bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5071: The functional relevance of Atypical Chemokine Receptor 1 (ACKR1/DARC) genetic isoforms in breast cancer
Authors: Jenkins Brittany D. , Martini Rachel N. , Brown Inasia , Davis Melissa B. 
Published: August 2018

Abstract
Chemokines and their receptors can interact to affect the host's anti-tumor response by influencing the migration of host immune cells indirectly via a chemokine gradient. The regulation and function of these receptors is paramount in ensuring an appropriate immune response to an inflammatory stimulus, especially in the case of cancer. One such receptor, Atypical Chemokine Receptor 1 (ACKR1/DARC), is a genetically diverse transmembrane GPCR that can buffer pro-inflammatory CXC- and CC- chemokine activity in circulation and within tissues, influencing leukocyte migration. While the basic immunological function of this receptor is known, the specific function of its two genetic isoforms, A and B, is not. These isoforms are produced by two alternative promoters and distinct mRNA splicing events. Isoform A is not split by introns, even in the untranslated regions, and offers homology to CXCL8. The alternative splice variant, Isoform B, does contain an intron, and follows the GT-AG splicing rule, including a novel exon coding for an additional 7 amino acids. This localizes to the N-terminus, making up part of the extracellular binding region of the receptor. We aim to determine if the two major ACKR1 isoforms have distinct functional abilities to bind or sequester pro-inflammatory chemokines in epithelial breast cell lines. By creating isoform specific overexpression and knockout constructs, and transiently transfecting the DNA into our subtype specific cell lines, we can use an ELISA assay to determine chemokine concentration in the media, and measure differences based on isoform specificity. Using immunofluorescence, we first show that ACKR1 and our two proinflammatory chemokines, CCL2 and CXCL8, are expressed on the surface of epithelial cells and colocalize. We then indicate that there is an isoform specific difference in chemokine concentration between different breast cancer subtypes, in addition to differences seen in overexpression and knockout cell lines. Determining the functionality of these two isoforms can help us better understand ACKR1's role in the immune system, and its potential role as a prognostic marker in breast cancer.
Citation Format: Brittany D. Jenkins, Rachel N. Martini, Inasia Brown, Melissa B. Davis. The functional relevance of Atypical Chemokine Receptor 1 (ACKR1/DARC) genetic isoforms in 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 5071.
Abstract 511: HPV mediates HNSCC carcinogenesis by exosomal exclusion of tumor suppressive miRNAs
Authors: Khullar Madhu , Singh Varinder , Dogra Nilambra , Sannigrahi Malay , Panda Naresh 
Published: August 2018

Abstract
Background: Exosomes are small vesicles between 40-150 nm in diameter that are secreted by various cell types, including tumor cells. Exosomes of cancer cells are known to be involved in tumor pathology and have altered expression of microRNAs (miRNAs). However, the effect of HPV-16 (Human Papilloma Virus-16) infection on miRNA content of exosomes released by infected HNSCC cells has not yet been explored.
Materials & Methods: Exosomes were isolated from media of cultured HPV positive 93VU-147T and HPV negative UPCI:SCC 116 HNSCC cells and were characterized by Transmission Electron Microscopy. Presence of exosomal marker CD63 was confirmed using western blotting. Small RNA seq of exoRNA of HPV positive and HPV negative cells was carried out. For validation of identified miRNAs, HPV16 E6E7 was cloned into pcDNA3.1(-ve) vector and was transfected into SCC116 cells and stable cells were selected using G418. Differentially expressed miRNAs were validated in cells and exosomes using Real Time PCR.
Results: Seven miRNAs 6724-5p, 6087, 4497, 4792, 4508, 199a-3p and 199b-3p were found to be significantly upregulated in HPV positive HNSCC exosomes as compared to HPV negative HNSCC exosomes from NGS data. Upregulation of these miRNAs was further confirmed in exosomes derived from HPV positive 93VU-147T cells and SCC116 E6E7 cells as compared to HPV negative cells (SCC 116 (3.1-ve) (vector only transfected SCC 116) cells. Expression of these miRNAs was significantly downregulated in 93VU14T and SCC116 E6E7 (HPV +ve) cells as compared to HPV negative cells. Three of these miRNAS (4792, 199a-3p and 199b-3p) are known tumor suppressor miRNAs. miRNA 6724-5p, a novel miRNA was found to be down regulated the most in HPV +ve cells. We identified CBX6, PDK2 and FOXK1 which are known to be involved in carcinogenesis, as its target genes through Targetscan. Expression of these genes was found to be significantly upregulated in HPV positive 93VU-147T cells and SCC116 E6E7 cells as compared to HPV negative cells indicating tumor suppressive role of miRNA 6724-5p in carcinogenesis.
Conclusion: Our results suggest that HPV may mediate HNSCC carcinogenesis by exosomal exclusion of tumor suppressive miRNAs.
Citation Format: Madhu Khullar, Varinder Singh, Nilambra Dogra, Malay Sannigrahi, Naresh Panda. HPV mediates HNSCC carcinogenesis by exosomal exclusion of tumor suppressive miRNAs [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 511.
Abstract 5127: Eradication of the gut microbiota reduces cancer burden in multiple models by modulating the immune system
Authors: Sethi Vrishketan , Kurtom Saba , Tarique Mohd , Giri Bhuwan , Garg Bharti , Lavania Shweta , Ferrantella Anthony , Malchiodi Zoe , Hellmund Leonor , Jacob Harrys Charles , Dawra Rajinder , Banerjee Sulagna , Roy Sabita , Ramakrishnan Sundaram , Saluja Ashok , Dudeja Vikas 
Published: August 2018

