bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3559: Protein secretion rates of VEGF and CA9 in normoxia and hypoxia
Authors: Lee Sandy Che-Eun Serena , Levitin Fiana , Hulme Stephanie , Rumantir Ryan , Sykes Jenna , Koritzinsky Marianne 
Published: September 2020

Abstract
Tumor hypoxia results in poor patient outcome due to treatment resistance as well as biological changes that stimulate angiogenesis, vasculogenesis, migration, invasion and immune suppression. These hypoxia-induced adverse biological changes are often mediated by membrane bound or secreted proteins through transcriptional and translational upregulation. Thus, understanding the regulation of how secreted proteins in hypoxia can therefore reveal novel therapeutic targets. Proteins that traverse through the secretory pathway form disulfide bonds in the endoplasmic reticulum (ER). Recent data from our lab have demonstrated that disulfide bond formation remains incomplete in ER cargo proteins like LDLR and Flu-HA in the absence of oxygen. To address whether hypoxia-induced proteins were likewise impaired, radioactive pulse chase assays were performed to measure disulfide bond formation and secretion capacity under both normoxic and hypoxic conditions. Here, we demonstrate that both hypoxia induced proteins carbonic anhydrase 9 (CA9) and vascular endothelial growth factor (VEGF) complete disulfide bond formation and are secreted with equal kinetics under hypoxia and normoxia. These proteins hence have a superior ability to be expressed in the absence of oxygen. Additionally, in a global in silico analysis of all proteins that traverse through the ER, we discovered that hypoxia-induced proteins on average contain fewer free cysteines and shorter-range disulfide bonds in comparison to other proteins. These traits may contribute to their superior ability to form correct disulfide bonds in hypoxia. These data show that the ability of proteins to form native disulfide bonds in hypoxia varies widely which can ultimately contribute to their expression in the extracellular space.
Citation Format: Sandy Che-Eun Serena Lee, Fiana Levitin, Stephanie Hulme, Ryan Rumantir, Jenna Sykes, Marianne Koritzinsky. Protein secretion rates of VEGF and CA9 in normoxia and hypoxia [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 3559.
Abstract 3572: Merlin deficiency induces redox imbalance in breast cancer
Authors: Mota Mateus , Metge Brandon , Shevde-Samant Lalita 
Published: September 2020

Abstract
Merlin is encoded by the NF2 gene and, as a tumor suppressor, stalls cell proliferation by contact-dependent growth inhibition. Prior work from our laboratory has established that Merlin levels are significantly decreased in breast tumor tissues representing advanced grade. Moreover, Merlin expression is completely lost in cases representing metastatic breast cancer. Therefore, we mimicked Merlin deficiency by stably knocking down NF2 in non-metastatic breast cancer cells. Recognizing the role of metabolic reprogramming in tumor progression, we undertook untargeted metabolomics analysis - this effort identified low levels of reduced glutathione (GSH) in Merlin-deficient cells. Given the role of GSH as the most abundant antioxidant cofactor, we explored if a major reactive oxygen species (ROS) clearance mechanism is compromised in Merlin-deficient breast cancer cells. Indeed, accumulated levels of ROS were detected in Merlin-deficient cells, suggesting that Merlin deficiency causes redox imbalance. Quenching of elevated ROS levels attenuated migration and invasion capabilities indicating a role of ROS in intensifying malignant behaviors upon Merlin deficiency. Furthermore, dysregulated STAT3 activity upregulated the expression of NADPH oxidase (NOX) enzymes in Merlin-deficient breast cancer cells compared to their control counterparts. These findings were also recapitulated in non-tumorigenic Nf2 −/- mouse embryonic fibroblasts further supporting the key role of Merlin in these phenotypes. In conclusion, ROS accumulation and increased malignancy in Merlin-deficient cells may be the result of a dysregulated cellular redox management system.
Citation Format: Mateus Mota, Brandon Metge, Lalita Shevde-Samant. Merlin deficiency induces redox imbalance in 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 3572.
Abstract 3615: Profiling of BRCA1 & BRCA2 mutations in Egyptian colorectal cancer patients via next generation sequencing
Authors: El-Din Youssef Amira Salah , Touny Ahmed Osama , Hassan Zeinab K. , Eldin Mohammed Mohey , Lotfy Mai M. , Nassar Auhood , El-Hadidi Mohamed , Kishk Ali , sayed ola , Zekri Abdel-Rahman N. 
Published: September 2020

