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Cancer Science

XiaoGang Zhang, Li Jin, Zhen Tian, Jing Wang, Yuan Yang, JinFeng Liu, Yi Chen, ChunHua Hu, TianYan Chen, YingRen Zhao, YingLi He
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related mortality worldwide. The expression of nitric oxide synthase (NOS) and the inhibition of autophagy have been linked to cancer cell death. However, the involvement of serum nitric oxide (NO), the expression of NOS, and autophagy have not been investigated in HCC. In the present study, we first established that the NO level was significantly higher in HBV-related HCC than in the liver cirrhosis control (53.60±19.74 μmol/L vs 8...
January 18, 2019: Cancer Science
Katsuaki Ieguchi, Yoshiro Maru
The biological functions of the Eph/ephrin system have been intensively investigated and well documented so far since its discovery in 1987. Although the Eph/ephrin system has been implicated in pathological settings such as Alzheimer's disease and cancer, the molecular mechanism of the Eph/ephrin system in those diseases is not well understood. Especially in cancer, recent studies have demonstrated that most of Eph and ephrin are up- or down-regulated in various types of cancer, and have been implicated in tumor progression, tumor malignancy, and prognosis...
January 18, 2019: Cancer Science
Yoshio Sakai, Masaki Miyazawa, Takuya Komura, Takeshi Yamada, Alessandro Nasti, Keiko Yoshida, Hisashi Takabatake, Masatoshi Yamato, Taro Yamashita, Tatsuya Yamashita, Eishiro Mizukoshi, Mai Okuzono, Tuyen Thuy Bich Ho, Kazunori Kawaguchi, Takashi Wada, Masao Honda, Shuichi Kaneko
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy associated with an extremely poor prognosis. Chemotherapy, such as gemcitabine (GEM), is the only treatment for PDAC patients who are not suitable for radical surgical treatment; however, its anti-tumor efficacy is limited. In this study, we investigated the host immune system response in murine PDAC models undergoing GEM treatment. We found that PDAC tumor tissues were infiltrated with a substantial number of Gr-1+ myeloid cells and had relatively small numbers of CD4+ and CD8+ cells...
January 18, 2019: Cancer Science
Cheng Gu, Judong Luo, Xujing Lu, Yiting Tang, Yan Ma, Yifei Yun, Jianping Cao, Juhua Cao, Zeyu Huang, Xifa Zhou, Shuyu Zhang
Radiotherapy has been widely used for the clinical management of esophageal squamous cell carcinoma. However, radioresistance remains a serious concern that prevents the efficacy of ESCC radiotherapy. REV7, the structural subunit of eukaryotic DNA polymerase ζ, has multiple functions in bypassing DNA damage and modulating mitotic arrest in human cell lines. However, the expression and molecular function of REV7 in ESCC progression remains unclear. In this study, we first examined the expression of REV7 in clinical ESCC samples, and we found higher expression of REV7 in ESCC tissues compared to matched adjacent or normal tissues...
January 18, 2019: Cancer Science
Tadamichi Denda, Daisuke Sakai, Tetsuya Hamaguchi, Naotoshi Sugimoto, Takashi Ura, Kentaro Yamazaki, Hirofumi Fujii, Takeshi Kajiwara, Takako Eguchi Nakajima, Shin Takahashi, Satoshi Otsu, Yoshito Komatsu, Fumio Nagashima, Toshikazu Moriwaki, Taito Esaki, Takeo Sato, Michio Itabashi, Eiji Oki, Toru Sasaki, Yoshinori Sunaga, Samira Ziti-Ljajic, Claire Brillac, Takayuki Yoshino
Aflibercept targets vascular endothelial growth factor. This study involved assessing the efficacy, safety, and pharmacokinetics of aflibercept plus 5-fluorouracil/levofolinate/irinotecan (FOLFIRI) as a second-line treatment for metastatic colorectal cancer (mCRC) in Japanese patients. Aflibercept (4 mg/kg) plus FOLFIRI was administered every 2 weeks in 62 patients with mCRC until disease progression, unacceptable toxicity, or patient withdrawal. Tumors were imaged every 6 weeks. The primary endpoint was objective response rate (ORR); secondary endpoints were progression-free survival, overall survival, safety, and pharmacokinetics of aflibercept, irinotecan, and 5-fluorouracil...