Abstract
Introduction: Bacteria residing in the human body outnumber ‘human' cells and most of these bacteria exist in the gut. This gut microbiome forms a unique and dynamic metagenome which changes with nutrition and even disease state. A growing body of evidence has implicated the role of the gut microbiome in modulating our immune system. We aimed to investigate this association in murine models of cancer. Methods: C57BL/6 mice were either orally given saline or a gut sterilizing cocktail of poorly absorbable broad-spectrum antibiotics. These mice were used to model multiple cancers, viz. subcutaneous injection of melanoma cells derived from Tyr::CreER; Braf V600E/+;Ptenlox5/lox5 mice, subcutaneous injection of pancreatic cancer cells derived from KPC (Kras LSL.G12D/+; p53 R172H/+ ;Pdx::Cre) mice, intrasplenic injection of KPC pancreatic cancer cells and intrasplenic injection of B16-F10 melanoma cells. The tumors were immunophenotyped through flow cytometry and immunostained for multiple antigens. Mice plasma was used for chemokine analysis. To confirm the role of immunity, subcutaneous experiments were repeated in mice carrying a Rag1tm1Mom mutation (RAG1 knockout), thereby having an immature adaptive immune system. Results: Gut microbiome depletion reduced tumor burden across all four subcutaneous and hepatic metastases models. This effect disappeared when experiments were repeated in immunosuppressed RAG1 knockout mice. Antibiotic-treated tumors had increased TNF-secreting macrophages and NKT cells as well a higher number of iNOS staining cells in the microenvironment. Plasma from antibiotic-treated tumor-bearing mice had decreased levels of CXCL12, a chemokine known to cause tumor immunosuppression. Conclusion: Eradication of the gut microbiota decreases tumor burden by activating the anti-cancer immune system
Citation Format: Vrishketan Sethi, Saba Kurtom, Mohd Tarique, Bhuwan Giri, Bharti Garg, Shweta Lavania, Anthony Ferrantella, Zoe Malchiodi, Leonor Hellmund, Harrys Charles Jacob, Rajinder Dawra, Sulagna Banerjee, Sabita Roy, Sundaram Ramakrishnan, Ashok Saluja, Vikas Dudeja. Eradication of the gut microbiota reduces cancer burden in multiple models by modulating the immune system [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 5127.
Abstract 514: Lncrna uca1 interacts directly with angiomotin to activate Hippo-YAP signaling in epithelial ovarian cancer
Authors: Lin Xianzhi , Spindler Tassja J. , Gayther Simon A. , Lawrenson Kate 
Published: August 2018

