tbuckley/cabot-search huggingface dataset:
Metallothionein-1 as a biomarker of altered redox metabolism in hepatocellular carcinoma cells exposed to sorafenib
Authors: Aline Houessinon, Catherine Franois, Chloé Sauzay, Christophe Louandre, Gaelle Mongelard, Corinne Godin, Sandra Bodeau, Shinichiro Takahashi, Zuzana Saidak, Laurent Gutierrez, Jean-Marc Regimbeau, Nathalie Barget, Jean-Claude Barbare, Nathalie Ganne, Bruno Chauffert, Romain Coriat, Antoine Galmiche
Journal: Molecular Cancer (2016)

Sorafenib, a kinase inhibitor active against various solid tumours, induces oxidative stress and ferroptosis, a new form of oxidative necrosis, in some cancer cells. Clinically-applicable biomarkers that reflect the impact of sorafenib on the redox metabolism of cancer cells are lacking.We used gene expression microarrays, real-time PCR, immunoblot, protein-specific ELISA, and gene reporter constructs encoding the enzyme luciferase to study the response of a panel of cancer cells to sorafenib. Tumour explants prepared from surgical hepatocellular carcinoma (HCC) samples and serum samples obtained from HCC patients receiving sorafenib were also used.We observed that genes of the metallothionein-1 (MT1) family are induced in the HCC cell line Huh7 exposed to sorafenib. Sorafenib increased the expression of MT1G mRNA in a panel of human cancer cells, an effect that was not observed with eight other clinically-approved kinase inhibitors. We identified the minimal region of the MT1G promoter that confers inducibility by sorafenib to a 133 base pair region containing an Anti-oxidant Response Element (ARE) and showed the essential role of the transcription factor NRF2 (Nuclear factor erythroid 2-Related Factor 2). We examined the clinical relevance of our findings by analysing the regulation of MT1G in five tumour explants prepared from surgical HCC samples. Finally, we showed that the protein levels of MT1 increase in the serum of some HCC patients receiving sorafenib, and found an association with reduced overall survival.These findings indicate that MT1 constitute a biomarker adapted for exploring the impact of sorafenib on the redox metabolism of cancer cells.
99mTc Sestamibi Thyroid Scan in Amiodarone-Induced Thyrotoxicosis Type I
Authors: Niraj R. Patel, Luis A. Tamara, Ho Lee
Journal: Clinical Nuclear Medicine (2016)

Amiodarone-induced thyrotoxicosis (AIT) type I describes inducement of clinical hyperthyroidism by excessive thyroidal iodine in the setting of latent Graves disease, and therapy differs from that used for AIT type II. A 65-year-old man previously on amiodarone for atrial fibrillation developed clinical hyperthyroidism. Diagnosis of AIT was made, but the type was not clear. Tc sestamibi thyroid scan showed diffusely increased uptake and retention in an enlarged thyroid gland, a pattern consistent with AIT type I. Methimazole was initiated and controlled the thyrotoxicosis. I iodide thyroid scan and uptake study performed later was consistent with Graves disease.
Enzyme Activities and Extrinsic Proteins in Plasma Membranes From Normal Liver and Morris Hepatoma 5123tc 2
Authors: M. Barclay, O. Terebus-Kekish
Journal: JNCI Journal of the National Cancer Institute (1973)

Considerable specific activities for 5′-nucleotidase and Na+-K+-ATPase were in plasma membranes from normal liver and the lipoprotein subunits isolated from them. This suggested a high degree of metabolism involving the substrates and end products of these enzymes. The specific and relative specific activities of these important enzymes were greatly diminished in membranes from the Morris hepatoma 5123tc; this indicated that certain metabolic processes did not function at a normal level in these plasma membranes.
Case 22-1983
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, William E. Harmon, Robert T. McCluskey
Journal: New England Journal of Medicine (1983)

Presentation of Case First admission. A 12-year-old boy was admitted to the hospital because of renal failure.He was well until two weeks earlier, when symptoms of an upper-respiratory-tract infection developed. One week later a throat culture yielded a growth of streptococci. Ampicillin was begun but was subsequently replaced by cephalexin because of a question of penicillin allergy. Later erythromycin was given, but the patient was unable to swallow tablets or a liquid preparation. During the next few days a petechial rash developed over the lower portions of the legs, accompanied by arthralgia in the knees, elbows, and wrists, . . .
Probiotics have no effect on gut microbiota in healthy people, review suggests
Authors: Susan Mayor
Journal: BMJ (2016)

Probiotics have no consistent effect on the gut microbiota in healthy people, a systematic review has shown.1

