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Objective: To evaluate the efficacy and safety of zoledronic acid in the treatment of bone pain in patients with bone metastasis from solid tumor or multiple myeloma., Methods: A randomized, double-blind, double-simulated and multi-center phase III clinical trail with pamidronate as control was conducted. Patients with moderate to severe bone pain (VAS > 50 mm) induced by solid tumor or multiple myeloma were randomized to receive intravenous zoledronic acid 4 mg or pamidronate 90 mg. Then the change of VAS and urinary NTX/Cr and CTX/Cr were observed in two groups., Results: From July 2005 to September 2006, 228 patients with bone pain induced by bone metastasis from 15 cancer centers were randomize into two groups: 116 patients in zoledronic acid group and 112 patients in pamidronate group. The VAS value was decreased gradually after treatment in these two groups. Significant improvement in bone pain after treatment were observed both in zoledronic acid group and the control group when compared with baseline VAS on D8 (-11.77% vs. -10.87%), D15 (-24.60% vs. -21.06%) and D28 (-32.37% vs. -31.26%) (P< or =0.0001), but no significant difference existed between two groups (P =0.6587). Compared with baseline, urine NTX/Cr and CTX/Cr level were decreased rapidly after treatment in both groups, the nadir was on D8, the median decreased on D28, which was -36.9% vs. -32.1% for NTX/Cr (P = 0.7922) and -63.2% vs. -47.9% for CTX/Cr (P =0.834). The frequently observed adverse events were pyrexia (19.0% vs. 31.3%), vomiting (6.0% vs. 8.9%), nausea (4.3% vs. 4.5%), fatigue (3.4% vs. 2.7%) and constipation (2.6% vs. 1.8%) in the two groups. Compared with baseline, the serum creatinine level was not significantly increased throughout the study., Conclusion: Intravenous injection of 4 mg zoledronic acid can significantly reduce bone pain and bone resorption marker in urine in the Chinese patients with bone metastasis from solid tumor or multiple myeloma, which is tolerable and also comparable to pamidronate in the efficacy and safety.

Objective: To investigate the role of first pass dynamic 16-slice spiral computed tomography in the evaluation of tumor angiogenesis in patients with non-small cell lung cancer (NSCLC) and to assess its importance in predicting pathologic characteristics., Methods: The first pass dynamic 16-slice spiral computed tomography was performed in 33 patients with NSCLC. Their peak heights (PH) were measured with dynamic evaluation software. Their angiogenesis were labelled by anti-CD34 monoclonal antibody. The first pass peak heights (PH) in 33 patients with NSCLC were compared with their microvessel densities (MVD) and their relationships were assessed by linear regression analysis., Results: Among the 33 patients with NSCLCs, the mean first pass PH and MVD of N1-2 were significantly higher than those at stage No (P < 0.01). The first pass PH of 33 NSCLC was correlated positively with MVDs. To differentiate stage N0 from stage N1-2 with 12 HU cutoff value of the first pass PH, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 88.0%, 75.0%, 84.8%, 91.7% and 66.7%, respectively., Conclusion: The first pass dynamic contrast enhanced CT may be a predictor of tumor angiogenesis in patients with NSCLC and its pathologic characteristics, and may be helpful to improve the accuracy of lymph node staging with conventional CT.

