tbuckley/cabot-search huggingface dataset:
Abstract 2068: Combination erlotinib and cisplatin causes decrease angiogenesis in lung adenocarcinoma.
Authors: Jasmine G. Lee, Reen Wu
Journal: Cancer Research (2013)

Abstract Introduction: Platinum based agents such as cisplatin have been traditionally used to for the treatment of lung cancer, and tyrosine kinase inhibitors such as erlotinib are being used more readily. Combinations of anti-cancer agents are becoming more popular due to the anticipation that combination treatment is more effective than individual drug treatments. In this study, we evaluate the anti-cancer effects of combination erlotinib and cisplatin in in vitro cell lines and in in vivo mice models. In addition, as studies of cisplatin and erlotinib in other cancer types show potential to inhibit angiogenesis, we examine whether these agents are able to target angiogenesis in lung adenocarcinoma. Method: Three individual lung adenocarcinoma cell lines (PC9, A549, and H292) were utilized. Each cell line had four treatment groups: control, erlotinib only, cisplatin only, and combination erlotinib and cisplatin. Alamar Blue Assay was utilized to evaluate for in vitro cell death following two day treatments. PC9 cells were injected into the left flank of nude mice for in vivo experiments. Erlotinib and/or cisplatin treatments were injected directly into the tumor and tumor measurements were made every 2 days for a total of 14 days. Western blot analysis of VEGFR, p-VEGFR, and CD31was performed for both in vitro and in vivo samples. Hematoxylin and eosin (H&amp;E) staining and 3,3′-Diaminobenzidine (DAB) staining for CD31 were done on tumor samples. Results: Combination treatment in EGFR mutated PC9 cells led to significantly higher cell death compared to other treatment groups (P&amp;lt;0.0001); the effect was synergistic. In EGFR wild type A549 and H292 cell lines there were no significant differences. Similar to results from cell cultures, in vivo studies of combination treatment showed significant inhibition of tumor growth compared to other treatment groups (p=0.001). On western blot analysis, there were significantly lower levels of p-VEGFR (p&amp;lt;0.0001) and CD31 (p=0.0291) in the combination group compared to all other groups. H&amp;E staining shows significantly lower density of blood vessel and DAB staining of CD31in the combination group compared to other groups. Conclusions: Combination low dose erlotinib and cisplatin is able to induce synergistic cell death. This effect, however, may be specific to EGFR mutated lung adenocarcinoma. Combination treatment also demonstrated the ability to inhibit tumor growth in mice. The inhibition of tumor growth may be secondary to inhibition of angiogenesis. Citation Format: Jasmine G. Lee, Reen Wu. Combination erlotinib and cisplatin causes decrease angiogenesis in lung adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2068. doi:10.1158/1538-7445.AM2013-2068
Present status of autoimmune hepatitis in Japan - correlating the characteristics with international criteria in an area with a high rate of HCV infection
Authors: Gotaro Toda, Mikio Zeniya, Fumitoki Watanabe, Michio Imawari, Kendo Kiyosawa, Mikio Nishioka, Takao Tsuji, Masao Omata
Journal: Journal of Hepatology (1997)
Spontaneous photo-onycholysis
Authors: R.A. LOGAN, J.L.M. HAWK
Journal: British Journal of Dermatology (1985)

Journal Article Spontaneous photo‐onycholysis Get access R.A. LOGAN, R.A. LOGAN Department of Photobiology, St John's Hospital for Diseases of the Skin, 5 Lisle Street, London, WC2H 7BJ, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.L.M. HAWK J.L.M. HAWK Department of Photobiology, St John's Hospital for Diseases of the Skin, 5 Lisle Street, London, WC2H 7BJ, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue 5, 1 November 1985, Pages 605–610, https://doi.org/10.1111/j.1365-2133.1985.tb02386.x Published: 01 November 1985 Article history Accepted: 15 April 1985 Published: 01 November 1985
Profibrillatory Effects of Intracoronary Thrombus in Acute Regional Ischemia of the In Situ Porcine Heart
Authors: Ruben Coronel, Francien J. G. Wilms-Schopman, Michiel J. Janse
Journal: Circulation (1997)