Molecular sequencing techniques have enabled detailed identification of the diversity and functional capacity of micro-organisms in the gut, leading to claims that a wide range of conditions, including colorectal cancer and type 2 diabetes, may be associated with disease …
P0644 : HCC risk scores: Application of the CU-HCC, GAG-HCC and page-B scores to chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF)
Authors: W.R. Kim, R. Loomba, T. Berg, R. Aguilar Schall, L. Yee, P. Dinh, J.F. Flaherty, E.B. Martins, I. Jacobson, S. Fung, S. Gurel, M. Buti, P. Marcellin
Journal: Journal of Hepatology (2015)
Mitochondrial OXA Translocase Plays a Major Role in Biogenesis of Inner-Membrane Proteins
Authors: Sebastian B. Stiller, Jan Höpker, Silke Oeljeklaus, Conny Schütze, Sandra G. Schrempp, Jens Vent-Schmidt, Susanne E. Horvath, Ann E. Frazier, Natalia Gebert, Martin van der Laan, Maria Bohnert, Bettina Warscheid, Nikolaus Pfanner, Nils Wiedemann
Journal: Cell Metabolism (2016)

The mitochondrial inner membrane harbors three protein translocases. Presequence translocase and carrier translocase are essential for importing nuclear-encoded proteins. The oxidase assembly (OXA) translocase is required for exporting mitochondrial-encoded proteins; however, different views exist about its relevance for nuclear-encoded proteins. We report that OXA plays a dual role in the biogenesis of nuclear-encoded mitochondrial proteins. First, a systematic analysis of OXA-deficient mitochondria led to an unexpected expansion of the spectrum of OXA substrates imported via the presequence pathway. Second, biogenesis of numerous metabolite carriers depends on OXA, although they are not imported by the presequence pathway. We show that OXA is crucial for the biogenesis of the Tim18-Sdh3 module of the carrier translocase. The export translocase OXA is thus required for the import of metabolite carriers by promoting assembly of the carrier translocase. We conclude that OXA is of central importance for the biogenesis of the mitochondrial inner membrane.
Refusal of Recommended Chemotherapy for Ovarian Cancer: Risk Factors and Outcomes; a National Cancer Data Base Study
Authors: Sumer K Wallace, Jeff F Lin, William A Cliby, Gary S Leiserowitz, Ana I Tergas, Robert E Bristow
Journal: Journal of the National Comprehensive Cancer Network (2016)

To identify risk factors associated with refusal of recommended chemotherapy and its impact on patients with epithelial ovarian cancer (EOC).We identified patients in the National Cancer Data Base diagnosed with EOC from January 1998 to December 2011. Patients who refused chemotherapy were identified and compared with those who received recommended, multiagent chemotherapy. Univariate and multivariable analyses were performed using chi-square test with Bonferroni correction, binary logistic regression, log-rank test, and Cox proportional hazards modeling. The threshold for statistical significance was set at a P value of less than 0.05.From a cohort of 147,713 eligible patients, 2,707 refused chemotherapy. These patients were compared with 92,212 patients who received recommended multiagent chemotherapy. Older age, more medical comorbidities, not having insurance, and later year of diagnosis were directly and significantly associated with chemotherapy refusal when analyzed using multivariable logistic regression. In addition, lower-than-expected facility adherence to NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Ovarian Cancer, treatment at low-volume center, lower grade, and higher stage were all significantly and independently associated with chemotherapy refusal. Median overall survival of patients who received multiagent chemotherapy was significantly longer than that of those who refused chemotherapy (43 vs 4.8 months; P<.0005). After controlling for known patient, facility, and disease prognostic factors, chemotherapy refusal is significantly associated with increased risk of death.Refusal of recommended chemotherapy carries significant risk of early death from ovarian cancer. Our data demonstrate that the decision to refuse chemotherapy is multifactorial and, in addition to unalterable factors (eg, stage/grade, age), involves factors that can be changed, including facility type and payor. Efforts at addressing these discrepancies in care can improve compliance with chemotherapy recommendations in the NCCN Guidelines for Ovarian Cancer and outcomes.
Phase II randomized trial of radiation therapy, cetuximab, and pemetrexed with or without bevacizumab in patients with locally advanced head and neck cancer
Authors: A. Argiris, J.E. Bauman, J. Ohr, W.E. Gooding, D.E. Heron, U. Duvvuri, G.J. Kubicek, D.M. Posluszny, M. Vassilakopoulou, S. Kim, J.R. Grandis, J.T. Johnson, M.K. Gibson, D.A. Clump, J.T. Flaherty, S.I. Chiosea, B. Branstetter, R.L. Ferris
Journal: Annals of Oncology (2016)
Juniors will get chance to vote on contract proposals, says BMA
Authors: Abi Rimmer
Journal: BMJ (2016)

Junior doctors in England will have the chance to vote on proposals for a new contract regardless of the outcome of fresh talks, the BMA has said.

