bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 872: Noninvasive monitoring of endogenous Pdl1 expression by using a dual reporter system
Authors: Zhou Min , Liu Xinjian , Li Fang , Li Chuan-Yuan 
Published: July 2017

Abstract
Programmed death-ligand 1 (Pdl1) is a key immune checkpoint protein facilitating tumor escape from host immune system. Clinical approval of anti-PD1 and anti-PDL1 antibodies for the treatment of a variety of malignancies underscores the promise of immune checkpoint therapy. Further progress in this promising area of research is likely to come from better understanding of the mechanisms for regulation of immune checkpoint proteins such as PDL1. In the present study, we designed a dual reporter imaging system to monitor Pdl1 expression by use of the CRSPR-Cas9 technology. A fusion reporter that consists of eGFP and Luc2 was introduced into downstream of the endogenous Pdl1 gene, right before the stop codon, through CRISPR-Cas9 mediated homologous recombination. A P2A self-cleaving motif is inserted between the fusion reporter gene (eGFP-Luc2) and Pdl1. The reporter system was introduced into two murine tumor cell lines, 4T1 and B16F10. In vitro, an increase in eGFP intensity and bioluminescence of the reporter cells was observed after exposure to ionizing radiation or IFN-gamma, which has been reported to upregulate the expression of Pdl1. In vivo, we were able to observe radiation induced increase in bioluminescence signals from tumor established by use of the reporter cells. Our study therefore provided proof of principle for the use of our endogenous Pdl1 reporter imaging system to monitor the expression levels of Pdl1 in vitro and in vivo noninvasively and serially.
Citation Format: Min Zhou, Xinjian Liu, Fang Li, Chuan-Yuan Li. Noninvasive monitoring of endogenous Pdl1 expression by using a dual reporter system [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 872. doi:10.1158/1538-7445.AM2017-872
Abstract 875: Improved resection and prolonged overall survival with PD-1-IRDye800CW fluorescent probe-guided surgery and PD-1 adjuvant immunotherapy
Authors: Du Yang , Tian Jie 
Published: July 2017

Abstract
Purpose: An intraoperative technique to accurately identify microscopic tumor residuals could be applied to decrease the risk of positive surgical margins. Several lines of evidence support the expression and immunotherapeutic effect of PD-1 in breast cancer. Here, we sought to develop a fluorescence labeled PD-1 probe for in vivo breast tumor imaging and image-guided surgery. The efficacy of PD-1 monoclonal antibody (mAb) as adjuvant immunotherapy after surgery was also assessed.
Experimental Design: A near-infrared dye labeled PD-1-IRDye800CW probe was developed and examined for its application in tumor imaging and image-guided tumor resection in an immunocompetent 4T1 mammary mouse tumor model that recapitulates clinical metastatic cancer. Fluorescence molecular imaging (FMI) was performed to monitor probe biodistribution and intraoperative imaging. Bioluminescence imaging (BLI) was carried out concurrently to monitor tumor growth and evaluate post-surgical tumor residuals, recurrences, and metastases.
Results: The PD-1-IRDye800CW probe exhibited a specific and stable signal at the tumor region compared to the IgG control, and exhibited the highest tumor-to-background ratio (TBR) 8 h post-injection (11.62 ± 0.79), approximately 5 fold higher than the IgG control (2.13 ± 0.30). Furthermore, PD-1-IRDye800CW guided surgery combined with PD-1 adjuvant immunotherapy inhibited tumor regrowth and microtumor metastases, as determined by BLI imaging, and thus improved survival rate with no obvious side effects.
Conclusions: Our study demonstrated the feasibility of using PD-1-IRDye800CW for breast tumor imaging and image-guided tumor resection. Moreover, we found that PD-1 mAb adjuvant immunotherapy reduces cancer recurrences and metastases emanating from minimal tumor residuals.
Citation Format: Yang Du, Jie Tian. Improved resection and prolonged overall survival with PD-1-IRDye800CW fluorescent probe-guided surgery and PD-1 adjuvant 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 875. doi:10.1158/1538-7445.AM2017-875
Abstract 877: Real-time imaging of adherent and non-adherent cell interactions: utility of an automated microfluidic trap platform to recapitulate in vivo cell culture microenvironment
Authors: Kannan Rekha , Yeh Victor , Helton James , Cappione Amedeo 
Published: July 2017

