tbuckley/cabot-search huggingface dataset:
Screening for Hepatitis C Virus Infection: A Review of the Evidence for the U.S. Preventive Services Task Force
Authors: Roger Chou, Elizabeth C. Clark, Mark Helfand
Journal: Annals of Internal Medicine (2004)

Background: Hepatitis C virus (HCV) is the most common bloodborne pathogen in the United States and is an important cause of patient morbidity and mortality, but it is unclear whether screening to identify asymptomatic infected persons is appropriate. Purpose: To synthesize the evidence on risks and benefits of screening for HCV infection. Data Sources: MEDLINE (through February 2003), Cochrane Clinical Trials Registry (2002, Issue 2), reference lists, and experts. Study Selection: Controlled studies of screening and antiviral therapy and observational studies on other interventions, risk factors, accuracy of antibody testing, work-up, harms of biopsy, and long-term outcomes. Data Extraction: Using preset criteria, the authors assessed the quality of included studies and abstracted information about settings, patients, interventions, and outcomes. Data Synthesis: There are no published trials of screening for HCV infection. Approximately 2% of U.S. adults have HCV antibodies, with the majority having chronic infection. Risk factor assessment could identify adults at substantially higher risk. Antiviral treatment can result in a sustained virologic response rate of 54% to 56%, but no trials have been done specifically in asymptomatic patients likely to be identified by screening. Data are insufficient to determine whether treatment improves long-term outcomes. There are no data to estimate the benefit from counseling or immunizations. Although risks of biopsy and treatment appear minimal or self-limited, data on other adverse effects of screening, such as labeling or anxiety, are sparse. Conclusions: Antiviral treatment can successfully eradicate HCV, but data on long-term outcomes in populations likely to be identified by screening are lacking. Although the yield from targeted screening, particularly in intravenous drug users, would be substantially higher than in the general population, data are inadequate to accurately weigh the overall benefits and risks of screening in otherwise healthy asymptomatic adults.
Tumor-dependent Kinetics of Partial Pressure of Oxygen Fluctuations during Air and Oxygen Breathing
Authors: L. Isabel Cárdenas-Navia, Daohai Yu, Rod D. Braun, David M. Brizel, Timothy W. Secomb, Mark W. Dewhirst
Journal: Cancer Research (2004)

Abstract The primary purpose of this study was to examine the kinetics of partial pressure of oxygen (pO2) fluctuations in fibrosarcoma (FSA) and 9L tumors under air and O2 breathing conditions. The overall hypothesis was that key factors relating to oxygen tension fluctuations would vary between the two tumor types and as a function of the oxygen content of the breathing gas. To assist in the interpretation of the temporal data, spatial pO2 distributions were measured in 10 FSA and 8 9L tumors transplanted into the subcutis of the hind leg of Nembutal-anesthetized (50 mg/kg) Fischer 344 rats. Recessed-tip oxygen microelectrodes were inserted into the tumor, and linear pO2 measurements were recorded in 50-μm steps along a 3-mm path, and blood pressure was simultaneously measured via femoral arterial access. Additionally, pO2 was measured at a single location for 90 to 120 minutes in FSA (n = 11) or 9L tumors (n = 12). Rats were switched from air to 100% O2 breathing after 45 minutes. Temporal pO2 records were evaluated for their potential radiobiological significance by assessing the number of times they crossed a 10-mm-Hg threshold. In addition, the data were subjected to Fourier analysis for air and O2 breathing. FSA and 9L tumors had spatial median pO2 measurements of 4 and 1 mm Hg, respectively. 9L had more low pO2 measurements ≤2.5 mm Hg than did FSA, whereas between 2.5 and 10 mm Hg this pattern was reversed. Pimonidazole staining patterns in FSA and 9L tumors supported these results. Temporal pO2 instability was observed in all experiments during air and O2 breathing. Threshold analyses indicated that the 10 mm Hg threshold was crossed 2 to 5 times per hour, independent of tumor type. However, the magnitude of 9L pO2 fluctuations was approximately eight times greater than FSA fluctuations, as assessed with Fourier transform analysis (Wilcoxon, P &amp;lt; 0.005). O2 breathing significantly increased median pO2 in FSA from 3 to 8 mm Hg (P &amp;lt; 0.005) and caused a significant increase in frequency and magnitude of pO2 fluctuations. One hundred percent O2 breathing had no effect on 9L tumor pO2, and it decreased the magnitude of pO2 fluctuations with borderline significance. These results show that these two tumors differ significantly with respect to spatial and temporal oxygenation conditions under air and O2 breathing. Fluctuations of pO2 of the type reported herein are predicted to significantly affect radiotherapy response and could be a source for genetic instability, increased angiogenesis, and metastases.
EpCAM As a Target in Cancer Therapy
Authors: Olivier Gires, Patrick A. Bauerle
Journal: Journal of Clinical Oncology (2010)

