tbuckley/cabot-search huggingface dataset:
Abstract B48: STAT3 pathway in fibroblasts aggravates invasiveness of lung cancer cells in the tumor microenvironment
Authors: Ju-Hee Kang, Ha Jung Lee, Hyun Jin Jung, Min Woo Kim, Seung Hyun Oh
Journal: Cancer Research (2020)

Abstract Cancer-associated fibroblasts (CAF), as one of the major components of tumor microenvironment, have a significant role in cancer development and progression. CAF also supports the survival and chemo-induced resistance of cancer cells. Among various signaling pathways involved in cancer cell and CAF interaction, the signal transducers and activators of transcription (STAT3) pathway has been investigated a lot, but its own role in CAF itself is not yet clearly defined. In this paper, we established CAF using MRC5, which is a stable lung fibroblast cell line, by culturing with conditioned medium from lung cancer cells. Then, by using a STAT3 inhibitor, STX-0119, and STAT3 siRNA, we examined whether the blocking of STAT3 pathway in MRC5 affects chemotherapeutic resistance or invasiveness of A549 lung cancer cells. We found out that STAT3 inhibition in fibroblasts did not prevent CAF-induced resistance of A549 cells on proliferation, but it did attenuate the invasiveness and migration of A549 cells. These results suggest that the combination of a low dose of a STAT3 inhibitor, which would be high enough to inactivate the CAF around the tumor cells, and an anticancer drug can be taken as an approach to cancer treatment. Citation Format: Ju-Hee Kang, Ha Jung Lee, Hyun Jin Jung, Min Woo Kim, Seung Hyun Oh. STAT3 pathway in fibroblasts aggravates invasiveness of lung cancer cells in the tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B48.
A Unique N-Phenylbenzamide Inhibitor Targeting Non-Receptor Tyrosine Kinases Potently Suppresses AML Cell Growth In Vitro and In Vivo
Authors: Mark C Weir, Sherry Shu, Sabine Hellwig, Ravi Patel, Li Chen, Li Tan, Nathanael Gray, Thomas Smithgall
Journal: Blood (2017)
Abstract IA01: Plasma DNA-based molecular diagnostics: Fragments, circles and beyond
Authors: Yuk Ming Dennis Lo
Journal: Clinical Cancer Research (2020)

Abstract My group has a longstanding interest in the diagnostic applications of cell-free DNA in plasma. For example, we have pioneered noninvasive prenatal testing (NIPT) and the use of plasma DNA for cancer screening. We believe that understanding the fundamental biology of circulating DNA is essential to further advance the field. In this regard, we have been particularly interested in the fragmentation patterns of cell-free DNA in plasma. We have shown that cell-free fetal DNA molecules in the plasma of pregnant women are shorter than those of maternal origin. The differential size profiles between circulating fetal and maternal DNA have enabled the use of plasma DNA size as an independent metric for NIPT. In the area of cancer liquid biopsy, we have used circulating Epstein-Barr virus (EBV) DNA as an example of tumor-derived DNA in plasma. Hence, circulating EBV DNA molecules are also short fragments of DNA. In another example, we have used hepatocellular carcinoma as a model system and have found that circulating tumor-derived DNA molecules have a shorter size profile than those of nontumoral origin. We are exploring enzymes that might be involved in the fragmentation of plasma DNA. We have shown that mice in which both copies of the Dnase1l3 gene have been knocked out have a larger size profile of circulating DNA. We have also developed a plasma DNA end motif metric to measure the effect of disruption of this nuclease system. In addition to the fragmentation of linear DNA in plasma, my group is also interested in exploring the presence of nonlinear DNA in plasma. Hence, we have used mitochondrial DNA (mtDNA) as a model system as mtDNA exists as a circular molecule inside mitochondria. Interestingly, we have observed the existence of both linear and circular mtDNA in plasma. Using liver and bone marrow transplantation models, we have shown that the circular form is predominantly of hematopoietic origin while the linear form is predominantly from the liver. Plasma mtDNA topologics thus holds information on the origin of circulating DNA. These studies therefore demonstrate some of the exciting findings that can be revealed through the study of plasma DNA fragmentomics and topologics. We believe that such new biologic understandings will drive new diagnostic applications. Citation Format: Yuk Ming Dennis Lo. Plasma DNA-based molecular diagnostics: Fragments, circles and beyond [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA01.
Abstract IA23: Phospho-RNA-seq: A liquid biopsy approach for cell-free mRNA/lncRNA profiling
Authors: Maria D. Giraldez, Ryan M. Spengler, Alton Etheridge, Annika J. Goicochea, Missy Tuck, Sung W. Choi, David J. Galas, Muneesh Tewari
Journal: Clinical Cancer Research (2020)

