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Cancer Science

Yasuo Takashima, Kenichi Horisawa, Miyako Udono, Yasuyuki Ohkawa, Atsushi Suzuki
Hepatocellular carcinoma (HCC) accounts for a large proportion of liver cancer cases and has an extremely poor prognosis. Therefore, novel innovative therapies for HCC are strongly desired. As gene therapy tools for HCC, two hepatic transcription factors (TFs), HNF4A and HNF1A, have been employed to suppress proliferation and extinguish cancer-specific characteristics of target cells. However, our present data demonstrated that single transduction of HNF4A or HNF1A had only a limited effect on suppression of HCC cell proliferation...
September 16, 2018: Cancer Science
Yuta Takahashi, Kazuhiko Shien, Shuta Tomida, Shinsuke Oda, Takehiro Matsubara, Hiroki Sato, Ken Suzawa, Eisuke Kurihara, Yusuke Ogoshi, Kei Namba, Takahiro Yoshioka, Hidejiro Torigoe, Hiromasa Yamamoto, Junichi Soh, Shinichi Toyooka
In patients presenting with synchronous or metachronous multiple lung cancer (MLC), it is important, to distinguish between multiple primary lung cancer (MP) and intrapulmonary metastasis (IM). This study was aimed at investigating the mutational profiles of synchronous/metachronous MLC, and to compare the classification of paired tumors by multiplex gene mutation analysis with the histopathological evaluation. We performed targeted sequencing of 20 lung cancer-related oncogenes using the next generation sequencing (NGS) in 82 tumors from 37 MLC patients who underwent surgical resection at our department...
September 14, 2018: Cancer Science
Yu Chen, Masahiro Takikawa, Shuichi Tsutsumi, Yoko Yamaguchi, Atsushi Okabe, Mayuna Shimada, Tastuya Kawase, Akane Sada, Issei Ezawa, Yuhei Takano, Kisaburo Nagata, Yutaka Suzuki, Kentaro Semba, Hiroyuki Aburatani, Rieko Ohki
The PHLDA family (Pleckstrin Homology Like Domain Family) of genes consists of 3 members: PHLDA1, 2 and 3. PHLDA3 and PHLDA2 are phosphatidylinositol (PIP) binding proteins and function as repressors of Akt. Both have tumor suppressive functions, mainly through Akt inhibition. Several reports suggest that PHLDA1 also has a tumor suppressive function, however the precise molecular functions of PHLDA1 remain to be elucidated. Through a comprehensive screen for p53 target genes, we identified PHLDA1 as a novel p53 target, and we show that PHLDA1 has the ability to repress Akt in a manner similar to that of PHLDA3 and PHLDA2...
September 11, 2018: Cancer Science
Tessa Ya Sung Le Large, Btissame El Hassouni, Geert Kazemier, Sander R Piersma, Hanneke W M van Laarhoven, Maarten F Bijlsma, Cornelia R Jimenez, Elisa Giovannetti
No abstract text is available yet for this article.
September 8, 2018: Cancer Science
Xiaoze Wang, Atsushi Enomoto, Liang Weng, Yasuyuki Mizutani, Shaniya Abudureyimu, Nobutoshi Esaki, Yuta Tsuyuki, Chen Chen, Shinji Mii, Naoya Asai, Hisashi Haga, Sumire Ishida, Kenji Yokota, Masashi Akiyama, Masahide Takahashi
Pathological observations show that cancer cells frequently invade the surrounding stroma in collective groups rather than through single cell migration. Here, we studied the role of the actin-binding protein Girdin, a specific regulator of collective migration of neuroblasts in the brain, in collective cancer cell migration. We found that Girdin was essential for the collective migration of the skin cancer cell line A431 on collagen gels as well as their fibroblast-led collective invasion in an organotypic culture model...
