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Cancer Science

Katsutoshi Sato, Rikako Azuma, Takashi Imai, Takashi Shimokawa
Our aim was to evaluate whether repetition of C-ion (carbon ion beam) irradiation induces radioresistance as well as repeated X-ray irradiation in cancer cell lines, and to find the key molecular pathway for radioresistance by comparing radioresistant cancer cells with their parental cells. A mouse squamous cell carcinoma cell line, NR-S1, and radioresistant cancer cells, NR-S1-C30 (C30) and NR-S1-X60 (X60) established by repetition of C-ion and X-ray irradiation respectively, were used. X-ray and C-ion sensitivity, changes in lysosome, mitochondria, intracellular ATP and ROS (reactive oxygen species) level, and mTOR (mechanistic target of rapamycin) signaling were evaluated...
July 18, 2017: Cancer Science
Ryuichi Mizuno, Go Kimura, Satoshi Fukasawa, Takeshi Ueda, Tsunenori Kondo, Hidehiko Hara, Sunao Shoji, Kent Kanao, Hayakazu Nakazawa, Kazunari Tanabe, Shigeo Horie, Mototsugu Oya
The objective of this prospective study was to identify baseline angiogenic and inflammatory markers in serum as well as the baseline levels of immune cells in whole blood to predict progression free survival in patients with metastatic renal cell carcinoma treated with sunitinib. Blood samples were collected at baseline in all 90 patients to analyse serum angiogenic and inflammatory marker together with peripheral blood immunological marker. The association between each marker and sunitinib efficacy was analyzed...
July 12, 2017: Cancer Science
Song Yi Park, Jee-Hye Shin, Sun-Ho Kee
β-catenin is a central player in Wnt signaling, and activation of Wnt signaling is associated with cancer development. E-cadherin in complex with β-catenin mediates cell-cell adhesion, which suppresses β-catenin-dependent Wnt signaling. Recently, a tumor-suppressive role for E-cadherin has been reconsidered, as re-expression of E-cadherin was reported to enhance the metastatic potential of malignant tumors. To explore the role of E-cadherin, we established an E-cadherin-expressing cell line, EC96 cells, from AGS cells that featured undetectable E-cadherin expression and a high level of Wnt signaling...
July 12, 2017: Cancer Science
Rui Zhang, Min Ma, Gang Dong, Rong-Rong Yao, Jing-Huan Li, Qiong-Dan Zheng, Yin-Ying Dong, Hui Ma, Dong-Mei Gao, Jie-Feng Cui, Zheng-Gang Ren, Rong-Xin Chen
The aggravated behaviors of hepatocellular carcinoma (HCC) will occur after inadequate thermal ablation. However, its underlying mechanisms are not fully understood. Here, we assessed whether the increased matrix stiffness after thermal ablation could promote the progression of residual HCC. Heat-treated residual HCC cells were cultured on the tailorable 3D gel with different matrix stiffness simulating the changed physical environment after thermal ablation and then were explored the mechanical alterations of matrix stiffness on cell phenotypes...
July 12, 2017: Cancer Science
Yuji Shibayama, Tomohide Tsukahara, Makoto Emori, Kenji Murata, Emi Mizushima, Yoshihiko Hirohashi, Takayuki Kanaseki, Munehide Nakatsugawa, Terufumi Kubo, Toshihiko Yamashita, Noriyuki Sato, Toshihiko Torigoe
Chemotherapy has improved the prognosis of patients with sarcomas. However, it may suppress anti-tumor immunity. Recently, we reported a novel CD8(+) memory T cell population with a chemo-resistance property, "young memory" T (TYM ) cells. In this study, we investigated the proportion and function of TYM cells in peripheral blood of healthy donors and sarcoma patients who received chemotherapy and those who did not. The proportion of TYM cells was significantly decreased in patients compared with that in healthy donors...