Abstract Measuring disease biomarkers in biofluids to detect and monitor pathophysiologic events in tissues has enormous appeal. While detecting specific DNA sequences in blood plasma has been successful in informing about the presence of cancers, viruses, and a range of pathogens, this approach does not provide gene expression information, which could reveal more detailed information about disease activity. Measuring cell-free RNA in plasma would provide such information and has the potential to be more sensitive, given that one DNA molecule in a cell gives rise often to thousands or more RNA molecules. However, with the exception of microRNAs, broad sequencing of cell-free messenger RNA (mRNA) profiles in plasma has been generally challenging. We discovered that a major barrier to cell-free RNA sequencing from plasma is that the large majority of mRNAs are both fragmented and have modified phosphorylation states at their 5’ and 3’ ends that make them invisible to standard small RNA-seq methods. We present a modified RNA-seq methodology, called phospho-RNA-seq, which revealed thousands of mRNA in blood plasma. The key to this approach is (i) the incorporation of T4-polynucleotide kinase treatment to change the phosphorylation states at the RNA ends, and (ii) a stringent bioinformatics analysis pipeline to reduce false positive alignments. Phospho-RNA-seq identified cohorts of gene transcripts in plasma, including ones expressed in a tissue-specific manner. As proof-of-concept validation of the approach for biomarker identification, we used phospho-RNA-seq to longitudinally profile plasma specimens collected from patients undergoing hematopoietic stem cell transplantation. We detected bone marrow-enriched and liver-enriched transcript sets in plasma, which tracked with bone marrow recovery and hepatic injury, respectively. By providing expanded access to the transcriptome in plasma and potentially other biofluids, phospho-RNA-seq enables the discovery of new cell-free RNA biomarker signatures for a wide variety of liquid biopsy applications. Citation Format: Maria D. Giraldez, Ryan M. Spengler, Alton Etheridge, Annika J. Goicochea, Missy Tuck, Sung W. Choi, David J. Galas, Muneesh Tewari. Phospho-RNA-seq: A liquid biopsy approach for cell-free mRNA/lncRNA profiling [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA23.
RETRACTED ARTICLE: CircTLK1 promotes the proliferation and metastasis of renal cell carcinoma by sponging miR-136-5p
Authors: Jianfa Li, Chenchen Huang, Yifan Zou, Jing Ye, Jing Yu, Yaoting Gui
Journal: Molecular Cancer (2020)

