Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0279530 (bone cancer)
 1,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From August 1989 to December 1990, we collected 1523 cases of malignancy at Tri-service General Hospital (TSGH), and 470 cases (30.9%) of these malignancy had pain complaint. Moreover, we found that 68.1% (79/116 cases) of malignancy with bony metastasis had pain complaint. These informations were obtained from medical records. By counting the site of these 1523 cases, the leading sites in sequence were lung (207 cases), stomach (164 cases), cervix uteri (132 cases), breast (117 cases) and colon (91 cases). Regarding the incidence of cancer pain among these malignancy, bone cancer had the highest incidence (75.0%), followed by tongue (66.7%), brain (65.7%), liver (62.3%) and pancreas (60.0%). There was no difference of the incidence of cancer pain between male and female. The incidences of cancer pain in different age groups were different; the young patients had higher incidence than elderly patients. The analgesics for cancer pain used most frequently by physicians at TSGH were nonsteroid anti-inflammatory drugs and meperidine. Although the therapeutic management of cancer pain has been advancedly developed, we found that the treatments of cancer pain by physicians at TSGH were not aggressive enough. Therefore, promotion of the concept in advanced pain control and techniques is our important task in the near future.
 ...
PMID:[The study of cancer pain and its correlates]. 175 62

Samarium-153 ethylenediaminetetramethylene phosphonic acid ([153Sm]EDTMP) has been proposed to palliate pain resulting from osteoblastic metastatic bone cancer. Encouraging results in dogs with primary malignant bone cancer provided the catalysis for human biodistribution studies in five patients with metastatic skeletal carcinoma. The objective was to assess the preferential localization of [153Sm]EDTMP in bony lesions and compare it to the 99mTc-labeled phosphonates. Blood clearance of [153Sm]EDTMP was rapid with minimal accumulation in nonosseous tissues. Both radiopharmaceuticals showed identical lesion uptake in 23 paired lesions (p greater than 0.05). This indicates that the two radiopharmaceuticals concentrate in metastatic skeletal lesions by the same mechanism and since [153Sm]EDTMP emits beta radiation it may be therapeutically useful in ameliorating metastatic bony cancer pain.
 ...
PMID:Human pharmacokinetics of samarium-153 EDTMP in metastatic cancer. 247 81

The cancer-related event that is most disruptive to the cancer patient's quality of life is pain. To begin to define the mechanisms that give rise to cancer pain, we examined the neurochemical changes that occur in the spinal cord and associated dorsal root ganglia in a murine model of bone cancer. Twenty-one days after intramedullary injection of osteolytic sarcoma cells into the femur, there was extensive bone destruction and invasion of the tumor into the periosteum, similar to that found in patients with osteolytic bone cancer. In the spinal cord, ipsilateral to the cancerous bone, there was a massive astrocyte hypertrophy without neuronal loss, an expression of dynorphin and c-Fos protein in neurons in the deep laminae of the dorsal horn. Additionally, normally non-noxious palpation of the bone with cancer induced behaviors indicative of pain, the internalization of the substance P receptor, and c-Fos expression in lamina I neurons. The alterations in the neurochemistry of the spinal cord and the sensitization of primary afferents were positively correlated with the extent of bone destruction and the growth of the tumor. This "neurochemical signature" of bone cancer pain appears unique when compared to changes that occur in persistent inflammatory or neuropathic pain states. Understanding the mechanisms by which the cancer cells induce this neurochemical reorganization may provide insight into peripheral factors that drive spinal cord plasticity and in the development of more effective treatments for cancer pain.
 ...
PMID:Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain. 1059 70

Bone cancer pain is common among cancer patients and can have a devastating effect on their quality of life. A chief problem in designing new therapies for bone cancer pain is that it is unclear what mechanisms drive this distinct pain condition. Here we show that osteoprotegerin, a secreted 'decoy' receptor that inhibits osteoclast activity, also blocks behaviors indicative of pain in mice with bone cancer. A substantial part of the actions of osteoprotegerin seems to result from inhibition of tumor-induced bone destruction that in turn inhibits the neurochemical changes in the spinal cord that are thought to be involved in the generation and maintenance of cancer pain. These results demonstrate that excessive tumor-induced bone destruction is involved in the generation of bone cancer pain and that osteoprotegerin may provide an effective treatment for this common human condition.
 ...
PMID:Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord. 1080

