tbuckley/cabot-search huggingface dataset:
Effects of Angiopoietin-2-Blocking Antibody on Endothelial Cell–Cell Junctions and Lung Metastasis
Authors: Tanja Holopainen, Pipsa Saharinen, Gabriela D’Amico, Anita Lampinen, Lauri Eklund, Raija Sormunen, Andrey Anisimov, Georgia Zarkada, Marja Lohela, Hanna Heloterä, Tuomas Tammela, Laura E. Benjamin, Seppo Ylä-Herttuala, Ching Ching Leow, Gou Young Koh, Kari Alitalo
Journal: JNCI Journal of the National Cancer Institute (2012)

Angiopoietin-2 (Ang2), a ligand for endothelial TEK (Tie2) tyrosine kinase receptor, is induced in hypoxic endothelial cells of tumors, where it promotes tumor angiogenesis and growth. However, the effects of Ang2 on tumor lymphangiogenesis and metastasis are poorly characterized. We addressed the effect of Ang2 on tumor progression and metastasis using systemic Ang2 overexpression in mice carrying tumor xenografts, endothelium-specific overexpression of Ang2 in VEC-tTA/Tet-OS-Ang2 transgenic mice implanted with isogenic tumors, and administration of Ang2-blocking antibodies to tumor-bearing immunodeficient mice. Fisher's exact test was used for analysis of metastasis occurrence, and repeated measures one-way analysis of variance was used for the analysis of primary tumor growth curves. Unpaired t test was used for all other analyses. All statistical tests were two-sided. Adenoviral expression of Ang2 increased lymph node and lung metastasis in tumor xenografts. The metastatic burden in the lungs was increased in transgenic mice in which Ang2 expression was induced specifically in the vascular endothelium (tumor burden per grid, VEC-tTA/Tet-OS-Ang2 mice [n = 5] vs control mice [n = 4]: 45.23 vs 12.26 mm2, difference = 32.67 mm2, 95% confidence interval = 31.87 to 34.07, P < .001). Ang2-blocking antibodies reduced lymph node and lung metastasis, as well as tumor lymphangiogenesis, and decreased tumor cell homing to the lungs after intravenous injection. In the lung metastases, Ang2 overexpression decreased endothelial integrity, whereas the Ang2-blocking antibodies improved endothelial cell–cell junctions and basement membrane contacts of metastasis-associated lung capillaries. At the cellular level, the Ang2-blocking antibodies induced the internalization of Ang2-Tie2 receptor complexes from endothelial cell–cell junctions in endothelial–tumor cell cocultures. Our results indicate that blocking Ang2 inhibits metastatic dissemination in part by enhancing the integrity of endothelial cell–cell junctions.
Muscle Mass in Elderly Colorectal Cancer is Unrelated to Plasma Myoglobin Concentration
Authors: S.M. Nyasavajjala, A. Selby, W. Hildebrandt, J.P. Williams, R. Singh, K. Smith, S. Liptrot, J.N. Lund, M.J. Rennie
Journal: International Journal of Surgery (2010)
Nanomaterials for Photo-Based Diagnostic and Therapeutic Applications
Authors: Jyothi U. Menon, Parth Jadeja, Pranjali Tambe, Khanh Vu, Baohong Yuan, Kytai T. Nguyen
Journal: Theranostics (2013)

