tbuckley/cabot-search huggingface dataset:
Abstract 357: Intra-placental gene transfer of Insulin Like Growth Factor 1 Reprograms Altered Myocardial Gene Expression In Growth Restricted Mouse Model with Cardiac Dysfunction
Authors: khaled R omar, Tarek Alsaeid, Charles Klanke, Ahmed Lababidi, Mounira Habli
Journal: Circulation Research (2014)

Background: Intrauterine growth restriction (IUGR), defined as birth weight &lt;10% for gestational age, is a risk factor for adult onset cardiovascular disease. We demonstrated that Intraplacental gene transfer of adenoviral insulin growth factor1 (Ad IGF1) rescues IUGR induced cardiac dysfunction in a surgical IUGR mouse model. The underlying molecular mechanism is unknown. We hypothesize that Ad IGF1 reprograms altered gene expression involved in collagen deposition in myocardium (Col1A1, CTGF, SRF, OPN, TGFβ) Method: Laparotomy was performed on pregnant C57 mice at embryonic day 18 and pups were divided into 3 groups. Control: Sham operated; IUGR: by ligation of a uterine artery branch; IUGR+IGF1: injection of Ad IGF1 after ligation. Pups were delivered and followed up with cross-sectional (2D) and Doppler transthoracic echocardiography until 36 week. Hearts were collected and RNA extracted for gene expression analysis by qPCR at 36 week. Data were analyzed using ANOVA Result: At week 36, IUGR mice showed significantly reduced EF (41 ± 6 vs 53 ± 7 vs 57 ± 9) compared to SHAM &amp; IUGR+IGF1 (Fig A). IUGR showed significantly increased LVID;d (3.8 ± 0.3 vs 3.1± 0.49 vs 2.9 ± 0.4) as compared to SHAM &amp; IUGR+IGF1 (Fig B). IUGR hearts demonstrated significantly increased CTGF (1.7± 0.6 vs 0.9 ± 0.3 vs 0.8 ± 0.2), and Col1A1 (2.4 ± 0.2 vs. 1.6 ± 0.4 vs 1.4 ± 0.5), as compared to SHAM &amp; IUGR+IGF1(Fig C). No differences were detected in the other genes Conclusion: AdIGF1 gene transfer rescues IUGR induced cardiac dysfunction and reprograms myocardial gene expression of CTGF&amp;COL1A1. These changes may represent a potential epigenetic regulation that reprograms the fetus and attenuates the risk of adult onset CVD
Treatment of poor-risk metastatic renal carcinoma patients with combination gemcitabine, capecitabine, and bevacizumab at a tertiary cancer center
Authors: L. Miller, L. S. Lal, N. M. Tannir, S. DaCosta Byfield, B. Atkinson, C. Feng, J. K. Lau, L. Yin, E. Jonasch
Journal: Journal of Clinical Oncology (2009)

e16112 Background: Treatment of poor risk metastatic renal carcinoma (mRCC) is challenging, and empiric combinations may be attempted in practice once conventional therapies fail. These combinations may lead to formal clinical trials. Evaluation of mRCC patients given an empiric combination of gemcitabine (gem) capecitabine (cap), and bevacizumab (bev) at a tertiary care center was performed. Methods: After obtaining IRB approval, non investigational use of gem in combination with cap and bev in mRCC patients was identified using institutional databases. Collected data included demographics, previous therapies, number of metastatic sites, MSKCC risk stratification variables, prior nephrectomy status, drug therapy duration, and progression-free survival (PFS). Descriptive statistics were employed for data analysis. Results: Thirty-six patients were included in the analysis, with a median age of 55.5 years. Seventeen patients (47%) had previously received a tyrosine kinase inhibitor (TKI). Twenty-two patients (61%) had clear cell histology, 13 patients (36%) had sarcomatoid features, 20 patients (56%) had undergone previous nephrectomy, 20 patients (56%) had four or more sites of metastasis and 27 patients (75%) were diagnosed within 1 year of therapy. Initial treatment consisted of gem (908.61 mg/m 2 ) every 2 weeks, cap (2.75 grams/day), and bev (828.82 mg) every 2 weeks. The median PFS for the study population was 5.83 months. The subset of TKI patients had a median PFS of 5.4 months. Therapy was relatively well tolerated with only 3 patients discontinuing one or more of the drugs due to adverse reactions. Thirteen of the patients started a TKI post discontinuation of the triple therapy. Conclusions: The triple therapy combination in this retrospective evaluation provides promising efficacy and acceptable tolerability in patients with poor prognosis mRCC. Based on these observations, a phase II is now underway assessing gemcitabine, capecitabine and becacizumab in patients with sarcomatoid RCC. [Table: see text]
Osteoarthrosis and Sport
Authors: I D Adams
Journal: Journal of the Royal Society of Medicine (1979)

