| 21. |
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| 22. |
- Johansson, Senia, et al.
(author)
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Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells
- 2001
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In: Anti-Cancer Drugs. - 0959-4973 .- 1473-5741. ; 12:5, s. 475-83
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Journal article (peer-reviewed)abstract
- The saponin digitonin, the aglycone digitoxigenin and five cardiac glycosides were evaluated for cytotoxicity using primary cultures of tumor cells from patients and a human cell line panel (representing different cytotoxic drug-resistance patterns). Of these seven compounds, proscillaridin A was the most potent (IC(50): 6.4--76 nM), followed by digitoxin, and then ouabain, digoxin, lanatoside C, digitoxigenin and digitonin. Correlation analysis of the log IC(50) values for the cell lines in the panel showed that compound cytotoxicity was only slightly influenced by resistance mechanisms that involved P-glycoprotein, topoisomerase II, multidrug resistance-associated protein and glutathione-mediated drug resistance. Digitoxin and digoxin expressed selective toxicity against solid tumor cells from patients, while proscillaridin A expressed no selective toxicity against either solid or hematological tumor cells. The results revealed marked differences in cytotoxicity between the cardiac glycosides, both in potency and selectivity, and modes of action for cytotoxicity that differ from that of commonly used anticancer drugs.
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| 23. |
- Jönsson, Peter, et al.
(author)
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Methotrexate concentrations in cerebrospinal fluid and serum, and the risk of central nervous system relapse in children with acute lymphoblastic leukaemia
- 2007
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In: Anti-Cancer Drugs. - 0959-4973. ; 18:8, s. 941-948
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Journal article (peer-reviewed)abstract
- The aim of the study was to characterize the relationship between the pharmacolkinetics of methotrexate in serum and concentrations in the cerebrospinal fluid, and to analyse the association to risk of a central nervous system relapse in children with acute lymphoblastic leukaemia. In this retrospective study, 353 children with acute lymphoblastic leukaemia treated with high-dose methotrexate according to the Nordic Society of Pediatric Haematology and Oncology-92 acute lymphoblastic leukaemia protocol were studied. Data from 18 patients with a subsequent central nervous system relapse and 335 event-free patients were available. In 34 patients the methotrexate concentrations were monitored repeatedly during each 24-h methotrexate intravenous infusion and a cerebrospinal fluid sample was taken at the end of the infusion. Using statistics separating interindividual and intraindividual variability, methotrexate concentration in cerebrospinal fluid was found to be significantly dependent upon both serum concentrations at the end of infusion and the area under the concentration curve in serum (P<0.0017 and <0.002, respectively). The logistic regression analysis revealed that high patient median serum methotrexate concentrations at the end of infusion were significantly associated with decreased risk for a central nervous system relapse in the standard risk group (P=0.02) and the number of courses with a calculated cerebrospinal fluid concentration of more than 1 mu mol/l (P=0.048) with a decreased risk of a central nervous system relapse in the combined (standard risk and intermediate) risk group. In conclusion, methotrexate concentrations in cerebrospinal fluid are dependent on methotrexate concentrations in serum and serum area under the concentration curve. Multivariate analysis indicates that an increased exposure to methotrexate is related to decreased risk for central nervous system relapse.
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| 24. |
- Karlson, J., et al.
