Tinzaparin

Wong, Nina N.

doi:10.1097/00132580-200209000-00009

Cited by 3 publications

(1 citation statement)

References 44 publications

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“…Low molecular weight heparins (LMWHs) are currently used for antithrombotic treatment (2,3); antithrombin limits the coagulation process, while its anticoagulant activity is stimulated by heparin (4). Tinzaparin is a LMWH-anticoagulant used for the treatment of deep vein thrombosis (5), and is recommended for optimum antithrombotic interventions in the secondary prophylaxis of cancer patients (6) with renal failure (7) and brain tumors (8). Several studies (9)(10)(11)(12)(13)(14)(15)(16)(17), reviewed for experimental models (18), have shown the anticancer properties of tinzaparin However, in local tumor growth, tinzaparin failed to impede cellular proliferation in an in vitro model of human breast cancer cells (11).…”

Section: Introductionmentioning

confidence: 99%

Tinzaparin inhibits VL30 retrotransposition induced by oxidative stress and/or VEGF in HC11 mouse progenitor mammary cells: Association between inhibition of cancer stem cell proliferation and mammosphere disaggregation

et al. 2021

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Tinzaparin is an anticoagulant and antiangiogenic drug with inhibitory properties against tumor growth. VEGF stimulates angiogenesis, while an association between reactive oxygen species (ROS) and angiogenesis is involved in tumor progression. The present study aimed to investigate the effect of tinzaparin on VL30 retrotransposition-positive mouse HC11 mammary stem-like epithelial cells, previously reported to be associated with induced mammosphere/cancer stem cell (CSC) generation and tumorigenesis. Under 24 h serum starvation, 15.2% nominal retrotransposition frequency was increased to 29%. Additionally, while treatment with 3–12 ng/ml VEGF further induced retrotransposition frequency in a dose-dependent manner (up to 40.3%), pre-incubation with tinzaparin (2 IU/ml) for 0.5–4 h reduced this frequency to 18.3% in a time-dependent manner, confirmed by analogous results in NIH3T3 fibroblasts. Treatment with 10–40 pg/ml glucose oxidase (GO) for 24 h induced HC11 cell retrotransposition in a dose-dependent manner (up to 82.5%), while a 3 h pre-incubation with tinzaparin (1 or 2 IU/ml) elicited a 13.5 or 25.5% reduction in retrotransposition, respectively. Regarding tumorigenic VL30 retrotransposition-positive HC11 cells, treatment with 2 IU/ml tinzaparin for 5 days reduced proliferation rate in a time-dependent manner (up to ~55%), and after 3 weeks, disaggregated soft agar-formed foci, as well as low-adherent mammospheres, producing single mesenchymal-like cells with a ~50% reduced retrotransposition. With respect to the VL30 retrotransposition mechanism: While 12 ng/ml VEGF increased the level of VL30 and endogenous reverse transcriptase (enRT) transcripts ~1.41- and ~1.16-fold, respectively, subsequent tinzaparin treatment reduced both endogenous/ROS- and VEGF-induced levels 1.15- and 0.40-fold (VL30) and 0.60- and 0.52-fold (enRT), respectively. To the best of our knowledge, these data demonstrate for the first time, the novel inhibition activity of tinzaparin against ROS- and VEGF-induced VL30 retrotransposition, and the proliferation and/or aggregation of mouse HC11 mammosphere/tumor-initiating CSCs, thus contributing to the inhibition of VL30 retrotransposition-induced primary tumor growth.

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Section: Introductionmentioning

confidence: 99%

Tinzaparin inhibits VL30 retrotransposition induced by oxidative stress and/or VEGF in HC11 mouse progenitor mammary cells: Association between inhibition of cancer stem cell proliferation and mammosphere disaggregation

et al. 2021

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Antimetastatic effect of tinzaparin, a low-molecular-weight heparin

