tbuckley/cabot-search huggingface dataset:
Integrated PET-CT improves accuracy in staging of NSCLC compared with PET and CT alone
Authors: K Ryanna
Journal: Thorax (2003)

▴ Lardinois D, Weder W, Hany TF, et al . Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med2003;348:2500–7 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Positron emission tomography (PET) is increasingly used in the evaluation of non-small cell lung cancer. However, PET is imprecise in defining abnormal anatomy and computed tomography (CT) is superior. Scanners have been developed that incorporate PET and CT within the same … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.aulast%253DLardinois%26rft.auinit1%253DD.%26rft.volume%253D348%26rft.issue%253D25%26rft.spage%253D2500%26rft.epage%253D2507%26rft.atitle%253DStaging%2Bof%2BNon-Small-Cell%2BLung%2BCancer%2Bwith%2BIntegrated%2BPositron-Emission%2BTomography%2Band%2BComputed%2BTomography%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa022136%26rft_id%253Dinfo%253Apmid%252F12815135%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa022136&link_type=DOI [3]: /lookup/external-ref?access_num=12815135&link_type=MED&atom=%2Fthoraxjnl%2F58%2F9%2F789.atom [4]: /lookup/external-ref?access_num=000183577200004&link_type=ISI
Composition of Coronary Thrombus in Acute Myocardial Infarction
Authors: Johanne Silvain, Jean-Philippe Collet, Chandrasekaran Nagaswami, Farzin Beygui, Kathryn E. Edmondson, Anne Bellemain-Appaix, Guillaume Cayla, Ana Pena, Delphine Brugier, Olivier Barthelemy, Gilles Montalescot, John W. Weisel
Journal: Journal of the American College of Cardiology (2011)
Outcomes of Noninvasive Ventilation for Acute Exacerbations of Chronic Obstructive Pulmonary Disease in the United States, 1998–2008
Authors: Divay Chandra, Jason A. Stamm, Brian Taylor, Rose Mary Ramos, Lewis Satterwhite, Jerry A. Krishnan, David Mannino, Frank C. Sciurba, Fernando Holguín
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

The patterns and outcomes of noninvasive, positive-pressure ventilation (NIPPV) use in patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease (COPD) nationwide are unknown.
Short-hairpin RNA-induced suppression of adenine nucleotide translocase-2 in breast cancer cells restores their susceptibility to TRAIL-induced apoptosis by activating JNK and modulating TRAIL receptor expression
Authors: Ji-Young Jang, Yoon-Kyung Jeon, Yun Choi, Chul-Woo Kim
Journal: Molecular Cancer (2010)

Abstract Background Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL; apo2 ligand) induces apoptosis in cancer cells but has little effect on normal cells. However, many cancer cell types are resistant to TRAIL-induced apoptosis, limiting the clinical utility of TRAIL as an anti-cancer agent. We previously reported that the suppression of adenine nucleotide translocase-2 (ANT2) by short-hairpin RNA (shRNA) induces apoptosis of breast cancer cells, which frequently express high levels of ANT2. In the present study, we examined the effect of RNA shRNA-induced suppression of ANT2 on the resistance of breast cancer cells to TRAIL-induced apoptosis in vitro and in vivo . Results ANT2 shRNA treatment sensitized MCF7, T47 D, and BT474 cells to TRAIL-induced apoptosis by up-regulating the expression of TRAIL death receptors 4 and 5 (DR4 and DR5) and down-regulating the TRAIL decoy receptor 2 (DcR2). In MCF7 cells, ANT2 knockdown activated the stress kinase c-Jun N-terminal kinase (JNK), subsequently stabilizing and increasing the transcriptional activity of p53 by phosphorylating it at Thr81; it also enhanced the expression and activity of DNA methyltransferase 1 (DNMT1). ANT2 shRNA-induced overexpression of DR4/DR5 and TRAIL sensitization were blocked by a p53 inhibitor, suggesting that p53 activation plays an important role in the transcriptional up-regulation of DR4/DR5. However, ANT2 knockdown also up-regulated DR4/DR5 in the p53-mutant cell lines BT474 and T47 D. In MCF7 cells, ANT2 shRNA treatment led to DcR2 promoter methylation and concomitant down-regulation of DcR2 expression, consistent with the observed activation of DNMT1. Treatment of the cells with a demethylating agent or JNK inhibitor prevented the ANT2 shRNA-induced down-regulation of DcR2 and activation of both p53 and DNMT1. In in vivo experiments using nude mice, ANT2 shRNA caused TRAIL-resistant MCF7 xenografts to undergo TRAIL-induced cell death, up-regulated DR4/DR5, and down-regulated DcR2. Co-treatment with ANT2 shRNA and TRAIL efficiently suppressed tumor growth in these mice. Conclusions ANT2 suppression by shRNA might be exploited to overcome TRAIL-resistance in cancer.
Neurodegeneration in Alzheimer's disease: caspases and synaptic element interdependence
Authors: Dale E. Bredesen
Journal: Molecular Neurodegeneration (2009)