Abstract
The long noncoding RNA (lncRNA) urothelial cancer associated 1 (UCA1) is upregulated in multiple cancers, including epithelial ovarian cancer (EOC). Our present study aims to dissect the functional and mechanistic role of UCA1 in EOC. We first explored the effects of stable UCA1 knockout mediated by CRISPR/Cas9 genome editing. The effects of UCA1 loss were more profound in vivo, as UCA1 knockout significantly impaired tumor growth in a mouse xenograft model. Pathways downstream of UCA1 were catalogued using reverse phase protein arrays, which revealed that YAP signaling is activated in UCA1-overexpressing ovarian cancer cells. To characterize the UCA1 interactome, in vivo RNA antisense purification (UCA1-iRAP) experiments were performed using a modified ChIRP and RAP protocol to isolate in vivo RNA direct interactomes based on hybridization of short (20 base) biotinylated probes at a physiologically relevant temperature (37°C). UCA1-iRAP was performed using an EOC cell model, and proteins extracted were profiled by mass spectrometry (MS). Altogether, 19 unique proteins were reproducibly detected by UCA1-iRAP-MS. Interestingly 16 of these UCA1-associated proteins were not previously known RNA-binding proteins. Integration of UCA1-iRAP-MS data with multilayered functional characteristics of UCA1 knockout/knockdown identified angiomotin (AMOT), a known Hippo-YAP signaling modulator, as potential interacting partner for UCA1. The interaction between UCA1 and AMOT was confirmed using both Western blotting for AMOT using UCA1-iRAP proteins, and RT-qPCR for UCA1 RNA after AMOT immunoprecipitation in 3 independent EOC cell lines. Knockdown experiments showed that AMOT is required for UCA1 to activate the expression of YAP target genes, including CYR61 and AXL. Our results indicate that UCA1 interacts directly with AMOT to promote cell growth by activation of Hippo-YAP signaling in EOC, and for the first time identify UCA1 as a novel upstream regulator of YAP signaling. Moreover, the optimized iRAP method we developed in this study can be readily applied to characterizing the protein, DNA, and RNA interactomes of noncoding or coding transcripts implicated other complex traits.
Citation Format: Xianzhi Lin, Tassja J. Spindler, Simon A. Gayther, Kate Lawrenson. Lncrna uca1 interacts directly with angiomotin to activate Hippo-YAP signaling in epithelial ovarian 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 514.
Abstract 5140: Lipoxins and their role in Kaposi's sarcoma-associated herpesvirus (KSHV) infection and pathogenesis
Authors: Sharma-Walia Neelam , Chandrasekharan Jayashree A. 
Published: August 2018

Abstract
Lipoxins are host anti-inflammatory molecules, which play a vital role in restoring tissue homeostasis. The efficacy of lipoxins and their analog epilipoxins in treating inflammation and related diseases have been well documented. Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL) are two well-known inflammation-related diseases caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Controlling inflammation is one of the strategies adopted to treat KS and PEL, a primary motivation for exploring and evaluating the therapeutic potential of using lipoxins. Our study demonstrates how KSHV manipulates and downregulates the secretion of the anti-inflammatory lipoxin A4 in host cells and the viral factors involved in this process using in vitro KS and PEL cells as models. Presence of lipoxin receptor [ALX/Formyl peptidyl receptor (FPR)] in human KS patient tissue sections and in vitro KS and PEL cell models offers a novel possibility for treating KS and PEL with lipoxins. Treating de novo KSHV-infected endothelial cells with lipoxin and epilipoxin creates an anti-inflammatory environment by decreasing levels of NFκB, AKT, ERK1/2, COX-2, and 5-lipoxygenase. Lipoxin treatment on CRISPR/CAS9 technology-mediated ALX/FPR gene-deleted U2OS cells revealed the importance of the lipoxin receptor ALX for effective lipoxin signaling. A viral miRNA cluster was identified as the primary factor contributing to the downregulation of lipoxin A4 secretion in host cells. The KSHV miRNA cluster probably targets enzyme 15-lipoxygenase, which is involved in lipoxin A4 synthesis. Lipoxin treatment in KSHV-infected cells has been shown to reduce cell proliferation and cell survival. Latency factor LANA-1 levels were found to decrease on lipoxin and epilipoxin treatment. Several pro-apoptotic gene levels were upregulated on lipoxin treatment. Several host transcription factors were found to play an important role in regulating KSHV life cycle. This study provides a new insight into the treatment of KS and PEL using nature's own anti-inflammatory molecule, lipoxin.
Citation Format: Neelam Sharma-Walia, Jayashree A. Chandrasekharan. Lipoxins and their role in Kaposi's sarcoma-associated herpesvirus (KSHV) infection and pathogenesis [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 5140.
Abstract 5141: Streptococcus gallolyticus in colorectal cancer development
Authors: Xu Yi , Kumar Ritesh , Taylor John , Xu Juan 
Published: August 2018

