tbuckley/cabot-search huggingface dataset:
Abstract 169: Discovery of clinically distinct CLL subgroups by integrative mapping of large-scale genetic, epigenetic, expression and clinical data
Authors: Binyamin A. Knisbacher, Ziao Lin, Chip Stewart, Cynthia K. Hahn, Kristen E. Stevenson, Donna S. Neuberg, José I. Martín-Subero, Xose S. Puente, Elias Campo, Catherine J. Wu, Gad Getz
Journal: Cancer Research (2020)

Abstract Chronic lymphocytic leukemia (CLL) accounts for one third of all diagnosed leukemias. It exhibits tremendous clinical variability, ranging from indolent disease kinetics to a fast progressing aggressive disease. Two large-scale studies by our groups, each analyzing more than 500 CLL subjects, have shown that a large part of this clinical variability can be explained by underlying molecular features of the cancerous B-cells, including genetic and epigenetic alterations. Despite this progress, patients do not yet fully benefit from these discoveries in their treatment plans, and prognosis is not tailored to them based on the molecular features of their cancer. To achieve precision medicine, we compile a large dataset of multi-omic and clinical data from over 1100 CLL patients. Our extensive cohort confers power to detect novel driver genes, doubling the number of known drivers (114 total) and identifying drivers specific to major CLL subtypes, such as IGHV-mutated and IGHV-unmutated. The analysis identifies recurrent copy number alterations, order-of-event timing and mutational processes acting in CLL. We integrate these with expression data from 700 CLL RNA-seqs and epigenetic data to define molecular subtypes that present differential clinical outcomes. Altogether, this work delineates the molecular landscape of CLL and sets the stage for improved classification, prognostics and treatment of CLL patients. Citation Format: Binyamin A. Knisbacher, Ziao Lin, Chip Stewart, Cynthia K. Hahn, Kristen E. Stevenson, Donna S. Neuberg, José I. Martín-Subero, Xose S. Puente, Elias Campo, Catherine J. Wu, Gad Getz. Discovery of clinically distinct CLL subgroups by integrative mapping of large-scale genetic, epigenetic, expression and clinical data [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 169.
Abstract 1285: Functional analysis of ZFHX4 as a novel therapeutic target in ovarian cancer
Authors: Yoshiko Oyama, Shogo Shigeta, Keita Tsuji, Hideki Tokunaga, Muneaki Shimada, Nobuo Yaegashi
Journal: Cancer Research (2020)

Abstract [Introduction] Ovarian cancer is one of the most lethal gynecologic malignancies. More than half of the patients are diagnosed in advanced stages of disease where the prognosis is poor due to the inevitable acquired resistance to platinum agents. Although maintenance therapy with PARP inhibitors or bevacizumab has been proven to improve patient survival, platinum sensitivity is still the most important prognostic factor. Thus, novel therapeutic strategies effective for platinum-resistant cases or to overcome platinum-resistance are required. Zinc Finger Homeobox 4 (ZFHX4) has been known as one of the major transcription regulators in nerve and muscle differentiation. Although not fully elucidated, recent researches including our genome-wide exploration indicate ZFHX4 is also involved in carcinogenesis and cancer progression. The objective of this study was to investigate the potential of ZFHX4 as a novel therapeutic target in ovarian cancer by analyzing clinical database and cell model experiments. [Methods] Correlations between ZFHX4 mRNA expression and overall survival in 61 ovarian cancer cases treated at our institute and in the cases registered in TCGA database respectively were assessed by log-lank test. RNAi knockdown was introduced to several ovarian cancer cells to investigate the influence of ZFHX4 on cancer cell proliferation. Scratch assay was performed to assess the effect of RNAi knockdown on cell migration ability. Cells were also treated with cisplatin after 72 hours of siRNA transfection to assess the influence of ZHFX4 on platinum sensitivity. [Results] Both in our clinical dataset and TCGA data, the overall survival was significantly poor in the group in which ZFHX4 is highly expressed. In cell model assay, ZFHX4 knockdown significantly suppressed ovarian cancer cell proliferation. Decreased motility was observed in the cells treated with siRNA targeting ZFHX4 by scratch assay. Furthermore, ZFHX4 knockdown increased cisplatin sensitivity in ovarian cancer cells. [Conclusions] Altogether, our results suggest ZFHX4 functions to promote cancer cell proliferation, migration and platinum-resistance. Interruption of ZFHX4 function independently or in combination with platinum agents has a potential to bring benefit for the treatment of ovarian cancer. Citation Format: Yoshiko Oyama, Shogo Shigeta, Keita Tsuji, Hideki Tokunaga, Muneaki Shimada, Nobuo Yaegashi. Functional analysis of ZFHX4 as a novel therapeutic target 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 1285.
Abstract 2080: Tissue-specific tumorigenesis in multiple endocrine neoplasia type I
Authors: Juliet C. Gardiner, Steven K. Libutti
Journal: Cancer Research (2020)