Commenting on the BMA’s decision to re-enter negotiations with the government, Johann Malawana, chair of the association’s Junior Doctors Committee, said that the BMA would call for “any contract offer—agreed or not—to be put to a referendum of junior doctors.”

The BMA and the government returned to talks on a new contract for junior doctors in England on Monday 9 May.1 The move came …
Critical Roles Of The IDH2 Mutation In Development and Maintenance Of Acute Myeloid Leukemia
Authors: Yoko Ogawara, Takuo Katsumoto, Yukiko Aikawa, Yutaka Shima, Yuki Kagiyama, Hironori Matsunaga, Takahiko Seki, Issay Kitabayashi
Journal: Blood (2013)
An Association between Atherosclerosis and Venous Thrombosis
Authors: Paolo Prandoni, Franca Bilora, Antonio Marchiori, Enrico Bernardi, Francesco Petrobelli, Anthonie W.A. Lensing, Martin H. Prins, Antonio Girolami
Journal: New England Journal of Medicine (2003)

In about a third of patients with venous thromboembolism, the cause of the disorder is unexplained. In patients with atherosclerosis, activation of both platelets and blood coagulation and an increase in fibrin turnover are detectable, which may lead to thrombotic complications. Whether atherosclerosis is associated with an increased risk of venous thrombosis is unknown.We performed ultrasonography of the carotid arteries in 299 unselected patients who had deep venous thrombosis of the legs without symptomatic atherosclerosis and in 150 control subjects. Patients with spontaneous thrombosis, patients with secondary thrombosis from acquired risk factors, and control subjects were assessed for plaques.At least one carotid plaque was detected in 72 of the 153 patients with spontaneous thrombosis (47.1 percent; 95 percent confidence interval, 39.1 to 55.0), 40 of the 146 with secondary thrombosis (27.4 percent; 95 percent confidence interval, 20.2 to 34.6), and 48 of the 150 control subjects (32.0 percent; 95 percent confidence interval, 24.5 to 39.5). The odds ratios for carotid plaques in patients with spontaneous thrombosis, as compared with patients with secondary thrombosis and with controls, were 2.3 (95 percent confidence interval, 1.4 to 3.7) and 1.8 (95 percent confidence interval, 1.1 to 2.9), respectively. In a multivariate analysis that accounted for risk factors for atherosclerosis, the strength of this association did not change.There is an association between atherosclerotic disease and spontaneous venous thrombosis. Atherosclerosis may induce venous thrombosis, or the two conditions may share common risk factors.
Adverse Health Effects of Intermittent vs Continuous Androgen Deprivation Therapy for Metastatic Prostate Cancer
Authors: Stephen B. Strum, Mark C. Scholz
Journal: JAMA Oncology (2016)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Oncology journal
Abstract 17499: ETC-1002 Incrementally Lowers Low Density Lipoprotein-cholesterol in Patients With Hypercholesterolemia Receiving Stable Statin Therapy
Authors: Christie M Ballantyne, Diane E MacDougall, Janice R Margulies, Paula L Robinson, Jeffrey C Hanselman, Narendra D Lalwani
Journal: Circulation (2015)

Background: ETC-1002 is an oral investigational drug that modulates hepatic adenosine triphosphate-citrate lyase to reduce cholesterol biosynthesis and may be beneficial in treating patients with elevated LDL-C despite using stable statin therapy. Methods: A double-blind, parallel group, placebo-controlled multicenter trial evaluated patients (n=134) with baseline LDL-C of 115-220 mg/dL while taking atorvastatin ≤20 mg, simvastatin ≤20 mg, rosuvastatin ≤10mg or pravastatin ≤40 mg randomized to ETC-1002 120 mg, ETC-1002 180 mg, or placebo once daily for 12 weeks. Results: ETC-1002 120 mg (p=0.0055) and 180 mg (p&lt;0.0001) lowered LDL-C significantly more than placebo (primary endpoint) as an add-on to statin therapy. ETC-1002 also lowered (p&lt;0.05) apolipoprotein B, non-high density lipoprotein-cholesterol, total cholesterol and LDL particle number more than placebo. C-reactive protein was also reduced with ETC-1002 120 mg (22%, p=0.26) and 180 mg (30%, p=0.08) versus 0% with placebo. Adverse events (AEs), muscle-related AEs, discontinuations due to AEs and levels of clinical safety labs were generally similar compared with placebo. Conclusion: In patients with elevated LDL-C despite stable statin therapy, ETC-1002 produces incremental LDL-C lowering and is well-tolerated.
P85 CHOLANGIOCARCINOMA (CCA) EXPRESS CHEMOKINE RECEPTOR CXCR7: IMPORTANT ROLE OF CXCR7 IN MEDIATING CXCL12 INDUCED CCA CELLS CHEMOTAXIS AND SURVIVAL
Authors: A. Gentilini, K. Roumbouts, M. Pinzani, A. Caligiuri, C. Raggi, P. Invernizzi, C. Raschioni, F. Marra
Journal: Journal of Hepatology (2014)
Early-Labeled Peak of Bile Pigment in Man
Authors: Stephen H. Robinson, Roger Lester, John F. Crigler, Maria Tsong
Journal: New England Journal of Medicine (1967)

