tbuckley/cabot-search huggingface dataset:
Synergistic potentiation of tumor necrosis factor-induced lung cancer cell death by 17-Allylamino-17-Demethoxygeldanamycin through blocking the nuclear factor-κB pathway
Authors: Xia Wang, Wei Ju, Jordan J. Renouard, James Aden, Steven A. Belinsky, Yong Lin
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

1365 

Tumor necrosis factor (TNF) is a potential cancer therapeutic agent because of its ability to induce cancer cell death. However, most lung cancer cells are resistant to TNF-induced death, the mechanism of which has not been well elucidated. Nuclear factor κB (NF-κB), a survival signal induced by TNF, has been implicated in resistance to TNF-induced apoptosis in cancer cells. Heat shock protein 90 (Hsp90) regulates the stability and function of receptor-interaction proteins (RIP) and IκB kinase β (IKKβ), the key components of the TNF-induced NF-κB activation pathway. Therefore, suppression of HSP90 function may sensitize cancer cells to TNF-induced death. In this study, we examined the effect of the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17AAG) on TNF-induced cell death in lung cancer cells. Exposure to 17AAG caused a significant reduction of RIP and IKKβ levels in H460 cells. A synergistic cytotoxicity was detected when TNF treatment followed 17AAG pre-exposure that caused RIP and IKKβ degradation, suggesting that the 17AAG sensitizes cells to TNF-induced cell death by blocking the TNF-induced NF-κΒ pathway. This was supported by further results, including suppressed IκBα phosphorylation and degradation, and decreased NF-κΒ activity detected by Western blot and reporter assay, respectively. The induction of NF-κB targeted anti-apoptosis genes was also suppressed in 17AAG-treated cells. Importantly, the potentiation of cell death by 17AAG was abolished in NF-κB-disabled cells expressing a nondegradable IκBα mutant (IκBαAA). These results suggest that the synergistic cytotoxicity seen with 17AAG and TNF treatment is resulted from blockage of TNF-induced NF-κB activation. The other components of the TNF receptor-I signaling cascade such as TRADD, TRAF2 and FADD were not altered in 17 AAG-treated cells. When treated with 17AAG, the TNF-induced c-Jun N-terminal protein kinase (JNK) activation was enhanced and sustained. 17AAG and TNF co-treatment-induced cytotoxicity is mainly apoptotic, which was demonstrated both morphologically and biochemically, suggesting that the TNF-induced apoptosis pathway was triggered by 17AAG. A similar synergism for inducing apoptosis was also observed in 17AAG and TNF-related apoptosis-inducing ligand (TRAIL) treated lung cancer cells. Our results suggest that NF-κB plays a key role in the resistance of lung cancer cells to TNF and TRAIL, and that disabling this survival signal with 17AAG followed by TNF or TRAIL treatment could be an effective new therapeutic strategy for this deadly malignancy.
Abstract 14709: Exercise Training in Patients with Heart Failure and Preserved Ejection Fraction: A Meta-analysis of Randomized Control Trials
Authors: Akhil Parashar, Ambarish Pandey, Dharam Kumbhani, Jalaj Garg, Sunil Agarwal, Jarett Berry
Journal: Circulation (2014)

Background: Heart failure with preserved ejection fraction (HFPEF) is common and characterized by exercise intolerance and lack of proven effective therapies. Exercise training has been shown to be effective in improving cardiorespiratory fitness (CRF) in patients with systolic heart failure. In this meta-analysis, we aim to evaluate the effects of exercise training on CRF, quality of life and diastolic function in patients with HFPEF. Methods: Randomized controlled clinical trials that evaluated the efficacy of exercise training in patients with HFPEF were included in this meta-analysis. Primary outcome of the study was change in CRF (measured as change in peak oxygen uptake). Impact of exercise training on quality of life (estimated using Minnesota living with heart failure score), left ventricular systolic and diastolic function was also assessed. Results: The study included 276 patients that were enrolled in 6 randomized controlled trials. In the pooled data analysis, HFPEF patients undergoing exercis...
The Medical Student's Manual of Chemistry.
Authors: R.A. M.D. Witthaus
Journal: JAMA (1902)

