tbuckley/cabot-search huggingface dataset:
Deregulation of a Hox Protein Regulatory Network Spanning Prostate Cancer Initiation and Progression
Authors: James L. Chen, Jianrong Li, Kyle J. Kiriluk, Alex M. Rosen, Gladell P. Paner, Tatjana Antic, Yves A. Lussier, Donald J. Vander Griend
Journal: Clinical Cancer Research (2012)

Abstract Purpose: The aberrant activity of developmental pathways in prostate cancer may provide significant insight into predicting tumor initiation and progression, as well as identifying novel therapeutic targets. To this end, despite shared androgen-dependence and functional similarities to the prostate gland, seminal vesicle cancer is exceptionally rare. Experimental Design: We conducted genomic pathway analyses comparing patient-matched normal prostate and seminal vesicle epithelial cells to identify novel pathways for tumor initiation and progression. Derived gene expression profiles were grouped into cancer biomodules using a protein–protein network algorithm to analyze their relationship to known oncogenes. Each resultant biomodule was assayed for its prognostic ability against publically available prostate cancer patient gene array datasets. Results: Analyses show that the embryonic developmental biomodule containing four homeobox gene family members (Meis1, Meis2, Pbx1, and HoxA9) detects a survival difference in a set of watchful-waiting patients (n = 172, P = 0.05), identify men who are more likely to recur biochemically postprostatectomy (n = 78, P = 0.02), correlate with Gleason score (r = 0.98, P = 0.02), and distinguish between normal prostate, primary tumor, and metastatic disease. In contrast to other cancer types, Meis1, Meis2, and Pbx1 expression is decreased in poor-prognosis tumors, implying that they function as tumor suppressor genes for prostate cancer. Immunohistochemical staining documents nuclear basal-epithelial and stromal Meis2 staining, with loss of Meis2 expression in prostate tumors. Conclusion: These data implicate deregulation of the Hox protein cofactors Meis1, Meis2, and Pbx1 as serving a critical function to suppress prostate cancer initiation and progression. Clin Cancer Res; 18(16); 4291–302. ©2012 AACR.
Pulmonary Effects of Indoor- and Outdoor-Generated Particles in Children with Asthma
Authors: Jane Q. Koenig, Therese F. Mar, Ryan W. Allen, Karen Jansen, Thomas Lumley, Jeffrey H. Sullivan, Carol A. Trenga, Timothy V. Larson, L.-Jane S. Liu
Journal: Environmental Health Perspectives (2005)

Most particulate matter (PM) health effects studies use outdoor (ambient) PM as a surrogate for personal exposure. However, people spend most of their time indoors exposed to a combination of indoor-generated particles and ambient particles that have infiltrated. Thus, it is important to investigate the differential health effects of indoor- and ambient-generated particles. We combined our recently adapted recursive model and a predictive model for estimating infiltration efficiency to separate personal exposure (E) to PM2.5 (PM with aerodynamic diameter ≤2.5 μm) into its indoor-generated (Eig) and ambient-generated (Eag) components for 19 children with asthma. We then compared Eig and Eag to changes in exhaled nitric oxide (eNO), a marker of airway inflammation. Based on the recursive model with a sample size of eight children, Eag was marginally associated with increases in eNO [5.6 ppb per 10-μg/m3 increase in PM2.5; 95% confidence interval (CI), −0.6 to 11.9; p = 0.08]. Eig was not associated with eNO (−0.19 ppb change per 10μg/m3). Our predictive model allowed us to estimate Eag and Eig for all 19 children. For those combined estimates, only Eag was significantly associated with an increase in eNO (Eag: 5.0 ppb per 10-μg/m3 increase in PM2.5; 95% CI, 0.3 to 9.7; p = 0.04; Eig: 3.3 ppb per 10-μg/m3 increase in PM2.5; 95% CI, −1.1 to 7.7; p = 0.15). Effects were seen only in children who were not using corticosteroid therapy. We conclude that the ambient-generated component of PM2.5 exposure is consistently associated with increases in eNO and the indoor-generated component is less strongly associated with eNO.
Effect of polyI:C cotreatment on halothane-induced liver injury in mice
Authors: Linling Cheng, Qiang You, Hao Yin, Michael Holt, Christopher Franklin, Cynthia Ju
Journal: Hepatology (2008)

