tbuckley/cabot-search huggingface dataset:
The inhibition of CuZn superoxide dismutase (SOD1) by ATN-224, a second generation tetrathiomolybdate, interferes with multiple signaling pathways in tumor and endothelial cells in vitro
Authors: Jose C. Juarez, Mari M. Manuia, Oscar Betancourt, Andrew P. Mazar, Fernando Donate
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4687 

Tetrathiomolybdate (TM) is a copper binding drug that has demonstrated anti-tumor and anti-angiogenic activity in a number of preclinical studies as well as preliminary evidence of anti-tumor activity in cancer patients. However, very little is understood about the mechanism of action of TM at the molecular level. ATN-224 is a second generation analogue of TM that is currently entering several Phase II cancer trials. ATN-224 inhibits CuZn superoxide dismutase (SOD1), which catalyzes the dismutation of superoxide anion (O2-) into H2O2 and O2. In endothelial cells, SOD1 inhibition results in reduced phosphorylation of ERK1/2 mediated by FGF-2 and VEGF. This leads to suppression of proliferation in vitro and the inhibition of angiogenesis in vivo . In the present study, we demonstrate that ATN-224 inhibition of SOD1 also leads to the inhibition of EGF, IGF-1 and PDGF mediated ERK phosphorylation in a variety of tumor cell lines (A431, HT-29 and U87). This inhibition appears to occur at the level of the growth factor receptor, since (i) ATN-224 mediated SOD1 inhibition in A431 cells decreases EGF mediated phosphorylation of EGFR; and, (ii) ATN-224 treatment of U87 glioma cells stimulated with PDGF decreases levels of the PDGF receptor. In contrast to endothelial cells, where ATN-224 inhibits proliferation but does not cause cell death, the induction of apoptosis is observed in tumor cells treated with ATN-224. Further, EGF, PDGF and IGF-1 have been reported to elicit an increase in H2O2 by activating superoxide producing enzymes when bound to their receptors. Superoxide produced in this way is then converted into H2O2, which inactivates phosphatases by oxidizing an essential cysteine residue in the active site. SOD1 inhibition mediated by ATN-224 in A431 cells impedes the H2O2 mediated inactivation of PTEN and other phosphatases, suggesting that the preservation of phosphatase activity contributes to ATN-224 inhibition of growth factor mediated signaling. These results support the inhibition of SOD1 by ATN-224 as a novel therapeutic strategy for the inhibition of multiple signaling pathways implicated in tumor growth and angiogenesis.
GAO: Medicare Ads Were Illegal
Authors: Brian Vastag
Journal: JAMA (2004)

more social and quicker with language. “They both involved [play] objects and communication and sharing,” she said. Her team is continuing to follow the children, who are now 7 and 8 years old. The researchers are also in the midst of a study with mothers of children with autism; the mothers are trained in various directed communication strategies and are then videotaped interacting with their children during structured play sessions.
Abstract 4331: Lowering glucose increases nutlin-3 toxicity against melanomas irrespective of BRAF,NRAS or p53 mutations
Authors: Manuel Rieber, Valery Chavez-Perez, Mary Strasberg-Rieber
Journal: Cancer Research (2014)