Abstract Background Circular RNAs (circRNAs), a novel type of noncoding RNA (ncRNA), are covalently linked circular configurations that form via a loop structure. Accumulating evidence indicates that circRNAs are potential biomarkers and key regulators of tumor development and progression. However, the precise roles of circRNAs in renal cell carcinoma (RCC) remain unknown. Methods Through circRNA high-throughput sequencing of RCC cell lines, we identified the circRNA TLK1 (circTLK1) as a novel candidate circRNA derived from the TLK1 gene. qRT-PCR detected the mRNA, circRNA and miRNA expression levels in RCC tissues and cells. Loss-of function experiments were executed to detect the biological roles of circTLK1 in the RCC cell phenotypes in vitro and in vivo. RNA-FISH, RNA pull-down, dual-luciferase reporter, western blot and immunohistochemistry assays were used to investigate the molecular mechanisms underlying the functions of circTLK1. Results circTLK1 is overexpressed in RCC, and expression is positively correlated with distant metastasis and unfavorable prognosis. Silencing circTLK1 significantly inhibited RCC cell proliferation, migration and invasion in vitro and in vivo. circTLK1 was mainly distributed in the cytoplasm and positively regulated CBX4 expression by sponging miR-136-5p. Forced CBX4 expression reversed the circTLK1 suppression-induced phenotypic inhibition of RCC cells. Moreover, CBX4 expression was positively correlated with VEGFA expression in RCC tissues. CBX4 knockdown significantly inhibited VEGFA expression in RCC cells. Conclusion Collectively, our findings demonstrate that circTLK1 plays a critical role in RCC progression by sponging miR-136-5p to increase CBX4 expression. circTLK1 may act as a diagnostic biomarker and therapeutic target for RCC.
Thrombectomy for Stroke in the Public Health Care System of Brazil
Authors: Sheila O. Martins, Francisco Mont’Alverne, Letícia C. Rebello, Daniel G. Abud, Gisele S. Silva, Fabrício O. Lima, Bruno S.M. Parente, Guilherme S. Nakiri, Mário B. Faria, Michel E. Frudit, João J.F. de Carvalho, Eduardo Waihrich, José A. Fiorot, Fabrício B. Cardoso, Raquel C.T. Hidalgo, Viviane F. Zétola, Fernanda M. Carvalho, Ana C. de Souza, Francisco A. Dias, Diego Bandeira, Maramélia Miranda Alves, Mário B. Wagner, Leonardo A. Carbonera, Jamary Oliveira-Filho, Daniel C. Bezerra, David S. Liebeskind, Joseph Broderick, Carlos A. Molina, José E. Fogolin Passos, Jeffrey L. Saver, Octávio M. Pontes-Neto, Raul G. Nogueira
Journal: New England Journal of Medicine (2020)

Randomized trials involving patients with stroke have established that outcomes are improved with the use of thrombectomy for large-vessel occlusion. These trials were performed in high-resource countries and have had limited effects on medical practice in low- and middle-income countries.
Adrenal and Bone Metastases as the Initial Presentation of Endometrial Carcinoma Diagnosed by 18F-FDG PET/CT
Authors: Minggang Su, Jiangming Sun, Qiuping Fan, Rong Tian
Journal: Clinical Nuclear Medicine (2020)

Abstract Adrenal and bone metastases as the initial presentation of endometrial carcinoma are rare. We report a case of endometrial carcinoma in a 47-year-old woman with initial manifestation as right chest wall pain, which was suspected as adrenal cortical carcinoma with rib metastasis after diagnostic CT scan. However, uterine and pelvic bone lesions were revealed by staging FDG PET/CT. Eventually, endometrial carcinoma with adrenal and bone metastases was confirmed pathologically.
Abstract PHA03: Coordinate translational control of KRAS signaling pathway in pancreatic adenocarcinoma
Authors: Kamini Singh, Hans-Guido Wendel
Journal: Cancer Research (2020)

Abstract G-quadruplex (GQ) elements are conserved translational control elements that induce a requirement for RNA helicase activity for efficient mRNA translation. Computational structure analyses identify GQ elements in the 5´UTRs of mRNAs encoding KRAS and key downstream signaling molecules. KRAS is a key oncogene in pancreatic ductal adenocarcinoma (PDAC) and many other cancers, and except for the specific G12C KRAS mutation we do not have pharmacologic inhibitors. We find that KRAS and downstream signaling molecules, including PI3K, RALA, RAC2, MYC, MET, and YAP1, strictly depend on the RNA helicase eIF4A for their translation. This implies a potential utility for eIF4A/DDX2 inhibitors such as the silvestrol analogue CR31B. Indeed, CR31B shows nanomolar cell kill in vitro and in vivo efficacy across xenograft, primary PDX, and murine PDAC models. Together, our study reveals a signature of coordinate and eIF4A/DDX2 dependent oncogene translation in PDAC that is potentially accessible to therapeutic attack. This abstract is also being presented as Poster A18. Citation Format: Kamini Singh, Hans-Guido Wendel. Coordinate translational control of KRAS signaling pathway in pancreatic adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr PHA03.
Abstract 11411: Plasminogen Facilitates Foam Cell Formation by Macrophages Utilizing H2B and PAR1
Authors: Lahoucine Izem, Katarzyna Bialkowska, Elzbieta Pluskota, Marvin T Nieman, Edward F Plow
Journal: Circulation (2019)

