| 2014 | A phase II evaluation of AMG 102 (rilotumumab) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study. | Gynecol Oncol | This open-label, multi-institutional phase II trial evaluated activity and safety of rilotumumab (AMG 102), a monoclonal antibody that targets HGF (hepatocyte growth factor), the ligand for the MET receptor, in women with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer.Women were eligible for treatment with rilotumumab if they had measurable disease, a performance status of 0, 1 or 2, previously received platinum-based therapy with a progression-free interval of <12 months or a second recurrence, and adequate bone marrow and organ function. Patients received rilotumumab 20mg/kg IV every 14 days until evidence of unacceptable toxicity or disease progression. The study utilized co-dual primary endpoints of tumor response and six-month PFS to assess the efficacy of rilotumumab. Secondary endpoints included the frequency and severity of adverse events and the duration of progression-free and overall survival.Thirty-one women enrolled and received rilotumumab. All were eligible for analysis. One patient achieved a complete response (3.2%; 90% CI 0.2-14%), and two women had 6-month PFS (6.5%; 90% CI 1.1-19%). Most adverse events were grade 1 or 2, with no grade 4 adverse events. Grade 3 adverse events were gastrointestinal (4), metabolic (3) anemia (3), a thromboembolic event (1), ventricular tachycardia (1), hypotension during infusion (1) and fatigue (1). The study was stopped after the first stage of accrual.Rilotumumab was well-tolerated, but had limited activity. The level of activity does not warrant further evaluation of rilotumumab as a single agent in patients with ovarian cancer. |
| 2005 | Inflammatory markers and hepatocyte growth factor in sustained hemodialysis hypotension. | Artif Organs | Hypotension is an important complication of hemodialysis. The pathogenesis of this complication remains unclear. The role of chronic inflammation in chronic dialysis-associated hypotension has not been investigated. A total of 38 dialysis patients with chronic hypotension were identified. Their demographic and biochemical data, inflammatory markers (high sensitivity C-reactive protein [hs-CRP] and interleukin-6 [IL-6]), hepatocyte growth factor (HGF), leptin, and adiponectin levels were measured and compared with those of another 87 nonhypotensive dialysis patients. No between-group differences in their clinical features, underlying renal disease were found. Levels of serum albumin, leptin, adiponectin, and HGF were similar between the two groups. The serum albumin levels were inversely correlated with hs-CRP and IL-6. Adiponectin was negatively correlated with hs-CRP and leptin. HGF showed a positive relation with hs-CRP. No association was found between adiponectin and HGF. Therefore, chronic inflammation is prevalent in the dialysis population, and serum HGF level is associated with inflammation but not with chronic dialysis hypotension. |
| 2001 | Low-density lipoprotein apheresis and changes in plasma components. | Ther Apher | Several different techniques of low-density lipoprotein (LDL) apheresis are available for management of severe hypercholesterolemia. Among them, the adsorption system with a dextran-sulfate cellulose (DSC) column is most widely used. In addition to adsorption of LDL, DSC adsorbs plasma constituents that have the following characteristics: proteins containing apolipoprotein B (Lp[a]); proteins involved in the initial contact phase of the intrinsic coagulation pathway (coagulation factor XII, high-molecular-weight kininogen and prekallikrein); factors with lipophilic characteristics (coagulation factor VII, coagulation factor VIII, and vitamin E); and proteins with adhesive or other characteristics (von Willebrand factor, fibronectin, serum amyloid P component, hepatocyte growth factor). The adsorption of these proteins seems to ameliorate prevention or regression of atherosclerosis. Moreover, plasma treatment by the DSC column may be useful for treatment of inexorable diseases, such as amyloidosis. On the other hand, the DSC column generates bradykinin by activation of the initial contact phase of the intrinsic coagulation pathway. Bradykinin generation may explain the functional improvement in the circulatory system, as well as hypotension during LDL apheresis, which is observed in patients taking ACE inhibitors. |
| 2000 | Association of human hepatocyte growth factor with hemodialysis hypotension. | Hypertens Res | Hypotension is a major cardiovascular complication of hemodialysis, and enhanced production of nitric oxide (NO) may be involved in hemodialysis hypotension. Human hepatocyte growth factor (hHGF), which induces endothelial proliferation, causes NO-mediated hypotension in animals. Because heparin, which is routinely used during hemodialysis, increases circulating hHGF concentration in humans, circulating hHGF may be involved in hemodialysis hypotension via increased NO production. To investigate the involvement of hHGF in NO production and hypotension in hemodialysis patients, we measured concentrations of serum hHGF and plasma NO3-, an index of endogenous NO production, in 114 patients undergoing maintenance hemodialysis. The mean serum hHGF concentration before dialysis was greater (p<0.01) in subjects with lower blood pressure (BP) (mean BP before dialysis < or =75 mmHg, n=16, 0.251+/-0.050 ng/ml) than in those with middle BP (mean BP before dialysis 76 to 109 mmHg, n=75, 0.143+/-0.016 ng/ml) or higher BP (mean BP before dialysis > or =110 mmHg, n=23, 0.088+/-0.017 ng/ml). The mean serum hHGF concentration after dialysis was higher in subjects with lower BP (1.854+/-0.242 ng/ml) than in those with middle BP (1.280+/-0.120 ng/ml) or higher BP (0.688+/-0.130 ng/ml). Serum hHGF concentration was positively correlated with plasma NO3- concentration (r=0.608, p=0.0001, n=114). Circulating hHGF may participate in the mechanism of chronic hemodialysis hypotension by affecting endogenous NO production. |