tbuckley/cabot-search huggingface dataset:
Persistent Activation of Stat3 Signaling Induces Survivin Gene Expression and Confers Resistance to Apoptosis in Human Breast Cancer Cells
Authors: Tanya Gritsko, Ann Williams, James Turkson, Satoshi Kaneko, Tammy Bowman, Mei Huang, Sangkil Nam, Ibrahim Eweis, Nils Diaz, Daniel Sullivan, Sean Yoder, Steve Enkemann, Steven Eschrich, Ji-Hyun Lee, Craig A. Beam, Jin Cheng, Susan Minton, Carlos A. Muro-Cacho, Richard Jove
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Signal transducer and activator of transcription 3 (Stat3) protein is persistently activated in breast cancer and promotes tumor cell survival. To gain a better understanding of the role of constitutive Stat3 signaling in breast cancer progression, we evaluated the expression profile of potential Stat3-regulated genes that may confer resistance to apoptosis. Experimental Design: Stat3 signaling was blocked with antisense oligonucleotides in human MDA-MB-435s breast cancer cells and Affymetrix GeneChip microarray analysis was done. The candidate Stat3 target gene Survivin was further evaluated in molecular assays using cultured breast cancer cells and immunohistochemistry of breast tumor specimens. Results: Survivin, a member of the inhibitor of apoptosis protein family, was identified as a potential Stat3-regulated gene by microarray analysis. This was confirmed in Survivin gene promoter studies and chromatin immunoprecipitation assays showing that Stat3 directly binds to and regulates the Survivin promoter. Furthermore, direct inhibition of Stat3 signaling blocked the expression of Survivin protein and induced apoptosis in breast cancer cells. Direct inhibition of Survivin expression also induced apoptosis. Increased Survivin protein expression correlates significantly (P = 0.001) with elevated Stat3 activity in primary breast tumor specimens from high-risk patients who were resistant to chemotherapy treatment. Conclusions: We identify Survivin as a direct downstream target gene of Stat3 in human breast cancer cells that is critical for their survival in culture. Our findings suggest that activated Stat3 signaling contributes to breast cancer progression and resistance to chemotherapy by, at least in part, inducing expression of the antiapoptotic protein, Survivin.
ON THE CHARACTER OF PROTEIN METABOLISM IN CHRONIC NEPHRITIS
Authors: P. A. Levene, L. Kristeller, D. Manson
Journal: The Journal of Experimental Medicine (1909)

1. For the study of the character of nitrogen metabolism in nephritis the nitrogen intake of the patient needs to he regulated in such a manner that it should not exceed the nitrogen value which the diseased kidneys are capable of eliminating. 2. The eliminating capacity of the kidneys can he established in the following manner: the patient is placed on a diet containing a low proportion of protein (equivalent to about 5 grams of nitrogen) and a sufficient supply of calories. To this diet from day to day varying quantities of urea are added and the nitrogen output for every twenty-four hours is estimated. The highest nitrogen output under this condition is regarded as the maximum of the eliminating capacity of the kidneys for nitrogenous substances. 3. In the observations recorded in this communication the nitrogen output of the patient on the standard diet remained at 5.5 grams per day. The addition to the diet of 1.5 to 3 grams of nitrogen in form of urea caused a rise in the intake not exceeding 6.25 grams. On the basis of this, the diet was regulated so as not to exceed a nitrogen intake of 7 grams. 4. Comparing the rate of elimination of nitrogen after the administration of glycin, alanin, and asparagin with that after the administration of urea, there was noted a slower rate after the administration of the first two acids, and an equal rate after the administration of asparagin (probably owing to the presence of an acid amid group in the molecule). 5. After the administration of excessive protein in addition to the standard diet, there was noted a much lower rate of nitrogen elimination than was to be expected in a normal man, on the basis of the work of Falta. 6. Of the total nitrogen removed in excess over that on the standard diet in our patient, 80 per cent. was in the form of urea, while in normal man, as calculated from the tables of Folin, one finds the proportion of urea to vary between 90 and 100 per cent., while in a normal dog the proportion is always 100 per cent. 7. On the basis of these observations it was concluded that in our patient the rate of conversion of protein into simple nitrogenous substances and into urea is below the normal. 8. The patient remained for four months in a condition of nitrogenous equilibrium, and otherwise in good health, on a diet containing about 6.5 grams of nitrogen and 3,000 calories, which were reduced to 2,500 calories to prevent constant gain in weight. 9. From this it seems suggestive that also for dietetic-therapeutic purposes it may be of importance to establish the eliminating efficiency of the kidneys for nitrogenous substances.
The influence of early exposure to tobacco smoke for pulmonary disease
Authors: Akinori Ebihara, Asuka Nagai, Takayuki Nakano, Tokuzen Iwamoto, Ichiro Kuwahira
Journal: European Respiratory Journal (2011)

