Biomedical subjects

Shaker A Mousa

Publications and source records attributed to Shaker A Mousa.

61 records · Page 4Linked to original sources

PubMed2002

The low molecular weight heparin, tinzaparin, in thrombosis and beyond.

Standard unfractionated heparin (UFH) has been in clinical use for over 50 years. The commercial use of low molecular weight heparins (LMWHs) began in the mid 1980s for hemodialysis and the prophylaxis of deep vein thrombosis (DVT). Initially, the clinical development of LMWHs was concentrated on the European continent. Subsequently, LMWHs were introduced in North America as well. In the initial stages of development of these drugs only nadroparin, dalteparin and enoxaparin were used. Subsequently, several other LMWHs such as ardeparin, tinzaparin, reviparin and parnaparin were introduced. LMWHs constitute a group of important medications with total sales reaching nearly 2.5 billion dollars with expanded indications reaching far beyond the initial indications for the prophylaxis of post-surgical DVT. This review highlights the pharmacology of tinzaparin. Unlike other LMWHs, tinzaparin is prepared by enzymatic hydrolysis with heparinase, while various chemical depolymerization methods are used for the synthesis of other LMWHs. As compared with the standard heparin, LMWHs have different pharmacodynamic, and pharmacokinetic properties; they also differ in clinical benefits.

Anticoagulants↗

PubMed2002

The alpha v integrin antagonists as novel anticancer agents: an update.

Integrins are involved in many cellular processes, including some pathological ones associated with various cancers, both solid tumours and metastases. Since integrins are involved in such critical processes as gene expression, which lead to cellular proliferation, migration, survival and angiogenesis, they represent potential targets for therapeutic intervention. The alpha(v)beta(3) integrin is one of the most widely studied integrins because it is one of the most promiscuous. Published studies provide compelling evidence that small molecule antagonists have the potential to treat both solid tumours and metastases, serve as diagnostic imaging agents and be used for site-directed delivery of drugs to solid tumours. The alpha(v)beta(3) integrin antagonists also inhibit blood vessel formation associated with tumour growth. Therapeutic candidates have included antibodies, cyclic peptides, peptidomimetics and small molecules. A number of potent small-molecule antagonists of the alpha(v)beta(3) integrin have now been identified and are progressing in the clinic. This review focuses on the role of alpha(v)beta(3) in cancer. The rationale for the development of the therapeutic and diagnostic candidates based on the key role of alpha(v)beta(3) is discussed.

Angiogenesis Inhibitors↗

PubMed2002

Anticoagulants in thrombosis and cancer: the missing link.

Many cancer patients reportedly have hypercoaguable state, with recurrent thrombosis due to the impact of cancer cells and chemotherapy on the coagulation cascade. A number of retrospective studies showed that cancer patients are at higher risk of developing venous thromboembolism. In addition to the pathological mechanisms associated with tumor-mediated increase in thrombotic events, cancer therapies including chemotherapy, immobilization, cancer surgery and the use of central venous catheters contribute toward a hypercoaguable state and are therefore independent risk factors of venous thromboembolism in cancer patients. Studies have demonstrated that unfractionated heparin or low molecular weight heparin (LMWH) interferes with various processes involved in tumor growth and metastasis. These processes might include fibrin formation, binding of heparin to angiogenic growth factors--such as basic fibroblast growth factor and VEGF--modulation of tissue factor, release of tissue factor pathway inhibitor and other mechanisms. Clinical trials have suggested an improved efficacy of LMWH, as compared with UFH on the survival of cancer patients with deep vein thrombosis. Similarly, the impact of warfarin on the survival of cancer patients with thromboembolic disorders was demonstrated. Recent studies from our laboratory defined the role of the LMWH (tinzaparin), warfarin, antifactor VIIa and recombinant tissue factor pathway inhibitor in the modulation of angiogenesis, tumor growth and tumor metastasis.

Animals↗

PubMed2002

Antithrombotics and thrombolytics in stroke.

Although angioplasty, stenting and thrombolysis of the cerebral circulation are being attempted with increasing frequency, antithrombotic and antiplatelet regimens have not yet been standardized in the treatment of stroke. Safety and efficacy of antithrombotic therapies during cerebrovascular interventions may depend onclinical presentation and carotid lesion characteristics. Platelet glycoprotein (GP) IIb/IIIa receptor antagonists might have potential value as a monotherapy or as an adjunctive therapy with thrombolytics or interventional procedures. However, the risk of cerebral hemorrhage may be higher in patients with acute stroke than in subjects with transient ischemic attack (TIA) or partial occlusion. For high-risk cerebrovascular lesions such as basilar artery, atherothrombosis or acute carotid artery occlusion, initial experience suggests that platelet GPIIb/IIIa receptor antagonists may have implications in reducing acute re-occlusion rates during the various interventional procedures. The aim of this paper is to review the use of antithrombotics as prophylaxis treatment in stroke, in addition, to comparing the benefits/risks of using thrombolytics as acute intervention.

Atrial Fibrillation↗

PubMed2002

Heparin and low molecular weight heparin in thrombosis and beyond.

Despite efforts in finding and developing new anticoagulants, unfractionated heparin and low molecular weight heparin (LMWH) will continue to play a pivotal role in the management of thrombotic disorders. While bleeding and heparin-induced thrombocytopenia represent major side effects of this drug, it has remained the anticoagulant of choicefor the prophylaxis and treatment of arterial and venous thrombotic disorders, surgical anticoagulation and interventional usage. Understanding the heparin structure led to the development of LMWHs, synthetic heparinomimetics, antithrombin and anti-Factor Xa agents.

Animals↗

PubMed2002

Vitronectin receptors in vascular disorders.

Various integrin antagonist candidates, including antibodies, cyclic peptides, peptidomimetics and non-peptides, have been clinically evaluated and have been shown to successfully modulate certain disease processes. The most advanced integrin antagonists in clinical development include intravenous platelet alphaIIb/beta3 integrin antagonists, leukocyte alpha4/beta1 integrin antagonists and vascular alpha v/beta3 antagonists. This review will focus on the key role of the alpha v integrin (alpha v/beta3 and alpha v/beta5) in vascular disorders, such as angiogenesis-mediated disorders and vascular restenosis.

Animals↗

PubMedDate not supplied

Antiangiogenesis and anticancer efficacy of TA138, a novel alphavbeta3 antagonist.

BACKGROUND: Angiogenesis is a complex process involving endothelial cell migration, proliferation, invasion, and tube formation. Inhibition of these processes might have implications in various angiogenesis-mediated disorders. MATERIALS AND METHODS: The antiangiogenic efficacy of the novel alphavbeta3 antagonist TA138 was examined using in vivo and in vitro model systems. RESULTS: The in vitro studies demonstrated the ability of TA138 and RP747 (conjugated TA138) to inhibit endothelial cell migration toward vitronectin, with an IC50=0.04 and 0.045 microM, respectively. Furthermore, utilizing the chick chorioallantoic membrane models, TA138 inhibited basic fibroblast growth factor-induced neovascularization. CONCLUSION: TA138 might be a useful tool for the inhibition of angiogenesis associated with human tumor growth, or other pathological neovascularization processes. RP747 demonstrated antitumor efficacy in 1 spontaneous tumor model (c-neu oncomouse model, alphavbeta3 positive cells) and in 1 xenograft model (HCT116 human tumor colon carcinoma, alphavbeta3 negative cells) injected subcutaneously into nude mice.

Adenocarcinoma↗