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)

Mandibular symphyseal resection requires composite reconstructions, often with unsatisfactory morphofunctional results. Seven patients with advanced squamous cell carcinoma of the floor of the mouth underwent block resection with immediate reconstruction, using the removed mandible treated with liquid nitrogen and covered with a free forearm flap. In all cases, the resection was radical and no major postoperative complications occurred. Two patients died in 6 months for distant metastases and regional recurrence. In the other 5 patients, no local recurrence occurred at a mean follow-up of 52 months (36-70). Immediate cosmetic and functional results were good. Of the 5 patients, 4 had late complications requiring further surgery. This technique of bone reimplantation produces no donor site morbidity, perfect immediate morphological result, and is of low cost. The free forearm flap is effective in sealing the oral cavity, though further clinical and experimental studies are necessary to reduce late local complications.
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PMID:Composite reconstruction in advanced cancer of the mouth floor: autogenous frozen-thawed mandibular bone and free flaps. 1720 73

Osteosarcoma is one of the most common primary malignant tumors of the bone in children and adolescents. Some patients continue to have a poor prognosis, as they have metastatic disease and frequent occurrence of drug resistance. Zoledronate is a nitrogen-containing bisphosphonate that has been used for the treatment of hypercalcemia and bone metastasis, because it induces apoptosis in osteoclasts and tumor cells by inhibiting the isoprenylation of intracellular small G proteins. Besides inhibiting isoprenylation, little is known about the manner by which bisphosphonates inhibit cellular proliferation and induce apoptosis. This prompted us to investigate the inhibitory effects of zoledronate in human osteosarcoma cell lines, HOS and MG63. HOS cells accumulated in S phase around 6 h after treatment with 10 microM zoledronate, followed by apoptosis. When HOS cells were treated with zoledronate, ATM kinase and its substrate, check-point kinase (Chk)1, were phosphorylated. Zoledronate also induced phosphorylation of cdc25a (Thr506) in HOS cells, which is a substrate of Chk1, and its phosphorylation is known to be critical for S phase arrest. Following treatment with zoledronate, phosphorylated histone H2AX (gamma-H2AX) displayed patterns of nuclear foci in HOS cells. As gamma-H2AX accumulates at dsDNA breaks, these results demonstrate that zoledronate induced DNA damage and S phase arrest, accompanied by activation of the ATM/Chk1/cdc25 pathway in a human osteosarcoma cell line.
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PMID:Zoledronate-induced S phase arrest and apoptosis accompanied by DNA damage and activation of the ATM/Chk1/cdc25 pathway in human osteosarcoma cells. 1761 84

Cancer patients, particulary those with bone metastatses, are at high risk of skeletal complications. Patients with advanced cancer and bone metastatses freguently experience debilitating skeletal complications that can substantially affect their quality of life.Many types of cancer metastasize to the bone, but breast and prostate cancer account for roughly 70-80% of bone metastatses. Bisphosphonates have emerged as a leading therapeutic intervention for the treatment and prevention of sceletal complications of malignancy. Bisphosphonates have a variety of activities in bone and can effectively normalize serum calcium, delay the onset and reduce the incidence of sceletal complications, and may reduce bone pain. Zoledronic Acid is highly potent, new-generation, nitrogen-containing bisphosphonate that has superior potency and pharmacologic properties compared with other bisphosphonates. It has been shown to be highly effective in the treatment of osteolitic, mixed and osteoblastic bone metastatses in patients with breast cancer and prostate cancer.
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PMID:Zoledronic Acid in the treatment of bone metastases from the breast and prostate carcinoma. 1803 35

During comprehensive treatment using bisphosphonates in cases showing skeletal metastases or those with breakdowns in the skeletal metabolism in the form of osteoporosis, the patients developed complications in the form of osteonecrosis of the jaw. The complication resides in a defect in vascularisation of the skeletal tissue, which is brought about by the properties of nitrogen molecules found in modern bisphosphonates. The ailment in the jaw is provoked by the extraction of a tooth. The wound on the bone does not heal and the alveolitis is accompanied by excruciating pain and can deteriorate into extensive ostitis with bare necrotic ends of the bone. At the beginning, the treatment of the affected part of the jaw is guarded and conservative, followed later by surgical removal of the necrotically deteriorating bone, sequestrotomy or partial resection of the bone without damaging the wholeness of the jaw, always accompanied with effective anti-biotic therapy. As in cancer patients where radiation will be used, treatment with bisphosphonates requires dental examination and indicated extraction of teeth within a preventive strategy. Any resulting complications should be seen-to by a jaw specialist.
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PMID:[Osteonecrosis of the jaw following complex tumour treatment using bisphosphonates]. 1818 Dec 84

