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RoFo : Fortschritte Auf Dem Gebiete Der... Mar 2021Chondrogenic tumors are the most frequent primary bone tumors. Malignant chondrogenic tumors represent about one quarter of malignant bone tumors. Benign chondrogenic... (Review)
Review
BACKGROUND
Chondrogenic tumors are the most frequent primary bone tumors. Malignant chondrogenic tumors represent about one quarter of malignant bone tumors. Benign chondrogenic bone tumors are frequent incidental findings at imaging. Radiological parameters may be helpful for identification, characterization, and differential diagnosis.
METHODS
Systematic PubMed literature research. Identification and review of studies analyzing and describing imaging characteristics of chondrogenic bone tumors.
RESULTS AND CONCLUSIONS
The 2020 World Health Organization (WHO) classification system differentiates between benign, intermediate (locally aggressive or rarely metastasizing), and malignant chondrogenic tumors. On imaging, typical findings of differentiated chondrogenic tumors are lobulated patterns with a high signal on T2-weighted magnetic resonance imaging (MRI) and ring- and arc-like calcifications on conventional radiography and computed tomography (CT). Depending on the entity, the prevalence of this chondrogenic pattern differs. While high grade tumors may be identified due to aggressive imaging patterns, the differentiation between benign and intermediate grade chondrogenic tumors is challenging, even in an interdisciplinary approach.
KEY POINTS
· The WHO defines benign, intermediate, and malignant chondrogenic bone tumors. · Frequent benign tumors: osteochondroma and enchondroma; Frequent malignant tumor: conventional chondrosarcoma. · Differentiation between enchondroma versus low-grade chondrosarcoma is challenging for radiologists and pathologists. · Pain, deep scalloping, cortical destruction, bone expansion, soft tissue component: favor chondrosarcoma. · Potential malignant transformation of osteochondroma: progression after skeletal maturity, cartilage cap thickness (> 2 cm adult; > 3 cm child). · Potentially helpful advanced imaging methods: Dynamic MRI, texture analysis, FDG-PET/CT.
CITATION FORMAT
· Engel H, Herget GW, Füllgraf H et al. Chondrogenic Bone Tumors: The Importance of Imaging Characteristics. Fortschr Röntgenstr 2021; 193: 262 - 274.
Topics: Adult; Bone Neoplasms; Child; Chondroma; Chondrosarcoma; Humans; Osteochondroma; Positron Emission Tomography Computed Tomography
PubMed: 33152784
DOI: 10.1055/a-1288-1209 -
JCI Insight May 2023Mesenchymal chondrosarcoma affects adolescents and young adults, and most cases usually have the HEY1::NCOA2 fusion gene. However, the functional role of HEY1-NCOA2 in...
Mesenchymal chondrosarcoma affects adolescents and young adults, and most cases usually have the HEY1::NCOA2 fusion gene. However, the functional role of HEY1-NCOA2 in the development and progression of mesenchymal chondrosarcoma remains largely unknown. This study aimed to clarify the functional role of HEY1-NCOA2 in transformation of the cell of origin and induction of typical biphasic morphology of mesenchymal chondrosarcoma. We generated a mouse model for mesenchymal chondrosarcoma by introducing HEY1-NCOA2 into mouse embryonic superficial zone (eSZ) followed by subcutaneous transplantation into nude mice. HEY1-NCOA2 expression in eSZ cells successfully induced subcutaneous tumors in 68.9% of recipients, showing biphasic morphologies and expression of Sox9, a master regulator of chondrogenic differentiation. ChIP sequencing analyses indicated frequent interaction between HEY1-NCOA2 binding peaks and active enhancers. Runx2, which is important for differentiation and proliferation of the chondrocytic lineage, is invariably expressed in mouse mesenchymal chondrosarcoma, and interaction between HEY1-NCOA2 and Runx2 is observed using NCOA2 C-terminal domains. Although Runx2 knockout resulted in significant delay in tumor onset, it also induced aggressive growth of immature small round cells. Runx3, which is also expressed in mesenchymal chondrosarcoma and interacts with HEY1-NCOA2, replaced the DNA-binding property of Runx2 only in part. Treatment with the HDAC inhibitor panobinostat suppressed tumor growth both in vitro and in vivo, abrogating expression of genes downstream of HEY1-NCOA2 and Runx2. In conclusion, HEY1::NCOA2 expression modulates the transcriptional program in chondrogenic differentiation, affecting cartilage-specific transcription factor functions.
