Honokiol, a Small Molecular Weight Natural Product, Inhibits Angiogenesis in Vitro and Tumor Growth in Vivo

Natural products comprise a major source of small molecular weight angiogenesis inhibitors. We have used the transformed endothelial cell line SVR as an effective screen of natural product extracts to isolate anti-angiogenesis and anti-tumor compounds. Aqueous extracts of Magnolia grandiflora exhibit potent activity in our SVR proliferation assays. We found that the small molecular weight compound honokiol is the active principle of magnolia extract. Honokiol exhibited potent anti-proliferative activity against SVR cells in vitro. In addition, honokiol demonstrated preferential inhibition of primary human endothelial cells compared with fibroblasts and this inhibition was antagonized by antibodies against TNF alpha-related apoptosis-inducing ligand. In vivo, honokiol was highly effective against angiosarcoma in nude mice. Our preclinical data suggests that honokiol is a systemically available and non-toxic inhibitor of angiogenesis and should be further evaluated as a potential chemotherapeutic agent

Pathophysiology and management of thrombosis in cancer: 150 years of progress

The association of thrombosis with cancer has been recognized since the middle of the nineteenth century. It remains a common and serious complication of the cancer itself, as well as chemotherapy. Thrombosis is the second leading cause of death in cancer patients, second only to the cancer itself. For many years the treatment options for managing thrombosis in cancer had been static, but the past decade has seen significant evolution in the management, with the clear superiority of low molecular weight heparin over warfarin for secondary prevention of thrombosis. This article will review the understanding and management of thrombosis in cancer

Use of Direct Oral Anticoagulants for Treating Venous Thromboembolism in Patients With Cancer

For patients with cancer who experience venous thromboembolism (VTE), low-molecular-weight heparin (LMWH) remains the standard of care in the NCCN Guidelines for VTE, but under certain conditions direct oral anticoagulants (DOACs) are acceptable alternatives. A growing body of literature suggests that DOACs may more effective than LMWHs in preventing recurrences, but they do carry some increased risk of bleeding. Most of this risk is seen in patients with gastrointestinal or urinary pathology or implanted devices. DOACs are also acceptable when the pain, cost, and inconvenience of LMWHs are expected to be obstacles to compliance. Through careful patient selection, most patients can be treated successfully with a DOAC, although for most patients with gastrointestinal or urinary pathology, LMWH remains the safer choice

Unidentifiable Thrombophilia

The term “thrombophilia” is generally used to designate states of hypercoagulability caused by an inherent abnormality of the coagulation system, resulting in an increased risk of thrombosis. Abnormalities of blood flow or the blood vessel wall, the other two components of Virchow’s triad that increase the risk of thrombosis, are not considered a thrombophilia

Thrombocytopenia Associated with Repletion of Lron in Lron-Deficiency Anemia

Two patients with iron deficiency experienced rapid decreases in their platelet levels following initiation of replacement therapy with oral ferrous Sulfate or ferrous gluconate. The first patient, whose pretreatment platelet count was 168,000 per mm3, developed marked thrombocytopenia (platelet count, 21,000 per mm3) on the sixth day of iron repletion. The second patient’s platelet level feil from 725,000 to 105,000 per mm3 on the tenth day of therapy. In both instances, platelet levels gradually returned to normal levels. The data suggest that the administration of oral iron resulted in an acute reduction in platelet production. The mechanism(s), prevalence, and clinical significance of thrombocytopenia following iron repletion in patients with iron deficiency anemia remain unknown

A New Generation of Oral Direct Anticoagulants

After more than 50 years of thrombosis treatment and prophylaxis being based on heparin and vitamin K antagonists, a new generation of oral, direct anticoagulants is now available. The past 5 years have brought a strikingly large number of trials that evaluated these new oral anticoagulants in a range of clinical trials, particularly nonvalvular atrial fibrillation, thrombosis prophylaxis after major joint replacement surgery, treatment of venous thromboembolic events, and, most recently, acute coronary syndrome. These studies have been notably similar in design between the drugs for specific indication. This review focuses on the 3 drugs that either have recently been approved by the US Food and Drug Administration (dabigatran and rivaroxaban) or have the most mature phase III clinical data (apixaban)