tbuckley/cabot-search huggingface dataset:
Abstract 2449: A novel function of FTO in ovarian cancer stem cells through m6A RNA demethylation
Authors: Hao Huang, Yinu Wang, Manoj Kandpal, Guangyuan Zhao, Horacio Cardenas, Yanrong Ji, Edward Tanner, Jianjun Chen, Ramana Davuluri, Daniela Matei
Journal: Cancer Research (2020)

Abstract Introduction: N6-Methyladenosine (m6A) is the most abundant internal modification in mammalian messenger RNAs (mRNAs). Although previous studies have showed that RNA methylation is reversible and plays important roles in various cellular processes, such as metabolism, stem cell development, and self-renewal, its functions in cancer remain elusive. The fat mass- and obesity-associated protein (FTO) is an m6A demethylase and was described as an oncogenic factor in leukemia and brain tumors. We hypothesized that RNA demethylation could be involved in the process of ovarian cancer initiation or progression.Methods: Here we measured FTO expression in ovarian tumors compared to fallopian tube epithelium (FTE) and in ovarian cancer stem cells (CSCs) compared to non-CSCs. To investigate its functions we used overexpression and siRNA-mediated knockdown. Colony, sphere formation and tumor initiation assays were carried out. RNA-Seq and MeRIP-Seq were used to investigate the mechanism by which FTO-mediated m6A modifications altered stemness in OC cells. Results: FTO was expressed at lower levels in ovarian tumors compared to FTE and in ovarian CSCs compared to non-CSCs (P&amp;lt;0.01). Overexpression of FTO inhibited the tumorigenic CSC population, its ability to form colonies and spheres, and to initiate tumors in vivo. This phenotype was not recapitulated by overexpression of mutant FTO, lacking enzymatic activity. Integrated RNA-sequencing and genome wide m6A mapping revealed significant transcriptomic changes associated with FTO overexpression and loss of m6A, involving pathways related to cell stem signaling, RNA transcription, DNA repair, and mRNA splicing. FTO augmented second messenger 3', 5'-cyclic adenosine monophosphate (cAMP) signaling and suppressed stemness features of ovarian cancer cells by reducing mRNA stability of two phosphodiesterase genes (PDE1C and PDE4B). Conclusions: Our results point to a new function of FTO in high grade serous ovarian cancer as a regulator of cAMP hydrolysis through post-transcriptional gene modifications. Citation Format: Hao Huang, Yinu Wang, Manoj Kandpal, Guangyuan Zhao, Horacio Cardenas, Yanrong Ji, Edward Tanner, Jianjun Chen, Ramana Davuluri, Daniela Matei. A novel function of FTO in ovarian cancer stem cells through m6A RNA demethylation [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 2449.
Abstract 14252: Psychosocial and Psychiatric Assessment Among Patients With Cardiac Syndrome X, Tako-Tsubo Cardiomyopathy and Previous Acute Myocardial Infarction
Authors: Magdalena Maria Cattaneo, Micol Provenzi, Emanuele Pravata, Marco Moccetti, Alain Kaelin, Isabella Sudano, Filippo Crea, Costanzo Limoni, Carlo Calanchini, Augusto Gallino, Mattia Cattaneo
Journal: Circulation (2018)

Introduction: Little evidence suggests a role of psychosocial and psychiatric mechanisms in Cardiac Syndrome X (CSX) and Tako-Tsubo Cardiomyopathy (TTC). However, no studies have performed a comple...
Endoscopy-guided percutaneous stapled pancreatic cystgastrostomy and necrosectomy
Authors: Harshit S. Khara, Jon D. Gabrielsen, David L. Diehl, Ryan D. Horsley
Journal: Endoscopy (2020)

Endoscopic ultrasound (EUS)-guided transmural drainage of symptomatic pancreatic fluid collections using plastic or metal stents has become first-line therapy [1] [2]. However, stents can become occluded despite direct endoscopic necrosectomy (DEN) of the walled-off necrosis (WON), and an alternative management plan is required.
Quality of Care and Outcomes Among Medicare Advantage vs Fee-for-Service Medicare Patients Hospitalized With Heart Failure
Authors: Jose F. Figueroa, Rishi K. Wadhera, Austin B. Frakt, Gregg C. Fonarow, Paul A. Heidenreich, Haolin Xu, Barbara Lytle, Adam D. DeVore, Roland Matsouaka, Clyde W. Yancy, Deepak L. Bhatt, Karen E. Joynt Maddox
Journal: JAMA Cardiology (2020)

