Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human prostate contains two major acid phosphatase isoenzymes, 2 and 4. Isoenzyme 2 is a glycoprotein with slow electrophoretic mobility. Treatment with sialidase increases its electrophoretic mobility to approach that of isoenzyme 4 which contains no carbohydrate. The identical protein structure of isoenzyme 2 and 4 was revealed by their antigenic identity. Serum acid phosphatase isoenzyme 5 is a different protein species and has no antigenic relationship to isoenzymes 2 and 4. Our results indicate that the elevation of isoenzyme 5 in late stages of prostatic carcinoma with bone metastases is attributable to increased osteoclastic activity.
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PMID:Antigenic and molecular relationship of human prostatic acid phosphatase isoenzymes. 742 81

In a retrospective analytical study the authors evaluated in 86 patients, mean age 69 years (range 55-85 years), with a newly diagnosed untreated prostate carcinoma the sensitivity, specificity, positive and negative predictive value of specific prostatic antigen (PSA), acid phosphatase (AP), alkaline phosphatase (AP') and pain in relation to possible affection of bones by secondaries. The authors found a highly negative predictive value for assessment of bone metastases when PSA values were lower than 10 ng/ml (96%), at levels under 20 ng/ml (94%) and a highly positive predictive value at levels higher than 50 ng/ml (97%). When AP and AP' are negative and there is no pain the occurrence of secondaries is of low probability. These results make it possible to differentiate some patients where scintigraphy of the skeleton is not inevitable. This procedure can be applied above all in patients where radical prostatectomy is not indicated.
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PMID:[Levels of prostate-specific antigen, acid phosphatase, alkaline phosphatase and pain in the prediction of bone metastases in patients with newly diagnosed prostatic carcinoma]. 753 51

The asymptomatic patient who has been treated with a curative intent by surgery or irradiation for cancer of the prostate needs only a PSA and a baseline bone scan for his initial (post-treatment) follow-up. Rising serum PSA levels which still remain in the moderate range may signal a local recurrence, but this must be documented histologically. The therapeutic options to consider for a documented local recurrence include pelvic irradiation for the previously operated patient, or surgery for a post-irradiation recurrence. A serum PSA which rises to high levels following treatment will often be associated with distant metastases, and this is more certain if the original tumor was locally advanced and/or the histology was poorly differentiated or aneuploid. A newly elevated serum acid phosphatase in a treated patient with prostate cancer will usually signify disseminated disease also. Whether to wait until a patient becomes symptomatic from a recurrence or to initiate endocrine treatment solely on the basis of a rising serum marker still remains a point of controversy. The overall survival of Stage D2 patients has not been prolonged by endocrine manipulations which were instituted before symptoms of widespread dissemination appeared. The routine use of periodic imaging studies to follow asymptomatic patients with prostate cancer after they have received treatment cannot be justified for clinical decision-making purposes. On the other hand, in treated patients who develop new symptoms suggesting bone metastases, radionuclide scans which are correlated carefully with the patient's symptoms and with radiographs of "hot" areas on the scans are indicated. When a suspected diagnosis of metastatic disease still remains in doubt, elevated serum tumor markers may provide additional evidence. Imaging studies can also be used to guide percutaneous biopsies of suspected metastases in bones (radionuclide scans and radiographs), or of persistent tumor in an irradiated prostate gland or at the urethro-vesical junction after surgery (TRUS). Since cancer of the prostate often progresses slowly and disseminated disease remains incurable at this time, some degree of uncertainty about the presence of metastases or of recurrent local disease might be safer and less costly than the use of multiple diagnostic studies and aggressive treatment (including endocrine manipulations) in nonsymptomatic patients.
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PMID:Surveillance of patients with prostate cancer after treatment: the roles of serologic and imaging studies. 768 12

