bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5148: Secreted ccdc80 from hepatic stellate cell promote invasion and epithelial-mesenchymal transition in hepatocellular carcinoma
Authors: Kim Kwang Seock , Lee SaeHwan , Jun Nayoung , Kwon Hyog Young 
Published: August 2018

Abstract
Liver cirrhosis is the most important risk factor for hepatocellular carcinoma (HCC) and hepatic stellate cell (HSC) has pivotal role in developing cirrhosis by producing various extracellular matrix (ECM). HSC are essential mediators of tumor microenvironment of HCC through remodeling of ECM and angiogenesis. We found that CCDC80 expression is upregulated in activated HSCs from RNA-sequencing with human fetal stellate cell. However, the role of CCDC80 was not well known in hepatocarcinogenesis. First, we validated mRNA expression of CCDC80 was increased in activated HSC lines and protein expression was also increased in cultured media. Functional analysis of knockdown CCDC80 was investigated in both HCC and HSC cell lines, and HCC cell lines were analyzed for proliferation (MTT assay), migration (using transwell), invasion (using Matrigel-coated transwell), and wound healing assay with condition media of CCDC80 knockdown HSCs. Expression of epithelial-mesenchymal transition (EMT) markers in HCC was evaluated with conditioned media. Knockdown of CCDC80 resulted in reduced cell proliferation and significantly reduced invasion, migration and wound healing behaviors of HCC cell lines. Expression of E-cadherin was increased and snail and vimentin expression were decreased in HCC cell lines cultured with conditioned media of CCDC80 knockdown HSCs. The associations between CCDC80 and EMT markers were validated in CCDC80 transfected HSC cell line compared with control. Taken together, secreted CCDC80 from HSCs affected the aggressiveness and EMT of HCC cell lines. CCDC80 might be a novel biomarker and therapeutic target for patients with HCC.
Citation Format: Kwang Seock Kim, SaeHwan Lee, Nayoung Jun, Hyog Young Kwon. Secreted ccdc80 from hepatic stellate cell promote invasion and epithelial-mesenchymal transition in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5148.
Abstract 5154: Semaphorin 6A attenuates the migration capability of lung cancer cells via the NRF2/HMOX1 axis
Authors: Chen Li-Han , Liao Che-Yu , Chuang Eric Y. , Tsai Mong-Hsun 
Published: August 2018

Abstract
Cell migration is a fundamental feature of cancer recurrence. Since recurrence is correlated with high mortality in lung cancer, it follows that reducing cell migration would decrease recurrence and increase survival rates. The goal of this study was to determine the role of SEMA6A in cell migration. Semaphorin 6A (SEMA6A), a protein initially known as a regulator of axonal guidance, is down-regulated in lung cancer tissue, and low levels of SEMA6A are associated with cancer recurrence. Thus, we hypothesized that SEMA6A could suppress cancer cell migration. In this study, we found that the migration capability of H1299 lung cancer cells decreased with SEMA6A overexpression, while it increased with SEMA6A silencing. Reduction in migration was observed only with the full length protein and not with the extracellular ectodomain construct, suggesting that a reverse signaling mechanism is used to mediate the effects of SEMA6A on migration. Moreover, silencing of the cellular homeostasis protein HMOX1 and/or the transcription factor NRF2 reversed the migration-suppressing effect of SEMA6A and the SEMA6A-driven alterations in expression of PLAU and IGFBP3, both downstream effectors of HMOX1. Taken together, these results demonstrate that SEMA6A is a potential suppressor of migration that functions through the NRF2/HMOX1 axis. Our results explain why low SEMA6A is linked to high recurrence in the clinical setting and suggest that SEMA6A could be useful as a biomarker or target in lung cancer therapy.
Citation Format: Li-Han Chen, Che-Yu Liao, Eric Y. Chuang, Mong-Hsun Tsai. Semaphorin 6A attenuates the migration capability of lung cancer cells via the NRF2/HMOX1 axis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5154.
Abstract 5159: FLOT1 is associated with HGF mediated cell invasion and proliferation by increased MMP9
Authors: Koh Sung Ae , Lee Kyung Hee , Kim Jae Ryong , Kim Sang woon , Jang Byung Ik 
Published: August 2018

