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Cancer Science

Yoshihiro Ohue, Hiroyoshi Nishikawa
Regulatory T (Treg) cells suppress abnormal/excessive immune responses to self- and non-self-antigens to maintain immune homeostasis. In tumor immunity, Treg cells are involved in tumor development and progression by inhibiting anti-tumor immunity. There are several Treg-cell immune suppressive mechanisms: inhibition of co-stimulatory signals via CD80 and CD86 expressed by dendritic cells through CTLA-4, IL-2 consumption via high-affinity IL-2 receptors with high CD25 (IL-2 receptor ∝ chain) expression, secretion of inhibitory cytokines, metabolic modulation of tryptophan and adenosine, and direct killing of effector T cells...
May 18, 2019: Cancer Science
Young-Heon Kim, Seung Bum Lee, Sehwan Shim, Areumnuri Kim, Ji-Hye Park, Won-Suk Jang, Sun-Joo Lee, Jae Kyung Myung, Sunhoo Park, Su-Jae Lee, Min-Jung Kim
Hyaluronic acid synthase2 (HAS2) is suggested to play a critical role in malignancy and is abnormally expressed in many carcinomas. However, its role in colorectal cancer (CRC) malignancy and specific signaling mechanisms remain obscure. Here, we report that HAS2 was markedly increased in both CRC tissue and malignant CRC cell lines. Depletion of HAS2 in HCT116 and DLD1 cells, which express high levels of HAS2, critically increased sensitivity of radiation/oxaliplatin-mediated apoptotic cell death. Moreover, down-regulation of HAS2 suppressed migration, invasion, and metastasis in nude mice...
May 17, 2019: Cancer Science
Li Song, Shoubao Ma, Longpei Chen, Liyan Miao, Min Tao, Haiyan Liu
The presence of IL-17- producing T cells has recently been reported in non-small cell lung cancer (NSCLC) patients. However, the long-term prognostic significance of these populations in NSCLC patients remains unknown. In this study, we collected peripheral blood from 82 NSCLC patients and 22 normal healthy donors (NCs). The percentages of IL-17-producing CD4+ T (Th17), CD8+ T (Tc17) and γδT cells (γδT17) were measured to determine their association with clinical outcomes and overall survival (OS) in NSCLC...
May 17, 2019: Cancer Science
Shimpei Matsui, Koji Okabayashi, Masashi Tsuruta, Kohei Shigegta, Ryo Seishima, Takashi Ishida, Takayuki Kondo, Yoshiyuki Suzuki, Hirotoshi Hasegawa, Masayuki Shimoda, Shinya Sugimoto, Toshiro Sato, Yuko Kitagawa
The incidence of colorectal cancer (CRC) has been on the rise, which is linked to the increasing prevalence of obesity based on global epidemiological evidence. Although chronic inflammation is implicated in tumor development, the mechanisms underlying obesity-associated CRC remain unknown. Here, we sought to identify the inflammatory cytokines and their roles in obesity-related colorectal tumorigenesis using cytokine array analyses in a mouse model. Colorectal tumorigenesis was induced through intraperitoneal administration of azoximethane once a week for 6 weeks in 6 weeks female of wild-type (WT) C57Black / 6J and its obesity diabetes model mouse KK / TaJcl, KK-Ay / TaJcl...
May 17, 2019: Cancer Science
Masamichi Takahashi, Shunichiro Miki, Kenji Fujimoto, Kohei Fukuoka, Yuko Matsushita, Yoshiko Maida, Mami Yasukawa, Mitsuhiro Hayashi, Raku Shinkyo, Kiyomi Kikuchi, Akitake Mukasa, Ryo Nishikawa, Kenji Tamura, Yoshitaka Narita, Akinobu Hamada, Kenkichi Masutomi, Koichi Ichimura
Glioblastoma is one of the most devastating human malignancies for which a novel efficient treatment is urgently required. This pre-clinical study shows that eribulin, a specific inhibitor of TERT-RdRP, is an effective anticancer agent against glioblastoma. Eribulin inhibited the growth of four TERT promoter mutation-harboring glioblastoma cell lines in vitro at sub-nanomolar concentrations. In addition, it suppressed the growth of glioblastoma cells transplanted subcutaneously or intracerebrally to mice, and significantly prolonged the survival of mice harboring brain tumors at a clinically equivalent dose...
