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Cancer Science

Cover image for Vol. 105 Issue 5

May 2014

Volume 105, Issue 5

Pages May cover–May cover, i–iii, 499–622

  1. COVER IMAGE

    1. Top of page
    2. COVER IMAGE
    3. ISSUE INFORMATION
    4. IN THIS ISSUE
    5. REVIEW ARTICLE
    6. ORIGINAL ARTICLES
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      Bone resorption facilitates osteoblastic bone metastasis by insulin-like growth factor and hypoxia. Von Kossa staining showing aberrant bone formation due to bone metastasis of murine osteosarcoma LM8 cells. (page May cover)

      Takahiro Kuchimaru, Takuya Hoshino, Tomoya Aikawa, Hisataka Yasuda, Tatsuya Kobayashi, Tetsuya Kadonosono and Shinae Kizaka-Kondoh

      Version of Record online: 7 MAY 2014 | DOI: 10.1111/cas.12401

  2. ISSUE INFORMATION

    1. Top of page
    2. COVER IMAGE
    3. ISSUE INFORMATION
    4. IN THIS ISSUE
    5. REVIEW ARTICLE
    6. ORIGINAL ARTICLES
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      Issue Information (pages i–ii)

      Version of Record online: 7 MAY 2014 | DOI: 10.1111/cas.12258

  3. IN THIS ISSUE

    1. Top of page
    2. COVER IMAGE
    3. ISSUE INFORMATION
    4. IN THIS ISSUE
    5. REVIEW ARTICLE
    6. ORIGINAL ARTICLES
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  4. REVIEW ARTICLE

    1. Top of page
    2. COVER IMAGE
    3. ISSUE INFORMATION
    4. IN THIS ISSUE
    5. REVIEW ARTICLE
    6. ORIGINAL ARTICLES
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      Not just gRASping at flaws: Finding vulnerabilities to develop novel therapies for treating KRAS mutant cancers (pages 499–505)

      Hiromichi Ebi, Anthony C. Faber, Jeffrey A. Engelman and Seiji Yano

      Version of Record online: 26 MAR 2014 | DOI: 10.1111/cas.12383

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      Mutations in Kirsten rat-sarcoma (KRAS) are well appreciated to be major contributors of human cancers through dysregulation of multiple growth and survival pathways. The main effector pathways of KRAS and current approaches to develop combination therapies targeting these KRAS-effector pathways are discussed. Also, other approaches targeting KRAS, including synthetic lethal screening are summarized.

  5. ORIGINAL ARTICLES

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    2. COVER IMAGE
    3. ISSUE INFORMATION
    4. IN THIS ISSUE
    5. REVIEW ARTICLE
    6. ORIGINAL ARTICLES
    1. CARCINOGENESIS

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      Inhibitors of differentiation-1 promotes nitrosopyrrolidine-induced transformation of HPV 16-immortalized cervical epithelial cell (pages 506–511)

      Lingxia Xie, Jinke Li, Yi Zhang, Bao Liu, Xue Peng, Yong Lin, Wenming Xu and Lina Hu

      Version of Record online: 15 APR 2014 | DOI: 10.1111/cas.12398

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      Our study suggests that Id-1 promotes cervical epithelial transformation, which sheds lights on cervical cancer development and implies Id-1 as a potential target for cervical cancer prevention and therapy.

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      Inhibition of histone methyltransferase EZH2 depletes leukemia stem cell of mixed lineage leukemia fusion leukemia through upregulation of p16 (pages 512–519)

      Koki Ueda, Akihide Yoshimi, Yuki Kagoya, Satoshi Nishikawa, Victor E. Marquez, Masahiro Nakagawa and Mineo Kurokawa

