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Cancer Science

Yongbing Chi, Qinqin Jin, Xinghui Liu, Limin Xu, Xiaoxue He, Yan Shen, Qiang Zhou, Jue Zhang, Mingming Jin
The involvement of the RGS17 oncogene in promotion of non-small cell lung cancer (NSCLC) has been reported, but the regulation mechanism in NSCLC remains unclear. MicroRNAs (miRNAs) negatively regulate gene expression, and their dysregulation has been implicated in tumorigenesis. To understand the role of microRNAs in RGS17-induced NSCLC, we showed that miR-203 was downregulated during tumorigenesis, and inhibited the proliferation and invasion of lung cancer cells. We then determined if miR-203 regulated NSCLC by targeting RGS17...
September 16, 2017: Cancer Science
Goro Kasuya, Hitoshi Ishikawa, Hiroshi Tsuji, Yasuo Haruyama, Gen Kobashi, Daniel K Ebner, Koichiro Akakura, Hiroyoshi Suzuki, Tomohiko Ichikawa, Jun Shimazaki, Hirokazu Makishima, Takuma Nomiya, Tadashi Kamada, Hirohiko Tsujii
The treatment outcomes of patients with high-risk localized prostate cancer (PC) after carbon-ion radiotherapy (CIRT) combined with long-term androgen deprivation therapy (LTADT) were analyzed, and compared with those of other treatment modalities, focusing on PC-specific mortality (PCSM). A total of 1247 patients were enrolled in three phase II clinical trials of fixed-dose CIRT between 2000 and 2013. Excluding patients with T4 disease, 608 patients with high- or very-high-risk PC, according to the National Comprehensive Cancer Network classification system, who received CIRT with LTADT were evaluated...
September 16, 2017: Cancer Science
Lan Huang, Jingyao Lian, Xinfeng Chen, Guohui Qin, Yujia Zheng, Yi Zhang
There is increasing evidence that cytoskeleton remodeling is involved in cancer progression. Wiskott-Aldrich syndrome Protein (WASP) family represents a key regulator of actin cytoskeleton remodeling. However, the underlying mechanism of WASP family in cancer progression remains elusive. Here, we studied the role of WASP and SCAR Homolog (WASH), a recently identified WASP family member, in human esophageal squamous cell carcinoma (ESCC). Using three human ESCC cell lines, we found that WASH expression was significantly elevated in cancer stem-like cells enriched by sphere formation assay...
September 15, 2017: Cancer Science
Kisato Nosaka, Masako Iwanaga, Yoshitaka Imaizumi, Kenji Ishitsuka, Kenichi Ishizawa, Yoji Ishida, Masahiro Amano, Takashi Ishida, Naokuni Uike, Atae Utsunomiya, Koichi Ohshima, Kazuhiro Kawai, Junji Tanaka, Yoshiki Tokura, Kensei Tobinai, Toshiki Watanabe, Kaoru Uchimaru, Kunihiro Tsukasaki
Adult T-cell leukemia-lymphoma (ATL) is a mature T-cell malignancy associated with human T-cell leukemia virus type I (HTLV-1) infection. Japan is the most endemic country for HTLV-1 and ATL in the world. Recent nationwide studies of Japanese blood donors reported that HTLV-1 carriers spread from endemic areas to non-endemic areas. Therefore, the latest information on nationwide epidemiological and clinical data for ATL is necessary to guide clinical practice. We conducted a multicenter, hospital-based survey of newly diagnosed ATL patients from 2010 to 2011...
September 14, 2017: Cancer Science
Chao He, Shuhua Wu, Aidi Gao, Ye Su, Han Min, Zeng-Fu Shang, Jinchang Wu, Li Yang, Wei-Qun Ding, Jundong Zhou
An aberrantly elevated expression of DNA polymerase ι (Pol ι) is significantly associated with poor prognosis of patients with esophageal squamous cell carcinoma (ESCC), yet the mechanisms behind remain obscure. Based on the RNA-Seq transcriptome and real-time PCR analysis, we identified ETS-1 as a candidate gene involved in Pol ι-mediated progression of ESCC. Wound-healing and transwell assay indicated that down-regulation of ETS-1 attenuates Pol ι-mediated invasiveness of ESCC. Signaling pathway analysis showed that Pol ι enhances ETS-1 phosphorylation at threonine-38 through the Erk signaling pathway in ESCC cells...
