tbuckley/cabot-search huggingface dataset:
Fibroblast Growth Factor Receptor 1 Gene Amplification Is Associated With Poor Survival and Cigarette Smoking Dosage in Patients With Resected Squamous Cell Lung Cancer
Authors: Hye Ryun Kim, Dae Joon Kim, Dae Ryong Kang, Jin Gu Lee, Sun Min Lim, Chang Young Lee, Sun Young Rha, Mi Kyung Bae, Young Joo Lee, Se Hoon Kim, Sang-Jun Ha, Ross Andrew Soo, Kyung Young Chung, Joo Hang Kim, Ji Hyun Lee, Hyo Sup Shim, Byoung Chul Cho
Journal: Journal of Clinical Oncology (2012)

Purpose To investigate the frequency and the prognostic role of fibroblast growth factor receptor 1 (FGFR1) amplification in patients with surgically resected squamous cell carcinoma of the lung (SCCL) and the association between smoking and FGFR1 amplification. Patients and Methods Gene copy number of FGFR1 was investigated in microarrayed tumors from 262 patients with SCCL who had tumor tissue as well as smoking and survival data available. Gene copy number was evaluated by fluorescent in situ hybridization, and an FGFR1-amplified tumor (FGFR1 amp + ) was prespecified as a tumor with nine or more copies of FGFR1. Results Among 262 patients, the frequency of FGFR1 amp + was 13.0%. Patients with FGFR1 amp + had significantly shorter disease-free survival (DFS; 26.9 v 94.6 months; P &lt; .001) as well as shorter overall survival (OS; 51.2 v 115.0 months; P = .002) than those without FGFR1 amp + . Multivariate modeling confirmed that patients with FGFR1 amp + had a significantly greater risk of recurrence and death than those without FGFR1 amp + after adjusting for sex, smoking status, pathologic stage, and adjuvant chemotherapy (DFS: adjusted hazard ratio [AHR], 2.24; 95% CI, 1.45 to 3.45; P &lt; .001; OS: AHR, 1.83; 95% CI, 1.15 to 2.89; P = .01). The frequency of FGFR1 amp + was significantly higher in current smokers than in former smokers and never-smokers (28.9% v 2.5% v 0%; P trend &lt; .001). As the smoking dosage increased, so did the incidence of FGFR1 amp + (P trend = .002). Conclusion FGFR1 amplification is an independent negative prognostic factor in surgically resected SCCL and is associated with cigarette smoking in a dose-dependent manner. FGFR1 amplification is a relevant therapeutic target in Asian patients with SCCL.
Targeted Antiangiogenesis Gene Therapy Using Targeted Cationic Microbubbles Conjugated with CD105 Antibody Compared with Untargeted Cationic and Neutral Microbubbles
Authors: Yu Zhou, Haitao Gu, Yan Xu, Fan Li, Shaojing Kuang, Zhigang Wang, Xiyuan Zhou, Huafeng Ma, Pan Li, Yuanyi Zheng, Haitao Ran, Jia Jian, Yajing Zhao, Weixiang Song, Qiushi Wang, Dong Wang
Journal: Theranostics (2015)

Objective This study aimed to develop targeted cationic microbubbles conjugated with a CD105 antibody (CMB105) for use in targeted vascular endothelial cell gene therapy and ultrasound imaging.We compared the results with untargeted cationic microbubbles (CMB) and neutral microbubbles (NMB).Methods CMB105 were prepared and compared with untargeted CMB and NMB.First, the microbubbles were characterized in terms of size, zeta-potential, antibody binding ability and plasmid DNA loading capacity.A tumor model of subcutaneous breast cancer in nude mice was used for our experiments.The ability of different types of microbubbles to target HUVECs in vitro and tumor neovascularization in vivo was measured.The endostatin gene was selected for its outstanding antiangiogenesis effect.For in vitro experiments, the transfection efficiency and cell cycle were analyzed using flow cytometry, and the transcription and expression of endostatin were measured by qPCR and Western blotting, respectively.Vascular tube cavity formation and tumor cell invasion were used to evaluate the antiangiogenesis gene therapy efficiency in vitro.Tumors were exposed to ultrasound irradiation with different types of microbubbles, and the gene therapy effects were investigated by detecting apoptosis induction and changes in tumor volume.Results CMB105 and CMB differed significantly from NMB in terms of zeta-potential, and the DNA loading capacities were 16.76±1.75μg, 18.21±1.22μg, and 0.48±0.04μg per 5×10 8 microbubbles, respectively.The charge coupling of plasmid DNA to CMB105 was not affected by the presence of the CD105 antibody.Both CMB105 and CMB could target to HUVECs in vitro, whereas only CMB105 could target to tumor neovascularization in vivo.In in vitro experiments, the transfection efficiency of CMB105 was 24.7-fold higher than the transfection efficiency of NMB and 1.47-fold higher than the transfection efficiency of CMB (P<0.05).With ultrasound-targeted Ivyspring
Optimal glycemic control is associated with a lower rate of target vessel revascularization in treated type II diabetic patients undergoing elective percutaneous coronary intervention
Authors: Roberto A Corpus, Peter B George, John A House, Simon R Dixon, Steven C Ajluni, William H Devlin, Gerald C Timmis, Mamtha Balasubramaniam, William W O'Neill
Journal: Journal of the American College of Cardiology (2004)
A Step in the Maturation of the Field of Lifestyle Change Interventions
Authors: William J. McCarthy
Journal: Journal of Clinical Oncology (2007)

