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Veterinary Pathology Sep 2015Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and... (Review)
Review
Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone.
Topics: Animals; Bone Neoplasms; Cell Line, Tumor; Disease Models, Animal; Dogs; Female; Humans; Mammary Neoplasms, Animal; Mice; Neoplasm Metastasis; Rats; X-Ray Microtomography
PubMed: 26021553
DOI: 10.1177/0300985815586223 -
Acta Bio-medica : Atenei Parmensis Jan 2018Osteoid osteoma is a benign bone neoplasm with a reported incidence of 2-3% among all bone primary tumors. Although it is a small and benign lesion, it is often cause of... (Review)
Review
Osteoid osteoma is a benign bone neoplasm with a reported incidence of 2-3% among all bone primary tumors. Although it is a small and benign lesion, it is often cause of patient complaint and discomfort. It is generally characterized by a long lasting, unremitting pain that typically exacerbates at night, often leading to sleep deprivation and functional limitation of the skeletal segment involved, with a significant reduction of patient daily life activities and consequent worsening of the overall quality of life. Over decades, complete surgical resection has represented the only curative treatment for symptomatic patients. In the last years, new percutaneous ablation techniques, especially radiofrequency ablation, have been reported to be a safe and effective alternative to classical surgery, with a low complication and recurrence rate, and a significant reduction in hospitalization cost and duration. The aim of this article is to provide an overview about the radiofrequency thermal ablation procedure in the treatment of osteoid osteoma.
Topics: Bone Neoplasms; Humans; Imaging, Three-Dimensional; Magnetic Resonance Imaging, Interventional; Osteoma, Osteoid; Radiofrequency Ablation; Radiography, Interventional
PubMed: 29350646
DOI: 10.23750/abm.v89i1-S.7021 -
Current Osteoporosis Reports Dec 2018Prostate cancer bone metastasis is the lethal progression of the disease. The disease frequently presents with osteoblastic lesions in bone. The tumor-induced bone can... (Review)
Review
PURPOSE OF REVIEW
Prostate cancer bone metastasis is the lethal progression of the disease. The disease frequently presents with osteoblastic lesions in bone. The tumor-induced bone can cause complications that significantly hamper the quality of life of patients. A better understanding of how prostate cancer induces aberrant bone formation and how the aberrant bone affects the progression and treatment of the disease may improve the therapies for this disease.
RECENT FINDINGS
Prostate cancer-induced bone was shown to enhance tumor growth and confer therapeutic resistance in bone metastasis. Clinically, Radium-223, an alpha emitter that selectively targets bone, was shown to improve overall survival in patients, supporting a role of tumor-induced bone in prostate cancer progression in bone. Recently, it was discovered that PCa-induced aberrant bone formation is due, in part, from tumor-associated endothelial cells that were converted into osteoblasts through endothelial-to-osteoblast (EC-to-OSB) conversion by tumor-secreted BMP4. The unique bone-forming phenotype of prostate cancer bone metastasis plays a role in prostate cancer progression in bone and therapy resistance. Therapies that incorporate targeting the tumor-induced osteoblasts or EC-to-OSB conversion mechanism may reduce tumor-induced bone formation and improve therapy outcomes.
Topics: Bone Neoplasms; Cell Differentiation; Disease Progression; Humans; Male; Neoplasm Metastasis; Neoplasm Staging; Osteoblasts; Prostatic Neoplasms
PubMed: 30203251
DOI: 10.1007/s11914-018-0480-6 -
Cellular Physiology and Biochemistry :... 2018Distant metastases are the major cause of mortality in cancer patients. Bone metastases may cause bone fractures, local pain, hypercalcemia, bone marrow aplasia, and... (Review)
Review
Distant metastases are the major cause of mortality in cancer patients. Bone metastases may cause bone fractures, local pain, hypercalcemia, bone marrow aplasia, and spinal cord compression. Therefore, the management of bone metastases is important in cancer treatment. Normal bone remodeling is regulated by osteoprotegerin ligand (OPGL), receptor activator of NF-κB ligand (RANKL), parathyroid hormone-related protein (PTHrP), and other cytokines. In the tumor microenvironment, tumor cells induce a vicious cycle that promotes osteoblastic and osteolytic lesions. Studies support the idea that distant metastases may occur due to the immunosuppressive function of myeloid-derived suppressor cells (MDSCs). These cells inhibit T cells and natural killer (NK) cells and differentiate into tumor-associating macrophages (TAMs), monocytes, and dendritic cells (DCs). In this review, we summarize studies focusing on the role of MDSCs in bone metastasis and provide a strong foundation for developing anticancer immune treatments and anticancer therapies, in general.
