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

Bone diseases such as osteoporosis or bone metastases are a continuously growing problem in the ageing populations across the world. In recent years, great efforts have been made to develop specific and sensitive biochemical markers of bone turnover that could help in the assessment and monitoring of bone turnover. The amino- and carboxyterminal cross-linked telopeptides of type I collagen (NTX-I and CTX-I, respectively) are two widely used bone resorption markers that attracted great attention due to their relatively high sensitivity and specificity for the degradation of type I collagen, and their rapid adaptation to automated analyzers. However, the clinical performance of both markers differs significantly depending on the clinical situation. These differences have caused considerable confusion and uncertainty. If used correctly, both markers have great potential to improve the management of many bone diseases. We here review the biochemistry, analytical background and clinical performance of NTX-I and CTX-I, as documented in the accessible literature until March 2008.
 ...
PMID:The amino- and carboxyterminal cross-linked telopeptides of collagen type I, NTX-I and CTX-I: a comparative review. 1842

Zoledronic acid (Zometa, ZOL) and cytotoxic chemotherapy agents have been reported to have synergistic antitumor activities. However, there is limited data on the effects of combination therapies on the development of bone metastasis in animal models of lung cancer. The purpose of this study was to establish a human lung adenocarcinoma cell line with high bone metastatic potential in an immunodeficient mouse model and to evaluate the synergistic inhibitory activity of zoledronate and paclitaxel (P) on bone metastasis in nude mice. A human lung adenocarcinoma cell line with high bone metastatic potential (SPC-A1-BM) was established by 10 rounds of in vivo selection. Cells were inoculated into the cardiac ventricle of NIH-BNX mice, which were treated 8 days later with: ZOL (0.2 mg/kg s.c. twice weekly) alone, P (6.0 mg/kg every week, i.p.) alone, P + ZOL, or vehicle (10 mice per group). Tumor growth was evaluated with bone scans, X-rays and in situ immunohistochemistry. Serum n-telopeptide of type I collagen (NTX) was measured by ELISA. Survival was assessed using the Kaplan-Meier method. Bone scan, radiographic and histological assessments revealed fewer bone metastases in all treatment groups vs. vehicle, with P + ZOL significantly reducing the incidence of bone metastases detected by bone scans (P=0.020) and X-rays (P=0.036). A histological analysis revealed marginal differences in the number of bone metastases between P + ZOL and vehicle (P=0.058). There was a trend towards differences in survival between the groups (P=0.1511) and survival was significantly longer for the P + ZOL group vs. vehicle (P=0.022). Compared with vehicle and ZOL alone, cancerous cells in the bone of mice treated with P + ZOL expressed higher levels of Bax and lower levels of Bcl-2 and Bcl-xl. ZOL produced a trend towards reduced NTX levels vs. vehicle and P + ZOL produced a profound reduction in NTX vs. vehicle (P=0.022). The results of this study indicated that zoledronate enhanced the efficacy of paclitaxel synergistically, by reducing the incidence of bone metastasis from lung cancer and prolonging survival in a mouse model of non-small cell lung cancer with a high potential for metastasis to bone.
 ...
PMID:Synergistic inhibitory activity of zoledronate and paclitaxel on bone metastasis in nude mice. 1869 9

The aim of our study was to investigate the sex- and age-related changes of serum Dickkopf-1 (Dkk-1), a soluble inhibitor of the Wnt signaling pathway, in healthy individuals and in patients with breast cancer (BC) and bone metastases (BM) using a new ELISA. Association of serum Dkk-1 with markers of bone turnover was also investigated. Serum Dkk-1 measurements were performed using a commercial sandwich ELISA in 150 healthy men, 175 healthy pre- and postmenopausal women (20-65 years), 22 women with BC and BM (mean age 63 years), and 16 women with BC and metastases at sites other than bone (mean age 53 years). Intra- and interassay coefficients of variation were below 7% and 12%, respectively. The detection limit was determined to be 0.018 microg/L. In healthy women and men, Dkk-1 did not change with age. Serum Dkk-1 modestly correlated with serum bone alkaline phosphatase (r = 0.19, P = 0.013) and serum C-terminal cross-linking telopeptide of type I collagen (r = 0.19, P = 0.014) in women but not in men. Dkk-1 levels were higher in women with BC and BM (5.57 +/- 5.50 microg/L) than in healthy age-matched controls (3.47 +/- 1.47 microg/L, P < 0.0001) and women with metastases at sites other than bone (3.57 +/- 1.66 microg/L, P = 0.0003). In conclusion, serum Dkk-1 is stable with age in healthy women and men and increases in patients with BC and BM. Measurements of circulating Dkk-1 with this new ELISA may be useful for the clinical investigation of patients with malignant bone diseases.
 ...
PMID:Assessment of circulating Dickkopf-1 with a new two-site immunoassay in healthy subjects and women with breast cancer and bone metastases. 1925 61

