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Hedgehog signaling activation in human cancer and its clinical implications

Hedgehog signaling activation in human cancer and its clinical implications PDF Author: Jingwu Xie
Publisher: Springer Science & Business Media
ISBN: 1441984356
Category : Medical
Languages : en
Pages : 223

Book Description
Understanding the role of hedgehog signaling in cancer is critically important for novel cancer therapeutics. The hedgehog pathway is a major pathway regulating cell differentiation, tissue polarity, stem cell maintenance and cell proliferation. It is known by now that activation of this pathway occurs in a variety of human cancer, including basal cell carcinomas (BCCs), medulloblastomas, leukemia, gastrointestinal, lung, ovarian, breast and prostate cancers. This book provides insightful views suitable for graduate students, medical students, undergraduate students, basic and clinical scientists, cancer patients as well as the general public.

Hedgehog signaling activation in human cancer and its clinical implications

Hedgehog signaling activation in human cancer and its clinical implications PDF Author: Jingwu Xie
Publisher: Springer Science & Business Media
ISBN: 1441984356
Category : Medical
Languages : en
Pages : 223

Book Description
Understanding the role of hedgehog signaling in cancer is critically important for novel cancer therapeutics. The hedgehog pathway is a major pathway regulating cell differentiation, tissue polarity, stem cell maintenance and cell proliferation. It is known by now that activation of this pathway occurs in a variety of human cancer, including basal cell carcinomas (BCCs), medulloblastomas, leukemia, gastrointestinal, lung, ovarian, breast and prostate cancers. This book provides insightful views suitable for graduate students, medical students, undergraduate students, basic and clinical scientists, cancer patients as well as the general public.

The Role of the Sonic Hedgehog Pathway for Prostate Cancer Progression

The Role of the Sonic Hedgehog Pathway for Prostate Cancer Progression PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 39

Book Description
The hedgehog pathway plays a critical role in the development of prostate. In the previous funding period, we reported activation of hedgehog signaling in advanced and metastatic tumors. Here we report molecular mechanisms by which activated hedgehog signaling alter cell functions. In one cancer cell line, NCI-H209, we detected promoter methylation of Su(Fu). Ectopic expression of Su(Fu) in NCI-H209 cells down-regulates hedgehog target gene expression and leads to inhibition of BrdU incorporation, a marker for cell proliferation. Thus, inactivation of Su(Fu) is a mechanism by which hedgehog signaling is activated in human cancer. We also investigated the molecular basis by which PKA affects Gli1 activity. We find that activation of PKA retains Gli1 in the cytoplasm. Conversely, inhibition of PKA activity promotes nuclear accumulation of Gli1. Mutation analysis identifies T374 as a major PKA site determining Gli1 protein localization. In the three dimension structure, T374 resides adjacent to the basic-residue cluster of the nuclear localization signal (NLS). Mutation of this residue to Asp (Gli1/T374D) results in more cytoplasmic Gli1 whereas a mutation to Lys (Gli1/T374K) leads to more nuclear Gli1. These data provide evidence to support a model that PKA regulates Gli1 localization, in part, through modulating the NLS function.

Signal Transduction in Cancer

Signal Transduction in Cancer PDF Author: David A. Frank
Publisher: Springer Science & Business Media
ISBN: 1402073402
Category : Medical
Languages : en
Pages : 358

Book Description
One of the most exciting areas of cancer research now is the development of agents which can target signal transduction pathways that are activated inappropriately in malignant cells. The understanding of the molecular abnormalities which distinguish malignant cells from their normal counterparts has grown tremendously. This volume summarizes the current research on the role that signal transduction pathways play in the pathogenesis of cancer and how this knowledge may be used to develop the next generation of more effective and less toxic anticancer agents. Series Editor comments: "The biologic behavior of both normal and cancer cells is determined by critical signal transduction pathways. This text provides a comprehensive review of the field. Leading investigators discuss key molecules that may prove to be important diagnostic and/or therapeutic targets."

The Role of Hedgehog Signaling in Hepatitis B Virus X Protein Mediated Hepatocellular Carcinoma

The Role of Hedgehog Signaling in Hepatitis B Virus X Protein Mediated Hepatocellular Carcinoma PDF Author: Vaishnavi Sambandam
Publisher:
ISBN:
Category :
Languages : en
Pages : 119

Book Description
Hepatitis B virus encoded X protein (HBx) contributes centrally to the pathogenesis of hepatocellular carcinoma (HCC). Aberrant activation of the Hedgehog (Hh) pathway has been linked to cancer. Thus, experiments were designed to test the hypothesis that HBx contributes to HCC via activation of Hh signaling. HBx expression correlated with up-regulation of Hh markers in human liver cancer cell lines, in HBx transgenic mice that developed HCC and in liver samples from HBV infected patients with HCC. The findings in human samples provide clinical validation of those in the HBx transgenic mice (HBxTg), and underscore the relevance of these transgenic mice to disease pathogenesis. Further, blockade of Hh signaling inhibited HBx stimulation of cell migration, anchorage independent growth, HCC tumorigenesis in HBx transgenic mice and tumor growth in xenograft model. These results suggest that the ability of HBx to promote cancer is at least partially dependent upon Hh activation and that activation of Hh signaling appears to be important for the development of HBx associated HCC. HBx also activates pathways that stimulate downstream Hh signaling, such as PI3K/AKT and Ras/Raf/MEK, also referred as non-canonical Hh signaling. Upon canonical Hh inhibition, compensatory activation of these pathways was seen in the presence of HBx in liver cancer cell lines and in HBxTg mice. Individual inhibition of these pathways also down-regulated Gli2 expression in HBx positive cell lines. These data suggests that in addition to canonical Hh signaling, activation of PI3K/AKT and ERK pathways by HBx leads to up-regulation of Gli2 expression in HBV-mediated HCC. This work identifies Hh pathway inhibition as a therapeutic strategy to slow tumor development and this work could lead to combination therapies that target Hh, AKT and ERK pathways, which may prevent or delay the appearance/progression of HCC.

