The in-vitro effect of antineoplastic agents on proliferative activity and cytoskeletal components of plaque-derived smooth-muscle cells from human coronary arteries

Voisard, Rainer; Pc, Dartsch; Seitzer, U; Hannekum, A; Roth, D.; Kochs, Matthias; Hombach,

doi:10.1097/00019501-199310000-00014

Cited by 20 publications

(9 citation statements)

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“…In a very schematic way, elastic recoil, thrombosis, leukocyte attack, reactive cell migration and proliferation, apoptosis, production of extracellular matrix and arterial remodeling are the main events after coronary injury [12]. Our group has, among others, studied the antiproliferative effect of potential antirestenotic agents [18][19][20]. Despite positive in vitro and experimental data, systemic clinical trials have failed [5].…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative profile of sirolimus and mycophenolate mofetil: impact of the SI/MPL ratio

Voisard

Geçgüner

Baur

et al. 2005

International Journal of Cardiology

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Section: Introductionmentioning

confidence: 99%

Antiproliferative profile of sirolimus and mycophenolate mofetil: impact of the SI/MPL ratio

Voisard

Geçgüner

Baur

et al. 2005

International Journal of Cardiology

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“…In comparison to the strong antiproliferative effects in human vascular smooth muscle cells described earlier by our group after administration of cytostatic agents [23], steroid agents [24], and immunosuppressive agents [25] the antiproliferative effects of ganciclovir are comparable with inhibitory effects of 41.8% (500 μg/mL) and 100% (5000 μg/mL), respectively.…”

Section: Discussionmentioning

confidence: 62%

Direct inhibitory effects of Ganciclovir on ICAM-1 expression and proliferation in human coronary vascular cells (SI/MPL-ratio: >1)

et al. 2011

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SummaryBackgroundTreatment of the human cytomegalovirus (HCMV) infection with ganciclovir has beneficial indirect effects on the complex interactions of HCMV with restenosis, atherosclerosis, and transplant vascular sclerosis. The current study reports on direct effects of ganciclovir on expression of ICAM-1 and cell proliferation, key events of coronary atherosclerosis/restenosis. A potential clinical relevance of the data will be evaluated with the help of SI/MPL-ratio’s.Material/MethodsDefinition of the SI/MPL-ratio: relation between significant inhibitory effects in vitro/ex vivo and the maximal plasma level after systemic administration in vivo (ganciclovir: 9 μg/ml). Part I of the study investigated in cytoflow studies the effect of ganciclovir (0.05–5000 μg/mL) on TNF-a induced expression of intercellular adhesion molecule 1 (ICAM-1) in endothelial cells derived from umbilical veins (HUVEC), human coronary endothelial cells (HCAEC), and human coronary smooth muscle cells (HCMSMC). Part II of the study analysed the effect of ganciclovir (0.05–5000 μg/mL) on cell proliferation (HUVEC, HCAEC, and HCMSMC). In part III cytotoxic effects of ganciclovir (0.05–5000 μg/mL) were studied (HUVEC, HCAEC, and HCMSMC).ResultsGanciclovir caused slight but significant inhibitory effects on expression of ICAM-1 in HUVEC, HCAEC, and HCMSMC. In all three cell types studied strong dose depending significant antiproliferative effects of ganciclovir were detected. Partially, the antiproliferative effects of ganciclovir were caused by cytotoxic effects.ConclusionsSI/MPL-ratio’s >1 in HCAEC and HCMSMC indicate that the inhibitory effects of gancliclovir on ICAM-1-expression and cell proliferation may only be expected in vivo following local high dose administration e.g. in drug eluting stents (DES).

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“…With this system the cell concentration can be analyzed simultaneously in three different size ranges: cell debris, dead cells, and viable cells can be determined in one measurement. [39] BJAB cells were seeded at a density of 1 10 5 cells per mL and were treated with different concentrations of 3; untreated cells served as control. After 24 h incubation the cells were resuspended, and 100 mL from each well was diluted in CASYton (10 mL; ready-to-use isotonic saline solution) for immediate automated count.…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial Mode of Action of a Thymidine‐Based Cisplatin Analogue Breaks Resistance in Cancer Cells

Onambele

Koth

Czaplewska

et al. 2010

Chemistry A European J

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Cisplatin analogue complexes with platinum(II) and palladium(II) starting from 3',5'-diamino-3',5'-dideoxy-thymidines were synthesized, both with the D-erythro- and D-threo configurations. Complexes of the general formula [MCl(2)L] were obtained and characterized. NMR spectroscopic measurements and single crystal X-ray structure analysis showed that the metal centers are coordinated to the ligands by the amino groups in 3'- and 5'-positions and not through the thymine moiety. All ligands and complexes showed no significant in vitro activities except thymiplatin (cis-dichloro(3',5'-diamino-3',5'-dideoxy-D-threo-thymidine)platinum(II)). Detailed in vitro studies on the apoptosis pathway in lymphoma (BJAB), leukemia (NALM-6), and melanoma cells (Mel-HO) as well as on transfected or resistant cell lines were carried out. Thymiplatin significantly induced an apoptotic response, which was found to be associated with the loss of mitochondrial membrane potential and with caspase activation. The activity was shown to be independent of Fas-associated protein with death domain (FADD), but dependent on Bcl-2 expression. As a consequence, for thymiplatin a mitochondrial mode of action could be assigned. Moreover, the compound showed activity in cells resistant to common drugs, such as daunorubicin and vincristin, and showed synergistic effects with doxorubicin, vincristin, cytarabin, and daunorubicin.

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The in-vitro effect of antineoplastic agents on proliferative activity and cytoskeletal components of plaque-derived smooth-muscle cells from human coronary arteries

Cited by 20 publications

References 0 publications

Antiproliferative profile of sirolimus and mycophenolate mofetil: impact of the SI/MPL ratio

Antiproliferative profile of sirolimus and mycophenolate mofetil: impact of the SI/MPL ratio

Direct inhibitory effects of Ganciclovir on ICAM-1 expression and proliferation in human coronary vascular cells (SI/MPL-ratio: >1)

Mitochondrial Mode of Action of a Thymidine‐Based Cisplatin Analogue Breaks Resistance in Cancer Cells

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