bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 510: A novel role for Olig2 in the regulation of glioma invasion
Authors: Singh Shiv K. , Giannonatti Nicole , Kupp Robert , Cascio Costanza Lo , Mehta Shwetal 
Published: August 2015

Abstract
Glioblastoma multiforme (GBM) are highly infiltrative, aggressive and lethal primary brain tumors in adults that are resistant to conventional treatments. A major clinical obstacle in the treatment of GBMs is the ability of glioma cells to invade the surrounding brain parenchyma, preventing their complete surgical resection. Several studies have shown that invasive glioma stem cells (GSCs) extend beyond the surgically resected regions. These invasive cells are the cause for tumor recurrence and poor prognosis in GBM patients. The molecular and cellular mechanism involved in the regulation of the switch from proliferation to invasion/migration in GBM is poorly understood. We investigated the role of Olig2, a Central Nervous System (CNS) specific transcription factor, in promoting the switch from proliferating to invading glioma cell. Genetically relevant murine glioma model as well as patient-derived glioma stem cells (GSCs) were utilized to identify the effect of Olig2 on glioma invasion. Functionally, Olig2-mediated invasion was assessed by 3D-transwell invasion assays, organotypic slice cultures as well as PDX tumors in immunocompromised mice. In addition, murine and patient-derived GSCs were utilized to identify direct genetic targets of Olig2 involved in glioma invasion by ChIP-seq and RNA-seq.
Our data demonstrate that Olig2-expressing murine glioma stem/progenitor-like cells are highly invasive as compared to Olig2 knockout cells. We further corroborated the requirement of Olig2 for glioma invasion in patient-derived GSCs by utilizing shRNA-mediated knockdown of Olig2. Olig2 depletion resulted in reduced glioma cell invasion in at least four independent human GSCs. Recent studies have shown that activation of transcription factors such as Zeb1 and Twist1 occurs in invasive high grade gliomas. We show that knockdown of Olig2 in murine as well as human GSCs leads to a significant decrease in the expression of invasion genes such as Zeb1, Vimentin, Twist1, and Stat3 as compared to control cells. In conclusion, our studies highlight a novel role for the Olig2 signalling network in promoting the switch from proliferation to invasion in GBM, and provide a plausible target for inhibiting glioma invasion.
Citation Format: Shiv K. Singh, Nicole Giannonatti, Robert Kupp, Costanza Lo Cascio, Shwetal Mehta. A novel role for Olig2 in the regulation of glioma invasion. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 510. doi:10.1158/1538-7445.AM2015-510
Abstract 5108: Oscillatory calcium signal drives melanoma invasion and metastasis
Authors: Sun Jianwei , Lu Fujian , He Huifang , Cheng Heping , Yang Shengyu 
Published: August 2015

Abstract
Ca2+ signaling has been increasingly implicated in cancer invasion and metastasis, and yet the underlying mechanisms remained largely unknown. Here, we report that STIM1- and Orai1- mediated Ca2+ oscillations promote melanoma invasion by orchestrating invadopodium assembly and extracellular matrix (ECM) degradation. Ca2+ oscillation signals facilitate invadopodial precursor assembly by activating Pyk2 phosphorylation at tyrosine 402, which directly binds to and activates Src to promote invadopoium assembly. Disruption of Ca2+ oscillations inhibited invadopodium assembly. Futhermore, STIM1 and Orai1 regulate the proteolysis activity of individual invadopodium. Mechanistically, Orai1 blockade inhibits the recycling of MT1-MMP to the plasma membrane and entraps MT1-MMP in the endocytic compartment to inhibit ECM degradation. STIM1 knockdown significantly inhibited melanoma lung metastasis in a xenograft mouse model, implicating the importance of this pathway in metastatic dissemination. Our findings provide a novel mechanism for Ca2+ -mediated cancer cell invasion and shed new light on the spatiotemporal organization of store-operated Ca2+ signals during melanoma invasion and metastasis.
Note: This abstract was not presented at the meeting.
Citation Format: Jianwei Sun, Fujian Lu, Huifang He, Heping Cheng, Shengyu Yang. Oscillatory calcium signal drives melanoma invasion and metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5108. doi:10.1158/1538-7445.AM2015-5108
Abstract 5132: Evaluation of multi-marker in tissue-derived cancer cells from patients with epithelial ovarian carcinoma
Authors: Lee Shin-Wha , Lee Sang-Eun , Lee Ha-Young , Kim Dae-Yeon , Kim Jong-Hyeok , Kim Yong-Man , Kim Young-Tak , Nam Joo-Hyun 
Published: August 2015

