Mechanism Of Hypoxia Regulated Gamma Secretase In Notch Mediated Breast Cancer Metastasis

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Mechanism of Hypoxia-regulated Gamma-secretase in Notch-mediated Breast Cancer Metastasis

Author : Jennifer Chien Villa
Publisher :
ISBN 13 :
Total Pages : 260 pages
Book Rating : 4.:/5 (858 download)

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Book Synopsis Mechanism of Hypoxia-regulated Gamma-secretase in Notch-mediated Breast Cancer Metastasis by : Jennifer Chien Villa

Download or read book Mechanism of Hypoxia-regulated Gamma-secretase in Notch-mediated Breast Cancer Metastasis written by Jennifer Chien Villa and published by . This book was released on 2012 with total page 260 pages. Available in PDF, EPUB and Kindle. Book excerpt: Notch signaling is responsible for critical developmental events from cell-fate determination to proliferation, while the aberrant activation of Notch signaling has been associated with breast cancer malignancies. Notch activation is initiated through the binding of Notch ligands (Jagged/Serrate Family) to Notch receptors (Notch1-4), followed by successive cleavages by TACE and ?-secretase to subsequently release the Notch intracellular domain (NICD) for nuclear transcription. Due to the crucial role of ?-secretase in mediating the release NICD, research in ?-secretase regulation and function in breast cancer is essential for the implementation of effective ?-secretase inhibitors (GSIs). Tumor hypoxia contributes to therapeutic resistance and the metastatic progression of breast cancer. It has been reported that hypoxia can promote Notch signaling through stabilizing the ?-secretase cleaved product NICD. However, little is known if hypoxia also modulates ?-secretase activity. In our study, we showed that ?-secretase activity of breast cancer lines were enhanced under hypoxia. Furthermore, we demonstrated that hypoxia did not elevate the level of ?-secretase subunits including Presenilin, Nicastrin, Aph-1 and Pen2, but rather directly increased the amount of active complex formed. We found that Hif-1? engaged with the active enzyme complex to regulate ?-secretase activity. More importantly, the increased invasive potential of breast cancer cells in hypoxic setting could be diminished with ?-secretase inhibition using a sulfonamide GSI (GSI-34), indicating that ?-secretase plays a critical role in the migration and invasion of breast cancer. Finally, we showed that both GSI treatment and knockout of Notch signaling significantly reduced metastasis to distant lung organ in mice using 4T1 mammary fatpad metastasis model. These studies together demonstrated that the administration of GSI-34 could be used to ameliorate the progression of metastatic lesion from highly aggressive hypoxic tumor types. In addition, breast cancer is a heterogeneous disease that can be characterized by distinct molecular signatures. To date, there are no target-based therapies to combat triple-negative Basal B breast cancer subtypes. In our study, we showed hat the highly invasive Basal B breast cancer subtypes exhibited unique properties that contribute to the aggressiveness and resistance of this cell type to therapy. First, breast cancer cells expressed Notch receptors and ligands, and most importantly, were active in Notch signaling. Secondly, we demonstrated that Basal B subtype breast cancer cells differ in ?-secretase activity for the cleavage of Notch and APP and in ?-secretase active site conformation. Basal B cells exhibited differential response to ?-secretase inhibition, leading to decreased DNA synthesis and clonogenic survival. Collectively, these above studies demonstrated that ?-secretase is a unique target for the treatment of hypoxic and aggressive breast cancer. We also provided mechanistic evidence to support ?-secretase mediated Notch signaling in cancer metastasis by showing the potential used of GSIs for the treatment of highly aggressive breast cancer types. These studies will ultimately provide prognostic and therapeutic value for the management of breast cancer malignancies.

Proteasome Inhibitors in Cancer Therapy

Author : Julian Adams
Publisher : Springer Science & Business Media
ISBN 13 : 1592597947
Total Pages : 319 pages
Book Rating : 4.5/5 (925 download)

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Book Synopsis Proteasome Inhibitors in Cancer Therapy by : Julian Adams

Download or read book Proteasome Inhibitors in Cancer Therapy written by Julian Adams and published by Springer Science & Business Media. This book was released on 2004-05-25 with total page 319 pages. Available in PDF, EPUB and Kindle. Book excerpt: A panel of leading academic and pharmaceutical investigators takes stock of the remarkable work that has been accomplished to date with proteasome inhibitors in cancer, and examines emerging therapeutic possibilities. The topics range from a discussion of the chemistry and cell biology of the proteasome and the rationale for proteasome inhibitors in cancer to a review of current clinical trials underway. The discussion of rationales for testing proteasome inhibitors in cancer models covers the role of the proteasome in NF-kB activation, the combining of conventional chemotherapy and radiation with proteasome inhibition, notably PS-341, new proteasome methods of inhibiting viral maturation, and the role of protesome inhibition in the treatment of AIDS. The authors also document the development of bortezomib (VelcadeTM) in Phase I clinical trials and in a multicentered Phase II clinical trials in patients with relapsed and refractory myeloma.

