tbuckley/cabot-search huggingface dataset:
Inherent and Tumor-Driven Immune Tolerance in the Prostate Microenvironment Impairs Natural Killer Cell Antitumor Activity
Authors: Christine Pasero, Gwenaëlle Gravis, Mathilde Guerin, Samuel Granjeaud, Jeanne Thomassin-Piana, Palma Rocchi, Maria Paciencia-Gros, Flora Poizat, Mélanie Bentobji, Francine Azario-Cheillan, Jochen Walz, Naji Salem, Serge Brunelle, Alessandro Moretta, Daniel Olive
Journal: Cancer Research (2016)

The field of immunotherapy for solid tumors, such as prostate cancer, has been recently focusing on therapies that can counter tumor-mediated immunosuppression. Precise quantification and characterization of the immune infiltrates in tumors is crucial to improve treatment efficacy. Natural killer (NK) cells, major components of the antitumor immune system, have never been isolated from prostate tumors, despite their suspected role in disease progression. Here, we examined the frequency, phenotype, and functions of NK cells infiltrating control and tumor prostate tissues. NK cell infiltrates in prostate tissues were mainly CD56 (NCAM1)-positive and displayed an unexpected immature, but activated, phenotype with low or no cytotoxic potential. Furthermore, we show that TGFβ1 (TGFB1) is highly secreted into the prostate environment and partly mediates the immunosuppressive effects on NK cells. In addition to this basal level of immunotolerance to NK cells, the prostate environment became further resistant to NK cell-mediated immunity upon cancer cell infiltration. Coculture experiments revealed that prostate cancer cells induced the expression of inhibitory receptor (ILT2/LILRB1) and downregulated the expression of activating receptors NKp46 (NCR1), NKG2D (KLRK1), and CD16 (FCGR3) by NK cells, thus preventing their recognition of tumor cells. Notably, blood levels of NKp46 were also decreased in prostate cancer patients and were inversely correlated with levels of prostate-specific antigen, the main prognostic factor in prostate cancer. Our study shows that a strong immunosuppressive environment impairs NK cell function at multiple levels in prostate cancer and provides a rationale for the design of therapies that restore NK cell efficiency in the prostate tumor microenvironment. Cancer Res; 76(8); 2153-65. ©2016 AACR.
ACCESO ENDOSCOPICO TRANSURETRAL PARA EL TRATAMIENTO DE PATOLOGIA MIXTA UROLOGICO-DIGESTIVA
Authors: JR Armengol Miró, M Abu-Suboh Abadia, J Dot Bach, J Armengol Bertroli, A Benages Curell, M Masachs Peracaula, X Zhang, JC Salord Oses, L Rivero, D Castillo, SV Kantsevoy
Journal: Endoscopy (2012)

Objetivo: Desde los inicios de la endoscopia digestiva se ha establecido una estrecha colaboración con otras especialidades, para la resolución conjunta de casos complejos El objetivo de la comunicación es presentar tres casos de que tratamiento endoscópico con endoscopia flexible de complicaciones urológicas. Material y método: CASO 1: Paciente de 77 años de edad con antecedentes de tuberculosis que requirió nefroueterectomía derecha y colocistoplastia a los 30 años por secuela urinaria post tuberculosis y lobectomía pulmonar a los 32 años. El paciente acude a urgencias por oliogoanúria y astenia con creatinina 6mg/dl. Por ecografía hay dilatación del tracto urinario y una masa en la neovejiga. El TC muestra engrosamiento de la pared de la vejiga compatible con tumor de vejiga. Se realiza una cistoscopia que muestra una formación polipoide vellosa de 5cm. de diámetro y un pólipo velloso de 1,5cm. de diámetro inaccesibles al instrumental de urología transuretral. Mediante un endoscopio de pequeño calibre (Olympus GIF-XP 180N) se efectuó una resección endoscópica transuretral de las lesiones con asa de polipectomía y técnica de piecemeal.
Abstract 4311: EphB2 receptor controls proliferation/migration dichotomy of glioblastoma by interacting with focal adhesion kinase
Authors: Shervin D. Wang, Prakash Rath, Bachchu Lal, Jean-Philippe Richard, Yunqing Li Li, C. Rory Goodwin, John Laterra, Shuli Xia
Journal: Cancer Research (2012)