May 17, 2019: Cancer Science
Bofang Liu, Ye Zhang, Yibo Fan, Shuo Wang, Zhi Li, Mingming Deng, Ce Li, Jin Wang, Rui Ma, Xiaoxun Wang, Yan Wang, Ling Xu, Kezuo Hou, Xiaofang Che, Yunpeng Liu, Xiujuan Qu
Gastric cancer (GC) is a common cause of cancer-related death worldwide. Due to the lack of reliable diagnostic or prognostic biomarkers for GC, patient prognosis is still poor. Therefore, there is an urgent need for studies examining the underlying pathogenesis of GC in order to find effective biomarkers. LRRN1 (Leucine-rich repeat neuronal protein-1) is a type I transmembrane protein that plays an important role in the process of nerve development and regeneration. However, its role in cancer, especially gastric cancer (GC), remains unclear...
May 13, 2019: Cancer Science
Rie Iida-Norita, Minaho Kawamura, Yasuhiro Suzuki, Shin Hamada, Atsushi Masamune, Toru Furukawa, Yasufumi Sato
Vasohibin-2 (VASH2) is expressed in various cancers and promotes their progression. We recently reported that pancreas cancer patients with higher VASH2 expression exhibited poorer prognosis. Here, we sought to characterize the role of VASH2 in pancreatic cancer. We used LSL-K-rasG12D; LSL-Trp53R172H; Pdx1-Cre (KPC) mice, a mouse model of pancreatic ductal adenocarcinoma (PDAC), and cells isolated from them (KPC cells). Knockdown of Vash2 from PDAC cells did not affect their proliferation, but decreased their migration...
May 9, 2019: Cancer Science
Shanxun Yu, Daolu Yang, Yunyao Ye, Pei Liu, Zhenyao Chen, Tianyao Lei, Jiaze Pu, Longfa Liu, Zhaoxia Wang
The number of documented long non-coding RNAs (lncRNAs) has dramatically increased, and their biological functions and underlying mechanisms in pathological processes, especially cancer, remain to be elucidated. Actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) is a 6810nt lncRNA located on chromosome 4p16.1 that was first reported to be upregulated in esophageal adenocarcinoma (EAC) tissues and cell lines. Here we reported that AFAP1-AS1, recruiting and binding to lysine-specific demethylase 1 (LSD1), was generally overexpressed in human non-small cell lung cancer (NSCLC) tissues using qRT-PCR...
May 8, 2019: Cancer Science
Masako Imaoka, Keiji Tanese, Yohei Masugi, Mutsumi Hayashi, Michiie Sakamoto
Expression of programmed cell death ligand 1 (PD-L1) on tumor cells contributes to cancer immune evasion by interacting with programmed cell death 1 on immune cells. Interferon gamma (IFN-γ) has been reported as a key extrinsic stimulator of PD-L1 expression, yet its mechanism of expression is poorly understood. This study analyzed the role of CD74 and its ligand macrophage migration inhibitory factor (MIF) on PD-L1 expression, by immunohistochemical (IHC) analysis of melanoma tissue samples and in vitro analyses of melanoma cell lines treated with IFN-γ and inhibitors of the MIF-CD74 interaction...
May 8, 2019: Cancer Science
Yu Jin Kim, Dan Bi Yu, Mingi Kim, Yoon-La Choi
Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are the most common types of liposarcoma. Although WDLPS and DDLPS patients receive intensive treatment including radical surgery and systemic therapy, their overall 5-year survival rates are 90% and 30%, respectively, indicating that DDLPS is clinically more aggressive. We examined whether adipogenic stimulation induces adipogenesis in human WDLPS/DDLPS cells by using dexamethasone, indomethacin, insulin, and 3-isobutyl-1-methylxanthine (IBMX), all putative medications or drugs...
