tbuckley/cabot-search huggingface dataset:
Abstract 1416: Long non-coding RNA GAN1 inhibits tumor progression by regulating the mir-26a/PTEN axis in lung cancer
Authors: Rui-qi Wang, Xiao-Ran Long, Mei-Yin Zhang, Dong-Ni Chen, Zhe-Sheng Wen, Shi-Juan Mai, Hui-Yun Wang
Journal: Cancer Research (2020)

Abstract Background: Long non-coding RNA has been reported to be involved in many cancers. To explore the role of lncRNA in non-small-cell lung cancer (NSCLC), we detected lncRNA expression profile with a custom microarray and found that lnc-GAN1 was significantly downregulated in NSCLC. In this study, we aimed to explore the clinical significance, biological function and mechanism of lnc-GAN1 in NSCLC. Methods: We firstly analyzed relationship between the lncGAN1 expression and clinical features and survival in NSCLC patients from two medical centers. We secondly examined the biological function of lncGAN1 in lung cancer cells with Cell viability, colony formation, migration, invasion, cell cycle and apoptosis assays. Then, we localized the distribution of lnc-GAN1 in lung cancer cells using RNA-FISH and analyzed the interaction between lnc-GAN1 and mir-26a-5p with Dual luciferase reporter and RNA immunoprecipitation (RIP) assay. Finally, the xenograft tumor model was employed to assess tumor suppression role of GAN1. Results: lnc-GAN1 is notably downregulated in NSCLC tissues compared with normal lung tissues and associated with small tumor size, poor overall survival (OS) and disease-free survival in NSCLC patients. In vitro experiments, lnc-GAN1 expression suppresses proliferation, colony formation, cell cycle progression and apoptosis of lung cancer cells. lnc-GAN1 was mainly observed in cytoplasm of lung cancer cells with FISH and subcellular fraction analysis. RNA-seq analysis showed that the genes in cell cycle pathway were changed obviously when lnc-GAN1 was overexpressed. Mechanistically, lnc-GAN1 functions as a sponge of miR-26a-5p, which directly targets PTEN. Ectopically expressed lnc-GAN1 increased the mRNA and protein levels of PTEN and decreased miR-26a-5p level in lung cancer cells. Furthermore, mir-26a-5p mimics caused a decrease in both lnc-GAN1 and PTEN expressions while mir-26a-5p inhibitors led to an increase in both lnc-GAN1 and PTEN levels. Finally, In vivo experiments demonstrated that lnc-GAN1 could suppress tumor growth compared with control vector in nude mice. Conclusions: our study discovered that lnc-GAN1 is significantly downregulated and associated with survival in NSCLC patients, and plays a tumor suppressor role by inhibiting miR-26a-5p and upregulating PTEN expression in lung cancer, which suggest that lnc-GAN1 is a potential prognostic biomarker and innovative therapeutic target in NSCLC. Citation Format: Rui-qi Wang, Xiao-Ran Long, Mei-Yin Zhang, Dong-Ni Chen, Zhe-Sheng Wen, Shi-Juan Mai, Hui-Yun Wang. Long non-coding RNA GAN1 inhibits tumor progression by regulating the mir-26a/PTEN axis in lung 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 1416.
Deficiency of Adenosine Deaminase 2 in Adults and Children: Experience From India
Authors: Aman Sharma, GSRSNK Naidu, Vikas Sharma, Saket Jha, Aaadhar Dhooria, Varun Dhir, Prateek Bhatia, Vishal Sharma, Sagar Bhattad, K. G. Chengappa, Vikas Gupta, Durga Prasanna Misra, Pallavi Pimpale Chavan, Sourabh Malaviya, Rajkiran Dudam, Banwari Sharma, Sathish Kumar, Rajesh Bhojwani, Pankaj Gupta, Vikas Agarwal, Kusum Sharma, Manphool Singhal, Manish Rathi, Ritambhra Nada, Ranjana W. Minz, Ved Chaturvedi, Amita Aggarwal, Rohini Handa, Alice Grossi, Marco Gattorno, Zhengping Huang, Jun Wang, Ramesh Jois, V. S. Negi, Raju Khubchandani, Sanjay Jain, Juan I. Arostegui, Eugene P. Chambers, Michael S. Hershfield, Ivona Aksentijevich, Qing Zhou, Pui Y. Lee
Journal: Arthritis & Rheumatology (2020)

