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)

The efficacy of cytotoxic therapy in different anatomical sites can be studied by analyzing the anatomical distribution of recurrences following adjuvant therapy or the rate of response according to site of metastasis. Cumulated data from 7 adjuvant studies showed that the relative reduction in the rate of recurrence was 37% for local and regional recurrences versus 25% for distant metastases. There are only sparse and inconclusive data concerning the anatomical pattern of recurrence according to type of adjuvant chemotherapy. Thus, the majority of trials have not demonstrated significant differences in distribution of metastases in patients receiving different types of adjuvant systemic therapy. The available data on the rate of response in relation to metastatic site showed higher response rates in soft tissue metastases (55%), compared to visceral and bone metastases (40%). Cumulated data from 12 trials showed no differences in response rates between different soft tissue lesions (skin, subcutaneous tissue, lymph nodes, breast), or between metastases demonstrated by paraclinical tests (lung, liver, bone). However, there was a tendency for soft tissue lesions to have a higher response rate (55-60%) than visceral and bone metastases (31-44%). The reason for the observed differences is unknown. At the time of diagnosis soft tissue lesions may be smaller (with better blood supply) than visceral lesions. This might increase the likelihood of response, since experimental data show that the response rate is inversely correlated with tumour burden and tumour size. Another explanation is based on the hypothesis of site-specific clonal selection of tumour cells, which differ with respect to sensitivity to cytotoxic agents. However, the observed differences can also be ascribed to methodological errors or differences in assessing response of tumours at specific sites. Thus, the false positive response rate in soft tissue lesions, evaluated by physical examination, is approximately 20% compared with less than 10% in lung lesions evaluated by x-rays.
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PMID:Site-specific effect of chemotherapy in patients with breast cancer. 162 38

The authors reviewed 89 patients treated for cerebellar medulloblastoma between 1970 and 1989 to determine the impact of changing treatment (high-dose posterior fossa radiation therapy and chemotherapy) on the pattern of failure in medulloblastoma. Between 1970 and 1983, 50 patients (median follow-up, 110 months) were treated with surgery and postoperative craniospinal irradiation (CSI). Nineteen of the 50 (38%) recurred in the central nervous system (CNS). Isolated systemic (bone) metastases occurred in six. The median time to the development of bone metastases was 12 months. Since 1984, 39 patients (median follow-up, 27 months) were treated with preradiation chemotherapy consisting of cisplatin and vincristine for 9 weeks before initiation of CSI. Nine of the 39 (23%) patients recurred in the CNS. There were no systemic failures in this cohort. The actuarial 5-year disease-free survival was 55 +/- 7% for the earlier cohort and 72 +/- 8% for the later cohort (P equals 0.3). Posterior fossa recurrence was associated with radiation therapy to this area. The cumulative incidence of posterior fossa relapse was 50 +/- 13% in patients who received less than 5300 cGy and 18 +/- 7% in those who received 5300 cGy or more (P equals 0.005). All six bone relapses were in patients treated with CSI alone and 5300 cGy or more to the posterior fossa for a 5-year cumulative incidence of bone metastases of 18 +/- 7% compared with 0% for patients treated with 5300 cGy or more and chemotherapy (P equals 0.03). The authors concluded that high-dose radiation therapy has altered the pattern of relapse with an increase in systemic recurrence after radiation therapy alone that is now equivalent to the risk of recurrence in the posterior fossa. Chemotherapy may be indicated in an attempt to decrease this high risk of systemic metastases.
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PMID:The change in patterns of relapse in medulloblastoma. 189 59

We assessed the results of treatment in 283 patients with lung or bone metastases from differentiated thyroid carcinoma who were followed for up to 40 yr (median, 44 months) after the discovery of the metastases. The survival rates from the time of discovery of the metastases were 53% at 5 yr, 38% at 10 yr, and 30% at 15 yr; 156 patients died. Multivariate analysis revealed that only 4 variables had an independent prognostic significance for survival. They were extensive metastases, older age at discovery of the metastases, absence of radioiodine uptake by the metastases, and moderately differentiated follicular cell type. The site of metastases (lung or bone) was not a prognostic factor for survival after treatment of metastatic disease. Remission was achieved in 79 patients after metastases were found. The only predictive factor for 5-yr disease-free survival after treatment of metastases was the initial extent of disease. Our results suggest that the aim of management should be to detect and treat metastases in patients with thyroid cancer as early as possible.
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PMID:Long-term results of treatment of 283 patients with lung and bone metastases from differentiated thyroid carcinoma. 374 9

