tbuckley/cabot-search huggingface dataset:
Efficient Mitochondrial Glutamine Targeting Prevails Over Glioblastoma Metabolic Plasticity
Authors: Kristell Oizel, Cynthia Chauvin, Lisa Oliver, Catherine Gratas, Fanny Geraldo, Ulrich Jarry, Emmanuel Scotet, Marion Rabe, Marie-Clotilde Alves-Guerra, Raluca Teusan, Fabien Gautier, Delphine Loussouarn, Vincent Compan, Jean-Claude Martinou, François M. Vallette, Claire Pecqueur
Journal: Clinical Cancer Research (2017)

Purpose: Glioblastoma (GBM) is the most common and malignant form of primary human brain tumor in adults, with an average survival at diagnosis of 18 months. Metabolism is a new attractive therapeutic target in cancer; however, little is known about metabolic heterogeneity and plasticity within GBM tumors. We therefore aimed to investigate metabolic phenotyping of primary cultures in the context of molecular tumor heterogeneity to provide a proof of concept for personalized metabolic targeting of GBM.Experimental Design: We have analyzed extensively several primary GBM cultures using transcriptomics, metabolic phenotyping assays, and mitochondrial respirometry.Results: We found that metabolic phenotyping clearly identifies 2 clusters, GLNHigh and GLNLow, mainly based on metabolic plasticity and glutamine (GLN) utilization. Inhibition of glutamine metabolism slows the in vitro and in vivo growth of GLNHigh GBM cultures despite metabolic adaptation to nutrient availability, in particular by increasing pyruvate shuttling into mitochondria. Furthermore, phenotypic and molecular analyses show that highly proliferative GLNHigh cultures are CD133neg and display a mesenchymal signature in contrast to CD133pos GLNLow GBM cells.Conclusions: Our results show that metabolic phenotyping identified an essential metabolic pathway in a GBM cell subtype, and provide a proof of concept for theranostic metabolic targeting. Clin Cancer Res; 23(20); 6292-304. ©2017 AACR.
Phase II study of intraperitoneal docetaxel plus capecitabine/cisplatin for gastric cancer with peritoneal metastasis: XP+IP DOC trial.
Authors: Ryoji Fukushima, Hironori Ishigami, Hiroto Miwa, Motohiro Imano, Daisuke Kobayashi, Yasushi Tsuji, Akio Hidemura, Tetsuya Kusumoto, Takeshi Omori, Hiroshi Yabusaki, Norifumi Ohashi, Mitsuhiko Ota, Hironori Yamaguchi, Joji Kitayama
Journal: Journal of Clinical Oncology (2017)

4039 Background: Intraperitoneal (IP) chemotherapy with taxanes provides sustained high local concentrations, and the efficacy of IP paclitaxel (PTX) has been shown in ovarian cancer. We previously reported the safety and efficacy of IP PTX plus systemic chemotherapy in clinical trials. Capecitabine/cisplatin (XP) is one of the standard regimens for the first-line treatment of advanced gastric cancer worldwide. We designed a new regimen combining IP docetaxel (DOC) with XP, and the recommended dose of IP DOC was determined to be 10 mg/m 2 in a phase I study. A phase II study of XP plus IP DOC was performed in gastric cancer patients with peritoneal metastasis. Methods: Gastric cancer patients with peritoneal metastasis confirmed by diagnostic imaging, laparoscopy or laparotomy were enrolled. DOC was administered intraperitoneally at 10 mg/m 2 on days 1 and 8. Cisplatin was administered intravenously at 80 mg/m 2 on day 1, and capecitabine was administered at 1000 mg/m 2 bid for 14 consecutive days, repeated every 21 days. The primary endpoint was the 1-year overall survival (OS) rate. Secondary endpoints were response rate, negative conversion rate on peritoneal cytology and safety. Results: Out of 50 patients enrolled, 48 patients received protocol treatment, and were evaluated for OS and toxicity. The median number of courses was 6 (range 1-15). The 1-year OS rate was 75% (95% confidence interval, 60-85%). The best overall response was stable disease in all the three patients with target lesions. Cancer cells ceased to be detected by peritoneal cytology in 28 (76%) of 37 patients. Nineteen patients underwent gastrectomy after response to chemotherapy. The incidences of grade 3/4 hematological and non-hematological toxicities were 42% and 48%, respectively. The frequent grade 3/4 toxicities included neutropenia (21%), leukopenia (8%), anemia (29%), anorexia (25%) and nausea (17%). Infection of the intraperitoneal port was observed in one patient. There were no treatment-related deaths. Conclusions: Combination chemotherapy of XP plus IP DOC regimen is well tolerated and active in gastric cancer patients with peritoneal metastasis. Clinical trial information: UMIN000016469.
Plaunotol inhibits gastric cancer cells by induction of apoptosis
Authors: Jun Yamada, Kazushige Kawai, Nelson H. Tsuno, Joji Kitayama, Kentaro Yazawa, Yurai Okaji, Masahiro Asakage, Takeshi Tsuchiya, Satomi Yoneyama, Takuya Osada, Nobukazu Hori, Koki Takahashi, Hirokazu Nagawa
Journal: Cancer Research (2005)

