1: Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma.
Science of the Month - April 2022
New England Journal of Medicine.
Doki Y, Ajani JA, Kato K, Xu J, Wyrwicz L, Motoyama S, Ogata T, Kawakami H, Hsu CH, Adenis A, El Hajbi F, Di Bartolomeo M, Braghiroli MI, Holtved E, Ostoich SA, Kim HR, Ueno M, Mansoor W, Yang WC, Liu T, Bridgewater J, Makino T, Xynos I, Liu X, Lei M, Kondo K, Patel A, Gricar J, Chau I, Kitagawa Y. * CheckMate 648 Trial Investigators
For a long time, the standard of care for metastatic or recurrent esophageal squamous-cell carcinoma has been systemic chemotherapy with cytotoxic anticancer drugs, but the prognosis has been extremely poor. Recently, nivolumab and ipilimumab—antibody drugs targeting tumor-cell programmed death-1 (PD-1), which suppresses the function of antigen-specific T cells in tumor tissue, and cytotoxic T-lymphocyte antigen-4 (CTLA-4)—have been developed as immune checkpoint inhibitors and have shown efficacy in many types of cancer. This international, multicenter, phase III trial was designed to evaluate the efficacy of nivolumab plus chemotherapy and nivolumab plus ipilimumab versus chemotherapy alone. A total of 970 patients were enrolled. As a result, both the nivolumab-plus-chemotherapy group and the nivolumab-plus-ipilimumab group demonstrated superiority to the chemotherapy-alone group with respect to the primary endpoint of overall survival. This study is the world's first to report the efficacy of a two-drug immune checkpoint inhibitor combination therapy for esophageal cancer. In addition to improving treatment outcomes for metastatic or recurrent esophageal squamous-cell carcinoma, there are high expectations for verifying its efficacy in perioperative chemotherapy for surgically resectable esophageal cancer.
(Yuko Kitagawa, 65th Graduating Class, Department of Surgery (General and Gastroenterological))
2: Coupling of angiogenesis and odontogenesis orchestrates tooth mineralization in mice
J Exp Med
(2022) 219 (4): e20211789. DOI：10.1084/jem.20211789
Tomoko Matsubara, Takahito Iga, Yuki Sugiura, Dai Kusumoto, Tsukasa Sanosaka, Ikue Tai-Nagara, Norihiko Takeda, Guo-Hua Fong, Kosei Ito, Masatsugu Ema, Hideyuki Okano, Jun Kohyama, Makoto Suematsu, Yoshiaki Kubota
Teeth are harder than bone, making them the hardest structures in the human body. Because their hardness made it nearly impossible to perform experiments such as cutting sections, as is done with other soft tissues, the process by which teeth harden was poorly understood. In this study, we first succeeded in cleanly sectioning mouse teeth by making various improvements to conventional methods. Applying this method, we then established an imaging technique to observe dental vasculature three-dimensionally at the single-cell level. Using this technique to observe the developmental process of dental blood vessels in detail, we discovered a unique population of vascular endothelial cells that cluster around odontoblasts—the cells responsible for tooth hardening. These endothelial cells promote odontoblast maturation and supply minerals necessary for hardening, such as phosphorus. Furthermore, when we created genetically modified mice in which only these specific vascular endothelial cells were ablated, we found that the teeth failed to harden. This research holds promise for future applications in the regeneration of teeth lost to cavities, periodontal disease, or other causes.
(Yoshiaki Kubota, 79th Graduating Class, Department of Anatomy)