Abstract While a germline heterozygous mutation in the Multiple Endocrine Neoplasia type 1 (MEN1) gene predisposes tumor formation in specific tissues such as the endocrine pancreas, parathyroid glands and anterior pituitary, this tissue-specific tumorigenesis is not dependent on MEN1 mutations alone. In fact, a homozygous deletion of Men1 in mouse pancreatic exocrine tissue does not result in tumor formation, suggesting a tissue-specific mechanism. Loss of menin activates a menin-interacting protein retinoblastoma-binding-protein 5 (RBBP5). Since RBBP5 transcriptionally regulates DNA methyltransferase 1 (DNMT1), this causes global DNA hypermethylation and subsequent tumorigenesis in MEN1-target endocrine tissues. We hypothesize that while RBBP5 is ubiquitously expressed, it exclusively binds to the DNMT1 promoter in MEN1-target-tissues through its recruitment by tissue-specific factors. Using chromatin immunoprecipitation, we demonstrated that Rbbp5 is bound to the Dnmt1 promoter in MEN1-target-tissues, while not in non-target tissues. Following a high-throughput genome-wide approach, we identified two candidate factors that may recruit Rbbp5 to the Dnmt1 promoter. Immunohistochemistry showed MEN1-target-tissue-specific expression of these target factors. Co-immunoprecipitation revealed MEN1-target-tissue-specific binding of Rbbp5 to the factors. In conclusion, Rbbp5 binds the Dnmt1 promoter in MEN1-target-tissues and we have identified candidates for Rbbp5 recruitment to the Dnmt1 promoter that must be tested further to determine their role in the observed tissue specificity of MEN1-related tumorigenesis. Citation Format: Juliet C. Gardiner, Steven K. Libutti. Tissue-specific tumorigenesis in multiple endocrine neoplasia type I [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 2080.
Early Formula Supplementation Trends by Race/Ethnicity Among US Children Born From 2009 to 2015
Authors: Ruowei Li, Cria G. Perrine, Erica H. Anstey, Jian Chen, Carol A. MacGowan, Laurie D. Elam-Evans, Deborah A. Galuska
Journal: JAMA Pediatrics (2020)

This article was corrected on October 5, 2020, to correct errors in Figure 1.The labels for 1.0 and 1.5 on the y-axis of the forest plot graph were reversed.Also, the square indicating the prevalence for site 14 was displaced from its true value, 2.21%, to approximately 2.75%; this square was also larger than it should have been.The errors have been corrected.
SAT0232 Management of chronic musculoskeletal pain
Authors: M Pileckyte, N Misiuniene
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> Of the study were to explore the management of sufferers with chronic musculoskeletal pain (CMP) syndromes. <h3>Methods</h3> A random sample of subjects was selected in the vicinity of two main outpatient clinics of the city Kaunas. All subjects aged 25–74 were requested to indicate on a mannequin any pain which had been lasting at least 24 h since the last month. Subjects who met the ACR 1990 definition for chronic widespread pain (CWP) and subjects who satisfied the standard definition of chronic low back pain (CBP) but not the ACR definition for CWP were interviewed according to a standard questionnaire. A follow-up screening of all the subjects was carried out after 6 months. Subjects who still reported CWP and CBP were classified as "persistent" CWP and CBP sufferers. Outpatient medical records of all these subjects were analysed. <h3>Results</h3> The study population comprised 1,404 subjects, 1,030 being aged 25–74. The response rate was 83.01%. The average age of respondents was 49.29 ± 13.09, 61.64% being females. The prevalence of CWP was 18.60% and CBP- 12.28%. After 6 months 88.68% of subjects with CWP and 72.38% with CBP participated in the follow-up screening. "Persistent" CWP was present in 79.43% and "persistent" CBP- in 47.37% of respondents. The majority of subjects with CWP (98.08%) and CBP (88.89%) consulted the general practitioner (GP) during the last year, mainly because of CMP. Many CWP (54.90%) and CBP (37.50%) sufferers consulted the GP 6–10 times during the last year. They were ordered a lot of investigations by the GP and were referred to specialists for medical advice (e.g., to a neurologist- 56.86% of CWP and 66.67% of CBP sufferers but to a rheumatologist- only 3.92% of CWP and 16.67% of CBP sufferers). The diagnosis was altered only in a very few cases. CBP was poorly diagnosed and fibromyalgia syndrome was not diagnosed at all by the GP. CMP patients were treated mainly with nonsteroidal anti-inflammatory drugs. No one received antidepressants, only 29.41% of CWP and 54.17% of CBP sufferers were prescribed rehabilitation procedures, but often they were hospitalised (27.45% of CWP and 29.17% of CBP cases) during the last year. Quite a big number of CWP sufferers experienced either short-time or permanent disability. <h3>Conclusion</h3> CMP syndromes are common in the outpatient population. More attention and priority for education of medical professionals concerning early diagnosis and appropriate treatment of CMP should be given by responsible health care authorities.
A Curve Ball
Authors: Mitsuru Mukaigawara, Reza Manesh, Mitsuyo Kinjo, Shuichi Sugita, Andrew P.J. Olson
Journal: New England Journal of Medicine (2020)

