bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1983: Real-time imaging of exosomes dynamic of cross-talking and cell trafficking in 3D Gelfoam® histoculture
Authors: Yamamoto Mako , Miwa Shinji , Hiroshima Yukihiko , Yano Shuya , Uehara Fuminari , Matsumoto Yasunori , Suetsugu Atsushi , Homma Kimi , Hoffman Robert M. 
Published: May 2015

Abstract
Exosomes are small membrane vesicles (30-100 nm) released by many types of cells during normal physiological processes and are thought to play an important role in cell-to-cell communication to promote tumor metastasis. Exosomes contain diffusible factors, such as cytokines, growth factors and extracellular matrix molecules and also mediate local and systemic cell communication through the horizontal transfer of information, such as mRNAs, microRNAs and proteins. However, the exosome dynamics and trafficking between cancer cells and tumor stromal cells in a metastatic niche are still unclear. In this study, in order to image the movement of cancer cell-derived exosomes, we developed a confocal time lapse imaging system to use green fluorescent protein (GFP)-tagged CD63, which is a general marker of exosomes, expressed in breast cancer cells cultured on 3-dimentional Gelfoam® histoculture. We demonstrated that 3D Gelfoam® culture enabled imaging of structural cell-to-cell contact between neighboring cells and exosome behavior in real-time. This system makes it possible to monitor real-time exosome dynamics and cross-talking between cancer cells and other cells and to identify the mechanism of exosome release and uptake such as in a metastatic niche.
Citation Format: Mako Yamamoto, Shinji Miwa, Yukihiko Hiroshima, Shuya Yano, Fuminari Uehara, Yasunori Matsumoto, Atsushi Suetsugu, Kimi Homma, Robert M. Hoffman. Real-time imaging of exosomes dynamic of cross-talking and cell trafficking in 3D Gelfoam® histoculture. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1983. doi:10.1158/1538-7445.AM2014-1983
Abstract 2002: A novel candidate metastasis-associated protein, MAP40, differentially expressed in highly metastatic breast cancer cells reveals an essential role in tumor metastasis
Authors: Kim Mijin , Kim Seong-Jin 
Published: May 2015

Abstract
Metastasis is the underlying cause of death in the majority of patients with breast cancer who succumb to their disease, but the fundamental mechanisms remain poorly understood. Here we have found a novel candidate of metastasis-associated protein, MAP40, which is highly expressed membrane protein in the metastatic breast cancer cell lines. Using the public microarray datasets, we also found that MAP40 is significantly increased in the basal type of breast tumors compared to the luminal subtype. We undertook the lentivirus-based system to functionally silence MAP40 gene in basal-like breast cancer cell lines. Knockdown of MAP40 results in a significant reduction of cell migration and invasiveness as well as suppression of anchorage-independent growth in basal-like breast cancer cells. Additionally, depletion of MAP40 induces E-cadherin expression, while integrin β1 protein level is suppressed. Together with results from studies in animal models suggest that MAP40 may promote tumor formation and direct metastasis of breast cancer in vivo. Ongoing studies to find interacting partners and downstream genes will allow us to further understand its mechanism in metastasis.
This work was supported by a National Research Foundation grant of Korea (2009-0081756) funded by the Korea government.
Citation Format: Mijin Kim, Seong-Jin Kim. A novel candidate metastasis-associated protein, MAP40, differentially expressed in highly metastatic breast cancer cells reveals an essential role in tumor metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2002. doi:10.1158/1538-7445.AM2014-2002
Abstract 2007: Hypoxia induced TGF-β regulates Semaphorin7A to promote a pro-tumorigenic mesenchymal phenotype in mammary cells
Authors: Garcia-Areas Ramon A. , Libreros Stephania , Amat Samantha , Castro-Silva Camila , Schilling Kathy , Iragavarapu-Charyulu Vijaya 
Published: May 2015

