tbuckley/cabot-search huggingface dataset:
Treatment of Cytomegalovirus Retinitis with a Sustained-Release Ganciclovir Implant
Authors: David C. Musch, Daniel F. Martin, Judy F. Gordon, Matthew D. Davis, Baruch D. Kuppermann
Journal: New England Journal of Medicine (1997)

Sustained-release, intraocular implants that deliver ganciclovir are an alternative method for the treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS).We conducted a randomized study of 188 patients with AIDS and newly diagnosed cytomegalovirus retinitis. The patients were randomly assigned to treatment with an implant delivering 1 microg of ganciclovir per hour, an implant delivering 2 microg of ganciclovir per hour, or intravenous ganciclovir. The primary outcome we studied was progression of cytomegalovirus retinitis.The median time to progression of retinitis was 221 days with the 1-microg-per-hour implant (75 eyes), 191 days with the 2-microg-per-hour implant (71 eyes), and 71 days with ganciclovir administered intravenously (76 eyes; P<0.001). The risk of progression of retinitis was almost three times as great among patients treated with intravenous ganciclovir as among those treated with a ganciclovir implant (risk ratio, 2.8; P<0.001). However, the risk of disease in the initially uninvolved eye was lower with intravenous ganciclovir than with a ganciclovir implant (risk ratio, 0.5; P=0.19). Patients treated with intravenous ganciclovir were also less likely to have extraocular cytomegalovirus infections (0, vs. 10.3 percent in the two implant groups; P=0.04).For the treatment of cytomegalovirus retinitis, the sustained-release ganciclovir implant is more effective than intravenous ganciclovir, but patients treated with a ganciclovir implant alone remain at greater risk for the development of cytomegalovirus disease outside of the treated eye.
S99 Effects Of Differential Tnf Receptor Signalling In Modulating Neutrophil-endothelial Interactions In The Pulmonary Microvasculature
Authors: A. Proudfoot, J. Juss, S. Appleby, P. Morley, J. Cordy, A. Bayliffe, M. Hind, E. Chilvers, M. Griffiths, C. Summers
Journal: Thorax (2014)

<h3></h3> Neutrophil recruitment into the bronchoalveolar space is central to the pathogenesis of acute respiratory distress syndrome injury (ARDS), and occurs via interaction with the lung microvascular endothelium. Tumour Necrosis Factor (TNF) is a key mediator in these processes, activating endothelial cells and inducing changes in microvascular permeability, as well as priming neutrophils (a pre-requisite for neutrophil-mediated tissue damage) and modulating neutrophil lifespan. TNF signals through two cell surface receptors, TNFR1 and TNFR2 initiating distinct signalling pathways and cellular responses. In a human <i>in vivo</i> model of ARDS, selective TNFR1 antagonism attenuated pulmonary inflammation (O’Kane <i>et al</i>, Thorax 2013; 63:A50). Using TNF receptor specific muteins and a novel highly selective TNFR1 antagonist, we investigated the role of differential TNFR signalling on neutrophil-pulmonary microvascular endothelial cell interactions. TNF-induced alterations in the expression of the neutrophil cell surface molecules CD11b, CD62L, TNFR1 and TNFR2 were all modulated via TNFR1. TNFR1 was also the dominant receptor mediating reactive oxygen species generation by TNF-primed, fMLP-stimulated neutrophils. We further examined the role of TNF receptors in modulating neutrophil apoptosis; whilst engagement of both TNFR1 and 2 was required to induce early neutrophil apoptosis, TNFR1 antagonism reversed TNF-induced late survival to constitutive levels of apoptosis. TNFR1 antagonsim of human pulmonary microvascular endothelial monolayers significantly reduced TNF-induced production of IL-1beta, IL-6 and IL-8 (p &lt; 0.05), endothelial permeability and the release of the endothelial injury markers sICAM-1, sVCAM-1 and sE-selectin (p Collectively, these results suggest that TNFR1 regulates multiple components of neutrophil-endothelial interactions. Selective TNFR1 antagonism may offer a novel therapeutic approach in ARDS; phase II clinical trials of this therapy are scheduled.
Abstract 3082: TGF-β synergistically stimulates malignant mesothelioma growth with defects in the Hippo pathway by inducing CTGF expression
Authors: Makiko Fujii, Takeshi Toyoda, Hayao Nakanishi, Yasushi Yatabe, Ayuko Sato, Yasue Matsudaira, Hidemi Ito, Hideki Murakami, Yutaka Kondo, Eisaku Kondo, Tohru Tsujimura, Toyoaki Hida, Hirotaka Osada, Yoshitaka Sekido
Journal: Cancer Research (2012)