Drug-induced liver injury (DILI) is a challenging problem in drug development and clinical practice. Patient susceptibility to DILI is multifactorial, making these reactions difficult to predict and prevent. Clinical observations have suggested that concurrent bacterial and viral infections represent an important risk factor in determining patient susceptibility to developing adverse drug reactions, although the underlying mechanism is not clear. In the present study, we employed the viral RNA mimetic (polyinosinic-polycytidylic acid [polyI:C]) to emulate viral infection and examined its effect on halothane-induced liver injury. Although pretreatment of mice with polyI:C attenuated halothane hepatotoxicity due to its inhibitory effect on halothane metabolism, posttreatment significantly exacerbated liver injury with hepatocellular apoptosis being significantly higher than that in mice treated with polyI:C alone or halothane alone. The pan-caspase inhibitor z-VAD-fmk suppressed liver injury induced by polyI:C/posthalothane cotreatment, suggesting that the increased hepatocyte apoptosis contributes to the exacerbation of liver injury. Posttreatment with polyI:C also caused activation of hepatic Kupffer cells (KCs) and natural killer (NK) cells and upregulated multiple proapoptotic factors, including tumor necrosis factor-α (TNF-α), NK receptor group 2, member D (NKG2D), and Fas ligand (FasL). These factors may play important roles in mediating polyI:C-induced hepatocyte apoptosis. Conclusion: This is the first study to provide evidence that concurrent viral infection can inhibit cytochrome (CYP)450 activities and activate the hepatic innate immune system to proapoptotic factors. DILI may be attenuated or exacerbated by pathogens depending on the time of infection. (HEPATOLOGY 2009;49:215–226.)
Batf coordinates multiple aspects of B and T cell function required for normal antibody responses
Authors: Briana C. Betz, Kimberly L. Jordan-Williams, Chuanwu Wang, Seung Goo Kang, Juan Liao, Michael R. Logan, Chang H. Kim, Elizabeth J. Taparowsky
Journal: The Journal of Experimental Medicine (2010)

Batf belongs to the activator protein 1 superfamily of basic leucine zipper transcription factors that includes Fos, Jun, and Atf proteins. Batf is expressed in mouse T and B lymphocytes, although the importance of Batf to the function of these lineages has not been fully investigated. We generated mice (BatfΔZ/ΔZ) in which Batf protein is not produced. BatfΔZ/ΔZ mice contain normal numbers of B cells but show reduced numbers of peripheral CD4+ T cells. Analysis of CD4+ T helper (Th) cell subsets in BatfΔZ/ΔZ mice demonstrated that Batf is required for the development of functional Th type 17 (Th17), Th2, and follicular Th (Tfh) cells. In response to antigen immunization, germinal centers were absent in BatfΔZ/ΔZ mice and the maturation of Ig-secreting B cells was impaired. Although adoptive transfer experiments confirmed that this B cell phenotype can be driven by defects in the BatfΔZ/ΔZ CD4+ T cell compartment, stimulation of BatfΔZ/ΔZ B cells in vitro, or by a T cell–independent antigen in vivo, resulted in proliferation but not class-switch recombination. We conclude that loss of Batf disrupts multiple components of the lymphocyte communication network that are required for a robust immune response.
Evaluation of CD20, CD22, and HLA-DR Targeting for Radioimmunotherapy of B-Cell Lymphomas
Authors: John M. Pagel, Anastasia Pantelias, Nathan Hedin, Shani Wilbur, Laura Saganic, Yukang Lin, Donald Axworthy, Donald K. Hamlin, D. Scott Wilbur, Ajay K. Gopal, Oliver W. Press
Journal: Cancer Research (2007)