Topics: Bone Neoplasms; Bone Remodeling; Cell Adhesion Molecules; Cytokines; Humans; Immune System; Myeloid-Derived Suppressor Cells; Neoplasm Metastasis; Tumor Microenvironment; Wnt Signaling Pathway
PubMed: 29689559
DOI: 10.1159/000489184 -
Critical Reviews in Oncology/hematology Feb 2014The mechanisms underlying malignant cell metastasis to secondary sites such as bone are complex and no doubt multifactorial. Members of the small integrin-binding ligand... (Review)
Review
The mechanisms underlying malignant cell metastasis to secondary sites such as bone are complex and no doubt multifactorial. Members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) family, particularly bone sialoprotein (BSP) and osteopontin (OPN), exhibit multiple activities known to promote malignant cell proliferation, detachment, invasion, and metastasis of several osteotropic cancers. The expression level of BSP and OPN is elevated in a variety of human cancers, particularly those that metastasize preferentially to the skeleton. Recent studies suggest that the "osteomimicry" of malignant cells is not only conferred by transmembrane receptors bound by BSP and OPN, but includes the "switch" in gene expression repertoire typically expressed in cells of skeletal lineage. Understanding the role of BSP and OPN in tumor progression, altered pathophysiology of bone microenvironment, and tumor metastasis to bone will likely result in development of better diagnostic approaches and therapeutic regimens for osteotropic malignant diseases.
Topics: Animals; Bone Neoplasms; Bone and Bones; Gene Expression Regulation, Neoplastic; Humans; Integrin-Binding Sialoprotein; Neoplasm Metastasis; Osteopontin
PubMed: 24071501
DOI: 10.1016/j.critrevonc.2013.08.013 -
Journal of Digital Imaging Apr 2019Bone cancer originates from bone and rapidly spreads to the rest of the body affecting the patient. A quick and preliminary diagnosis of bone cancer begins with the...
Bone cancer originates from bone and rapidly spreads to the rest of the body affecting the patient. A quick and preliminary diagnosis of bone cancer begins with the analysis of bone X-ray or MRI image. Compared to MRI, an X-ray image provides a low-cost diagnostic tool for diagnosis and visualization of bone cancer. In this paper, a novel technique for the assessment of cancer stage and grade in long bones based on X-ray image analysis has been proposed. Cancer-affected bone images usually appear with a variation in bone texture in the affected region. A fusion of different methodologies is used for the purpose of our analysis. In the proposed approach, we extract certain features from bone X-ray images and use support vector machine (SVM) to discriminate healthy and cancerous bones. A technique based on digital geometry is deployed for localizing cancer-affected regions. Characterization of the present stage and grade of the disease and identification of the underlying bone-destruction pattern are performed using a decision tree classifier. Furthermore, the method leads to the development of a computer-aided diagnostic tool that can readily be used by paramedics and doctors. Experimental results on a number of test cases reveal satisfactory diagnostic inferences when compared with ground truth known from clinical findings.
Topics: Bone Neoplasms; Humans; Magnetic Resonance Imaging; Neoplasm Grading; Neoplasm Staging; Radiographic Image Interpretation, Computer-Assisted; Support Vector Machine; X-Rays
PubMed: 30367308
DOI: 10.1007/s10278-018-0145-0 -
Molecules (Basel, Switzerland) Jul 2014The development of bone metastases requires multistep and multicellular machinery consisting not only of processes shared with any type of metastases (formation of a... (Review)
Review
The development of bone metastases requires multistep and multicellular machinery consisting not only of processes shared with any type of metastases (formation of a pre-metastatic niche, chemotaxis of tumor cells into the host tissue, tumor cells escape from the microvasculature), but also biological interactions that are strictly related to the particular bone microenvironment (bone marrow colonization by cancer cells, osteomimicry, deregulation of bone homeostasis). MiRNAs are highly conserved, small RNAs molecules that regulate gene expression. The functional consequence of miRNA deregulation lies in the mRNA targets whose expression is altered. MiRNA networks acting as upstream regulators of these genes interfere with the initial steps of tumor local invasion and cancer cell intravasation, mainly by regulating the epithelial-mesenchymal transition, the motility, invasiveness and survival abilities of these cells. The miRNA-mediated regulation on the steps of bone tropism, anchorage, homing and finally bone colonization is more tissue specific, being dependent on the expression pattern of target miRNAs in bone marrow sinusoids, bone cells and microenvironment. In that, miRNA specific expression signatures that can distinguish between primary tumors from their corresponding bone metastases might be determinants of clinical aggressiveness. In this review, we focus on the current advances on functions and molecular mechanisms by which miRNAs exert their biological roles in regulating bone metastases development.
