bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1964: Identification of a novel molecule target for the detection, prediction, and treatment of peritoneal metastasis of gastric cancer
Authors: Kanda Mitsuro , Tanaka Haruyoshi , Shimizu Dai , Kobayashi Daisuke , Tanaka Chie , Takami Hideki , Hayashi Masamichi , Iwata Naoki , Niwa Yukiko , Yamada Suguru , Fujii Tsutomu , Nakayama Goro , Sugimoto Hiroyuki , Koike Masahiko , Fujiwara Michitaka , Kodera Yasuhiro 
Published: July 2017

Abstract
Background: Advanced gastric cancer (GC) frequently recurs because of undetected micrometastases even when disease is localized and patients undergo curative resection. Moreover, peritoneal metastasis is fatal. We aimed to develop novel diagnostic and therapeutic targets specific for peritoneal metastasis of GC to improve management.
Methods: We conducted a metastatic pathway-specific transcriptome analysis to identify candidate biomarkers comprising 340 patients allocated to discovery and validation sets (1:2) to evaluate the diagnostic and predictive value. The mRNA and protein levels in primary GC tissues were compared with patients’ clinical characteristics and survival. The effects of siRNA-mediated knockdown on phenotype and fluorouracil sensitivity of GC cells were evaluated in vitro, and the therapeutic effects of siRNAs were evaluated using a mouse xenograft model.
Results: Synaptotagmin VIII (SYT8) was identified as a candidate biomarker specific to peritoneal metastasis. SYT8 levels were elevated in the validation set comprising patients with peritoneal recurrence or metastasis. High SYT8 levels were significantly and specifically associated with peritoneal metastasis, and served as an independent prognostic marker for peritoneal recurrence-free survival of patients with stage II/III GC. The survival difference between high and low SYT8 levels was associated with patients who received adjuvant chemotherapy. Inhibition of SYT8 expression by GC cells correlated with decreased invasion, migration, and fluorouracil resistance. Intraperitoneal administration of SYT8-siRNA inhibited the growth of peritoneal nodules and prolonged survival of mice engrafted with GC cells.
Conclusions: SYT8 expression represents a promising diagnostic and predictive biomarker for peritoneal metastasis of GC.
Citation Format: Mitsuro Kanda, Haruyoshi Tanaka, Dai Shimizu, Daisuke Kobayashi, Chie Tanaka, Hideki Takami, Masamichi Hayashi, Naoki Iwata, Yukiko Niwa, Suguru Yamada, Tsutomu Fujii, Goro Nakayama, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera. Identification of a novel molecule target for the detection, prediction, and treatment of peritoneal metastasis of gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1964. doi:10.1158/1538-7445.AM2017-1964
Abstract 1965: A novel biocompatible fluorescent nanoparticle enables enhanced live cell tagging and tracking of cancer cells
Authors: Asbrock Nick , Chu Vi , Su Kevin , Tang Ben Zhong , Liu Bin 
Published: July 2017

Abstract
Metastasis is the leading cause of cancer mortality. Metastasis is a multi-step process which includes local tumor cell invasion, cell migration into the vasculature, exit of cells from the circulation and colonization at the distal tissue sites. Long-term noninvasive cell tracking by fluorescent probes is of great importance to life science and biomedical engineering. Current methods used to fluorescently tag cancer cells have been limited by short signal duration, high background auto-fluorescence or lengthy cell line generation using GFP. We have developed a biocompatible fluorescent nanoparticle which relies on Aggregation Induced Emission (AIE) technology that are highly resistant to fluorescent signal quenching. These particles enable highly efficient live cell fluorescent tagging while retaining fluorescent signal for up to 10 days in vitro and 21 days in vivo. These nanoparticles will open new avenues in the development of fluorescent probes for following biological processes such as carcinogenesis.
Citation Format: Nick Asbrock, Vi Chu, Kevin Su, Ben Zhong Tang, Bin Liu. A novel biocompatible fluorescent nanoparticle enables enhanced live cell tagging and tracking of cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1965. doi:10.1158/1538-7445.AM2017-1965
Abstract 1968: A novel mechanism of metastasis: Extracellular ATP promotes invasion and metastasis independent of purinergic receptor signaling
Authors: Cao Yanyang , Wang Xuan , Chen Xiaozhuo 
Published: July 2017

