tbuckley/cabot-search huggingface dataset:
Phase I/II study of iodine 131 metaiodobenzylguanidine in chemoresistant neuroblastoma: a United Kingdom Children's Cancer Study Group investigation.
Authors: L S Lashford, I J Lewis, S L Fielding, M A Flower, S Meller, J T Kemshead, D Ackery
Journal: Journal of Clinical Oncology (1992)

PURPOSE The goal of this study was to evaluate the toxicity of iodine 131 metaiodobenzylguanidine (mIBG) in metastatic neuroblastoma. PATIENTS AND METHODS A multicenter phase I study of 131I mIBG has been undertaken by the United Kingdom Children's Cancer Study Group (UKCCSG) in children with advanced chemoresistant neuroblastoma. Activity prescription was based on a prescribed whole-body radiation dose, which was established for individual patients by performing an initial tracer investigation with 75 MBq of 131I mIBG. An activity was derived from this pharmacokinetic study that would deliver an initial whole-body-absorbed radiation dose of 1 Gy. Subsequent dose escalations were based on observed toxicity. RESULTS Twenty-five patients, aged 1 to 10 years, were treated with prescribed whole-body dose levels of 1.0 Gy (n = 2), 2.0 Gy (n = 13), and 2.5 Gy (n = 10). This necessitated administration of 2.4 to 12.1 GBq of activity. Hematologic, hepatic, kidney, and adrenal toxicity were observed, with bone marrow suppression being the principal dose-limiting toxicity. Bone marrow toxicity increased with prescribed whole-body-absorbed radiation dose, with 80% of patients developing grade 3 or 4 thrombocytopenia at a prescribed whole-body radiation dose of 2.5 Gy. Objective evidence of tumor response was seen in soft tissue (primary or nodal disease), bone, and bone marrow, with an overall response rate of 33% (partial response, n = 8; static disease, n = 9; progressive disease, n = 7). CONCLUSIONS This study has established an effective method of activity prescription that predicts subsequent toxicity, with the maximally tolerated dose being sufficient activity to deliver a whole-body-absorbed radiation dose of 2.5 Gy. The objective response rate is comparable to other single agents in chemoresistant neuroblastoma and suggests that 131I mIBG may be a useful method for targeting radiotherapy in metastatic neuroblastoma.
A pilot study: 131I-Antitenascin monoclonal antibody 81c6 to deliver a 44-Gy resection cavity boost
Authors: David A. Reardon, Michael R. Zalutsky, Gamal Akabani, R. Edward Coleman, Allan H. Friedman, James E. Herndon, Roger E. McLendon, Charles N. Pegram, Jennifer A. Quinn, Jeremy N. Rich, James J. Vredenburgh, Annick Desjardins, Sridharan Guruangan, Susan Boulton, Renee H. Raynor, Jeanette M. Dowell, Terence Z. Wong, Xiao-Guang Zhao, Henry S. Friedman, Darell D. Bigner
Journal: Neuro-Oncology (2008)

