The dissemination of malignant gastric cells to the peritoneum occurs frequently, usually as an early event in disease, and results in poor patient prognosis. Surgery and chemotherapy offer limited therapeutic success. The low-pathogenic human enterovirus, Echovirus 1 (EV1), is an oncolytic virus that selectively targets and destroys malignant prostate and ovarian cancer xenografts in vivo. Lytic EV1 infection requires the cell surface expression of alpha(2)beta(1), an integrin involved in the dissemination of gastric cancer cells to the peritoneum. Herein, we evaluated the capacity of EV1 for anti-neoplastic cell action in gastric peritoneal carcinomatosis. Flow cytometric analysis demonstrated that alpha(2)beta(1) was abundantly surface expressed on a panel of gastric cancer cell lines, rendering the majority of lines highly susceptible to in vitro lytic EV1 infection and supportive of efficient viral progeny production. A bioluminescent MKN-45-Luc SCID mouse model of peritoneal dissemination was developed to allow real-time non-invasive monitoring of peritoneal tumor burden. Employing this mouse model, we demonstrated a therapeutic dose-response for escalating oncolytic EV1 doses. Taken together, these results emphasize the exciting potential for EV1 as a single or adjunct therapy for the control of the peritoneal dissemination of gastric cancer.
Little is known about the amino acid composition of horse sweat, but significant fluid losses can occur during exercise with the potential to facilitate substantial nutrient losses. Sweat and plasma amino acid compositions for Standardbred horses were assessed to determine losses during a standardised training regime. Two cohorts of horses 2013 (n=5) and 2014 (n=6) were assessed to determine baseline levels of plasma and sweat amino acids. An amino acid supplement designed to counter losses in sweat during exercise was provided after morning exercise daily for 5 weeks (2013, n=5; 2014, n=4). After the supplementation period, blood and sweat samples were collected to assess amino acid composition changes. From baseline assessments of sweat in both cohorts, it was found that serine, glutamic acid, histidine and phenylalanine were present at up to 9 times the corresponding plasma concentrations and aspartic acid at 0-2.2 μmol/l in plasma was measured at 154-262 μmol/l in sweat. In contrast, glutamine, asparagine, methionine and cystine were conserved in the plasma by having lower concentrations in the sweat. The predominant plasma amino acids were glycine, glutamine, alanine, valine, serine, lysine and leucine. As the sweat amino acid profile did not simply reflect plasma composition, it was proposed that mechanisms exist to generate high concentrations of certain amino acids in sweat whilst selectively preventing the loss of others. The estimated amino acid load in 16 l of circulating plasma was 3.8-4.3 g and the calculated loss via sweat during high intensity exercise was 1.6-3.0 g. Following supplementation, total plasma amino acid levels from both cohorts increased from initial levels of 2,293 and 2,044 µmol/l to post-supplementation levels of 2,674 and 2,663 µmol/l respectively (P<0.05). It was concluded that the strategy of providing free amino acids immediately after exercise resulted in raising resting plasma amino acid levels.
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