Cancer Science

Cover image for Vol. 107 Issue 4

Early View (Online Version of Record published before inclusion in an issue)

Edited By: Yusuke Nakamura

Impact Factor: 3.523

ISI Journal Citation Reports © Ranking: 2014: 73/211 (Oncology)

Online ISSN: 1349-7006

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  1. 1 - 23
  1. Original Articles

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      Identification of ganglioside GM2 activator playing a role in cancer cell migration through proteomic analysis of breast cancer secretomes

      Jihye Shin, Gamin Kim, Jong Won Lee, Ji Eun Lee, Yoo Seok Kim, Jong-Han Yu, Seung-Taek Lee, Sei Hyun Ahn, Hoguen Kim and Cheolju Lee

      Article first published online: 27 APR 2016 | DOI: 10.1111/cas.12935

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      Our integrated approach using the secretome analysis for BC cancer cells and publicly available datasets, allowed selection of candidate biomarkers of BC. Of the 12 candidate biomarkers of BC, we were able to show that GM2A plays a key role in migration of BC cells in the current study. Although, Western blot and ELISA data do not provide strong evidence that GM2A is useful as a screening marker for BC, we were able to find that both specificity and sensitivity of GM2A were increased for ER negative patients in comparison with ER positive patients.

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      Y-632 inhibits heat shock protein 90 (Hsp90) function by disrupting the interaction between Hsp90 and Hsp70/Hsp90 organizing protein, and exerts antitumor activity in vitro and in vivo

      Wenqian Wang, Yang Liu, Zhixin Zhao, Chengying Xie, Yongping Xu, Youhong Hu, Haitian Quan and Liguang Lou

      Article first published online: 27 APR 2016 | DOI: 10.1111/cas.12934

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      Y -632 is a promising Hsp90 inhibitor with novel mechanisms. Y -632 inhibits Hsp90 through disrupting Hsp90-Hop interaction. Hsp90-Hop interaction disruption results from Y -632 induced thiol oxidation.

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      TP53 mutation at early stage of colorectal cancer progression from two types of laterally spreading tumors

      Eiji Sakai, Masaki Fukuyo, Keisuke Matsusaka, Ken Ohata, Noriteru Doi, Kiyoko Takane, Nobuyuki Matsuhashi, Junichi Fukushima, Atsushi Nakajima and Atsushi Kaneda

      Article first published online: 27 APR 2016 | DOI: 10.1111/cas.12930

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      We conducted targeted exon sequencing study of flat, early colorectal lesions, so-called laterally spreading tumors (LSTs), to gain insight into involvement of molecular alterations in progression of colorectal cancer through de novo pathway. APC mutation was frequently involved by adenoma stages in both granular-type LST (LST-G) and non-granular LST (LST-NG), suggesting its involvement in tumor initiation in LSTs. TP53 mutation was involved during cancer development from adenoma to cancer for both LST-G and LST-NG, but was involved at earlier stage in LST-NG.

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      Clinical prognostic value of DNA methylation in hepatoblastoma: Four novel tumor suppressor candidates

      Shohei Honda, Masashi Minato, Hiromu Suzuki, Masato Fujiyoshi, Hisayuki Miyagi, Masayuki Haruta, Yasuhiko Kaneko, Kanako C. Hatanaka, Eiso Hiyama, Takehiko Kamijo, Tadao Okada and Akinobu Taketomi

      Article first published online: 27 APR 2016 | DOI: 10.1111/cas.12928

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      Using genome-wide methylation analysis and bisulfite pyrosequencing with specimens from hepatoblastoma tumors, GPR180, MST1R, OCIAD2 and PARP6 were identified as novel tumor suppressor candidates. The methylation status of those genes was significantly associated with a poor prognosis, age at diagnosis and the presence of metastatic tumors in 74 hepatoblastoma cases.

  2. Review Articles

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      Genetic abnormalities associated with acute lymphoblastic leukemia

      Takafumi Yokota and Yuzuru Kanakura

      Article first published online: 27 APR 2016 | DOI: 10.1111/cas.12927

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      Recent technical advances in next-generation sequencing have shed light on genetic abnormalities in hematopoietic stem/progenitor cells as the precursor to pathogenesis of acute lymphoblastic leukemia. These findings are directly relevant to clinical hematology, and could contribute to accurate diagnosis, effective monitoring of residual disease, and patient-oriented therapies.

