397 research outputs found
PyMT-Maclow: A novel, inducible, murine model for determining the role of CD68 positive cells in breast tumor development
No full textCD68+ tumor-associated macrophages (TAMs) are pro-tumorigenic, pro-angiogenic and are associated with decreased survival rates in patients with cancer, including breast cancer. Non-specific models of macrophage ablation reduce the number of TAMs and limit the development of mammary tumors. However, the lack of specificity and side effects associated with these models compromise their reliability. We hypothesized that specific and controlled macrophage depletion would provide precise data on the effects of reducing TAM numbers on tumor development. In this study, the MacLow mouse model of doxycycline-inducible and selective CD68+ macrophage depletion was crossed with the murine mammary tumor virus (MMTV)-Polyoma virus middle T antigen (PyMT) mouse model of spontaneous ductal breast adenocarcinoma to generate the PyMT-MacLow line. In doxycycline-treated PyMT-MacLow mice, macrophage numbers were decreased in areas surrounding tumors by 43%. Reducing the number of macrophages by this level delayed tumor progression, generated less proliferative tumors, decreased the vascularization of carcinomas and down-regulated the expression of many pro-angiogenic genes. These results demonstrate that depleting CD68+ macrophages in an inducible and selective manner delays the development of mammary tumors and that the PyMT-MacLow model is a useful and unique tool for studying the role of TAMs in breast cancer
Tumour cells expressing single VEGF isoforms display distinct growth, survival and migration characteristics
No full textVascular endothelial growth factor-A (VEGF) is produced by most cancer cells as multiple isoforms, which display distinct biological activities. VEGF plays an undisputed role in tumour growth, vascularisation and metastasis; nevertheless the functions of individual isoforms in these processes remain poorly understood. We investigated the effects of three main murine isoforms (VEGF188, 164 and 120) on tumour cell behaviour, using a panel of fibrosarcoma cells we developed that express them individually under endogenous promoter control. Fibrosarcomas expressing only VEGF188 (fs188) or wild type controls (fswt) were typically mesenchymal, formed ruffles and displayed strong matrix-binding activity. VEGF164- and VEGF120-producing cells (fs164 and fs120 respectively) were less typically mesenchymal, lacked ruffles but formed abundant cell-cell contacts. On 3D collagen, fs188 cells remained mesenchymal while fs164 and fs120 cells adopted rounded/amoeboid and a mix of rounded and elongated morphologies respectively. Consistent with their mesenchymal characteristics, fs188 cells migrated significantly faster than fs164 or fs120 cells on 2D surfaces while contractility inhibitors accelerated fs164 and fs120 cell migration. VEGF164/VEGF120 expression correlated with faster proliferation rates and lower levels of spontaneous apoptosis than VEGF188 expression. Nevertheless, VEGF188 was associated with constitutively active/phosphorylated AKT, ERK1/2 and Stat3 proteins. Differences in proliferation rates and apoptosis could be explained by defective signalling downstream of pAKT to FOXO and GSK3 in fs188 and fswt cells, which also correlated with p27/p21 cyclin-dependent kinase inhibitor over-expression. All cells expressed tyrosine kinase VEGF receptors, but these were not active/activatable suggesting that inherent differences between the cell lines are governed by endogenous VEGF isoform expression through complex interactions that are independent of tyrosine kinase receptor activation. VEGF isoforms are emerging as potential biomarkers for anti-VEGF therapies. Our results reveal novel roles of individual isoforms associated with cancer growth and metastasis and highlight the importance of understanding their diverse actions
The use of nuclear track autoradiography in the study of the distribution of Thorium and its products in living organisms.