From a prospective database of 614 consecutive men with newly diagnosed prostatic cancer an audit of outcome was studied in 169 men who presented with bone metastases and subsequently received hormonal manipulation in the form of monotherapy. The cohort was divided into 2 groups according to serum alkaline and acid phosphatase enzyme levels. Men with normal alkaline phosphatase levels (41.5%) had a better prognosis (median survival 38 months) than those with elevated levels at presentation (58.5%) (median survival 19 months). This difference was highly significant. A similar stratification on prostatic acid phosphatase levels did not yield any prognostic significance. With regard to cause-specific survival, serum alkaline phosphatase was an even more powerful prognosticator, with a median survival of 45 and 21 months for patients with normal and elevated levels respectively. Thus monotherapy is recommended for metastatic prostate cancer patients with normal serum alkaline phosphatase, but for those with elevated alkaline phosphatase the alternative avenues of treatment must be explored.
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PMID:Audit and its impact in the management of advanced prostatic cancer. 826 6

Eighty-two patients with advanced prostatic carcinoma were treated with a long-acting luteinizing hormone releasing hormone (LHRH) agonist (Zoladex depot, Zeneca Pharmaceuticals, England). The outcome of the treatment was monitored on the basis of the following prognostic factors: local stage, number of bone metastases, histological differentiation grade and prostate-specific acid phosphatase (PAP), alkaline phosphatase (AF) and testosterone levels. The patients were followed-up until disease progression or until death. The mean weight of the prostate decreased from 48.1 g to 17.4 g (P < 0.00001) during the first year of treatment. Statistically there was a significant difference in regard to appearance of progression between different clinical stages (P < 0.00001). The prognosis was poorest in patients with more than 10 metastases at the primary stage. If the PAP level was initially higher (over 20 micrograms/L), the prognosis was very poor. Statistically there was a significant difference between the high PAP level and the slightly elevated or normal PAP (P < 0.02 and P < 0.005, respectively). Alkaline phosphatase (AF) appeared to be a good prognostic factor. The prognosis was particularly poor, if the AF level exceeded 1000 U/L (P < 0.00001 and P < 0.05, compared with normal AP and slightly elevated AP level, respectively). Surprisingly, a high pre-treatment testosterone level worsened the prognosis during the LHRH agonist treatment (P < 0.01, compared to patients with normal testosterone level). This is a new finding and controversial to the findings reported before.
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PMID:Prognostic factors of advanced prostatic carcinoma. 829 78

Bone scintigraphy with 99mtechnetium-labelled polyphosphonates is the most sensitive test for early detection of skeletal metastases. Bone metastases are a major factor in prognosis and have a considerable influence on the therapy selected. In patients with prostate cancer, we recommend routine bone scintigraphy in the initial staging. Follow-up bone scans are indicated whenever a patient develops pain, an elevated level of acid phosphatase, or a rise in prostate specific antigen (PSA). Routine bone scans are not necessary for the initial staging of patients with renal cell carcinomas, bladder carcinomas and testicular tumours. Scans should be routinely performed, however, in patients with bone pain or elevated alkaline phosphatase or when radiological findings are inconclusive. Bone scanning is necessary in patients with neuroblastoma, both for the initial diagnosis and during follow-up in all cases with known skeletal involvement. In addition, bone scintigraphy should be performed in cases of recurrent or suspected malignant phaeochromocytoma as a complement to scintigraphy with iodine-123- or iodine-131-MIBG, respectively. Even though skeletal scintigraphy is a very sensitive test, it lacks specificity. This can be compensated, however, by careful interpretation of the scan in the light of the patient's history and the clinical findings. As a positive side-effect, bone scanning--especially in the form of multiphase scintigraphy--may detect renal abnormalities, concurrent diseases or complications in the upper or lower urinary tract. If scintigraphic findings are doubtful, plain film radiographs are required or, in selected cases, bone biopsy must be performed.
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PMID:[Nuclear medicine diagnosis and therapy in urology. Diagnosis of bone metastases]. 847 16

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.
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PMID:A rat model of bone cancer pain. 1193 69

