Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteoblasts and osteoclasts are the two major bone cells involved in the bone remodeling process. Osteoblasts are responsible for bone formation while osteoclasts are the bone-resorbing cells. The major event that triggers osteogenesis and bone remodeling is the transition of mesenchymal stem cells into differentiating osteoblast cells and monocyte/macrophage precursors into differentiating osteoclasts. Imbalance in differentiation and function of these two cell types will result in skeletal diseases such as osteoporosis, Paget's disease, rheumatoid arthritis, osteopetrosis, periodontal disease, and bone cancer metastases. Osteoblast and osteoclast commitment and differentiation are controlled by complex activities involving signal transduction and transcriptional regulation of gene expression. Recent advances in molecular and genetic studies using gene targeting in mice enable a better understanding of the multiple factors and signaling networks that control the differentiation process at a molecular level. This review summarizes recent advances in studies of signaling transduction pathways and transcriptional regulation of osteoblast and osteoclast cell lineage commitment and differentiation. Understanding the signaling networks that control the commitment and differentiation of bone cells will not only expand our basic understanding of the molecular mechanisms of skeletal development but will also aid our ability to develop therapeutic means of intervention in skeletal diseases.
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PMID:Signaling networks that control the lineage commitment and differentiation of bone cells. 1919 55

Pain is one of the most severe and debilitating symptoms associated with several forms of cancer. Various types of carcinomas and sarcomas metastasize to skeletal bones and cause spontaneous bone pain and hyperalgesia, which is accompanied by bone degradation and remodeling of peripheral nerves. Despite recent advances, the molecular mechanisms underlying the development and maintenance of cancer-evoked pain are not well understood. Several types of non-hematopoietic tumors secrete hematopoietic colony-stimulating factors that act on myeloid cells and tumor cells. Here we report that receptors and signaling mediators of granulocyte- and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF) are also functionally expressed on sensory nerves. GM-CSF sensitized nerves to mechanical stimuli in vitro and in vivo, potentiated CGRP release and caused sprouting of sensory nerve endings in the skin. Interruption of G-CSF and GM-CSF signaling in vivo led to reduced tumor growth and nerve remodeling, and abrogated bone cancer pain. The key significance of GM-CSF signaling in sensory neurons was revealed by an attenuation of tumor-evoked pain following a sensory nerve-specific knockdown of GM-CSF receptors. These results show that G-CSF and GM-CSF are important in tumor-nerve interactions and suggest that their receptors on primary afferent nerve fibers constitute potential therapeutic targets in cancer pain.
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PMID:Hematopoietic colony-stimulating factors mediate tumor-nerve interactions and bone cancer pain. 1952 66

Dedifferentiated chordoma is a rare primary malignant bone cancer. Most cases of dedifferentiated chordoma (DC) are transformed from recurrent chordoma after surgical resection or radiation. The prognosis of DC is extremely poor because of the aggressive nature of the tumor and the potential distant metastases. We report a case of de novo DC of the sacrum in a patient without prior surgical procedure or radiation treatment. A complete review of reported cases sourced from reports published in English literature is discussed and expanded upon and conclusions on the treatment of DC are presented.
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PMID:De novo dedifferentiated chordoma of the sacrum: a case report and review of the literature. 1952 13

Mass spectrometric analysis of the low-molecular-weight (LMW) range of the serum/plasma proteome is revealing the existence of large numbers of previously unknown peptides and protein fragments, predicted to be derived from circulating low-abundance proteins. While genomics and proteomics are the primary discovery research tool, recent innovations in high-throughput proteomics are now standard practice for biomarker and target discovery. Surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS) is the current mainstay for serum or plasma analysis, although other methods are emerging as alternative high-throughput approaches. From a proteomics perspective, the bone cancers, such as myeloma, breast and prostate cancer bony metastases, and osteosarcoma, are likely among the least studied. As recent advances in proteomic technology have thrust the bone cancer field into the era of proteomics, a review of the current status of the proteome as it relates to the skeletal consequences of malignancy seems reasonable.
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PMID:The promise of bone cancer proteomics. 2039 40

In the United States, cancer is the second most common cause of death and it is expected that about 562,340 Americans will have died of cancer in 2009. Bone cancer pain is common in patients with advanced breast, prostate, and lung cancer as these tumors have a remarkable affinity to metastasize to bone. Once tumors metastasize to bone, they are a major cause of morbidity and mortality as the tumor induces significant skeletal remodeling, fractures, pain, and anemia. Currently, the factors that drive cancer pain are poorly understood. However, several recently introduced models of bone cancer pain, which closely mirror the human condition, are providing insight into the mechanisms that drive bone cancer pain and guide the development of mechanism-based therapies to treat the cancer pain. Several of these mechanism-based therapies have now entered human clinical trials. If successful, these therapies have the potential to significantly enlarge the repertoire of modalities that can be used to treat bone cancer pain and improve the quality of life, functional status, and survival of patients with bone cancer.
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PMID:Bone cancer pain. 2053 32