Abstract Malignant mesothelioma (MM) arises from the serosal cells of the pleural, peritoneal and pericardial cavities with poor prognosis because of its frequent diagnosis in advanced stages. The primary cause of this disease has often been linked to asbestos exposure, and the number of patients worldwide is expected to peak in the next two decades. There is no known curative therapy for MM and further understanding in molecular mechanism is needed to identify new candidates for targeted treatment. We found that the TGF-β pathway is associated with oncogenic mutations and loss of the tumor suppressor NF2, and induces pro-oncogenic biological activities. Loss of NF2 is one of the genetic lesions which have been related to the growth of human MM. The NF2 gene is responsible for neurofibromatosis type II syndrome and encodes Merlin which negatively regulates YAP function. Nearly 75% MM cases have inactivating mutations in the NF2 gene or in downstream signaling molecules of Hippo signaling cascade. We examined a functional interaction between the Hippo and TGF-β pathways and found that endothelin-1 and connective tissue growth factor (CTGF) are the only proteins affected by these two pathways in MM cells. The CTGF promoter contains both a YAP/TEAD-binding site and a consensus Smad-binding site adjacent to each other. The expression of CTGF induced by TGF-β in MM cell lines was greatly affected by the existence of YAP, by its binding with Smad3, forming a complex on CTGF promoter lesion. Knocking down CTGF expression in MM cells prolonged the survival of mice, and a significant association was seen between CTGF expression and extracellular matrix deposition in MM xenografts and in patient tissue specimens. This study elucidates a novel molecular mechanism induced by the TGF-β pathway, which may be applicable to malignancies with defective NF2 and of mesenchymal origin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3082. doi:1538-7445.AM2012-3082
Hypovitaminosis D in a Sunny Country
Authors: Ghada El-Hajj Fuleihan, Mary Deeb
Journal: New England Journal of Medicine (1999)

entitled "Cat Scratch Disease" might convey the misleading message that masses assumed to be caused by either B. henselae (cat scratch), as shown, or mycobacteria (e.g., Mycobacterium avium complex and others) should be treated with direct puncture and drainage.Such an erroneous approach frequently leads to a draining sinus with an avoid-The New England Journal of Medicine Downloaded from nejm.org
Abstract 1407: A transgenic mouse model for the Hedgehog pathway effector GLI1 induced mammary gland tumors.
Authors: Jens H. Norum, Agneta Andersson, Maria Kasper, Therese Sørlie, Rune Toftgård
Journal: Cancer Research (2013)

Abstract Increased expression of the Hedgehog (Hh) signaling pathway effector GLI1 in breast cancer patients has been shown to correlate inversely with disease free and overall survival. Activation of the Hh signaling pathway is known to promote proliferation of breast cancer cells and stimulate mammosphere formation. In addition, the Hh signaling pathway has been reported activated in CD44 positive breast cancer stem cells. Despite the evidence supporting a role for Hh signaling in breast cancer development and maintenance, the model systems to study the Hh pathway in breast carcinogenesis are limited. We used a transgenic mouse model to show that GLI1 expression in the mammary gland cause tumor formation. The GLI1 induced primary tumors showed different histological characteristics, suggesting that the GLI1 expression influenced the tumor initiating cells. The GLI1 induced primary tumors were orthotopically transplanted on NOD/SCID mice and we have established serial transplantable tumor lines. The different histological characteristics of the individual primary tumors have been maintained for &amp;gt;10 serial transplantations in NOD/SCID mice. The stem cell marker CD44 is expressed in the mouse mammary gland ducts. The CD44 positive cell population is increased in the GLI1 induced tumors. The G protein coupled receptor (GPCR) like protein Lgr5 has been suggested as a stem cell marker in several tissues, including mammary gland. We show that cells in the basal layer of the adult mammary gland ducts express Lgr5. The Lgr5 positive cell population is increased in the GLI1 induced tumors, suggesting a basal like characteristic of these tumors. Taken together, our data show that expression of GLI1 in the mammary gland result in formation of mammary gland tumors with heterogeneous histological characteristics. The cell populations identified by the stem cell markers CD44 or Lgr5 are increased in the GLI1 induced tumors compared with the normal mammary gland. Furthermore, we have established serial transplantable GLI1 induced mammary gland tumor lines. These serial transplantable tumor lines are novel tools to address the role of GLI1 expression in breast carcinogenesis. Citation Format: Jens H. Norum, Agneta Andersson, Maria Kasper, Therese Sørlie, Rune Toftgård. A transgenic mouse model for the Hedgehog pathway effector GLI1 induced mammary gland tumors. [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 1407. doi:10.1158/1538-7445.AM2013-1407
Reply to Linghu et al.
Authors: H. Mori, H. Kobara, S. Fujihara, N. Nishiyama, T. Masaki
Journal: Endoscopy (2011)