Extensive genetic, biochemical, and histological evidence has implicated the amyloid-beta peptide (Abeta) in Alzheimer's disease pathogenesis, and several mechanisms have been suggested, such as metal binding, reactive oxygen species production, and membrane pore formation. However, recent evidence argues for an additional role for signaling mediated by the amyloid precursor protein, APP, in part via the caspase cleavage of APP at aspartate 664. Here we review the effects and implications of this cleavage event, and propose a model of Alzheimer's disease that focuses on the critical nature of this cleavage and its downstream effects.
The next steps in next-gen sequencing of cancer genomes
Authors: D. Neil Hayes, William Y. Kim
Journal: Journal of Clinical Investigation (2015)

The necessary infrastructure to carry out genomics-driven oncology is now widely available and has resulted in the exponential increase in characterized cancer genomes. While a subset of genomic alterations is clinically actionable, the majority of somatic events remain classified as variants of unknown significance and will require functional characterization. A careful cataloging of the genomic alterations and their response to therapeutic intervention should allow the compilation of an "actionability atlas" and the creation of a genomic taxonomy stratified by tumor type and oncogenic pathway activation. The next phase of genomic medicine will therefore require talented bioinformaticians, genomic navigators, and multidisciplinary approaches to decode complex cancer genomes and guide potential therapy. Equally important will be the ethical and interpretable return of results to practicing oncologists. Finally, the integration of genomics into clinical trials is likely to speed the development of predictive biomarkers of response to targeted therapy as well as define pathways to acquired resistance.
Block of proliferation 1 (BOP1) plays an oncogenic role in hepatocellular carcinoma by promoting epithelial-to-mesenchymal transition
Authors: Kit-Ying Chung, Ibis K.-C. Cheng, Arthur K.-K. Ching, Jian-Hong Chu, Paul B.-S. Lai, Nathalie Wong
Journal: Hepatology (2011)

