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Cancer Science

Jiao Liu, Yangguang Shao, Yuxin He, Ke Ning, Xi Cui, Furong Liu, Zhenning Wang, Feng Li
MORC2 (microrchidia family CW-type zinc finger 2) is a newly identified chromatin remodeling protein that functions in diverse biological processes including gene transcription. NDRG1 is a metastasis suppressor and a prognostic biomarker for colorectal cancer (CRC). However, the relationship between MORC2 and NDRG1 transcriptional regulation and the roles of MORC2 in CRC remain elusive. Here, we showed that MORC2 down-regulated NDRG1 mRNA, protein levels and promoter activity in CRC cells. We also found that MORC2 bound to the -446~-213bp region of the NDRG1 promoter...
November 8, 2018: Cancer Science
Limin Niu, Xingguo Song, Ning Wang, Linlin Xue, Xianrang Song, Li Xie
Accumulating evidence supports a role for exosomal protein in diagnosis. The purpose of this study was to identify the tumor-derived exosomal biomarkers in the serum that improve the diagnostic value in Chinese non-small cell lung cancer (NSCLC) patients. Serum exosomes were isolated from healthy donors (n=46) and NSCLC patients (n=125) by ultracentrifugation and were characterized using TEM, qNano and immunoblotting. Proteomic profiles (by mass spectrometry) revealed multiple differentially expressed proteins in the healthy and NSCLC groups...
November 8, 2018: Cancer Science
Qiaoming Zhi, Huo Chen, Fei Liu, Ye Han, Daiwei Wan, Zhihua Xu, Yuting Kuang, Jin Zhou
Podocalyxin-like protein (PODXL), a transmembrane glycoprotein with anti-adhesive properties, has been proved to associate with an aggressive tumor phenotype and poor prognosis of several cancers. To elucidate the biological significance of PODXL and its molecular mechanism in gastric cancer (GC), we investigated the expression of PODXL in GC samples, and assessed its effects on biological behaviors and the related signaling pathways in vitro and in vivo. Moreover, the possible and closely interacted partners of PODXL were identified...
November 8, 2018: Cancer Science
Da-Wei Tian, Zhou-Liang Wu, Li-Ming Jiang, Jie Gao, Chang-Li Wu, Hai-Long Hu
Neddylation has been researched in many different human carcinomas. However, the roles of neural precursor cell expressed, developmentally down-regulated 8 (NEDD8) in bladder cancer were still unknown. Our study was the first study which systematically investigated the possible functions of NEDD8 in bladder cancer (BC) progression. We performed immunohistochemistry to explore the associations between the expression of NEDD8 in tumor tissues and clinical outcomes of patients. RT-qPCR and western blot were used to detect the expressional levels of genes...
November 8, 2018: Cancer Science
Satomi Watanabe, Hidetoshi Hayashi, Koji Haratani, Shigeki Shimizu, Junko Tanizaki, Kazuko Sakai, Hisato Kawakami, Kimio Yonesaka, Junji Tsurutani, Yosuke Togashi, Kazuto Nishio, Akihiko Ito, Kazuhiko Nakagawa
The efficacy of programmed cell death-1 (PD-1) blockade in patients with non-small cell lung cancer (NSCLC) positive for epidermal growth factor receptor (EGFR) gene mutations has been found to be limited, but the underlying mechanisms for this poor response have remained obscure. Given that the recognition by T cells of tumor antigens presented by major histocompatibility complex class I (MHC-I) molecules is essential for an antitumor immune response, we examined the effects of EGFR tyrosine kinase inhibitors (TKIs) on MHC-I expression in NSCLC cell lines...
November 3, 2018: Cancer Science
Masaki Hara, Yuko Takeba, Taroh Iiri, Yuki Ohta, Masanori Ootaki, Minoru Watanabe, Daiki Watanabe, Satoshi Koizumi, Takehito Otsubo, Naoki Matsumoto
Vasoactive intestinal peptide (VIP) is a modulator of inflammatory responses. VIP receptors are expressed in several tumor types, such as colorectal carcinoma. The study described herein was conducted to confirm the presence of VIP and its receptors (VPAC1 and VPAC2) in surgically resected hepatocellular carcinoma (HCC) tissues and in HCC cell line Huh7. The mechanism responsible for apoptosis of HCC cells was then examined because VIP treatment (10-10 M) significantly suppressed proliferation of Huh7 cells...
