tbuckley/cabot-search huggingface dataset:
Abstract 363: Class I HDAC Inhibition Causes Selective Activation of Pro-Survival Kinases at Reperfusion in Post-Ischemic Hearts
Authors: Sverre E Aune, Daniel J Herr, Donald R Menick
Journal: Circulation Research (2014)

Background: Histone deacetylase (HDAC) enzymes inhibit gene expression through chromatin compaction and exacerbate myocyte death following ischemia-reperfusion (IR) in the heart. In our prior study, disinhibition of antioxidant gene and protein expression was achieved through 24 hour pretreatment with entinostat, a class I HDAC inhibitor, and was correlated with improved heart contractile recovery from IR. Additionally, ERK1/2 was phosphorylated, indicating activation of the reperfusion injury survival kinase (RISK) pathway. HDAC inhibitors also enhance posttranslational acetylation of nonhistone proteins through unmasking of acetyltransferase activity, which may influence heart survival from injury. Hypothesis: We hypothesized that inhibition of class I HDACs during reperfusion in postischemic hearts would activate the RISK pathway and improve contractile recovery. Methods: Hearts from male Sprague-Dawley rats (n=4/group) were isolated and perfused in Langendorff mode. Global ischemia was induced by cessation of perfusion for 30 min, followed by 60 min of reperfusion, during which hearts were perfused with vehicle or 10, 100 or 1000 nM entinostat. Results are reported vs vehicle as mean±SE. Results: At the end of reperfusion, rate pressure product (mm hg/min) was improved with 10 nM entinostat (17226±1187, p&lt;0.001) vs vehicle (11024±1810), as were +dP/dtmax, -dP/dtmax, and developed pressure. The improvement in pressure development with 10 nM entinostat was due primarily to prevention of end diastolic dysfunction in reperfusion. LV function was not significantly preserved in hearts treated with 100 or 1000 nM entinostat. Hearts reperfused with 10 nM entinostat showed reduced infarct area (35%) vs vehicle (64%), along with increased shuttling of 14-3-3 protein, Akt and phospho-ERK from cytoplasm to nucleus. These effects were reduced with higher concentrations of inhibitor. Notably, histone acetylation was increased with higher concentrations of entinostat, but not with 10 nM. Conclusions: Inhibition of class I HDACs during reperfusion resulted in specific activation of RISK members without acetylation of histone, indicating that acetyltransferase enzymes may mediate activation of pro-survival kinases in the IR heart.
Reversal of multidrug resistance.
Authors: B A Chabner, W Wilson
Journal: Journal of Clinical Oncology (1991)

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.1991.9.1.4 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 1670643 Reversal of multidrug resistance. B A ChabnerxB A ChabnerSearch for articles by this author , W WilsonxW WilsonSearch for articles by this author https://doi.org/10.1200/JCO.1991.9.1.4 First Page PDF © 1991 by American Society of Clinical Oncology
Preliminary results of capecitabine - oxaliplatin (XELOX) in hepatocellular carcinoma (HCC): A phase II trial of the Fédération Francophone de Cancérologie Digestive (FFCD 2003–03 trial)
Authors: V. Boige, J.-L. Raoul, J.-P. Pignon, O. Bouche, E. Boucher, J.-F. Blanc, J.-F. Seitz, L. Bedenne, N. Dupouy, M. Ducreux
Journal: Journal of Clinical Oncology (2005)