January 18, 2019: Cancer Science
Issay Morii, Yukiko Iwabuchi, Sumiko Mori, Masaki Suekuni, Toyoaki Natsume, Kazumasa Yoshida, Nozomi Sugimoto, Masato T Kanemaki, Masatoshi Fujita
MCM8 and MCM9 are paralogues of the MCM2-7 eukaryotic DNA replication helicase proteins and play a crucial role in a homologous recombination-mediated repair process to resolve replication stress by fork stalling. Thus, deficiency of MCM8-9 sensitizes cells to replication stress caused, for example, by platinum compounds that induce inter-strand crosslinks. It is suggested that cancer cells undergo more replication stress than normal cells due to hyper-stimulation of growth. Therefore, it is possible that inhibiting MCM8-9 selectively hypersensitizes cancer cells to platinum compounds and poly(ADP-ribose) polymerase inhibitors, both of which hamper replication fork progression...
January 16, 2019: Cancer Science
Haiyan Ma, Dan Yan, Yina Wang, Wei Shi, Tianshu Liu, Chongqiang Zhao, Shengqi Huo, Jialin Duan, Jingwen Tao, Maocai Zhai, Pengcheng Luo, Junyi Guo, Lei Tian, Lulu Mageta, David Jou, Cuntai Zhang, Chenglong Li, Jiayuh Lin, Jiagao Lv, Sheng Li, Li Lin
The IL-6/GP130/STAT3 pathway is emerging as a target for the treatment of hepatocellular carcinoma. IL-6 binds to IL-6R, forming a binary complex, which further combines with glycoprotein GP130 to transduce extracellular signaling by activating STAT3. Therefore, blocking the interaction between IL-6 and GP130 might inhibit the IL-6/GP130/STAT3 signaling pathway and its biological effects. It has been reported that Bazedoxifene acetate (BAZ), a selective estrogen receptor modulator (SERM) approved by Food and Drug Administration (FDA), could inhibit IL-6/GP130 protein-protein interactions (PPI)...
January 16, 2019: Cancer Science
Yoshiaki Maru, Kunishige Onuma, Masako Ochiai, Toshio Imai, Yoshitaka Hippo
Inactivation of the Adenomatous Polyposis Coli (APC) gene is an initiating and the most relevant event in the majority of sporadic cases with colorectal cancer, providing a rationale for using Apc-mutant mice as the disease model. Whereas carcinogenesis has been observed only at the organism level, the recent development of organoid culture technique has enabled long-term propagation of intestinal stem cells in a physiological setting, raising the possibility that organoids could serve as an alternative platform for modeling colon carcinogenesis...
January 13, 2019: Cancer Science
Shinichi Namba, Kazuhito Sato, Shinya Kojima, Toshihide Ueno, Yoko Yamamoto, Yosuke Tanaka, Satoshi Inoue, Genta Nagae, Hisae Iinuma, Shoichi Hazama, Soichiro Ishihara, Hiroyuki Aburatani, Hiroyuki Mano, Masahito Kawazu
The silencing of tumor suppressor genes by promoter CpG island (CGI) methylation is an important cause of oncogenesis. Silencing of MLH1 and BRCA1, two examples of oncogenic events, results from promoter CGI methylation. Interestingly, both MLH1 and BRCA1 have a divergent promoter, from which another gene on the opposite strand is also transcribed. Although studies have shown that divergent transcription is an important factor in transcriptional regulation, little is known about its implication in aberrant promoter methylation in cancer...
January 13, 2019: Cancer Science
Shoko Mase, Keiko Shinjo, Haruhito Totani, Keisuke Katsushima, Atsushi Arakawa, Satoru Takahashi, Hung-Cheng Lai, Ru-Inn Lin, Michael W Y Chan, Mayumi Sugiura-Ogasawara, Yutaka Kondo
Serous ovarian cancer is the most frequent type of epithelial ovarian cancer. Despite the use of surgery and platinum-based chemotherapy, many patients suffer from recurrence within 6 months, termed platinum-resistance. Currently, the lack of relevant molecular biomarkers for the prediction of the early recurrence of serous ovarian cancers is linked to the poor prognosis. To identify an effective biomarker for early recurrence, we analyzed the genome-wide DNA methylation status characteristic of early recurrence after treatment...
