tbuckley/cabot-search huggingface dataset:
18F-FDG PET/CT and MRI Findings in a Patient With Anti-GABAB Receptor Encephalitis
Authors: Minggang Su, Dongkun Xu, Rong Tian
Journal: Clinical Nuclear Medicine (2015)

Autoimmune synaptic encephalitis can occur as paraneoplastic neurological syndromes, which are dysfunctions of the nervous system in cancer patients. One such rare but treatable form is associated with GABAB (γ-aminobutyric acid-B) receptor antibody. We report a 55-year-old man with small cell lung cancer who presented with 3 weeks of progressive seizures, memory impairment, and behavioral disorder. His cerebrospinal fluid anti-GABAB receptor antibody titer was elevated. F-FDG PET/CT revealed pronounced medial temporal hypermetabolism with gross hypometabolism in the rest of the brain. There were no associated abnormalities on MRI. He showed improvement after immunotherapy and chemoradiotherapy.
Abstract 2120: Platinum-based cancer chemotherapeutics inhibit STAT signaling by blocking the SH2 domain.
Authors: W. Joost Lesterhuis, Stanleyson V. Hato, Carl G. Figdor, Susumu Takahashi, Cornelis J.A. Punt, Akira Asai, I. Jolanda M. De Vries
Journal: Cancer Research (2013)