  3. Original Articles

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      Enhanced efficacy against cervical carcinomas through polymeric micelles physically incorporating the proteasome inhibitor MG132

      Yoko Matsumoto, Yuichiro Miyamoto, Horacio Cabral, Yu Matsumoto, Kazunori Nagasaka, Shunsuke Nakagawa, Tetsu Yano, Daichi Maeda, Katsutoshi Oda, Kei Kawana, Nobuhiro Nishiyama, Kazunori Kataoka and Tomoyuki Fujii

      Article first published online: 27 APR 2016 | DOI: 10.1111/cas.12926

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      We focused on the ubiquitin proteasome inhibitor MG132 as the anticancer agent against cervical cancer cells, and physically incorporated it into micellar nanomedicines for achieving selective delivery to solid tumors and improving its in vivo efficacy. These MG132-loaded polymeric micelles (MG132/m) showed strong tumor inhibitory in vivo effect against HPV-positive tumors from HeLa and CaSki cells, and even in HPV-negative tumors from C33A cells.

  4. Review Articles

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      Medulloblastoma stem cells: Promising targets in medulloblastoma therapy

      Guo-Hao Huang, Qing-Fu Xu, You-Hong Cui, Ningning Li, Xiu-Wu Bian and Sheng-Qing Lv

      Article first published online: 27 APR 2016 | DOI: 10.1111/cas.12925

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      In this paper,we review the current knowledge of MB stem cells (MBSCs), highlight the molecular mechanisms in relation to MB relapse and LMD, and relate these to the need to develop more effective therapies for MB patients.

  5. Original Articles

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      Live imaging of transforming growth factor-β activated kinase 1 activation in Lewis lung carcinoma 3LL cells implanted into syngeneic mice and treated with polyinosinic:polycytidylic acid

      Saori Takaoka, Yuji Kamioka, Kanako Takakura, Ai Baba, Hiroaki Shime, Tsukasa Seya and Michiyuki Matsuda

      Article first published online: 27 APR 2016 | DOI: 10.1111/cas.12923

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      The TAK1 FRET biosensor enables visualization of the stress response in vivo.

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      Phase I study of a new cancer vaccine of ten mixed peptides for advanced cancer patients

      Satoru Iwasa, Yasuhide Yamada, Yuji Heike, Hirokazu Shoji, Yoshitaka Honma, Nobukazu Komatsu, Satoko Matsueda, Akira Yamada, Michi Morita, Rin Yamaguchi, Natsuki Tanaka, Akihiko Kawahara, Masayoshi Kage, Shigeki Shichijo, Tetsuro Sasada and Kyogo Itoh

      Article first published online: 26 APR 2016 | DOI: 10.1111/cas.12919

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      A phase I study of a new cancer vaccine (KRM-10), consisting of a mixture of 10 different short peptides, was conducted for patients with advanced gastrointestinal cancers. The KRM-10 vaccine consisting of 20 mg of peptides was determined as the optimal dose for a coming phase II trial because of its safety, and also for demonstrating the most potent activity for augmenting the immune response of the three doses tested.

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      Development of DS-5573a: A novel afucosylated mAb directed at B7-H3 with potent antitumor activity

      Akiko Nagase-Zembutsu, Kenji Hirotani, Michiko Yamato, Junko Yamaguchi, Takehiko Takata, Makoto Yoshida, Keisuke Fukuchi, Mitsuhiro Yazawa, Shu Takahashi and Toshinori Agatsuma

      Article first published online: 26 APR 2016 | DOI: 10.1111/cas.12915

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      We developed a novel afucosylated humanized anti-B7-H3 monoclonal antibody, DS-5573a. We found that this mAb has potent antitumor activity against B7-H3-expressing cancer cells via natural killer cells and macrophages. Our results suggest that DS-5573a has potential as a therapeutic mAb to address unmet medical needs in B7-H3 positive-cancer patients.

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      Selective activator protein-1 inhibitor T-5224 prevents lymph node metastasis in an oral cancer model

      Daisuke Kamide, Taku Yamashita, Koji Araki, Masayuki Tomifuji, Yuya Tanaka, Shingo Tanaka, Shunichi Shiozawa and Akihiro Shiotani

      Article first published online: 26 APR 2016 | DOI: 10.1111/cas.12914

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      AP-1 inhibitor T-5224 prevents lymph node metastasis in head and neck cancer model.

