Suppression of angiogenesis by the antitumor agent titanocene dichloride

Bastaki, Maria; Missirlis, Eleftheria; Klouras, Nicolaos; Karakiulakis, George; Maragoudakis, Michael E.

doi:10.1016/0014-2999(94)90408-1

Cited by 20 publications

(8 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Complexes 8 and 4 exhibit ag reat vascular-disrupting activity on the CAM with perfused vasculature reductionso f5 3 and 49 %, respectively.I ntravenous administration of the ruthenium analogue of 8 at ad ose of 50 mm induced an antivascular effect represented by ad ecrease in the number of branching points per mm 2 on the CAM capillary bed by 42 %, [36] less than that observedf or 4.Asimilard ecrease in the number of branching points per mm 2 on the CAM capillaryb ed (by 39 %) was obtained after treatmentw ith sunitinib at 30 mm,t hat is, at ad ose sixfold higher (topicala dministration between EDD 7a nd 9. [50] Various other organometallic compounds, some with bioactive ligands knownt oi nhibit vascularization,h ave been shown to have antiangiogenic properties, including compounds based on titanium, [51][52][53][54] vanadium, [55,56] cobalt, [57] ruthenium, [42,44,[58][59][60][61] iridium, [62,63] platinum, [64] and gold. [65] However,d irect comparisons between these compounds tends to be problematic due to the different modelsa nd protocols used to determine antiangiogenic activity.An otable differencei nt he morphologyo ft he remaining vasculature was observed with 4,l eading to the complete disappearance of capillaries, with only smallp erfused vessels observed.…”

Section: In Vivo Activityi Nthe Chickenc Am Modelmentioning

confidence: 99%

Anticancer Organometallic Osmium(II)‐p‐cymene Complexes

et al. 2015

View full text Add to dashboard Cite

Osmium compounds are attracting increasing attention as potential anticancer drugs. In this context, a series of bifunctional organometallic osmium(II)-p-cymene complexes functionalized with alkyl or perfluoroalkyl groups were prepared and screened for their antiproliferative activity. Three compounds from the series display selectivity toward cancer cells, with moderate cytotoxicity observed against human ovarian carcinoma (A2780) cells, whereas no cytotoxicity was observed on non-cancerous human embryonic kidney (HEK-293) cells and human endothelial (ECRF24) cells. Two of these three cancer-cell-selective compounds induce cell death largely via apoptosis and were also found to disrupt vascularization in the chicken embryo chorioallantoic membrane (CAM) model. Based on these promising properties, these compounds have potential clinical applications.

show abstract

Section: In Vivo Activityi Nthe Chickenc Am Modelmentioning

confidence: 99%

Anticancer Organometallic Osmium(II)‐p‐cymene Complexes

et al. 2015

View full text Add to dashboard Cite

show abstract

“…18 Drugs that promote early and marked angiogenesis enhanced collagen type I deposition 60 whereas suppression of angiogenesis by anti-tumor drugs was associated with decreased collagen synthesis. 61 Delayed neovascularization was also associated with a decrease in collagen type I and TGFβ, the major promoter of collagen type I gene expression. 62 Transcriptional activity of the α1(I)-collagen promoter has been correlated with the formation of capillary-like structures by endothelial cells, 63 and with the stimulation of microvascular endothelial cells to form solid cords that resemble the precapillary structures found during angiogenesis.…”

Section: Discussionmentioning

confidence: 98%

Halofuginone inhibits tumor growth in the polyoma middle T antigen mouse via a thrombospondin-1 independent mechanism

Yee¹,

Connolly²,

Pines³

et al. 2006

Cancer Biology & Therapy

View full text Add to dashboard Cite

“…Taking together the cumulative data generated from various phase I and phase II protocols, it was suggested to stop further clinical development of this compound when used as cytotoxic agent near the maximum tolerated dose. Still interesting is the fact that, with nontoxic dose regimens, TD showed anti-angiogenic properties in in vitro studies [9,10]. For such a use of cytotoxic agents it seems to be necessary to apply these drugs in a metronomic fashion [11,12], which means to administer them continuously in a very low-dose (e.g., constant infusion or daily oral dosing).…”

Section: Discussionmentioning

confidence: 99%

Phase I Clinical Trial of a Day-1, -3, -5 Every 3 WeeksPhase I Clinical Trial of Day-1, -3, -5 Every 3 Weeks Schedule with Titanocene Dichloride (MKT 5) in Patients with Advanced Cancer. (Phase I Study Group of the AIO of the German Cancer Society)

Mross¹,

Robben-Bathe²,

Edler³

et al. 2000

Oncol Res Treat

View full text Add to dashboard Cite

Background: Titanocene dichloride (TD) is an organometallic compound with antiproliferative properties in vitro and promising antitumor activity in preclinical in vivo models. The drug interferes with DNA, blocks the S/G₂ phase of the cell cycle and shows antiangiogenic properties. The purpose of this study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of a ‘split’ dose administration schedule (days 1, 3, 5 q 3 weeks). Patients and Method: Patients with progressive advanced cancer and a creatinine clearance > 60 ml/min qualified for a treatment with TD after standard therapies (radio-, chemo-, hormone therapy) failed. A total of 10 patients (4 females, 6 males) with a median age of 58 (range 49–68) years were treated with 80 mg/m² TD at days 1, 3 and 5 (repeated at day 22). The drug was administered as light-protected infusion within 1 h. Results: Significant side effects were as follows: nausea/vomiting, appetite loss, renal toxicity (elevation of serum creatinine and proteinuria) and liver toxicity (bilirubin and alkaline phosphatase elevation), but no myelosuppression. At the starting dose (3 x 80 = 240 mg/m² TD), renal (3 patients) or liver toxicity (1 patient) of grade 3 was judged as DLT. No further dose escalation was possible. No objective tumor remission was observed. Conclusion: The tolerability of TD cannot be improved by splitting the total dose in to three treatments every other day. Compared to previous phase I data using a 3-weekly and a 1-weekly schedule, the ‘split’ dose administration allowed no further increase of the total drug dose per treatment cycle. Thus, dose intensification by alterations of the application mode does not seem to be possible.

show abstract

Suppression of angiogenesis by the antitumor agent titanocene dichloride

Cited by 20 publications

References 17 publications

Anticancer Organometallic Osmium(II)‐p‐cymene Complexes

Anticancer Organometallic Osmium(II)‐p‐cymene Complexes

Halofuginone inhibits tumor growth in the polyoma middle T antigen mouse via a thrombospondin-1 independent mechanism

Phase I Clinical Trial of a Day-1, -3, -5 Every 3 WeeksPhase I Clinical Trial of Day-1, -3, -5 Every 3 Weeks Schedule with Titanocene Dichloride (MKT 5) in Patients with Advanced Cancer. (Phase I Study Group of the AIO of the German Cancer Society)

Contact Info

Product

Resources

About