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Query: UMLS:C0279530 (bone cancer)
 1,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although bone cancer pain can be severe and is relatively common, very little is known about the basic mechanisms that generate and maintain this debilitating pain. To begin to define the mechanisms that give rise to bone cancer pain, a mouse model was developed using the intramedullary injection and containment of osteolytic sarcoma cells in the mouse femur. These tumor cells induced bone destruction as well as ongoing and movement-evoked pain behaviors similar to that found in patients with bone cancer pain. In addition, there was a significant reorganization of the spinal cord that received sensory input from the cancerous bone, and this reorganization was significantly different from that observed in mouse models of chronic neuropathic or inflammatory pain. To determine whether this mouse model of bone cancer could be used to define the basic mechanisms giving rise to bone cancer pain, we targeted excessive osteoclast activity using osteoprotegerin, a secreted decoy receptor that inhibits osteoclast activity. Osteoprotegerin blocked excessive tumor-induced, osteoclast-mediated bone destruction, and significantly reduced ongoing and movement-evoked pain, and the neurochemical reorganization of the spinal cord. These data suggest that this model can provide insight into the mechanisms that generate bone cancer pain and provide a platform for developing and testing novel analgesics to block bone cancer pain.
Pain Med 2000 Dec
PMID:Bone cancer pain: from mechanism to model to therapy. 1510 76

Tumors including sarcomas and breast, prostate, and lung carcinomas frequently grow in or metastasize to the skeleton where they can induce significant bone remodeling and cancer pain. To define products that are released from tumors that are involved in the generation and maintenance of bone cancer pain, we focus here on endothelin-1 (ET-1) and endothelin receptors as several tumors including human prostate and breast have been shown to express high levels of ETs and the application of ETs to peripheral nerves can induce pain. Here we show that in a murine osteolytic 2472 sarcoma model of bone cancer pain, the 2472 sarcoma cells express high levels of ET-1, but express low or undetectable levels of endothelin A (ETAR) or B (ETBR) receptors whereas a subpopulation of sensory neurons express the ETAR and non-myelinating Schwann cells express the ETBR. Acute (10 mg/kg, i.p.) or chronic (10 mg/kg/day, p.o.) administration of the ETAR selective antagonist ABT-627 significantly attenuated ongoing and movement-evoked bone cancer pain and chronic administration of ABT-627 reduced several neurochemical indices of peripheral and central sensitization without influencing tumor growth or bone destruction. In contrast, acute treatment (30 mg/kg, i.p.) with the ETBR selective antagonist, A-192621 increased several measures of ongoing and movement evoked pain. As tumor expression and release of ET-1 has been shown to be regulated by the local environment, location specific expression and release of ET-1 by tumor cells may provide insight into the mechanisms that underlie the heterogeneity of bone cancer pain that is frequently observed in humans with multiple skeletal metastases.
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PMID:Endothelin and the tumorigenic component of bone cancer pain. 1520 37

Although bone cancer pain can be severe and is relatively common, as it frequently arises from metastases from breast, prostate, and lung tumours, very little is known about the basic mechanisms that generate and maintain this chronic pain. To begin to define the mechanisms that give rise to bone cancer pain, we have developed mouse and rat models using the intramedullary injection and containment of tumour cells into the femur. These tumour cells induced bone remodelling as well as ongoing and movement evoked pain behaviours similar to that found in patients with bone cancer pain. In addition there is a significant reorganization of the spinal cord that received sensory input from the cancerous bone and this reorganization generated a neurochemical signature of bone cancer pain that is both dramatic and significantly different from that observed in mouse and rat models of chronic neuropathic or inflammatory pain. These models have provided insight into the mechanisms that drive cancer pain and have begun to allow the development of mechanism-based therapies. Together these advances should reduce tumour-induced pain and suffering and significantly improve the quality of life of cancer patients.
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PMID:Mechanisms that generate and maintain bone cancer pain. 1528 53