An intracoronary thrombus during regional ischemia is related to life-threatening arrhythmias. The electrophysiological consequences of a thrombus are unknown.In open chest pigs, regional ischemia was induced by intracoronary injection of a thrombus (protocol 1). In protocol 2, coronary ligation was followed by injection of heparinized blood. Three consecutive episodes of ischemia (10 minutes) and reperfusion (20 minutes) were studied in protocols 3 and 4 (ligation). During the former, an intracoronary thrombus started the third period of ischemia. Multiple (78) local electrograms were recorded simultaneously, and activation patterns were determined. In a first period of ischemia, ventricular fibrillation (during the first 10 minutes) occurred more often after intracoronary thrombosis than during the other protocols (4/7 versus 2/19, P<.05) despite similar size of the ischemic tissue. The incidence of delayed arrhythmias (between 15 and 30 minutes) was not different. Epicardial activation delay was larger 2 to 4 minutes after intracoronary thrombosis compared with ligation. ST elevation was larger with than without a thrombus (2 minutes of ischemia, 12.9+/-4.1 versus 8.2+/-3.0 mV; +/-SD, P<.05). In protocols 3 and 4 the second period and third period of ischemia were similar irrespective of the presence of an intracoronary thrombus.More conduction slowing underlies the profibrillatory effect of an intracoronary thrombus relative to coronary ligation. After preconditioning with ischemia, the profibrillatory effects are no longer detectable.
Re: Tamoxifen May Be an Effective Treatment for BRCA1-Related Breast Cancer Irrespective of Estrogen Receptor Status
Authors: V. Cappelletti, S. Veneroni, D. Coradini, S. Oriana, G. Tomasic, M. Younes, M. G. Daidone
Journal: JNCI Journal of the National Cancer Institute (2003)
Synapses and Sisyphus: life without paraplegin
Authors: Harris A. Gelbard
Journal: Journal of Clinical Investigation (2004)

The family of neurodegenerative diseases known as hereditary spastic parapareses have diverse genetic loci, yet there is a remarkable convergence in the neuropathologic and neurologic phenotype. A report describing the construction of a transgenic mouse with a deletion of a nuclear-encoded mitochondrial protein involved in the regulation of oxidative phosphorylation suggests that this family of diseases may reflect activation of a final common pathway involving synaptic dysfunction that progresses to destruction of the presynaptic nerve terminal and axon.
Changes in Drug Utilization during a Gap in Insurance Coverage: An Examination of the Medicare Part D Coverage Gap
Authors: Jennifer M. Polinski, William H. Shrank, Haiden A. Huskamp, Robert J. Glynn, Joshua N. Liberman, Sebastian Schneeweiss
Journal: PLoS Medicine (2011)

Nations are struggling to expand access to essential medications while curbing rising health and drug spending. While the US government's Medicare Part D drug insurance benefit expanded elderly citizens' access to drugs, it also includes a controversial period called the "coverage gap" during which beneficiaries are fully responsible for drug costs. We examined the impact of entering the coverage gap on drug discontinuation, switching to another drug for the same indication, and drug adherence. While increased discontinuation of and adherence to essential medications is a regrettable response, increased switching to less expensive but therapeutically interchangeable medications is a positive response to minimize costs.We followed 663,850 Medicare beneficiaries enrolled in Part D or retiree drug plans with prescription and health claims in 2006 and/or 2007 to determine who reached the gap spending threshold, n = 217,131 (33%). In multivariate Cox proportional hazards models, we compared drug discontinuation and switching rates in selected drug classes after reaching the threshold between all 1,993 who had no financial assistance during the coverage gap (exposed) versus 9,965 multivariate propensity score-matched comparators with financial assistance (unexposed). Multivariate logistic regressions compared drug adherence (≤ 80% versus >80% of days covered). Beneficiaries reached the gap spending threshold on average 222 d ±79. At the drug level, exposed beneficiaries were twice as likely to discontinue (hazard ratio [HR] = 2.00, 95% confidence interval [CI] 1.64-2.43) but less likely to switch a drug (HR = 0.60, 0.46-0.78) after reaching the threshold. Gap-exposed beneficiaries were slightly more likely to have reduced adherence (OR = 1.07, 0.98-1.18).A lack of financial assistance after reaching the gap spending threshold was associated with a doubling in discontinuing essential medications but not switching drugs in 2006 and 2007. Blunt cost-containment features such as the coverage gap have an adverse impact on drug utilization that may conceivably affect health outcomes.
Detection of a gamma interferon-induced protein IP-10 in psoriatic plaques.
Authors: A B Gottlieb, A D Luster, D N Posnett, D M Carter
Journal: The Journal of Experimental Medicine (1988)