November 3, 2018: Cancer Science
Rui Wang, Hong-Bo Bao, Wen-Zhong Du, Xiao-Feng Chen, Huai-Lei Liu, Da-Yong Han, Li-Gang Wang, Jia-Ning Wu, Chun-Lei Wang, Ming-Chun Yang, Zhan-Wen Liu, Na Zhang, Lei Teng
Gliomas are the most common central nervous system tumors. They exhibit malignant characteristics indicating rapid proliferation and a high invasive capacity and are associated with a poor prognosis. In our previous study, p68 was overexpressed in glioma cells and correlated with both the degree of glioma differentiation and poor overall survival. Downregulating p68 significantly suppressed proliferation in glioma cells. Moreover, we found that the p68 gene promoted glioma cell growth by activating the NF-κB signaling pathway via a downstream molecular mechanism that remains incompletely understood...
November 2, 2018: Cancer Science
Chen Yang, Siqi Wu, Xiaobo Wu, Xuejian Zhou, Shengming Jin, Haowen Jiang
Circular RNA UVRAG (circUVRAG), a kind of non-coding RNA, is derived and cyclized by part of the exon from the UVRAG gene. However, the role of circUVRAG in bladder cancer (BLCA) has not been reported. The purpose of this study was therefore to characterize the role of circUVRAG in BLCA. Bioinformatics analysis showed the interactive relationships among circUVRAG, miR-223, and fibroblast growth factor receptor2 (FGFR2). Quantitative real-time PCR was used to detect the expression of circUVRAG in BLCA cell lines...
November 2, 2018: Cancer Science
Shunsuke Kimura, Masafumi Seki, Kenichi Yoshida, Yuichi Shiraishi, Masaharu Akiyama, Katsuyoshi Koh, Toshihiko Imamura, Atsushi Manabe, Yasuhide Hayashi, Masao Kobayashi, Akira Oka, Satoru Miyano, Seishi Ogawa, Junko Takita
Molecular mechanisms involved in the relapse of T-cell acute lymphoblastic leukemia (T-ALL) are not fully understood, although activating NOTCH1 signaling due to NOTCH1/FBXW7 alterations is a major oncogenic driver. To unravel the relevance of NOTCH1/FBXW7 mutations associated with relapse, we performed whole exome sequencing in 30 pediatric T-ALL cases, of which 11 diagnosis-relapse paired cases were further investigated to track the clonal evolution of relapse using amplicon-based deep sequencing. NOTCH1/FBXW7 alterations were detected in 73...
November 2, 2018: Cancer Science
Wataru Usuba, Fumihiko Urabe, Yusuke Yamamoto, Juntaro Matsuzaki, Hideo Sasaki, Makiko Ichikawa, Satoko Takizawa, Yoshiaki Aoki, Shumpei Niida, Ken Kato, Shin Egawa, Tatsuya Chikaraishi, Hiroyuki Fujimoto, Takahiro Ochiya
Bladder cancer is the ninth leading cause of cancer death worldwide. The major problem in bladder cancer is primarily the high recurrence rate after drug treatment and resection. Although conventional screening methods, such as cystoscopy, urinary cytology and ultrasound sonography, have become widely used in a clinical setting, the diagnostic performance of these modalities is unsatisfactory due to low accuracy or high invasiveness. Since circulating miRNA profiles have recently been reported as an attractive tool for liquid biopsy in cancer screening, here, we performed global miRNA profiling of 392 serum samples of bladder cancer patient with 100 non-cancer samples and 480 samples of other types of cancer as controls...
November 1, 2018: Cancer Science
Akifumi Uchida, Naohiko Seki, Keiko Mizuno, Shunsuke Misono, Yasutaka Yamada, Naoko Kikkawa, Hiroki Sanada, Tomohiro Kumamoto, Takayuki Suetsugu, Hiromasa Inoue
The prognosis of patients with advanced-stage lung squamous cell carcinoma (LUSQ) is poor, and effective treatment protocols are limited. Our continuous analyses of antitumor microRNAs (miRNAs) and their oncogenic targets have revealed novel oncogenic pathways in LUSQ. Analyses of our original miRNA expression signatures demonstrated that both strands of miR-144 (miR-144-5p, the passenger strand; miR-144-3p, the guide strand) showed decreased expression in cancer tissues. Additionally, low expression of miR-144-5p significantly predicted a poor prognosis in patients with LUSQ by The Cancer Genome Atlas database analyses (overall survival [OS]: p = 0...