Topics: Animals; Mice; Bone Neoplasms; Cell Differentiation; Chondrosarcoma, Mesenchymal; Core Binding Factor Alpha 1 Subunit; Mice, Nude; Oncogene Proteins, Fusion
PubMed: 37212282
DOI: 10.1172/jci.insight.160279 -
Biomedicine & Pharmacotherapy =... Mar 2024Optineurin (OPTN) is a widely expressed multifunctional articulatory protein that participates in cellular or mitochondrial autophagy, vesicular transport, and... (Review)
Review
Optineurin (OPTN) is a widely expressed multifunctional articulatory protein that participates in cellular or mitochondrial autophagy, vesicular transport, and endoplasmic reticulum (ER) stress via interactions with various proteins. Skeletal development is a complex biological process that requires the participation of various osteoblasts, such as bone marrow mesenchymal stem cells (BMSCs), and osteogenic, osteoclastic, and chondrogenic cells. OPTN was recently found to be involved in the regulation of osteoblast activity, which affects bone metabolism. OPTN inhibits osteoclastogenesis via signaling pathways, including NF-κB, IFN-β, and NRF2. OPTN can promote the differentiation of BMSCs toward osteogenesis and inhibit lipogenic differentiation by delaying BMSC senescence and autophagy. These effects are closely related to the development of bone metabolism disorders, such as Paget's disease of bone, rheumatoid arthritis, and osteoporosis. Therefore, this review aims to explore the role and mechanism of OPTN in the regulation of bone metabolism and related bone metabolic diseases. Our findings will provide new targets and strategies for the prevention and treatment of bone metabolic diseases.
Topics: Humans; Adenocarcinoma; Arthritis, Rheumatoid; Autophagy; Biological Transport; Bone Diseases, Metabolic; Membrane Transport Proteins; Cell Cycle Proteins; Bone and Bones; Animals
PubMed: 38350370
DOI: 10.1016/j.biopha.2024.116258 -
Cellular and Molecular Life Sciences :... Nov 2019The human chondromodulin-1 (Chm-1, Chm-I, CNMD, or Lect1) gene encodes a 334 amino acid type II transmembrane glycoprotein protein with characteristics of a furin... (Review)
Review
The human chondromodulin-1 (Chm-1, Chm-I, CNMD, or Lect1) gene encodes a 334 amino acid type II transmembrane glycoprotein protein with characteristics of a furin cleavage site and a putative glycosylation site. Chm-1 is expressed most predominantly in healthy and developing avascular cartilage, and healthy cardiac valves. Chm-1 plays a vital role during endochondral ossification by the regulation of angiogenesis. The anti-angiogenic and chondrogenic properties of Chm-1 are attributed to its role in tissue development, homeostasis, repair and regeneration, and disease prevention. Chm-1 promotes chondrocyte differentiation, and is regulated by versatile transcription factors, such as Sox9, Sp3, YY1, p300, Pax1, and Nkx3.2. Decreased expression of Chm-1 is implicated in the onset and progression of osteoarthritis and infective endocarditis. Chm-1 appears to attenuate osteoarthritis progression by inhibiting catabolic activity, and to mediate anti-inflammatory effects. In this review, we present the molecular structure and expression profiling of Chm-1. In addition, we bring a summary to the potential role of Chm-1 in cartilage development and homeostasis, osteoarthritis onset and progression, and to the pathogenic role of Chm-1 in infective endocarditis and cancers. To date, knowledge of the Chm-1 receptor, cellular signalling, and the molecular mechanisms of Chm-1 is rudimentary. Advancing our understanding the role of Chm-1 and its mechanisms of action will pave the way for the development of Chm-1 as a therapeutic target for the treatment of diseases, such as osteoarthritis, infective endocarditis, and cancer, and for potential tissue regenerative bioengineering applications.
Topics: Animals; Cartilage; Heart Diseases; Homeostasis; Humans; Membrane Proteins; Neoplasms; Osteoarthritis
PubMed: 31317206
DOI: 10.1007/s00018-019-03225-y -
European Review For Medical and... Feb 2021Long noncoding RNAs (lncRNAs) are important participants in biological processes including cell proliferation, differentiation and death, as well as pathogenesis of... (Review)
Review
Long noncoding RNAs (lncRNAs) are important participants in biological processes including cell proliferation, differentiation and death, as well as pathogenesis of various diseases. LncRNA differentiation antagonizing non-protein coding RNA (DANCR) is an emerging regulator in cell metabolism and many diseases besides cancers. DANCR is negative in epidermal, osteoblastic and endoderm differentiation, but positive in chondrogenic differentiation of progenitor cells. It is protective for calcification of the ligamentum flavum, stroke, acute myocardial infarction and arterial calcification, but a risk factor for bone loss, fracture healing and idiopathic pulmonary fibrosis. In addition, DANCR is a potential target for improving tissue regeneration. Mechanically, DANCR, a cytoplasmic lncRNA, sponges corresponding microRNAs or interacts with various proteins. This review aims to summarize the role of DANCR in progenitor cells and provide perspectives for further studies.