September 8, 2018: Cancer Science
Satomi Yogosawa, Kiyotsugu Yoshida
The tumor suppressor p53 plays an important role in cancer prevention. Under normal conditions, p53 is maintained at a low level. However, in response to various cellular stresses, p53 is stabilized and activated, which in turn initiates DNA repair, cell-cycle arrest, senescence and apoptosis. Post-translational modifications of p53 including phosphorylation, ubiquitination, and acetylation at multiple sites are important to regulate its activation and subsequent transcriptional gene expression. Particularly, phosphorylation of p53 plays a critical role for modulating its activation to induce apoptosis in cancer cells...
September 6, 2018: Cancer Science
In-Gyu Kim, Jei-Ha Lee, Seo-Yeon Kim, Hai-Min Hwang, Tae-Rim Kim, Eun-Wie Cho
Microenvironment, such as hypoxia common to cancer, plays a critical role in the epithelial-to-mesenchymal transition(EMT) program, which is a major route of cancer metastasis and confers γ-radiation resistance to cells. Here we showed that transgelin 2 (TAGLN2), an actin-binding protein, is significantly induced in hypoxic lung cancer cells and that Snail1 is increased simultaneously, which induces EMT by downregulating E-cadherin expression. Forced TAGLN2 expression induced severe cell death, however, a small population of cells surviving after forced TAGLN2 overexpression showed γ-radiation resistance, which might promote tumor relapse and recurrence...
September 6, 2018: Cancer Science
Xinran Liu, Yangkai Li, Xia Zhang, Xin-Yuan Liu, Anlin Peng, Yuchen Chen, Lijing Meng, Hong Chen, Yu Zhang, Xiaoping Miao, Ling Zheng, Kun Huang
Kinesin family member 20B (KIF20B, also known as MPHOSPH1) is a kinesin protein which plays a critical role in cytokinesis. Previously, we and others have demonstrated the oncogenic role of KIF20B in several cancers; however, the exact mechanisms underlying its tumorigenic effects remain unclear. Here we showed overexpression of KIF20B in human hepatocellular carcinoma (HCC), and reported a negative correlation between KIF20B level and prognosis of patients. Mechanistically, reducing KIF20B blockades mitotic exit of HCC cells at telophase in a spindle assembly checkpoint independent manner...
September 6, 2018: Cancer Science
Ming-Min Chang, Meng-Shao Lai, Siou-Ying Hong, Bo-Syong Pan, Hsin Huang, Shang-Hsun Yang, Chia-Ching Wu, H Sunny Sun, Jih-Ing Chuang, Chia-Yih Wang, Bu-Miin Huang
Fibroblast growth factor 9 (FGF9) promotes cancer progression, however, its role in cell proliferation related to tumorigenesis remains elusive. We investigated how FGF9 affected MA-10 mouse Leydig tumor cell proliferation and found that FGF9 significantly induced cell proliferation by activating ERK1/2 and Rb phosphorylations within 15 minutes. Subsequently, the expressions of E2F1 and the cell cycle factors, cyclin D1, cyclin E1 and CDK4 in G1 phase and cyclin A1, CDK2 and CDK1 in S-G2/M phases were increased at 12 hours after FGF9 treatment; and cyclin B1 in G2/M phases were induced at 24 hours after FGF9 stimulation, whereas the phosphorylations of p53, p21 and p27 weren't affected by FGF9...
September 6, 2018: Cancer Science
Li-Ling Lin, Chao-Cheng Huang, Min-Tsui Wu, Wen-Ming Hsu, Jiin-Haur Chuang
The innate immune receptors such as toll-like receptor 3 (TLR3), melanoma differentiation-associated 5 (MDA5), and retinoic acid-inducible gene I (RIG-I), have been shown to be differentially expressed in neuroblastoma (NB) and promote dsRNA poly(I:C)-induced NB suppression in vitro and in vivo. However, the role of another important innate immune cytosolic sensor - laboratory of genetics and physiology 2 (LGP2) in the cancer behavior of NB remains unclear. Here we demonstrated that the expression levels of LGP2 were either low or undetectable in all NB cell lines tested with or without MYCN amplification...
