tbuckley/cabot-search huggingface dataset:
Abstract A33: Mediator is an intrinsically dynamic complex critical to Hsf1-activated transcription
Authors: Jayamani Anandhakumar, Yara Moustafa, Surabhi Chowdhary, Amoldeep S. Kainth, David S. Gross
Journal: Cancer Research (2016)

Abstract Mediator is an evolutionarily conserved transcriptional coactivator that plays a vital role in the regulation of RNA polymerase II (Pol II) transcribed genes in eukaryotes as diverse as yeast and human. It consists of a tri-modular core complex comprised of Head, Middle and Tail modules and a dissociable Cdk8/Kinase module (CKM). Although it has been assumed that core Mediator in the model eukaryote S. cerevisiae (budding yeast) exists as a stable 21-subunit complex based on cell-free assays, its structural state in vivo is unclear. We have obtained evidence that the Tail module is highly dynamic, and that a subcomplex consisting of Tail subunits Med2, Med3 and Med15 can be independently recruited to the UAS/promoter regions of Heat Shock Factor 1 (Hsf1)-regulated genes in response to acute thermal stress. Med2-Med3-Med15 autonomy is revealed by ChIP analysis following the “anchoring away” of select Mediator core subunits located in either Middle or Tail module. Such conditional depletion leads to a 60-80% reduction in HSP gene transcription. We additionally observed that Hsf1 can recruit the CKM independently of the core complex, and that both core Mediator and CKM recruitment occurs independently of SAGA. Collectively, our results indicate that yeast Mediator is intrinsically dynamic and that multiple species, including CKM-Mediator, the 21-subunit core complex, the Med2-Med3-Med15 Tail Triad and the four-subunit CKM, can be independently recruited by Hsf1 to its target genes. Citation Format: Jayamani Anandhakumar, Yara Moustafa, Surabhi Chowdhary, Amoldeep S. Kainth, David S. Gross. Mediator is an intrinsically dynamic complex critical to Hsf1-activated transcription. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr A33.
A Mechanism for Cancer-Associated Membranous Nephropathy
Authors: Elion Hoxha, Thorsten Wiech, Phillip R. Stahl, Gunther Zahner, Nicola M. Tomas, Catherine Meyer-Schwesinger, Ulrich Wenzel, Matthias Janneck, Oliver M. Steinmetz, Ulf Panzer, Sigrid Harendza, Rolf A.K. Stahl
Journal: New England Journal of Medicine (2016)

To the Editor: An association between membranous nephropathy and malignant tumors has been known for decades. 1 It was hypothesized that circulating, preformed immune complexes containing tumor antigens deposit in the glom-eruli and induce membranous nephropathy; however, this hypothesis no longer appears to explain how subepithelial immune deposition occurs. 2 The in situ binding of antibodies to endogenous antigens, which is strongly supportedThe New England Journal of Medicine Downloaded from nejm.
Efficacy of the Priority Review Voucher Program
Authors: David B. Ridley, Jennifer Dent, Christopher Egerton-Warburton
Journal: JAMA (2016)

To the Editor Dr Kesselheim and colleagues1 assessed the priority review voucher program, which rewards companies for US Food and Drug Administration (FDA) registration of treatments for rare pediatric or neglected diseases. We have a more optimistic view of the program.
Pediatric Surgery
Authors: W. Hardy Hendren
Journal: New England Journal of Medicine (1973)

CancerCancer is second only to trauma as the leading cause of death in childhood. It is with considerable hope that pediatricians and surgeons view certain developments that may have promise in pediatric neoplasia. For example, Folkman255 has shown that a diffusable factor that is mitogenic for capillary endothelium can be isolated from animal and human tumor cells. To grow larger than 2 to 3 mm, a tumor requires neovascularization of its environment. The hope is that tumor growth can be suppressed by discovery of an appropriate antiangiogenesis agent. Also of interest is the demonstration in fetal and adult tissues . . .
HCP-15BEVACIZUMAB IN HIGH GRADE GLIOMA PATIENTS FOLLOWING INTRACRANIAL HEMORRHAGE (ICH) - A REVIEW OF FIVE CASES
Authors: Xuling Lin, Mariza Daras, Craig Nolan, Igor Gavrilovic, Ingo Mellinghoff, Lisa DeAngelis, Thomas Kaley
Journal: Neuro-Oncology (2015)

