bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3968: Exploring cancer datasets in the integrative genomics viewer (IGV)
Authors: Robinson James T. , Thorvaldsdottir Helga , Mesirov Jill 
Published: August 2012

Abstract
Cancer genome characterization studies, such as The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), are producing a flood of diverse data including whole-genome sequencing scans, expression profiles, high-resolution SNP and copy number data, and epigenetic profiles. These diverse datasets are enabling researchers to study the cancer genome in unprecedented detail. However, their sheer size and diversity presents significant challenges to downstream interpretation. While much progress has been made in automated analysis, human review enabled by intuitive and responsive visualizations remains an essential component of data analysis. The Integrative Genomics Viewer (IGV) was developed to address this need by providing researchers with an intuitive, user-friendly, interactive visualization tool for exploration of diverse genomic datasets. IGV has extensive support for both next-generation and micro-array based platforms, and for integration of these data types with clinical and phenotypic data. It provides an intuitive interface similar to online mapping tools such as Google Maps, enabling smooth zooming and panning at all resolution scales, from whole genome to base pairs. Data can be annotated, filtered, grouped, and sorted in a variety of ways. This ability to dynamically and flexibly integrate multiple different datasets, and view them at any scale, allows investigators to elucidate complex biological relationships that are not otherwise readily apparent. In this presentation we describe the IGV, with emphasis on recent features focused on data integration and interpretation, developed in close collaboration with cancer researchers. Specifically (1) a multi-locus pathway view which supports simultaneous viewing of data in multiple genomic regions defined by pathways or gene sets, (2) integration with external tools such as Mutation Assessor and PolyPhen, to provide views and data to asses the functional significance of somatic events, and (3) a flexible, interactive charting capability to enable detailed exploration of inter-dependencies between data types at a specific locus or set of loci. These features will be illustrated in the context of use cases drawn from the TCGA glioblastoma multiforme and ovarian datasets.
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 3968. doi:1538-7445.AM2012-3968
Abstract 397: Soluble Tumor Necrosis Factor Receptor shed by breast tumor cells modulates macrophage migration
Authors: Rego Stephen , Ricci Krista , Swamydas Muthulekha , Dreau Didier 
Published: August 2012

Abstract
Tumor necrosis factor alpha (TNFα) present within the tumor microenvironment, especially in breast tumor with a strong inflammatory component, promotes tumor death. TNFα also stimulates the migration of immune cells including macrophages to the tumor site. Breast cancer cells express both TNFR1 and TNFR2, the cell surface receptors for TNFα. The breast tumor microenvironment also contains soluble forms of TNFR1 and TNFR2. We investigated the origins and effects of soluble TNFR1 and TNFR2 on monocyte/macrophage cell migration. Our results indicate that both sTNFR1 and sTNFR2 were shedded by tumor cells but also by stroma cells including adipocytes. In addition, the amounts of sTNFR2 shedded by adipocytes and 4T1 mammary tumor cells were significantly higher than the amounts of sTNFR2 shedded by normal murine epithelial NMuMG cells (p&lt;0.05). The migration of M2 subtype macrophages but not of M1 subtype macrophages derived from either murine bone derived monocytes, J774 or Raw cells toward 4T1 mammary tumor cells’ conditioned media was significantly increased following treatment of 4T1 cells with the sheddase inhibitor TAPI-0 (p&lt;0.05). Indeed, TAPI-0 treatment decreased sTNFR2 concentrations in 4T1-conditioned media (p&lt;0.05). These observations suggest a role for sTNFR1 and sTNFR2 in the dynamic interplays between immune and tumor cells during breast progression. (This works is supported by grants from the Department of Defense Era of Hope research program (BC044778) and the National Science Foundation EFRI program (CBE0736007)
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 397. doi:1538-7445.AM2012-397
Abstract 4249: Development of Champions Tumorgraft models in rare cancer types for preclinical investigation and drug discovery
Authors: Friedman Jay A. , Kilonzo Christine , Albee Lee , James Meredith , Lu Bin , Bruckheimer Elizabeth 
Published: August 2012