Abstract Glioblastoma multiforme (GBM) are the most frequent and aggressive primary brain tumors in adults. Uncontrolled proliferation and abnormal cell migration are two prominent spatially and temporally disassociated characteristics of GBMs. In this study, we investigated the role of the receptor tyrosine kinase EphB2 in controlling the proliferation/migration dichotomy of GBM. We studied EphB2 gain-of-function and loss-of function in glioblastoma-derived stem-like neurospheres (GBM-SCs), whose in vivo growth pattern closely replicates human GBM. EphB2 expression stimulated GBM neurosphere cell migration and invasion, and inhibited neurosphere cell proliferation in vitro. In parallel, EphB2 silencing increased tumor cell proliferation and decreased tumor cell migration. EphB2 was found to increase tumor cell invasion in vivo using an internally controlled dual-fluorescent xenograft model. Xenografts derived from EphB2 overexpressing GBM neurospheres also showed decreased cellular proliferation. The non-receptor tyrosine kinase focal adhesion kinase (FAK) was found to be co-associated with and highly activated by EphB2 expression and FAK activation facilitated focal adhesion formation, cytoskeleton structure change and cell migration in EphB2-expression GBM neurosphere cells. Taken together, our findings indicate that EphB2 has pro-invasive and anti-proliferative actions in GBM stem-like neurospheres mediated, in part, by interactions between EphB2 receptors and FAK. These novel findings suggest that tumor cell invasion can be therapeutically targeted by inhibiting EphB2 signaling and that optimal anti-tumor responses to EphB2 targeting may require the concurrent use of anti-proliferative agents. 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 4311. doi:1538-7445.AM2012-4311
Response of Growth-Retarded Patients with Hand–Schüller–Christian Disease to Growth Hormone Therapy
Authors: Glenn D. Braunstein, Salvatore Raiti, James W. Hansen, Peter O. Kohler
Journal: New England Journal of Medicine (1975)

Five patients with growth retardation due to Hand–Schüller–Christian disease were treated for a maximum of two years with human growth hormone, which was administered intramuscularly, three times per week, in doses of 2 IU. All patients experienced a significant increment in growth rate in comparison to the year before the therapy. During the first year of therapy the mean growth rate was 7.5 cm—an increase of 5.2 cm over the pretreatment year (p< 0.01). The growth rate during the second year of treatment was less, with a mean increase of 2.8 cm per year (P<0.05). These results are similar to the response of patients with idiopathic growth hormone deficiency and add further evidence that the growth retardation associated with Hand–Schüller–Christian disease is due to an acquired growth hormone secretory deficiency. (N Engl J Med 292:332–333, 1975)
A4.3 Differences of bone WNT regulators expression between fragility fractures and osteoarthritis patients
Authors: AM Rodrigues, J Caetano-Lopes, V Oliveira, B Vidal, MJ Gonçalves, A Sepriano, M Sarmento, J Monteiro, JE Fonseca, H Canhão
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Introduction</h3> The importance of Wnt signalling, a crucial pathway for osteoblast differentiation and a master bone mass regulator as been recently highlighted. With this study, we aim to compare bone expression of Wnt regulators between fragility fracture and osteoarthritis patients. <h3>Methods</h3> Patients submitted to total hip replacement surgery either due to a fragility fracture or to osteoarthritis, at the Orthopedics department of Hospital de Santa Maria, were recruited. Clinical risk factors (CRFS) for osteoporotic fractures were collected. RNA was extracted from a small trabecular bone sample and analysed by quantitative real-time protein chain reaction (RT-PCR). Immunohistochemistry analysis for DKK1 and SOST was also performed. <h3>Results</h3> 118 patients submitted to total hip replacement surgery, 55 due to fragility fracture, were evaluated. Fragility fracture patients were predominantly women (84% vs 49%, p&lt;0.001), significantly older (80 ± 7 vs 68 ± 12, p &lt; 0.001) and had significantly more previous fragility fractures than the osteoarthritis group (33% vs 5%, p &lt; 0.001). Univariate analysis showed that RANKl/OPG ratio, a marker of osteoclastogenisis, was significantly higher in the fragility fracture group (p &lt; 0.001). On the other hand osteocalcin expression, a marker of osteoblast maturation was significantly lower in fragility fracture group (p &lt; 0.001). Regarding Wnt regulators, WNT 10b (β = -0,398, p &lt; 0.001) and DKK1 (β = -0,387, p &lt; 0.001) expression was significantly higher in osteoarthritis group even after adjusting for age and gender. In multivariate analysis SOST (β = 0.236, p = 0.0411) was significantly higher in the fragility fracture group. Semi-quantitative analysis of immunohistochemistry results for DKK1 revealed a significantly higher staining scores (p = 0.04) in the osteoarthritis group. <h3>Conclusion</h3> In fragility fracture patients, bone SOST expression is upregulated. In osteoarthritis patients, DKK1 gene expression and protein staining is significantly higher than in fragility fractures. These results improve the knowledge of WNT disturbances in these two diseases and can be of help to identify new treatment targets.
P35 The combined gold assessment, muscle weakness and walking distance: Abstract P35 Table 1.
Authors: JM Seymour, MA Spruit, J Moxham, EFM Wouters, MI Polkey
Journal: Thorax (2013)