Abstract: Genomic amplification of regional chromosome 8q24 is a common event in human cancers. In hepatocellular carcinoma (HCC), a highly aggressive malignancy that is rapidly fatal, recurrent 8q24 gains can be detected in &gt;50% of cases. In this study, attempts to resolve the 8q24 region by way of array comparative genomic hybridization for affected genes in HCC revealed distinctive gains of block of proliferation 1 ( BOP1 ). Gene expression evaluation in an independent cohort of primary HCC (n = 65) revealed frequent BOP1 up-regulation in tumors compared with adjacent nontumoral liver (84.6%; P &lt; 0.0001). Significant associations could also be drawn between increased expressions of BOP1 and advance HCC staging ( P = 0.004), microvascular invasion ( P = 0.006), and shorter disease-free survival of patients ( P = 0.02). Examination of expression of C-MYC , a well-known oncogene located in proximity to BOP1 , in the same series of primary HCC cases did not suggest strong clinicopathologic associations. Functional investigations by small interfering RNA–mediated suppression of BOP1 in HCC cell lines indicated significant inhibition on cell invasion ( P &lt; 0.005) and migration ( P &lt; 0.05). Overexpression of BOP1 in the immortalized hepatocyte cell line L02 showed increase cellular invasiveness and cell migratory rate ( P &lt; 0.0001). In both gene knockdown and ectopic expression assays, BOP1 did not exert an effect on cell viability and proliferation. Evident regression of the epithelial-mesenchymal transition (EMT) phenotype was readily identified in BOP1 knockdown cells, whereas up-regulation of epithelial markers (E-cadherin, cytokeratin 18, and γ-catenin) and down-regulation of mesenchymal markers (fibronectin and vimentin) were seen. A corresponding augmentation of EMT was indicated from the ectopic expression of BOP1 in L02. In addition, BOP1 could stimulate actin stress fiber assembly and RhoA activation. Conclusion: Our findings underline an important role for BOP1 in HCC invasiveness and metastasis potentials through inducing EMT and promoting actin cytoskeleton remodeling. (HEPATOLOGY 2011;)
Erythropoietin: High Profile, High Scrutiny
Authors: Jeffrey Crawford
Journal: Journal of Clinical Oncology (2007)

Recombinant human erythropoietin has enjoyed a high profile status throughout its history in medicine. The isolation and purification of erythropoietin and the subsequent cloning of the humanprotein,followedbyclinicaltrialsdemonstratingthereversal of anemia in renal dialysis patients in the 1980s ushered in the era of biotechnology. 1 In the 1990s, randomized clinical trials demonstrated that recombinant human erythropoietin was also effectiveintreatmentofanemiaincancerpatientsreceivingchemotherapy. 2 Subsequent open label trials described the impact of erythropoietic therapy in patients with anemia related to cancer chemotherapy. 3-5 While these trials lacked a control group, the results were very high profile because of the thousands of patients treated. These data correlated the relationship, not only between rising hemoglobin and reduction in transfusion requirement, but also in defining the relationships between anemia, fatigue, and quality of life measures. 6 These results were further validated in a subsequent randomized placebo-controlled study. 7 These open label trials also were fundamental to defining the incremental improvement in quality of life measures with increasing hemoglobin levels in cancer chemotherapy patients, with an optimum hemoglobin level of 12 g/dL. 8 Based on these data and extensive
Systemic sclerosis after interferon-alfa therapy for myeloproliferative disorders
Authors: L. Beretta, M. Caronni, M. Vanoli, R. Scorza
Journal: British Journal of Dermatology (2002)

Journal Article Systemic sclerosis after interferon‐alfa therapy for myeloproliferative disorders Get access L. Beretta, L. Beretta Clinical Immunology and Allergology Unit, IRCCS Ospedale Maggiore and University of Milan, Via F. Sforza 35–20122 Milano, Italy E‐mail: Raffaella.scorza@unimi.it Search for other works by this author on: Oxford Academic Google Scholar M. Caronni, M. Caronni Clinical Immunology and Allergology Unit, IRCCS Ospedale Maggiore and University of Milan, Via F. Sforza 35–20122 Milano, Italy E‐mail: Raffaella.scorza@unimi.it Search for other works by this author on: Oxford Academic Google Scholar M. Vanoli, M. Vanoli Clinical Immunology and Allergology Unit, IRCCS Ospedale Maggiore and University of Milan, Via F. Sforza 35–20122 Milano, Italy E‐mail: Raffaella.scorza@unimi.it Search for other works by this author on: Oxford Academic Google Scholar R. Scorza R. Scorza Clinical Immunology and Allergology Unit, IRCCS Ospedale Maggiore and University of Milan, Via F. Sforza 35–20122 Milano, Italy E‐mail: Raffaella.scorza@unimi.it Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 147, Issue 2, 1 August 2002, Page 385, https://doi.org/10.1046/j.1365-2133.2002.48901.x Published: 01 August 2002
Transgenic mouse models for the chronic hepatitis B surface antigen carrier state: Transfection a deux
Authors: Adrian M. Di Bisceglie, Jay H. Hoofnagle
Journal: Hepatology (1986)