Abstract Despite the promise of radioimmunotherapy using anti-CD20 antibodies (Ab) for the treatment of relapsed patients with indolent non-Hodgkin lymphoma (NHL), most patients treated with conventional doses of 131I-tositumomab or 90Y-ibritumomab eventually relapse. We did comparative assessments using conventional radioimmunotherapy targeting CD20, CD22, and HLA-DR on human Ramos, Raji, and FL-18 lymphoma xenografts in athymic mice to assess the potential for improving the efficacy of radioimmunotherapy by targeting other NHL cell surface antigens. Results of biodistribution studies showed significant differences in tumor localization consistent with variable antigenic expression on the different lymphoma cell lines. Interestingly, the radioimmunoconjugate that yielded the best tumor-to-normal organ ratios differed in each tumor model. We also explored administering all three 111In-1,4,7,10-tetra-azacylododecane N,N′,N″,N‴-tetraacetic acid antibodies in combination, but discovered, surprisingly, that this approach did not augment the localization of radioactivity to tumors compared with the administration of the best single radiolabeled Ab alone. These data suggest that conventional radioimmunotherapy using anti-CD20, anti–HLA-DR, or anti-CD22 Abs is effective when used singly and provides targeted uptake of radiolabel into the tumor that is dependent on the levels of antigen expression. Improvements in tumor-to-normal organ ratios of radioactivity cannot be achieved using directly labeled Abs in combination but may be afforded by novel pretargeting methods. [Cancer Res 2007;67(12):5921–8]
Systemic Therapy of Malignant Human Melanoma Tumors by a Common Cold-Producing Enterovirus, Coxsackievirus A21
Authors: Darren R. Shafren, Gough G. Au, Tam Nguyen, Nicole G. Newcombe, Erin S. Haley, Leone Beagley, E. Susanne Johansson, Peter Hersey, Richard D. Barry
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The incidence of malignant melanoma continues to increase worldwide; however, treatment of metastatic melanoma remains unsatisfactory, and there is an urgent need for development of effective targeted therapeutics. A potential biological target on the surface of malignant melanoma cells is the up-regulated expression of intercellular adhesion molecule (ICAM)-1 and decay-accelerating factor (DAF), relative to surrounding benign tissue. Coxsackievirus A21 (a common cold virus) targets and destroys susceptible cells via specific viral capsid interactions with surface-expressed virus receptors comprising ICAM-1 and DAF. Experimental Design: The oncolytic capacity of a genetically unmodified wild-type common cold-producing human enterovirus (Coxsackievirus A21, CAV21) was assessed against in vitro cultures and in vivo xenografts of malignant human melanoma cells. Results: In vitro studies established that human melanoma cells endogenously express elevated levels of ICAM-1/DAF and were highly susceptible to rapid viral oncolysis by CAV21 infection, whereas ICAM-1/DAF-expressing peripheral blood lymphocytes were refractile to infection. In vivo studies revealed that the tumor burden of nonobese diabetic severe combined immunodeficient mice bearing multiple s.c. melanoma xenografts was rapidly reduced by oncolysis mediated by a single administration of CAV21. The antitumor activity of CAV21 was characterized by highly efficient systemic spread of progeny CAV21, with oncolysis of tumors also occurring at sites distant to the primary site of viral administration. Conclusions: Overall, the findings presented herein demonstrate an important proof of principle using administration of replication-competent CAV21 as a potential biological oncolytic agent in the control of human metastatic melanoma.
Localization of amyloid-related serum protein SAA-like material to intermediate (10 nm) filaments of cultured human embryonal fibroblasts.
Authors: E Linder, V P Lehto, I Virtanen, S Stenman, J B Natvig
Journal: The Journal of Experimental Medicine (1977)

Further studies are presented on the intracellular localization of the amyloid-related serum protein SAA previously shown to be produced by embryonal fibroblasts. In cultured embryonal fibroblasts, the fine fibrillar cytoplasmic immunofluorescence obtained by anti-SAA was distinguished from that of microfilaments and microtubules. By using electron microscopy and cells treated with drugs known to specifically alter intracellular fibrils, SAA was localized to 10-nm intermediate size filaments. These filaments form characteristic perinuclear bundles upon treatment with drugs such as demecolcine or vinblastine which disrupt micotubules. The results indicate that SAA is a constituent of the intracellular cytoskeleton.
New validated prognostic models and prognostic calculators in patients with low-grade gliomas diagnosed by central pathology review: a pooled analysis of EORTC/RTOG/NCCTG phase III clinical trials
Authors: T. Gorlia, W. Wu, M. Wang, B. G. Baumert, M. Mehta, J. C. Buckner, E. Shaw, P. Brown, R. Stupp, E. Galanis, D. Lacombe, M. J. van den Bent
Journal: Neuro-Oncology (2013)