Abstract Platinum-based drugs form the corner stone of many treatment schedules in cancer. Their main mechanism of actions is the covalent binding to DNA, leading to the formation of platinum-DNA adducts and thereby inducing apoptosis. Recently, other so called off-target effects of these drugs have been described. These include the induction of immunogenic cell death and the downregulation of inhibitory molecule Programmed Death-Ligand 2 by inactivation of signaling molecule/transcription factor STAT6, a member of the Signal Transducer and Activator of Transcription (STAT) protein family. STAT proteins play crucial roles in the pathogenesis and progression of cancer and much research is being conducted to identify inhibitors of STAT signaling for use in cancer treatment. Here, we investigated the potential of platinum-based chemotherapeutics to inhibit STAT signaling. We found that treatment of tumor cells of various origins with platinum drugs inhibit the activation of STAT proteins and leads to loss of cytokine-induced and constitutive STAT protein phosphorylation. Concurrently, a decrease of STAT protein nuclear accumulation was evident by confocal microscopy analysis. This resulted in a downregulation of STAT-regulated tumorigenic genes such as Bcl-xL, MCL-1, VEGF and survivin. Non-STAT target genes were not affected. Analysis of the known STAT inactivation pathways showed that these were not activated nor enhanced by treatment with platinum drugs. Finally, using a biochemical alphascreen-based assay, we demonstrated that platinum compounds directly interact with STAT proteins and inhibit binding to the SH2 domain. These findings provide novel insight into the mechanism of action of platinum drugs and show for the first time that these clinically used compounds directly affect important cellular signaling pathways. These results indicate that part of the efficacy of these drugs may be derived from their inhibition of STAT signaling and they provide important leads for the development of novel innovative treatment schedules in cancer that exploit the STAT-inhibiting effect of platinum drugs, for example by potentiating targeted therapies or immunotherapy. Citation Format: W. Joost Lesterhuis, Stanleyson V. Hato, Carl G. Figdor, Susumu Takahashi, Cornelis J.A. Punt, Akira Asai, I. Jolanda M. De Vries. Platinum-based cancer chemotherapeutics inhibit STAT signaling by blocking the SH2 domain. [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 2120. doi:10.1158/1538-7445.AM2013-2120
AB0910 Once-Weekly Teriparatide is Effective for Glucocorticoid-Induced Osteoporosis Patients with Collagen Diseases
Authors: T. Seno, A. Yamamoto, Y. Kukida, A. Tominaga, T. Kida, A. Nakabayashi, K. Fujioka, H. Nagahara, K. Murakami, W. Fujii, R. Oda, T. Kubo, M. Kohno, Y. Kawahito
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Glucocorticoid-induced osteoporosis (GIOP) patients are at very high risk of fractures. Unfortunately, only a small minority of GC users receive effective preventive, diagnostic, and therapeutic interventions. Intermittent administration of teriparatide (TPTD) is the only currently available anabolic agent to stimulate osteoblast activity. Daily TPTD was more efficacious than alendronate in increasing lumbar spine BMD in men and pre- and postmenopausal women. Recently, once-weekly TPTD was provided, which had both rapid and powerful anti-fracture efficacy. It has unique feature; serum NTx is decreasing after administration for patients with primary osteoporosis contrast to daily TPTD. Once-weekly TPTD is expected to be effective for GIOP, but it has not been reported. <h3>Objectives</h3> To examine the efficacy of once-weekly TPTD for patients with GIOP and collagen diseases. <h3>Methods</h3> We registered GIOP patients with collagen diseases treated with once-weekly TPTD at our department. They were treated with PSL for at least 6 months and had inadequate response for bisphosphonates. We measured YAM (Young Adult Mean), serum NTx (cross-linked N-terminal telopeptides of type I collagen), BAP (Bone alkaline phosphatase), Ca, FRAX at baseline, 6 months, 12months and 18 months after starting once-weekly TPTD. We calculated the change rate of those values to baseline. The continuous variables were compared using ANOVA and Wilcoxon matched-pairs single rank test. <h3>Results</h3> 12 GIOP patients with collagen diseases were registered into this study, and 9 patients completed (6 systemic lupus erythematosus, 2 rheumatoid arthritis, 1 adult onset still disease; 7 female, 2 male; Age 57.4±11.1). Only one new fracture event, that was lumbar compression fracture, occurred during the study period despite the patient had many fractures before this treatment. The change rate of lumbar spine YAM was significantly improved at 18 months (<i>p</i>=0.041, ANOVA; <i>p</i>=0.019, Wilcoxon matched-pairs single rank test). Femoral neck YAM (<i>p</i>=0.477, ANOVA), serum NTx (<i>p</i>=0.555), BAP (<i>p</i>=0.936), Ca and FRAX were not significantly changed. Interestingly, the change rate of serum NTx was increased during this GIOP study despite the rate was decreased in primary osteoporosis previously reported. <h3>Conclusions</h3> Our study shows that once-weekly teriparatide is effective for GIOP patients with collagen diseases, and its dosing period needs 18 months. Mean % change of serum NTx was increased in GIOP patients in spite of primary osteoporosis. <h3>References</h3> Bone 2006;39:244–52. J Bone Miner Res 2010;25:472–81. Osteoporos Int 2009;20:2095–104. J Bone Miner Metab 2004;22:569–76. <h3>Disclosure of Interest</h3> None declared
A fractured duodenal self-expanding metal stent in a patient with pancreatic cancer
Authors: Jörg Trojan, Thomas Vogl, Stefan Zeuzem, Jörg Albert
Journal: Endoscopy (2014)

A 65-year-old man with biliary and duodenal obstruction due to metastatic adenocarcinoma of the pancreas underwent placement of an uncovered biliary self-expanding metal stent (SEMS). Subsequently, palliative chemotherapy with gemcitabine and nab-paclitaxel was initiated. Because the patient developed worsening symptoms of gastric outlet obstruction, an uncovered, 12-cm duodenal SEMS (Niti S-enteral D type, diameter 20 smm; TaeWoong Medical, Seoul, South Korea) was placed 4 weeks later.
ANTICOAGULATION CONTROL IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION TREATED WITH VITAMIN K ANTAGONIST THERAPY FOR 12 MONTHS OR MORE IN PRIMARY CARE IN THE UK
Authors: Essra Ridha, Robert Donaldson, Cinira Lefevre, Sreeram Ramagopalan, Steven Lister, Aaron Jenkins, David Evans, Ian Minns, Laure Lacoin
Journal: Journal of the American College of Cardiology (2016)
Somatostatin Receptor Scintigraphy for Early Detection of Regional and Distant Metastases of Medullary Carcinoma of the Thyroid
Authors: Y Krausz, A Rosler, H Guttmann, S Ish-Shalom, N Shibley, R Chisin, B Glaser
Journal: Clinical Nuclear Medicine (1999)

