Esophageal squamous cell carcinoma (ESCC) is the most common primary esophageal malignancy. Telmisartan, an angiotensin II type 1 (AT1) receptor blocker (ARB) and a widely used antihypertensive, has been shown to inhibit proliferation of various cancer types. This study evaluated the effects of telmisartan on human ESCC cell proliferation in vitro and in vivo and sought to identify the microRNAs (miRNAs) involved in these antitumor effects. We examined the effects of telmisartan on three human ESCC cell lines (KYSE150, KYSE180, and KYSE850). Telmisartan inhibited proliferation of these three cell lines by inducing S-phase arrest, which was accompanied by decreased expression of cyclin A2, cyclin-dependent kinase 2, and other cell cycle-related proteins. Additionally, telmisartan reduced levels of phosphorylated ErbB3 and thrombospondin-1 in KYSE180 cells. Furthermore, expression of miRNAs was remarkably altered by telmisartan in vitro. Telmisartan also inhibited tumor growth in vivo in a xenograft mouse model. In conclusion, telmisartan inhibited cell proliferation and tumor growth in ESCC cells by inducing cell-cycle arrest.

Galectin-9 (Gal-9) enhances tumor immunity mediated by T cells, macrophages, and dendritic cells. Its expression level in various cancers correlates with prognosis. Furthermore, Gal-9 directly induces apoptosis in various cancers; however, its mechanism of action and bioactivity has not been clarified. We evaluated Gal-9 antitumor effect against esophageal squamous cell carcinoma (ESCC) to analyze the dynamics of apoptosis-related molecules, elucidate its mechanism of action, and identify relevant changes in miRNA expressions. KYSE-150 and KYSE-180 cells were treated with Gal-9 and their proliferation was evaluated. Gal-9 inhibited cell proliferation in a concentration-dependent manner. The xenograft mouse model established with KYSE-150 cells was administered with Gal-9 and significant suppression in the tumor growth observed. Gal-9 treatment of KYSE-150 cells increased the number of Annexin V-positive cells, activation of caspase-3, and collapse of mitochondrial potential, indicating apoptosis induction. c-Jun NH₂-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) phosphorylation were activated and could be involved in apoptosis. Therefore, Gal-9 induces mitochondria-mediated apoptosis of ESCC and inhibits cell proliferation in vitro and in vivo with JNK and p38 activation.

Background: The recently developed endoscopic full-thickness resection technique requires reliable closure. The main closure methods are the purse-string suture (PSS) technique and over-the-scope clip (OTSC) technique; however, basic data on the closure strength of each technique are lacking. This study was performed to compare the closure strengths of these two methods in an ex vivo porcine model. Methods: In the traction test, a virtual 5-cm full-thickness closure line was closed by the following six methods three times each: conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture. The primary endpoint was the tension at the starting point of dehiscence, measured in Newtons (N) by an automatic traction machine. In the leak test, a 15-mm gastric full-thickness defect was closed by PSS or OTSC six times each, and the closed stomach was then pressurized in a water container. The primary endpoint was the leak pressure when air bubbles appeared. The secondary endpoints were the procedure time and presence of complete inverted closure. Results: The mean tension was 2.16, 3.68, 5.15, 18.30, 19.30, and 62.40 N for conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture, respectively. Complete inverted closure was observed for seromuscular PSS, seromuscular OTSC, and surgical suture. The mean leak pressure was 13.7 and 24.8 mmHg in the PSS and OTSC group, respectively (P < 0.01). The mean procedure time was 541 and 169 s in the PSS and OTSC group, respectively (P < 0.01). Complete inverted closure was observed in OTSC alone. Conclusion: The OTSC, which allows complete inverted closure, showed greater closure strength than PSS. Considering the size limitation suitable for single OTSC, a therapeutic strategy for closing the larger size is further warranted.