Abstract
Objective: The objective of this study is to refine a simple, rapid and reproducible method for the isolation and characterization of epithelial ovarian cancer (EOC) cells from ovarian tumor tissues and to evaluate the intracellular expression of CK-7, CA-125, HE4 and FOLR-1 in primary ovarian cancer cells.
Methods: Fourteen patients diagnosed with papillary serous adenocarcinoma of ovary were selected in ASAN Medical Center. Isolation of tumor EOC cells involves the mechanical disruption of the tumor tissue and placed directly into culture with very little manipulation. Primary ovarian cancer cells were monitored after initial plating and every day for following 15 days. Confocal laser scanning microscopy was used for the imaging of intracellular immunofluorescence of CK-7, CA-125, HE4 and FOLR-1.
Results: Two days after plating primary ovarian cancer cells began to adhere to the plate by the presence of small adherent clusters. The primary ovarian cancer cells became a confluent monolayer and displayed the typical epithelial cobblestone morphology. The mean duration of passage was 8.5 days, it was revealed variously in the primary ovarian cancer cells. Immunofluorescent detection of CK-7 expression in EOC cells demonstrates the epithelial origin, however their expression was not constant. CA-125, HE-4 and FOLR-1 were expressed by all tissue-derived EOC cells. The expression pattern of CA-125, HE-4 and FOLR-1 was different in each patient and that was not correlated with the serum level of CA-125.
Conclusions: The isolation and characterization of tissue-derived cancer cells from patients with EOC using the expression of CK-7, CA-125, HE4 and FOLR-1 were reasonable method. This result could provide clinically relevant models suitable for investigation of the ex vivo biological characteristics of ovarian cancers.
Citation Format: Shin-Wha Lee, Sang-Eun Lee, Ha-Young Lee, Dae-Yeon Kim, Jong-Hyeok Kim, Yong-Man Kim, Young-Tak Kim, Joo-Hyun Nam. Evaluation of multi-marker in tissue-derived cancer cells from patients with epithelial ovarian carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5132. doi:10.1158/1538-7445.AM2015-5132
Abstract 5141: A comprehensive system of congenic mouse melanoma models for evaluation of immune therapies
Authors: Meeth Katrina M. , Damsky William E. , Bosenberg Marcus 
Published: August 2015

Abstract
There has been longstanding interest in the relationship between the immune system and malignant melanoma, the deadliest form of skin cancer. Melanoma has been the tumor of choice for the evaluation of a wide variety of therapeutic approaches that rely on stimulation of the immune system to combat cancer. The striking responses to immune checkpoint inhibitors noted in some melanoma patients have now been observed in several other malignancies, including renal cell carcinoma, lung cancer, and prostate cancer. These findings are very encouraging, however the specific mechanisms of response and reasons why only a subset of patients respond to therapy are not known. The extraordinary potential of immune therapies in cancer suggests that human-relevant mouse models of cancer are required to understand mechanisms of response and to optimize therapy so that a larger proportion of patients respond.
We have generated and evaluated a series of genetically engineered mouse models driven by alterations in Braf, Pten, Cdkn2a, beta catenin, p53, and Nras that reflect the genetic diversity of the vast majority of human melanoma. We have backcrossed 6 of these models to C57Bl/6, generated tumors, and isolated a series of over 20 congenic mouse melanoma cell lines. Several independent lines have been isolated for each melanoma genotype generated. Injection of these lines into C57Bl/6J mice results in reproducible tumor formation in the absence of co-injection of Matrigel. We are in the process of characterizing the tumor microenvironment in each of the models using flow cytometry and a novel quantitative imaging approach of histological sections, which produces flow cytometry-like data, but retains spatial and morphologic information that can be utilized to characterize much smaller tumors. This series of congenic lines represents an ideal set of models for the study of cancer immunology and responses to immune therapies.
Citation Format: Katrina M. Meeth, William E. Damsky, Marcus Bosenberg. A comprehensive system of congenic mouse melanoma models for evaluation of immune therapies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5141. doi:10.1158/1538-7445.AM2015-5141
Abstract 5148: NR5A2 is essential for pancreas development and affects pancreas carcinogenesis
Authors: Nissim Sahar , Weeks Olivia , Hedgepeth John , Wucherpfennig Julia , Wang Xiao-Xu , Kimmelman Alec , Goessling Wolfram 
Published: August 2015

Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers today. A genome-wide association study (GWAS) has implicated the nuclear receptor NR5A2 in modulating risk for pancreatic cancer. While a role for this gene in pancreatic cancer has not been previously recognized, it plays an important role in stem cell pluripotency and metabolism. Using the zebrafish model, we demonstrate that genetic or pharmacologic inhibition of nr5a2 activity results in absence of exocrine pancreas, while leaving endocrine pancreas unaffected, indicating an essential role in pancreas organ formation. Further, we localize nr5a2 expression to the endodermal bud that gives rise to the exocrine pancreas, consistent with a role for nr5a2 in regulating differentiation of pancreas progenitors. In resected human PDAC specimens and in vitro cell lines, we find that NR5A2 expression is altered compared to normal ductal epithelium. Moreover, shRNA knockdown of NR5A2 dramatically alters proliferation of PDAC cell lines, supporting the hypothesis that NR5A2 is involved in pancreatic carcinogenesis. These data support a model that NR5A2 regulates the proliferation and differentiation of exocrine pancreas progenitor cells during development. We postulate that loss-of-function of NR5A2 results in dysregulation of these processes in the adult pancreas by driving acinar cells to acquire properties of progenitor cells, and therefore is an important step in pancreas oncogenesis.
Note: This abstract was not presented at the meeting.
Citation Format: Sahar Nissim, Olivia Weeks, John Hedgepeth, Julia Wucherpfennig, Xiao-Xu Wang, Alec Kimmelman, Wolfram Goessling. NR5A2 is essential for pancreas development and affects pancreas carcinogenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5148. doi:10.1158/1538-7445.AM2015-5148
Abstract 5175: Preclinical monitoring of prostate cancer lesions in bone by intravital multiphoton microscopy
Authors: Dondossola Eleonora , Alexander Stephanie , Alexander Steve , Holzapfel Boris , Logothetis Christopher , Hutmacher Dietmar , Friedl Peter 
Published: August 2015

Abstract
Bone metastases are a major complication in patients with advanced prostate cancer (PCa) and frequent cause of therapy resistance. Besides cell intrinsic mechanisms, signals received from the bone microenvironment critically contribute to support PCa cell survival and growth. Recent advances in intravital microscopy enable to investigate this complex PCa cell-microenvironment interaction and allow preclinical examination of tumor responses to both conventional and targeted therapy.
We developed a window model amenable to intravital multiphoton microscopy (MPM) to longitudinally monitor PCa lesions in humanized neobone established in the dermis of the mouse. Tissue engineered bone constructs, TEBCs, were generated by functionalizing polymeric polycaprolactone scaffolds with human mesenchymal stem cells differentiated to osteoblasts, and characterized in vitro for cell distribution and calcium deposition. After in vivo implantation, TEBC maturation was monitored by μCT, MPM and histological analysis over time to generate a miniaturized-neobone with defined cortical thickness (50-60 μm) suitable for intravital imaging through a body window. PCa (PC3) lesions, after implantation into the bone cavity, were longitudinally monitored for growth and niche development, using multi-parameter recording of: collagen/bone matrix (SHG), bone surface (THG), blood vessels/stromal phagocytes (fluorescent dextran), and PC3 cells (nuclear H2BeGFP, cytoplasmatic DsRed2).
By combining innovative tissue engineering with optical windows, state-of-the-art fluorescence reporter technology and intravital MPM, this model will provide mechanistic and applied insight into the therapy response of bone metastasis.
Citation Format: Eleonora Dondossola, Stephanie Alexander, Steve Alexander, Boris Holzapfel, Christopher Logothetis, Dietmar Hutmacher, Peter Friedl. Preclinical monitoring of prostate cancer lesions in bone by intravital multiphoton microscopy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5175. doi:10.1158/1538-7445.AM2015-5175
Abstract 5176: Chemotherapy alters the natural history of metastatic progression
Authors: Aiello Nicole M. , Bajor David L. , Pham Minh N. , Vonderheide Robert H. , Stanger Ben Z. 
Published: August 2015

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a 5-year survival rate of less than 6%. Metastatic disease accounts for a majority of PDAC-related deaths, even for patients with no evidence of metastasis at the time of resection. In this study we sought to understand the natural history of metastatic colonization and the cellular mechanisms governing the metastatic cascade. Using an autochthonous PDAC mouse model combined with a lineage-labeling approach, we have tracked and characterized the various stages of metastatic progression, from single cells to macroscopic lesions. PDAC tumors primarily metastasize to the liver, where small lesions of 10 cells or less reside closest to portal veins and exhibit a high frequency of epithelial-mesenchymal transition (EMT). Larger metastatic lesions exhibit reduced EMT and are hypovascular, resembling primary PDAC tumors. Metastases gradually accumulate desmoplasia as they grow, which consists of myofibroblasts, leukocytes and extracellular matrix components including collagen, hyaluronic acid, fibronectin and SPARC. Treatment with gemcitabine and nab-paclitaxel reduces overall metastatic burden and shifts the size distribution of metastases toward small lesions of 10 cells or less. Single seeded cells in particular seem to be protected from chemotherapy-induced killing, while larger lesions that have accumulated a desmoplastic stroma are more susceptible. Our results demonstrate that chemotherapy has direct measurable effects on metastatic burden, which may explain the improved outcomes for PDAC patients who receive adjuvant chemotherapy.
Citation Format: Nicole M. Aiello, David L. Bajor, Minh N. Pham, Robert H. Vonderheide, Ben Z. Stanger. Chemotherapy alters the natural history of metastatic progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5176. doi:10.1158/1538-7445.AM2015-5176
Abstract 5184: Synaptonemal complex protein 3 is associated with lymphangiogenesis in non-small cell lung cancer
Authors: Kitano Haruhisa , Chung Joon-Yong , Hanaoka Jun , Inoue Shuhei , Yoshinori Doki , Fukuoka Junya , Hewitt Stephen M. 
Published: August 2015