Abstract
Little progress has been achieved in the treatment of the rare cancers such as Ewing Sarcoma (ES), Merkel cell carcinoma (MCC), and osteosarcoma. ES is a rare bone malignancy that affects children and young adults and there has been little improvement in survival rates for patients with metastatic or recurrent disease despite aggressive treatment. MCC is a rare malignant cutaneous tumor of the elderly and optimal treatment strategies remains unclear for these patients. Poor clinical outcome is seen especially those MCC patients with regional lymph node metastases and distant metastases. Osteosarcoma arises in bone and affects adolescents and young adults. There has been no significant improvement in prognosis since the advent of multi-agent chemotherapy. A significant limitation in sorting out the complexities of these rare tumors and evaluating therapeutic strategies is the lack of preclinical models. To overcome this challenge, we have embarked on a mission to establish and characterize Champions TumorgraftTM models within these rare tumor indications. The Champions Tumorgraft utilizes the implantation of primary human tumors in immune-deficient mice in a manner that preserves the biological properties of the original human tumor. In this preliminary work, we reveal several new Champion TumorgraftTM models of ES, MCC, and osteosarcoma along with their tumor histology, mutational status, and chemosensitivity profiles to several standard of care compounds. These rare Champion TumorgraftTM models represent invaluable tools for preclinical research and drug discovery to find promising new therapies for this high unmet clinical need.
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 4249. doi:1538-7445.AM2012-4249
Abstract 4254: Human neuroendocrine Bon 1 cells as a three-dimensional model for the study of human neuroendocrine tumor therapy
Authors: Xu Eugenia Y. , Wong Chung , Levine Arnold J. , Vosburgh Evan 
Published: August 2012

Abstract
Pancreatic neuroendocrine tumors are rare tumors, with an incidence of one to two per 100000 individuals per year, and they account for 1-2% of all pancreatic neoplasms. Currently, much needed is to develop the therapeutical drugs for patients with pancreatic neuroendocrine tumors. Human pancreatic neuroendocrine BON 1 cell line is widely used for testing the therapeutic drugs in vitro. Here, we develop an alternative research model that better mimics the in vivo tumor tissue organization and microenvironments. This method produces in vitro three-dimensional (3D) tumor spheroids from human pancreatic BON1 cells. The 3D tumor spheroids generated in vitro exhibit the characteristics of avascular tumors. Structurally and genetically the 3D spheroids show similarity to the xenograft BON1 tumor and are more tumorigenic than 2D monolayer BON1 cells. We also present how to use these 3D spheroids to screen the therapeutic drugs. This method will help us establish human neuroendocrine tumor spheroids for cancer therapy.
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 4254. doi:1538-7445.AM2012-4254
Abstract 4268: Gene signature of host irradiation from Trp53 null mammary tumors detects radiation-preceded human cancers and has prognostic value for sporadic human breast cancer
Authors: Nguyen David H. , Fredlund Erik , Zhao Wei , Perou Charles M. , Balmain Allan , Mao Jian-Hua , Barcellos-Hoff Mary Helen 
Published: August 2012

Abstract
The microenvironment mediates many important aspects of tumorigenesis, providing complementary mechanisms that work in concert with mutagenic challenges to initiate and promote tumor development. To test the effect of ionizing radiation, a carcinogen known to act via the microenvironment, we employed a radiation-genetic chimera in which an irradiated mouse was transplanted with unirradiated Trp53 null mammary epithelium. Host irradiation not only decreased tumor latency, but unexpectedly enriched for tumors that were negative for estrogen receptor-α (Cancer Cell 19:40-51, 2011). Using gene expression microarrays we identified a profile containing 323 genes (323-IHC) that could separate the tumors that arose in irradiated hosts from those that arose in naive mice. To evaluate the relevance of an irradiated microenvironment in human cancer, the 323-gene expression signature was applied to expression profiles of sporadic or radiation-preceded human cancers. Clustering using the 323-IHC was able to detect radiation history in thyroid carcinomas from Chernobyl and radiotherapy associated sarcomas even though there was no overlap with the differential gene profiles published for either data set, demonstrating the relevance of microenvironment reprogramming as one of the fundamental facets of radiation carcinogenesis. We next utilized a gene expression data set representing 1,608 human breast cancers compiled from 10 independent studies. Clustering of these samples, using genes from our mouse-derived radiation signature that were also present on the breast cancer gene expression platform, segregated four subgroups that were enriched for intrinsic subtypes, and two major groups with differential relapse-free and overall survival. A 72-gene centroid derived from the 323-IHC classified the breast cancers as either similar to tumors from host-irradiation, or similar to tumors from non-irradiated hosts. Classification of the human breast cancer expression profiles revealed an association between host-irradiation and estrogen receptor negative, basal-like breast cancers. Thus, the biology represented in the 323-IHC signature is present in human cancers and associates with etiology and clinical outcome.
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 4268. doi:1538-7445.AM2012-4268
Abstract 428: Post-translational phosphorylation is essential for nanog-mediated tumorigenesis
Authors: Xie Xiujie , Piao Longzhu , Cavey Greg S. , Teknos Theodoros N. , Pan Quintin 
Published: August 2012

