bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5145: PAH-metabolizing microorganism in the oral cavity of smokers
Authors: Adami Guy R. , Tao Lin , Pavlova Sylvia , Green Stefan J. , Naqib Ankur , Salameh Benjamin , Tang Jessica L. , Schwartz Joel L. 
Published: August 2018

Abstract
Certain soil microorganisms have been identified as being not only resistant to polycyclic aromatic hydrocarbons (PAHs) but also capable of metabolizing these compounds. We hypothesized that a subset of oral bacteria may be enriched by the altered oral environment of the tobacco smoker with relatively high levels of PAHs. We identified microorganisms that survived long term in minimal media with PAH as the sole carbon source and showed they were much more likely to be isolated from smokers. To start to determine their contribution to oral health, we measured their level in vivo on two mucosal surfaces. On both gingival and lateral border of the tongue mucosa, a group of bacteria were seen to be at lower relative numbers in those exposed to cigarette smoke, while a minority increased. Three taxons were shown to be enriched on gingiva on the family, Streptococcaceae, or genus level, Staphylococcus and Granulicatella. On tongue, genera Mogibacterium and Dialister were enriched. Of bacteria genera that survived harsh PAH exposure in vitro, one was found at substantial levels in the oral mucosal microbiome. Staphylococcus was enriched approximately 6x in smokers, suggesting that the reason for its increase in smokers is due to its resistance to PAH. We will report on this and other oral microbes that can metabolize PAHs. This study highlights the possibility that the oral microbiome can metabolize PAHs like those in cigarette smoke, resulting in carcinogenic products that may contribute to the cancer process in vivo.
Citation Format: Guy R. Adami, Lin Tao, Sylvia Pavlova, Stefan J. Green, Ankur Naqib, Benjamin Salameh, Jessica L. Tang, Joel L. Schwartz. PAH-metabolizing microorganism in the oral cavity of smokers [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 5145.
Abstract 5146: Administration of Parabacteroides distasonis in the attenuation of colorectal tumorigenesis in a carcinogenic murine model of colorectal cancer
Authors: Gacasan Camilo Anthony G. 
Published: August 2018

Abstract
Colorectal cancer (CRC) is the second leading cause of related deaths in the United States. Interindividual differences in genetic background result in a complex and dynamic system between the gut microbiome and variable phenotypic response to diet as it relates to CRC risk. Previous research from our laboratory investigated CRC susceptibility in an azoxymethane (AOM) murine model using FVB/NJ (FVB) and C57Bl/6J (B6) mice fed a ketogenic (high fat, no carbohydrate) American (high fat, high carbohydrate) or standard (moderate fat, moderate carbohydrate) mouse chow. Tumor multiplicity was dependent on both strain and diet with a four-fold increase reported in FVB mice fed ketogenic diet relative to those fed standard chow. This response was not observed in FVB mice fed the American diet or in B6 mice on any of the three diets. A subsequent study that investigated the physiological response to diet in multiple genetic backgrounds revealed a decrease in the abundance of the bacterial species Parabacteroides distasonis in FVB mice fed a ketogenic diet. This established an emphasis on the interaction between variable response to diet, gut microbiome and further implications to gut health. To further investigate this relationship in FVB mice we are using an AOM-induced carcinogenic model on FVB mice fed a ketogenic diet supplemented with a biweekly gavage of P. distasonis. Upon necropsy, tumor load of mice receiving the experimental gavage will be compared to the control mice. Droplet digital PCR will be used to quantify the absolute abundance of P. distasonis in fecal samples at several time points before and after the initiation of diet and administration of AOM. Ultimately, we aim to determine the relationship between P. distasonis and CRC tumorigenesis, which will lead to a further understanding of the etiology of colorectal cancer.
Citation Format: Camilo Anthony G. Gacasan. Administration of Parabacteroides distasonis in the attenuation of colorectal tumorigenesis in a carcinogenic murine model of colorectal 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 5146.
Abstract 515: Integrative analysis of LncRNA-drug interactions in cancer identified EPIC1 as an oncogenic lncRNA that regulates breast cancer tumorigenesis and iBET resistance through regulating MYC transcriptional activity
Authors: Wang Yue , Wang Zehua , Yang Bo , Zhang Min , Yang Da 
Published: August 2018

