bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-042: High ITGB1 & RhoC expressions are indicators of recurrence in patients with primary colorectal cancer
Authors: Ha Ye Jin , Tak Ka Hee , Kim Chan Wook , Lee Jong Ryul , Cho Dong-Hyung , Kim Yong Sung , Kim Seon-Kyu , Kim Jin Cheon 
Published: August 2019

Abstract
Colorectal cancer (CRC) is the main cause of cancer mortality worldwide. Its poor prognosis is mainly ascribed to high recurrence rates. Identifying novel prognostic biomarkers and therapeutic key points for management is crucial and important. To develop prognostic biomarkers that can discriminate CRC patients with high risk of postoperative recurrence, we conducted RNA-seq analysis using primary cancer tissues from 130 CRC patients with (n=58) or without (n=72) systemic recurrence. Among differentially expressed genes between with or without recurrence, we identified eleven candidate genes (AK2, BID, CDC25A, EIF4A2, HSPB1, ITGB1, MAP4K4, MMP12, PTGES3, RHOC, TERF21P) (P &lt; 0.01). Then, the expression level of the best candidate gene was validated by quantitative real-time polymerase chain reaction (qRT-PCR) in the additional 79 CRC patients with (n=40) or without (n=39) systemic recurrence. Among these genes, qRT-PCR showed that AK2, EIF4A2, ITGB1 and RhoC were upregulated. To the relevance of their molecular function and biological process, Cell Counting Kit-8 assay, migration, invasion assay and gelatin zymograpy were performed after knockdown or overexpression of candidate genes in CRC cell lines. ITGB1 or RhoC stimulated colon cancer cell proliferation, promoted cell invasion and migration, whereas the opposite pattern was observed in ITGB1 or RhoC-overexpressing CRC cells. Western blotting experiments revealed that ITGB1 and RhoC overexpression downregulated E-cadherin and upregulated N-cadherin, Snail/Slug, Vimentin protein levels, whereas ITGB1 and RhoC knockdown had the opposite effects These results suggested that ITGB1 and RhoC promoted colon cancer cell proliferation, migration and invasion through EMT switch signaling pathway. Our results indicate that ITGB1 and RhoC may be biomarkers to predict recurrence and future therapeutic targets of CRC.
Citation Format: Ye Jin Ha, Ka Hee Tak, Chan Wook Kim, Jong Ryul Lee, Dong-Hyung Cho, Yong Sung Kim, Seon-Kyu Kim, Jin Cheon Kim. High ITGB1 & RhoC expressions are indicators of recurrence in patients with primary colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-042.
Abstract LB-059: Hyperglycemia enhances cancer immune evasion by inducing alternative macrophage polarization through increased O-GlcNAcylation
Authors: Mantuano Natalia Rodrigues , Stanczak Michal , Oliveira Isadora , Filardy Alessandra , Silva Ronan , Zippelius Alfred , Todeschini Adriane Regina , Laubli Heinz 
Published: August 2019

Abstract
Epidemiological studies have shown diabetes mellitus (DM) to significantly increase the risk for cancer and cancer progression. Hyperglycemia is the most important characteristic of DM and directly correlates with a poor prognosis in cancer patients. While enhanced availability of glucose can directly fuel tumor cell proliferation, the effect on the tumor immune microenvironment is less well known. Here, we demonstrate in vitro and in different murine tumor models that hyperglycemia induces an increased flux through the hexosamine biosynthetic pathway (HBP) in tumor-associated macrophages (TAMs) resulting in an upregulation of O-GlcNAcylation. Increased O-GlcNAcylation was associated with alternative M2 polarization of TAMs and reduced anti-tumor immunity. The effect of hyperglycemia on tumor growth was dependent on an intact adaptive immunity. Furthermore, inhibition of M2 polarization by the addition of anti-CSF1R antibodies abrogated the effect of hyperglycemia on tumor growth. Similarly, treatment of mice with inhibitors of the HBP or O-GlcNAcylation reduced M2 polarization of TAMs and reversed immune evasion of growing tumors. Finally, we find enhanced M2 polarization in chronically hyperglycemic patients with colorectal cancer compared to non-diabetic normoglycemic patients. Our findings provide a new and targetable mechanism of cancer immune evasion, advocating for strict control of hyperglycemia in cancer patients.
Citation Format: Natalia Rodrigues Mantuano, Michal Stanczak, Isadora Oliveira, Alessandra Filardy, Ronan Silva, Alfred Zippelius, Adriane Regina Todeschini, Heinz Laubli. Hyperglycemia enhances cancer immune evasion by inducing alternative macrophage polarization through increased O-GlcNAcylation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-059.
Abstract LB-067: Cargocytes: A novel cell therapy platform to drive anti-tumor immunity
Authors: Klemke Richard L. , Wang Huawei , Liu Bei , Alarcon Christina , Watson Felicia 
Published: August 2019