Objective: To study the molecular mechanisms of nm23-H1 for regulating PKC signal pathway before and after transfection with nm23-H1 gene., Methods: Using Western-blot, Boyden-chamber, MTT and laser scanning confocal microscopy (LSCM) techniques to detect the distribution of PKC in cytosol and plasma membrane, changes of invasion and proliferation activity, PKC translocation status and changes of intracellular Ca(2+) concentration among different human pulmonary carcinoma cells with transfected or untransfected nm23-H1 gene, and changes of the three cell lines after treatment with Calphostin C, a PKC inhibitor., Results: (1) The expression of PKCalpha, PKCbeta II on L9981 and L9981-pLXSN cell membrane, which was in activated status, was remarkably higher than those in L9981-nm23-H1 cell line (P < 0.001). The expression of PKCalpha, PKCbeta II in cytosol in L9981 and L9981-pLXSN cell lines, which was in inactivated status, was lower than those in L9981-nm23-H1 cell line (P < 0.001). It means that the PKC signal pathway was activated in L9981 and L9981-pLXSN cell lines. (2) PKCalpha and PKCbeta II mainly located in nuclei and perinuclear area in L9981 and L9981-pLXSN cells, which were in active status, and the Ca(2+) concentration in these cells was obviously higher than that in L9981-nm23-H1 cell line (P < 0.01). In L9981-nm23-H1 cell line, which was transfected with nm23-H1 gene, PKCalpha and PKCbeta II mainly located in soluble cytosolic section, in an inactive status. (3) The invasion and proliferation ability of L9981 and L9981-pLXSN lung cancer cells was higher than that of L9981-nm23-H1 cell line (P < 0.001). There was no statistically significant difference between L9981 and L9981-pLXSN cell lines (P > 0.05). (4) After treated with PKC inhibitor Calphstin C, the expression of PKC and PKCbeta II in membrane in L9981 and L9981-pLXSN cell lines was down-regulated (P < 0.001), PKCalpha and PKCbeta II were mainly located in cytosolic area, mainly in an inactive status, and the Ca(2+) concentration was found to be decreased in all the three cell lines. The invasion and proliferation ability of the three lung cancer cell lines were obviously decreasing (P < 0.001). However, the invasion and proliferation ability of L9981-nm23-H1 lung cancer cell line was still lower than that of L9981 and L9981-pLXSN lung cancer cell lines (P < 0.001). There was also no significant difference between L9981 and L9981-pLXSN cell lines (P > 0.05)., Conclusion: The results of this study suggest that nm23-H1 gene might inhibit the invasion and metastasis of lung cancer cells by down-regulating PKC signaling pathway. The Ca(2+) in cells might be involved in this process.

Objective: To analyze the effects and side effects of paclitaxel liposome formula on breast cancer and non-small cell lung cancer, compared with traditional taxol., Methods: 129 patients from multicenters were prospectively randomized into a test group, given paclitaxel liposome at 135 mg/m(2) each session, and a control group, given traditional taxol at 135 mg/m(2) each session. Both groups received these regimens combined with ADM or DDP for two cycles (3 weeks per cycle)., Results: Of 129 cases, 128 were eligible for the analysis of side effects and 126 for the overall response rate. The complete remission rate, partial remission rate and overall response rate were 1.6%, 33.3%, 34.9% in the test group and 6.3%, 22.2%, 28.6% in the control group. There was no significant difference between the two groups. Though there was no significant difference in hematological toxicity between the two groups, the toxicity from the mixed solvent of polyethoxylated castor oil and ethanol was significantly lower in the test group than that in the control group., Conclusion: Paclitaxel liposome combined with ADM or DDP in the treatment of advanced breast cancer and non-small-cell lung cancer, being similarly effective as taxol, can significantly lower the incidence of serious hypersensitive reactions.

Objective: To evaluate the specificity, sensitivity and their clinical significance of detecting CK19 mRNA expression by nested RT-PCR for molecular diagnosis of micrometastasis in the peripheral blood and bone marrow of patients with non-small cell lung cancer., Methods: CK19 mRNA expression was detected by nested RT-PCR in peripheral blood and bone marrow samples from 59 lung cancer patients, with samples of 11 benign pulmonary lesion patients and 20 healthy adults as control., Results: The sensitivity of nested RT-PCR was 10(-6). The positive rates of micrometastasis were 33.89% (20/59) in peripheral blood and 22.03% (13/59) in bone marrow, with a highly positive correlation existing between the two groups (P < 0.05). The micrometastasis in peripheral blood and bone marrow was closely correlated with the pathological classification and cell differentiation (P < 0.05) and P-TNM stage (P < 0.01). No CK19 mRNA expression was found in the samples from patients with benign pulmonary lesion or healthy adult volunteers., Conclusion: The peripheral blood and bone marrow from patients with non-small cell lung cancer possesses micrometastasis that can not be detected by common methods. Nested RT-PCR technique shows favorable specificity and sensitivity in detecting the condition with definite clinical prospects.