tbuckley/cabot-search huggingface dataset:
Abstract 12954: Impairment of the Compensatory Natriuretic Peptide Response to Myocardial Infarction in the Aged is Associated With Adverse Cardiorenal Repair and Heart Failure
Authors: S. J Sangaralingham, Tomoko Ichiki, Gerald E Harders, Horng H Chen, John C Burnett
Journal: Circulation (2014)

Introduction: The incidence of post-myocardial infarction (MI) heart failure (HF) is increasing in the elderly. Studies have demonstrated that B-type natriuretic peptide (BNP) mediates critical cardiorenal compensatory and protective actions through guanylyl cyclase receptor A and cGMP activation. Such actions include natriuresis, diuresis and suppression of adverse cardiorenal remodelling. Hypothesis: While the mechanism of this increased risk may be multifactorial, we hypothesized that an impairment of the compensatory protective BNP/cGMP axis in both the aged kidney and heart contributes to post-MI HF. Methods: 20 month old Fischer rats were randomized into two groups: Sham-operated (S) and MI(produced by left coronary artery ligation). Cardiorenal structure and function were assessed at 4 weeks and included mean arterial pressure(MAP), LV EF, LV chamber dimension, proteinuria, sodium (Na) excretion and fibrosis by picrosirius red staining. Plasma BNP and cGMP levels were assessed by RIA. Data presented as mean±SE,*P&lt;0.05. Results: LV EF (S:78±2, MI:46±3 %*) was significantly reduced in aged MI rats, despite no difference in LV fibrosis in the remote region and no change in MAP compared to aged sham rats. Post-MI HF was evident and characterized by a significant reduction in Na excretion (S:0.20±0.03, MI:0.13±0.01 mEq/day*) as well as significant increases in LV dilatation (S:7.2±0.1, MI:8.3±0.2 mm*) and cardiac hypertrophy (S:2.78±0.06, MI:3.25±0.16 mg/g*) in aged MI rats. Notably, plasma BNP (S:9±1, MI:11±2 pg/ml) failed to increase and plasma cGMP (S:44±6, MI:27±3 mm*) was significantly reduced in the MI group. Importantly, MI in the aged rat resulted in a significant loss in total renal mass (S:2739±83, MI:2351±68 mg*), consistent with renal atrophy, while no changes in proteinuria or renal fibrosis were observed. Conclusions: Post-MI dysfunction of the protective BNP/cGMP axis in the aged rat was associated with various cardiorenal abnormalities including renal atrophy, which may contribute to the pathophysiology of HF. This pre-clinical model provides new insights into post-MI HF and may be used to examine therapeutic strategies using natriuretic peptides to protect the heart and kidney in the elderly post-MI population.
Characterization of Two New Imatinib-Responsive Fusion Genes Generated by Disruption of PDGFRB in Eosinophilia-Associated Chronic Myeloproliferative Disorders.
Authors: Christoph Walz, Georgia Metzgeroth, Claudia Schoch, Torsten Haferlach, Rudiger Hehlmann, Andreas Hochhaus, Nicholas C.P. Cross, Andreas Reiter
Journal: Blood (2006)
Abstract 3489: A novel investigation into chemotherapy-induced peripheral neuropathy using iPSC-derived human neurons
Authors: Masaaki Komatsu, Heather E. Wheeler, Claudia Wing, Shannon Delaney, M Eileen Dolan
Journal: Cancer Research (2014)