The aim of this study was to investigate several bone markers in Non-Small Cell Lung (NSCLC) and Small Cell Lung (SCLC) patients experiencing or not secondary bony disease. Fasting serum levels of bone formation, bone resorption, and osteoclastogenesis markers were determined in 22 NSCLC patients with bone metastases, 18 without bone metastasis, and 28 SCLC patients. A total of 29 healthy volunteers were also included in the study. Decreased osteocalcin (OC) serum levels and increased osteopontin and ligand of the receptor of nuclear factor kB (RANKL) serum levels were detected in NCSLC patients with bone metastases while increased C-terminal cross-linking telopeptide of type I collagen and increased RANKL/OPG (osteoprotegerin) ratio were detected in SCLC patients. Increased serum levels of OPG were observed in all lung cancer patients. OPG may be actively involved in the development of lung cancer metastasis. Furthermore, OC, OPN, and RANKL in NSCLC and CTX and RANKL in SCLC patients may also have a broader role in the pathogenesis and spread of lung cancer. They also provide useful information in identifying the group of patients that may benefit from a more rigorous treatment.
 ...
PMID:Serum bone turnover markers may be involved in the metastatic potential of lung cancer patients. 1937 66

Spontaneous development of osteoblastic lesions of prostate cancer (PCa) in mice is modeled by orthotopic (intraprostatic) deposition of neoplastic cells followed by an extremely long latency associated with low incidence of spontaneous bone metastasis. Intracardial injection results in overt bone metastases only with osteoclastic PCa cells (i.e., PC-3). Herein, we report that androgen independent osteoblastic PCa cells readily colonize bone when in a high remodeling state. SCID/Beige mice were subjected to periods of intermittent human parathyroid hormone 1-34 (hPTH) exposure, followed by an intracardiac infusion of osteoblastic C4-2 PCa cells. At the time of PCa infusion, analysis of bone turnover markers from mice treated with hPTH revealed significant increases in osteocalcin (55.06 +/- 7.5 vs. 74.01 +/- 18.5 ng/ml) and TRAcP-5b (3.3 +/- 0.6 vs. 4.81 +/- 0.8 U/l), but no change in type I collagen C-terminal teleopeptide levels relative to control mice. Analysis of femoral cancellous bone architecture revealed significant increases in bone mineral density, trabecular thickness (0.056 +/- 0.002 vs. 0.062 +/- 0.001 mm) and porosity, but significant decreases in connectivity density and trabecular number in hPTH treated mice relative to controls. By 8 weeks post-infusion, 70% of mice pre-treated with hPTH demonstrated detectable serum prostate specific antigen (PSAs) ranging between 2 and 18.8 ng/ml. Immuno-histochemical labeling of femurs for PSA and pan-Cytokeratin revealed the presence of significant tumor cell nests in marrow and trabecular spaces. These results suggest that: (1) local bone physiology is an important factor for developing osteoblastic/sclerotic PCa bone metastases in murine hosts; (2) the establishment of osteosclerotic PCa bone metastases in mice is enhanced by alterations that drive bone formation.
 ...
PMID:Osteosclerotic prostate cancer metastasis to murine bone are enhanced with increased bone formation. 1942 79

The purpose of this study was to investigate various serum markers of bone turnover in non-small cell lung cancer patients (NSCLC) in the presence or absence of bone metastasis. Our retrospective study included 79 newly diagnosed NSCLC patients. Group A included 51 patients with bone metastasis and group B included 28 patients that never developed bone metastasis. The measurement of bone formation markers, bone resorptive markers and osteoclastogenesis markers as well as routine biochemical analysis was determined. Patients with bone metastasis had an increase in receptor activator of nuclear factor kappaB ligand, osteopontin and osteoprotegerin. Patients who later developed bone metastasis had decreased osteocalcin and tartrate-resistant acid phosphatase isoform 5b levels (TRACP-5b). We also found an unusually low TRACP-5b/RANKL ratio for patients who have or later developed metastasis. In patients that never developed bone metastases, cross-linked carboxy-terminal telopeptide of type I collagen was increased. Positive correlations were found between osteopontin and TRACP-5b, and also between bone alkaline phosphatase with osteocalcin and TRACP-5b. In conclusion, serum markers of bone turnover may be able to determine the time-to-tumor progression, metastatic potential and overall survival of the NSCLC patient. In addition, they may contribute to a more accurate follow-up and tailored treatment options.
 ...
PMID:The clinical significance of serum markers of bone turnover in NSCLC patients: surveillance, management and prognostic implications. 1944 81