Patients with metastatic breast, lung or prostate cancer frequently have significant bone cancer pain. In the present report we address, in a single in vivo mouse model, the effects the bisphosphonate alendronate has on bone cancer pain, bone remodeling and tumor growth and necrosis. Following injection and confinement of green fluorescent protein-transfected murine osteolytic tumor cells into the marrow space of the femur of male C3H/HeJ mice, alendronate was administered chronically from the time the tumor was established until the bone cancer pain became severe. Alendronate therapy reduced ongoing and movement-evoked bone cancer pain, bone destruction and the destruction of sensory nerve fibers that innervate the bone. Whereas, alendronate treatment did not change viable tumor burden, both tumor growth and tumor necrosis increased. These data emphasize that it is essential to utilize a model where pain, skeletal remodeling and tumor growth can be simultaneously assessed, as each of these can significantly impact patient quality of life and survival.
Pain 2004 Sep
PMID:Bone cancer pain: the effects of the bisphosphonate alendronate on pain, skeletal remodeling, tumor growth and tumor necrosis. 1532 21

In a quest for more effective radiopharmaceuticals for pain palliation of metastatic bone cancer, this paper relates results obtained with ((117m)Sn labelled) Sn(II) complexed to the bone seeking bisphosphonate, N,N-dimethylenephosphonate-1-hydroxy-3-aminopropylidenediphosphonate (APDDMP). APDDMP is synthesised from the known bone cancer pain palliation agent 1-hydroxy-3-aminopropylidenediphosphonate (APD, Pamindronate). This work is performed to utilise the idea that the low bone marrow radio toxicity of (117m)Sn could afford a highly effective radiopharmaceutical in pain palliation but also in the curative treatment of bone metastasis. Complex-formation constants of APDDMP with the important blood plasma metal-ions, Ca(2+), Mg(2+), Zn(2+) as well as the added metal ion, Sn(2+) were measured by glass electrode potentiometry at 25 degrees C and I = 150 mM. Blood plasma models were constructed using the computer code ECCLES and the results compared with those gathered from tests on a rodent model. The ((117m)Sn-labelled) Sn(II)-APDDMP complex was found to have only some liver and bone uptake although a high trabecular to normal bone ratio was recorded. From the blood plasma model this was shown to be primarily due to the high affinity of APDDMP for Ca(II) causing some of the Sn(II)-APDDMP complex to dissociate. High kidney uptake and excretion as well as high bladder uptake was recorded which was shown to be due to the dissociation of the Sn(II)-APDDMP complex in blood plasma. Animal model observations could be explained by the blood plasma modelling.
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PMID:Comparison of the predicted in vivo behaviour of the Sn(II)-APDDMP complex and the results as studied in a rodent model. 1533 4

Although bone cancer pain can be severe and is relatively common, as it frequently arises from metastases from breast, prostate and lung tumours, relatively little is known about the basic mechanisms that generate and maintain this chronic pain. To begin to define the mechanisms that give rise to bone cancer pain, we developed a mouse model using the intramedullary injection and containment of osteolytic sarcoma cells into the mouse femur. These tumour cells induced bone destruction as well as ongoing and movement evoked pain behaviours similar to that found in patients with bone cancer pain. In addition, there was a significant neurochemical reorganization of sensory neurons that innervate the tumour bearing bone as well as in the spinal cord segments that received sensory input from the cancerous bone. This reorganization generated a neurochemical signature of bone cancer pain that was different from that observed in mouse models of chronic neuropathic or inflammatory pain. These data suggest that there is an inflammatory, neuropathic and tumorigenic component to bone cancer pain. Therefore defining when and how these different components drive bone cancer pain may allow the development of more selective analgesic agents to treat this chronic pain state.
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PMID:A mechanism-based understanding of bone cancer pain. 1546 52

