tbuckley/cabot-search huggingface dataset:
<i>Pten</i> in the Breast Tumor Microenvironment: Modeling Tumor–Stroma Coevolution
Authors: Julie A. Wallace, Fu Li, Gustavo Leone, Michael C. Ostrowski
Journal: Cancer Research (2011)

Solid human tumors and their surrounding microenvironment are hypothesized to coevolve in a manner that promotes tumor growth, invasiveness, and spread. Mouse models of cancer have focused on genetic changes in the epithelial tumor cells and therefore have not robustly tested this hypothesis. We have recently developed a murine breast cancer model that ablates the PTEN tumor suppressor pathway in stromal fibroblasts. Remarkably, the model resembles human breast tumors both at morphologic and molecular levels. We propose that such models reflect subtypes of tumor-stromal coevolution relevant to human breast cancer, and will therefore be useful in defining the mechanisms that underpin tumor-stroma cross-talk. Additionally, these models should also aid in molecularly classifying human breast tumors on the basis of both the microenvironment subtypes they contain as well as on the tumor subtype.
Leukosis and Marek's Disease Viruses of Feral Red Jungle Fowl and Domestic Fowl in Malaya2
Authors: Robin A. Weiss, Peter M. Biggs
Journal: JNCI Journal of the National Cancer Institute (1972)

The incidence of Marek's disease virus (MDV) and avian RNA leukosis viruses (ALV) was studied in Red Jungle Fowl and domestic fowl in Malaya by assays of sera for specific antibodies to the viruses and by assays of embryonic tissues for congenital infections. Antibodies to MDV were found in all fowl populations (in 100% of domestic fowl but in less than 10% of Red Jungle Fowl). Antibodies to ALV of subgroups A and B were widespread among both domestic and Red Jungle Fowl. One congenital infection with subgroup A ALV was found in a domestic fowl embryo. The type specificity of antisera to A and B ALV varied among major locations. Red jungle Fowl carried a genetically transmitted viral genome of subgroup E specificity which could be activated from embryonic cell cultures by infection with ALV or by treatment with 4-nitroquinoline-1-oxide. The Red Jungle Fowl embryonic cells synthesized group-specific antigen and were able to complement defective Rous sarcoma virus. Red jungle Fowl cells were susceptible to all ALV subgroups. The significance of these findings to the ecology and evolution of avian tumor viruses and their hosts is discussed.
Bcl-XL and Bcl-2 repress a common pathway of cell death.
Authors: D T Chao, G P Linette, L H Boise, L S White, C B Thompson, S J Korsmeyer
Journal: The Journal of Experimental Medicine (1995)

The effect of Bcl-xL upon the developmental death of T cells was assessed by generating transgenic mice that expressed Bcl-xL within all thymocyte subsets. Bcl-xL protected thymocytes from a variety of apoptotic stimuli, including gamma irradiation, glucocorticoids, and anti-CD3 treatment. Bcl-xL altered thymocyte maturation, resulting in increased numbers of CD3int/hi and CD4-8+ thymocytes. Overall, the phenotype of Bcl-xL transgenics was essentially indistinguishable from a Bcl-2 transgenic model. Overexpression of Bcl-xL or Bcl-2 resulted in the down-regulation of the other molecule, providing further evidence of their reciprocal regulation. In a genetic test of redundancy, the Bcl-xL transgene rescued mature T cells in Bcl-2 null mice. Immunoprecipitation indicated that Bcl-xL, like Bcl-2, heterodimerized with the death-promoting molecule Bax in thymocytes. This in vivo model argues that Bcl-xL, like Bcl-2, functions in a common pathway to repress cell death.
Interferon regulatory factor 3 deficiency leads to interleukin-17-mediated liver ischemia-reperfusion injury
Authors: Patrizia Loi, Qing Yuan, David Torres, Sandrine Delbauve, Marie-Aline Laute, Marie-Claude Lalmand, Michel Pétein, Stanislas Goriely, Michel Goldman, Véronique Flamand
Journal: Hepatology (2012)