5903   BACKGROUND AND AIM: Plaunotol, a kind of isoprenoid, is an anti-gastric ulcer agent, available for clinical use since more than 20 years ago in Japan and Thailand. Some kinds of isoprenoids, such as docetaxel, paclitaxel, or geranylgeraniol, have been reported to have strong anti-cancer activities, but the effect of Plaunotol on cancer has not been evaluated. Here, we aimed to investigate the anti-tumor effect of Plaunotol on gastric cancer. METHODS: The gastric adenocarcinoma cell lines, namely MKN-45, and AZ-521, were used. Plaunotol was kindly gifted by Sankyo Co. Ltd., and tested at various concentrations (10, 20, 30 and 40 μmol/L). The proliferative activity of gastric cancer cells was assessed by the MTS assay. The annexin V / PI staining, and the TUNEL assay were used to analyze the induction of apoptosis. In addition, to clarify the mechanisms of the apoptosis induction, the activation of caspases-8, -9 and -3 was evaluated by flow-cytometry. RESULTS: Plaunotol treatment for 24h dose-dependently inhibited the proliferative activity of both gastric cancer cell lines tested. This inhibitory effect was dependent on induction of apoptosis, as confirmed by the annexin V / PI staining and the TUNEL assay. Both the caspase-8 and caspase-9 cascades were activated in the apoptosis induced by Plaunotol. CONCLUSION: Plaunotol dose-dependently inhibited the proliferative activity of gastric cancer cell lines, by induction of cell apoptosis. It should be a promising anti-gastric cancer agent, and since it is already available for clinical use in Japan and Thailand, and, in contrast to docetaxel and paclitaxel, which have strong side-effects, is proved to have little adverse effects, clinical trials should be started to confirm its properties in human beings.
Abstract 278: Targeted Anticancer Drug Sorafenib Impairs Vascular Network Formation by Human Cardiac Microvascular Endothelial Cells
Authors: Eugene Konorev, Zuyue Sun, Frederick Taylor, Jay Malmo
Journal: Circulation Research (2012)

Sorafenib is a novel multikinase inhibitor drug that is approved for the treatment of renal cell carcinoma and hepatocellular carcinoma, and is being tested in other common types of cancers. Recent clinical trials revealed that the use of this agent is associated with such cardiovascular complications as hypertension and reduced left ventricular ejection fraction. Sorafenib is known to inhibit Raf kinase, as well as VEGFR2 and PDGF receptor tyrosine kinase activities. We set out to test the hypothesis that sorafenib suppresses cardiac endothelial functions and angiogenesis. We treated human cardiac microvascular endothelial cells (HCMVEC) with VEGF, FGF2, and PDGF-BB in order to examine effects of sorafenib on signaling pathways activated by these pro-angiogenic factors. We determined in these studies that VEGFR2 tyrosine kinase was the most sensitive target of sorafenib in human cardiac endothelial cells. As a result, sorafenib inhibited proliferation and viability of HCMVEC. In order to examine effects of sorafenib on cardiac angiogenesis, we used a co-culture assay of HCMVEC with human cardiac fibroblasts. Sorafenib suppressed the formation of vascular networks in this in vitro assay with an IC50 of approximately 30 nM. In an in vivo Matrigel plug assay, VEGF and FGF2 were admixed into Matrigel before injecting it to mice in order to induce vascular growth within the plug. Control plugs exhibited robust development of vascular networks while sorafenib (daily injections of 30 mg/kg) severely inhibited vascular growth within the plugs. Taken together, this data provide the evidence that endothelial cells present a viable target of sorafenib in the heart.
A MALT lymphoma prognostic index
Authors: Catherine Thieblemont, Luciano Cascione, Annarita Conconi, Barbara Kiesewetter, Markus Raderer, Gianluca Gaidano, Maurizio Martelli, Daniele Laszlo, Bertrand Coiffier, Armando Lopez Guillermo, Valter Torri, Franco Cavalli, Peter W. Johnson, Emanuele Zucca
Journal: Blood (2017)
A meta-analysis of low-dose aspirin for the prevention of pregnancy-induced hypertensive disease
Authors: T. F. Imperiale
Journal: JAMA (1991)