Three patients are described who had regional and distant metastases of medullary thyroid cancer detected by somatostatin receptor scintigraphy but not by CT; two had minimal disease that was amenable to surgery. The first patient had been followed for 2 years before having a repeated scan and positive CT, with subsequent surgical removal of metastatic paratracheal nodes. The plasma calcitonin level, however, did not approach normal values after surgery, and a third scan showed persistence of focal uptake in the left paratracheal area of the lower neck, whereas CT was negative. At repeated exploration, a tumor mass of medullary carcinoma, embedded in lymphatic tissue, was removed. Nine months after the last surgical procedure, calcitonin and carcinoembryonic antigen levels were normal. The second patient underwent microdissection of the mediastinum and removal of two metastatic nodes that were demonstrable only by the scintigraphic technique. The plasma calcitonin level subsequently became normal. The third patient, with multiple endocrine neoplasia IIB and associated pheochromocytoma, had bony metastatic involvement of the left shoulder, demonstrable initially on somatostatin receptor scintigraphy and subsequently with radioiodinated metaiodobenzylguanidine but not on CT.
Case 23-2009
Authors: Michael J.G. Somers, Amita Sharma, P. Ellen Grant, Alexander R. Guimaraes, Eveline E. Schneeberger
Journal: New England Journal of Medicine (2009)

A 13-year-old boy was admitted to the hospital because of headache, nausea, seizures, renal failure, and hypertension. Three weeks earlier, headaches, fatigue, and anorexia developed, with constipation and occasional nausea and vomiting. On the day of admission, nausea and vomiting became severe; episodes of numbness of the right leg and dizziness occurred, and he came to the emergency department, where he was found to be hypertensive with renal failure. A diagnostic procedure was performed.
950 A NEW NON-INVASIVE PREDICTIVE MODEL OF INFLAMMATORY ACTIVITY IN PATIENTS WITH TYPE I AUTOIMMUNE HEPATITIS
Authors: K. Gutkowski, T. Kacperek-Hartleb, M. Hartleb, M. Kajor, W. Mazur, W. Zych, B. Walewska-Zielecka, A. Habior
Journal: Journal of Hepatology (2012)
Abstract 2034: The Fbw7 tumor suppressor: Genetic and biochemical approaches to study a dimeric ubiquitin ligase
Authors: Elizabeth A. Larimore, Markus Welcker, Bruce E. Clurman
Journal: Cancer Research (2012)