      Version of Record online: 30 MAR 2014 | DOI: 10.1111/cas.12386

      Leukemia stem cells (LSCs) are main cause of relapse or refractoriness to conventional chemotherapy. Although eradicating LSCs are ideal goal for anti-leukemia therapy, drugs targeting LSCs have scarcely been identified. Polycomb group proteins are associated with controlling stemness including activity of cancer stem cells, and can be pharmacologically targeted by a selective inhibitor of H3K27, DZNep. To our surprise, EZH2 inhibition by DZNep or shRNA not only suppressed MLL fusion leukemia proliferation but also reduced LSCs frequency. Dysregulation of p16 is supposed to be responsible for the effect. We also show that EZH2 are highly enriched around the transcription-start-site of p16, together with H3K27 methylation marks in MLL/ENL cells. Although high expression of Hoxa9 in MLL fusion leukemia is supposed to be responsible for the recruitment of EZH2, our data also suggests that there may be some other mechanisms independent of Hoxa9 activation to suppress p16 expression. We believe that these findings would help us to develop LICs targeted therapy for MLL fusion leukemia.

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      Quercetin enhances apoptotic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in ovarian cancer cells through reactive oxygen species (ROS) mediated CCAAT enhancer-binding protein homologous protein (CHOP)-death receptor 5 pathway (pages 520–527)

      Liu Yi, Yang Zongyuan, Gong Cheng, Zhang Lingyun, Yu GuiLian and Gong Wei

      Version of Record online: 11 APR 2014 | DOI: 10.1111/cas.12395

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      Mitochondrial proteins (ROS) are mediating the apoptotic process, downstream or in parallel, CHOP might be a crucial player for DR5 upregulation and cancer cell killing by quercetin. IRE1a-JNK signaling could also be considered to be the major ER-stress pathway for quercetin induced CHOP expression, thus contributing to the enhanced apoptotic death of ovarian cancer cells to TRAIL. Quercetin could be an attractive candidate for combined chemotherapy against cancer.

    4. CELL, MOLECULAR, AND STEM CELL BIOLOGY

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      Saracatinib impairs the peritoneal dissemination of diffuse-type gastric carcinoma cells resistant to Met and fibroblast growth factor receptor inhibitors (pages 528–536)

      Hideki Yamaguchi, Miho Takanashi, Nachi Yoshida, Yuumi Ito, Reiko Kamata, Kiyoko Fukami, Kazuyoshi Yanagihara and Ryuichi Sakai

      Version of Record online: 24 MAR 2014 | DOI: 10.1111/cas.12387

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      Saracatinib impaired peritoneal dissemination of 44As3Luc scirrhous gastric carcinoma cells that are resistant to Met and FGFR inhibition.

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      Gene expression profiling of Epstein–Barr virus-positive diffuse large B-cell lymphoma of the elderly reveals alterations of characteristic oncogenetic pathways (pages 537–544)

      Harumi Kato, Kennosuke Karube, Kazuhito Yamamoto, Jun Takizawa, Shinobu Tsuzuki, Yasushi Yatabe, Teru Kanda, Miyuki Katayama, Yukiyasu Ozawa, Kenji Ishitsuka, Masataka Okamoto, Tomohiro Kinoshita, Koichi Ohshima, Shigeo Nakamura, Yasuo Morishima and Masao Seto

      Version of Record online: 9 APR 2014 | DOI: 10.1111/cas.12389

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      EBV-positive diffuse large B-cell lymphoma (DLBCL) of the elderly is newly classified as a subtype of DLBCL in the 4th WHO classification. Comprehensive genetic analysis has not been investigaed. We identified the activation of JAK-STAT and NF-κB pathways was characteristic of the disease.

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      Suppression of REV7 enhances cisplatin sensitivity in ovarian clear cell carcinoma cells (pages 545–552)

      Kaoru Niimi, Yoshiki Murakumo, Naoki Watanabe, Takuya Kato, Shinji Mii, Atsushi Enomoto, Masato Asai, Naoya Asai, Eiko Yamamoto, Hiroaki Kajiyama, Kiyosumi Shibata, Fumitaka Kikkawa and Masahide Takahashi

      Version of Record online: 7 APR 2014 | DOI: 10.1111/cas.12390

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      Immunohistochemical analysis of 137 epithelial ovarian cancer specimens revealed that high levels of REV7 expression were detected in clear cell carcinomas (CCC), and were associated with poor prognosis of advanced epithelial ovarian cancer. REV7 depletion in CCC cells enhanced sensitivity to cisplatin in vitro and in vivo, suggesting that REV7 could be a molecular target for CCC therapy.