The report by Vallance et al in this issue represents another important step in the maturation of the field of lifestyle change interventions applied to cancer survivors. If oncologist attitudes are an indication, there is already a consensus that exercise is beneficial (62.0%), important (55.8%), and safe (63.1%) for patients with cancer during treatment. Despite these positive attitudes, only 28% of oncologists had recommended exercise to their patients in the last month. The field must continue to mature in terms of its scientific sophistication and credibility of its conclusions to justify to policy makers the expenditure of resources necessary to make exercise central to the rehabilitation of the cancer patient, as it is has been for two decades to the rehabilitation of the older coronary heart disease patient. The report by Vallance et al addresses some of the weaknesses noted in reviews of the literature evaluating the impact of physical activity interventions on breast cancer survivor outcomes. However, further maturation of the field will require more attention to causal mechanisms and mediational pathways, to issues involving adherence to the prescribed lifestyle changes, to identifying more cost-effective ways to expose patients to the physical activity prescription, and to tailoring type, frequency, duration, and intensity of physical activity prescription to the specific needs of patients.
Postoperative chemoradiotherapy for gastric cancer
Authors: S.H. Park, D.Y. Kim, J.S. Heo, D.H. Lim, C.K. Park, K.W. Lee, S.H. Choi, T.S. Sohn, S. Kim, J.H. Noh, Y.I. Kim, J.O. Park, K. Kim, W.S. Kim, C.W. Jung, Y.H. Im, M.H. Lee, K. Park, C.H. Park, W.K. Kang
Journal: Annals of Oncology (2003)
Silencing of Transforming Growth Factor-β1 <i>In situ</i> by RNA Interference for Breast Cancer: Implications for Proliferation and Migration <i>In vitro</i> and Metastasis <i>In vivo</i>
Authors: Lakisha D. Moore, Tatyana Isayeva, Gene P. Siegal, Selvarangan Ponnazhagan
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Overexpression of transforming growth factor (TGF)-β has been implicated in promoting immune suppression, tumor angiogenesis, tumor cell migration, and invasion in many cancers, including carcinoma of the breast. Thus, targeted down-regulation of TGF-β1 expression in breast cancer in situ and determination of its implications would provide new treatment approaches for disease management. Experimental Design: Small interfering RNA constructs targeting TGF-β1 were validated and used to develop clonal derivatives of the metastatic breast cancer cell line MDA-MB-435. The cells were used in several in vitro analyses, including migration, invasion, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, apoptosis, and signaling assays. A wound-healing assay was used to determine migration of the cells in culture and a Boyden chamber transwell assay was used for invasion. Further, the clones were used in an in vivo mouse model for the kinetics of tumor growth and gene expression in the primary site and in lungs upon metastasis. Results: Inhibition of TGF-β1 expression in MDA-MB-435 cells showed a 35% decrease in migration and a 55% decrease in invasion in vitro, with a 50% increase in proliferation and no effect on apoptosis. In vivo analysis indicated a 90% decrease in the number of mice bearing macroscopic lung metastases; however, the primary tumors did not show any difference in the growth kinetics when compared with the parental MDA-MB-435 cells. Analysis of TGF-β signaling pathways in the clonal derivatives showed a decrease in Smad2 activation and an increase in AKT and extracellular signal-regulated kinase activation. Interestingly, analysis of TGF-β receptor expression showed a decrease in both receptor I and II expression in TGF-β1 silenced cells. These results suggest that inhibition of TGF-β1 ligand may act as a negative feedback loop to disrupt the function of all TGF-β isoforms. Conclusions: Therapies targeting the TGF-β signaling pathway may be more effective in late-stage disease to prevent organ metastasis but not primary tumor formation and may be combined with other tumor-targeted therapies normally limited by increased circulating TGF-β levels.
Improved performance of epidemiologic and genetic risk models for rheumatoid arthritis serologic phenotypes using family history
Authors: Jeffrey A Sparks, Chia-Yen Chen, Xia Jiang, Johan Askling, Linda T Hiraki, Susan Malspeis, Lars Klareskog, Lars Alfredsson, Karen H Costenbader, Elizabeth W Karlson
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> To develop and validate rheumatoid arthritis (RA) risk models based on family history, epidemiologic factors and known genetic risk factors. <h3>Methods</h3> We developed and validated models for RA based on known RA risk factors, among women in two cohorts: the Nurses' Health Study (NHS, 381 RA cases and 410 controls) and the Epidemiological Investigation of RA (EIRA, 1244 RA cases and 971 controls). Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC) in logistic regression models for the study population and for those with positive family history. The joint effect of family history with genetics, smoking and body mass index (BMI) was evaluated using logistic regression models to estimate ORs for RA. <h3>Results</h3> The complete model including family history, epidemiologic risk factors and genetics demonstrated AUCs of 0.74 for seropositive RA in NHS and 0.77 for anti-citrullinated protein antibody (ACPA)-positive RA in EIRA. Among women with positive family history, discrimination was excellent for complete models for seropositive RA in NHS (AUC 0.82) and ACPA-positive RA in EIRA (AUC 0.83). Positive family history, high genetic susceptibility, smoking and increased BMI had an OR of 21.73 for ACPA-positive RA. <h3>Conclusions</h3> We developed models for seropositive and seronegative RA phenotypes based on family history, epidemiological and genetic factors. Among those with positive family history, models using epidemiologic and genetic factors were highly discriminatory for seropositive and seronegative RA. Assessing epidemiological and genetic factors among those with positive family history may identify individuals suitable for RA prevention strategies.
Interferon responsiveness in patients infected with hepatitis C virus 1b differs depending on viral subtype
Authors: I Nakano, Y Fukuda, Y Katano, H Toyoda, K Hayashi, T Hayakawa, T Kumada, S Nakano
Journal: Gut (2001)

