1: Omega-3 fatty acid epoxides produced by PAF-AH2 in mast cells regulate pulmonary vascular remodeling
Science of the Month - July 2022
Nature Communications,
Nature Communications, 2022, vol. 13, issue 1, 1-13
Hidenori Moriyama, Jin Endo, Masaharu Kataoka, Yuta Shimanaka, Nozomu Kono, Yuki Sugiura, Shinichi Goto, Hiroki Kitakata, Takahiro Hiraide, Naohiro Yoshida, Sarasa Isobe, Tsunehisa Yamamoto, Kohsuke Shirakawa, Atsushi Anzai, Yoshinori Katsumata, Makoto Suematsu, Kenjiro Kosaki, Keiichi Fukuda, Hiroyuki Arai & Motoaki Sano
Pulmonary hypertension is an intractable disease that causes right heart failure due to increased pulmonary vascular resistance, and its pathogenetic mechanism has not yet been fully elucidated. The authors focused on inflammatory cells and bioactive lipids that accumulate around pulmonary blood vessels to clarify this mechanism. As a result, they found that mast cells, a type of inflammatory cell, produce metabolites of omega-3 fatty acids from fish oil (epoxidized omega-3 fatty acids), which suppress abnormal fibrosis in pulmonary blood vessels. Furthermore, through animal experiments and whole-exome sequencing of genomic information from patients with pulmonary hypertension, they revealed that PAF-AH2, the enzyme that produces these epoxidized omega-3 fatty acids, is deeply associated with the condition. They also demonstrated that supplementary administration of these lipids could be a therapeutic approach to improve pulmonary hypertension. These research findings are expected to lead not only to the elucidation of a new mechanism but also to the creation of novel therapies that address the root cause of the disease. Future applications in personalized medicine based on genetic information are also anticipated.
(Hidenori Moriyama, Department of Cardiology, 90th Class)
2: Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L) : a multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial.
Lancet.
Saji H, Okada M, Tsuboi M, Nakajima R, Suzuki K, Aokage K, Aoki T, Okami J, Yoshino I, Ito H, Okumura N, Yamaguchi M, Ikeda N, Wakabayashi M, Nakamura K, Fukuda H, Nakamura S, Mitsudomi T, Watanabe SI, Asamura H.
Unlike the papers in the basic medical sciences field introduced in this section, this study presents the results of a multicenter collaborative study on a comparative trial between surgical procedures in pure surgery, a rarity in recent times. The current standard treatment for stage I non-small-cell lung cancer is curative surgery by lobectomy. However, a randomized controlled trial was planned between lobectomy and segmentectomy based on the hypothesis that for small lung cancers 2 cm or less in diameter with no lymph node metastasis, a smaller resection (segmentectomy) could provide equivalent curability while preserving lung function. The author was involved in this JCOG clinical trial as a Principal Investigator (PI). This clinical trial is a "non-inferiority trial" designed to establish the superiority of segmentectomy in terms of both postoperative respiratory function and prognosis. The interpretation of the results is complex. Although the superiority of segmentectomy in postoperative respiratory function was not demonstrated, the unexpected finding that the prognosis for the segmentectomy group was significantly better than that of the lobectomy group led to the conclusion that segmentectomy should become the new standard of care. This remains a point of much debate. This large-scale comparative trial in pure surgery is a first for thoracic surgery in Japan and has garnered significant international attention.
(Hisao Asamura, Department of Surgery (Thoracic), 62nd Class)
Other Published Papers
1: T Cell Responses to the Microbiota.
Annual Review of Immunology.
Ivanov, II, Tuganbaev T, Skelly AN, Honda K.