This study describes the first known model of bone cancer pain in the rat. Sprague-Dawley rats receiving intra-tibial injections of syngeneic MRMT-1 rat mammary gland carcinoma cells developed behavioural signs indicative of pain, including: mechanical allodynia, difference of weight bearing between hind paws and mechanical hyperalgesia. The development of the bone tumour and structural damage to the bone was monitored by radiological analysis, quantitative measurement of mineral content and histology. Intra-tibial injections of 3 x 10(3) or 3 x 10(4) syngeneic MRMT-1 cells produced a rapidly expanding tumour within the boundaries of the tibia, causing severe remodelling of the bone. Radiographs showed extensive damage to the cortical bone and the trabeculae by day 10-14 after inoculation of 3 x 10(3) MRMT-1 cells, and by day 20, the damage was threatening the integrity of the tibial bone. While both mineral content and mineral density decreased significantly in the cancerous bone, osteoclast numbers in the peritumoural compact bone remained unchanged. However, tartarate-resistant acid phosphatase staining revealed a large number of polykariotic cells, resembling those of osteoclasts within the tumour. No tumour growth was observed after the injection of heat-killed MRMT-1 cells. Intra-tibial injections of 3 x 10(3) or 3 x 10(4) MRMT-1 cells, heat-killed cells or vehicle did not show changes in body weight and core temperature over 19-20 days. The general activity of animals after injection with live or heat-killed MRMT-1 cells was higher than that of the control group, however, the activity of the MRMT-1 treated group declined during the progress of the disease. Rats receiving intra-tibial injections of MRMT-1 cells displayed the gradual development of mechanical allodynia and mechanical hyperalgesia/reduced weight bearing on the affected limb, beginning on day 12-14 or 10-12 following injection of 3 x 10(3) or 3 x 10(4) cells, respectively. These symptoms were not observed in rats receiving heat-killed cells or vehicle. Behavioural data suggest a reasonable time window for evaluation of anti-nociceptive agents between day 14 and 20 after cancer cell inoculation in this model. Acute treatment with morphine (1-3mg/kg, subcutanously (s.c.)) produced a dose-dependent reduction in the response frequency of hind paw withdrawal to von Frey filament stimulation 17 or 19 days following intra-tibial injections of 3 x 10(3) MRMT-1 cells. A significant reduction in the difference in hind limb weight bearing was also observed. Acute treatment with celebrex (10-30 mg/kg, s.c.) did not affect mechanical allodynia or difference in weight bearing in rats 20 days following treatment with 3 x 10(3) MRMT-1 cells. Although the pathophysiology of cancer pain is largely unknown, significant enhancement of glial fibrillary acidic protein (GFAP) staining in the corresponding segments of the ipsilateral spinal cord highlights the possible involvement of astrocytes. In summary, the induction of bone cancer in the rat by the syngeneic MRMT-1 mammary tumour cell line provides a valid pre-clinical model for pain associated with bone metastases. Significant mechanical hyperalgesia and allodynia develops in association with the progression of the tumour in the bone marrow cavity, while the general condition of the animal remains satisfactory. While acute treatment with morphine has some analgesic effect on hind limb sparing the selective COX-2 inhibitor, celebrex, has no influence on the pain-related behavioural changes in this model.
 ...
PMID:A rat model of bone cancer pain. 1193 69