In an attempt to establish a model of the healthy carrier state in hepatitis B virus (HBV) infections, transgenic mice expressing HBV genes were produced. Fertilized one-cell eggs were microinjected with subgenomic fragments of HBV DNA containing the coding regions for the HBV surface antigen (HBsAg) and pre-S and×antigens. Either the normal (HBV) or metallothionein promoters were used to obtain expression of the HBV genes. There was no evidence of viral replication or tissue pathology. The integrated HBV DNA sequences were inherited in a normal Mendelian fashion. Three of 16 transgenic mice expressed HBV-encoded gene products to which they were immunologically tolerant. Expression was not tissue specific and may be influenced by the genomic integration site and cellular factors. Both HBsAg and pre-S antigen were detectable within the cytoplasm of hepatocytes and renal tubular epithelial cells. High serum concentrations of HBsAg were detectable and the secreted product appeared authentic as judged by mean density, morphology, mean particle diameter, polypeptide composition, and antigenicity. The absence of tissue pathology in these immunologically tolerant animals supports the hypothesis that cellular injury under these conditions is not a direct consequence of expression of the pre-S or HBs regions of the HBV genome. Two transgenic mice were obtained that contain in their chromosomes the complete hepatitis B virus (HBV) genome except for the core gene. These mice secrete particles of HBV surface antigen (HBsAg) in the serum. In one mouse, HBV DNA sequences that had integrated at two different sites were shown to segregate independently in the first filial generation (F1) and only one of the sequences allowed expression of the surface antigen. Among these animals the males produced five to ten times more HBsAg than the females. A 2.1-kilobase messenger RNA species comigrating with the major surface gene messenger RNA is expressed specifically in the liver in the two original mice. The results suggest that the HBV sequences introduced into the mice are able to confer a tissue-specific expression to the S gene. In addition, the HBV transgenic mice represent a new model for the chronic carrier state of hepatitis B virus infection.
P187 INNATE ANTIVIRAL RESPONSES IN HBeAg NEGATIVE PATIENTS WITH CHRONIC HEPATITIS B (CH-B) UNDER LONG-TERM NUCLEOS(T)IDE ANALOGUE (NUC) TREATMENT: IMPLICATIONS FOR FUTURE IMMUNE THERAPIES
Authors: C. Boni, P. Lampertico, L. Talamona, T. Giuberti, F. Invernizzi, S. Schivazappa, A. Alfieri, A. Cavalli, C. Cavallo, M. Colombo, G. Missale, C. Ferrari
Journal: Journal of Hepatology (2014)
Phase I Trial of Yttrium-90—Labeled Anti—Prostate-Specific Membrane Antigen Monoclonal Antibody J591 for Androgen-Independent Prostate Cancer
Authors: Matthew I. Milowsky, David M. Nanus, Lale Kostakoglu, Shankar Vallabhajosula, Stanley J. Goldsmith, Neil H. Bander
Journal: Journal of Clinical Oncology (2004)

