Concurrent measurement of the survival of two populations of rabbit platelets labeled with either two PKH lipophilic dyes or two concentrations of biotin

Rand, Margaret L.; Wang, H.; Mody, Meera; Chu, In-Sun; Treutiger, I.; Nguyen, Augustin; Packham, MA; Freedman, John

doi:10.1002/cyto.10055

Cited by 13 publications

(15 citation statements)

References 25 publications

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“…We used a platelet transfusion model as a positive control for the platelet substitutes. The survival time of the transfused platelets was comparable to that obtained from the 51 Cr and 111 In‐labelled platelets evaluated in previous reports (Packham et al , 1992; Franco et al , 1994), whereas the mean percentage of recovery was similar to the that in previous reports (Packham et al , 1992; Franco et al , 1994; Rand et al , 2002). Furthermore, confirmation of a dose‐dependent reduction in the bleeding time after administering PRP to severe thrombocytopenic rabbits established a positive control for comparison with platelet substitutes.…”

Section: Discussionsupporting

confidence: 87%

Haemostatic effects of polymerized albumin particles carrying fibrinogen γ‐chain dodecapeptide as platelet substitutes in severely thrombocytopenic rabbits

Okamura

Fujie

Nogawa

et al. 2008

Transfusion Medicine

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Our purpose was to produce a platelet substitute that could enhance haemostatic ability using rabbits with severe thrombocytopenia. We have developed polymerized albumin particles (polyAlb) for treatment of bleeding and focused on a dodecapeptide, HHLGGAKQAGDV (H12), as a useful ligand for activated platelet. This sequence occurs only at the carboxy-terminus of the fibrinogen gamma-chain (gamma 400-411). H12 was conjugated to the surface of polyAlb modified with poly(ethylene glycol) (PEG) chains to produce blood-compatible particles (H12-PEG-polyAlb) that had prolonged blood residence time and enhanced stability in vitro and in vivo. The H12-PEG-polyAlb was administered intravenously to rabbits with severe thrombocytopenia, and the ear bleeding time was measured in order to evaluate the haemostatic effect. The H12-PEG-polyAlb significantly shortened the ear bleeding time of severely thrombocytopenic rabbits and showed no effect on the inhibition or promotion of endogenous and exogenous coagulation activities. Furthermore, we could assess the haemostatic capacity of the H12-PEG-polyAlb, based on the relationship between transfused platelet count and the bleeding time. The H12-PEG-polyAlb may be a suitable candidate for an alternative to human platelet concentrates infused to treat bleeding in patients with severe thrombocytopenia.

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Section: Discussionsupporting

confidence: 87%

Haemostatic effects of polymerized albumin particles carrying fibrinogen γ‐chain dodecapeptide as platelet substitutes in severely thrombocytopenic rabbits

Okamura

Fujie

Nogawa

et al. 2008

Transfusion Medicine

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“…To test the use of this antibody to visualize platelets, we labeled platelets with PKH26 and then asked whether the antibody allowed microscopic detection of these labeled platelets. PKH26 labeling does not activate platelets, nor does it affect platelet response to thrombin or ADP (41). PKH26-labeled platelets were incubated with mouse melanoma cells B16F10-GFP in tissue culture resulting in aggregates of platelets surrounding the tumor cells.…”

Section: Resultsmentioning

confidence: 99%

Coagulation Facilitates Tumor Cell Spreading in the Pulmonary Vasculature during Early Metastatic Colony Formation

Im¹,

Fu²,

Wang³

et al. 2004

Cancer Research

266

210

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Coagulation has long been known to facilitate metastasis. To pinpoint the steps where coagulation might play a role in the metastasis, we used three-dimensional visualization of direct infusion of fluorescence labeled antibody to observe the interaction of tumor cells with platelets and fibrinogen in isolated lung preparations. Tumor cells arrested in the pulmonary vasculature were associated with a clot composed of both platelets and fibrin(ogen). Initially, the cells attached to the pulmonary vessels were rounded. Over the next 2 to 6 hours, they spread on the vessel surface. The associated clot was lysed coincident with tumor cell spreading. To assess the importance of clot formation, we inhibited coagulation with hirudin, a potent inhibitor of thrombin. The number of tumor cells initially arrested in the lung of hirudin-treated mice was essentially the same as in control mice. However, tumor cell spreading and subsequent retention of the tumor cells in the lung was markedly inhibited in the anticoagulated mice. These associations of the tumor cells with platelets were independent of tumor cell expression of P-selectin ligands. This work identifies tumor cell spreading onto the vascular surface as an important component of the metastatic cascade and implicates coagulation in this process.