Abstract
Cancer is one of the top deadliest diseases in the US and worldwide. Metastasis, the dissemination of cancer cells from the primary tumors to distant organs, is responsible for 90% of solid tumor-related deaths. Tumor invasion and metastasis is a multistep process in which loss of cell-cell adhesion, increased proteolysis, and cell motility has been shown to be critical steps. Extracellular ATP is potentially a very important factor involved in tumor invasion and metastasis because both cell detachment and migration require energy, which is known to be mainly provided by ATP. Recent studies have indicated that the extracellular microenvironment of tumors contains much higher concentrations of ATP than normal tissues of the same cell origins. Our recent studies demonstrated that extracellular ATP is taken up by cancer cells through macropinocytosis and other endocytosis and promotes cancer cell growth, survival, and drug resistance (1-3). Based on all these, we hypothesized that extracellular ATP (eATP) plays critical roles in the regulation of tumor cell detachment, motility, invasion and tumor metastasis initiation. It was previously shown that ATP-induced purinergic receptor (PR) signaling is involved in metastasis. Our hypothesis is different in that eATP also mediates invasion and metastasis independent of PR signaling. Various bioassays were used in human non-small cell lung cancer (NSCLC) A549 cells to test our hypothesis. Our results show that eATP treatment led to a substantially increased number of floating cancer cells, and these cells were viable and formed clones in a clonogenic assay. This indicates that eATP induces cancer cell detachment. Moreover, treatment of eATP also induces cell migration in cell wounding and Transwell migration assays. In vitro invasion assay showed that eATP induced a dose-and time-dependent increase in the invasive capacities of the A549 cells. Western blot analysis indicates that eATP treatment reduced the expression of cell-cell adhesion molecule E-cadherin. PR inhibitors only slightly attenuated these effects. All these suggest novel ATP mechanisms independent of the PR signaling that are unreported before and imply novel targets for inhibiting/preventing metastasis.
References
1. Qian et al. Cancer Letters 351; 242-251 (2014).
2. Chen, Qian, and Wu. Free Radical Biol Med 79; 253-263 (2015)
3. Qian et al. Mol Cancer Res 14(11); 1087-1096 (2016)
Citation Format: Yanyang Cao, Xuan Wang, Xiaozhuo Chen. A novel mechanism of metastasis: Extracellular ATP promotes invasion and metastasis independent of purinergic receptor signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1968. doi:10.1158/1538-7445.AM2017-1968
Abstract 1976: Dried blood imaging and immunoassay: Spot formation, particle migration, and tumor cell detection
Authors: Shen Quanxu , Hong Bin 
Published: July 2017

Abstract
Blood droplet, when dried, forms a structured sedimentation pattern with central flat, corona ring and peripheral rim. This pattern can be fine-tuned with the blood formula. Surfactant is critical to promote the gelation process, eliminate the film cracking and delamination, and hence, suppress the coffee-ring effect. Additionally, surfactant restrains the shrinkage of the dried film. Without surfactant, the contraction was 100~150µm for 20µL of blood; decreased with surfactant added; fully stopped at 10% of concentration. Drying at room temperature with surfactant formed a flat disc-shaped deposit, while at 37°C, volcanic protuberance was developed. The size of the protuberance depended on the concentration of the surfactant primarily, and the anticoagulant type, evaporation velocity, and blood volume. To monitor the dynamic desiccation process, video recording of the evaporating drop was employed. It revealed a quick dislocation of the leukocyte-resembling beads to the outer region of the blood spot, reportedly at velocity of 10µm/sec. The use of 1 and 10µm sized beads further demonstrated layered convective flow below the surface. Beads migrated outward primarily before gelation, inward slightly during solidification, and ultimately settled down across the spot. The movement of beads was found in the range of a few hundred microns to millimeters before and after desiccation for a 50µL drop. Notably, plasma proteins and saline have influenced the bead distribution more than the surfactant. After plasma removal and mixing with surfactant, the majority of beads were dragged to the periphery, compared with many beads for no plasma and surfactant, some for whole blood with surfactant, and none for whole blood without surfactant. For a thick blood film, detection of embedded cells and beads can be difficult. Experiments showed that beam of longer wavelength, 532nm, was capable of visualizing all fluorescent cells and beads. Dried blood spot (DBS) assay has been widely used for newborn metabolic testing and DNA analysis. To detect rare tumor cells in DBS, the dried pattern was optimized to eliminate the artifacts, stabilize the cells, and enrich the targeted cell. DBS assay holds greater potential for cancer detection when the medical resource is limited.
Note: This abstract was not presented at the meeting.
Citation Format: Quanxu Shen, Bin Hong. Dried blood imaging and immunoassay: Spot formation, particle migration, and tumor cell detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1976. doi:10.1158/1538-7445.AM2017-1976
Abstract 1982: β-arrestin 2 mediates tumor growth and metastasis in renal cell carcinoma cells
Authors: Masannat Jude , Zhang Yushan , Purayil Hamsa , Mahmud Iqbal , Daaka Yehia 
Published: July 2017