The purpose of this study was to determine the feasibility and assess the efficacy and toxicity, among newly diagnosed malignant glioma patients, of administering (131)I-labeled murine antitenascin monoclonal antibody 81C6 ((131)I-81C6) into a surgically created resection cavity (SCRC) to achieve a patient-specific, 44-Gy boost to the 2-cm SCRC margin. A radioactivity dose of (131)I-81C6 calculated to achieve a 44-Gy boost to the SCRC was administered, followed by conventional external beam radiotherapy (XRT) and chemotherapy. Twenty-one patients were enrolled in the study: 16 with glioblastoma multiforme (GBM) and 5 with anaplastic astrocytoma. Twenty patients received the targeted 44-Gy boost (+/-10%) to the SCRC. Attributable toxicity was mild and limited to reversible grade 3 neutropenia or thrombocytopenia (n = 3; 14%), CNS wound infections (n = 3; 14%), and headache (n = 2; 10%). With a median follow-up of 151 weeks, median overall survival times for all patients and those with GBM are 96.6 and 90.6 weeks, respectively; 87% of GBM patients are alive at 1 year. It is feasible to consistently achieve a 44-Gy boost dose to the SCRC margin with patient-specific dosing of (131)I-81C6. Our study regimen ((131)I-81C6 + XRT + temozolomide) was well tolerated and had encouraging survival. To determine if selection of good-prognosis patients affects outcome associated with this approach, the U.S. Food and Drug Administration has approved a trial randomizing newly diagnosed GBM patients to either our study regimen or standard XRT plus temozolomide.
Two-Stage Phase I Dose-Escalation Study of Intratumoral Reovirus Type 3 Dearing and Palliative Radiotherapy in Patients with Advanced Cancers
Authors: Kevin J. Harrington, Eleni M. Karapanagiotou, Victoria Roulstone, Katie R. Twigger, Christine L. White, Laura Vidal, Debbie Beirne, Robin Prestwich, Kate Newbold, Merina Ahmed, Khin Thway, Christopher M. Nutting, Matt Coffey, Dean Harris, Richard G. Vile, Hardev S. Pandha, Johann S. DeBono, Alan A. Melcher
Journal: Clinical Cancer Research (2010)

Abstract Purpose: To determine the safety and feasibility of combining intratumoral reovirus and radiotherapy in patients with advanced cancer and to assess viral biodistribution, reoviral replication in tumors, and antiviral immune responses. Experimental Design: Patients with measurable disease amenable to palliative radiotherapy were enrolled. In the first stage, patients received radiotherapy (20 Gy in five fractions) plus two intratumoral injections of RT3D at doses between 1 × 108 and 1 × 1010 TCID50. In the second stage, the radiotherapy dose was increased (36 Gy in 12 fractions) and patients received two, four, or six doses of RT3D at 1 × 1010 TCID50. End points were safety, viral replication, immunogenicity, and antitumoral activity. Results: Twenty-three patients with various solid tumors were treated. Dose-limiting toxicity was not seen. The most common toxicities were grade 2 (or lower) pyrexia, influenza-like symptoms, vomiting, asymptomatic lymphopenia, and neutropenia. There was no exacerbation of the acute radiation reaction. Reverse transcription-PCR (RT-PCR) studies of blood, urine, stool, and sputum were negative for viral shedding. In the low-dose (20 Gy in five fractions) radiation group, two of seven evaluable patients had a partial response and five had stable disease. In the high-dose (36 Gy in 12 fractions) radiation group, five of seven evaluable patients had partial response and two stable disease. Conclusions: The combination of intratumoral RT3D and radiotherapy was well tolerated. The favorable toxicity profile and lack of vector shedding means that this combination should be evaluated in newly diagnosed patients receiving radiotherapy with curative intent. Clin Cancer Res; 16(11); 3067–77. ©2010 AACR.
Population Studies of Rheumatic Diseases on a Coastal Island: PART II. ANTINUCLEAR FACTORS AND ANTITHYROID ANTIBODIES
Authors: R. L. F. Nienhuis, E. Mandema, A. Jansz
Journal: Annals of the Rheumatic Diseases (1963)

16 r-.1:160 0 0 2 4 16+ 2 4 6 Total .. 0
Stable gene transfer and expression in human primary T cells by the Sleeping Beauty transposon system
Authors: Xin Huang, Andrew C. Wilber, Lei Bao, Dong Tuong, Jakub Tolar, Paul J. Orchard, Bruce L. Levine, Carl H. June, R. Scott McIvor, Bruce R. Blazar, Xianzheng Zhou
Journal: Blood (2005)
Whole-genome sequence of Schistosoma haematobium
Authors: Neil D Young, Aaron R Jex, Bo Li, Shiping Liu, Linfeng Yang, Zijun Xiong, Yingrui Li, Cinzia Cantacessi, Ross S Hall, Xun Xu, Fangyuan Chen, Xuan Wu, Adhemar Zerlotini, Guilherme Oliveira, Andreas Hofmann, Guojie Zhang, Xiaodong Fang, Yi Kang, Bronwyn E Campbell, Alex Loukas, Shoba Ranganathan, David Rollinson, Gabriel Rinaldi, Paul J Brindley, Huanming Yang, Jun Wang, Jian Wang, Robin B Gasser
Journal: Nature Genetics (2012)

