bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 129: Apoptosis & anti-proliferative nature of Aescin on 7,12 dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinogenesis via downregulating Notch signaling
Authors: Ramadoss Hemavardhini , Kathiresan Suresh , Gupta Sanjay 
Published: September 2020

Abstract
Worldwide, oral squamous cell carcinoma (OSCC) is the sixth most common cancer & ranked as second most common cancer in India. The most implicated etiologic factors in the development of oral cancer is the use of tobacco, alcohol & also HPV infection. Aescin, a pentacyclic triterpenoid saponin mixtures derived from Aesculus hippocastanum L (horse chestnut) that has been used as traditional herbal medicine, exists the pharmacodynamic properties, anti- edematous, anti-inflammatory & antitumor. The present study, Tumors were induced by applying 0.5% DMBA topically to hamster buccal pouch (HBP) thrice a week for 14 weeks & Aescin was orally administered at a various dose of 40 mg/kg body weight on alternate days of DMBA painting. We observed, reduced the tumor incidence, diminished lipid peroxidation, & elevation of antioxidants, liver marker enzymes by Aescin. Furthermore, aescin induced apoptosis in DMBA induced tumor bearing animals significantly inhibited cell to cell communication of Notch-1, Notch-2 & its ligand & Jagged-1 leads to inhibited expression of the Notch downstream signaling target Hes-1 & Hey-1 analyzed by immunohistochemical analysis. These results clearly suggest that Aescin prevents lipid peroxidation, protects the antioxidant defense system, prohibit the dysplasia & anti-carcinogenic potential. we concluded; the results provide an important new insight of Notch signaling pathway & aescin might be developed as a potential chemo preventive agent for oral cancer.
Key words: Oral cancer, aescin, antioxidant, apoptosis, chemopreventive, Notch signaling
Citation Format: Hemavardhini Ramadoss, Suresh Kathiresan, Sanjay Gupta. Apoptosis & anti-proliferative nature of Aescin on 7,12 dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinogenesis via downregulating Notch signaling [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 129.
Abstract 130: CpG binding protein promotes cell proliferation through H3K4 methylation in ovarian cancer
Authors: Yang Liu-qing , Hu Han-yin , Han Yao , Zhu Heng-Yan , Wang Xiao-min , Ao Lei , Xu Ying , Huang Xuan , Che Xuan , Wang Li-Zhong , Jiang Ya-Bo , Xu Chun-wei , Cheng Shu-Qun , Heger Michal , Pan Wei-wei 
Published: September 2020

Abstract
E3 ubiquitin ligase CRL4 complex activation requires cullin neddylation. MLN4924, a NEDD8-activating enzyme (NAE) inhibitor, reportedly blocked cullin neddylation and inactivated cullin (CUL)-RING E3 ligases (CRLs). Studies have shown that MLN4924 inhibits cell proliferation and survival. We examined the oncostatic and cytotoxic properties of MLN4924 in ovarian cancer. MLN4924 blocked human cancer cell proliferation in nude mice by inhibiting CpG binding protein CFP1 expression. Loss of CFP1 reduced cell growth, promoted apoptosis, and increased senescence. CFP1-dependent H3K4 trimethylation is necessary to maintain the expression of target genes in ovarian cancer cells. We identified bone marrow stromal cell antigen 2 (BST2) and noggin (NOG) as direct targets of CFP1. Their expression was selectively induced by CFP1 deletion. Furthermore, deletion of NOG and overexpression of BST2 prevented the growth-inhibitory effect of CFP1 loss. Our study further demonstrated that CRL4 inactivation reduced CFP1 transcription and trimethylation on lysine 4 of histone H3, which in turn inhibited cell proliferation and induced apoptosis. Therefore, CRL4 constitutes a druggable target in ovarian cancer.
Citation Format: Liu-qing Yang, Han-yin Hu, Yao Han, Heng-Yan Zhu, Xiao-min Wang, Lei Ao, Ying Xu, Xuan Huang, Xuan Che, Li-Zhong Wang, Ya-Bo Jiang, Chun-wei Xu, Shu-Qun Cheng, Michal Heger, Wei-wei Pan. CpG binding protein promotes cell proliferation through H3K4 methylation in ovarian cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 130.
Abstract 1332: Cancer-Immu portal: An open resource for exploring immunotherapy-related multidimensional cancer genomic profiles
Authors: Yang Jing , Liu Qi , Shyr Yu 
Published: September 2020

