bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3880: Exploring the role of up-regulated genes in highly metastatic oral cancer subline using spontaneous metastatic mouse model.
Authors: Muramatsu Tomoki , Kozaki Ken-ichi , Imoto Seiya , Yamaguchi Rui , Miyano Satoru , Inazawa Johji 
Published: August 2014

Abstract
Metastasis is one of the critical factors contributing to poorer prognosis and QOL in cancer patients. Although this mechanism has been gradually revealed, there are few genes found as useful diagnostic markers or molecular targets for clinical application so far. In this study, we attempted to establish in vitro/in vivo metastatic models using a human oral squamous cell carcinoma cell lines (HOC313). We first carried out in vivo selection of high-metastatic tumor cells by means of sequential subcutaneous (s.c.) implantation (1×107 cells) of this cell line into SCID mice, resulting in the establishment of a highly metastatic subline which metastasized to axillary lymph nodes and lung. Moreover, we developed the imaging system using parent cells and highly metastatic cells. Then, to explore metastasis-related genes and signaling pathways, we performed integrative analyses using array CGH, cDNA microarray and the systems biological approach based on their data sets. Then we identified copy number aberrations (CNAs) of chromosome 19 and differentially expressed genes between parent cells and high-metastatic cells. Up regulated genes in high-metastatic cells are related with cell growth, migration, invasion and metastatic ability. Among these, one gene was closely associated with migration, invasion and metastasis. Moreover, when knocking down of this gene, we observed morphological change from mesenchymal phenotype to epithelial phenotype. Further analyses of these genes may ultimately lead to the development of novel modalities of diagnosis and therapy for cancer metastasis.
Citation Format: Tomoki Muramatsu, Ken-ichi Kozaki, Seiya Imoto, Rui Yamaguchi, Satoru Miyano, Johji Inazawa. Exploring the role of up-regulated genes in highly metastatic oral cancer subline using spontaneous metastatic mouse model. [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 3880. doi:10.1158/1538-7445.AM2013-3880
Abstract 3896: A metabolic enzyme as a pro-angiogenic activator in premalignant mammary cells.
Authors: Gonzalez-Guerrico Anatilde M. , Espinoza Ingrid , Lupu Ruth 
Published: August 2014

Abstract
A crucial step in cancer progression is the development of a high-density vascular network, the angiogenic switch. During carcinogenesis breast angiogenesis occurs at hyperplasia before atypia, reaching maximum vascularization between ductal carcinoma in situ and invasive carcinoma. Altered energy metabolism is an early hallmark of several human malignancies. Fatty Acid Synthase (FASN) is a metabolic enzyme that catalyzes the synthesis of Palmitate from Malonyl CoA. With the exception of liver and adipose tissue, normal cells have low levels of FASN and activity. Here we show that FASN expression is progressively up-regulated in the early steps of human breast carcinogenesis. While under hypoxia FASN expression is downregulated in non-transformed breast epithelial cells that form normal ducts. In pre-malignant breast cancer lesions under similar conditions, FASN expression is upregulated. These data suggest a link between FASN-hypoxia-progression. In addition, we observed that in early stages of breast carcinogenesis, FASN regulates the expression of hypoxia genes, which in turn results in increase vascularization and angiogenic markers. Forced expression of FASN in non-transformed breast epithelial cells resulted in increased activity of HIF-1α and upregulation of VEGF expression. Furthermore, FASN-expressing non-transformed breast epithelial cells under hypoxia conditions produced the necessary factors to stimulate angiogenesis, as measured by tube formation and migration in HUVEC cells. These data provide evidence that FASN promotes pro-angiogenesis under hypoxia at the early onset of breast carcinoma; thus, it could be considered as a target for breast cancer chemoprevention.
Citation Format: Anatilde M. Gonzalez-Guerrico, Ingrid Espinoza, Ruth Lupu. A metabolic enzyme as a pro-angiogenic activator in premalignant mammary cells. [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 3896. doi:10.1158/1538-7445.AM2013-3896
Abstract 3897: A novel function for threonyl-tRNA synthetase as a stimulator of angiogenesis and endothelial cell migration.
Authors: Williams Tamara , Mirando Adam , Francklyn Christopher , Lounsbury Karen M. 
Published: August 2014

