Bone Cancer ：Primary Bone Cancers and Bone Metastases ( 2 )

Publication subTitle ：Primary Bone Cancers and Bone Metastases

Publication series ：2

Author： Heymann Dominique

Publisher： Elsevier Science‎

Publication year： 2014

E-ISBN: 9780124167285

P-ISBN(Paperback): 9780124167216

P-ISBN(Hardback): 9780124167216

Subject： R58 Endocrine disease and metabolic disease;R62 The orthopedic surgery (surgery) to repair;R73 Oncology

Language： ENG

Access to resources Favorite

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Description

Bone Cancer, Second Edition comprehensively investigates key discoveries in the field of bone biology over the last five years that have led to the development of entirely new areas for investigation, such as therapies which combine surgery and biological approaches. The Second Edition expands on the original overview of bone cancer development (physiology and pathophysiology), with key chapters from the first edition, and offers numerous new chapters describing the new concepts of bone cancer biology and therapy, for both primary bone tumors as well as bone metastases. Each chapter has been written by internationally recognized specialists on the bone cancer microenvironment, bone metastases, osteoclast biology in bone cancer, proteomics, bone niche, circulating tumor cells, and clinical trials.

Given the global prevalence of breast and prostate cancers, knowledge of bone biology has become essential for everyone within the medical and cancer research communities. Bone Cancer continues to offer the only translational reference to cover all aspects of primary bone cancer and bone metastases – from bench to bedside: development (cellular and molecular mechanisms), genomic and proteomic analyses, clinical analyses (histopathology, imaging, pain monitoring), as well as new therapeutic approaches and clinical trials for primary bone tumors and bone metastases.

Presents a comprehensive, translational source for all aspects of primary bone

Chapter

Part I - Basic aspects of bone cancers

Section 1 - Epidemiology of bone cancer

Chapter 1 - Epidemiology of primary bone tumors and economical aspects of bone metastases

Introduction

Incidence of primary bone tumors

Age

Gender

Site distribution

Incidence of bone tumors as a secondary event

Racial differences in incidence of primary bone tumors

Incidence of bone metastases

Pathology of bone metastases

Cost of illness

Economical burden of bone metastasis

Conclusions

References

Section 2 - Bone microenvironmentand bone cancer

Chapter 2 - Tumor–bone interactions: there is no place like bone

Introduction

Making its way to bone

Disseminated tumor cells and dormancy in bone

Induction of osteolysis by cancer cells in bone

Induction of bone formation by cancer cells in bone

Suppression of bone formation

The bone microenvironment support cancer cell growth

Conclusion

References

Chapter 3 - Stem cell niches in the bone–bone marrow organ and their significance for hematopoietic and non-hematopoietic cancer

Introduction

The concept of a niche

Niche and microenvironment

Osteoblastic and endothelial niches

Bone marrow stromal cells and the niche

The heterotopic transplantation system

An adaptive niche

Modeling the niche and probing its significance in disease

The niche in early metastatic growth

Acknowledgments

References

Chapter 4 - Deregulation of osteoblast differentiation in primary bone cancers

Introduction

Normal osteoblastogenesis: general process and major regulatory mechanisms

Deregulated genes in bone tumors

Tumor suppressor genes

Oncogenes

Transcription factors

Deregulated signaling pathways in bone tumors

Bone morphogenetic protein BMP and transforming growth factor-β (TGF-β) signaling

Receptor tyrosine kinase signaling

Intracellular signaling pathways

Wnt signaling

Deregulation of local regulatory mechanisms in bone tumors

Cell–cell interactions

Cell–matrix interactions

Microenvironmental factors

Conclusions and perspectives

Acknowledgments

References

Chapter 5 - Contribution of osteoclasts to the bone–tumor niche

Introduction

Osteoclastogenesis

Bone resorption

The vicious cycle of tumor–bone metastases

Tumor-derived factors stimulating osteoclasts

Bone-derived factors stimulating tumor cells

Other ways osteoclasts contribute to the bone-tumor niche

References

Chapter 6 - Involvement of osteocytes in cancer bone niche

Introduction

Osteocytes: A multifunctional bone cell

Short overview of RANK/RANKL/osteoprotegerin and canonical Wnt signaling pathways

Central role of osteocytes in bone remodeling through RANKL and sclerostin regulation

Deregulation of RANK/RANKL and Wnt pathways in malignancy

Is there a direct link between malignant cells and osteocytes?