The pathologic features of psoriatic plaques are inflammation and increased epidermal turnover. IP-10, a cytokine the expression of which is induced by gamma-interferon, is a member of a family of soluble mediators with inflammatory and growth-promoting activities. IP-10 protein was detected in keratinocytes and the dermal infiltrate from active psoriatic plaques using an affinity-purified rabbit anti-IP-10 antibody in immunoperoxidase studies. Successful treatment of active plaques decreased IP-10 expression in plaques. These results were corroborated by Northern blot analysis with an IP-10 cDNA probe. We have previously detected activated T cells and HLA-DR keratinocytes in active psoriatic plaques. Since IP-10 is detected in delayed cellular immune responses, the present study further points to the role of ongoing cellular immune responses in the pathogenesis of psoriasis.
Abstract 5487: The requirements for dasatinib sensitivity in human melanoma cell lines
Authors: Jiri Vachtenheim, Jiri Réda, Lubica Ondrušová, Petra Zakova
Journal: Cancer Research (2014)

Abstract Mutated BRAF oncogene, which fuels unregulated MAPK pathway in most melanomas, can be targeted by a small-molecule drug vemurafenib. However, most of patients develop an acquired resistance during treatment or have an intrinsic resistance to this drug. Nonreceptor SRC tyrosine kinase is deregulated in most cancer cell types and can be efficiently inhibited by a small-molecule inhibitor dasatinib, an anticancer drug which is already used for the treatment of some cancers and is in final clinical trials for other tumor types. Although SRC does not have its own canonical pathway, it is capable of activating and augmenting different signaling routes in cancer cells. We found that melanoma tumor cell lines analysed up to date are generally resistant to dasatinib. The exception to this rule was Hbl, a very sensitive cell line whose cells were completely killed by a 10 nM of dasatinib in a few days. The difference in resistance of melanoma cell lines to dasatinib did not depend on primary versus metastatic cell origin or the presence of BRAF or NRAS mutations. Instead, the dasatinib sensitivity was dependent on its ability to inhibit completely both the MAPK and AKT/mTOR signaling pathways. This inhibition was at least as prominent as the inhibition by specific inhibitors of the two pathways. SRC has been reported previously to have links to this signaling pathways with the capacity to inhibit them in some cell types. Moreover, extensive cross-talk exists between the two pathways. Similar results were observed in several other cell lines derived mostly from lung and colorectal cancers. Our data indicate that the singular therapy of melanoma by dasatinib only would bring no benefit to patients, except for the cases (probably rare) where dasatinib strongly blocks both MAPK and AKT signaling pathways in tumor cells. More molecular knowledge about the effects of the powerful anticancer drug dasatinib is required in order to be used for the treatment of melanoma. This work was supported by grant IGA no. NT/14005-3 from the Ministry of Health (Czech Rep.) and by Institutional research project PRVOUK-P25/LF1/2. Citation Format: Jiri Vachtenheim, Jiri Réda, Lubica Ondrušová, Petra Zakova. The requirements for dasatinib sensitivity in human melanoma cell lines. [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 5487. doi:10.1158/1538-7445.AM2014-5487
Clinical Mechanism of the Cystic Fibrosis Transmembrane Conductance Regulator Potentiator Ivacaftor in G551D-mediated Cystic Fibrosis
Authors: Steven M. Rowe, Sonya L. Heltshe, Tanja Gonska, Scott H. Donaldson, Drucy Borowitz, Daniel Gelfond, Scott D. Sagel, Umer Khan, Nicole Mayer-Hamblett, Jill M. Van Dalfsen, Elizabeth Joseloff, Bonnie W. Ramsey
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator recently approved for patients with CF age 6 and older with the G551D mutation.To evaluate ivacaftor in a postapproval setting and determine mechanism of action and response of clinically relevant markers.We conducted a longitudinal cohort study in 2012-2013 in G551D CF patients age 6 and older with no prior exposure to ivacaftor. Study assessments were performed at baseline, 1, 3, and 6 months after ivacaftor initiation. Substudies evaluated mucociliary clearance, β-adrenergic sweat secretion rate, gastrointestinal pH, and sputum inflammation and microbiology Measurements and Main Results: A total of 151 of 153 subjects were prescribed ivacaftor and 88% completed the study through 6 months. FEV1 % predicted improved from baseline to 6 months (mean absolute change, 6.7%; P < 0.001). Similarly, body mass index improved from baseline to 6 months (mean change, 0.8 kg/m(2); P < 0.001). Sweat chloride decreased from baseline to 6 months (mean change, -53.8 mmol/L; 95% confidence interval, -57.7 to -49.9; P < 0.001), reflecting augmented CFTR function. There was significant improvement in hospitalization rate (P < 0.001) and Pseudomonas aeruginosa burden (P < 0.01). Significant improvements in mucociliary clearance (P < 0.001), gastrointestinal pH (P = 0.001), and microbiome were also observed, providing clinical mechanisms underlying the therapeutic benefit of ivacaftor.Significant clinical and physiologic improvements were observed on initiation of ivacaftor in a broad patient population, including reduced infection with P. aeruginosa. Biomarker studies substantially improve the understanding of the mechanistic consequences of CFTR modulation on pulmonary and gastrointestinal physiology.
18F-FDG PET/CT, 99mTc-MIBI, and MRI in the Prediction of Outcome of Patients With Multiple Myeloma
Authors: Rosa Fonti, Leonardo Pace, Claudio Cerchione, Lucio Catalano, Barbara Salvatore, Serena De Luca, Fabrizio Pane, Marco Salvatore, Silvana Del Vecchio
Journal: Clinical Nuclear Medicine (2015)