Abstract
In mammalian systems, several aminoacyl-tRNA synthetases are known to have distinct non-canonical functionality. For the first time, we demonstrate that human threonyl-tRNA synthetase (TARS) induces angiogenesis through endothelial cell signaling, and this induction can be blocked by the borrelidin derivative compound BC194. Upon stimulation with vascular endothelial growth factor (VEGF) or tumor necrosis factor-alpha (TNF-α), human endothelial cells secrete TARS into the extracellular space. Extracellular TARS induces and BC194 inhibits angiogenesis in both in vitro tube formation assays and in vivo chick chorioallantoic membrane assays. Furthermore, the anti-angiogenic effects of BC194 are specific to its inhibition of TARS angiogenic activity rather than an indirect stress response. Additional evidence supports a stimulatory role for TARS in endothelial cell migration as a mechanism for its angiogenic activity. Taken together, these findings reveal a previously undefined function for TARS as an angiogenesis inducer stimulated by hypoxic and inflammatory signals. Detecting or intervening in the non-canonical extracellular TARS signaling pathway may thus provide a novel means of diagnosing or treating angiogenesis and inflammatory responses involved in cancer.
Citation Format: Tamara Williams, Adam Mirando, Christopher Francklyn, Karen M. Lounsbury. A novel function for threonyl-tRNA synthetase as a stimulator of angiogenesis and endothelial cell migration. [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 3897. doi:10.1158/1538-7445.AM2013-3897
Abstract 390: Expression of the actin-binding protein Anillin is a prognostic biomarker for primary ER positive breast cancer.
Authors: Magnusson Kristina , Gremel Gabriela , Pontén Fredrik , Jirström Karin 
Published: August 2014

Abstract
Identification of novel prognostic and predictive factors is important for individualizing prognosis and treatment for cancer patients. The present study aimed at examining the potential prognostic value of Anillin (ANLN) expression in breast cancer. ANLN, an actin-binding protein required for cytokinesis, was discovered using the Human Protein Atlas as being differentially expressed in breast cancer and, thus, a potential prognostic biomarker. The purpose of the Human Protein Atlas project (www.proteinatlas.org) is to generate validated antibodies towards the entire human proteome and to use these antibodies for protein profiling in normal tissues and cancer cells. The freely available Human Protein Atlas provides an opportunity to use antibody-based proteomics as a high-throughput strategy to discover novel cancer biomarkers of potential clinical relevance. ANLN has been shown to be up-regulated in several human tumor types including lung, renal and pancreatic tumors. For the purpose of the current study, tissue microarrays with tumor samples from three independent breast cancer cohorts were analyzed by immunohistochemistry (IHC). SiRNA mediated ANLN knockdown of breast cancer cell lines followed by western blot or IHC on cytospin was done for antibody validation. Cell viability assay and cell cycle assay was used to study the function of ANLN knocked breast cancer cells. The majority of breast tumors displayed moderate to strong nuclear positivity in slightly varying fractions, generally below 25%. High nuclear fraction of ANLN was associated with large tumor size, high histological grade, high proliferation and estrogen receptor (ER) negativity. Furthermore, high nuclear expression of ANLN was significantly associated with poor prognosis for patients with ER positive breast tumors in all three cohorts. SiRNA mediated ANLN knockdown was found to induce low cell viability for ER positive breast cancer cells but not for ER negative breast cancer cells. In addition, cell cycle studies showed that ANLN knockdown yielded a shift to G2/M phase, in both ER positive and ER negative breast cancer cells. In conclusion, our results strongly suggest that ANLN can be used as a prognostic biomarker for ER positive breast cancer patients.
Citation Format: Kristina Magnusson, Gabriela Gremel, Fredrik Pontén, Karin Jirström. Expression of the actin-binding protein Anillin is a prognostic biomarker for primary ER positive breast cancer. [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 390. doi:10.1158/1538-7445.AM2013-390
Abstract 3905: Radiation-induced angiogenic signaling pathway in endothelial cells isolated from normal and cancer tissue of human breast.
Authors: Oh Eun-Taex , Park Moon-Taek , Song Min-Jeong , Lee Hyemi , Park Heon Joo 
Published: August 2014

Abstract
Despite the strong possibility that the endothelial cells (ECs) of tumors and normal tissues may differ in various aspects, most previous studies on ECs have used normal cells. Here, we purified ECs from tumorous and normal human breast tissues, and studied the effect of radiation on angiogenesis and the relevant molecular mechanisms in these cells. We found that in normal tissue-derived endothelial cells (NECs), 4 Gy irradiation increased tube formation, MMP-2 expression and ERK pathway activation. In cancer-derived endothelial cells (CECs), however, 4 Gy irradiation significantly reduced tube formation, increased the production of angiostatin and interleukin-6 (IL-6), and up-regulated AKT and JNK pathway activation. Knockdown experiments showed that siMMP-2 efficiently inhibited tube formation by irradiated NECs, while siPlasminogen effectively attenuated the irradiation-induced suppression of tube formation and the up-regulation of angiostatin in CECs. Moreover, siIL-6 clearly inhibited the irradiation-induced generation of angiostatin in CECs. Inhibition of ERK with a pharmacological inhibitor or siRNAs markedly suppressed irradiation-induced tube formation and MMP-2 up-regulation in NECs, while the inhibition of either AKT or JNK with pharmacological inhibitor or siRNA treatment of CECs clearly attenuated the irradiation-induced inhibition of tube formation and the up-regulation of angiostatin and IL-6. These observations collectively demonstrate that there are distinct differences in the radiation responses of NECs and CECs, and might provide important clues for improving the efficacy of radiation therapy.
Citation Format: Eun-Taex Oh, Moon-Taek Park, Min-Jeong Song, Hyemi Lee, Heon Joo Park. Radiation-induced angiogenic signaling pathway in endothelial cells isolated from normal and cancer tissue of human breast. [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 3905. doi:10.1158/1538-7445.AM2013-3905
Abstract 3918: Validation of ATX-Red imaging as a potential companion diagnostic for autotaxin-expressing cancers.
Authors: Madan Damian , Ferguson Colin , Lee Won Yong , Testa Charles , Prestwich Glenn 
Published: August 2014