September 4, 2018: Cancer Science
Lu Liu, Yang Liu, Xiaojia Liu, Na Zhang, Genxiang Mao, Qingxuan Zeng, Mingxiao Yin, Danqing Song, Hongbin Deng
Resibufogenin (RB), one of the major active compounds of the traditional Chinese medicine Chansu, has received considerable attention for its potency in cancer therapy. However, the anticancer effects and the underlying mechanisms of RB on pancreatic cancer remain elusive. Here we found that RB inhibited the viability and induces caspase-dependent apoptosis in human pancreatic cancer cells Panc-1 and Aspc. RB-induced apoptosis was through inhibition of constitutive nuclear factor κB (NF-κB) activity and its target genes expression, which was caused by downregulation of TGF-β-activated kinase 1(TAK1) level and suppression of IKK activity in Panc-1 and Aspc cells...
August 31, 2018: Cancer Science
Chia-Lang Fang, Chih-Chan Lin, Han-Kun Chen, You-Cheng Hseu, Shih-Ting Hung, Ding-Ping Sun, Yih-Huei Uen, Kai-Yuan Lin
Although gastric cancer (GC) is one of the most common cancers, knowledge of its development and carcinogenesis is limited. To date, the expression of ubiquitin-specific protease 3 (USP3) in all types of cancer, including GC, is still unknown. The present study explored the involvement of USP3 in the carcinogenesis and prognosis of GC. We measured USP3 expression in normal and GC tissues and cell lines. The correlations between USP3 protein level and clinicopathologic parameters, as well as the significance of USP3 protein level for disease-free survival were assessed...
August 31, 2018: Cancer Science
Fei Chang, Yunpeng Zhang, Jun Mi, Qian Zhou, Fuxiang Bai, Xin Xu, David E Fisher, Qinfeng Sun, Xunwei Wu
Rho Kinase (ROCK) plays crucial roles in the proliferation and migration of different type cells. ROCK inhibitor Y-27632 was previously reported to inhibit melanoma cell growth, and ROCK signaling was suggested to be therapeutic target for treating melanoma. However, the negative effect of Y-27632 on melanoma cells was mainly seen from studies on murine B16 melanoma cells. Here we reported that ROCK inhibitor actually promoted human melanoma cell growth and migration in vitro. Y-27632 increased the growth and migration of BRAF mutated melanoma cells, but had negative effect on wildtype melanoma cells or primary melanocytes...
August 31, 2018: Cancer Science
Taku Sato, Tomoki Muramatsu, Minoru Tanabe, Johji Inazawa
Distant metastasis to liver, lung, brain, or bone occurs via circulating tumor cells (CTCs). We hypothesized that a subset of CTCs had more malignant features than tumor cells at the primary site. We established a highly malignant cell line, Panc-1-CTC, derived from the human pancreatic cancer cell line Panc-1 using an in vivo selection method. Panc-1-CTC cells exhibited more profound migratory and invasive abilities than its parent cell line in vitro. In addition, Panc-1-CTC cells had a higher tumor-forming ability than parent cells in vivo...
August 29, 2018: Cancer Science
Takashi Kanemura, Hiroshi Miyata, Tomoki Makino, Koji Tanaka, Keijiro Sugimura, Mika Hamada-Uematsu, Yu Mizote, Hiroaki Uchida, Yasuhiro Miyazaki, Tsuyoshi Takahashi, Yukinori Kurokawa, Makoto Yamasaki, Hisashi Wada, Kiyokazu Nakajima, Shuji Takiguchi, Masaki Mori, Yuichiro Doki, Hideaki Tahara
Milk fat globule- epidermal growth factor- factor 8 (MFG-E8) is secreted from macrophages and is known to induce immunological tolerance mediated by regulatory T-cells (Tregs). However, the roles of the MFG-E8 that is expressed by cancer cells have not yet been fully examined. MFG-E8 expression was examined using immunohistochemistry in surgical samples from 134 patients with esophageal squamous cell carcinoma. The relationships between MFG-E8 expression levels and clinicopathological factors, including tumor-infiltrating lymphocytes (TILs), were evaluated...
