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Inflammation and de-differentiation in pancreatic carcinogenesis

World Journal of Clinical Cases 2018年第15期6卷 882-891页

作者： Takahiro Seimiya Motoyuki Otsuka Takuma Iwata Eri Tanaka Tatsunori Suzuki Kazuma Sekiba Mari Yamagami rei ishibashi Kazuhiko Koike Department of Gastroenterology Graduate School of Medicine The University of Tokyo

Pancreatic cancer is a malignancy with an extremely poor prognosis. Chronic pancreatitis is a well-known risk factor for pancreatic cancer. Inflammation is thought to influence carcinogenesis through DNA damage and activation of intracellular signaling pathways. Many transcription factors and signaling pathways co-operate to determine and maintain cell identity at each phase of pancreatic organogenesis and cell differentiation. Recent studies have shown that carcinogenesis is promoted through the suppression of transcription factors related to differentiation. Pancreatitis also demonstrates transcriptional changes, suggesting that multifactorial epigenetic changes lead to impaired differentiation. Taken together, these factors may constitute an important framework for pancreatic carcinogenesis. In this review, we discuss the role of inflammation and de-differentiation in the development of pancreatic cancer, as well as the future of novel therapeutic applications.

关键词： Pancreatitis Inflammation Organogenesis Differentiation Transcription factor Pancreatic cancer

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Hepatitis B virus pathogenesis: Fresh insights into hepatitis B virus RNA

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World Journal of Gastroenterology 2018年第21期24卷 2261-2268页

作者： Kazuma Sekiba Motoyuki Otsuka Motoko Ohno Mari Yamagami Takahiro Kishikawa Tatsunori Suzuki rei ishibashi Takahiro Seimiya Eri Tanaka Kazuhiko Koike Department of Gastroenterology Graduate School of MedicineThe University of Tokyo

Hepatitis B virus(HBV) is still a worldwide health concern. While divergent factors are involved in its pathogenesis, it is now clear that HBV RNAs, principally templates for viral proteins and viral DNAs, have diverse biological functions involved in HBV pathogenesis. These functions include viral replication, hepatic fibrosis and hepatocarcinogenesis. Depending on the sequence similarities, HBV RNAs may act as sponges for host mi RNAs and may deregulate mi RNA functions, possibly leading to pathological consequences. Some parts of the HBV RNA molecule may function as viralderived mi RNA, which regulates viral replication. HBV DNA can integrate into the host genomic DNA and produce novel viral-host fusion RNA, which may have pathological functions. To date, elimination of HBVderived covalently closed circular DNA has not been achieved. However, RNA transcription silencing may be an alternative practical approach to treat HBVinduced pathogenesis. A full understanding of HBV RNA transcription and the biological functions of HBV RNA may open a new avenue for the development of novel HBV therapeutics.

关键词： Hepatitis B virus Hepatitis B virus RNA MicroRNA Smc5/6 Viral replication Hepatic fibrosis Genome integration Hepatocellular carcinoma

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