Slab-selective inversion-prepared 3D SSFP MR angiography had high sensitivity, specificity, accuracy, and NPV for RAS detection, without the need for contrast material. However, RAS severity was overestimated in some patients.
ADH-1 is the first anti-N-cadherin compound tested in humans. In N-cadherin-positive patients, ADH-1 showed an acceptable toxicity profile, linear PK and hints of antitumour activity in gynaecological cancers.
A fetal head volume estimate exceeding MRI-measured pelvic capacity is a frequent finding in nulliparas with cesarean birth due to cephalopelvic disproportion. An appropriate prospective study to determine the benefits of an antepartum diagnosis of cephalopelvic disproportion in high-risk nulliparas is warranted.
At MR angiography of the distal run-off vessels, Gd-BOPTA yielded higher specificity and a significantly smaller number of nonassessable segments than Gd-DOTA. The diagnostic accuracy of the two gadolinium chelates at peripheral MR angiography was comparable in the renal to popliteal arteries.
Purpose: The vascular disrupting agent ombrabulin rapidly reduces tumor blood flow and causes necrosis in vivo. A phase I dose-escalation study was designed to determine the recommended phase II dose (RP2D) of single-agent ombrabulin administered once every three weeks in patients with advanced solid malignancies.Experimental Design: Ombrabulin (30-minute infusion) was escalated from 6 to 60 mg/m 2 , with RP2D cohort expansion. Safety, tumor response, pharmacokinetics, and pharmacodynamic biomarkers were evaluated.Results: Eleven dose levels were evaluated in 105 patients. Two patients had dose-limiting toxicities in cycle 1 during escalation: grade 3 abdominal pain at 50 mg/m 2 , grade 3 tumor pain/grade 3 hypertension at 60 mg/m 2 , and the RP2D was 50 mg/m 2 (39 patients). Common toxicities were headache, asthenia, abdominal pain, nausea, diarrhea, transient hypertension, anemia, and lymphopenia. No clinically significant QTc prolongations or left ventricular ejection fraction (LVEF) decreases occurred. Ombrabulin was rapidly converted to its active metabolite RPR258063 (half-life 17 minutes and 8.7 hours, respectively), both having dose-proportional exposure. Weak inhibition of CYP2C19-mediated metabolism occurred at the clinical doses used and there was no effect on CYP1A2 and CYP3A4. A patient with rectal cancer had a partial response and eight patients had stable disease lasting four months or more. Circulating endothelial cells (CEC), VEGF, and matrix metalloproteinase (MMP)-9 levels increased significantly six to 10 hours postinfusion in a subset of patients.
Conclusions:The recommended schedule for single-agent ombrabulin is 50 mg/m 2 every 3 weeks. CECs, VEGF, and MMP-9 are potential biomarkers of ombrabulin activity.
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