The efficacy of radionuclide bone scans in monitoring metastatic bone activity remains controversial. Objective measurement of bone tumor burden would be useful for the evaluation of new therapies for metastatic carcinoma of the prostate. The recent discovery of the urinary excretion of pyridinoline (cross-link of mature collagen found in cartilage and bone) and deoxypyridinoline (collagen cross-link specific to bone) measured by high pressure liquid chromatography has provided sensitive specific indexes of cartilage and bone breakdown in rheumatoid arthritis, osteoporosis and metabolic bone diseases. We compared the urinary excretion of deoxypyridinoline,pyridinoline and hydroxyproline relative to urinary creatinine (nmol./mmol.creatinine) in 27 patients with benign prostatic hyperplasia (patient age 70.0 +/- 8.5 years, standard deviation), 29 with clinically confined prostate cancer (age 70.2 +/- 9.7 years), and 26 with prostate cancer and bone metastases (age 71.1 +/- 7.7 years). No diurnal variation of deoxypyridinoline or pyridinoline urinary excretion was detected in 5 patients with metastases. Urinary excretion of pyridinoline and deoxypyridinoline was significantly greater in patients with metastatic carcinoma of the prostate compared with patients with either benign prostatic hyperplasia (Mann-Whitney-Wilcoxon rank sum analysis, p < 0.00004 and 0.002, respectively) or localized prostate cancer (Mann-Whitney-Wilcoxon, p < 0.00001 and 0.00005, respectively). Urinary hydroxyproline levels failed to separate the 3 groups. Pyridinoline and deoxypyridinoline excretion in prostate cancer patients with metastases directly correlated with bone scan Soloway scores (r = 0.55, p < 0.005 and r = 0.57, p < 0.004 respectively), whereas serum prostate specific antigen did not (r = 0.36, p = 0.08). Serial measurements of pyridinoline and deoxypyridinoline progressively increased in 3 patients with clinical progression documented by new metastatic lesions by bone scan. Measurement of pyridinoline and deoxypyridinoline excretion cannot diagnose metastatic disease. However, these markers should be evaluated further for quantitative assessment of bone metastases.
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PMID:Collagen cross-link metabolites in urine as markers of bone metastases in prostatic carcinoma. 751 Mar 46

1. Drug disposition of incadronate in the nude rat with bone metastases induced by A375 human melanoma cells was studied after intravenous administration. 2. The pharmacokinetics of incadronate (plasma concentration, urinary excretion and bone uptake) in rat with bone metastases was not markedly different from that in the control rat. This compound, however, was selectively taken up in the bone region around metastatic tumour nests. 3. Drug concentrations in the bone region around tumour nests were 3-10 micrograms/g, these levels being higher than the IC50 (0.35 microgram/ml) for the inhibitory effect of this drug on osteoclasts in vitro. 4. In contrast, concentrations in the tumour nest itself was < 0.7 microgram/g, being markedly lower than the IC50 (35 micrograms/ml) for the inhibitory effect on the proliferation of tumour cells in vitro. 5. These results strongly suggest that pharmacological action of incadronate in mouse with bone metastases (inhibitory effect on the growth of metastatic tumour in bone) is caused not by the direct action on the tumour cells but by the distribution of the drug in the perifocal bone region followed by inhibition of the activity of osteoclasts, resulting in inhibition of the osteolytic process, which is necessary for the progress of metastatic tumour.
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PMID:Drug disposition of incadronate, a new bisphosphonate, in rats with bone metastases. 917 88

One-third of women with breast cancer will develop bone metastases and eventually die from disease progression at these sites. Therefore, we analyzed the ability of human MG-63 osteoblast-like cells (MG-63 cells), MG-63 conditioned media (MG-63 CM), insulin-like growth factor I (IGF-I), and transforming growth factor beta 1 (TGF-beta1) to alter the effects of adriamycin on cell cycle and apoptosis of estrogen receptor negative (ER-) MDA-MB-231 and positive (ER+) MCF-7 breast cancer cells, using cell count, trypan blue exclusion, flow cytometry, detection of DNA fragmentation by simple agarose gel, and the terminal deoxynucleotidyl transferase (TdT)-mediated nick end-labeling method for apoptosis (TUNEL assay). Adriamycin arrested MCF-7 and MDA-MB-231 cells at G2/M phase in the cell cycle and inhibited cell growth. In addition, adriamycin arrested the MCF-7 cells at G1/G0 phase and induced apoptosis of MDA-MB-231 cells. Exogenous IGF-I partially neutralized the adriamycin cytotoxicity/cytostasis of cancer cells. MG-63 CM and TGF-beta1 partially neutralized the adriamycin cytotoxicity of MDA-MB-231 cells but enhanced adriamycin blockade of MCF-7 cells at G1/G0 phase. MG-63 osteoblast-like cells inhibited growth of MCF-7 cells while promoting growth and rescued MDA-MB-231 cells from adriamycin apoptosis in a collagen co-culture system. These data suggest that osteoblast-derived growth factors can alter the chemotherapy response of breast cancer cells. Conceivably, host tissue (bone)-tumor cell interactions can modify the clinical response to chemotherapy in patients with advanced breast cancer.
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PMID:Chemotherapy cytotoxicity of human MCF-7 and MDA-MB 231 breast cancer cells is altered by osteoblast-derived growth factors. 1020 74