Abstract
Objectives: Nanog is a transcription factor intimately involved in embryonic stem cell pluripotency. Emerging evidence indicates that Nanog plays a critical role in oncogenesis, in part through regulation of the cancer initiating cell population. We investigated the role of post-translational phosphorylation as a regulatory mechanism to control Nanog function in head and neck squamous cell carcinoma (HNSCC). Methods: Liquid chromatography-mass spectrometry/mass spectrometry was used to identify the PKC∈-mediated phosphorylation sites on Nanog. Phosphorylation-insensitive Nanog mutants (T200A and T280A) were generated and assessed for in vitro and in vivo phenotype. Chromatin immunoprecipitation (ChIP) and co-immunoprecipitation experiments were performed to determine Nanog recruitment and association with p300. ChIP, electrophorectic mobility shift assay, and luciferase reporter assay were used to assess Nanog regulation of Bmi-1. Forward and reverse genetic experiments were carried out to determine the role of the Nanog-Bmi-1 signaling node in HNSCC. Results: Phosphopeptide mapping identified that Nanog is phosphorylated by PKC∈ at multiple resides, including T200 and T280. Phosphorylation-insensitive Nanog mutants (T200A and T280A) showed a loss-of-function phenotype due to impaired p300, a transcriptional co-activator, recruitment resulting in a defect in target gene promoter activation. Ectopic expression of phosphorylation-insensitive Nanog mutants in HNSCC cells significantly reduced cell proliferation, colony formation, invasion, migration, and the cancer initiating cell population. Additionally, in vivo tumor initiating ability was severely compromised in HNSCC cells expressing phosphorylation-insensitive Nanog mutants; 87.5% (14/16), 12.5% (1/8), and 0% (0/8) for empty vector, T200A, and T280A, respectively. Nanog occupied the promoter of Bmi-1 at two distinct regions to directly regulate Bmi-1 levels. Genetic ablation and rescue experiments demonstrate that Bmi-1 is a critical downstream signaling node for the pleotropic pro-oncogenic effects of Nanog. Conclusion:Taken together, our study revealed, for the first time, that post-translational phosphorylation of Nanog is essential to directly regulate Bmi-1 and promote tumorigenesis.
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 428. doi:1538-7445.AM2012-428
Abstract 4290: Visualizing immune surveillance in lung metastasis progression
Authors: Zal M. Anna , Bartkowiak Todd , Chodaczek Grzegorz , Papanna Veena , Shanmugasundaram Meenakshi , Zal Tomasz 
Published: August 2012

Abstract
As stipulated by the Paget and Fuchs’ “seed and soil” analogy, the establishment of metastases depends on the microenvironment of target tissue; as such, it also depends on the tissue immunosurveillance system. Anti-tumor immune responses are subdued in advanced tumors by various immune suppressory mechanisms, such as by tumor associated CD4 FoxP3 regulatory T-reg cells. But how immune suppression sets in at the sites of metastasis, and how it could be overcome there remains unclear. Using multiphoton and confocal microscopy, we have visualized the immune cell's dynamics that is triggered by various metastatic cancers in the lungs. We found that single, blood-carried cancer cells that settle in the capillary bed triggered strikingly rapid recruitment of CD11c dendritic cells (DCs), which were heterogeneous. Some of those DCs wrapped around the singular cancer cells while other probed their intracellular content by acquiring tumor-derived vesicles. These phagocytic DCs then carried away their cargo towards the draining lymph nodes, thereby initiating tumor antigen cross-presentation. After 24-48 hours, micrometastases became surrounded by T cells that were highly enriched in T-reg. The motility patterns and cell depletion experiments showed that T-reg largely ignored tumor cells but were attracted by the phagocytic tumor-associated DCs. In result of these interactions, the phagocytic DCs became the foci of highly dynamic three-cell interactions between T-reg and the effector T cells, sequestering most T cells at the tumor margin. In this context, we tested the impact of immunomodulatory therapies. The immune cell dynamics that we uncovered in metastases was responsive to therapeutic immune modulation aimed at the tumor-associated phagocytic DCs and also at Programmed Death (PD-1) pathways. Taken together, our intravital dynamic imaging results highlight the duality of metastasis-associated phagocytic DCs. On the one hand, these cells provide tumor antigen cross-presentation and recruit T cells to nascent secondary tumors, but on the other hand, they aid metastasis progression by promoting early on the contact of tumor-infiltrating T cells with T-reg.
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 4290. doi:1538-7445.AM2012-4290
Abstract 4292: In vivo and in vitro imaging of Cyclooxygenase-2 in tumor
Authors: Wong Kenneth , Urban Konnie , Ang Angel , Zhang Ning , Singh Rajendra , Kim Jae-Beom 
Published: August 2012

