bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1489: Differential gene expression profiles between normal cervical tissue and high-grade squamous intraepithelial lesion expressing p16 and high-risk HPV E6/E7 mRNA
Authors: Benedetti Ines , Barrios Lia , Reyes Niradiz 
Published: August 2018

Abstract
Background:
HPV is necessary but not sufficient for development of uterine cervix carcinoma. There are genetic factors that influence the progression of premalignant lesions. Gene expression profile differences between healthy and premalignant lesion could contribute to identify potential biomarkers for each step of cervical tumor progression.
Design:
A female patient with an initial diagnosis of low grade squamous intraepithelial lesion (SIL) was invited to participate in the study. During follow-up a high grade SIL was observed by colposcopy, and two samples were obtained from the lesion: one sample was processed for histopathologic diagnosis, and additionally stained by IHC with p16 antibody; the other sample, along with a matched sample of healthy tissue taken distantly from the lesion were stored in a nucleic acids preservation reagent for subsequent analysis of gene expression. Differences in gene expression between healthy tissue and high grade SIL tissue were assessed in triplicate using the cDNA gene expression Illumina microarray Human-HT-12-V4. A statistical p value was computed comparing expression levels from the tissue lesion and healthy tissue. Genes with a fold-change ≥ 2 and a p value &lt;0.05 were regarded as differentially expressed. Additionally, two cervix swabs were obtained for detection of HPV DNA by PCR, and for assessment of high risk HPV E6/E7 mRNA expression by RT-PCR.
Results:
Histopathological evaluation of the lesion confirmed a high grade squamous intraepithelial lesion, with positive p16 staining. HPV-18 DNA was detected and E6/E7 HPV 18 mRNA expression was confirmed. Gene expression analysis detected 33 overexpressed genes, including TMEM45A, SPRR2B, KRT16 and RBP1, and 30 underexpressed genes, including SPARCL1, GCNT3, TMPRSS11b
and ESR1, in high grade SIL compared to healthy uterine cervical tissue. Overexpressed genes belonged to important cellular pathways, such as queratinization, defensins, cytoskeletal signaling, cellular adhesion and extracellular matrix remodeling. Underexpressed genes belonged to metabolic pathways, cell trafficking, and chemokine signaling, among others.
Conclusions:
Microarray analysis identified differential expression between healthy cervical tissue and high grade SIL with confirmed HPV-18 transforming infection. Differentially expressed genes belonged to important cellular pathways. Further studies are required to evaluate the usefulness of these genes as risk markers for progression.
Citation Format: Ines Benedetti, Lia Barrios, Niradiz Reyes. Differential gene expression profiles between normal cervical tissue and high-grade squamous intraepithelial lesion expressing p16 and high-risk HPV E6/E7 mRNA [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 1489.
Abstract 1496: Different effects of lncRNA NDRG1-OT1_v4 fragments on regulating NDRG1 transcription in breast cancer cells under hypoxia
Authors: Yeh Chingching , Tsai Mong-Hsun , Chuang Eric , Lai Liang-Chuan 
Published: August 2018

Abstract
Hypoxia is a crucial factor in aggressiveness of solid tumor by driving multiple signaling pathways. Recent researchers indicated that long non-coding RNA (lncRNA) could promote or inhibit tumor aggressiveness by regulating gene expression. Previous studies in our laboratory found the expression of lncRNA NDRG1-OT1_v4 significantly increased under hypoxia by next-generation sequencing (NGS). Moreover, it was discovered that the NDRG1-OT1_v4 inhibited NDRG1 at both mRNA and protein levels of NDRG1. At the protein level, NDRG1-OT1_v4 improved NDRG1 degradation via ubiquitin-mediated proteolysis pathway. However, the repressive mechanism of NDRG1 at RNA level was still unknown. In this studies, we found that NDRG1-OT1_v4 decreased the NDRG1 promoter activities when we overexpressed NDRG1-OT1_v4 under hypoxia. The fragment (150-263 nt) of NDRG1-OT1_v4 repressed NDRG1 promoter activity significantly by increasing the binding affinity of hnRNPA1. On the other hand, another fragment (264-392 nt) of NDRG1-OT1_v4 improved NDRG1 promoter activity by recruiting HIF-1 alpha. In conclusion, we found a novel mechanism that different fragments of same lncRNA could cause opposite effects on the identical target gene. Keywords: Hypoxia, LncRNA, NDRG1-OT1_v4, NDRG1, HIF-1 alpha, hnRNPA1
Citation Format: Chingching Yeh, Mong-Hsun Tsai, Eric Chuang, Liang-Chuan Lai. Different effects of lncRNA NDRG1-OT1_v4 fragments on regulating NDRG1 transcription in breast cancer cells under hypoxia [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 1496.
Abstract 15: PA28γ contributes to tumor angiogenesis through regulation of IL-6 and CCL2 in oral squamous cell carcinoma
Authors: Zeng Xin , Li Jing , Liu Jiajia , Ji Ning , Feng Hui , Chen Qianming 
Published: August 2018

