Serum alkaline phosphatase predicts survival outcomes in patients with skeletal metastatic nasopharyngeal carcinoma

OBJECTIVE: Bone metastasis is frequently associated with nasopharyngeal carcinoma. The diagnosis and follow-up of bone metastatic patients usually relies on skeletal X-ray and bone scintigraphy, which are time-consuming and costly. This study aimed to evaluate whether serum alkaline phosphatase offers clinical value in predicting the clinical response and survival outcome for skeletal metastatic nasopharyngeal carcinoma. METHODS: Serum alkaline phosphatase was measured at baseline and then before each cycle of treatment in 416 nasopharyngeal carcinoma patients with bone metastasis. The correlations between the pre-treatment and post-treatment alkaline phosphatase levels and the treatment efficacy were analyzed using the chi-square test. Survival was analyzed using the Kaplan–Meier method and then compared using the log-rank test. RESULTS: Patients with elevated pre-treatment alkaline phosphatase (>110 IU/L) had significantly worse progression-free survival (P<0.001) and overall survival (P<0.001) than those with a normal level of this marker (≤110 IU/L). Patients with elevated post-treatment alkaline phosphatase had worse progression-free survival (P<0.001) and overall survival (P<0.001) compared with those with a normal level. Patients with normal pre-treatment and post-treatment alkaline phosphatase showed the most favorable prognosis. The Cox multivariate analysis revealed that only the pre-treatment and post-treatment alkaline phosphatase levels were independent prognostic factors for progression-free survival (HR ϝ 1.656, P<0.001; HR ϝ 2.226, P<0.001) and for overall survival (HR ϝ 1.794, P<0.001; HR ϝ 2.657, P<0.001). CONCLUSIONS: Serum alkaline phosphatase appears to be a significant independent prognostic index in patients with skeletal metastatic nasopharyngeal carcinoma, which could reflect the short-term treatment response ...

Cyclooxygenase-2 promotes cell proliferation, migration and invasion in U2OS human osteosarcoma cells

Osteosarcoma is the most common primary bone tumor, but the pathogenesis is not well understood. While cyclooxygeanse-2 (COX-2) is known to be closely associated with tumor growth and metastasis in several kinds of human tumors, the function of COX-2 in osteosarcoma is unclear. Therefore, to investigate the function of COX-2 in osteosarcoma, we established stable cell lines overexpressing COX-2 in U2OS human osteosarcoma cells. COX-2 overexpression as well as prostaglandin E(2) treatment promoted proliferation of U2OS cells. In addition, COX-2 overexpression enhanced mobility and invasiveness of U2OS cells, which was accompanied by increases of matrix metalloproteinase-2 and -9 (MMP-2 and -9) activities. Selective COX-2 inhibitors, NS-398 and celecoxib, inhibited cell proliferation and abrogated the enhanced mobility, invasiveness and MMP activities induced by COX-2 overexpression. These results suggest that COX-2 is directly associated with cell proliferation, migration and invasion in human osteosarcoma cells, and the therapeutic value of COX-2 inhibitors should be evaluated continuously.

Collagenase specificity in chondrosarcoma metastasis

The treatment of some mesenchymal malignancies has made significant gains over the past few decades with the development of effective systemic therapies. In contrast, the treatment of chondrosarcoma has been limited to surgical resection, with the most significant prognostic indicators being surgical margins and histologic grade. We have reported that MMP-1/TIMP-1 gene expression serves to prognosticate for tumor recurrence in this group of patients. This led to the hypothesis that collagenase activity facilitates cell egression from the cartilaginous matrix. In the current study we examine the specificity of collagenase gene expression in archival human chondrosarcoma samples using semi-quantitative PCR. Messenger RNA was affinity extracted and subject to reverse transcription. The subsequent cDNA was amplified using novel primers and quantitated by densitometry. Ratios of gene expression were constructed and compared to disease-free survival. The data demonstrate that the significance of the MMP-1/TIMP-1 ratio as a predictor of recurrence is confirmed with a larger number of patients. Neutrophil collagenase or MMP-8 was observed in only 5 of 29 samples. Collagenase-3 or MMP-13 was observed in all samples but the level did not correlate with disease-free survival. Since the collagenases have similar activity for fibrillar collagens and cleave the peptide in the same location, post-transcriptional regulatory mechanisms may account for the observed specificity. The determination of the MMP-1/TIMP-1 gene expression ratio not only serves to identify those patients at risk for recurrence but may also serve as a novel therapeutic avenue as an adjunct to surgical resection