Conclusions and perspectives

References

Chapter 7 - Role of mesenchymal stem cells in bone cancer; initiation, propagation and metastasis

Introduction to the mesenchymal stem cell

Initiation: MSCs as progenitors of bone tumors

Cartilaginous tumors

Ewing sarcomas

Osteosarcomas

Propagation: Cancer stem cells in bone sarcoma

Metastasis: MSCs prepare the road for metastasis

Niche

Seed and soil and exosomes

Conclusion

References

Chapter 8 - Gap junction in bone remodeling and in primary bone tumors: osteosarcoma and Ewing sarcoma

Introduction

Gap junction channels

Connexins

Regulation of intercellular communication

Regulation of unitary conductance

Regulation of the channel number

Role of gap junctions in bone remodeling

Bone remodeling

Connexin and bone remodeling

Gap junction in primary bone cancers

Primary bone tumors

Gap junction and primary bone tumors: osteosarcoma and Ewing sarcoma

Conclusion and perspectives

References

Chapter 9 - Macrophages and pathophysiology of bone cancers

Introduction

Macrophage differentiation, polarization and activation status

Tumor associated macrophages

Macrophages in intravasation

Macrophages in extravasation

Macrophages in metastasis formation

Therapeutic interests on macrophages in bone cancer

Strategies interfering with cancer cell/TAM crosstalk

TAM depletion or polarization modulation strategies

Conclusion

Acknowledgment

References

Chapter 10 - Cytokines and bone cancers

Introduction

Clinical observational studies on cytokines and bone cancer development

Cytokines in cancer cell metastasis to bone

The first steps of tumor invasion in bone

Cancer-induced bone disease

Cytokines and primary bone cancers

Multiple myeloma

Primary bone sarcomas

Conclusions and perspectives

References

Chapter 11 - Technical aspects: how do we best prepare bone samples for proper histological analysis?

Introduction

Bone biopsy in humans or large animals

Bone fixation

Microcomputed tomography (MicroCT)

Dehydration and infiltration

Bone embedding

Purification of MMA

Preparation of accelerated MMA medium for infiltration and embedding

Fast infiltration and embedding method

Embedding

Sectioning

Staining methods

Osteoid tissue and calcified bone

Argentophilic proteins (AgNOR method)

Histoenzymatic identification of osteoclast by TRAcP staining

Mast cell identification in mastocytosis

Living osteocytes in the bone matrix

Acknowledgments

References

Section 3 - Markers of bone cancer(cells, genes and proteins)

Chapter 12 - Bone remodeling markers and bone cancer

Introduction

Diagnostic use

Prognostic use

Monitoring of anti-tumor therapy

Conclusions and perspectives

References

Chapter 13 - Cancer stem cells in representative bone tumors: osteosarcoma, Ewing sarcoma and metastases from breast and prostat...

Introduction: the cancer stem cell theory and isolation assays

CSC evidence and origin in osteosarcoma

Stem cell features in Ewing tumor of bone

Bone metastasis stem cells

Conclusion: Limits of CSC evidence and therapeutic implications

References

Chapter 14 - Homeobox genes from the Dlx family and bone cancers

Introduction

Dlx homeobox genes

Dlx homeobox gene origin

Chromosomic organization and structure of Dlx homeobox genes

Dlx homeobox gene transcripts

DLX homeoproteins

The homeodomain

Other conserved domains

Biochemical peculiarities of DLX homeoproteins

Binding with other proteins

Dlx homeobox gene expressions and functions in skeleton

Embryonic development – morphogenesis

Limb development

Craniofacial development

Bone growth – histogenesis

Dlx and osteoblast differentiation in membranous bones

Dlx and chondroblast differentiation in endochondral bones

Dlx and osteoclastogenesis

Dlx homeobox genes and cancers

Dlx expression in non-osseous cancers

Dlx expression in bone tumors

Bone metastasis: secondary bone tumors

Primary bone tumors

Conclusions

References

Chapter 15 - MicroRNA implication in therapeutic resistance and metastatic dissemination of bone-associated tumors

Introduction

MicroRNAs and metastasis

MiR-21

MiR-17-92

Let-7

MiR-221 and miR-222

MiR-126

MiR-200 family

MiR-155

MicroRNAs and chemoresistance

MicroRNAs and efflux pumps

MicroRNAs and apoptotic pathways

MicroRNAs, cell cycle control and proliferation

MicroRNAs and EMT

MicroRNAs and DNA damage

MicroRNAs as predictive treatment biomarkers

Conclusion and perspectives

References

Chapter 16 - Hypoxia and angiogenesis: from primary tumor to bone metastasis

Introduction

Angiogenesis

Angiogenic switch

Vascular endothelial growth factor

Hypoxia

Hypoxia inducible factors

Hypoxia and tumor progression

Angiogenesis and tumor progression

Angiogenesis in metastatic bone cancer

Models to study angiogenesis

Anti-angiogenic treatments for bone cancer

Pre-clinical studies

Clinical trials

Conclusion and perspectives

Part II - Primary bone tumors

Section 1 - Specific biological aspects

Chapter 17 - Modeling osteosarcoma: in vitro and in vivo approaches

Introduction

In vitro approaches

In vivo approaches

Murine models

Spontaneous disease models

Induced models

Genetically engineered mouse models (GEMM)