Abstract Fbw7, the human ortholog of yeast Cdc4, is the substrate-recognition component of a cullin-RING ubiquitin ligase and regulates a number of oncoprotein substrates including cyclin E, c-Myc, Notch, and c-Jun. A growing number of additional pro-growth and pro-survival factors have been more recently described as Fbw7 targets. Accordingly, Fbw7 is a tumor suppressor and is mutated in approximately ten percent of human malignancies. Its loss leads to chromosomal instability and tumorigenesis. Fbw7 binds its substrates after they become phosphorylated within a consensus sequence called a Cdc4 phospho-degron (CPD). CPD phosphorylation creates a high-affinity binding site for Fbw7, which brings the ligase machinery into proximity with the substrate, leading to ubiquitylation and proteasomal degradation of the substrate. Interestingly, Fbw7 contains a conserved dimerization domain and we can show the protein primarily forms dimers in cells. One Fbw7 dimer contains two substrate-binding interfaces and may make two independent CPD contacts, but the physiologic function of Fbw7 dimerization is still elusive. Using gene-targeting, we studied the effects of ablating Fbw7 dimerization in vivo and found endogenous cyclin E and c-Myc regulation are moderately affected. Using purified Fbw7 monomers or dimers in in vitro ubiquitylation assays, we observed that a dimeric ligase is able to conjugate ubiquitin moieties onto a wider variety of substrate lysine residues than can the monomeric ligase. This is likely due to the greater spatial reach of the dimer. Additionally, preliminary data shows that the dimer may be capable of catalyzing the formation of non-K48-linked polyubiquitin chains, whereas the monomer is not. Cancer-associated mutations in Fbw7 most often target three arginine residues that form a pocket for binding phosphorylated substrate CPDs. Mutation of any of these arginines render Fbw7 unable to bind substrates and properly regulate their abundance. However, these mutations occur typically in only one allele. Dimerization of Fbw7 may explain why such heterozygous mutations are sufficient for tumorigenesis: the mutant form may dominantly inhibit enzyme function of the wild-type allele through dimerization. We have generated hetero-typic Fbw7 dimers containing one wild-type and one mutant protein in each dimer and are currently studying its binding and ubiquitylation capabilities. Given the importance of Fbw7 and its substrates in tumor-progression pathways, the results of this study will further our understanding of human tumor suppression. 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 2034. doi:1538-7445.AM2012-2034
Fatal Circulatory Collapse in Premature Infants Receiving Chloramphenicol
Authors: Lafayette E. Burns, Joan E. Hodgman, Alonzo B. Cass
Journal: New England Journal of Medicine (1959)

A SURVEY was made of premature infants born twenty-four hours or longer after spontaneous rupture of the fetal membranes, because of a higher mortality in this group than in the premature infants whose membranes had ruptured at birth. Routinely, these infants had been placed on antibiotics shortly after birth because of assumed exposure to infection. The role of antibiotics in this higher mortality was questioned. A comparative study of these infants on different treatment schedules was conducted from March, 1958, to February, 1959. This paper is a report of that study.MethodAll premature infants delivered in the birth suites . . .
Corticosteroid Administration and Localized Leukocyte Mobilization in Man
Authors: William P. Peters, James F. Holland, Hansjoerg Senn, Walter Rhomberg, Tarit Banerjee
Journal: New England Journal of Medicine (1972)

Mobilization of leukocytes into a serum-filled chamber was quantitatively measured in duplicate in normal subjects during two control periods and while they were receiving prednisone or dexamethasone. The normal mobilization of leukocytes from blood to chamber serum (71.6 X 106 per square centimeter of abrasion surface per 24 hours) was slightly decreased by prednisone (62.8 X 106 per square centimeter per 24 hours) but significantly increased by dexamethasone (132.3 X 106 per square centimeter per 24 hours). By calculation the clearance of granulocytes from blood to serum was significantly decreased by prednisone. This difference in the effect of the two steroids may be of relevance when extravascular granulocytes are of importance in defense against bacterial invasion during corticosteroid treatment.
Anaritide in Acute Tubular Necrosis
Authors: Robin L. Allgren, Thomas C. Marbury, S. Noor Rahman, Lawrence S. Weisberg, Andrew Z. Fenves, Richard A. Lafayette, Richard M. Sweet, Fredric C. Genter, Brenda R.C. Kurnik, John D. Conger, Mohamed H. Sayegh
Journal: New England Journal of Medicine (1997)

Atrial natriuretic peptide, a hormone synthesized by the cardiac atria, increases the glomerular filtration rate by dilating afferent arterioles while constricting efferent arterioles. It has been shown to improve glomerular filtration, urinary output, and renal histopathology in laboratory animals with acute renal dysfunction. Anaritide is a 25-amino-acid synthetic form of atrial natriuretic peptide.
Antacid Titration in the Prevention of Acute Gastrointestinal Bleeding
Authors: Paul R. Hastings, John J. Skillman, Leonard S. Bushnell, William Silen
Journal: New England Journal of Medicine (1978)