Abstract Chemotherapy-induced peripheral neuropathy (CIPN) is the major dose-limiting side effect of many anti-cancer drugs including taxanes, vinca alkaloids and platinating agents. These drugs represent standard of care for common cancers, however there are no effective treatments and no means to identify patients at risk for CIPN. The mechanisms underlying CIPN have not been precisely determined and few human neuronal models to study CIPN exist. Recent technology has allowed for the differentiation of induced pluripotent stem cells (iPSC) to human neurons. We have utilized genetically diverse human neurons as a model to study the effects on chemotherapy on neuronal health and on neurite morphology including neurite outgrowth, processes and branching. Upon treatment of human neurons with paclitaxel, vincristine or cisplatin (1 nM to 100 µM) for 72 hours, we identified reproducible decreases in cell median neurite process length per magnitude of drug concentration of 12-14%, 6-18% and 2-4%, respectively. No decrease in neurite length was observed with hydroxyurea, an agent that does not cause neuropathy. The morphological changes differed across drugs, with vincristine treatment showing the most dramatic effect on neurite outgrowth, paclitaxel showing an intermediate effect, and cisplatin showing no effect up to 1 µM of drug. To determine whether the model could be used for evaluation of genes important in CIPN, we used siRNA to decrease expression of TUBB2A, a gene known to be associated with paclitaxel-induced neuropathy. Transient knockdown of TUBB2A caused decreases of mean neurite process length (interaction P = 2.2 x 10-8) and total neurite outgrowth (interaction P = 1.8 x 10-10) of neurons 48 hours post-paclitaxel treatment. We are using this novel approach to screen agents that may be used to prevent or treat CIPN. Citation Format: Masaaki Komatsu, Heather E. Wheeler, Claudia Wing, Shannon Delaney, M Eileen Dolan. A novel investigation into chemotherapy-induced peripheral neuropathy using iPSC-derived human neurons. [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 3489. doi:10.1158/1538-7445.AM2014-3489
Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease
Authors: S Mackinnon, EB Papadopoulos, MH Carabasi, L Reich, NH Collins, F Boulad, H Castro-Malaspina, BH Childs, AP Gillio, NA Kernan
Journal: Blood (1995)
Bortezomib as brief neoadjuvant therapy for localized high-risk prostate cancer (PCa) followed by radical prostatectomy (RP)
Authors: G. Sonpavde, A. Frolov, V. Macdonell, T. G. Hayes, M. P. Mims, G. E. Ayala, T. M. Wheeler, T. C. Thompson, M. M. Ittman, D. Kadmon
Journal: Journal of Clinical Oncology (2009)

5127 Background: Neoadjuvant therapy may provide an important paradigm for the discovery of active agents for the therapy of PCa. Bortezomib is a proteasome inhibitor with preclinical activity in PCa. A rationale can be made to study brief preoperative bortezomib before RP to determine feasibility and biologic activity. Methods: A phase II trial was designed to evaluate bortezomib 1.6mg/m 2 as intravenous bolus weekly for 4 weeks followed by RP 24–72 hours after the last dose. Histological evidence of adenocarcinoma of the prostate was required with clinical stage T 1c or T 2a with Gleason 8–10 disease, or clinical stage T 2b -T 2c with Gleason grade 7 and PSA of &gt;10 ng/mL, or clinical stage T 3 . Results: Accrual is complete with 40 patients enrolled, of whom 38 completed neoadjuvant bortezomib followed by RP and are evaluable. The median age was 60.2 years. No pathologic complete responses were noted. Cytopathic effects (cytolysis, nuclear pyknosis) were commonly seen compared to baseline tumor. Upregulation of apoptosis, proliferation and phosphorylated (p)-Akt have been previously reported in a subset of patients by our group (Ayala GE et al, Clin Cancer Res. 2008;14:7511–8). Two of 8 evaluable patients had a &gt;50% decrease in serum PSA with bortezomib treatment; 3 others had PSA declines of 14%, 25%, and 45%, respectively; 1 patient had no change, and 2 displayed PSA increases. Therapy was feasible with generally manageable toxicities, and surgical morbidities did not increase. A comprehensive toxicity analysis will be presented. Feasibility of surgery, extraprostatic extension, positive margin and lymph node positive rates will be compared with matched historical controls and these data will be presented. Conclusions: Bortezomib is feasible as neoadjuvant therapy preceding RP for PCa and demonstrates biologic activity. Given the upregulation of proliferation and pAkt, the further evaluation of bortezomib may be warranted in randomized trials in combination with chemotherapy or Akt inhibitors. [Table: see text]
Extracellular vesicles derived from Staphylococcus aureus induce atopic dermatitis-like skin inflammation
Authors: S.-W. Hong, M.-R. Kim, E.-Y. Lee, J. H. Kim, Y.-S. Kim, S. G. Jeon, J.-M. Yang, B.-J. Lee, B.-Y. Pyun, Y. S. Gho, Y.-K. Kim
Journal: Allergy (2010)