Topics: Humans; Neoplasms; RNA, Long Noncoding; Stem Cells
PubMed: 33629310
DOI: 10.26355/eurrev_202102_24848 -
Radiology. Imaging Cancer Mar 2023Purpose To evaluate if ferumoxytol can improve the detection of bone marrow metastases at diffusion-weighted (DW) MRI in pediatric and young adult patients with cancer.... (Clinical Trial)
Clinical Trial
Purpose To evaluate if ferumoxytol can improve the detection of bone marrow metastases at diffusion-weighted (DW) MRI in pediatric and young adult patients with cancer. Materials and Methods In this secondary analysis of a prospective institutional review board-approved study (ClinicalTrials.gov identifier NCT01542879), 26 children and young adults (age range: 2-25 years; 18 males) underwent unenhanced or ferumoxytol-enhanced whole-body DW MRI between 2015 and 2020. Two reviewers determined the presence of bone marrow metastases using a Likert scale. One additional reviewer measured signal-to-noise ratios (SNRs) and tumor-to-bone marrow contrast. Fluorine 18 (F) fluorodeoxyglucose (FDG) PET and follow-up chest CT, abdominal and pelvic CT, and standard (non-ferumoxytol enhanced) MRI served as the reference standard. Results of different experimental groups were compared using generalized estimation equations, Wilcoxon rank sum test, and Wilcoxon signed rank test. Results The SNR of normal bone marrow was significantly lower at ferumoxytol-enhanced MRI compared with unenhanced MRI at baseline (21.380 ± 19.878 vs 102.621 ± 94.346, respectively; = .03) and after chemotherapy (20.026 ± 7.664 vs 54.110 ± 48.022, respectively; = .006). This led to an increased tumor-to-marrow contrast on ferumoxytol-enhanced MRI scans compared with unenhanced MRI scans at baseline (1397.474 ± 938.576 vs 665.364 ± 440.576, respectively; = .07) and after chemotherapy (1099.205 ± 864.604 vs 500.758 ± 439.975, respectively; = .007). Accordingly, the sensitivity and diagnostic accuracy for detecting bone marrow metastases were 96% (94 of 98) and 99% (293 of 297), respectively, with the use of ferumoxytol-enhanced MRI compared with 83% (106 of 127) and 95% (369 of 390) with the use of unenhanced MRI. Conclusion Use of ferumoxytol helped improve the detection of bone marrow metastases in children and young adults with cancer. Pediatrics, Molecular Imaging-Cancer, Molecular Imaging-Nanoparticles, MR-Diffusion Weighted Imaging, MR Imaging, Skeletal-Appendicular, Skeletal-Axial, Bone Marrow, Comparative Studies, Cancer Imaging, Ferumoxytol, USPIO © RSNA, 2023 ClinicalTrials.gov registration no. NCT01542879 See also the commentary by Holter-Chakrabarty and Glover in this issue.
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Male; Young Adult; Bone Marrow Neoplasms; Bone Neoplasms; Ferrosoferric Oxide; Magnetic Resonance Imaging; Prospective Studies
PubMed: 36999999
DOI: 10.1148/rycan.220080 -
Pharmacology & Therapeutics Jan 2012Progranulin (PGRN) is abundantly expressed in epithelial cells, immune cells, neurons, and chondrocytes, and reportedly contributes to tumorigenesis. PGRN is a crucial... (Review)
Review
Progranulin (PGRN) is abundantly expressed in epithelial cells, immune cells, neurons, and chondrocytes, and reportedly contributes to tumorigenesis. PGRN is a crucial mediator of wound healing and tissue repair. PGRN also functions as a neurotrophic factor and mutations in the PGRN gene resulting in partial loss of the PGRN protein cause frontotemporal dementia. PGRN has been found to be a novel chondrogenic growth factor and to play an important role in cartilage development and inflammatory arthritis. Although research has shown that PGRN exhibits anti-inflammatory properties, the details about the exact molecular pathway of such effects, and, in particular, the PGRN binding receptor, have not been identified so far. Recently, researchers have shown that PGRN binds to tumor necrosis factor (TNF)-receptors (TNFR), interfering with the interaction between TNFα and TNFR. They further demonstrated that mice deficient in PGRN are susceptible to collagen-induced arthritis, an experimental model of rheumatoid arthritis, and that administration of PGRN reversed the arthritic process. An engineered protein made of three PGRN fragments (Atsttrin), displayed selective TNFR binding and was more active than natural PGRN. Both PGRN and Atsttrin prevented inflammation in various arthritis mouse models and inhibited TNFα-induced intracellular signaling pathways. Thus, PGRN is a key regulator of inflammation and it may mediate its anti-inflammatory effects, at least in part, by blocking TNF binding to its receptors. As we discuss here, TNFR-based interventions may both stimulate and suppress the growth of cancer cells, and the same may be true in analogy for Atsttrin as a new player.