<h3>Introduction</h3> The revised 2013 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines propose a composite assessment and drug treatment according to exacerbation risk and symptoms (into category A, B C or D). It is unclear how muscle weakness and exercise capacity relate to these categories, however, pulmonary rehabilitation is proposed for groups B, C and D. We wished to quantify the frequency of these deficits in the GOLD composite assessment categories. <h3>Methods</h3> A cohort of secondary care chronic obstructive pulmonary disease (COPD) patients in the United Kingdom and The Netherlands has been previously described (Eur Respir J. 2010;36:81–8). Using previously reported lower limits of normal, patients with quadriceps maximum voluntary contraction (QMVC) weakness and/or reduced six-minute walking test (SMWT) performance, were retrospectively identified in this cohort. Patients were divided into the revised GOLD combined assessment categories using spirometry and Medical Research Council (MRC) dyspnoea score. Phenotypes were further compared with self-reported medication use. <h3>Results</h3> The original cohort comprised 351 patients (mean (SD) age 63(10) years), 59% males) with measured spirometry and quadriceps maximum voluntary contraction strength. Table 1 shows frequency of QMVC weakness and reduced SMWT performance in the different combined GOLD assessment categories. The majority of patients (58%) were in the most severe category (D). There was no statistical difference in the frequency of quadriceps weakness between categories. Reduced SMWT performance differed significantly between categories (Chi-square P &lt; 0.001). Reduced SMWT performance was less common than muscle weakness in category A (P = 0.025). Logistic regression suggested that normal (preserved) quadriceps strength and SMWT performance were associated with long-acting beta agonist (LABA) use (OR 1.99, 95% CI 1.02 to 3.88, P = 0.043, and OR 2.00, 95% CI 1.01 to 4.00, P = 0.049 respectively), independent of assessment category and other COPD medication. <h3>Discussion</h3> GOLD assessment category A may contain individuals who would benefit from pulmonary rehabilitation. Quadriceps weakness was more common than reduced walking capacity in this category. Exacerbation history and COPD assessment test (CAT) score were not recorded in this cohort and may have produced different results. A prospective investigation of LABA use on exercise capacity and muscle strength in COPD may be indicated.
A5.28 Semaphorin3A is a Potent B Cell Regulatory Molecule in SLE
Authors: Zahava Vadasz, Elias Toubi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background/Purpose</h3> Semaphorin3A (sem3A) is an important regulatory molecule, previously reported to play a role in the pathogenesis of rheumatoid arthritis and later by us in lupus glomerulonephritis. In addition, sema3A was shown to be a marker of T regulatory cells. A subpopulation of B cells, namely B regulatory cells (Bregs), was recently identified by us as CD19+CD25<sup>high</sup>IL-10<sup>high</sup>TGF-β<sup>high</sup>, and demonstrated to be of high sema3A expression. We therefore asked whether serum levels of sema3A is altered in SLE patients, whether sema3A expression on B regs of these patients is different, and finally, whether the addition of soluble sema3A to cultured B cells improves their regulatory and or pro-inflammatory properties. <h3>Materials and Methods</h3> Serum from SLE patients, RA patients (disease control) and normal controls was analysed for sema3A levels and was correlated with clinical parameters of SLE. The expression of sema3A on Bregs was compared between SLE patients and normal individuals. In addition to this, the expression of CD72 and TGF-β (inhibitory molecules), and TLR-9 in B cells were assessed in both groups following the addition of recombinant sema3A to cultured B cells. <h3>Results</h3> 1. Serum sema3A levels were significantly lower in SLE patients comparing to that of RA patients and much lower than in normal controls (55.04 ± 16.30 ng/ml versus 65.54 ± 14.82 ng/ml, versus 74.41 ± 17.60 ng/ml, respectively, P &lt; 0.0001). 2. Sema3A levels were inversely correlated with SLE disease severity, kidney involvement and anti-cardiolipin-ab. 3. Sema3A expression on Bregs was significantly lower in SLE patients comparing normal individuals (52.2 ± 5.8% versus 82.6 ± 6.4%, P &lt; 0.0001, respectively). 4. The expression of both CD72 and TGF-β was significantly decreased (37.88%, 8.6% respectively) in Bregs of SLE patients versus that on normal Bregs (49.26%, 14.74%, respectively; P = 0.001). However, following the addition of sema3A to cultured B cells, a significant increase of TGF- β and CD72 was noticed (altered in SLE patients, when compared to that of normal individuals). 5. The addition of sema3A to CpG-ODN stimulated B cells from SLE patients reduced TLR-9 expression by almost 50%. <h3>Conclusions</h3> 1. This is the first study where sema3A is shown to be altered in both serum and on Breg cells of SLE patients. 2. Sema3A enhances the regulatory properties of Bregs, but this effect is shown to be altered in SLE. 3. Sema3A should be considered a future therapeutic tool in SLE.
Use of covered self-expandable metallic stents in post-endoscopic sphincterotomy bleeding
Authors: G. Mavrogenis, D. Coumaros
Journal: Endoscopy (2011)