Abstract
Streptococcus gallolyticus subsp. gallolyticus (Sg) has been reported to have a strong clinical correlation with colorectal cancer (CRC) for several decades. Our recent data indicates that Sg is able to actively promote the development of colon tumor and thus is also functionally important to CRC. Further investigations into the Sg-CRC connection revealed that there are variations among Sg strains with respect to their ability to stimulate target host cell proliferation and tumor growth. The ability of Sg to adhere to colon cancer cells and to colonize colonic epithelium in vivo appears to be important. The results suggest that direct interactions between specific Sg factors and colonic epithelial receptors/structures are required to trigger downstream signaling events leading to increased host cell proliferation. Furthermore, we observed that the effect of Sg is also dependent on the host genetic background, suggesting a dynamic and complex interactions between Sg and the host. In addition to the requirement for beta-catenin signaling as we previously reported, we observed that Sg activates yes-associated protein 1 (YAP1), a downstream effector in the Hippo signaling pathway. YAP1 activation is required for Sg to stimulate target host cell proliferation. YAP1 and the Hippo pathway are known to be involved in the development CRC. Bacterial activation of YAP1 has not been described before. Thus, our results suggest a novel mechanism by which bacteria contribute to the development of cancer. Studies are on-going to further investigate the molecular details of this mechanism.
Citation Format: Yi Xu, Ritesh Kumar, John Taylor, Juan Xu. Streptococcus gallolyticus in colorectal cancer development [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 5141.
Abstract 5162: Oligodendrocytes might up-regulate the invasiveness of glioblastoma cells via Angiopoietin-2 signaling pathway
Authors: Kawashima Toshiyuki 
Published: August 2018

Abstract
Background & Aims: Glioblastoma (GBM, WHO Grade IV) is considered as the most lethal neoplasm of all solid cancers due to its inherent intensive invasiveness. GBM may arise de novo, or following progression from lower grade gliomas. Recently, solid tumor progression has been recognized as the product of an evolving crosstalk between the cancer cells and its surrounding glial cells. The intensive invasion activity of GBM cells might be regulated by surrounding normal cells such as oligodendrocytes or fibroblasts. In this study, we evaluated the interactive factors between GBM cells and normal glial cells to determine the role of oligodendrocytes in regulating the invasiveness of glioblastoma cells. Methods: Two GBM cell lines, T98G and U251, were used. Two oligodendrocyte cell lines, ODC1 and ODC2, were derived one each from surgical tissues of patients with low-grade glioma (WHO Grade II). Two fibroblasts cell lines, GF1 and GF2, were derived one each from surgical tissues of patients with GBM. Oligodendrocytes and fibroblasts were confirmed by immuno-histochemical staining. The invasive property of GBM cells was analyzed in the presence or absence of conditioned medium from oligodendrocytes or fibroblasts by wound-healing assay and Boyden chamber invasion assay. The proliferation ability of GBM cells was examined by MTT assay. Subsequently Cytokine array was used to examine the cytokines and growth factors in the conditioned medium from oligodendrocytes or fibroblasts. Results: Oligodendrocyte cells, ODC1 and ODC2 cells, significantly (p&lt;0.01) increased the migration and invasion ability of GBM cells, T98G and U251. In contrast, fibroblasts, GF1 and GF2 cells, did not affect the migration and invasion ability of GBM cells. Cytokine array indicated that Angiopoietin-2 was found in the conditioned medium from oligodendrocytes, but not that from fibroblasts. Angiopoietin-2 significantly (p&lt;0.01) increased the invasiveness of GBM, but not their proliferation ability.
Conclusion: Oligodendrocytes might up-regulation of the invasiveness of GBM cells via angiopoietin-2 signaling pathway. Hence, angiopoietin-2 can be considered as a promising target for the treatment of malignant gliomas.
Citation Format: Toshiyuki Kawashima. Oligodendrocytes might up-regulate the invasiveness of glioblastoma cells via Angiopoietin-2 signaling pathway [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 5162.
Abstract 5163: Rab11 regulates focal adhesion kinase dynamics in sarcoma cell migration
Authors: Kao Ling-Yi , Wei Wan-Chen , Chiu Hsiang-Ling , Wu Yi-Che , Chao Wei-Ting 
Published: August 2018