Abstract
Adoptive cell therapy has emerged as a powerful new tool to treat cancer and other diseases. However, the clinical utility of many cell-based therapies is limited by inadequate production of therapeutic factors, production of unwanted factors, unwanted engraftment into the tumor, and poor controllability resulting in poor pharmacokinetics. Genetic and bioengineering strategies can overcome many limitations, but modification of genomic DNA or the introduction of new genetic material into therapeutic cells raises substantial safety concerns, ultimately making FDA approval difficult. To address these limitations, we developed a novel platform for cell-based therapies in which any cell type, including immortalized cells, can be extensively engineered and loaded with therapeutic cargo, and then rendered safe for patient administration through removal of the nucleus. Enucleated cells (Cargocytes) retain many desired biologic functions (endogenous and engineered), such as viability up to 72 hours, retention of cell surface markers/proteins, secretion of bioactive molecules, robust in vitro and in vivo chemotaxis, and delivery of a wide range of cancer-fighting cargos. Using this technology, we demonstrate that Cargocytes derived from hTERT-immortalized mesenchymal stem cells (hTERT MSCs) and engineered to express therapeutic levels of IL-12 can potently activate an anti-tumor immune response in a preclinical mouse model of triple negative breast cancer. hTERT MSC-derived Cargocytes robustly delivered IL-12 to the tumor with definable pharmacokinetics, activated known IL-12 biomarkers, and induced infiltration of tumor-fighting immune cells that inhibited tumor growth and improved animal survival. In addition, co-administration of Cargocytes secreting IL-12 and anti-PD-L1 antibodies further improved animal survival without notable adverse events. Collectively, our findings indicate that Cargocytes provide a new means to deliver powerful immunomodulatory biologics to malignant tumors in a safe and controllable manner. The genetic tractability and excellent safety profile of the Cargoycte platform enables bioengineering of a wide range of designer therapeutics derived from genetically modified cells, immortalized stem cells, and even cancer cells, each with improved clinically relevant functions.
Citation Format: Richard L. Klemke, Huawei Wang, Bei Liu, Christina Alarcon, Felicia Watson. Cargocytes: A novel cell therapy platform to drive anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-067.
Abstract LB-068: Tomivosertib (eFT508), a potent and highly selective inhibitor of MNK1 and MNK2, enhances CAR T cell activity through modulating T cell differentiation
Authors: Goel Vikas K. , Sharma Rajesh K. , Staunton Jocelyn , Stumpf Craig R. , Young Nathan P. , Thompson Peggy A. , Chiang Gary G. , Webster Kevin R. 
Published: August 2019