Robin Gasser and his colleagues report the whole-genome sequence of Schistosoma haematobium. They include comparisons to the genome sequences of S. mansoni and S. japonicum, the two other species that cause schistosomiasis in humans. Schistosomiasis is a neglected tropical disease caused by blood flukes (genus Schistosoma; schistosomes) and affecting 200 million people worldwide1. No vaccines are available, and treatment relies on one drug, praziquantel2. Schistosoma haematobium has come into the spotlight as a major cause of urogenital disease, as an agent linked to bladder cancer1,3 and as a predisposing factor for HIV/AIDS4,5. The parasite is transmitted to humans from freshwater snails1. Worms dwell in blood vessels and release eggs that become embedded in the bladder wall to elicit chronic immune-mediated disease6 and induce squamous cell carcinoma7. Here we sequenced the 385-Mb genome of S. haematobium using Illumina-based technology at 74-fold coverage and compared it to sequences from related parasites8,9. We included genome annotation based on function, gene ontology, networking and pathway mapping. This genome now provides an unprecedented resource for many fundamental research areas and shows great promise for the design of new disease interventions.
A Novel Imaging Approach for Early Detection of Prostate Cancer Based on Endogenous Zinc Sensing
Authors: Subrata K. Ghosh, Pilhan Kim, Xiao-an Zhang, Seok-Hyun Yun, Anna Moore, Stephen J. Lippard, Zdravka Medarova
Journal: Cancer Research (2010)

Abstract The early detection of prostate cancer is a life-saving event in patients harboring potentially aggressive disease. With the development of malignancy, there is a dramatic reduction in the zinc content of prostate tissue associated with the inability of cancer cells to accumulate the ion. In the current study, we used endogenous zinc as an imaging biomarker for prostate cancer detection and progression monitoring. We employed a novel fluorescent sensor for mobile zinc (ZPP1) to detect and monitor the development of prostate cancer in a transgenic mouse model of prostate adenocarcinoma, using in vivo optical imaging correlated with biological fluid-based methods. We showed that the progression of prostate cancer could be monitored in vivo judging by the decreasing zinc content in the prostates of tumor-bearing mice in an age-dependent manner. In a novel quantitative assay, we determined the concentration of mobile zinc in both prostate cell lysates and mouse prostate extracts through simple titration of the ZPP1 sensor. Our findings fulfill the promise of zinc-based prostate cancer diagnostics with the prospect for immediate clinical translation. Cancer Res; 70(15); 6119–27. ©2010 AACR.
Anthracycline-based chemotherapy as primary treatment for intravascular lymphoma
Authors: A.J.M. Ferreri, E. Campo, A. Ambrosetti, F. Ilariucci, J.F. Seymour, R. Willemze, G. Arrigoni, G. Rossi, A. López-Guillermo, E. Berti, M. Eriksson, M. Federico, S. Cortelazzo, S. Govi, N. Frungillo, S. Dell'Oro, M. Lestani, S. Asioli, E. Pedrinis, M. Ungari, T. Motta, R. Rossi, T. Artusi, P. Iuzzolino, E. Zucca, F. Cavalli, M. Ponzoni
Journal: Annals of Oncology (2004)
Renal Hyperfiltration Is a Determinant of Endothelial Function Responses to Cyclooxygenase 2 Inhibition in Type 1 Diabetes
Authors: David Z.I. Cherney, Judith A. Miller, James W. Scholey, Rania Nasrallah, Richard L. Hébert, Maria G. Dekker, Cameron Slorach, Etienne B. Sochett, Timothy J. Bradley
Journal: Diabetes Care (2010)