Abstract
Cancer immunotherapy that blocks immune checkpoint molecules, such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein-1 /ligand-1 (PD-1/PD-L1), has revolutionized anticancer therapy. Since the first approval of ipilimumab (anti-CTLA-4) for the treatment of unresectable or metastatic melanoma, FDA has granted dozens of approval of immune checkpoint blockade (ICB) drugs for many cancers, including non-small cell lung cancer, urothelial cancer, renal cell carcinoma, Hodgkin's lymphoma, head and neck cancer, microsatellite instability or mismatch repair deficient cancers, gastric cancer, colorectal cancer, hepatocellular carcinoma and Merkel cell carcinoma. Although patients with advanced-stage cancers have opportunity to get durable benefits from ICB treatment, only a minority of them responds to ICB, which highlights the need of the predictive biomarkers for guiding the selection of patients. Meanwhile, driven by the advances of technologies, such as next-generation sequencing and single-cell technologies, the field of immunotherapy-related cancer genomic is evolving rapidly, providing unprecedented opportunities to draw a comprehensive picture about immuno-genomic connection. In recent years, large amount of immuno-genomic data were generated, however, most of them are scattered in literatures and are not readily accessible to the community. To provide easy access to those valuable immuno-genomic datasets, we developed Cancer-Immu (http://bioinfo.vanderbilt.edu/database/Cancer-Immu/), which collected 2799 samples from 13 cancer types with both ICB response outcome and genomic profiling by either bulk sequencing or single-cell technologies Cancer-Immu allows interactive exploration of associations between ICB responsiveness and a variety of known and novel genomic features (genetic, transcriptomics, immune cell, and single cell populations) across multiple cancer types. Additionally, Cancer-Immu enables users to analyse their own datasets independently or co-analyse with existing data to identify and validate signatures of interest. Cancer-Immu, provides a platform for immunotherapy response evaluations, reduces barriers between researchers and complex genomic data, and facilitates discoveries in cancer immunotherapy, such as guiding combination treatments, repositioning existing drugs, and even developing novel agents.
Citation Format: Jing Yang, Qi Liu, Yu Shyr. Cancer-Immu portal: An open resource for exploring immunotherapy-related multidimensional cancer genomic profiles [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1332.
Abstract 1333: High-quality multi-omic analysis of FFPE samples
Authors: Lund Jim , Bailey Shannon , Ekram Muhammad , Shahbazian David , Memeo Lorenzo , Hofman Paul , Williams Richard , Gulcher Jeff 
Published: September 2020

Abstract
Next-generation sequencing analysis of formalin-fixed, paraffin-embedded (FFPE) samples has the potential to lead to major advances in cancer treatment and prevention. These samples present a great opportunity for research because they are associated with clinical records, and millions of samples exist that can be used for retrospective analyses. We previously reported high quality whole-genome sequencing (WGS) results from FFPE tissue with an average of 98% of the genome covered at 20X or greater depth for samples as old as 15 years. In this study, we show high-quality results from performing multi-omic analysis including RNA sequencing (RNA-seq), WGS, methylation array, and microRNA sequencing (miRNA-seq) from the same archival sample. This demonstrates that multiomic analysis of existing cancer samples is technically feasible and opens up multi-omic analysis of these archival FFPE tissues.
Using archival samples derived from breast, non small-cell lung, colorectal, and melanoma tumors, we extracted high-quality, high molecular weight DNA using the WuXi NextCODE SeqPlus method, and RNA was extracted using a rRNA depletion method. Using these extracts, we performed WGS, methylation chip array, RNA-seq, and miRNA-seq analyses. The resulting WGS data had high uniform coverage, and high-quality data was produced from the methylation chips. Results from the FFPE samples were compared to those found in the TCGA data. Analysis of mutation calls in these WGS samples revealed high concordance with those produced from the fresh-frozen whole-exome sequenced TCGA samples. Methylation patterns from our data clustered with samples of the same cancer type in the TCGA dataset. We also saw a similar clustering with the RNA-seq and miRNA-seq results when compared to the TCGA data. In addition, we found that RNA expression was correlated with promoter methylation, and gene expression changes affected by mutation and methylation were identified. In summary, we found an overall clustering of the FFPE samples with samples of the same cancer type and no systemic differences between fresh and FFPE samples were observed. These data demonstrate the feasibility of performing comprehensive, multi-omic profiling of archival FFPE tissues.
Citation Format: Jim Lund, Shannon Bailey, Muhammad Ekram, David Shahbazian, Lorenzo Memeo, Paul Hofman, Richard Williams, Jeff Gulcher. High-quality multi-omic analysis of FFPE samples [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1333.
Abstract 134: Targeting NLMP prevents drug adaptive prostate cancer evolution
Authors: Xie Yingqiu , Fan Haiyan , Manarbek Limara , Nurkesh Ayan A. , Yang Qing , Maipas Aisulu , Chen Zhenbang 
Published: September 2020