Abstract
Aim: This study aimed to sequence BRCA1 & BRCA2 genes to identify the frequency of the detected genetic mutations in the disease progression of colorectal cancer (CRC) and to estimate colorectal cancer risks in those BRCA mutation carriers.
Material and methods: 140 biopsy samples were collected from Egyptian patients categorized into inflammatory bowel disease (IBD) (n=20), colonic polyp (CP) (n=38) and CRC (n=62) patients as well as subjects with chronic colitis served as a control group (n=20). The libraries were performed using Qiaseq UMI-based targeted panel and sequenced via Ion proton sequencer. The detected genetic variants at 500x were annotated against Cosmic, dbSNP, exac all, Polyphen2, Sift and Clinvar databases.
Results: Analysis revealed that BRCA1 gene harbored 26, 19, 8 and 11 variants in the CRC, CP, IBD and control groups; respectively. Exon 10 was the most affected exon harbored 7 pathogenic variants in the CRC group. Two out of 7 were the most frequently detected common pathogenic variants associated with disease progression from colitis to CRC (c.1961delA (11%) & c.3214delC (16%). Moreover, 3 common begnin SNP variants were found to be related to ethnicity (c.3548A&gt;G (58%), c.2612C&gt;T (60%), c.4900A&gt;G (69%).
Moreover, BRCA2 gene harbored 48, 29, 24 and 18 variants in the CRC, CP, IBD and control groups respectively. Exon 2, 11, 23 were the most affected exons harbored 12 pathogenic variants in the CRC group. Four out of 12 were the most frequently detected common pathogenic variants associated with disease progression from colitis to CRC (c.3860delA (8%), c.5351delA (18%), c.9097delA (24%) & c.36delT (34%).
Conclusion: Our data showed that BRCA1 & BRCA2 genes analyzed by Next-Generation Sequencing (NGS) identifies large number of pathogenic and begnin variants that are crucial for understanding CRC predisposition and early detection. Also, developing personalized therapies that efficiently target the individual CRC-specific mutations.
Key words: Egyptian Colorectal cancer, BRCA1, BRCA2, pathogenic, begnin, Next Generation Sequencing
Citation Format: Amira Salah El-Din Youssef, Ahmed Osama Touny, Zeinab K. Hassan, Mohammed Mohey Eldin, Mai M. Lotfy, Auhood Nassar, Mohamed El-Hadidi, Ali Kishk, ola sayed, Abdel-Rahman N. Zekri. Profiling of BRCA1 & BRCA2 mutations in Egyptian colorectal cancer patients via next generation sequencing [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 3615.
Abstract 3619: High quality library preparation and accurate sequencing from highly damaged matched patient sample sets
Authors: Heider Margaret R. 
Published: September 2020

Abstract
Preparation of high quality next-generation sequencing (NGS) libraries is critical for accurate identification of disease-causing mutations, but clinical scientists are often limited by the input DNA quality. In cancer genomics, a common source of DNA is formalin-fixed, paraffin-embedded (FFPE) tissue from patient biopsy, and in most cases high quality fresh or frozen tissue samples are not available. FFPE DNA poses many notable challenges for preparing NGS libraries, including low input amounts and extensive damage from fixation, storage, and extraction methods. Sequencing artifacts arising from damaged DNA bases raise the level of apparent mutations, making it more difficult to discern true, low frequency, disease-related variants from noise.
We developed a second-generation, multi-enzyme DNA repair mix (V2) that is designed to repair the most prevalent damage types found in FFPE DNA including cytosine deamination, oxidative damage, abasic sites, nicks, and gaps. We tested the application of the V2 enzymatic repair mix in Illumina library preparation for DNA samples extracted from a series of matched patient sample sets, which included: FFPE normal and tumor tissue, and frozen normal and tumor tissue for each patient. Following this, we performed target enrichment, deep sequencing, and variant calling analyses.
Our library preparation workflow integrates enzymatic repair upstream of Illumina library preparation without an additional bead purification step, maximizing library yield and complexity from precious FFPE samples. Rescue of damaged DNA molecules for library conversion and repair of damaged DNA bases improved on-target rate, coverage uniformity, and duplication rates. With a matched frozen sample for each FFPE specimen, we demonstrate that repair of damaged DNA bases improves sequencing accuracy by reducing the number of false-positive variant calls. We propose that enzymatic repair enables researchers to capture as much useable, accurate data from poor quality FFPE samples as possible.
Citation Format: Margaret R. Heider. High quality library preparation and accurate sequencing from highly damaged matched patient sample sets [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 3619.
Abstract 362: The regulation of SOX7 and its tumor suppressive role in oral squamous cell carcinoma
Authors: Ahn Chi-Hyun , Hong Kyoung Ok , Shin Ji-Ae , Hong Seong-Doo , Cho Sung-Dae 
Published: September 2020

