tbuckley/cabot-search huggingface dataset:
972. Gene-Modified Human Glioma Cells Producing Soluble Human Plasminogen Kringle 5 Peptide Suppress Brain Tumor Progression
Authors: Sabrina R. Perri, Josephine Nalbantoglu, Borhane Annabi, Zafiro Koty, Richard Béliveau, Jacques Galipeau
Journal: Molecular Therapy (2004)

Objective: Glioblastoma multiforme is one of the most highly vascularized tumors in humans. Therefore, the development of a potent anti-angiogenic gene therapy strategy for brain cancer represents an attractive alternative to existing therapeutic interventions and circumvents the pitfalls associated with direct recombinant anti-angiogenic protein delivery. Amongst the known human angiogenic inhibitors, the fifth kringle (K5) of plasminogen has been found to enhance the angiostatic potency of angiostatin, a cleavage product of human plasminogen. We propose that the K5 domain may serve as a potent angiostatic agent on its own and that it may act as a useful therapeutic transgene within a cancer gene therapy strategy. To test this hypothesis, we have developed a K5-expressing retroviral vector and have characterized the angiostatic activity of the de novo produced K5 peptide in vitro and tested its efficacy in vivo using an orthotopic brain cancer model. Methods: To assess the endothelial cell inhibitory properties of retrovector-generated K5 peptide, the 363bp human plasminogen K5 domain cDNA was His-tagged and cloned into a bicistronic retroviral vector comprising the enhanced green fluorescent protein reporter gene. Upon transfection of K5 retrovector plasmid into 293GPG retroviral packaging cells, single clones were drug selected and characterized. Kringle 5 retroparticles were then used to transduce U87 human glioma cells, whereby single clones were isolated and characterized. Results: Southern blot analysis on K5 transduced U87 glioma cells using a GFP cDNA-specific probe suggests unrearrangement upon integration into the genome of transduced glioma cells. Anti-His immunoblot analysis on conditioned culture media collected from K5 transduced U87 glioma cells revealed a major 18kDa protein consistent with the predicted MW of soluble K5, which was capable of inhibiting HUVEC migration up to 75±3% (p<0.0005) and disrupting capillary tube formation. Upon intracerebral implantation of U87-GFP and U87-K5 glioma cells in nude mice, hematoxylin and eosin-stained brain tissue sections reveal that U87-K5 implanted mice possess significantly reduced tumor volumes as compared to the mock implanted mice 32 days post-implantation (Figure 1).
Abstract 1826: Altered expression of miRNAs in acquired trastuzumab resistance
Authors: Karen Howe, Alex J. Eustace, Giuseppe Gullo, Brigid Browne, Sinead Aherne, John Crown, Norma O'Donovan
Journal: Cancer Research (2014)

Abstract HER2 positive breast cancer accounts for approximately 20-25 % of breast cancers. Trastuzumab, a humanised monoclonal antibody, is approved for the treatment of HER2 positive breast cancer. However, patients with metastatic HER2 positive breast cancer frequently develop resistance to trastuzumab. The aim of this study is to investigate microRNAs (miRNAs) in cell line models of acquired trastuzumab resistance to identifty altered miRNAs which may be biomarkers of resistance. The trastuzumab resistant cell line, SKBR3-T was established by continuous exposure to trastuzumab (10 µg/ml) for 6 months. MiRNA extracted from SKBR3, and SKBR3-T was profiled using Taqman low density arrays (TLDA). Six differentially regulated miRNAs were identified in the SKBR3-T cells. qRT-PCR assays confirmed that four were significantly altered in the SKBR3-T compared to SKBR3 cells: miR-224 1.6 fold down-regulated (p=0.01), miR-221 5.8 fold up-regulated (p=0.04), miR-222 was 3.8 fold up-regulated (p=0.01) and miR-9 was 2.2 fold up-regulated (p=0.04). In another model of acquired trastuzumab resistance, BT474-Tr, miR-221 and -222 were also up-regulated, miR224 expression was switched off. No significant change in miR-9 was observed in BT474-Tr. We analysed expression of the four miRNAs in a panel of HER2 positive cell lines which included 6 innate trastuzumab resistant cell lines and 3 innately sensitive cell lines. miR-224 was significantly down-regulated in the 6 resistant cell lines and miR-221 was significantly up-regulated in 3 of the 6 resistant cell lines, compared to the sensitive cell lines. miR-222 and miR-9 were not consistently altered in the resistant cell lines compared to the sensitive cell lines. We analysed expression of these miRNAs in a small cohort of patients who showed durable complete response (pCR) (9 %) following treatment with trastuzumab and chemotherapy [1], and a control group of patients whose disease progressed following treatment. miRNA was extracted from FFPE tumor samples (n=12) and analysed by qRT-PCR. The mean levels of expression of miR-9, -221, and -222 were higher in non-responders (n=6) than responders (n=6) and the mean levels of miR-224 were lower in the non-responders compared to responders. These results suggest that miR-9, -221, -222 and -224 may be potential biomarkers of trastuzumab resistance. 1. Gullo, G., et al., Durable complete response following chemotherapy and trastuzumab for metastatic HER2-positive breast cancer. Annals of Oncology, 2012. Citation Format: Karen Howe, Alex J. Eustace, Giuseppe Gullo, Brigid Browne, Sinead Aherne, John Crown, Norma O'Donovan. Altered expression of miRNAs in acquired trastuzumab resistance. [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 1826. doi:10.1158/1538-7445.AM2014-1826
956. Suppression of Tumor Metastasis by Adenoviral-Mediated MRP-1/CD9 Expression
Authors: Yi Lu, Jun Zhang, Bogdan Ceacareanu, Aviv Hassid, Lisa K. Jennings
Journal: Molecular Therapy (2004)