Abstract
The study of breast cancer relies heavily upon the identification of tumor-associated proteins that are involved with tumor growth and development. Our lab has discovered that mammary tumor cells express high levels of a novel protein known as Semaphorin7A (SEMA7A). After analyzing breast tissue samples collected at Boca Raton Regional Hospital, we have found that normal human mammary epithelial cells express negligible mRNA levels of SEMA7A, while the malignant mammary tumor cells express elevated levels of SEMA7A. Additionally, our laboratory has established a murine model of mammary cell lines that parallels our human findings. Currently, we have correlated high levels of SEMA7A with increasing tumor malignancy and metastasis. However, it is still unknown what factors could induce the production of SEMA7A in mammary tumors. Recent studies have proven that the expression and induction of SEMA7A in normal endothelial cells is regulated under a hypoxic-response element in the promoter of its gene. Although hypoxia is an established tumorigenic factor, it is unknown if the increased hypoxic conditions in breast tumors could induce SEMA7A. In this study we have investigated if exposing mammary cells to hypoxia induces the expression of pro-tumorgenic SEMA7A. Our results show that SEMA7A is up-regulated in 4T07 and 4T1 mammary tumor cells after hypoxic exposure via TGF-β activation of the PI3/AKT pathway. Furthermore, we have found that shRNA silencing of the SEMA7A in 4T1 mammary cells attenuates the activation of pro-angiogenic and mesenchymal genes even after hypoxic stimuli. In vivo, these cells show a reduced proliferation and metastatic potential. We therefore postulate an exciting new role for SEMA7A as a TGF-β effector that promotes tumorigenesis during breast cancer progression.
Citation Format: Ramon A. Garcia-Areas, Stephania Libreros, Samantha Amat, Camila Castro-Silva, Kathy Schilling, Vijaya Iragavarapu-Charyulu. Hypoxia induced TGF-β regulates Semaphorin7A to promote a pro-tumorigenic mesenchymal phenotype in mammary cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2007. doi:10.1158/1538-7445.AM2014-2007
Abstract 2011: ETV4 promotes pancreatic cancer progression and metastasis
Authors: Tyagi Nikhil , Srivastava Sanjeev K. , Bhardwaj Arun , Arora Sumit , Grizzle William E. , Owen Laurie B. , Singh Ajay P. , Singh Seema 
Published: May 2015

Abstract
Pancreatic cancer is a highly metastatic disease with a 5 year survival rate of ∼6.0% after diagnosis. The poor outcome of pancreatic cancer is largely due to its highly aggressive nature and lack of effective therapies against metastatic disease. Therefore, it is imperative to identify novel molecular targets driving metastatic progression of pancreatic cancer. ETV4, proto-oncogenic transcription factor, has been shown to be expressed aberrantly in various cancers types and to play important roles in pathobiology; however, its roles in pancreatic cancer have not been defined. We investigated the pathological significance of ETV4 in pancreatic cancer by its silencing in two highly metastatic pancreatic cancer cell lines, Colo357 and ASPC1, and by forced overexpression in weakly tumorigenic BXPC3 cells. Silencing of ETV4 led to decreases in growth, clonogenicity, motility and invasiveness of pancreatic cancer cells, whereas its overexpression had opposite effects. Furthermore, our data demonstrate a correlation with changes in the expression of mesenchymal (N-cadherin, Vimentin, Slug and Snail) and epithelial (E-cadherin) markers upon ETV4 modulation, indicating its role in epithelial to mesenchymal transition (EMT). More importantly, our in vivo studies in an orthotopic mouse model of pancreatic cancer demonstrated a direct association of ETV4 overexpression with tumorigenicity and metastatic potential of pancreatic cancer cells. In summary, our studies establish a functional role of ETV4 in pancreatic cancer pathogenesis.
Citation Format: Nikhil Tyagi, Sanjeev K. Srivastava, Arun Bhardwaj, Sumit Arora, William E. Grizzle, Laurie B. Owen, Ajay P. Singh, Seema Singh. ETV4 promotes pancreatic cancer progression and metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2011. doi:10.1158/1538-7445.AM2014-2011
Abstract 2013: NEDD9 depletion leads to MMP14 inactivation by TIMP2 and prevents invasion and metastasis
Authors: Pugacheva Elena N. , McLaughlin Sarah , Ice Ryan , Rajulapati Anuradha , Kozyulina Polina , Livengood Ryan , Kozyreva Varvara , Loskutov Yuriy , Ivanov Alexey , Weed Scott 
Published: May 2015