Objective Deficiency of adenosine deaminase 2 (DADA2) is a potentially fatal monogenic syndrome characterized by variable manifestations of systemic vasculitis, bone marrow failure, and immunodeficiency. Most cases are diagnosed by pediatric care providers, given the typical early age of disease onset. This study was undertaken to describe the clinical phenotypes and treatment response both in adults and in children with DADA2 in India. Methods A retrospective analysis of pediatric and adult patients with DADA2 diagnosed at various rheumatology centers across India was conducted. Clinical characteristics, diagnostic findings, and treatment responses were analyzed in all subjects. Results In total, 33 cases of DADA2 were confirmed in this cohort between April 2017 and March 2020. Unlike previous studies, nearly one‐half of the confirmed cases presented during adulthood. All symptomatic patients exhibited features of vasculitis, whereas constitutional symptoms and anemia were more common in pediatric patients. Cutaneous and neurologic involvement were common, and 18 subjects had experienced at least one stroke. In addition, the clinical spectrum of DADA2 was expanded by recognition of novel features in these patients, including pancreatic infarction, focal myocarditis, and diffuse alveolar hemorrhage. Treatment with tumor necrosis factor inhibitors (TNFi) was initiated in 25 patients. All of the identified disease manifestations showed marked improvement after initiation of TNFi, and disease remission was achieved in 19 patients. Two cases were complicated by tuberculosis infection, and 2 deaths were reported. Conclusion This report presents the first case series of patients with DADA2 from India, diagnosed by adult and pediatric care providers. The findings raise awareness of this syndrome, particularly with regard to its presentation in adults.
Thirty‐six COVID‐19 cases preventively vaccinated with mumps‐measles‐rubella vaccine: All mild course
Authors: Désirée E. Larenas‐Linnemann, Fernanda Rodríguez‐Monroy
Journal: Allergy (2020)

Dr Larenas Linnemann reports personal fees from Allakos, Amstrong, Astrazeneca, Boehringer Ingelheim, Chiesi, DBV Technologies, Grunenthal, GSK, MEDA, Menarini, MSD, Novartis, Pfizer, Novartis, Sanofi, Siegfried, UCB, Alakos, Gossamer, grants from Sanofi, Astrazeneca, Novartis, UCB, GSK, TEVA, Boehringer Ingelheim, Chiesi, Purina institute, outside the submitted work. RN. Rodriguez-Monroy has nothing to disclose.
Abstract 1320: The landscape of somatic substitutions in the repetitive genome across cancer types
Authors: Maxime Tarabichi, Jonas Demeulemeester, Annelien Verfaillie, Peter Van Loo, Tomasz Konopka
Journal: Cancer Research (2020)

Abstract Somatic mutation calling from bulk DNA sequencing is a complex problem susceptible to elevated false positive rates. High mapping quality is considered an important feature of reliable variant calls. At the resolution of short reads, ~10% of the genome displays high sequence similarity with at least one other genomic region and is assigned low mapping quality by alignment algorithms. These low-mapping-quality regions represent recurrent blind spots for mutation callers, which discard many of the variants they harbor, overlooking true biological variation. Here, we developed a pipeline to call substitutions in the low-mapping-quality genome. We used a published thesaurus approach to annotate the variant positions with their high-similarity links. We trained a classifier to emulate high-quality consensus calls made in unique regions using 20 features unrelated to mapping quality, reaching ~95% accuracy in those regions. In an independent sample more than 90% of the thesaurus calls were validated through linked-read sequencing. We then applied the classifier to all candidate substitutions of 2,658 cancer whole genomes from the PCAWG/ICGC consortium including variants falling in low-mapability regions. We retrieve hidden thesaurus variants genome-wide in ~6% of the genome, including genic, coding, and promoter regions. Thesaurus calls are directly proportional in numbers to somatic calls falling in the low-mapping-quality genome and share a similar trinucleotide context spectrum. Rescuing these mutations reveal hidden signal in known cancer genes, including PIK3CA, and excess of mutations genome-wide in promoter, untranslated, and coding regions of many other genes. We also find potential excess of non-synonymous mutations, including in genes from the TRIM and POTE families, having been previously implicated in multiple cancer types. Altogether, we developed a pipeline to call somatic substitutions in the low-mapping-quality genome and uncovered hidden somatic changes along the genomes of human cancers. In the future, this pipeline could be extended to indels and structural variants, and applied to the study of de novo germline variants. Citation Format: Maxime Tarabichi, Jonas Demeulemeester, Annelien Verfaillie, Peter Van Loo, Tomasz Konopka. The landscape of somatic substitutions in the repetitive genome across cancer types [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 1320.
Abstract 6356: Discovery of seleno allyl hybrid compounds, the Se incorporated mimics of naturally occurring garlic based allylic compounds, as potential anticancer agents
Authors: Irene Talavera, Nora Astrain, Miguel Barajas, Ignacio Encío, Arun K. Sharma, Carmen Sanmartín, Daniel Plano
Journal: Cancer Research (2020)