A 70-year-old man presented to the emergency department after an episode of altered mental status. Two days before presentation, he began having increased urinary frequency and decreased urine volume after eating a rice cake made with potato. On the day of presentation, he appeared disoriented and he fell.
Abstract 3657: Analysis of the regulation of PD-L1 expression and methyl transferases levels following inhibition of histone deacetylases in cancer cells
Authors: Umamaheswari Natarajan, Thiagarajan Venkatesan, Theodore L. Mathuram, Jayanta K. Das, Appu Rathinavelu
Journal: Cancer Research (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 3559: Protein secretion rates of VEGF and CA9 in normoxia and hypoxia
Authors: Sandy Che-Eun Serena Lee, Fiana Levitin, Stephanie Hulme, Ryan Rumantir, Jenna Sykes, Marianne Koritzinsky
Journal: Cancer Research (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.
Trends in the Prevalence of Self-reported Heart Failure by Race/Ethnicity and Age From 2001 to 2016
Authors: Leah Rethy, Lucia C. Petito, Thanh Huyen T. Vu, Kiarri Kershaw, Rupal Mehta, Nilay S. Shah, Mercedes R. Carnethon, Clyde W. Yancy, Donald M. Lloyd-Jones, Sadiya S. Khan
Journal: JAMA Cardiology (2020)

<h3>Importance</h3> Despite recent advances in therapies for heart failure (HF), deaths from HF are increasing, with persistent disparities between Black and White adults. Recent national trends in the prevalence of HF need to be clarified to appropriately allocate resources and develop effective preventive interventions. <h3>Objectives</h3> To examine the prevalence of ambulatory HF overall and by race/ethnicity and age and the temporal changes in HF prevalence between 2001 and 2016. <h3>Design, Setting, and Participants</h3> This cross-sectional study of nationally representative data collected biennially through the National Health and Nutrition Examination Survey (NHANES) from January 1, 2001, to December 31, 2016, assessed nonpregnant adults 35 years and older who self-identified as non-Hispanic Black, non-Hispanic White, or Mexican American. Data analysis was performed from November 16, 2019, to April 12, 2020. <h3>Exposures</h3> Survey period, race/ethnicity, and age group. <h3>Main Outcomes and Measures</h3> Age-standardized prevalence was calculated within 4-year survey periods (2001-2004, 2005-2008, 2009-2012, and 2013-2016) based on self-report of ambulatory HF overall and by race/ethnicity and age group (35-64 and ≥65 years). Weighted multivariable logistic regression was used to examine trends in ambulatory HF prevalence over time by race/ethnicity and age group. <h3>Results</h3> A total of 26 097 participants (mean [SD] age, 55.9 [10.7] years; 13 192 [52%] female; 6519 [12%] non-Hispanic Black; and 4906 [7%] Mexican American) were studied. Overall age-standardized prevalence (per 100 000 population) of ambulatory HF was 3184 (95% CI, 2641-3728) from 2001 to 2005 and 3045 (95% CI, 2651-3438) from 2013 to 2016. The prevalence of ambulatory HF was highest among non-Hispanic Black adults: from 2013 to 2016, HF prevalence (per 100 000 population) was 5017 (95% CI, 3755-6279) among non-Hispanic Black adults, 2746 (95% CI, 2313-3179) among non-Hispanic White adults, and 2508 (95% CI, 1154-3862) among Mexican American adults. Differences between White and Black adults in HF prevalence were also present in younger and middle-aged adults (eg, 35-64 years of age in 2013-2016: 3864 [95% CI, 2369-5359] for non-Hispanic Black adults vs 1297 [95% CI, 878-1716] for non-Hispanic White adults). <h3>Conclusions and Relevance</h3> This study found that a high burden of ambulatory HF persisted between 2001 and 2016 in the US. Disparities were most prominent by age group. Alongside prevention and aggressive management of risk factors, targeted efforts aimed at mitigating racial disparities are needed.
Phase Angle From Bioelectrical Impedance for the Assessment of Sarcopenia in Cirrhosis With or Without Ascites
Authors: Astrid Ruiz-Margáin, Jesse J. Xie, Berenice M. Román-Calleja, Margaret Pauly, Michelle G. White, Mónica Chapa-Ibargüengoitia, Alejandro Campos-Murguía, José A. González-Regueiro, Ricardo U. Macias-Rodríguez, Andres Duarte-Rojo
Journal: Clinical Gastroenterology and Hepatology (2020)
Inhaled nanobodies against COVID-19
Authors: Gustavo Martinez-Delgado
Journal: Nature reviews. Immunology (2020)