Medicare Advantage (MA), a private insurance plan option, now covers one-third of all Medicare beneficiaries. Although patients with cardiovascular disease enrolled in MA have been reported to receive higher quality of care in the ambulatory setting than patients enrolled in fee-for-service (FFS) Medicare, it is unclear whether MA is associated with higher quality in patients hospitalized with heart failure, or alternatively, if incentives to reduce utilization under MA plans may be associated with worse care.To determine whether there are differences in quality of care received and in-hospital outcomes among patients enrolled in MA vs FFS Medicare.Observational, retrospective cohort study of patients hospitalized with heart failure in hospitals participating in the Get With the Guidelines-Heart Failure registry.Medicare Advantage enrollment.In-hospital mortality, discharge disposition, length of stay, and 4 heart failure achievement measures.Of 262 626 patients hospitalized with heart failure, 93 549 (35.6%) were enrolled in MA and 169 077 (64.4%) in FFS Medicare. The median (interquartile range) age was 78 (70-85) years for patients enrolled in MA and 78 (69-86) years for patients enrolled in FFS Medicare. Standard mean differences in age, sex, prevalence of comorbidities, or objective measures on admission, including vital signs and laboratory values, were less than 10%. After adjustment, there were no statistically significant differences in receipt of evidence-based β-blockers when indicated; angiotensin-converting enzyme inhibitor, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors at discharge; measurement of left ventricular function; and postdischarge appointments by Medicare insurance type. Patients enrolled in MA, however, had higher odds of being discharged directly home (adjusted odds ratio [AOR], 1.16; 95% CI, 1.13-1.19; P < .001) relative to patients enrolled in FFS Medicare and lower odds of being discharged within 4 days (AOR, 0.97; 95% CI, 0.93-1.00; P = .04). There was no significant difference in in-hospital mortality between patients with MA and patients with FFS Medicare (AOR, 0.98; 95% CI, 0.92-1.03; P = .42).Among patients hospitalized with heart failure, no observable benefit was noted in quality of care or in-hospital mortality between those enrolled in MA vs FFS Medicare, except lower use of post-acute care facilities. As MA continues to grow, it will be important to ensure that participating private plans provide an added value to the patients they cover to justify the higher administrative costs compared with traditional FFS Medicare.
Prevalence and Location of Indoor Tanning Among High School Students in New Jersey 5 Years After the Enactment of Youth Access Restrictions
Authors: Jerod L. Stapleton, Mary Hrywna, Elliot J. Coups, Cris Delnevo, Carolyn J. Heckman, Baichen Xu
Journal: JAMA Dermatology (2020)

