bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1430: Automation of both sample preparation and analysis of a cell migration assay
Authors: Burroughs Sarah E. , Hulkower Keren I. , Schicktanz Simone , Fronczak Jennifer A. , Boettcher Karin , Cloutier Timothy E. 
Published: June 2012

Abstract
Cell migration is a critical event in the process of angiogenesis. Aberrant cell migration can contribute to metastatic cancer and other diseases. Understanding the signaling pathways involved in regulating migration is crucial for discovering new targets to develop drugs that inhibit migration and angiogenesis. Because cell migration is a phenotypic or whole-cell event, it can be challenging to conduct and quantitatively analyze such cell-based assays in a consistent and efficient manner. Automation of such assays allows researchers to analyze more conditions than would be feasible with manual methods. With advances in migration plate technology and automated liquid handling, it is now possible to increase one's capacity to run these important assays. However, liquid handling automation parameters are critical and must be optimized so as not to interfere with the biology or its analysis. Here we demonstrate a successful automation of the sample preparation the Platypus Oris® Pro 384-Well Cell Migration Assay on a PerkinElmer JANUS® Automated Liquid Handling Workstation. In addition, quantitation of such assays is now possible with multi-mode detection and High Content Screening (HCS) technologies. Analysis of cell migration using the Operetta® / Harmony® HCS platform and the EnSpire™ multilabel plate reader shows the assay to be a robust and reproducible quantification of cell motility. Using these methods the authors demonstrate statistically significant inhibition of this phenotypic cellular process by a variety of compounds, including cytochalasin D and the MEK inhibitor U0126.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1430. doi:10.1158/1538-7445.AM2011-1430
Abstract 1448: Interaction between decorin and E-cadherin/beta-catenin signaling attenuates colorectal cancer growth and metastasis in vitro and in decorin knockout mice
Authors: Bi Xiuli , Yang George R. , Gou Yuan , Pohl Nicole , Guzman Grace , Kajdacsy-Balla Andre , Iozzo Renato V. , Yang Wancai 
Published: June 2012

Abstract
Decorin is a small leucine-rich proteoglycan. Previous studies have demonstrated that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene caused intestinal tumor formation in mice, which was linked to a downregulation of p21, p27kip1 and E-cadherin and an upregulation of β-catenin signaling. However, the regulation of E-cadherin by decorin and its implication in cancer formation and metastasis is largely unknown. Using manipulated colorectal cancer cells and decorin knockout mouse model (Dcn-/- mice), we found that increasing decorin expression in colorectal cancer cells delayed cancer cell growth, accelerated apoptosis, and importantly, attenuated cancer cell migration, invasion and wound healing. Mechanistic study revealed that the attenuation of cancer cell malignancy was resulted from the interaction between decorin and E-cadherin, a protein that regulates cell-cell adhesion, epithelial-mesenchymal transition and metastasis. First, overexpression of decorin led to upregulation of E-cadherin through increasing of E-cadherin protein stability, while E-cadherin mRNA and promoter activity were not affected; Second, co-immunoprecipitation assay showed that decorin physically bound E-cadherin. In addition, the upregulation of E-cadherin was associated with reduction of β-catenin, c-myc and CDK4. cDNA microarray analysis also showed that the levels of two proteins involved in metastasis were altered, the extracellular proteinase inhibitor (EXPI) was significantly downregulated and Claudin 2 was upregulated in intestinal epithelial cells of the Dcn-/- mice. Moreover, loss of decorin accelerated murine cancer cell MC38 growth and invasion in the flank of Dcn-/- mice. Taken together, our results provide direct evidence that decorin-mediated inhibition of colorectal cancer formation and metastasis is through the interaction between decorin and E-cadherin/beta-catenin signaling.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1448. doi:10.1158/1538-7445.AM2011-1448
Abstract 1460: AKAP12 regulates melanoma tumor growth and metastasis
Authors: Finger Elizabeth C. , Banh Alice , Rankin Erinn B. , Vilalta Marta , Krieg Adam J. , Broome-Powell Marianne , Giaccia Amato J. 
Published: June 2012