Abstract
Renal Cell Carcinoma (RCC) is one of the most lethal urological cancers worldwide, with incidence and mortality rates increasing in the past two decades. The disease does not present early clinical symptoms and is commonly diagnosed at the metastatic stage, leaving the 5-year survival rate at ≈ 10-20%. For a wide array of neoplasms, many key molecular determinants involved in mediating the process of tumor cell growth, invasion, and colonization at a secondary site (i.e. metastasis) have been reported. However, few molecular predictors have been identified for RCC, rendering the mechanism(s) underlying RCC metastases poorly understood. This results in the lack of effective treatment for patients with advanced RCC.
G protein-coupled receptors (GPCRs) and their effectors, such as the arrestin proteins, have been implicated in tumor growth, metastasis, and angiogenesis. Arrestin proteins are well known for their function in the desensitization and trafficking of GPCRs, but have also been implicated in unique signaling pathways to regulate fundamental cellular functions, including cell cycle progression, cell migration, and survival. Furthermore, arrestin involvement has been identified in a number of breast, colorectal, lung, and hematological malignancies. However, the role of arrestin proteins in RCC is yet to be determined. Our preliminary data show that β-arrestin 2 (βarr2) protein levels correlate with growth and metastatic potential in several RCC cell lines, including ACHN and SN12C. We hypothesize that βarr2 regulates RCC tumor progression, specifically through involvement in proliferation, invasion, and metastatic processes. To test our hypothesis, we used genetic-based loss of function approaches such as interfering RNA and CRISPR/Cas9. βarr2 knockdown results indicated a role in RCC malignancy as it significantly reduces the migration and invasion of RCC cell lines in vitro. βarr2 knockout (KO) impaired 3D spheroid formation of these cells and induced morphological changes compared to control cells as observed under confocal microscopy imaging. Moreover, epithelial marker E-cadherin expression levels were elevated while mesenchymal markers twist1, twist2 and vimentin levels were decreased in the βarr2 KO cells compared to control, indicating a mesenchymal to epithelial transition. In vivo data support our hypothesis that βarr2 plays a critical role in tumor growth and metastasis. Our data suggests a role for βarr2 in RCC malignancy and present a possible target in development of therapies for patients with advanced RCC.
Citation Format: Jude Masannat, Yushan Zhang, Hamsa Purayil, Iqbal Mahmud, Yehia Daaka. β-arrestin 2 mediates tumor growth and metastasis in renal cell carcinoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1982. doi:10.1158/1538-7445.AM2017-1982
Abstract 1987: Inhibition of collagen receptor discoidin domain receptor-1 (DDR1) reduces gastric cancer cell motility and metastasis
Authors: Yuge Ryo , Kitadai Yasuhiko , Takigawa Hidehiko , Tanaka Shinji , Chayama Kazuaki , Yasui Wataru 
Published: July 2017