Several state governments have enacted bans on the use of indoor tanning beds at tanning salons among minors, but studies of the association of such restrictions with tanning behavior have produced mixed results. Little is known about the prevalence of tanning in nonsalon locations that are typically not covered by restrictions. Evidence that age bans are associated with a reduction in tanning bed use is needed to support policy makers' efforts to expand tanning regulations.To determine the prevalence and location of indoor tanning among New Jersey youths after a 2013 statewide indoor tanning ban for minors younger than 17 years.This survey study comprised 4 biennial (2012-2018) and representative cross-sectional surveys conducted among 12 659 high school students (grades 9-12) in New Jersey.The main outcome was the frequency of indoor tanning in the past year. Location of tanning bed use (ie, tanning salons or nonsalon locations, such as private residences or gyms) was also assessed.Survey responses from a total of 12 659 high school students (6499 female [51%]; mean [SD] age, 15.8 [1.3] years) were analyzed across the 4 survey waves. Tanning prevalence among students younger than 17 years (ie, younger than the legal tanning age) was 48% lower in 2018 compared with 2012 (adjusted odds ratio, 0.52; 95% CI, 0.33-0.81; P = .002). Tanning prevalence was 72% lower among female students 17 years or older (adjusted odds ratio, 0.28; 95% CI, 0.18-0.44; P < .001). Prevalence rates were not significantly different for male students 17 years or older and for racial/ethnic minority students. The prevalence of tanning in salons and private residences was similar among students younger than 17 years.This study suggests that the prevalence of tanning in New Jersey has begun to decrease among all youths younger than the legal tanning age and among female students of legal age in the 5 years after a statewide tanning ban. These findings provide valuable evidence to policy makers to support ongoing state-level efforts to enact age-specific bans on indoor tanning. The unique assessment of tanning location demonstrates the need for both greater enforcement of existing tanning salon regulations to ensure compliance and broadening restrictions to cover nonsalon tanning locations.
Reducing Vasopressor Exposure in Patients With Vasodilatory Hypotension
Authors: Saurabh Kumar Das, Nang Sujali Choupoo, Sumit Ray
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
FRI0022 Acth therapy in rheumatoid arthritis: is there any place of it?
Authors: GP Balint, B Rojkovich, J Korda
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To evaluate the effect, efficacy and side effects of a single injection of i.m. ACTH (2 mg of tetracosactide) in RA patients requiring steroid treatment. <h3>Methods</h3> In a pilot study 11 RA patients, fulfilling the ACR criteria were treated with a single i.m. injection of 2 mg of tetracosactide (Cortrosyn depot, Organon) in an open trial. All patients were female, with the average age of 48,9 years, disease duration of 5,2 years. 4 patients have a disease duration less than one year, 5 received also 5-7,5 mg daily prednisolon treatment. None of the four patients with disease duration less than one year had any DMARD treatment, but all the others had. Patients with hypertension, diabetes, know hypersensitivity to drugs, inclination to water retention were excluded. Joint pain (VAS), number of tender and swollen joints, duration of morning stiffness and patients? global assessment were measured before the injection and on the 3rd, 7th, 14th, 21st, 28th days thereafter. CRP levels were also measured. <h3>Results</h3> All clinical parameters and the CRP level improved significantly (p &lt; 0,005) on the 3rd, 7th and 14th day, but on the 21st and 28th days there was no significant difference as compared with the initial values. There was no difference in respond-rate between prednisolon treated and non-treated patients. Side effects: slight elevation of blood pressure was observed in 5, water retention in 2 patients in the first 3–4 days. The side effects were considered as unacceptable in one patient having blood pressure elevation up to 170/100 Hgmm and water retention. Out of the 4 patients with disease duration less than one year, 3 patients had continued ACTH treatment by administering 2 mg-s of tetracosactide in 1–3 week?s intervals, as bridging therapy. Two other patients on DMARDs still receive ACTH injections, one of them monthly and the other bimonthly. <h3>Conclusion</h3> ACTH treatment of RA may be reassessed, especially in young patients requiring bridging therapy or continuous steroid treatment. It may correct the slightly deficient hypothalamo-pituitary-adrenal axis in RA patients and may prevent drug-induced hypadrenia.
Abstract 3071: VERU-111, a novel orally bioavailable tubulin inhibitor, overcomes taxane resistance in metastatic triple-negative breast cancer
Authors: Shanshan Deng, Raisa I. Krutilina, Deanna N. Parke, Hao Chen, Duane D. Miller, Tiffany N. Seagroves, Wei Li
Journal: Cancer Research (2020)