The primary aim of the study was to correlate pain development during bone cancer growth with objectively obtained tumor-induced changes in bone morphology. Additionally morphine sensitivity of this bone pain was evaluated. Mice were injected into the femur with osteolytic NCTC2472 cells, and behaviorally followed during a 3-week period. During the observation period increasing pain behavior was observed in tumor-bearing animals. Tumor mice exhibited spontaneous and movement-evoked lifting, the latter evoked through non-noxious palpation of the tumor. Limb use during forced ambulation on a rotarod decreased to substantial non-use of the affected limb by day 23. On day 23, micro-computer tomography scans of the tumor-bearing bones were evaluated for bone destruction. Different bone parameters indicative of osteolysis or fragmentation were significantly correlated with pain behavior. In a separate group of mice the effects of different morphine doses on pain behavior were evaluated on days 17 and 21 of tumor growth. Spontaneous lifting and movement-evoked lifting were sensitive to morphine treatment, although stress-induced analgesia due to repeated restraint might minimize movement-evoked lifting in mice. Limb use during forced ambulation was only slightly ameliorated by high morphine doses.
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PMID:Bone cancer pain model in mice: evaluation of pain behavior, bone destruction and morphine sensitivity. 1550 Dec 99

Cancer-induced bone diseases are common and can have a devastating impact at the end of life. One of the most difficult sequelae of cancer is metastases to the skeleton, an event that results in bone destruction and bone cancer pain. Bone cancer pain is usually progressive as the disease advances, and is particularly difficult to treat. Recently, experimental models of bone cancer pain have been developed and have provided seminal insight in understanding the pathophysiology of bone cancer pain. Animal models of bone cancer provided the finding that bone destruction (osteolysis) is associated with pain, and it has been determined that cancer-induced osteolysis is mediated by osteoclasts. Having established that RANK ligand contributed to cancer-induced osteoclastogenesis, it was determined that disruption of the RANKL-RANK axis with OPG inhibited tumor-induced osteoclastogenesis and decreased bone cancer pain.
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PMID:Bone cancer pain and the role of RANKL/OPG. 1561 97

Pain often discloses the existence of bone tumors in children. The complex physiopathology of pain in malignant bone tumors remains largely unknown and is currently investigated. Cancer-related bone pain is independent from the type and the location of the tumor, and from the number and size of the malignant lesions. It does not necessarily increase with tumor growth. Pain, which is the most common early symptom of bone cancer, may also be present at every step of the disease. It may arise from postsurgery injury, side effects of chemo- or radiotherapy, tumor evolution, secondary sequels of treatments, phantom pain. Tumor eradication using cancer therapeutic strategies is the major etiological treatment option for bone cancer pain. Symptom control requires multidisciplinary medical management with drugs effective against bone lysis, analgesics, drugs with anti-neuropathic activity, as well as non-pharmacological techniques and psycho-social management. This psycho-social management must be tailored to the specific needs of teenagers who are particularly prone to this pathological manifestation. Measures to prevent the occurrence of residual chronic pain must be implemented, whereas children and their family should be clearly informed of the risks and of analgesic options available.
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PMID:[Cancer-related bone pain in children]. 1569 47

The most common cancers, such as those affecting the breast, prostate, and lung have a strong predilection to metastasize to bone. Bone metastasis frequently results in pain, pathologic fractures, hypercalcemia, and spinal cord compression. Pain can have a devastating effect on the quality of life in advanced cancer patients and is a serious complication of cancer. Although significant advances are being made in cancer treatment and diagnosis, the basic neurobiology of bone cancer pain is poorly understood. New insights into the mechanisms that induce cancer pain now are coming from animal models. Chemicals derived from tumor cells, inflammatory cells, and cells derived from bone appear to be involved simultaneously in driving this frequently difficult-to-control pain state. Understanding the mechanisms involved in the pathophysiology of bone cancer pain will improve both our ability to provide mechanism-based therapies and the quality of life of cancer patients.
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PMID:Pathophysiology of bone cancer pain. 1572 43


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