Abstract
The scaffolding protein NEDD9 is an established pro-metastatic marker in several cancers. Nevertheless, the molecular mechanisms of NEDD9 driven metastasis in cancers remain ill defined. Here, using a comprehensive breast cancer (BCa) tissue microarray, we show that increased levels of NEDD9 protein significantly correlated with the transition from carcinoma in situ to invasive carcinoma. NEDD9 expression is crucial for the mesenchymal invasion of cancer cells at the primary site but not at the metastatic site. Depletion of NEDD9 is sufficient to suppress invasion, leading to decrease in circulating tumor cells (CTCs) and lung metastases in xenograft models. Mechanistically, NEDD9 localizes to invasive pseudopods and is required for local matrix degradation via regulation of MMP14 trafficking. Depletion of NEDD9 impaired invasion of cancer cells through inactivation of MMP14 by excess TIMP2 on the cell surface. Re-expression of NEDD9 is sufficient to restore the activity of MMP14 and the invasive properties of BCa cells. Collectively, these findings uncover critical steps in invasion of BCa cells with potential strategy to target metastasis through manipulation of NEDD9.
Citation Format: Elena N. Pugacheva, Sarah McLaughlin, Ryan Ice, Anuradha Rajulapati, Polina Kozyulina, Ryan Livengood, Varvara Kozyreva, Yuriy Loskutov, Alexey Ivanov, Scott Weed. NEDD9 depletion leads to MMP14 inactivation by TIMP2 and prevents invasion and metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2013. doi:10.1158/1538-7445.AM2014-2013
Abstract 2020: Spheroid culture of primary colorectal cancer cells from liver metastases as an in vitro model of patient tumors
Authors: Jeppesen Maria , Hagel Grith , Vainer Ben , Harling Henrik , Thastrup Ole , Jorgensen Lars Nannestad , Thastrup Jacob 
Published: May 2015

Abstract
More than 65 % of patients with colorectal cancer require chemotherapeutic treatment during the course of their disease. However, colorectal tumors demonstrate pronounced heterogeneity, leading to significant individual variation in sensitivity to standard chemotherapeutic drugs. Tools for assessing chemosensitivity and tailoring therapeutic regimens to the individual patient are therefore urgently needed. A promising approach is to isolate viable cancer cells from patient tissue and to test the chemosensitivity of the individual tumor in vitro.
The aim of the current study was to establish primary colorectal cancer cell cultures from patient liver metastases and investigate if the cultured cells retained important characteristics of the original tumor. Small cell clusters were isolated from metastatic tissue and allowed to form cell spheroids in suspension culture. The cell composition of patient spheroids was characterized by immunostaining with cell type specific antibodies. Cancer stem cells were identified by staining for the markers CD44, CD166 and Lgr5. Spheroid size was monitored over time and growth curves established for each patient. The distribution of proliferating and apoptotic cells in the spheroids was assessed by staining for specific markers. Overall, the 3-D culture system was verified as a tumor model by comparing the results obtained for the spheroids to paraffin-embedded sections of the original tumors.
Successful spheroid culture was obtained from more than 80 % of tissue samples. Immunostaining confirmed that the primary cultures were composed of epithelial cells with minimal contamination by other cell types. Cell morphology and expression of intestinal markers confirmed their malignant nature and colorectal origin. The dominating cell populations of the original tumor could generally be identified in the derived spheroids as well. The spheroids demonstrated significant growth in vitro with no decrease in proliferation or increase in apoptosis during short-term culture. In summary, spheroid cultures of colorectal cancer cells can be established from liver metastases of individual patients with a high success rate and the spheroids retain important cellular characteristics of the original tumor. Spheroid culture therefore represents a promising technique for establishing primary cultures for chemotherapeutic screening of the individual patient.
Citation Format: Maria Jeppesen, Grith Hagel, Ben Vainer, Henrik Harling, Ole Thastrup, Lars Nannestad Jorgensen, Jacob Thastrup. Spheroid culture of primary colorectal cancer cells from liver metastases as an in vitro model of patient tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2020. doi:10.1158/1538-7445.AM2014-2020
Abstract 2026: Analysis of the impact of compounds derived from marine organisms on 3D co-spheroids generated from multiple myeloma cells and stromal cell types
Authors: Ganesan Jayanthi , Weber Holger , Umber Sarah , Siedentopf Oliver , Feger Daniel , García-Fernández Luis F. , Ávila Miguel Aracil , Kubbutat Michael H.G. , Ehlert Jan E. 
Published: May 2015