May 8, 2019: Cancer Science
Takeshi Ito, Atsuko Nakamura, Ichidai Tanaka, Yumi Tsuboi, Teppei Morikawa, Jun Nakajima, Daiya Takai, Masashi Fukayama, Yoshitaka Sekido, Toshiro Niki, Daisuke Matsubara, Yoshinori Murakami
CADM1 (cell adhesion molecule-1) is a member of the immunoglobulin superfamily that functions as a tumor suppressor of lung tumors. We herein demonstrated that CADM1 interacts with Hippo pathway core kinases and enhances the phosphorylation of YAP1, and also that the membranous co-expression of CADM1 and LATS2 predicts a favorable prognosis in lung adenocarcinoma. CADM1 significantly repressed the saturation density elevated by YAP1 overexpression in NIH3T3 cells. CADM1 significantly promoted YAP1 phosphorylation on Ser 127 and down-regulated YAP1 target gene expression at confluency in lung adenocarcinoma cell lines...
May 8, 2019: Cancer Science
Xuan Yang, Bi-Si Miao, Chuan-Yuan Wei, Rui-Zhao Dong, Ping-Ting Gao, Xin-Yu Zhang, Jia-Cheng Lu, Chao Gao, Xiao-Ying Wang, Hui-Chuan Sun, Jian Zhou, Jia Fan, Ai-Wu Ke, Guo-Ming Shi, Jia-Bin Cai
LSH (lymphoid-specific helicase) is overexpressed in tumor tissues and its overexpression was associated with poor prognosis in several cancers. However, its role and molecular mechanism of LSH in hepatocellular carcinoma (HCC) remains largely unknown. Here, we report that LSH was overexpressed in tumor tissues of HCC, and overexpression of LSH was associated with poor prognosis from public HCC database, and validated by clinical samples from our department. Ectopic LSH expression promoted the growth of HCC cells in vivo and in vitro...
May 7, 2019: Cancer Science
Takuya Tsujino, Nobuhiko Sugito, Kohei Taniguchi, Ryo Honda, Kazumasa Komura, Yuki Yoshikawa, Tomoaki Takai, Koichiro Minami, Yuki Kuranaga, Haruka Shinohara, Yoshihisa Tokumaru, Kazuki Heishima, Teruo Inamoto, Haruhito Azuma, Yukihiro Akao
It has been well established that microRNA (miR) - 143 is down-regulated in human bladder cancer. Recent precision medicine demonstrated that mutations in BC are frequently observed in FGFR3, RAS and PIK3CA genes, all of which are correlate with RAS signaling networks. We have previously demonstrated that miR-143 suppresses cell growth by inhibiting RAS signaling networks, in several cancers including BC. In the present study, we demonstrated that the synthetic miR-143 negatively regulated the RNA-binding protein Musashi-2 (MSI2) in BC cell lines...
May 7, 2019: Cancer Science
Yajing Chu, Yangpeng Chen, Mengke Li, Deyang Shi, Bichen Wang, Yu Lian, Xuelian Cheng, Xiaomin Wang, Mingjiang Xu, Tao Cheng, Jun Shi, Weiping Yuan
Molecular genetic changes of acute myeloid leukemia (AML) plays crucial roles in leukemogenesis, including recurrent chromosome translocations, epigenetic/spliceosome mutations, and transcription factor aberrations. Six1, a transcription factor of the Sine oculis homeobox (Six) family, has been shown to transform normal hematopoietic progenitors into leukemia in cooperation with Eya. However, the specific role and the underlying mechanism of Six1 in leukemia maintenance remain unexplored. Here, we showed increased expression of SIX1 in AML patients and murine leukemia stem cells (c-Kit+ cells, LSCs)...
May 3, 2019: Cancer Science
Chun-Mei Fan, Jin-Peng Wang, Yan-Yan Tang, Jin Zhao, Shu-Yi He, Fang Xiong, Can Guo, Bo Xiang, Ming Zhou, Xiao-Ling Li, Yong Li, Gui-Yuan Li, Wei Xiong, Zhao-Yang Zeng
Novel diagnostic and prognostic biomarkers of cancers are needed to improve precision medicine. Circular RNAs act as important regulators in cancers at the transcriptional and post-transcriptional levels. The circular RNA circMAN1A2 is highly expressed in nasopharyngeal carcinoma according to our previous RNA-seq data; however, the expression and functions of circMAN1A2 in cancers are still obscure. Therefore, in this study, we evaluated the expression of circMAN1A2 in the sera of patients with nasopharyngeal carcinoma and other malignant tumors and analyzed its correlations with clinical features and diagnostic values...