Abstract Many synthetic derivatives of natural products have been found to exhibit biological activity towards cancer. One prominent example of such natural products are the garlic-based compounds. Given the well stablished preventive effects shown by garlic and some of its allylic components and a well-established chemopreventive and therapeutic effects shown by selenium (Se) compounds, we pursued to design Se-allyl hybrid compounds in order to increase efficacy as compared to naturally occurring allylic compounds. A total of 18 new selenoallyl (SeAl) compounds were designed following two different synthetic approaches. SeAl functionality was chosen to mimic the garlic bioactive allylic components. All the synthesized compounds were screened against colorectal (HT29 and HCT116) and mammary (MCF-7) cancer cell lines (48h treatment). Four most active compounds identified were submitted to the NCI Developmental Therapeutic Program (DTP). Two out of the four compounds were selected for the dose-response assay against a panel of 60 cancer cell lines. Both the compounds exhibited impressive cytotoxicity - lethal dose 50 (LD50) values below 9.2 µM in most of the melanoma and ovarian cancer cell lines tested (8 out of 9 for melanoma and 5 out of 7 for ovarian cancer cells for both compounds). Additionally, the Se-allyl derivative bearing an aspirin substituent presented a significant tumor size inhibition in a castration-resistant prostate cancer xenograft model at a dose of 4 mg/kg given intraperitoneally. Thus, this compound has the potential to be a promising candidate for prostate cancer treatment and potentially other cancers. To conclude, we firmly believe, based on the evidences obtained and presented herein, that structural modifications involving the hybridization approach with Se and naturally occurring allylic compounds could stand as a novel toolkit for anticancer drug development. Citation Format: Irene Talavera, Nora Astrain, Miguel Barajas, Ignacio Encío, Arun K. Sharma, Carmen Sanmartín, Daniel Plano. Discovery of seleno allyl hybrid compounds, the Se incorporated mimics of naturally occurring garlic based allylic compounds, as potential anticancer agents [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 6356.
Abstract 4743: Genetic characteristics of PanNETs, Rectal NETs, Thoracic NETs and its correlation with efficacy of chemotherapy
Authors: Yihebali Chi, Weili Liu, Lijie Zuo, Yuehua Wang, Weijing Cai, Susheng Shi, Yanying Ge, Rui Li, Lijie Song, Yiqi Yang, Zheng Liu, Xiaowu Dou, Hong Zhao
Journal: Cancer Research (2020)