4128 Background: Chemotherapy has low efficacy in HCC, a poor prognostic disease. Evaluation of new drug combination is needed. The trial was designed to evaluate the efficacy of XELOX in HCC. Methods: Inclusion criteria: measurable HCC, unresectable or unsuitable for local treatment; Child-Pugh A or B, CLIP < 4. The patients (pts) received every three weeks: capecitabine 2000 mg/m2 d1-d14, oxaliplatine 130 mg/m2 as a 2-hour infusion d1. The main endpoint was tumor response. Results: From December 2003 to September 2004, 50 pts were included in this phase II trial: 44 men, 6 women; median age (range) 68 years [24–82]; Pugh score A, 42 pts and B, 8 pts; CLIP 0–1, 17 pts, CLIP 2–3, 28, CLIP unknown, 5 pts. The median number of cycles was 5.5 [1 - 12]. Treatment is ongoing in 6 pts. The main reasons for stopping treatment were progression (19 pts) and death (8 pts). Grade 3–4 toxicity: neutropenia 2 pts; febrile neutropenia 1 pt; thrombopenia 5 pts; diarrhea 8 pts; vomiting 2 pts; mucositis 1 pt; sensitive neuropathy 1 pt; cardiac 1 pt. There were two toxic deaths: one due to myocardial infarction following grade 3 diarrhea and the other one due to a sepsis occuring during febrile neutropenia. Overall response (35 evaluable pts): partial response 4 pts, stable disease 24 pts. After a median follow-up of 7 months, 6-month overall survival was 55%. Conclusion: The combination of capecitabine and oxaliplatin has limited efficacy in hepatocellular carcinoma. Updated results will be presented at the meeting. Supported by an unrestricted grant from Roche. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche, sanofi-aventis Roche, sanofi-aventis Roche
Comparative Study of Histochemical Patterns in Non-Neoplastic and Neoplastic Gastric Epithelium: A Study of Japanese in Hawaii&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: G. N. Stemmermann, M.D.
Journal: JNCI Journal of the National Cancer Institute (1967)

The distribution of mucosubstances and enzymes in nonneoplastic and neoplastic gastric epithelial cells was studied in Japanese people of Hawaii. The mucosubstances of the infant's surface cells differed From those of the adult in that they stained as acid, rather than neutral, mucosubstances. This characteristic was lost by the body epithelium after that of the pyloric antrum. The fetal and neonatal pylorus contained isolated cells with the histochemical characteristics of intestinal cells. Intestinal epithelium was found in the pylorus of all patients with gastric cancer and gastric ulcer. The staining reactions of chief cells suggested that they contained a sulfomucin. Some cancer cells also showed these reactions. The enzymes and mucosubstances noted in the gastric carcinomas varied from patient to patient and even from cell to cell in the same tumor. They did not consistently resemble any one non-neoplastic gastric or intestinal epithelial cell, nor could the histochemical characteristics of a tumor be correlated with the degree of its morphologic differentiation. These studies suggest that cell regeneration after injury may proceed from a stem cell along several lines and permit the development of mature gastric and intestinal cell types and carcinoma. They also support the view that intestinal metaplasia is not an obligatory precursor of gastric cancer. This study also demonstrated that mitotic figures of gastric carcinoma are periodic acid-Schiff, periodic acid diamine, and periodic acid-phenylhydrazine-Schiff-positive. This reaction was not found in nondividing cancer nuclei or in non-neoplastic nuclei and was abolished after exposure to ribonucleas.
Thomas Linthorn Bradbeer
Authors: C. Bradbeer
Journal: BMJ (2015)

<h3>SUMMARY</h3> <i>S</i>-Acylation is a reversible protein post-translational modification mediated by Protein <i>S</i>-acyltransferases (PATs). Here, we demonstrate that three plant immune receptors P2K1 (DORN1), FLS2 and CERK1, representing three distinct families of receptor like-kinases, are <i>S</i>-acylated by <i>Arabidopsis</i> PAT5 and PAT9 on the plasma membrane (PM). Mutations in <i>Atpat5</i> and <i>Atpat9</i> resulted in an elevated plant immune response, increased phosphorylation and decreased degradation of FLS2, P2K1 and CERK1 during immune signaling. Mutation of key cysteine residues <i>S</i>-acylated in these receptors resulted in a similar phenotype as exhibited by <i>Atpat5</i>/<i>Atpat9</i> mutant plants. The data indicate that <i>S</i>-acylation also controls localization of the receptors in distinct PM nanodomains and, thereby, controls the formation of specific protein-protein interactions. Our study reveals that <i>S</i>-acylation plays a critical role in mediating spatiotemporal dynamics of plant receptors within PM nanodomains, suggesting a key role for this modification in regulating the ability of plants in respond to external stimuli.
New Option for Gout
Authors: Rebecca Voelker
Journal: JAMA (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 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
Direct effects of the selective CYP17 lyase (L) inhibitor, VT-464, on the androgen receptor (AR) and its oral activity in an F876L tumor mouse xenograft model.
Authors: William R. Moore, John D. Norris, Suzanne Wardell, Joel Robert Eisner, William J. Hoekstra, Robert J. Schotzinger, Donald P. McDonnell
Journal: Journal of Clinical Oncology (2015)