To cite this article: Hong S-W, Kim M-R, Lee E-Y, Kim JH, Kim Y-S, Jeon SG, Yang J-M, Lee B-J, Pyun B-Y, Gho YS, Kim Y-K. Extracellular vesicles derived from Staphylococcus aureus induce atopic dermatitis-like skin inflammation. Allergy 2011; 66: 351–359. Background: Recently, we found that Staphylococcus aureus produces extracellular vesicles (EV) that contain pathogenic proteins. Although S. aureus infection has been linked with atopic dermatitis (AD), the identities of the causative agents from S. aureus are controversial. We evaluated whether S. aureus-derived EV are causally related to the pathogenesis of AD. Methods: Extracellular vesicles were isolated by the ultracentrifugation of S. aureus culture media. The EV were applied three times per week to tape-stripped mouse skin. Inflammation and immune dysfunction were evaluated 48 h after the final application in hairless mice. Extracellular vesicles-specific IgE levels were measured by ELISA in AD patients and healthy subjects. Results: The in vitro application of S. aureus EV increased the production of pro-inflammatory mediators (IL-6, thymic stromal lymphopoietin, macrophage inflammatory protein-1α, and eotaxin) by dermal fibroblasts. The in vivo application of S. aureus EV after tape stripping caused epidermal thickening with infiltration of the dermis by mast cells and eosinophils in mice. These changes were associated with the enhanced cutaneous production of IL-4, IL-5, IFN-γ, and IL-17. Interestingly, the serum levels of S. aureus EV-specific IgE were significantly increased in AD patients relative to healthy subjects. Conclusion: These results indicate that S. aureus EV induce AD-like inflammation in the skin and that S. aureus-derived EV are a novel diagnostic and therapeutic target for the control of AD.
BCRP-mediated resistance to the EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib
Authors: Clara Lemos, Ietje Kathmann, Elisa Giovannetti, Gerrit Jansen, Godefridus Peters
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3246 

The Breast Cancer Resistance Protein (BCRP) is an ATP-binding cassette (ABC) transporter known to confer cellular resistance to a wide spectrum of drugs. The EGFR TKI gefitinib has been described both as a substrate and inhibitor of BCRP, but contradictory data have been published regarding this subject. Less information is available concerning the ability of BCRP to transport erlotinib, although a preliminary study has suggested that erlotinib is a substrate of BCRP.    In this study we aimed to investigate whether BCRP expression in different cell lines is a determinant for gefitinib and erlotinib cellular resistance. In this study, two colon cancer cell lines (Caco2 and WiDr) were used with constitutive BCRP expression, which may vary upon growth in medium containing supraphysiological concentrations of folic acid (2.3 μM; high folate, HF) as compared to cells gradually adapted to more physiological concentrations of folates (1 nM or 2.5 nM folic acid (FA) or leucovorin (LV); low folate, LF). Additionally, we used MCF-7/MR cells, a breast cancer cell line with acquired resistance to mitoxantrone (MR) due to BCRP overexpression.    Caco2-LF/LV showed increased BCRP protein expression compared with the HF cell line, which was associated with 1.8-fold resistance to gefitinib, a phenotype that could be completely reverted by the BCRP specific inhibitor Ko143. WiDr-LF cells also showed slightly increased BCRP expression compared with the HF cells, but no differences in gefitinib sensitivity were observed. Both Caco2-LF/LV and WiDr-LF cells showed 2.4- and 2.3-fold resistance to erlotinib, respectively, compared with the HF counterparts, which mechanistically seems BCRP-unrelated, as Ko143 had no effect on erlotinib activity. Additionally, in MCF-7/MR cells, gefitinib and erlotinib sensitivity was almost unchanged when BCRP was blocked with Ko143. As BCRP had different impact on gefitinib resistance in different cell lines, we investigated whether our observations were associated with the BCRP C421A SNP; however, all cells lines showed the same genotype. Interestingly, Caco2 cells displayed more potent gefitinib sensitivity (IC50: 200 - 600 nM) as compared to WiDr and MCF-7/MR cells (IC50: 7.5 - 10 μM). These sensitivity profiles were consistent with EGFR expression in the different cell lines, being much higher in Caco2 cells than in WiDr and MCF-7/MR cells.    In conclusion, our study demontrates that BCRP is a major determinant of gefitinib resistance in cells with constitutively high EGFR expression. Conversely, in cells with low or no expression of EGFR, and thus intrinsically resistant to gefitinib, BCRP does not confer additional resistance. Our data also suggests that BCRP is not a determinant of erlotinib resistance.    Supported by FCT (SFRH/BD/16883/2004).
ABC of Urology
Authors: S. J Vernon, M. G Coulthard, H. J Lambert
Journal: BMJ (1996)