Purpose To determine the maximum-tolerated dose (MTD), toxicity, human antihuman antibody (HAHA) response, pharmacokinetics, organ dosimetry, targeting, and preliminary efficacy of yttrium-90–labeled anti–prostate-specific membrane antigen monoclonal antibody J591 ( 90 Y-J591) in patients with androgen-independent prostate cancer (PC). Patients and Methods Patients with androgen-independent PC and evidence of disease progression received indium-111–J591 for pharmacokinetic and biodistribution determinations followed 1 week later by 90 Y-J591 at five dose levels: 5, 10, 15, 17.5, and 20 mCi/m 2 . Patients were eligible for up to three re-treatments if platelet and neutrophil recovery was satisfactory. Results Twenty-nine patients with androgen-independent PC received 90 Y-J591, four of whom were re-treated. Dose limiting toxicity (DLT) was seen at 20 mCi/m 2 , with two patients experiencing thrombocytopenia with non–life-threatening bleeding episodes requiring platelet transfusions. The 17.5-mCi/m 2 dose level was determined to be the MTD. No re-treated patients experienced DLT. Nonhematologic toxicity was not dose limiting. Targeting of known sites of bone and soft tissue metastases was seen in the majority of patients. No HAHA response was seen. Antitumor activity was seen, with two patients experiencing 85% and 70% declines in prostate-specific antigen (PSA) levels lasting 8 and 8.6 months, respectively, before returning to baseline. Both patients had objective measurable disease responses. An additional six patients (21%) experienced PSA stabilization. Conclusion The recommended dose for 90 Y-J591 is 17.5 mCi/m 2 . Acceptable toxicity, excellent targeting of known sites of PC metastases, and biologic activity in patients with androgen-independent PC warrant further investigation of 90 Y-J591 in the treatment of patients with PC.
The Use of Preliminary Scientific Evidence in Public Health: A Case Study of XMRV
Authors: Kumanan Wilson, Katherine Atkinson, Jennifer Keelan
Journal: PLoS Medicine (2014)

Kumanan Wilson and colleagues explain how the rapid response to XMRV as a novel pathogen has highlighted some challenges pertaining to policy-making and editorial responsibilities. The impact on policy and the propagation of the initial scientific information may not cease if the evidence is disproven and retracted from the peer-reviewed literature, which creates a challenge for regulators and scientific journals. Please see later in the article for the Editors' Summary
A STUDY OF BACILLUS PYOGENES
Authors: J. Howard Brown, Marion L. Orcutt
Journal: The Journal of Experimental Medicine (1920)

Bacillus pyogenes is probably quite common in this country, as it is known to be in Europe. A careful study of twelve strains from cattle and one from a hog has disclosed the following characteristics which have not been reported or have been in dispute. Bacillus pyogenes is Gram-positive and pleomorphic, producing forms ranging from short chains of streptococcoid elements to branching filaments. It is hemolytic, producing the beta type of hemolysis in blood agar. It is not hemoglobinophilic, though its growth is greatly favored by some higher protein material such as egg albumin, serum, or blood. It ferments xylose in addition to the substances previously reported. The coagulation of milk by Bacillus pyogenes is primarily an enzyme coagulation and the subsequent digestion of the curd takes place in an acid medium. The intravenous injection of rabbits was invariably fatal. The lesions most commonly developed were those of the bones. Paralysis was frequently produced, and in each case was caused by lesions in the vertebrae exerting pressure against the ventral columns of the spinal cord. Muscle abscesses were also frequently produced. The authors regard the organism as belonging to the Corynebacteria rather than to the influenza group.
Atopic dermatitis and allergic reactions to individual fragrance chemicals
Authors: J. M. L. White, I. R. White, I. Kimber, D. A. Basketter, D. A. Buckley, J. P. McFadden
Journal: Allergy (2009)