Photo-based diagnosis and treatment methods are gaining prominence due to increased spatial imaging resolution, minimally invasive modalities involved as well as localized treatment. Recently, nanoparticles (NPs) have been developed and used in photo-based therapeutic applications. While some nanomaterials have inherent photo-based imaging capabilities, others including polymeric NPs act as nanocarriers to deliver various fluorescent dyes or photosensitizers for photoimaging and therapeutic applications. These applications can vary from Magnetic Resonance Imaging (MRI) and optical imaging to photothermal therapy (PTT) and chemotherapy. Materials commonly used for development of photo-based NPs ranges from metal-based (gold, silver and silica) to polymer-based (chitosan, dextran, poly ethylene glycol (PEG) and poly lactic-co-glycolic acid (PLGA)). Recent research has paved the way for multi-modal 'theranostic' (a combination of therapy and diagnosis) nano-carriers capable of active targeting using cell-specific ligands and carrying multiple therapeutic and imaging agents for accurate diagnosis and controlled drug delivery. This review summarizes the different materials used today to synthesize photo-based NPs, their diagnostic and therapeutic applications as well as the current challenges faced in bringing these novel nano-carriers into clinical practices.
Targeting RNA Polymerase I with an Oral Small Molecule CX-5461 Inhibits Ribosomal RNA Synthesis and Solid Tumor Growth
Authors: Denis Drygin, Amy Lin, Josh Bliesath, Caroline B. Ho, Sean E. O'Brien, Chris Proffitt, Mayuko Omori, Mustapha Haddach, Michael K. Schwaebe, Adam Siddiqui-Jain, Nicole Streiner, Jaclyn E. Quin, Elaine Sanij, Megan J. Bywater, Ross D. Hannan, David Ryckman, Kenna Anderes, William G. Rice
Journal: Cancer Research (2010)

Abstract Deregulated ribosomal RNA synthesis is associated with uncontrolled cancer cell proliferation. RNA polymerase (Pol) I, the multiprotein complex that synthesizes rRNA, is activated widely in cancer. Thus, selective inhibitors of Pol I may offer a general therapeutic strategy to block cancer cell proliferation. Coupling medicinal chemistry efforts to tandem cell- and molecular-based screening led to the design of CX-5461, a potent small-molecule inhibitor of rRNA synthesis in cancer cells. CX-5461 selectively inhibits Pol I–driven transcription relative to Pol II–driven transcription, DNA replication, and protein translation. Molecular studies demonstrate that CX-5461 inhibits the initiation stage of rRNA synthesis and induces both senescence and autophagy, but not apoptosis, through a p53-independent process in solid tumor cell lines. CX-5461 is orally bioavailable and demonstrates in vivo antitumor activity against human solid tumors in murine xenograft models. Our findings position CX-5461 for investigational clinical trials as a potent, selective, and orally administered agent for cancer treatment. Cancer Res; 71(4); 1418–30. ©2010 AACR.
HISTAMINE-INDUCED VANIL-MANDELIC-ACIDURIA IN THE SCHIZOPHRENIC AND THE NON-SCHIZOPHRENIC PSYCHIATRIC PATIENT
Authors: PAUL KOCH, PIERRE LEFEBVRE, ROGER LEMIEUX, CAMILLE LAURIN
Journal: American Journal of Psychiatry (1962)

Intramuscular histamine can be used to confirm a diagnosis of schizophrenia in the young schizophrenic male. It will increase his urinary excretion of vanil-mandelic acid significantly. Histamine induced vanil-mandelic-aciduria will neither occur in the non-schizophrenic psychiatric male patient nor in any psychiatric woman patient, schizophrenic or not.
A randomised controlled study of the effect of cholinesterase inhibition on colon function in patients with diabetes mellitus and constipation
Authors: Adil E Bharucha, Phillip Low, Michael Camilleri, Erica Veil, Duane Burton, Yogish Kudva, Pankaj Shah, Tonette Gehrking, Alan R Zinsmeister
Journal: Gut (2012)