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
Coming Clean for Your Birthday
Authors: Sylvia S. Villarreal
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
Bronchodilation test in patients with allergic rhinitis
Authors: G. Ciprandi, A. Signori, M. A. Tosca, I. Cirillo
Journal: Allergy (2011)

To cite this article: Ciprandi G, Signori A, Tosca MA, Cirillo I. Bronchodilation test in patients with allergic rhinitis. Allergy 2011; 66: 694–698. Background: Allergic rhinitis (AR) may be considered a risk factor for the onset of asthma. Recently, it has been reported that forced expiratory flow between 25% and 75% of vital capacity (FEF25–75) may predict a positive response to bronchodilation test in asthmatic children. The aim of this study was to evaluate a large group of adult AR patients to investigate the frequency of response to bronchodilation test and FEF25–75 values. Methods: One thousand four hundred and sixty-nine consecutive patients suffering from persistent AR were evaluated. Clinical examination, spirometry, and bronchodilation test were performed in all patients. Results: In this study, 62.9% of patients had reversibility to bronchodilation test and 17.8% had impaired FEF25–75 values (≤65% of predicted). Impaired FEF25–75 values associated with longer rhinitis duration may predict reversibility to bronchodilation test (OR = 11.3; P < 0.001). In addition, a FEF25–75 cutoff value ≤71% of predicted may already discriminate patients with reversibility. Conclusions: This study highlights that about two-thirds of patients with persistent AR may be considered at risk of becoming asthmatic. This finding should be adequately considered as a precocious spirometry may allow the early detection of patients prone to develop asthma and consequently to treat them.
Abstract 139: Activating ERBB4 mutations in non-small cell lung cancer
Authors: Kari J. Kurppa, Konstantin Denessiouk, Mark S. Johnson, Klaus Elenius
Journal: Cancer Research (2015)

Abstract Genes encoding the ErbB receptor tyrosine kinases (EGFR/ERBB1, ERBB2, ERBB3, and ERBB4) are key regulators of cellular proliferation, survival, and differentiation, and thus represent potent proto-oncogenes. In particular, mutations or copy number variations of EGFR or ERBB2 are present in human malignancies and serve as predictive markers for targeted therapies. Recent efforts to comprehensively characterize the mutational landscape of human cancers have identified frequent somatic mutations in ERBB4 in various cancer types, such as non-small cell lung cancer (NSCLC), melanoma, and colorectal cancer. However, the significance of mutated ERBB4 in cancer remains elusive. Here, we have functionally characterized nine ERBB4 mutations previously identified in lung adenocarcinoma. Four out of the nine mutations, Y285C, D595V, D931Y and K935I, were found to be activating, increasing both basal and ligand-induced ErbB4 phosphorylation. According to structural analysis, the four activating mutations were located at critical positions at the dimerization interfaces of the ErbB4 extracellular (Y285C, D595V) and kinase (D931Y and K935I) domains. Consistently, the mutations enhanced ErbB4 dimerization and increased the trans activation in ErbB4 homodimers and ErbB4/ErbB2 heterodimers. The expression of the activating ERBB4 mutants promoted survival of NIH 3T3 cells in the absence of serum. Interestingly, serum starvation of NIH 3T3 cells expressing the ERBB4 mutants only moderately increased the phosphorylation of canonical ErbB signaling pathway effectors Erk1/2 and Akt as compared to wild-type ERBB4. In contrast, the mutations clearly enhanced the proteolytic release of signaling-competent ErbB4 intracellular domain. These results suggest the presence of activating, oncogenic mutations of ERBB4 in non-small cell lung cancer. Citation Format: Kari J. Kurppa, Konstantin Denessiouk, Mark S. Johnson, Klaus Elenius. Activating ERBB4 mutations in non-small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 139. doi:10.1158/1538-7445.AM2015-139
Abstract 3009: Membrane pseudokinase PTK7 regulates metastasis
Authors: Vladislav Golubkov, Yong Zhang, Natalie Prigozhina, Robert M. Hoffman, Alex Strongin
Journal: Cancer Research (2014)