Abstract
The study of dynamic cell processes and their interactions is of crucial importance to understand the complexities of tissue microenvironments. Simulation of in vivo cell culture microenvironments can greatly improve biologic relevance of cell-cell interaction studies, and so there is an ongoing demand for heuristic optimization of cell co-culture devices and protocols. One particularly challenging task is establishing real-time image analysis while co-culturing non-adherent cells in contact with adherent cell layers under precisely controlled environmental parameters. To address this challenge, we present a novel microfluidic approach to trap two different cell types in precise locations in order to image and study their interactions over time. The platform utilizes a well plate format that contains multiple microfluidic units. Each unit consists of a 3 mm x 3 mm x 40 µm (L x W x H) chamber for culture, and an array of microscopic trap areas tailored to the dimensions of the cells of interest, typically ~15 µm. The micro-scale geometries of the traps physically confine non-adherent cells, and co-cultures can be achieved by trapping the non-adherent cells over a monolayer of cells. The microfluidic plate is integrated with a system which enables perfusion-based nutrient supply along with gas and temperature control for long-term cell culture. Each chamber within the plate can be addressed by programmable and on-demand perturbation of up to 6 reagents, enabling uninterrupted real-time live cell imaging assays. We present here the use of this microfluidic platform to replicate tumor microenvironment by maintaining adjacent co-cultures of cancer and immune cells. We have successfully imaged and cultured monolayers of tumor cell lines for 7 days followed by subsequent loading and trapping of immune (non-adherent) cells. In conclusion, the microfluidic platform enables unique co-cultures with environmental control and real-time imaging to facilitate the investigation of cell-cell interactions in a wide range of applications such as drug response and screening in tumor microenvironments, invasion, evasion pathways and other mechanisms governing cell-cell interactions.
Citation Format: Rekha Kannan, Victor Yeh, James Helton, Amedeo Cappione. Real-time imaging of adherent and non-adherent cell interactions: utility of an automated microfluidic trap platform to recapitulate in vivo cell culture microenvironment [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 877. doi:10.1158/1538-7445.AM2017-877
Abstract 881: CD44-specific supramolecular hydrogels for fluorescence molecular imaging of EMT induced BRAF &lt;V600E&gt; mutant thyroid cancer cells
Authors: Byeon Hyung Kwon , Ku Minhee , Yang Yeon Ju , Cho Min Hee , Oh Yoojung , Kim Jae Wook , Ban Myung Jin , Kim Ji-Hoon , Kim Da Hee , Kim Joo Hyun , Yang Jaemoon , Koh Yoon Woo 
Published: July 2017