Amirkhosravi

Mousa

Amaya

et al. 2003

Journal of Thrombosis and Haemostasis

106

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To cite this article: Amirkhosravi A, Mousa SA, Amaya M, Francis JL. Antimetastatic effect of tinzaparin, a low-molecular-weight heparin. J Thromb Haemost 2003; 1: 1972±6. See also lorio A et al. Low-molecular-weight heparin for the long-term treatment of symptomatic venous thromboembolism: meta-analysis of the randomized comparisons with oral anticoagulants. This issue, pp. 1906±13.Summary. The importance of coagulation activation in cancer patients is suggested by the clinical ®nding of hypercoagulability, experimental enhancement of metastasis and angiogenesis by coagulation factors such as tissue factor (TF) and thrombin and the possible antitumor effects of anticoagulant agents. Tinzaparin is a low-molecular-weight heparin (LMWH) with a relatively high molecular weight distribution and high sulfate to carboxylate ratio. In addition to its ability to inhibit thrombin and factor Xa, tinzaparin is particularly effective at releasing endothelial tissue factor pathway inhibitor (TFPI), the natural inhibitor of both procoagulant and non-coagulant effects of TF. The present study was undertaken to investigate the effect of tinzaparin on lung metastasis using a B16 melanoma model in experimental mice. Tinzaparin's anticoagulant effect in mice and its ability to release TFPI from human endothelial cells at various time points were demonstrated. Subcutaneous (s.c.) injection of tinzaparin (10 mg kg À1 ) 4 h before intravenous administration of melanoma cells (2.0 Â 10 5 ) markedly (89%) reduced lung tumor formation (3 AE 2) compared with controls (31 AE 23; P < 0.001). In a second group of animals, tinzaparin (10 mg kg À1 , s.c.) administered daily for 14 days following the initial (pretumor cell) dose, before assessment of lung seeding, reduced tumor formation by 96% (P < 0.001). No bleeding problems were observed in any of the tinzaparintreated animals, despite a 4-fold prolongation of the whole blood clotting time after a single s.c. dose of tinzaparin (10 mg kg À1 ). Administration of tumor cells (2 Â 10 6 ) caused a rapid and signi®cant fall in platelet count 15 min after injection (a sensitive marker of intravascular coagulation) in controls (939 AE 37 vs. 498 AE 94 Â 10 6 mL À1 , P < 0.01), but this was prevented by tinzaparin treatment (921 AE 104 Â 10 6 mL À1 ). These data provide further experimental evidence to support the potential for LMWH as antimetastatic agents.

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Efficacy of anticoagulants and platelet inhibitors in cancer-induced thrombosis

Cloonan

DiNapoli

Mousa

2007

Blood Coagulation &Amp; Fibrinolysis

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The efficacy of anticoagulants, low-molecular-weight heparins (LMWHs), the antiplatelet glycoprotein IIb/IIIa antagonist, or combinations on cancer-activated thrombosis was determined using thromboelastography. The LMWHs tinzaparin and enoxaparin (0.179, 1.79, 17.9 microg) were incubated in human citrated whole blood (n = 4) and then activated by calcium chloride (11 mmol/l) or Colo205 (cell count 10). Concentrations of 9.9, 17.9 and 179 microg glycoprotein IIb/IIIa antagonist, XV454, and combinations with each LMWH were carried out and activated under the same conditions. The experiment was repeated with tissue factor substituting for the Colo205 to induce platelet/fibrin clot formation. Parameters tested in the thrombelastography analysis included clotting time, rate of clot formation due to fibrin formation, clot kinetics, and clot strength related to platelet count (maximum amplitude). Tinzaparin (1.79 microg), enoxaparin (1.79 microg), and XV454 (17.9 microg) significantly reduced the angle by 64, 26 and 27%, respectively, in cancer-induced clotting. Significant reductions in the maximum amplitude occurred in tinzaparin 1.79 microg (31%), enoxaparin 1.79 microg (11%), and XV454 17.9 microg (59%). An overall antithrombotic additive effect occurred when each LMWH (1.79 microg) was combined with XV454 (17.9 microg). The results between cancer-activated and tissue factor-activated blood were similar. The study concludes that an additive effect is present between LMWHs and a glycoprotein IIb/IIIa antagonist in reducing cancer-mediated thrombosis.

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Tinzaparin

Cited by 3 publications

References 44 publications

Tinzaparin inhibits VL30 retrotransposition induced by oxidative stress and/or VEGF in HC11 mouse progenitor mammary cells: Association between inhibition of cancer stem cell proliferation and mammosphere disaggregation

Tinzaparin inhibits VL30 retrotransposition induced by oxidative stress and/or VEGF in HC11 mouse progenitor mammary cells: Association between inhibition of cancer stem cell proliferation and mammosphere disaggregation

Antimetastatic effect of tinzaparin, a low-molecular-weight heparin

Efficacy of anticoagulants and platelet inhibitors in cancer-induced thrombosis

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