Topics: Animals; Arthritis, Experimental; Autoimmune Diseases; Humans; Intercellular Signaling Peptides and Proteins; Ligands; Neoplasms; Neurodegenerative Diseases; Progranulins; Receptors, Tumor Necrosis Factor
PubMed: 22008260
DOI: 10.1016/j.pharmthera.2011.10.003 -
Current Problems in Diagnostic Radiology 2023Chondrogenic tumors are typically well recognized on radiographs, but differentiation between benign and malignant cartilaginous lesions can be difficult both for the... (Review)
Review
Chondrogenic tumors are typically well recognized on radiographs, but differentiation between benign and malignant cartilaginous lesions can be difficult both for the radiologist and for the pathologist. Diagnosis is based on a combination of clinical, radiological and histological findings. While treatment of benign lesions does not require surgery, the only curative treatment for chondrosarcoma is resection. This article (1) emphasizes the update of the WHO classification and its diagnostic and clinical effects; (2) describes the imaging features of the various types of cartilaginous tumors, highlighting findings that can help differentiate benign from malignant lesions; (3) presents differential diagnoses; and (4) provides pathologic correlation. We attempt to offer valuable clues in the approach to this vast entity.
Topics: Humans; Bone Neoplasms; Chondrosarcoma; World Health Organization; Diagnosis, Differential
PubMed: 36797102
DOI: 10.1067/j.cpradiol.2023.01.005 -
Journal of Comparative Pathology Jan 2022A 9-year-old intact male Brazilian Mastiff dog with a 1-year history of progressive severe swelling in all four limbs and significant locomotory difficulty was...
A 9-year-old intact male Brazilian Mastiff dog with a 1-year history of progressive severe swelling in all four limbs and significant locomotory difficulty was euthanized due to unresponsiveness to medical management. Macroscopically, the distal phalanx of the 5 digit of the left hindlimb was replaced by a cutaneous, non-ulcerated, 3.0 cm diameter, multilobulated, black, firm nodule. The cortical bones of the appendicular skeleton were thickened and partially effaced by infiltrative coalescing nodules (0.1-1.0 cm diameter). The lungs, heart, pleura, mesentery, adrenal glands and kidneys were infiltrated by similar nodules (0.5-3.5 cm diameter). Histological evaluation of the masses revealed a non-encapsulated malignant neoplasm composed of spindloid to polygonal cells that contained variable amounts of intracytoplasmic melanin and were arranged in haphazardly interlacing streams and bundles supported by scant fibrovascular stroma with myxoid and chondroid matrix formation. Neoplastic cells had intense cytoplasmic labeling for S100 and 10% had moderate cytoplasmic immunoreactivity for Melan-A. To the authors' knowledge, this is the first description of a canine metastatic digital chondrogenic melanocytic tumour with strongly suggestive chondroid differentiation of neoplastic melanocytes.
Topics: Animals; Bone Neoplasms; Brazil; Dog Diseases; Dogs; Male; Melanocytes; Melanoma; Skin Neoplasms
PubMed: 35152967
DOI: 10.1016/j.jcpa.2021.10.010 -
Molecular Medicine Reports Jun 2019Activin receptor‑like kinases (ALKs), members of the type I activin receptor family, belong to the serine/threonine kinase receptors of the transforming growth... (Review)
Review
Activin receptor‑like kinases (ALKs), members of the type I activin receptor family, belong to the serine/threonine kinase receptors of the transforming growth factor‑β (TGF‑β) superfamily. ALKs mediate the roles of activin/TGF‑β in a wide variety of physiological and pathological processes, ranging from cell differentiation and proliferation to apoptosis. For example, the activities of ALKs are associated with an advanced tumor stage in prostate cancer and the chondrogenic differentiation of mesenchymal stem cells. Therefore, potent and selective small molecule inhibitors of ALKs would not only aid in investigating the function of activin/TGF‑β, but also in developing treatments for these diseases via the disruption of activin/TGF‑β. In recent studies, several ALK inhibitors, including LY‑2157299, SB‑431542 and A‑83‑01, have been identified and have been confirmed to affect stem cell differentiation and tumor progression in animal models. This review discusses the therapeutic perspective of small molecule inhibitors of ALKs as drug targets in tumor and stem cells.
Topics: Activin Receptors; Activins; Animals; Cell Differentiation; Humans; Mesenchymal Stem Cells; Neoplasms; Signal Transduction; Small Molecule Libraries; Transforming Growth Factor beta
PubMed: 31059090
DOI: 10.3892/mmr.2019.10209