Hypoxia and Cancer Metastasis

Author : Daniele M. Gilkes
Publisher : Springer
ISBN 13 : 3030127346
Total Pages : 160 pages
Book Rating : 4.0/5 (31 download)

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Book Synopsis Hypoxia and Cancer Metastasis by : Daniele M. Gilkes

Download or read book Hypoxia and Cancer Metastasis written by Daniele M. Gilkes and published by Springer. This book was released on 2019-06-14 with total page 160 pages. Available in PDF, EPUB and Kindle. Book excerpt: The present book is an attempt to provide a detailed review of studies that clarify our current understanding of the role of hypoxia in the progression of primary cancer to metastatic disease. It will enable researchers to discover the critical cellular changes that occur under hypoxic conditions and play a role in metastatic dissemination, from the activation of hypoxia-inducible factors, HIF-1 and HIF-2, to the transcriptional profile changes that occur in cancer cells and promote cancer cell survival under detrimental conditions. Readers will discover the methods and challenges involved in imaging and quantifying the degree of hypoxia in a primary tumor. We will provide an understanding of the hypoxia-induced phenotypes that influence heterogeneity, alter the secretome and tumor microenvironment, modify cellular metabolism, and promote immune suppression and resistance to chemotherapy. Finally, we will uncover the therapeutic strategies that are being devised to target the hypoxic microenvironment in the hopes of preventing metastasis and improving the efficacy of standard-of-care cancer treatments. This work is an up to date source of information on the challenges and complexity of the hypoxic tumor microenvironment. Basic and translational scientists, post-doctoral fellows, graduate students, and those interested in how tumors metastasize will find this book a reference that details how hypoxia influences metastatic disease.

The Theory of the Gene

Author : Thomas Hunt Morgan
Publisher :
ISBN 13 :
Total Pages : 392 pages
Book Rating : 4.:/5 (4 download)

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Book Synopsis The Theory of the Gene by : Thomas Hunt Morgan

Download or read book The Theory of the Gene written by Thomas Hunt Morgan and published by . This book was released on 1926 with total page 392 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Kidney Development, Disease, Repair and Regeneration

Author : Melissa Helen Little
Publisher : Academic Press
ISBN 13 : 012800438X
Total Pages : 615 pages
Book Rating : 4.1/5 (28 download)

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Book Synopsis Kidney Development, Disease, Repair and Regeneration by : Melissa Helen Little

Download or read book Kidney Development, Disease, Repair and Regeneration written by Melissa Helen Little and published by Academic Press. This book was released on 2015-08-06 with total page 615 pages. Available in PDF, EPUB and Kindle. Book excerpt: Kidney Development, Disease, Repair and Regeneration focuses on the molecular and cellular basis of kidney development, exploring the origins of kidney lineages, the development of kidney tissue subcompartments, as well as the genetic and environmental regulation of kidney development. Special coverage is given to kidney stem cells and possible steps towards kidney repair and regeneration. Emphasis is placed on the fetal origins of postnatal renal disease and our current understanding of the molecular basis of damage and repair. Biomedical researchers across experimental nephrology and developmental biology will find this a key reference for learning how the underlying developmental mechanisms of the kidney will lead to greater advances in regenerative medicine within nephrology. Offers researchers a single comprehensive resource written by leaders from both the developmental biology and the experimental nephrology communities Focuses on understanding the molecular basis of organogenesis in the kidney as well as how this can be affected both genetically and environmentally Explains the underlying developmental mechanisms which influence the kidney’s inherent repair capacity Demonstrates how a deeper understanding of mechanisms will lead to greater advances in regenerative medicine

Cellular Proteolytic Systems

Author : Aaron J. Ciechanover
Publisher : Wiley-Liss
ISBN 13 :
Total Pages : 256 pages
Book Rating : 4.3/5 (91 download)

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Book Synopsis Cellular Proteolytic Systems by : Aaron J. Ciechanover

Download or read book Cellular Proteolytic Systems written by Aaron J. Ciechanover and published by Wiley-Liss. This book was released on 1994-11-03 with total page 256 pages. Available in PDF, EPUB and Kindle. Book excerpt: The field of cellular proteolysis is advancing rapidly and has great potential impact in a variety of research and clinical areas, including AIDS and cancer research and treatment. The editors, pioneers in the field of cellular and protein research, describe our current understanding of the three major cellular proteolytic systems: the ubiquitin system, the lysosomal and vacuolar systems, and physiological and pathophysiological cellular proteolysis.