ACCORDING to our present knowledge bilirubin is derived exclusively from the catabolism of heme, most of which is present in the hemoglobin of erythroid cells. Thus, most of the bilirubin produced under normal conditions originates from red blood cells at the end of their physiologic life-span. In human subjects given a labeled precursor of heme, such as glycine-15N or 14C, a large late peak of labeled bile pigment is observed in the feces between ninety and one hundred and fifty days after isotope administration,1 , 2 conforming to the average erythrocyte life-span of one hundred and twenty days. In addition, however, . . .
Signaling from maize organ primordia via FASCIATED EAR3 regulates stem cell proliferation and yield traits
Authors: Byoung Il Je, Jeremy Gruel, Young Koung Lee, Peter Bommert, Edgar Demesa Arevalo, Andrea L Eveland, Qingyu Wu, Alexander Goldshmidt, Robert Meeley, Madelaine Bartlett, Mai Komatsu, Hajime Sakai, Henrik Jönsson, David Jackson
Journal: Nature Genetics (2016)
Hepatocellular Carcinoma In Elderly Patients: final results of The Italian Cohort Of GIDEON (Global Investigational of therapeutic DEcisions in HCC and of its treatment with sorafeNib) Study
Authors: T. Zolfino, V. Lorusso, S. D'Angelo, D. Sansonno, L. Giannitrapani, A. Benedetti, V. Montesarchio, A.F. Attili, A. Buonadonna, S. Barni, A. Gasbarrini, M. Pirisi, U. Cillo, A. Picciotto, E. Villa, P. Giovanis, G. Pinotti, C. Saitta, C. Erminero, M. de Giorgio, B. Daniele
Journal: Annals of Oncology (2015)
741. Delivery of Human Tissue Kallikrein Gene Mediates Reductions in Blood Pressure and the Levels of Plasma Insulin and Blood Glucose in Fructose-Induced Hypertensive Rats with Diabetes
Journal: Molecular Therapy (2002)

Objective Tissue kallikrein cleaves kininogen substrate to produce the potent vasodilating peptide kinin, which plays important roles in cardiovascular diseases. Hypertension is a multigene disease and is usually companied with diabetes or hyperinsulinemia. In this study, we investigated therapeutic effects of kallikrein gene delivery on the hvpertension as well as diabetes in fructose-induced hvpertensive rats with hyperinsulinemia. Methods Male Sprague-Dawley rats were fed with high-fructose (10%)water to develop mild hvpertensive models. Plasmid pr-D-NA3.1 carrving human tissue kallikrein cDNA (HK)(2.5 microgram/kg body weight for each rat)was delivered into high fructose-induced hypertensive rats (n = 6) after 2 weeks through the sublingual vein and empty plasmid was in-jected as control group (n = 6) . The caudal arterial pressure was measured twice a week for 5 weeks until the ani-mals were sacrificed. The blood was collected for determination of the Ievels of blood glucose and insulin before plasmid injection and sacrificed, respectively. Results A single intravenous injection of pcDNA-HK resulted in a signifi-cant reduction in blood pressure beginning 3 days after injection and the effect lasted for 3 weeks. And it is very sur-prised that the Ievels of plasma insulin and blood glucose were reduced to normal levels in HK-treated rats, although all animals were kept in feeding with 10% fructose water. But the rats in control had nothings changed compared with those before plasmid injection. The expression of human kallikrein was detected in rat main organs by Westem Blot and in blood and urine by ELISA in pcDNA-HK treated rats. Conclusion These results indicate that human kallikrein gene transfer induces a dominantly reduction in high blood pressure as well as the high levels of plasma in-sulin and glucose in fructose-induced hypertensive rats with hyperinsulinemia and hvperglvcemia, which raises the feasibility of applving HK gene to treat hurnan diabetes and hypertension.
Case 46-1984
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Jerome S. Brody, Eugene J. Mark
Journal: New England Journal of Medicine (1984)