Abstract Triple-negative breast cancer (TNBC) has aggressive clinical features strongly associated with poorer overall prognosis and higher mortality rates relative to other molecular subtypes. FDA-approved drugs, such as paclitaxel, are effective in treating TNBC. Yet, treatment failure is commonly observed due to the development of acquired chemoresistance, which remains a clinical challenge for TNBC therapy. We have shown that orally administered VERU-111 inhibits MDA-MB-231 xenograft growth with similar efficacy to paclitaxel, but without acute toxicity, and represses metastases originating from the mammary fat pad. To better understand the effect of VERU-111 on taxane-resistant TNBC, we generated a panel of paclitaxel-resistant TNBC sublines (MDA-MB-231/TxR, MDA-MB-468/TxR, SUM159/TxR and Hs578T/TxR) by gradually exposing paclitaxel to parental lines. MTS assays were used to confirm the chemoresistance of each subline to paclitaxel. VERU-111 maintained its potency against all four taxane-resistant sublines. We further investigated the underlying mechanisms of VERU-111 action and found that it inhibited taxane-resistant TNBC cell proliferation by inducing mitotic arrest and apoptosis via disruption of microtubule stability. In vivo, relative to paclitaxel, VERU-111 significantly inhibited tumor growth in an orthotopic MDA-MB-231/TxR model and reduced lung metastases originating from the mammary fat pad. VERU-111 induced tumor necrosis, anti-angiogenesis and apoptosis in both taxane-sensitive and taxane-resistant TNBC models in vivo. In addition to the MDA-MB-231/TxR model, we also tested the efficacy of VERU-111 in a multidrug-resistant PDX model, HCI-10. VERU-111 significantly inhibited HCI-10 primary tumor growth and suppressed the growth of lymph node metastases present prior to therapy and suppressed lung, liver and kidney metastases at the endpoint. In contrast, paclitaxel had no efficacy to repress tumor growth or metastasis in this model, and in fact, stimulated liver metastasis. Taken together, our data demonstrate that VERU-111 is a new generation of oral tubulin inhibitor that potently inhibits the growth of taxane-sensitive and taxane-resistant TNBC. Therefore, VERU-111 therapy is a promising strategy for the treatment of metastatic TNBC patients, including those patients who progress on taxanes. Citation Format: Shanshan Deng, Raisa I. Krutilina, Deanna N. Parke, Hao Chen, Duane D. Miller, Tiffany N. Seagroves, Wei Li. VERU-111, a novel orally bioavailable tubulin inhibitor, overcomes taxane resistance in metastatic triple-negative breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3071.
Abstract 3530: Investigating aneuploidy, CIN and mechanisms of DNA content reduction in cancer
Authors: Mara Mandelia, Kostas Drosopoulos, Spiros Linardopoulos
Journal: Cancer Research (2020)

Abstract Chromosomal instability (CIN) is a form of genomic instability that refers to a dynamic state in which the cells are constantly changing the number and/or the structure of their chromosomes. CIN leads to aneuploidy, a state in which a cell's set of chromosomes deviates from the euploid set. Causes of aneuploidy include errors during DNA replication, mitosis and cell fusion events. Furthermore, aneuploidy has been shown to promote tumorigenesis and tumor progression, but also to reduce cell fitness or induce cell death, especially when high levels of aneuploidy are present. Nevertheless, antimitotic drugs that induce high levels of aneuploidy, such as Paclitaxel, are not always effective in the clinic. In this study, we aim to investigate the mechanisms by which cancer cells tolerate aneuploidy, to elucidate the mechanisms by which cell fusion can lead to aneuploidy and resistance to paclitaxel and to identify new targets in aneuploidy and CIN. Towards this direction, aneuploid clones of pseudo-diploid cancer cells were generated after treatment with anti-mitotic drugs and single cell sorting and were characterized by cell cycle profile, metaphase spreads and CGH or SNP profile. Furthermore, CIN was induced by inhibition of CENP-E or ATM or impairment of the SWI/ SNF complex and quantified by induction of chromosome missegregation and micronuclei formation. Interestingly, several near tetraploid clones that were isolated after anti-mitotic drug treatment, reduced their DNA content to near diploid during propagation in culture. Thus, we hypothesize that cancer cells may utilize specific mechanisms to change their DNA content and maintain tolerable levels of aneuploidy. By time-lapse microscopy, we observed that cells treated with Paclitaxel, can increase their DNA content by abortive mitosis, cytokinesis failure or by undergoing cell fusion. Interestingly, these multinucleated cells could reduce their DNA content by undergoing independent mitosis, independent nucleus catastrophe or independent nucleus separation (cell exodus). We identify cell exodus, as a potential mechanism by which cells can recover after treatment with Paclitaxel. Inhibition of ROCK pathway, that stabilizes actin filaments and prevents cellular contractility, reduced cell fusion and exodus events and delayed cell recovery after paclitaxel treatment. Finally, in order to identify new targets in CIN and aneuploidy, we setup sgRNA loss of function screening conditions in the generated CIN and aneuploid cell models and we aim to identify genes that are essential for the survival of aneuploid and/or CIN cancer cells. Citation Format: Mara Mandelia, Kostas Drosopoulos, Spiros Linardopoulos. Investigating aneuploidy, CIN and mechanisms of DNA content reduction in 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 3530.
Abstract 11231: Cost-Effectiveness Analysis of Adult Patients Receiving Extracorporeal Membrane Oxygenation - Taiwan’s Experiences
Authors: Jou Wei Lin, Hsi-Yu Yu, Yih-Sharng Chen
Journal: Circulation (2019)