Breast Cancer and Surgery

Author : Nilufer Bulut
Publisher : BoD – Books on Demand
ISBN 13 : 1789235669
Total Pages : 228 pages
Book Rating : 4.7/5 (892 download)

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Book Synopsis Breast Cancer and Surgery by : Nilufer Bulut

Download or read book Breast Cancer and Surgery written by Nilufer Bulut and published by BoD – Books on Demand. This book was released on 2018-11-21 with total page 228 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book 'Breast Cancer and Surgery' summarizes the treatment options from the onset of breast carcinogenesis to early-local advanced and metastatic breast cancer. Chemotherapy alternatives, drug resistance and local and surgical treatment preferences are extensively discussed and this information is especially directed at clinicians, researchers, and students. This book includes a comparison between different chemotherapy agents and targeted therapies with published phase II-III studies. The importance of palliative care and dietary supplements administered during the treatment course in reducing the comorbidity of patients is emphasized. Photodynamic treatments have been included in this book. A comprehensive and up-to-date information exchange that can be accessed through a single source is provided to all researchers interested in breast cancer.

The Epithelial-to-Mesenchymal Transition (EMT) in Cancer

Author : Joëlle Roche
Publisher : MDPI
ISBN 13 : 3038427934
Total Pages : 261 pages
Book Rating : 4.0/5 (384 download)

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Book Synopsis The Epithelial-to-Mesenchymal Transition (EMT) in Cancer by : Joëlle Roche

Download or read book The Epithelial-to-Mesenchymal Transition (EMT) in Cancer written by Joëlle Roche and published by MDPI. This book was released on 2018-04-09 with total page 261 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a printed edition of the Special Issue "The Epithelial-to-Mesenchymal Transition (EMT) in Cancer" that was published in Cancers

Molecular Mechanisms of Notch Signaling

Author : Tilman Borggrefe
Publisher : Springer
ISBN 13 : 3319895125
Total Pages : 417 pages
Book Rating : 4.3/5 (198 download)

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Book Synopsis Molecular Mechanisms of Notch Signaling by : Tilman Borggrefe

Download or read book Molecular Mechanisms of Notch Signaling written by Tilman Borggrefe and published by Springer. This book was released on 2018-07-20 with total page 417 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book describes the Notch signaling pathway with a focus on molecular mechanisms. The Notch signaling pathway is a seemingly simple pathway that does not involve any second messenger. Upon ligand binding two consecutive proteolytic cleavages of the NOTCH receptor release the Notch intracellular domain from the membrane. The Notch intracellular domain migrates into the nucleus and activates gene expression. Recently, new technologies allowed us to better understand this pivotal signaling cascade and revealed new regulatory mechanisms. The different chapters cover many aspects of the Notch signaling focusing on the mechanisms governing the receptor/ligand interaction as well as on the downstream intracellular signaling events. Aspects of both canonical and non-canonical signaling are discussed and the function of Notch signaling in physiological and pathological contexts are elucidated. This book is not only intended for experts but it should also be a useful resource for young, sprouting scientists or interested scientists from other research areas, who may use this book as a stimulating starting point for further discoveries and developments.

Innovations for Next-Generation Antibody-Drug Conjugates

Author : Marc Damelin
Publisher : Springer
ISBN 13 : 3319781545
Total Pages : 358 pages
Book Rating : 4.3/5 (197 download)

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Book Synopsis Innovations for Next-Generation Antibody-Drug Conjugates by : Marc Damelin

Download or read book Innovations for Next-Generation Antibody-Drug Conjugates written by Marc Damelin and published by Springer. This book was released on 2018-05-29 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: Antibody-drug conjugates (ADCs) stand at the verge of a transformation. Scores of clinical programs have yielded only a few regulatory approvals, but a wave of technological innovation now empowers us to overcome past technical challenges. This volume focuses on the next generation of ADCs and the innovations that will enable them. The book inspires the future by integrating the field’s history with novel strategies and cutting-edge technologies. While the book primarily addresses ADCs for solid tumors, the last chapter explores the emerging interest in using ADCs to treat other diseases. The therapeutic rationale of ADCs is strong: to direct small molecules to the desired site of action (and away from normal tissues) by conjugation to antibodies or other targeting moieties. However, the combination of small and large molecules imposes deep complexity to lead optimization, pharmacokinetics, toxicology, analytics and manufacturing. The field has made significant advances in all of these areas by improving target selection, ADC design, manufacturing methods and clinical strategies. These innovations will inspire and educate scientists who are designing next-generation ADCs with the potential to transform the lives of patients.