<h3>Background.</h3> —Pregnancy-induced hypertension (PIH), defined as either isolated hypertension after the 20th week of gestation or hypertension with proteinuria (preeclampsia), occurs in 5% to 15% of pregnancies and is associated with maternal and neonatal morbidity. Previous clinical trials with small numbers of patients have suggested that aspirin in doses of 60 to 150 mg/d during the second and third trimesters reduces the risk of PIH and improves maternal and neonatal outcomes. <h3>Objective.</h3> —We performed a meta-analysis of the six published controlled trials to estimate more precisely (1) the magnitude of protection of aspirin from PIH; (2) the effect of aspirin on severe low-birth-weight infants, cesarean section, and perinatal mortality; and (3) the risk of adverse effects. <h3>Methods.</h3> —We critically and independently evaluated study methods, assigned a quality score to each trial, and abstracted quantitative outcomes data. For each outcome, both relative risk (RR) and the number needed to be treated were calculated. <h3>Results.</h3> —Among 394 subjects from six trials, the RR of PIH among women who took aspirin was 0.35 (95% confidence interval [Cl], 0.22 to 0.55) and the number needed to be treated was 4.4, meaning that between four and five highrisk women would need to be treated with aspirin to prevent one case of PIH. Aspirin reduced the risk of severe low birth weight among newborns by 44% (RR = 0.56; 95% Cl, 0.36 to 0.88) and reduced the risk of cesarean section by 66% overall (RR = 0.34; 95% Cl, 0.25 to 0.48), although the specific indications for cesarean section were generally not described. There was no effect on fetal and neonatal death (RR=0.88; 95% Cl, 0.32 to 2.46), and there were no maternal or neonatal adverse effects associated with taking aspirin. <h3>Conclusion.</h3> —This meta-analysis suggests that low-dose aspirin reduces the risks of PIH and severe low birth weight, with no observed risk of maternal or neonatal adverse effects. (<i>JAMA</i>. 1991;266:261-265)
Facts and values: on the acceptability of risks in children’s sport using the example of rugby — a narrative review
Authors: Kenneth Lincoln Quarrie, John H M Brooks, Nicholas Burger, Patria A Hume, Steve Jackson
Journal: British Journal of Sports Medicine (2017)

A clash of values has been identified between those who assert that: 1. all childhood injuries, regardless of origin, are inherently undesirable and should be prevented and; 2. those who believe that some measure of injury to children is an acceptable compromise for the physical benefits associated with physical activity and the development of abilities to appraise and deal with risks. A debate regarding whether the tackles and collisions permitted in schools’ rugby represent acceptable risks, and what steps should be taken if they do not, exemplifies the issue. Questions regarding the magnitude of injury risks in sport are issues of fact and can be quantified via the results of injury surveillance studies. Risks are neither high nor low in isolation; they are relatively high or low with reference to other activities or across groups participating in an activity. Issues of the acceptability of a given degree of risk are value dependent. Research regarding perceptions of risk reveals wide variations in the degree of risk people view as acceptable. Factors impacting on risk perception include whether the risks are well known and understood, whether they are ‘dread’ risks and the degree to which people undertake the risks voluntarily and feel they have control over them. Based on the evidence currently available, the risks to children playing rugby do not appear to be inordinately high compared with those in a range of other childhood sports and activities, but better comparative information is urgently needed. Further evidence, however, should not necessarily be expected to result in the resolution of acceptable risk debates—pre-existing values shape our perspectives on whether new evidence is relevant, valid and reliable.
Flow cytometry based monocyte subset analysis accurately distinguishes chronic myelomonocytic leukemia from myeloproliferative neoplasms with associated monocytosis
Authors: M M Patnaik, M M Timm, R Vallapureddy, T L Lasho, R P Ketterling, N Gangat, M Shi, A Tefferi, E Solary, K K Reichard, D Jevremovic
Journal: Blood Cancer Journal (2017)