July 12, 2017: Cancer Science
Kazuaki Kita, Masayuki Shiota, Masako Tanaka, Asuka Otsuka, Masaki Matsumoto, Minoru Kato, Satoshi Tamada, Hiroshi Iwao, Katsuyuki Miura, Tatsuya Nakatani, Shuhei Tomita
Androgen deprivation therapy (ADT) is initially effective for treating patients with advanced prostate cancer; however, the prostate cancer gradually becomes resistant to ADT, which is termed castration-resistant prostate cancer (CRPC). Androgen receptor splice variant 7 (AR-V7), one of the causes of CRPC, is correlated with the resistance to a new-generation AR antagonist (enzalutamide) and poor prognosis. Heat shock protein 70 (Hsp70) inhibitor is known to decrease the levels of full-length AR (AR-FL), but little is known about its effects against CRPC cells expressing AR-V7...
July 10, 2017: Cancer Science
Yasuaki Yamakawa, Hiroshi Tazawa, Joe Hasei, Shuhei Osaki, Toshinori Omori, Kazuhisa Sugiu, Tadashi Komatsubara, Kouji Uotani, Tomohiro Fujiwara, Aki Yoshida, Toshiyuki Kunisada, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara
Osteosarcoma is an aggressive malignant bone tumor that causes bone destruction. Although tumor-specific replicating oncolytic adenovirus OBP-301 induces an antitumor effect in an osteosarcoma tumor, it cannot prevent bone destruction. Zoledronic acid (ZOL) is a clinically available agent that inhibits bone destruction. In this study, we investigated the potential of combination therapy with OBP-301 and ZOL against osteosarcomas with bone destruction. The antitumor activity of OBP-301 and ZOL in monotherapy or combination therapy was assessed using 3 human osteosarcoma cell lines (143B, MNNG/HOS, SaOS-2)...
July 7, 2017: Cancer Science
Ayumi Ohya, Kazuhiro Yamanoi, Hisashi Shimojo, Chifumi Fujii, Jun Nakayama
Pancreatic cancer is lethal, as it is often detected late. Thus novel biomarkers of precursor lesions are needed to devise timely therapies. Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) are major precursors of pancreatic cancer. In normal gastric mucosa, gastric gland mucin-specific O-glycans are unique in having α1,4-linked N-acetylglucosamine (αGlcNAc) residues attached to MUC6. Recently we reported that αGlcNAc functions as a tumor suppressor for differentiated-type gastric adenocarcinoma (Karasawa et al...
July 7, 2017: Cancer Science
Shunsuke Kitajima, Chiaki Takahashi
The RB tumor suppressor regulates the G1/S transition during cell cycle progression by modulating the activity of E2F transcription factors. The RB pathway plays a central role in the suppression of most of cancers, and RB mutation was initially discovered by virtue of its role in tumor initiation. However, as cancer genome sequencing has evolved to profile more advanced and treatment resistant cancers, it has become increasingly clear that in the majority of cancers somatic RB inactivation occurs during tumor progression...
July 5, 2017: Cancer Science
Hongxi Chen, Zhipeng Zhang, Yebin Lu, Kun Song, Xiwu Liu, Fada Xia, Weijia Sun
Dysregulation of microRNA (miRNA) expression in various cancers and their role in cancer progression is well documented. The purpose of this study was to investigate the biological role of miR-372 in human pancreatic adenocarcinoma (HPAC). We collected 20 pairs of HPAC tissues and adjacent non-cancerous tissues to detect miR-372 expression levels. We transfected BXPC-3 and PANC-1 cells with miR-372 inhibitor/ mimics to study their effect on cell proliferation, apoptosis, invasion, migration and autophagy. In addition, miR-372 mimics and a tumor protein UNC51-like kinase 1 (ULK1) siRNA were co-transfected into BXPC-3 and PANC-1 cells to explore the mechanism of miR-372 and ULK1 on HPAC tumorigenesis...
July 5, 2017: Cancer Science
Daisuke Matsubara, Manabu Soda, Taichiro Yoshimoto, Yusuke Amano, Yuji Sakuma, Azusa Yamato, Toshihide Ueno, Shinya Kojima, Tomoki Shibano, Yasuyuki Hosono, Masahito Kawazu, Yoshihiro Yamashita, Shunsuke Endo, Koichi Hagiwara, Masashi Fukayama, Takashi Takahashi, Hiroyuki Mano, Toshiro Niki
The major driver mutations of lung cancer, the EGFR mutations and EML4-ALK fusion, are mainly detected in terminal respiratory unit (TRU)-type lung adenocarcinomas, which typically show lepidic and/or papillary patterns, but are rarely associated with a solid or invasive mucinous morphology. In order to elucidate the key genetic events in non-TRU-type lung cancer, we conducted whole-exome sequencing on 43 non-TRU-type lung adenocarcinomas based on morphology (17 acinar, 9 solid, 2 enteric adenocarcinomas, and 15 adenocarcinomas with a mucinous morphology)...