Allergic contact dermatitis prevalence is reported as equal in atopic and nonatopic dermatitis. Atopic dermatitis is under-represented in those with allergic contact dermatitis to agents having cutaneous and dietary exposure. We compared rates of atopic dermatitis between patients with allergic contact dermatitis arising out of individual fragrance chemicals with known oral/cutaneous exposure against exclusively cutaneous exposure.Between 1982 and 2007, 37 065 dermatitis patients were tested with Fragrance mix I. Those who were positive were tested for individual fragrance allergy. Chemicals were categorized according to whether their exposure pattern was solely cutaneous, oral or mixed. Current and past atopic dermatitis rates were compared between the whole population and groups allergic to individual fragrances. Age and gender were controlled.Cinnamic alcohol and cinnamal allergy groups had reduced rates of both 'current' [24/266 (9.0%) P = 0.0008, 38/364 (10.4%) P = 0.0005] and 'past' atopic dermatitis [44/266 (16.5%) P = 0.009, 70/346 (19.2%) P = 0.037]. Atopic dermatitis rates in groups allergic to Evernia prunastri and hydroxycitronellal (cutaneous exposure only) were not reduced [120/597 (20.1%) and 41/153 (26.8%)]. Groups allergic to cinnamic alcohol (P < 0.0001, P < 0.0001) and cinnamal (P < 0.0001, P < 0.004) had reductions in 'current' and 'past' atopic dermatitis, compared with Evernia prunastri.Patients allergic to individual fragrances with dietary exposure have reduced rates of atopic dermatitis. This suggests that patients with atopic dermatitis have heightened oral tolerance to dietary haptens, in contrast to the known close association of atopic dermatitis with food-protein allergy. Haptens may interfere with food protein tolerance by binding to soluble protein to alter its configuration and immunogenic profile.
STUDIES ON IMMUNOLOGICAL RELATIONSHIPS AMONG THE PNEUMOCOCCI
Authors: John Y. Sugg, Lurline V. Richardson, James M. Neill
Journal: The Journal of Experimental Medicine (1929)

Mice vaccinated with yeast were protected against subsequent infection with Type II pneumococci, but not against Types I or III. While the protection was not universal, as high a percentage of mice acquired active anti-Type II immunity, as was obtained by vaccination of another group of mice with Type II pneumococci themselves. This specific protection of mice by active immunization with the yeast antigen, is probably due to the same immunological relationship responsible for the anti-Type II reactivity of the antisera of rabbits immunized with yeast antigen.
Phase 1b Dose Escalation Study of Erlotinib in Combination with Infusional 5-Fluorouracil, Leucovorin, and Oxaliplatin in Patients with Advanced Solid Tumors
Authors: Axel-R. Hanauske, Jim Cassidy, Javier Sastre, Claus Bolling, Robert J. Jones, Ashok Rakhit, Scott Fettner, Ulrich Brennscheidt, Andrea Feyereislova, Eduardo Díaz-Rubio
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Erlotinib (Tarceva) is a potent epidermal growth factor receptor (HER1) inhibitor. Infusional 5-fluorouracil (5-FU), leucovorin, and oxaliplatin (FOLFOX) is a standard therapy for colorectal cancer. This trial assessed the maximum tolerated dose (MTD), safety, preliminary efficacy, and pharmacokinetics of erlotinib combined with FOLFOX. Experimental Design: Patients with advanced solid tumors were sequentially enrolled into three cohorts (cohort 1: 100 mg/d erlotinib, 65 mg/m2 oxaliplatin, 200 mg/m2 leucovorin, 400 mg/m2 bolus 5-FU, and 400 mg/m2 continuous infusion 5-FU; cohort 2: oxaliplatin increased to 85 mg/m2 and 5-FU infusion increased to 600 mg/m2; and cohort 3: erlotinib increased to 150 mg/d). Results: Thirty-two patients were enrolled (23 with colorectal cancer): no dose-limiting toxicities (DLT) were observed in cohort 1. In cohort 2, two of nine patients experienced a DLT (both diarrhea). In cohort 3, two of nine patients had a DLT (diarrhea and staphylococcal septicemia). Cohort 3 determined the MTD cohort and expanded to 17 patients in total. The most common adverse events were diarrhea, nausea, stomatitis, and rash (primarily mild/moderate). No pharmacokinetics interactions were observed. One patient (colorectal cancer) had a complete response, seven patients had a partial response, and nine had stable disease. Conclusions: The MTD was defined as follows: 150 mg/d erlotinib, 85 mg/m2 oxaliplatin; 200 mg/m2 leucovorin, 400 mg/m2 bolus 5-FU, and 600 mg/m2 infusion 5-FU. At the MTD, the combination was well tolerated and showed antitumor activity, warranting further investigation in patients with advanced colorectal cancer and other solid tumors.