Anticancer research
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Anticancer research · May 2004
The prognostic value of plasma soluble urokinase plasminogen activator receptor (suPAR) levels in stage III ovarian cancer patients.
The level of the urokinase plasminogen activator receptor (uPAR) is elevated in tumor tissue from several forms of cancer. uPAR is shed from the cell surface and the soluble form, soluble urokinase plasminogen activator receptor (suPAR), has been detected in several body fluids. High plasma levels of suPAR in patients with colorectal cancer and high serum levels of suPAR in patients with recurrent metastatic breast cancer have been associated with poor prognosis. In patients with ovarian cancer (OC) it has been shown that the level of suPAR is very high in ascites and cystic fluid and that high serum levels of suPAR were associated with shorter survival of the patients. ⋯ When different cut-off levels of plasma suPAR were considered (2.74 ng/ml, 3.25 ng/ml and 4.18 ng/ml), no significant differences in survival could be detected (p=0.58, p=0.68 and p=0.05). Multivariate Cox regression analysis showed that the only independent prognostic factors were radicality after primary surgery (RH=5.34; 95% CI, 2.34-12.20; p<0.0001) and preoperative serum TN (RH=0.69, 95% CI, 0.57-0.82; p<0.0001), whereas plasma suPAR (4.18 ng/ml), age, histological type of tumour and serum CA 125 had no independent prognostic value. In conclusion, preoperative plasma suPAR level was of no prognostic value in this cohort of Danish stage III OC patients.
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Anticancer research · May 2004
Clinical TrialPhase I study of combination therapy with S-1 and docetaxel (TXT) for advanced or recurrent gastric cancer.
S-1, an oral fluorouracil antitumor drug, and docetaxel have both been identified as effective agents for the treatment of gastric cancer. The two drugs have incompletely overlapping principal toxicities, which constitute the rationale for evaluating the effects of a combination of S-1 and docetaxel in this phase I study. The aim of this phase I study was to determine the maximum-tolerated dose (MTD) and the recommended dose of docetaxel with a fixed dose of S-1 in patients with advanced or recurrent gastric cancer. ⋯ The drug combination showed a good safety profile, with neutropenia being a common but manageable adverse reaction. Moreover, the responses observed in the study suggest that the drug combination shows a high degree of efficacy in patients with advanced and or recurrent gastric cancer.
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Anticancer research · May 2004
Selective induction of G2/M arrest and apoptosis in HL-60 by a potent anticancer agent, HMJ-38.
We previously reported that HMJ-38 was the most potent 2-phenyl-4-quinozolinone derivative in inhibiting tubulin polymerization and showed significant cytotoxicity against several human tumor cell lines. In this work, we studied its cytotoxic effect on HL-60 leukemia cells and the underlying mechanisms. We first investigated the effects of HMJ-38 on viability, cell cycle and induction of apoptosis in HL-60 and normal human peripheral blood mononuclear cells (PBMC). ⋯ Pre-incubating cells with ERK inhibitors (U0126 and PD98059) attenuated the HMJ-38-induced ERK activation and apoptosis. Nevertheless, cells remained arrested in G2/M. These results suggest that HMJ-38 is a potent anticancer drug and it shows a remarkable action on cell cycle before commitment for apoptosis is reached.
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Anticancer research · May 2004
Topotecan-induced alterations in the amount and stability of human DNA topoisomerase I in solid tumor cell lines.
Human DNA topoisomerase I (topo 1) is an essential nuclear enzyme involved in vital cellular processes and the sole target of antitumor drugs of the camptothecin (CPT) family. The CPT derivative topotecan (Tpt, Hycamtin) is currently used in clinic, its effectiveness varying considerably for different types of cancer. The purpose of this study was to compare time- and dose-dependent cellular responses to Tpt in terms of alterations in the amount and stability of topo 1 in lung adenocarcinoma (A-549), ovarian adenocarcinoma (CaOv-3), colorectal adenocarcinoma (HT-29) and breast adenocarcinoma (MCF-7) cell lines. ⋯ The data obtained indicate that Tpt-induced time- and dose-dependent effects on the amount and stability of topo 1 are involved in the mechanisms of Tpt activity against different solid tumor cell lines.