BACKGROUND: Bevacizumab is approved for the treatment of recurrent glioblastoma (GBM) and has been associated with clinical improvement and steroid reduction. ICH is a contraindication to bevacizumab therapy. However, in patients with symptomatic enhancing tumors and poor Karnofsky performance status, bevacizumab may be the only beneficial treatment option. METHODS: We retrospectively reviewed patients with recurrent malignant glioma who were treated with bevacizumab despite prior ICH at our center. RESULTS: Five patients (3 males; 2 females) with a median age of 51 years (range 20-60 years) were identified. All patients developed intratumoral bleed (three grade 2; two grade 1); one was receiving bevacizumab and two were on anticoagulation for systemic venous thrombosis. The mean volume of ICH was 9.4 cm3 (range 0.2-39.5 cm3). After a median duration of 61 days (range 14-140 days) from the ICH, bevacizumab was started or resumed at the standard dose of 10 mg/kg every two weeks. Brain imaging performed immediately prior to bevacizumab treatment showed persistent or evolving hemorrhage in four patients and complete resolution of ICH in one patient. Following bevacizumab therapy, all patients achieved initial clinical improvement. One patient received bevacizumab while intubated, was successfully extubated but developed other systemic complications, and died 42 days after receiving bevacizumab; post-bevacizumab CT brain scan was stable without ICH progression. The other four patients were followed clinically and radiographically for a median duration of 4 months (range 1.4-22 months) and did not demonstrate any evidence of recurrent or worsening ICH on brain imaging. CONCLUSIONS: In this case series, although small, bevacizumab use was safe in patients with recurrent malignant glioma following ICH for which no other meaningful treatment options existed.
Preabortion Medication
Authors: Rajindar K. Wadhwa
Journal: JAMA (1974)

<h3>To the Editor.—</h3> We would like to comment on preoperative medication for therapeutic abortions. General anesthesia for therapeutic abortions on outpatients should be undertaken with great caution because of the possible aspiration of gastric contents. Proper selection of preoperative medication can reduce the possibility of this life-threatening complication. Factors associated with the first trimester of pregnancy, ie, morning sickness and emotional problems, can induce nausea and vomiting. Also, the patient might ingest liquids or solid food before coming to the hospital. Some anesthetic agents or anesthetic technics can induce nausea and vomiting. In our study, 60 patients were selected at random and divided into three groups of 20 each. Group A, the control group, received<i>no</i>preoperative medication. Group B was given<i>diazepam</i>, and group C<i>hydroxyzine hydrochloride</i>. All patients were given atropine, 0.4 mg intramuscularly one hour before surgery. Narcotics were avoided intentionally. The incidence of nausea preoperatively was
Total Parenteral Nutrition
Authors: C R Fleming, D B McGill, H N Hoffman, R A Nelson
Journal: Annals of Internal Medicine (1992)

Total parenteral nutrition (TPN) is a relatively new innovation in patient care which allows us to replace and maintain essential nutrients in patients in whom oral or tube feedings are contraindicated or inadequate. Insertion of a catheter into a large central vein permits one to concentrate hypertonic dextrose calories in normal daily fluid requirements. In addition, TPN solutions contain synthetic amino acids or protein hydrolysates, macroelements, electrolytes, and vitamins. Indications for TPN include intestinal fistulas, severe short bowel syndrome, unresolving pancreatitis, advanced inflammatory bowel disease, delayed postoperative gastrointestinal function, developmental anomalies of the intestinal tract, protracted diarrhea of infancy, and hypermetabolic states. Complications encountered in patients receiving TPN are catheter-related mechanical problems, infections, and metabolic abnormalities. In select patients, who otherwise would require repeated hospitalizations for malnutrition, encouraging results have been achieved by the use of TPN in the home.
Development of a national EUCAST challenge panel for antimicrobial susceptibility testing
Authors: S. Desmet, J. Verhaegen, Y. Glupzcynski, J. Van Eldere, P. Melin, H. Goossens, D. Piérard, P. Declercq, K. Lagrou, A. Boel, R. Cartuyvels, O. Denis, W. Vandewal, V. Saegeman
Journal: Clinical Microbiology and Infection (2016)
Intervertebral Disk Calcification in Children
Authors: R Jawish, P Rigault, J P Padovani, P Mouterde, P Touzet, J P Chaumien
Journal: JAMA (1963)