Abstract BACKGROUND: Melanomas are commonly characterized by mutually exclusive BRAF V600Emutations (∼60%) or NRASQ61 mutations (∼15%). Although targeted therapy with vemurafenib is initially efficient in melanoma with BRAF mutations, tumor recurrence occurs including emergence of resistant melanoma cells with secondary N-RASQ61K mutations. Recently it was demonstrated that nutlin-3, an HDM2 antagonist capable of restoring p53 tumor suppressor function synergized with vemurafenib against BRAF V600E wt p53 melanomas. Although nutlin-3 was initially believed to be non-genotoxic, it can originate p53 mutations which are infrequent in primary melanomas. OBJECTIVES: Since tumor growth increases metabolic demand and glucose consumption, we investigated whether lowering glucose with glycolytic inhibitors increases nutlin-3 toxicity against melanomas irrespective of BRAF, NRAS or p53 status. EXPERIMENTAL: Metabolic activity/proliferation of melanoma cells harbouring BRAF, NRAS or p53 mutations was quantitated by fluorometric studies, crystal violet staining was used to determine differential cell survival, and mechanisms of cell death were studied by protein array immune blotting. RESULTS: Restricting glucose increases nutlin-3 toxicity against wt p53 melanoma cells harbouring BRAF or NRAS, even if the latter have p53 mutations. Responses occur through mechanisms dependent and independent of p53 serine 15-phosphorylation and p21/CIP1/CDNK1A. CONCLUSION: Elimination of melanoma cells irrespective of their BRAF, NRAS or p53 mutational status may be helped by joint use of glucose-lowering agents together with nutlin-3. Citation Format: Manuel Rieber, Valery Chavez-Perez, Mary Strasberg-Rieber. Lowering glucose increases nutlin-3 toxicity against melanomas irrespective of BRAF,NRAS or p53 mutations. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4331. doi:10.1158/1538-7445.AM2014-4331
Social and emotional factors and decisions of advanced cancer patients (ACP) to enter an early-phase (EP) clinical trial.
Authors: Daniel Paul Dohan, James Wiley, Sarah B. Garrett, Laura Trupin, Fay J. Hlubocky, Christopher Daugherty, Anne Reinert, Pamela N. Munster
Journal: Journal of Clinical Oncology (2014)

223 Background: We explored how social and emotional factors shaped decisions by ACP to enter an EP trial. Methods: Mixed-methods longitudinal cohort study including validated surveys and open-ended interviews. ACP were recruited at an academic medical center with an EP trials program. Patients were eligible if treating oncologists deemed them likely to exhaust standard treatment in 6-12 months but before being offered EP study enrollment. Surveys measured symptoms, quality of life, decisional preferences, emotions, and demographics. 60 minute semi-structured interviews were audio recorded and transcribed. SAS (statistical) and Atlas.ti (thematic coding) were use for analysis. Results: Of 82 patients in the ACP cohort, 16% went on to initiate EP trial entry. No social and emotional factors were associated with EP initiation except ACP who reported both not “feeling down” and feeling “in control of things in your life” (Table) were more likely to initiate. In interviews, many EP initiates expressed hopefulness and a desire to actively respond to their illness. While none believed they could control their illness, some ACP attributed their sense of control over things to their relationship with their oncologist, and others attributed it to informational networks. Conclusions: A feeling of control and absence of depressive symptoms may be associated with ACP initiation of an EP trial. Further exploration of qualitative data documenting the dynamics of EP decision-making is needed. [Table: see text]
Determination of cytomegalovirus DNA load for monitoring of cytomegalovirus disease and antiviral treatment in solid organ transplant patients, comparing limiting-dilution PCR and hybrid capture assay with cytomegalovirus isolation
Authors: Lisbeth Barkholt, Karin Loré, Gunnar Tydén, Ilona Lewensohn-Fuchs, Jan Andersson, Bo-Göran Ericzon, Göran Lundgren, Anneka Ehrnst
Journal: Clinical Microbiology and Infection (1999)
Selling a Medical School's Name
Authors: Jay S Loeffler, Edward C Halperin
Journal: JAMA (2008)

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
Pharmacological targeting of miR-155 via the NEDD8-activating enzyme inhibitor MLN4924 (Pevonedistat) in FLT3-ITD acute myeloid leukemia
Authors: J Khalife, H S Radomska, R Santhanam, X Huang, P Neviani, J Saultz, H Wang, Y-Z Wu, H Alachkar, M Anghelina, A Dorrance, J Curfman, C D Bloomfield, B C Medeiros, D Perrotti, L J Lee, R J Lee, M A Caligiuri, F Pichiorri, C M Croce, R Garzon, M L Guzman, J H Mendler, G Marcucci
Journal: Leukemia (2015)
Third of Irish doctors regret going into medicine
Authors: Doug Payne
Journal: BMJ (2000)

A survey by the Irish Medical Organisation shows that 42% of the country's junior doctors regret their career choice, compared with a quarter of both GPs and consultants.

