tbuckley/cabot-search huggingface dataset:
Malignant melanoma in childhood: clinical course and response to chemotherapy.
Authors: F A Hayes, A A Green
Journal: Journal of Clinical Oncology (1984)

Malignant melanoma is uncommon in patients less than 20 years of age, and little is known about the response to chemotherapy in this age group. We report here a series of 18 children, of whom ten with metastatic disease were treated with cyclophosphamide, vincristine, and dactinomycin. Only two of nine evaluable patients failed to show an objective response to therapy. Five of ten patients treated are alive and free of tumor 12 to 80 months from the start of chemotherapy. Three have been in remission for more than five years. Results suggest that melanoma in this age group may be more responsive to chemotherapy than melanoma in adult patients and that a trial of this therapy in a larger number of children with evaluable disease is warranted.
Important differences exist between second generation antidepressants
Authors: J. J Ferguson, P. J Smith, M. G V Jenkins
Journal: BMJ (1995)

patients with cancers before the skin cancer were retained in the analysis or not (Frisch et al, unpublished data).This argues against Sasieni and Bataille's proposal.By no means do we consider our observations to be evidence of a causal role for ultraviolet light in the pathogenesis of non-Hodgkin's lymphoma.Sasieni and Bataille and Robert Newton suggest that immunosuppression rather, than ultraviolet light explains our findings.We do not disagree with this.As we suggested in our paper, one of the possible mechanisms that link skin cancers and non-Hodgkin's lymphoma is the local and systemic immunological dysregulation caused by ultraviolet light.34The considerable indirect support for such an association5 needs further consideration.
Sequential co-delivery of miR-21 inhibitor followed by burst release doxorubicin using NIR-responsive hollow gold nanoparticle to enhance anticancer efficacy
Authors: Yu Ren, Ruirui Wang, Lizhang Gao, Ke Li, Xuan Zhou, Hua Guo, Chaoyong Liu, Donglin Han, Jianguo Tian, Qing Ye, Ye Tony Hu, Duxin Sun, Xubo Yuan, Ning Zhang
Journal: Journal of Controlled Release (2016)
O-013 A global risk gene score predicts early and late tumor recurrence after resection of hepatocellular carcinoma
Authors: J. Dekervel, D. Popovic, H. van Malenstein, P. Windmolders, L. Libbrecht, A. Bulle, B. de Moor, F. Nevens, E. Van Cutsem, C. Verslype, J. van Pelt
Journal: Annals of Oncology (2015)
Physical activity: what is already being done and how we can avert 1 million deaths annually in future
Authors: Carl Johan Sundberg
Journal: British Journal of Sports Medicine (2016)

Physical inactivity is a major and increasing contributor to poor health and premature death across the world. People can increase their health-enhancing physical activity (PA) levels through a combination of personal efforts and a supportive and conducive environment. Healthcare has a key role to play, but needs more knowledge, organisation and incentives to fulfil its potential.

Physical inactivity caused over 5.3 million deaths, or 9% of premature mortality, worldwide in 2008.1 If physical inactivity were decreased by 25%, more than 1 million annual deaths could be averted. The health improvement of enhanced PA is largely due to the lower risk of cardiovascular disease, metabolic disease and cancer. Equally importantly, increased PA also improves quality of life and helps to prevent or treat mental health disorders.

A decreasing number of people across the world reach the PA levels recommended by …
Tiotropium add-on therapy in adolescents with moderate asthma: A 1-year randomized controlled trial
Authors: Eckard Hamelmann, Eric D. Bateman, Christian Vogelberg, Stanley J. Szefler, Mark Vandewalker, Petra Moroni-Zentgraf, Mandy Avis, Anna Unseld, Michael Engel, Attilio L. Boner
Journal: Journal of Allergy and Clinical Immunology (2016)