Abstract
Skin cancer, which accounts for at least half of all cancers in the United States, is predicted to affects 1 in 5 Americans in their lifetime. Melanoma, the most serious form of skin cancer, is also the leading cause of all skin cancer deaths. This study demonstrates that AKAP12 (SSeCKS, AKAP250, gravin), a hypoxia-inducible scaffold protein, is considerably increased at the protein and RNA level in melanoma cell lines. In addition, there is a significant increase in RNA expression in primary and metastatic tumors when compared to normal specimens, as well as patients with poor prognosis, as measured by diminished 5- year survival. AKAP12 functions to dock many kinases and signaling proteins that regulate cell adhesion, spreading and migration, including: PKC, Src and F-actin. Since these processes are critical for tumor cell metastasis, we hypothesize that AKAP12 could be a central regulator of cancer progression. Stable knockdown of AKAP12 in two melanoma cell lines demonstrate decreases in invasion, migration and clonogenic potential in vitro, as well reduced colony forming abilities in conditions requiring anchorage-independent growth in soft agar. In vivo studies in a metastatic model of melanoma demonstrate a statistically significant decrease in tumors within the lungs of the AKAP12 knockdown groups, highlighting the importance of AKAP12 in metastatic disease. An orthotopic model also demonstrates decreased primary tumor growth and metastatic potential in mice injected with AKAP12 knocked down cells. Additionally, changes in cell morphology characteristic of increased motility and invasiveness are seen in cells containing AKAP12 but not those in which it had been knocked down. While this scaffold protein has been found to act as a tumor suppressor in several tissue types (lung, colon, prostate), we have uncovered its novel oncogenic properties in metastatic melanoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1460. doi:10.1158/1538-7445.AM2011-1460
Abstract 1472: MRP4 and PGT, members of the COX-2 pathway, may contribute to breast cancer progression
Authors: Kochel Tyler , Kundu Namita , Ma Xinrong , Reader Jocelyn , Brodie Angela , Fulton Amy M. 
Published: June 2012

Abstract
Prostaglandin E2 (PGE2) is the major product of the cyclooxygenase 2 (COX-2) enzyme. PGE2 is a substrate of multiple drug resistance-associated protein 4 (MRP4) which exports it from the cell. PGE2 can then signal through any of its four GPCR-family receptors EP1-4. Each receptor is connected to a different cell function including adenylate cyclase activation, calcium flux, and inositol trisphosphate mobilization. Alternatively, extracellular PGE2 can be imported through prostaglandin transporter (PGT) and inactivated by 15-hydroxy prostaglandin dehydrogenase (15-PGDH). PGE2 plays a role in tumor progression as evidenced by the anti-tumor activity of COX-2 inhibitors. Adverse effects of these inhibitors have forced a search to identify other potential therapeutic targets in the COX-2 pathway (such as the receptors, transporters, and associated metabolic enzymes of PGE2). We hypothesize that disregulation of the COX-2 pathway can lead to increased metastatic potential in breast cancer. High extracellular PGE2 in the tumor microenvironment can stem from high COX-2 expression or elevated eicosanoid export activity. Continued prostaglandin signaling is thought to occur due to the interplay between increased expression of the exporting protein (MRP4) shuttling PGE2 into the pericellular space and decreased expression of the importing protein (PGT) removing PGE2 from the pericellular space. Higher concentrations of PGE2 in the pericellular space allow for increased signaling through PGE2 receptors EP1-4. Using a panel of breast cancer cell lines, we demonstrate that highly metastatic tumor cells can express low levels of COX-2, but still actively signal through PGE2 receptors. MRP4 mRNA and protein expression is increased in tumor cell lines with high metastatic potential while expression of PGT mRNA and protein is decreased in these cells when compared to cells with lower metastatic potential. This should lead to higher concentrations of extracellular PGE2 in the tumor microenvironment. Additionally, we have examined MCF7 cells stably transfected with aromatase and an anastrozole-resistant derivative of this cell line for expression of COX-2, EP4, EP1, MRP4 and PGT. At the mRNA level, COX-2, EP1, MRP4 and PGT decrease in the aromatase inhibitor-resistant cells. EP4 mRNA levels increase in the resistant cells. Examining the relative expression levels of all key members in the COX-2 pathway as they relate to tumor progression could highlight new therapeutic targets under this classification of breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1472. doi:10.1158/1538-7445.AM2011-1472
Abstract 1482: Role of TGF-beta signaling and mechanism of osteoblastic tumorigenesis in prostate cancer
Authors: Mishra Sweta , Tang Yuping , Werner Sherry L , Sun LuZhe 
Published: June 2012