Genotype 1b of hepatitis C virus (HCV) comprises mainly three subtypes, each named for its geographic prevalence (worldwide, W; Japan, J; and not in Japan, NJ).To characterise the newly identified subtypes of genotype 1b and to review factors associated with response to interferon (IFN) for each subtype.Chronic hepatitis patients (80 men and 41 women; mean age 48.5 years, range 20.7--69.3) with HCV genotype 1b (W type, n=41; J type, n=38) or genotype 2a (n=42) were treated according to the same IFN protocol. Forty four patients (36.4%) negative for serum HCV RNA six months after cessation of treatment were considered complete responders.Factors associated with complete response were investigated.Genotype 2a patients had lower viral loads (odds ratio 0.11 (95% confidence intervals (CI) 0.049--0.256)) and a better IFN response (odds ratio 0.25 (95% CI 0.117--0.552)) than genotype 1b patients whereas W type and J type patients had similar viral loads and responses to IFN. IFN response in W type patients was associated with female sex (odds ratio 0.23 (95% CI 0.055--0.983)) and low viral load (odds ratio 84.00 (95% CI 14.04--502.6)) whereas response in J type patients was related to transfusion history (odds ratio 7.20 (95% CI 1.443--35.91)), low viral load (odds ratio 117.0 (95% CI 17.82--768.3)), and genetic mutation in the interferon sensitivity determining region of the virus (odds ratio 0.08 (95% CI 0.013--0.553)). Multivariate analysis found low viral load (odds ratio 64.19 (95% CI 14.66--281.06)) to be the only significant independent factor associated with IFN response.Factors associated with IFN responsiveness in HCV infection differ with viral subtype.
Marked increase of the growth factors pleiotrophin and fibroblast growth factor-2 in serum of testicular cancer patients
Authors: A. Aigner, P. Brachmann, J. Beyer, R. Jäger, D. Raulais, M. Vigny, A. Neubauer, A. Heidenreich, S. Weinknecht, F. Czubayko, G. Zugmaier
Journal: Annals of Oncology (2003)
Identification of an alternative Gαq-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes
Authors: Guixiu Shi, Santiago Partida-Sánchez, Ravi S. Misra, Michael Tighe, Michael T. Borchers, James J. Lee, Melvin I. Simon, Frances E. Lund
Journal: The Journal of Experimental Medicine (2007)