More than half of all chronic cancer pain arises from metastases to bone, and bone cancer pain is one of the most difficult of all persistent pain states to fully control. Several tumor types including sarcomas and breast, prostate, and lung carcinomas grow in or preferentially metastasize to the skeleton where they proliferate, and induce significant bone remodeling, bone destruction, and cancer pain. Many of these tumors express the isoenzyme cycloxygenase-2 (COX-2), which is involved in the synthesis of prostaglandins. To begin to define the role COX-2 plays in driving bone cancer pain, we used an in vivo model where murine osteolytic 2472 sarcoma cells were injected and confined to the intramedullary space of the femur in male C3HHeJ mice. After tumor implantation, mice develop ongoing and movement-evoked bone cancer pain-related behaviors, extensive tumor-induced bone resorption, infiltration of the marrow space by tumor cells, and stereotypic neurochemical alterations in the spinal cord reflective of a persistent pain state. Thus, after injection of tumor cells, bone destruction is first evident at day 6, and pain-related behaviors are maximal at day 14. A selective COX-2 inhibitor was administered either acutely [NS398; 100 mg/kg, i.p.] on day 14 or chronically in chow [MF. tricyclic; 0.015%, p.o.] from day 6 to day 14 after tumor implantation. Acute administration of a selective COX-2 inhibitor attenuated both ongoing and movement-evoked bone cancer pain, whereas chronic inhibition of COX-2 significantly reduced ongoing and movement-evoked pain behaviors, and reduced tumor burden, osteoclastogenesis, and bone destruction by >50%. The present results suggest that chronic administration of a COX-2 inhibitor blocks prostaglandin synthesis at multiple sites, and may have significant clinical utility in the management of bone cancer and bone cancer pain.
 ...
PMID:Simultaneous reduction in cancer pain, bone destruction, and tumor growth by selective inhibition of cyclooxygenase-2. 1249 78

The recent development of rodent models of bone cancer pain has started to provide the basis for demonstrating the particular neurochemical and behavioral entity of cancer pain. Behaviourally, both spontaneous pain and hyperalgesia related to mechanical, but not thermal, noxious stimuli have been described in cancer-bearing animals. We have carried out a histological and behavioural study focused on the reactivity to noxious heat in C3H/HeJ mice receiving an intratibial injection of 10(5) NCTC 2472 cells. These cells, able to induce an osteosarcoma, break through bone into soft tissues 2 weeks after cell inoculation, producing a macroscopical increase of the limb size from the fourth week. Thermal reactivity is diminished during the first 2 weeks after cell implantation, this hypoalgesia being reversed by the administration of naloxone (10 mg/kg). In contrast, during the fourth and fifth weeks after NCTC 2472 cell implantation, an increased nociceptive heat reactivity, instead of hypoalgesia, was obtained. This thermal hyperalgesia was prevented by the systemic administration of morphine (15 mg/kg). Throughout the whole period studied, mice showed signs of spontaneous pain behaviour that reached its maximum 3 weeks after inoculation. In conclusion, we show that the presence of thermal heat hyperalgesia is preceded by an initial opioid-mediated hypoalgesic state, in this murine model of bone cancer pain.
 ...
PMID:Initial thermal heat hypoalgesia and delayed hyperalgesia in a murine model of bone cancer pain. 1267 70

Chronic pain, especially neuropathic pain and cancer pain, is often not adequately treated by currently available analgesics. Animal models provide pivotal systems for preclinical study of pain. This article reviews some of the most widely used or promising new models for chronic pain. Partial spinal ligation, chronic constriction injury, and L5/L6 spinal nerve ligation represent three of the best characterized rodent models of peripheral neuropathy. Recently, several mouse and rat bone cancer pain models have been reported. Primary or permanent cultures of sensory neurons have been established to study the molecular mechanism of pain, especially for neurotransmitter release and signal transduction. The emerging gene microarray, genomics and proteomics methods may be applied to throughly characterize these cells. Each model is uniquely created with distinct mechanisms, it is therefore essential to report and interpret results in the context of a specific model.
 ...
PMID:Animal and cellular models of chronic pain. 1293 39

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.
 ...
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.
 ...
PMID:Mechanisms that generate and maintain bone cancer pain. 1528 53


1 2 3 4 5 6 7 8 9 Next >>