The Cancer Degradome

The Cancer Degradome

Author: Dylan Edwards

Publisher: Springer Science & Business Media

Published: 2008-09-16

Total Pages: 921

ISBN-13: 0387690573

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This book covers recent knowledge of the composition of the Degradome, how it can be studied using modern approaches such as transcriptomics and mass spectrometry; and many other relevant subjects, including new approaches to targeting proteolysis for therapy.


Degradome-focused RNA Interference Screens to Identify Proteases Important for Breast Cancer Cell Growth

Degradome-focused RNA Interference Screens to Identify Proteases Important for Breast Cancer Cell Growth

Author: Lena Hölzen

Publisher:

Published: 2022

Total Pages: 0

ISBN-13:

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Abstract: Proteases are known to promote or impair breast cancer progression and metastasis. However, while a small number of the 588 human and 672 murine protease genes have been extensively studied, others were neglected. For an unbiased functional analysis of all genome-encoded proteases, i.e., the degradome, in breast cancer cell growth, we applied an inducible RNA interference library for protease-focused genetic screens. Importantly, these functional screens were performed in two phenotypically different murine breast cancer cell lines, including one stem cell-like cell line that showed phenotypic plasticity under changed nutrient and oxygen availability. Our unbiased genetic screens identified 252 protease genes involved in breast cancer cell growth that were further restricted to 100 hits by a selection process. Many of those hits were supported by literature, but some proteases were novel in their functional link to breast cancer. Interestingly, we discovered that the environmental conditions influence the degree of breast cancer cell dependency on certain proteases. For example, breast cancer stem cell-like cells were less susceptible to depletion of several mitochondrial proteases in hypoxic conditions. From the 100 hits, nine proteases were functionally validated in murine breast cancer cell lines using individual knockdown constructs, highlighting the high reliability of our screens. Specifically, we focused on mitochondrial processing peptidase (MPP) subunits alpha (Pmpca) and beta (Pmpcb) and discovered that MPP depletion led to a disadvantage in cell growth, which was linked to mitochondrial dysfunction


Peptidomics of Cancer-Derived Enzyme Products

Peptidomics of Cancer-Derived Enzyme Products

Author:

Publisher: Academic Press

Published: 2017-10-18

Total Pages: 190

ISBN-13: 0128126396

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Peptidomics of Cancer-Derived Enzyme Products, Volume 42, the latest in The Enzymes series, is ideal for researchers in biochemistry, molecular and cell biology, pharmacology, and cancer, with this volume featuring high-caliber, thematic articles on the topic of peptidomics of cancer-derived enzyme products. Specific chapters cover Circulating peptidome and tumor-resident proteolysis, Colon tumor secretopeptidome, Chemoenzymatic method for glycomics, Human plasma peptidome for pancreatic cancer, Lipoproteomics and quantitative proteomics, Salivaomics: Protein markers/extracellular RNA/DNA in saliva, and Enzyme-responsive vectors for cancer therapy. Presents some of the most recent advances in the identification and function of enzymes changes in cancer Features authoritative expertise from recognized contributors to the field


Tumor-Associated Fibroblasts and their Matrix

Tumor-Associated Fibroblasts and their Matrix

Author: Margareta M. Mueller

Publisher: Springer Science & Business Media

Published: 2011-07-28

Total Pages: 453

ISBN-13: 9400706596

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During the last 20 years it has become increasingly clear that the tumor micro-environment, the tumor stroma with its cellular end extracellular components, plays an crucial role in regulating tumor growth and progression. This book on “Tumor-associated fibroblasts and their matrix” as part of the series on “Tumor-Microenvironment” is the first comprehensive discussion of these two main players of the tumor microenvironment. The best experts in this new area of tumor research and therapy review the role of these major components in the tumor stroma in the process of tumor development and progression. They discuss their interaction with other players such as blood vessels and immune cells, and show novel perspectives for tumor therapy. This compilation of excellent contributions of the best known experts in this important field in cancer research and therapy is a must for all scientists engaged in basic and clinical research. Increasing evidence of successful targeting of both cellular and matrix components in tumor therapy renders this book of particular interest for scientists engaged in pharmaceutical industry searching for new components for cancer therapy.