Abstract Interferon regulatory factor 3 (IRF3) is an important transcription factor in Toll-like receptor 4 (TLR4) signaling, a pathway that is known to play a critical role in liver ischemia-reperfusion injury. In order to decipher the involvement of IRF3 in this setting, we first compared the intensity of hepatic lesions in IRF3-deficient versus wildtype mice. We found increased levels of blood transaminases, enhanced liver necrosis, and more pronounced neutrophil infiltrates in IRF3-deficient mice. Neutrophil depletion by administration of anti-Ly6G monoclonal antibody indicated that neutrophils play a dominant role in the development of severe liver necrosis in IRF3-deficient mice. Quantification of cytokine genes expression revealed increased liver expression of interleukin (IL)-12/IL-23p40, IL-23p19 messenger RNA (mRNA), and IL-17A mRNA in IRF3-deficient versus wildtype (WT) mice, whereas IL-27p28 mRNA expression was diminished in the absence of IRF3. The increased IL-17 production in IRF3-deficient mice was functionally relevant, as IL-17 neutralization prevented the enhanced hepatocellular damages and liver inflammation in these animals. Evidence for enhanced production of IL-23 and decreased accumulation of IL-27 cytokine in M1 type macrophage from IRF3-deficient mice was also observed after treatment with lipopolysaccharide, a setting in which liver gamma-delta T cells and invariant natural killer T cells were found to be involved in IL-17A hyperproduction. Conclusion : IRF3-dependent events downstream of TLR4 control the IL-23/IL-17 axis in the liver and this regulatory role of IRF3 is relevant to liver ischemia-reperfusion injury. (Hepatology 2013)
Transaminase in Myocardial Infarction
Authors: J. C. Meenan
Journal: BMJ (1957)

Saccadic suppression, a behavioral phenomenon in which perceptual thresholds are elevated before, during, and after saccadic eye movements, is an important mechanism for maintaining perceptual stability. However, even during fixation, the eyes never remain still, but undergo movements including microsaccades, drift, and tremor. The neural mechanisms for mediating perceptual stability in the face of these “fixational” movements are not fully understood. Here, we investigated one component of such mechanisms: a neural correlate of microsaccadic suppression. We measured the size of short-latency, stimulus-induced visual bursts in superior colliculus neurons of adult, male rhesus macaques. We found that microsaccades caused ∼30% suppression of the bursts. Suppression started ∼70 ms before microsaccade onset and ended ∼70 ms after microsaccade end, a time course similar to behavioral measures of this phenomenon in humans. We also identified a new behavioral effect of microsaccadic suppression on saccadic reaction times, even for continuously presented, suprathreshold visual stimuli. These results provide evidence that the superior colliculus is part of the mechanism for suppressing self-generated visual signals during microsaccades that might otherwise disrupt perceptual stability.
Temperate bacteriophages of pseudomonas aeruginosa as markers of bacterial adaptation in CF and non-CF bronchiectasis
Authors: Francesca Everest, Mohammad Tariq, Anthony De Soyza, Audrey Perry, John Perry, Stephen Bourke, Stephen Cummings, Clare Lanyon, Darren Smith
Journal: European Respiratory Journal (2014)

Introduction . Temperate bacteriophages infect and subvert their bacterial host range driving  Pseudomonas aeruginosa  (PA) adaptation in the chronic lung.   Aim.  To stratify PA in the Cystic Fibrosis (CF) and non-CF Bronchiectasis (nCFBR) lung utilising the co-evolution of phages and bacteria, specifically viral infectivity as a marker of increased bacterial adaptation.   Methods.  Temperate phages were chemically induced from 47 CF and 47 nCFBR PA isolates and cross infected across all 94 PA isolates. The data was modelled alongside clinical data using interaction modelling (Biolayout 3D).   Results.  Phages from a CF PA background successfully infected 66% and 69% of PA isolated from CF and BR backgrounds. Conversely, BR phages had poor infectivity on CF PA bacteria with only 31% infection of CF and 49% infection of BR PA isolates. The data was used to construct 2 models of infectivity in R (confidence levels >80%, integrity 0.5). Using age as a discriminator in the CF phage infectivity model, paediatric PA isolates were easily infected by phage but adult PA strains were not. The Biolayout 3D model visualises these corresponding profiles of phage infectivity, where limited adaptation by paediatric PA (CF) phages correlates to infectivity from the BR PA background.   Conclusion.  This study demonstrates the level of adaptation and evolution of both the phage and bacteria based on phage infection. We also show that phages isolated from BR PA are less adapted to infect PA bacteria from the CF lung. We determine that phages of BR and early CF PA colonisation have similar levels/profiles of infectivity, possibly alluding to lower levels of bacterial adaptation in the lung.
Potent Metalloporphyrin Peroxynitrite Decomposition Catalyst Protects Against the Development of Doxorubicin-Induced Cardiac Dysfunction
Authors: Pál Pacher, Lucas Liaudet, Péter Bai, Jon G. Mabley, Pawel M. Kaminski, László Virág, Amitabha Deb, Éva Szabó, Zoltán Ungvári, Michael S. Wolin, John T. Groves, Csaba Szabó
Journal: Circulation (2003)