Abstract
Emerging evidence suggests that lncRNAs can serve as promising biomarkers and therapeutic targets in cancer. Here, by integrating multiple dimensional pharmacogenomic data of 11,950 lncRNA in 5,605 tumors and 1,005 cancer cell lines, we build lncRNA drug response models for 265 anti-cancer compounds across 27 cancer types. Our study reveals the cancer cell lines can realistically recapitulate patient tumors in IncRNA genomic and epigenetic alterations. Using Elastic Net (EN) regression model combined with bootstrap cross validation, our analysis identified 162,327 unique lncRNA-drug interactions. The robustness of lncRNA based EN-models is validated by independent cancer cell line drug response data. By applying lncRNA EN-models of 49 FDA approved drugs to TCGA pan-cancer patient samples across 21 caner types, we have shown that the cancer cell line based EN-models could readily predict chemotherapy responses in patients with breast, stomach, thyroid, and colon rectal cancer. Further lncRNA-protein coding gene co-expression analysis reveals that drug-predictive lncRNAs regulated drug-metabolism and drug-target pathways, which provide underlying mechanism for lncRNAs' regulation of drug response. This analysis has identified a novel intergenic lncRNA, EPIC1, regulates breast cancer tumorigenesis and iBET (Bromodomain Inhibitors) resistance through directly interacting with MYC and regulating MYC transcriptional activity. Knockdown of EPIC1 in breast cancer cells leads to inhibition of colony formation, cell cycle arrest, and suppression of tumor growth in vitro and in vivo. Overexpression of EPIC1 increased MYC target expression, breast tumorigenesis in vitro and in vivo, and promote iBET resistance in breast cancer. Mechanistically, EPIC1 directly interacts with MYC through EPIC1's 129-283 nt region. EPIC1 knockdown reduces the occupancy of MYC protein to the promoters of its target genes (e.g., p21, CCNA2, CDC20, and CDC45) without influencing MYC expression. The oncogenic effect of EPIC1 can be abolished by MYC knockdown. To our best knowledge, this is the first study to link noncoding genotypes with drug response phenotypes in both cancer cell lines and patient tumors.
Citation Format: Yue Wang, Zehua Wang, Bo Yang, Min Zhang, Da Yang. Integrative analysis of LncRNA-drug interactions in cancer identified EPIC1 as an oncogenic lncRNA that regulates breast cancer tumorigenesis and iBET resistance through regulating MYC transcriptional activity [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 515.
Abstract 5150: Loss of CYLD promotes cell invasion via ALK5 stabilization in oral squamous cell carcinoma
Authors: Shinriki Satoru , Jono Hirofumi , Maeshiro Manabu , Nakamura Takuya , Guo Jianying , Li Jian-Dong , Yoshida Ryoji , Shinohara Masanori , Nakayama Hideki , Matsui Hirotaka , Ando Yukio 
Published: August 2018