Human OS models

Additional models to consider

Canine OS

Zebrafish models of OS

Conclusions

Acknowledgments

References

Chapter 18 - Stemness markers of osteosarcoma

Introduction

Cancer stem cells

Stemness markers of osteosarcoma

Conclusions

References

Chapter 19 - Molecular pathology of osteosarcoma

Introduction

Genomic instability and genetic changes

Chromosomal alterations

Chromothripsis

Alternative length of telomeres (ALT)

Tumor suppressor gene dysfunction in osteosarcoma

Retinoblastoma pathway

TP53

Oncogenes in osteosarcoma

RECQ helicases

microRNA involvement

Genes involved in osteosarcoma metastasis

Molecular insights into therapeutics

Conclusion

Acknowledgments

References

Chapter 20 - Gene and proteomic profiling of osteosarcoma

Introduction

Genetic alterations: classical oncogenes and tumor suppressors

Other oncogenic alterations

Classical signaling pathways

Markers of disease progression

Factors contributing to chemoresistance

Factors contributing to OS metastasis

Markers derived from proteomics

Other markers influencing the phenotype

Conclusions and future perspectives

References

Chapter 21 - Ewing sarcoma family of tumors

Introduction

Clinical features and pathogenesis

Epidemiology

Morphology and pathogenesis

Clinical presentation

Diagnosis and staging

Diagnosis

Staging and prognostic indicators

Treatment

Localized disease

Recurrent and metastatic disease

Therapeutic targets for Ewing sarcoma

IGF-1R +/– mTOR

CD99

EWSR1-FLI1 fusion proteins

Conclusion

References

Chapter 22 - Biology of Ewing sarcoma

Introduction

Ewing sarcoma’s oncogenes

The cell of origin of Ewing sarcoma

Other genetic events

Roles of EWS-ETS fusions

DNA-binding capacities

EWS-ETS modulated genes

EWS-ETS modulated pathways

Chromatin modifications

Interaction with microenvironment

Understanding metastatic disease

Conclusion

References

Chapter 23 - Osteoclast-rich lesions of bone: a clinical and molecular overview

Osteoclast-rich neoplasms of bone

Giant cell tumor of bone

Definition

Epidemiology

Sites of involvement and imaging

Molecular genetics

Morphology

Stromal cell population

The osteoclast

Conventional treatment

New therapeutic approaches

Multicentric giant cell tumors

Metastatic giant cell tumors

Malignant transformation of giant cell tumors

Aneurysmal bone cyst

The cherubism phenotype: cherubism, noonan-like/multiple giant cell lesion of the jaw and neurofibromatosis

Cherubism

Noonan syndrome

Neurofibromatosis type 1

Conclusion

References

Chapter 24 - Markers for bone sarcomas

Introduction

Markers for osteogenic sarcomas

Markers in high-grade osteosarcomas

High-grade conventional osteosarcomas

Diagnostic markers

Prognostic markers

Telangiectatic osteosarcoma

Markers in low-grade osteosarcomas

Markers for chondrogenic sarcomas

Markers in central and periosteal chondrosarcomas

Diagnostic markers

Prognostic markers

Markers in peripheral chondrosarcomas

Markers in clear cell chondrosarcomas

Markers for Ewing family sarcomas and small blue cell tumors

Ewing-like sarcomas

Differential diagnosis between ESFT and mesenchymal chondrosarcoma

Differential diagnosis between ESFT and small cell osteosarcoma

Markers in other primary bone sarcomas

Markers in notochordal tumors

Markers in adamantinoma

Epithelioid bone hemangioendothelioma

Conclusion

References

Chapter 25 - Margins and bone tumors – what are we talking about?

Introduction

Margins, a mainstay in bone tumor management

Characterization of margins

What is an adequate margin?