October 30, 2018: Cancer Science
Yae Jin Yoon, Young-Hwan Kim, Yu-Jin Lee, Jiyeon Choi, Cheol-Hee Kim, Dong Cho Han, Byoung-Mog Kwon
Inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling pathway has been considered to be a novel therapeutic strategy to treat human cancers with constitutively active STAT3. During the screening of natural products to find STAT3 inhibitors, we identified 2'-hydroxycinnamaldehyde (HCA) as a STAT3 inhibitor, which was isolated from the stem bark of Cinnamomum cassia. In this study, we found that HCA inhibited constitutive and inducible STAT3 activation in STAT3-activated DU145 prostate cancer cells...
October 30, 2018: Cancer Science
Kazue Watanabe, Tomohide Tsukahara, Shingo Toji, Shogo Saitoh, Yoshihiko Hirohashi, Munehide Nakatsugawa, Terufumi Kubo, Takayuki Kanaseki, Hidekazu Kameshima, Takeshi Terui, Noriyuki Sato, Toshihiko Torigoe
For the efficacy of peptide vaccination immunotherapy for patients with cancer, endogenous expression of the target peptide/HLA on cancer cells is required. However, it is difficult to evaluate the expression status of a peptide/HLA complex because of the lack of a soluble T cell receptor (TCR) that reacts with TAA with high avidity. In this study, we developed two soluble TCR-multimers that were each directed to tumor-associated antigens (TAAs), survivin2B and PBF in the context of HLA-A24 (SVN-2B TCR-multimer and PBF TCR-multimer, respectively), from CTL clones that were established from peptide-vaccinated patients...
October 30, 2018: Cancer Science
Guiling Shi, Xiaoli Zheng, Xiaojing Wu, Siqi Wang, Yijia Wang, Fei Xing
Paclitaxel is widely used chemotherapy drug, but development of resistance leads to treatment failure. Tumor cells that are treated with a sublethal dose of paclitaxel for a long period of time exhibit the epithelial-mesenchymal transition (EMT) phenotype, which leads to metastasis and resistance. All-trans retinoic acid (ATRA) is always used in combination with paclitaxel and can reverse the EMT in many types of cancer cells. The ability of ATRA to reverse the EMT in chemoresistant cells is still unknown. In this study, the ability of ATRA to reverse EMT in paclitaxel-resistant cells was investigated...
October 30, 2018: Cancer Science
Masanari Umemura, Md Rafikul Islam, Hidenobu Fukumura, Itaru Sato, Yusuke Kawabata, Kousuke Matsuo, Rina Nakakaji, Akane Nagasako, Makoto Ohtake, Takayuki Fujita, Utako Yokoyama, Tomohiro Nakayama, Haruki Eguchi, Yoshihiro Ishikawa
We previously identified a novel nanomagnetic particle, N,N'-bis(salicylidene)ethylenediamineiron [Fe(Salen)]. Fe(Salen) exhibits not only anti-tumor effects but also magnetic properties. We found that Fe(Salen) can be used for magnet-guided drug delivery and visualization of accumulated drug by magnetic resonance imaging (MRI) because of its magnetism. In addition, Fe(Salen) can generate heat by itself when exposed to an alternating current magnetic field (AMF), resulting in a hyperthermia effect. Here, we partly elucidated the anti-tumor mechanism of Fe(Salen) and performed an intravenous repeated dose toxicity study to decide the therapeutic amount...
October 29, 2018: Cancer Science
Jun Deng, Mei Peng, Zhiren Wang, Sichun Zhou, Di Xiao, Jiating Deng, Xue Yang, Jingyuan Peng, Xiaoping Yang
The success of targeted drug therapies for treating cancer patients has been largely attracted broad attention both in academic community and social society. However, rapidly developed acquired resistance is becoming a newly recognized major challenge to make these therapies continuously efficiency. Metformin is one of well-known natural compounds derived from French plant lilac with low toxicity. Our previous work has highlighted research progress of combination of clinically applied chemotherapies and metformin via different mechanisms...
