi:10.1158/1538-7445.AM2013-809