Bisphosphonates are widely used in the management of metastatic disease to bone and in diseases of altered bone turnover. Recently, multiple-case series and retrospective studies have established a relationship between necrotic bone lesions localized to the jaw and the use of chronic bisphosphonate therapy. This condition has been named bisphosphonate-related osteonecrosis of the jaw (BRONJ). To evaluate the potential risks associated with this new and emerging complication, stage-specific management strategies and guidelines have been developed. In view of the widespread use of chronic bisphosphonate therapy, the observation of an associated risk of osteonecrosis of the jaw should alert practitioners to monitor for this previously unrecognized complication and to reevaluate the indications for and the duration of bisphosphonate therapy in patients with osteopenia/osteoporosis and cancer. Morbidity associated with BRONJ might be prevented or reduced by implementing prevention strategies and establishing early diagnostic procedures. The current widespread use of bisphosphonates as an inhibitor of bone resorption is directly attributable to their efficacy in improving the quality of life for patients with metastatic bone cancer, osteoporosis, and Paget's disease.
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PMID:Bisphosphonate-related osteonecrosis of the jaw: an overview. 2094 80

Osteosarcoma is the most common type of malignant bone cancer, accounting for 35% of primary bone malignancies. Because cancer cells utilize glucose as their primary energy substrate, the expression and regulation of glucose transporters (GLUT) may be important in tumor development and progression. GLUT expression has not been studied previously in human osteosarcoma cell lines. Furthermore, although insulin and insulin-like growth factor (IGF-I) play an important role in cell proliferation and tumor progression, the role of these hormones on GLUT expression and glucose uptake, and their possible relation to osteosarcoma, have also not been studied. We determined the effect of insulin and IGF-I on GLUT expression and glucose transport in three well-characterized human osteosarcoma cell lines (MG-63, SaOs-2, and U2-Os) using immunocytochemical, RT-PCR and functional kinetic analyses. Furthermore we also studied GLUT isoform expression in osteosarcoma primary tumors and metastases by in situ hybridization and immunohistochemical analyses. RT-PCR and immunostaining show that GLUT1 is the main isoform expressed in the cell lines and tissues studied, respectively. Immunocytochemical analysis shows that although insulin does not affect levels of GLUT1 expression it does induce a translocation of the transporter to the plasma membrane. This translocation is associated with increased transport of glucose into the cell. GLUT1 is the main glucose transporter expressed in osteosarcoma, furthermore, this transporter is regulated by insulin in human MG-63 cells. One possible mechanism through which insulin is involved in cancer progression is by increasing the amount of glucose available to the cancer cell.
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PMID:Insulin regulates GLUT1-mediated glucose transport in MG-63 human osteosarcoma cells. 2132 33

Over the past few years, significant progress has been made in cancer therapy. Indeed, the lifespan of cancer patients has significantly increased. Although patients live longer, cancer-related pain remains a daily problem affecting their quality of life, especially when metastases reach the bone. In patients coping with cancer-induced bone pain, morphine and NSAIDs, often used in combination with other medications, are the most commonly used drugs to alleviate pain. However, these drugs have dose-limiting side effects. Morphine and other routinely used opioids are mu opioid receptor (MOPR) agonists. The MOPR is responsible for most opioid-related adverse effects. In the present study, we revealed potent analgesic effects of an intrathecally-administered selective delta opioid receptor (DOPR) agonist, deltorphin II, in a recently developed rat bone cancer model. Indeed, we found that deltorphin II dose-dependently reversed mechanical allodynia 14 days post-surgery in this cancer pain model, which is based on the implantation of mammary MRMT-1 cells in the femur. This effect was DOPR-mediated as it was completely blocked by naltrindole, a selective DOPR antagonist. Using the complete Freund's adjuvant model of inflammatory pain, we further demonstrated that deltorphin II was equipotent at alleviating inflammatory and cancer pain (i.e. similar ED50 values). Altogether, the present results show, for the first time, that activation of spinal DOPRs causes significant analgesia at doses sufficient to reduce inflammatory pain in a rat bone cancer pain model. Our results further suggest that DOPR represents a potential target for the development of novel analgesic therapies to be used in the treatment of cancer-related pain.
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PMID:Spinal activation of delta opioid receptors alleviates cancer-related bone pain. 2145 44

Metastatic events to the bone occur frequently in numerous cancer types such as breast, prostate, lung, and renal carcinomas, melanoma, neuroblastoma, and multiple myeloma. Accumulating evidence suggests that the inflammatory cytokine interleukin (IL)-6 is frequently upregulated and is implicated in the ability of cancer cells to metastasize to bone. IL-6 is able to activate various cell signaling cascades that include the STAT (signal transducer and activator of transcription) pathway, the PI3K (phosphatidylinositol-3 kinase) pathway, and the MAPK (mitogen-activated protein kinase) pathway. Activation of these pathways may explain the ability of IL-6 to mediate various aspects of normal and pathogenic bone remodeling, inflammation, cell survival, proliferation, and pro-tumorigenic effects. This review article will discuss the role of IL-6: 1) in bone metabolism, 2) in cancer metastasis to bone, 3) in cancer prognosis, and 4) as potential therapies for metastatic bone cancer.
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PMID:Clinical significance of interleukin (IL)-6 in cancer metastasis to bone: potential of anti-IL-6 therapies. 2162

Bone metastases are a common feature of many cancers and patients with a previous history of cancer may present with bony symptoms to many different specialties. It is, however, easy to mistakenly diagnose secondary bone cancer in patients who have abnormal imaging, when the cause of the symptoms and the abnormal imaging results is benign disease. In this review, common diagnostic mistakes are described with examples of imaging of both benign and malignant bony disease. The relative risk of developing bone metastases in different cancers is discussed, as well as the rationale of different therapies for proven bony metastases, such as radiotherapy, bisphosphonate therapy, orthopaedic intervention and vertebroplasty.
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PMID:Diagnosis and management of bone metastases. 2218 72


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