Abstract
Accumulating evidences suggest that a unique set of receptor tyrosine kinases, known as discoidin domain receptors (DDRs), play a role in cancer progression by interaction with their surrounding collagen matrix. Although abnormal expression of DDRs is reported in some human cancers, little is known about the expression and function of DDRs in gastric cancer progression. In this study, we investigated expression and the role of DDR1 in the tumor progression of human gastric cancer. The expression and distribution of DDR1 was analyzed by immunohistochemistry in 127 human gastric cancer cases, and the expression level of DDR1 in 7 human gastric cancer cell lines was analyzed by RT-PCR and western blotting. Proliferation, migration, invasion, and tube formation assays were conducted in DDR1 silenced gastric cancer cells. The effect of DDR1 on the tumor growth and metastasis were examined in orthotopically implanted nude mice model and a model of liver metastasis. DDR1 was expressed in human gastric cancer cell lines, and expression of DDR1 in human gastric tumor was associated with poor prognosis. Among 7 gastric cancer cell lines, MKN74 expressed DDR1 at highest level. DDR1-silenced MKN74 cells showed unaltered proliferation activity. In contrast, migration, invasion, and tube formation were significantly reduced. When examined in an orthotopic nude mouse model, DDR1-silenced implanted tumor significantly decreased angiogenesis and lymphangiogensesis, thereby leading to reduction of lymph node metastasis and liver metastasis. We showed that treatment of DDR1 inhibitor also inhibited lymph node metastasis in an orthotopic nude mouse model These results suggest that DDR1 is involved in GC tumor progression and metastasis. DDR1 could be not only an independent prognostic classifier, but also a promising therapeutic target in patients with GC.
Citation Format: Ryo Yuge, Yasuhiko Kitadai, Hidehiko Takigawa, Shinji Tanaka, Kazuaki Chayama, Wataru Yasui. Inhibition of collagen receptor discoidin domain receptor-1 (DDR1) reduces gastric cancer cell motility and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1987. doi:10.1158/1538-7445.AM2017-1987
Abstract 1999: Cofactor Paragon: a novel tool to analyze the tumor microenvironment using RNAseq
Authors: Bloom Ryan , Talwar Raman , Hiken Jeff , Armstrong Jon 
Published: July 2017

Abstract
The impact of cancer immunotherapy on clinical cancer care is growing rapidly. However, there are several mechanisms by which a tumor can avoid recognition and/or elimination by the immune system. Immune recognition, activation, and infiltration are each required for effective clearance of a tumor by the immune system. Impairment of any one of these mechanisms requires a different therapeutic strategy or combination of strategies to significantly address. The development of new multi-modal biomarker technologies that have the ability to provide insight into each of these factors in a cost-effective manner is essential to effectively guide treatment choice for patients and to discover new therapeutic targets.
We have developed Paragon, which is an RNA sequencing based panel that utilizes novel informatics technologies to provide a comprehensive picture of a tumor’s transcriptomic and immune micro-environment. There are three distinct outputs of Paragon: measurement of the expression levels of ten immune checkpoint genes, quantification of the total mutational burden of the tumor, and the levels of infiltration of 24 different immune cell subtypes within the tumor microenvironment. These outputs collectively inform the various mechanisms that tumors use to evade recognition and clearance by the immune system.
We show that Cofactor Paragon accurately reports on gene expression, mutational burden and infiltrating leukocytes compared to gold standard methods from just 20 ng of FFPE tumor RNA. We further analyze the data to show the correlation between mutational burden and infiltrating CD4+ and CD8+ T-cell levels. Finally, we show how Paragon can identify expression of genes involved in inhibitory tumor metabolism that correlate with resistance to PD-1 blockade therapy. These results position Cofactor Paragon as a novel tool that can help identify ideal therapeutic strategies in immuno-oncology.
Citation Format: Ryan Bloom, Raman Talwar, Jeff Hiken, Jon Armstrong. Cofactor Paragon: a novel tool to analyze the tumor microenvironment using RNAseq [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1999. doi:10.1158/1538-7445.AM2017-1999
Abstract 2008: Intestinal microbiota may dynamically facilitate the anti-PD-L1 immunotherapy
Authors: Xue Jia , Wang Zhun , Guo Sheng , Cai Jie , Ouyang Davy , Cai Bin , Chen Gang , Liu Jie , Dong Xin , Li Henry 
Published: July 2017

