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The antineoplastic effect of low-molecular-weight heparins - a literature review.

ABSTRACT: There is some evidence for the antitumor effect of heparins, especially the low-molecular-weight ones. The authors discuss the potential mechanism of this antineoplastic effect and present results from several in vitro and in vivo experiments. The clinical trials concerning the impact of low-molecular-weight heparins on the tumor and on the patients' survival are described. The objective was to find out if heparins could be administered as an antitumor drug, independently of their anticoagulatory properties. The antitumor role of tissue factor, heparinase, chemokines, stromal proteins, cellular interactions as well as angiogenesis and immunology seems certain. The results of the available studies seem promising but large clinical trials are necessary in order to confirm the antineoplastic effect of the low-molecular-weight heparins and to approve them for standard anticancer treatment. It could be a breakthrough in modern oncology.

SUBMITTER: Bochenek J

PROVIDER: S-EPMC3685354 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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The antineoplastic effect of low-molecular-weight heparins - a literature review.

Bochenek Justyna J Püsküllüoğlu Mirosława M Krzemieniecki Krzysztof K

Contemporary oncology (Poznan, Poland) 20130315 1

There is some evidence for the antitumor effect of heparins, especially the low-molecular-weight ones. The authors discuss the potential mechanism of this antineoplastic effect and present results from several in vitro and in vivo experiments. The clinical trials concerning the impact of low-molecular-weight heparins on the tumor and on the patients' survival are described. The objective was to find out if heparins could be administered as an antitumor drug, independently of their anticoagulator ...[more]

PMID: 23788954

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Project description:Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity in the presence of circulating antiphospholipid antibodies (aPL). Different pathogenic mechanisms for aPL-mediated pregnancy failure have been proposed. In particular a direct effect of aPL on both maternal and fetal side of the placental tissue has been reported, since their reactivity with ?2-glycoprotein I (?2GPI) makes them adhere to trophoblast and human endometrial endothelial cell (HEEC) membranes. ?2GPI can be recognized by aPL that, once bound, interfere with both trophoblast functions and with the HEEC differentiation.APS patients can be successfully treated with Low Molecular Weight Heparin (LMWH). Recent reports suggest that LMWH acts through mechanisms alternative to its well known anticoagulant effect, because of its ability to bind ?2GPI. In our previous studies, we showed that LMWH is able to reduce the aPL binding to trophoblasts and restore cell invasiveness and differentiation. So far, however, no study has described its effects on endometrial angiogenesis.The aim of our research was to evaluate whether two LMWHs, tinzaparin and enoxaparin, have an effect on the aPL-inhibited endometrial angiogenesis. This prompted us to investigate: (i) in vitro HEEC angiogenesis through a Matrigel assay; (ii) VEGF secretion by ELISA; (iii) matrix metalloproteinase-2 (MMP-2) activity by gelatin zymography; (iv) Nuclear Factor-?B (NF-?B) DNA binding activity by colorimetric assay; (v) STAT-3 activation by a sandwich-ELISA kit. Furthermore, using an in vivo murine model we investigated the LMWHs effects on angiogenesis.We demonstrated that the addition of LMWHs prevents aPL-inhibited HEEC angiogenesis, both in vitro and in vivo, and is able to restore the aPL inhibited NF-?B and/or STAT-3 activity, the VEGF secretion and the MMPs activity.The demonstration of a beneficial role for LMWHs on the aPL-inhibited HEEC angiogenesis might provide additional mechanisms whereby this treatment protects early pregnancy in APS.

Project description:New SARS-CoV-2 variants of concern and waning immunity demonstrate the need for a quick and simple prophylactic agent to prevent infection. Low molecular weight heparins (LMWH) are potent inhibitors of SARS-CoV-2 binding and infection in vitro. The airways are a major route for infection and therefore inhaled LMWH could be a prophylactic treatment against SARS-CoV-2. We investigated the efficacy of in vivo inhalation of LMWH in humans to prevent SARS-CoV-2 attachment to nasal epithelial cells in a single-center, open-label intervention study. Volunteers received enoxaparin in the right and a placebo (NaCl 0.9%) in the left nostril using a nebulizer. After application, nasal epithelial cells were retrieved with a brush for ex-vivo exposure to either SARS-CoV-2 pseudovirus or an authentic SARS-CoV-2 isolate and virus attachment as determined. LMWH inhalation significantly reduced attachment of SARS-CoV-2 pseudovirus as well as authentic SARS-CoV-2 to human nasal cells. Moreover, in vivo inhalation was as efficient as in vitro LMWH application. Cell phenotyping revealed no differences between placebo and treatment groups and no adverse events were observed in the study participants. Our data strongly suggested that inhalation of LMWH was effective to prevent SARS-CoV-2 attachment and subsequent infection. LMWH is ubiquitously available, affordable, and easy to apply, making them suitable candidates for prophylactic treatment against SARS-CoV-2. IMPORTANCE New SARS-CoV-2 variants of concern and waning immunity demonstrate the need for a quick and simple agent to prevent infection. Low molecular weight heparins (LMWH) have been shown to inhibit SARS-CoV-2 in experimental settings. The airways are a major route for SARS-CoV-2 infection and inhaled LMWH could be a prophylactic treatment. We investigated the efficacy of inhalation of the LMWH enoxaparin in humans to prevent SARS-CoV-2 attachment because this is a prerequisite for infection. Volunteers received enoxaparin in the right and a placebo in the left nostril using a nebulizer. Subsequently, nasal epithelial cells were retrieved with a brush and exposed to SARS-CoV-2. LMWH inhalation significantly reduced the binding of SARS-Cov-2 to human nasal cells. Cell phenotyping revealed no differences between placebo and treatment groups and no adverse events were observed in the participants. Our data indicated that LMWH can be used to block SARS-CoV-2 attachment to nasal cells. LMWH was ubiquitously available, affordable, and easily applicable, making them excellent candidates for prophylactic treatment against SARS-CoV-2.

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The antineoplastic effect of low-molecular-weight heparins - a literature review.

Publications

The antineoplastic effect of low-molecular-weight heparins - a literature review.

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