An understanding of differential gene expression in highly metastatic osteosarcoma could provide gene targets for treatment of metastases. We compared gene expression profiles of high- (LM7) and low- (LM2) metastatic SaOS2-derived cell lines in an in vitro tissue culture model and examined several differentially regulated genes in vivo in a murine orthotopic xenograft model. We hypothesized an orthotopic inoculation of LM2 and LM7 cells would establish a primary lesion and the gene expression profile of cells grafted in this fashion would resemble the gene expression profile observed in an in vitro model. Thirty-five days after inoculation, animals were euthanized and both tibiae were harvested and rapidly frozen in liquid nitrogen. Human-specific GAPDH mRNA was present in two of four tibias inoculated with LM2 cells and three of four tibias inoculated with LM7 cells. Tibiae displaying the presence of human cells were assayed by semiquantitative reverse transcriptase polymerase chain reaction. We observed poor correspondence of in vitro to in vivo gene expression for either cell line. Accordingly, in vitro osteosarcoma gene expression data must be interpreted with caution until confirmed in vivo. Our orthotopic injection model allowed in vivo study of differential gene expression between these two cell lines but did not show radiographic evidence of an established primary lesion.
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PMID:Metastatic osteosarcoma gene expression differs in vitro and in vivo. 1851 56

We evaluated the possible induction of a systemic immune response to increase anti-tumour activity by the re-implantation of destructive tumour tissue treated by liquid nitrogen in a murine osteosarcoma (LM8) model. The tumours were randomised to treatment by excision alone or by cryotreatment after excision. Tissue from the tumour was frozen in liquid nitrogen, thawed in distilled water and then re-implanted in the same animal. In addition, some mice received an immunological response modifier of OK-432 after treatment. We measured the levels of interferon-gamma and interleukin-12 cytokines and the cytotoxicity activity of splenocytes against murine LM8 osteosarcoma cells. The number of lung and the size of abdominal metastases were also measured. Re-implantation of tumour tissue after cryotreatment activated immune responses and inhibited metastatic tumour growth. OK-432 synergistically enhanced the anti-tumour effect. Our results suggest that the treatment of malignant bone tumours by reconstruction using autografts containing tumours which have been treated by liquid nitrogen may be of clinical value.
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PMID:Re-implantation of tumour tissue treated by cryotreatment with liquid nitrogen induces anti-tumour activity against murine osteosarcoma. 1875 69

The paper describes the synthesis and characterization of a new platinum dinuclear complex (2) bearing a nitrogen-containing geminal bisphosphonate (NBP, 1), structurally related to the commercial drug risedronate. NBPs themselves have shown in quite a few cases to be endowed with anticancer activity, therefore the new platinum complex has two potential antitumor moieties (the NBP ligand and the platinum residue) and could have high affinity for bone tumors or metastases (due to the presence of NBP). The free bisphosphonate (1) has been crystallized by a sol-gel method and characterized by X-ray diffraction analysis. The platinum complex (2) has been found to have a dinuclear structure with the bisphosphonate bridging two platinum moieties in a W conformation.
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PMID:A new dinuclear platinum complex with a nitrogen-containing geminal bisphosphonate as potential anticancer compound specifically targeted to bone tissues. 1876 Apr 82