Background:  Smoking is a very serious problem for COPD, lung cancer and other chronic pulmonary diseases. However, there are few studies on early exposure to tobacco smoke. Smoking rate in Japan decreased to 21.8%. However it is still higher in the northern area (Hokkaido). In particularly, it is 31.0% in Erimo town (southernmost extreme of Hokkaido), which is higher than that of any other cities in Hokkaido. The reason is that when parents smoked, the child set fire to tobacco and handed it as a custom in 19409s. Because a hand was wet while fishing, they were not able to set fire themselves.   Aim:  We evaluated the influence of early exposure to tobacco smoke on prevalence of COPD and lung cancer.   Methods:  Using the results of the medical checkup carried out at the Erimo town health division and the Town clinic, we analyzed about 6000 residents9 epidemiologic data.   Results:  Majority of residents were found exposed to tobacco smoke actively or passively from a young age. Housemate smoking rate was 81.0%. The mortality of chronic respiratory disease was 71.4 per 100,000 person-years that was far exceeded from the national average (11.4 per 100,000 person-years). COPD prevalence (465.5 per 100,000 person-years) was significantly higher than the national average (136.2 per 100,000 person-years). Lung cancer prevalence was also very high (877.2 per 100,000 person-years).   Conclusion:  Early exposure to tobacco smoke in childhood significantly increases prevalence of COPD and lung cancer. In Japan, young generation showed still high smoking rates (14.3% aged 209s, 18.0% aged 309s). Smoking cessation is the most important intervention to prevent disease progression.
Quantifying the risk of sports injury: a systematic review of activity-specific rates for children under 16 years of age
Authors: Anneliese B Spinks, Roderick J McClure
Journal: British Journal of Sports Medicine (2007)

Injuries caused by sports and other forms of physical activity in young children constitute a significant public health burden. It is important to quantify this risk to ensure that the benefits of sport participation are not outweighed by the potential harms. This review summarises the literature reporting exposure-based injury rates for various forms of physical activity in children aged 15 years and younger. Forty eight studies were found, of which 27 reported injury rates per hourly based exposure measured and 21 reported injury rates according to some other measure. Fourteen different sports and activities were covered, mostly team ball sports, with soccer being the most widely studied. Injury definition and the method of ascertaining and measuring injuries differed between studies, which created a large variation in reported injury rates that did not necessarily represent actual differences in injury risk between activities. The highest hourly based injury rates were reported for ice hockey, and the lowest were for soccer, although the range of injury rates for both of these activities was wide. Very few studies have investigated sports-related injuries in children younger than 8 years or in unorganised sports situations.
Reduction of blood loss by restoration of platelet levels using fresh autologous blood after cardiopulmonary bypass
Authors: J. G. Wagstaffe, A. D. Clarke, P. W. Jackson
Journal: Thorax (1972)

Two methods of taking off two units of blood before bypass, storing it at 4° C, and giving it after heparin reversal at the end of bypass are described and compared. When the blood was taken into acid citrate dextrose before the patient was heparinized, the platelet count increased by 22,000/mm<sup>3</sup> and blood loss was reduced by 26·7% (a significant decrease). Blood, taken after heparin was given, gave a similar platelet increase after retransfusion but the resulting decrease in blood loss was 17·6% (a non-significant decrease). Neither difficulties nor complications were noted using the technique in 38 patients.
A new transcriptional role for matrix metalloproteinase-12 in antiviral immunity
Authors: David J Marchant, Caroline L Bellac, Theo J Moraes, Samuel J Wadsworth, Antoine Dufour, Georgina S Butler, Leanne M Bilawchuk, Reid G Hendry, A Gordon Robertson, Caroline T Cheung, Julie Ng, Lisa Ang, Zongshu Luo, Karl Heilbron, Michael J Norris, Wenming Duan, Taylor Bucyk, Andrei Karpov, Laurent Devel, Dimitris Georgiadis, Richard G Hegele, Honglin Luo, David J Granville, Vincent Dive, Bruce M McManus, Christopher M Overall
Journal: Nature Medicine (2014)
Fibroblast Growth Factor-23 Mitigates Hyperphosphatemia but Accentuates Calcitriol Deficiency in Chronic Kidney Disease
Authors: Orlando Gutierrez, Tamara Isakova, Eugene Rhee, Anand Shah, Julie Holmes, Gina Collerone, Harald Ju[Combining Diaeresis]ppner, Myles Wolf
Journal: Journal of the American Society of Nephrology (2005)

