bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A42: The role of M1 and M2 macrophage in the cycling phase of breast cancer
Authors: Walker Nykia D. , Elias Michael , Greco Steve , Rameshwar Pranela 
Published: May 2019

Abstract
Breast cancer malignancy is the second leading cause of death among women. The majority of deaths associated with cancer, from solid tumors are the result of metastasis and not from the primary tumor site Clinical evidence indicates that breast cancer (BC) cells (BCC) can exist in dormancy within the bone marrow (BM), for &gt;10 years. Methods by which BCCs adapt dormancy as well as reversed dormancy into metastatic cells are highly significant for the development of new and safe therapies. This research focuses on the BM because it is the preferred organ for dormant BCCs. Furthermore, in several cases, the BM has been identified as a source of BCCs during clinical resurgence. A subset of BCCs with tumor initiating property (cancer stem cells, CSCs) has been identified as those responsible for dormancy and chemoresistance. We will take advantage of our working hierarchy of BCCs to determine how M2 macrophage (MΦ) facilitates dormancy or clinical resurgence into metastatic cells. The mechanisms by which dormancy occurs followed by later resurgence into metastatic role for the BM microenvironment to facilitate CSC dormancy. CSCs can form gap junctional intercellular communication (GJIC) with stroma, by release of miRNA, which induces cycling quiescence. MΦ are classified into two subsets, either M1 or M2 type. M1 are mostly pro-inflammatory (classically activated to kill microorganisms and tumor cells), while M2 are non-inflammatory (alternatively activated to promote tissue repair). M2 MΦ is one cell type that comprises the stromal compartment inside the BM hematopoietic microenvironment. We studied how activated MSCs can influence M1 or M2 polarization. Our supporting studies indicate that M2 MΦ can arrest BCCs in G1/G0, while M1 MΦ can induce cell cycle progression. Activated MSCs transitioned M2 into M1 phenotype whereas inactivated MSCs maintains M2 MΦ phenotype. Here we present how the transitional changes in M2 to M1 MΦ affect the behavior of the CSCs within the BM stromal compartment.
Citation Format: Nykia D. Walker, Michael Elias, Steve Greco, Pranela Rameshwar. The role of M1 and M2 macrophage in the cycling phase of breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A42.
Abstract A44: Metastatic latency and immune evasion mediated by autocrine WNT inhibition
Authors: Malladi Srinivas , Macalinao Danilo G. , Jin Xin , He Lan , Massague Joan 
Published: May 2019

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR06) of the Conference Proceedings.
Citation Format: Srinivas Malladi, Danilo G. Macalinao, Xin Jin, Lan He, Joan Massague. Metastatic latency and immune evasion mediated by autocrine WNT inhibition. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A44.
Abstract A52: Dissection of cancer cells extravasation through human vascularized 3D microfluidic model: The major role of talin-1
Authors: Gilardi Mara , Bersini Simone , Kamm Roger Dale , Moretti Matteo , Vanoni Marco 
Published: May 2019

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR07) of the Conference Proceedings.
Citation Format: Mara Gilardi, Simone Bersini, Roger Dale Kamm, Matteo Moretti, Marco Vanoni. Dissection of cancer cells extravasation through human vascularized 3D microfluidic model: The major role of talin-1. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A52.
Abstract A54: Intravital microscopy of prostate cancer lesions in bone: Kinetics of osteolysis and therapy response
Authors: Dondossola Eleonora , Alexander Stephanie , Alexander Steve , Holzapfel Boris , Logothetis Christopher , Hutmacher Dietmar , Friedl Peter 
Published: May 2019

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR04) of the Conference Proceedings.
Citation Format: Eleonora Dondossola, Stephanie Alexander, Steve Alexander, Boris Holzapfel, Christopher Logothetis, Dietmar Hutmacher, Peter Friedl. Intravital microscopy of prostate cancer lesions in bone: Kinetics of osteolysis and therapy response. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A54.
Abstract A56: Identification of an ErbB2+ early disseminating cancer cell subpopulation with metastatic potential
Authors: Harper Kathryn , Sosa Maria Soledad , Hosseini Hedayatollah , Valderas Alvaro Avivar , Nagi Chandandaneep , Davis Roger , Klein Christoph , Entenberg David , Condeelis John , Farias Eduardo , Aguirre-Ghiso Julio 
Published: May 2019

