tbuckley/cabot-search huggingface dataset:
16-kDa Prolactin Inhibits Endothelial Cell Migration by Down-Regulating the Ras-Tiam1-Rac1-Pak1 Signaling Pathway
Authors: Sok-Hyong Lee, Jeannette Kunz, Sue-Hwa Lin, Li-yuan Yu-Lee
Journal: Cancer Research (2007)

Abstract Angiogenesis plays a key role in promoting tumorigenesis and metastasis. The 16-kDa fragment of prolactin (16k PRL) is an NH2-terminal natural breakdown fragment of the intact 23-kDa prolactin and has been shown to have potent antiangiogenic and antitumor activities. The mechanism(s) involved in the action of 16k PRL in endothelial cells remains unclear. In this study, we showed that 16k PRL reduced rat aortic endothelial cell (RAEC) migration in a wound-healing assay and in a Matrigel tube formation assay, suggesting that 16k PRL inhibits endothelial cell migration, an important activity involved in angiogenesis and tumorigenesis. We further investigated how 16k PRL attenuates endothelial cell migration. We first showed that RAEC migration is mediated through the Rho GTPase Rac1, as Rac1 inhibition by the Rac1-specific inhibitor NSC27366 or Rac1 knockdown by small interfering RNA both blocked RAEC migration. We next showed that 16k PRL reduced the activation of Rac1 in a concentration-dependent manner. Furthermore, 16k PRL inhibition of Rac1 is mediated through the suppression of T lymphoma invasion and metastasis 1 (Tiam1) and its upstream activator Ras in a phosphoinositide-3-kinase–independent manner. 16k PRL also down-regulated the phosphorylation of the downstream effector of Rac1, p21-activating kinase 1 (Pak1), and inhibited its translocation to the leading edge of migrating cells. Thus, 16k PRL inhibits cell migration by blocking the Ras-Tiam1-Rac1-Pak1 signaling pathway in endothelial cells. [Cancer Res 2007;67(22):11045–53]
Dynamic diastologic stress echocardiography with minimal exercise enables prediction of exercise tolerance in patients with congestive heart failure
Authors: Toshinori Yuasa, Yutaka Otsuji, Bo Yu, Takeshi Uemura, Kenichi Nakashiki, Kunitsugu Takasaki, Yoshihisa Noguchi, Naoko Mizukami, Toshihiro Morita, Tsuyoshi Fukudome, Amdadul Haque, Keiko Yuge, Yasuyuki Kamogawa, Akira Kisanuki, Shinichi Minagoe, Chuwa Tei
Journal: Journal of the American College of Cardiology (2003)
Erythema Multiforme/Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis in Lenalidomide-Treated Patients
Authors: Carmen P. Castaneda, Nancy A. Brandenburg, Robert Bwire, Graham H. Burton, Jerome B. Zeldis
Journal: Journal of Clinical Oncology (2008)

The patient is now working full time and continues to be asymptomatic, but has mild liver function abnormalities and serologic evidence of hepatitis C, possibly related to platelet transfusions given at the time of splenectomy.His blood counts remain normal, and a peripheral-blood analysis in June 2006 showed no evidence of an abnormal lymphocyte clone.Because of the patient's young age, his initial pathology specimens were reviewed by pathologists at University of California, San Francisco (M.
How can we improve our assessment of inflammation in clinical studies of COPD that use bronchial biopsies?
Authors: Q. Hamid
Journal: European Respiratory Journal (2006)

In this issue of the European Respiratory Journal , Gamble et al. 1 have retrospectively examined the sources of biological variability in the quantification of inflammatory cells in endobronchial biopsies using immunostained samples. The samples were taken from 51 subjects with chronic obstructive pulmonary disease (COPD) that were obtained from a clinical trial published by the same group. They reported that the distribution of variance contributed by different sources was similar for different inflammatory cell types. Using immunocytochemistry for CD8+ cells, the largest contribution to intersubject variability was time between biopsies of the placebo-treated group followed by airway generation, biopsy, zone and section. They concluded that examining one section of one biopsy from each of two airway generations would require a sample size of 32 subjects per group to show a difference of one doubling or halving in CD8+ cells. This would compare with a group of 47 subjects, if only one airway generation was sampled. They suggested that more than one airway generation should be examined in order to maximise the statistical power to detect a difference between study groups.