Presentation of CaseA 63-year-old man was admitted to the hospital because of dyspnea.He was well until 26 months earlier, when weakness developed. He was referred to this hospital, where physical examination was negative. The hematocrit was 30.6 per cent; the white-cell count was 600, with 28 per cent neutrophils, 12 per cent band forms, 44 per cent lymphocytes, and 16 per cent monocytes; the platelet count was 122,000. An electrocardiogram and x-ray films of the chest were normal. Microscopical examination of a needle-aspirated specimen of bone marrow revealed acute myelogenous leukemia. A regimen of TAD (thioguanine, cytarabine [cytosine . . .
Metabolic Testing for Adults in a State Medicaid Program Receiving Antipsychotics
Authors: Elaine H. Morrato, Elizabeth J. Campagna, Sarah E. Brewer, L. Miriam Dickinson, Deborah S. K. Thomas, Benjamin F. Miller, James Dearing, Benjamin G. Druss, Richard C. Lindrooth
Journal: JAMA Psychiatry (2016)

Medicaid quality indicators track diabetes mellitus and cardiovascular disease screening in adults receiving antipsychotics and/or those with serious mental illness.To inform performance improvement interventions by evaluating the relative importance of patient, prescriber, and practice factors affecting metabolic testing.A retrospective cohort study was conducted using Missouri Medicaid administrative claims data (January 1, 2010, to December 31, 2012) linked with prescriber market data. The analysis included 9316 adults (age, 18-64 years) who were starting antipsychotic medication. Secondary analysis included the subset of adults (n = 1813) for whom prescriber knowledge, attitudes, and behavior survey data were available. Generalized estimating equations were performed to identify factors associated with failure to receive annual testing during antipsychotic treatment (adjusted odds ratio [OR], <1 favor testing). Data analysis was performed from October 1, 2014, to February 18, 2016.Oral second-generation antipsychotics.A medical claim for glucose or lipid testing occurring within 180 days before and after the antipsychotic prescription claim.The 9317 patients (mean [SD] age, 37.6 [12.0] years) initiated antipsychotic medication in a variety of prescriber specialty-settings: 24.3%, community mental health center (CMHC); 27.6%, non-CMHC behavioral health; 24.3%, primary care practitioners; and 23.8%, other/unknown. Annual testing rates were 79.6% for glucose and 41.2% for lipids. Failure to test glucose and lipids was most strongly associated with patient factors and health care utilization. To illustrate by using findings from glucose modeling (reported as adjusted OR [95% CI]), lower failure to receive testing was associated with older age (40-49 vs 18-29 years; 0.64 [0.55-0.74]), diagnosis of schizophrenia or bipolar disorder (0.55 [0.44-0.67]), cardiometabolic comorbidity (dyslipidemia, 0.28 [0.22-0.37]), hypertension (0.59 [0.50-0.69]), and greater outpatient utilization (>6 encounters vs none; 0.33 [0.28-0.39]). Analysis incorporating prescriber practice information found lower failure to receive glucose testing if the patient received care at a CMHC (0.74 [0.64-0.85]) or if the initiating prescriber was a primary care practitioner (0.81 [0.66-1.00]). However, the initiating prescriber specialty-setting was not associated with lipid testing.Compared with prior reports, progress has been made to improve diabetes screening, but lipid screening remains particularly underutilized. Medicaid performance improvement initiatives should target all prescriber settings and not just behavioral health.
Therapeutic substitution could reduce US drug spending by nearly 10%, study finds
Authors: Michael McCarthy
Journal: BMJ (2016)

The routine use of therapeutic substitution—where cheaper, chemically different compounds from the same therapeutic drug class are substituted for higher priced brand name drugs—could reduce US drug spending by nearly 10%, a new study in JAMA Internal Medicine has found.1

Unlike generic substitution—where a generic equivalent of a brand name drug is used—therapeutic substitution replaces the brand name drug with a drug with a different active ingredient but the same therapeutic effect, such as reducing blood pressure …
AID is required for germinal center–derived lymphomagenesis
Authors: Laura Pasqualucci, Govind Bhagat, Mila Jankovic, Mara Compagno, Paula Smith, Masamichi Muramatsu, Tasuku Honjo, Herbert C Morse, Michel C Nussenzweig, Riccardo Dalla-Favera
Journal: Nature Genetics (2007)