OBJECTIVE Our aim was to examine the effect of cyclooxygenase 2 (COX2) inhibition on endothelial function in subjects with type 1 diabetes analyzed on the basis of renal filtration status. RESEARCH DESIGN AND METHODS Flow-mediated dilation (FMD) was determined in type 1 diabetic subjects and hyperfiltration (glomerular filtration rate ≥135 ml/min/1.73 m2, n = 13) or normofiltration (glomerular filtration rate ≥135 ml/min/1.73 m2, n = 11). Studies were performed before and after celecoxib (200 mg daily for 14 days) during euglycemia and hyperglycemia. RESULTS Baseline parameters were similar in the two groups. Pretreatment, FMD was augmented in normofiltering versus hyperfiltering subjects during clamped euglycemia (10.2 ± 5.3% vs. 5.9 ± 2.3%, P = 0.003). COX2 inhibition suppressed FMD in normofiltering (10.2 ± 5.3% to 5.8 ± 3.4%, P = 0.006) versus hyperfiltering subjects (ANOVA interaction, P = 0.003). CONCLUSIONS Systemic hemodynamic function, including the response to COX2 inhibition, is related to filtration status in diabetic subjects and may reflect general endothelial dysfunction.
Where Does HIV Live?
Authors: Justin Stebbing, Brian Gazzard, Daniel C. Douek
Journal: New England Journal of Medicine (2004)

This survey of the cellular and anatomical sites of infection by human immunodeficiency virus (HIV) discusses the mechanisms of attachment of the virus to cells, the cellular receptors through which the virus enters cells, and the all-important reservoir of HIV, which persists despite antiretroviral therapy.
Microprocessor of microRNAs: regulation and potential for therapeutic intervention
Authors: Kevin J Beezhold, Vince Castranova, Fei Chen
Journal: Molecular Cancer (2010)

Abstract MicroRNAs (miRNAs) are a class of small, noncoding RNAs critically involved in a wide spectrum of normal and pathological processes of cells or tissues by fine-tuning the signals important for stem cell development, cell differentiation, cell cycle regulation, apoptosis, and transformation. Considerable progress has been made in the past few years in understanding the transcription, biogenesis and functional regulation of miRNAs. Numerous studies have implicated altered expression of miRNAs in human cancers, suggesting that aberrant expression of miRNAs is one of the hallmarks for carcinogenesis. In this review, we briefly discuss most recent discoveries on the regulation of miRNAs at the level of microprocessor-mediated biogenesis of miRNAs.
Islet Cell Hyperinsulinism in Adults and Children
Authors: R. Dale Liechty
Journal: JAMA (1974)

Classical hyperinsulinism is a relatively uncommon disease of the islets of Langerhans, characterized by hypersecretion of insulin and, sometimes, proinsulin. Neuropsychiatric symptoms and obesity predominate. All 13 of our patients had benign or malignant tumors or hyperplasia, confirmed by operation or biopsy. One of nine adults and one of four infants died. The latter, if they fail to respond to glucose, require emergency surgery. (<i>JAMA</i>230:1538-1543, 1974)
HIF in Kidney Disease and Development
Authors: Lakshman Gunaratnam, Joseph V. Bonventre
Journal: Journal of the American Society of Nephrology (2009)

Tissue hypoxia is a pathologic feature of many human diseases including cancer, myocardial infarction, stroke, and kidney disease. An evolutionarily conserved oxygen-sensing mechanism enables cells to adapt and maintain homeostasis under hypoxic conditions by transcriptional activation of a host of genes that mediate metabolic adaptation, angiogenesis, energy conservation, erythropoiesis, and cell survival. The hypoxia-inducible factors (HIFs) comprise a family of oxygen-sensitive basic helix-loop-helix proteins that control the cellular transcriptional response to hypoxia. Inappropriate activation of the HIF system is linked to the development and/or progression of many human malignancies including clear cell renal cancer. HIFs are now postulated to play contrasting protective and pathogenic roles in acute and chronic kidney diseases, respectively. In this review, we discuss the mechanisms of oxygen sensing in renal cells and highlight the role of hypoxia and HIF activation under physiologic conditions and in renal development as well as in acute and chronic kidney diseases.
A Preliminary Note on the Influence of the Anthrax Virus on Tuberculosis
Authors: T. J. Bokenham
Journal: BMJ (1892)