Flow cytometry based monocyte subset analysis accurately distinguishes chronic myelomonocytic leukemia from myeloproliferative neoplasms with associated monocytosis
Exercise Training Improves but Does Not Normalize Left Ventricular Systolic and Diastolic Function in Adolescents With Type 1 Diabetes
Authors: Silmara Gusso, Teresa Pinto, James C. Baldi, José G.B. Derraik, Wayne S. Cutfield, Tim Hornung, Paul L. Hofman
Journal: Diabetes Care (2017)

OBJECTIVE To determine the impact of 20 weeks of exercise training in aerobic capacity on left ventricular function and glycemic control in adolescents with and without type 1 diabetes. RESEARCH DESIGN AND METHODS Fifty-three adolescents with type 1 diabetes (aged 15.6 years) were divided into two groups: exercise training (n = 38) and nontraining (n = 15). Twenty-two healthy adolescents without diabetes (aged 16.7 years) were included and, with the 38 participants with type 1 diabetes, participated in a 20-week exercise-training intervention. Assessments included VO2max and body composition. Left ventricular parameters were obtained at rest and during acute exercise using MRI. RESULTS Exercise training improved aerobic capacity (10%) and stroke volume (6%) in both trained groups, but the increase in the group with type 1 diabetes remained lower than trained control subjects. Increased stroke volume in adolescents with type 1 diabetes resulted from greater left ventricular contractility (9% increase in ejection fraction and an 11% reduction in end-systolic volumes) and, to a lesser extent, improved left ventricular filling (6%), suggesting that impaired diastolic function can be affected by exercise training in adolescents with type 1 diabetes. Insulin use decreased by ∼10%, but no change in glycemic status was observed. CONCLUSIONS These data demonstrate that in adolescents, the impairment in left ventricular function seen with type 1 diabetes can be improved, although not normalized, with regular intense physical activity. Importantly, diastolic dysfunction, a common mechanism causing heart failure in older subjects with diabetes, appears to be partially reversible in this age group.
Platelets as autonomous drones for hemostatic and immune surveillance
Authors: Jackson LiangYao Li, Alexander Zarbock, Andrés Hidalgo
Journal: The Journal of Experimental Medicine (2017)

Platelets participate in many important physiological processes, including hemostasis and immunity. However, despite their broad participation in these evolutionarily critical roles, the anucleate platelet is uniquely mammalian. In contrast with the large nucleated equivalents in lower vertebrates, we find that the design template for the evolutionary specialization of platelets shares remarkable similarities with human-engineered unmanned aerial vehicles in terms of overall autonomy, maneuverability, and expendability. Here, we review evidence illustrating how platelets are uniquely suited for surveillance and the manner in which they consequently provide various types of support to other cell types.
Abstract 267: The Impact of Modulating Afterload on Cardiac Progenitor Cells
Authors: Kazumasa Unno, Michael Bauer, Angelos Oikonomopoulos, Konstantina Sereti, Ronglih Liao
Journal: Circulation Research (2012)