R P D Cooke and colleagues offer further sup- portive evidence for the adequacy of single doses of gentamicin in febrile neutropenic patients.Their approach of halving the dose if the trough concentration of gentamicin is 1-2 mg/l may be overcautious, since serum concentrations of aminoglycosides have not been shown to have much predictive value for efficacy or toxicity.5
New Guidelines Released for Managing Cough
Authors: Tracy Hampton
Journal: JAMA (2006)

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
Abstract 2611: Function blocking ERBB3 antibody inhibits adaptive response to RAF inhibitor
Authors: Curtis Harrison Kugel, Edward J. Hartsough, Michael A. Davies, Andrew E. Aplin
Journal: Cancer Research (2014)

Abstract ERBB3/HER3 is a member of the EGFR family of receptor tyrosine kinase. Our lab recently showed that treating melanoma cells with the FDAapproved small molecule BRAF inhibitor vemurafenib leads to an increase in ERBB3 signaling when grown in the presence of its ligand neuregulin (NRG1). Here, we show that targeting ERBB3 with a monoclonal antibody inhibits its activation and downstream signaling in the presence of vemurafenib and NRG1. This inhibition of ERBB3 led to a decrease in proliferation and increase in apoptosis in vitro as measured by EdU and AnnexinV/PI staining. Targeting ERBB3 in combination with mutant BRAF in vivo resulted in a delay of tumor re-growth in immune deficient mice compared to targeting mutant BRAF alone. Taken together, these results indicate that targeting ERBB3 in combination with mutant BRAF in melanoma may help enhance the initial effects of vemurafenib in the clinic. Citation Format: Curtis Harrison Kugel, Edward J. Hartsough, Michael A. Davies, Andrew E. Aplin. Function blocking ERBB3 antibody inhibits adaptive response to RAF inhibitor. [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 2611. doi:10.1158/1538-7445.AM2014-2611
The association between systemic inflammation, statin therapy, and saphenous vein endothelial function in patients undergoing coronary artery bypass surgery
Authors: Aziz U Momin, Narbeh Melikian, Stephen Wheatcroft, David Grieve, Ahmad El-Gamel, Michael Marrinan, Jatin Desai, Catherine Driver, Roy Sherwood, Ajay Shah, Mark Kearney
Journal: Circulation (2006)
Abstract 22: Resuscitation Guidelines 2005 Improve CPR Effectiveness Parameters
Authors: Roman Fleischhackl, Bernhard Roessler, Heidrun Losert, Cosima Wandaller, jasmin arrich, Martina Mittlboeck, Klaus Hoerauf, Hans Domanovits, Fritz Sterz
Journal: Circulation (2006)

Background: Due to major changes of the resuscitation guidelines we studied differences in Cardio-pulmonary Resuscitation (CPR) performed by volunteers, comparing the Guidelines 2000 (Group A) and ...
Selenoprotein P influences colitis-induced tumorigenesis by mediating stemness and oxidative damage
Authors: Caitlyn W. Barrett, Vishruth K. Reddy, Sarah P. Short, Amy K. Motley, Mary K. Lintel, Amber M. Bradley, Tanner Freeman, Jefferson Vallance, Wei Ning, Bobak Parang, Shenika V. Poindexter, Barbara Fingleton, Xi Chen, Mary K. Washington, Keith T. Wilson, Noah F. Shroyer, Kristina E. Hill, Raymond F. Burk, Christopher S. Williams
Journal: Journal of Clinical Investigation (2015)