Abstract Studies by others indicate that the membrane pseudokinase 7 (PTK7) regulates canonical and non-canonical Wnt pathways and controls orientation of cells in a tissue plane (planar cell polarity, PCP). There is still no clear understanding of the PTK7 role in cancer: Is it pro-tumorigenic or anti-tumorigenic? Our live cell imaging and cell invasion studies suggest that full-length PTK7 expressed in HT1080 fibrosarcoma cells inhibits directed cell motility, lamellipodia polarization and cell invasion. Using the fluorescence imaging we demonstrated that the expression of full-length PTK7 in HT1080-RFP cells in nude mice significantly reduces lung colonization (metastasis). The pro-invasive membrane type-1 matrix metalloprotease (MT1-MMP/MMP-14) coupled with an ADAM/ADAMTS family member(s) directly cleave PTK7 at the cell surface and reverse the inhibitory anti-invasive signal of full-length PTK7. Ectodomain proteolysis was a prerequisite for the intramembrane cleavage of the residual fragments of PTK7 by γ-secretase. The resulting C-terminal PTK7 fragment translocated to the cell nucleus. To identify the molecular mechanisms downstream of PTK7 proteolysis, we used genome-wide transcriptional profiling and kinome analysis. Full-length PTK7 and the PTK7 mutants representing the cleaved PTK7 forms differentially regulated the expression of multiple genes and induced signaling pathways associated with cell movement, Wnt signaling and cancer. We believe that the regulation of PTK7 proteolysis opens new possibilities to control Wnt signaling, cancer cell invasion and metastasis. Citation Format: Vladislav Golubkov, Yong Zhang, Natalie Prigozhina, Robert M. Hoffman, Alex Strongin. Membrane pseudokinase PTK7 regulates metastasis. [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 3009. doi:10.1158/1538-7445.AM2014-3009
Theories in health care and research: Theories of consent
Authors: P. Alderson, C. Goodey
Journal: BMJ (1998)

This is the third in a series of six articles on the importance of theories and values in health research

Series editor: Priscilla Alderson

Consent is understood differently by various disciplines and professions, and also in various theoretical models.1 In this article we review the advantages and limitations of theories about real consent, constructed consent, functionalist and critical consent, and postmodern choice. The article shows how an analysis of theories can clarify practical knowledge about the advantages of and problems in obtaining consent, which will help everyday practice and research.

### Summary points

Consent is understood and discussed in contradictory ways when people rely on different theoretical models

Positivism assumes that there is real consent in the factual exchange of medicolegal information

Social constructionism shows how consent can be a complex, ambiguous process, not a simple event

Functionalists see consent as a formality, whereas critical theorists see it as a vital protection

Postmodern theories illuminate the confusions that arise when choice itself is assumed to matter more than any of the options chosen

Consent is too complex to be explained by any one theoretical model

Positivism distinguishes factual concepts defined through dichotomies: informed/ignorant, competent/incompetent, free choice/coercion. Medicine, psychology, analytical philosophy, 2 3 and law 4 5 tend to assume positivist concepts of consent. The appropriate information, including percentage risks, for obtaining informed consent is treated almost as a “thing” which doctors give to patients. It is assessed by checking how patients recall and recount standard details of the information they have been given.