We randomized 100 critically ill patients at risk of developing acute gastrointestinal ulceration and bleeding into two groups. One (51 patients) received antacid prophylaxis, and the other (49 patients) received no specific form of prophylaxis. Hourly antacid titration kept the pH of the gastric contents above 3.5. Two of the 51 patients who received antacid prophylaxis had gastrointestinal bleeding. Twelve of the 49 control patients bled (P<0.005). Of the 12 patients in the control group who bled, seven were placed on antacid medication, and all seven apparently stopped bleeding. Analysis of all the patients showed that an increasing prevalence of respiratory failure, sepsis, peritonitis, jaundice, renal failure and hypotension was correlated with a greater frequency of bleeding. No patients required operative treatment to control bleeding. These data indicate that the occurrence of acute gastrointestinal bleeding in critically ill patients can be reduced by antacid titration. (N Engl J Med 298:1041–1045, 1978)
Relation of Obesity to Longevity
Authors: Louis I. Dublin
Journal: New England Journal of Medicine (1953)

THIS symposium, devoted to the subject of obesity, is a good indication of the growing awareness of the medical and public-health professions of the importance of obesity in the national health picture. Over the years vast changes have taken place in the daily life of people, and the eating habits that were formerly suitable for farmers, factory workers and housewives who had to do a great deal of manual labor are no longer suitable in the highly mechanized America of 1952. The pleasures of eating, however, are just as real today as they ever were, and there is no lack . . .
Intense Dose-Dense Epirubicin (E), Paclitaxel (T), Cyclophosphamide (C) (Iddetc) is Highly Effective in Adjuvant Therapy of Node-Positive Breast Cancer Patients (Pts). an Analysis of the Gbg, Ago-B, and Noggo Study Groups
Authors: C. Thomssen, G. von Minckwitz, C. Jackisch, H.J. Lueck, A. Schneeweiss, H. Tesch, D. Elling, N. Harbeck, B. Conrad, T. Fehm, J. Huober, V. Müller, I. Bauerfeind, S. Loibl, V. Nekljudova, M. Untch, V. Moebus
Journal: Annals of Oncology (2014)
A7.14 Identification of new inhibitors of angiogenesis in a novel 3d model of rheumatoid arthritis synovial angiogenesis
Authors: CX Maracle, P Kucharzewska, B Helder, H Olsson, SW Tas
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background/objective</h3> Angiogenesis contributes to rheumatoid arthritis (RA) pathogenesis, however, many models focus solely on endothelial cells (EC). We developed a 3D-spheroid model including both EC and RA fibroblast-like-synoviocytes (FLS) to study angiogenesis associated with RA and to test efficacy of several inhibitors targeting this process. Previous work demonstrated a role for the non-canonical NF-κB pathway and its main regulator, NF-kB inducing kinase (NIK) in pathological angiogenesis. Here we aim to use the 3D model to further characterise its contribution to neovascularization. <h3>Methods</h3> Human umbilical vein EC (HUVEC) were combined with RA FLS in spheroids and placed in a collagen gel. Spheroids were stimulated with RA synovial fluid (SF), growth factors (GF), LT or LIGHT. To establish NIK dependency in EC, EC were pre-transfected with a non-targeting or NIK-targeting siRNA before incorporation into spheroids. Pharmacological inhibitors were also added to determine their ability to abrogate EC sprouting induced by 10% RASF. Sprouting was imaged by confocal microscopy and quantified using the Leica QWin Plus software. <h3>Results</h3> Spheroids formed sprouts under all conditions with significant increases observed upon stimulation with LT, LIGHT, 10% RA SF (p &lt; 0.05) and growth factors (p &lt; 0.01), as compared to basal levels. LT and LIGHT induced sprout formation was NIK dependent as spheroids containing HUVEC transfected with NIK targeting siRNA had reductions in vessel formation (p &lt; 0.05) as compared to controls. Anginex blocked sprout formation induced not only by growth factors, but also by that induced by RA SF (p &lt; 0.05). Inhibitors of the non-canonical NF-kB pathway were able to attenuate cumulative sprout growth promoted by LT, LIGHT and RA SF (p &lt; 0.05). <h3>Conclusion</h3> The 3D model is an effective tool for studying synovial angiogenesis in that it incorporates several elements essential to the process namely EC, RA FLS and immune cell factors found in RA SF. Using this system, we have further demonstrated a role for activation of the non-canonical NF-kB pathway, and its central regulator NIK, in neovascularization associated with RA. Moreover, we have shown this method to be useful for testing inhibitors of angiogenesis and found that targeting of non-canonical NF-kB signalling to be an effective method of blocking pathological angiogenesis.
DERIVATION AND VALIDATION OF A NOVEL RISK SCORE FOR PREDICTING INTRACRANIAL HEMORRHAGE IN PATIENTS WITH PULMONARY EMBOLISM TREATED WITH THROMBOLYTIC THERAPY: THE PE-ICH SCORE
Authors: Saurav Chatterjee, Anasua Chakraborty, Partha Sardar, Jay Giri
Journal: Journal of the American College of Cardiology (2016)
Abstract 4227: Sensitizing resistant ovarian cancer to chemotherapy through inhibition of small GTPases
Authors: Kirill Goncharov, Reema R. Zeineldin
Journal: Cancer Research (2012)