Innovative Medicine

Innovative Medicine PDF Author: Kazuwa Nakao
Publisher: Springer
ISBN: 4431556516
Category : Science
Languages : en
Pages : 330

Book Description
This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.

Stem Cells – From Hype to Real Hope

Stem Cells – From Hype to Real Hope PDF Author: Khawaja Husnain Haider
Publisher: Walter de Gruyter GmbH & Co KG
ISBN: 3110587041
Category : Medical
Languages : en
Pages : 220

Book Description
This book is a compilation of the bench experience of leading experts from various research labs involved in the cutting edge area of research. The authors describe the use of stem cells both as part of the combinatorial therapeutic intervention approach and as tools (disease model) during drug development, highlighting the shift from a conventional symptomatic treatment strategy to addressing the root cause of the disease process. The book is a continuum of the previously published book entitled "Stem Cells: from Drug to Drug Discovery" which was published in 2017.

Liver Growth and Repair

Liver Growth and Repair PDF Author: A. Strain
Publisher: Springer Science & Business Media
ISBN: 9780412712609
Category : Medical
Languages : en
Pages : 1320

Book Description
Nelson Fausto The Greek myth of Prometheus with its picture of a vulture feasting on its chained victimhas traditionallyprovided a visualimageofliverregeneration. Itis apowerful and frightening representationbut ifone were to substitute the vulture by a surgeon and Prometheus by a patient laying on a properly prepared operating table, the outcomeoftheprocedurewould not differ significantlyfrom that describedbyGreek poets. Yet few of us who work in the field have stopped long enough to ask where this myth originated. Did the poet observe a case of liver regeneration in a human being? Was it brilliant intuition or perhaps, literally, just a 'gut feeling' of a poet looking for good rhymes that led to the prediction that livers grow when part of the tissueisremoved? Thisbookdoesnotattemptto solve these historical issues. Itdoes, instead, cover in detail some of the major modem themes of research on liver regen eration, injury and repair. As indicated in Dr. N. Bucher's chapter, the modem phase ofexperimental studies on liver regeneration started in 1931 with the publication by Higgins and Anderson of a method to perform a two-thirds resection of the liver of a rat. The technique described has 3 remarkable features: 1) it is highly reproducible, resulting in the removal of 68% of the liver, 2) it has minimal if any mortality, and 3) it consists only of blood vessel ligation and does not involve cutting through or wounding hepatic tissue.

Sunlight, Vitamin D and Skin Cancer

Sunlight, Vitamin D and Skin Cancer PDF Author: Jörg Reichrath
Publisher: Springer Nature
ISBN: 3030462277
Category : Medical
Languages : en
Pages : 428

Book Description
The third edition is a comprehensive and updated overview of positive and negative effects of UV-exposure, with a focus on Vitamin D and skin cancer. Researchers, oncologists,and students will be provided with the most significant and timely information related to topics such as the epidemiology of skin cancer, the immune system and skin cancer, ultraviolet damage, DNA repair and Vitamin D in Nonmelanoma skin cancer and malignant melanoma. There have been a number of new, scientific findings in this fast moving field that necessitated a thoroughly updated and revised edition including new Vitamin D metabolites and skin cancer, new findings on the beneficial effects of UV and solar UV and skin cancer, adverse effects of sun protection and sunscreens, sun exposure and mortality, and more. The book will summarize essential, up-to-date information for every clinician or scientist interested in how to balance the positive and negative effects of UV‐exposure to minimize the risks of developing vitamin D deficiency and skin cancer.

Molecular Biology of the Cell

Molecular Biology of the Cell PDF Author:
Publisher:
ISBN: 9780815332183
Category : Cells
Languages : en
Pages : 0

Book Description


Hedgehog-Gli Signaling in Human Disease

Hedgehog-Gli Signaling in Human Disease PDF Author: Ariel Ruiz i Altaba
Publisher: Springer Science & Business Media
ISBN: 0387337776
Category : Medical
Languages : en
Pages : 240

Book Description
Hedgehog-GLI Signaling in Human Disease represents the first compilation of up-to-date reviews by top-level scientists in this important field of research. The chapters cover a wide spectrum of related interests, from the molecular bases of morphogen function, to human genetics to cancer research. The aim of the book is to disseminate information on this exciting field, to allow students, scientists and the public in general to gain access current information from research leaders and to provide a book that encompasses different aspects of research showing the fusion of basic research in model systems and medicine. This is a timely primer on how a system of cell communication, Hedgehog-GLI signaling, plays a critical role in human disease and thus provides the background for the development of novel and rational therapies.