Positivist surveys dominate research about consent; mainly they measure information given. The essence of consent (patients' thoughts, feelings, and values as they evaluate information and make and express their decision) is far harder to observe or record—and too subjective and elusive to count as hard data. Problems in real …
Abstract 11684: Impaired Cortical Pain Processing in Patients With Silent Myocardial Ischemia
Authors: Antonino Di Franco, Gaetano A Lanza, Massimiliano Valeriani, Angelo Villano, Giulio Russo, Alfonso Sestito, Daniela Virdis, Costanza Pazzaglia, Filippo M Sarullo, Paolo M Rossini, Filippo Crea, Catello Vollono
Journal: Circulation (2014)

Purpose: In the present study, we investigated whether the function of brain areas specifically devoted to nociception presents any abnormalities in patients with silent myocardial ischemia (MI), as compared to those with symptomatic MI. Methods: We studied 3 groups of individuals: 1) 11 asymptomatic, non-diabetic patients with documented obstructive coronary artery disease (CAD) (67±10 years, 6 men; group 1); 2) 10 patients with obstructive CAD and a clinical pattern of chronic stable angina (66.5±10 years, 6 men; group 2); 3) 14 apparently healthy subjects matched for age and gender to patients (63.2±9 years, 8 men; group 3). Patients with any chronic pain syndrome other than anginal chest pain were excluded. Cortical nociception function was assessed by cortical laser evoked potentials (LEPs) recording in response to chest skin stimulation by cutaneous CO2 laser pulses. Specifically, the N2/P2 wave of LEPs, which reflects cortical pain processing, was measured. Three sequences of painful stimuli (at the intensity of 2.5 times the individual sensory threshold) were applied, separated by 5-minute intervals. Results: N2/P2 amplitude during the first sequence of chest skin stimuli was 9.3±4.0, 14.0±7.3 and 15.5±6.4 μV in group 1, group 2 and group 3, respectively (p=0.03). N2/P2 amplitude decreased across the three sequences of pain stimuli in group 2 (-37.5±14 %) and group 3 (-23.0±15 %), but not in group 1 (-0.14±37 %) (comparison among groups, p=0.015). Conclusion: CAD patients with silent MI show a reduced amplitude of N2/P2 LEP component and inadequate habituation to painful stimuli, compared to symptomatic angina CAD patients and healthy controls. This pattern is likely due to thalamic gate modulation of pain signals and can contribute to the lack of pain perception during MI in these patients.
Abstract 16397: Cardiac Deletion of Dicer Protects Against Acute Myocardial Ischemia-Reperfusion Injury
Authors: Lijuan Chen, Mi Zhou, Muhammad Ashraf, Neal Weintraub, Yaoliang Tang
Journal: Circulation (2011)

Objective: MicroRNAs (miRNA) are small, endogenous, conserved, noncoding RNAs that down-regulate protein production by translational repression. Dicer, a RNase III endonuclease essential for microR...
Associations between muscle wasting and BODE index in chronic obstructive pulmonary disease
Authors: Min Kwang Byun
Journal: European Respiratory Journal (2014)

Background: Muscle wasting is one of the extrapulmonary features reflects exercise capacity and physical activity in chronic obstructive pulmonary disease (COPD). To assess the muscle wasting, dynamometer handgrip strength and fat free mass (FFM) were measured. Methods: We evaluated 76 patients with stable COPD in outpatient clinic. We measured the BODE index (body mass index; BMI, the forced expiratory volume in one second; FEV 1 , modified medical research council scale; mMRC, 6 minute walk test; 6MWT) and COPD assessment test (CAT) score at outpatient clinic visit. The average value of 3 times handgrip strengths, the FFM were measured and compared with BODE index and CAT score. Results: The mean age was 68.8±1.3 years and 62 patients (84.2%) were male. The average of FEV 1  was 66±28. Handgrip strength was well correlated with FFM (P=0.000). Handgrip strength showed significant correlations with mMRC (P=0.000) and 6MWT(P=0.013)  . FFM showed weak correlations with mMRC (P=0.754) and 6MWT (P=0.681). Both handgrip strength and FFM didn9t show significant correlation with BODE index score (handgrip strength: P=0.191, FFM: P=0.477) and CAT score (handgrip strength: P=0.173, FFM: P=0.833). Conclusions: Handgrip strength was the reliable method to evaluate the muscle wasting in stable COPD. Handgrip strength showed a significant correlations with mMRC and 6MWT, didn9t show correlations with the BODE index score and CAT score.
314. mRNA Production Is the Major Factor Limiting Autogene-Based Cytoplasmic Expression
Authors: Jonathan D. Finn, Ian MacLachlan, Pieter R. Cullis
Journal: Molecular Therapy (2004)