August 29, 2018: Cancer Science
Hiroaki Fujiwara, Keisuke Tateishi, Hiroyuki Kato, Takuma Nakatsuka, Keisuke Yamamoto, Yasuo Tanaka, Hideaki Ijichi, Naminatsu Takahara, Suguru Mizuno, Hirofumi Kogure, Saburo Matsubara, Yosuke Nakai, Kazuhiko Koike
Cholangiocarcinoma is a life-threatening disease of poor prognosis. Although genome analysis unraveled some genetic mutation profiles in cholangiocarcinoma, it remains unknown whether such genetic abnormalities relate to the effects of anti-cancer drugs. Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are exclusively found in almost 20% of intrahepatic cholangiocarcinoma (ICC). Recently, the anti-cancer effects of BET inhibitors including JQ1 have been demonstrated in various tumors. In this study, we report that the anti-growth effect of JQ1 differs among ICC cells and IDH1 mutation sensitizes ICC cells to JQ1...
August 28, 2018: Cancer Science
Shi Xu, Sze-Kwan Lam, Paul Ning-Man Cheng, James Chung-Man Ho
Small cell lung cancer (SCLC) accounts for about 13% of all lung cancer cases. SCLC is characterized by frequent relapse, and current treatments lack tumor specificity. Arginine is a nonessential amino acid for human normal cells but critical to some tumor cells that cannot synthesize arginine. Therefore, arginine deprivation has become a potential therapeutic option for selected tumors. BCT-100 is a pegylated arginase that has demonstrated anticancer activity in arginine auxotrophic tumors, such as melanoma, hepatocellular carcinoma and acute myeloid leukemia...
August 28, 2018: Cancer Science
Taisuke Akimoto, Masanari Umemura, Akane Nagasako, Makoto Ohtake, Takayuki Fujita, Utako Yokoyama, Haruki Eguchi, Tetsuya Yamamoto, Yoshihiro Ishikawa
We previously reported the efficacy of anti-cancer therapy with hyperthermia using an alternating magnetic field (AMF) and a magnetic compound. In the course of the study, unexpectedly, we found that an AMF enhances the cytotoxicity of Compound C, an activated protein kinase (AMPK) inhibitor, although this compound is not magnetic. We thus examined the cellular mechanism of AMF-induced cytotoxicity of Compound C in cultured human glioblastoma (GB) cells. An AMF (280 kHz, 250 Arms) for 30 minutes significantly enhanced the cytotoxicity of Compound C and promoted apoptosis towards several human GB cell lines in vitro...
August 28, 2018: Cancer Science
Hang Yin, Xiaoyuan Wang, Xue Zhang, Yan Wang, Yangyang Zeng, Yudi Xiong, Tianqi Li, Rongjie Lin, Qian Zhou, Huan Ling, Fuxiang Zhou, Yunfeng Zhou
Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant carcinomas and its molecular mechanisms remain unclear. Long noncoding RNAs (lncRNAs) could bind sites of miRNAs which affect the expression of mRNA according to the competing endogenous (ceRNA) theory. The aim of the present study was to construct a ceRNA network and identify key lncRNAs to predict survival prognosis. We identified differentially expressed mRNAs, lncRNAs and miRNAs between tumor tissues and normal tissues from The Cancer Genome Atlas database...
August 27, 2018: Cancer Science
Wenyue Liu, Jingwei Zhang, Xuequan Yao, Chao Jiang, Ping Ni, Lingge Cheng, Jiali Liu, Suiying Ni, Qianying Chen, Qingran Li, Kai Zhou, Guangji Wang, Fang Zhou
Bevacizumab (Bv) can be used synergistically with fluoropyrimidine-based chemotherapy to treat colorectal cancer. Whether and how it affects delivery of fluoropyrimidine drugs is unknown. The present study aimed to explore the effect of Bv on delivery of 5-FU to tumor and the underlying mechanism from metabolic perspective. Bv enhanced the anti-tumor effects of 5-FU in LoVo colon cancer xenograft mice and increased 5-FU concentration in tumors without affecting hepatic 5-FU metabolism. Interestingly, Bv remarkably up-regulated thymidine phosphorylase (TP) in tumor which mediated metabolic activation of 5-FU...
August 27, 2018: Cancer Science
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