TRAIL-induced cell death and caspase-8 activation are inhibited by cisplatin but not carboplatin.

OBJECTIVE: Platinum (Pt) based drugs including cisplatin and carboplatin are widely used as anticancer drugs in various human cancers. Many studies have shown that chemotherapeutic agents synergistically enhance cell death induced by death ligands. However it has been recently reported that cisplatin may inhibit tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death through inactivation of caspases. Thus, we investigated whether carboplatin also inhibits TRAIL-induced cell death. METHODS: HeLa cells were treated with TRAIL in the presence of cisplatin or carboplatin, and cell death was analyzed using the crystal violet staining method. Caspase activation was checked through detection of Bid cleavage by Western blotting using anti-Bid antibody. RESULTS: Cisplatin inhibits TRAIL-induced cell death in HeLa cells; however, carboplatin enhanced TRAIL-induced cell death. Whereas cisplatin inhibited caspase-8-mediated Bid cleavage, carboplatin had no effect on caspase-8 activity. CONCLUSION: Although cisplatin and carboplatin are platinum-containing cancer therapeutic agents, they have the opposite effects on TRAIL-induced cell death.

The efficacy of sonographic morphology indexing and serum CA-125 for preoperative differentiation of malignant from benign ovarian tumors in patients after operation with ovarian tumors.

OBJECTIVE: To evaluate the value of sonographic morphology indexing (MI) system and serum CA-125 levels in the assessment of the malignancy risk in patients with ovarian tumors. METHODS: From September 2000 to July 2006, 202 patients who underwent surgery for ovarian tumors were reviewed retrospectively. In all patients, the MI score and serum CA-125 level were measured preoperatively. The association of the final pathologic diagnosis with the MI score and serum CA-125 level were examined. RESULTS: There were 26 malignant tumors out of 141 ovarian tumors with a MI >/=5 (18%). With a cut-off value of 5, the sensitivity, specificity, PPV, and NPV of MI scores were 0.743, 0.293, 0.181, and 0.845, respectively. There were 22 malignant tumors out of 54 ovarian tumors with serum CA-125 >30 u/ml (41%). With a cut-off value of 30 u/ml, the sensitivity, specificity, PPV, and NPV of serum CA-125 level were 0.667, 0.808, 0.407, and NPV 0.925, respectively. On ROC curve, the optimal cut-off value of MI score was 6.5-7.5 and that of serum CA-125 level was 25.6-28.5 u/ml. With a cut-off value of 7, the sensitivity and 1-specificity of MI score were 0.875-0.917 and 0.023-0.203, respectively. After the exclusion of teratoma cases, the sensitivity and 1-specificity of MI score were 0.875-0.917 and 0.046-0.138, respectively. With a cut-off value of 25.6-28.5 u/ml, the sensitivity and 1-specificity of serum CA-125 level were 0.958 and 0.203-0.215, respectively. CONCLUSION: The sonographic MI system is an accurate and simple method to differentiate a malignant tumor from a benign ovarian tumor. The accuracy of the sonographic MI system improved when the serum CA-125 level was considered and ovarian teratomas were excluded.