The aim of this study was to compare the relative contribution of 18F-FDG PET/CT, 99mTc-MIBI, and MRI in predicting progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM) patients.Thirty-three newly diagnosed MM patients had been evaluated in a previous study by 18F-FDG PET/CT, 99mTc-MIBI, and spine and pelvis MRI reporting focal lesions and diffuse bone marrow involvement. Twenty-seven patients were then subjected to a mean follow-up period of 58 months, whereas 6 patients were lost.18F-FDG PET/CT, 99mTc-MIBI, and MRI were positive in 26, 24, and 22 patients, respectively, showing diffuse bone marrow involvement in 12, 21, and 17 patients and a total of 185, 56, and 39 focal lesions, respectively. At follow-up, 18 patients showed complete or partial remission, whereas 9 patients developed progressive disease, 7 of which died of myeloma. Univariate and subsequent multivariate analysis showed that F-FDG PET/CT focal uptake and Tc-MIBI focal and diffuse uptake predicted PFS (P = 0.0006), whereas 18F-FDG PET/CT focal uptake and 99mTc-MIBI focal uptake predicted OS (P = 0.0010). Although MRI diffuse pattern predicted PFS at univariate analysis (P = 0.0376), it was not retained in the model at multivariate analysis. Receiver operating characteristic curve analysis showed that the number of focal lesions best discriminating for PFS and OS prediction was 4 and 11 for 18F-FDG PET/CT and 2 in both cases for 99mTc-MIBI, respectively. By Kaplan-Meier analysis and log-rank testing, PFS and OS at follow-up were significantly better in patients showing a number of focal lesions at F-FDG PET/CT or Tc-MIBI lower than the respective cutoff (P = 0.03, P = 0.004, and P < 0.0001, respectively). Finally, PFS was significantly better in patients showing absent/faint diffuse Tc-MIBI uptake than in those having moderate/intense diffuse uptake (P = 0.0012).18F-FDG PET/CT and 99mTc-MIBI may be useful in predicting PFS and OS in myeloma patients.
Safety of adjuvanted pandemic influenza A (H1N1) 2009 vaccines
Authors: F. DeStefano, C. Vellozzi, L. B. Schonberger, R. T. Chen
Journal: BMJ (2011)

Risk of Guillain-Barre syndrome, if any, is smaller than for 1976 swine flu vaccines

Guillain-Barre syndrome has been a focus of safety monitoring since the report in 1976 of an increased risk of almost one extra case per 100 000 influenza vaccinations of swine origin.1 Subsequent studies have shown either no increased risk or a slightly increased risk (1-2 per million vaccinees) after vaccination for seasonal flu.2 The spread of the 2009 pandemic influenza A (H1N1) virus, which contained genes of swine origin, resulted in the development and widespread use of influenza A (H1N1) monovalent vaccines (2009 H1N1 vaccines).3 These included formulations containing oil in water adjuvants that had not previously been widely used in flu vaccines in Europe. Although available evidence suggested that the adjuvanted vaccines had acceptable safety profiles,3 data on the risk of rare adverse events, such as Guillain-Barre syndrome, were limited.

In the linked study (doi:10.1136/bmj.d3908), Dieleman and colleagues report the first data on adjuvanted 2009 H1N1 vaccines and the risk of Guillain-Barre syndrome from a …
249 ACCURATE PERSONALIZATION OF PEG-IFN+RBV TREATMENT DURATION BASED ON THE DECLINE OF HCV INFECTED CELLS COMPUTED DURING THE 1ST MONTH OF THERAPY
Authors: P. Colombatto, V. Romagnoli, L. Civitano, P. Ciccorossi, A.M. Maina, F. Oliveri, B. Coco, B. Cherubini, F. Bonino, M.R. Brunetto
Journal: Journal of Hepatology (2010)
Blood Cadmium and Estimated Glomerular Filtration Rate in Korean Adults
Authors: Young Hwangbo, Virginia M. Weaver, Maria Tellez-Plaza, Eliseo Guallar, Byung-Kook Lee, Ana Navas-Acien
Journal: Environmental Health Perspectives (2011)