Briefly, we performed aseptic procedures in the same manner as those in a routine surgical operation. We completely disinfected the operative field and the endoscopic route from the oral cavity to the gastric cavity. First, we placed a split barrel (TOP Corp., Tokyo, Japan) to enable the insertion of two endoscopes. Then, using the disinfectant povidine iodine, we disinfected the patient’s entire face and the mouth piece connected to the overtube. Through the overtube, a conventional endoscope was used to place a duodenal balloon into the stomach. After proper balloon placement, the endoscope was removed while spraying 1 % povidine iodine over the balloon, gastric cavity (antrum, corpus, and fundus), esophagus, and overtube. At this point, the endoscope was considered to be contaminated, and thus a second endoscope that had been sterilized with ethylene oxide gas was inserted while spraying sodium thiosulfate hydrate to neutralize the povidine iodine. After completely neutralizing the povidine iodine, we used physiological saline to wash the gastric cavity, esophagus, and overtube. We then completed the sterilization routine by aspirating accumulated fluid in the gastric cavity.
Abstract 5203: Domains that distinguish Akt1 from Akt2 in cell migration
Authors: Sharmila B. Natarajan, Guo-Lei Zhou, Jeffrey M. Field
Journal: Cancer Research (2010)

Abstract Domains that distinguish Akt1 from Akt2 in cell migration Sharmila B. Natarajan, Guo-Lei Zhou and Jeffrey Field Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 The Akt family of kinases, Akt1, Akt2 and Akt3 are activated in many cancers where they play critical role in cell survival, metabolism and migration. There are distinctive roles for Akt1 and Akt2 in cell migration where, depending on the cell type, loss of Akt1 can either stimulate or inhibit cell migration. Previous work from our lab demonstrated that loss of Akt2 stimulated cell motility and that, based on chimeras, the kinase domains of Akt1 and Akt2 are interchangeable. Specificity is conferred by the PH domain and a linker domain that separates the PH domain from the kinase domain. To address regions that are required to rescue Akt1 knockouts, which have reduced cell motility, we performed rescue experiments with mouse embryo fibroblasts from Akt1 knockout mice. Our results are in concordance with a study by E. K. Kim et al., (Cell Signaling, 2008) where they found that the linker region is again likely to confer specificity. Importantly, we found that a new construct, in which only the linker domain of Akt1 was swapped into Akt2, stimulated cell migration of Akt1 knockouts. Additionally, we find that both Akt1 and Akt2 associate with the Pak protein kinase but through different mechanisms. These studies suggest that differences in interaction with Pak may underlie the opposing effects of Akt1 and Akt2 on cell migration. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5203.
Port-Site Metastasis After Laparoscopic Removal of an Isolated Adrenal Metastasis in a Patient With Breast Cancer Detected With FDG PET/CT
Authors: Kornélia Kajáry, Péter Molnár, Zsolt Lengyel, Szabolcs Szakáll
Journal: Clinical Nuclear Medicine (2013)

Adrenal metastasis from breast cancer rarely occurs in the course of this disease. Laparoscopic surgery has increased in the therapy for malignant tumors because of its lower morbidity and mortality compared with conventional surgical methods. However, complications such as the appearance of a port-site metastasis may also occur. Clinical examination and conventional cross-sectional imaging usually reveal this only at advanced stage. The authors reported on a case with abdominal wall port-site metastasis detected with 18F-FDG PET/CT 33 months after the laparoscopic removal of a late-onset, PET/CT-verified adrenal metastasis from lobular breast cancer.
AORTIC ANNULUS SIZING FOR TRANSAPICAL HEART VALVE IMPLANTATION: AN AGREEMENT ANALISYS OF DIFFERENT THREE-DIMENSIONAL TRANSOESOPHAGEAL ECHOCARDIOGRAPHIC MODALITIES AND CARDIAC COMPUTED TOMOGRAPHY SCAN
Authors: Vincenzo Polizzi, Pino Paolo Giuseppe, Giampaolo Luzi, Diego Bellavia, Rosario Fiorilli, Claudia Chialastri, Andrea Madeo, Myriam Lo Presti, Joseph Malouf, Vitaliano Buffa, Francesco Musumeci
Journal: Journal of the American College of Cardiology (2015)
Severe Hypoprothrombinemia Following Propylthiouracil Treatment of Thyrotoxicosis
Authors: Charles G. Craddock, Donald Shotton, Charles L. Crockett, Byrd S. Leavell
Journal: New England Journal of Medicine (1951)