Abstract
Previously, the authors have identified that the acquired drug resistance to BRAF inhibitor, PLX4032 in BRAF (V600E) mutant anaplastic thyroid cancer promotes not only tumor progression and proliferation, but also migration and invasion of cancer through upregulated epithelial-to-mesenchymal transition (EMT). The underlying mechanism to the acquired resistance to BRAF inhibition involves c-Met-mediated reactivation of PI3K/AKT pathway. Therefore combinatorial dual targeted therapy of BRAF and c-Met inhibition has shown to reverse EMT and show maximal antitumor effect. Previously, the authors have developed a novel in vivo imaging strategy using CD44-targetable near-infrared (NIR)-sensitive supramolecular hydrogels (NIRSHs) for the recognition of CD44-expressing cancer cells. In the present study, we applied this NIR-sensitive molecular imaging probe in detecting the upregulated EMT changes in PLX4032-treated 8505C cells. The CD44-targetable NIRSHs were fabricated by polyplexing Cy5.5-conjugated polyethyleimine and hyaluronic acid in an aqueous medium. Ectopic xenograft mouse models were prepared by injecting 8505C cells at the flank of male athymic nude BALB/c mice, aged 6 weeks. After confirming tumor formation at 3 weeks post-injection, the mice were randomly divided into four groups and were each treated under different conditions; DMSO, PLX4032, PHA665752, PLX4032 and PHA665752. After 3 weeks, the pre-established NIRSH probes were injected and confirmed by IVIS imaging. The injected NIRSH probes showed highest uptake in the PLX4032 single treatment group and lowest uptake in the PLX4032 and PHA665752 combination group. Sizes of tumor were verified by MRI which showed correlations with the NIRSH fluorescence imagings. The results suggest that CD44-targetable NIRSHs imaging shows potential as a non-invasive in vivo imaging tool in detecting the increased invasion potential of cancer cells and monitoring appropriate therapeutic effects.
Citation Format: Hyung Kwon Byeon, Minhee Ku, Yeon Ju Yang, Min Hee Cho, Yoojung Oh, Jae Wook Kim, Myung Jin Ban, Ji-Hoon Kim, Da Hee Kim, Joo Hyun Kim, Jaemoon Yang, Yoon Woo Koh. CD44-specific supramolecular hydrogels for fluorescence molecular imaging of EMT induced BRAF &lt;V600E&gt; mutant thyroid 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 881. doi:10.1158/1538-7445.AM2017-881
Abstract 887: Magnetic relaxometry detection of stealth, antibody-targeted micellar iron oxide nanoparticles in-vivo
Authors: Aburto Rebeca Romero , Sokolov Konstantin , Kulp Adam M. , Vreeland Erika C. , Lu Zhen , Bast Robert C. , Hazle John D. , Mathieu Kelsey B. 
Published: July 2017

Abstract
Magnetic relaxometry (MRX) has the potential to provide unprecedented sensitivity in early detection of cancer by sensing changes in magnetic relaxation of iron oxide (Fe3O4) nanoparticles targeted to cancer biomarkers and is expected to exceed the detection limits of established clinical modalities. MRX uses superconducting quantum interference device (SQUID) sensors to measure Neél relaxation of bound particles. Our strategy was to develop molecular specific Fe3O4 nanoparticles using amphiphilic functionalized phospholipids that allow for clinical translation of the MRX technology. To accomplish this, we used automated, controlled rate, direct infusion of an organic phase mixture of phospholipids and nanoparticles into water to produce monodisperse micellar nanoparticles with a mean diameter of 75±12 nm and surface charge of -10mV. The particles were determined to be stable in various biological media, including human plasma, for more than 24 hours with no detectable formation of a protein corona. Furthermore, in-vivo studies in healthy mice showed blood circulation times of more than 2 hours, as well as minimal MRX signals during this time. Additionally, we developed maleimide conjugation chemistry for epidermal growth factor receptor (EGFR) antibody attachment to micellar nanoparticles. We have achieved molecular specific labeling of cancer cells over-expressing EGFR. In the future, we will evaluate the MRX signal impact from injecting EGFR-conjugated nanoparticles into tumor-bearing mice.
Citation Format: Rebeca Romero Aburto, Konstantin Sokolov, Adam M. Kulp, Erika C. Vreeland, Zhen Lu, Robert C. Bast, John D. Hazle, Kelsey B. Mathieu. Magnetic relaxometry detection of stealth, antibody-targeted micellar iron oxide nanoparticles in-vivo [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 887. doi:10.1158/1538-7445.AM2017-887
Abstract 895: Fucosylation inhibits invadopodia formation and melanoma invasion
Authors: Keeley Tyler S. , Lau Eric , Yang Shengyu 
Published: July 2017