Abstract
Recent clinical evidence suggests that cells are capable of disseminating from pre-invasive breast cancer lesions. It has been proposed that these early disseminating cancer cells (eDCCs) lodge into secondary sites, enter a state of dormancy, escape conventional therapy, and potentially evolve through different pathways from the primary tumor to form metastases. However, the mechanisms that endow these early cancer cells to disseminate and their behavior in target organs remain unknown. Here we show that ErbB2+ early cancer cells, while non-tumorigenic are highly efficient in disseminating. While a majority of these eDCCs remain dormant in target organs they are still endowed with a metastatic capacity. We identified an ErbB2HIGH/p38LOW/E-cadherinLOW/PRHI population of early cancer cells, which undergo a Wnt-dependent EMT and disseminate. Based on this signature we propose that these early cancer cells tap into motility programs similar to what is seen during branching morphogenesis (PRHI/WntHI/p38LOW) in order to disseminate. Using intra-vital imaging of transgenic ErbB2-T-CFP pre-malignant lesions we imaged this process at high resolution revealing that ErbB2HIGH/p38LOW/E-cadherinLOW cells display activate cancer cell motility, invadopodia formation and intravasation capacity. This correlated with CK8/18+/HER2+ circulating cancer cells as well as eDCCs in the lung and bone marrow of mice, a process that was enhanced following 2 weeks of systemic p38α/β inhibition. We conclude that during stages previously considered non-invasive, some HER2+ cancer cells can aberrantly activate an invasive morphogenetic program causing early dissemination that is normally restricted by active p38 signaling. These eDCCs carry latent metastatic initiating capacity and may contribute to relapse, altering our understanding of metastasis onset and how it might be targeted effectively.
Citation Format: Kathryn Harper, Maria Soledad Sosa, Hedayatollah Hosseini, Alvaro Avivar Valderas, Chandandaneep Nagi, Roger Davis, Christoph Klein, David Entenberg, John Condeelis, Eduardo Farias, Julio Aguirre-Ghiso. Identification of an ErbB2+ early disseminating cancer cell subpopulation with metastatic potential. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A56.
Abstract A64: Development of a cloud-based histology database for collaborative cancer research
Authors: Cheng Ke 
Published: May 2019

Abstract
Background: Cancer research is highly dependent on histopathology analysis for diagnosis, prognosis, and treatment. However, the majority of valuable histology data is stored in private archives on glass slides and local hard drives, and not shared like bioinformatics data. Lack of centrally-located data leads to repetitive, redundant research and makes it difficult for cancer researchers to work collaboratively by limiting widespread access and image sharing. Development of a virtual slide database on a scalable IT infrastructure will improve cancer histology data viewing and searching resulting in enhanced global scientific collaboration, allowing cancer to be fought cooperatively instead of individually.
Design: The main repository for WizBase is a relational database powered by Amazon Web Services with online viewing, collaboration and long-term archiving of WSIs. We will also create ontology parameters and tagging approach using 3 types metadata: Type I, classification parameters, specimen information and experimental details captured at order submission; Type II, ontology terms and annotation added upon visualization of the slide by HistoWiz and slide owners; and Type III, crowd-sourced tags and collaborative comments not requiring formality or standardization.
Results: We have developed a robust IT infrastructure allowing for viewing, tagging and searching of histology images. HistoWiz viewer is the first Cloud based viewer that allows users to instantly view their histology slides on any mobile device without the need to download any files, software or plugins. Furthermore, we have establish ontology parameters (such as metastasis, necrosis, neovascularization) for the classification and tagging of digital pathology cancer images, and slide metadata are captured during online order submission. Finally, through defined field and free text tagging of the slide metadata, users can search for slides meeting specific criteria. Searches based on similarity to a particular subject slide metadata allows ranking slide relevancy. The crowdsourced database currently has &gt;10,000 histology slides and is growing at a rate of 300% per year.
Conclusion: WizBaseTM is the first centralized Cloudbased WSI database for cancer histopathology with an image tagging web application to facilitate histology-driven data mining. WizBaseTM can be regarded as the scientific hybrid of a microscopy product with the viewing power of Google Earth combined with the search and crowdsourcing of Flickr.
Citation Format: Ke Cheng. Development of a cloud-based histology database for collaborative cancer research. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A64.
Abstract B03: Formation of lymph node metastases is not angiogenesis dependent
Authors: Jones Dennis , Jeong Han-Sin , Liao Shan , Wattson Daniel A. , Cui Cheryl H. , Duda Dan G. , Willett Christopher G. , Jain Rakesh K. , Padera Timothy P. 
Published: May 2019