Abstract
Chimeric antigen receptor (CAR) T cells have shown great promise in treating hematopoietic malignancies, such as leukemia and non-Hodgkin’s lymphoma. The efficacy and durability of CAR T cell therapy have been correlated with higher levels of T stem cell memory (TSCM) and T central memory (TCM) populations. Accordingly, various strategies to enrich these CAR T cell populations are of intense interest. It is well-established that the PI3K/mTOR pathway plays an important role in T cell activation and differentiation, and perturbations in this pathway can enhance T cell memory populations. Work from our group has demonstrated that MNK modifies mTOR signaling and T cell differentiation. Here, we demonstrate that the MNK1/2 inhibitor tomivosertib can substantially increase TCM and TSCM populations in both primary murine and human T cells. Tomivosertib treatment of murine OT-I T cells biases T cell differentiation towards a TCM (CD8+ CD44+ CD62L+) population upon SIINFEKL peptide stimulation in vitro without adverse effects on T cell proliferation, interferon-γ production or cytotoxic function. Similar effects are seen in vivo, where tomivosertib treatment also enriches the TCM cell pool in a SIINFEKL vaccine-induced OT-I adoptive T cell transfer model, which results in increased persistence as demonstrated by a higher memory-recall T cell response upon re-challenge. Furthermore, addition of tomivosertib during production of human CAR (anti-CD19 scFv-4-1BB-CD3ζ) T cells leads to a significantly increased population of TSCM (CD8+ CD45RO CD45RA+ CD27+ CD95+) cells. Based on these data, the combination of tomivosertib with CD19-directed CAR T cells was assessed in the CD19+ Pfeiffer DLBCL model in vivo. Daily oral administration of tomivosertib in combination with CD19-directed CAR T cells results in improved efficacy in comparison to either monotherapy alone, consistent with tomivosertib promoting and maintaining TSCM populations in vivo. Tomivosertib is currently in multiple Phase II clinical trials as a monotherapy or in combination with checkpoint inhibitors.
Citation Format: Vikas K. Goel, Rajesh K. Sharma, Jocelyn Staunton, Craig R. Stumpf, Nathan P. Young, Peggy A. Thompson, Gary G. Chiang, Kevin R. Webster. Tomivosertib (eFT508), a potent and highly selective inhibitor of MNK1 and MNK2, enhances CAR T cell activity through modulating T cell differentiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-068.
Abstract LB-099: Prostate cancer-secreted CCN3/NOV promotes osteoblast differentiation via Wnt signal pathway and miR-608 suppression
Authors: Chen Po-Chun , Chao Chia-Chia , Chang An-Chen , Tang Chih-Hsin 
Published: August 2019

Abstract
Objective: NOV/CCN3 is a secreted protein that interacts with the extracellular matrix and thereby regulates many cellular functions, including cell division, chemotaxis, apoptosis, adhesion, motility, and ion transport. Recently, CCN3 expression have been implicated in progression of various cancer, and our previous study indicates that CCN3 increases the migration and invasion of prostate cancer (PCa) cells by regulation of ICAM-1 expression. Our research group also review the pivotal role CCN3 in bone metastasis of PCa by modulating the tumor-bone microenvironment. Moreover, evidence has highlighted the pivotal role of osteoblasts in osteoblastic bone metastasis in PCa.
Material and Methods: MC3T3-E1 osteoblast cells were incubated with conditioned media collected from PCa cells. The cell proliferation and osteogenic differentiation were evaluated by MTT assay and Alizarin red S staining. The osteogenic markers were also examined by Western blot and QPCR. Furthermore, the Wnt activation was tested by Western blot and luciferase reporter assay. Pretreatment with chemical inhibitor of Wnt was used to determine the regulatory role of Wnt in osteogenic differentiation in response to PCa CM. Finally, expression of miR-608 was investigated by QPCR and mimic miR-608 was used to certify the role of miR-608 in osteogenic differentiation in response to PCa CM.
Results: Here, we show that PCa-secreted CCN3 increases expression of osteoblastic differentiation factors including BMPs, Runx2 and Osterix. Furthermore, this effect is regulated by Wnt signal pathway or miR-608 repression. The present study supposes that PCa-secreted CCN3 can promote osteoblastic bone metastasis in PCa by activating Wnt signal and inhibition of miR-608 expression. Our present study provides an opportunity to develop CCN3 as a therapeutic target that prevents bone metastasis in PCa.
Citation Format: Po-Chun Chen, Chia-Chia Chao, An-Chen Chang, Chih-Hsin Tang. Prostate cancer-secreted CCN3/NOV promotes osteoblast differentiation via Wnt signal pathway and miR-608 suppression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-099.
Abstract LB-133: Tumor-promoting activity of CCL8 in involution-associated breast cancer
Authors: Farmaki Eleni , Kaza Vimala , Chatzistamou Ioulia , Kiaris Hippokratis 
Published: August 2019