<h3>Objectives</h3> Chronic constipation in diabetes mellitus is associated with colonic motor dysfunction and is managed with laxatives. Cholinesterase inhibitors increase colonic motility. This study evaluated the effects of a cholinesterase inhibitor on gastrointestinal and colonic transit and bowel function in diabetic patients with constipation. <h3>Design</h3> After a 9-day baseline period, 30 patients (mean±SEM age 50±2 years) with diabetes mellitus (18 type 1, 12 type 2) and chronic constipation without defaecatory disorder were randomised to oral placebo or pyridostigmine, starting with 60 mg three times a day, increasing by 60 mg every third day up to the maximum tolerated dose or 120 mg three times a day; this dose was maintained for 7 days. Gastrointestinal and colonic transit (assessed by scintigraphy) and bowel function were evaluated at baseline and the final 3 and 7 days of treatment, respectively. Treatment effects were compared using analysis of covariance, with gender, body mass index and baseline colonic transit as covariates. <h3>Results</h3> 19 patients (63%) had moderate or severe autonomic dysfunction; 16 (53%) had diabetic retinopathy. 14 of 16 patients randomised to pyridostigmine tolerated 360 mg daily; two patients took 180 mg daily. Compared with placebo (mean±SEM 1.98±0.17 (baseline), 1.84±0.16 (treatment)), pyridostigmine accelerated (1.96±0.18 (baseline), 2.45±0.2 units (treatment), p&lt;0.01) overall colonic transit at 24 h, but not gastric emptying or small-intestinal transit. Treatment effects on stool frequency, consistency and ease of passage were significant (p≤0.04). Cholinergic side effects were somewhat more common with pyridostigmine (p=0.14) than with placebo. <h3>Conclusions</h3> Cholinesterase inhibition with oral pyridostigmine accelerates colonic transit and improves bowel function in diabetic patients with chronic constipation. <h3>Clinical trial registration number</h3> TrialRegNo (NCT 00276406).
IL-25: The Missing Link Between Allergy, Viral Infection, and Asthma?
Authors: Evangelos Andreakos, Nikolaos G. Papadopoulos
Journal: Science Translational Medicine (2014)

Interleukin 25 boosts proinflammatory and proasthmatic responses in the allergic lung and emerges as a key determinant of virally induced asthma exacerbations and as a therapeutic target for asthma (Beale et al ., this issue).
Medically unexplained symptoms in frequent attenders of secondary health care: retrospective cohort study
Authors: S. Reid
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To estimate the prevalence of medically unexplained symptoms in patients who most frequently attend outpatient services. <b>Design:</b> Retrospective cohort study over three years with review of case notes. <b>Setting:</b> Secondary care services in the South Thames (West) NHS region. <b>Participants:</b> Outpatient attenders with new appointments in 1993. <b>Main outcome measures:</b> Number of outpatient appointments, and number of consultation episodes for medically unexplained conditions. <b>Results:</b> Medical records of 361 of 400 sampled frequent attenders were examined, and 971 consultation episodes were recorded. Ninety seven (27%) had one or more consultation episodes in which the condition was medically unexplained; 208 (21%) of the 971 consultation episodes were medically unexplained. Abdominal pain, chest pain, headache, and back pain were commonly found to be medically unexplained. <b>Conclusions:</b> Medically unexplained symptoms present in most hospital specialties and account for a considerable proportion of consultations by frequent attenders in secondary care. <h3>What is already known on this topic</h3> Frequent attenders in all medical settings account for a disproportionate amount of healthcare resources In primary care, frequent attenders commonly present with symptoms that remain medically unexplained <h3>What this study adds</h3> Medically unexplained symptoms are also common among frequent attenders in secondary care and present in most specialties Symptoms that are particularly likely to remain unexplained in this group include gastrointestinal complaints, back pain, and headache
Hernia of a Diverticulum, a True Littre's Hernia
Authors: T. R. Smith
Journal: BMJ (1901)