Hyperphosphatemia, calcitriol deficiency, and secondary hyperparathyroidism (SHPT) are common complications of chronic kidney disease (CKD). Fibroblast growth factor-23 (FGF-23) is a novel phosphaturic hormone that also inhibits renal 1alpha-hydroxylase activity and thus may be involved in the pathogenesis of SHPT. Several hypotheses were tested: that FGF-23 increases as renal function declines; is linearly associated with serum phosphate levels; is associated with increased phosphaturia independent of parathyroid hormone (PTH); and is associated with decreased calcitriol levels independent of renal function, hyperphosphatemia, and vitamin D stores. FGF-23, PTH, 25(OH)D3, calcitriol, calcium, phosphate, and urinary fractional excretion of phosphate (Fe(PO4)) were measured in 80 CKD patients. Multiple linear regression was used to test the hypotheses. FGF-23 and PTH were inversely associated with estimated GFR (eGFR), whereas calcitriol levels were linearly associated with eGFR. Hyperphosphatemia and hypocalcemia were present in only 12 and 6% of patients, respectively, all of whose eGFR was <30. Increased Fe(PO4) was associated with decreased eGFR, and both increased FGF-23 and PTH were independently associated with increased Fe(PO4). Increased FGF-23 and decreased 25(OH)D3 were independent predictors of decreased calcitriol, but the effects on calcitriol levels of renal function itself and hyperphosphatemia were completely extinguished by adjusting for FGF-23. It is concluded that FGF-23 levels increase early in CKD before the development of serum mineral abnormalities and are independently associated with serum phosphate, Fe(PO4), and calcitriol deficiency. Increased FGF-23 may contribute to maintaining normal serum phosphate levels in the face of advancing CKD but may worsen calcitriol deficiency and thus may be a central factor in the early pathogenesis of SHPT.
Reply to Yuri Tolkach, Markus Kuczyk, Florian Imkamp's Letter to the Editor re: Eric A. Klein, Matthew R. Cooperberg, Cristina Magi-Galluzzi, et al. A 17-gene Assay to Predict Prostate Cancer Aggressiveness in the Context of Gleason Grade Heterogeneity, Tumor Multifocality, and Biopsy Undersampling. Eur Urol 2014;66:550–60
Authors: Eric A. Klein, Matthew R. Cooperberg, Peter R. Carroll
Journal: European Urology (2014)
The effects of amino acid supplementation on hormonal responses to resistance training overreaching
Authors: William J. Kraemer, Nicholas A. Ratamess, Jeff S. Volek, Keijo Häkkinen, Martyn R. Rubin, Duncan N. French, Ana L. Gómez, Michael R. McGuigan, Timothy P. Scheett, Robert U. Newton, Barry A. Spiering, Mikel Izquierdo, Francesco S. Dioguardi
Journal: Metabolism (2006)
Pancreatic hypertrophy with acinar cell nodules after longterm fundectomy in the rat.
Authors: M Chu, L Franzen, S Sullivan, S Wingren, J F Rehfeld, K Borch
Journal: Gut (1993)