THE following report concerns a case of severe hemorrhagic diathesis appearing during the course of propylthiouracil treatment of thyrotoxicosis. The fundamental defect was a marked prolongation of the prothrombin time, transient in nature. The case is unusual in two respects. First, the prothrombin deficiency occurred as an isolated phenomenon without evidence of liver damage or depression of white blood cells; second, the hemorrhagic tendency was quickly ameliorated by the administration of fresh homologous human serum and whole blood.Case ReportE. L. M., a 16-year-old schoolgirl, was admitted to the University of Virginia Hospital June 10, 1949, because of profuse . . .
Abstract 3433: A furin/MMP-14 signaling cascade processes BAI1 into a novel secreted anti-angiogenic and anti-tumorigenic factor, Vasculostatin-40 (Vstat40)
Authors: Sarah Cork, Eric M. Sandberg, Balveen Kaur, Hui Mao, Zhaobin Zhang, Jeffrey Olson, Erwin G. Van Meir
Journal: Cancer Research (2010)

Abstract Mechanisms of vascular development and maintenance in the brain are not well-understood, but vascular integrity is compromised in many neurological diseases, particularly highly aggressive glioblastoma multiforme (GBM), which co-opts the existing vasculature and induces extensive angiogenesis. Brain angiogenesis inhibitor 1 (BAI1), a brain-enriched transmembrane receptor, has been proposed to be an endogenous regulator of brain angiostasis, but its mechanisms of action are largely unknown. In the present work, we investigate the proteolysis of extracellular BAI1 using genetic and molecular biology techniques to show that the large extracellular domain of BAI1 is proteolytically cleaved to generate an abundant product of 40 kDa we named Vasculostatin-40 (Vstat40). We demonstrate that cleavage of Vstat40 from BAI1 is dependent on a two-step process of proteolytic activation. In the final step of the cascade, Vstat40 is directly processed from extracellular BAI1 by membrane type-matrix metalloproteinase 1 (MMP-14). We show that the upstream activity of proprotein convertases, primarily furin, plays an important role in facilitating this processing event. We confirm the significance of Vstat40 as an important angio-regulatory factor by demonstrating that it inhibits angiogenesis in culture in a CD36-dependent manner. Finally, we present data on the effect of Vstat40 on intracranial glioma growth using an orthotopic xenograft model in order to illustrate its potential as a future therapeutic. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3433.
SAT0269 Self esteem in patients with ankylosing spondylitis and its relationships with disease-specific variables and psychological status
Authors: H. Bahouq, H. Rkain, F. Allali, N. Hajjaj Hassouni
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ankylosing spondylitis (AS) is a chronic disease, which causes deformities and workforce decline. This, in turn, might lead to psychological distress and less self esteem. <h3>Objectives</h3> Our objective was to determine the relationship between self esteem, psychological well-being and disease parameters in AS patients. <h3>Methods</h3> One hundred patients (30 women, 70 men, mean age 38.88±12.6 years) were included in this cross-sectional study according to the modified New York criteria for AS. Psychological status was assessed by the Hospital Anxiety and Depression Scale including the depression and anxiety subscales. Pain, disease activity and functional status were respectively assessed by visual analogue scale, the Bath Ankylosing Spondylitis Disease Activity Index and the Bath Ankylosing Spondylitis Functional Index. Finally, to assess fatigue and self esteem we have used Multidimensional Assessment of Fatigue and Rosenberg scale for self esteem. <h3>Results</h3> Only 29% of AS patients have a good self esteem. Patients who had low self esteem were suffering from depression and anxiety more than patients with good self esteem (respectively 69 vs. 6.9%; p&lt;0.0001 and 33.8 vs. 6.9%; p=0.005). Low self esteem correlated with the disease activity (r= -0.48), functional status (r= -0.44), fatigue (r= -0.57), depression (r= -0.76), anxiety (r= -0.53) (for all p&lt;0.0001) and pain (r= -0.29; p=0.004)). Multivariate logistic regression analysis revealed that depression (OR=1.526; IC 95% (1.205-1.932); p&lt;0.0001) and disease activity (OR=1.595; IC 95% (1.015-2.506; p=0.04) were the independent risk factors of low self esteem. <h3>Conclusions</h3> This study suggests that AS patients are suffering from a low self esteem. Disturbance of self esteem in this chronic rheumatism seems to be closely related to an active disease and a bad psychological status. Those results should be confirmed by larger studies. <h3>Disclosure of Interest</h3> None Declared
GE-06 * IDENTIFICATION OF TARGETABLE MUTATIONS IN RARE PEDIATRIC BRAIN TUMORS BY CLINICAL WHOLE EXOME SEQUENCING
Authors: F. Y. Lin, A. Bavle, D. Wheeler, R. Gibbs, S. Lam, J. Su, M. Chintagumpala, A. Adesina, A. Roy, S. E. Plon, D. W. Parsons
Journal: Neuro-Oncology (2015)