This is a timely paper that addresses an important issue in tissue analyses of inflammatory cells in chronic airway disease. I have seen many papers in the last few years that examine the effect of anti-inflammatory drugs using small numbers of patients and limited numbers of biopsies and sections. The quality of these papers has been variable and, in some cases, weak conclusions were drawn. This was due to a number of factors, including pressure to publish, limited resources and lack of experience in the analysis of immunoreactive cells. Adequate knowledge of the pathology of COPD and statistics is essential for developing …
Dosimetric Measurements in Isolated Human Coronary Arteries
Authors: Christoph Hanefeld, Schgofa Amirie, Dieter Borchardt, Peter Grewe, K.-M. Müller, Maria Kissler, Andreas Mügge
Journal: Circulation (2002)

Intravascular brachytherapy is being applied more and more in patients with coronary artery disease for the prevention of restenosis subsequent to balloon angioplasty, in particular after stent implantation. Several radiation sources (beta- and gamma-emitters) are available in clinical routine. It was the purpose of this study to compare the radiation doses at the level of the adventitia in diseased and stented human coronary arteries for (192)Ir and (90)Sr/Y emitters in routine use. In contrast to previously published work, we performed dosimetry instead of calculating depth-dose distribution by use of the Monte Carlo system.Postmortem calcified human coronary artery segments were stented and placed in an organ bath. Commercially available gamma-emitters ((192)Ir; Cordis Checkmate) and beta-emitters ((90)Sr/Y; Novoste Beta-Cath) were used. Relative dose distributions along the adventitia were measured by a specially designed scintillation detector system. Whereas dose perturbations caused by stents and calcified plaque were negligible for the (192)Ir source, radiation from the beta source was significantly impaired (as much as 40%) at the level of the adventitia (3.0-mm vessel diameter). Dose perturbation was clearly dependent on the extent and severity of calcification, less affected by stent material.Dose perturbation caused by calcified plaque and metallic stents is significant for beta-sources. This dosimetric difference between beta- and gamma-emitters in diseased coronary arteries should be considered when calculating doses in intravascular brachytherapy.
Endoscopic ultrasound-guided biopsy in the chest: little to lose, much to gain
Authors: P. Vilmann, S. S. Larsen
Journal: European Respiratory Journal (2005)

Tissue diagnosis of pathological lesions located in the mediastinum has been difficult to obtain by nonsurgical methods, well protected as it is by the bony covering of the thorax and the surrounding lungs. A variety of lesions involve the mediastinum either as primary tumours or as secondary deposits from both benign and malignant diseases. It is therefore of paramount clinical importance to develop safe and accurate minimally invasive methods that are able to tissue diagnose such lesions in order to plan specific treatments.

The most frequent cancer involving the mediastinum is nonsmall cell lung cancer (NSCLC) accounting for ∼80% of lung cancers. The prognosis of NSCLC is poor and closely related to the stage of disease. NSCLC usually metastasises first to hilar and mediastinal lymph nodes. Subsequently, haematogenous metastasis to distant sites may occur. The treatment of NSCLC is stage dependent, and is in general by either surgical resection, provided no spread outside the lung is found (stage I and II), or induction chemotherapy followed by resection, in patients with ipsilateral mediastinal lymph node metastases (stage IIIA), or chemo-/radiotherapy alone, provided contralateral mediastinal- or distant metastases are present (stage IIIB and IV).

When traditional pre-operative staging methods are used, ∼10% of operations for NSCLC result in explorative thoracotomy without tumour resection, due to advanced mediastinal disease not detected pre-operatively. In addition, 25–35% of the apparently curative resections are unsuccessful because of early post-operative recurrent disease 1. Therefore, surgery may be considered futile or unnecessary in up to 45% of patients operated on, apparently because the stage of the disease is more advanced than expected pre-operatively. It is therefore important to develop methods that …
What is the origin of pancreatic adenocarcinoma?
Authors: Parviz M Pour, Krishan K Pandey, Surinder K Batra
Journal: Molecular Cancer (2003)