The effect of gastric fundectomy with hypergastrinaemia on the pancreas in rats was studied for 14 months. Rats with hypercholecystokininaemia that had had a pancreaticobiliary diversion (PBD) operation and sham operated rats served as controls. Fundectomised rats showed a significant increase in pancreatic weight and total DNA and protein content compared with sham operated rats. DNA flow cytometry showed a significantly higher ratio of tetraploid to diploid nuclei in pancreatic tissue after fundectomy than after sham operation. Mean values of all these variables were significantly lower after fundectomy than after PBD. Acidophilic atypical acinar cell foci of the pancreas were diagnosed in both fundectomised and PBD operated rats, but not in sham operated controls. The volume density and 3H-thymidine labelling index of the acidophilic atypical acinar cell foci were significantly lower after fundectomy than after PBD. Changes consistent with pancreatic adenoma were diagnosed in the PBD group only. In conclusion, fundectomy lasting about half of the life span in rats causes pancreatic hyperplasia and hypertrophy, as well as development of acidophilic atypical acinar cell foci. Although hypergastrinaemia is a prominent feature, it may not be the only factor responsible for this pancreaticotrophical effect of fundectomy.
Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers
Authors: Carlo Sidore, Fabio Busonero, Andrea Maschio, Eleonora Porcu, Silvia Naitza, Magdalena Zoledziewska, Antonella Mulas, Giorgio Pistis, Maristella Steri, Fabrice Danjou, Alan Kwong, Vicente Diego Ortega del Vecchyo, Charleston W K Chiang, Jennifer Bragg-Gresham, Maristella Pitzalis, Ramaiah Nagaraja, Brendan Tarrier, Christine Brennan, Sergio Uzzau, Christian Fuchsberger, Rossano Atzeni, Frederic Reinier, Riccardo Berutti, Jie Huang, Nicholas J Timpson, Daniela Toniolo, Paolo Gasparini, Giovanni Malerba, George Dedoussis, Eleftheria Zeggini, Nicole Soranzo, Chris Jones, Robert Lyons, Andrea Angius, Hyun M Kang, John Novembre, Serena Sanna, David Schlessinger, Francesco Cucca, Gonçalo R Abecasis
Journal: Nature Genetics (2015)
Polysomy 17 and HER-2 Amplification: True, True, and Unrelated
Authors: Carol L. Rosenberg
Journal: Journal of Clinical Oncology (2008)

Approximately 25% of breast cancers overexpress the human epidermal growth factor receptor 2 (HER-2) protein, usually as a result of high copy number of its gene (amplification) on chromosome 17q12-21. HER-2 signaling promotes cell proliferation, and overexpression or gene amplification are associated with poor prognosis. 1 Inviewofthis,trastuzumab(Herceptin;Genentech,SouthSan Francisco, CA), a humanized monoclonal immunoglobulin G antibody, was developed to specifically target the extracellular domain of HER-2. 2 Becausetrastuzumabisbotheffectiveandtoxicinsomepatients, identifyingpatientswhowillbenefitisofgreatimportance.Currently, patient selection is based on the determination of HER-2 status, because trastuzumab is expected to be effective only against HER-2‐ positive breast cancers. The definition of HER-2 positive has evolved over time, and guidelines to standardize testing and interpretation havebeenproposed. 3,4 Evenwithsuchguidelines,patientselectionfor
Idiopathic azygos vein aneurysm: a rare cause of mediastinal mass
Authors: M. Gallego, R. M Mirapeix, E. Castaner, C. Domingo, J. M Mata, A. Marin
Journal: Thorax (1999)

Venous aneurysm of the azygos arch is a very rare cause of mediastinal mass and is usually an incidental finding on chest radiography. Nowadays the diagnosis is made by non-invasive tests such as thoracic CT scanning and/or magnetic resonance imaging. The case is described of an asymptomatic woman in whom a mediastinal mass due to an azygos vein aneurysm was diagnosed by non-invasive procedures, the aetiology of which, in all probability, was idiopathic.
Posttranslational processing of secretory component in the rat jejunum by a brush border metalloprotease.
Authors: D J Ahnen, J R Singleton, T C Hoops, T M Kloppel
Journal: Journal of Clinical Investigation (1986)

Secretory component (SC) is a glycoprotein that mediates the transcellular transport of polymeric immunoglobulins into external secretions. SC is synthesized and inserted into the plasma membrane of epithelial cells and hepatocytes as a transmembrane protein, where it serves as a receptor for polymeric immunoglobulins. SC is posttranslationally cleaved to a soluble protein before secretion into external fluids. In the rat jejunum, we observed that the molecular weights of both the major membrane and soluble forms of SC were 10,000-20,000 smaller than the comparable hepatic forms of the glycoprotein. We therefore set out to determine the reason for the differences in size of SC between these two tissues. The smaller size of jejunal SC was not due to the action of pancreatic proteases or differential glycosylation but was due to proteolysis by a jejunal brush border protease. The protease was characterized as a metalloprotease, with a pH optimum of approximately 5. It is present in jejunal, ileal, and renal tubular brush borders as an integral membrane constituent. When the protease was inhibited in vivo, conversion of jejunal secretory component to the smaller size was partially prevented. Thus, in the rat jejunum, SC undergoes two posttranslational proteolytic events: conversion of membrane secretory component to the soluble form and conversion of soluble SC to a smaller size by a previously undescribed brush border protease.
Right ventricular angiotensin converting enzyme activity and expression is increased during hypoxic pulmonary hypertension
Authors: N Morrell
Journal: Cardiovascular Research (1997)