CD38 controls the chemotaxis of leukocytes to some, but not all, chemokines, suggesting that chemokine receptor signaling in leukocytes is more diverse than previously appreciated. To determine the basis for this signaling heterogeneity, we examined the chemokine receptors that signal in a CD38-dependent manner and identified a novel “alternative” chemokine receptor signaling pathway. Similar to the “classical” signaling pathway, the alternative chemokine receptor pathway is activated by Gαi2-containing Gi proteins. However, unlike the classical pathway, the alternative pathway is also dependent on the Gq class of G proteins. We show that Gαq-deficient neutrophils and dendritic cells (DCs) make defective calcium and chemotactic responses upon stimulation with N-formyl methionyl leucyl phenylalanine and CC chemokine ligand (CCL) 3 (neutrophils), or upon stimulation with CCL2, CCL19, CCL21, and CXC chemokine ligand (CXCL) 12 (DCs). In contrast, Gαq-deficient T cell responses to CXCL12 and CCL19 remain intact. Thus, the alternative chemokine receptor pathway controls the migration of only a subset of cells. Regardless, the novel alternative chemokine receptor signaling pathway appears to be critically important for the initiation of inflammatory responses, as Gαq is required for the migration of DCs from the skin to draining lymph nodes after fluorescein isothiocyanate sensitization and the emigration of monocytes from the bone marrow into inflamed skin after contact sensitization.
Gene Tree Parsimony of Multilocus Snake Venom Protein Families Reveals Species Tree Conflict as a Result of Multiple Parallel Gene Loss
Authors: Nicholas R. Casewell, Simon C. Wagstaff, Robert A. Harrison, Wolfgang Wüster
Journal: Molecular Biology and Evolution (2010)

The proliferation of gene data from multiple loci of large multigene families has been greatly facilitated by considerable recent advances in sequence generation. The evolution of such gene families, which often undergo complex histories and different rates of change, combined with increases in sequence data, pose complex problems for traditional phylogenetic analyses, and in particular, those that aim to successfully recover species relationships from gene trees. Here, we implement gene tree parsimony analyses on multicopy gene family data sets of snake venom proteins for two separate groups of taxa, incorporating Bayesian posterior distributions as a rigorous strategy to account for the uncertainty present in gene trees. Gene tree parsimony largely failed to infer species trees congruent with each other or with species phylogenies derived from mitochondrial and single-copy nuclear sequences. Analysis of four toxin gene families from a large expressed sequence tag data set from the viper genus Echis failed to produce a consistent topology, and reanalysis of a previously published gene tree parsimony data set, from the family Elapidae, suggested that species tree topologies were predominantly unsupported. We suggest that gene tree parsimony failure in the family Elapidae is likely the result of unequal and/or incomplete sampling of paralogous genes and demonstrate that multiple parallel gene losses are likely responsible for the significant species tree conflict observed in the genus Echis. These results highlight the potential for gene tree parsimony analyses to be undermined by rapidly evolving multilocus gene families under strong natural selection.
Inhibiting long chain fatty Acyl CoA synthetase increases basal and agonist-stimulated NO synthesis in endothelium*1
Authors: M WEIS
Journal: Cardiovascular Research (2004)

Endothelial nitric oxide synthase (eNOS) activation/deactivation is associated with cyclic depalmitoylation/repalmitoylation of specific Cys residues. The mechanism of depalmitoylation has been identified recently, but repalmitoylation remains undefined. We hypothesized that long chain fatty acyl CoA synthetase (LCFACoAS) modulates endothelial nitric oxide synthase repalmitoylation by limiting palmitoyl CoA availability.Human coronary endothelial cells were treated with triacsin-C, an inhibitor of long chain fatty acyl CoA synthetase, for 24 h. Media nitrite accumulation, eNOS activity, and eNOS palmitoylation were measured. Methacholine-induced NO synthesis or vascular relaxation were measured in endothelium-intact rat aortae in the presence and absence of triacsin-C.Triacsin-C significantly reduced incorporation of [3H] palmitate into immunoreactive endothelial nitric oxide synthase and over a concentration range of 0.1 to 10 microM, increased media nitrite accumulations 2- to 2.5-fold over baseline. Total in vitro catalytic activity of nitric oxide synthase in triacsin-C treated cells did not differ significantly from control. Triacsin-C significantly increased methacholine-induced NO synthesis in the isolated rat aorta, and significantly enhanced methacholine-induced relaxation of rat aortic rings.These data are consistent with the interpretation that inhibition of palmitoylation increases endothelial nitric oxide synthase activity without changing endothelial nitric oxide synthase expression, suggesting that inhibiting palmitoylation increases the catalytically active fraction of endothelial nitric oxide synthase.
Origin and interstate spread of a New York City multidrug-resistant Mycobacterium tuberculosis clone family
Authors: P. J. Bifani
Journal: JAMA (1996)