Metastasis, the major cause of deaths of cancer patients, is a complex multi-step process in which cell motility plays an important role. The motility related protein-1, MRP-1/CD9 (or CD9), is a tetraspanin membrane glycoprotein and it has been implicated in playing roles in cell adhesion, spreading, and motility. In this study, a replication-deficient recombinant adenovirus expressing CD9 (Ad-CD9) was generated. By using a highly metastatic breast cancer cell line JygMC(A) as the model, we evaluaed the effects of adenoviral-mediated CD9 expression on suppression of tumor metastasis and related biological and biochemical parameters. By comparing with untreated or control virus-treated cells, Ad-CD9 transduced JygMC(A) cells had an increased cell motility and increased adhesion to laminin and fibronectin but unchanged adhesion to matrigel. Overexpression of CD9 in JygMC(A) cells suppressed cell growth and decreased in vitro invasion ability of cells to penetrate matrigel. Moreover, Ad-CD9 transduced JygMC(A) cells formed less metastasis in the lungs and livers in nude mice than control groups in a spontaneous metastasis animal model. These results suggest that CD9 may act as a tumor suppressor and/or anti-metastasis gene. Adenoviral-mediated CD9 gene transfer may have a potential for cancer gene therapy to suppress tumor growth and metastases.
Ensuring Competency and Professionalism Through State Medical Licensing
Authors: Humayun J. Chaudhry, J. Daniel Gifford, Arthur S. Hengerer
Journal: JAMA (2015)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Book: Chronic fatigue and its syndromes
Authors: R. Mayou
Journal: BMJ (1999)

Oxford University Press, £25, pp 416 ISBN 0 19 262181 5 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> This is an important book. The preface warns that it may offend those with strong beliefs that chronic fatigue is an exclusively physical syndrome or that it is entirely of psychological origins. Any who are offended will have been exceptionally resistant to the scholarship and the weight and breadth of the evidence as well as to a readable style that has more vigour and humanity than is usual in medical monographs. The authors fully accept chronic fatigue syndrome as a real illness and one … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Atrial Tachycardia Arising From the Coronary Sinus Musculature
Authors: Nitish Badhwar, Jonathan M. Kalman, Paul B. Sparks, Peter M. Kistler, Mehran Attari, Marcie Berger, Randall J. Lee, Jasbir Sra, Melvin M. Scheinman
Journal: Journal of the American College of Cardiology (2005)
Reporting and registering nonmelanoma skin cancers: a compelling public health need
Authors: A.C. Geller, S.M. Swetter
Journal: British Journal of Dermatology (2012)