DR. PERRONCITO has recently announced the results of some experiments which were undertaken with a view of ascertain- ing the influence of vaccination against anthrax upon the suscQptib'llity of animals to tuberculosis.1He was led to make this inquiry by observation of the fact that in Italy the districts in which protective vaccination of cattle against anthrax had been adopted on a large scale were remarkably free from tuberculous disease.He has stated that (1) cattle vac- cinated against anthrax are insusceptible to tuberculosis;
Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease
Authors: Javier Gutierrez-Achury, Alexandra Zhernakova, Sara L Pulit, Gosia Trynka, Karen A Hunt, Jihane Romanos, Soumya Raychaudhuri, David A van Heel, Cisca Wijmenga, Paul I W de Bakker
Journal: Nature Genetics (2015)
Novel Competitive Inhibitor of NAD(P)H Oxidase Assembly Attenuates Vascular O <sub>2</sub> <sup>−</sup> and Systolic Blood Pressure in Mice
Authors: F. E. Rey, M. E. Cifuentes, A. Kiarash, M. T. Quinn, P. J. Pagano
Journal: Circulation Research (2001)

We previously reported enhanced expression of the p67 phox and gp91 phox components of NAD(P)H oxidase in angiotensin (Ang) II–induced hypertension, suggesting de novo assembly in response to Ang II. To examine the direct involvement of NAD(P)H oxidases in Ang II–induced O 2 − production, we designed a chimeric peptide that inhibits p47 phox association with gp91 phox in NAD(P)H oxidase (gp91ds- tat ). This was achieved by linking a 9-amino acid peptide (aa) derived from HIV-coat protein ( tat ) to a 9-aa sequence of gp91 phox (known to interact with p47 phox ). As a control, we constructed a chimera containing tat and a scrambled gp91 sequence (scramb- tat ). We found that gp91ds- tat decreased O 2 − levels in aortic rings treated with Ang II (10 pmol/L) but had no effect on either the O 2 − -generating enzyme xanthine oxidase or potassium superoxide–generated O 2 − . We infused vehicle, Ang II (0.75 mg · kg −1 · d −1 ), Ang II+gp91ds- tat (10 mg · kg −1 · d −1 ), or Ang II+scramb- tat intraperitoneally in C57Bl/6 mice and measured systolic blood pressure (SBP) on days 0, 3, 5, and 7 of infusion. SBP increased by day 3 in mice given Ang II and Ang II+scramb- tat but was significantly lower with Ang II+gp91- tat . On day 7, SBP was still significantly inhibited in mice given Ang II+gp91ds- tat , whereas Ang II–induced O 2 − production was inhibited throughout the aorta as detected by dihydroethidium staining, consistent with the ability of this inhibitor to block the various vascular NAD(P)H oxidase isoforms. These data support the hypothesis that inhibition of the interaction of p47 phox and gp91 phox (or its homologues) can block O 2 − production and attenuate blood pressure elevation in mice.
Estrogens and the Aging Process
Authors: M. Edward Davis
Journal: JAMA (1966)