Background— Increased oxidative stress and dysregulation of nitric oxide have been implicated in the cardiotoxicity of doxorubicin (DOX), a commonly used antitumor agent. Peroxynitrite is a reactive oxidant produced from nitric oxide and superoxide in various forms of cardiac injury. Using a novel metalloporphyrinic peroxynitrite decomposition catalyst, FP15, and nitric oxide synthase inhibitors or knockout mice, we now delineate the pathogenetic role of peroxynitrite in rodent models of DOX-induced cardiac dysfunction. Methods and Results— Mice received a single injection of DOX (25 mg/kg IP). Five days after DOX administration, left ventricular performance was significantly depressed, and high mortality was noted. Treatment with FP15 and an inducible nitric oxide synthase inhibitor, aminoguanidine, reduced DOX-induced mortality and improved cardiac function. Genetic deletion of the inducible nitric oxide synthase gene was also accompanied by better preservation of cardiac performance. In contrast, inhibition of the endothelial isoform of nitric oxide synthase with N -nitro- l -arginine methyl ester increased DOX-induced mortality. FP15 reduced the DOX-induced increase in serum LDH and creatine kinase activities. Furthermore, FP15 prevented the DOX-induced increase in lipid peroxidation, nitrotyrosine formation, and metalloproteinase activation in the heart but not NAD(P)H-driven superoxide generation. Peroxynitrite neutralization did not interfere with the antitumor effect of DOX. FP15 also decreased ischemic injury in rats and improved cardiac function and survival of mice in a chronic model of DOX-induced cardiotoxicity. Conclusions— Thus, peroxynitrite plays a key role in the pathogenesis of DOX-induced cardiac failure. Targeting peroxynitrite formation may represent a new cardioprotective strategy after DOX exposure or in other conditions associated with peroxynitrite formation, including myocardial ischemia/reperfusion injury.
Chemoprevention of Skin Carcinogenesis by Phenylretinamides: Retinoid Receptor–Independent Tumor Suppression
Authors: Hui Xu, Satish Cheepala, Elisabeth McCauley, Kevin Coombes, Lianchun Xiao, Susan M. Fischer, John L. Clifford
Journal: Clinical Cancer Research (2006)

Abstract Fenretinide [N-(4-hydroxyphenyl)retinamide or 4-HPR] is a synthetic retinoid analogue with antitumor and chemopreventive activities. N-(4-Methoxyphenyl)retinamide (4-MPR) is the most abundant metabolite of 4-HPR detected in human serum following 4-HPR therapy. We have shown in in vitro studies that 4-HPR and 4-MPR can act independent of the classic nuclear retinoid receptor pathway and that 4-HPR, but not 4-MPR, can also activate nuclear retinoid receptors. In this study, we have compared the chemopreventive effects of topically applied 4-HPR and 4-MPR with the primary biologically active retinoid, all-trans retinoic acid (ATRA), in vivo in the mouse skin two-stage chemical carcinogenesis model. All three retinoids suppressed tumor formation but the effect of 4-HPR and 4-MPR, and not of ATRA, was sustained after their discontinuation. The tumor-suppressive effects of 4-HPR and 4-MPR were quantitatively and qualitatively similar, suggesting that the two may be acting through the same retinoid receptor–independent mechanism(s). We further explored this effect in vitro by analyzing primary cultures of mouse keratinocytes treated with the same retinoids. All three could induce apoptosis with a 48-hour treatment and only ATRA and 4-HPR induced an accumulation of cells in the G1 phase of the cell cycle. This finding is consistent with our previous results showing that the effects of phenylretinamides on the cell cycle are retinoid receptor dependent whereas apoptosis induction is not. A microarray-based comparison of gene expression profiles for mouse skin treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) alone and TPA + 4-HPR or TPA + 4-MPR reveals a high degree of coincidence between the genes regulated by the two phenylretinamides. We propose that 4-HPR may exert therapeutic and chemopreventive effects by acting primarily through a retinoid receptor–independent mechanism(s) and that 4-MPR may contribute to the therapeutic effect of 4-HPR by acting through the same retinoid receptor–independent mechanism(s).
Hepatocellular carcinoma in type I glycogen storage disease
Authors: Joachim Limmer, Wolfgang E. Fleig, Dorothea Leupold, Reinhard Bittner, Hans Ditschuneit, Hans-Günter Berger
Journal: Hepatology (1988)

