Avid Bioservices Inc (CDMO)

[jazzbeerman]

more beautiful Bavi / Cisplatin synergy -

Bavi not only seems to add no toxicity to chemo as stated by PPHM,

Bavi also could/should make chemo safer / improve Cisplatin's safety profile


J Thromb Haemost. 2007 Oct 8


Chemotherapy-induced thrombin generation via procoagulant endothelial microparticles is independent of tissue factor activity.

Lechner D, Kollars M, Gleiss A, Kyrle PA, Weltermann A.

Department of Medicine I, Medical University of Vienna, Vienna, Austria.

Background: Cisplatin-based chemotherapy predisposes cancer patients to thromboembolic events.
Objectives: In this study, we investigated whether endothelial damage, via formation of procoagulant endothelial microparticles (EMP), contributes to cisplatin-related hypercoagulability. Methods: Cell viability and caspase-3/7 activities were assessed in two EC lines (HUVEC, HMVEC-L) after exposure to cisplatin (1, 2.5, 5, 10, and 20 muM) for up to 120 h. Counts and procoagulant activity of EMP were measured by flow cytometry and a thrombin generation assay, respectively. Tissue factor (TF) antigen and TF-dependent procoagulant activity of EMP were determined by ELISA and a novel functional assay. Results: By inducing apoptosis, cisplatin dose-and time-dependently decreased viability of confluent HUVEC and HMVEC-L endothelial cells. Progression of endothelial cell death was accompanied by an increased release of EMP (relative increase at 20 muM cisplatin for 48 h versus control: HUVEC 6.5-fold, p < 0.001; HMVEC-L 18.4-fold, p < 0.001). EMP were highly procoagulant (relative increase at 20 muM cisplatin for 48 h versus control: HUVEC 2.5-fold, p < 0.001; HMVEC-L 5.9-fold, p < 0.001). EMP-driven thrombin generation, however, was not dependent on TF: TF expression and TF procoagulant activity levels on microparticles were only marginal and EMP-associated thrombin generation remained unchanged when the extrinsic pathway was blocked by omission of factor VIIa and/or incubation with an anti-human TF-antibody. In contrast, blocking of phospholipids by annexin V markedly diminished EMP-associated procoagulant activity. Conclusions:In vitro, cisplatin induced the release of EMP which showed TF-independent procoagulant activity.

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17922809&ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

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