A TRUE LITTRE'S HERNIA.[D2c.14, Y90.satisfactorily for weeks together without any attention, and its temperature does not alter to an extent that is appreciable to an ordinary thermometer.The apparatus is simple, but difficult of explanation in a few words.My excuse for entering into minute detail is that I have desired to render myself clearly understood.There are probably not a few who have felt the, want of such a contrivance, and who, like myself, have been informed by instrument makers that an electrical regulator was an im- possibility.Before closing, I desire to acknowledge my indebtedness to Mr. Weatherby, engineer, for constructing the apparatus and for valuable practical suggestions, and to Mr. A. 0. Cossor, Farringdon Road, for making the thermostat
Prevention of UV radiation–induced immunosuppression by IL-12 is dependent on DNA repair
Authors: Agatha Schwarz, Akira Maeda, Kerstin Kernebeck, Harry van Steeg, Stefan Beissert, Thomas Schwarz
Journal: The Journal of Experimental Medicine (2005)

The immunostimulatory cytokine IL-12 is able to antagonize immunosuppression induced by solar/ultraviolet (UV) radiation via yet unknown mechanisms. IL-12 was recently found to induce deoxyribonucleic acid (DNA) repair. UV-induced DNA damage is an important molecular trigger for UV-mediated immunosuppression. Thus, we initiated studies into immune restoration by IL-12 to discern whether its effects are linked to DNA repair. IL-12 prevented both UV-induced suppression of the induction of contact hypersensitivity and the depletion of Langerhans cells, the primary APC of the skin, in wild-type but not in DNA repair-deficient mice. IL-12 did not prevent the development of UV-induced regulatory T cells in DNA repair-deficient mice. In contrast, IL-12 was able to break established UV-induced tolerance and inhibited the activity of regulatory T cells independent of DNA repair. These data identify a new mechanism by which IL-12 can restore immune responses and also demonstrate a link between DNA repair and the prevention of UV-induced immunosuppression by IL-12.
GMODWeb: a web framework for the generic model organism database
Authors: Brian D O'Connor, Allen Day, Scott Cain, Olivier Arnaiz, Linda Sperling, Lincoln D Stein
Journal: Genome biology (2008)

The Generic Model Organism Database (GMOD) initiative provides species-agnostic data models and software tools for representing curated model organism data. Here we describe GMODWeb, a GMOD project designed to speed the development of model organism database (MOD) websites. Sites created with GMODWeb provide integration with other GMOD tools and allow users to browse and search through a variety of data types. GMODWeb was built using the open source Turnkey web framework and is available from http://turnkey.sourceforge.net.
Regulation of Connexin43 Gap Junctional Conductance by Ventricular Action Potentials
Authors: Xianming Lin, Mark Crye, Richard D. Veenstra
Journal: Circulation Research (2003)

Transjunctional voltage regulates cardiac gap junctional conductance, but the kinetics of inactivation were considered too slow to affect cardiac action potential propagation. Connexin43 (Cx43) is abundantly expressed in the atrial and ventricular myocardium and the rapid ventricular conduction tissues (ie, His-Purkinje system) of the mammalian heart and is important to conduction through these cardiac tissues. The kinetics of Cx43 voltage gating were examined at peak action potential voltages using simulated ventricular myocardial action potential waveforms or pulse protocols exceeding 100-mV transjunctional potentials. Junctional current responses approximate the action potential morphology but conductance calculations reveal a 50% to 60% decline from peak to near constant plateau values. Junctional conductance recovers during phase 3 repolarization and early diastole to initial values. The bases for these transient changes in junctional conductance are the rapid decay kinetics in tens of milliseconds at peak transjunctional voltages (Vj) of 130 mV and the gradual increase in junctional conductance as Vj returns toward 0 mV. The decay time constants change e-fold per 22.1 mV above the half-inactivation voltage for Cx43 gap junctions of +/-58 mV. A realistic dynamic model for changes in junctional resistance between excitable and nonexcitable cells during cardiac action potential propagation was developed based on these findings. This dynamic model of cardiac gap junctions will further our understanding of the role gap junctions play in the genesis and propagation of cardiac arrhythmias. The full text of this article is available online at http://www.circresaha.org.
Radiation-Guided Drug Delivery to Mouse Models of Lung Cancer
Authors: Ghazal Hariri, Heping Yan, Hailun Wang, Zhaozhong Han, Dennis E. Hallahan
Journal: Clinical Cancer Research (2010)