Plasminogen (Plg) is the zymogen form of plasmin, the serine protease primarily responsible for degrading fibrin within blood clots. Plg mediates many of its functions by binding to the Plg recepto...
Management of Cancer and Health After the Clinic Visit: A Call to Action for Self-Management in Cancer Care
Authors: Doris Howell, Deborah K Mayer, Richard Fielding, Manuela Eicher, Irma M Verdonck-de Leeuw, Christoffer Johansen, Enrique Soto-Perez-de-Celis, Claire Foster, Raymond Chan, Catherine M Alfano, Shawna V Hudson, Michael Jefford, Wendy W T Lam, Victoria Loerzel, Gabriella Pravettoni, Elke Rammant, Lidia Schapira, Kevin D Stein, Bogda Koczwara
Journal: JNCI Journal of the National Cancer Institute (2020)

Individuals with cancer and their families assume responsibility for management of cancer as an acute and chronic disease. Yet, cancer lags other chronic diseases in its provision of proactive self-management support in routine, everyday care leaving this population vulnerable to worse health status, long-term disability, and poorer survival. Enabling cancer patients to manage the medical and emotional consequences and lifestyle and work changes due to cancer and treatment is essential to optimizing health and recovery across the continuum of cancer. In this paper, the Global Partners on Self-Management in Cancer puts forth six priority areas for action: Action 1: Prepare patients and survivors for active involvement in care; Action 2: Shift the care culture to support patients as partners in cocreating health and embed self-management support in everyday health-care provider practices and in care pathways; Action 3: Prepare the workforce in the knowledge and skills necessary to enable patients in effective self-management and reach consensus on core curricula; Action 4: Establish and reach consensus on a patient-reported outcome system for measuring the effects of self-management support and performance accountability; Action 5: Advance the evidence and stimulate research on self-management and self-management support in cancer populations; Action 6: Expand reach and access to self-management support programs across care sectors and tailored to diversity of need and stimulation of research to advance knowledge. It is time for a revolution to better integrate self-management support as part of high-quality, person-centered support and precision medicine in cancer care to optimize health outcomes, accelerate recovery, and possibly improve survival.
Sex, Gender, and Precision Medicine
Authors: Sanne A. E. Peters, Mark Woodward
Journal: JAMA Internal Medicine (2020)

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Abstract A32: Targeting RON-mediated metabolic vulnerabilities in recurrent/progressive breast cancer
Authors: Brian G. Hunt, Christina A. Wicker, Jennifer Bourn, Elyse Lower, Vinita Takiar, Susan E. Waltz
Journal: Cancer Research (2020)

Abstract Despite advances in clinical detection, molecular subtyping, and targeted therapeutics, breast cancer (BC) is the second leading cause of cancer-related death in women. Recurrent and metastatic disease is the underlying cause of BC mortality. Due to fear of recurrence, BC is the most overtreated cancer, creating significant ethical and financial burdens. Through a discovery-based genomics approach, the RON receptor tyrosine kinase was identified as a predictor of BC recurrence. We and others have shown that RON overexpression occurs in more than half of all BCs and that RON levels are a predictor of metastasis and poor survival. Through evaluation of human breast tumor tissue, we provide the first line of evidence that RON overexpression occurs independent of molecular subtype and provide prognostic evidence of RON expression as a biomarker of BC recurrence. Further, we identified glycolysis and cholesterol biosynthesis, two potentially therapeutically targetable processes, as being significantly upregulated by RON. To test the efficacy of reducing cholesterol as a therapy for BC with RON expression, we treated two independent, spontaneous murine breast cancer models with inhibitors directed at RON and/or cholesterol biosynthesis (atorvastatin). Our studies show that either RON or cholesterol inhibition reduced BC progression and that combination treatments blocked progression further. Current studies are under way to determine the mechanisms by which RON promotes metabolic pathway dependency and to directly test in a novel murine model of BC recurrence if targeting these pathways provides a survival benefit. We anticipate that our studies will serve as the scientific underpinnings for rationally designed new combinatorial therapeutic strategies to decrease the morbidity and mortality associated with advanced breast cancer. Citation Format: Brian G. Hunt, Christina A. Wicker, Jennifer Bourn, Elyse Lower, Vinita Takiar, Susan E. Waltz. Targeting RON-mediated metabolic vulnerabilities in recurrent/progressive breast cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr A32.
Abstract B11: Whole-exome sequencing analysis of urine transrenal tumor DNA in metastatic colorectal cancer patients
Authors: Giovanni Crisafulli, Benedetta Mussolin, Andrea Cassingena, Monica Montone, Alice Bartolini, Ludovic Barault, Antonio Martinetti, Federica Morano, Filippo Pietrantonio, Andrea Sartore-Bianchi, Salvatore Siena, Federica Di Nicolatonio, Silvia Marsoni, Alberto Bardelli, Giulia Siravegna
Journal: Clinical Cancer Research (2020)