Abstract
Background: To date, antiangiogenic therapy has failed to improve overall survival in cancer patients when used in the adjuvant setting (local-regional disease with no detectable systemic metastasis). The presence of lymph node metastases worsens prognosis, however their reliance on angiogenesis for growth has not been reported.
Methods: Here, we introduce a novel chronic lymph node window (CLNW) model to facilitate new discoveries in the growth and spread of lymph node metastases. We use the CLNW in multiple models of spontaneous lymphatic metastases in mice to study the vasculature of metastatic lymph nodes. We further test our results in patient samples. Finally, we test the ability of antiangiogenic therapy to inhibit metastatic growth in the CLNW.
Results: We reveal the surprising lack of sprouting angiogenesis during metastatic growth, despite the presence of hypoxia in some lesions. Treatment with two different antiangiogenic therapies showed no effect on the growth or vascular density of lymph node metastases. We confirmed these findings in clinical specimens, including the lack of reduction in blood vessel density in lymph node metastases in patients treated with bevacizumab.
Conclusion: We provide pre-clinical and clinical evidence that sprouting angiogenesis does not occur during the growth of lymph node metastases, and thus reveal a new mechanism of treatment resistance to antiangiogenic therapy in adjuvant settings. The targets of clinically approved angiogenesis inhibitors are not active during early cancer progression in the lymph node, suggesting that inhibitors of sprouting angiogenesis as a class will not be effective in treating lymph node metastases.
Citation Format: Dennis Jones, Han-Sin Jeong, Shan Liao, Daniel A. Wattson, Cheryl H. Cui, Dan G. Duda, Christopher G. Willett, Rakesh K. Jain, Timothy P. Padera. Formation of lymph node metastases is not angiogenesis dependent. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B03.
Abstract B08: Keap1–Nrf2 interaction suppresses cell motility in lung adenocarcinomas by targeting the S100P protein
Authors: Hua Kuo-Tai , Kuo Min-Liang 
Published: May 2019

Abstract
Purpose: Kelch-like ECH-associated protein 1 (Keap1) is an E3 ligase participated in the cellular defense response against oxidative stress through nuclear factor erythroid-2–related factor 2 (Nrf2). However, the role of Keap1 in regulating cancer motility is still controversial. We investigated the contribution of the Keap1–Nrf2 axis in the progression of non-small cell lung cancer (NSCLC).
Experimental Design: The expression of Keap1 and Nrf2 was examined via immunohistochemistry, real-time PCR, and Western blot analysis in a cohort of NSCLC tissues and cells. A series of in vivo and in vitro assays was performed to elucidate the contribution of the Keap1–Nrf2 axis in lung cancer mobility and progression.
Results: Keap1 expression was decreased in specimens from NSCLC patients with lymph node metastasis compared with patients without metastasis. Higher Keap1 expression levels were correlated with the survival ofNSCLC patients. Moreover,manipulation of Keap1 expression affected cell migration/invasion abilities. Depletion of Nrf2 relieved the migration promotion imposed by Keap1 suppression. Mechanistic investigations found that S100Pwas downregulated in both Keap1-overexpressing and Nrf2-knockdown NSCLC cells. Overexpression of Keap1 and knockdown of Nrf2 both suppressed S100P expression in NSCLC cells. Knockdown of S100P inhibited cell migration in highly invasive NSCLC cells and also relieved the migration promotion imposed by Keap1 suppression in weakly invasive NSCLC cells.
Conclusions: Our findings suggest that Keap1 functions as a suppressor of tumor metastasis by targeting the Nrf2/S100P pathway in NSCLC cells. In addition, overexpression of Keap1 may be a novel NSCLC treatment strategy and/or useful biomarker for predicting NSCLC progression.
Citation Format: Kuo-Tai Hua, Min-Liang Kuo. Keap1–Nrf2 interaction suppresses cell motility in lung adenocarcinomas by targeting the S100P protein. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B08.
Abstract B10: Transcriptome analysis of mouse PDA subtypes
Authors: Balli David , Aiello Nicole , Norgard Robert , Li Jingyang , Sahmoud Amine , Stanger Ben 
Published: May 2019