Abstract Purpose: The purpose of this study was to achieve improved cancer-specific delivery and bioavailability of radiation-sensitizing chemotherapy using radiation-guided drug delivery. Experimental Design: Phage display technology was used to isolate a recombinant peptide (HVGGSSV) that binds to a radiation-inducible receptor in irradiated tumors. This peptide was used to target nab-paclitaxel to irradiated tumors, achieving tumor-specificity and enhanced bioavailability of paclitaxel. Results: Optical imaging studies showed that HVGGSSV-guided nab-paclitaxel selectively targeted irradiated tumors and showed 1.48 ± 1.66 photons/s/cm2/sr greater radiance compared with SGVSGHV-nab-paclitaxel, and 1.49 ± 1.36 photons/s/cm2/sr greater than nab-paclitaxel alone (P &amp;lt; 0.05). Biodistribution studies showed &amp;gt;5-fold increase in paclitaxel levels within irradiated tumors in HVGGSSV-nab-paclitaxel–treated groups as compared with either nab-paclitaxel or SGVSGHV-nab-paclitaxel at 72 hours. Both Lewis lung carcinoma and H460 lung carcinoma murine models showed significant tumor growth delay for HVGGSSV-nab-paclitaxel as compared with nab-paclitaxel, SGVSGHV-nab-paclitaxel,and saline controls. HVGGSSV-nab-paclitaxel treatment induced a significantly greater loss in vasculature in irradiated tumors compared with unirradiated tumors, nab-paclitaxel, SGVSGHV-nab-paclitaxel, and untreated controls. Conclusions: HVGGSSV-nab-paclitaxel was found to bind specifically to the tax-interacting protein-1 (TIP-1) receptor expressed in irradiated tumors, enhance bioavailability of paclitaxel, and significantly increase tumor growth delay as compared with controls in mouse models of lung cancer. Here we show that targeting nab-paclitaxel to radiation-inducible TIP-1 results in increased tumor-specific drug delivery and enhanced biological efficacy in the treatment of cancer. Clin Cancer Res; 16(20); 4968–77. ©2010 AACR.
Outcome Analysis for Patients With Elevated Serum Tumor Markers at Postchemotherapy Retroperitoneal Lymph Node Dissection
Authors: Stephen D.W. Beck, Richard S. Foster, Richard Bihrle, Lawrence H. Einhorn, John P. Donohue
Journal: Journal of Clinical Oncology (2005)

Purpose To evaluate the therapeutic benefit of postchemotherapy retroperitoneal lymph node dissection (PCRPLND) in patients with persistently elevated serum tumor markers. Patients and Methods One hundred fourteen patients with metastatic germ cell cancer with elevated serum tumor markers after first-line (50 patients) or second-line chemotherapy (64 patients) who underwent PCRPLND between 1977 and 2000 with a minimum follow-up of 2-years were included in this retrospective study. Results The 5-year overall survival was 53.9%. Sixty-one patients (53.5%) are alive with a medium follow-up of 72 months. Fifty-three patients died of disease, with a medium time to death of 8.0 months. Mean preoperative serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (βHCG) levels were 483 ng/mL and 555 mU/mL, respectively, with no difference in 5-year survival (P = .2). Retroperitoneal pathology revealed germ cell cancer in 53.5% of patients, teratoma in 34.2% of patients, and fibrosis in 12.2% of patients, with 5-year survival rates of 31.4%, 77.5%, and 85.7%, respectively (P &lt; .0001). Predictors of retroperitoneal pathology included an increasing serum AFP or βHCG, βHCG more than 100 ng/mL, redo retroperitoneal lymph node dissection (RPLND), and second-line chemotherapy. Poor prognostic variables by multivariable analysis included βHCG status, serum AFP level, redo RPLND, and germ cell cancer in the resected specimen. Conclusion A subset of patients with elevated serum tumor markers after chemotherapy is curable with surgery. The prognostic factors predictive of outcome in this analysis include an increasing βHCG, serum AFP level, redo RPLND, and germ cell cancer in the resected specimen. These factors, along with clinical and surgical experience, should aid in determining the appropriate integration of surgery and chemotherapy in this population.
Phase II Trial of Ixabepilone As Second-Line Treatment in Advanced Endometrial Cancer: Gynecologic Oncology Group Trial 129-P
Authors: Don S. Dizon, John A. Blessing, D. Scott McMeekin, Sudarshan K. Sharma, Paul DiSilvestro, Ronald D. Alvarez
Journal: Journal of Clinical Oncology (2009)