Abstract
Cancer immunotherapies, e.g. the antibody against programmed death ligand 1 (PD-L1), a checkpoint inhibitor, have witnessed great successes in treating certain cancers in recent years. Recent data have also demonstrated that gut microbiota are important modulators on anticancer immunotherapy1,2. Heterogeneity in patient outcome seems to suggest complex communications between microbiota and host antitumor immunity. To this end, we tested an engineered chimeric MC38 mouse cell line, hPDL1-MC38-HuCELL™ via human PD-L1 knock-in procedure, where MC38 CRC syngeneic cell is derived from C57BL/6. After treatment of PD-L1 antibodies (cD7A8 and BMS PD-L1 of different dose regimens), we observed significantly different drug responses among the mice from three different Chinese rodent suppliers: the mice from Vendor 1 showed no tumor progression after treatment with a variety of doses while no favorable response was observed in mice from Vendor 2 and Vendor 3. To deeply study the gut microbiota of these mice, we performed 16S ribosomal RNA sequencing on untreated mice from three groups (5 replicates for each). Global diversity analysis by Quantitative Insights Into Microbial Ecology (QIIME) tool revealed a clear separation in the three sources of mice: the microbiota composition of Vendor 2 and Vendor 1 are relatively closer to each other whereas the Vendor 3 mice are different, suggesting that the main difference seen between Vendor 1/2 and 3 in the original composition of gut microbiota is not the key impact for the observed anti-PD-L1 efficacy, and there should be other complex dynamics impacted anti-PD-L1 treatment, which remains unknown. Moreover, a group of 27 taxa were identified with significant difference in abundance (Kruskal-Wallis test, p-value &lt; 0.05) across the groups, such as Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae, which confirmed the previous data1. In conclusion, intestinal microbiota dynamically facilitate anti-PD-L1 efficacy and reversely anti-PD-L1 treatment could influence reconstruction of gut microbiota.
References 1. Sivan A, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 2015;350(6264):1084-9. 2. Vétizou M, et al., Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 2015;350(6264):1079-84. 3. Caporaso JG, et al., QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7(5):335-6.
Citation Format: Jia Xue, Zhun Wang, Sheng Guo, Jie Cai, Davy Ouyang, Bin Cai, Gang Chen, Jie Liu, Xin Dong, Henry Li. Intestinal microbiota may dynamically facilitate the anti-PD-L1 immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2008. doi:10.1158/1538-7445.AM2017-2008
Abstract 2010: BTK inhibitor BGB-3111 demonstrates anti-tumor activity in solid tumor models
Authors: Hu Nan , Zhang Jiye , He Min , Zhang Shuo , Liu Yong , Wang Lai 
Published: July 2017

Abstract
Background BGB-3111 is a novel, irreversible, second generation BTK inhibitor with better selectivity profile and DMPK property compared to ibrutinib. It has demonstrated promising anti-tumor activities in patients with advanced B cell malignancies. Given BTK is expressed in all hematopoietic lineages except for T lymphocytes, it is reasonable to explore the immune modulatory effect of BGB-3111. In this study, we sought to investigate the anti-tumor activity of BGB-3111 in solid tumor models.
Methods Cell viability was assessed with Cell Titer Glo® assay and half maximal inhibitory concentrations (IC50) were estimated. In vivo activity was assessed in subcutaneous mouse xenograft models. Treatments were administered by oral gavage and individual body weight and tumor volume was recorded twice weekly.
Results In vitro studies showed that MDA-MB-436 cells are insensitive to BGB-3111, which do not expresse BTK. In both human breast cancer MDA-MB-436 and human A431 epidermoid carcinoma subcutaneous xenograft models, the tumor cells were co-injected with peripheral blood mononuclear cells (PBMCs) of healthy donors. In MDA-MB-436 model, BGB-3111 (15 mg/kg, BID) single agent significantly induced tumor growth inhibition (TGI) of 55%, whereas showed no anti-tumor effect if no PBMCs co-injected. Furthermore, co-treatment of BGB-3111 (15 mg/kg, BID) and anti-PD-1 antibody BGB-A317 (10 mg/kg, QW) demonstrated enhanced therapeutic effect in A431 allogeneic model. Interestingly, in BCLU200 and BCLU054 NSCLC primary tumor xenograft models (without PBMC co-injection), BGB-3111 (15 mg/kg, BID) also demonstrated significant anti-tumor activity.
Conclusions In summary, BGB-3111 showed interesting activity in solid tumor models, suggesting BTK inhibitor might have potential to be used beyond hematology malignancies. .
Citation Format: Nan Hu, Jiye Zhang, Min He, Shuo Zhang, Yong Liu, Lai Wang. BTK inhibitor BGB-3111 demonstrates anti-tumor activity in solid tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2010. doi:10.1158/1538-7445.AM2017-2010