Conclusion

References

Chapter 26 - Cytogenetics of bone tumors

Introduction

Cartilage tumors

Osteochondroma

Chondroma

Chondroblastoma

Chondromyxoid fibroma

Chondrosarcoma

Osteogenic tumors

Fibrogenic tumors

Fibrohistiocytic tumors

Ewing sarcoma/primitive neuroectodermal tumor

Giant cell tumor

Notochordal tumors

Chordoma

Vascular tumors

Myogenic, lipogenic, neuronal, and epithelial tumors

Tumors of undefined neoplastic nature

Conclusion

References

Chapter 27 - Genetic aspects of bone tumors

Introduction

Cartilaginous neoplasms

Benign

Osteochondroma

Chondroma

Chondroblastoma

Malignant

Conventional chondrosarcoma

Dedifferentiated chondrosarcoma

Bone-forming tumors

Benign

Osteoid osteoma

Osteoblastoma

Malignant

Osteosarcoma

Ewing sarcoma

Giant cell tumors of the bone

Conclusion and perspectives

References

Chapter 28 - Cytogenetic and molecular genetic alterations in bone tumors

Introduction

Techniques for detecting genetic alterations in bone tumors

Genetic alterations in bone tumor entities

Central and periosteal chondrogenic tumors

Peripheral chondrogenic tumors

Mesenchymal chondrosarcoma

Other chondrogenic tumors

Osteogenic tumors

Ewing sarcoma

Fibrosarcoma of bone

Giant cell tumor of bone

Chordoma

Epithelioid hemangioendothelioma

Aneurysmal bone cyst

Fibrous dysplasia

Undifferentiated high-grade pleomorphic sarcoma

Conclusions and perspectives

References

Chapter 29 - Genetics of giant cell tumors of bone

Introduction

Pathophysiology

Cytogenetic analyses of GCT

Molecular analysis of GCT

Conclusions

References

Section 2 - Pre-clinical and clinicalaspects

Chapter 30 - Mammalian models of bone sarcomas

General considerations

Importance of animal models of bone sarcoma

Criteria for a representative bone sarcoma model

Types of animal models and modes of tumor induction

Osteosarcoma models

Syngeneic and xenogeneic models

Syngeneic: K7, K12 and K7M2

Xenogeneic: SAOS-2 and SAOS-LM-sublines (SAOS-LM2 to SAOS-LM7)

Genetically engineered models of osteosarcoma

Rat models of osteosarcoma

Canine osteosarcoma

Chondrosarcoma models

Ewing sarcoma models

Conclusions and outlook

References

Chapter 31 - Zebrafish models for studying bone cancers: mutants, transgenic fish and embryos

Advantages of zebrafish models for cancer research

Osteochondroma

Ewing sarcoma

Osteosarcoma

References

Chapter 32 - Imaging of bone sarcomas

Introduction

Imaging techniques

Radiography

Magnetic resonance imaging

Computed tomography

Nuclear medicine: bone scintigraphy and PET/CT (positron emission tomography/computed tomography)

Imaging characteristics and considerations of specific sarcoma types

Ewing sarcoma

Incidence

Location

Imaging considerations

Osteosarcoma

Incidence

Osteosarcoma subtypes

Conventional

Telangiectatic osteosarcoma

Parosteal

Periosteal

Low-grade central osteosarcoma (LGCOS)

Chondrosarcoma

Incidence

Chondrosarcoma subtypes

Conventional

Dedifferentiated chondrosarcoma

Chordoma

Incidence

Imaging considerations

Adamantinoma

Incidence

Location

Imaging considerations

Conclusion

References

Chapter 33 - New therapeutic targets in Ewing sarcoma: from pre-clinical proof-of-concept to clinical trials

Introduction

Therapeutic options for Ewing sarcoma

EWS-FLI1 inhibition

Inhibition of growth factor signaling pathways

IGF-1R/PI3K/AKT/mTOR signaling pathway

Multitarget inhibitors

Cell growth inhibition

Resistance to cell death

Targeting tumor microenvironment

Inhibition of angiogenesis

Inhibition of hypoxia

Targeting the pro-inflammatory microenvironment

Targeting the bone microenvironment

Epigenetic targeting

Other pathways

Camptothecins

Hedgehog pathway inhibitors (SHH/PATCH/Smo/GLI)

Hsp 90 inhibitors

Retinoids

Conclusions

References

Chapter 34 - Therapeutic approaches for bone sarcomas

Introduction

Work-up and Staging

Surgery

Reconstruction

Computer-assisted navigation

Chemotherapy

Radiation therapy

Therapeutic approaches for primary metastatic and recurrent disease

Follow-up

Conflict of Interest Statement

References

Chapter 35 - Chondrosarcoma of bone: diagnosis and therapy

Introduction

Classification

Classic chondrosarcoma (grade I–III)