Abstract
Prostate cancer is the second leading cause of cancer death in men with 80% of deaths occurring due to bone metastasis. Transforming growth factor-beta (TGFβ) signaling is important for the regulation of bone mass and matrix properties. The role of TGFβ signaling in prostate cancer-induced bone metastasis is unclear due in part to a lack of prostate cancer cell lines that can efficiently induce bone metastasis and osteoblastic lesions in animal models. We have previously shown that a newly established human prostate cancer cell line, PacMetUT1, produces a large amount of active TGFβ1 and induces extensive bone metastases in calvaria, rib, femur, and tibia when inoculated in the left cardiac ventricle of male nude mice. Experimental data from our lab demonstrated that stable knockdown of TGFβ1 using a short hairpin-RNA resulted in a decreased tumor incidence and bone formation when the cells were directly injected into the right tibias of male nude mice. Systemic administration of either a small inhibitor of TGFβ type I receptor kinase or a pan-TGFβ binding protein also decreased osteoblastic intratibial tumor lesions. However, the mechanism by which prostate cancer cells metastasize to bone and how they induce formation of osteoblastic lesions remains to be intensively investigated. We hypothesize that TGFβ and other growth factors released from tumor cells can induce aromatase gene expression and activity in bone cells leading to an enhanced estradiol synthesis which would lead to an increase in bone formation as estrogen is a known osteogenic factor. We examined the effect of TGFβ1 and BMP-4/7 treatment on aromatase expression in pre-osteoblastic cells in vitro. In vitro treatment with 5ng/ml of TGFβ1 and 25ng/ml of BMP-4/7 resulted in an increase in aromatase expression in 2T3, a mouse mesenchymal stem cell and in 63 year old male mesenchymal stem cells (MSC) at the protein level. Furthermore, TGFβ resulted in an induction of Smad-1/5 signaling pathway in these pre-osteoblastic cells. Transient knockdown of Smad-1/5 expression in male MSC by siRNA, resulted in a decreased aromatase expression. Our results demonstrate TGFβ to be a major driver of osteoblastic tumorigenesis in PacMetUT1 cells, and Smad-1/5-dependent aromatase upregulation by TGFβ superfamily ligands in pre-osteoblastic cells. Future studies will delineate whether the induction of aromatase mediates osteoblastic bone metastasis in vivo, and if combination treatment of TGFβ and aromatase inhibitors can be used as a novel therapeutic strategy for bone metastatic prostate cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1482. doi:10.1158/1538-7445.AM2011-1482
Abstract 1488: SOX2 promotes tumor metastasis by stimulating the process of epithelial-mesenchymal transition
Authors: Li Xuefei , Jia Xianpei , Xu Yingxi , Chen Yanan , Chen Si , Xiang Rong , Li Na 
Published: June 2012

