The 7th Kiyoko and Paul Bourdarie-Goto Scientific Prize

April 12, 2019


The 7th Kiyoko and Paul Bourdarie-Goto Scientific Prize
Winner Tadashi AKIBA, M.D., Ph.D.
    Executive Director, The Jikei University
    Chief, The Jikei University Kashiwa Hospital
    Professor, Division of Thoracic Surgery, Department of Surgery, Graduate School of Medicine, The Jikei University
Paper Vitamin D Supplementation and Survival of Patients with Non-small Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial
(Clinical Cancer Research, 2018 Sep 1;24(17):4089-4097)
Reason for Selection
(Dr. Jun NAKAJIMA,
Chairman of the Advisory Committee)
Dr. Tadashi Akiba performed a prospective, randomized, double-blind clinical trial with his colleagues to clarify the effectiveness of vitamin D (25-hydroxyvitamin D (25(OH) D)) supplement intake for patients with non-small cell lung cancer. He showed that intake of vitamin D supplement improves postoperative survival rate of a subset of early stage lung adenocarcinoma patients whose serum level of vitamin D were low. Several retrospective observational studies have suggested at weak evidence level that the lower serum level of vitamin D may increase the risk of carcinogenesis and recurrence. However, Dr. Akiba concluded from his study that vitamin D supplement intake improves 5-year recurrence-free survival rate. The result will contribute to the advancement of primary/tertiary prevention of lung cancer onset. It is also attractive that vitamin D is inexpensive and easily available.
Message from the Awardee I am honored to have received such a wonderful award. I would like to thank the co-researcher Professor Urashima. Founder of the Jikei University, Kanehiro Takaki, overcame beriberi, a vitamin B1 deficiency, before vitamins were discovered. Higher serum vitamin D levels were reported to be associated with better survival in patients with early-stage lung cancer than lower. However, because of the studies’ observational nature, whether lower vitamin D level is merely a precursor to relapse and death or a lower vitamin D level is causally related to shorter survival cannot be determined. To clarify this, a randomized, double-blind, placebo-controlled trial using vitamin D was performed in patients with lung cancer as the first trial in the world. By restricting the analysis to the subgroup with early-stage adenocarcinoma with vitamin D insufficient, the vitamin D group showed significantly better 5-year survival than the placebo group. The hardest point was enrolling patients. This Vitamin D and Cancer Project, we have already expanded to patients with digestive tract cancers and obtained similar results. Moreover, we are going to expand this vitamin D project toward patients with head and neck cancer.
Kiyoko and Paul Bourdarie-Goto Scientific Prize-Special Award
Winner Sachie HIRATSUKA-NAKAMURA, M.D., Ph.D.
Professor, Department of Biochemistry and Molecular Biology, Shinshu University School of Medicine
Paper Hepato-entrained B220CD11cNK1.1cells regulate pre-metastatic niche formation in the lung
(EMBO Molecular Medicine, 2018; 10: e8643)
Reason for Selection
(Dr. Jun NAKAJIMA,
Chairman of the Advisory Committee)
Dr. Sachie Hiratsuka-Nakamura and her colleagues revealed with the aid of in vivo cell tracking method, that a subset of natural killer cells located in the liver suppresses cancer metastasis in the microscopic tissue environment of cancer. This is a unique and new discovery, and research results are expected to be applied to other organs including lung.
Message from the Awardee It has been well known that a primary tumor metastasizes the preference organ. In an adaptation of Paget’s “seed and soil” concept (Paget, 1889) – which states that tumor cells (the “seeds”) form metastatic nodules if they encounter hospitable “soil” in a distant organ – We first proposed that primary tumors prepare the distant soil (= milieu) in a so called “pre-metastatic phase” in 2002. This term describes a period during which a distant organ is rendered more hospitable towards circulating tumor cells with metastatic potential, by the presence of a distant primary tumor.
In case of pulmonary metastasis, many factors from the primary tumor stimulate the lung environment prior to tumor cell arrival. Recently, we discovered that estimated pre-metastatic soil in the lungs in cancer patients. The pre-metastatic soil contains a complex mixture of factors that either inhibit or promote metastasis. However, inflammatory immune cells gradually function to be pro-metastatic rather than anti-metastatic. In this paper, we tried to find out anti-metastatic cells in pre- and post- metastatic niche. We found a specific immune cell population that was educated in liver and accumulated in lung niche via circulation from liver, and capable of eliminating pre-metastatic soil, and killing metastatic tumor cells. Thus, we consider that these can be applied to human studies. We now try to discover and generate “anti-metastatic immune cells” that work in cancer patients.