Thirty one intervertebral space calcifications (I.S.C.) were studied in 21 children (12 boys, 9 girls), with mean age of 7 years; 25 calcifications had been followed for an average of 71.5 months. The main symptom was pain (Crisis) which relieved in a delay of 1 month in 70 per cent of cases. "Crisis" and radiographic fragmentation of the calcification are both criteria of going out of 18 calcifications, in a delay ranged from 28 days to 6 months. The calcification appears as a sign which disclose a general disease of spine, interesting vertebral body, growth plate, and disc; therefore we have observed 15 lesions due to growth disorders in 16 cervical I.S.C., at dorsal level we have described 4 cases of intrasomatic cavitation containing calcified material, opened in the intervertebral space. This growth disturbance has been noted either on first radiograph, or has appeared later, after disappearance of the I.S.C.; we found more over absence of listel and lesion of multiple plates distant from the calcification. This disease is identified to vertebral osteochondrosis where residual deformities are more worrying than the benign calcification; they have concluded management of I.S.C. as early as possible to avoid great deformities of vertebral bodies.
Phase I open label liver-directed gene therapy clinical trial for acute intermittent porphyria
Authors: Delia D’Avola, Esperanza López-Franco, Bruno Sangro, Astrid Pañeda, Nadina Grossios, Irene Gil-Farina, Alberto Benito, Jaap Twisk, María Paz, Juan Ruiz, Manfred Schmidt, Harald Petry, Pauline Harper, Rafael Enríquez de Salamanca, Antonio Fontanellas, Jesús Prieto, Gloria González-Aseguinolaza
Journal: Journal of Hepatology (2016)

Acute intermittent porphyria (AIP) results from porphobilinogen deaminase (PBGD) haploinsufficiency, which leads to hepatic over-production of the neurotoxic heme precursors porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) and the occurrence of neurovisceral attacks. Severe AIP is a devastating disease that can only be corrected by liver transplantation. Gene therapy represents a promising curative option. The objective of this study was to investigate the safety of a recombinant adeno-associated vector expressing PBGD (rAAV2/5-PBGD) administered for the first time in humans for the treatment of AIP.In this phase I, open label, dose-escalation, multicenter clinical trial, four cohorts of 2 patients each received a single intravenous injection of the vector ranging from 5×10(11) to 1.8×10(13) genome copies/kg. Adverse events and changes in urinary PBG and ALA and in the clinical course of the disease were periodically evaluated prior and after treatment. Viral shedding, immune response against the vector and vector persistence in the liver were investigated.Treatment was safe in all cases. All patients developed anti-AAV5 neutralizing antibodies but no cellular responses against AAV5 or PBGD were observed. There was a trend towards a reduction of hospitalizations and heme treatments, although ALA and PBG levels remained unchanged. Vector genomes and transgene expression could be detected in the liver one year after therapy.rAAV2/5-PBGD administration is safe but AIP metabolic correction was not achieved at the doses tested in this trial. Notwithstanding, the treatment had a positive impact in clinical outcomes in most patients.Studies in an acute intermittent porphyria (AIP) animal model have shown that gene delivery of PBGD to hepatocytes using an adeno-associated virus vector (rAAV2/5-PBG) prevent mice from suffering porphyria acute attacks. In this phase I, open label, dose-escalation, multicenter clinical trial we show that the administration of rAAV2/5-PBGD to patients with severe AIP is safe but metabolic correction was not achieved at the doses tested; the treatment, however, had a positive but heterogeneous impact on clinical outcomes among treated patients and 2 out of 8 patients have stopped hematin treatment.The observational phase was registered at Clinicaltrial.gov as NCT 02076763. The interventional phase study was registered at EudraCT as n° 2011-005590-23 and at Clinicaltrial.gov as NCT02082860.
FRI0469 The Additive Value of Nailfold Videocapillaroscopy Patterns to Disease-Specific Autoantibodies in Discrimination of Patients with Systemic Sclerosis at Risk for Severe Organ Involvement
Authors: I. Markusse, J. Meijs, B. de Boer, J. Bakker, P. Schippers, A. Schouffoer, N. Ajmone Marsan, L. Kroft, M. Ninaber, T. Huizinga, J. de Vries-Bouwstra
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Severe nailfold videocapillaroscopy (NVC) patterns in patients with systemic sclerosis (SSc) are associated with a high risk of organ involvement. Previously, the association between anti-topoisomerase (anti-Scl70) and anti-centromere (ACA) and specific NVC patterns has been explored. Whether anti-ribonucleoprotein (anti-RNP) and anti-RNA polymerase III (anti-RNAP3) associate with specific NVC patterns, and whether the combination of different autoantibodies and NVC pattern contributes to better discrimination of patients at risk for organ involvement remains unclear. <h3>Objectives</h3> To explore the association between clinical phenotype and the combination of autoantibodies and NVC pattern in a large cohort. <h3>Methods</h3> For this cross-sectional study, data on NVC scleroderma patterns (early, active, late) and ACA, anti-Scl-70, anti-RNP and anti-RNAP3 were investigated in 287 patients of the Leiden Systemic Sclerosis Cohort. Logistic regression analysis, with NVC pattern and autoantibodies as independent and disease characteristic as dependent variables were performed, adjusted for age, disease duration and the use of immunosuppressive or vasoactive drugs. Under the assumption of a linear relationship within NVC patterns from mild to severe, it was entered as a continuous variable in the order: no specific SSc pattern, early, active and late pattern. A separate analysis was performed for each autoantibody and each clinical feature. <h3>Results</h3> 253/287 patients (88%) had a specific scleroderma NVC pattern; 29 (10%) early, 121 (42%) active and 103 (36%) late pattern. 107 patients (37%) were ACA positive (+), 69 patients (24%) were anti-Scl-70+, 26 patients (9%) were anti-RNP+ and 13 patients (5%) were anti-RNAP3+. The table shows the associations between NVC pattern sand clinical features stratified for autoantibody. <h3>Conclusions</h3> Strikingly, the association between NVC pattern and clinical features was stable and independent of specific autoantibodies. Even in ACA+ patients severe NVC patterns were associated with lung involvement. These data suggest that the combination of NVC pattern and autoantibodies contributes to discrimination of SSc patients that need extensive organ screening and follow-up. <h3>Disclosure of Interest</h3> I. Markusse: None declared, J. Meijs Grant/research support from: unrestricted educational grant of Actelion Pharmaceuticals Nederland BV (Woerden, The Netherlands), B. de Boer: None declared, J. Bakker: None declared, P. Schippers: None declared, A. Schouffoer: None declared, N. Ajmone Marsan: None declared, L. Kroft: None declared, M. Ninaber: None declared, T. Huizinga: None declared, J. de Vries - Bouwstra: None declared
Abstract P4-08-03: DEAD-box RNA helicase DP103 as a novel regulator of Wnt/β-catenin signaling pathway and promotes cancer stem cell-like behavior in triple negative breast cancers
Authors: W Cai, JK Cheong, E Edison, A Banerjee, TZ Tan, L Gaboury, EM Yousef, JP Thiery, PE Lobie, DM Virshup, CT Yap, AP Kumar
Journal: Cancer Research (2016)