The severity of oxaliplatin (L-OHP)-induced peripheral sensory neuropathy (PSN) exhibits substantial interpatient variability, and some patients suffer from long-term, persisting PSN. To identify single-nucleotide polymorphisms (SNPs) predicting L-OHP-induced PSN using a genome-wide association study (GWAS) approach. A large prospective GWAS including 1379 patients with stage II/III colon cancer who received L-OHP-based adjuvant chemotherapy (mFOLFOX6/CAPOX) under the phase II (JOIN/JFMC41) or the phase III (ACHIVE/JFMC47) trial. Firstly, GWAS comparison of worst grade PSN (grade 0/1 versus 2/3) was carried out. Next, to minimize the impact of ambiguity in PSN grading, extreme PSN phenotypes were selected and analyzed by GWAS. SNPs that could predict time to recovery from PSN were also evaluated. In addition, SNPs associated with L-OHP-induced allergic reactions (AR) and time to disease recurrence were explored. No SNPs exceeded the genome-wide significance (P < 5.0 × 10^-8) in either GWAS comparison of worst grade PSN, extreme PSN phenotypes, or time to recovery from PSN. An association study focusing on AR or time to disease recurrence also failed to reveal any significant SNPs. Our results highlight the challenges of utilizing SNPs for predicting susceptibility to L-OHP-induced PSN in daily clinical practice.

White globe appearance (WGA) is defined as a microendoscopic white lesion with a globular shape underlying the gastric epithelium and is considered a marker of gastric cancer. We recently reported that endoscopically visualized white spot (WS) corresponding to WGA appeared on the nonatrophic mucosa of patients with acid-suppressing agents (A-SA) use. We evaluated patients undergoing routine esophagogastroduodenoscopy and divided the patients into an A-SA group (n = 112) and a control group (n = 158). We compared the presence of WS in both groups. We also compared WS-positive- (n = 31) and -negative (n = 43) groups within the A-SA group regarding these patients’ backgrounds and serum gastrin concentrations. Comparing the A-SA group with controls, the prevalence of WS was significantly higher (31/112 vs. 2/158; p < 0.001). The number of patients with high serum gastrin concentrations was significantly higher in the WS-positive group (18/31) vs. the WS-negative group (5/43) (p < 0.001). Within the A-SA group, the prevalence of WS was also significantly higher in patients taking potassium-competitive acid blockers vs. proton-pump inhibitors (21/31 vs. 10/31, p < 0.001). The WS-positive group had a significantly greater percentage of patients, with a high serum gastrin level (p < 0.001). WS may be associated with hypergastrinemia and potassium-competitive acid blockers.

EB-TACE has recently been performed because of its lower hepatotoxicity compared to cTACE in less advanced HCC. However, local recurrence at the tumor margins is often observed after DEB-TACE. cTACE involves filling the intratumoral sinusoids with lipiodol-containing anticancer drugs and accumulating in the drainage area, which is the first site of HCC recurrence. The aim of this study is to evaluate the therapeutic effect of DEB-TACE followed by cTACE in HCC patients. Between 2014 and 2020, 65 patients with Barcelona clinic liver cancer (BCLC) stage B (intermediate stage) of HCC were enrolled and divided into two groups: one group received DEB-TACE followed by cTACE (cTACE group) and the other group received only DEB-TACE (non-cTACE group). Sixty-five patients were medically followed. The median observation time was 14 ± 13.1 months after the first DEB-TACE and outcomes were analyzed for multiple factors. Results: The complete response rate was significantly higher in the cTACE group than in the non-TACE group. The analysis showed that the only factor that increased the CR rate in the cTACE group was the total tumor number (less than four). The OS rate of CR patients was higher than that of non-CR patients in the cTACE group. Adverse events in the cTACE group included severe thrombocytopenia but only in one of twenty-seven patients. Conclusions: The combined therapy with DEB-TACE followed by cTACE may be a new effective therapeutic strategy for the intermediate stage of HCC patients.