TOTHEEDITOR: In their editorial, Schmoll and Arnold 1 discussed possible reasons for the ultimate failure of anti– epithelial cell-cell adhesion molecule (EpCAM) murine monoclonal antibody edrecolomab in the treatment of patients with colorectal cancer. 2-4 While we appreciate their analysis and conclusions, certain aspects are missing or need correction that may be important for the future development of anti-EpCAM therapies and better understanding of EpCAM as a target. Like for every targeted therapy, the level of EpCAM target expression will have an impact on the outcome of a trial. This was evident for the human anti-EpCAM antibody adecatumumab in patients with metastatic breast cancer. 5 Although a high level and frequency of EpCAM expression can be assumed for patients with colorectal cancer, 6 none of the previous trials prospectively or retrospectively analyzed patients for levels of EpCAM expression on tumor tissue. Particularly for a low-affinity antibody, such as edrecolomab, it may be of importance that tumor cells express EpCAM at a high and not just at an intermediate level. Even for the high-affinity antibody trastuzumab only patients with a high level ofHER2 target expression are eligible for treatment. Future studies will certainly benefit from stratifying patients for their level of EpCAM target expression.
Treatment failure in tuberculosis
Authors: J. R. Panickar, W. Hoskyns
Journal: European Respiratory Journal (2006)

Treatment of latent tuberculosis (TB) infection with 3 months of rifampicin/isoniazid is a major part of preventive TB programmes. The effectiveness of treatment of latent TB infection can only be assessed by rates of subsequent breakdown and there are few outcome data for this combination of rifampicin/isoniazid. Therefore, the aim of the present study was to estimate the failure rate following treatment for the latent TB infection. A questionnaire survey was carried out in all parents of children aged <16 yrs who completed treatment for latent TB infection at Leicester Royal Infirmary (Leicester, UK) over the period 1997-2003. Cases of treatment failure were identified by reviewing all re-referrals to the clinic, identifying children developing TB while on treatment and by postal questionnaire to all patients discharged. Of the 400 eligible children, 344 (86%) replied. Three children who had latent TB infection subsequently developed TB disease over the time period. Of those three patients, one developed chest radiograph signs at the end of treatment and two presented with symptoms within 2 yrs of completing treatment. Overall, the mean treatment failure rate was 0.87% (95% confidence interval 0.3-2.5) or 2.2 cases per 1,000 patient-yrs. In conclusion, rates of tuberculosis breakdown after treatment for latent tuberculosis infection with 3 months rifampicin/isoniazid are acceptably low.
Electrocardiogram
Authors: Shlomo Stern
Journal: Circulation (2006)

ase presentation: A 22-yearold male, previously healthy, came to the outpatient clinic soon after an episode that he described as "near fainting" during complete rest, but at the time he was feeling strong anger because of a dispute with his friends.The physical examination was normal, but the resting 12-lead ECG, taken for the first time in his life, showed alterations diagnosed as Brugada syndrome (Figure).Holter monitoring showed the typical signs of the syndrome with no other abnormalities.The patient was referred for further evaluation, including family search for this syndrome, which turned out negative.Currently, implantation of an implantable cardioverter-defibrillator is being considered in a tertiary hospital for this patient.
Patterns of gastritis in patients with gastro-oesophageal reflux disease
Authors: D J Bowrey, G W B Clark, G T Williams
Journal: Gut (1999)

