Safety and efficacy of trabectedin when administered in the inpatient versus outpatient setting: Clinical considerations for outpatient administration of trabectedin.

Background: The results of the randomized, phase 3 ET743-SAR-3007 trial demonstrated that trabectedin had a significantly longer progression-free survival (PFS) compared with dacarbazine in patients with advanced leiomyosarcoma/liposarcoma after the failure of prior chemotherapy. Patients randomized to trabectedin received a 24-hour intravenous infusion either in an inpatient or outpatient setting. Herein, the authors reported the safety, efficacy, and patient-reported outcomes based on first infusion site of care.

Pirfenidone for diabetic nephropathy.

Pirfenidone is an oral antifibrotic agent that benefits diabetic nephropathy in animal models, but whether it is effective for human diabetic nephropathy is unknown. We conducted a randomized, double-blind, placebo-controlled study in 77 subjects with diabetic nephropathy who had elevated albuminuria and reduced estimated GFR (eGFR) (20 to 75 ml/min per 1.73 m²).

Pirfenidone is renoprotective in diabetic kidney disease.

Although several interventions slow the progression of diabetic nephropathy, current therapies do not halt progression completely. Recent preclinical studies suggested that pirfenidone (PFD) prevents fibrosis in various diseases, but the mechanisms underlying its antifibrotic action are incompletely understood. Here, we evaluated the role of PFD in regulation of the extracellular matrix.

Stimulation of urinary TGF-beta and isoprostanes in response to hyperglycemia in humans.

TGF-beta and oxidant stress have been considered to play key roles in the pathogenesis of diabetic vascular complications; however, the stimulus for these factors in humans is not clear. The purpose of this in vivo study was to determine whether transient hyperglycemia in humans is sufficient to increase renal production of TGF-beta1 and urinary isoprostanes in normal humans. A hyperglycemic clamp procedure was performed on 13 healthy volunteers.

Transforming growth factor-beta: a clinical target for the treatment of diabetic nephropathy.

Diabetic nephropathy is continuing to rise in incidence, despite awareness of tight glycemic control and blood pressure. The identification that matrix accumulation is driven by transforming growth factor-beta (TGF-beta) has led to a concerted effort to apply antifibrotic strategies for this disorder. Recent studies have not only demonstrated the beneficial effects of blocking TGF-beta on matrix accumulation but have also found that blocking TGF-beta may have important hemodynamic effects that are relevant to diabetic complications.

TGF-beta-induced Ca(2+) influx involves the type III IP(3) receptor and regulates actin cytoskeleton.

Ca(2+) influx has been postulated to modulate the signaling pathway of transforming growth factor-beta (TGF-beta); however, the underlying mechanism and functional significance of TGF-beta-induced stimulation of Ca(2+) influx are unclear. We show here that TGF-beta stimulates Ca(2+) influx in mesangial cells without Ca(2+) release. The influx of Ca(2+) is prevented by pharmacological inhibitors of inositol 1,4,5-trisphosphate receptors (IP(3)R) as well as specific antibodies to type III IP(3)R (IP(3)RIII) but not to type I IP(3)R (IP(3)RI).