July 5, 2017: Cancer Science
Jing Gao, Haixing Wang, Wanchun Zang, Beifang Li, Guanhua Rao, Lei Li, Yang Yu, Zhongwu Li, Bin Dong, Zhihao Lu, Zhi Jiang, Lin Shen
Overcoming tumor heterogeneity is a major challenge for personalized treatment of gastric cancer, especially for human epidermal growth factor receptor-2 targeted therapy. Analysis of circulating tumor DNA allows a more comprehensive analysis of tumor heterogeneity than traditional biopsies in lung cancer and breast cancer, but little is known in gastric cancer. We assessed mutation profiles of ctDNA and primary tumors from 30 patients with advanced gastric cancer, then performed a comprehensive analysis of tumor mutations by multiple biopsies from 5 patients, and finally analyzed the concordance of HER2 amplification in ctDNA and paired tumor tissues in 70 patients...
July 5, 2017: Cancer Science
Lin Fu, Huaping Fu, Jianlin Qiao, Yifan Pang, Keman Xu, Lei Zhou, Qingyun Wu, Zhenyu Li, Xiaoyan Ke, Kailin Xu, Jinlong Shi
CPNE3, a member of a Ca(2+) -dependent phospholipid-binding protein family, was identified as a ligand of ERBB2 and has a more general role in carcinogenesis. Here, we identified the prognostic significance of CPNE3 expression in acute myeloid leukemia (AML) patients based on two datasets. In the first microarray datasets (n=272), high CPNE3 expression (CPNE3(high) ) was associated with adverse overall survival (OS, P < 0.001) and event-free survival (EFS, P < 0.001) comparing to low CPNE3 expression (CPNE3(low) )...
July 3, 2017: Cancer Science
Kohei Otsubo, Kaname Nosaki, Chiyo K Imamura, Hiroaki Ogata, Akitaka Fujita, Shinya Sakata, Fumihiko Hirai, Gouji Toyokawa, Eiji Iwama, Taishi Harada, Takashi Seto, Mitsuhiro Takenoyama, Takeshi Ozeki, Taisei Mushiroda, Mieko Inada, Junji Kishimoto, Kenji Tsuchihashi, Kentaro Suina, Osamu Nagano, Hideyuki Saya, Yoichi Nakanishi, Isamu Okamoto
Splice variant isoforms of CD44 (CD44v) are a marker of cancer stem cells (CSCs) in solid tumors. They stabilize the xCT subunit of the transporter system xc(-) and thereby promote synthesis of the antioxidant glutathione. Salazosulfapyridine (SASP) is an inhibitor of xCT and suppresses the proliferation of CD44v-positive cancer cells. Chemotherapy-naïve patients with advanced nonsquamous non-small cell lung cancer were enrolled in a dose-escalation study (standard 3 + 3 design) of SASP in combination with cisplatin and pemetrexed...
July 1, 2017: Cancer Science
Akihiro Matsumoto, Yuki Takahashi, Makiya Nishikawa, Kohei Sano, Masaki Morishita, Chonlada Charoenviriyakul, Hideo Saji, Yoshinobu Takakura
Exosomes are extracellular vesicles released by various cell types and play roles in cell-cell communication. Several studies indicate that cancer cell-derived exosomes play important pathophysiological roles in tumor progression. Biodistribution of cancer cell-derived exosomes in tumor tissue is an important factor for determining their role in tumor proliferation; however, limited studies have assessed the biodistribution of exosomes in tumor tissues. In the present study, we examined the effect of cancer-cell derived exosomes on tumor growth by analyzing their biodistribution...