Topics: Animals; Bone Neoplasms; Humans; MicroRNAs; Neoplasm Metastasis; RNA, Neoplasm; Tumor Microenvironment
PubMed: 25019555
DOI: 10.3390/molecules190710115 -
Theranostics 2017Diagnosing bone metastases with traditional anatomic modalities, such as MRI and CT, is limited by sensitivity, and conventional bone radiotracers are only indirect...
Diagnosing bone metastases with traditional anatomic modalities, such as MRI and CT, is limited by sensitivity, and conventional bone radiotracers are only indirect markers of cancer activity. Fortunately, molecular imaging is uniquely capable of providing radiotracers such as fluciclovine and radiolabeled choline, that actually target tumors in the bone. The merits of research in imaging osseous metastases in animal models using these radiotracers and the implications for future clinical translation are discussed.
Topics: Animals; Bone Neoplasms; Carboxylic Acids; Cyclobutanes; Disease Models, Animal; Molecular Imaging; Neoplasm Metastasis; Positron-Emission Tomography
PubMed: 28638486
DOI: 10.7150/thno.20622 -
Journal of Orthopaedics and... Jun 2015Metastases are the most common malignancies involving bone; breast, prostate, lung and thyroid are the main sites of primary cancer. However, up to 30 % of patients... (Review)
Review
UNLABELLED
Metastases are the most common malignancies involving bone; breast, prostate, lung and thyroid are the main sites of primary cancer. However, up to 30 % of patients present with bone metastases of unknown origin, where the site of the primary neoplasm cannot be identified at the time of diagnosis despite a thorough history, physical examination, appropriate laboratory testing and modern imaging technology (CT, MRI, PET). Sometimes only extensive histopathological investigations on bone specimens from biopsy can suggest the primary malignancy. At other times, a bone lesion can have such a highly undifferentiated histological appearance that a precise pathological classification on routine hematoxylin-eosin-stained section is not possible. The authors reviewed the relevant literature in an attempt to investigate the epidemiology of the histological primaries finally identified in patients with bone metastases from occult cancer, and a strategy of management and treatment of bone metastases from occult carcinomas is suggested. Lung, liver, pancreas and gastrointestinal tract are common sites for primary occult tumors. Adenocarcinoma is the main histological type, accounting for 70 % of all cases, while undifferentiated cancer accounts for 20 %. Over the past 30 years, lung cancer is the main causative occult primary for bone metastases and has a poor prognosis with an average survival of 4-8 months. Most relevant literature focuses on the need for standardized diagnostic workup, as surgery for bone lesions should be aggressive only when they are solitary and/or the occult primaries have a good prognosis; in these cases, identification of the primary tumor may be important and warrants special diagnostic efforts. However, in most cases, the primary site remains unknown, even after autopsy. Thus, orthopedic surgery has a mainly palliative role in preventing or stabilizing pathological fractures, relieving pain and facilitating the care of the patient in an attempt to provide the most appropriate therapy for the primary tumor as soon as possible.
LEVEL OF EVIDENCE
5.
Topics: Biopsy; Bone Neoplasms; Diagnostic Imaging; Humans; Neoplasms, Unknown Primary; Orthopedics; Pain Management; Survival Rate
PubMed: 25726410
DOI: 10.1007/s10195-015-0344-0 -
Cells Jun 2021Immunotherapies provide a potential treatment option for currently incurable bone metastases. Bone marrow is an important secondary lymphoid organ with a unique immune... (Review)
Review
Immunotherapies provide a potential treatment option for currently incurable bone metastases. Bone marrow is an important secondary lymphoid organ with a unique immune contexture. Even at non-disease state immune cells and bone cells interact with each other, bone cells supporting the development of immune cells and immune cells regulating bone turnover. In cancer, tumor cells interfere with this homeostatic process starting from formation of pre-metastatic niche and later supporting growth of bone metastases. In this review, we introduce a novel concept osteoimmuno-oncology (OIO), which refers to interactions between bone, immune and tumor cells in bone metastatic microenvironment. We also discuss therapeutic opportunities of targeting immune cells in bone metastases, and associated efficacy and safety concerns.
Topics: Animals; Bone Neoplasms; Humans; Immunotherapy; Neoplasm Metastasis; Tumor Microenvironment
PubMed: 34204474
DOI: 10.3390/cells10061529