SUMMARY   The many possible predisposing factors in sport and personal memory of a disabled ex-athlete ensure the thought of a firm connection between sport and osteoarthrosis. A superficial review of the available literature appears to support this view.  The capacity of a ‘normal’ joint to withstand large stresses is extremely great and there is no definite evidence that wear and tear or trauma alone, without an alteration in joint mechanics, causes the development of osteoarthrosis. The early correction of any, even the most minor, biomechanical fault is particularly important in sport as the hard use to which an athlete puts his joints makes the development of osteoarthrosis most likely.  Prevention of osteoarthrosis must be considered in the sports context where adequate treatment, discouragement of an athlete continuing to play whilst injured, advice on change to a less demanding sport or total exclusion must be considered. The simple requirement of complete rehabilitation with more exacting criteria of recovery should be stressed. The one case of severe osteoarthrosis reported in the personal series was associated with gross ligamentous laxity in both knees. He sustained a torn meniscus and anterior cruciate ligament, spent six weeks in plaster and played a competitive match one week later. There is no way in which that footballer could have been ready to play.  The reported series on osteoarthrosis in sportsmen and review of the literature on various bone changes suggest that it is doubtful if the diagnosis of osteoarthrosis should be made on the basis of minor variations from normal which may be an adaptation to the demands placed upon the tissues rather than be a degenerative process.  I would suggest that osteoarthrosis is not common in sportsmen and that the commonly used criteria for the diagnosis of early osteoarthrosis be applied with caution to subjects in whom there is a history of prolonged strenuous sporting activity.
Elderly CML Patients On Early Applied High Dose Imatinib Achieve Molecular Remissions As Fast As Younger Patients In Contrast To Patients On Standard Dose Imatinib: A Subanalysis Of The German CML-Study IV
Authors: Ulrike Proetel, Nadine Pletsch, Michael Lauseker, Lida Kalmanti, Annette Schreiber, Martin C. Müller, Benjamin Hanfstein, Stefan W. Krause, Dominik Heim, Gabriela M. Baerlocher, Wolf-Karsten Hofmann, Elisabeth Lange, Hermann Einsele, Martin Wernli, Stephan Kremers, Rudolf Schlag, Lothar Müller, Matthias Hänel, Hartmut Link, Bernd Hertenstein, Markus Pfirrmann, Andreas Hochhaus, Joerg Hasford, Rüdiger Hehlmann, Susanne Saussele
Journal: Blood (2013)
Prolonged disease-free survival after high-dose sequential chemo-radiotherapy and haemopoietic autologous transplantation in poor prognosis Hodgkin's disease
Authors: A.M. Gianni, S. Siena, M. Bregni, F. Lombardi, L. Gandola, P. Valagussa, G. Bonadonna
Journal: Annals of Oncology (1991)
Prognostic Value of Longitudinal Strain of Right Ventricle in Patients With Stable Coronary Artery Disease
Authors: Wei-Ting Chang, Wei-Chuan Tsai, Yen-Wen Liu, Cheng-Han Lee, Ping-Yen Liu, Ju-Yi Chen, Yi-Heng Li, Liang-Miin Tsai
Journal: Circulation (2013)
Metastatic colorectal cancer (mCRC): Recent patterns of chemotherapy and monoclonal antibody (MoAb) therapy in clinical practice
Authors: G. P. Hess, P. F. Wang, D. Quach, B. Barber
Journal: Journal of Clinical Oncology (2009)