INTRODUCTION: Recent genomic studies have provided significant insight into the pathogenesis of pediatric central nervous system (CNS) tumors. However, little is known about the genetic events underlying rare CNS tumor types, which often present significant diagnostic and therapeutic challenges. The BASIC3 clinical exome sequencing study of children with newly-diagnosed tumors offers an opportunity to investigate the genetic basis of these rare CNS tumors. METHODS: Tumor and germline whole exome sequencing (WES) is performed in a CLIA-certified laboratory on fresh-frozen tumor and matched normal blood samples from children with newly-diagnosed CNS and non-CNS solid tumors. Additional research genomic studies, including transcriptome sequencing, are also conducted with specific consent. RESULTS: 67 children with CNS tumors have been enrolled on study to date, including several rare diagnoses. For example, WES of a malignant epithelioid glioneuronal tumor with two known BRAF alterations (BRAF-V600E and KIAA1549-BRAF fusion) also identified a nonsense mutation in TSC1 (p.Q829X), suggesting the theoretical utility of combined BRAF and mTOR inhibition for this patient. WES of a pilocytic astrocytoma with anaplasia with known KIAA1549-BRAF fusion revealed a pathogenic mutation in ACVR1 (p.R206H), which has been previously reported in high grade gliomas and is currently the target of investigational agents. CONCLUSIONS: Tumor WES has the potential to reveal somatic mutations of biological and clinical significance (for both diagnostics and therapeutics) that are not detectable by standard clinical testing in rare pediatric CNS tumors. Further molecular interrogation of both tumor types is ongoing, including evaluation of additional cases, complementary genomic studies including transcriptome sequencing and copy number arrays, and evaluation of intra-tumoral genetic heterogeneity. Orthotopic xenograft models and cell lines derived from the same primary CNS tumors are being generated to allow for additional biologic and pre-clinical studies as indicated.
Abstract 5120: Large-scale proteome analysis reveals complex molecular abnormalities in gastric cancer
Authors: Tiannan Guo, Yi Zhu, Wai Har Ng, Oi Lian Kon, Siu Kwan Sze
Journal: Cancer Research (2011)

Abstract Cancer proteomes have not been comprehensively studied on a genome-wide scale. In this work, we have catalogued the proteome of a human gastric cancer cell line, SNU5, by integrative analysis of multiple proteomic data sets generated from mitochondria, nucleus and membranes, in addition to the phosphoproteome and whole cell proteome. We report a total of 10440 proteins, of which 8578 were identified with at least two unique spectra and 7042 with more than one unique peptide. We localized gastric cancer proteins to specific organelles at higher resolution than in current knowledgebases. Proteins in sub-organelles such as the Cajal body were identified. Bioinformatic analysis suggests that the proteome map can be a tool of disease taxonomy. Seventeen oncogenesis-associated signaling pathways, including mitochondrial dysfunction, HGF signaling pathway and Eph receptor pathway, were over-represented in the gastric cancer proteome. We also documented the expression of more than 100 protein kinases in gastric cancer. Selected proteins were further investigated in primary gastric cancer tissues. Our approach demonstrates that bioinformatic integration of proteomic data sets substantially increases the depth of proteomic studies. This deep proteome map of cancer cells should aid understanding of the systems biology of gastric cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5120. doi:10.1158/1538-7445.AM2011-5120