January 11, 2019: Cancer Science
Dong Dong, Lufang Zhang, Changsen Bai, Na Ma, Wei Ji, Li Jia, Aimin Zhang, Pengyu Zhang, Li Ren, Yunli Zhou
Prostate cancer (PCa) death primarily occurs due to metastasis of the cells, but little is known about the underlying molecular mechanisms. This study aimed to evaluate the expression of UNC5D, a newly identified tumor suppressor gene, analyze its epigenetic alterations, and elucidate its functional relevance to PCa metastasis. Meta-analysis of publicly available microarray datasets revealed that UNC5D expression was frequently down-regulated in PCa tissues and inversely associated with the PCa metastasis. These results were verified in clinical specimens by real-time PCR and immunohistochemistry assays...
January 11, 2019: Cancer Science
Tomonori Iyoda, Satoru Yamasaki, Masami Kawamura, Motoki Ueda, Kon Son, Yoshihiro Ito, Kanako Shimizu, Shin-Ichiro Fujii
Recent immunotherapies have demonstrated clinical success. In particular, vaccines based on particulate antigen (Ag) are expected to be implemented based on their efficacy. In the current study, we describe a strategy entailing Ag-encapsulating poly(ethylene glycol)-modified liposomes (PGL-Ag) as antigen protein delivery devices and show that the success of the liposome depends on the antigen-presenting cell (APC) capacity; after administration of PGL-Ag, dendritic cells (DCs) in particular take up the Ag and subsequently prime T cells...
January 10, 2019: Cancer Science
Kazuaki Harada, Fumie Ihara, Mariko Takami, Toshiko Kamata, Naoko Mise, Hiroko Yoshizawa, Tomoro Hishiki, Takeshi Saito, Keita Terui, Mitsuyuki Nakata, Shugo Komatsu, Takayuki Ikeuchi, Toshinori Nakayama, Hideo Yoshida, Shinichiro Motohashi
Dendritic cells (DCs) play a key role in the initiation of both antitumor immunity and immunological tolerance. It has been demonstrated that exposure to soluble factors produced by tumor cells modulates DC functions and induces tolerogenic DC differentiation. In this study, we investigated the effects of neuroblastoma cell line-derived soluble factors on DC differentiation. Monocytes isolated from healthy volunteers were incubated with IL-4 and granulocyte-macrophage colony-stimulating factor in the presence of culture supernatants from neuroblastoma cell lines...
January 10, 2019: Cancer Science
Jing-Song Chen, Jiong-Qiang Huang, Bing Luo, Shi-Hao Dong, Rong-Chang Wang, Ze-Kun Jiang, Ying-Kang Xie, Wei Yi, Guang-Ming Wen, Jian-Feng Zhong
The catalytic subunit p110δ of phosphoinositide 3-kinase (PI3K) encoded by PIK3CD has been implicated in some human solid tumors. However, its roles in colorectal cancer (CRC) remain largely unknown. Here we found that PIK3CD was overexpressed in colon cancer tissues and CRC cell lines and was an independent predictor for overall survival (OS) of patients with colon cancer. The ectopic overexpression of PIK3CD significantly promoted CRC cell growth, migration and invasion in vitro and tumor growth in vivo...
January 8, 2019: Cancer Science
Makoto Nishio, Toshiaki Takahashi, Hiroshige Yoshioka, Kazuhiko Nakagawa, Tatsuro Fukuhara, Kazuhiko Yamada, Masao Ichiki, Hiroshi Tanaka, Takashi Seto, Hiroshi Sakai, Kazuo Kasahara, Miyako Satouchi, Shi Rong Han, Kazuo Noguchi, Takashi Shimamoto, Tetufumi Kato
Pembrolizumab, a humanized monocolonal antibody against programmed death 1 (PD-1), has been shown to improve overall survival (OS) in patients with previously treated advanced non-small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1%. We report safety and efficacy results from the phase 1b KEYNOTE-025 study, which evaluated pembrolizumab in Japanese patients with previously treated NSCLC. Eligible patients had histologically/cytologically confirmed advanced NSCLC with PD-L1 TPS ≥1%, and had received ≥1 platinum-doublet chemotherapy...
