tbuckley/cabot-search huggingface dataset:
Inhibition of telomerase activity and cell growth by curcumin in human brain tumour cells
Authors: Aik Kia Khaw, M. Prakash Hande
Journal: Cancer Research (2007)

1218  Curcumin, a polyphenolic compound derived from turmeric which commonly found in Asian diet, has been well known of its potent anti-tumourigenic and anti-proliferative property at certain doses. Its apoptosis-inducing effect and targeting of NF-Kappa B pathway have been recently reported, however, the other molecular mechanism(s) of action of this drug remain to be elucidated. Telomerase, a reverse transcriptase that maintains telomere length, is highly activated in tumor cells and practically absent in somatic cells and hence considered a potential marker for tumorigenesis Telomerase, therefore, has been proposed to represent a novel and potentially selective target for cancer therapy. In our present study, we have investigated the anti-proliferative activity, DNA damage induction, telomere-telomerase regulation in human glioblastoma (A172, KNS60 and U251) and medulloblastoma cell line (ONS76) following different doses of curcumin. Normal human primary fibroblasts and BJ1-hTERT cell line were used as control cell types. Curcumin induced a dose-dependent effect (doses from 0 to 100 µM) on cell viability in the different brain tumour cell lines. Telomerase-positive cell lines used in the study exhibited higher sensitivity to curcumin compared to the normal human fibroblasts. Curcumin concentrations which induced LC50 for each cell line were selected for subsequent experiments. LC 50 concentrations were higher for normal cells (90 µM) compared to the telomerase positive cancer cell lines (30 to 50 µM). Most of the brain tumour cell lines showed higher percentage of cells in sub-G1 phase except the glioblastoma cell line (A172).The extent of DNA damage induced by curcumin was measured by single cell gel electrophoresis (comet) assay. Normal human fibroblasts displayed greater DNA damage compared to the cancer cell lines. Inhibition of telomerase activity was seen in all the telomerase-positive cell lines tested following treatment with curcumin. Long-term treatment with curcumin has also resulted in significant telomere shortening in cancer cell lines. Curcumin suppressed key signalling pathways which are elevated in cancer cell lines as analysed by gene expression analysis. Results from the present study suggest that telomerase status plays an important role in the induction of cell cycle arrest, anti-proliferative effect and apoptosis in human brain tumour cell lines by curcumin.
Loss of Dnmt3a Dysregulates Hematopoietic Homeostasis and Myeloid Skewing Via the PI3Kinase Pathway: PI3Kα/β Inhibition Corrects Extramedullary Hematopoiesis and Myeloid Skewing Due to Loss of Dnmt3a
Authors: Lakshmi Reddy Palam, Baskar Ramdas, Katelyn Pickerell, Reuben Kapur
Journal: Blood (2019)
Abstract 19043: An Increased Level of Arginine Methylation Correlates With Starvation-induced Autophagy in the Heart
Authors: Risa Mukai, Toshiro Saito, Junichi Sadoshima
Journal: Circulation (2017)

Autophagy is a bulk degradation mechanism for proteins and organelles that protects cells against stress by contributing to the maintenance of the quality control of proteins and organelles and the...
Erratum: Effects of long-term, moderate-intensity oral anticoagulation in addition to aspirin in unstable angina (Journal of the American College of Cardiology (2000) 37 (475-484))
Authors: R Ahuad-Guerrero, M Basara, R Bastianelli, J Beloscar, JO Bono, R Castellanos, G Covelli, J Cubillos, C Dizeo, AA Fernandez, C Ferrara, A Gambarte, R Garcia Duran, L Gastaldi, C Girono, L Gitelman, G Heumann, L Keller, L Lobo-Marquez, H Locatelli, SM Macin, R Manzur, L Mariano, G Martino, E Marzetti, R Memoli, G Mercau, J Muntaner, R Nordaby, I Perillo, G Quijano, R Quijano, JL Ramos, C Salazar, S Salzberg, G Sans, C Secotaro, S Soifer, C Sosa, E Terna, H Torre, E Tuero, G Uceda, J Amerena, C Armstrong, N Bayley, K Beaumont, I Beinart, J Berry, J Botha, A Buncle, R Burton, R Cannon, D Colquhoun, G Derwent-Smith, D Dobson, A Edwards, F Ekin, J Garrett, J Gault, C Gnanaharan, K Gunawardane, R Hendriks, J Horowitz, D Hunt, J Hurley, B Jackson, K Judge, M Knapp, G Koch, EG Lane, A Loxton, A MacIsaac, S MacKinley, G Nelson, R Newman, D Owensby, C Peeler, S Poropat, K Roberts, M Sallaberger, J Sampson, B Singh, C Singh, W Sleep, V White, R Ziffer, Jam Abrantes, DC Albuquerque, RM Alhadas, AC Amaral, AC Assumpção, Arf Azevedo, GA Barcellos, C Blacher, Acc Carvalho, Rbp Castro, W Cirillo, OR Coelho
Journal: Journal of the American College of Cardiology (2001)
National, regional, and global burdens of disease from 2000 to 2016 attributable to alcohol use: a comparative risk assessment study
Authors: Kevin Shield, Jakob Manthey, Margaret Rylett, Charlotte Probst, Ashley Wettlaufer, Charles D H Parry, Jürgen Rehm
Journal: The Lancet Public Health (2020)

