Many types of cancer cells require a supply of fatty acids (FA) for growth and survival, and interrupting de novo FA synthesis in model systems causes potent anticancer effects. We hypothesized that, in addition to synthesis, cancer cells may obtain preformed, diet-derived FA by uptake from the bloodstream. This would require hydrolytic release of FA from triglyceride in circulating lipoprotein particles by the secreted enzyme lipoprotein lipase (LPL), and the expression of CD36, the channel for cellular FA uptake. We find that selected breast cancer and sarcoma cells express and secrete active LPL, and all express CD36. We further show that LPL, in the presence of triglyceride-rich lipoproteins, accelerates the growth of these cells. Providing LPL to prostate cancer cells, which express low levels of the enzyme, did not augment growth, but did prevent the cytotoxic effect of FA synthesis inhibition. Moreover, LPL knockdown inhibited HeLa cell growth. In contrast to the cell lines, immunohistochemical analysis confirmed the presence of LPL and CD36 in the majority of breast, liposarcoma, and prostate tumor tissues examined (n = 181). These findings suggest that, in addition to de novo lipogenesis, cancer cells can use LPL and CD36 to acquire FA from the circulation by lipolysis, and this can fuel their growth. Interfering with dietary fat intake, lipolysis, and/or FA uptake will be necessary to target the requirement of cancer cells for FA. Mol Cancer Ther; 10(3); 427–36. ©2011 AACR.

You or a family member may have developed a blood clot in one of the deep veins in the body (ie, a deep vein thrombosis, or DVT) or had a blood clot that traveled to the lungs (ie, a pulmonary embolism, or PE). As part of your medical care, your doctor may have evaluated you for conditions that may have contributed to developing a blood clot. Thrombophilia is a condition in which there is an increased tendency to form blood clots. It may be hereditary and conferred by genes inherited from one or more parents, or it may be acquired through situations such as surgery, cancer, pregnancy, or certain medications (eg, some contraceptive and menopausal hormone replacement products). The two most common hereditary thrombophilia conditions are the factor V Leiden and prothrombin 20210 gene mutations, both of which have been the subject of previous Cardiology Patient Pages.1,2 This Cardiology Patient Page will describe deficiencies in the natural anticoagulants, protein C, protein S, and antithrombin that may result in either hereditary or acquired thrombophilia. Blood flows through blood vessels to deliver oxygen and nutrients to all the body's tissues. When a blood vessel is injured, a process called coagulation causes blood to form clots that stop the bleeding from the damaged blood vessel. Once coagulation begins, other substances in the blood, the natural anticoagulants, act as brakes to limit coagulation to the specific area of damage, thus avoiding formation of clots large enough to obstruct normal blood flow. There is a delicate balance at work to ensure that there is enough—but not too much—clotting ability in the blood. Too little clotting ability leads to bleeding problems, whereas too much clotting ability (thrombophilia) can lead to blood clot formation. The state of this balance between bleeding and clotting differs …

Summary: Renal impairment (RI) is a major complication of multiple myeloma (MM). This study aimed to characterize the single‐dose pharmacokinetics (PK) of the oral proteasome inhibitor, ixazomib, in cancer patients with normal renal function [creatinine clearance (CrCl) ≥90 ml/min; n = 20), severe RI (CrCl <30 ml/min; n = 14), or end‐stage renal disease requiring haemodialysis (ESRD; n = 7). PK and adverse events (AEs) were assessed after a single 3 mg dose of ixazomib. Ixazomib was highly bound to plasma proteins (~99%) in all renal function groups. Unbound and total systemic exposures of ixazomib were 38% and 39% higher, respectively, in severe RI/ESRD patients versus patients with normal renal function. Total ixazomib concentrations were similar in pre‐ and post‐dialyser samples collected from ESRD patients; therefore, ixazomib can be administered without regard to haemodialysis timing. Except for anaemia, the incidence of the most common AEs was generally similar across groups, but grade 3 and 4 AEs were more frequent in the severe RI/ESRD groups versus the normal group (79%/57% vs. 45%), as were serious AEs (43%/43% vs. 15%). The PK and safety results support a reduced ixazomib dose of 3 mg in patients with severe RI/ESRD.

Key Points Rapid initiation of eculizumab mitigates progression of carfilzomib-induced aHUS. Development of carfilzomib-induced aHUS may be associated with heterozygous CFHR3-CFHR1 deletion.

Key Points: EPO-EPOR signaling reduces UCB CD34+ HSPC engraftment through inhibition of BM homing and enhancement of erythroid differentiation. When used in clinical UCB transplantation, HBO therapy is safe and reduces EPO serum levels, potentially improving blood count recovery.