Abstract
SRY-related HMG-box 7(SOX7), a transcription factor belonging to the SOX family, has been reported to be down-regulated in some types of cancers. However, its biologic role in oral squamous cell carcinoma (OSCC) remains unknown. We found expression of SOX7 protein was decreased in OSCC tissues compared with normal oral mucosa. SOX7 expression in patients with OSCC was inversely associated with positive lymph node metastasis, advanced TNM stage, and poor prognosis. These results were in accordance with data obtained from our in vitro experiments on the OSCC cell lines. Moreover, ectopic expression of SOX7 suppressed cell proliferation, migration, and invasion in HSC-4 and SCC-9 cells. Importantly, we discovered that SOX7 expression likely inhibited vasculogenic mimicry formation associated with clinically poor outcome and impaired expression of VE-cadherin in OSCC cell lines as well as lung cancer and breast cancer cells. Our findings suggest that SOX7 could be a potential marker for predicting the prognosis of patients with OSCC and plays an important role as a tumor suppressor in oral tumorigenesis and progression. This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning [2017R1D1A1B03029317, 2018R1D1A1B07043080, and 2019R1A2C1085896].
Citation Format: Chi-Hyun Ahn, Kyoung Ok Hong, Ji-Ae Shin, Seong-Doo Hong, Sung-Dae Cho. The regulation of SOX7 and its tumor suppressive role 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 362.
Abstract 3641: Successful classification of hematological neoplasm by array profile
Authors: Grace Colin , Boneva Temenuzhka , Nacheva Elisabeth P. 
Published: September 2020

Abstract
In addition to structural chromosome aberrations resulting in fusion genes, the genome profile of haematological malignancies is characterized by copy number changes (gains and losses) relative to the ploidy level. Array comparative genome hybridization (aCGH)1 Combined with FISH and/or multiplex PCR array screening offers a reliable tool for assessment of genome complexity in haematological malignancies in diagnostic settings.
The aCGH assay in our diagnostic algorithm uses 8 × 60K SurePrint G3 (Agilent, USA). The slides are scanned to measure the fluorescence ratio (FR), software evaluates imbalances.
We recognize that the raw data in the form of log ratios, some 64,000 data points, contain sufficient information to identify the disease category without resorting to converting the log ratios to gains and losses and mapping them to individual chromosomes, a process open to operator interpretation.
As an alternative and bearing in mind the current interest in machine learning, we attempted to auto-classify the data for the modest collection of 2,300 patient samples in our archive, according to their WHO classification. We were able to collect 175 samples for each group classified as myelodisplasia (MDS), acute myeloid leukemia (AML), myeloma (MM) and chronic lymphocytic leukemia (CLL),
We used a Logistic Regression Classifier implemented in Mathematica 12. The classifier took only 2 minutes on average to complete the training. We took a total of 700 array sample files, each of 59,032 data points, of which 100 were randomly selected as a validation set. The balance of 600 files, distributed evenly and randomly over the 4 test diseases were used as a training set. We used a Confusion Matrix to evaluate and display the results as shown in the table.
Confusion MatrixAMLCLLMDSMMTotalAML1609025CLL0150116MDS0116017MM1021417Predicted17162715
In spite of the small training set we correctly classified the MDS (16/17), CLL (15/16) and MM (14/17), 9 AML were reported as MDS a due to sharing genome imbalances. There was also confusion between the B cell disorders, MM and CLL known to carry overlapping genome aberrations.
The auto classification offered by this method is a promising attempt to support a speedy and reliable assessment of genome complexity. There is no doubt that a better classifier would have been created with a larger training set.
1 Kallioniemi A et al., Kallioniemi OP, Sudar DA, Rutovitz D, Gray JW, Waldman F, Pinkel D (1992). “Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors”. Science. 258 (5083): 818-821).
Citation Format: Colin Grace, Temenuzhka Boneva, Elisabeth P. Nacheva. Successful classification of hematological neoplasm by array profile [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 3641.
Abstract 3650: A noncanonical histone target of NSD2 may contribute to oncogenesis
Authors: Weiss Nicole , Luo Minkui 
Published: September 2020

Abstract
The NSD family of protein lysine methyltransferases (PKMTs), containing members NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1, cause epigenetic aberrations when dysregulated in cancer and are thus attractive therapeutic targets. These enzymes share a canonical activity catalyzing the dimethylation of histone 3 lysine 36 (H3K36me2), a mark associated with gene activation. In cancer, these enzymes are often overexpressed, amplified, or mutated, resulting in increased global H3K36me2 and transcriptional activation. In addition to transcriptional regulation, NSD2 has also been reported to be involved in pathways such as DNA replication and repair, which cannot be readily rationalized via its H3K36 methylation activity. This suggests that NSD2 has unidentified substrates that carry out its additional biological function(s), nonredundant with NSD1/3. Furthermore, NSD2 has a recurring glutamate to lysine mutation in the catalytic SET domain at 1099 (E1099K), which results in gain-of-function activity on H3K36. Our preliminary data has shown that NSD2 has noncanonical histone targets that are augmented by NSD2 E1099K to drive oncogenesis. We are using cell based approaches to dissect its downstream biology to reveal NSD2's oncogenic potential.
Citation Format: Nicole Weiss, Minkui Luo. A noncanonical histone target of NSD2 may contribute to oncogenesis [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 3650.
Abstract 3657: Analysis of the regulation of PD-L1 expression and methyl transferases levels following inhibition of histone deacetylases in cancer cells
Authors: Natarajan Umamaheswari , Venkatesan Thiagarajan , Mathuram Theodore L. , Das Jayanta K. , Rathinavelu Appu 
Published: September 2020