Abstract
We recently reported that nuclear localized membrane proteins (NLMP) play essential roles in drug adaptive mediated cancer evolution. Nuclear receptor tyrosine kinases (nRTKs), one of NLMP family, are aberrantly elevated in many human cancers. For example, nMET promotes cancer evolution through stem cell mediated drug resistance and homeostasis of cell survival. However, MET inhibitor mediated adaptive resistance frequently occurs by which nMET induction and other signaling mechanisms are involved. We previously showed androgen deprivation therapy (ADT) can induce nMET accumulation in castration resistant prostate cancer (CRPC) patient specimens, while membrane MET is primarily elevated in naïve prostate cancer (PCa) tumors. In addition to androgen deprivation enhanced NLMP, DNA damage targeting chemotherapy can also induce adaptive escape for survival while nonstem cell-like nMET expressing cells may undergo clearance by cell death through cell cycle arrest induced by p21 and DNA damage response as we reported previously. Here we further applied carbon nanodots to examine the combination effect on CRPC cells survival to target NLMP. We found beet derived carbon nanodots can enter into nucleus and induce DNA damage in PC3 cells. The DNA damage is prevented in nucleolus region and opposed by BRCA1 in nucleus. Most importantly, carbon nanodots suppressed tumor growth of PC3 cells in xenograft models in vivo in a PARP-dependent manner. Finally, we found beet derived carbon nanodots exhibit stem cell marker, phosphatase-like nanozyme activity and promote phosphatase activity. Thus, potential stemness induced by carbon nanodots may interfere the efficiency of anti-cancer by DNA damage. Then we applied phosphatase inhibitor for further enhanced inhibition of cell growth by targeting PARP with AZD-2281 in combination of carbon nanodots and phosphatase inhibitor. Our findings reveal for the first time that targeting CRPC by carbon nanodots can be a novel avenue for inhibiting RTK/nRTK/nMET in nucleus of prostate cancer cells. Taken together, our data suggest green carbon nanozyme mediated combination therapy with RTK/MET/NLMP inhibitors would be an innovation in targeted therapy to prevent drug resistance.
Citation Format: Yingqiu Xie, Haiyan Fan, Limara Manarbek, Ayan A. Nurkesh, Qing Yang, Aisulu Maipas, Zhenbang Chen. Targeting NLMP prevents drug adaptive prostate cancer evolution [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 134.
Abstract 1348: Optimizing experimental design for high-parameter protein analysis using BD AbSeq technology
Authors: Narayan Punya , Song Hye-Won , Nakamoto Margaret , Walczak Elisabeth , Lazaruk Katherine , Mortimer Stefanie 
Published: September 2020