In a previous study, the European Organisation for Research and Treatment of Cancer (EORTC) reported a scoring system to predict survival of patients with low-grade gliomas (LGGs). A major issue in the diagnosis of brain tumors is the lack of agreement among pathologists. New models in patients with LGGs diagnosed by central pathology review are needed. Data from 339 EORTC patients with LGGs diagnosed by central pathology review were used to develop new prognostic models for progression-free survival (PFS) and overall survival (OS). Data from 450 patients with centrally diagnosed LGGs recruited into 2 large studies conducted by North American cooperative groups were used to validate the models. Both PFS and OS were negatively influenced by the presence of baseline neurological deficits, a shorter time since first symptoms (<30 wk), an astrocytic tumor type, and tumors larger than 5 cm in diameter. Early irradiation improved PFS but not OS. Three risk groups have been identified (low, intermediate, and high) and validated. We have developed new prognostic models in a more homogeneous LGG population diagnosed by central pathology review. This population better fits with modern practice, where patients are enrolled in clinical trials based on central or panel pathology review. We could validate the models in a large, external, and independent dataset. The models can divide LGG patients into 3 risk groups and provide reliable individual survival predictions. Inclusion of other clinical and molecular factors might still improve models' predictions.
ARTIFICIAL MAINTENANCE MEDIA FOR CELL AND ORGAN CULTIVATION
Authors: Lillian E. Baker, Albert H. Ebeling
Journal: The Journal of Experimental Medicine (1939)

Several media designed for maintaining the life of cells and organs outside the body have been described. Cultures from a pure strain of fibroblasts have been maintained in these media in vital condition and with little or no proliferation for periods varying from 43 to 56 days. One of these media is very simple, inexpensive, and easy to prepare; and one is serumless.
Assisted reproduction practice in Europe: legal and ethical aspects
Authors: J. Schenker
Journal: Human Reproduction Update (1997)

This report describes the ethical and legal aspects of assisted reproductive technologies (ART) that have been instituted in European countries. The data were collected from questionnaires circulated to fertility centres in 39 countries in Europe. Ninety six ART centres were located in 30 of these countries. Nine countries do not offer ART services. According to the survey, there are approximately 516 centres in Europe, which represent approximately 60% of the world ART centres. The survey included information regarding regulation of ART services, access to these services, attitude toward genetic material donation, cryopreservation of pre-embryos, surrogacy, manipulation of gametes and pre-embryos, research on pre-embryos and multiple fetal pregnancy reduction. At present, the majority of countries in Europe do not have established legislation pertaining to the various aspects of ART practice. The study reviews the ethical and legal aspects of ART practice in Europe.
Common Respiratory Viruses in Lower Airways of Patients with Acute Hypersensitivity Pneumonitis
Authors: AZZEDDINE DAKHAMA, RICHARD G. HEGELE, GENEVIèVE LAFLAMME, EVELYNE ISRAëL-ASSAYAG, YVON CORMIER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Hypersensitivity pneumonitis (HP), a lung disease with "flulike" symptoms, results from repeated exposures to well defined, nonpathogenic antigens. This study examined whether respiratory viruses are present in the lower airways, the likely site of hypersensitivity reaction, in patients with HP. The polymerase chain reaction (PCR) method was used to test for 10 common respiratory viruses in bronchoalveolar lavage (BAL) cells obtained from patients with acute HP and from unexposed healthy volunteers. Immunocytochemistry was subsequently used to localize viral proteins within BAL cells. The results of PCR showed that influenza A virus was the most frequently detected virus in the BAL cells of our study patients (six of 13) and control subjects (two of six). Influenza A proteins were detected within alveolar macrophages in nine of 13 patients and in two of six control subjects. The number of total BAL cells, but not lymphocytes, was higher in patients with documented influenza A proteins than in patients with no influenza A proteins (p = 0.017) and correlated with the proportion of influenza-A-positive alveolar macrophages (r = 0.7; p = 0.036). This report documents the presence of viruses in the lower airways of patients with acute HP. The findings may imply a potential role for influenza A in the modulation of HP during antigen exposure.
Akt signaling pathway: a target for radiosensitizing human malignant glioma
Authors: Emmanuel Chautard, Gaëlle Loubeau, Andrei Tchirkov, Jacques Chassagne, Claudine Vermot-Desroches, Laurent Morel, Pierre Verrelle
Journal: Neuro-Oncology (2010)

Radiation therapy plays a central role in the treatment of glioblastoma, but it is not curative due to the high tumor radioresistance. Phosphatidyl-inositol 3-kinase/protein kinase B (Akt) and Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways serve to block the apoptosis process, keeping cells alive in very toxic environments such as chemotherapy or ionizing radiation. In the present study, from a panel of 8 human malignant glioma cell lines, investigations on the relationship between intrinsic radioresistance and Akt or STAT3 basal activation were done. Secondly, the impact of down-modulation of Akt or STAT3 signaling on in vitro intrinsic radiosensitivity was evaluated. Using a clonogenic cell survival assay, our results revealed a significant correlation between the basal Akt activation and the surviving fraction at 2 Gy (SF2). In contrast, no correlation was found between STAT3 activation and SF2. According to this, down-modulation of Akt with a specific chemical inhibitor (Akt inhibitor IV) demonstrated a significant enhancement of radiation sensitivity on glioma cells in a clonogenic survival assay. On the contrary, down-modulation of STAT3 signaling with a specific chemical inhibitor (JSI-124) or a neutralizing gp130 antibody failed to radiosensitize glioma cells. These data indicate that the Akt intercept node could be a more relevant therapeutic target than STAT3 for radiosensitizing human malignant glioma.
Acute myeloid leukaemia after treatment with razoxane
Authors: E.A. CAFFREY, M.G. DAKER, J.J. HORTON
Journal: British Journal of Dermatology (1985)