January 7, 2019: Cancer Science
Yao Zhou, Weihong Niu, Yanwei Luo, Hui Li, Yong Xie, Heran Wang, Yukun Liu, Songqing Fan, Zheng Li, Wei Xiong, Xiaoling Li, Caiping Ren, Ming Tan, Guiyuan Li, Ming Zhou
The tumor suppressor p53 is a master regulator of apoptosis and plays key roles in cell cycle checkpoints. p53 responds to metabolic changes and alters metabolism through several mechanisms in cancer. Lactate dehydrogenase A (LDHA), a key enzyme in glycolysis, is highly expressed in a variety of tumors and catalyzes pyruvate to lactate. In this study, we first analyzed the association and clinical significance of p53 and LDHA in breast cancer expressing wild-type p53 and found that LDHA mRNA levels are negatively correlated with wild-type p53 but not mutation p53 mRNA levels, and low p53 and high LDHA expression are significantly associated with poor overall survival rates...
January 7, 2019: Cancer Science
Wei Yang, Lingwei Meng, Kai Chen, Chenyu Tian, Bing Peng, Lei Zhong, Chunhui Zhang, Xin Yang, Jun Zou, Shengyong Yang, Linli Li
Despite tremendous efforts, the clinical prognosis of pancreatic ductal adenocarcinoma (PDAC) remains disappointing. There is an urgent need to develop more effective treatment strategies to improve the prognosis of patients with PDAC. In this study, we evaluate the anti-PDAC effects of LY-1816, which is a new multi-kinase inhibitor developed by us. In in vitro assays, LY-1816 showed significant inhibition effect on the proliferation, migration, and invasion of human PDAC cells, and induced PDAC cell apoptosis...
January 7, 2019: Cancer Science
Ling Zha, Yuri Kitamura, Tetsuhisa Kitamura, Rong Liu, Masayuki Shima, Norio Kurumatani, Tomoki Nakaya, Junko Goji, Tomotaka Sobue
Occupational asbestos exposure occurs in many workplaces and is a well-known cause of mesothelioma and lung cancer. However, the association between non-occupational asbestos exposure and those diseases is not clearly described. The aim of this study was to investigate cause-specific mortality among the residents of Amagasaki, a city in Japan with many asbestos factories, and evaluate the potential excess mortality due to established and suspected asbestos-related diseases. The study population consisted of 143,929 residents in Amagasaki City before 1975 until 2002, aged ≥40 years on January 1, 2002...
January 7, 2019: Cancer Science
Taishi Nakamura, Kohei Fukuoka, Yoshiko Nakano, Kai Yamasaki, Yuko Matsushita, Satoshi Yamashita, Junji Ikeda, Naoko Udaka, Reo Tanoshima, Norio Shiba, Kensuke Tateishi, Shoji Yamanaka, Tetsuya Yamamoto, Junko Hirato, Koichi Ichimura
In the revised World Health Organization classification 2016, anaplastic pleomorphic xanthoastrocytoma (PXA) has been newly defined as a variant of the PXA entity. Furthermore, some anaplastic PXA were reported to have extremely poor prognosis which showed a type of pediatric glioblastoma (GBM) molecular profile. Recent integrated molecular classification for primary central nervous system tumors proposed some differences between histological and molecular features. Herein, in a genome-wide molecular analysis, we show an extreme aggressive anaplastic PXA that resulted in a pediatric GBM molecular profile...
January 4, 2019: Cancer Science
Akira Ooshima, Jinah Park, Seong-Jin Kim
Smad3, a major transcription factor in transforming growth factor-β (TGF-β) signaling, plays critical roles in both tumor-suppressive and pro-oncogenic functions. Upon TGF-β stimulation, the linker region of Smad3 becomes phosphorylated concurrently with the C-terminal phosphorylation that is essential for the canonical TGF-β signaling. The Smad3 linker region contains serine/threonine phosphorylation sites and can be phosphorylated by intracellular kinases, such as the mitogen-activated protein kinase (MAPK) family, cyclin-dependent kinase (CDK) family and glycogen synthase kinase-3β (GSK-3β)...
December 27, 2018: Cancer Science
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