Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Samarium-153 lexidronam (153Sm-EDTMP) is FDA approved for painful osteoblastic bone metastases that image on bone scan. 153Sm-EDTMP decay has a therapeutic beta-emission and a gamma-photon for bone scan imaging. Monitoring of osteosarcoma radiation treatment effectiveness was performed with bone, CT, MRI and PET/CT fusion imaging. Bone scan and PET/CT improved in 5 out of 9 and 16 out of 18 osteosarcoma sites, respectively. 153Sm-EDTMP targets multiple sites of disease, with a single administration. Side effects of 153Sm-EDTMP (0.5-2.5 mCi/kg) have been minimal and include transient thrombocytopenia and neutropenia. 153Sm-EDTMP can be combined with radiation therapy, bisphosphonates and/or chemotherapy to synergistically improve palliation. This article reviews the rationale, indications and monitoring of standard-dose samarium and investigational high-dose 153Sm-EDTMP treatment of cancer involving bone.
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PMID:Samarium for osteoblastic bone metastases and osteosarcoma. 1685 31

Between 1986 and 2002, 42 patients with synchronous multifocal osteosarcoma were treated with two different protocols of neoadjuvant chemotherapy. When feasible, the primary and secondary tumours were excised as a combined procedure. After initial chemotherapy 26 patients were excluded from simultaneous excision of all their secondary bone lesions as their disease was too advanced. In 12 patients only isolated excision of the primary lesion was possible. For 16 patients simultaneous operations were conducted to excise the primary and secondary lesions. This involved two supplementary sites in 15 patients and four additional sites in one patient. Of these, 15 attained remission but 12 relapsed and died (11 within two years). Three patients remained disease-free at five, six and 17 years. The histological response to pre-operative chemotherapy of the primary and secondary lesions was concordant in 13 of the 16 patients who underwent simultaneous operations at more than one site. The prognosis for synchronous multifocal osteosarcoma remains poor despite combined chemotherapy and surgery. The homogeneous histological responses in a large proportion of the primary and secondary lesions implies that synchronous multifocal osteosarcoma tumours are not multicentric in origin, but probably represent bone-to-bone metastases from a single tumour.
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PMID:Treatment and prognosis for synchronous multifocal osteosarcoma in 42 patients. 1687 8

We here propose guidelines for the diagnosis and management of Paget's disease of bone (PDB) in Japan. These guidelines provide basic information on the epidemiology, pathophysiology, clinical signs and symptoms, diagnosis, indications for treatment, and available therapy, including orthopedic surgery. PDB is a chronic disorder characterized by focal abnormalities of bone turnover. The characteristic feature of PDB is excessive osteoclastic bone resorption coupled to increased and disorganized bone formation. The most common symptom of PDB is pain in involved bones. The most serious complication of PDB is malignant bone or soft-tissue tumor. PDB is uncommon in Japan; our survey in 2003 found 169 patients with PDB. The prevalence of PDB in Japan is 0.15/100 000; in patients aged 55 years or more, the proportion reaches 0.41/100 000. A careful medical history and physical examination are essential for the diagnosis. The diagnosis of PDB is based on finding the typical features on radiographs. Bone scintigraphy and measurement of serum alkaline phosphatase are sensitive means of screening for PDB. Since PDB is a rare disease in Japan, bone biopsy is quite often used to exclude bone metastases. The only evidence-based indication for treatment of PDB is pain in involved bones. In Japan, etidronate and calcitonin are approved by the Ministry of Health, Labour and Welfare for treating PDB, but currently risedronate is also under development for treating PDB in Japan. Indications for surgical intervention in PDB include unstable fractures, osteoarthritis, malignant soft-tissue tumor, osteosarcoma, and bone deformity.
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PMID:Guidelines for diagnosis and management of Paget's disease of bone in Japan. 1693 67

Synchronous multifocal osteosarcoma (SMOS), defined as more than one bone lesion at presentation, is a rare variant form of osteosarcoma. The onset is usually in childhood or early adolescence without pulmonary metastasis. The prognosis has been dismal. Whether SMOS represents a true multicentic origin or merely bone-to-bone metastases remains controversial. Here, we report a case of SMOS in a 10-year-old girl, with the dominant primary sclerotic tumor arising from the right distal femur. Despite aggressive chemotherapy and limb salvage surgery, she died of progressive multiple axial skeletal and symmetrical metaphyseal long bone diseases within one year after diagnosis. No pulmonary metastasis was found before she died.
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PMID:Synchronous multifocal osteosarcoma: report of one case. 1707 69