Abstract
Ectopic expression of SOX2 has been reported in a variety of tumor tissues and contributes to cell proliferation and tumorigenesis by transcriptional regulation of the target genes; however the role of SOX2 in tumor metastasis and the underlying mechanisms remain largely elusive. Here we used immunohistochemistry to analyze the expression of SOX2 in the tissues of human breast and lymph nodes and found that SOX2 was highly expressed in breast cancer tissues and the metastasised lymph node, also the expression of SOX2 was closely correlated with the TNM stage and histological grade. We further demonstrated that SOX2 improved the migration and invasion properties of breast cancer and prostate cancer cells by facilitating the process of epithelial-mesenchymal transition (EMT). Investigation of the molecular mechanism revealed that SOX2 regulated EMT by β-catenin signaling pathway. Our findings prove that SOX2 plays a pivotal role in the metastasis of human breast cancer and prostate cancer and suggest that SOX2 has the potential to be developed as the diagnosis marker for breast and prostate cancer metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1488. doi:10.1158/1538-7445.AM2011-1488
Abstract 1500: A novel nutrient mixture exhibits antitumor activity in human fibrosarcoma cell line HT-1080
Authors: Roomi M. Waheed , Jariwalla Neil , Roomi Nusrath , Rath Matthias , Niedzwiecki Aleksandra 
Published: June 2012

Abstract
Introduction: Fibrosarcoma, an aggressive and highly metastatic cancer of connective tissue, is generally associated with poor prognosis. Cancer mortality usually results from tumor invasion of local tissue and metastasis to vital organs. We investigated the effect of a specific nutrient mixture (PB) of quercetin, cruciferex, curcumin, green tea extract and resveratrol on human fibrosarcoma cell line HT-1080 for viability, MMP expression, invasion, apoptosis and morphology.
Material and Methods: Human fibrosarcoma cell line HT-1080 (ATCC) was cultured in DEM media, supplemented with 10% FBS and antibiotics in 24-well tissue plates. At near confluence, cells were treated with PB at 0, 10, 25, 50, 75 and 100 mcg/mL, in triplicate at each dose. Cells were also treated with PMA (100 ng/mL) for MMP-9 induction. Cell proliferation was assayed by MTT assay, MMP by zymography, invasion through Matrigel, apoptosis using green caspase detection, and morphology by H&E staining.
Results: PB inhibited proliferation of human fibrosarcoma cells HT-1080 by 50% at 10 mcg/mL, 60% at 25 mcg/mL and 80% at 50-100 mcg/mL, and inhibited the secretion of both MMP-2 and MMP-9 in a dose-dependent manner, with total inhibition at 50 mcg/mL concentration. Invasion through Matrigel was inhibited 100% at 25 mcg/mL PB. PB also induced apoptosis in a dose- dependent fashion. H&E staining showed slight morphological changes at higher concentrations.
Conclusion: These results suggest that PB is a potential therapeutic agent for fibrosarcoma, with potent anti-metastatic activity, because it inhibited fibrosarcoma cell proliferation, MMP-2 and -9 expression, invasion through Matrigel and apoptosis, important parameters for cancer prevention.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1500. doi:10.1158/1538-7445.AM2011-1500
Abstract 1515: Disruption of circadian rhythmicity in liver metastasis of colorectal cancer
Authors: Huisman Sander A. , van Ginhoven T.M. , van den Berg J.W. , Roest H.P. , Tamanini F. , Destici E. , IJzermans J.N.M. , van der Horst G.T.J. , de Bruin R.W.F. 
Published: June 2012