Abstract Background: Neuroendocrine tumors (NETs) are clinical heterogeneous. To date, no studies have focused on the genetic characteristics of NETs at different anatomical sites in the Chinese cohort. We aim to explore the genetic similarities or differences between NETs at different sites, and evaluate the predictive indicators of chemotherapy based on Temozolomide. Methods: The patients were from a prospective clinical study STEM (from a single institute, NCT03204032, NCT03204019). This cohort included 47 patients with NETs, including 14 Pancreatic NETs (PanNETs), 11 Rectal NETs, 14 Thoracic NETs, and 8 Others. Whole exome sequencing (WES) was performed. Results: A total of 76,057 somatic mutations were detected in 16,510 genes. The median tumor mutation burden (TMB) was 13.4, 10.5, 11.0 and 11.9 in PanNETs, Rectal NETs, Thoracic NETs and Others, respectively. After sequencing depth filtering, they were 3.5, 3.9, 3.3 and 3.6, respectively. Low intra-tumoral heterogeneity (ITH) was observed in NETs. The median ITH index was 2, 2.5, 2.5 and 2 in PanNETs, Rectal NETs, Thoracic NETs and Others, respectively; the median Shannon diversity index (SDI) was 0.23, 0.13, 0.23 and 0.24, respectively. The driver gene mutations varied in NETs at different sites. The recurrently mutated driver genes were MEN1, ATM, TSC2, PLXNB2, MUC6, AMER1 and USP9X for PanNETs; APC, APOB and FAT1 for Rectal NETs; KMT2B and CACNA1A for Thoracic NETs. Copy number analysis showed that copy number loss frequently occurred in all NETs. The median copy number variation burden (CNV burden) was 34.0, 10.9, 16.1 and 11.6 in PanNETs, Rectal NETs, Thoracic NETs and Others, respectively. The CNV burden of PanNETs was higher than others. Based on the results of CNVs, NETs at different sites could be distinguished by linear discriminant analysis (LDA). We analyzed the correlation between genetic characteristics and progression-free survival (PFS). As a result, NETs with higher TMB (&amp;gt;10 /Mb, P=0.043) or higher CNV burden (&amp;gt;20, P=0.047) showed statistically longer PFS. More patients should be included to find a correlation between genetic characteristics and PFS. Conclusions: NETs at different sites harbored different somatic driver mutations, and copy number loss was widespread in NETs. NETs with higher TMB or higher CNV burden showed statistically longer PFS. Citation Format: Yihebali Chi, Weili Liu, Lijie Zuo, Yuehua Wang, Weijing Cai, Susheng Shi, Yanying Ge, Rui Li, Lijie Song, Yiqi Yang, Zheng Liu, Xiaowu Dou, Hong Zhao. Genetic characteristics of PanNETs, Rectal NETs, Thoracic NETs and its correlation with efficacy of chemotherapy [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 4743.
Efficient and rapid conversion of human astrocytes and ALS mouse model spinal cord astrocytes into motor neuron-like cells by defined small molecules
Authors: An-Dong Zhao, Hua Qin, Meng-Li Sun, Kui Ma, Xiao-Bing Fu
Journal: Military Medical Research (2020)

Motor neuron degeneration or loss in the spinal cord is the characteristic phenotype of motor neuron diseases or spinal cord injuries. Being proliferative and located near neurons, astrocytes are considered ideal cell sources for regenerating neurons.We selected and tested different combinations of the small molecules for inducing the conversion of human and mouse astrocytes into neurons. Microscopic imaging and immunocytochemistry analyses were used to characterize the morphology and phenotype of the induced neurons while RT-qPCR was utilized to analyze changes in gene expression. In addition, whole-cell patch-clamp recordings were measured to examine the electrophysiological properties of induced neurons.The results showed that human astrocytes could be rapidly and efficiently converted into motor neuron-like cells by treatment with defined small molecules, with a yield of over 85% motor neuron-like cells attained. The induced motor neuron-like cells expressed the pan-neuronal markers TUJ1, MAP2, NeuN, and Synapsin 1 and motor neuron markers HB9, ISL1, CHAT, and VAChT. During the conversion process, the cells did not pass through a proliferative neural progenitor cell intermediate. The induced motor neurons were functional, showing the electrophysiological properties of neurons. The same chemical cocktail could induce spinal cord astrocytes from an amyotrophic lateral sclerosis mouse model carrying a SOD1 mutation to become motor neuron-like cells that exhibited a decrease in cell survival and an increase in oxidative stress compared to that observed in wild-type MNs derived from healthy mice. Moreover, the chemical induction reduced oxidative stress in the mutant astrocytes.The results of the present study demonstrated the feasibility of chemically converting human and mouse astrocytes into motor neuron-like cells that are useful for neurodegenerative disease modeling and regenerative medicine.
Abstract 5863: Improved conversion in extraction, library construction, and capture improve sensitivity for variants in liquid biopsy samples
Authors: Nicole Roseman, Shilpa Parakh, Hsiao-Yun Huang, Kevin Lai, Timothy Barnes, Lyn Lewis, Ushati Das Chakravarty, Anastasia Potts, Alisa Jackson, Amy Yoder, Jessica Sheu, Tzu-Chun Chen
Journal: Cancer Research (2020)