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“…12 In order to observe the tumor cell-platelet interactions in lung vessels, platelets were labeled with PKH26 (red), which can not activate platelets and can guarantee the molecules on the platelet surface in its native conformation. 30 At first, we tested the binding ability of A375 cells and B16F10 cells to mouse platelets in vivo. A375-GFP or B16F10-GFP cells (green) and PKH26 labeled platelets (red) were intravenously injected into C57BL/6 mice.…”

Section: The Tumor Cell-platelet Interactions and Lung Metastasis Canmentioning

confidence: 99%

Modified heparins inhibit integrin α_IIbβ₃ mediated adhesion of melanoma cells to platelets in vitro and in vivo

Zhang

Liu

Gao

et al. 2009

Intl Journal of Cancer

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The adhesion of tumor cells with platelets is important in the process of tumor metastasis. A huge work has indicated that antiadhesion is an effective strategy for metastasis inhibition. In this article, we assess the role of platelet integrin a IIb b 3 in adhesion of melanoma cells to platelets and the effects of heparin and modified heparins on the adhesion in vitro and in vivo. We show that platelet integrin a IIb b 3 is involved in the interaction of human melanoma A375 cells with platelets, and the high affinity epitope resides on the a IIb subunit rather than b 3 subunit. Heparin sulfatelike proteoglycans on tumor cell surface are implicated in the adhesion of A375 cells to integrin a IIb b 3 . We also show that RO-heparin, CR-heparin, N-2,3-DS-heparin and 2,3-O-DS-heparin can significantly inhibit A375 cells binding to the CHO cells expressing integrin a IIb b 3 under static and flow conditions, and remarkably inhibit the adhesion of A375 cells to the immobilized platelet layers under flow conditions. We find that A375 cells and B16F10 cells are arrested in the pulmonary vessels and adhered to platelets, and the initial interaction of tumor cells with platelets in lung vessel and long-term establishment of metastatic foci can be inhibited by heparin as well as CR-heparin and N-2,3-DS-heparin. These data suggest that modified heparins can inhibit tumor cellplatelet interaction mediated by platelet integrin a IIb b 3 and modified heparins may be a potential substitute for heparin in inhibiting tumor metastasis. ' UICCKey words: metastasis; adhesion; platelet; Integrin a IIb b 3; ; modified heparin Hematogenous metastasis of tumor cells is a cascade of events in which tumor cells separate from a primary tumor, intravasate into the bloodstream, evade innate immune surveillance, adhere to vascular endothelial cells of distant organs, and extravasate into tissue to generate new colonies. 1,2 It is well accepted that within vasculature circulating the interactions of tumor cells with platelets enhance tumor dissemination. Platelets may limit the ability of NK cells to lyse tumor cells and shield tumor cells from high shear forces that could potentially damage the tumor cells. 3,4 Furthermore, platelets facilitate the adhesion of tumor cells to vascular endothelium and release a number of growth factors, such as platelet-derived growth factor (PDGF), angiogenic growth factor, vascular endothelial growth factor (VEGF) and angiopoietin-1, which are required for metastasis and angiogenesis.Several studies support the view that tumor cell-associated platelets facilitate tumor cell metastasis. It has been shown that the elimination of circulating platelets with anti-platelet antibody result in a significant diminution of metastasis in several transplantable murine tumor models. 5,6 In addition, inhibition of platelet activation can decrease the metastatic potential of circulating tumor cells. 7,8 It is well known that platelets specifically express a IIb b 3, which has been reported to be involved in the interactio...

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Concurrent measurement of the survival of two populations of rabbit platelets labeled with either two PKH lipophilic dyes or two concentrations of biotin

Cited by 13 publications

References 25 publications

Haemostatic effects of polymerized albumin particles carrying fibrinogen γ‐chain dodecapeptide as platelet substitutes in severely thrombocytopenic rabbits

Haemostatic effects of polymerized albumin particles carrying fibrinogen γ‐chain dodecapeptide as platelet substitutes in severely thrombocytopenic rabbits

Coagulation Facilitates Tumor Cell Spreading in the Pulmonary Vasculature during Early Metastatic Colony Formation

Modified heparins inhibit integrin α_IIbβ₃ mediated adhesion of melanoma cells to platelets in vitro and in vivo

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Concurrent measurement of the survival of two populations of rabbit platelets labeled with either two PKH lipophilic dyes or two concentrations of biotin

Cited by 13 publications

References 25 publications

Haemostatic effects of polymerized albumin particles carrying fibrinogen γ‐chain dodecapeptide as platelet substitutes in severely thrombocytopenic rabbits

Haemostatic effects of polymerized albumin particles carrying fibrinogen γ‐chain dodecapeptide as platelet substitutes in severely thrombocytopenic rabbits

Coagulation Facilitates Tumor Cell Spreading in the Pulmonary Vasculature during Early Metastatic Colony Formation

Modified heparins inhibit integrin αIIbβ3 mediated adhesion of melanoma cells to platelets in vitro and in vivo

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Modified heparins inhibit integrin α_IIbβ₃ mediated adhesion of melanoma cells to platelets in vitro and in vivo