To study the drug delivery to tumor by utilization of an oligopeptide transport activity, we examined the accumulation of dipeptides and the peptide‐mimetic anti‐cancer drug, bestatin, a substrate of oligopeptide transporter PepT1. Firstly, we established HeLa cells stably expressing human peptide transporter (hPepT1) (HeLa‐hPepT1). Secondly, we constructed an experimental model by inoculation of HeLa‐hPepT1 cells subcutaneously into Balb/c nu/nu mice to demonstrate the contribution of PepT1 to the tissue‐selective drug delivery. The accumulations of a hydrolysis‐resistant dipeptide [3H]carnosine and bestatin in solid tumors formed by HeLa‐hPepT1 or HeLa‐pcDNA3, which are transfected with vector DNA (pcDNA3) were measured. After I.V. administration, tissue‐to‐plasma concentration ratios (Kp) of both compounds, in HeLa‐hPepT1 tumor was significantly greater than that of [14C]inulin, a marker for extracellular fluid space, those of dipeptides in muscle, or those in HeLa‐pcDNA3 tumor. Furthermore, bestatin exhibited growth inhibition of HeLa‐hPepT1 in vitro. In vivo, repeated oral administration of bestatin for 28 days suppressed the growth of HeLa‐hPepT1 tumor specifically. When HT‐1080 cells, which may naturally express oligopeptide transport activity, were transplanted, Kp of [3H]carnosine was significantly increased in comparison with that in muscle. In addition, oligopeptide transport activities among various human cell lines were examined. These results provide the first demonstration for the selective delivery of oligopeptides to tumors by specific oligopeptide transport activity. Int. J. Cancer 88:274–280, 2000. © 2000 Wiley‐Liss, Inc.

To study the drug delivery to tumor by utilization of an oligopeptide transport activity, we examined the accumulation of dipeptides and the peptide-mimetic anti-cancer drug, bestatin, a substrate of oligopeptide transporter PepT1.

No abstract

e21665 Background: The oral transmucosal fentanyl disintegrating tablet, Abstral, is a formulation by which fentanyl can be rapidly absorbed across the oral mucosa producing rapid onset analgesia, and which may be effective for breakthrough cancer pain. It can be administered for the patients who cannot take the oral medicine. It has been marketed since 2014 in Japan. Methods: We selected patients who were administered Abstral for breakthrough cancer pain between 2014 and 2016 at Toyama University Hospital in Japan. We retrospectively investigated administration reasons based on medical record of those patients. Results: There were 111 patients who were administered Abstral. Primary lesions of lung/Gastrointestin/others were 43/52/16, respectively. ECOG PS 0-2/3-4 were 27/84, respectively. The median age was 66 y.o. (range 35-91 y.o.). Regularly using opioid were fentanyl patch prescribed for all patients. Median dose of fentanyl patch was 25mcg/hr (range 12.5-250mcg/hr). 90 patients (81%) had difficulties in the administration of oral medicine, which was the main reason of Abstral administration. Four patients (4%) were to reduce constipation and vomiting as side effects of oxycodone. Seven patients (6%) were to start a fentanyl patch. Three patients (3%) were assessed poor effect for short-acting opioid. Only seven patients (6%) were expected of rapid onset of analgesia effect. Abstral was administered in 27 patients (24%) during aggressive treatment such as chemotherapy administration and in 84 patients (76%) after aggressive treatment. Conclusions: The oral transmucosal fentanyl was administered for the patients who cannot take the oral medicine in Japan while it is expected to be administered to those who want to relieve breakthrough pain fast. Affirming a common understanding of the efficacy of the oral transmucosal fentanyl and breakthrough cancer pain is necessary in Japan.

The effects of organic food additives on pitting corrosion of aluminum alloys were studied in a neutral solution of sodium chloride. The advance of corrosion was estimated by time variation of the rest potential, anodic and cathodic polarization curves and polarization resistance. Pit depth was evaluated with an optical microscope and photoacoustic spectroscopy (PAS) was newly applied to evaluate the spatial distribution of corrosion pits.Results obtained were as follows. 1) Organic substances that showed an inhibiting effect, decreasing the maximum pit depth, were : for 3003 alloy DL-thioctic acid, caffein anhydride and L-tryptophan ; for 5052 alloy casein ; and for 6063 alloy pyridoxine hydrochloride and hydantoin. 2) In the presence of an organic substance as pitting corrosion inhibitor, obtained corrosion potential at pH7 shifted to the noble side, and these results support the evaluated results for the maximum pit depth.In an acid solution of pH3, obtained corrosion current decreased in the presence of the organic substance. These results suggests the possibility of an inhibitive effect inside the pits as well as outside the pits.