Almost a third of all doctors said they would reject medicine if they were back at school; 36% of female doctors who responded said they would not choose medicine again, compared with 29% of male respondents.

The survey, Turning Vision into Reality , also shows rising concern over a broad range of issues. Workload …
Brief Report: Genome‐Wide Association Study Identifies <i>ITPR2</i> as a Susceptibility Gene for Kashin‐Beck Disease in Han Chinese
Authors: Feng Zhang, Yan Wen, Xiong Guo, Yingang Zhang, Xi Wang, Tielin Yang, Hui Shen, Xiangding Chen, Qing Tian, Hong‐Wen Deng
Journal: Arthritis & Rheumatology (2014)

Kashin-Beck disease (KBD) is a chronic osteochondropathy, the pathogenesis of which remains elusive. The aim of this study was to identify susceptibility genes for KBD by conducting a 2-stage genome-wide association study (GWAS).Ninety patients with grade II or grade III KBD with extreme KBD phenotypes and 1,627 healthy control subjects were enrolled in the initial GWAS. Affymetrix Genome-Wide Human SNP Array 6.0 was used for genotyping. For the replication study, 9 single-nucleotide polymorphisms (SNPs) of the significant gene identified by the GWAS (ITPR2) were tested in an independent validation sample composed of 559 patients with KBD and 467 healthy control subjects.The GWAS identified significant association (P = 1.58 × 10(-8) ) between KBD and a novel locus, ITPR2 SNP rs10842750. The replication study showed significant associations with KBD at 9 ITPR2 SNPs, including rs10842750 (P = 5.97 × 10(-3) ), rs16931011 (P = 1.29 × 10(-3) ), rs1531928 (P = 4.95 × 10(-3) ), rs4414322 (P = 4.40 × 10(-3) ), rs11048570 (P = 4.53 × 10(-3) ), rs11048572 (P = 4.43 × 10(-3) ), rs2017510 (P = 4.58 × 10(-3) ), rs9669395 (P = 5.77 × 10(-3) ), and rs1002835 (P = 4.85 × 10(-3) ). In patients with KBD, the genotype score for rs10842750 was also correlated with KBD clinical severity grades (P = 0.013).Our results strongly suggest that ITPR2 is a novel susceptibility gene for KBD in Han Chinese. This study may provide new insights into the pathogenesis and rationale for treatment of KBD as well as other osteoarthritides with similar articular cartilage lesions.
Abstract 888: Development of a urine DNA based marker panel for early detection of liver cancer
Authors: Sitong Chen, Surbhi Jain, Selena Lin, Ying-Hsiu Su, Wei Song
Journal: Cancer Research (2014)