Abstract
Multiple myeloma (MM) is a severe leukemic disease of plasma B-cells in the bone marrow to which there is currently no cure. Stromal components such as mesenchymal stromal cells (MSC) or endothelial cells (EC) are suspected to play a central role in mediating resistance during treatment of patients. In the attempt to identify novel drugs for the treatment of MM in extracts of marine organisms, we established 3D co-spheroid systems which would allow to factor in micro-environmental signals already in the early phase of drug discovery. We report on the establishment of both an angiogenesis and a proliferation assay using 3D co-spheroids combining MM cells together with either endothelial or mesenchymal stromal cells, respectively. These co-spheroid systems were applied to characterize a variety of compounds for their anti-angiogenic activity on EC or anti-proliferative activity on MM as well as MSC.
Funded by European Union Seventh Framework Program (FP7/2007-13) under Grant Agreement Nr.278570
Citation Format: Jayanthi Ganesan, Holger Weber, Sarah Umber, Oliver Siedentopf, Daniel Feger, Luis F. García-Fernández, Miguel Aracil Ávila, Michael H.G. Kubbutat, Jan E. Ehlert. Analysis of the impact of compounds derived from marine organisms on 3D co-spheroids generated from multiple myeloma cells and stromal cell types. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2026. doi:10.1158/1538-7445.AM2014-2026
Abstract 2028: A novel human gastric primary cell culture system for modelling Helicobacter pylori infection in vitro
Authors: Schlaermann Philipp , Meyer Thomas F. 
Published: May 2015

Abstract
The significance of bacterial infections in the initiation of human cancers is increasingly being recognized. A well established example is Helicobacter pylori, a causative agent of gastric adenocarcinoma. Current research largely relies on the use of transformed human cell lines as in vitro models of these infections. Obviously, this concept is largely artificial and especially inappropriate when it comes to investigations on the mechanisms of cancerogenesis. A primary cell system would be preferable in order to approximate the in vivo situation, however, previous attempts to establish such models are hampered by the limited growth and reproducibility of normal human primary cell cultures. Here, we report on the establishment of specific long-term culture conditions that allow the formation of 3-dimensional human gastric organoids with epithelial domains that have the capacity to self-renew and can be maintained in culture indefinitely. Interestingly, these 3-dimensional structures can be transferred into 2-dimensional primary cell layers, which provide ideal conditions to study infections in vitro. We expect that our novel human gastric primary cell model will facilitate investigations on the mechanisms underlying infection and is suited to open up avenues of approach to investigations on the initial processes of cellular transformation from normal to a transformed cell stages including the tumor-promoting capacity of the gastric pathogen H. pylori.
Citation Format: Philipp Schlaermann, Thomas F. Meyer. A novel human gastric primary cell culture system for modelling Helicobacter pylori infection in vitro. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2028. doi:10.1158/1538-7445.AM2014-2028
Abstract 203: Inhibiting invasion and stemness in glioblastoma by thymosin beta 4 gene silencing: a new therapeutic target
Authors: Wirsching Hans-Georg , Krishnan Shanmugarajan , Florea Ana-Maria , Frei Karl , Krayenbühl Niklaus , Hasenbach Kathy , Reifenberger Guido , Weller Michael , Tabatabai Ghazaleh 
Published: May 2015