Optical Imaging of Cancer

Optical Imaging of Cancer

Author: Eben Rosenthal

Publisher: Springer Science & Business Media

Published: 2009-10-03

Total Pages: 278

ISBN-13: 0387938745

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To describe principles of optical imaging including chemistry and physics of fluorescence, limitations/advantages of optical imaging compared to metabolic and anatomic imaging. Describe hardware adapted for small animal imaging and for clinical applications: endoscopes and operative microscopes. Outline FDA approved and newer optical imaging probes. Include discussion of chemistry and linkage to other proteins. Review current techniques to image cancer and the development of techniques to specifically image cancer cells. Review use of exploiting differences in tissue autofluorescence to diagnose and treat cancer. Include agents such as 5-aminoleculinic acid. Review mechanisms that require proteolytic processing within the tumor to become active fluorophores. Review use of cancer selective proteins to localize probes to cancer cells: include toxins, antibodies, and minibodies. Introduction of plasmids, viruses or other genetic material may be used to express fluorescent agents in vivo. This chapter will review multiple vectors and delivery mechanisms of optical imaging cassettes.Preclinical investigations into the use of optical contrast agents for the detection of primary tumors in conventional and orthotopic models will be discussed. Preclinical investigations into the use of optical contrast agents for the detection of metastatic tumors in mouse models will be discussed. Use of targeted and non-specific optical contrast agents have been used for the detection of sentinel lymph node detection. These applications and how they differ from other applications will be discussed. Because of the unique difficulty of identifying tumor from normal tissue in brain tissue, a separate chapter would be needed. More clinical data is available for this cancer type than any other. Discussion of potential clinical applications for optical imaging and an assessment of the potential market.


Extracellular Targeting of Cell Signaling in Cancer

Extracellular Targeting of Cell Signaling in Cancer

Author: James W. Janetka

Publisher: John Wiley & Sons

Published: 2018-07-23

Total Pages: 482

ISBN-13: 1119300185

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International experts present innovative therapeutic strategies to treat cancer patients and prevent disease progression Extracellular Targeting of Cell Signaling in Cancer highlights innovative therapeutic strategies to treat cancer metastasis and prevent tumor progression. Currently, there are no drugs available to treat or prevent metastatic cancer other than non-selective, toxic chemotherapy. With contributions from an international panel of experts in the field, the book integrates diverse aspects of biochemistry, molecular biology, protein engineering, proteomics, cell biology, pharmacology, biophysics, structural biology, medicinal chemistry and drug development. A large class of proteins called kinases are enzymes required by cancer cells to grow, proliferate, and survive apoptosis (death) by the immune system. Two important kinases are MET and RON which are receptor tyrosine kinases (RTKs) that initiate cell signaling pathways outside the cell surface in response to extracellular ligands (growth factors.) Both kinases are oncogenes which are required by cancer cells to migrate away from the primary tumor, invade surrounding tissue and metastasize. MET and RON reside on both cancer cells and the support cells surrounding the tumor, called the microenvironment. MET and RON are activated by their particular ligands, the growth factors HGF and MSP, respectively. Blocking MET and RON kinase activation and downstream signaling is a promising therapeutic strategy for preventing tumor progression and metastasis. Written for cancer physicians and biologists as well as drug discovery and development teams in both industry and academia, this is the first book of its kind which explores novel approaches to inhibit MET and RON kinases other than traditional small molecule kinase inhibitors. These new strategies target key tumorigenic processes on the outside of the cell, such as growth factor activation by proteases. These unique strategies have promising potential as an improved alternative to kinase inhibitors, chemotherapy, or radiation treatment.


Tumor Microenvironment

Tumor Microenvironment

Author: Dietmar W. Siemann

Publisher: John Wiley & Sons

Published: 2011-06-24

Total Pages: 407

ISBN-13: 1119956927

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The microenvironment in which a tumor originates plays a critical role in its initiation and progression. Tumor Microenvironment reviews the importance of tumor microenvironment in cancer management. Particular emphasis is placed on discussing how the unique characteristics of the tumor microenvironment not only impact disease progression and response to conventional anticancer therapies, but have also led to the identification of potential new therapeutic targets and treatment possibilities for cancer patients. Tumor Microenvironment also reviews the fundamental basis of target development, preclinical assessment, and the current clinical status of these therapies.