<h3>BACKGROUND</h3> The cause of inflammation in cardiac mucosa at the gastro-oesophageal junction (GOJ) is unclear, both gastro-oesophageal reflux disease (GORD) and<i>Helicobacter pylori </i>having been implicated. <h3>AIMS</h3> To describe patterns of gastritis in patients with symptomatic GORD. <h3>METHODS</h3> In 150 patients (126 normally located Z-line, 24 Barrett9s oesophagus) with symptoms of GORD, biopsies were taken of the GOJ, corpus, and antrum. Inflammation was assessed using the updated Sydney System. <h3>RESULTS</h3> For the 126 patients with a normally located Z-line, biopsies of the GOJ revealed cardiac mucosa in 96, fundic mucosa in 29, and squamous mucosa in one. Inflammation in glandular mucosa at the GOJ was present in 99/125 specimens (79%), including 87/96 (91%) with cardiac mucosa and 12/29 (41%) with fundic mucosa. Inflammation in fundic mucosa was closely related to<i>H pylori</i> and active inflammation was only seen in its presence. Inflammation in cardiac mucosa was less closely linked to <i>H pylori</i>. When<i>H pylori</i> was present in cardiac mucosa (28/96, 29%) active inflammation was usually present (25/28, 89%). However, active inflammation was also found in 34/68 (50%) cardiac mucosa specimens without <i>H pylori</i>. Overall, 28/87 (32%) biopsies with carditis were colonised with<i>H pylori</i> and 59/87 (68%) were not. In<i>H pylori</i> colonised patients, inflammation was seen throughout the stomach, while in non-colonised patients, it was confined to cardiac mucosa. <h3>CONCLUSIONS</h3> Patients with symptomatic GORD had a high prevalence of carditis. This was of two types, <i>H pylori</i> associated and unassociated. Except on Giemsa staining, the two were morphologically identical, suggesting mediation by a similar immunological mechanism.
Human Bone Marrow–Derived Mesenchymal Stem Cells for Intravascular Delivery of Oncolytic Adenovirus Δ24-RGD to Human Gliomas
Authors: Raymund L. Yong, Naoki Shinojima, Juan Fueyo, Joy Gumin, Giacomo G. Vecil, Frank C. Marini, Oliver Bogler, Michael Andreeff, Frederick F. Lang
Journal: Cancer Research (2009)

Delta24-RGD is an infectivity-augmented, conditionally replicative oncolytic adenovirus with significant antiglioma effects. Although intratumoral delivery of Delta24-RGD may be effective, intravascular delivery would improve successful application in humans. Due to their tumor tropic properties, we hypothesized that human mesenchymal stem cells (hMSC) could be harnessed as intravascular delivery vehicles of Delta24-RGD to human gliomas. To assess cellular events, green fluorescent protein-labeled hMSCs carrying Delta24-RGD (hMSC-Delta24) were injected into the carotid artery of mice harboring orthotopic U87MG or U251-V121 xenografts and brain sections were analyzed by immunofluorescence for green fluorescent protein and viral proteins (E1A and hexon) at increasing times. hMSC-Delta24 selectively localized to glioma xenografts and released Delta24-RGD, which subsequently infected glioma cells. To determine efficacy, mice were implanted with luciferase- labeled glioma xenografts, treated with hMSC-Delta24 or controls, and imaged weekly by bioluminescence imaging. Analysis of tumor size by bioluminescence imaging showed inhibition of glioma growth and eradication of tumors in hMSC-Delta24-treated animals compared with controls (P < 0.0001). There was an increase in median survival from 42 days in controls to 75.5 days in hMSC-Delta24-treated animals (P < 0.0001) and an increase in survival beyond 80 days from 0% to 37.5%, respectively. We conclude that intra-arterially delivered hMSC-Delta24 selectively localize to human gliomas and are capable of delivering and releasing Delta24-RGD into the tumor, resulting in improved survival and tumor eradication in subsets of mice.
<i>JCO</i> and the Public Trust
Authors: Daniel G. Haller
Journal: Journal of Clinical Oncology (2005)