Abstract Demonstrate performance of a complete automation and reagent workflow for analysis of cfDNA from bodily fluids. The efficient extraction of cfDNA from bodily fluids is a unique challenge due to the very low concentrations of nucleic acid. The extraction process along with library preparation is a laborious workflow, where human variability can lead to increased variability in the downstream analysis. Integrated DNA Technology (IDT) and Beckman Coulter (BC) have teamed up to provide a complete automation and reagent workflow for analysis of low frequency variants in cfDNA. The Apostle MiniMax™ High Efficiency Isolation Kit from BC provides complex, utilized magnetic nanoparticles to effectively capture cfDNA. IDT's library prep kit utilizes novel chemistry to maximize conversion, suppress adapter-dimer formation, reduce chimera rates, and facilitate double strand consensus analysis to call ultra-low frequency variants. Finally, IDT's xGen™ hybrid capture products maintain high library diversity and on-target rates to enable low frequency variant calling regardless of panel size. The Biomek i5 and i7 Hybrid workstations bring out the best performance from these reagents. The Biomek NGS workstations protocol is written with a modular design with safe stop points, making it customizable for each lab. The automated protocol uses Beckman's Demonstrated Method Interface tools which include: Biomek Method Launcher to run the method without going into Biomek software, Method Options Selector to choose the run parameters with a user friendly interface, Guided labware Setup to set the deck with labware based on the run parameters, DeckOptix Final Check software to help reduce deck setup errors. We demonstrate the performance of this complete workflow with a range of plasma inputs (4-8 mL). Using control samples with known variant frequencies, the workflow yields high library complexity, 100% positive predictive value, and reliable detection of &amp;lt;0.5% mutant allele frequency variants. With real cfDNA, the workflow demonstrates both high cfDNA and sequencing library yields along with high library complexity. The combination of these reagents on the Biomek workstations provides a robust and reproducible solution for the analysis of cfDNA. Citation Format: Nicole Roseman, Shilpa Parakh, Hsiao-Yun Huang, Kevin Lai, Timothy Barnes, Lyn Lewis, Ushati Das Chakravarty, Anastasia Potts, Alisa Jackson, Amy Yoder, Jessica Sheu, Tzu-Chun Chen. Improved conversion in extraction, library construction, and capture improve sensitivity for variants in liquid biopsy 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 5863.
Abstract 1988: Enabling personalized biomarker discovery in challenging oncology samples by coupling a novel library preparation chemistry with hybridization capture
Authors: Karissa Scott, Ushati Das Chakravarty, Hsiao-Yun Huang, Timothy Barnes, Kevin Lai, Jessica Sheu, Tzu-Chun Chen, Ramses Lopez, Lynette Lewis, Anastasia Potts, Steven Henck
Journal: Cancer Research (2020)

Abstract Discovery and identification of new, targetable biomarkers is driven by comprehensive tumor profiling using next generation sequencing (NGS). However, converting tissue samples into NGS libraries is often challenging due to the low quantity and quality of DNA in such samples. Here we present sensitive and accurate detection of low-frequency variants by combining a novel library preparation optimized for low-input and degraded samples with IDT's xGen hybridization capture. The library preparation is enabled by an engineered mutant ligase and proprietary sequencing adapters that together prevent chimeras, suppress dimer-formation, enable double strand consensus calling, and maximize conversion. We demonstrate the performance of these reagents with archived tissue samples collected from five individuals with lung cancer. These matched samples consisted of DNA isolated from formalin-fixed paraffin-embedded (FFPE) tumor, DNA isolated from fresh-frozen normal tissue, and cell-free DNA (cfDNA) isolated from plasma. Sequencing libraries were prepared from 250 ng of tumor and healthy samples and 10 ng of cfDNA. Libraries were captured using a pan-cancer panel designed to simultaneously detect copy number variations, indels, rearrangements, and microsatellite instability across 532 oncogene targets. For each individual, tumor-associated mutations were identified using single-stranded consensus calling of variants found in tumor but not normal samples. As cfDNA has been correlated to disease progression, we wanted to determine if tumor-associated variants could be identified in the matched cfDNA samples. Custom capture panels were designed and delivered within 5 business days to target each individual's tumor-associated mutations. Relevant cfDNA samples were captured with these custom panels, sequenced, and variants were called after double stranded consensus calling. Mutations called from both FFPE tumor and cfDNA samples were verified by droplet digital PCR. By combining a high conversion library preparation with efficient hybridization capture and double stranded consensus calling, we have demonstrated an effective approach to extract information from difficult samples. Citation Format: Karissa Scott, Ushati Das Chakravarty, Hsiao-Yun Huang, Timothy Barnes, Kevin Lai, Jessica Sheu, Tzu-Chun Chen, Ramses Lopez, Lynette Lewis, Anastasia Potts, Steven Henck. Enabling personalized biomarker discovery in challenging oncology samples by coupling a novel library preparation chemistry with hybridization capture [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 1988.