Intracellular dissolution of inhaled particles is an important pathway of clearance of potentially toxic materials. To study this process, monolayers of human and canine alveolar macrophages (AM) were maintained alive and functional in vitro for more than 2 wk. Complete phagocytosis of moderately soluble, monodisperse 57Co3O4 test particles of four different sizes was obtained by optimizing the cell density of the monolayer and the particle-to-cell ratio. The fraction of the initial particle mass that was soluble increased over time when the particles were ingested by AM but remained constant when in culture medium alone. Smaller particle sizes had a faster characteristic intracellular dissolution rate constant than did larger particles. The dissolution rates differed between AM obtained from two human volunteers as compared to those obtained from six mongrel dogs. These in vitro dissolution rates were very similar to in vivo translocation rates previously obtained from human and canine lung clearance studies after inhalation of the same or similar monodisperse, homogeneous 57Co3O4 test particles. We believe an important clearance mechanism for inhaled aerosol particles deposited in the lungs can be simulated in vitro in a cell culture system.

A novel radiosensitization treatment involving the injection of hydrogen peroxide and sodium hyaluronate, using ultrasonic guidance, into a tumor immediately prior to intraoperative radiotherapy (IORT) was established for patients with stage IVa locally advanced unresectable pancreatic cancer. The aim of the present study was to assess the safety and efficacy of this novel treatment, termed Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas-IORT (KORTUC and IORT). In total, 12 patients were treated with KORTUC-IORT, external-beam radiotherapy and systemic chemotherapy using gemcitabine hydrochloride and S-1. For evaluation of the therapeutic and adverse effects, contrast-enhanced computed tomography was conducted prior to the treatment, and one and six months following KORTUC-IORT. Medical examinations were performed every month at the regularly scheduled follow-up visits. The one- and two-year survival rates were 75 and 25%, respectively, and the median survival time was 16 months. All treatments associated with KORTUC-IORT were well-tolerated by the patients, with a small number of adverse effects and no serious complications. It was identified that the delivery of KORTUC-IORT is safe and effective, in combination with external-beam radiotherapy and systemic chemotherapy, for patients with locally advanced unresectable pancreatic cancer.

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