Abstract
The flotillin protein family, including flotillin-1 (FLOT1 ) and flotillin-2 (FLOT2), have been known as markers of lipid rafts. Recentely, FLOT1 was reported that FLOT1 overexpression was found in several advanced cancer including breast, colorectal, prostate tumors, and renal cell carcinomas and correlate with poor prognosis in advanced tumors. The purpose of this study is to identify the role of HGF upregulated FLOT1 associated with cancer cell proliferation and invasion in gastric cancer. We used cell culture, western blotting, RT-PCR, MTT assays, CHIP assay, zymography and FLOT 1 knock-down with short hairpin RNA (shRNA). First, we confirmed that the expression level of FLOT1 was up-regulated by HGF(hepatocyte growth factor). To determine the role for FLOT1, we used the knock down cell of FLOT1. FLOT1 -sh RNA cells showed a decreased level of MMP9 and NFkB. We also examined to confirm the role of HGF-mediated FLOT1. HGF-mediated cell proliferation and in vitro invasion was decreased in FLOT1 knock down cell. We perforomed the zymography to evaluate the activity of MMP9 . The activity of MMP9 was decreased in FLOT1 knock down cell. The level of AKT phosphorylation was decreased in the knock down cell of FLOT1. Also, We identified the putative binding site of NFkB in MMP9 promotor region and confirmed the function by CHIP assay. Our study showed that upregulation FLOT1 by HGF increased the level of MMP9 through AKT/NFkB pathway and associated with cell proliferation and invasion in gastric cancer.
Citation Format: Sung Ae Koh, Kyung Hee Lee, Jae Ryong Kim, Sang woon Kim, Byung Ik Jang. FLOT1 is associated with HGF mediated cell invasion and proliferation by increased MMP9 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5159.
Abstract 5161: DARPP-32 and t-DARPP promote non-small cell lung cancer growth through regulation of IKKα-dependent cell migration and Akt/Erk-mediated cell survival
Authors: Alam Sk. Kayum , Astone Matteo , Liu Ping , Hall Stephanie R. , Coyle Abbygail M. , Dankert Erin N. , Hoffman Dane K. , Zhang Wei , Kuang Rui , Roden Anja C. , Mansfield Aaron S. , Hoeppner Luke H. 
Published: August 2018

Abstract
Lung cancer is the leading cause of cancer-related death worldwide. In this study, we demonstrate that elevated expression of dopamine and cyclic adenosine monophosphate-regulated phosphoprotein, Mr 32000 (DARPP-32) and its truncated splice variant t-DARPP promotes lung tumor growth, while abrogation of DARPP-32 expression in human non-small cell lung cancer (NSCLC) cells reduces tumor growth in orthotopic mouse models. We observe a novel physical interaction between DARPP-32 and inhibitory kappa B kinase-α (IKKα) that promotes NSCLC cell migration through non-canonical nuclear factor kappa-light-chain-enhancer of activated B cells 2 (NF-κB2) signaling. Bioinformatics analysis of 513 lung adenocarcinoma patients reveals elevated t-DARPP isoform expression is associated with poor overall survival. Histopathological investigation of 62 human lung adenocarcinoma tissues also showed that t-DARPP expression is elevated with increasing tumor (T) stage. Our data suggest that DARPP-32 is a negative prognostic marker associated with increasing stages of NSCLC and may represent a novel therapeutic target.
Citation Format: Sk. Kayum Alam, Matteo Astone, Ping Liu, Stephanie R. Hall, Abbygail M. Coyle, Erin N. Dankert, Dane K. Hoffman, Wei Zhang, Rui Kuang, Anja C. Roden, Aaron S. Mansfield, Luke H. Hoeppner. DARPP-32 and t-DARPP promote non-small cell lung cancer growth through regulation of IKKα-dependent cell migration and Akt/Erk-mediated cell survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5161.
Abstract 5165: Patterning of individual cellular behavior in collective invasion
Authors: Guo Chin-Lin , Sanchez Emilio , Fong Eileen 
Published: August 2018