Results from phase III clinical trials in adults and phase II clinical trials in children and adolescents demonstrate that tiotropium is an effective treatment when added to inhaled corticosteroid (ICS) maintenance therapy.We sought to assess the efficacy and safety of once-daily tiotropium Respimat added to ICSs with or without a leukotriene receptor antagonist in a phase III trial in adolescent patients with moderate symptomatic asthma.In this 48-week, double-blind, placebo-controlled, parallel-group study, 398 patients aged 12 to 17 years were randomized to receive 5 μg (2 puffs of 2.5 μg) or 2.5 μg (2 puffs of 1.25 μg) of once-daily tiotropium or placebo (2 puffs) administered through the Respimat device every evening, each as add-on treatment to ICS background therapy, with or without a leukotriene receptor antagonist; long-acting β2-agonist therapy was not permitted during the study.Improvement in peak FEV1 within 3 hours after dosing at 24 weeks (primary end point) was statistically significant with both tiotropium doses compared with placebo: 5 μg of tiotropium, 174 mL (95% CI, 76-272 mL); 2.5 μg of tiotropium, 134 mL (95% CI, 34-234 mL). Significant improvements in trough FEV1 at week 24 (a secondary end point) were observed with the 5-μg dose only. Trends for improvement in asthma control and health-related quality of life over the 48-week treatment period were observed.Once-daily tiotropium significantly improved lung function and was safe and well tolerated when added to at least ICS maintenance therapy in adolescent patients with moderate symptomatic asthma. Larger responses were observed with the 5-μg tiotropium dose.
Long-term psychosocial effects of childhood exposure to parental problem drinking
Authors: S F Greenfield, M S Swartz, L R Landerman, L K George
Journal: American Journal of Psychiatry (1993)

The effects of childhood exposure to parental problem drinking remain unclear because of inconsistent findings and methodologic difficulties in previous studies. The authors used a large community sample to examine whether exposure to parental problem drinking in childhood was related to a greater number of psychiatric symptoms and impaired social and occupational functioning in adulthood.The study used self-report data from the Piedmont Health Survey, a project of the Epidemiologic Catchment Area program, which were collected from a stratified random sample of 2,936 adults residing in a five-county catchment area in North Carolina. The National Institute of Mental Health Diagnostic Interview Schedule was used to measure the subjects' lifetime psychiatric symptoms. Social and occupational functioning were assessed with two scales measuring social support, a scale measuring occupational prestige, and an occupational problem index. Regression analyses were used to determine whether exposure to parental problem drinking in childhood was associated with adverse psychosocial outcomes in adulthood.Adults who had been exposed to parental problem drinking in childhood were more likely to manifest psychiatric symptoms and marital instability, but they showed no difference from the rest of the sample in occupational functioning.Exposure to parental problem drinking in childhood is positively associated with specific adverse effects in adulthood even after controlling for other confounding childhood risk factors.
A Factor From Plasma-Derived Human Serum That Inhibits the Growth of the Mammary Cell Line MCF-7: Characterization and Purification&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M L Dell'Aquila, D A Pigott, D L Bonaquist, E V Gaffney
Journal: JNCI Journal of the National Cancer Institute (1984)

A protein that inhibits the replication of a malignant human mammary cell line, MCF-7, was purified to apparent homogeneity from human plasma-derived serum (PDS). Serum fractionation was accomplished by molecular sieve chromatography on Sephadex G-100 and Sephadex G-100 superfine columns. Further purification was accomplished by ion-exchange chromatography, with the use of DEAE-Sephacel followed by preparative polyacrylamide gel electrophoresis (PAGE) under nondenaturing conditions. Active fractions analyzed by sodium dodecyl sulfate (SDS)-PAGE showed one band with an apparent molecular weight of 53,000. Assays for the stability of those PDS fractions with the greatest growth-inhibitory activity and specificity for MCF-7 cells revealed that activity was retained during incubation at pH 2-10. Exposure to 6 M urea also had no effect on inhibitory activity. The activity was significantly reduced by incubation at 70 degrees C for 1 hour, exposure to 0.1% SDS, and treatment with chymotrypsin. Isoelectrofocusing showed two isoelectric points, 5.1 and 6.8.
Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper
Authors: S. Champiat, O. Lambotte, E. Barreau, R. Belkhir, A. Berdelou, F. Carbonnel, C. Cauquil, P. Chanson, M. Collins, A. Durrbach, S. Ederhy, S. Feuillet, H. François, J. Lazarovici, J. Le Pavec, E. De Martin, C. Mateus, J.-M. Michot, D. Samuel, J.-C. Soria, C. Robert, A. Eggermont, A. Marabelle
Journal: Annals of Oncology (2015)
Role Of Base Excision Repair Associated AP Nuclease Activity In The Induction Of Homologous Recombination Repair Pathway and Survival Of MM Cells Following DNA Damage
Authors: Subodh Kumar, Jagannath Pal, Jialan Shi, Puru Nanjappa, Maria Gkotzamanidou, Masood Shammas, Nikhil Munshi
Journal: Blood (2013)
Surface Glycopeptide Change Triggered by Contact Between Normal Cells From Rat Liver and Their Simian Virus 40-Transformed Cells From the Same Virus
Authors: M Yokota, I Kato, K Onodera, T Kadosaka, Y Aoi
Journal: JNCI Journal of the National Cancer Institute (1979)

