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Role of Reactive Oxygen Species in N-(4-hydroxyphenyl)retinamide-induced Cell Death in HTLV-I-transformed Cells and Malignant T Cell Lines

Author : Ghada Mahmoud Abou-Lteif
Publisher :
Page : 176 pages
File Size : 49,72 MB
Release : 2008
Category :
ISBN :

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N-(4-hydroxyphenyl)retinamide (HPR) is a synthetic retinoid that inhibits growth and induces apoptosis in many human cell lines including those that are resista nt to natural retinoids. Adult T-cell leukemia-lymphoma (ATL) is an aggressive peripheral T-cell malignancy caused by human T-cell lymphotropic virus type I (H TLV-I). ATL carries a poor prognosis with a mean survival time of less than eig ht months, in the acute form, mainly due to acquired resistance to chemotherapy. The viral transactivator protein Tax plays a critical role in HTLV-I-induced t ransformation and apoptosis resistance. We have previously shown that HPR inhibits proliferation and induces apoptosis i n all tested ATL and HTLV-I-negative malignant T cell lines, while no effect is observed on normal lymphocytes (Darwiche 2004). The mechanisms of HPR-induced c ell death are complex and involve signaling pathways mediated by free radicals o r reactive oxygen species (ROS). Using ATL as a model, we aim at deciphering th e mechanisms generating ROS and apoptosis of malignant T cells in response to HP R. We will explore the involvement of ROS in HPR-induced apoptosis, the contrib ution of the different biochemical pathways of ROS generation in relation to HPR -induced cell death; and Tax modulation of HPR induced ROS accumulation and ROS- induced cell death. We identified HPR-induced ROS generation as the key mediator of cell cycle arres t and apoptosis of malignant T cells. Pre-treatment with antioxidants inhibited ROS generation, prevented HPR-induced ceramide accumulation, cell cycle arrest, cytochrome c release, caspase-activation and apoptosis. The expression of the HTLV-I oncoprotein Tax abrogated HPR-induced ROS accumulation in HTLV-I-infected cells, which explains their lower sensitivity to HPR. Of the enzyme systems fr equently implicated in ROS generation, only phospholipase A2 (PLA2) and lipooxyg enase (LOX) were shown to be involved in ROS generation and growth suppression i n response to HPR in HTLV-I-negative malignant T cells Defining the mechanism of free radical induction by HPR may support a potential therapeutic role for this synthetic retinoid in ATL and HTLV-I-negative T-cell l ymphomas.

Cancer Research

Author :
Publisher :
Page : 1076 pages
File Size : 13,44 MB
Release : 2005-10
Category : Cancer
ISBN :

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Methods in Cellular Imaging

Author : Ammasi Periasamy
Publisher : Springer
Page : 473 pages
File Size : 35,39 MB
Release : 2013-05-27
Category : Science
ISBN : 1461475139

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Advances in technology have revolutionized the development of light microscopy techniques in biomedical research, thus improving visualization of the microstructure of cells and tissues under physiological conditions. Fluorescence microscopy methods are non-contact and non-invasive and provide high spatial and temporal resolution that other laboratory techniques cannot. This well-illustrated book targets graduate students and scientists who are new to the state-of-the-art fluorescence microscopy techniques used in biological and clinical imaging. It explains basic concepts and imaging procedures for wide-field, confocal, multiphoton excitation, fluorescence resonance energy transfer (FRET), lifetime imaging (FLIM), spectral imaging, fluorescence recovery after photobleaching (FRAP), optical tweezers, total internal reflection, high spatial resolution atomic force microscopy (AFM), and bioluminescence imaging for gene expression. The usage of these techniques in various biological applications, including calcium, pH, membrane potential, mitochondrial signaling, protein-protein interactions under various physiological conditions, and deep tissue imaging, is clearly presented. The authors describe the approaches to selecting epifluorescence microscopy, the detectors, and the image acquisition and processing software for different biological applications. Step-by-step directions on preparing different digital formats for light microscopy images on websites are also provided.