The relatively low levels of transfection that can be achieved by current gene delivery systems have limited the therapeutic utility of gene transfer. This is especially true for non-viral gene delivery systems, where the levels of gene expression achieved are usually well below the levels achieved by viral gene transfer systems. Previous work from our laboratory describes an enhanced dual promoter autogene-based cytoplasmic expression system that gives rise to levels of gene expression 20 fold higher than that of a CMV nuclear expression plasmid control. Here we describe various strategies to increase the levels of autogene based gene expression by changing variables such as the type of nuclear promoter, phage RNAP gene, and IRES sequence. It was found that none of these changes demonstrated a significant increase in gene expression. However determination of the mRNA levels achieved using quantitative RNase protection assays and immunofluorescence experiments, revealed transgene mRNA levels up to 10 times higher than all other mRNA in the transfected cell combined. It follows that mRNA production is a major factor limiting autogene based cytoplasmic expression.
63. Re-Directed Herpes Simplex Virus Infection by a Soluble, Bi-Specific Adapter Protein for gD in Combination with Nectin-1 Blocking Agents
Authors: Maria Vera, Laura Martinez, Mikel Zaratiegui, Carlos M. Rodriguez, Jesus Prieto, Puri Fortes
Journal: Molecular Therapy (2004)

One of the landmarks of advanced liver cirrhosis is the decrease of serum IGF-I levels probably due to its diminished synthesis from liver parenchyma. Patients with liver cirrhosis have a number of systemic derangements related to the reduced levels of circulating IGF-I. The administration of recombinant IGF-I in physiological doses reverts these symptoms and partially, the cirrhosis state. Recombinant viruses expressing a therapeutic protein are being used as an alternative for recombinant protein administration. We decided to study the efficiency of an IGF-I expressing recombinant vector based on Simian Virus 40 virus (SV40) to prevent liver cirrhosis in a rat model. Recombinant SV40 vectors have several advantages for this purpose. They efficiently infect hepatocytes, they have a long-term expression and they are non-immunogenic. We have produced recombinant viruses expressing firefly luciferase (rSVLuc) and rat IGFI-I (rSVIGF-I). Expression, secretion and activity of IGF-I by rSVIGF has been demonstrated in vitro by RIA and AKT activation in 3T3 cells. rSVLuc mouse liver infection has been visualised with a CCD camera for more than six moths. Luciferase liver expression in rSVLuc infected mice increased during liver regeneration, after CCl4 administration and in response to IGF-I. Healthy male Wistar rats were mock infected or intraportaly infected with rSVLuc or rSVIGF-I. Cirrhosis was induced by CCl4 inhalations during 36 weeks. rSVIGF-I infected rats had normal levels of transaminases, bilirubin and IGF-I binding proteins (IGFBPs) and a significant increase in IGFBP3, regulated by IGF-I. Control groups, saline and rSVLUC treated rats, had altered serum parameters, a significant decrease in testis weight and an increase in liver fibrosis formation. Quantitative RT-PCR from liver samples showed an increase in collagen, Timp1a and MIP1a expression and a decrease in IGF-I, HGF and IGFBP3 expression in control groups vs rSVIGF-I infected rats. These results indicate that the rSVIGF-I vector could be an efficient alternative for prevention and treatment of liver cirrhosis development.
Functional characterization of an IL-7–dependent CD4+CD8αα+ Th3-type malignant cell line derived from a patient with a cutaneous T-cell lymphoma
Authors: Eva Poszepczynska, Martine Bagot, Hamid Echchakir, Denis Martinvalet, Mohamed Ramez, Dominique Charue, Laurence Boumsell, Armand Bensussan
Journal: Blood (2000)