September 14, 2017: Cancer Science
Noriko Koga, Fukuko Moriya, Kayoko Waki, Akira Yamada, Kyogo Itoh, Masanori Noguchi
This randomized phase II study investigated the immunological efficacy of herbal medicines (HMs) using Hochu-ekki-to and Keishi-bukuryo-gan in combination with personalized peptide vaccination (PPV) for castration-resistant prostate cancer (CRPC). Seventy patients with CRPC were assigned to two arms; PPV plus HMs or PPV alone. Two to four peptides were chosen from 31 peptides derived from cancer antigens for the eight-time subcutaneous injection of PPV according to the patient's human leukocyte antigen type and levels of antigen-specific immunoglobulin G (IgG) titer before PPV treatment...
September 12, 2017: Cancer Science
Takuya Komura, Hisashi Takabatake, Kenichi Harada, Masatoshi Yamato, Masaki Miyazawa, Keiko Yoshida, Masao Honda, Takashi Wada, Hirohisa Kitagawa, Tetsuo Ohta, Shuichi Kaneko, Yoshio Sakai
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy known, with an extremely poor prognosis due to the lack of an efficient diagnostic scheme and no radical treatment option, except surgery. Therefore, understanding the pathophysiology of, and finding a novel biomarker to detect, PDAC should be prioritized. We observed an increase in mRNA expression of the cysteine protease inhibitor cystatin A (CSTA) in CD4+T cells in peripheral blood cells of 9 patients with PDAC, compared with the expression in 7 healthy volunteers...
September 12, 2017: Cancer Science
Takashi Suzuki, Dhisa Minerva, Koichi Nishiyama, Naohiko Koshikawa, Mark Andrew Joseph Chaplain
We study angiogenesis using mathematical models describing the dynamics of tip cells. We review the basic ideas of angiogenesis models and its numerical simulation technique to produce realistic computer graphics images of sprouting angiogenesis. We examine the classical model of Anderson-Chaplain using fundamental concepts of mass transport and chemical reaction with ECM degradation included. Then we construct two kind of numerical schemes, model-faithful and model-driven ones, where new techniques of numerical simulation are introduced, such as the transient probability, particle velocity, and Boolean variables...
September 11, 2017: Cancer Science
Yuji Kumakura, Susumu Rokudai, Misaki Iijima, Bolag Altan, Tomonori Yoshida, Halin Bao, Takehiko Yokobori, Makoto Sakai, Makoto Sohda, Tatsuya Miyazaki, Masahiko Nishiyama, Hiroyuki Kuwano
This study aims to explore the expression level of ΔNp63 in esophageal squamous cell carcinoma (ESCC). To investigate the association between ΔNp63 (p40) expression and ESCC biology, we compared the levels of ΔNp63 expression in normal and tumor tissues, with a specific focus on the diagnostic value of ΔNp63 in ESCC. We analyzed 160 consecutive patients with ESCC who underwent surgical resection without neoadjuvant-chemotherapy at Gunma University Hospital between September 2000 and January 2010. The clinicopathological characteristics and survival of patients were subclassified based on the expression of ΔNp63 as determined by immunohistochemistry, demonstrating that ΔNp63 was highly expressed in 75...
September 11, 2017: Cancer Science
Kota Fukumoto, Tran B Nguyen, Shigeru Chiba, Mamiko Sakata-Yanagimoto
Angioimmunoblastic T-cell lymphoma (AITL) is an age-related malignant lymphoma, characterized by immune system-dysregulated symptoms. Recent sequencing studies have clarified the recurrent mutations in ras homology family member A (RHOA) and in genes encoding epigenetic regulators, tet methyl cytosine dioxygenase 2 (TET2), DNA methyl transferase 3 alpha (DNMT3A), and isocitrate dehydrogenase 2, mitochondrial (IDH2), as well as those related to the T-cell receptor signaling pathway in AITL. In this review, we will focus on how this genetic information has changed the understanding of the developmental process of AITL and will in future lead to individualized therapies for AITL patients...
