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Division of Innovative Pathology and Laboratory Medicine (Kashiwa Campus)
Takeshi Kuwata, Masato Sugano, Eiji Yoshikawa, Shigeo Yoshida, Emiko Yoshikawa, Megumi Imamiya
Introduction
The Division of Innovative Pathology and Laboratory Medicine (IPLM) was newly established at the Exploratory Oncology Research and Clinical Trial Center (EPOC) in 2016. The aim of the LPMN is to develop new diagnostic technologies, reagents, and devices in pathology and laboratory medicine field.
Our team and what we do
To achieve our goal, the activities of the IPLM are closely collaborated with the Department of Pathology and Clinical Laboratories in the National Cancer Center Hospital East (NCCHE) and the Division of Pathology as well as other divisions in the EPOC.
Research activities
We are conducting the DEF (Discovery and Establishment of new biomarkers For gastric cancer) study, in which patient-derived xenografts (PDX) and cell lines have been established from surgically resected gastric cancers as well ascites. The aim of this study is to establish reliable bio-resources for supporting activities of new drug development in academia as well as pharmaceuticals. In 2016, a total of 80 samples were registered in the study, and 14 and 16 passage-competent PDX and cell lines were established, respectively (Figure 1). As a result, we have successfully established a total of 30 gastric cancer PDX and 21 novel gastric cancer cell lines. Expression of selected receptor tyrosine-kinases, HER2, EGFR and MET, have been evaluated in all PDX models. NGS-based gene mutation profiles are also added in some PDX models.
Education
We are participating in a weekly clinical conference with the Department of Pathology and Clinical Laboratories in the NCCHE. We also hold a biweekly progress research meeting in the EPOC as well as a monthly research meeting with the Division of Pathology in the EPOC. We presented our research data in scientific meetings including annual meeting of the Japanese Society of Pathology and have published in well-recognized scientific journals.
Future prospects
Our goal is to develop new diagnostic technologies, reagents and devices required for providing precision medicine to all cancer patients. For this purpose we will use our experiences at the NCCHE and conduct translational/reverse-translational researches. In 2017, we will open a genetic testing division and provide clinical sequence service in the NCCHE.
Figure 1. An established gastric cancer PDX model showing strong HER2 expression
List of papers published in 2016
Journal
1.Kuboki Y, Yamashita S, Niwa T, Ushijima T, Nagatsuma A, Kuwata T, Yoshino T, Doi T, Ochiai A, Ohtsu A. Comprehensive analyses using next-generation sequencing and immunohistochemistry enable precise treatment in advanced gastric cancer. Ann Oncol, 27:127-133, 2016
2.Yokoyama T, Nakatake M, Kuwata T, Couzinet A, Goitsuka R, Tsutsumi S, Aburatani H, Valk PJM, Delwel R, Nakamura T. MEIS1-mediated transactivation of synaptotagmin-like 1 promotes CXCL12/CXCR4 signaling and leukemogenesis. J Clin Invest, 126:1664-1678, 2016
3.Hisakane K, Saruwatari K, Fujii S, Kirita K, Umemura S, Matsumoto S, Yoh K, Niho S, Ohmatsu H, Kuwata T, Ochiai A, Gemma A, Tsuboi M, Goto K, Ishii G. Unique intravascular tumor microenvironment predicting recurrence of lung squamous cell carcinoma. J Cancer Res Clin Oncol, 142:593-600, 2016
4.Sekihara K, Hishida T, Ikemura S, Saruwatari K, Morise M, Kuwata T, Fujii S, Kojima M, Ochiai A, Funai K, Aokage K, Yoshida J, Tsuboi M, Ishii G. The association of intravascular stromal cells with prognosis in high-grade neuroendocrine carcinoma of the lung. J Cancer Res Clin Oncol, 142:905-912, 2016
5.Saruwatari K, Ikemura S, Sekihara K, Kuwata T, Fujii S, Umemura S, Kirita K, Matsumoto S, Yoh K, Niho S, Ohmatsu H, Ochiai A, Kohrogi H, Tsuboi M, Goto K, Ishii G. Aggressive tumor microenvironment of solid predominant lung adenocarcinoma subtype harboring with epidermal growth factor receptor mutations. Lung Cancer, 91:7-14, 2016
6.Matsuzawa R, Kirita K, Kuwata T, Umemura S, Matsumoto S, Fujii S, Yoh K, Kojima M, Niho S, Ohmatsu H, Ochiai A, Tsuboi M, Goto K, Ishii G. Factors influencing the concordance of histological subtype diagnosis from biopsy and resected specimens of lung adenocarcinoma. Lung Cancer, 94:1-6, 2016
7.Suzuki S, Aokage K, Hishida T, Yoshida J, Kuwata T, Yamauchi C, Tsuboi M, Ishii G. Interstitial growth as an aggressive growth pattern in primary lung cancer. J Cancer Res Clin Oncol, 142:1591-1598, 2016
8.Naito M, Aokage K, Saruwatari K, Hisakane K, Miyoshi T, Hishida T, Yoshida J, Masato S, Kojima M, Kuwata T, Fujii S, Ochiai A, Sato Y, Tsuboi M, Ishii G. Microenvironmental changes in the progression from adenocarcinoma in situ to minimally invasive adenocarcinoma and invasive lepidic predominant adenocarcinoma of the lung. Lung Cancer, 100:53-62, 2016