Abstract
Collective invasion is one of the most important factors accounting for the aggressiveness of solid tumors. Such behavior depends on interactions between tumor cells and between tumor and its surrounding miroenvironment, including stroma cells and extracellular matrix (ECM), which to a certain extent, can be observed in normal cells. Previously we have shown that epithelial cells can use cell-ECM-cell interaction to develop long-range (&gt; 600 microns) invasive patterns. Here, using artificial wounding assay, we show that normal epithelial cells can develop two coexisting, orthogonal migration patterns at the tissue boundary, leading to a periodic patterning of invasion. Such patterning depends on microtubule dynamic instability and results in ROCK activation and YAP1 nuclear translocation, a process to induce epithelial-mesenchymal transition (EMT). Surprisingly, we found that both overexpression and knockdown of an EMT marker, vimentin, can enhance collective invasion, suggesting that the role of vimentin in EMT might be context dependent and needs to be revisited.
Citation Format: Chin-Lin Guo, Emilio Sanchez, Eileen Fong. Patterning of individual cellular behavior in collective invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5165.
Abstract 5180: MicroRNA and triple negative breast cancer
Authors: YI BIN , Ma Ruixia , Xi Yaguang 
Published: August 2018

Abstract
In 2017, a total of 252,710 new cases and 40,610 deaths from breast cancer in the United States were estimated by the American Cancer Society. Breast cancer is the most common malignancy and the second leading cause of death among American women. In this application, we will focus on triple negative breast cancer (TNBC), which is viewed by oncologists as a problematic and unpredictable sub-category of breast cancer because of higher rates of recurrence and poorer prognosis. TNBC accounts for up to 20% of all breast cancers and is highly prevalent in minority and young women. On average, 70% of women with metastatic TNBC die within 5 years, regardless of chemotherapy or other treatments. As such, there is an urgent medical need to develop more effective drugs to manage this deadly disease that raises a health disparity concern, especially in the State of Louisiana. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used drugs for the treatment of pain, fever, and inflammation. Epidemiological studies have reported that the long term use of NSAIDs can prevent the occurrence multiple types of cancers, including breast cancer. However, their long term use for chemoprevention is not recommended because of toxicities associated with cyclooxygenase (COX) inhibition and the suppression of physiologically important prostaglandins. Our results show that the NSAID, sulindac sulfide (SS) and two non-COX inhibitory derivatives, sulindac sulfide amide (SSA) and sulindac benzylamine (SBA), can significantly inhibit the growth of the major subtypes of TNBC cells (basal-like, mesenchymal, and luminal). In addition, the compounds significantly inhibit tumor cell invasion. While studying the mechanism, we found that four oncogenic miRNAs, miR-10b, miR-17, miR-21, and miR-9 can be downregulated by SS and derivatives, and they were reported to promote tumor metastasis exclusively. Therefore, we conclude that those oncogenic miRNAs are involved in anti-invasive activities of SS and derivatives in TNBC cells.
Citation Format: BIN YI, Ruixia Ma, Yaguang Xi. MicroRNA and triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5180.
Abstract 5181: KSRP suppresses cell invasion and metastasis through miR-23a-mediated EGR3 mRNA degradation in non-small cell lung cancer
Authors: Pan Ke-Fan , Chien Ming-Hsien , Lee Wei-Jiunn , Hsiao Michael , Hua Kuo-Tai 
Published: August 2018

Abstract
KH-type splicing regulatory protein (KSRP) is a single-strand RNA binding protein which regulates mRNA stability either by binding to AU-rich elements (AREs) of mRNA 3′UTR or by facilitating miRNA biogenesis to target mRNA. Unlike its well-characterized function at the molecular level in maintaining RNA homeostasis, the role of KSRP in cancer progression remains largely unknown. Here we investigate the role of KSRP in non-small cell lung cancer (NSCLC). We first examined KSRP expression by immunohistochemistry in a cohort containing 196 NSCLC patients and observed a strong positive correlation between KSRP expression and survival of NSCLC patients. Multivariate analysis further identified KSRP as an independent prognostic factor. Manipulating KSRP expression significantly affected in vitro cell mobility and in vivo metastatic ability of NSCLC cells. Microarray analysis identified an ARE-containing gene, EGR3, as a downstream effector of KSRP in NSCLC. Interestingly, we found that KSRP decreased EGR3 mRNA stability in an ARE-independent manner. By screening KSRP-regulated miRNAs in NSCLC cells, we further found that miR-23a directly binds to EGR3 3′UTR, reducing EGR3 expression and thereby inhibiting NSCLC cell mobility. Our findings implicate a targetable KSRP/miR-23a/EGR3 signaling axis in advanced tumor phenotypes
Citation Format: Ke-Fan Pan, Ming-Hsien Chien, Wei-Jiunn Lee, Michael Hsiao, Kuo-Tai Hua. KSRP suppresses cell invasion and metastasis through miR-23a-mediated EGR3 mRNA degradation in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5181.
Abstract 5192: Detection of disseminated prostate cancer cells in bone marrow using tyramide signal amplification
Authors: Roy Sounak , Valkenburg Kenneth C. , Pienta Kenneth J. 
Published: August 2018