Abstract
Background: Liver metastases of colorectal cancer are a major cause of cancer related mortality. Resection of hepatic metastasis prolongs life, but 25% of the functional reserve of the liver should remain after resection to allow adequate liver regeneration. An effective means to downsize the tumor and enable resection is the use of chemotherapeutics. Efficacy and adverse side effects of chemotherapy may vary considerably over a 24 hour period. Chronotherapy (circadian rhythm adjusted chemotherapy) could take advantage of the fact that there may be asynchronies in circadian rhythm between normal and cancer tissue. In addition, genetic or functional disruption of the circadian clock may result in genomic instability and accelerated carcinogenisis and tumor growth.
A more thorough understanding of circadian rhytmicity may help in elucidating the role of the clock in tumorigenesis and tumor growth and develop more effective chronotherapeutic chemotherapy treatment schedules. Therefore, in this study we investigated the 24-hour expression levels of key circadian clock genes in colorectal liver metastasis and adjacent healthy liver tissue in the mouse.
Materials and methods: Male BALB/c mice were injected with C26 colorectal carcinoma cells into the spleen. Three weeks after tumor inoculation, a hepatectomy was performed at 6 different timepoints over a 24-hour period (n=4 per timepoint) to compare circadian rhythmicity in tumor and adjacent healthy tissue. RNA was isolated and RT-PCR was performed on 5 clock genes: Rev-erbα, Per2, Per1, DBP, and Bmal1 and a clock independent gene induced by feeding (Acss2).
Results: Healthy liver tissue showed normal 24-hour oscillations of all 5 clock genes, consistent with normal circadian rhytmicity. In colorectal liver metastasis however, 24-hour oscillations were completely absent in all clock genes except Per2. Per2 oscillations were similar in tumor and adjacent liver tissue, although expression levels in tumor tissue were lower. Since Per2 may also be induced by feeding, we determined the expression of the food induced gene Acss2, which is independent of circadian rhythm. Acss2 levels rose in response to feeding, followed by a rise in Per2, strongly suggesting that the increased expression of Per2 was induced by feeding.
Conclusion: Our data demonstrate the absence of circadian rhythm in hepatic metastasis of C26 coloncarcinoma in vivo. The difference between tumor and healthy tissue in this model may provide new clues to further understand the biology, and optimize treatment of hepatic metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1515. doi:10.1158/1538-7445.AM2011-1515
Abstract 1517: Retinoblastoma tumor development: Role of tumor-associated macrophages and their sub-type in LHBETATAG retinal tumor progression
Authors: Pina Yolanda , Decatur Christina , Houston Samuel , Shah Nikesh , Cavalcante Ludimila , Murray Timothy 
Published: June 2012

Abstract
Purpose: The purpose of the current study is to establish the distribution of tumor associated macrophages (TAMs) during tumor development in a transgenic retinoblastoma mouse model, study the contribution of bone-marrow derived macrophages in these tumors, and assess the supportive role of TAMs in retinoblastoma tumor growth.
Methods: Macrophage infiltration in transgenic retinoblastoma tumors was assessed by immunohistochemistry at different time points in tumorigenesis. To establish the origin of TAMs in transgenic retinoblastoma tumors, 107 bone marrow cells from green fluorescent protein (GFP) positive 16-week-old mice were transplanted into age-matched, irradiated LHBETATAG mice via tail vein injections. Macrophage depletion was performed by subconjuctival (SC) delivery of liposomal clodronate.
Results: TAMs’ density increased from 4- to 12-weeks of age in mice with small to medium-sized tumors (p=0.037), and remained stable in the later stages of the disease (i.e., 16-week-old with large tumors; p=0.20). 38% of TAMs (2.5 ± 3.2 cells per 400X hpf) in 16-week old mice were GFP-positive, bone marrow-derived macrophages. Total TAM depletion was correlated with a significant decrease in the expression levels of MMP-9 (p=0.014) and mature vessels (p&lt;0.001), and a nonsignificant decrease in the density of neovessels (p=0.94). The density of M2-polarized TAMs did not change significantly following TAM depletion (p=0.68). Following M1-polarized TAM depletion, the tumor burden increased (p=0.056).
Conclusions: The current study expands our understanding of the complex role that macrophages play in retinoblastoma. Macrophage modulation in the tumor microenvironment is a critical factor in retinoblastoma tumor development.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1517. doi:10.1158/1538-7445.AM2011-1517