263 Background: MDV3100 inhibits binding of androgens to AR and abiraterone is known to block androgen production through CYP17 inhibition; both are effective treatments for castration-resistant prostate cancer (CRPC, yet cross-resistance to both agents is problematic. The AR mutations F876L and T877A increase resistance to MDV3100 (M) or abiraterone (A), respectively. A regimen resistance is likely mediated through T877A activation by stimulatory progesterone (P4), pregnenolone (P5), or prednisone. The oral, non-steroidal L-inhibitor, VT-464, in phase 2 CRPC studies without prednisone coadministration, does not increase P4 or P5. Methods: The effects of VT-464, A, and M on AR transcription activity and cell proliferation were assessed and compared using reporter assays, and their oral effects in an M-resistant (F876L) human tumor mouse model were also assessed. Results: VT-464 competitively antagonized (Schild analysis) wild-type AR (IC50 =18 µM) and its potency was not decreased by AR overexpression (VCaP IC50=7.4μM). VT-464 fully antagonized AR T877A (IC50=0.52 μM) and inhibited LNCaP cell (AR T877A mutation) proliferation (IC50=0.70 μM) with potency similar to M. In contrast to M, VT-464 fully inhibited F876L (IC50=2.5 μM). VT-464 did not activate any AR forms up to the highest concentration tested (60 μM). In vivo, greater F876L tumor inhibition was observed with oral VT-464 compared to oral M or abiraterone acetate. Conclusions: VT-464 more potently antagonized mutated AR forms associated with A or M resistance than wild-type; AR antagonism contributed to xenograft activity and appears relevant to its clinical pharmacology. Due to its high L inhibition selectivity and potent mutant AR antagonist activity, VT-464 has a suitable profile for the treatment of early- or late-stage CRPC patients. VT-464 has advanced into phase 2 studies funded by Innocrin (NCT#02012920), the NCI (NCT02130700), and PCF in M- and A-resistant populations.
Abstract 18935: Left Ventricular Remodeling Following Alcohol Septal Ablation in Patients with Hypertrophic Cardiomyopathy: Assessment by Cardiac Magnetic Resonance Imaging
Authors: Utpal N Sagar, Ernesto Salcedo, Bertron Groves, John Messenger, Robert A Quaife
Journal: Circulation (2012)

