Inhibition of experimental lung metastases of Lewis lung carcinoma cells by chemically modified heparin with reduced anticoagulant activity

Involvement of Highly Sulfated Chondroitin Sulfate in the Metastasis of the Lewis Lung Carcinoma Cells

“…2), suggesting an important role for cell sur- face CS/DS in the metastatic process. The involvement of the cell surface CS/DS in the metastasis prompted us to explore the possibility that the administration of CS/DS preparations inhibits the metastatic process, as in the case of heparin/HS in the previous work by us (36) and others (37).…”

Low-Anticoagulant Heparins in the Treatment of Metastasis

“…Of the available low anticoagulant heparin derivatives (Casu et al, 2008;Fryer et al, 1997;Kragh & Loechel, 2005;Lapierre et al, 1996;Ono et al, 2002;Rao et al, 2010;Stevenson et al, 2007;Wang et al, 2002;Yoshitomi et al, 2004), only ODSH has been proven safe from major adverse events in humans ) data on file with FDA) and only ODSH is free from the potential to induce HIT . The concept that P-selectin is the key molecule in metastasis is based on the attenuation of metastasis in animal models.…”

“…However, shortly after its initial discovery, it was reported that heparin had an inhibitory effect on tumor growth in animals (Goerner, 1930). This initial observation led to intensive investigation with regard to heparin's anticancer and anti-metastatic properties (Casu et al, 2010;Casu et al, 2008;Hettiarachchi et al, 1999;Kragh & Loechel, 2005;Lapierre et al, 1996;Lever & Page, 2002;Ono et al, 2002;Ornstein & Zacharski, 1999;Smorenburg et al, 1996;Stevenson et al, 2005;Stevenson et al, 2007;Vlodavsky et al, 2006;Yip et al, 2006;Yoshitomi et al, 2004). The usefulness of heparin as an anticancer drug has been hindered by its anticoagulant effect at therapeutic doses required to inhibit cancer growth and spread.…”

Old and new applications of non-anticoagulant heparin

“…[99] Astenose Adjuvant in cardiovascular intervention c [113] ROH Heparanase antiangiogenesis inhibitor b [114] ROH P selectin inhibitor [115] LAC-HP antimetastatic b [116] ROH Integrin-melanoma cell binding inhibitor a [117] ROH Antianemic as hepicdine inhibitor b [118] ROH Antinflammation-human elastase inhibitors a [118] gs-LMWH ORG 31733 HIV-1 and HIV-2 inhibitor a [120] SR 80258 Allergic airway response inhibitor b [121] Vasoflux Anticoagulant independent from AT activity, coadjuvant in myocardial infarction therapy d [108,109] NAC from Tinzaparin Antimetastatic b [122] gs-LMWH antimalarial, parasite adhesion, inhibitor b [44] DF01 -Tafoxiparin Labor pain attenuation d [111] M-402 Nocuparanib Metastasis and multiple pathway inhibitor d [110] DFX 232-Sevuparin Antimalarial, distrupting "Plasmodium falciparium" rosettes d [112]]-Preventive activity of vasoocclusion in sickle severe hereditary anemia d S-NACH Anticancer increasing tumor chemo-responsiveness c [35] gs-ULMWH RO-Fondaparinux Antinflammation b [123] Undersulfated RO ST1514" Antinflammatory -heparanase inhibitor b [124] Antiangiogenic, as FGF-2 and VEGF inhibitors b [125,126] N-acylated gs-heparins …”