Treatment of hepatocellular carcinoma with autologous platelets encapsulating sorafenib or lenvatinib: A novel therapy exploiting tumor-platelet interactions.

Hepatocellular carcinoma (HCC) activates platelets through the action of adjacent sinusoidal cells. Activated platelets bind to tumor-associated endothelial cells and release growth factors that promote tumor progression. We hypothesized that platelets encapsulated with tumor inhibitors would function as drug carriers for tumor therapy. We propose a therapeutic strategy for HCC using autologous platelets encapsulating multiple tyrosine kinase inhibitors in a rat chemically induced HCC model. Sorafenib or lenvatinib was encapsulated in platelets isolated from tumor-bearing rats in vitro. The rats were divided into groups that received repeated intravenous injections (twice a week for 10 weeks) of the following materials: placebo, sorafenib (SOR), lenvatinib (LEN), autologous platelets, autologous platelets encapsulating sorafenib (SOR-PLT) and autologous platelets encapsulating lenvatinib (LEN-PLT). The therapeutic effect was then analyzed by ultrasonography (US) and histopathological analysis. Histopathological and US analysis demonstrated extensive tumor necrosis in the tumor tissue of SOR-PLT or LEN-PLT, but not in other experimental groups. By liquid chromatography-mass spectrometry, more abundant sorafenib was detected in tumor tissues after SOR-PLT administration than in surrounding normal tissues, but no such difference in sorafenib level was observed with SOR administration. Therefore, the use of autologous platelets encapsulating drugs might be a novel therapeutic strategy for HCC.

Onset-to-device time of patients who arrive at off-hours: Importance of prehospital management and public awareness for patients with ST-segment elevation myocardial infarction.

AIM: The influence of the time of arrival at the hospital on the door-to-device (DTD) time has been investigated; however, the influence on the onset-to-device (OTD) time is unclear in ST-segment elevation myocardial infarction (STEMI) patients. The aim of this study was to investigate the relationship between the time of arrival at the hospital and the OTD time in STEMI patients. METHODS: We evaluated 377 STEMI patients who underwent primary percutaneous coronary intervention (pPCI) between January 2008 and December 2014. RESULTS: During the study period, 222 patients arrived at our hospital between 9 AM and 9 PM (on-hours group) and 155 patients arrived between 9 PM and 9 AM (off-hours group). The DTD time was longer in the off-hours group than in the on-hours group (50.4 vs 39.3 minutes; P<.001), while the OTD time was longer in the on-hours group than in the off-hours group (285.7 vs 184.5 minutes, P<.001). The 30-day mortality and peak creatinine kinase levels were similar between the groups. Transfer from a non-pPCI-capable facility to our hospital was more common in the on-hours group than in the off-hours group (49.1% vs 15.5%, P<.001). The OTD time was shorter in patients who directly visited our hospital than in those who were transferred (172.9 vs 338.5 minutes, P<.001). CONCLUSIONS: The OTD time might be markedly longer in STEMI patients who arrive at the hospital during on-hours than in those who arrive at the hospital during off-hours because of the underuse of emergency medical services at STEMI onset.