Objective: To determine whether local cardiac angiotensin converting enzyme (ACE) expression is upregulated during the development of hypoxia-induced right ventricular hypertrophy. Methods: ACE activity was measured in membrane preparations from the right ventricle and left ventricle plus septum in normoxic rats and animals exposed to chronic hypoxia for 8 and 14 days. Local cardiac ACE expression was studied by immunohistochemistry using a monoclonal antibody to ACE (9B9). Results: In the normal rat heart, ACE expression was confined to vascular endothelium, the valvular endocardium, and localized regions of parietal endocardium. We found that the development of pulmonary hypertension and right ventricular hypertrophy were associated with 2.6- and 3.4-fold increases in membrane-bound right ventricular ACE activity by 8 and 14 days of hypoxia, respectively. Right ventricular ACE activity was positively correlated with the degree of right ventricular hypertrophy (r=0.83, P<0.001). In contrast, left ventricular plus septal ACE activity was significantly reduced by approximately 40 and 60% by 8 and 14 days of hypoxia, respectively, compared to controls. In the right ventricle of chronically hypoxic rats, immunohistochemistry demonstrated increased ACE expression in areas of myocardial fibrosis. Interestingly, increased ACE expression was noted in the right ventricular epicardium in chronically hypoxic rats. In the free wall of the left ventricle there was a significant reduction in the number of myocardial capillaries which expressed ACE in chronically hypoxic rats. Conclusion: Chronic hypoxia has a differential effect on left and right ventricular ACE activity and that the sites of altered ACE expression are highly localized. We speculate that locally increased right ventricular ACE activity and expression may play a role in the pathogenesis of right ventricular hypertrophy secondary to hypoxic pulmonary hypertension.
AMPK Reverses the Mesenchymal Phenotype of Cancer Cells by Targeting the Akt–MDM2–Foxo3a Signaling Axis
Authors: Chih-Chien Chou, Kuen-Haur Lee, I-Lu Lai, Dasheng Wang, Xiaokui Mo, Samuel K. Kulp, Charles L. Shapiro, Ching-Shih Chen
Journal: Cancer Research (2014)

Abstract In cancer cells, the epithelial–mesenchymal transition (EMT) confers the ability to invade basement membranes and metastasize to distant sites, establishing it as an appealing target for therapeutic intervention. Here, we report a novel function of the master metabolic kinase AMPK in suppressing EMT by modulating the Akt–MDM2–Foxo3 signaling axis. This mechanistic link was supported by the effects of siRNA-mediated knockdown and pharmacologic activation of AMPK on epithelial and mesenchymal markers in established breast and prostate cancer cells. Exposure of cells to OSU-53, a novel allosteric AMPK activator, as well as metformin and AICAR, was sufficient to reverse their mesenchymal phenotype. These effects were abrogated by AMPK silencing. Phenotypic changes were mediated by Foxo3a activation, insofar as silencing or overexpressing Foxo3a mimicked the effects of AMPK silencing or OSU-53 treatment on EMT, respectively. Mechanistically, Foxo3a activation led to the transactivation of the E-cadherin gene and repression of genes encoding EMT-inducing transcription factors. OSU-53 activated Foxo3a through two Akt-dependent pathways, one at the level of nuclear localization by blocking Akt- and IKKβ-mediated phosphorylation, and a second at the level of protein stabilization via cytoplasmic sequestration of MDM2, an E3 ligase responsible for Foxo3a degradation. The suppressive effects of OSU-53 on EMT had therapeutic implications illustrated by its ability to block invasive phenotypes in vitro and metastatic properties in vivo. Overall, our work illuminates a mechanism of EMT regulation in cancer cells mediated by AMPK, along with preclinical evidence supporting a tractable therapeutic strategy to reverse mesenchymal phenotypes associated with invasion and metastasis. Cancer Res; 74(17); 4783–95. ©2014 AACR.