Cadmium is a nephrotoxicant at high exposure levels. Few studies have evaluated the role of cadmium in kidney function at low-exposure levels.We evaluated the association of blood cadmium with estimated glomerular filtration rate (eGFR) in the Korean adult population.We evaluated 1,909 adults ≥ 20 years of age who participated in the 2005 Korean National Health and Nutrition Examination Survey and had blood cadmium determinations. eGFR was calculated using the Modification of Diet in Renal Disease equation.Blood cadmium geometric means were 1.57 μg/L for men and 1.49 μg/L for women. The difference in eGFR levels that compared participants in the highest versus lowest cadmium tertiles, after multivariable adjustment, was -1.85 [95% confidence interval (CI): -3.55, -0.16] mL/min per 1.73 m2 in women and 0.67 (-1.16, 2.50) mL/min per 1.73 m2 in men. Among men, the association between blood cadmium and eGFR was modified by blood lead levels (p-value for interaction = 0.048). The fully adjusted differences in eGFR levels for a 2-fold increase in blood cadmium levels were -1.14 (-3.35, 1.07) and 1.84 (0.54, 3.14) mL/min per 1.73 m2 in men with blood lead levels below and above the median (2.75 μg/dL), respectively.Elevated blood cadmium levels were associated with lower eGFR in women, which supports the role of cadmium as a risk factor for chronic kidney disease. In men, there was no overall association, although elevated blood cadmium levels were associated with higher eGFR levels in men with high blood lead levels and nonstatistically associated with lower eGFR levels in men with low blood lead levels.
Early Versus Delayed Angiotensin-Converting Enzyme Inhibition Therapy in Acute Myocardial Infarction
Authors: Marc A. Pfeffer, Sally C. Greaves, J. Malcolm O. Arnold, Robert J. Glynn, Frances S. LaMotte, Richard T. Lee, Francis J. Menapace, Elliot Rapaport, Paul M. Ridker, Jean-Lucien Rouleau, Scott D. Solomon, Charles H. Hennekens
Journal: Circulation (1997)

Background Although ACE inhibitor therapy has been shown to reduce mortality in patients with acute myocardial infarction (MI), the optimal dose and the timing of its initiation have not been determined. Methods and Results In a double-blind trial of 352 patients with anterior MI, we compared the safety and effectiveness of early (day 1) versus delayed (day 14) initiation of the ACE inhibitor ramipril (10 mg) on echocardiographic measures of left ventricular (LV) area and ejection fraction (EF). An early, low-dose ramipril (0.625 mg) arm was also evaluated. Clinical events did not differ. During the first 14 days, the risk of manifesting a systolic arterial pressure of ≤90 mm Hg was increased in both ramipril groups. LVEF increased in all groups during this period, but the early, full-dose ramipril group had the greatest improvement in EF (increase: full, 4.9±10.0; low, 3.9±8.2%; delayed, 2.4±8.8%; P for trend &lt;.05) and was the only group that did not demonstrate a significant increase in LV diastolic area. Conclusions The results of the present study demonstrated that in patients with anterior MI, the early use of ramipril (titrated to 10 mg) attenuated LV remodeling and was associated with a prompter recovery of LVEF. The use of low-dose regimen did not prevent hypotension and had only intermediate benefits on LV size and function. The more favorable effects on LV topography of the early use of full-dose ramipril support the results of the major clinical trials, which have demonstrated an early survival benefit of ACE inhibition.
Abuse of Benzodiazepines
Authors: Siong-Chi Lin
Journal: JAMA (1989)

<h3>To the Editor.—</h3> The recent article by Woods et al<sup>1</sup>presented a good literature review of benzodiazepine use and abuse based on the reinforcing model of behavioral pharmacology. However, some of the conclusions and recommendations in the article created a sense of unease in those of us who work in a tertiary referral facility and regularly see patients suffering from iatrogenically fostered benzodiazepine dependence. Woods et al<sup>1</sup>concluded that "there is virtually no recreational or inappropriate use of benzodiazepines among patients for whom these drugs are prescribed" and that "psychological dependence is not a substantial risk of benzodiazepine therapy." A collection of seven cases at our institution that documented alprazolam dependence as defined by<i>DSM-III</i>(revised) criteria for psychoactive substance dependence was reported recently.<sup>2</sup>Between 1986 and 1988, two hundred ninety-three patients were treated in our Alcoholism and Drug Dependence Unit who were diagnosed as having benzodiazepine