Abstract
Oral squamous cell carcinoma (OSCC) has a very poor prognosis because of its highly invasive nature, and the 5-year survival rate has not changed appreciably for the past 30 years. Although cylindromatosis (CYLD), a deubiquitinating enzyme, is thought to be a potent tumor suppressor, its biological and clinical significance in OSCC is largely unknown. This study aimed to clarify the roles of CYLD in OSCC progression. Our immunohistochemical analyses revealed significantly reduced CYLD expression in invasive areas in OSCC tissues, whereas CYLD expression was conserved in normal epithelium and carcinoma in situ. Furthermore, downregulation of CYLD by siRNA led to acquisition of mesenchymal features and increased migratory and invasive properties in OSCC cells and HaCaT keratinocytes. It is interesting that CYLD knockdown promoted TGF-β signaling by inducing stabilization of TGF-β receptor I (ALK5) in a cell autonomous fashion. In addition, the response to exogenous TGF-β stimulation was enhanced by CYLD downregulation. The invasive phenotypes induced by CYLD knockdown were completely blocked by an ALK5 inhibitor. Also, lower CYLD expression was significantly associated with the clinical features of deep invasion, poor overall survival, and increased Smad3 phosphorylation, which is an indicator of activation of TGF-β signaling in invasive OSCC. These findings suggest that downregulation of CYLD promotes invasion with mesenchymal transition via ALK5 stabilization in OSCC cells.
Citation Format: Satoru Shinriki, Hirofumi Jono, Manabu Maeshiro, Takuya Nakamura, Jianying Guo, Jian-Dong Li, Ryoji Yoshida, Masanori Shinohara, Hideki Nakayama, Hirotaka Matsui, Yukio Ando. Loss of CYLD promotes cell invasion via ALK5 stabilization in oral squamous cell 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 5150.
Abstract 516: Long noncoding RNA NEAT1 promotes lung metastasis of soft tissue sarcoma
Authors: Huang Jianguo , Xu Eric , Sachdeva Mohit , Robinson Timothy , Qin Xiaodi , Zhang Dadong , Owzar Kouros , Gokgoz Nalan , Seto Andrew , Andrulis Irene , Wunder Jay , Okada Tomoyo , Singer Samuel , Lazar Alexander , Rubin Brian , Kirsch David G. 
Published: August 2018

Abstract
Soft tissue sarcomas (STS) are malignant tumors from diverse mesenchymal tissues. About 40% STS patients develop fatal lung metastasis with a median survival of 15 months. The mechanisms driving the development of lung metastasis in sarcoma patients are poorly understood. Therefore, our lab has developed a genetically engineered mouse model (GEMM) of high-grade primary STS with conditional mutations in Kras and Trp53 (KP) where 40% of mice tumors develop lung metastasis. This KP model recapitulates human patients with Undifferentiated Pleomorphic Sarcoma (UPS), one of the most common subtypes of STS diagnosed in adults. RNA sequencing (RNA-Seq) was performed on paired primary and lung metastases in KP mouse sarcomas and determined that the expression of the long non-coding RNA (lncRNA) Neat1 is increased in lung metastases compared to paired primary tumors. Real time PCR (qPCR) in 22 paired KP mouse primary sarcomas and lung metastases further confirmed that Neat1 is significantly upregulated in lung metastases. In addition, RNA-Seq data from 5 pairs of human primary sarcomas and matched lung metastases also showed that NEAT1 levels are increased in lung metastases. Furthermore, NEAT1 RNA in situ hybridization (ISH) on tissue microarrays (TMAs) of human primary UPS and lung metastases determined that the expression of NEAT1 is upregulated in lung metastases. Next, CRISPR/Cas9 technology was applied to delete Neat1 in primary mouse sarcoma cells and loss of expression of Neat1 was confirmed by qPCR and northern blot in knockout (KO) clones. In addition, loss of Neat1 significantly reduced lung metastasis in vivo following tail vein injection of these modified cells into nude mice. To further test that loss of Neat1 reduces lung metastasis in primary sarcoma mouse model, primary tumors with Neat1 deletion are generated in GEMMs using in vivo CRISPR/Cas9 technology and KrasLSL-G12D/+; Trp53Flox/Flox; Neat1-/- (KPN) mouse model. Finally, RNA-Seq and capture hybridization analysis of RNA targets (CHART) are performed to determine mechanisms by which Neat1 regulates lung metastasis. Overall, these results suggest that upregulation of Neat1 promotes lung metastasis of soft tissue sarcoma and NEAT1 is a potential target to prevent or treat lung metastasis in sarcoma patients.
Citation Format: Jianguo Huang, Eric Xu, Mohit Sachdeva, Timothy Robinson, Xiaodi Qin, Dadong Zhang, Kouros Owzar, Nalan Gokgoz, Andrew Seto, Irene Andrulis, Jay Wunder, Tomoyo Okada, Samuel Singer, Alexander Lazar, Brian Rubin, David G. Kirsch. Long noncoding RNA NEAT1 promotes lung metastasis of soft tissue sarcoma [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 516.
Abstract 5166: Lysyl oxidase regulates cell surface EGFR, and directionality of cancer cell invasion
Authors: Tang Haoran , Springer Caroline , Marais Richard 
Published: August 2018