July 1, 2017: Cancer Science
Tadaaki Nishikawa, Koji Matsumoto, Kenji Tamura, Hiroyuki Yoshida, Yuichi Imai, Aki Miyasaka, Takuma Onoe, Satoshi Yamaguchi, Chikako Shimizu, Kan Yonemori, Tatsunori Shimoi, Mayu Yunokawa, Hao Xiong, Silpa Nuthalapati, Hideyuki Hashiba, Tsukasa Kiriyama, Terri Leahy, Philip Komarnitsky, Keiichi Fujiwara
Veliparib (ABT-888) is a potent, orally bioavailable poly(ADP-ribose) polymerase-1 and -2 inhibitor. This phase 1 study evaluated the tolerability, pharmacokinetic profile, safety, and preliminary antitumor activity of single-agent veliparib in Japanese patients with advanced solid tumors. Eligible patients were assigned to treatment with veliparib at 200 mg or 400 mg dose; veliparib was self-administered orally twice daily on days 1-28 of 28-day cycles. Dose escalation, following a 3+3 design, defined dose-limiting toxicities, the maximum tolerated dose, and the recommended phase 2 dose...
June 30, 2017: Cancer Science
Zhao Jing, Tian Chen, Xuebang Zhang, Shixiu Wu
Elective nodal irradiation (ENI) might improve overall survival in patients with inoperable esophageal cancer. We conducted a retrospective analysis to assess the long-term survival and toxicity of esophageal cancer patients treated with ENI versus conventional-field irradiation (CFI). All data in the present study were based on our institutional experience from 2000 to 2005 of patients with inoperable esophageal cancer treated with ENI or CFI plus concurrent two cycles of paclitaxel/cisplatin. Based on the inclusion and exclusion criteria, 89 patients were included in the analysis...
June 30, 2017: Cancer Science
Yuki Shimizu, Hideki Amano, Yoshiya Ito, Tomohiro Betto, Sakiko Yamane, Tomoyoshi Inoue, Nobuyuki Nishizawa, Yoshio Matsui, Mariko Kamata, Masaki Nakamura, Hidero Kitasato, Wasaburo Koizumi, Masataka Majima
Liver metastases from colorectal cancer (CRC) are a clinically significant problem. The renin-angiotensin system (RAS) is involved in the tumor growth and metastases. This study was designed to evaluate the role of angiotensin II subtype receptor 1a (AT1a) in the formation of liver metastasis in CRC. A model of liver metastasis was made by intra-splenic injection of mouse colon cancer (CMT-93) into AT1a knockout mice (AT1aKO) and wild-type (C57BL/6) mice (WT). As compared with WT, the liver weight and liver metastatic rate were significantly lower in AT1aKO...
June 29, 2017: Cancer Science
Taro Shimizu, Amr S Abu Lila, Miho Nishio, Yusuke Doi, Hidenori Ando, Masami Ukawa, Yu Ishima, Tatsuhiro Ishida
Immune modulation of the tumor microenvironment has been reported to participate to the therapeutic efficacy of many chemotherapeutic agents. Recently, we reported that liposomal encapsulation of oxaliplatin (l-OHP) within PEGylated liposomes conferred a superior antitumor efficacy to free l-OHP in murine colorectal carcinoma-bearing mice via permitting preferential accumulation of the encapsulated drug within tumor tissue. However, the contribution of the immune-modulatory properties of liposomal l-OHP and/or free l-OHP to the overall antitumor efficacy was not elucidated...
June 23, 2017: Cancer Science
Takatsune Shimizu, Walied A Kamel, Sayaka Yamaguchi-Iwai, Yumi Fukuchi, Akihiro Muto, Hideyuki Saya
Osteosarcoma is the most common type of primary bone tumor, and novel therapeutic approaches for this disease are urgently required. To identify effective agents, we screened a panel of FDA-approved drugs in AXT cells, our newly established mouse osteosarcoma line, and identified calcitriol as a candidate compound with therapeutic efficacy for this disease. Calcitriol inhibited cell proliferation in AXT cells by blocking cell cycle progression. From a mechanistic standpoint, calcitriol induced endoplasmic reticulum (ER) stress, which was potentially responsible for downregulation of cyclin D1, activation of p38 MAPK, and intracellular production of reactive oxygen species (ROS)...
June 23, 2017: Cancer Science
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