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      Bone resorption facilitates osteoblastic bone metastatic colonization by cooperation of insulin-like growth factor and hypoxia (pages 553–559)

      Takahiro Kuchimaru, Takuya Hoshino, Tomoya Aikawa, Hisataka Yasuda, Tatsuya Kobayashi, Tetsuya Kadonosono and Shinae Kizaka-Kondoh

      Version of Record online: 3 APR 2014 | DOI: 10.1111/cas.12391

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      Bone resorption facilitates cancer cell colonization of osteoblastic bone metastasis. We revealed that insulin-like growth factor-1 released from the bone during bone resorption and hypoxia-inducible factor activity cooperatively promote cancer cell colonization in hypoxic bone marrow.

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      Identification of novel targets for antiangiogenic therapy by comparing the gene expressions of tumor and normal endothelial cells (pages 560–567)

      Tsuguteru Otsubo, Yasuhiro Hida, Noritaka Ohga, Hideshi Sato, Toshihiro Kai, Yasushi Matsuki, Hideo Takasu, Kosuke Akiyama, Nako Maishi, Taisuke Kawamoto, Nobuo Shinohara, Katsuya Nonomura and Kyoko Hida

      Version of Record online: 19 APR 2014 | DOI: 10.1111/cas.12394

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      We identified 131 genes that were differentially upregulated in mTECs. Functional analysis using siRNA-mediated gene silencing revealed five novel TEC markers that were involved in the proliferation or migration of mTECs. The expression of DEF6 and TMEM176B was upregulated in tumor vessels of human renal cell carcinoma (RCC) specimens, suggesting that they are potential targets for antiangiogenic intervention for RCC.

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      An inhibition of p62/SQSTM1 caused autophagic cell death of several human carcinoma cells (pages 568–575)

      Kaito Nihira, Yasuhiro Miki, Katsuhiko Ono, Takashi Suzuki and Hironobu Sasano

      Version of Record online: 9 APR 2014 | DOI: 10.1111/cas.12396

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      p62/SQSTM1 (p62) is a multifunctional protein implicated in several signal transduction pathways and selectively degraded by autophagy, a process for lysosomal degradation of protein and organelle. Results of our present study revealed that p62-silencing resulted in the formation of mis-regulated multilayer autophagosomes and an autophagic cell death, and p62 can therefore be an attractive target for the development of anti-neoplastic agents.

    10. CLINICAL RESEARCH

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      Incidence and prediction of invasive disease and nodal metastasis in preoperatively diagnosed ductal carcinoma in situ (pages 576–582)

      Tomo Osako, Takuji Iwase, Masaru Ushijima, Rie Horii, Yasuyoshi Fukami, Kiyomi Kimura, Masaaki Matsuura and Futoshi Akiyama

      Version of Record online: 26 MAR 2014 | DOI: 10.1111/cas.12381

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      Most patients with a preoperative diagnosis of ductal carcinoma in situ of the breast had no metastasis or only micrometastasis in axillary nodes, even though invasive disease was found on final pathology. Predictors of the invasive disease were not completely consistent with those of nodal metastasis. Therefore, the selective application of sentinel node biopsy in patients with a higher risk of invasive disease may not accurately identify the patients with a higher likelihood of sentinel node metastasis.