Background: Treatment of HOCM using percutaneous alcohol septal ablation (ASA) reduces left ventricular outflow tract (LVOT) gradient and symptoms. The question of whether reduced LVOT gradient translates into lower LV wall stress is still unanswered. We propose that that ASA results in decreased LVOT gradient, leading to favorable LV remodeling related to lower circumferential wall strain (CWS). This reduction in wall strain will decrease LV mass to a greater extent than the amount of myocardium involved in the infarct alone. Methods: Forty-two HOCM patients who underwent ASA between 2002-10 and had cardiac magnetic resonance (CMR) tagged imaging were included. LVOT gradients were assessed both by catheterization and echocardiography. CWS was assessed on CMR images using specialized software (HARP, Diagnosoft). LV mass and infarct size were independently determined using two separate software packages (ARGUS and Diagnosoft). Doppler echocardiography was used to evaluate both resting and peak LVOT gradients. Statistical T-test was performed for data analysis. Results: After ASA, peak LVOT gradients decreased significantly from 112.5±24.2 to 65.3±45.4 mm Hg, p &lt;0.0001. Shown in the figure is the significant reduction in mean LV circumferential strain in these patients with a mean and maximum follow-up of 8 and 24 months, respectively. There was a significant decrease in LV Mass (225.5±79.5 to 205.1±78.7 g, p&lt;0.0001). The mean LV mass post-ASA corrected for infarct size was 212.5±95 g. The mean decrease in LV mass was significantly greater than the mean infarct size (21.2±24 g vs. 13.0±10.3 g, p=0.02). Conclusion: ASA reduced LVOT gradient and resulted in reduced CWS by CMR, which resulted in favorable LV remodeling, as demonstrated by a decrease in LV mass greater than the infarct size alone.
Phase II study of intrabuccally-administered amplitude-modulated electromagnetic fields in patients with advanced hepatocellular carcinoma
Authors: F. P. Costa, A. C. de Oliveira, R. Meirelles, M. M. Machado, R. Surjan, M. Chammas, B. Bottger, D. Morgan, A. Barbault, B. Pasche
Journal: Journal of Clinical Oncology (2009)

e15573 Background: Over the past few years we have identified tumor-specific frequencies for several common forms of cancer. The goal of this study was to assess the tolerability and effectiveness of electromagnetic fields amplitude-modulated at tumor-specific frequencies and administered by means of an intrabuccal spoon-shaped probe in patients with advanced hepatocellular carcinoma (HCC). Methods: From October 2005 to July 2007, patients with advanced HCC and Child-Pugh A or B were recruited in a phase II study. Three daily 60 min outpatient treatments were administered until disease progression or death. Imaging studies were performed every eight weeks. The primary efficacy end point was progression-free survival ≥ 6 months. Secondary efficacy end points were progression-free survival and overall survival. Results: A total of 41 patients were enrolled, 17 had Child-Pugh A, 20 Child-Pugh B disease. The median age was 64.0 years. Seventeen patients (34.1%) were progression-free for more than 6 months. Median progression-free and overall survivals were 4.8 months (95% CI 2.3–6.0) and 6.9 months (95 CI 4.8–11.1). As of December 2008, four patients are alive and two patients, who are still undergoing therapy, remain progression-free for 30.4 and 30.7 months, respectively. Four patients had partial response (9.8%) and sixteen had stable disease for at least 12 weeks (39.0%) according to the RECIST criteria resulting in 48.8% disease control. All responses were confirmed by independent review. There were no NCI grade 2, 3 or 4 toxicities. One patient developed grade 1 mucositis and one patient grade 1 fatigue. Conclusions: In patients with advanced HCC and impaired hepatic function, treatment with amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of anti-tumor effects, which are long-lasting in some patients. No significant financial relationships to disclose.
Decision on folic acid fortification in Europe must consider both risks and benefits
Authors: A David Smith, Helga Refsum, Jacob Selhub, Irwin H Rosenberg
Journal: BMJ (2016)

We are worried by the following statement in a recent editorial on the safety of folic acid fortification: “No important adverse effects have been identified to date, probably because a modest level of fortification has proved very effective in preventing these devastating birth defects.”1 It is unusual in medicine to claim that a treatment is safe just because it is effective in treating or preventing one condition—objective evidence is needed on overall safety and the side effect profile in all people exposed to the “treatment,” not only those who benefit. It seems that WHO also has not fully assessed the possible harmful effects of folic acid because its guideline on folate and neural tube defects (NTDs) states: “high folic acid intake has not reliably been shown to be associated with negative health effects.”2

The editorial’s claim that half of all NTDs could be prevented by mandatory fortification in Europe is misleading, because the effectiveness of fortification depends on the baseline prevalence of NTDs, …
Erratum to “Dermal delivery of HSP47 siRNA with NOX4-modulating mesoporous silica-based nanoparticles for treating fibrosis” [Biomaterials 66 (2015) 41–52]
Authors: Jingga Morry, Worapol Ngamcherdtrakul, Shenda Gu, Shaun M. Goodyear, David J. Castro, Moataz M. Reda, Thanapon Sangvanich, Wassana Yantasee
Journal: Biomaterials (2015)
Dactinomycin in <i>NPM1</i>-Mutated Acute Myeloid Leukemia
Authors: Brunangelo Falini, Lorenzo Brunetti, Maria Paola Martelli
Journal: New England Journal of Medicine (2015)

