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Effects of NF-κB manipulation on cancer-associated bone disease

Abbreviations AR Androgen receptor BCRs B cell receptors CAPE Caffeic and phenethyl ester CD4 Cluster of differentiation 40 CRPC Castration-resistant prostate cancer ER Estrogen receptor GSK-3β Glycogen synthase kinase-3 beta HER2 Human epidermal growth factor receptor 2 IKK IκB kinase IL-1R IL-1 receptor IL-1β Interleukin 1 beta IκBα NF-κB inhibitor alpha mCRPC Metastatic CRPC NBD NEMO-binding domain NEMO NF-κB essential modulator NF-κB Nuclear factor kappa-light-chain-enhancer of…

Growth factors, cytokines, and pediatric malignant primary bones tumors

Introduction Primary bone tumors constitute a heterogeneous family of rather rare neoplasms corresponding to oncogenic conversion of cells from the lineages implicated in bone formation and homeostasis: the osteoblastic, the chondroblastic, and the osteoclastic lineages. Part of the primary bone tumors belongs to the pediatric neoplasms and two of those are particularly malignant, namely the osteosarcoma (OS) and the Ewing's sarcoma (ES). The oncogenic event leading…

Macrophages and pathophysiology of bone cancers

Research highlights Several reciprocal signaling mechanisms drive tissue level evolution in tumor development. Tumor-associated macrophages are key players in the bone-metastatic process. Tumor metabolism is an important regulator of tumor immunity. Therapies modulating tumor macrophage function are being developed. Acknowledgments The authors thank Adjunct Professor Maija Hollmén, University of Turku, for critical reading of this chapter. Introduction Macrophages have been found to have a pivotal role…

The immune environment of bone sarcomas

Introduction Despite advances in our understanding of cancer biology, the development of standardized, effective local control measures with surgery and radiation, and the emergence of targeted therapies, bone sarcoma survival rates remain unchanged for more than 30 years. Bone sarcomas still represent therapeutic challenges, and the low success of targeted therapies in these tumors highlights the fact that we have to take their environment particularly the…

Immune functions of osteoclasts: new insights for bone cancers

Research highlights Osteoclasts are not only bone-resorbing cells. They are also monocytic cells with innate immune functions. Osteoclasts participate in immune suppression to promote the development of bone cancer. Osteoclasts display phenotypic and functional diversity and some osteoclast subsets are more prone to immune tolerance and immune suppression, making them interesting therapeutic targets in bone cancer. Acknowledgments The work was supported by the Agence Nationale de…

Osteocytes and bone tumor niche

Introduction Osteocytes are terminally differentiated cells of the osteoblast lineage. They are the most abundant cell type of the bone, representing 95% of all bone cells in skeletally mature adult bone tissue [ ]. Osteocytes are considered permanent residents of skeletal tissue, with an estimated half-life of 25 years [ ], whereas osteoblasts survive for up to 3 months and osteoclasts have a life span of…

Technical approaches for studying the communications between osteocytes and cancer cells

Introduction Osteocyte biology and their role in regulating bone homeostasis Osteocytes are the most abundant cells in the bone, playing an essential role in mechanosensation, mechanotransduction, and communication with other bone cells. They originated from osteoblasts and are surrounded by self-produced osteoid matrix [ ]. Being entrapped throughout a mineralized matrix, the stellate-shaped processes of osteocytes extend from the cell bodies located in lacunar to all…

The role of mesenchymal stem cells in bone cancer: initiation, propagation, and metastasis

Introduction to the mesenchymal stem cell Multipotent stem cells are of great interest in biomedical research, since they have the potential to produce all kinds of tissues that can be used to repair damaged organs. In a time when human life span is extended, the opportunity to replace body parts that have become dysfunctional as a result of aging or because of surgery, vascular failure, or…

Osteomimicry: old concepts and new findings

Research highlights Bone is the primary target tissue for metastases in patients affected by breast and prostate cancers. Bone metastases represent the paradigm of the “seed and soil theory.” Osteomimicry refers to the capacity of CTCs to acquire a molecular profile resembling that of bone-resident cells. Recent studies have demonstrated an osteomimetic profile in CTCs of patients carrying bone metastases. Acknowledgments This review was supported by…