Abstract Platinum- or paclitaxel-resistance is a major problem in women with advanced ovarian cancer (OVCA) and that confers a poor prognosis for patients. Consequently there is a great need to identify new drugs and drug targets for the management of residual and recurrent metastatic OVCA. About 90% of OVCA starts on the ovarian surface epithelium, but individual cells or multicellular aggregates (MCAs) shed into the peritoneal cavity and contribute to OVCA's metastasis into adjacent organs. These MCAs are resistant to apoptosis and to radio- and chemo-therapy. In OVCA, resistance to chemotherapy and apoptosis has been linked to the small GTPases, Rac1 and Cdc42, and their downstream effectors. Identifying compounds that disperse MCAs through disrupting adhesions would sensitize this resistant subpopulation to chemotherapy. We hypothesize that inhibition of one or both of these GTPases disrupts MCAs and sensitizes drug-resistant OVCA cells to respond to chemotherapeutic agents. We assessed if chemical inhibition of Rac1 or Cdc42 would sensitize drug-resistant OVCA monolayers and in vitro MCAs to cisplatin's cytotoxicity. The OVCA cell lines evaluated were OVCA 429 and SKOV-3ip. The inhibitors we used included: (1) NSC 23766, a Rac1-specific inhibitor, (2) ML141, a Cdc42-specific inhibitor, (3) Toxin B, an inhibitor of Rac, Cdc42 and Rho, and (4) R-naproxen, an inhibitor of Rac1 and Cdc42 (based on our data). We found that Rac1 and Cdc42 inhibitors disperse MCAs in a liquid overlay assay. Furthermore, these inhibitors sensitized OVCA cells to cisplatin's cytotoxic effect. Finding drugs that increase efficacy of chemotherapeutic agents against resistant OVCA cell populations is of particular importance. Thus far, GTPases have not been extensively examined as therapeutic targets, but they offer new opportunities for OVCA therapy. Our findings indicate that Rac1 and Cdc42 inhibitors disperse MCAs and improve their response to chemotherapeutic agents. This could increase the effectiveness of intraperitoneal chemotherapy and improve patient outcomes and survival. Since one of these inhibitors is R-Naproxen (an FDA approved off-patent drug), it has potential for rapid clinical application. 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 4227. doi:1538-7445.AM2012-4227