Dedifferentiated chondrosarcoma (ddCS)

Mesenchymal chondrosarcoma

Clear cell chondrosarcoma

Secondary chondrosarcoma

Difficulties in making the diagnosis of chondrosarcoma

Biopsy of chondrosarcoma

Diagnosis of low-grade chondrosarcoma

Therapy and prognosis

High-grade chondrosarcoma

Surgery

Chemotherapy/radiotherapy

Therapy low-grade chondrosarcoma

Outlook for new therapeutic approaches

Conclusions

References

Chapter 36 - Apoptosis and drug resistance in malignant bone tumors

Introduction

Osteosarcoma

The Fas/Fas ligand pathway

The TRAIL pathway

Drug-induced apoptosis

Paclitaxel

Histone deacetylase inhibitors

Proteasome inhibitors

Flavopiridol

Zoledronic acid

Statins

Inhibition of glutathione S-transferase P1 (GSTP)

Apoptosis-relevant genes as prognostic markers

Apoptosis in Ewing sarcoma

The Fas/Fas ligand pathway

The TRAIL pathway

CD99-induced apoptosis

Drug-induced apoptosis

Treosulfan

Fenretinide

Zoledronic acid

Proteasome inhibitors

PARP inhibitors

Aurora kinase inhibitors

Apoptosis-relevant genes as prognostic markers

Apoptosis in chondrosarcoma

References

Chapter 37 - Giant cell tumors of bone

Introduction

Epidemiology

Histology

Clinical presentation

Radiology

Treatment

RANKL and GCTB: how understanding of pathogenesis drove development of highly active targeted therapy

Clinical studies of RANKL inhibitors

Denosumab

Conclusion

Acknowledgments

References

Part III - Bone metastases

Section 1 - Specific biological aspects

Chapter 38 - EMT process in bone metastasis

Introduction

EMT in physiological processes and cancer

EMT in primary tumor and metastatic dissemination

EMT and metastasis to the bone

EMT and cancer stem cells

EMT, circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) in the bone marrow

MET and outgrowth of metastasis

Bone marrow-derived cells in EMT and MET regulation

Therapeutic targets in bone metastasis and EMT

Perspective

References

Chapter 39 - Histopathology of skeletal metastases

Introduction

Several primary tumors with a predilection for skeletal metastasis

Breast

Prostate

Lung

Kidney

Thyroid

Other primary tumors

Metastatic carcinoma of unknown primary site

Conclusion

References

Chapter 40 - Disseminated tumor cells in bone marrow of cancer patients

Introduction

Biology of DTC

Molecular determinants of metastatic spread

Cancer dormancy

Metastatic stem cells

Clinical relevance of DTC in bone marrow

Breast cancer

Colorectal cancer

Lung cancer

Prostate cancer

DTC and cancer therapy

Conclusions

Acknowledgments

References

Chapter 41 - MicroRNA-mediated regulation of bone metastasis formation: from primary tumors to skeleton

Introduction

Development of skeletal metastases

Cancer cells escape the primary tumor

Cancer cells colonize the bone marrow

Cancer cells alter bone remodeling to promote skeletal lesions

Deregulation of microRNA expression modulates multiple steps of the metastatic cascade

Experimental evidence for the involvement of microRNAs in the metastatic cascade leading to bone metastasis formation

Involvement of microRNAs in the early stage of metastatic dissemination to bone

miR-335, miR-126, miR-206

miR-143, miR-145

miR-373, miR-520c

miR-34a/miR-7

miR-10b

Involvement of microRNAs in the tumor cell homing and colonization of bone marrow

miR-203

miR-30s family

miR-17-92 cluster

miR-218

miR-204, miR-211, miR-379

miR-33a and miR-336

Concluding remarks

References

Chapter 42 - Myeloma and osteoclast relationship

Introduction

Osteoclastogenesis: molecular mechanisms

Pathophysiology of MM-induced osteoclastogenesis

Role of RANKL/RANK/OPG system

Role of chemokines in MM-induced bone destruction

Other factors involved in MM-induced OC activation

Role of osteocytes in the activation of OCs in MM

OCs support MM cell survival: the vicious loop

Therapeutic implications

Bisphosphonates

New OC inhibitors in MM

Conclusions

References

Section 2 - Pre-clinical andclinical aspects

Chapter 43 - In vivo models used in studies of bone metastases

Introduction

Models used in the studies of breast cancer bone metastases

Xenograft models

Intracardiac injection