Abstract Hepatocellular carcinoma (HCC) or liver cancer is an aggressive disease and one of the fastest growing cancers in incidence in the United States. The 5 year survival rate drops dramatically from a poor 26% in early stages to a mere 2% in later stages of the disease. Currently, the only available biomarker for early detection is serum alpha-fetoprotein which can identify only 40-60% of cases. We aim to improve the poor disease prognosis by developing a screening test capable of detecting liver cancer in its earlier stages. Since cancer is a disease of the genome and epigenome, if we can detect these underlying genetic mutations and epigenetic modifications in the periphery, we should be able to effectively detect cancer early. We have previously shown that urine contains fragmented, cell-free, cancer related DNA, both mutated and methylated, derived from the circulation of cancer patients. We have also demonstrated that the concentration of tumor-derived DNA in plasma and in urine is similar in patients with tumors. Hence, we propose the use of a panel of HCC-associated genetic and epigenetic methylation DNA biomarkers to develop a sensitive, noninvasive urine screening test for HCC. In order to detect these markers in the circulation derived urine DNA, we developed short amplicon (∼50 bp) PCR based assays targeting HCC-associated mutations in TP53, CTNNB1, hTERT genes and HCC associated methylation in GSTP1, RASSF1A and CDKN2A. Urine DNA isolated from hepatitis, cirrhosis and HCC patients were tested in each of the assays and analyzed. Panel performance parameters such as sensitivity, specificity and area under the receiver operating curve were calculated for individual markers and then as a group in order to evaluate their ability to distinguish HCC patients from hepatitis and cirrhosis subjects. The potential of this urine test in the early detection of HCC is discussed. Citation Format: Sitong Chen, Surbhi Jain, Selena Lin, Ying-Hsiu Su, Wei Song. Development of a urine DNA based marker panel for early detection of liver cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 888. doi:10.1158/1538-7445.AM2014-888
Effects of patupilone (epothilone B; EPO906), a novel chemotherapeutic agent, in hepatocellular carcinoma: An in-vitro study
Authors: Eve P. Choi, Daisy M. S. Yau, Cesar S. C. Wong, Tony S. K. Mok
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4734 

The epothilones are a new class of microtubule-stabilizing drugs with promising antiproliferative effects in ovarian, breast, lung, colon, and prostate cancer. To date, little data have been reported on the effects of epothilones in hepatocellular carcinoma (HCC). In this study, the cytotoxic effects of patupilone were assessed in a panel of HCC cell lines, and were compared with doxorubicin (standard treatment for HCC) and other microtubule-stabilizing agents, ie, paclitaxel and docetaxel. The following 8 HCC cell lines were used: PLC/PRF/5, HepG2, Hep3B, SNU-387, SNU-398, SNU-423, SNU-449, and SNU-475. Cells were treated with various concentrations of patupilone, paclitaxel, docetaxel, or doxorubicin for 72 hours; 50% inhibitory concentrations (IC50s) were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Patupilone was found to be the most effective drug in all 8 HCC cell lines. All cell lines (except SNU-449) were 4- to 18-fold more sensitive to patupilone than to paclitaxel and docetaxel, and 58- to 220-fold more sensitive than to doxorubicin. SNU-449, the most resistant cell line, was 3- to 30-fold more resistant to paclitaxel, docetaxel, and doxorubicin when compared with the other 7 cell lines. However, the IC50 of patupilone in SNU-449 was 1.140 nmol, which was 108- to 528-fold lower than the IC50s of the other 3 agents in SNU-449. The results confirmed that patupilone was more potent than paclitaxel, docetaxel, and doxorubicin in this panel of 8 HCC cell lines. A clinical study of this novel chemotherapeutic agent in patients with HCC is warranted.
Paclitaxel-Eluting Coronary Stents in Patients With Diabetes Mellitus
Authors: Ajay J. Kirtane, Stephen G. Ellis, Keith D. Dawkins, Antonio Colombo, Eberhard Grube, Jeffrey J. Popma, Martin Fahy, Martin B. Leon, Jeffrey W. Moses, Roxana Mehran, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2008)
Abstract 141: Deletion of <i>Ptpn11</i> (Shp2) in Cardiomyocytes Leads to Dilated Cardiomyopathy
Authors: Maria I Kontaridis, Wentien Yang, Kendra Bence, Darragh Cullen, Bo Wang, Natalya Bodyak, Qingen Ke, Aleksander Hinek, Peter Kang, Ronglih Liao, Benjamin G Neel
Journal: Circulation (2007)