Abstract
Background: PA28γ has been shown to promote tumor development and progression. Although PA28γ has been suggested to play a role in tumor angiogenesis, direct evidence for the molecular mechanisms underlying this phenomenon have not been investigated.
Methods: Oral squamous cell carcinoma (OSCC) stable cell lines with varying levels of PA28γ expression were constructed. EA.hy926 human endothelial cells were co-cultured with these lines to evaluate the influence of PA28γ on EA.hy926 cell proliferation, migration, invasion, and tube formation. Using a subcutaneous xenotransplantation tumor model of under-expressing PA28γ HSC-3 cells, we explored effects on tumor angiogenesis in nude mice. We performed screens of the different angiogenesis-related genes and cytokines being expressed using PCR and cytokine chips to identify candidates with the potential to affect tumor angiogenesis. Then, candidates were verified using Western blot, and neutralization tests immunohistochemistry. Finally human OSCC clinical cohort was used to validate.
Results: PA28γ could enhance the ability of OSCC cells to interact with endothelial cells, thereby recruit endothelial cells and induce angiogenesis. Ablation of PA28γ inhibits tumor-induced angiogenesis in xenografts mice model in vivo. In vivo zebrafish model experiments showed that depleted PA28γ remarkably blocked the formation of intersegmental vessels in zebrafish embryos. Furthermore, Angiogenesis-related PCR, cytokine chips and Western blot analysis indicated that PA28γ through regulate IL-6 and CCL2 expression, thereby subsequent activation of the Stat3/VEGF and PI3K/MMP-1 axis to promote angiogenesis. Neutralization or block results IL-6 and CCL2 has an essential role in PA28γ-controlled promotes of angiogenesis. In addition, clinical OSCC cohort validate that PA28γ positively correlates with IL-6 or CCL2 expression.
Conclusion: Collectively, our data show that PA28γ contributes to the tumor angiogenesis, by regulating IL-6 and CCL2. PA28γ thus represents a novel therapeutic target for treating PA28γ-positive OSCC cancers.
Citation Format: Xin Zeng, Jing Li, Jiajia Liu, Ning Ji, Hui Feng, Qianming Chen. PA28γ contributes to tumor angiogenesis through regulation of IL-6 and CCL2 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 15.
Abstract 150: Elucidating the molecular mechanisms of cutaneous melanoma development from melanocyte stem cells
Authors: Moon Hyeongsun , Donahue Leanne , Zhu Jerry , White Andrew 
Published: August 2018

Abstract
Cutaneous melanoma is the most lethal form among all skin cancers. Multiple genetic etiologies have been identified in primary and metastatic tumors, however, the cellular origin for cutaneous melanoma and their related molecular mechanisms required for early steps of melanoma initiation have not been well defined. Although great progress has been made in the development of targeted therapies for malignant melanoma, knowledge on the factors that can cause tumor formation would provide valuable insight for melanoma prevention and control. Here, our study aims to determine potential means of prevention by identifying the extrinsic environmental factors and cellular conditions responsible for melanoma initiation particularly from tumor-competent melanocyte stem cells. In the study, adult stem cells have been discovered as a compelling candidate for melanoma formation. We also found that quiescent stem cells are relatively unable to develop melanocytic tumors. On the other hand, environmental and physiological stresses can significantly alter the status of melanocyte stem cells which in turn causes melanoma development. Screening the genetic changes that occur in the melanoma-competent stem cells in tumor initiation stages can help to elucidate which molecular pathways may cause the formation of cutaneous melanoma. Our data will provide a new framework for the early initiation steps of cutaneous melanoma from quiescent but tumor-prone stem cells, with the ultimate goal to find better preventative measurements and targeted therapy for cutaneous melanoma.
Citation Format: Hyeongsun Moon, Leanne Donahue, Jerry Zhu, Andrew White. Elucidating the molecular mechanisms of cutaneous melanoma development from melanocyte stem cells [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 150.
Abstract 1507: Multiple mechanisms of Myb gene activation revealed through transcriptome analysis of salivary gland adenoid cystic carcinoma
Authors: Frerich Candace , Brayer Kathryn , Painter Brandon , Ness Scott 
Published: August 2018