Surface glycopeptide changes triggered by mixed culture of normal cells from rat liver cell line WIRL-3 and simian virus 40-transformed cells from the same line were studied. In addition, biologic responses of the normal cells and the transformed cells to three kinds of surface glycopeptides derived from the normal cells, the transformed cells, and these cells in mixed culture were investigated. Surface glycopeptide derived from the mixed culture showed a quantitative increase and a qualitative change in the glycopeptide structure, not detected in the surface glycopeptide of normal cells and transformed cells cultured separately. The surface glycopeptide changes observed in the mixed culture were mainly ascribable to normal cells responding to transformed cells, and a surface glycopeptide change in normal cells induced a qualitative surface glycopeptide change in transformed cells. Differences in biologic response of normal cells and transformed cells to the above three surface glycopeptides were investigated with the use of inhibition of [3H]thymidine uptake of the cells by the three different surface glycopeptide preparations. The inhibition rates of uptake in normal cells were 30% by all three surface glycopeptides (200 microgram/ml culture medium); inhibition rates in transformed cells were 65% by mixed-culture surface glycopeptide, 50% by normal cell-surface glycopeptide, and 35% by transformed cell-surface glycopeptide.
Does Baseline Absolute Neutrophil-To-Lymphocyte Ratio (Nlr) Correlate with Pathological Complete Response (Pcr) in Neoadjuvant Breast Cancer (Bc)?
Authors: N. Coleman, F. Mohamad Rom, A. Brennan, K. Bennett, A.K. Jayaram, M.J. Kennedy
Journal: Annals of Oncology (2014)
Abstract 16639: Sex Differences in Progression of Aortic Stenosis and Cardiovascular Outcome. A SEAS Substudy
Authors: Dana Cramariuc, Barbara P Rogge, Mai Tone Lønnebakken, Kurt Boman, Edda Bahlmann, Christa Gohlke-Bärwolf, John B Chambers, Terje R Pedersen, Eva Gerdts
Journal: Circulation (2013)

Background: Women with aortic stenosis (AS) have better left ventricular (LV) systolic function than men, as well as more concentric LV geometry in advanced disease stages. Sex differences in LV adaptation and prognosis during progression of AS have been less explored. Methods: Doppler echocardiography and cardiovascular events were recorded during a median follow-up of 4.3 years in 979 men and 632 women aged 28-86 (mean 67±10) years participating in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study. LV geometry was assessed by LV mass/height2.7 and relative wall thickness, thus categorizing patients with normal LV mass/height2.7 as having normal geometry or concentric remodeling, and patients with LV hypertrophy as having eccentric or concentric hypertrophy. Study outcomes were AS-related events and ischemic cardiovascular events, as well as total mortality. Results: Women and men had similar progression of AS (annual reduction in aortic valve area index of 0.02cm2/m2) during follow-up. Prevalenc...
Phase I/II study of the combination of 5-azacytidine(5-AC), all-trans retinoic acid (ATRA) and valproic Acid (VPA) in patients with myelodysplastic syndrome (MDS) and leukemia
Authors: A. O. Soriano, H. Yang, S. Verstovsek, W. Wierda, C. Koller, Z. Estrov, S. Ouzounian, H. Kantarjian, J. Issa, G. Garcia-Manero
Journal: Journal of Clinical Oncology (2006)