Patients suffering from Type I glycogen storage disease frequently develop hepatic tumors. Some of these were classified as carcinoma, with the majority of tumors representing benign adenomata. However, no evidence exists of malignant transformation of adenomata in these patients. Here, we describe the occurrence of a hepatocellular carcinoma in the adenomata-bearing liver of the elder of two sisters suffering from Type I glycogen storage disease at the age of 20 years, 6 years after the diagnosis had been made. Surprisingly, α-fetoprotein levels were normal throughout the entire course of this patient, whereas the younger sister had elevated levels despite the absence of malignant lesions. Thus, the clinical significance of α-fetoprotein remains unclear in both cases. Nocturnal feeding, although performed continuously over the 6 years after the diagnosis, had obviously failed to prevent the development of hepatic tumors in both patients.
Sibling Donor and Recipient Immune Modulation With Atorvastatin for the Prophylaxis of Acute Graft-Versus-Host Disease
Authors: Mehdi Hamadani, Laura F. Gibson, Scot C. Remick, Sijin Wen, William Petros, William Tse, Kathleen M. Brundage, Jeffrey A. Vos, Aaron Cumpston, Pamela Bunner, Michael D. Craig
Journal: Journal of Clinical Oncology (2013)

Graft-versus-host disease (GVHD) is major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Atorvastatin is a potent immunomodulatory agent that holds promise as a novel and safe agent for acute GVHD prophylaxis.
Incidence and aetiology of sudden cardiac death in young athletes: an international perspective
Authors: M Borjesson, A Pelliccia
Journal: British Journal of Sports Medicine (2009)

The incidence of sudden cardiac death (SCD) among young athletes is estimated to be 1–3 per 100 000 person years, and may be underestimated. The risk of SCD in athletes is higher than in non-athletes because of several factors associated with sports activity that increase the risk in people with an underlying cardiovascular abnormality. A clear gender difference in the incidence of SCD exists in young athletes, with the risk in male athletes being up to 9 times higher than in female athletes. The most common causes of SCD in young athletes is underlying inherited/congenital cardiac disease, such as cardiomyopathies, congenital coronary anomalies and ion channelopathies. Blunt chest trauma also may cause ventricular fibrillation in a structurally normal heart, known as commotio cordis. Although geographical differences in the causes of SCD in young athletes have been reported, these disparities are more likely to be related to the type and implementation of pre-participation screening leading to the identification of athletes at risk, rather than reflecting a truly different ethiology. More studies are needed to clarify the role of ethnicity in the prevalence of diseases known to cause SCD in young athletes.
IFI16 is an innate immune sensor for intracellular DNA
Authors: Leonie Unterholzner, Sinead E Keating, Marcin Baran, Kristy A Horan, Søren B Jensen, Shruti Sharma, Cherilyn M Sirois, Tengchuan Jin, Eicke Latz, T Sam Xiao, Katherine A Fitzgerald, Søren R Paludan, Andrew G Bowie
Journal: Nature Immunology (2010)
The Role of Thymidylate Synthase as a Molecular Biomarker
Authors: Antontello DiPaolo, Edward Chu
Journal: Clinical Cancer Research (2004)

Significant advances have been made in the treatment of advanced colorectal cancer. At present, there are four main active drugs to treat the disease, and they include the fluoropyrimidines, 5-fluorouracil (5-FU) and capecitabine, irinotecan, and oxaliplatin. Over the past few years, intense
T cells sensitized to synthetic HLA-DR3 peptide give evidence of continuous presentation of denatured HLA-DR3 molecules by HLA-DP.
Authors: H S de Koster, D C Anderson, A Termijtelen
Journal: The Journal of Experimental Medicine (1989)

T cell clones raised against a synthetic peptide, identical to the third hypervariable region of the DR3 BI chain, were tested for secondary proliferative responses against a panel of PBLs. All seven DR3 DPw3+ stimulators could induce proliferation. DR3- DPw3+ PBLs were recognized when the synthetic peptide was added to the cultures. Inhibition studies with mAbs showed that in both cases the HLA-DP molecule is involved in the recognition of both types of stimulators. We conclude that the clones recognize the DR3 peptide presented by HLA-DPw3. This stimulus can be obtained in two different ways: (a) by addition of synthetic peptide to DPw3+ PBLs or (b) by using DR3 DPw3+ stimulator cells where DR3 peptides are present in the culture as a product of denaturation of the DR3 molecule. Because all DR3 DPw3+ PBLs tested could stimulate the line and clones, we assume that the presentation of the DR3 peptide by DP is a naturally and continuously occurring phenomenon.
Inhibition of human platelet aggregation and cytoplasmic calcium response by calcium antagonists: studies with aequorin and quin2.
Authors: J A Ware, P C Johnson, M Smith, E W Salzman
Journal: Circulation Research (1986)