Alcohol use has increased globally, with varying trends in different parts of the world. This study investigates gender, age, and geographical differences in the alcohol-attributable burden of disease from 2000 to 2016.This comparative risk assessment study estimated the alcohol-attributable burden of disease. Population-attributable fractions (PAFs) were estimated by combining alcohol exposure data obtained from production and taxation statistics and from national surveys with corresponding relative risks obtained from meta-analyses and cohort studies. Mortality and morbidity data were obtained from the WHO Global Health Estimates, population data were obtained from the UN Population Division, and human development index (HDI) data were obtained from the UN Development Programme. Uncertainty intervals (UIs) were estimated using a Monte Carlo-like approach.Globally, we estimated that there were 3·0 million (95% UI 2·6-3·6) alcohol-attributable deaths and 131·4 million (119·4-154·4) disability-adjusted life-years (DALYs) in 2016, corresponding to 5·3% (4·6-6·3) of all deaths and 5·0% (4·6-5·9) of all DALYs. Alcohol use was a major risk factor for communicable, maternal, perinatal, and nutritional diseases (PAF of 3·3% [1·9-5·6]), non-communicable diseases (4·3% [3·6-5·1]), and injury (17·7% [14·3-23·0]) deaths. The alcohol-attributable burden of disease was higher among men than among women, and the alcohol-attributable age-standardised burden of disease was highest in the eastern Europe and western, southern, and central sub-Saharan Africa regions, and in countries with low HDIs. 52·4% of all alcohol-attributable deaths occurred in people younger than 60 years.As a leading risk factor for the burden of disease, alcohol use disproportionately affects people in low HDI countries and young people. Given the variations in the alcohol-attributable burden of disease, cost-effective local and national policy measures that can reduce alcohol use and the resulting burden of disease are needed, especially in low-income and middle-income countries.None.
Long‐term safety and efficacy of the PI3K inhibitor copanlisib in patients with relapsed or refractory indolent lymphoma: 2‐year follow‐up of the CHRONOS‐1 study
Authors: Martin Dreyling, Armando Santoro, Luigina Mollica, Sirpa Leppä, George Follows, Georg Lenz, Won Seog Kim, Arnon Nagler, Maria Dimou, Judit Demeter, Muhit Özcan, Marina Kosinova, Krimo Bouabdallah, Franck Morschhauser, Don A. Stevens, David Trevarthen, Javier Munoz, Liana Rodrigues, Florian Hiemeyer, Ashok Miriyala, Jose Garcia‐Vargas, Barrett H. Childs, Pier Luigi Zinzani
Journal: American Journal of Hematology (2019)