Abstract Despite recent advances in breast cancer therapeutics, mortality of metastatic triple negative breast cancer (TNBC) subtype remains high; due to their lack of hormone receptors expression for targeted therapy. Aberrant activation of Wnt/β-catenin signaling has been associated with breast cancers; where 40% of total breast cancers have elevated β-catenin levels with increased Wnt activity. Recently, we identified DEAD-box RNA helicase DP103 as a novel prognostic biomarker and metastasis-driving oncogene; highly expressed in TNBC subtype. Interestingly, we found high DP103 expression to be positively correlated with high β-catenin expression in clinical specimens (n=400). This led us to hypothesize a possible role of DP103 in modulating the Wnt/β-catenin pathway in TNBCs. Depletion of DP103 in metastatic TNBC cells decreases Wnt/β-catenin activity and expression of downstream Wnt target genes, while overexpression of DP103 increases Wnt activity. Depletion of DP103 also decreases phosphorylation of LRP6 and several important Wnt modulators required for downstream Wnt activation. Moreover, induction of Wnt/β-catenin signaling in Wnt responsive TNBC cells also significantly increased DP103 expression, indicating a possible positive feedback loop. Both canonical and non-canonical Wnt signaling is known to independently promote stem cell growth in mammospheres. Herein, we will also provide evidence on the role of DP103 in promoting breast cancer stem cell-like properties. Collectively, our data show a novel regulatory role of DP103 in the Wnt/β-catenin signaling pathway and in promoting breast cancer stem cell-like behavior, presenting itself as a potential drug target in TNBC patients. Citation Format: Cai W, Cheong JK, Edison E, Banerjee A, Tan TZ, Gaboury L, Yousef EM, Thiery JP, Lobie PE, Virshup DM, Yap CT, Kumar AP. DEAD-box RNA helicase DP103 as a novel regulator of Wnt/β-catenin signaling pathway and promotes cancer stem cell-like behavior in triple negative breast cancers. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-08-03.
Treatment of chronic hepatitis D with the entry inhibitor myrcludex B: First results of a phase Ib/IIa study
Authors: Pavel Bogomolov, Alexander Alexandrov, Natalia Voronkova, Maria Macievich, Ksenia Kokina, Maria Petrachenkova, Thorsten Lehr, Florian A. Lempp, Heiner Wedemeyer, Mathias Haag, Matthias Schwab, Walter E. Haefeli, Antje Blank, Stephan Urban
Journal: Journal of Hepatology (2016)
THE TREATMENT OF EXOPHTHALMIC GOITER
Authors: S F HAINES
Journal: JAMA (1924)