Abstract
Epigenetic alterations are known to play important roles in cancer initiation and progression. Therefore, deregulation of epigenetic modifications is considered as a hallmark of cancer; therefore many components of this process are being explored as therapeutic targets. PD-L1 is expressed in most cancer cells, which confers aggressive growth ability and allows the cancers to escape from the immune system of the body. The effects of PD-L1 are mediated through PD-1, also known as CD279, which is normally expressed on the surface of lymphoid and non-lymphoid derived cells. The binding of PD-L1 to the PD-1 receptor mediates immune checkpoint inhibition to regulate T-cell responses. When we analyzed the levels of PD-L1, the expression was high in HCC827 cells, followed by H460, H1975, H226, SJSA1, and U87MG cells. Treatment of HCC827 cells with SAHA, which is a broad-spectrum HDAC inhibitor, was able to reduce the PD-L1 levels in time and dose dependent manner in HCC827. Also, the PD-L1 levels were found to be negatively correlated to the p21 expression following HDAC inhibition. The qRT-PCR analysis revealed significant decreases in the levels of methyltransferase enzymes such as DNMT3A, DNMT3B, PRMT1, SUV39H1, KAT6B, NSD1, SETD1B, and WHSC1. Analysis of the protein levels also confirmed significant reductions following treatment with SAHA. While decreasing the levels of the methyltransferases, SAHA treatment was able to increase the levels of acetylated forms of H2B, H3, and H4. Since acetylation mediated unwinding of the DNA is generally responsible for the increased expression of various genes, it is interesting to see a concomitant reduction in the levels of some of the crucial methyltransferases that are known to produce inhibitory effects. It is suspected that the decrease in the PD-L1, PRMT1, SUV39H1, and DNMT3A levels following HDAC inhibition may be mainly due to reduced transcription. However, it is not clear whether p21 has any negative control on the transcription of the affected genes. Additional studies are required to fully understand the actual mechanisms that may be involved in the regulation of PD-L1 and methyltransferases expression by HDAC inhibitors. (This research was supported by the Royal Dames of Cancer Research Inc., Fort Lauderdale, Florida).
Citation Format: Umamaheswari Natarajan, Thiagarajan Venkatesan, Theodore L. Mathuram, Jayanta K. Das, Appu Rathinavelu. Analysis of the regulation of PD-L1 expression and methyl transferases levels following inhibition of histone deacetylases in cancer cells [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 3657.
Abstract 3658: Brd4-bound enhancers drive critical sex differences in glioblastoma
Authors: Kfoury-Beaumont Najla , Qi Zongtai , Wilkinson Michael , Broestl Lauren , Berrett Kristopher , Moudgil Arnav , Sankararaman Sumithra , Chen Xuhua , Gertz Jay , Mitra Robi , Rubin Joshua B. 
Published: September 2020

Abstract
Sex can be an important determinant of cancer phenotype and exploring sex-specific tumor biology holds promise for identifying novel therapeutic targets and new approaches to cancer treatment. In an established model of glioblastoma, we discovered transcriptome-wide sexual dimorphism in gene-expression that was concordant with sex differences in H3K27ac marks, large Brd4-bound enhancer usage, and Brd4 co-localization with Myc and p53. The sex-specific enhancer usage drove sex differences in stem cell function and tumorigenicity. Moreover, male and female GBM cells exhibited opposing responses to pharmacological or genetic inhibition of Brd4. Brd4 knockdown or inhibition decreased male GBM cell clonogenicity and in vivo tumorigenesis, while increasing both in female GBM cells. These results were validated in male and female patient-derived GBM cell lines. Thus, for the first time, Brd4 activity is revealed to drive a sexually dimorphic stem cell and tumorigenic phenotype, resulting in diametrically opposite responses to BET inhibition in male and female glioblastoma cells. This has critical implications for the clinical evaluation and use of BET inhibitors.
Citation Format: Najla Kfoury-Beaumont, Zongtai Qi, Michael Wilkinson, Lauren Broestl, Kristopher Berrett, Arnav Moudgil, Sumithra Sankararaman, Xuhua Chen, Jay Gertz, Robi Mitra, Joshua B. Rubin. Brd4-bound enhancers drive critical sex differences in glioblastoma [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 3658.