Abstract Background: The analysis of circulating free tumor DNA (ctDNA) in blood, commonly referred to as liquid biopsy, is being used to characterize patients with solid cancers. Tumor-specific genetic variants can also be present in DNA isolated from other body fluids such as urine. Unlike blood, urine sampling is noninvasive, can be self-performed, and allows recurrent longitudinal monitoring. The features of tumor DNA that clears from the glomerular filtration barrier (transrenal tumor DNA, hereafter trtDNA) are largely unexplored. Patients and Methods: Specimens were collected from 24 patients with KRAS or BRAF mutant metastatic colorectal cancer (mCRC). Driver mutations were assessed by droplet digital PCR (ddPCR) in ctDNA from plasma and trtDNA from urine. Whole-exome sequencing (WES) was performed in DNA isolated from tissue, plasma, and urine. Results: Out of the 24 CRC cases, only four had sufficient DNA to allow WES analyses in urine and plasma. We found that tumor alterations reside primarily in low-molecular-weight fragments. In patients where trtDNA was more than 2.69% of the urine-derived DNA, cancer-specific molecular alterations, mutational signatures, and copy number profiles identified in urine DNA are comparable with those detected in plasma ctDNA. Conclusions: With current technologies, WES analysis of trtDNA is feasible in a small fraction of mCRC patients. Tumor-related genetic information is mainly present in shorter DNA fragments. Although the limited amounts of trtDNA pose analytical challenges, enrichment of low-molecular-weight DNA and optimized computational tools improve detection of tumor-specific genetic information in urine. Citation Format: Giovanni Crisafulli, Benedetta Mussolin, Andrea Cassingena, Monica Montone, Alice Bartolini, Ludovic Barault, Antonio Martinetti, Federica Morano, Filippo Pietrantonio, Andrea Sartore-Bianchi, Salvatore Siena, Federica Di Nicolatonio, Silvia Marsoni, Alberto Bardelli, Giulia Siravegna. Whole-exome sequencing analysis of urine transrenal tumor DNA in metastatic colorectal cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B11.
Covid-19: Better data on outbreaks will help control infection, say experts
Authors: Shaun Griffin
Journal: BMJ (2020)

Registered deaths mentioning covid-19 in England and Wales are continuing to decline, with 1822 deaths in the week ending 29 May, 767 fewer than the previous week, show figures from the Office for National Statistics.1

However, the covid-19 death rate is declining slowly and has a “long tail,” reflecting ongoing issues in care homes and SARS-CoV circulating in hospitals, said Carl Heneghan, director of the Centre for Evidence Based Medicine at the University of Oxford.

At a Science Media Centre briefing on 9 June he said that, to support testing and tracking efforts, the Care Quality Commission and Public Health England should learn from Northern Ireland, where data are provided on active outbreaks of covid-19 in care homes and when these are …
Ten things we learned about COVID-19
Authors: Maurizio Cecconi, Guido Forni, Alberto Mantovani
Journal: Intensive Care Medicine (2020)

The virusSARS-CoV-2 contains over 30,000 RNA bases.A proofreading mechanism keeps this large genome from accumulating frequent mutations.The large spike protein (S) forms a sort of crown on the surface of the viral particles.Its receptor-binding domain interacts with high affinity with angiotensin-converting enzyme 2 (ACE2) receptors on the surface of host cells.After the binding, two host cell proteases (Furin and TMPRLRS) cleave spike proteins and their exposed fusion peptides fuse the virus membrane with the membrane of the host cells.The virus RNA enters cells of the upper and lower respiratory tract, and it is translated into viral proteins.Other entry points are under investigation.The cell dies releasing millions of new viruses that infect other cells and other individuals [1].