4120 Background: New systemic chemotherapies, particularly the MoAbs, bevacizumab (BMab), cetuximab (CMab), and panitumumab (PMab) have advanced therapy for mCRC. However, the optimal combination and sequencing of these and other chemotherapies are not established, and little is known about their patterns of use in clinical practice. We examined the frequency, patterns of use, and dosing changes of MoAbs across lines of therapy. Methods: The dataset consists of Varian and Impac electronic medical records for 304,654 cancer patients from 91 practice sites across 19 states. Inclusion/exclusion criteria were applied: ≥18 years old, newly diagnosed with mCRC or developed metastases during 1/1/2004 - 1/31/2008, and could be observed ≥3 months beyond their dates of metastases. Patients on a clinical trial at any time during the analysis were excluded. Results: The study sample included 1,655 patients (52% male, mean age 61.9 years). 11% received all five therapeutic classes: fluoropyrimidines, irinotecan, oxaliplatin, EGFR MoAbs (PMab and CMab), and VEGF MoAb (BMab). 19% received at least 3 treatment classes. BMab, fluorouracil, leucovorin, oxaliplatin (BMab+FOLFOX) was the most frequently observed 1 st line regimen in 26% of patients. Across the study period more patients received BMab than PMab or CMab (69%, 7%, and 22%, respectively, for any exposure); 55% received BMab for 1 st -line therapy. A BMab dose increase within a line of therapy was recorded in 22% of patients for 1 st -line, 21% for 2 nd -line, and 15% for 3 rd -line. Among patients who continued BMab from 1 st to 2 nd line (N=239) and 2 nd to 3 rd line (N=88), 44% and 39%, respectively had a dose increase (mean/month 890mg to 1078mg, and 844mg to 1053mg). Conclusions: The most frequent 1 st -line chemo regimen was FOLFOX. BMab was the most commonly administrated MoAb. Trends toward dose-escalation of BMab were observed both within lines of therapy and across lines of therapy. [Table: see text]
Combined Assessment of Phospholipase A2 Receptor Autoantibodies and Glomerular Deposits in Membranous Nephropathy
Authors: Hua-Zhang Qin, Ming-Chao Zhang, Wei-Bo Le, Qiang Ren, Da-Cheng Chen, Cai-Hong Zeng, Lei Liu, Ke Zuo, Feng Xu, Zhi-Hong Liu
Journal: Journal of the American Society of Nephrology (2016)

Serum phospholipase A2 receptor antibodies (SAbs) and glomerular phospholipase A2 receptor antigen (GAg) deposits have been observed in idiopathic membranous nephropathy (IMN). However, the clinical application of these two biomarkers, particularly GAg deposition, needs to be further evaluated. We measured SAb concentration by ELISA and GAg deposition by immunofluorescence in 572 patients with biopsy-proven IMN. Overall, 68.5% of patients (392 of 572) had detectable SAb (SAb+), and 98.7% of patients who were SAb+ (387 of 392) and 70.6% of patients who were SAb- (127 of 180) had GAg deposition (GAg+). Compared with patients who were SAb-/GAg+, patients who were SAb+/GAg+ exhibited higher levels of proteinuria (P<0.001) and a lower chance of proteinuria remission (P<0.001). In 52 patients who underwent repeat biopsies, patients who did not achieve remission had a higher SAb+ rate on the first biopsy than patients who went into remission (P=0.001). Furthermore, SAb+ levels persisted in patients who did not achieve remission but significantly decreased in patients who achieved remission by the second biopsy. Patients who did not achieve remission also had a higher GAg+ rate on the first biopsy than patients who achieved remission (P<0.01). Sustained GAg+ deposits correlated with disease relapse. In conclusion, combining the measurements of SAb levels and detection of GAg deposition may provide additional information regarding diagnoses, treatment response, and disease relapse in patients with IMN.
A randomized multicenter phase III study comparing weekly versus every 3 week carboplatin (C) plus paclitaxel (P) in patients with advanced ovarian cancer (AOC): Multicentre Italian Trials in Ovarian Cancer (MITO-7)– European Network of Gynaecological Oncological Trial Groups (ENGOT-ov-10)–Gynecologic Cancer Intergroup (GCIG ) trial.
Authors: Sandro Pignata, Giovanni Scambia, Rossella Lauria, Francesco Raspagliesi, Pierluigi Benedetti Panici, Gennaro Cormio, Dionyssios Katsaros, Roberto Sorio, Giovanna Cavazzini, Gabriella Ferrandina, Enrico Breda, Viviana Murgia, Cosimo Sacco, Nuria Maria Asensio Sierra, Carmela Pisano, Vanda Salutari, Beatrice E. Weber, Eric Pujade-Lauraine, Ciro Gallo, Francesco Perrone
Journal: Journal of Clinical Oncology (2013)