Abstract
Approximately 28,000 men die of prostate cancer (PCa) each year in the US, and 90-100% of them are due to bone metastasis. It has been demonstrated that PCa cells detach from the primary tumor, “home” to bone, and develop into these incurable metastases. Existing methods of detecting cells early that can lead to bone metastasis have limited sensitivity and current efforts involve liquid biopsy assays to capture and detect disseminated and circulating tumor cells (DTCs and CTCs respectively). A significant challenge during this detection lies in the optimization of the signal-to-noise ratio during immunofluorescent staining. Noise during immunostaining can originate from endogenous immune cells and other bone marrow matrix components and lead to false staining which reduces sensitivity. We have developed an optimized protocol to reduce background noise from these factors while also enhancing signal using tyramide signal amplification (TSA). Following immuno-staining with PCa cell-specific markers, TSA amplifies beyond primary and secondary antibody binding using horseradish peroxidase (HRP) and fluorophore binding. To further apply this novel signal amplification protocol to the visualization of disseminated tumor cells in bone marrow, we will detect, quantify, and image parental and modified PCa cells injected into murine blood. We have previously shown that C-X-C chemokine receptor 4 causes PCa cells to home to bone. We have stably overexpressed CXCR4 in several PCa cell lines and will be able to determine the role of CXCR4 expression on the development of bone metastases. This robust protocol will be quickly modifiable for automated staining to yield higher throughput analysis.
Citation Format: Sounak Roy, Kenneth C. Valkenburg, Kenneth J. Pienta. Detection of disseminated prostate cancer cells in bone marrow using tyramide signal amplification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5192.
Abstract 5201: Differences in tumor microenvironments between primary lung tumors and brain metastases in lung cancer patients: Therapeutic implications for immune checkpoint inhibitors
Authors: Kim Ryul , Keam Bhumsuk , Kim Sehui , Kim Miso , Kim Se Hyun , Kim Jin Wook , Kim Yu Jung , Kim Tae Min , Jeon Yoon Kyung , Kim Dong-Wan , Chung Doo Hyun , Lee Jong Seok , Heo Dae Seog 
Published: August 2018

Abstract
Background: We aimed to compare intra- and extracranial responses to immune checkpoint inhibitors (ICIs) in lung cancer with brain metastases (BM), and to explore tumor microenvironments of the brain and lungs focusing on the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway.
Methods: Two cohorts of lung cancer patients with BM were analyzed. Cohort 1 included 18 patients treated with nivolumab or pembrolizumab, and intra- and extracranial responses were assessed. Cohort 2 comprised 20 patients who underwent both primary lung surgery and brain metastasectomy. Specimens from cohort 2 were subjected to immunohistochemical analysis for the following markers: CD3, CD4, CD8, FOXP3, and PD-1 on tumor infiltrating lymphocytes (TIL) and PD-L1 on tumor cells.
Results: Seven patients (38.9%) in cohort 1 showed progressive disease in both primary and intracranial lesions. Although the other 11 patients exhibited a partial response or stable disease in the primary lesion, eight showed a progression in BM. Interestingly, PD-1+ TILs were significantly decreased in BM (P=0.034). For fifteen patients with adenocarcinoma, more distinctive patterns were observed in CD3+ (P=0.078), CD8+ (P=0.055), FOXP3+ (P=0.016), and PD-1+ (P=0.016) TILs.
Conclusions: There may be discordant responses to an ICI of lung cancer between primary lung lesion and BM based on discrepancies in the tumor microenvironment. The diminished infiltration of PD-1+ TILs in tumor tissue within the brain may be one of the major factors that hinder the response to anti-PD-1 antibody in BM.
Citation Format: Ryul Kim, Bhumsuk Keam, Sehui Kim, Miso Kim, Se Hyun Kim, Jin Wook Kim, Yu Jung Kim, Tae Min Kim, Yoon Kyung Jeon, Dong-Wan Kim, Doo Hyun Chung, Jong Seok Lee, Dae Seog Heo. Differences in tumor microenvironments between primary lung tumors and brain metastases in lung cancer patients: Therapeutic implications for immune checkpoint inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5201.
Abstract 5228: Mammary gland tumors in progesterone receptor transgenic mice
Authors: Gibson Katelin A. , Goodman Merit L. , Hagan Christy R. 
Published: August 2018