    11. DRUG DISCOVERY AND DELIVERY

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      Antitumor effect of fibrin glue containing temozolomide against malignant glioma (pages 583–591)

      Shigeo Anai, Takuichiro Hide, Tatsuya Takezaki, Jun-ichiro Kuroda, Naoki Shinojima, Keishi Makino, Hideo Nakamura, Shigetoshi Yano and Jun-ichi Kuratsu

      Version of Record online: 19 APR 2014 | DOI: 10.1111/cas.12397

      Fibrin glue containing temozolomide has the anti-tumor effect against malignant glioma with the sustained release.

    12. GENETICS, GENOMICS AND PROTEOMICS

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      High-resolution genomic copy number profiling of primary intraocular lymphoma by single nucleotide polymorphism microarrays (pages 592–599)

      Ludan Wang, Aiko Sato-Otsubo, Sunao Sugita, Hiroshi Takase, Manabu Mochizuki, Yoshihiko Usui, Hiroshi Goto, Takatoshi Koyama, Hiroki Akiyama, Osamu Miura, Seishi Ogawa and Ayako Arai

      Version of Record online: 1 APR 2014 | DOI: 10.1111/cas.12388

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      The genetic features of primary intraocular lymphoma (PIOL) have not yet been elucidated. We carried out single nucleotide polymorphism array karyotyping of IOL using genomic DNA extracted from vitreous fluid. Recurrent copy number gain regions in PIOLs were detected most frequently on chromosome 1q followed by 18q and 19q. There was a correlation between gain of the IL-10 gene located on 1q and intravitreal interleukin-10 concentration, which was higher in IOL than in benign uveitis.

    13. PATHOLOGY

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      GATA4 immunolocalization in breast carcinoma as a potent prognostic predictor (pages 600–607)

      Kiyoshi Takagi, Takashi Moriguchi, Yasuhiro Miki, Yasuhiro Nakamura, Mika Watanabe, Takanori Ishida, Masayuki Yamamoto, Hironobu Sasano and Takashi Suzuki

      Version of Record online: 19 MAR 2014 | DOI: 10.1111/cas.12382

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      In this study, we explored the possible roles of GATA4 in human breast cancer. GATA4 immunoreactivity was positively associated with distant metastasis, and outcome analyses revealed that GATA4 immunoreactivity was associated with shorter disease-free and breast cancer-specific survival of the patients. These data may suggest important roles of GATA4 in the process of breast cancer progression.

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      Duodenal follicular lymphoma: Comprehensive gene expression analysis with insights into pathogenesis (pages 608–615)

      Katsuyoshi Takata, Motohiko Tanino, Daisuke Ennishi, Akira Tari, Yasuharu Sato, Hiroyuki Okada, Yoshinobu Maeda, Naoe Goto, Hiroshi Araki, Mai Harada, Midori Ando, Masaya Iwamuro, Mitsune Tanimoto, Kazuhide Yamamoto, Randy D. Gascoyne and Tadashi Yoshino

      Version of Record online: 6 APR 2014 | DOI: 10.1111/cas.12392

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      In the present study, we examined 10 DFL, 18 NFL, 10 gastric MALT lymphoma samples by gene expression analysis. Gene expression profiles of the 3 lymphoma types were compared using 2918 differentially expressed genes (DEGs) and results suggested that DFL shares characteristics of MALT lymphoma. Increased expression of CCL20 and MAdCAM-1 and co-expression of CCL20 and CCR6 may play an important role in tumorigenesis in DFL.

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      Diagnostic approach for cancer cells in urine sediments by 5-aminolevulinic acid-based photodynamic detection in bladder cancer (pages 616–622)

      Makito Miyake, Yasushi Nakai, Satoshi Anai, Yoshihiro Tatsumi, Masaomi Kuwada, Sayuri Onishi, Yoshitomo Chihara, Nobumichi Tanaka, Yoshihiko Hirao and Kiyohide Fujimoto

      Version of Record online: 6 APR 2014 | DOI: 10.1111/cas.12393

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      The ALA-based fluorescence detection assays detected bladder cancer cells in urine sediments of low-grade and low-stage bladder urothelial cells at higher rate than conventional urine markers. The ALA-based assay are promising tool for the management of bladder cancer.

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