Abstract
Adenoid cystic carcinoma (ACC) of the salivary gland is a rare head and neck malignancy with poor long-term prognosis. Hallmark chromosomal translocations result in MYB to NFIB (t(6;9)) and MYBL1 to NFIB (t(8;9)) gene fusions. Gene rearrangement and aberrant expression of the MYB and MYBL1 genes, along with the encoded transcription factors, are the oncogenic driver in the majority of ACC tumors. Previous RNA-sequencing (RNA-seq) data collected from FFPE fixed ACC tumors illustrated MYB and MYBL1 elicit similar gene expression profiles in ACC, suggesting these transcription factors drive ACC oncogenes via similar mechanisms. Using these RNA-seq data we have identified EN1 and SOX4 as important Myb regulated genes and demonstrated activation of their promoters in reporter gene assays. We hope to utilize these reporters in high-throughput screens to identify new drug candidates for ACC. We have utilized RNA-seq data to identify an additional mechanism leading to MYB overexpression that appears unique to ACC tumors. In these tumors transcription of the MYB gene is aberrantly activated through use of an alternative promoter located within the first intron of the gene. Transcripts originating from this promoter have been confirmed in an ACC tumor via 5'RACE and the resulting Myb protein has a small N-terminal truncation eliminating the epitope recognized by a common Myb antibody. The alternative promoter is active and regulated in a cell type specific manner in reporter gene assays. Previous studies have shown chromosomal translocations juxtapose NFIB enhancers to activate MYB gene transcription. ChIP and 3C assays in fresh frozen ACC tumors will be utilized to test the hypothesis that NFIB enhancers are specifically recruited to the alternative MYB promoter, thereby activating gene transcription. Thus, multiple mechanisms lead to the aberrant over-expression and truncation of MYB and drives ACC oncogenesis.
Citation Format: Candace Frerich, Kathryn Brayer, Brandon Painter, Scott Ness. Multiple mechanisms of Myb gene activation revealed through transcriptome analysis of salivary gland adenoid cystic 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 1507.
Abstract 151: Phenotypic selection screening reveals Annexin A2 as a pancreatic cancer stem cell target
Authors: Hurt Elaine M. , Flynn Matt , Hynes Paul , Cabrera M. Carla , Thomas Suneetha B. , Vlerken-Ysla Lilian van , Slater Louise , Sandercock Alan , Rust Steven , Minter Ralph , Herbst Ronald 
Published: August 2018