Calcium antagonists inhibit platelet aggregation, but whether this action is due to inhibition of the effect of agonists on cytoplasmic ionized calcium concentration is unknown. We studied this problem by loading gel-filtered platelets with either quin2 or aequorin and stimulating them with epinephrine, arachidonate, thrombin, the calcium ionophore A23187, 1-oleoyl-2-acetyl glycerol, or adenosine diphosphate in media with or without extracellular calcium. In response to all of these agonists, aequorin indicated an increase in cytoplasmic calcium that accompanied or preceded platelet aggregation. In calcium-containing media, verapamil, nifedipine, and diltiazem inhibited these effects in a concentration-dependent fashion, except for those produced by thrombin and A23187. Removal of extracellular calcium with EGTA reduced the calcium response to arachidonate, adenosine diphosphate, and 1-oleoyl-2-acetyl glycerol, and the calcium response and aggregation were further inhibited by the calcium antagonists. In general, strong inhibition of the aequorin cytoplasmic calcium signal by approximately 100 microM concentrations of nifedipine, verapamil, and diltiazem was correlated with inhibition of platelet aggregation, but high concentrations of the inhibitors were required. Since inhibition by the calcium antagonists of the cytoplasmic calcium response and aggregation exceeded the effect of simple removal of extracellular calcium, these drugs may affect internal redistribution of calcium in human platelets.
Testing for HIV without permission
Authors: R Vaughan
Journal: BMJ (1987)

that the recent American paper should have quoted three papers from the Royal College of Radiologists' study in Britain but ignored the two papers from Scotland on skull fracture as a risk factor for intracranial haematoma and the guidelines from the neurosurgeons, which were all published in the BM7.The criteria for performing skull radiography in these guidelines were largely derived from the conclusions of the Royal College of Radiologists' study in the absence of more adequate data.Our current studies aim at improving information about the clinical features that correlate with a skull fracture and refining the risk factors for an intracranial haematoma, both in adults and in children.
De novo acute megakaryoblastic leukemia with p210 BCR/ABL and t(1;16) translocation but not t(9;22) Ph chromosome
Authors: Xiao Min, Zhang Na, Liu Yanan, Li Chunrui
Journal: Journal of Hematology & Oncology (2011)

Abstract Acute megakaryoblastic leukemia (AMKL) is a type of acute myeloid leukemia (AML), in which majority of the blasts are megakaryoblastic. De novo AMKL in adulthood is rare, and carries very poor prognosis. We here report a 45-year-old woman with de novo AMKL with BCR/ABL rearrangement and der(16)t(1;16)(q21;q23) translocation but negative for t(9;22) Ph chromosome. Upon induction chemotherapy consisting of homoharringtonine, cytarabine and daunorubicin, the patient achieved partial hematological remission. The patient was then switched to imatinib plus one cycle of CAG regimen (low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor), and achieved complete remission (CR). The disease recurred after 40 days and the patient eventually died of infection. To the best of our knowledge, this is the first report of de novo AMKL with p210 BCR/ABL and der(16)t(1;16)(q21;q23) translocation but not t(9;22) Ph chromosome.
Effects of an Inhibitor of Cholesteryl Ester Transfer Protein on HDL Cholesterol
Authors: Margaret E. Brousseau, Ernst J. Schaefer, Megan L. Wolfe, LeAnne T. Bloedon, Andres G. Digenio, Ronald W. Clark, James P. Mancuso, Daniel J. Rader
Journal: New England Journal of Medicine (2004)

Decreased high-density lipoprotein (HDL) cholesterol levels constitute a major risk factor for coronary heart disease; however, there are no therapies that substantially raise HDL cholesterol levels. Inhibition of cholesteryl ester transfer protein (CETP) has been proposed as a strategy to raise HDL cholesterol levels.
Hedgehog Fights Back: Mechanisms of Acquired Resistance against Smoothened Antagonists
Authors: Ciara Metcalfe, Frederic J. de Sauvage
Journal: Cancer Research (2011)

Acquired resistance to targeted therapies threatens the value of these otherwise very promising agents. The recent description of resistance to the Hedgehog pathway inhibitor vismodegib (GDC-0449) in a medulloblastoma patient who had a dramatic initial response has spurred efforts to understand potential mechanisms of drug resistance. Elucidating these mechanisms will play a significant role in informing strategies to overcome this meaningful limitation.
Nomograms to predict survival and the risk for developing local or distant recurrence in patients with rectal cancer treated with optional short-term radiotherapy
Authors: W. van Gijn, R.G.P.M. van Stiphout, C.J.H. van de Velde, V. Valentini, G. Lammering, M.A. Gambacorta, L. Påhlman, K. Bujko, P. Lambin
Journal: Annals of Oncology (2015)