A 66-year-old female presented with a swollen lump in the left breast. She was diagnosed as having advanced breast cancer of stage T4N3 (supraclavicular lymph node) M1 (bone). The administration of CEF and TAM failed to improve her condition. After the treatment regimen was changed to combined chemoendocrine therapy with CPA, EPI, 5'-DFUR, and MPA, the areas of bone metastases were reduced. However, MPA caused side-effects (acute obstruction of the lower limb), and thus the treatment was discontinued after 4 months. Subsequently, the treatment combination was changed to CPA, EPI, 5'-DFUR, and fadrozole hydrochloride hydrate. After one year of the treatment, a complete response (CR) was obtained with the disappearance of the supraclavicular lymph node and bone metastases. After EPI reached the maximum administration amount, the remaining CPA, 5'-DFUR and fadrozole hydrochloride hydrate oral administrations were continued. As of 3 years and 10 months after the onset of the chemoendocrine therapy, CR has been maintained with suppression of the primary and metastatic lesions, without degrading the patient's quality of life.
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PMID:[Efficacy of combined chemoendocrine therapy with doxifluridine, cyclophosphamide, and fadrozole hydrochloride hydrate in a case of stage T4N3M1 breast cancer]. 1083 48

The plasmatic activities of total alkaline phosphatase (ALP) (E.C. 3.1.3.1), high molecular weight-ALP (high Mr-ALP) and bone-ALP isoenzymes, were determined in healthy individuals and in patients with: neoplasia without metastases, hepatic metastases, bone metastases and mixed metastases (hepatic and bone). Variables were individually used to assess incidence of metastases and percentages of false negative and false positive results were calculated. The three values were then used together to assess metastases incidence and sensitivity, specificity, positive predictive value, negative predictive value and predictive capacity were estimated. We conclude that none of the variables per se are reliable for the diagnosis of metastases. On the other hand, the three values show high percentages of sensitivity, specificity, positive predictive value, negative predictive value and a high probability (0.93) of accurate diagnosis when applied to a larger population, with similar prevalence values.
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PMID:Alkaline phosphatase isoenzymes for the diagnosis of metastatic tumors and lymphomas of liver and bone. 1105 Aug 6

Patients with metastatic colorectal carcinoma (CRC) often develop bone metastases with a high risk of complications. Ibandronate is a novel single-nitrogen bisphosphonate that has been shown to be effective for treating bone metastases from breast cancer. A randomized, placebo-controlled trial was conducted to evaluate the efficacy and safety of ibandronate in patients with bone metastases from CRC. The primary efficacy end point was the proportion of patients with skeletal-related events (defined as pathologic fracture, spinal cord compression, radiation therapy to bone, change in antineoplastic therapy or surgery to bone). Secondary end points included time to first skeletal event, skeletal morbidity rate (events/year) and time to progression of bone lesions. In 73 patients with CRC, treatment with intravenous ibandronate 6 mg administered via a 15-min infusion significantly reduced the proportion of patients with skeletal events (39% vs. 78% with placebo; P = 0.019) and prolonged the time to first event by at least 6 months (median >279 vs. 93 days with placebo; P = 0.009). Ibandronate also significantly reduced the skeletal morbidity rate (mean 2.36 vs. 3.14 with placebo; P = 0.018) and prolonged time to progression of bone lesions (214 days vs. 81 days with placebo; P = 0.018). Ibandronate was well tolerated with very rare grade 3 or 4 toxicity. Furthermore, the incidence of renal adverse events was comparable with placebo and there were no clinically relevant changes in serum creatinine. Ibandronate provided significant clinical benefits for patients with bone metastases secondary to CRC. These results indicate that ibandronate may be an effective treatment for patients with metastatic bone disease following CRC. Larger studies are required for further assessment.
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PMID:Ibandronate is effective in preventing skeletal events in patients with bone metastases from colorectal cancer. 1794 70

The skeleton is the second most frequent site of metastasis. However, only a restricted number of solid cancers, especially those of the breast and prostate, are responsible for the majority of the bone metastases. Metastatic bone disease is a major cause of morbidity, characterised by severe pain and high incidence of skeletal and haematopoietic complications (fractures, spinal cord compression and bone marrow aplasia) requiring hospitalisation. Despite the frequency of skeletal metastases, the molecular mechanisms for their propensity to colonise bone are poorly understood and treatment options are often unsatisfactory. TGF-beta and the signalling pathway it controls appears to play major roles in the pathogenesis of many carcinomas, both in their early stages, when TGF-beta acts to arrest growth of many cell types, and later in cancer progression when it contributes, paradoxically, to the phenotype of tumour invasiveness. Here we discuss some novel insights of the TGF-beta superfamily-including BMPs and their antagonists-in the formation of bone metastasis. Increasing evidence suggests that the TGF-beta superfamily is involved in bone homing, tumour dormancy, and development of micrometastases into overt bone metastases. The established role of TGF-beta/BMPs and their antagonists in epithelial plasticity during embryonic development closely resembles neoplastic processes at the primary site as well as in (bone) metastasis. For instance, the tumour-stroma interactions occurring in the tissue of cancer origin, including epithelium-to-mesenchyme transition (EMT), bear similarities with the role of bone matrix-derived TGF-beta in skeletal metastasis formation.
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PMID:TGF-beta and BMP7 interactions in tumour progression and bone metastasis. 1800 74


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