Abstract
High-throughput single cell RNA sequencing (RNA-seq) has recently emerged as a powerful tool for profiling complex cell populations. While traditional single cell RNA-seq captures information about transcript expression, recent technological advances using oligo-conjugated antibodies enable simultaneous detection of proteins alongside mRNA in high-throughput sequencing. This multiomic technology enables high parameter protein analysis that can simultaneously discriminate 100 protein markers. However, experiment workflow time and cost can escalate quickly with high plexy assays. To address these issues we investigated a number of methods to decrease cost and assay time while maintaining data quality using the BD® AbSeq on the BD Rhapsody™ Single-Cell Analysis sequencing system. To begin, we investigated the performance of 20 core proteins when used in a 20plex, 40plex, 60plex, 80plex, or 100plex in model cells. Results from 3 experiments showed that performance was maintained as plexy increased, however rigorous experimental approaches must be followed to minimize impact on specificity or sensitivity. After establishing performance of this 20plex we investigated pre-cocktailing of antibodies as a method to shorten the day-of-experiment workflow, and mixing of oligo-labeled and unlabeled antibodies to high-expressing proteins (“signal muting”) as a way to decrease sequencing costs. Results showed a decrease in specificity as soon as 24 hours after the cocktailing of antibodies and increasing non-specific binding with longer cocktail storage times. On the other hand, signal muting was effective at decreasing sequencing requirements by up to 70%, without impacting data for high expressors. Together these results can be used to aid in optimizing experimental design when working with high-plex AbSeq protein panels, to better harness the information gained from multiomic single cell sequencing data. For Research Use Only. Not for use in diagnostic or therapeutic procedures.BD, the BD Logo, and Rhapsody are trademarks of Becton, Dickinson and Company or its affiliates. © 2019 BD. All rights reserved.
Citation Format: Punya Narayan, Hye-Won Song, Margaret Nakamoto, Elisabeth Walczak, Katherine Lazaruk, Stefanie Mortimer. Optimizing experimental design for high-parameter protein analysis using BD AbSeq technology [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1348.
Abstract 1349: Improved human exome sequencing workflow with the most complete coverage
Authors: Hong Manqing , Min Bosun , Roseman Nicole , Star Ekaterina , Rusch Timothy , Datta Krishnalekha , Groenewold Steve , Ren Longhui , Zhou Jinglie , Lai Kevin , Wang Xiaohui , Downey Nick , Giorda Kristina , Wang Alexandra , Wang Yu , Lewis Lynette A. , Lau Patrick J. , Henck Steven 
Published: September 2020

Abstract
Consisting of only ~2% of the human genome, the exome accounts for ~85% of genetic disorders. Efficient sequencing of the human exome with complete and high coverage depth at low cost is invaluable for furthering research in clinical applications. IDT's xGen Exome Panel has proven to be a high performing option. Here, we present the updated xGen Exome Research Panel v2.0 in direct comparison with two other leading commercial human exome panels, using workflows per manufacturer's specifications.
NA12878 genomic DNA libraries were pooled together for 8-plex captures for all three platforms and sequenced on the Illumina NextSeq 500. Equivalent number of reads per sample were analyzed against a universal human exome target space to compare across the different exome panels. IDT's Exome NGS solution provided significantly highest on-target percentage at &gt;90% as well as the greatest depth of coverage at &gt;96% bases covered at &gt;20X and &gt;98% bases covered at &gt;10X. Importantly, IDT's platform also reported the most complete gene-level coverage, demonstrated by minimal exon drop-outs in difficult-to-target genes.
While 8-plex is the upper limit supported by other suppliers, IDT's platform supports 12-plex workflow. The higher multiplex in combination with high coverage and on-target performance enables IDT to present the lowest total sequencing cost per sample. Since IDT hybridization capture baits are individually synthesized and qualified with the same high standards as standalone oligonucleotide products, lot-to-lot variability is negligible. This presents researchers with an option they can rely on for long-term use and places the focus on the true variabilities of the sample. In conclusion, this study demonstrates xGen Exome Research Panel v2.0, when combined with IDT's DNA Library Prep Kit, provides researchers with a complete Exome NGS solution that is competitive both in performance and sequencing cost.
Citation Format: Manqing Hong, Bosun Min, Nicole Roseman, Ekaterina Star, Timothy Rusch, Krishnalekha Datta, Steve Groenewold, Longhui Ren, Jinglie Zhou, Kevin Lai, Xiaohui Wang, Nick Downey, Kristina Giorda, Alexandra Wang, Yu Wang, Lynette A. Lewis, Patrick J. Lau, Steven Henck. Improved human exome sequencing workflow with the most complete coverage [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1349.
Abstract 1395: Hsa_circ_005379 competitively binds to miR-182-5p to mediate PTEN expression in oral squamous cell carcinoma
Authors: Shen Yuehong , Su Wen , Yang Hongyu 
Published: September 2020