Abstract
Cyclooxygenase-2 (Cox-2) is a biomarker for tumor progression and inflammatory diseases. It is known that normal tissues express minimal amounts of Cox-2 proteins while inflammatory and malignant tumor cells express high levels. Thus, inhibition of Cox-2 is a strategy in the treatment of tumor progression and inflammatory diseases. Recently, many different kinds of molecular imaging reagents for Cox-2 have been developed. Among them, an indomethacin-based Cox-2 probe, fluorocoxib, has been shown to bind to Cox-2 in vitro and in vivo. The binding specificity to Cox-2 was shown using cell culture and tumor xenograph models. In our present study, in order to optimize fluorocoxib imaging conditions, we utilized HCT116 and HT29 cells as low and high Cox-2 expressers, respectively. First, cultured cells were grown overnight on cover slips. Cells were then fixed with paraformaldehyde and incubated with fluorocoxib probe. Multispectral images were taken using a camera equipped with liquid crystal tunable filters. Spectral unmixing was applied to these images to enhance fluorocoxib signals. Our results indicate that HCT116 cells express fair amounts of Cox-2 protein. We also transplanted HCT116 and HT29 cells into the flank regions of nu/nu mice subcutaneously. After tumors grew to sufficient size (∼100 mm3) we injected fluorocoxib intravenously and monitored probe binding to the tumors. Whole animal in vivo imaging indicated that fluorocoxib binds to HT29 tumors after 3 hours. All the probes were eliminated from the animals by 24 hours. On the other hand, HCT116 tumors did not show strong binding of fluorocoxib as expected. However, HCT116 tumors did show some weak binding at the 3 and 6 hr time points. Once there was no longer any probe detected in vivo, we dissected the primary tumors from the HCT116 and HT29 implantations. Tissue sections were made with paraffin embedded tumors. After deparaffinization, tissue sections were incubated with fluorocoxib and fluorescent images were taken using multispectral imaging technology. Spectral unmixing data confirmed that HCT116 tumor sections showed fair amounts of Cox-2 probe expression. The amount of binding was also quantitated using a corresponding software package. Our results demonstrated that fluorescent biomarker probes can be imaged in vitro and in vivo non-invasively. Furthermore, we showed that the expression level can be quantitated using spectral unmixing imaging technology.
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 4292. doi:1538-7445.AM2012-4292
Abstract 4296: Ultrasmall gadolinium-loaded polymer nanoparticles for imaging in glioblastoma
Authors: Himes Benjamin , Zhou Jiangbing , Patel Toral , Coman Daniel , Hyder Fahmeed , Saltzman Mark 
Published: August 2012

Abstract
Glioblastoma multiforme (GBM) is a devastating disease for which prognosis remains exceptionally poor even with maximal intervention. A central challenge in the treatment of GBM is realizing effective drug delivery to the tumor and surrounding brain tissue, due to the inability of many drugs to cross the blood-brain barrier (BBB). The use of nanoparticles comprised of biodegradeable polymer as vehicles for intracranial drug delivery circumvents the BBB and allows for sustained, controlled release of drug in a targeted area. Nanoparticle encapsulation also protects therapeutic payloads from premature degradation in the microenvironment. However, effective distribution of nanoparticles in brain tissue has emerged as a potential hurdle to therapeutic efficacy. To this end we have synthesized ultrasmall poly(lactic-co-glycolic acid) (PLGA) nanoparticles 60-80nm in size, which demonstrate pronounced improvement in volume of distribution relative to larger particles. This enables particle diffusion into normal brain tissue, where the pore size of the extracellular matrix is limited to 38-64nm, allowing for drug delivery to the infiltrative edge to the tumor. Further, as the utility of these nanoparticles lies in their ability to deliver drug in a clinically relevant area, it is vital to develop a translatable means of imaging intracranial particle delivery to ensure adequate distribution. To address this issue we have developed gadolinium-loaded ultrasmall PLGA nanoparticles. These particles are detectable by MRI and distribute over a wide area when administered with the aid of convection-enhanced delivery (CED). These particles, composed entirely of FDA-approved materials, provide a diagnostic means to visualize distribution of nanoparticles in a clinically applicable capacity.
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 4296. doi:1538-7445.AM2012-4296