Abstract
The role of progesterone and its receptor, the progesterone receptor, in breast cancer remains controversial. Although years of clinical trial data have shown that synthetic progesterone (progestins) increases breast cancer risk, the role for native progesterone in breast cancer development is the source of much debate. PR is post-translationally modified, primarily through phosphorylation, by many mitogenic kinases, including ck2, cdk2 and MAPK. These phosphorylation events on PR dictate many aspects of PR biology, including promoter specificity and transcriptional co-factor interactions. Ck2, a mitogenic kinase shown to be upregulated in breast cancer, has been shown to phosphorylate PR and regulate transcription of a certain subset of PR target genes. In an effort to determine how this translates to murine mammary gland tumor formation, we created a bi-transgenic mouse overexpressing both PR and ck2 in the murine mammary gland. We studied long-term tumor formation in the PR/ck2 bi-transgenic mice, as compared to the single transgene controls (PR only or ck2 only), in both virgin and multiparous mice. Our preliminary data suggest a number of interesting results. First, tumor development is the highest in the PR transgenic mice, as compared to ck2 alone or PR/ck2 bi-transgenic mice. This is of particular interest as previous studies in PR transgenic mice failed to show mammary gland tumor formation, despite the presence of dysplastic mammary gland tissue. Moreover, the rate of tumor formation appears to be unaffected by parity: virgin and multiparous mice develop tumors at the same rate. This is in contrast to ck2 single-transgenic mice, where multiparty increases the rate of tumor formation (as observed by us and others). Interestingly, and most significantly to our studies, the combination of ck2 and PR appears to slow tumor formation rates as compared to either single transgenic mouse control. This phenotype is potentiated by pregnancy, as all multiparous PR/ck2 bi-transgenic animals still remain tumor free. These data, while still preliminary, suggest that ck2-dependent modification of PR may prevent mammary gland tumor formation, suggesting that PR regulation of a subset of genes (those genes regulated by ck2-phopshorylation) may drive anti-proliferative, tumor-preventing gene programs.
Citation Format: Katelin A. Gibson, Merit L. Goodman, Christy R. Hagan. Mammary gland tumors in progesterone receptor transgenic mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5228.
Abstract 5235: An investigation of the potential effects of the atypical PKC-ι inhibitor ICA-1 on ovarian cancer proliferation and survival, in estrogen dependent and independent systems
Authors: Smalley Tracess , Acevedo-Duncan Mildred 
Published: August 2018

Abstract
Ovarian cancer is the most lethal gynecological cancer diagnosis. There is no efficient screening process for ovarian cancers and the average stage of diagnosis is stage III. Atypical PKCs (PKC-ζ and PKC-ι/λ) have been shown to be overexpressed in various malignant cells lines and to be linked to pathways for cellular proliferation and survival. Many investigations suggest that the hormone estrogen regulates cellular proliferation in an ERα dependent manner. Little research shows the effects of estrogen on ERα and β negative cells and its role in cellular proliferation. In this investigation, ovarian cell lines (HEY, COV644, T80) were treated with the atypical PKC-ι inhibitor ICA-1 nucleoside variant in two different systems, with and without estrogen, and assayed to determine the effects on proliferation and cellular survival. These assays included protein quantification, cell proliferation, and wound healing. Our preliminary data suggests that PKC-ι is a novel target in carcinogenesis and inhibition of this protein decreases the rate of proliferation. Our results also suggest that estrogen has a significant effect on cell proliferation, even in estrogen receptor negative cells.
Citation Format: Tracess Smalley, Mildred Acevedo-Duncan. An investigation of the potential effects of the atypical PKC-ι inhibitor ICA-1 on ovarian cancer proliferation and survival, in estrogen dependent and independent systems [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5235.