Heart failure is the leading cause of death in the U.S. Delineating the pathways that regulate cardiomyocyte function is essential to understanding the pathogenesis of cardiac disease. Many cardiomyocyte signaling pathways activate protein tyrosine kinases, yet the role of protein tyrosine phosphatases (PTPs) in the heart is unknown. Here, we show that mice with cardiac-specific deletion of Ptpn11 , the gene encoding the SH2 domain-containing PTP Shp2, rapidly develop a compensated dilated cardiomyopathy without an intervening hypertrophic phase. Primary Shp2 deficient cardiomyocytes are defective in Erk/MAPK activation in response to a variety of soluble agonists and pressure overload. Our results identify Shp2 as the first PTP known to have a critical role in cardiac function, suggest that Shp2’s cardio-protective role is mediated via control of the Erk/MAPK pathway, and have important implications for the pathogenesis of cardiac defects in the human genetic diseases Noonan Syndrome and LEOPARD Syndrome, which are caused by PTPN11 mutations.
Reflex sympathetic dystrophy
Authors: K P Bhatia, C D Marsden
Journal: BMJ (1995)

Secondly, can the outcome of chronic anterior uveitis be predicted from the subtype of juvenile chronic arthritis with which it is associated?In other words, is there any sense in screening the subtypes at different frequencies?There is no doubt that the risk of developing chronic anterior uveitis varies with the subtype of juvenile chronic arthritis.Children with systemic onset juvenile chronic arthritis, rheumatoid factor positive polyarthritis, or spondyloarthritis are unlikely to develop chronic anterior uveitis, and as such probably do not warrant screening.However, there is little evidence to suggest that the outcome of the uveitis is related to the subtype of the arthritis.The risk of chronic anterior uveitis should determine who is enrolled in a screening programme, but the frequency of screening should be independent of the risk of chronic anterior uveitis and be based instead on the natural history ofthe disease.3M Rawes's assertion that joint aspiration for septic arthritis is associated with a poorer outcome because it results in late referral to orthopaedic surgeons is debatable.'An urgent diagnostic arthrocentesis may not only decompress the joint space but may also allow the initial choice of broad spectrum antibiotics to be modified appropriately in the light of microbiological evidence.4Rawes also implies that arthrotomy and joint washout is the treatment of choice for all forms of septic arthritis in children.There is evidence that some forms of septic arthritis may be successfully treated with a single aspiration of the affected joint and appropriate antibiotic cover, raising the possibility that arthrotomy may be sometimes an unnecessarily invasive surgical procedure.'For further informed debate on this important subject, Wilson and Di Paola's call for a multicentre, controlled, prospective clinical trial of treatment in childhood septic arthritis must be answered.6
Quality improvement report: Effect of multifaceted intervention promoting early switch from intravenous to oral acetaminophen for postoperative pain: controlled, prospective, before and after study
Authors: C. Ripouteau, O. Conort, J. P. Lamas, G.-R. Auleley, G. Hazebroucq, P. Durieux
Journal: BMJ (2000)

<h3>Abstract</h3> <i>Problem</i> Need to improve the efficiency of postoperative pain management by early switching from intravenous to oral acetaminophen. <i>Design</i> Implementation of local guidelines aimed at improving nurses9 and doctors9 behaviour. A controlled, prospective, before and after study evaluated its impact on appropriateness and costs. <i>Background and setting</i> Orthopaedic surgery department (intervention) and all other surgical departments (control) of a university hospital. Five anaesthetists and 30 nurses of orthopaedic department participated in study. <i>Key measures for improvement</i> Reducing number of acetaminophen injections per patient, reducing consumption of acetaminophen injections; cost savings over a one year period. <i>Strategies for improvement</i> Multifaceted intervention included a local consensus process, short educational presentation, poster displayed in all nurses9 offices, and feedback of practices six months after implementation of guidelines. <i>Effects of change</i> Mean number of acetaminophen injections per patient decreased from 6.81 before intervention to 2.36 six months after. Monthly consumption of acetaminophen injections per 100 patients decreased by 320.9 (95% confidence interval 192.4 to 449.4) in intervention department and remained unchanged in control departments. Annual cost reduction was projected to be £15 100. <i>Lessons learnt</i> Simple and locally implemented guidelines can improve practices and cut costs. Educational interventions can improve professionals9 behaviour when they are based on actual working practices, use interactive techniques such as discussion groups, and are associated with other effective implementation strategies.