Bone metastases occur in 20-40% of patients with lung cancer. Recent studies demonstrate a direct antiproliferative effect of 3rd generation bisphosphonates (BPs) on lung tumors, which may influence the survival. Therefore, we examined the clinical impact of zoledronic acid (ZOL; Zometa), a 3rd generation BP, with a focus on the survival, time to progression and pain effect in lung cancer patients with bone metastases. Lung cancer patients (n = 144, Stage IV) with evidence of metastasis bone scan were included. Eighty-seven of 144 experienced bone pain and received ZOL, 4 mg i.v. every 21 days (Group A), whereas the other 57 patients received no ZOL (Group B). All patients were treated with a combination chemotherapy consisted of docetaxel 100 mg/m(2) and carboplatin AUC = 6. It was found that Group A had a statistically significant longer survival (p < 0.01) when compared to Group B. A statistically significant positive correlation was found between the number of cycles of therapy with ZOL and total patient survival (p < 0.01, Pearson correlation) and time to progression (p < 0.01). Pain effect of ZOL had no significant difference between the 2 groups of patients (p > 0.05). Urine N-telopeptide of type I collagen (NTx) levels decreased in patients with NTx < or = 29 nM BCE/mM creatinine at baseline after treatment with ZOL. The results of our study suggest that the addition of ZOL increases overall survival in lung cancer patients with bone metastases. The longer period of receiving ZOL, the better effect on survival and time to progression.
 ...
PMID:The impact of zoledronic acid therapy in survival of lung cancer patients with bone metastasis. 1952 84

Bone metastases frequently occur in patients with advanced solid tumors, particularly breast and prostate cancers, and nearly all patients with multiple myeloma have some degree of skeletal involvement. The strides made in treating these primary tumors have extended median survival times and thereby increased patient risk for skeletal-related events (SREs), including pathologic fractures, spinal cord compression, need for palliative radiation therapy or surgery to bone, and hypercalcemia. Bisphosphonates, inhibitors of osteoclastic bone resorption that were first established as treatment of osteoporosis, have been shown to prevent and/or delay SREs related to malignancy. The results of a large, randomized phase 3 study comparing zoledronic acid and pamidronate in breast cancer or multiple myeloma patients with osteolytic lesions showed that the incidence of SREs, time to first SRE, and risk of developing a SRE were similar between treatment groups. However, in patients with solid tumors (excluding breast or prostate cancer) metastatic to the bone, only zoledronic acid has demonstrated clinical efficacy. Although bone turnover marker levels, such as N-telopeptide of type I collagen, have been shown to correlate with clinical response, additional studies are needed to validate their ability to predict response to bisphosphonate therapy.
 ...
PMID:Bisphosphonates in oncology: evidence for the prevention of skeletal events in patients with bone metastases. 1992 Sep 19

The use of serum alkaline phosphatase (ALP) isoenzymes as markers of breast cancer metastases and treatment efficacy has received little attention. Twenty-six breast cancer women (56+/-13 years, all post-menopausal) were prospectively evaluated during their first and third course of chemotherapy (4-week interval). Serum samples were analyzed for ALP isoenzymes (bone, liver, and intestine) using a lectin affinity electrophoresis kit (Hydragel 15 ISO-PAL, Sebia) adapted on a semi-automated Hydrasys system (Sebia). Results were compared with imaging techniques for the presence of metastases; bone ALP isoenzyme (B-ALP) results were compared with C-Terminal degradation products of type I collagen (S-CTX) (CrossLaps, IDS Nordic). Serum B-ALP, but not S-CTX, confirmed the presence of bone metastases (BM) (n=15) with 67/100% sensitivity/specificity (using a 69 UI/L ROC cut-off); ROC AUC was 0.806 (P=0.0004) (NS for S-CTX). Chemotherapy reduced serum B-ALP by 24% over 4 weeks (P=0.0012); there was no change for S-CTX. There was no specific clinical pattern for other ALP isoenzymes (liver and intestine). In conclusion, serum B-ALP, but not S-CTX, could help confirm the presence of BM in breast cancer patients.
 ...
PMID:Lectin affinity electrophoresis of serum alkaline phosphatase in metastasized breast cancer. 2008 50

Zoledronic acid has direct and indirect antitumor effects. However, the optimal regimen for breast cancer patients remains to be determined. This study aimed to compare biomarker changes between a weekly low dose (metronomic arm) and a conventional dosage of zoledronic acid (conventional arm), and to explore correlations between biomarkers and progression-free survival (PFS). Sixty breast cancer patients with bone metastases were randomized to receive either zoledronic acid 1 mg IV weekly for 4 doses or a single dose of zoledronic acid 4 mg IV. Administration of other treatments was delayed for 1 month. Serial blood samples were collected on days 1, 15, 29, and at 3 months. Serum VEGF alteration was the primary endpoint. Compared to the conventional arm, the metronomic arm resulted in a significantly greater reduction in serum levels of VEGF and N-telopeptide of type I collagen (NTx) over time during the first month of treatment. Serum CA 15-3 level stabilized over time in the metronomic arm, but increased in the conventional arm. Independent prognostic factors for PFS included chemotherapy received (HR, 8.042; P = 0.000), estrogen receptor status (HR, 2.837; P = 0.020), VEGF levels at 3 months after intervention (HR, 2.026; P = 0.045), and baseline NTx (HR, 1.051; P = 0.001). Metronomic low-dose zoledronic acid is more effective than the conventional regimen and generates sustained reductions in circulating VEGF and NTx levels, as well as stabilization of serum CA 15-3 levels (ClinicalTrials.gov number, NCT00524849).
 ...
PMID:Biomarker alterations with metronomic use of low-dose zoledronic acid for breast cancer patients with bone metastases and potential clinical significance. 2088 5


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