Bone, a fertile soil for tumor development

Abbreviations (BMP) Bone morphogenic protein (CXCL) C-X-C motif ligand (CXCL12) C-X-C motif chemokine 12 (CXCR4) C-X-C chemokine receptor type 4 (DKK1) Dickkopf Wnt signaling pathway inhibitor 1 (FGFs) Fibroblast growth factors (HSC) Hematopoietic stem cell (IFNγ) Interferon γ (IGF) Insulin-like growth factor (IL-11) Interleukin 11 (IL-1β) Interleukin 1β (IL-6) Interleukin 6 (IL-8) Interleukin 8 (M-CSF) Macrophage colony-stimulating factor (MCP-1) Monocyte chemoattractant protein-1 (MDSCs) Myeloid-derived suppressor cells…

Bone niche and bone metastases

Introduction Breast cancer is a worldwide public health threat and the most common type of female malignancy. Bone metastasis is the primary cause of mortality of breast cancer patients [ ]. Metastasis to any organ is a life-threatening and commonly incurable condition, yet the biology of bone niche and bone metastasis may be the most unique and dynamic among the different organs that host metastatic disease.…

Technical aspects: how do we best prepare bone samples for proper histological analysis?

Introduction Histological analysis of bone is a critical step for the diagnosis of malignancies. It allows direct identification of malignant cells inside marrow spaces in case of bone metastases or hematological disorders. Bone biopsy is superior to marrow aspiration because the microarchitecture of the bone marrow is preserved, a parameter that is especially important in hematological disorders. Because marrow cells are in direct contact with bone…

Artificial intelligence for bone cancer imaging

Research highlights AI can integrate clinical information to stratify patients to personalized imaging procedures. AI can aid radiologists in the detection of tumors in other organ systems. Due to sparse data, the characterization of bone tumors is limited to date. AI can enable ultralow-dose imaging. AI can facilitate treatment monitoring and surveillance. Introduction Imaging tests, such as magnetic resonance imaging (MRI), computed tomography (CT), and positron…

Use of machine learning in bone cancers

Introduction The medical field, including medical imaging, is amassing data at an increasingly higher rate. Computer-based software, developed to automatically find patterns and infer unknown information from recorded data, is becoming a key component in both medical research and clinical practice. Machine learning (ML)-based software has received special attention in the medical field in the last decade, with a significant number of publications claiming to demonstrate…

Zebrafish models for studying bone tumors

Advantages of zebrafish models for cancer research Zebrafish is a preeminently suitable model organism for cancer research and has been shown to complement murine model systems to assay tumor cell malignancy, progression, and drug screening after xenotransplantation [ ]. A high conservation of (proto-)oncogenes and tumor suppressor genes between zebrafish and human, renders the zebrafish model ideal for identifying clinically relevant genes and compounds. In addition,…

In vivo models used in studies of bone metastases

Introduction In human disease, bone metastasis is a slow process often developing years after the initial tumor is diagnosed and treated. Bone metastases are commonly only detected when patients present with late-stage symptomatic disease, at a point when extensive bone lesions have developed [ , ]. Bone is an inaccessible site that is not routinely biopsied or otherwise sampled, and studies using human material are further…

Mammalian models of bone sarcomas

Acknowledgments We thank Ms Séverine (Université de Nantes, FR) for providing the micro-CT images and M Jérome Amiaud and Ms Céline Charrier (Université de Nantes, FR) for the histological preparation. You’re Reading a Preview Become a Clinical Tree membership for Full access and enjoy Unlimited articles Become membership If you are a member. Log in here

Epidemiology of primary bone tumors and economical aspects of bone metastases

Acknowledgments The authors are indebted to Prof. E Hauben for involvement in the previous version of this book chapter. Primary bone tumors are rare and as such they form a difficult category of tumors for appropriate recognition and classification both for treating clinicians as well as radiologists and pathologists. They account for less than 0.2% of the malignancies registered in the SEER database [ ]. The…

Cancer: lessons to learn from the past

Research highlights Paleopathology produces a body of evidence that illustrates the history of oncological diseases in a diachronic perspective. Cancer geographic and temporal ubiquity is not an exclusive phenomenon of the recent times. Malignant neoplasms, expressed by bone metastatic disease and primary bone cancers, affected humans around the world since the Pleistocene. To fully understand cancer in the past, collaboration between modern oncological researchers and paleopathologists…

Valerian (Valeriana officinalis)

Uses Treatment of: Insomnia (valerian is present in virtually all herbal sleep aids) Anxiety Depression Htn GI hyperactivity Headaches Muscle spasms Benzodiazepine withdrawal Perioperative Risks Potential for valerian withdrawal exists if usage is stopped suddenly after chronic high-dose administration. This withdrawal can present as delirium, tachycardia, and diaphoresis. Chronic dosing with high-dose valerian has been linked with cardiac failure and emergence delirium. You’re Reading a Preview…