LBA5501 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Saturday, June 1, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Reproducibility of Results in “Near-Replicate” Carcinogenesis Bioassays&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: L S Gold, C Wright, L Bernstein, M deVeciana
Journal: JNCI Journal of the National Cancer Institute (1987)

Reproducibility of results was examined in 70 “near-replicate” comparisons consisting of 2 or more long-term carcinogenesis bioassays of the same chemical administered by the same route and using the same sex and strain of rodent. Overall, there was good reproducibility of positivity, target site, and carcinogenic potency in hamsters, mice, and rats. The published authors' opinions about whether the test was positive disagreed in only 9 of the 70 comparisons. Among the 35 comparisons in which all tests of the chemical were positive, 33 of the near-replicates had at least 1 identical target site. The carcinogenic potency values estimated from near-replicate tests in these 35 comparisons were within a factor of 2 of each other in 40% of the comparisons, within a factor of 5 in 80%, and within a factor of 10 in 90%. For the few cases in which the carcinogenic response was not reproduced, analyses suggest two explanations: In mice the discrepant cases tended to have shorter experiment times than average; in both rats and mice the discrepant results tended to be tests of weakly active compounds.
Diabetes Mellitus and Prevention of Late Myocardial Infarction After Coronary Stenting in the Randomized Dual Antiplatelet Therapy Study
Authors: Ian T. Meredith, Jean-François Tanguay, Dean J. Kereiakes, Donald E. Cutlip, Robert W. Yeh, Kirk N. Garratt, David P. Lee, P. Gabriel Steg, W. Douglas Weaver, David R. Holmes, Ralph G. Brindis, Jaroslaw Trebacz, Joseph M. Massaro, Wen-Hua Hsieh, Laura Mauri
Journal: Circulation (2016)

Patients with diabetes mellitus (DM) are at high risk for recurrent ischemic events after coronary stenting. We assessed the effects of continued thienopyridine among patients with DM participating in the Dual Antiplatelet Therapy (DAPT) Study as a prespecified analysis.After coronary stent placement and 12 months treatment with open-label thienopyridine plus aspirin, 11 648 patients free of ischemic or bleeding events and who were medication compliant were randomly assigned to continued thienopyridine or placebo, in addition to aspirin, for 18 more months. After randomization, patients with DM (n=3391), in comparison with patients without DM (n=8257), had increased composite outcome of death, myocardial infarction (MI), or stroke (6.8% versus 4.3%, P<0.001), increased death (2.5% versus 1.4%, P<0.001), and MI (4.2% versus 2.6%, P<0.001). Among patients with DM, in a comparison of continued thienopyridine versus placebo, rates of stent thrombosis were 0.5% versus 1.1%, P=0.06, and rates of MI were 3.5% versus 4.8%, P=0.058; and among patients without DM the rates were 0.4% versus 1.4%, P<0.001 (stent thrombosis, P interaction=0.21) and 1.6% versus 3.6%, P<0.001 (MI, P interaction=0.02). Bleeding risk with continued thienopyridine was similar among patients with or without DM (interaction P=0.61).In patients with DM, continued thienopyridine beyond 1 year after coronary stenting is associated with reduced risk of MI, although this benefit is attenuated in comparison with patients without DM.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00977938.
A Manual of the Parasitic Protozoa of Man.
Journal: JAMA (1926)

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
Intralymphatic Pollen-Specific Immunotherapy for Nasal Allergy: Clinical Efficacy and Effects on the Induction of Pollen- Specific Antibody
Authors: Tetsuya Terada, Syuji Omura, Yusuke Kikuoka, Megumi Yoshida, Manabu Suzuki, Shinpei Ichihara, Takahiro Ichihara, Takaki Inui, Ryo Kawata
Journal: Journal of Allergy and Clinical Immunology (2016)
Proteasomal Inhibition by Ixazomib Induces CHK1 and MYC-Dependent Cell Death in T-cell and Hodgkin Lymphoma
Authors: Dashnamoorthy Ravi, Afshin Beheshti, Nasséra Abermil, Frank Passero, Jaya Sharma, Michael Coyle, Athena Kritharis, Irawati Kandela, Lynn Hlatky, Michail V. Sitkovsky, Andrew Mazar, Ronald B. Gartenhaus, Andrew M. Evens
Journal: Cancer Research (2016)