Abstract
Patients with Pancreatic Adenocarcinoma (PDA) often present with advanced stage disease including widespread metastasis and have dismal 5-year survival rates. The molecular mechanism promoting PDA progression and metastasis remain poorly understood. We have previously demonstrated that tumor cells undergo Epithelial-to-Mesenchymal Transition (EMT) in mouse models of PDA [Rhim et al., 2012]. EMT is a developmental process where cells loss epithelial characteristics and transdifferentiate into a mesenchymal-like state that is highly associated with increased invasion and metastasis. To better understand molecular mechanisms of PDA development and metastatic disease, we subjected tumors cells from a lineage labeled mouse model of PDA to RNA sequencing to identify global transcriptional changes. Interestingly, we discovered that there are at least two distinct subtypes of PDA based on transcriptome profiling. Comparison of gene expression profiles from mouse PDA subtypes to established subtypes from human PDA datasets [Collisson et al., 2011] revealed that mouse PDA is transcriptionally similar to the human disease. Differences in transcriptional profiling between PDA subtypes may dictate response to chemotherapeutics and metastatic competency.
Citation Format: David Balli, Nicole Aiello, Robert Norgard, Jingyang Li, Amine Sahmoud, Ben Stanger. Transcriptome analysis of mouse PDA subtypes. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B10.
Abstract B12: Polymorphisms in the Arntl2 promoter affect metastatic susceptibility in breast cancer
Authors: Ha Ngoc-Han , Hunter Kent W. 
Published: May 2019

Abstract
Metastasis accounts for the majority of cancer-related deaths. Although exact mechanisms are unknown, studies in our laboratory have demonstrated that germline polymorphisms could alter tumorigenesis and metastasis. Our lab developed a mouse genetics approach to investigate the effect of inherited single nucleotide polymorphisms (SNPs) on metastasis by crossing inbred mice of various backgrounds and subsequent mapping of quantitative trait loci (QTL) responsible for the phenotype. Using this approach, we crossed a highly metastatic (FVB) and low metastatic (MOLF) mouse strain and identified Arntl2, a circadian rhythm transcription factor, as a gene with differential expression that predicted distant metastasis-free survival in breast cancer patients. shRNA-mediated reduction in Arntl2 expression suppressed lung metastases, establishing Arntl2 as a metastasis modifier. Initial analysis revealed no polymorphisms in coding regions that could account for the differential expression in FVB and MOLF. Therefore, we performed whole genome sequencing of MOLF to identify SNP differences between MOLF and FVB. Overlapping this analysis with DNAse hypersensitivity sites in mouse mammary tumor cell lines revealed 13 polymorphisms in the predicted promoter region of Arntl2. FVB and MOLF promoters exhibited differential promoter activity in vitro, suggesting that these SNPs could explain the difference in Arntl2 expression between these two strains. In order to validate the causative role of the SNPs in vivo, metastatic cell lines were engineered using CRISPR technology to specifically replace the FVB with the MOLF promoter. Substitution of this promoter reduced Arntl2 transcript levels and subsequently decreased pulmonary metastases, as expected. Since Arntl2 is a transcription factor, current studies are focused on identifying Arntl2-regulated genes to investigate the pathways that are involved in modulating metastasis. This study will have important implications regarding the function of circadian rhythm in cancer progression and provide a potential molecular mechanism to explain the increased risk of breast cancers in nightshift workers. Furthermore, to the best of our knowledge this would be the first example of genome editing to validate polymorphisms in transcriptional control elements associated with inherited susceptibility for metastasis.
Citation Format: Ngoc-Han Ha, Kent W. Hunter. Polymorphisms in the Arntl2 promoter affect metastatic susceptibility in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B12.
Abstract B15: RSK2 signals through stathmin to promote microtubule dynamics and tumor metastasis
Authors: Alesi Gina , Jin Lingtao , Li Dan , Magliocca Kelly , Kang Yibin , Chen Zhuo G. , Shin Dong M. , Khuri Fadlo R. , Kang Sumin 
Published: May 2019