September 10, 2017: Cancer Science
Yusuke Takahashi, Keishi Sugimachi, Ken Yamamoto, Atsushi Niida, Teppei Shimamura, Tetsuya Sato, Masahiko Watanabe, Junichi Tanaka, Shinei Kudo, Kenichi Sugihara, Kazuo Hase, Masato Kusunoki, Kazutaka Yamada, Yasuhiro Shimada, Yoshihiro Moriya, Yutaka Suzuki, Satoru Miyano, Masaki Mori, Koshi Mimori
Genome wide association studies are a powerful tool for searching for disease susceptibility loci. Several studies identifying SNPs connected intimately to the onset of colorectal cancer (CRC) have been published, but there are few reports of genome-wide association studies in Japan. To identify genetic variants that modify the risk of CRC oncogenesis, especially in the Japanese population, we performed a multi-stage genome wide association study using a large number of samples: 1,846 CRC cases and 2,675 controls...
September 4, 2017: Cancer Science
Ken Ito, Shusei Hamamichi, Takanori Abe, Tsuyoshi Akagi, Hiroshi Shirota, Satoshi Kawano, Makoto Asano, Osamu Asano, Akira Yokoi, Junji Matsui, Izumi O Umeda, Hirofumi Fujii
We previously reported that eribulin mesylate (eribulin), a tubulin-binding drug (TBD), could remodel tumor vasculature (i.e., increased tumor vessels and perfusion) in human breast cancer xenograft models; however, a role of this vascular remodeling in anti-tumor effects is not fully understood. Here, we investigated the effects of eribulin-induced vascular remodeling on anti-tumor activities in multiple human cancer xenograft models. Microvessel densities (MVDs) were evaluated by immunohistochemistry (CD31 staining), and anti-tumor effects were examined in 10 human cancer xenograft models...
September 4, 2017: Cancer Science
Hironori Tanaka, Shoichi Hazama, Michihisa Iida, Ryouichi Tsunedomi, Hiroko Takenouchi, Masao Nakajima, Yukio Tokumitsu, Shinsuke Kanekiyo, Yoshitaro Shindo, Shinobu Tomochika, Yoshihiro Tokuhisa, Kazuhiko Sakamoto, Nobuaki Suzuki, Shigeru Takeda, Shigeru Yamamoto, Shigefumi Yoshino, Tomio Ueno, Yoshihiko Hamamoto, Yusuke Fujita, Hiroaki Tanaka, Ko Tahara, Ryoichi Shimizu, Kiyotaka Okuno, Koji Fujita, Masahiko Kuroda, Yusuke Nakamura, Hiroaki Nagano
Many clinical trials of peptide vaccines have been conducted. However, these vaccines have provided clinical benefits in only a small fraction of patients. The purpose of this study was to explore microRNAs (miRNAs) as novel predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer. First, we performed microarray analysis of pretreatment cancer tissues in a phase I study, in which peptide vaccines alone were administered. Candidate miRNAs were selected by comparison of the better prognosis group with the poorer prognosis group...
August 31, 2017: Cancer Science
Se-Lim Kim, Soo Teik Lee, In Suk Min, Young Ran Park, Ju Hyung Lee, Dae-Ghon Kim, Sang-Wook Kim
Lipocalin 2 (LCN2), a member of the lipocalin superfamily, plays an important role in oncogenesis and progression in various types of cancer. However, the expression pattern and functional role of LCN2 in colorectal cancer (CRC) is still poorly understood. The purpose of this study was to investigate whether LCN2 is associated with proliferation and the epithelial-mesenchymal transition (EMT) in CRC and to elucidate the underlying signaling pathways. LCN2 was preferentially expressed in CRC cells compared to normal tissues...
August 31, 2017: Cancer Science
Kyoko Hida, Nako Maishi, Kosuke Akiyama, Hitomi Ohmura-Kakutani, Chisaho Torii, Noritaka Ohga, Takahiro Osawa, Hiroshi Kikuchi, Hirofumi Morimoto, Masahiro Morimoto, Masanobu Shindoh, Nobuo Shinohara, Yasuhiro Hida
Tumor blood vessels play an important role in tumor progression and metastasis. We previously reported that tumor endothelial cells (TECs) exhibit several altered phenotypes compared with normal endothelial cells (NECs). For example, TECs have chromosomal abnormalities and are resistant to several anticancer drugs. Furthermore, TECs contain stem-like populations with high aldehyde dehydrogenase (ALDH) activity (ALDH(high) TEC). ALDH(high) TECs had proangiogenic properties compared with ALDH(low) TECs. However, the association between ALDH(high) TECs and drug resistance remains unclear...
