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Background/aim: Immune checkpoint blockade has achieved great success as a targeted immunotherapy for solid cancers. However, small molecules that inhibit programmed death 1/programmed death ligand 1 (PD-1/PD-L1) binding are still being developed and have several advantages, such as high bioavailability. Previously, we reported a novel PD-1/PD-L1-inhibiting small compound, SCL-1, which showed potent antitumor effects on PD-L1 + tumors. These effects were dependent on CD8 + T-cell infiltration and PD-L1 expression on tumors. The present study investigated the in vivo antitumor activity of SCL-1 in various mouse syngeneic tumor models., Materials and Methods: Twelve syngeneic mice models of tumors, such as colon, breast, bladder, kidney, pancreatic, non-small cell lung cancers, melanoma, and lymphomas, were used for in vivo experiments. Tumor mutation burden (TMB) was analyzed by whole exome sequencing (WES) using reference DNA from mouse blood. The proportion of CD8 + T-cells infiltrating tumors before and after treatment was assessed using flow cytometry and immunohistochemistry (IHC)., Results: SCL-1 had a markedly greater antitumor effect (11 sensitive tumors and 1 resistant tumor among the 12 tumor types) than the anti-mouse PD-1 antibody (8 sensitive tumors and 4 resistant tumors). In addition, the tumor growth inhibition rate (%) was more closely associated with TMB in the SCL-1 group than in the anti-PD-1 antibody group. Furthermore, in vivo experiments using PD-L1 gene knockout and lymphocyte-depletion technologies demonstrated that the antitumor activity of SCL-1 was dependent on CD8 + T-cell infiltration and PD-L1 expression in tumors., Conclusion: SCL-1 has great potential as an oral immunotherapy that targets immune checkpoint molecules in cancer treatment., (Copyright © 2025, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Laparoscopic surgery for gastric cancer has become widely used; minimally invasive surgery has become the mainstream of treatment. This randomized controlled trial (RCT) aimed to compare long-term quality of life (QoL) and weight loss rates in patients who underwent single-port laparoscopic gastrectomy (SLG) or multi-port laparoscopic gastrectomy (MLG) for gastric cancer., Methods: This single-center RCT compared MLG and SLG in patients with clinical stage I gastric cancer, all of which underwent distal gastrectomy between April 2016 and September 2018. A total of 101 patients were evaluated for eligibility; all were randomized into either the SLG group (n = 50) or MLG group (n = 51). Blood tests, weight measurements, and postoperative questionnaires (DAUGS20, EORTC QLQ-C30, PGSAS-45) were performed at 3, 6, 12, and 36 months after surgery to compare the QoL., Results: At six months postoperatively, there was a higher trend toward lower weight loss in the SLG group compared with the MLG group. At 1, 3, 6, and 36 months postoperatively, the neutrophil-to-lymphocyte ratio was significantly lower in the SLG group than that in the MLG group. The QoL, as measured using the postoperative questionnaires, was generally comparable. However, some favorable results, such as fewer diarrheas, were achieved., Conclusions: SLG was partially superior to MLG in terms of long-term QoL, in addition to assurance of esthetics and reduced pain. In addition, systemic inflammatory markers and weight loss rates were lower, suggesting a potential long-term benefit. SLG may be an option for stage I gastric cancer surgery. Further follow-up and multicenter studies should be considered., Competing Interests: Declarations. Disclosures: Kohei Fujita, Takeshi Omori, Hisashi Hara, Naoki Shinno, Masayoshi Yasui, Hiroshi Wada, Hirofumi Akita, Masayuki Ohue, Hiroshi Miyata, and Shuji Takiguchi have declared no conflict of interests. Ethical approval: This study was approved by the Institutional Review Board of the Osaka International Cancer Institute (number 1512046225) and follows the Declaration of Helsinki (1975). Written informed consent was obtained from all patients. The study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000022218)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)