Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Desmoplastic small round cell tumor (DSRCT) is a rare malignant neoplasm typically involving the abdominal cavity of a young male. Extra-abdominal occurrence of this tumor is very rare. We report a 10-year-old girl with primary DSRCT arising within the left femur. The patient presented with knee pain, and radiological findings were strongly suggestive of osteogenic sarcoma. In addition to the typical microscopic appearance and immunophenotype, RT-PCR demonstrated the chimeric transcript of EWS-WT1, which is diagnostic of DSRCT. Pulmonary metastases were present at initial staging studies, but no abdominal or pelvic lesion was present. Despite chemotherapy and complete tumor excision, the patient developed progressive lung and bone metastases and died 3 years after initial presentation. This is the second reported case of primary DSRCT of bone with genetic confirmation.
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PMID:Primary desmoplastic small round cell tumor of the femur. 1847 May 11

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

Metastatic bone disease is often associated with bone pain, pathologic fractures, and nerve compression syndromes. Effective therapies to inhibit the progression of bone metastases would have important clinical benefits. Therefore, we developed a novel calcium phosphate-binding liposome for a bone-targeting drug delivery system. We synthesized a novel amphipathic molecule bearing a bisphosphonate (BP) head group to recognize and bind to hydroxyapatite (HA). We demonstrated that the liposomes having BP moieties show high affinity for HA. Doxorubicin-loaded liposomes adsorbed on the surface of HA significantly reduce the number of viable human osteosarcoma MG63 cells. This shows that the liposomes can be excellent carriers for anticancer drugs because they specifically target bone tissue. This calcium phosphate-binding liposome system could be used with many drugs for bone-related diseases such as osteoporosis, rheumatoid arthritis, and multiple myeloma.
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PMID:Synthesis of calcium phosphate-binding liposome for drug delivery. 1952 21

Organic anion transporting polypeptides (OATP) were identified as transmembrane transporters for various endo- and exogenous organic compounds (hormones, prostaglandins, anticancer drugs). OATP expression had been shown in different tissues, but not in bone tumors. Therefore, the expression pattern of all known eleven human OATPs was analyzed by quantitative RT-PCR in 21 human bone tumor specimens (osteosarcomas, bone metastases and benign aneurysmal bone cysts). Transcriptional expression of OATP1A2, 1C1, 2A1, 2B1, 3A1, 4A1, 4C1 and 5A1, but not of OATP1B1, 1B3 and 6A1 was observed in malignant and non-malignant tumor specimens at varying level. Importantly, OATP3A1, 4A1, 2B1 and 1C1 mRNA levels were significantly higher in aneurysmal bone cysts as compared to osteosarcomas. Elevated mRNA levels of OATP2A1, 1A2, and 4C1 in metastases from kidney cancer and of OATP5A1 in prostate cancer suggest that the OATP expression pattern in metastases is comparable to that of the primary tumors. Different to tissue, OATP expression in osteosarcoma cell lines HOS and MG-63, normal human osteoblast outgrowth cells (hOB) and bone marrow stromal cells (BMSC) is limited to OATP3A1 and OATP4A1. High OATP expression levels, particularly in benign bone tumors, suggest an important role of these transporters for providing hormones, their conjugates, prostaglandins and drugs in bone cells. Thereby, they may influence bone resorption and formation.
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PMID:Different expression patterns of organic anion transporting polypeptides in osteosarcomas, bone metastases and aneurysmal bone cysts. 1988 3

Radiation can be shown to produce satisfactory results in the treatment of simple bone cyst, chondroma, angioma, and benign giant-cell tumour. It is of particular value in benign giant-cell tumour where there are grounds for the opinion that it should largely replace surgical methods.Surgery remains the methods of choice in the treatment of osteogenic sarcoma but where the lesion is inaccessible growth restraint may be obtained by the use of X-ray therapy.Radiation, as a palliative measure, is of definite value in the treatment of bone metastases.Myelomata are uniformly responsive to X-ray therapy, which is capable of prolonging life and relieving pain in these cases.It is probable that radiation therapy is superior to surgery in treatment of Ewing's tumour if the diagnosis be made at an early stage of the disease.Direct invasion of the bone by tumour should not be considered a contra-indication to radiation therapy, particularly if the tumour is of a type known to be radio-sensitive.
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PMID:Radiation Therapy in Tumours of Bone: (Section of Radiology). 1999 47


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