The concept of pancreatic cancer origin is controversial. Acinar, ductal or islet cells have been hypothesized as the cell of origin. The pros and cons of each of these hypotheses are discussed. Based on the world literature and recent observations, pancreatic cells seem to have potential for phenotypical transdifferentiation, i.e ductal-islet, ductal-acinar, acinar-ductal, acinar-islet, islet-acinar and islet-ductal cells. Although the possibility is discussed that cancer may arise from either islet, ductal or acinar cells, the circumstances favoring the islet cells as the tumor cell origin include their greater transdifferentiation potency into both pancreatic and extrapancreatic cells, the presence of a variety of carcinogen-metabolizing enzymes, some of which are present exclusively in islet cells and the growth factor-rich environment of islets.
Sequential Velocity Development in the Ascending and Descending Aorta of the Dog
Authors: Herman L. Falsetti, Kenneth M. Kiser, Gerald P. Francis, Edward R. Belmore
Journal: Circulation Research (1972)

A conical hot-film probe was used to measure instantaneous velocities in the ascending and descending aorta of anesthetized open-chest dogs. From these point measurements, the radial distributions of velocity were obtained over one cardiac cycle. In general, the hot-film measurements confirmed the observation that the velocity profiles tend to be flat with the highest rates of shear confined to the region of the wall. There were, however, significant variations in the detail from one dog to another. These variations in the shape of the profiles probably are a consequence of many geometrical factors, which include valve inlet geometry, configuration and orientation of the valve plane, and aortic curvature and branching in the descending aorta.
A CORRELATION BETWEEN THE HISTOLOGICAL CHANGES AND THE FATE OF LIVING TUBERCLE BACILLI IN THE ORGANS OF REINFECTED RABBITS
Authors: Max B. Lurie
Journal: The Journal of Experimental Medicine (1933)

1. Immunity to reinfection is a function of the increased capacity of the mononuclear phagocytes to destroy tubercle bacilli and varies directly with the extent of the primary lesion; however it is rarely sufficient to annihilate completely the microorganism. This acquired immunity is superimposed on the natural resistance of a given organ. 2. In the presence of sufficient immunity, such as occurs with the persistence of an extensive primary lesion, small numbers of tubercle bacilli are destroyed by the mononuclear cells in situ without local or general infiltration of the tissues by polymorphonuclear or mononuclear leucocytes. Larger numbers of bacilli are destroyed within 24 hours by an accelerated formation of sharply localized nodules of mononuclear phagocytes. These progress no further and are absorbed or result in inconspicuous microscopic collections of epithelioid and giant cells. 3. In the presence of less immunity, such as occurs when the primary lesion has almost completely healed, the immediate inflammatory reaction is more intense and diffuse and persists longer. It results in a less rapid disappearance of the bacilli and in a more extensive formation of tubercles. These appear much earlier than in the normal animal and soon resolve. 4. Tubercle bacilli of reinfection may be destroyed even though the primary lesion in the lung and kidney is progressive. This is due to an unhindered extracellular multiplication of the bacilli in the caseous foci that undergo softening and excavation. Resistance may be overwhelmed by the spread of tremendous numbers of living bacilli from these foci through the bronchi or renal tubules, while the moderate numbers of reinfecting bacilli reaching the organs by way of the blood stream are destroyed.
Epistasis between serine protease inhibitor Kazal-type 5 (SPINK5) and thymic stromal lymphopoietin (TSLP) genes contributes to childhood asthma
Authors: Jocelyn M. Biagini Myers, Lisa J. Martin, Melinda Butsch Kovacic, Tesfaye B. Mersha, Hua He, Valentina Pilipenko, Mark A. Lindsey, Mark B. Ericksen, David I. Bernstein, Grace K. LeMasters, James E. Lockey, Gurjit K. Khurana Hershey
Journal: Journal of Allergy and Clinical Immunology (2014)
Hereditary porcine membranoproliferative glomerulonephritis type II is caused by factor H deficiency.
Authors: K Høgåsen, J H Jansen, T E Mollnes, J Hovdenes, M Harboe
Journal: Journal of Clinical Investigation (1995)