Abstract
Lysyl oxidase (LOX) remodels the tumour microenvironment by cross-linking the extracellular matrix. LOX overexpression is associated with poor cancer outcomes. We find that LOX regulates the epidermal growth factor receptor (EGFR) to drive tumour progression. LOX regulates EGFR by suppressing TGFβ1 signalling through the secreted protease HTRA1. This increases the expression of Matrilin2 (MATN2), an EGF-like domain containing protein that traps EGFR at the cell surface to facilitate its activation by EGF. A novel pharmacological inhibitor of LOX, CCT365623, disrupts EGFR cell surface retention in vitro and delays the growth of primary tumour cells in vivo. In addition to its role in controlling primary tumour growth, LOX expression is also implicated in the processes of cancer cell invasion, and thereby the process of metastasis. Notably, we find that when LOX is depleted or inhibited, cancer cells are no longer able to sence a chemo-attractive gradient, and invade in a directional manner. Importantly, LOX produced by both cancer cells and fibroblasts can mediate this behaviour. Together, we show that LOX regulates EGFR cell surface retention to drive tumour progression. We also find that LOX does not regulate cancer cell invasion per se, but rather that it regulates the directionality of cancer cell migration, and both the cancer and stromal cells appear to contribute to this behaviour.
Citation Format: Haoran Tang, Caroline Springer, Richard Marais. Lysyl oxidase regulates cell surface EGFR, and directionality of cancer cell 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 5166.
Abstract 5168: Understanding the role of integrins in breast cancer
Authors: Adorno-Cruz Valery , Liu Xia , Liu Huiping 
Published: August 2018

Abstract
Breast cancer is a highly prevalent disease and the second-leading cancer related death in women. Mortality rates have declined a 38% in recent years thanks to early detection and development of treatments. However, the five year survival rate of patients with a distant metastasis is only 26%. Hence, it is important to identify key players that mediate or promote the migration of cells to other organs. Integrins are cell surface receptors that mediate cell adhesion to the extracellular matrix. They are involved in roles such as cell migration and proliferation. In this project we seek to understand the role of integrin α2 in breast cancer metastasis. It has been previously reported that integrin α2 is a metastasis suppressor of a Her2+ model of breast cancer. However, its role in triple negative breast cancer is unknown. We found the integrin α2 gene (ITGA2) a target of has-miR-206 which controls metastasis and stemness of breast cancer. We hypothesize integrin α2 has a metastasis regulating role in triple negative breast cancer. The triple negative breast cancer cell line, MDA-MB-231 has been used to characterize the role of integrin α2 in migration, cell viability and lung colonization of mice injected though tail vein injection. Lung colonization of breast cancer cells in NSG mice is significantly altered by the knockdown expression of integrin α2. Consistent with the phenotypes in migration and invasion. Taken together, these results suggest integrin α2 regulates breast cancer metastasis through modified cell migration and lung colonization.
Citation Format: Valery Adorno-Cruz, Xia Liu, Huiping Liu. Understanding the role of integrins 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 5168.
Abstract 5183: Using transposon elements to elucidate the genetic mechanisms of HCC-associated lung metastases
Authors: Lo Lilian H. , Chiu Amy P. , Li Xiao-Xiao , Tschida Barbara R. , Rowlands Dewi K. , Largaespada David A. , Keng Vincent W. 
Published: August 2018