The Journal of Clinical Oncology (JCO) prides itself in publishing the highest quality research.Articles published in the Journal are highly cited, ranking JCO among the best peer-reviewed journals in oncology.The American Society of Clinical Oncology (ASCO) and the JCO editors take seriously the responsibility of ensuring that every published article contains trustworthy data that remain free from allegations of potential conflicts of interest in the publication process.The peer review process itself is structured to preclude editorial decisions based on potential conflicts of the reviewers and editors, but further steps are necessary to ensure the continued credibility of the Journal and the trust of the readership and the public. Concerns About Conflicts of InterestIn addition to the readers, conflicts of interest can affect three participants in the publication of scientific articles: editors, reviewers, and authors.Since its inception, the JCO has had a strict conflict of interest policy that conforms to the "Uniform Requirements for Manuscripts Submitted to Biomedical Journals," a set of standards developed by the International Committee of Medical Journal Editors (ICMJE). 1 The Journal has always practiced the principle of disclosure-the cornerstone of any conflict of interest policy.The Editorin-Chief and the Associate Editors annually disclose all potential conflicts of interest relative to their journal activities; these disclosures are reviewed by ASCO leadership.When manuscripts are submitted for which an editor may have a potential conflict of interest, that editor is prevented from having any knowledge or contact
Immunologic Aspects of Pernicious Anemia
Authors: W. James Irvine
Journal: New England Journal of Medicine (1965)

THERE were two facts that suggested that immunologic factors may be of importance in the study of Addisonian (pernicious) anemia. In the first place, this condition has a high incidence in patients with thyroid disease,1 in which autoimmune phenomena are a frequent occurrence.2 Secondly, the histology of the gastric mucosa in pernicious anemia is characterized by atrophy of the specialized cells of the body of the stomach, and this is accompanied by a variable but often marked degree of lymphocytic infiltration.Antibody to Gastric Parietal-Cell CytoplasmBy the method of complement fixation, the serum of 75 per cent of patients . . .
A Dual Phosphoinositide-3-Kinase α/mTOR Inhibitor Cooperates with Blockade of Epidermal Growth Factor Receptor in <i>PTEN</i>-Mutant Glioma
Authors: Qi-Wen Fan, Christine K. Cheng, Theodore P. Nicolaides, Christopher S. Hackett, Zachary A. Knight, Kevan M. Shokat, William A. Weiss
Journal: Cancer Research (2007)

Abstract We have shown previously that blockade of epidermal growth factor receptor (EGFR) cooperates with a pan-selective inhibitor of phosphoinositide-3-kinase (PI3K) in EGFR-driven glioma. In this communication, we tested EGFR-driven glioma differing in PTEN status, treating with the EGFR inhibitor erlotinib and a novel dual inhibitor of PI3Kα and mTOR (PI-103). Erlotinib blocked proliferation only in PTENwt cells expressing EGFR. Although erlotinib monotherapy showed little effect in PTENmt glioma, PI-103 greatly augmented the antiproliferative efficacy of erlotinib in this setting. To address the importance of PI3K blockade, we showed in PTENmt glioma that combining PI-103 and erlotinib was superior to either monotherapy or to therapy combining erlotinib with either rapamycin (an inhibitor of mTOR) or PIK-90 (an inhibitor of PI3Kα). These experiments show that a dual inhibitor of PI3Kα and mTOR augments the activity of EGFR blockade, offering a mechanistic rationale for targeting EGFR, PI3Kα, and mTOR in the treatment of EGFR-driven, PTEN-mutant glioma. [Cancer Res 2007;67(17):7960–5]
Positron Emission Tomography–Computed Tomography (PET-CT) After Induction Therapy Is Highly Predictive of Patient Outcome in Follicular Lymphoma: Analysis of PET-CT in a Subset of PRIMA Trial Participants
Authors: Judith Trotman, Marion Fournier, Thierry Lamy, John Francis Seymour, Anne Sonet, Andrea Janikova, Ofer Shpilberg, Emmanuel Gyan, Hervé Tilly, Jane Estell, Cecily Forsyth, Didier Decaudin, Bettina Fabiani, Jean Gabarre, Bruno Salles, Eric Van Den Neste, Danielle Canioni, Etienne Garin, Michael Fulham, Thierry Vander Borght, Gilles Salles
Journal: Journal of Clinical Oncology (2011)