Introduction: The objective of this study was to construct a model for predicting in-hospital mortality in the patients receiving extracorporeal membrane oxygenation (ECMO) and subsequently to perf...
Shaping Waves of Bone Morphogenetic Protein Inhibition During Vascular Growth
Authors: Pierre J. Guihard, Yina Guo, Xiuju Wu, Lily Zhang, Jiayi Yao, Medet Jumabay, Yucheng Yao, Alan Garfinkel, Kristina I. Boström
Journal: Circulation Research (2020)

The BMPs (bone morphogenetic proteins) are essential morphogens in angiogenesis and vascular development. Disruption of BMP signaling can trigger cardiovascular diseases, such as arteriovenous malformations.A computational model predicted that BMP4 and BMP9 and their inhibitors MGP (matrix gamma-carboxyglutamic acid [Gla] protein) and CV2 (crossveinless-2) would form a regulatory system consisting of negative feedback loops with time delays and that BMP9 would trigger oscillatory expression of the 2 inhibitors. The goal was to investigate this regulatory system in endothelial differentiation and vascular growth.Oscillations in the expression of MGP and CV2 were detected in endothelial cells in vitro, using quantitative real-time polymerase chain reaction and immunoblotting. These organized temporally downstream BMP-related activities, including expression of stalk-cell markers and cell proliferation, consistent with an integral role of BMP9 in vessel maturation. In vivo, the inhibitors were located in distinct zones in relation to the front of the expanding retinal network, as determined by immunofluorescence. Time-dependent changes of the CV2 location in the retina and the existence of an endothelial population with signs of oscillatory MGP expression in developing vasculature supported the in vitro findings. Loss of MGP or its BMP4-binding capacity disrupted the retinal vasculature, resulting in poorly formed networks, especially in the venous drainage areas, and arteriovenous malformations as determined by increased cell coverage and functional testing.Our results suggest a previously unknown mechanism of temporal orchestration of BMP4 and BMP9 activities that utilize the tandem actions of the extracellular antagonists MGP and CV2. Disruption of this mechanism may contribute to vascular malformations and disease.
Interleukin-17–induced neutrophil extracellular traps mediate resistance to checkpoint blockade in pancreatic cancer
Authors: Yu Zhang, Vidhi Chandra, Erick Riquelme Sanchez, Prasanta Dutta, Pompeyo R. Quesada, Amanda Rakoski, Michelle Zoltan, Nivedita Arora, Seyda Baydogan, William Horne, Jared Burks, Hanwen Xu, Perwez Hussain, Huamin Wang, Sonal Gupta, Anirban Maitra, Jennifer M. Bailey, Seyed J. Moghaddam, Sulagna Banerjee, Ismet Sahin, Pratip Bhattacharya, Florencia McAllister
Journal: The Journal of Experimental Medicine (2020)

Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy with an immunosuppressive microenvironment that is resistant to most therapies. IL17 is involved in pancreatic tumorigenesis, but its role in invasive PDAC is undetermined. We hypothesized that IL17 triggers and sustains PDAC immunosuppression. We inhibited IL17/IL17RA signaling using pharmacological and genetic strategies alongside mass cytometry and multiplex immunofluorescence techniques. We uncovered that IL17 recruits neutrophils, triggers neutrophil extracellular traps (NETs), and excludes cytotoxic CD8 T cells from tumors. Additionally, IL17 blockade increases immune checkpoint blockade (PD-1, CTLA4) sensitivity. Inhibition of neutrophils or Padi4-dependent NETosis phenocopies IL17 neutralization. NMR spectroscopy revealed changes in tumor lactate as a potential early biomarker for IL17/PD-1 combination efficacy. Higher expression of IL17 and PADI4 in human PDAC corresponds with poorer prognosis, and the serum of patients with PDAC has higher potential for NETosis. Clinical studies with IL17 and checkpoint blockade represent a novel combinatorial therapy with potential efficacy for this lethal disease.