Abstract
Metastasis is responsible for over 90% of cancer related deaths. Complex signaling in cancer cells orchestrates the progression from a primary to a metastatic cancer. However, the mechanisms of these cellular changes remain elusive. We previously demonstrated that p90 ribosomal S6 kinase 2 (RSK2) promotes tumor metastasis. Here, we investigated the role of RSK2 in the regulation of microtubule dynamics and its potential implication in cancer cell invasion and tumor metastasis. Stable knockdown of RSK2 disrupted microtubule stability and decreased phosphorylation of stathmin, a microtubule destabilizing protein, at serine 16 in metastatic human cancer cells. We found that RSK2 directly binds and phosphorylates stathmin at the leading edge of cancer cells. Phosphorylation of stathmin by RSK2 reduced stathmin-mediated microtubule depolymerization. Moreover, overexpression of phospho-mimetic mutant stathmin S16D significantly rescued the decreased invasive and metastatic potential mediated by RSK2 knockdown in vitro and in vivo. Furthermore, stathmin phosphorylation positively correlated with RSK2 expression and metastatic cancer progression in primary patient tumor samples. Our finding demonstrates that RSK2 directly phosphorylates stathmin and regulates microtubule polymerization to provide a pro-invasive and pro-metastatic advantage to cancer cells. Therefore, the RSK2-stathmin pathway represents a promising therapeutic target and a prognostic marker for metastatic human cancers.
Citation Format: Gina Alesi, Lingtao Jin, Dan Li, Kelly Magliocca, Yibin Kang, Zhuo G. Chen, Dong M. Shin, Fadlo R. Khuri, Sumin Kang. RSK2 signals through stathmin to promote microtubule dynamics and tumor metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B15.
Abstract B23: Elucidating metastatic signaling networks in TNBC by investigating RKIP-regulated kinome
Authors: Yesilkanal Ali E. , Frankenberger Casey , Rabe Daniel C. , Johnson Gary L. , Rosner Marsha R. 
Published: May 2019

Abstract
Metastatic progression of tumors is the major cause of death in patients with triple negative breast cancer (TNBC), the most aggressive subtype of breast cancer. However, since metastasis is a multi-step process, unraveling its complexity is a major challenge. One effective way of tackling this question is to study natural blockers of the metastatic process, metastasis suppressors, and identify the mechanisms by which they regulate metastasis. Raf kinase inhibitory protein (RKIP), a protein that regulates kinase activity, is a suppressor of TNBC metastasis. Although RKIP inhibits the activity of key kinases such as Raf-1, GRK2, NIK/IKK in cultured cells, the kinase targets of RKIP in tumors are not known. To address this question, we used a mass spectrometry approach involving inhibitor-conjugated beads to identify kinases that are down-regulated by RKIP in human TNBC xenograft tumors. Our results identified novel targets of RKIP whose kinase activity is either down-regulated or up-regulated by RKIP. We used bioinformatics analysis to build RKIP-regulated signaling networks based upon RKIP-induced changes in kinase activity and related gene expression. Elucidating RKIP function at a systems level reveals the interplay between key metastatic signaling cascades, particularly in relation to cell migration and invasion, and can potentially identify novel anti-metastatic target combinations in TNBCs.
Citation Format: Ali E. Yesilkanal, Casey Frankenberger, Daniel C. Rabe, Gary L. Johnson, Marsha R. Rosner. Elucidating metastatic signaling networks in TNBC by investigating RKIP-regulated kinome. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B23.