Search results for "Mafosfamide"

The Impact of Insulin on Low-dose Metronomic Vinorelbine and Mafosfamide in Breast Cancer Cells

2021

Background/aim Breast cancer (BC) may be affected by diabetes and anti-diabetic medication, as well as its therapeutic agents. Low-dose metronomic chemotherapy (LDMC) is an available treatment option in BC. We investigated the impact of insulin on low-dose metronomic vinorelbine and mafosfamide in BC cell lines. Materials and methods Human BC cell lines T-47D, MCF-7, MDA-MB-231, BT-549 and non-tumorigenic breast cell line MCF-10A were exposed to 0.01 μg/ml and 10 μg/ml insulin in combination with low-dose metronomic vinorelbine or mafosfamide. The cell viability was determined after 24-72 hours using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Results Insulin, especi…

Treatment with the anti-tumor drugs, cis-platin and mafosfamide, does not affect the structure of prekinetochores in a human breast cancer cell line.…

1996

Abstract The goal of the present article was to determine whether a nuclear parameter, centromere structure of interphase cells, could serve as an indicator to assess cellular damage caused by anti-tumor drugs. These were cis-platin and mafosfamide, which are widely used for the management of solid tumors. To visualize the centromeres, we probed treated and untreated cells of a human breast cancer cell line, MX-1, with a human anti-centromere serum. The serum was obtained from a scleroderma patient and detects antigens associated with prekinetochores of the decondensed chromosomes. The DNA was simultaneously displayed by a specific fluorescent dye. The cells were grown on coverslips, incuba…

Apoptotic death induced by the cyclophosphamide analogue mafosfamide in human lymphoblastoid cells: Contribution of DNA replication, transcription in…

2007

Cyclophosphamide is one of the most often used anticancer drugs. Although DNA interstrand cross-links are considered responsible for its cytotoxicity, the mechanism of initiation and execution of cell death is largely unknown. Using the cyclophosphamide analogue mafosfamide, which does not need metabolic activation, we show that mafosfamide induces apoptosis dose and time dependently in lymphoblastoid cells, with clearly more apoptosis in p53(wt) cells. We identified two upstream processes that initiate apoptosis, DNA replication blockage and transcriptional inhibition. In lymphoblastoid cells, wherein DNA replication can be switched off by tetracycline, proliferation is required for induci…

Enhancement of the Mutagenicity of Ethylene Oxide and Several Directly Acting Mutagens by Human Erythrocytes and its Reduction by Xenobiotic Interact…

1999

According to the present state of knowledge mutagenicity or genotoxicity of the ulti mate genotoxic agents ethylene oxide or styrene oxide cannot be increased by further me tabolism. However, in the present study we demonstrate that mutagenicity of several ultimate genotoxic substances is increased by human erythrocytes. For instance mu tagenicity of mafosfamide, N-nitroso-N-methylurea, ethylene oxide, and styrene oxide to Salmonella typhimurium TA 1535 was increased 5.5-, 5.1-, 2.7-, and 2.3-fold, respectively, by addition of human erythrocyte homogenate to the preincubation mixture in the Ames test. On the other hand, the mutagenicity of cumene hydroperoxide, benzo[a]pyrene-4,5-oxide, and…

Protective effect of O6-methylguanine-DNA methyltransferase (MGMT) on the cytotoxic and recombinogenic activity of different antineoplastic drugs

1996

The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) removes alkyl groups from the O6 position of guanine in DNA and thus may protect cells against genotoxic effects of agents inducing this lesion. To analyze quantitatively the level of protection mediated by MGMT against antineoplastic drugs, we determined the cytotoxic and recombinogenic (sister-chromatid exchange inducing) effects of various chemotherapeutic agents in a pair of isogenic Chinese hamster cell lines deficient and proficient for MGMT, generated upon transfection with human MGMT cDNA. Furthermore, we compared the responses of the human cell lines HeLa MR (MGMT deficient) and HeLa S3 (MGMT proficient) to the va…

Xrcc2 deficiency sensitizes cells to apoptosis by MNNG and the alkylating anticancer drugs temozolomide, fotemustine and mafosfamide

2006

DNA double-strand breaks (DSBs) are potent killing lesions, and inefficient repair of DSBs does not only lead to cell death but also to genomic instability and tumorigenesis. DSBs are repaired by non-homologous end-joining and homologous recombination (HR). A key player in HR is Xrcc2, a Rad51-like protein. Cells deficient in Xrcc2 are hypersensitive to X-rays and mitomycin C and display increased chromosomal aberration frequencies. In order to elucidate the role of Xrcc2 in resistance to anticancer drugs, we compared Xrcc2 knockout (Xrcc2-/-) mouse embryonic fibroblasts with the corresponding isogenic wild-type and Xrcc2 complemented knockout cells. We show that Xrcc2-/- cells are hypersen…

2013

Regulatory T cells (Treg) play a pivotal role in the immune system since they inhibit the T cell response. It is well known that cyclophosphamide applied at low dose is able to stimulate the immune response while high dose cyclophosphamide exerts inhibitory activity. Data obtained in mice indicate that cyclophosphamide provokes a reduction in the number of Treg and impairs their suppressive activity, resulting in immune stimulation. Here, we addressed the question of the sensitivity of human Treg to cyclophosphamide, comparing Treg with cytotoxic T cells (CTL) and T helper cells (Th). We show that Treg are more sensitive than CTL and Th to mafosfamide, which is an active derivative of cyclo…