Patients with inflammatory bowel disease are at increased risk for colon cancer due to augmented oxidative stress. These patients also have compromised antioxidant defenses as the result of nutritional deficiencies. The micronutrient selenium is essential for selenoprotein production and is transported from the liver to target tissues via selenoprotein P (SEPP1). Target tissues also produce SEPP1, which is thought to possess an endogenous antioxidant function. Here, we have shown that mice with Sepp1 haploinsufficiency or mutations that disrupt either the selenium transport or the enzymatic domain of SEPP1 exhibit increased colitis-associated carcinogenesis as the result of increased genomic instability and promotion of a protumorigenic microenvironment. Reduced SEPP1 function markedly increased M2-polarized macrophages, indicating a role for SEPP1 in macrophage polarization and immune function. Furthermore, compared with partial loss, complete loss of SEPP1 substantially reduced tumor burden, in part due to increased apoptosis. Using intestinal organoid cultures, we found that, compared with those from WT animals, Sepp1-null cultures display increased stem cell characteristics that are coupled with increased ROS production, DNA damage, proliferation, decreased cell survival, and modulation of WNT signaling in response to H2O2-mediated oxidative stress. Together, these data demonstrate that SEPP1 influences inflammatory tumorigenesis by affecting genomic stability, the inflammatory microenvironment, and epithelial stem cell functions.
SGN-33 (Lintuzumab), a humanized anti-CD33 antibody, modulates the activity of CD33+ tumor-associated macrophages
Authors: May Sutherland, Mechtild Jonas, Changpu Yu, Timothy Lewis, Leia Smith, Steven Duniho, Julie McEarchern, Eric Sievers, Iqbal Grewal, Che-Leung Law
Journal: Cancer Research (2007)

4111  High numbers of tumor-associated macrophages (TAMs) found in inflammatory infiltrates associated with malignant tumors, including those of the breast, prostate, bladder, kidney, ovary, and lung, have been correlated with poor prognosis and reduced patient survival. It is hypothesized that TAMs produce growth factors including MCP-1, IL-6, and RANTES that support tumor growth and immunosuppressive cytokines including IL-10 and TGFβ-1, that interfere with an anti-tumor immune response. Therefore, inhibition of TAM activity may elicit anti-tumor responses. CD33, a sialoadhesion family member, is expressed by normal macrophages and monocytes. To investigate the role of CD33 in TAMs, we profiled CD33 expression using tumor micro-arrays, explored the interaction between tumor cells and macrophages, and assessed the ability of SGN-33, a humanized IgG1 anti-CD33 antibody, to inhibit macrophage function. A survey of several multi-tumor arrays showed that CD33+ macrophages were present in inflammatory infiltrates of 43% (150/346) of the core samples. To further characterize the interaction between macrophages and tumor cells, normal human CD33+ macrophages were treated with conditioned tumor cell media from cultures of multiple myeloma, acute myeloid leukemia, bladder carcinoma, or renal cell carcinoma cell lines. Under these conditions, the macrophages increased the production of inflammatory cytokines (TNF-α, IL-6, IL-1β) and chemokines (RANTES, MCP-1, IL-8). Incubation of macrophages with SGN-33 significantly reduced the syntheses of these factors by 50%. Analyses of the tumor cell conditioned media revealed that tumor cells produced interferon-γ (IFN-γ), TGF-β, and VEGF. Similarly, when macrophages were pre-activated with recombinant IFN-γ or TGF-β, subsequent incubation with SGN-33 reduced the syntheses of inflammatory cytokines and chemokines by up to 50%. Furthermore, SGN-33 reduced the migration of macrophages by 40% in response to chemoattractants such as conditioned tumor cell media. Ligation of CD33 by SGN-33 induced tyrosine phosphorylation of CD33 and the re-distribution of the protein tyrosine phosphatase SHP-1 to the plasma membrane via interaction with phosphorylated CD33. The mechanism by which recruited SHP-1 may alter macrophage response to IFN-γ or TGF-β is being investigated. Demonstration that SGN-33 reduced pro-inflammatory cytokines and tumor enhancing growth factors produced by TAMs suggests a novel mechanism by which anti-CD33 antibody therapy might elicit anti-tumor activity.
Virtual Patients Help Medical Students Link Basic Science With Clinical Care
Authors: Rebecca Voelker
Journal: JAMA (2003)

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