Abstract
Autotaxin (ATX), an autocrine motility factor highly upregulated in metastatic cancer, is a lysophospholipase D that produces the lipid second messenger lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC). Dysregulation of the lysolipid signaling pathway is central to the pathophysiology of numerous cancers, idiopathic pulmonary fibrosis, rheumatoid arthritis, and other inflammatory diseases. Consequently, the ATX/LPA pathway has emerged as an important source of biomarkers and therapeutic targets. Herein we describe development and validation of a fluorogenic analog of LPC (ATX-Red) that enables visualization of ATX activity in vivo. ATX-Red exhibits minimal fluorescence until it is activated by ATX, which significantly increases fluorescence in the near-infrared (NIR) region, the optimal spectral window for in vivo imaging. In mice with ATX-expressing breast cancer orthotopic tumors, ATX activated ATX-Red fluorescence. Injection of ATX-Red into the tail vein of tumor-bearing mice resulted in high fluorescence in the tumor and low fluorescence in healthy tissues. Indeed, tumor fluorescence directly correlated with ATX activity and expression levels. Pretreatment of mice with a known ATX inhibitor markedly and selectively decreased tumor fluorescence. Taken together, the data show that ATX-Red is an effective, non-invasive, and selective tool that enables intravital visualization and quantitation of ATX-expressing tumors and monitoring ATX activity in vivo in real time. ATX-Red has the potential to (1) identify pathological levels of ATX in specific tissues, (2) monitor the time course of therapeutic efficacy of candidate ATX inhibitors in living animal models of human disease, (3) serve as a companion diagnostic for following treatment regimens that target ATX in human patients and (4) serve as a companion diagnostic to select patients that would benefit from ATX-directed therapy.
Citation Format: Damian Madan, Colin Ferguson, Won Yong Lee, Charles Testa, Glenn Prestwich. Validation of ATX-Red imaging as a potential companion diagnostic for autotaxin-expressing cancers. [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 3918. doi:10.1158/1538-7445.AM2013-3918
Abstract 392: Delineating genomic heterogeneity in paired primary and metastatic colorectal cancer by massively parallel sequencing.
Authors: Brannon Angela Rose , Vakiani Efsevia , Scott Sasinya N. , Sylvester Brooke , Kania Krishan , Viale Agnes , Kemeny Nancy , Weiser Martin , Solit David B. , Berger Michael F. 
Published: August 2014

Abstract
Colorectal cancer (CRC) is the third most common cause of cancer and cancer death for men and women in the United States. While the genetic steps necessary for carcinogenesis are well-defined, the subsequent genetic alterations driving tumor evolution to metastasis are not well characterized. We have performed deep sequencing of 230 key cancer-associated genes in 60 patient-matched primary tumor, metastatic tumor, and normal samples from CRC patients. Genes were selected on the basis of recurrent and/or “actionable” mutations reported in human tumors. Our custom captured-based sequencing assay, termed IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets), provided a median sequence coverage of 644-fold, allowing for the identification of low frequency genetic events involving target genes. Somatic mutations, insertions/deletions (indels), and copy number alterations were identified and compared in both primary and metastatic samples. The most frequently mutated genes have all been previously implicated in CRC: APC, TP53, KRAS, PIK3CA, and SMAD4. Most genetic events were identical between primary and metastatic tumors; however, we identified particular alterations specific to the metastatic samples. The majority of these alterations were members of two important proliferative pathways, further lending credence that they might play an important role in metastatic progression. For patients with metastasis-specific mutations, we have sampled multiple microdissected regions from primary tumors to quantify the extent of intratumor heterogeneity and ascertain whether these differences are caused by sampling biases. The identification of these genetic variations between primary and metastatic tumors could have significant impact on biomarker analysis as well as treatment decisions for CRC patients.
Citation Format: Angela Rose Brannon, Efsevia Vakiani, Sasinya N. Scott, Brooke Sylvester, Krishan Kania, Agnes Viale, Nancy Kemeny, Martin Weiser, David B. Solit, Michael F. Berger. Delineating genomic heterogeneity in paired primary and metastatic colorectal cancer by massively parallel sequencing. [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 392. doi:10.1158/1538-7445.AM2013-392
Abstract 3920: In vivo tyrosinase reporter gene imaging with multispectral photoacoustic technology.
Authors: Heinmiller Andrew , Lakshman Minalini , Bates Dave , Needles Andrew , Theodoropoulos Catherine , Paproski Robert J. , Zemp Roger J. 
Published: August 2014