Inoculation of syngeneic MRMT-1 mammary tumour cells into one tibia of female rats produced tumour growth within the bone associated with a reduction in bone mineral density (BMD) and bone mineral content (BMC), severe radiological signs of bone destruction, together with the development of behavioural mechanical allodynia and hyperalgesia. Histological and radiological examination showed that chronic treatment with the bisphosphonate, zoledronic acid (30 microg/kg, s.c.), for 19 days significantly inhibited tumour proliferation and preserved the cortical and trabecular bone structure. In addition, BMD and BMC were preserved and a dramatic reduction of tartrate resistant acid phosphatase-positive polykaryocytes (osteoclasts) was observed. In behavioural tests, chronic treatment with zoledronic acid but not the significantly less effective bisphosphonate, pamidronate, or the selective COX-2 inhibitor, celebrex, attenuated mechanical allodynia and hyperalgesia in the affected hind paw. Zoledronic acid also attenuated mechanical hyperalgesia associated with chronic peripheral neuropathy and inflammation in the rat. In contrast, pamidronate or clodronate did not have any anti-hyperalgesic effect on mechanical hyperalgesia in the neuropathic and inflammatory pain models. We conclude that zoledronic acid, in addition to, or independent from, its anti-metastatic and bone preserving therapeutic effects, is an anti-nociceptive agent in a rat model of metastatic cancer pain. This unique property of zoledronic acid amongst the bisphosphonate class of compounds could make this drug a preferred choice for the treatment of painful bone metastases in the clinic.
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PMID:Disease modifying and anti-nociceptive effects of the bisphosphonate, zoledronic acid in a model of bone cancer pain. 1246 93

Diagnosis and follow-up of bone metastases in breast cancer patients usually rely on symptoms and imaging studies. Tartrate-resistant acid phosphatase 5b (TRACP 5b) is a specific marker of osteoclasts and is herein proposed as a marker of bone metastasis in breast cancer patients. An immunoassay using a monoclonal antibody, 14G6, was used to measure the activity of serum TRACP 5b at pH 6.1 in 30 early breast cancer patients without bone metastasis and in 30 aged-matched breast cancer patients with bone metastasis. Another 60 normal volunteers were recruited as controls. Bone alkaline phosphatase (BAP), a traditional marker of bone turnover, was also measured in selected cases. The overall mean TRACP 5b activity in normal women was 2.83 +/- 1.1 U/l, and it increased with age. The mean TRACP 5b activity in early breast cancer patients did not differ from that of the normal group (2.93 +/- 0.64 vs. 2.83 +/- 1.1 U/l; p = 0.66), whereas it was significantly higher in breast cancer patients with bone metastasis (5.42 +/- 2.5 vs. 2.83 +/- 1.1 U/l; p < 0.0001). BAP activity was significantly higher in breast cancer patients with bone metastasis than in early breast cancer patients (p = 0.004). Serum TRACP 5b activity correlated well with BAP activity in breast cancer patients with bone metastasis (p < 0.0001), but not in normal individuals or in patients without bone metastasis. TRACP 5b activity can be considered a surrogate indicator of bone metastasis in breast cancer patients.
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PMID:Tartrate-resistant acid phosphatase 5b as a serum marker of bone metastasis in breast cancer patients. 1515 86

Prognosis in prostate cancer is determined, in greater part, by the presence of metastases. Bone metastases can occur in any part of the skeleton even, for example, at the base of the skull. We present a case of a 78 year old male who, in December 2001, presented with paralysis of the third cranial nerve. The NMR and CAT scans were normal and circulating levels of PSA were elevated. He was referred to the Urology Service where the treatment guidelines included complete androgen block. Subsequently, he developed retro-orbital pain, divergent strabismus and palpebral ptosis. CAT and NMR indicated a soft tissue mass at the sphenoid level. Treatment was Gamma Knife Radio-surgery. Since August 2004, in conjunction with the latest rise in PSA, the patients general status deteriorated considerably and he was referred to the Oncology Service. There was an increase in the paralysis of the third, fourth and sixth cranial nerve (complete left ophthalmoplegia) and left-central facial paralysis. Metastases from prostate cancer can be disseminated via the lymphatic or the blood system. Currently, there are more metastases from large-size tumours. Metastases are critical in prostate cancer because of their adverse effect on the patients survival. Measurements of circulating levels of prostate specific antigen and prostate acid phosphatase are very useful in the clinical diagnosis of the primary tumour, or its metastases.
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PMID:[Ophthalmoplegia in a patient with prostate cancer and bone metastases]. 1623 78


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