Journal Article Reporting and registering nonmelanoma skin cancers: a compelling public health need Get access A.C. Geller, A.C. Geller Department of Society, Human Development and Health, Harvard School of Public Health, and Melanoma Epidemiology, Massachusetts General Hospital, Boston, MA, U.S.A Search for other works by this author on: Oxford Academic Google Scholar S.M. Swetter S.M. Swetter Dermatology Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, U.S.ADepartment of Dermatology, Pigmented Lesion and Melanoma Program, Stanford University Medical Center and Cancer Institute, Stanford, CA, U.S.A. E‐mail: ageller@hsph.harvard.edu Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 166, Issue 5, 1 May 2012, Pages 913–915, https://doi.org/10.1111/j.1365-2133.2012.10911.x Published: 01 May 2012
Applicability of evidence-based practice in public health: risk assessment on Q fever under an ongoing outbreak
Authors: F Forland, H De Carvalho Gomes, H Nokleby, A Escriva, D Coulombier, J Giesecke, A Jansen
Journal: Eurosurveillance (2012)

With reference to the Q fever outbreak in the Netherlands in 2009-10, we tested if an evidence-based approach, comparable to the methodology used in clinical medicine, was appropriate for giving public health advice under time constrains. According to the principles of evidence-based methodologies, articles were retrieved from bibliographic databases and categorised by type and size, outcome, strengths and limitations. The risk assessment was conducted in two months and involved six staff members. We retrieved and read 559 abstracts and selected approximately 150 full text articles. The most striking finding was the lack of sound scientific evidence behind standard treatment regimes for Q fever in pregnancy. Difficulties in applying existing evidence rating systems and in expressing uncertainties were identified as problems during the process. By systematically assessing the evidence on several questions about Q fever, we were able to draw new conclusions and specify earlier statements. We found it difficult to grade the mostly observational studies with the known evidence-based grading systems. There is need to develop new methods for grading evidence from different sources in the field of public health. We conclude that an evidence-based approach is feasible for providing a risk assessment within two to three months.
Systemic antipsoriatic therapy may reverse endothelial dysfunction
Authors: W.-H. Boehncke, S. Boehncke
Journal: British Journal of Dermatology (2011)

Journal Article Systemic antipsoriatic therapy may reverse endothelial dysfunction Get access W.‐H. Boehncke, W.‐H. Boehncke Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar S. Boehncke S. Boehncke Internal Medicine, Johann Wolfgang Goethe‐University, Theodor‐Stern‐Kai 7, D‐60590 Frankfurt am Main, Germany E‐mail: Boehncke@em.uni‐frankfurt.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 6, 1 June 2011, Pages 1397–1398, https://doi.org/10.1111/j.1365-2133.2011.10250.x Published: 01 June 2011
Emergence of vancomycin-resistant enterococci in a tertiary hospital in Crete, Greece: a cluster of cases and prevalence study on intestinal colonisation
Authors: A. Christidou, A. Gikas, E. Scoulica, J. Pediaditis, M. Roumbelaki, A. Georgiladakis, Y. Tselentis
Journal: Clinical Microbiology and Infection (2004)
Clinical guidelines: Legal and political considerations of clinical practice guidelines
Authors: B. Hurwitz
Journal: BMJ (1999)

In the 4th century BC, Plato explored the difference between skills grounded in practical expertise and those based solely on following instructions or obeying rules. Using the clinician as his model, he set up a thought experiment: doctors would be stripped of their clinical freedom—“no longer allowed unchecked authority”—but would form themselves into councils to determine majority views about how to practise medicine in all situations.1

Plato's notion of codifying the majority decisions of panels (composed of clinical and non-clinical members) and publishing their work in order to influence (Plato says to dictate) “the ways in which the treatment of the sick is practised”1 prefigures many of the impulses which animate the clinical guidelines movement today.

In Plato's view, important hallmarks of expertise include flexible responsiveness and “improvisatory ability”—an approach to practice endangered, he believed, by use of guidelines.1 However effective health care by guideline turned out to be—and Plato was prepared to concede its potential—it remained in his view a debased form of practice, firstly because guidelines presuppose an average patient rather than the particular patient whom a doctor is endeavouring to treat, and secondly because the knowledge and analysis that go into the creation of guidelines are not rooted in the mental processes of clinicians, but in the minds of guideline developers distant from the consultation. Similar concerns trouble present day clinicians (box).