We have recently described hereditary membranoproliferative glomerulonephritis type II in the pig. All affected animals had excessive complement activation, revealed as low plasma C3, elevated plasma terminal complement complex, and massive deposits of complement in the renal glomeruli, and eventually died of renal failure within 11 wk of birth. The aim of the present study was to investigate the cause of complement activation in this disease. Transfusion of normal porcine plasma to affected piglets inhibited complement activation and increased survival. Plasma was successively fractionated and the complement inhibitory effect of each fraction tested in vivo. A single chain 150-kD protein which showed the same complement inhibitory effect as whole plasma was finally isolated. Immunologic cross-reactivity, functional properties, and NH2-terminal sequence identified the protein as factor H. By Western blotting and enzyme immunoassay, membranoproliferative glomerulonephritis-affected piglets were demonstrated to be subtotally deficient in factor H. At 1 wk of age, median (range) factor H concentration was 1.6 mg/liter (1.1-2.3) in deficient animals (n = 13) and 51 mg/liter (26-98) in healthy littermates (n = 52). Our data show that hereditary porcine membrano-proliferative glomerulonephritis type II is caused by factor H deficiency.
Global Histone Modifications Predict Prognosis of Resected Non–Small-Cell Lung Cancer
Authors: Fabrice Barlési, Giuseppe Giaccone, Marielle I. Gallegos-Ruiz, Anderson Loundou, Simone W. Span, Pierre Lefesvre, Frank A.E. Kruyt, Jose Antonio Rodriguez
Journal: Journal of Clinical Oncology (2007)

Epigenetic modifications may contribute to the development and progression of cancer. We investigated whether epigenetic changes involving multiple histones influence prognosis of non-small-cell lung cancer (NSCLC) patients.We used immunohistochemistry to assess histone 3 lysine 4 dimethylation (H3K4diMe), and acetylation of histone 2A lysine 5 (H2AK5Ac), histone 2B lysine 12, histone 3 lysine 9 (H3K9Ac), and histone 4 lysine 8 in resected tumor samples of 138 NSCLC patients. Data were analyzed using a recursive partitioning analysis (RPA).The RPA classified the patients into seven distinct prognostic groups based on TNM stage (first node), histology, and histone modifications: H3K4diMe (< or 85% tumor cells), H3K9Ac (< or 68% tumor cells), and H2AK5Ac (< or 5% tumor cells). The seven groups were associated with significantly different disease-free (P < .0001) and overall survival (P < .0001). Interestingly, the four groups determined by stage I patients (below the first node) displayed dramatic differences in survival (median, 10 months in adenocarcinoma patients with H3K9Ac 68% v 147 months in nonadenocarcinoma patients with H3K4diMe 85%). A Cox model retained age and RPA groups as the sole independent factors significantly influencing overall survival.The prognostic influence of epigenetic changes involving multiple histones, in particular H2A and H3, is greater in early NSCLC, and evaluation of these changes may help in selecting early-stage NSCLC patients for adjuvant treatment. Our observations provide a rationale for the use of a combination of standard chemotherapy with drugs interacting with histone modifications, such as histone deacetylase inhibitors.
Effector T-Cell Infiltration Positively Impacts Survival of Glioblastoma Patients and Is Impaired by Tumor-Derived TGF-β
Authors: Jennifer Lohr, Thomas Ratliff, Andrea Huppertz, Yingzi Ge, Christine Dictus, Rezvan Ahmadi, Stefan Grau, Nobuyoshi Hiraoka, Volker Eckstein, Rupert C. Ecker, Thomas Korff, Andreas von Deimling, Andreas Unterberg, Philipp Beckhove, Christel Herold-Mende
Journal: Clinical Cancer Research (2011)

In glioma-in contrast to various other cancers-the impact of T-lymphocytes on clinical outcome is not clear. We investigated the clinical relevance and regulation of T-cell infiltration in glioma.T-cell subpopulations from entire sections of 93 WHO°II-IV gliomas were computationally identified using markers CD3, CD8, and Foxp3; survival analysis was then done on primary glioblastomas (pGBM). Endothelial cells expressing cellular adhesion molecules (CAM) were similarly computationally quantified from the same glioma tissues. Influence of prominent cytokines (as measured by ELISA from 53 WHO°II-IV glioma lysates) on CAM-expression in GBM-isolated endothelial cells was determined using flow cytometry. The functional relevance of the cytokine-mediated CAM regulation was tested in a transmigration assay using GBM-derived endothelial cells and autologous T-cells.Infiltration of all T-cell subsets increased in high-grade tumors. Most strikingly, within pGBM, elevated numbers of intratumoral effector T cells (T(eff), cytotoxic and helper) significantly correlated with a better survival; regulatory T cells were infrequently present and not associated with GBM patient outcome. Interestingly, increased infiltration of T(eff) cells was related to the expression of ICAM-1 on the vessel surface. Transmigration of autologous T cells in vitro was markedly reduced in the presence of CAM-blocking antibodies. We found that TGF-β molecules impeded transmigration and downregulated CAM-expression on GBM-isolated endothelial cells; blocking TGF-β receptor signaling increased transmigration.This study provides comprehensive and novel insights into occurrence and regulation of T-cell infiltration in glioma. Specifically, targeting TGF-β1 and TGF-β2 might improve intratumoral T-cell infiltration and thus enhance effectiveness of immunotherapeutic approaches.
Impaired sonic hedgehog pathway contributes to cardiac dysfunction in type 1 diabetic mice with myocardial infarction
Authors: Qing Xiao, Ning Hou, Yan-Ping Wang, Li-Shan He, Yan-Hua He, Gui-Ping Zhang, Quan Yi, Shi-Ming Liu, Min-Sheng Chen, Jian-Dong Luo
Journal: Cardiovascular Research (2012)