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      Infiltration of tumor-associated macrophages is involved in CD44 expression in clear cell renal cell carcinoma

      Chaoya Ma, Yoshihiro Komohara, Koji Ohnishi, Tetsu Shimoji, Nao Kuwahara, Yasuo Sakumura, Kozue Matsuishi, Yukio Fujiwara, Takanobu Motoshima, Wataru Takahashi, Sohsuke Yamada, Shohei Kitada, Naohiro Fujimoto, Toshiyuki Nakayama, Masatoshi Eto and Motohiro Takeya

      Article first published online: 14 APR 2016 | DOI: 10.1111/cas.12917

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      Cancer stem-like cells (CSCs) or cancer-initiating cells are now considered to be an important cell population related to cancer recurrence and the resistance to anti-cancer therapy. Tumor-associated macrophages (TAMs) are a main component of stromal cells and are related to cancer progression in clear cell renal cell carcinoma (ccRCC). Our findings suggest that TNF-alpha derived from TAMs is linked to CD44 overexpression via NF-kB signaling in ccRCC.

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      Gemcitabine enhances rituximab-mediated complement-dependent cytotoxicity to B cell lymphoma by CD20 upregulation

      Kazumi Hayashi, Eijiro Nagasaki, Shin Kan, Masaki Ito, Yuko Kamata, Sadamu Homma and Keisuke Aiba

      Article first published online: 7 APR 2016 | DOI: 10.1111/cas.12918

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      Gemcitabine treatment of diffuse large B cell lymphoma (DLBCL) cells induces up-regulation of surface CD20 expression in vitro. Combined treatment with gemcitabine and rituximab elicits high antitumor activity to DLBCL cells because of enhanced binding of rituximab to CD20.

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      Xenotransplantation elicits salient tumorigenicity of adult T-cell leukemia-derived cells via aberrant AKT activation

      Kazunori Yamaguchi, Tomoka Takanashi, Kentaro Nasu, Keiichi Tamai, Mai Mochizuki, Ikuro Satoh, Shoji Ine, Osamu Sasaki, Kennichi Satoh, Nobuyuki Tanaka, Hideo Harigae and Kazuo Sugamura

      Article first published online: 7 APR 2016 | DOI: 10.1111/cas.12921

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      In this study we were able to generate highly tumorigenic sublines from ATL-derived cell lines through serial xenotransplantation in immunodeficient NOG mice. We found aberrant activation of AKT signaling plays a pivotal role in the tumorigenic potential of the ATL cells.

  6. Review Articles

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      The Wnt7's Tale: A story of an orphan who finds her tie to a famous family

      Makoto Noda, Mario Vallon and Calvin J. Kuo

      Article first published online: 7 APR 2016 | DOI: 10.1111/cas.12924

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      A series of recent studies using genetically engineered mice and zebrafish as well as luciferase reporter assay in cultured cells led to the discovery of functional interactions among Reck, Gpr124, and Wnt7a/b in triggering canonical Wnt signaling with relevance to embryonic brain angiogenesis.

  7. Original Articles

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      Lenalidomide and low-dose dexamethasone in Japanese patients with newly diagnosed multiple myeloma: A phase II study

      Kenshi Suzuki, Atsushi Shinagawa, Toshiki Uchida, Masafumi Taniwaki, Hirokazu Hirata, Kenichi Ishizawa, Kosei Matsue, Yoshiaki Ogawa, Takayuki Shimizu, Maki Otsuka, Morio Matsumoto, Shinsuke Iida, Yasuhito Terui, Itaru Matsumura, Takashi Ikeda, Naoki Takezako, Yumi Ogaki, Shuichi Midorikawa, Vanessa Houck, Annette Ervin-Haynes and Takaaki Chou

      Article first published online: 30 MAR 2016 | DOI: 10.1111/cas.12916

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      The FIRST trial (MM-020) demonstrated that lenalidomide plus low-dose dexamethasone (Rd) reduced risk of multiple myeloma (MM) disease progression or death; however, no Japanese patients were included in the study. MM-025 evaluated the efficacy and safety of continuous Rd treatment in 26 Japanese patients with newly diagnosed MM (NDMM). The study results support the use of continuous Rd treatment in Japanese patients with NDMM.

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      Vasohibin-1 expression inhibits advancement of ovarian cancer producing various angiogenic factors

      Yoshifumi Takahashi, Yasushi Saga, Takahiro Koyanagi, Yuji Takei, Shizuo Machida, Akiyo Taneichi, Hiroaki Mizukami, Yasufumi Sato, Shigeki Matsubara and Hiroyuki Fujiwara

      Article first published online: 30 MAR 2016 | DOI: 10.1111/cas.12911

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      In the current study, the expression of sFlt-1 had no such effect on the high PDGF-producing ovarian cancer cells (KOC-2S) used here, whereas VASH1 expression inhibited tumor vascularization and growth, not only in high VEGF-producing cells (SHIN-3), but also in high PDGF-producing cells (KOC-2S).