6563 Background: The combination of a hypomethylating agent with a histone deacetylase inhibitor (HDACI) has synergistic activity. The combination of ATRA with either a hypomethylating agent or a HDACI restores ATRA sensitivity in resistant cells. The combination of VPA and ATRA has activity in patients with MDS. Based on this, we developed a phase I/II study of the combination of 5-AC, VPA and ATRA for patients with MDS or AML. Methods: The dose of 5-AC was fixed: 75 mg/m2 sq daily × 7. ATRA dose was: 45 mg/m2 orally daily × 5 starting on day 3. Three dose levels of VPA were studied: 50, 62.5 and 75 mg/kg orally daily × 7. The phase I portion of the study followed a 3+3 design. Patients with high risk MDS (≥10% blasts) or relapsed/refractory AML and patients older than 60 years with untreated disease and adequate renal, hepatic functions and performance status were eligible. Results: Nineteen patients were registered and 16 were evaluable. Median age was 68 years (5–78). All, but one patient with MDS had AML. Median number of prior therapies was 2 (0–5). Twelve patients (75%) had abnormal cytogenetics. At a VPA dose of 50 mg/kg, 1 of 6 patients developed grade 3 confusion; at 62.5 mg/kg, 0 of 6, and at 75 mg/kg, 2 of 6. One patient had a CR, 2 a complete marrow response (marrow blasts &lt; 5%), and 1 a CRP (same criteria as of CR but without complete platelet recovery), overall response rate was 30% of 13 patients that have completed 1 course. All 4 responses occurred during the first cycle. The CR occurred at a VPA dose of 75mg/kg. The other 3 responses occurred at 62.5 and 75 mg/kg. One out of 2 previously untreated older patients achieved a CR. To assess the hypomethylating effect of 5-AC, we used the LINE assay. Median LINE methylation pretreatment was 62.5% (57–67%), declined to 58% by day 7 and returned to baseline by day 0 of next cycle (p&lt;0.001). Analysis of histone acetylation and gene re-expression are ongoing. Conclusions: The combination of 5-AC with VPA and ATRA is well tolerated. The dose of 62.5 mg/kg daily × 7 is currently being expanded. Significant clinical activity was observed and the effects are potentially mediated by the synergistic action of the combination including induction of DNA hypomethylation and histone acetylation. [Table: see text]
THU0426 Ultrasound Identifies Additional Erosive Disease in Patients with Early Psoriatic Arthritis – Results from the Ticopa Study:
Authors: L.C. Coates, J.E. Freeston, J. Nam, P.G. Conaghan, P.S. Helliwell
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Previous studies have shown that around 25% of patients with psoriatic arthritis (PsA) have radiographic erosions at presentation but the level of erosive disease is usually very low. Previous data in established PsA has suggested a higher sensitivity for bone erosions with US compared to plain radiography. <h3>Objectives</h3> The aim of this analysis was to investigate how many early PsA patients had erosions only visible using US at presentation. <h3>Methods</h3> Within the Tight Control of Psoriatic Arthritis (TICOPA study), all patients had radiographs of the hands and feet at baseline and week 48. Patients seen in Leeds also underwent an US assessment of their most symptomatic or dominant hand assessing MCPs and PIPs at the same timepoints. The presence of erosions seen on radiographs and US were compared at an individual joint level and at a patient level. Joints with erosive changes seen only on US at baseline were checked at 48 weeks for presence of radiographic and/or ultrasound erosions. <h3>Results</h3> There were 89 patients who had US scans of the MCP and PIP joints with corresponding radiographs at baseline, the majority of whom had repeat scans at 48 weeks (n=74) contributing a total of 163 scans for analysis. In the majority of cases (81/89 91.0% of patients) there was no evidence of erosive disease on radiographs at baseline, however an additional 19 patients had erosions visible on US alone. 25 (3.5%) joints at baseline and 32 (5.6%) at 48 weeks showed erosive disease spread across the MCPs and PIPs (see table). At follow up, none of these erosions were visible on radiographs, with 13 of 23 joints re-scanned still showing erosions on US. <h3>Conclusions</h3> There was a low frequency of erosive disease seen in the TICOPA study with little progression over the 48 week study period. Of those with normal radiographs, 23% of patients had additional erosions in the fingers visualised on US, with less erosions identified in the middle MCP joints where US access can be limited. <h3>Disclosure of Interest</h3> L. Coates Grant/research support from: Pfizer, Consultant for: Pfizer, J. Freeston Grant/research support from: Pfizer, J. Nam Grant/research support from: Pfizer, P. Conaghan Grant/research support from: Pfizer, Consultant for: Pfizer, P. Helliwell Grant/research support from: Pfizer, Consultant for: Pfizer
MAP Kinase Inhibition Promotes T Cell and Anti-tumor Activity in Combination with PD-L1 Checkpoint Blockade
Authors: Peter J.R. Ebert, Jeanne Cheung, Yagai Yang, Erin McNamara, Rebecca Hong, Marina Moskalenko, Stephen E. Gould, Heather Maecker, Bryan A. Irving, Jeong M. Kim, Marcia Belvin, Ira Mellman
Journal: Immunity (2016)
Interleukin-30 (IL27p28) alleviates experimental sepsis by modulating cytokine profile in NKT cells
Authors: Jun Yan, Abhisek Mitra, Jiemiao Hu, Jeffery J. Cutrera, Xueqing Xia, Thomas Doetschman, Mihai Gagea, Lopa Mishra, Shulin Li
Journal: Journal of Hepatology (2016)
Pathologic and Clinical Features Of CD30+ Post-Transplant Lymphoproliferative Disorders: A Large Retrospective Single Institutional Study
Authors: Jordan M. Schecter, Daniela Hoehn, Philip Imus, Eleonora Alma, Suzanne Lentzsch, Bachir Alobeid, Manuela Orjuela, Owen A. O'Connor, Govind Bhagat
Journal: Blood (2013)
Abstract 017: Hyperglycemia-induced Posttranscriptional Modification Of Proinflammatory Cytokine Mrna Stability Is Mediated Via Hur/PKC-delta Signaling Pathway
Authors: Suresh K Verma, Alexander R Mackie, Erin E Vaughan, Tatiana V Abramova, Raj kishore, Prasanna Krishnamurthy
Journal: Circulation Research (2013)