Abstract
Cancer stem cells (CSCs) represent an important clinical entity given their role in tumor initiation, metastasis and patient relapse. Phenotypic selection allows for identification of novel antigens important in biological processes. Therefore, we undertook a phenotypic selection campaign using a designed ankyrin-repeat (DARPin) library to identify new cancer stem cell (CSC) targets. CSCs generated from late-stage pancreatic cancer patient-derived xenograft (PDX) models were used to pan a designed Ankyrin repeat (DARPin) library. The most prevalent target identified in this screen was Annexin A2 (ANXA2). ANXA2 is a member of the Annexin family that has diverse roles in cancer including proliferation and invasion and is widely expressed in cancer. Furthermore, expression of ANXA2 is linked to poor prognosis in pancreatic cancer. Targeting of Annexin A2 on the surface of pancreatic cancer cells using DARPins resulted in decreased frequency of CSCs both in vitro and in vivo in several pancreatic patient-derived xenografts. ANXA2 DARPins also reduced proliferation and tumor growth of HPAC cells both in vitro and in vivo. Mechanistically, we found that blocking ANXA2 resulted in decreased IL6 and IL8 secretion, two cytokines that have been linked to CSC expansion and survival. Additionally, we found that pharmacological blockade of ANXA2 resulted in decreased plasmin activation, a pathway that has been linked to dissemination of cancer cells. Together our data suggests that targeting of cell surface ANXA2 is effective at reducing CSCs and could be a novel target for the treatment of pancreatic cancer.
Citation Format: Elaine M. Hurt, Matt Flynn, Paul Hynes, M. Carla Cabrera, Suneetha B. Thomas, Lilian van Vlerken-Ysla, Louise Slater, Alan Sandercock, Steven Rust, Ralph Minter, Ronald Herbst. Phenotypic selection screening reveals Annexin A2 as a pancreatic cancer stem cell target [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 151.
Abstract 1514: Role of polycomb proteins in neuroendocrine prostate cancer
Authors: Connelly Zachary , Yang Shu , Blankenship Anthony , Yu Xiuping 
Published: August 2018

Abstract
Prostate cancer (PCa) is the most common non-skin cancer and the 3rd leading cause of cancer-related death in American men. Androgen ablation therapy has been the gold standard for treating advanced stage PCa since the 1960s. Initially, the PCa patients respond to hormone ablation very positively. However, over time these tumors almost always become resistant to androgen ablation therapy, and tumors begin to grow again. Recent studies found after failure of the new drugs that block androgen action, PCa has increased neuroendocrine phenotype. Understanding the mechanisms through which PCa cells gain neuroendocrine phenotype is critical for the development of novel therapeutics. Polycomb repressive complex are involved in early embryo development and carcinogenesis in several types of cancer including PCa. In this study, we evaluated the involvement of Polycomb proteins in neuroendocrine PCa. Using immunohistochemistry staining, we examined the expression of Polycomb protein EZH2 in advanced stage PCa. We found that EZH2 is highly expressed in both human and mouse neuroendocrine PCa. Also, we found when PCa cells are induced to undergo neuroendocrine differentiation, multiple Polycomb genes are induced. These data suggest that Polycomb genes play a role in the development of neuroendocrine PCa.
Citation Format: Zachary Connelly, Shu Yang, Anthony Blankenship, Xiuping Yu. Role of polycomb proteins in neuroendocrine prostate 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 1514.
Abstract 1515: NCOA3 promotes tumor growth by activating telomerase reverse transcriptase and predicts poor prognosis in hepatocellular carcinoma
Authors: Chen Miao , Li Wenbin , Li Yixin , Zhang Changlin , Qin Ge , Long Qian , Shi Dingbo , Guo Wei , Shi Shuihan , Zhang Kefang , Deng Wuguo 
Published: August 2018

Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer death worldwide. The rising incidence and mortality rate of HCC in most countries are due to an increased rate of chronic Hepatitis C virus infection, alcohol abuse and obesity. The molecular mechanisms leading to the development of HCC are complicated, consist of various genetic and epigenetic changes, and are associated with altered signaling pathways. Among these molecular events, elevated expression of human telomerase reverse transcriptase (TERT) is an important alteration in HCC and a hallmark of human cancers. TERT is highly expressed in HCC and positively correlated with the development of HCC. However, the detailed mechanism of TERT activation in HCC remains largely unclear. Here, we identified nuclear receptor coactivator-3 (NCOA3) as a TERT promoter-binding protein, which specifically bound to the -234~-144 region of the TERT promoter. Overexpression of NCOA3 enhanced TERT promoter activity and expression, and promoted HCC cell growth. Moreover, we demonstrated that NCOA3 interacted with the transcription factor SP1 to promote TERT expression. The clinical data showed that the expression of NCOA3 and TERT were positively correlated and elevated in HCC tissues, and HCC patients with high level of NCOA3/TERT had poor prognosis. Collectively, our study revealed that NCOA3 bound to the TERT promoter and activated TERT expression to promote HCC growth, indicating that the NCOA3/TERT signaling pathway could be a potential therapeutic target for HCC. [Funding support: This work was supported by the funds from the National Natural Science Foundation of China (81772925, 81472178, 81702761), the State “973 Program” of China (2014CB542005), and the Natural Science Foundation of Guangdong Province (2016A03031100, 2015A030313018, 2017A030313615)].
Citation Format: Miao Chen, Wenbin Li, Yixin Li, Changlin Zhang, Ge Qin, Qian Long, Dingbo Shi, Wei Guo, Shuihan Shi, Kefang Zhang, Wuguo Deng. NCOA3 promotes tumor growth by activating telomerase reverse transcriptase and predicts poor prognosis 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 1515.
Abstract 1520: Regulation of stemness by perturbation of OCT4-PP1 axis reduces malignancy of embryonal carcinoma
Authors: Song Bomin , Jang Hyonchol 
Published: August 2018