Follow-up of postmenopausal patients who have been on long-term estrogen replacement therapy has provided a large number of women for a prospective study of osteoporosis. The development of new and simple instrumentation has made it possible to evaluate bone changes easily and accurately in serial or survey studies. The degree of osteoporosis is determined by the transmission of low-energy radiation from radioactive iodine 125 through an in vivo bone sample. The measure used here is the linear absorption coefficient of overall bone of a phalanx. The results show that postmenopausal osteoporosis is prevented or retarded by estrogen replacement therapy as compared with an unsupplemented control group.
Infliximab maintains a high degree of clinical response in patients with active psoriatic arthritis through 1 year of treatment: results from the IMPACT 2 trial
Authors: A Kavanaugh, G G Krueger, A Beutler, C Guzzo, B Zhou, L T Dooley, P J Mease, D D Gladman, K de Vlam, P P Geusens, C Birbara, D G Halter, C Antoni
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objective:</b> To evaluate the efficacy and safety of infliximab through 1 year in patients with psoriatic arthritis (PsA) enrolled in the IMPACT 2 trial. <b>Methods:</b> In this double blind, placebo controlled, phase III study, 200 patients with active PsA were randomised to receive infusions of infliximab 5 mg/kg or placebo at weeks 0, 2, 6, and every 8 weeks thereafter through 1 year. Patients with persistent disease activity could enter early escape at week 16, and all remaining placebo patients crossed over to infliximab at week 24. Patients randomised to infliximab who had no response or who lost response could escalate their dose to 10 mg/kg starting at week 38. Clinical efficacy was assessed based on the proportion of patients achieving ACR 20 and PASI 75 responses. Major clinical response (that is, maintenance of ACR 70 response for 24 continuous weeks) was assessed for the first time in PsA. <b>Results:</b> Through 1 year of treatment, 58.9% and 61.4% of patients in the randomised infliximab and placebo/infliximab groups, respectively, achieved ACR 20; corresponding figures for PASI 75 were 50.0% and 60.3%. At week 54, major clinical response was achieved by 12.1% of patients in the infliximab group. The safety profile of infliximab through week 54 was consistent with that seen through week 24. Two malignancies occurred: basal cell skin cancer (placebo) and stage I Hodgkin's lymphoma (infliximab). <b>Conclusion:</b> Infliximab maintains a high degree of clinical efficacy and continues to be well tolerated in patients with PsA through 1 year of treatment.
Relation Between Progression and Regression of Atherosclerotic Left Main Coronary Artery Disease and Serum Cholesterol Levels as Assessed With Serial Long-Term (≥12 Months) Follow-Up Intravascular Ultrasound
Authors: Clemens von Birgelen, Marc Hartmann, Gary S. Mintz, Dietrich Baumgart, Axel Schmermund, Raimund Erbel
Journal: Circulation (2003)

Background— The relation between serum lipids and risk of coronary events has been established, but there are no data demonstrating directly the relation between serum low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol versus serial changes in coronary plaque dimensions. Methods and Results— We performed standard analyses of serial intravascular ultrasound (IVUS) studies of 60 left main coronary arteries obtained 18.3±9.4 months apart to evaluate progression and regression of mild atherosclerotic plaques in relation to serum cholesterol levels. Overall, there was (1) a positive linear relation between LDL cholesterol and the annual changes in plaque plus media (P&amp;M) cross-sectional area (CSA) ( r =0.41, P &lt;0.0001) with (2) an LDL value of 75 mg/dL as the cutoff when regression analysis predicted on average no annual P&amp;M CSA increase; (3) an inverse relation between HDL cholesterol and annual changes in P&amp;M CSA ( r =−0.30, P &lt;0.02); (4) an inverse relation between LDL cholesterol and annual changes in lumen CSA ( r =−0.32, P &lt;0.01); and (5) no relation between LDL and HDL cholesterol and the annual changes in total arterial CSA (remodeling). Despite similar baseline IVUS characteristics, patients with an LDL cholesterol level ≥120 mg/dL showed more annual P&amp;M CSA progression and lumen reduction than patients with lower LDL cholesterol. Conclusions— There is a positive linear relation between LDL cholesterol and annual changes in plaque size, with an LDL value of 75 mg/dL predicting, on average, no plaque progression. HDL cholesterol shows an inverse relation with annual changes in plaque size.