May 2, 2019: Cancer Science
Wenhua Liang, Minzhang Guo, Zhenkui Pan, Xiuyu Cai, Caichen Li, Yi Zhao, Hengrui Liang, Haiying Yang, Zhen Wang, Wenting Chen, Chuhong Xu, Xinyun Yang, Jianyu Sun, Ping He, Xia Gu, Weiqiang Yin, Jianxing He
This study aimed to analyze the association between driver mutations and predictive markers for some anti-tumor agents in non-small cell lung cancer (NSCLC). A cohort of 785 Chinese patients with NSCLC who underwent resection from March 2016 to November 2017 in the First Affiliated Hospital of Guangzhou Medical University was investigated. The specimens were subjected to hybridization capture and sequence of 8 important NSCLC-related driver genes. In addition, the slides were tested for PD-L1, excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1), thymidylate synthase (TS) and β-tubulin III by immunohistochemical staining...
April 29, 2019: Cancer Science
Bing-Dong Zhang, Yue-Rui Li, Li-Dan Ding, Yin-Yin Wang, Hong-Yi Liu, Bao-Qing Jia
Colorectal cancer (CRC) is one of the most common types of malignant tumor. Although many environmental and genetic factors have been proved to show high association with the occurrence and development of CRC, many mutations are detected in CRC. PTPN4/PTP-MEG1 is a widely expressed non-receptor protein tyrosine phosphatase. PTPN4 has been well studied to participate in many biological processes in the past three decades. In this study, we identified a nonsense mutation of PTPN4 with a mutation ratio of 90.90% from one case of rectal cancer, leading to loss-of-function in PTPN4 gene...
April 26, 2019: Cancer Science
Shr-Jeng Jim Leu, Tzong-Yi Lee, Shu-Wei Cheng, Meng-Ying Tsai, Yu-Shan Lin, Tzeon-Jye Chiou, Kai-Yao Huang, An-Na Chiang
We previously found that circulating β2 -glycoprotein I inhibits human endothelial cell migration, proliferation, and angiogenesis via diverse mechanisms. In the present study, we investigated the antitumor activities of β2 -glycoprotein I using structure-function analysis and mapped the critical region within the β2 -glycoprotein I peptide sequence that mediates anticancer effects. We constructed recombinant cDNA and purified different β2 -glycoprotein I polypeptide domains using a baculovirus expression system...
April 23, 2019: Cancer Science
Yuexia Peng, Xiyan Wang, Yunquan Guo, Fuhua Peng, Ningze Zheng, Bo He, Hui Ge, Liang Tao, Qin Wang
microRNA is expected to be a novel therapeutic tool for tumors. Gap junctions facilitate the transfer of microRNA, which exerts biological effects on tumor cells. However, the length of microRNA that can pass through certain gap junctions that are composed of specific connexin remains unknown. To address this question, the present study investigated the permeability of gap junctions composed of various connexin, including connexin 43, connexin 32 or connexin 37, to microRNAs consisting of 18 to 27 nucleotides in glioma cells and cervical cancer cells...
April 23, 2019: Cancer Science
Yuki Kiyozumi, Yoshifumi Baba, Kazuo Okadome, Taisuke Yagi, Yoko Ogata, Kojiro Eto, Yukiharu Hiyoshi, Takatsugu Ishimoto, Masaaki Iwatsuki, Shiro Iwagami, Yuji Miyamoto, Naoya Yoshida, Masayuki Watanabe, Hideo Baba
Indoleamine 2, 3-dioxygenase 1 (IDO1) is a primary enzyme that generates immunosuppressive metabolites. IDO1 plays a major role in tumor immunology and is a potential immune-based therapeutic target. We have reported that IDO1 protein expression was associated with an unfavorable clinical outcome in esophageal cancer. Recently, it has been reported that IDO1 expression is regulated by methylation of the IDO1 promoter. Thus, the aim of this study was to examine the relationship between IDO1 expression, IDO1 promoter methylation, and clinicopathological features in esophageal cancer...
April 23, 2019: Cancer Science
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