Abstract
OCT4 (encoded by pou5f1) is a master regulator of pluripotency and closely related to tumor malignancies. Its associations with cancer drug-resistance, recurrence and poor prognosis of the patients has been widely reported. As OCT4 transcriptional activity is directly and indirectly involved in the maintenance of cancer stemness, inhibition of OCT4 activity could be a strategy to reduced cancer malignancies by eliminating stemness. In this study, we investigated a way to regulate the stemness of embryonal carcinoma (EC) by perturbation of posttranslational modification of OCT4. First, to confirm the role of OCT4 in the maintenance of stemness in ECs, we generated the cells which are downregulated in OCT4 doxycycline-dependently. Down-regulation of OCT4 caused weaker alkaline phosphates staining, reduced tumor sphere formation, and reduced expression of stemness marker proteins. Also, the cells underwent retardation of proliferation, cell-cycle arrest in G1 phase, and eventual apoptosis by OCT4 downregulation. The most altered genes in ECs by OCT4 downregulation were networked to signaling pathways regulating pluripotent stem cells, Hippo signaling pathways and transcriptional misregulation in cancer. Second, to regulate OCT4 transcriptional activity, we used phosphorylation of serine 236th (S236) on OCT4. ECs cells, with which their endogenous OCT4 was substituted with an OCT4 phosphorylation-mimicking mutant (Serine 236 to aspartate; S236D), showed similar phenotype to those cells that were depleted in OCT4. Chemical inhibition or knockdown of PP1 (protein phosphatase 1), which remove the phosphorylation, induced accumulation of S236 phosphorylation, and also caused similar phenotype to those cells that were depleted in OCT4. Finally, to evaluate whether regulation of OCT4 can reduce tumor malignancy, we tested whether drug-tolerant persister cancer cells could be reduced by regulation of OCT4. Co-treatment of inhibits PP1 activity with cisplatin significantly reduced drug-resistant colonies compared with single treatment of cisplatin. These results suggested that stemness of ECs could be regulated by OCT4 posttranslational modifications and regulation of cancer stemness could reduce tumor malignancy.
Citation Format: Bomin Song, Hyonchol Jang. Regulation of stemness by perturbation of OCT4-PP1 axis reduces malignancy of embryonal 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 1520.
Abstract 1544: Subcutaneous adiposity is an independent predictor in metastases patients
Authors: Tsang Ngan M. 
Published: August 2018

Abstract
Background: The prognostic significance of muscle and adipose tissue in cancer patients provide an appropriate assessment of body composition in recent years. We investigated the independent prognostic significance of visceral and subcutaneous adipose on survival in metastases patients. Methods: We measured visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and muscle index in 959 metastases patients via computed tomography at L3 level. Univariate and multivariate cox proportional hazards model were used to determine mortality hazard ratio (HR) and were presented in corresponding 95% CI. Result: SATI and gender are independent predictors among patients with metastases disease. High SATI linked to lower mortality (HR:0.749; 95% CI: 0.640-0.877; p&lt;0.001) and longer overall survival (8.38 months; 95% CI, 0.10-137.42) in compared to low SATI patients (4.44 months; 95% CI, 0.03-108.36). Conclusion: The body composition appeared to be true determinants of the prognosis in metastases patients. The research provides an understanding of the association between subcutaneous adipose and the overall survival in metastases patients.
Citation Format: Ngan M. Tsang. Subcutaneous adiposity is an independent predictor in metastases patients [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 1544.