Notch Signaling as a Regulator of Tumor Immune Response

Author : Isabella Screpanti
Publisher : Frontiers Media SA
ISBN 13 : 2889716686
Total Pages : 193 pages
Book Rating : 4.8/5 (897 download)

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Book Synopsis Notch Signaling as a Regulator of Tumor Immune Response by : Isabella Screpanti

Download or read book Notch Signaling as a Regulator of Tumor Immune Response written by Isabella Screpanti and published by Frontiers Media SA. This book was released on 2021-11-24 with total page 193 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Functional Foods and Nutraceuticals

Author : Rotimi E. Aluko
Publisher : Springer Science & Business Media
ISBN 13 : 1461434807
Total Pages : 163 pages
Book Rating : 4.4/5 (614 download)

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Book Synopsis Functional Foods and Nutraceuticals by : Rotimi E. Aluko

Download or read book Functional Foods and Nutraceuticals written by Rotimi E. Aluko and published by Springer Science & Business Media. This book was released on 2012-06-05 with total page 163 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Functional food or medicinal food is any fresh or processed food claimed to have a health-promoting and/or disease-preventing property beyond the basic nutritional function of supplying nutrients, although there is no consensus on an exact definition of the term. This is an emerging field in food science, in which such foods are usually accompanied by health claims for marketing purposes, such as a company's ‘cereal is a significant source of fiber. Studies have shown that an increased amount of fiber in one's diet can decrease the risk of certain types of cancer in individuals.’ Functional foods are sometimes called nutraceuticals, a portmanteau of nutrition and pharmaceutical, and can include food that has been genetically modified. The general category includes processed food made from functional food ingredients, or fortified with health-promoting additives, like "vitamin-enriched" products, and also fresh foods (e.g., vegetables) that have specific claims attached. Fermented foods with live cultures are often also considered to be functional foods with probiotic benefits."

The Cancer Stem Cell Niche

Author : Susie Nilsson
Publisher : Academic Press
ISBN 13 : 0323853250
Total Pages : 246 pages
Book Rating : 4.3/5 (238 download)

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Book Synopsis The Cancer Stem Cell Niche by : Susie Nilsson

Download or read book The Cancer Stem Cell Niche written by Susie Nilsson and published by Academic Press. This book was released on 2021-02-09 with total page 246 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Cancer Stem Cell Niche, Volume Five in the Advances in Stem Cells and their Niches series, highlights new advances in the field, with this new volume presenting interesting chapters on a variety of timely topics, including Acute lymphoblastic leukemia and the bone marrow microenvironment, Stem cell niches in bone and their roles in cancer metastasis, The role of vasculature in cancer stem cell niches, The lung cancer stem cell niche, The prostate cancer stem cell niche: Genetic drivers and therapeutic approaches, Impact of prostate cancer stem cell niches on prostate cancer tumorigenesis and progression, The testicular cancer stem cell niche. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Advances in Stem Cells and their Niches series Includes the latest information on the Cancer Stem Cell Niche

How Do Metabolism, Angiogenesis, and Hypoxia Modulate Resistance?

Author : Matilde Esther LLeonart
Publisher : Frontiers Media SA
ISBN 13 : 2889668010
Total Pages : 175 pages
Book Rating : 4.8/5 (896 download)

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Book Synopsis How Do Metabolism, Angiogenesis, and Hypoxia Modulate Resistance? by : Matilde Esther LLeonart

Download or read book How Do Metabolism, Angiogenesis, and Hypoxia Modulate Resistance? written by Matilde Esther LLeonart and published by Frontiers Media SA. This book was released on 2021-05-25 with total page 175 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Molecular Mechanisms of Drug Resistance And Strategies of Sensitization in Breast Cancer, 2nd edition

Author : Yan Cheng
Publisher : Frontiers Media SA
ISBN 13 : 2832541844
Total Pages : 198 pages
Book Rating : 4.8/5 (325 download)

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Book Synopsis Molecular Mechanisms of Drug Resistance And Strategies of Sensitization in Breast Cancer, 2nd edition by : Yan Cheng