(author)
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Inhibition of tumor cell growth by monoterpenes in vitro : Evidence of a Ras-independent mechanism of action
- 1996
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In: Anti-Cancer Drugs. - : Ovid Technologies (Wolters Kluwer Health). - 0959-4973 .- 1473-5741. ; 7:4, s. 422-429
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Journal article (peer-reviewed)abstract
- (+)-Limonene (d-limonene) and related monoterpenes show chemopreventive activity against rodent mammary carcinoma and inhibit the growth of cancer cells in vitro, One suggested mechanism for the anti-tumorigenic effect of (+)-limonene is inhibition of the post-translational isoprenylation of growth controlling Pas oncoproteins. We have here examined the growth inhibitory effects of (+)-limonene and other related monoterpenes on PANC-1 pancreas carcinoma cells (carrying a K-ras mutation) and on 12V-H-ras-transformed rat fibroblasts, (+)- and (-)-perillyl alcohol, 7-methyl-perillyl alcohol, (+)-limonene oxide and (+)-perillic acid methyl ester were all found to efficiently inhibit cell growth at 1 mM, whereas (+)-limonene caused an approximately 50% growth reduction at 5 mM, Whereas BZA-BB, an inhibitor of Ras farnesyl transferase, was found to induce morphological reversion of 12v-H-ras-transformed cells, (+)-perillyl alcohol and (+)-limonene did not induce reversion. Furthermore, monoterpenes did not decrease MAP kinase enzyme activity or collagenase promoter activity in PANC-1 cells, two functions known to be down-stream from Pas, We conclude that although effective in inhibiting the growth of tumor cells harboring activated res oncogenes, limonene and (+)-perillyl alcohol are unlikely to act by inhibiting Ras function.
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| 25. |
- Laryea, Daniel, et al.
(author)
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Characterization of the cytotoxic properties of the benzimidazole fungicides, benomyl and carbendazim, in human tumour cell lines and primary cultures of patient tumour cells
- 2010
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In: Anti-Cancer Drugs. - 0959-4973 .- 1473-5741. ; 21:1, s. 33-42
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Journal article (peer-reviewed)abstract
- The benzimidazoles, benomyl and carbendazim, are fungicides suggested to target microtubules. Benomyl is metabolized to carbendazim, which has already been explored as an anticancer drug in phase 1 clinical trials. We further characterized the cytotoxic properties of benomyl and carbendazim in 12 human cell lines and in primary cultures of patient tumour cells with the overall aims of elucidating mechanisms of action and anticancer activity spectrum. Cytotoxicity was assessed in the short-term fluorometric microculture cytotoxicity assay and was correlated with the activity of other anticancer drugs and gene expression assessed by cDNA microarray analysis. Benomyl was generally more potent than its metabolite, carbendazim. Both showed high drug activity correlations with several established and experimental anticancer drugs, but modest association with established mechanisms of drug resistance. Furthermore, these benzimidazoles showed high correlations with genes considered relevant for the activity of several mechanistically different standard and experimental anticancer drugs, indicating multiple and broad mechanisms of action. In patient tumour samples, benomyl tended to be more active in haematological compared with solid tumour malignancies, whereas the opposite was observed for carbendazim. In conclusion, benomyl and carbendazim show interesting and diverse cytotoxic mechanisms of action and seem suitable as lead compounds for the development of new anticancer drugs.
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| 26. |
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| 28. |
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| 30. |
- Min, Liu, et al.
(author)
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Clinical efficacy of irinotecan plus raltitrexed chemotherapy in refractory esophageal squamous cell cancer
- 2020
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In: Anti-Cancer Drugs. - : LIPPINCOTT WILLIAMS & WILKINS. - 0959-4973 .- 1473-5741. ; 31:4, s. 403-410
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Journal article (peer-reviewed)abstract
- Our retrospective study assessed the efficacy and safety of irinotecan plus raltitrexed in esophageal squamous cell cancer (ESCC) patients who were previously treated with multiple systemic therapies. Between January 2016 and December 2018, records of 38 ESCC patients who underwent irinotecan plus raltitrexed chemotherapy after at least one line of chemotherapy were reviewed. Efficacy assessment was performed every two cycles according to the RECIST version 1.1. A total of 95 cycles of chemotherapy were administered, and the median course was 3 (range 2-6). There was no treatment-related death. Nine patients had partial response, 21 had stable disease and eight had progressive disease. The overall objective response rate was 23.68% (9/38) and the disease control rate was78.94% (30/38). After a median follow-up of 18.5 months, the median progression-free survival and overall survival were 105 and 221 days, respectively. There were five patients (13.15%) with grade 3/4 leukopenia, three patients (7.89%) with grade 3/4 neutropenia and one patient (2.63%) with grade 3/4 diarrhea. The combination of irinotecan plus raltitrexed was effective for pretreated ESCC patients. Further studies are needed to determine the optimal dose of the two drugs.
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