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
The treatment of children with unilateral Wilms' tumor.
Authors: D M Green, N E Breslow, G J D'Angio
Journal: Journal of Clinical Oncology (1993)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1993.11.6.1009 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8388917 The treatment of children with unilateral Wilms' tumor. D M GreenxD M GreenSearch for articles by this author , N E BreslowxN E BreslowSearch for articles by this author , G J D'AngioxG J D'AngioSearch for articles by this author https://doi.org/10.1200/JCO.1993.11.6.1009 PDF "The treatment of children with unilateral Wilms' tumor.." Journal of Clinical Oncology, 11(6), pp. 1009–1010© 1993 by American Society of Clinical Oncology
Correlation of EGFR-expression with safety and efficacy outcomes in SQUIRE: a randomized, multicenter, open-label, phase III study of gemcitabine–cisplatin plus necitumumab versus gemcitabine–cisplatin alone in the first-line treatment of patients with stage IV squamous non-small-cell lung cancer
Authors: L. Paz-Ares, M.A. Socinski, J. Shahidi, R.R. Hozak, V. Soldatenkova, R. Kurek, M. Varella-Garcia, N. Thatcher, F.R. Hirsch
Journal: Annals of Oncology (2016)

SQUIRE demonstrated addition of necitumumab to gemcitabine and cisplatin significantly improved survival in patients with stage IV sq-NSCLC. Here, we report additional outcomes for the subpopulation of patients with tumor epidermal growth factor receptor (EGFR) protein expression.Patients with pathologically confirmed stage IV sq-NSCLC were randomized 1:1 to receive a maximum of six 3-week cycles of gemcitabine (1250 mg/m(2) i.v., days 1 and 8) and cisplatin (75 mg/m(2) i.v., day 1) chemotherapy with or without necitumumab (800 mg i.v., days 1 and 8). Patients in the chemotherapy plus necitumumab group with no progression continued on necitumumab alone until disease progression or intolerable toxicity. SQUIRE included mandatory tissue collection. EGFR protein expression was detected by immunohistochemistry (IHC) in a central laboratory. Exploratory analyses were pre-specified for patients with EGFR protein expressing (EGFR > 0) and non-expressing (EGFR = 0) tumors.A total of 982 patients [90% of intention-to-treat (ITT)] had evaluable IHC results. The large majority of these patients (95%) had tumor samples expressing EGFR protein; only 5% had tumors without detectable EGFR protein. Overall survival (OS) for EGFR > 0 patients was significantly longer in the necitumumab plus gemcitabine-cisplatin group than in the gemcitabine-cisplatin group {stratified hazard ratio (HR) 0.79 [95% confidence interval (CI) 0.69, 0.92; P = 0.002]; median 11.7 months (95% CI 10.7, 12.9) versus 10.0 months (8.9, 11.4)}. Additionally, an OS benefit was seen in all pre-specified subgroups in EGFR > 0 patients. However, OS HR for EGFR = 0 was 1.52. Adverse events of interest with the largest difference between treatment groups in EGFR > 0 patients (Grade ≥3) were hypomagnesemia (10% versus <1%) and skin rash (6% versus <1%).In line with SQUIRE ITT, addition of necitumumab to gemcitabine-cisplatin significantly prolonged OS and was generally well tolerated in the subpopulation of patients with EGFR-expressing advanced sq-NSCLC. The benefit from addition of necitumumab to chemotherapy was not apparent in this analysis for the small subgroup of patients with non-EGFR-expressing tumors.NCT00981058.