Background/Aim: L-type amino acid transporter 1 (LAT1) is a promising molecular target for cancer therapy. The present study aimed to characterize the anti-cancer effects of JPH203, an LAT1-selective inhibitor, on gastrointestinal cancer cells. Materials and Methods: Three esophageal, two gastric, and two colon cancer cell lines were used. Cytotoxic effects of JPH203 were assessed by a WST-8 assay. LAT1 mRNA levels were determined by quantitative PCR. The inhibitory property of JPH203 against LAT1 function was examined by a transport assay. Results: JPH203 treatment significantly reduced the viability of all gastric and colon cancer cells. While LAT1 expression levels and inhibitory potencies of JPH203 on LAT1 functions were comparable among the cells, all the esophageal cells were resistant to JPH203. Conclusion: JPH203 was effective in reducing gastric and colon cancer cells. To clarify its cell type-dependent efficacy, identification of the causal factors for JPH203 resistance will be needed.
This is a retrospective study to evaluate the prevention of complications of metallic stent placement in patients with unresectable advanced esophageal cancer. A total of 87 patients were treated with 4 types of metal stents in the esophagus over a period of 18 years. Stent placement was technically successful. The most common prior treatment was chemoradiotherapy. There were no significant differences in the rate of patients with no complications among the prior treatments. Approximately, 30% of patients had the most common chest pain in complications. Stent placement within one month after the completion of chemoradiotherapy should be avoided for the prevention of the chest pain. There was no significant difference in the rate of patients with no complications by lesion location. The rate of no complications was higher for the Niti-S stent than the Gianturco Z-stent or Ultraflex stent. Of note, no complications were noted for the Niti-S ultrathin stent at all. Among cases of stent-related death, the most common type of complication was respiratory disorder caused by the stent that seems to be thick and hard. Therefore, the stent with thin and flexible characteristics like the Niti-S ultrathin stent will solve the various problems of esophageal stent placement.
A 65-year-old man with cT1bN0M0 stage I middle thoracic esophageal cancer underwent subtotal esophagectomy and gastric tube reconstruction through the posterior mediastinal route after preoperative carbon-ion radiotherapy and chemotherapy in a clinical trial. Anastomotic leakage occurred, but it spontaneously improved. At six months after the operation, he was rehospitalized with a cough and dysphagia. An esophago-bronchiole fistula and stenosis of the gastric tube were observed. He first underwent stent placement in the gastric tube. Two weeks later, the syringeal epithelium was burned by argon plasma coagulation after stent removal. Endoscopic occlusion was then performed for the fistula with two guidewire-assisted silicone spigots. Two weeks later, he was discharged on an oral diet, and he has not developed recurrence of the fistula or cancer for three years. This is the first report of endoscopic occlusion with a guidewire-assisted silicone spigot through the esophagus.
Introduction] L-type amino acid transporter 1 (LAT1) is responsible for cellular uptake of large neutral amino acids including several essential amino acids. Since LAT1 expression levels are significantly increased in various cancer tissues, it has long been acknowledged as a promising molecular target for cancer therapy. In this context, JPH203, a selective LAT1 inhibitor, has been developed, and its anti-cancer effects has been demonstrated in several cancer cell lines. However, since pharmacological characterization of JPH203 remains limited, it is important to clarify what types of cancer cells are sensitive or insensitive to this agent. Therefore, in this study, we aimed at characterizing its anti-cancer properties in several colon, esophagus, and stomach cancer cell lines, and also tried to identify determinant factors for the effects. [Methods] Colon (Lovo and HT29), esophagus (TE5, TE6, TE14 and TE15), and stomach (MKN1 and MKN45) cancer cells were used and cultured in a conventional method. Cytotoxic effects of JPH203 (uM, 72 hr) were examined by WST-8 assay. Dimethyl sulfoxide was used as a control. LAT1 mRNA expression levels were determined by quantitate real-time PCR. [Results] The results of cytotoxic assay showed that the viabilities of MKN1 and MKN45 cells, as well as Lovo and HT29 cells, were significantly reduced upon JPH203 treatment (50.4 ± 12.8%, 42.8 ± 1.5%, 17.3 ± 11.6%, and 61.5 ± 17.8%, compared to those of the control, respectively). In contrast, all TE cells were highly resistant to the treatment (91.1 ± 11.6%, 99.1 ± 11.6%, 79.8 ± 10.5%, 93.9 ± 5.8%, respectively), indicating that there is a significant difference in responsive profiles against JPH203 among cancer cells. To try to address a factor behind the difference, LAT1 expression levels of these cells were determined. The results showed that LAT1 mRNA expression were clearly observed in all cells examined, but these levels apparently did not correspond to their cytotoxic profiles. [Conclusion] Our results have demonstrated that cytotoxic effects of JPH203 are obviously cell-type dependent. Since the reason for this dependence does not seem to be solely explained by LAT1 expression levels, there should be unidentified factors determining JPH203 efficacy.
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