Abstract
Metastases account for most cancer-related deaths as a result of primary cancer spreading to distant sites. Amongst human hepatocellular carcinoma (HCC), there is a drastic decrease in the survival rate observed in patients with early stage localized HCC to late stage metastasis-associated HCC. Importantly, the genetic mechanisms associated with metastasis-associated HCC remains elusive. Therefore, a forward genetic screen in mice using Sleeping Beauty (SB) insertional mutagenesis system was developed to identify genes associated with metastasis-associated HCC.
Truncated version of the epidermal growth factor receptor (Egfr) gene was frequently detected in both mouse primary liver tumors and lung metastases, which was confirmed by DNA sequencing and RNA sequencing. This indicates the importance of Egfr mutations for liver tumorigenesis and the metastasis process. More importantly, additional candidate genes involved in the metastasis process were also identified by our forward genetic screen and showed to be relevant in human HCC patients at the M1 cancer metastasis stage. Taken together, our study shows that the SB screen yields a high fraction of relevant events in human liver cancer and can provide valuable information on the evolution of metastasis-associated HCC.
The authors declare that they have no competing interests.
Citation Format: Lilian H. Lo, Amy P. Chiu, Xiao-Xiao Li, Barbara R. Tschida, Dewi K. Rowlands, David A. Largaespada, Vincent W. Keng. Using transposon elements to elucidate the genetic mechanisms of HCC-associated lung metastases [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 5183.
Abstract 5184: Expression and role of regulator of G-protein signing 5 in squamous cell carcinoma of the tongue
Authors: Abe Yushi , Yano Hirohisa , Akiba Jun , kondou Reiichirou , Ogasawara Sachiko , Nakamura Ken , Kusukawa Zingo 
Published: August 2018

Abstract
Objective: Regulator of G-protein signing (RGS) 5 is a member of the RGS family and acts as GTPase-activating proteins for heterotorimeric G protein αsubunits, negatively regulating G-protein signaling. RGS5 was reportedly expressed in the heart, lung, skeletal muscle and small intestine and relates with tumor angiogenesis and gestational hypertension. It was reported that RGS5 was related with the invasion and metastasis of cancers, such as non-small lung cancer and hepatocellular carcinoma. In the present study, we examined RGS5 expression and its relation with invasion in squamous cell carcinoma (SCC) of the tongue. Materials and Methods: For immunohistochemical analysis for RGS5, we used SCC tissues of the tongue obtained from 43 patients who underwent resection at Kurume University Hospital from 2011 to 2015. The staining intensity was graded as 0, negative; 1, weak; 2, moderate; 3, strong. The staining intensity in the normal epithelium was used as an internal control. We examined relationship between RGS5 expression in invasive portions and clinicopathological features (e.g., lymph node metastasis, depth of tumor, and mode of invasion, and so forth). Mode of invasion was classified into 3 levels, i.e., IFNa (expansive), IFNc (invasive), IFNb (between INFa and INFc). Depth of tumor was measured and classified into 2 levels: &lt; 5 mm and ≥ 5mm. Comparison and estimation of cumulative survival rates were performed using the Kaplan-Meier curves and log rank test. Result: Non-cancerous squamous cells expressed RGS5 solely in nucleus. SCC cells in superficial portion of tumor nodules often expressed weak nuclear RGS5 expression. In invasive portions of the tumor nodules, SCC cells expressed significantly lower nuclear and higher cytoplasmic RGS5 expression. A significant correlation was found between the expression score of RGS5 at invasive portions and mode of invasion (P=0.009). When the 43 cases were subdivided into two groups, i.e., expression group (score 1-3) and non-expression group (score 0), significant differences were observed in mode of invasion (P=0.0042), lymph node metastasis (p=0.0314), depth of tumor (p=0.0239) between the two groups. The log-rank test revealed that postoperative early lymph node metastasis was significantly higher in the expression group (p= 0.0415). Conclusion: This study suggests that RGS5 expression is related with tumor invasion in SCC of the tongue and that RGS5 can be a predictor of postoperative early lymph node metastasis.
Citation Format: Yushi Abe, Hirohisa Yano, Jun Akiba, Reiichirou kondou, Sachiko Ogasawara, Ken Nakamura, Zingo Kusukawa. Expression and role of regulator of G-protein signing 5 in squamous cell carcinoma of the tongue [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 5184.