The utility of [(18)F]fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in assessing response at the end of induction therapy is well documented in Hodgkin's and diffuse large B-cell lymphomas, but its role in follicular lymphoma (FL) remains undetermined. We investigated the prognostic significance of PET-CT performed after first-line therapy in patients with FL treated in the prospective Primary Rituximab and Maintenance (PRIMA) study.Results of PET-CT scans performed after induction immunochemotherapy were recorded retrospectively. Patients went on to either observation or rituximab maintenance per protocol independent of the PET-CT result. Patient characteristics and outcomes were then evaluated.Of 122 PET-CT scans performed at the end of the induction immunochemotherapy, 32 (26%) were reported as positive by the local investigator. Initial demographic or disease characteristics did not differ between PET-CT-positive (PET-positive) and PET-CT-negative (PET-negative) patients. PET status correlated with conventional response criteria (P < .001). Patients remaining PET positive had a significantly (P < .001) inferior progression-free survival at 42 months of 32.9% (95% CI, 17.2% to 49.5%) compared with 70.7% (95% CI, 59.3% to 79.4%) in those who became PET negative. PET status, but not conventional response (complete response or complete response unconfirmed v partial response) according to IWC 1999, was an independent predictive factor for lymphoma progression. The risk of death was also increased in PET-positive patients (hazard ratio 7.0; P = .0011).[(18)F]FDG PET-CT status at the end of immunochemotherapy induction in patients with FL is strongly predictive of outcome and should be considered a meaningful clinical end point in future studies.
Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells.
Authors: R Schreck, B Meier, D N Männel, W Dröge, P A Baeuerle
Journal: The Journal of Experimental Medicine (1992)

Dithiocarbamates and iron chelators were recently considered for the treatment of AIDS and neurodegenerative diseases. In this study, we show that dithiocarbamates and metal chelators can potently block the activation of nuclear factor kappa B (NF-kappa B), a transcription factor involved in human immunodeficiency virus type 1 (HIV-1) expression, signaling, and immediate early gene activation during inflammatory processes. Using cell cultures, the pyrrolidine derivative of dithiocarbamate (PDTC) was investigated in detail. Micromolar amounts of PDTC reversibly suppressed the release of the inhibitory subunit I kappa B from the latent cytoplasmic form of NF-kappa B in cells treated with phorbol ester, interleukin 1, and tumor necrosis factor alpha. Other DNA binding activities and the induction of AP-1 by phorbol ester were not affected. The antioxidant PDTC also blocked the activation of NF-kappa B by bacterial lipopolysaccharide (LPS), suggesting a role of oxygen radicals in the intracellular signaling of LPS. This idea was supported by demonstrating that treatment of pre-B and B cells with LPS induced the production of O2- and H2O2. PDTC prevented specifically the kappa B-dependent transactivation of reporter genes under the control of the HIV-1 long terminal repeat and simian virus 40 enhancer. The results from this study lend further support to the idea that oxygen radicals play an important role in the activation of NF-kappa B and HIV-1.
Hypoadiponectinemia Is Associated With Progression Toward Type 2 Diabetes and Genetic Variation in the <i>ADIPOQ</i> Gene Promoter
Authors: Peter E.H. Schwarz, Gordon W. Towers, Sabine Fischer, Suresh Govindarajalu, Jan Schulze, Stephan R. Bornstein, Markolf Hanefeld, Francis Vasseur
Journal: Diabetes Care (2006)

Adiponectin encoded by the ADIPOQ gene modulates insulin sensitivity and glucose homeostasis. The aim of the current study was to investigate whether ADIPOQ gene variants in the promoter region predict adiponectin levels and type 2 diabetes progression.A total of 550 subjects with increased risk of type 2 diabetes were investigated; they underwent a 75-g oral glucose tolerance test, repeated after 3 years. Adiponectin levels were analyzed, and two ADIPOQ promoter variant single nucleotide polymorphisms, -11391G>A and -11377C>G, were genotyped.Tertiles of the adjusted adiponectin levels were associated with single nucleotide polymorphism -11391G>A and -11377C>G haplotypes (P < 0.0001). Carriers of the intermediate/high-level haplotype combination showed a bisected diabetes risk at the 3-year follow-up and were characterized by a "regression" of glucose tolerance. Evolution of disease status correlates with preexisting low adiponectin levels at inclusion rather than with variation in adiponectin levels.We present data that gene variants in the ADIPOQ promoter region are associated with variations in adiponectin levels and thus with future type 2 diabetes and disease progression.