We read with interest the article by Itoi et al. on the use of covered self-expandable metallic stents (SEMSs) for uncontrolled bleeding following endoscopic sphincterotomy [1]. We agree with the authors that the covered SEMS is a useful treatment modality for management of recurrent post-endoscopic sphincterotomy bleeding, after failure of or in combination with other endoscopic methods, which include: (a) injection (epinephrine, fibrin glue); (b) thermal methods (heater probe, electrocoagulation, argon plasma coagulation); and (c) mechanical methods (balloon tamponade, clipping) [2] [3] [4] [5].
Effect of ACTH on Induced Fever
Authors: Edward H. Kass, Maxwell Finland
Journal: New England Journal of Medicine (1950)

ONE of the most striking effects of the administration of pituitary adrenocorticotrophic hormone (ACTH) to patients with febrile illnesses is the prompt defervescence that is frequently observed. The fever may recur while ACTH is being administered, but it usually subsides again when the dose of the hormone is increased In many cases fever, toxicity and other clinical evidences of illness return after ACTH or Cortisone is withdrawn.1 2 3 Such observations suggest that these hormones may aid the host to resist the toxic effects of a given illness or, perhaps, obscure certain manifestations of disease by reducing the fever and altering the . . .
S35 Rapamycin inhibits IL-33-induced, nuocyte-driven airway inflammation
Authors: A. S. Mirchandani, R. J. Salmond, C. J. Bain, F. Y. Liew
Journal: Thorax (2011)