Osteosarcoma is the most common primary bone malignancy in children and is associated with rapid bone growth. Parathyroid hormone-related peptide (PTHrP) signaling via parathyroid hormone Type 1 receptor (PTHR1) is important for skeletal development and is involved in bone metastases in other tumors. The aim of this study was to investigate the status of PTHrP/PTHR1 and its possible role in osteosarcoma. In a preliminary screening, a higher level of PTHR1 mRNA, but not PTHrP, was found in 4 osteosarcoma xenografts as compared with 4 standard cell lines, or 5 patient derived cell lines (p < 0.05) using quantitative RT-PCR. It was therefore extended to 55 patient specimens, in which a significantly higher level of PTHR1 mRNA was detected in metastatic or relapsed samples than those from primary sites (p < 0.01). Cell behavior caused by PTHR1 overexpression was further studied in vitro using PTHR1 transfected HOS cell line as a model. Over-expression of PHTR1 resulted in increased proliferation, motility and Matrigel invasion without addition of exogenous PTHrP suggesting an autocrine effect. Importantly, the aggressiveness in PTHR1-expressing cells was completely reversed by RNAi mediated gene knockdown. In addition, PTHR1 over-expression led to delayed osteoblastic differentiation and upregulation of genes involved in extracellular matrix production, such as TGF-beta1 and connective tissue growth factor. When cocultured with bone marrow derived monocytes, PTHR1 transfected HOS cells induced a greater number of osteoclasts. This study suggests that PTHR1 over-expression may promote osteosarcoma progression by conferring a more aggressive phenotype, and forming a more favorable microenvironment.
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PMID:Over-expression of parathyroid hormone Type 1 receptor confers an aggressive phenotype in osteosarcoma. 1741 May 35

Although neuroblastoma is a relatively common malignancy of childhood and its dissemination to distant organs is often seen, metastasis to the mandible is rare. A 3-year-old boy which a mandibular soft tissue mass was the initial presenting symptom of disseminated neuroblastoma is reported. The results of biopsy were inconclusive and the differential diagnosis from the imaging studies included lymphoma, soft tissue sarcoma, and osteosarcoma. A metastatic work-up disclosed neuroblastoma of the adrenal gland origin with osseous and bone marrow metastases. Urinary catecolamines were also increased. Regarding the widespread features of the tumor and lack of adequate treatment at this stage of disease, a palliative chemotherapy was conducted, and the patient died one month after starting treatment. This case illustrates that neuroblastoma at a young age, with bone metastases and bone marrow involvement are predictive of the poor outcome of the disease. Therefore, detecting early stage metastasis is one of the essential factors for improving treatment of neuroblastoma patients.
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PMID:Metastatic neuroblastoma to the mandible in a 3-year-old boy: a case report. 1746 14

Radiation therapy can be an effective means to treat bone metastases, which occur in more than 50% of cancer patients. (153)Samarium lexidronam ((153)Sm-EDTMP; Quadramet, Cytogen) is a radiopharmaceutical designed for deposition into bone metastases. Bone scans can identify patients that may benefit from targeted radiation therapy with (153)Sm-EDTMP. As an unsealed source of radiation therapy, (153)Sm-EDTMP is simple to administer: 1 mCi/kg is given in a similar fashion to a bone scan injection ((99m)Tc-MDP bone scan injection is given at 0.2-0.35 mCi/kg. Therefore, both are administered intravenously. However, the radiation-absorbed dose and radiopharmaceutical energy are different). Nevertheless, despite simplicity of administration, (153)Sm-EDTMP is underutilized for improving cancer pain in the skeleton. Repeated cycles and combined treatment with other modalities such as bisphosphonates, chemotherapy and/or external beam radiation are possible. (153)Sm-EDTMP combined with bisphosphonates, chemotherapy and/or radiation may provide better palliation of bone metastases and also in bone-forming tumors (osteosarcoma). Encouraging experience using high-dose (153)Sm-EDTMP for total marrow irradiation in hematologic malignancies involving the bones (e.g., myeloma or acute leukemia) is also reviewed.
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PMID:Samarium lexidronam (153Sm-EDTMP): skeletal radiation for osteoblastic bone metastases and osteosarcoma. 1802 Sep 21