Dactinomycin is an old drug with activity in some childhood cancers; it acts as an inhibitor of RNA polymerase I. Its activity in acute myeloid leukemia has not been thoroughly examined. However, it has induced remissions in some patients with treatment-refractory disease.
Secondary Amenorrhoea after Total Body Irradiation in Pre-Puberty
Authors: A Albanese, A D Leiper, J Pritchard, R Stanhope
Journal: Journal of the Royal Society of Medicine (1996)

Bone marrow transplant (BMT) has been used as part of the overall treatment of refractory malignant diseases. High dose cyclophosphamide and total body irradiation (TBI) are frequently used as conditioning for BMT. Initial regimens included a single fraction of TBI, with doses varying from 7.5-1O Gy, but this was associated with a high incidence of late sequelae including multiple endocrinopathies 1 . A fractionated irradiation course over 3-4 days of a higher total dose, 12-15 Gy, of TBI is now used 1,2 . Successfully treated patients with childhood cancer have an increased risk, of developing second tumours. We describe a patient successfully treated for AML who developed multiple endocrine dysfunction and a second benign ovarian tumour.
Phase I/II trial of bevacizumab plus erlotinib for patients with recurrent non-small cell lung cancer: Correlation of treatment response with mutations of the EGFR tyrosine kinase gene
Authors: A. S. Tsao, R. Herbst, A. Sandler, S. Seshagiri, I. Wistuba, T. Henderson, D. Ramies, A. Goddard, D. Johnson, D. Eberhard
Journal: Journal of Clinical Oncology (2005)

7092 Background: Bevacizumab (Avastin) is a recombinant, humanized anti-VEGF monoclonal antibody. Erlotinib (Tarceva) is a potent, reversible, selective HER1/EGFR tyrosine-kinase (TK) inhibitor. Preclinical studies have shown that a combination of anti-VEGF and anti-HER1/EGFR therapies has at least an additive effect. We previously reported results of a phase I/II trial in which a combination of bevacizumab and erlotinib was given to 40 patients (pts) with advanced refractory NSCLC; the response rate was 20% and the median survival was 12.6 months. Given recent evidence of a somatic mutation in the gene encoding the EGFR TK domain, we analyzed available archival tissue from our study for the presence of this mutation. Methods: EGFR exons 18–21 and 23 were sequenced in tumors from 9 pts. Outcomes were correlated with EGFR mutations. Results: By RECIST criteria, the best treatment responses were 3 pts with partial responses (PR), 3 with stable disease, and 3 with progressive disease. Baseline characteristics for the PR pts are summarized in the table. An EGFR TK mutation in exon 20 (P772 H773insNS; H773Y) was found in 1 tumor. Conclusions: Although a high degree of correlation between response to TK inhibitor therapy and the EGFR TK mutation has been noted, we have thus far identified the mutation in only 1 of 3 tumors. Although these results are preliminary, they suggest that the combination of bevacizumab and erlotinib may provide benefit in a broader population than each agent individually. A 3-arm phase II trial of bevacizumab plus erlotinib and bevacizumab plus docetaxel vs docetaxel plus bevacizumab or placebo is currently underway. We plan to examine archival tissue from this study to establish the prognostic/predictive value of the EGFR TK mutation for combination therapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Genentech Genentech Genentech
Epicutaneous immunization with ovalbumin and CpG induces TH1/TH17 cytokines, which regulate IgE and IgG2a production
Authors: Monika Majewska-Szczepanik, Philip W. Askenase, Francis M. Lobo, Katarzyna Marcińska, Li Wen, Marian Szczepanik
Journal: Journal of Allergy and Clinical Immunology (2016)