Background: Increased hemodynamic stress induces left ventricular hypertrophy followed by heart failure. Accumulating evidence suggests that the adult mammalian heart possess regeneration ability through the action of resident stem/progenitor cell. However, the effects of hemodynamic fluctuation on cardiac progenitor cell proliferation and cardiac repair remain unknown. Results: Proliferation of Cardiac Side Population (CSP) cells and cardiomyocytes was evaluated in experimental models of Ascending Aortic Constriction (AAC)-induced left ventricular hypertrophy (LVH) in mice, over a period of seven weeks. Continuous AAC caused LVH while increasing the number of BrdU + CSP cells (one week post-AAC) and the amount of BrdU + cardiomyocytes (seven weeks post-AAC). To evaluate the effects of pressure fluctuation on CSP cell and cardiomyocyte proliferation we generated another group (de-AAC) in which the constriction was removed one week post-AAC. Interestingly, restoration of cardiac pressure further increased the proliferative capacity of CSP cells and cardiomyocytes. Conclusion: Our data show that restoration of hemodynamic stress confers favorable effects on cardiac repair through increase proliferation of CSP cells and cardiomyocytes. Thus, the hemodynamic state of the heart might be related to CSP cell proliferation and cardiomyogenesis.
A novel CFHR1-CFHR5 hybrid leads to a familial dominant C3 glomerulopathy
Authors: Shambhuprasad K. Togarsimalemath, Sidharth K. Sethi, Rajan Duggal, Moglie Le Quintrec, Pranaw Jha, Régis Daniel, Florence Gonnet, Shyam Bansal, Lubka T. Roumenina, Veronique Fremeaux-Bacchi, Vijay Kher, Marie-Agnes Dragon-Durey
Journal: Kidney International (2017)
Reporting of outcomes in randomized controlled trials on nail psoriasis: a systematic review
Authors: C.I. Busard, J.Y.C. Nolte, M.C. Pasch, P.I. Spuls
Journal: British Journal of Dermatology (2017)

Harmonization of outcome measures is needed to increase the value of clinical trials on nail psoriasis.To provide the first step in core outcome set (COS) development for nail psoriasis.A systematic review was performed to identify outcome instruments and corresponding outcome domains used in (ongoing) randomized controlled trials.Identified outcome domains included clinical signs, quality of life, symptoms and delivery of care. The Nail Psoriasis Severity Index (NAPSI) was the most commonly used measure to assess clinical signs (74% of studies). Other outcome instruments used included the Nail Area Severity score, composite fingernail score, a Physician's Global Assessment, individual nail features or a combination of these. Heterogeneity in type and reporting (e.g. NAPSI 50, NAPSI 75) of outcome instruments was high and characteristics were often insufficiently reported. In total 43% of studies assessed quality of life, with 3% of studies using a nail psoriasis-specific tool. Assessment of symptoms and delivery of care was limited.Heterogeneity in the type and reporting of nail psoriasis outcome instruments needs to be addressed in the process towards COS development. Sufficient reporting of instrument characteristics should be encouraged. As nail psoriasis is generally assessed secondarily to psoriasis of the skin or joints, collaboration between different research groups in COS development is needed.
Wet work exposure and hand eczema among healthcare workers: a cross-sectional study
Authors: N. Hamnerius, C. Svedman, O. Bergendorff, J. Björk, M. Bruze, A. Pontén
Journal: British Journal of Dermatology (2017)

Hand eczema is more common in healthcare workers than in the general population. Hands are subject to changing occupational exposures as a result of mandatory hygiene regulations for healthcare workers.To describe exposure to hygiene procedures and investigate the associations between occupational hand washing, use of nonsterile gloves and hand disinfectant, and self-reported hand eczema.This was a cross-sectional study; an electronic questionnaire was distributed to 28 762 hospital employees in southern Sweden. Nurses, assistant nurses or physicians constituted the group of healthcare workers analysed. Adjustments were made for sex, age, wet work at home, lifestyle factors and atopic dermatitis.In total, 12 288 (43%) responded, including 9051 healthcare workers. In this group the 1-year prevalence of self-reported hand eczema was 21%. On a daily basis, 30% reported hand washing with soap > 20 times at work, 45% used hand disinfectants > 50 times and 54% wore nonsterile gloves for > 2 h. After adjustment for confounding factors, a dose-dependent association with self-reported hand eczema was found for the daily number of hand washes with soap at work and time working with disposable gloves but not for alcoholic disinfectant use. Hand washing outside work was not associated with self-reported hand eczema in the adjusted multivariate analysis.In this study, we found a higher 1-year prevalence of self-reported hand eczema among Swedish healthcare workers than reported in the general population. Hand washing with soap and use of disposable gloves were associated with the occurrence of self-reported hand eczema in a dose-dependent way. Use of hand disinfectant was not associated with self-reported hand eczema.