Abstract
Lymphangiogenesis is a key component for tumor growth and metastasis in non-small cell lung cancer (NSCLC), and is a promising target in cancer therapy strategy. The axis of vascular endothelial growth factor-C (VEGF-C)/VEGF-D/VEGFR-3 is considered to be a major driver of lymphangiogenesis but the detailed mechanism of this process remains unclear. We recently showed that the expression of synaptonemal complex protein 3 (SCP3) is associated with poor prognosis and linked with lymph node metastasis in NSCLC. To investigate the possible lymphangiogenic significance of SCP3 in NSCLC, we assessed SCP3, VEGF-A, VEGF-B, VEGF-C, and VEGF-D expressions in archival tumor tissues from 89 NSCLC patients with lymph node metastasis by immunohistochemical staining. The positive staining of SCP3, VEGF-A, VEGF-B, VEGF-C and VEGF-D expressions were detected in 24 (27.0%), 22 (24.7%), 27 (30.3%), and 24 cases (27.0%), respectively. Notably, we have identified that the SCP3 expression is positively correlated with VEGF-C and VEGF-D (for both, p &lt; 0.001) whereas its expression is negatively correlated with VEGF-A and VEGF-B (p = 0.029 and p = 0.026, respectively). Furthermore, we have also detected the linkage between SCP3 and VEGF-C or VEGF-D expressions in human lung cancer cell lines. In multivariate analysis of patients with lymph node metastasis, SCP3 expression displayed the worse overall survival (HR = 1.86, p = 0.008). These data suggest that SCP3 is linked with lymphangiogenesis and provide insight into the SCP3-VEGF-C/VEGF-D axis based anti-lymphangiogenic therapy strategy.
Citation Format: Haruhisa Kitano, Joon-Yong Chung, Jun Hanaoka, Shuhei Inoue, Doki Yoshinori, Junya Fukuoka, Stephen M. Hewitt. Synaptonemal complex protein 3 is associated with lymphangiogenesis in non-small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5184. doi:10.1158/1538-7445.AM2015-5184
Abstract 5195: A novel, multimodal theranostic nanoprobe is effectively incorporated into melanoma brain metastatic cells
Authors: Aasen Synnøve N. , Eichler Tilo W. , Hruby Martin , Pospisilova Aneta , Stepanek Petr , Spriet Endy , Jirak Daniel , Skaftnesmo Kai Ove , Thorsen Frits 
Published: August 2015

Abstract
Metastatic cancer is a significant cause of death worldwide, despite continuing advances in research on diagnostics and therapy. To overcome unsuccessful drug delivery to the tumor tissue, several different nanoprobes have been designed, of which some have combined diagnostic and therapeutic properties. It is an advantage to use non-toxic, biodegradable materials in the design of nanoprobes, as such compounds are easily eliminated from the body. In this work we report for the first time the use of a recently developed nanoprobe to label melanoma metastatic cell lines, for multimodal imaging of cellular uptake and drug delivery. Our nanoprobe consisted of a backbone of glycogen, where the red fluorescent marker Dyo-615 for fluorescence microscopy and Gadolinium for MRI were incorporated.
Fluorescence microscopy showed effective labeling of human melanoma metastatic cells over 24 hours and cell viability was not affected by the labeling. The nanoprobe was found in the cytosol of the cells, and a gradual degradation of the probe inside the lysosomes could be observed. In vitro MRI relaxivity measurements showed significant reduction in T1 mapping times, compared to unlabeled cells. In vivo MRI studies showed that subcutaneous melanoma tumors in mice could be effectively visualized with T1 weighted MRI after intravenous injection of the nanoprobe, and the contrast enhancement was comparable to what was seen after using standard Omniscan contrast agent.
In summary, our biodegradable glycogen nanoprobe shows a high potential to be used further as a theranostic entity. The nanoprobe may offer additional advantages over MRI contrast agents, as tumor uptake of pharmaceuticals attached to the nanoprobe can be traced in real-time in vivo.
Citation Format: Synnøve N. Aasen, Tilo W. Eichler, Martin Hruby, Aneta Pospisilova, Petr Stepanek, Endy Spriet, Daniel Jirak, Kai Ove Skaftnesmo, Frits Thorsen. A novel, multimodal theranostic nanoprobe is effectively incorporated into melanoma brain metastatic cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5195. doi:10.1158/1538-7445.AM2015-5195