Abstract
Background: Oral squamous cell carcinoma (OSCC) is an oral and maxillofacial malignancy with a high incidence worldwide. Accumulating evidence indicates that circular RNAs (circRNAs) play a vital role in modulating tumor development. However, the mechanism of circRNA action in human OSCC remains largely unknown.
Methods: By using high-throughput transcriptome sequencing technology, we conducted a comprehensive study of circRNAs in human OSCC. The effect of CircRNA hsa_circ_0005379 on OSCC tissues and cell lines were monitored by qRT-PCR, transwell assay and western blot analysis. Xenograft mouse models were used to assess tumor growth and animal survival.
Results: CircRNA hsa_circ_0005379 was found to express significantly lower in OSCC tissue compared to paired non-cancerous matched tissue and is associated with tumor size and differentiation. Overexpression of has_circ_0005379 effectively inhibits migration, invasion, and proliferation of OSCC cells in vitro, and suppresses OSCC growth in nude mice. Mechanistic studies revealed that hsa_circ_0005379 may be involved in the regulation of epidermal growth factor receptor (EGFR) pathway.
Conclusions: Our findings provide evidence that hsa_circ_0005379 exerts regulatory functions and may be a new therapeutic target for OSCC treatment.
Citation Format: Yuehong Shen, Wen Su, Hongyu Yang. Hsa_circ_005379 competitively binds to miR-182-5p to mediate PTEN expression in oral squamous cell carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1395.
Abstract 1401: PVT1 exon 9 transcript regulates claudin 4 expression and migration in triple negative breast cancer
Authors: Levine Fayola A. , Ogunwobi Olorunseun O. 
Published: September 2020

Abstract
Breast cancer (BC) is a heterogeneous disease that is classically driven by the estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor 2 (EGFR2/HER2) signaling pathways. Triple negative breast cancer (TNBC), is a lethal subtype of invasive BC tumors that are ER-, PR- and HER2-. A subtype of TNBC is claudin low (CL). Dysregulation of claudin proteins disrupts tight junctions, consequently inducing the epithelial-to-mesenchymal transition (EMT) in cancers. This leads to enhanced motility and metastasis. Patients with CL TNBC have worse prognosis than patients with other BC subtypes. PVT1 is a long noncoding RNA (lncRNA) transcribed from the 8q24 genomic locus that has been implicated in multiple cancers including BC. Amplification of the 8q24 gene locus is a common event in many malignant diseases and is associated with poor clinical outcomes. Although previous research has implicated PVT1 as an important player in BC, the underlying molecular mechanisms of PVT1 in CL TNBC was previously unknown. We assessed PVT1 expression in BC, and we observed that PVT1 exons 4A, 4B, and 9 are significantly upregulated in MDA MB 231 cells (claudin low) and significantly downregulated in MDA MB 468 cells (claudin high), in comparison to T47D (ER+). We have confirmed that claudin expression, specifically claudins 1, 3, 4 and 7, are significantly higher in MDA MB 468 cells and significantly lower in MDA MB 231 cells. Knockdown of PVT1 exon 9 expression in the MDA MB 231 cell line, led to a significant reduction in migration when compared to cells transfected with a control scramble siRNA, indicating that PVT1 exon 9 regulates migration in CL TNBC. Interestingly, we observed that claudin 4 expression, and not claudins 1, 3 and 7, was increased in cells where PVT1 exon 9 was knocked down when compared to the control cells. This indicates that PVT1 exon 9 regulates claudin 4 protein stability in CL TNBC. We also assessed the expression of EMT markers (vimentin, fibronection, and caveolin) in MDA MB 231 cells. We observed no changes in EMT markers when PVT1 exon 9 is knocked down; however, our data suggests that EMT markers are more highly expressed in MDA MB 231 cells in comparison to MDA MB 468 cells. Taken together, our data indicate that PVT1 exon 9 regulates claudin expression and migration in CL TNBC, and may have implications for clinical outcomes in TNBC.
Citation Format: Fayola A. Levine, Olorunseun O. Ogunwobi. PVT1 exon 9 transcript regulates claudin 4 expression and migration in triple negative breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1401.