To determine whether isolates of Mycobacterium tuberculosis from New York and elsewhere that are resistant to four or more primary antimicrobial agents and responsible for widespread disease in the 1990s represent a newly emerged clone or a heterogeneous array of unrelated organisms.New York City area and selected locations in the United States.M tuberculosis isolates from 1953 patients in New York and multidrug-resistant isolates from six patients from other US communities.Convenience sample of all M tuberculosis strains (M tuberculosis isolates resistant to rifampin, streptomycin, isoniazid, and ethambutol, and sometimes ethionamide, kanamycin, capreomycin, or ciprofloxacin) submitted to the Public Health Research Institute Tuberculosis Center since 1991 and samples submitted to the Centers for Disease Control and Prevention from throughout the United States. The samples submitted were representative of the New York City strains of M tuberculosis.Characterization of resistant M tuberculosis strains studied by IS6110 and polymorphic GC-rich repetitive sequence (PGRS) hybridization patterns, multiplex polymerase chain reaction (PCR) analysis, and automated DNA sequencing of genes containing mutations associated with resistance to rifampin (rpoB), isoniazid (katG and inhA locus), and streptomycin (strA and rrs).Multidrug-resistant M tuberculosis isolates were recovered from 253 New York City patients and had the same or closely allied IS6110 and PGRS patterns, multiplex PCR type, and gene mutations associated with resistance to rifampin, isoniazid, and streptomycin. Isolates with these same molecular characteristics were recovered from patients in Florida and Nevada, health care workers in Atlanta, Ga, and Miami, Fla, and an individual who recently moved from New York City to Denver, Colo, and caused disease or skin test conversion in at least 12 people in a nursing home environment.The results document the molecular origin and spread of progeny of a closely related family of multidrug-resistant M tuberculosis strains that have recently shared a common ancestor and undergone clonal expansion. The multidrug-resistant phenotype in these organisms arose by sequential acquisition of resistance-conferring mutations in several genes, most likely as a consequence of antibiotic selection of randomly occurring mutants in concert with inadequately treated infections. Dissemination of these difficult-to-treat bacteria throughout New York City and to at least four additional US cities has adverse implications for tuberculosis control in the 21st century.
Direct evidence that coronary perfusion affects diastolic myocardial mechanical properties in canine heart
Authors: J. R Resar, R. M Judd, H. R Halperin, V. P Chacko, R. G Weiss, F. C P Yin
Journal: Cardiovascular Research (1993)

Objective: The effect of coronary perfusion on left ventricular chamber distensibility is only indirect evidence that perfusion alters the mechanical properties of the myocardium. The aim of this study was to demonstrate explicitly the effects of coronary perfusion on these mechanical properties. Methods: The effects of different levels of coronary perfusion were studied both on in-plane stress-strain relations and on transverse stiffness in an isolated, perfused canine interventricular septal preparation. Additionally, to determine the vascular compartment responsible for the mechanical effects of perfusion on tissue properties, we examined the in-plane stress-strain responses and transverse stiffness after embolisation of the vasculature with 15 μm microspheres. Results: The data show a clear dependence of tissue stress-strain properties on perfusion. The in-plane stress-strain relations were shifted to the left and transverse stiffness increased linearly as septal artery perfusion pressure increased. The dependence of both the in-plane stress-strain relations and transverse stiffness on perfusion was significantly decreased following embolisation. Conclusions: Myocardial tissue stiffness is directly related to perfusion. The linear relationship between transverse stiffness and perfusion makes it easier to assess the effects of perfusion on tissue stiffness than with in-plane stress-strain relations. Perfusion of capillaries and/or venules is largely responsible for these alterations in myocardial stiffness. Cardiovascular Research 1993;27:403-410