Patients with diabetes are predisposed to increased risk of cardiovascular diseases. Persistent interaction of infiltrating macrophages and resident fibroblasts play a critical role in cardiac fibrosis. However, the signaling mechanism is not clear. We hypothesized that macrophage ELAV1 (mRNA stabilizing protein) modulates profibrotic mediators and extracellular matrix turnover by binding to 3′UTR and regulating the mRNA stability of TGF-beta and MMP-9 in hyperglycemic conditions. Mice receiving intramyocardial injection of HuR-specific shRNA showed significant reduction in infarct size and fibrosis area. Reduced fibrosis was associated with decrease in TGF-beta and MMP-9 expression in the myocardium. Conditioned media (CM) from high glucose (HG) treated macrophages significantly increased profibrogenic response (increased mRNA expression of Col1a1, Col3a1 and fibronectin) in fibroblast cell line as compared to fibroblasts incubated with CM from low glucose (LG)-treated macrophages. Knockdown of ELAV1 in HG-treated macrophages abrogated the profibrotic effects in fibroblasts. Indirect immunofluroscence of bone marrow-derived macrophages (BMM) demonstrated that HG increases nuclear ELAV1 export to the cytoplasm. Pharmacological inhibition of Protein kinase C-delta (PKCd) blocked HG-induced ELAV1 nuclear to cytoplasmic translocation. In vitro, stable knockdown of ELAV1 in mouse macrophage cell line RAW 264.7 reduced mRNA expression of TGF-beta and MMP-9 following LPS challenge, accompanied by a marked reduction in the mRNA stability of these genes. Our study here establishes an ELAV1/TGF-beta/MMP-9/PKC-delta signaling axis in the macrophages controlling the profibrogenic responses in fibroblasts, the major contributor in the pathogenesis of fibrosis. Therefore, targeting this signaling pathway might be of therapy value for cardiac fibrosis in diabetic patients.
Oral contraceptives and myocardial infarction. (Letter to the editor)
Authors: Myhre E
Journal: BMJ (1973)

In the introduction to the article by Drs. Dorothy J. Radford and M.F.  Oliver (August 25 p. 428) references are cited to reports in which an association between oral contraception and the occurrence of myocardial infarction is claimed. 1 of the reports referred to is that by Hartveit (British medical Journal 1:  60 1965) which describes the case of a 32-year-old woman who died in Bergen Norway in 1964 apparently of the consequences of myocardial infarction. The same case has also been described by Hosteng (Tidsskrift for den Norske Laegeforening  85: 1692 1965).  References to both these reports can be found in a number of other later articles. As a result of legal proceedings directly concerned with this case I had the opportunity to study the case notes thoroughly and also to reexamine the  histological material. I subsequently came to the conclusion that this was not a case of myocardial infarction as a consequence of primary thrombosis but rather - and there were a number of positive indications to support my opinion - a case  of chronic myocarditis accompanied by coronary arteritis nueritis and pericarditis. The heart was dilated with large areas of mottled yellow color. Microscopical examination revealed pronounced and diffuse leucocyte infiltration with no  border zones including muscles vessels and nerves. A large number of scattered fibrous areas were found all of them showing leucocyte infiltration. No coagulation necrosis was found;  on the contrary the nuclei of the muscle fibers were large and prominent. In view of the foregoing I would suggest that there is no longer any justification for including the case described by Hartveit and Hosteng in lists of references on  the subject of oral contraceptives and myocardial infarction.(Full text)