Proteasome-regulated NF-κB has been shown to be important for cell survival in T-cell lymphoma and Hodgkin lymphoma models. Several new small-molecule proteasome inhibitors are under various stages of active preclinical and clinical development. We completed a comprehensive preclinical examination of the efficacy and associated biologic effects of a second-generation proteasome inhibitor, ixazomib, in T-cell lymphoma and Hodgkin lymphoma cells and in vivo SCID mouse models. We demonstrated that ixazomib induced potent cell death in all cell lines at clinically achievable concentrations. In addition, it significantly inhibited tumor growth and improved survival in T-cell lymphoma and Hodgkin lymphoma human lymphoma xenograft models. Through global transcriptome analyses, proteasomal inhibition showed conserved overlap in downregulation of cell cycle, chromatin modification, and DNA repair processes in ixazomib-sensitive lymphoma cells. The predicted activity for tumor suppressors and oncogenes, the impact on "hallmarks of cancer," and the analysis of key significant genes from global transcriptome analysis for ixazomib strongly favored tumor inhibition via downregulation of MYC and CHK1, its target genes. Furthermore, in ixazomib-treated lymphoma cells, we identified that CHK1 was involved in the regulation of MYC expression through chromatin modification involving histone H3 acetylation via chromatin immunoprecipitation. Finally, using pharmacologic and RNA silencing of CHK1 or the associated MYC-related mechanism, we demonstrated synergistic cell death in combination with antiproteasome therapy. Altogether, ixazomib significantly downregulates MYC and induces potent cell death in T-cell lymphoma and Hodgkin lymphoma, and we identified that combinatorial therapy with anti-CHK1 treatment represents a rational and novel therapeutic approach. Cancer Res; 76(11); 3319-31. ©2016 AACR.
Inhibiting Drivers of Non-mutational Drug Tolerance Is a Salvage Strategy for Targeted Melanoma Therapy
Authors: Michael P. Smith, Holly Brunton, Emily J. Rowling, Jennifer Ferguson, Imanol Arozarena, Zsofia Miskolczi, Jessica L. Lee, Maria R. Girotti, Richard Marais, Mitchell P. Levesque, Reinhard Dummer, Dennie T. Frederick, Keith T. Flaherty, Zachary A. Cooper, Jennifer A. Wargo, Claudia Wellbrock
Journal: Cancer Cell (2016)

Once melanomas have progressed with acquired resistance to mitogen-activated protein kinase (MAPK)-targeted therapy, mutational heterogeneity presents a major challenge. We therefore examined the therapy phase before acquired resistance had developed and discovered the melanoma survival oncogene MITF as a driver of an early non-mutational and reversible drug-tolerance state, which is induced by PAX3-mediated upregulation of MITF. A drug-repositioning screen identified the HIV1-protease inhibitor nelfinavir as potent suppressor of PAX3 and MITF expression. Nelfinavir profoundly sensitizes BRAF and NRAS mutant melanoma cells to MAPK-pathway inhibitors. Moreover, nelfinavir is effective in BRAF and NRAS mutant melanoma cells isolated from patients progressed on MAPK inhibitor (MAPKi) therapy and in BRAF/NRAS/PTEN mutant tumors. We demonstrate that inhibiting a driver of MAPKi-induced drug tolerance could improve current approaches of targeted melanoma therapy.
Bovine spongiform encephalopathy
Authors: M. Cullen, M. Bellis, K. Tocque
Journal: BMJ (1996)

Laparoscopy with local anaesthesia enables targeted tissue biopsy specimens to be obtained from the peritoneum, thus allowing a rapid diagnosis, while other conditions, such as peritoneal lymphoma and carcinomatosis, are excluded.Laparotomy, which is associated with a mortality of 3-12% in patients with tuberculous peritonitis,4 may also be avoided.If multiple pieces of matted bowel are found during the procedure and are of concern to the operator then a biopsy specimen need not be obtained, although even then the procedure may provide useful information.4Because of the advantages of laparoscopy, we believe that Hodgson's view is overcautious and that, if there are no contraindi- cations, the investigation should be considered early in management.