PURPOSE A phase II study was conducted to determine the response rate of ixabepilone (BMS-247550, National Cancer Institute (NCI)-supplied agent investigational new drug No. 59,699) in patients with persistent or recurrent endometrial cancer who have progressed despite standard therapy. PATIENTS AND METHODS Eligible patients had recurrent or persistent endometrial cancer and measurable disease. One prior chemotherapeutic regimen, which could have included either paclitaxel or docetaxel, was allowed. Patients received ixabepilone 40 mg/m(2) as a 3-hour infusion on day 1 of a 21-day cycle. Treatment was continued until disease progression or until unacceptable toxicity occurred. Results Fifty-two patients were entered on the study, and 50 of these were eligible. The median age was 64 years (range, 40 to 83 years). Prior treatment included radiation in 21 patients (42%) and hormonal therapy in eight patients (16%). All patients had prior chemotherapy, and 47 (94%) received prior paclitaxel therapy. The overall response rate was 12%; one patient achieved a complete remission (2%), and five achieved partial remission (10%). Stable disease for at least 8 weeks was noted in 30 patients (60%). The median progression-free survival (PFS) was 2.9 months, and the 6-month PFS was 20%. Major grade 3 toxicities were neutropenia (52%), leukopenia (48%), gastrointestinal (24%), neurologic (18%), constitutional (20%), infection (16%), and anemia (14%). CONCLUSION In a cohort of women with advanced or recurrent endometrial cancer who were previously treated with paclitaxel, ixabepilone showed modest activity of limited duration as a second-line agent.
Transgenic mice expressing rabbit C-reactive protein exhibit diminished chemotactic factor-induced alveolitis.
Authors: N Ahmed, R Thorley, D Xia, D Samols, R O Webster
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The acute phase protein, C-reactive protein (CRP), can increase more than a thousandfold during acute inflammatory states, and it is known to modulate neutrophil-mediated inflammatory responses. We have previously shown that CRP inhibits chemotaxis of C5a-stimulated neutrophils in vitro and that rabbits with elevated CRP blood levels exhibit diminished pulmonary vascular permeability and neutrophil infiltration in a model of alveolitis. To study the effect of CRP on alveolitis induced by different chemoattractants, transgenic mice capable of expressing rabbit CRP in a dietary-inducible fashion were treated with inflammatory doses of the chemoattractants. Intratracheal installation of FMLP (8 x 10(-10) mol), LTB4 (2 x 10(-11) mol), or IL-8 (5 x 10(-12) mol) in normal CF1 mice resulted in significant (p<0.05) influx of neutrophils and protein into the alveolar space. Transgenic mice with elevated plasma levels of CRP showed significantly (p<0.05) diminished infiltration of neutrophils into bronchoalveolar lavage fluid (BALF) and significant reduction in BALF protein compared with that in normal mice. Rabbit CRP (10 to 500 micrograms/ml) inhibited in vitro neutrophil chemotaxis in a concentration-dependent fashion when stimulated by the various chemoattractants examined. These data show that rabbit CRP can modify both in vivo and in vitro neutrophil responses to several classes of chemoattractants and that CRP has a significant protective effect in alveolitis by reducing neutrophil influx and protein leakage into the lung.