No full textA thesis presented by Gillian B Ward (M. Sc.) for the degree of Ph.D in the Faculty of Sciences (Physics applied to Medicine) in University of London. June 1955. Scanned with permission from the Author 22-06-15
The Effects of Type of Communication Issue and Initial Opinion Strength on Immediate and Delayed Opinion Change
No full textTitle: The Effects of Type of Communication Issue and Initial Opinion Strength on Immediate and Delayed Opinion Change, Author: Gillian M. Foster, Location: ThodeAn experiment was conducted to determine the effect on opinion change of communications concerning different types of issues when given to subjects with different initial opinion strengths. Opinion change was evaluated immediately, and after an interval of time. The results indicated that opinion change was greatest for issues of low involvement, and least for issues of high involvement, irrespective of the subject's initial opinion strength. The induced opinion change for the issues of high involvement was found to be retained longer than that for the low involvement issues.ThesisMaster of Arts (MA
Motives Of Murder In Gillian Flynn’s Dark Places (2009): A Humanistic Psychological Perspective
No full textThis research focuses on the identification issue of motives of murder in Dark Places (2009) novel by Gillian Flynn. The theory is used in this research is humanistic psychology by Abraham Maslow. The type of this study is used qualitative descriptive. The method of collecting data in this research is used note taking technique. This study used two data, namely primary data and secondary data. Dark Places novel by Gillian Flynn is the primary data source. Online journals, thesis and research paper that related with issue motive of murder are the secondary data. The purposes of this research are as follows to identify the character’s motives of committing the murder, to describe the motives of murder depicted in the novel and to reveal the reason why the author addressed the motive of murder in the novel. The results of this study are as follows (1) there are three motives of murder such as need for food, safety from fear and safety from anxiety, (2) the author depicted issue motives of murder through character, setting, event, and style, (3) the author addressed the issue motive of murder because the author wants to create a novel about dark things and trouble female character
First Degree Murder Reflected in Gillian Flynn's Gone Girl (2012) : A Sociological Prespective
No full textThis study aims to identify of the issue of first degree murder in Gone Girl (2012) novel by Gillian Flynn. This research uses theory of sociological prespective. The type of this study is qualitative descriptive. The method of collecting data in this research is note taking technique. This study has two data source, namely primary data and secondary data. Gone Girl novel by Gillian Flynn is the primary data source. Online journals, research paper, website, article and bibliography of the writer, that related with the issue of the murder are the secondary data. The purposes of this research are as follows to identify the indicator of first degree murder, to describe the first degree murder depicted in the novel and to reveal the reason why the author addressed the first degree murder in the novel. The results of this study are as follows (1) there are three indicators of first degree murder such as willfulness/intent, deliberation and premeditation, and malice aforethought (2) the author depicted the first degree murder through character, setting, event, and style, (3) the author addressed the issue of first degree murder because the author wanted to make a novel about dark things, breakage and trouble female character
Generation of a novel mouse model for the inducible depletion of macrophages in vivo.
No full textMacrophages play an essential role in tissue homeostasis, innate immunity, inflammation, and wound repair. Macrophages are also essential during development, severely limiting the use of mouse models in which these cells have been constitutively deleted. Consequently, we have developed a transgenic model of inducible macrophage depletion in which macrophage-specific induction of the cytotoxic diphtheria toxin A chain (DTA) is achieved by administration of doxycycline. Induction of the DTA protein in transgenic animals resulted in a significant 50% reduction in CD68+ macrophages of the liver, spleen, and bone over a period of 6 weeks. Pertinently, the macrophages remaining after doxycycline treatment were substantially smaller and are functionally impaired as shown by reduced inflammatory cytokine production in response to lipopolysaccharide. This inducible model of macrophage depletion can now be utilized to determine the role of macrophages in both development and animal models of chronic inflammatory diseases
The Psychopath Phenomenon Reflected In Gillian Flynn ’S Gone Girl Novel (2012): A Psychoanalytic Approach
No full textThis research is about The Psychopath Phenomenon Reflected in Gillian
Flynn’s Gone Girl novel (2012) which is analyzed by using Psychoanalytic
Approach. The objectives of this study are to describe the characteristic of
psychopath, to analyze types of psychopath, to analyze the cause of being of
psychopath, and to understand why the author opened psychopath to the public. This
research is a qualitative research. The primary data of this research is Gone Girl
(2012) a novel by Gillian Flynn. The secondary data are some selected references
and material related to the study. The researcher displays four conclusions in this
research. Firstly, everybody can be a psychopath and have five characteristics
namely, lack of remorse, grandiosity, compulsive lying, manipulative, anti - social
behavior. Secondly, there are two types of psychopath. Namely Con Artist and The
Victim. Con artist is a psychopath who is good at manipulating, fluent lying and
distorting the facts, and The Victim a psychopath who uses sex as a hook for
achieving the goal. Thirdly, the causes of psychopath. Family problem is one of the
causes someone to be a psychopath. And the last, Gillian Flynn take psychopath in
her books to show the dark side of woman
Anti-vascular agent Combretastatin A-4-P modulates Hypoxia Inducible Factor-1 and gene expression
No full textBackground
A functional vascular network is essential for the survival, growth and spread of solid tumours, making blood vessels a key target for therapeutic strategies. Combretastatin A-4 phosphate (CA-4-P) is a tubulin-depolymerising agent in Phase II clinical trials as a vascular disrupting agent. Not much is known of the molecular effect of CA-4-P under tumour conditions. The tumour microenvironment differs markedly from that in normal tissue, specifically with respect to oxygenation (hypoxia). Gene regulation under tumour conditions is governed by hypoxia inducible factor 1 (HIF-1), controlling angiogenic and metastatic pathways.
Methods
We investigated the effect of CA-4-P on factors of the upstream and downstream signalling pathway of HIF-1 in vitro.
Results
CA-4-P treatment under hypoxia tended to reduce HIF-1 accumulation in a concentration-dependent manner, an effect which was more prominent in endothelial cells than in cancer cell lines. Conversely, CA-4-P increased HIF-1 accumulation under aerobic conditions in vitro. At these concentrations of CA-4-P under aerobic conditions, nuclear factor κB was activated via the small GTPase RhoA, and expression of the HIF-1 downstream angiogenic effector gene, vascular endothelial growth factor (VEGF-A), was increased.
Conclusion
Our findings advance the understanding of signal transduction pathways involved in the actions of the anti-vascular agent CA-4-P
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