Abstract
Postpartum breast cancers that develop within 5 years after child birth have a poor prognosis because of increased risk of metastasis and remain a principal cause of mortality for young women. Therefore understanding the molecular physiology of postpartum breast cancers is imperative as it may provide novel therapeutic options. The increased risk for breast cancer immediately after pregnancy is linked to the extensive remodeling of the mammary gland that is designated as mammary involution. Immune cells such as macrophages and neutrophils, activated by a chemokine and cytokine cascade during involution, are actively involved in mammary gland remodeling and contribute to the disease development. Among the various chemokines activated in involution, the role of CCL8 in the development of postpartum breast cancer has not been addressed despite recent evidence demonstrating its role in metastatic disease. Our results show that CCL8 mRNA and protein levels increase in mammary gland during involution. Tumor growth studies involving CCL8-deficient animals that had been implanted with cancer cells prior to pregnancy or during involution indicated that CCL8 is tumor-promoting specifically following lactation, during involution. CCL8 is responsible for recruiting F4/80-positive macrophages to the mammary gland during the second phase of involution. Thus we asked if CCL8 promotes tumor development by recruiting macrophages in the involuting mammary gland. Our studies showed that CCL8 attracts primarily M2 type macrophages and that depletion of macrophages by liposomal clodronate abolished the tumor-promoting effect of CCL8 in the wt animals but did not affect CCL8KO animals, at which the M2 macrophages were already absent. These results illustrate the role of CCL8 in the development of postpartum breast cancer by recruiting M2 macrophages and suggest the potential value of targeting CCL8 for disease management.
Citation Format: Eleni Farmaki, Vimala Kaza, Ioulia Chatzistamou, Hippokratis Kiaris. Tumor-promoting activity of CCL8 in involution-associated breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-133.
Abstract LB-154: Differential predictive modeling to grasp disparities among sub-populations
Authors: Yoo Wonsuk 
Published: August 2019

Abstract
Background: Many of these practical applications typically produce huge data sets that contain several thousands of objects with hundreds (or even thousands) of features that describe each object. Automatic modeling, organizingand interpreting these large-scale data sets is increasingly part of various disciplines, such as health, medicine, and biology. The study aims to propose a new framework for constrained learning of predictive models where we enforce additional constraints for the models to be as similar as possible.
Methods: We develop a new task of differential predictive modeling to solve the problem of differences in the data distributions by developing a continuum of predictive models. To achieve this, we construct a new framework for constrained learning of predictive models where we enforce additional constraints for the models to be as similar as possible. The major distinction of our approach with the existing methods is that none of the existing methods explore the model distance based on building the similar tree concept. We compute the distance between two datasets from the structural information about the induced trees without referring back to the original data statistics or the model statistics. Our 29-state Medicaid dataset, which contains 100% of the claims for 90% of all African American and 90% of all Hispanic and Latino Medicaid enrollees in the entire U.S. geo-coded at the zip code and county levels.
Principal Findings: The goal of the disparities work is to capture the differences across different population groups and provide a better understanding that can explain these differences. Using this model, we could be able to measure the group difference in a particular minority group and compare these differences across the other subgroups. This is useful in ranking the groups where the disparity varies from the highest to the lowest. The novelty of our approach is that it captures the disparity of groups through a systematic comparison of multivariate models which cannot be done using any of the existing methods available in the machine learning methods.
Conclusions: This model has the potential to dictate more aggressive new therapeutic treatments for specific subsets of high-risk patients. This project proposes new research directions in exploratory tools needed by the domain experts analyzing their data. It will provide significant insights for data analysis that can be utilized in various domains of science. One of the ultimate goals of the proposed research is the development of a clinician-friendly software and web-based analysis tool to analyze the health disparity multivariate data using the prediction models.
Citation Format: Wonsuk Yoo. Differential predictive modeling to grasp disparities among sub-populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-154.
Abstract LB-158: Tribal sovereignty and approval for research in Native American communities
Authors: Goldtooth Carol , Teufel-Shone Nicolette , Gachupin Francine C. 
Published: August 2019