Safety profiles of oral PI3K inhibitors have resulted in US FDA black box warnings regarding fatal/serious toxicities. The approved intravenous PI3K inhibitor copanlisib has low incidence of severe toxicities and no black box warnings, but chronic treatment effects were unknown. We provide an update on safety and efficacy of copanlisib with a minimum 2-year follow-up of the CHRONOS-1 study. A total of 142 patients with histologically confirmed indolent B-cell lymphoma who had relapsed after or were refractory to ≥2 prior treatments received intravenous copanlisib 60 mg on days 1, 8, and 15 (28-day cycle). The primary efficacy endpoint was objective response rate (ORR) after ≥4 cycles (independent assessment). The predominant histology was follicular lymphoma (n = 104). The ORR was 60.6% (seven additional complete responses since primary analysis). Secondary endpoints of median duration of response, progression-free survival, and overall survival were 14.1 months (median follow-up, 16.1 months), 12.5 months (median follow-up, 14.0 months), and 42.6 months (median follow-up, 31.5 months), respectively. Median safety follow-up was 6.7 months; 26% of patients received treatment for >1 year. Common treatment-emergent adverse events (TEAEs) (all grade/grade 3/grade 4) were transient hyperglycemia (50.0%/33.1%/7.0%), diarrhea (35.2%/8.5%/0%), transient hypertension (29.6%/23.9%/0%), and neutropenia (28.9%/9.2%/14.8%). Serious AEs were largely unchanged, with no new cases of pneumonitis (4.2%), diarrhea (2.8%), or grade 5 events. Note, TEAEs showed no evidence for increased incidence or worsening following longer exposure in patients treated >1 year. Long-term follow-up of patients with relapsed/refractory indolent B-cell lymphoma treated with intravenous copanlisib demonstrated durable, enhanced responses without evidence of worsening TEAEs, as reported for orally administered PI3K inhibitors.
The role of reference frames in memory recollection
Authors: Giuseppe Riva, Daniele Di Lernia, Andrea Serino, Silvia Serino
Journal: Behavioral and Brain Sciences (2019)

Abstract In this commentary on Bastin et al., we suggest that spatial context plays a critical role in the encoding and retrieval of events. Specifically, the translation process between the viewpoint-independent content of a memory and the viewpoint-dependent stimuli activating the retrieval (mental frame syncing) plays a critical role in spatial memory recollection. This perspective also provides an explanatory model for pathological disturbances such as Alzheimer's disease.
Functionally Distinct Subsets of Monocytes in Mouse and Human Blood
Authors: Catherine S Rhee, Elizabeth W Scadden, Chea L Phillip, Bum-Kyu Lee, Meeta Mistry, Friedrich F Hoyer, Hiroki Kato, Giovanna Mantica, Jonghwan Kim, Matthias Nahrendorf, Michael K Mansour, David B Sykes, David T. Scadden
Journal: Blood (2019)
Self-assembling and self-formulating prodrug hydrogelator extends survival in a glioblastoma resection and recurrence model
Authors: Paula Schiapparelli, Pengcheng Zhang, Montserrat Lara-Velazquez, Hugo Guerrero-Cazares, Ran Lin, Hao Su, Rami W. Chakroun, Miguel Tusa, Alfredo Quiñones-Hinojosa, Honggang Cui
Journal: Journal of Controlled Release (2020)
Testing a new light therapy for the treatment of actinic keratosis
Authors: S. Mordon, A.S. Vignion-Dewalle, H. Abi-Rached, E. Thecua, F. Lecomte, C. Vicentini, P. Deleporte, H. Béhal, D. Kerob, T. Hommel, A. Duhamel, R.M. Szeimies, L. Mortier
Journal: British Journal of Dermatology (2020)