October 25, 2018: Cancer Science
Norihiro Ishii, Kenichiro Araki, Takehiko Yokobori, Kei Hagiwara, Gantumur Dorgormaa, Takahiro Yamanaka, Tadashi Handa, Mariko Tsukagoshi, Takamichi Igarashi, Akira Watanabe, Norio Kubo, Norifumi Harimoto, Atsushi Masamune, Kazuo Umezawa, Hiroyuki Kuwano, Ken Shirabe
Despite the recent advances in cancer treatment, pancreatic cancer is a highly malignant tumor type with a dismal prognosis and it is characterized by dense desmoplasia in the cancer tissue. Cancer associated fibroblasts (CAFs) are responsible for this fibrotic stroma and promote cancer progression. We previously reported that novel natural compound conophylline (CnP) extracted from the leaves of the tropical plant reduced liver and pancreatic fibrosis via suppression of stellate cells. However, there have been no studies to investigate the effects of CnP on CAFs, which is the aim of this work...
October 24, 2018: Cancer Science
Keiichiro Hattori, Mamiko Sakata-Yanagimoto, Manabu Kusakabe, Tohru Nanmoku, Yasuhito Suehara, Ryota Matsuoka, Masayuki Noguchi, Yasuhisa Yokoyama, Takayasu Kato, Naoki Kurita, Hidekazu Nishikii, Naoshi Obara, Shingo Takano, Eiichi Ishikawa, Akira Matsumura, Masafumi Muratani, Yuichi Hasegawa, Shigeru Chiba
Primary central nervous system lymphoma (PCNSL) is a rare subtype of lymphoma that arises within the brain or the eyes. PCNSL recurs within the CNS in most of relapsed cases, while extra-CNS relapse is experienced in rare cases. The present study aimed at identifying the presence of common precursor cells (CPC) for primary intra- and relapsed extra-CNS tumors, and further assessing the initiating events in the bone marrow (BM). Targeted deep sequencing was performed for 5 paired primary intra- and relapsed extra-CNS tumors of PCNSL...
October 24, 2018: Cancer Science
Kan Yonemori, Makoto Kodaira, Taroh Satoh, Toshihiro Kudo, Shunji Takahashi, Kenji Nakano, Yuichi Ando, Tomoya Shimokata, Joji Mori, Koichi Inoue, Gerard Joseph Oakley, Sachi Sakaguchi, Kenji Tamura
Olaratumab, a monoclonal antibody targeting human platelet-derived growth factor receptor α, plus doxorubicin significantly improved overall survival in patients with advanced soft-tissue sarcoma (STS) in a prior phase 1b/2 randomised trial. Subsequent exposure-response analysis suggested higher olaratumab exposures earlier might improve outcomes in patients at risk of early disease progression. This phase 1 study (3 treatment cohorts; minimum 6 patients each) investigated the safety, pharmacokinetics, and antitumor activity of olaratumab plus doxorubicin in Japanese patients with STS...
October 24, 2018: Cancer Science
Dan Li, En Wen, Yingjie Zhang, Zhouxue Wu, Haowen Pang, Peirong Ren, Changling Shang, Lijia He, Jianwen Zhang, Li Xiang, Hongru Yang, Qiaoli Liu, Qinglian Wen, Juan Fan, Sheng Lin, Jingbo Wu
To evaluate whether the patent single-channel applicator, which was modified from the traditional tandem applicator and wrapped with a oval-shield alloy around the source channel, has the same clinical efficacy and safety as the standard Fletcher-type applicator in the high-dose-rate brachytherapy for carcinoma of the cervix. Between December 2011 and February 2017, 299 patients with pathologically confirmed International Federation of Gynecology and Obstetrics (FIGO 2009) stage Ib2-IVa cervical cancer were received and finished the allocated intervention, with the first 151 patients, 71 in the Fletcher group and 80 in the patent single-channel group, satisfying the criteria for a preliminary analysis...
October 23, 2018: Cancer Science
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