Inhaled nanobodies against COVID-19Nanobodies (Nbs) are naturally occurring single-domain antibody fragments from camelid heavy-chain antibodies.They have unique biophysical properties, including small size and thermostability, that allow aerosolized administration.In this preprint, Gai et al. describe Nb phage display libraries from camels immunized with the SARS-CoV-2 spike receptorbinding domain (RBD).Out of 381 Nbs identified, 7 blocked the interaction between the virus entry receptor ACE2 and 8 RBD variants.Nb11-59, a candidate with the highest neutralizing activity, was further selected to validate its interaction with the RBD by structure prediction analysis.Production of Nb11-59 in a yeast expression system followed by its nebulization showed potential for rapid and high-quality manufacturing.
GONO-FOLFOXIRIプラスベバシズマブで治療した転移性大腸癌患者における循環プロ-および抗-血管新生因子の予備的分析 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Cremolini C, Loupakis F, Salvatore L, Fioravanti A, Schirripa M, Orlandi P, Masi G, Di Desidero T, Fornaro L, Canu B, Baldi G, Stasi I, Danesi R, Bocci G, Falcone A
Journal: Annals of Oncology (2010)
Impacts of COVID-19 on Liver Cancers: During and after the Pandemic
Authors: Stephen Lam Chan, Masatoshi Kudo
Journal: Liver Cancer (2020)

The pandemic of coronavirus disease 2019 (COVID-19) has diverted resources from healthcare services for patients with chronic medical illness such as cancer. COVID-19 also causes organ dysfunction, complicating cancer treatment. In most countries with an outbreak of COVID-19, modifications of cancer management have been adopted to accommodate the crisis and minimize the exposure of cancer patients to the infection. In countries where COVID-19 numbers are subsiding, medical teams should also be prepared to resume normal practices gradually. Here, we aim to review the literature on the impact of COVID-19 on patients with hepatocellular carcinoma (HCC) as well as discuss modifications to the management of HCC during and after recovery from the pandemic.Based on current data, 10-40% of patients with COVID-19 have hepatic injury characterized by an elevation of transaminases and/or hyperbilirubinemia. Multiple mechanisms contribute to the hepatic injury, including direct viral entry to hepatocytes/cholangiocytes, immune-mediated hepatitis, hypoxia, and drug-related hepatotoxicity. In patients with HCC, COVID-19 may exacerbate existing chronic liver disease and complicate the management of cancer. Cancer patients generally have a higher risk of infection and worse outcome, especially those who have recently undergone cancer treatment. Although HCC is under-represented in COVID-19 series, mitigation measures should be implemented to minimize the exposure of patients to the virus. A decision on the treatment of HCC should be balanced with consideration of the availability of medical resources, the level of infection risk of COVID-19, and the risk-benefit ratio of the individual patient. In areas where the COVID-19 outbreak is subsiding, clinicians should be prepared to manage a surge of HCC patients with higher disease burdens and complications.Mitigation measures to protect at-risk patients, such as those with cancers, from SARS-CoV-2 infection should be exercised and the impact of COVID-19 on this group of patients should be thoroughly studied.