Abstract
Photoacoustic imaging is a powerful tool for assessing tumor vasculature and oxygen saturation as well as detecting contrast agents for molecular imaging. Another exciting possibility is to visualize gene expression by using a reporter which produces a photoacoustic contrast agent. Tyrosinase is such a reporter in that its expression results in the production of melanin, which gives a strong photoacoustic signal. Here we describe the use of a commercially available photoacoustic (PA) imaging system (Vevo LAZR, VisualSonics, Toronto) to image inducible gene expression in subcutaneous xenograft tumors using tyrosinase as a reporter gene.
The photoacoustic imaging system generated light from a tunable laser (680 - 970 nm) which was delivered through fiber optic bundles integrated into a linear array transducer (LZ-250, fc = 21 MHz), mounted to a linear stepper motor for 3D imaging. Animals (n=3) having MCF-7 xenograft tumors on either flank transfected with (+TYR) or without (-TYR) doxycycline-regulated tyrosinase were imaged before and one week after the induction of tyrosinase expression. 3D images of the tumors were acquired using multiple wavelengths (680, 750, 800, 850, 900 and 950nm) and 2D images were acquired across the entire wavelength range of the laser to generate absorption curves for blood and melanin. To confirm the presence of melanin and distinguish it from the endogenous blood signal, one animal was exsanguinated and the tumor was imaged again. Approximately 1mm-thick slices of the tumors were taken and photographed for visual confirmation of the presence of melanin.
Comparison of pre- and post-doxycycline images of +TYR tumors clearly showed enhanced contrast in the tumor which closely matched the absorption spectrum of melanin. This signal persisted upon exsanguination. -TYR tumors showed signal which corresponded with the spectra of oxy and deoxy hemoglobin and changed little over the course of the experiment. Visual inspection of the excised sliced tumors revealed pigmentation in the +TYR tumors which was absent in the -TYR tumors.
Here we have shown the ability of the Vevo LAZR photoacoustic imaging system to visualize inducible reporter gene expression in vivo. This has implications for assessing genetically controlled cellular processes and their response to anti-cancer drugs but also for monitoring gene therapy for cancer treatment non-invasively.
Citation Format: Andrew Heinmiller, Minalini Lakshman, Dave Bates, Andrew Needles, Catherine Theodoropoulos, Robert J. Paproski, Roger J. Zemp. In vivo tyrosinase reporter gene imaging with multispectral photoacoustic technology. [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 3920. doi:10.1158/1538-7445.AM2013-3920
Abstract 3928: In vivo ERK1/2 reporting demonstrates the association and timing of ERK1/2 pathway reactivation and acquired resistance to RAF inhibitors.
Authors: Basile Kevin J. , Abel Ethan V. , Dadpey Neda , Aplin Andrew E. 
Published: August 2014

Abstract
Patients with V600 mutant BRAF positive metastatic melanoma are now treated with the RAF inhibitor, vemurafenib (Zelboraf), as a first line therapy. Although most patients treated with vemurafenib have tumor shrinkage, other patients exhibit disease progression. Furthermore, most patients who initially respond to the drug eventually develop acquired resistance to vemurafenib. Disease progression while on vemurafenib frequently correlates with ERK1/2 pathway reactivation but previous studies have been unable to precisely monitor the temporal changes in ERK1/2 activity. Here, we establish a cell-based ERK1/2 reporter system that provides quantitative analysis of RAF inhibitor action in mutant BRAF melanoma cells in vitro and in vivo. This system was utilized to show that the RAF inhibitor, PLX4720, effectively targets the ERK1/2 pathway in vivo and that ERK1/2 reactivation is associated with tumor re-growth. Levels of ERK1/2 reactivation varied substantially between tumors and were associated with several different molecular changes. These data present a new system from monitoring in vivo efficacy of ERK1/2 pathway inhibitors and identifying mechanisms of in vivo acquired resistance.
Citation Format: Kevin J. Basile, Ethan V. Abel, Neda Dadpey, Andrew E. Aplin. In vivo ERK1/2 reporting demonstrates the association and timing of ERK1/2 pathway reactivation and acquired resistance to RAF inhibitors. [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 3928. doi:10.1158/1538-7445.AM2013-3928