Abstract
Glioblastoma are incurable primary brain tumors with one of the worst 5-year survival rate among all cancers. Despite multimodality treatment involving neurosurgical intervention, radiation and temozolomide chemotherapy, the median overall survival is in the range of 15-16 months. Four large phase III trials investigating dose-dense temozolomide (RTOG0525) or the addition of the integrin inhitibor cilengitide (CENTRIC) or the addition of vascular endothelial growth factor (VEGF) antibody bevacizumab (RTOG 0828, AVAglio) to the current standard treatment failed to extend this range. Novel therapeutic targets are urgently needed. Thymosin beta 4 (TB4) is a pleiotropic actin-sequestering polypeptide that is involved in wound healing and developmental processes. TB4 gene silencing promotes differentiation of neural progenitor cells whereas TB4 overexpression initiates cortical folding of developing brain hemispheres. Moreover, TB4 is involved in migration invasion and epithelial to mesenchymal transition in other cancer entities, e.g. colon cancer. In the present study, we investigated the role of TB4 in malignant glioma.
TB4 expression increased with the grade of malignancy in gliomas and correlated with patient survival. In vitro, TB4 gene silencing decreased migration, invasion, growth and self-renewal, and promoted differentiation and the susceptibility to undergo apoptotic cell death upon nutrient depletion in LNT-229, U87MG and the glioma stem-cell line GS2, respectively. In vivo, survival of nude mice bearing tumors derived from TB4-depleted glioma cells was improved and the tumorigenicity of the GS2 glioma-initiating cell line was diminished. The gene expression pattern in TB4-silenced glioma cells was shifted from the mesenchymal towards the pro-neural gene signature. The clustering of differentially regulated genes involved TGF-beta and p53 signaling networks.
Taken together, our data indicate that TB4 may be a novel regulator of malignancy in glioblastoma and therefore a candidate therapeutic target.
Citation Format: Hans-Georg Wirsching, Shanmugarajan Krishnan, Ana-Maria Florea, Karl Frei, Niklaus Krayenbühl, Kathy Hasenbach, Guido Reifenberger, Michael Weller, Ghazaleh Tabatabai. Inhibiting invasion and stemness in glioblastoma by thymosin beta 4 gene silencing: a new therapeutic target. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 203. doi:10.1158/1538-7445.AM2014-203
Abstract 2058: Molecular imaging of glutaminolysis as a tool for evaluating therapeutic response in preclinical models of colorectal cancer
Authors: Hight Matthew R. , Schulte Michael L. , Saleh Samir , Ayers Gregory D. , Revetta Frank L. , Washington M. Kay , Coffey Robert J. , Manning H. Charles 
Published: May 2015

Abstract
The metabolic repertoire of cancer cells diverge significantly from that of normal cells. Energy production in cancer cells tends to depend on aerobic glycolysis, a feature that is routinely monitored by positron emission tomography (PET) imaging using 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG). In addition to predilection for glycolysis, cancer cells may possess other unique metabolic characteristics, such as increased consumption of glutamine. As with glucose, glutamine also serves as a key carbon source for ATP production and biosynthesis. Given this, quantitative measures of glutaminolysis may reflect critical processes in oncology. Accordingly, PET agents targeting glutamine uptake, such as 4-[18F]fluoro-glutamine ([18F]4F-GLN), have been reported and used in preclinical models of cancer.
The goal of this study was to elucidate the feasibility of using [18F]4F-GLN PET to predict response to targeted therapy within the context of colorectal cancer (CRC). Initially we validated expression of SLC1A5, the primary plasma membrane transporter of glutamine, in tumor and normal colon specimens for 58 patients with primary and advanced CRC. We found that SLC1A5 expression was elevated in over 80%of primary tumor specimens but did not correlate with grade or gender. Furthermore, elevated SLC1A5 expression correlated strongly with elevated Ki67, a molecular marker of proliferation.
Given this, we evaluated [18F]4F-GLN PET in preclinical models of V600EBRAF-expressing CRC as a means of detecting anti-proliferation responses to targeted therapeutics. Simulating a clinical study within the context of the Vanderbilt GI SPORE, the regimen included an inhibitor of mutant BRAF, a PI3K/mTOR inhibitor, and a combination there of. Strikingly, [18F]4F-GLN PET was found to correlate more closely to markers of anti-proliferative responses in vivo than analogously performed [18F]FDG PET imaging studies. We believe that these findings not only provide a greater understanding of the role that glutaminolysis plays in CRC but also illuminate the potential impact that glutaminolysis derived PET could have towards guiding drug development clinical trials as an imaging metric of early therapeutic response detection.
Citation Format: Matthew R. Hight, Michael L. Schulte, Samir Saleh, Gregory D. Ayers, Frank L. Revetta, M. Kay Washington, Robert J. Coffey, H. Charles Manning. Molecular imaging of glutaminolysis as a tool for evaluating therapeutic response in preclinical models of colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2058. doi:10.1158/1538-7445.AM2014-2058