The incidence and mortality of myocardial infarction (MI) in diabetic patients are higher than in non-diabetic patients; however, the mechanisms by which diabetes results in cardiac dysfunction are poorly understood. The present study tested the hypothesis that an impaired sonic hedgehog (Shh) pathway contributes to cardiac dysfunction in type 1 diabetic mice with MI.Adult male C57/B6 mice and streptozotocin-induced type 1 diabetic mice were used. Myocardial proteins of Shh, Patched-1 (Ptc1), and glioma-associated oncogene-1 (Gli1) were significantly decreased in type 1 diabetic mice at 10 weeks, and this was accompanied by cardiac dysfunction. Although myocardial proteins of Shh, Ptc1, and Gli1 were significantly increased 7 days after MI compared with the sham group in control mice, these proteins were markedly decreased in streptozotocin-induced diabetic mice. Treatment with Shh pathway agonist for 21 days significantly increased Ptc1 and Gli1 proteins, enhanced capillary density, reduced the percentage myocardial infarct, and then improved cardiac function in diabetic mice with MI compared with those with no drug treatment. This treatment had no effects in control mice with MI. Conversely, treatment with Shh pathway antagonist for 21 days significantly decreased Ptc1 and Gli1 proteins, reduced capillary density, enlarged the percentage myocardial infarct, and then exacerbated cardiac dysfunction in control mice with MI compared with those with no drug treatment.These findings indicate that in type 1 diabetic mice the myocardial Shh pathway is impaired and that the impaired Shh pathway contributes to cardiac dysfunction. Strategies that are aimed at augmenting the Shh pathway may offer useful means for improving diabetic cardiac dysfunction.
Survival Response to B-Cell Receptor Ligation Is Restricted to Progressive Chronic Lymphocytic Leukemia Cells Irrespective of Zap70 Expression
Authors: Pierre-Antoine Deglesne, Nathalie Chevallier, Rémi Letestu, Fanny Baran-Marszak, Taoufik Beitar, Célia Salanoubat, Laurence Sanhes, Joelle Nataf, Claudine Roger, Nadine Varin-Blank, Florence Ajchenbaum-Cymbalista
Journal: Cancer Research (2006)

Abstract Despite very similar gene expression profiles, the clinical course of B-cell chronic lymphocytic leukemia (B-CLL) is heterogeneous. Immunoglobulin VH (IgVH) mutational status and expression of B-cell receptor (BCR) signaling mediators have been associated with disease progression. However, the consequences of BCR engagement on cell survival and evolution of the disease remain unclear. We show here that B-CLL cell survival is dependent on the threshold of BCR stimulation induced by immobilized antibody, in contrast to soluble anti-μ F(ab)′2 antibody, which leads to apoptosis. Measurement of metabolic activity and apoptotic response discriminated two subgroups. “Nonresponders” showed low metabolic activity and unmodified apoptotic response upon BCR stimulation. In contrast, “responders” exhibited increased metabolic activity and inhibition of spontaneous apoptosis. This survival advantage was associated to a BCR-dependent activation profile leading to induction of cyclin D2/cyclin-dependent kinase 4 (cdk4) expression and G1 cell cycle progression. The ability to respond to BCR ligation correlated with an unfavorable clinical course and allowed to define an additional group of patients among IgVH-mutated cases exhibiting a risk of progression. Remarkably, we show that Zap70 expression was neither mandatory nor sufficient to generate downstream survival signals and cyclin D2/cdk4 up-regulation. In conclusion, BCR engagement has a significant effect on B-CLL cell survival, activation, and G1 progression. Furthermore, our results provide new insights in the physiopathology of progressive IgVH-mutated cases. (Cancer Res 2006; 66(14): 7158-66)