An actinic keratosis (AK) is an area (lesion) of sun‐damaged skin, mainly found on sun‐exposed parts of the body, particularly the forearms, backs of the hands, face, ears, bald scalp and the lower legs. Left untreated, there is a small risk that an AK could progress into a form of skin cancer called squamous cell carcinoma. One way of treating AK is called photodynamic therapy (PDT). The usual, or conventional, protocol for using PDT to treat AK is called C‐PDT. It involves applying a light‐sensitising cream to the skin which is activated by a high‐intensity red light about 2.5 hours later. This causes intense inflammation in the skin which destroys abnormal, but not normal, skin tissue. The main drawback of C‐PDT is the pain experienced by patients during the treatment. Due to this pain, many patients cannot complete the treatment. The authors of this study, based in France and Germany, proposed a new protocol for PDT of AK, called P‐PDT. P‐PDT involves a revised red light activation: the light intensity has been considerably reduced and the activation begins only 30 minutes after the molecule (cream) application. This revision was expected to increase the patient's tolerance. The primary aim of the study was to assess whether P‐PDT is at least as effective as C‐PDT in destroying AK. One of the secondary aims was to compare pain levels between P‐PDT and C‐PDT. Forty‐six patients with AKs of the head were included. These patients were treated with P‐PDT on one side of the head and with C‐PDT on the other side. With 94.2% disappearance of AKs six months after the treatment, P‐PDT was found to be at least as effective as C‐PDT, which had a disappearance rate of 94.9%. Moreover, from the pain levels reported by the patients for each protocol, P‐PDT is much less painful, or even painless, compared to C‐PDT. This summary relates to the study: The conventional protocol vs. a protocol including illumination with a fabric‐based biophotonic device (the Phosistos protocol) in photodynamic therapy for actinic keratosis: a randomized, controlled, noninferiority clinical study
Short-term transcriptional response to IL-17 receptor-A antagonism in the treatment of psoriasis
Authors: Lewis E. Tomalin, Chris B. Russell, Sandra Garcet, David Adrian Ewald, Paul Klekotka, Ajay Nirula, Hanne Norsgaard, Mayte Suàrez-Fariñas, James G. Krueger
Journal: Journal of Allergy and Clinical Immunology (2019)
Differential Expression of the Transcription Factor GATA3 Specifies Lineage and Functions of Innate Lymphoid Cells
Authors: Chao Zhong, Mingzhu Zheng, Kairong Cui, Andrew J. Martins, Gangqing Hu, Dan Li, Lino Tessarollo, Serguei Kozlov, Jonathan R. Keller, John S. Tsang, Keji Zhao, Jinfang Zhu
Journal: Immunity (2019)
Absolute lymphocyte count (ALC), absolute monocyte count (AMC), and ALC/AMC ratio to predict outcome in aggressive non-Hodgkin lymphoma (aNHL).
Authors: Noridza Rivera-Rodriguez, Fernando Cabanillas, Wandaly Ibis Pardo, Karen J. Santiago, Orestes Antonio Pavia, Margarita Bruno
Journal: Journal of Clinical Oncology (2012)

e18547 Background: Prognostic factors in NHL have been well studied in the pre-rituximab era. More recently, tumor infiltrating macrophages were found to confer an adverse prognosis. Porrata et al. at Mayo Clinic have described the ALC, AMC, and ALC/AMC ratio as important prognostic factors. We have evaluated pts with aNHL treated in the rituximab era to identify prognostic factors Methods: From January 2006 and April 2011, 89 pts with aNHL treated at our center were accrued. Initial treatment was R-CHOP based. 59 were entered on R-CHOP + GM-CSF protocol and the remainder were identified from our database. Results: Median age was 59 (25-89), 44% were male; histologies included DLBCL (n=75), high grade follicular lymphoma (n=11), and other (n=5). Median follow up = 27 mo. 3 year FFS and OS for the entire group: 78% and 83% respectively. On univariate analysis, FFS was superior for low IPI (0-2, p=0.01), normal B2 microglobulin (p=0.008), females (p=0.04), ALC &gt; 865 (p=0.001), ALC/AMC ratio of &gt;1.43 (p=0.02) but contrary to Porrata’s findings, there was no difference by AMC. In pts with low IPI, there was a significant difference in FFS and OS for those with an ALC &gt;865 (93% vs 56%, p=0.0008;96% vs 60%, p=0.0004). In females ALC had no prognostic value, but males with low ALC had a significantly worse FFS and OS (85 vs 34%, p=0.007; 91% vs 53%, p=0.006). Females with high AMC had superior FFS (p=.02) but the opposite trend was seen in males. On multivariate analysis, gender, B2-microglobulin, and combined IPI with ALC/AMC ratio &gt;1.43 remained as independent prognostic factors with gender being the most significant factor in the model. Conclusions: Prior to Rituximab, gender was not prognostic. Our findings suggest that: 1- favorable impact of Rituximab occurs mostly in females; this could be related to their immune system. 2- Both ALC and ALC/AMC ratio have prognostic significance, and can identify patients with favorable IPI who have poor outcome. This effect is particularly striking for males. To the best of our knowledge this is the first study to find an interaction between gender and ALC, and ALC/AMC as well as a divergent effect of gender and AMC on prognosis
Effect of pharmacologic inhibition of c-Jun N-terminal kinase (JNK) signaling pathway on cell proliferation and cell cycle progression in human granulosa cell tumor.
Authors: Ozgur Oktem, Meltem Muftuoglu, Filiz Senbabaoglu, Bulent Urman
Journal: Journal of Clinical Oncology (2013)

