Itraconazole Exerts Its Antitumor Effect in Esophageal Cancer By Suppressing the HER2/AKT Signaling Pathway.

Itraconazole, an FDA-approved antifungal, has antitumor activity against a variety of cancers. We sought to determine the effects of itraconazole on esophageal cancer and elucidate its mechanism of action. Itraconazole inhibited cell proliferation and induced G-phase cell-cycle arrest in esophageal squamous cell carcinoma and adenocarcinoma cell lines.

Concentration-dependent Early Antivascular and Antitumor Effects of Itraconazole in Non-Small Cell Lung Cancer.

Purpose: Itraconazole has been repurposed as an anticancer therapeutic agent for multiple malignancies. In preclinical models, itraconazole has antiangiogenic properties and inhibits Hedgehog pathway activity. We performed a window-of-opportunity trial to determine the biologic effects of itraconazole in human patients.

Bioanalytical method development and validation of a liquid chromatography-tandem mass spectrometry method for determination of β-lapachone in human plasma.

The purpose of this work was to develop and validate a rapid, sensitive and robust liquid chromatography tandem mass spectrometric method for the quantification of β-lapachone in human plasma and to use that method to analyze human clinical samples. Sample preparation for the developed method involved liquid-liquid extraction using ethyl acetate for extraction of β-lapachone and cryptotanshinone (internal standard) from human plasma. Chromatographic resolution was achieved on a Kinetex C18 column using a gradient elution and a chromatographic flow rate of 0.

An implanted port-catheter system for repeated hepatic arterial infusion of low-density lipoprotein-docosahexaenoic acid nanoparticles in normal rats: A safety study.

Background: In recent years, small animal arterial port-catheter systems have been implemented in rodents with reasonable success. The aim of the current study is to employ the small animal port-catheter system to evaluate the safety of multiple hepatic-artery infusions (HAI) of low-density lipoprotein-docosahexaenoic acid (LDL-DHA) nanoparticles to the rat liver.

Methods: Wistar rats underwent surgical placement of indwelling HAI ports.

Phase 1 study of ARQ 761, a β-lapachone analogue that promotes NQO1-mediated programmed cancer cell necrosis.

Background: NAD(P)H:quinone oxidoreductase 1 (NQO1) is a two-electron oxidoreductase expressed in multiple tumour types. ARQ 761 is a β-lapachone (β-lap) analogue that exploits the unique elevation of NQO1 found in solid tumours to cause tumour-specific cell death.

Methods: We performed a 3+3 dose escalation study of 3 schedules (weekly, every other week, 2/3 weeks) of ARQ 761 in patients with refractory advanced solid tumours.