Anticancer research
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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.
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Anticancer research · Mar 2004
Clinical TrialCellular immunomodulation and safety of standardized aqueous mistletoe extract PS76A2 in tumor patients treated for 48 weeks.
Non-selected tumor patients (n=12) with various solid carcinomas were treated continuously twice weekly over 48 weeks with the aqueous mistletoe extract PS76A2, standardized to active mistletoe lectin. The preparation was applied subcutaneously at a concentration of 15 ng mistletoe lectin per 0.5 ml. Cellular immune response and safety were determined at various times during and after the therapy. ⋯ The extensive laboratory diagnostics (haematology, clinical chemistry) showed that treatment with the standardized mistletoe extract PS76A2 was well tolerated by all patients. In single cases, local reactions at the injection sites were of a minor nature and reversible within two days. Summarizing, it can be stated that the standardized mistletoe extract PS76A2 significantly improved the immune status of tumor patients and was administered safely over a long period.
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Anticancer research · Jan 2004
Randomized Controlled Trial Multicenter Study Clinical TrialImpact of complementary mistletoe extract treatment on quality of life in breast, ovarian and non-small cell lung cancer patients. A prospective randomized controlled clinical trial.
Standardized aqueous mistletoe extracts have been applied to cancer patients for several decades as complementary medicine. A multicentric, randomized, open, prospective clinical trial was conducted in three oncological centers in the People's Republic of China in Bejing, Shenyang and Tianjin. Following the guidelines of "Good Clinical Practice" (GCP) this study was performed to get information on efficacy safety and side-effects of the standardized mistletoe extract (sME). ⋯ Only one serious AE was allocated to complementary treatment in each group (1 angioedema in sME group). All other side-effects of the sME (7 harmless local inflammatory reactions at subcutaneous injection site, 4 cases with fever) were self-limiting and did not demand therapeutic intervention. This study showed that complementary treatment with sME can beneficially reduce the side-effects of chemotherapy in cancer patients and thus improve quality of life.
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Anticancer research · Jan 2004
Clinical TrialPhase II study of weekly oxaliplatin and high-dose infusional 5-fluorouracil plus leucovorin in pretreated patients with metastatic colorectal cancer.
Chemotherapy with oxaliplatin, fluorouracil (5-FU) and leucovorin (LV) has proven efficacy in patients with advanced colorectal carcinoma (CRC), although the optimal dosage and administration schedule are still unclear. This phase II trial investigated the tolerability and activity of weekly oxaliplatin, high-dose infusional 5-FU and LV in pretreated patients with metastatic CRC. ⋯ The study demonstrated that this regimen has a favourable tolerability profile and is an active combination in the pretreated metastatic CRC patient, deserving further evaluation in phase III trials.