Download or read book Molecular Mechanisms of Drug Resistance And Strategies of Sensitization in Breast Cancer, 2nd edition written by Yan Cheng and published by Frontiers Media SA. This book was released on 2024-01-11 with total page 198 pages. Available in PDF, EPUB and Kindle. Book excerpt: Basic scientific background Breast cancer is one of the most common cancer and the most frequent cause of cancer death among women worldwide. Currently, subtyping breast cancers into hormone receptor (HR) positive, human epidermal growth factor receptor-2 overexpressing (HER2+), and triple negative breast cancer (TNBC) is the basis of diagnosing and treating this disease. The main treatment strategies for breast cancer include surgery, endocrine therapy, molecular targeted therapy, chemotherapy, radiotherapy, immunotherapy and gene therapy. However, resistance of breast cancer cells to chemotherapeutic agents, molecular targeted therapies and immunotherapy may occur either intrinsically or de nova, and is often ultimately responsible for treatment failure. Therefore, drug resistance poses a major challenge to breast cancer treatment. Current developments: Drug resistance in breast cancer is a complex clinical condition originating from a wide range of molecular alterations. The development of endocrine therapy resistance is believed to be associated with many cellular changes, such as ESR1 gene mutations, bypassing estrogen signaling pathway and altered tamoxifen metabolism. Meanwhile, changes in immune response, alternation of drug-binding property and downstream pathways are involved in the mechanisms of drug resistance in HER2+ breast cancer. In addition, resistance to chemotherapeutic agents predominantly arises from increased drug efflux and cross resistance. Current studies suggest that treatment strategies and therapeutics have to be designed specifically to each patient in different clinical situations. The use of modern genomic, proteomic and functional analytical techniques has contributed to identify novel genes and signaling networks involved in breast cancer drug resistance. Moreover, the use of high-throughput techniques in combination with bioinformatics and systems biology approaches has aided the interrogation of clinical samples and allowed the identification of molecular signatures and genotypes that predict responses to certain drugs. Despite much progress has been made in the field of breast cancer drug resistance, such as combination therapy and drug-loaded nanoparticles, the complexity and variability of drug resistance mechanism still inevitably lead to the continuous occurrence of drug resistance. Therefore, with the increasing amounts of anti-breast cancer agents, there are now unprecedented opportunities to understand and overcome drug resistance through further research into mechanisms and corresponding strategies, which will help achieve lasting disease control and bring survival benefits to patients with advanced cancer. Papers of interest: The current Research Topic of Frontiers in Pharmacology focuses on publishing Original Research, Review articles and Case Reports focusing on (a) elucidating mechanisms of drug resistance in breast cancer, target mutations, tumor microenvironment, undiscovered genes and signaling pathways; (b) promising drug delivery systems that can enhance the sensitivity of anti- breast cancer agents to various tumors; (c) strategies that can improve patient care during bio-chemotherapeutic treatments; (d) small molecule compounds that are effective against drug-resistant breast tumors (e) biomarkers of chemotherapy resistance in breast cancer patients and (f) in vitro and in vivo models. Guidelines for article of submission: - Authors must stick to the set guidelines for ethical practices by the Frontiers journals. - The main content of the article must have certain innovation and research significance. - The authors should describe the construction method of drug-resistant cell lines when using them for experiments in the article.

Molecular Mechanisms and Signaling in Endothelial Cell Biology and Vascular Heterogeneity

Author : Bin Ren
Publisher : Frontiers Media SA
ISBN 13 : 2889742520
Total Pages : 332 pages
Book Rating : 4.8/5 (897 download)

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Book Synopsis Molecular Mechanisms and Signaling in Endothelial Cell Biology and Vascular Heterogeneity by : Bin Ren

Download or read book Molecular Mechanisms and Signaling in Endothelial Cell Biology and Vascular Heterogeneity written by Bin Ren and published by Frontiers Media SA. This book was released on 2022-02-02 with total page 332 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Protein Tyrosine Phosphatases in Cancer

Author : Benjamin G. Neel
Publisher : Springer
ISBN 13 : 1493936492
Total Pages : 362 pages
Book Rating : 4.4/5 (939 download)

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Book Synopsis Protein Tyrosine Phosphatases in Cancer by : Benjamin G. Neel

Download or read book Protein Tyrosine Phosphatases in Cancer written by Benjamin G. Neel and published by Springer. This book was released on 2016-08-05 with total page 362 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book aims to bridge the gap in understanding how protein-tyrosine phosphatases (PTPs), which carry out the reverse reaction of tyrosine phosphorylation, feature in cancer cell biology. The expertly authored chapters will first review the general features of the PTP superfamily, including their overall structure and enzymological properties; use selected examples of individual PTP superfamily members, to illustrate emerging data on the role of PTPs in cancer; and will review the current status of PTP-based drug development efforts. Protein Tyrosine Phosphatases in Cancer,from renowned researchers Benjamin Neel and Nicholas Tonks, is invaluable reading for researchers in oncology, stem cell signaling,and biochemistry.