Weight Control and Physical Activity

Author : Harri Vainio
Publisher : IARC
Page : 346 pages
File Size : 12,10 MB
Release : 2002
Category : Health & Fitness
ISBN : 9789283230069

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Avoiding overweight and obesity is the best-established diet-related risk factor for cancer. The proportion of people who are overweight/obese is increasing, and the amount of physical activity is decreasing in most populations, including urban populations in many developing countries. The increasing prevalence of overweight/obesity is presumably due to the increasing availability of highly palatable, high-energy foods, and an increasing sedentary lifestyle due to mechanisation of both workplace and leisure activities. Overweight/obesity and reduced physical activity increases the risk of cancers in various organs. Maintaining a healthy body weight and regular physical activity is the second most important way to prevent cancer, after tobacco control. The suggestions of possible public health actions to tackle these risk factors include the promotion of balanced diets, which are not excessive in energy, and broad education and planning to enable and encourage physical activity during work and leisure. Recommendations and a full discussion of these topics are included in the sixth volume in this series of Handbooks.

Prognostic Factors in Cancer

Author : Paul Hermanek
Publisher : Springer Science & Business Media
Page : 303 pages
File Size : 47,32 MB
Release : 2012-12-06
Category : Medical
ISBN : 3642793959

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M. K. Gospodarowicz, P. Hermanek, and D. E. Henson Attention to innovations in cancer treatment has tended to eclipse the importance of prognostic assessment. However, the recognition that prognostic factors often have a greater impact on outcome than available therapies and the proliferation of biochemical, molecular, and genetic markers have resulted in renewed interest in this field. The outcome in patients with cancer is determined by a combination of numerous factors. Presently, the most widely recognized are the extent of disease, histologic type of tumor, and treatment. It has been known for some time that additional factors also influence outcome. These include histologic grade, lymphatic or vascular invasion, mitotic index, performance status, symptoms, and most recently genetic and biochemical markers. It is the aim of this volume to compile those prognostic factors that have emerged as important determinants of outcome for tumors at various sites. This compilation represents the first phase of a more extensive process to integrate all prognostic factors in cancer to further enhance the prediction of outcome following treatment. Certain issues surround ing the assessment and reporting of prognostic factors are also considered. Importance of Prognostic Factors Prognostic factors in cancer often have an immense influence on outcome, while treatment often has a much weaker effect. For example, the influence of the presence of lymph node involvement on survival of patients with metastatic breast cancer is much greater than the effect of adjuvant treatment with tamoxifen in the same group of patients [5].

Lymphoproliferative Diseases: Pathogenesis, Diagnosis, Therapy

Author : P.K. Pattengale
Publisher : Springer Science & Business Media
Page : 226 pages
File Size : 19,96 MB
Release : 1985-06-30
Category : Medical
ISBN : 9780898387254

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Proceedings of a symposium presented at the University of Southern California, Department of Pathology and the Kenneth J. Norris Cancer Hospital and Research Institute, Los Angeles, U.S.A., November 16-17, 1984

Cancer Survival in Developing Countries

Author : R. Sankaranarayanan
Publisher :
Page : 188 pages
File Size : 43,31 MB
Release : 1998
Category : Medical
ISBN :

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For the first time, comprehensive cancer survival data are published from developing countries, 10 populations in total from, Costa Rica, Cuba, China, India, the Philippines and Thailand. These data allow valid comparisons to be made with data from Europe and North America. An interesting finding is that for cancers associated with poor prognosis, the differences in survival between developed and developing countries were negligible. However, there are larger absolute differences for cancers of the large bowel, breast, cervix, ovary and testis, and for lymphoreticular malignancies. The publication provides a framework for investigating the problems in data gathering and patient follow-up, as well as methods for estimating cancer survival in developing countries.

Growth and Lactogenic Hormones

Author : L. Matera
Publisher : Gulf Professional Publishing
Page : 348 pages
File Size : 21,24 MB
Release : 2002-04-18
Category : Medical
ISBN : 9780444510518

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For more than seventy years evidence has accumulated documenting the existence of a bi-directional communication network between growth hormone and the immune system. In the past twenty years there has been a tremendous proliferation of information detailing the workings of the growth hormone and insulin-like growth factor axis. A multitude of growth factors and binding proteins have been identified. More and more evidence supporting the important role of the growth hormone IGF network in the well functioning of the normal immune system has been documented. Clearly the challenge today is not to prove, but to understand, the neuroimmune regulatory role of GLH in its entire complexity. The ultimate goal of this volume and of all the other volumes of this series is to promote the understanding of the science and to ease human suffering.