Abstract
Background: Melanoma is the most deadly skin cancer and metastasis is essentially responsible for all melanoma related death. Recently, fucose treatment has been shown to inhibit melanoma cell migration and invasion in vitro, and melanoma metastasis in a mouse model, suggesting that protein fucosylation could be exploited to prevent or suppress melanoma metastasis. Invadopodia are proteolytic actin-rich protrusions used by metastatic melanoma cells to degrade extracellular matrix and to promote invasion and metastasis. In this study, we investigated the mechanisms by which fucosylation regulate melanoma invasion and invadopodia formation
Method: The melanoma cells were treated with L-fucose-supplemented medium or infected with fucokinase-expressing lentivirus to increase protein fucosylation. shRNAs were also employed to knockdown fucokinase and to inhibit fucosylation in melanoma cells. The effects of fucosylation on invadopodia formation and extracellular matrix degradation were determined by phalloidin staining and degradation of fluorescently labeled gelatin thin film.
Results: Here, we show that the addition of L-fucose to complete media inhibits the ability of melanoma cells to form invadopodia in a dose-dependent manner. The overexpression of hFUK in WM793 cells showed a similar result as L-fucose treatment, where invadopodia formation was significantly reduced. In addition, we observed a significant decrease in the percentage of cells that have invadopodia during L-fucose supplementation or hFUK overexpression. In an invadopodia precursor assay, the hFUK-overexpressing cell line exhibited delayed FBS-stimulated invadopodia formation.
Conclusions: Our data suggest that fucose or the overexpression of hFUK reduces melanoma invasion by inhibiting invadopodia formation. Given that invadopodia formation was hindered within an hour after stimulation, we believe that invadopodia initiation is affected by increased fucosylation, resulting in fewer invadopodia and slower extracellular matrix degradation.
Citation Format: Tyler S. Keeley, Eric Lau, Shengyu Yang. Fucosylation inhibits invadopodia formation and melanoma invasion [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 895. doi:10.1158/1538-7445.AM2017-895
Abstract 9: Suppression of the invasion and growth of human head and neck squamous cell carcinomas via regulating STAT3 signaling and miR-21/β-catenin axis with HJC0152
Authors: Wang Yu , Wang Sinan , Wu Yansheng , Zhou Jia , Shen Qiang , Zhou Xuan 
Published: July 2017

Abstract
Signal transducer and activator of transcription 3 (STAT3) is involved in the tumor growth and metastasis of human head and neck squamous cell carcinoma (HNSCC) and is therefore a target with therapeutic potential. In this study, we show that HJC0152, a recently developed anticancer agent and a STAT3 signaling inhibitor, exhibits promising antitumor effects against HNSCC both in vitro and in vivo via inactivating STAT3 and downstream microRNA-21/β-catenin axis. HJC0152 treatment efficiently suppressed HNSCC cell proliferation, arrested the cell cycle at the G0/G1 phase, induced apoptosis, and reduced cell invasion in both SCC25 and CAL27 cell lines. Moreover, HJC0152 inhibited nuclear translocation of phosphorylated STAT3 at Tyr705 and decreased VHL/β-catenin signaling activity via regulation of microRNA-21. Loss-of-function of VHL remarkably compromised the antitumor effect of HJC0152 in both cell lines. In our SCC25-derived orthotopic mouse models, HJC0152 treatment significantly abrogated STAT3/β-catenin expression in vivo, which leading to a global decrease of tumor growth and invasion. With its favorable aqueous solubility and oral bioavailability, HJC0152 holds the potential to be translated into the clinic as a promising therapeutic strategy for patients with HNSCC.
Citation Format: Yu Wang, Sinan Wang, Yansheng Wu, Jia Zhou, Qiang Shen, Xuan Zhou. Suppression of the invasion and growth of human head and neck squamous cell carcinomas via regulating STAT3 signaling and miR-21/β-catenin axis with HJC0152 [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 9. doi:10.1158/1538-7445.AM2017-9
Abstract 901: The mechanobiome of pancreatic cancer: a viable, targetable drug space
Authors: Surcel Alexandra , Schiffhauer Eric S. , Thomas Dustin , Zhu Qingfeng , Anders Robert , Robinson Douglas 
Published: July 2017