e22004 Background: No data are available regarding the signaling pathways that controls the proliferation of granulosa cell tumors (GCT). Preliminary findings showing the activation of c-Jun N-terminal kinase (JNK) signaling pathway in the proliferating granulosa cells has led us to investigate the role of this pathway in human GCT. Methods: Human GCT line COV 434 was used. Cell proliferation was monitored real-time quantitatively for 120h using an impedance-based system. Two different pharmacologic JNK inhibitors SP600125 and AS601245 were used. Their inhibitory concentrations were determined in western blot. Cell cycle was analyzed with flow cytometry and apoptosis with yo-pro-1 staining. Results: First, the growth characteristics of this cell line was delineated (Table 1A). Then the cells were treated with the inhibitors at the indicated doses during the log phase. Their proliferation was significantly halted in a dose-dependent manner by both inhibitors (Table 1B). Furthermore, the cells failed to complete mitosis, and began to accumulate at G 2 in a dose dependent manner when JNK pathway was interrupted with AS601245 (59%) and SP600125 (39%) during G 2 /M transition compared to control cells (7%) proceeding through G 2 /M phase regularly (p&lt;0.001). Compared to 3.5% of control cells, 14% and 30% of the cells underwent apoptosis when treated with 50 µM SP600125 and AS601245, respectively. At 100 µM, the apoptotic fraction increased to 68% and 76%, respectively (p&lt;0.01). Conclusions: These results suggest that pharmacologic manipulation of JNK pathway may provide a therapeutic benefit in the treatment of GCT for which currently, no curative therapy exists beyond surgery. Funded by a Grant to Ozgur Oktem (TUBITAK109S164). [Table: see text]
The American Heart Association Takes on Vaping
Authors: Jennifer Abbasi
Journal: JAMA (2020)

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The combination of linagliptin, metformin and lifestyle modification to prevent type 2 diabetes (PRELLIM). A randomized clinical trial
Authors: Rodolfo Guardado-Mendoza, Sara Stephania Salazar-López, Mildred Álvarez-Canales, Diana Farfán-Vázquez, Yoscelina Estrella Martínez-López, Lilia M. Jiménez-Ceja, Erick L. Suárez-Pérez, Fabiola Angulo-Romero, Maria Lola Evia-Viscarra, María Luisa Montes de Oca-Loyola, Edgar G. Durán-Pérez, Franco Folli, Alberto Aguilar-García
Journal: Metabolism (2019)
Eligibility and Preventive Potential for New Evidence-Based Cardiovascular Drugs in Secondary Prevention
Authors: Martin Bødtker Mortensen, Michael Joseph Blaha, Børge Grønne Nordestgaard
Journal: JAMA Cardiology (2020)

Recently, 12 randomized clinical trials (RCTs) have demonstrated the efficacy of novel therapies for mainly secondary prevention of atherosclerotic cardiovascular disease. However, given the potential overlapping eligibility of the RCTs, along with the cost of the new therapies, there are uncertainty and questions about implementing these RCT findings in real-world clinical practice.To determine the eligibility and preventive potential for these new preventive therapies in a contemporary population.This population-based contemporary cohort study included 6292 patients with known ischemic heart disease (IHD) and 2277 with a previous myocardial infarction (MI) enrolled between November 2003 and February 2015. Analyses were performed in the Copenhagen General Population Study with a mean (SD) of 7.7 (3.5) years of follow-up. The data were analyzed between January and October 2019.We determined the drug eligibility and evidence-based potential for preventing major cardiovascular events of the 12 cardiovascular drugs tested in the following recent RCTs: IMPROVE-IT, PEGASUS, EMPA-REG, LEADER, SUSTAIN-6, FOURIER, CANVAS, REVEAL, CANTOS, COMPASS, ODYSSEY-OUTCOMES, and REDUCE-IT. The analyses were performed in patients with known IHD or with a previous MI at baseline.Of 6292 participants, 3861 (61%) were men and the mean (interquartile range) age was 69 (62-76) years. In patients with IHD or MI at baseline, eligibility for 1 or more new medications was 80% (n = 5036) and 99% (n = 2273), respectively, by meeting RCT enrollment criteria. Dividing the new therapies into 4 drug classes (lipid-modifying, antithrombotic, anti-inflammatory, and antidiabetic drugs), 2594 and 1834 patients with IHD or MI (41% and 81%, respectively) were eligible for 2 or more drug classes simultaneously. The 5-year estimated percentage of major cardiovascular events that could be prevented for each new therapy was 1% to 20% in patients with IHD or MI at baseline.Most patients with known IHD or previous MI are eligible for additional new secondary prevention therapies. This raises questions for the cardiovascular community and health care authorities about access to these potentially expensive therapies, including strategies for prioritizing their use.