Bisphosphonates (BPs), as inhibitors of osteoclasts, are widely used in the management of metastatic bone disease and in the prevention of osteomalacia and osteoporosis. Recent cases of bone necrosis of the jaws have been associated with the use of bisphosphonate therapy. A case is presented of a patient with osteonecrosis of the maxilla with a history of long-term bisphosphonate therapy for metastatic breast cancer. The authors treated the patient and suggest appropriate patient management guidelines with reference to current knowledge. Although a definitive treatment for bisphosphonate-associated osteonecrosis has not yet been established, clinicians must be aware of the pharmacologic properties of several bisphosphonates currently available and their indications, susceptible risk factors in the development of osteonecrosis of the jaws, the clinical signs and symptoms, and recommendations for patient management, including prevention and early recognition. BPs, potent inhibitors of osteoclast-mediated bone resorption, were first introduced more than 20 years ago. Since then, they have been used widely in the management of bone diseases, including hypercalcemia related to malignancy, myeloma-related bone disease, Paget's disease and osteoporosis. They have also been shown to inhibit tumor cell proliferation and inhibit angiogenesis. These additional features have made BPs useful in the treatment of metastatic disease, including breast and prostate cancer, resulting in a rise in the medical use of these drugs. However, recent reports suggest that BPs, particularly the nitrogen-containing BPs pamidronate (Aredia) and zoledronic acid (Zometa), both manufactured by Novartis of East Hanover, NJ, are capable of causing bisphosphonate-associated osteonecrosis of the jaw (BON). With 2.5 million patients treated with pamidronate and/or zoledronate worldwide, BON occurs in about one per 10,000 treated patients (Novartis, unpublished data, 2004). Currently, the total number of reported cases associated with alendronate (Fosamax, Merck and Co. Inc., White-house Station, NJ) the most commonly prescribed oral bisphosphonate, is approximately 170 worldwide (C. Arsver, oral communication, March 2006). This corresponds to a spontaneous BON incidence of approximately 0.7 cases per 100,000-years exposure. However, there is insufficient data to determine why the osteonecrosis reported seems to particularly affect the jaw, with a slightly higher rate in the mandible than the maxilla. This report concerns the management of a patient with BON. Information provided includes: the pharmacologic properties of the several bisphosphonates currently available; the pathobiological mechanism; the clinical presentation of the oral lesions; and recommendations for the oral management of patients who have received BP therapy, with consideration of a preventative approach based on current knowledge.
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PMID:Bisphosphonate-associated osteonecrosis: a clinician's reference to patient management. 1876 52

Bone is the most common organ for tumor metastasis, especially in patients with cancers of the breast or prostate. Bone metastases disrupt skeletal metabolism and result in considerable skeletal morbidity, including intractable, chronic bone pain, hypercalcemia of malignancy, pathologic fracture and spinal-cord compression. In addition to the chronic pain caused by bone metastases, skeletal-related events (SREs) such as pathologic fractures and spinal-cord compression can result in acute increases in pain. These effects can severely impair mobility and contribute to a general decrease in quality of life. Palliative options to treat bone metastases include radiotherapy, analgesics, surgery and bisphosphonates. These drugs bind to the surface of the bone and impair osteoclast-mediated bone resorption, and reduce the tumor-associated osteolysis that is initiated by the development of skeletal metastases. In addition to preventing SREs, bisphosphonates can palliate bone pain caused by a variety of solid tumors. This Review summarizes the clinical trial data of bisphosphonates for the prevention of SREs and the palliation of bone pain. Among these agents, nitrogen-containing bisphosphonates are recognized as the most effective, and zoledronic acid has demonstrated the broadest clinical utility.
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PMID:Effect of bisphosphonates on pain and quality of life in patients with bone metastases. 1919 May 92

Since osteonecrosis of the jaw was related to biphosphonate administration by Marx, studies showing clinical symptoms, drug and surgical therapies overwhelmed the literature. Furthermore, the literature demonstrated the correlation between chronic biphosphonate adsumption and osteonecrosis of the jaw onset. Nitrogen-containing biphosphonates are widely used for the management of metastatic cancer, for prevention and treatment of osteoporosis, for the treatment of Paget's disease, and for the management of acute hypercalcemia. According to our experience, the treatment of BRON-J's lesions is difficult and prolonged. For this reason, in order to avoid these complications it is mandatory to perform a risk staging in patients who must undergo biphosphonate administration. When pharmacologic treatments with antibiotics and local antiseptics are not able to control the development of BRON-J's complications, the clinicians should perform radical surgical treatments such as the resection of the bone involved.
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PMID:Biphosphonates-related osteonecrosis of the jaw: Clinical and physiopathological considerations. 1943 26


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