#### Summary points

Clinical guidelines cannot offer doctors thoughtproof mechanisms for improving medical care

However well linked to evidence, clinical guidelines need to be interpreted sensibly and applied with discretion

Under UK common law, minimum acceptable standards of clinical care derive from responsible customary practice, not from guidelines

If clinicians implement faulty guidelines it is they, rather than the authors of such guidelines, who are likely to increase their liability in negligence

The NHS Executive …
Abstract 15475: Elevated Plasma levels of Neutral Endpeptidase in Hypertension Patients Treated with Angiotensin Converting Enzyme Inhibitors
Authors: Koichi Sugamura, Seigo Sugiyama, Koichiro Fujisue, Yoshihiro HIrata, Hirofumi Kurokawa, Hirofumi Maeda, Eiichiro Yamamoto, Kenichi Tsujita, Koichi Kaikita, Seiji Hokimoto, Hisao Ogawa
Journal: Circulation (2014)

Background: Inhibiting Neutral Endpeptidase-24.11 (NEP) combined with angiotensin receptor blocker (ARB) has recently been employed as an effective treatment for hypertension (HT). Although soluble form of NEP (sNEP) is able to measure in human plasma, the relationship between plasma levels of sNEP and clinical condition is still unknown in HT patients. Methods: We consecutively measured plasma levels of sNEP and B-type natriuretic peptide (BNP) in 210 patients with HT (144 male, 66 female, mean age; 69.5±10.4) who were suspected cardiovascular disease with multiple risk factors from April 2013 to December 2013. The levels of plasma sNEP were measured by using commercially available ELISA kits (SEB785Hu, USCN life science inc.). Results: Plasma levels of sNEP were non-normally distributed in whole high-risk HT patients assessed by Shapiro-Wilk test (p&lt;0.01, median; 431.7 pg/ml, interquartile range; 302.0 to 540.9 pg/ml). sNEP levels were not significantly different among the patients with or without CAD [n=176, 431.7 pg/ml, (310.7 to 532.1) vs. n=34, 437.1 pg/ml, (284.4 to 574.6), p=0.851]. Plasma levels of sNEP were significantly greater in the HT patients treated with angiotensin converting enzyme inhibitors (ACEI) compared with those treated without ACEI [n=46, 493.4 pg/ml, (395.2 to 614.0) vs. n=164, 403.4 pg/ml, (299.6 to 523.8), p=0.012]. Plasma levels of sNEP were not significantly different between the patients with or without using ARB [n=107, 397.7 pg/ml, (284.8 to 506.8) vs. n=103, 456.4 pg/ml, (335.0 to 568.0), p=0.098]. There is no significant association between the plasma levels of sNEP and log BNP (ρ=0.018, P=0.801). Multivariable logistic regression analysis revealed that the administration of ACEI was independently associated with the higher levels of sNEP above median (odds ratio=2.48, 95% confidence interval; 1.23 to 5.03, p&lt;0.02). Conclusion: Among high risk patients with HT, patients treated with ACEI demonstrated significantly elevated levels of sNEP and the administration of ACEI was independently associated with the higher levels of sNEP. NEP could be up-regulated by ACEI and ARB did not significantly affect on NEP activity in HT patients. NEP could be effectively inhibited by a NEP-inhibitor in HT patients treated by ARB.
Abstract 2845: Expression of FGFR2b in gastric cancer as measured by immunohistochemistry with a highly specific monoclonal antibody
Authors: Amit M. Deshpande, Servando Palencia, David I. Bellovin, Abigael T. Gemo, Tina Giese, Bradley Stohr, Kristen L. Pierce, Gerrit Los
Journal: Cancer Research (2014)

