Increased survival with enzalutamide in prostate cancer after chemotherapy.

Background: Enzalutamide (formerly called MDV3100) targets multiple steps in the androgen-receptor-signaling pathway, the major driver of prostate-cancer growth. We aimed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy.

Methods: In our phase 3, double-blind, placebo-controlled trial, we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity.

Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study.

Background: MDV3100 is an androgen-receptor antagonist that blocks androgens from binding to the androgen receptor and prevents nuclear translocation and co-activator recruitment of the ligand-receptor complex. It also induces tumour cell apoptosis, and has no agonist activity. Because growth of castration-resistant prostate cancer is dependent on continued androgen-receptor signalling, we assessed the antitumour activity and safety of MDV3100 in men with this disease.

A randomized, placebo-controlled trial of latrepirdine in Huntington disease.

Objectives: To evaluate the safety and tolerability of latrepirdine in Huntington disease (HD) and explore its effects on cognition, behavior, and motor symptoms.

Design: Double-blind, randomized, placebo-controlled trial.

Setting: Multicenter outpatient trial.

Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer's disease: a randomised, double-blind, placebo-controlled study.

Background: Although treatments for Alzheimer's disease sometimes improve cognition, functional ability, or behaviour compared with baseline levels, such improvements are inconsistent across studies and measures, and effects diminish over time. More effective treatments are needed. We assessed the safety, tolerability, and efficacy of dimebon in the treatment of patients with mild-to-moderate Alzheimer's disease.

Prospective multicenter study of quality of life before and after lower extremity vein bypass in 1404 patients with critical limb ischemia.

Background: Patients with critical limb ischemia (CLI) have multiple comorbidities and limited life spans. The ability of infrainguinal vein bypass to improve quality of life (QoL) in patients with CLI has therefore been questioned. Prospective preoperative and postoperative QoL data for patients undergoing lower extremity vein bypass for CLI are presented.

Results of PREVENT III: a multicenter, randomized trial of edifoligide for the prevention of vein graft failure in lower extremity bypass surgery.

Objective: The PREVENT III study was a prospective, randomized, double-blinded, multicenter phase III trial of a novel molecular therapy (edifoligide; E2F decoy) for the prevention of vein graft failure in patients undergoing infrainguinal revascularization for critical limb ischemia (CLI).

Methods: From November 2001 through October 2003, 1404 patients with CLI were randomized to a single intraoperative ex vivo vein graft treatment with edifoligide or placebo. After surgery, patients underwent graft surveillance by duplex ultrasonography and were followed up for index graft and limb end points to 1 year.

Risk factors, medical therapies and perioperative events in limb salvage surgery: observations from the PREVENT III multicenter trial.

Objectives: Patients who require infrainguinal revascularization for critical limb ischemia (CLI) are at elevated risk for cardiovascular events. The PREVENT III study was a prospective, randomized, multicenter, phase 3 trial of edifoligide for the prevention of vein graft failure in patients with CLI. We examined the baseline characteristics, perioperative medical therapies, and 30-day incidence of major cardiovascular events in the PREVENT III cohort.

Design and rationale of the PREVENT III clinical trial: edifoligide for the prevention of infrainguinal vein graft failure.

Surgical bypass of peripheral arterial occlusive disease with autologous vein grafts provides an effective means of restoring blood flow to the lower extremity, and has been a standard therapy for patients with disabling claudication or critical limb ischemia (CLI). However, failure rates may run as high as 50% within 5 years. These graft failures occur as a result of neointimal hyperplasia, a ubiquitous biologic response of blood vessel walls to injury, which is characterized by the migration and proliferation of smooth muscle cells (SMC).

Prolonged treatment of human osteoarthritic chondrocytes with insulin-like growth factor-I stimulates proteoglycan synthesis but not proteoglycan matrix accumulation in alginate cultures.

Objective: To determine the level of anabolic response when chondrocytes isolated from human osteoarthritic cartilage are stimulated with 2 doses of insulin-like growth factor-I (IGF-I) for extended culture periods.

Methods: Human chondrocytes were isolated from knee cartilage removed at the time of joint replacement surgery for osteoarthritis (OA). The cells were cultured in alginate beads under serum-free conditions and treated with 100 ng/ml or 1000 ng/ml of human recombinant IGF-I.

Retroviral expression of a kinase-defective IGF-I receptor suppresses growth and causes apoptosis of CHO and U87 cells in-vivo.

Background: Phosphatidylinositol-3,4,5-triphosphate (PtdInsP3) signaling is elevated in many tumors due to loss of the tumor suppressor PTEN, and leads to constitutive activation of Akt, a kinase involved in cell survival. Reintroduction of PTEN in cells suppresses transformation and tumorigenicity. While this approach works in-vitro, it may prove difficult to achieve in-vivo.