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an annual mortality rate of 37,000 in the US alone. Its 5-year survival rate of ~6% remains relatively unchanged over the past 4 decades. Because PDAC has elevated rates of de novo and acquired resistance to traditional chemotherapies, we are exploring new drug spaces that target metastatic hepatic disease, the primary mortality factor for patients. Specifically, we have identified the cluster of proteins that sense and respond to mechanical stimuli - collectively known as the mechanobiome. This cytoskeletal machinery is responsible in large part for endowing metastatic cells with the ability to navigate through different tissue types. Based on their mechanoresponsiveness profile, we have predicted and identified via western blot and immunohistochemistry proteins in the mechanobiome that are upregulated in patient-derived pancreatic tissues. These proteins include non-muscle myosin IIA and IIC, alpha-actin-4, and filamin B. We are performing knockdown and overexpression studies of these isoforms on 2D and 3D behaviors - cell mechanics, migration, invasion, and tissue sphere formation and are poised to begin mouse studies on the metastatic sufficiency in altering the expression of these proteins. In addition, we are testing 4-HAP, a small molecule mechanics modulator that we previously identified that targets myosin IIC, thus affecting PDAC mechanics in PDAC murine models. Limited studies reveal that 4-HAP reduces metastasis. These data suggest that direct targeting of the mechanobiome may eventually expand treatment strategies for pancreatic cancer.
Citation Format: Alexandra Surcel, Eric S. Schiffhauer, Dustin Thomas, Qingfeng Zhu, Robert Anders, Douglas Robinson. The mechanobiome of pancreatic cancer: a viable, targetable drug space [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 901. doi:10.1158/1538-7445.AM2017-901
Abstract 903: CXCR4 and CXCR7 play distinct and overlapping roles in prostate cancer dissemination to bone
Authors: Roy Sounak , Valkenburg Kenneth C. , Pienta Kenneth J. 
Published: July 2017

Abstract
Approximately 28,000 men die of prostate cancer (PCa) each year in the US, and 90-100% of them will be due to bone metastasis. It has been demonstrated that PCa cells detach from the primary tumor and “home” to bone. Osteoblasts (bone-forming cells) secrete the chemoattractant stromal-derived factor 1 (SDF-1, also known as CXCL12), and PCa cells express the receptors for SDF-1, C-X-C chemokine receptors 4 and 7 (CXCR4 and CXCR7). PCa cells use these receptors to enter the chemoprotective bone microenvironment, specifically, the hematopoietic stem cell (HSC) niche in the endosteum. While small molecule inhibition of CXCR4 can mobilize PCa cells from the bone marrow microenvironment, it is unknown whether CXCR7 plays a compensatory role when CXCR4 is antagonized. SDF-1 is known to bind with greater affinity to CXCR7 compared to CXCR4 indicating a possible role of CXCR7 in tumor migration to the endosteal niche. Therefore, it is crucial to determine the individual and combined roles of CXCR4 and CXCR7 in the formation and treatment of PCa bone metastases. To answer these questions, first we assessed CXCR4 and CXCR7 expression across a panel of prostate cancer cell lines. We then transiently overexpressed and knocked down CXCR4 and CXCR7 in PCa cells and found CXCR4 and CXCR7 expression in vitro to directly correlate to cell viability and migration in PC3 PCa cells. To further test dissemination and metastasis in bone, we are making stable overexpression and knockout cells and will perform in vivo metastasis experiments. We have developed a novel immunofluorescence protocol for detecting and quantifying tumor cells in murine blood and bone marrow and will use this technique to determine the ability of PCa cells to disseminate to bone in the presence or absence of CXCR4 and/or CXCR7. This will be quickly translatable because we are currently running a first-in-prostate cancer clinical trial to determine whether small molecule inhibition of CXCR4 to mobilize PCa tumor cells from the bone marrow, combined with docetaxel, will benefit metastatic PCa patients. If we determine that CXCR7 plays a compensatory role in dissemination and/or metastasis, we will need to add CXCR7 inhibition to our treatment strategy to obtain the most efficient benefit for patients.
Citation Format: Sounak Roy, Kenneth C. Valkenburg, Kenneth J. Pienta. CXCR4 and CXCR7 play distinct and overlapping roles in prostate cancer dissemination to bone [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 903. doi:10.1158/1538-7445.AM2017-903