Journal Article Acute myeloid leukaemia after treatment with razoxane Get access E.A. CAFFREY, E.A. CAFFREY Department of Haematology, Guy's Hospital, London, SE1 9RT, U.K. Dr E.A.Caffrey, Department of Haematology, Guy's Hospital, London, SE1 9RT, U.K. Search for other works by this author on: Oxford Academic Google Scholar M.G. DAKER, M.G. DAKER Paediatric Research Unit, Guy's Hospital, London, SE1 9RT, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.J. HORTON J.J. HORTON Department of Dermatology, Guy's Hospital, London, SE1 9RT, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue 2, 1 August 1985, Pages 131–134, https://doi.org/10.1111/j.1365-2133.1985.tb02054.x Published: 01 August 1985 Article history Accepted: 04 February 1985 Published: 01 August 1985
Inositol hexakisphosphate kinase 1 regulates neutrophil function in innate immunity by inhibiting phosphatidylinositol-(3,4,5)-trisphosphate signaling
Authors: Amit Prasad, Yonghui Jia, Anutosh Chakraborty, Yitang Li, Supriya K Jain, Jia Zhong, Saurabh Ghosh Roy, Fabien Loison, Subhanjan Mondal, Jiro Sakai, Catlyn Blanchard, Solomon H Snyder, Hongbo R Luo
Journal: Nature Immunology (2011)
Quantitative Risk Assessment of Environmental Hazards
Authors: S L Brown
Journal: Annual Review of Public Health (1985)

Quantitative risk assessment may never become a rigorous scientific discipline because of the inherent difficulties in working with highly uncertain and often controversial data and methods, and because the predictions of risk assessment may not be subject to validation in their most important areas of application. However, the potential benefits of having quantitative estimates of risk may make quantitative risk assessment a valuable adjunct to traditional methods for making individual and social decisions about health hazards in the home, workplace, and general environment. Risk assessment, which is the process of estimating risks to populations exposed to hazardous agents or activities, must be distinguished from risk management, which is the process of forming and implementing a strategy for accepting or abating the risks. To the extent possible, these two processes should be kept separate. Quantitative risk assessment is in principle capable of estimating individual or lifetime excesses of specific health effects from exposures to a specified hazard. These excesses may be estimated on an absolute basis or expressed as a relative risk in comparison with the baseline risk that would exist without exposure. An individual risk is usually expressed in terms of the probability of developing the health effect in some time period following a specified exposure, whereas a population risk is the overall number of effects expected in a defined population with a defined distribution of exposure levels and patterns. The variation of risk with time after exposure may imply a constant absolute risk, a constant relative risk, or some other dependence on time, usually after a minimal latent period has elapsed. Risk estimates can rarely be made directly from observed human data, and models for extrapolating or projecting risk estimates from the conditions of observation to the actual conditions of exposure must be used. Dose-response relationships are used for extrapolating from high laboratory or occupational exposures to low exposures encountered more frequently in human populations. Thresholds of dose or nonlinear dose-response relationships may be related to nonlinear pharmacokinetics prior to the ultimate exposure of the critical organ to the proximate carcinogen or other hazardous agent. Time-response models estimate risks for periods after exposure longer than have been observed in epidemiologic studies. Extrapolations from experiments with laboratory animals to humans are made difficult because of great differences in size, lifespan, physiology, and metabolism between human and animal.(ABSTRACT TRUNCATED AT 400 WORDS)
One-year mortality and predictors of death among hospital survivors of acute respiratory distress syndrome
Authors: Chen Yu Wang, Carolyn S. Calfee, Devon W. Paul, David R. Janz, Addison K. May, Hanjing Zhuo, Gordon R. Bernard, Michael A. Matthay, Lorraine B. Ware, Kirsten Neudoerffer Kangelaris
Journal: Intensive Care Medicine (2014)