Abstract
Background: Native Americans (NAs) experience worse outcomes and lower chances of cancer survival than other racial groups in the US. Despite improvements in cancer screening techniques and major developments in cancer treatment in past decades, NA communities do not benefit equally from these advances. Furthermore, relatively little of the advancements in cancer research addresses the specific vulnerabilities and strengths in these communities. Community-based research with NA populations including cancer research is influenced by the ways tribes approach and approve research. Tribe specific approval processes are assertions of sovereignty and of tribal right to govern and manage activities on tribal lands. Researchers often interpret required tribal approval for research, presentation and publication as punitive and a barrier to timely research and dissemination.
Objective: An overview of the evolution and range of tribal research approval processes can address the cultural discordance faced by researchers and NA communities and supports researchers’ effort to gain approval to conduct much needed community-based cancer research.
Methods: This presentation outlines the diversity of tribal research processes, including established Tribal Institutional Review Boards (IRBs), Tribal Advisory boards, Tribal Council approval, and Indian Health Service (IHS) IRB approval. Guidance will be provided to inform the development of research study designs that meet the needs of the community and have the potential to guide cancer treatment practice and cancer prevention education. In addition, this review will demonstrate that respecting the distinct characteristics of separate tribes relative to experience with research and leadership oversight of research activities is important to obviate homogenization of NA communities and enhance the relevance of research.
Conclusion: Research design, implementation and interpretation are strengthened by tribal research approval processes by requiring researchers to justify their research methods, hypotheses and expected benefits to the community and NA populations. Concurrently, adhering to procedures, protocols and requirements established by tribal councils supports tribal sovereignty in action.
Citation Format: Carol Goldtooth, Nicolette Teufel-Shone, Francine C. Gachupin. Tribal sovereignty and approval for research in Native American communities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-158.
Abstract LB-175: Genome-wide scan of the effect of cis-eSNPs on gastric cancer in Chinese population
Authors: Ni Jing , Han Jing , Zhu Meng , Jin Guangfu , Hu Zhibin 
Published: August 2019

Abstract
Background: Previous genome-wide association studies (GWASs) have identified multiple single-nucleotide polymorphisms (SNPs) for gastric cancer risk. However, only a tiny fraction of heritability can be explained.
Methods: We performed a comprehensive analysis to evaluate the associations between cis-expression quantitative trait SNPs (eSNPs) and susceptibility to gastric cancer in two GWAS datasets, including 2,631 gastric cancer cases and 4,373 controls. Gene-based and pathway analysis were conducted by the sequence kernel association test (SKAT-C) and the adaptive rank truncated product (ARTP) method, respectively.
Results: A total of 314,518 eSNPs were remained after quality control, which mapped to 5,155 genes and 1,077 pathways. We identified six novel eQTL SNPs in unknown loci which can explain approximately 3.56% of the phenotypic variances combined with known GWAS related variants. Function analysis revealed that rs3129206 might affect the susceptibility of gastric cancer via regulating the expression of HSD17B8, while rs6930376 regulating the expression of PSORS1C3. Pathway-based analysis showed a total of seven potential pathways might account for the risk of gastric cancer (Pfdr&lt;0.1).
Conclusion: Our findings demonstrate an overview of the associations between eSNPs and gastric cancer risk in Chinese population, which provide insight into genes and pathways that may be biologically relevant for risk of gastric cancer.
Citation Format: Jing Ni, Jing Han, Meng Zhu, Guangfu Jin, Zhibin Hu. Genome-wide scan of the effect of cis-eSNPs on gastric cancer in Chinese population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-175.