August 29, 2017: Cancer Science
Asuka Tada, Sachiko Horie, Shiro Mori, Tetsuya Kodama
Systemic administration of drugs into the blood circulation is a standard treatment for the prevention of metastasis. However, systemic delivery cannot maintain sufficiently high concentrations of anticancer drugs in lymphatic nodes (LNs). Here, we show that administering cisplatin (CDDP) using a lymphatic drug delivery system (LDDS) has the potential to treat false-negative metastatic LNs. We found that in MXH10/Mo-lpr/lpr mice, which develop systemic swelling of LNs up to 10 mm in diameter, the accumulation of indocyanine green (ICG, which has a similar molecular weight to CDDP) in a target LN was greater for lymphatic delivery of ICG than for systemic (intravenous) administration...
August 28, 2017: Cancer Science
Justyna Kutkowska, Leon Strzadala, Andrzej Rapak
The highly selective multi-targeted agent - sorafenib - is an inhibitor of a number of intracellular signaling kinases with anti-proliferative, anti-angiogenic and pro-apoptotic effects in various types of tumors, including human non-small cell lung cancer (NSCLC). Betulin displays a broad spectrum of biological and pharmacological properties, including the anticancer and chemopreventive activity. Combination of drugs with different targets is a logical approach to overcome multilevel cross-stimulation among key signaling pathways in NSCLC progression...
August 28, 2017: Cancer Science
Masayuki Tsuneki, Takao Kinjo, Taisuke Mori, Akihiko Yoshida, Kayo Kuyama, Aoi Ohira, Takuya Miyagi, Kenzo Takahashi, Akira Kawai, Hirokazu Chuman, Naoya Yamazaki, Mikio Masuzawa, Hirofumi Arakawa
Human angiosarcoma is a rare malignant vascular tumor associated with extremely poor clinical outcome and generally arising in the skin of head and neck. However, little is known about the molecular pathogeneses and useful immunohistochemical markers of angiosarcoma. To investigate the mechanisms of angiosarcoma progression, we collected 85 cases of human angiosarcoma specimens with clinical records and used ISO-HAS-B patient derived angiosarcoma cells. As control subjects, 54 cases of hemangioma and 34 of pyogenic granuloma were collected...
August 28, 2017: Cancer Science
Makito Miyake, Yosuke Morizawa, Shunta Hori, Yoshihiro Tatsumi, Sayuri Onishi, Takuya Owari, Kota Iida, Kenta Onishi, Daisuke Goto, Yasushi Nakai, Satoshi Anai, Yoshitomo Chihara, Kazumasa Torimoto, Katsuya Aoki, Nobumichi Tanaka, Keiji Shimada, Noboru Konishi, Kiyohide Fujimoto
Collagen type 4 alpha 1 (COL4A1) and collagen type 13 alpha 1 (COL13A1) produced by urothelial cancer cells support the vital oncogenic property of tumor invasion. We investigated the diagnostic and prognostic capability of COL4A1 and COL13A1 in voided urine and compared the observed values with those of CYFRA21-1, NMP-22, and voided urine cytology in bladder cancer (BCa). We collected voided urine samples from 154 patients newly diagnosed with BCa, before surgery and from 61 control subjects. Protein levels of COL4A1, COL13A1, CYFRA21-1, and NMP-22 in urine supernatants were measured using enzyme-linked immunosorbent assays...
August 24, 2017: Cancer Science
Ryosuke Shintoku, Yuta Takigawa, Keiichi Yamada, Chisato Kubota, Yuhei Yoshimoto, Toshiyuki Takeuchi, Ichiro Koshiishi, Seiji Torii
In cancer cells the small compounds erastin and RSL3 promote a novel type of cell death called ferroptosis, which requires iron-dependent accumulation of lipid reactive oxygen species. Here we assessed the contribution of lipid peroxidation activity of lipoxygenases (LOXs) to ferroptosis in oncogenic Ras-expressing cancer cells. Several 12/15-LOX inhibitors prevented cell death induced by erastin and RSL3. Furthermore, siRNA-mediated silencing of ALOX15 significantly decreased both erastin- and RSL3-induced ferroptotic cell death, whereas exogenous overexpression of ALOX15 enhanced the effect of these compounds...
August 24, 2017: Cancer Science
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