Many extraocular masses involving the pediatric orbit have an osseous origin. The most common is the dermoid inclusion cyst; these cystic lesions may contain lipid and are most often found near the zygomaticofrontal suture, adjacent to an indolent-appearing erosion of bone. Some primary bone lesions may involve the orbit, producing a lytic or dense lesion with enlargement of the bone; these lesions include fibrous dysplasia, juvenile ossifying fibroma, and osteosarcoma. Fibrous dysplasia tends to produce a mass of ground-glass appearance with longitudinal osseous expansion, whereas juvenile ossifying fibroma is likely to produce a mixed lytic and sclerotic lesion and focal osseous enlargement. Osteosarcoma causes marked bone destruction and variable osteoid production. Langerhans cell histiocytosis, an idiopathic reticuloendothelial proliferative disorder, tends to involve the bones of the skull, especially the lateral orbital roof; it produces lytic destruction of bone with a sclerotic rim and a large intraorbital soft-tissue mass. Granulocytic sarcoma is a solid tumor that may occur in children with myelogenous leukemia. These tumors tend to arise in the subperiosteum of the lateral orbital wall, although they usually do not disrupt the bone. Finally, the orbit is a common site for bone metastases from neuroblastoma, which cause aggressive periosteal reaction in the orbital roof or lateral wall. The last three conditions are often bilateral. At imaging evaluation, osseous lesions may appear similar to each other and to nonosseous masses of the orbit. Knowledge of the pathologic features of these tumors and how these features are reflected in their imaging appearances may help radiologists differentiate them.
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PMID:From the Archives of the AFIP. Pediatric orbit tumors and tumorlike lesions: osseous lesions of the orbit. 1863 37

In a adolescent women aged 15 and 17 years respectively, severe heart failure developed within a few months of anthracycline chemotherapy given for osteosarcoma. In the guidelines of the European Society of Cardiology, malignancy with a remission duration of less than 5 years is an absolute contraindication to cardiac transplantation. Neither patient was eligible to receive a ventricular assist device (VAD) as a bridge to cardiac transplantation in the Netherlands, but they were accepted in Germany. One patient received a cardiac transplant 13 months later and at the last follow-up check she was in good health with a remission of 3 years. The other patient developed bone metastases 6 months after the VAD implantation. Cardiac transplantation was not a treatment option for her. Dose-dependent cardiotoxicity is a serious complication of the use of anthracyclines. In severe heart failure the prognosis is often worse than in adjuvantly treated malignancies like osteosarcoma. VAD may therefore be a valid option for patients with severe heart failure after anthracycline use for a malignancy. In cases of sustained remission VAD may be the bridge to transplantation.
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PMID:[Ventricular assist device implantation as a bridge to cardiac transplantation in two adolescents with end-stage cardiomyopathy and heart failure as a result of anthracycline use]. 1883 86

Primary and secondary bone tumors clearly deteriorate quality of life and the activity of daily living of patients. These undesirable diseases become a major social and economic burden. As both primary and secondary bone tumors develop in the unique bone tissue, it is therefore necessary to understand bone cell biology in tumor bone environment. Recent findings of the Receptor Activator of Nuclear Factor-kappaB ligand (RANKL)/RANK/osteoprotegerin (OPG) molecular triad, the key regulators of bone remodeling, opened new era of bone research. Although RANK is an essential receptor for osteoclast formation, activation and survival, functional RANK expression has been recently identified on several bone-associated tumor cells. When RANK is expressed on secondary bone tumor cells, it is implicated in tumor cell migration, whereas this is not the case for primary bone tumors. In any case, RANK is not involved in RANK-positive cell proliferation or death. In two models of bone metastases secondary to melanoma or prostate carcinoma, in vivo neutralization of RANKL by OPG resulted in complete protection from paralysis, due to metastases of vertebral body, and a marked reduction in tumor burden in bones, but not in other organs. OPG also decreased tumor formation and tumor burden in a mouse model of primary bone tumor, osteosarcoma. In all these models, tumor cells express RANK. These data revealed that local differentiation factors, such as RANKL, play an important role in cell migration in a metastatic tissue-specific manner. These findings substantiate the novel direct role of RANKL/RANK in bone-associated tumors, and its capability of representing new therapeutic targets.
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PMID:Receptor activator of nuclear factor-kappa B ligand (RANKL) stimulates bone-associated tumors through functional RANK expressed on bone-associated cancer cells? 1908 39


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