Abstract
Focal adhesion (FA) turnover has been demonstrated to play an important role in controlling cell migration and cancer metastasis. FA disassembly was shown to be regulated by endocytosis during cell migration. Rabs are a kind of GTPase that participate in various cellular vesicle transports; however, whether the Rabs play a role in mediating vesicle transport for FA formation is not clear. This study focuses on Rab11, which plays a role in endosome recycling, and examines whether Rab11 has regulatory function in FA formation during cell migration. Wild-type and deficient Rab11 were transfected into human HT1080 fibrosarcoma cells, the cell migration ability was determined by trans-well assay, the localization of Rab11 and focal adhesion molecules were monitored by confocal microscopy and the in vivo study was carried out with subcutaneous xenograft mouse model to evaluate the effect of Rab11 on tumor growth. Results showed Rab11 deficiency inhibited sarcoma cell migration; the Rab11 was also found colocalized with recycled β1 integrin and affected focal adhesion formation. The live image results demonstrated the inactive GDP form Rab11 has no effect on random cell migration; however, the Rab11 knockdown inhibited random cell migration. We further used immunofluorescence and immunoprecipitation and identified the physical interaction of Rab11 and FAK. In the in vivo study, wild-type Rab11 transfected cells increased the tumor volume in xenograft mouse, but not in Rab11-deficient cells. Taken together, the results suggested Rab11 affected cell migration by regulating focal adhesion dynamics through integrin recycling and the effect of Rab11 may be through protein-protein interaction other than GTP activation.
Citation Format: Ling-Yi Kao, Wan-Chen Wei, Hsiang-Ling Chiu, Yi-Che Wu, Wei-Ting Chao. Rab11 regulates focal adhesion kinase dynamics in sarcoma cell migration [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 5163.
Abstract 5171: Tfap2b overexpression contributes to tumor growth & progression of thyroid cancer through AKT&VEGF/PEDF signaling pathway
Authors: Fu Xiaoyan , Yang Zhongyuan , Chen Shuwei 
Published: August 2018

Abstract
TFAP2 is a family of transcription factors implicated in many aspects of development.TFAP2B is a member of the AP2 transcription factor family, which orchestrates a variety of cell processes. However, the roles of TFAP2B in regulating thyroid carcinogenesis remain largely unknown. Here, we investigated the regulatory effects of TFAP2B on thyroid cancer growth & identified the underlying mechanisms of actions in thyroid cancer cells.We examined the expression of TFAP2B in thyroid cancer cell lines & tumor tissues. We also analyzed the TNM staging of TFAP2B in thyroid cancer. Then we investigated the molecular mechanisms by which TFAP2B knockdown or overexpression regulated thyroid cancer cell growth, angiogenesis & apoptosis, & further confirmed the role of TFAP2B in tumor growth in a thyroid cancerxenograft mouse model.TFAP2B was expressed in thyroid cancer lines &tumortissues,especially in anaplastic thyroid cancer. Strong TFAP2B expression showed a positive correlation with the poor differentiation of patients with thyroid cancer . TFAP2B knockdown by siRNA significantly inhibited cell growth & induced apoptosis in thyroid cancer cells in vitro & in a thyroid cancersubcutaneous xenograft model, whereas TFAP2B overexpression promoted cell growth. The observed regulation of cell growth was accompanied by the TFAP2B-mediated modulation of the VEGF/PEDF-dependent signaling pathways in thyroid cancer cells.These results indicate that TFAP2B plays a critical role in regulating thyroid cancer growth & could serve as a promising therapeutic target or diagonistic biomarker for thyroid cancer .
Citation Format: Xiaoyan Fu, Zhongyuan Yang, Shuwei Chen. Tfap2b overexpression contributes to tumor growth & progression of thyroid cancer through AKT&VEGF/PEDF signaling pathway [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 5171.