Abstract Gastric cancer is the second leading cause of death from cancer worldwide. Amplification of the FGFR2 gene has been reported in ∼ 5 to 7% of gastric cancers, and several studies have also reported overexpression of the FGFR2 protein using immunohistochemistry (IHC). FGFR2 gene amplification and protein overexpression have also been shown to correlate with an aggressive disease phenotype, making FGFR2 an attractive therapeutic target. We have reported elsewhere at this meeting that the b-isoform of FGFR2 is predominantly expressed in these tumors and have developed a therapeutic antibody, FPA144, which specifically targets this isoform. Here we report initial development of a separate monoclonal antibody, FPT mAb, for use as a companion IHC diagnostic (CDx) for selecting patients with high levels of FGFR2b protein. In specificity studies using cells transfected with various FGFRs we show that FPT mAb specifically detects the b-isoform of FGFR2. In contrast, 7 commercially available anti-FGFR2 antibodies showed cross-reactivity with other FGF receptors. In an assay using cells with inducible FGFR2 gene expression, FPT mAb also was more sensitive for detection of FGFR2b than any of the commercially available antibodies. Furthermore, FPT mAb was able to detect FGFR2b protein expression in gastric cancer cases without FGFR2 gene amplification. We examined FGFR2b protein expression by IHC using the FPT mAb and FGFR2 gene amplification using FISH in 186 gastric cancer samples. 6% of samples showed amplification of the FGFR2 gene as measured by FISH (FGFR2:CEN10 &amp;gt;3), compared to 16.7% of samples positive for FGFR2b expression as measured by IHC (2-3+ staining in &amp;gt;50% of the tumor cells). In conclusion, we show that the FPT mAb is sensitive and specific for detecting by IHC the b-isoform of FGFR2 expressed in gastric cancers. Further, we demonstrate that more gastric tumors overexpress FGFR2b protein than bear amplifications of the FGFR2 gene. These results suggest that a potentially larger percentage of patients with gastric cancer may be appropriately identified as candidates for FGFR2b-specific therapies. Citation Format: Amit M. Deshpande, Servando Palencia, David I. Bellovin, Abigael T. Gemo, Tina Giese, Bradley Stohr, Kristen L. Pierce, Gerrit Los. Expression of FGFR2b in gastric cancer as measured by immunohistochemistry with a highly specific monoclonal antibody. [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 2845. doi:10.1158/1538-7445.AM2014-2845
Achieving high-sensitivity for clinical applications using augmented exome sequencing
Authors: Anil Patwardhan, Jason Harris, Nan Leng, Gabor Bartha, Deanna M. Church, Shujun Luo, Christian Haudenschild, Mark Pratt, Justin Zook, Marc Salit, Jeanie Tirch, Massimo Morra, Stephen Chervitz, Ming Li, Michael Clark, Sarah Garcia, Gemma Chandratillake, Scott Kirk, Euan Ashley, Michael Snyder, Russ Altman, Carlos Bustamante, Atul J. Butte, John West, Richard Chen
Journal: Genome Medicine (2015)
Abstract 15723: Vagus Nerve Stimulation Reduces Mean Arterial Pressure Through Structural and Electrical Remodeling of the Heart in Dahl Salt-Sensitive Rat Hypertension Model
Authors: Xueyi Xie, Steven W Lee, Tyler Senjem, Kevin Caron, John Osborn, Elena G Tolkacheva
Journal: Circulation (2014)

Hypertension (HTN) is one of the strongest risk factors for cardiovascular diseases, which leads to ventricular hypertrophy, systolic and diastolic dysfunctions. There is a clear need for novel and effective techniques to treat HTN and HTN-induced heart diseases, which are closely linked to autonomic nervous system imbalance. Here, we aimed to evaluate the use of intermittent vagal nerve stimulation (VNS) as a novel therapy for the treatment of HTN.  HTN was induced in 6 Dahl salt-sensitive rats after 6 weeks of high salt diet (8% NaCl). Rats were implanted with the pressure monitoring transmitters and either active (VNS, n=3) or non-functional (Sham, n=3) VNS stimulators. Intermittent VNS was activated at week 7, and mean arterial pressure (MAP) was monitored for 4 more weeks. Optical mapping was performed in isolated rat hearts, and action potential durations (APD), intra-ventricular heterogeneity of APD (μ) and conduction velocity (CV) were measured at different pacing cycle lengths (CL) both in right (RV) and left ventricles (LV) (data are shown for CL = 200 ms).  HTN was successfully induced in rats as the MAP was significantly increased from week 1 to week 6 (107 ± 0.8 vs 171 ± 9.2 mmHg, p  The tibial length normalized to heart weight ratio was reduced in VNS (0.33 ± 0.02 g/cm) in comparison to Sham rats (0.40 ± 0.01 g/cm, p  Optical mapping showed that, in VNS rats, APD was larger in LV (75 ± 1.1 ms) in comparison to RV (66 ± 2.5 ms, p  Our data indicate that VNS reduces MAP in hypertensive rats and results in beneficial structural and electrical remodeling effects of the heart.