<h3>Introduction</h3> IL-33 is an innate cytokine that promotes Th2 responses in both the innate and the adaptive immune systems, with an established role in allergic airway inflammation.1 The signalling pathway of IL-33/ ST2 is incompletely understood and the cells driving IL-33-mediated inflammation have remained elusive. Nuocytes, also known as natural helper cells, are a novel subpopulation of lineage negative innate cells that respond to IL-33 and IL-2.2 Rapamycin is a macrolide antibiotic that allosterically blocks mTOR, a serine-threonine kinase involved in numerous cellular signalling pathways. <h3>Aim</h3> To determine the role of mTOR in IL-33-induced airway inflammation and the effect of rapamycin on IL-33-induced nuocytes in the lung. <h3>Method</h3> BALB/c mice were treated with 1 μg of IL-33 intranasally for 5 consecutive days in the presence or absence of rapamycin. Bronchoalveolar lavage (BAL) for cellular and cytokine analysis was performed. Fluorescence-activated cell sorting (FACS) of lung digests were analysed for intracellular IL-5 and cell surface markers. <h3>Results</h3> IL-33 induced profound airway cellular infiltration noted in the BAL that was significantly inhibited by rapamycin. Cytokine levels from BAL fluid were also significantly reduced in mice treated with IL-33+ rapamycin. FACS analysis of lung digests demonstrated that IL-33 induced the expansion of lineage negative cells, in keeping with a population of nuocytes, which were the main source of IL-5 in the lung. Furthermore, this population of cells was suppressed by rapamycin. <h3>Discussion</h3> Intranasal IL-33 drives mTOR-dependant airway inflammation. Nuocytes are the main source of IL-5 in IL-33-driven airway inflammation. Rapamycin inhibits the production of IL-5 and IL-13 in vivo as well as the expansion of nuocytes in the lung.
Imatinib mesylate in newly diagnosed patients of chronic myeloid leukemia chronic phase: A comparative study
Authors: L. A. Jacob, P. P. Bapsy, K. Govindbabu, D. Lokanatha
Journal: Journal of Clinical Oncology (2007)

17521 Background: Two single centre experiences from India on the use of Imatinib mesylate in the treatment of chronic myeloid leukemia chronic phase (CML-CP) have shown somewhat similar results. While complete hematological response (CHR) achieved in the two studies was comparable to Western data, major cytogenetic response (MCR) and complete cytogenetic response (CCR) were much lower. Both studies had included newly diagnosed as well as previously treated patients. This study was undertaken to evaluate the efficacy and safety of imatinib mesylate, only in newly diagnosed patients of CML-CP and to compare the results obtained with those reported in literature. Methods: The study population included 100 newly diagnosed patients of CML-CP. Therapy was initiated with imatinib mesylate 400mg orally daily and patients monitored carefully for any adverse effects. After 6 months of treatment, bone marrow aspiration and cytogenetics were repeated to ascertain the response. In patients not achieving a MCR, the dose of imatinib was increased to 600mg daily and therapy continued. Results: In the present study, although imatinib produced CHR in 90% of the patients; only 50% achieved a MCR at 6 months and 55% at 12 months as compared to the 86- 87% reported in major trials involving newly diagnosed patients of CML-CP. The drug was safe and well tolerated. A comparison of patient characteristics with those in the Western studies revealed that majority of the Indian patients probably presented late in the disease course. A higher incidence of adverse genomic factors at diagnosis leading to rapid progression of disease could be the probable explanation for this. Conclusions: Thus based on our present study, we conclude that there is a difference in the efficacy profile of imatinib in Indian patients as compared to the West, the reasons for which needs to be investigated and validated. No significant financial relationships to disclose.
PCSK9 Inhibitors for Statin Intolerance?
Authors: David D. Waters, Priscilla Y. Hsue, Sripal Bangalore
Journal: JAMA (2016)

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ONE YEAR FOLLOW-UP RESULTS FROM PRESERVE-AMI: A RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED CLINICAL TRIAL OF INTRACORONARY INFUSION OF AUTOLOGOUS CD34+ CELLS IN PATIENTS WITH LEFT VENTRICULAR DYSFUNCTION POST STEMI
Authors: Arshed Quyyumi, Dean Kereiakes, David Shavelle, Timothy Henry, Ali Denktas, Ahmed Abdel-Latif, Catalin Toma, Gregory Barsness, Stephen Frohwein, Richard Schatz, Martin Cohen, Charles Davidson, Nabil Dib, Marc Klapholz, Gary Schaer, Alejandro Vasquez, Andrew Pecora, Thomas Moss, Pamela Hyde, Anna Maria Kanakaraj, Le Dich, Vitaly Druker, Candice Junge, Robert Preti, Douglas Losordo
Journal: Journal of the American College of Cardiology (2015)