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      SERPINI1 regulates epithelial–mesenchymal transition in an orthotopic implantation model of colorectal cancer

      Yasufumi Matsuda, Koh Miura, Junko Yamane, Hiroshi Shima, Wataru Fujibuchi, Kazuyuki Ishida, Fumiyoshi Fujishima, Shinobu Ohnuma, Hiroyuki Sasaki, Munenori Nagao, Naoki Tanaka, Kennichi Satoh, Takeshi Naitoh and Michiaki Unno

      Article first published online: 28 MAR 2016 | DOI: 10.1111/cas.12909

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      In order to characterize the properties of the EMT in 16 colorectal cell lines, the cells were first orthotopically implanted into nude mice, and the tumors that developed in vivo, as well as cells cultured in vitro, were immunostained for EMT markers E-cadherin and vimentin. Comparing the three phenotypic subgroups of the cancer cells, we found that SERPINI1 is an important regulator of the EMT and also examined the effect of the secreted SERPINI1 protein for the EMT.

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      Effect of food on the pharmacokinetics of TAS-102 and its efficacy and safety in patients with advanced solid tumors

      Takayuki Yoshino, Takashi Kojima, Hideaki Bando, Tomoko Yamazaki, Yoichi Naito, Hirofumi Mukai, Nozomu Fuse, Koichi Goto, Yuko Ito, Toshihiko Doi and Atsushi Ohtsu

      Article first published online: 28 MAR 2016 | DOI: 10.1111/cas.12912

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      This study demonstrates that postprandial administration after morning and evening meals is considered to be an adequate regimen for TAS-102. Furthermore, the results suggest that TAS-102 would be an effective treatment for various carcinomas, especially small cell lung, thymic, and colorectal cancers.

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      CD44 variant 9 is a potential biomarker of tumor initiating cells predicting survival outcome in hepatitis C virus-positive patients with resected hepatocellular carcinoma

      Anna Kakehashi, Naomi Ishii, Eiji Sugihara, Min Gi, Hideyuki Saya and Hideki Wanibuchi

      Article first published online: 28 MAR 2016 | DOI: 10.1111/cas.12908

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      The novel finding of the present study is that CD44 antigen splicing variant isoform 9 (CD44v9) is overexpressed in tumor cell populations within human and mouse hepatocellular carcinomas (HCCs). We have performed comparative proteome analysis in formalin-fixed paraffin embedded HCC sections and different immunohistochemical analyses and found that CD44v9+ cells of HCCs were predominantly negative for Ki67 and P-p38, indicating decrease of cell proliferation in the CD44v9+ tumor cell population, likely to be related to suppression of intracellular oxidative stress due to activation of Nrf2, DNA repair and inhibition of xenobiotic metabolism. In human HCV+ HCC cases CD44v9 positivity was correlated with poorer overall and recurrence-free survival and clinicopathological factors including younger age, a poorly differentiated invasive phenotype of HCC, thus suggesting that CD44v9 could be a novel biomarker of liver tumor initiating stem cells (TISCs) and a prognosis factor for HCV+ HCC patients associated with Nrf2-mediated resistance to oxidative stress.

  8. Review Articles

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      Role of hyaluronan in pancreatic cancer biology and therapy: Once again in the spotlight

      Norihiro Sato, Shiro Kohi, Keiji Hirata and Michael Goggins

      Article first published online: 18 MAR 2016 | DOI: 10.1111/cas.12913

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      We summarize our current understanding of the role of hyaluronan in the progression of pancreatic ductal adenocarcinoma and discuss possible therapeutic approaches targeting HA.

  9. Original Articles

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      Genetic variation frequencies in Wilms' tumor: A meta-analysis and systematic review

      Changkai Deng, Rong Dai, Xuliang Li and Feng Liu

      Article first published online: 18 MAR 2016 | DOI: 10.1111/cas.12910

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      Our paper is the first report about the pooled prevalence of genetic variations in Wilms' tumors based on a meta-analysis and systematic review of 70 original studies from 5174 papers and provides a more precise and comprehensive outcome for genetic tests and a basis for the prevention, early diagnosis and treatment of Wilms' tumors.

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      Multikinase inhibitor regorafenib inhibits the growth and metastasis of colon cancer with abundant stroma

      Hidehiko Takigawa, Yasuhiko Kitadai, Kei Shinagawa, Ryo Yuge, Yukihito Higashi, Shinji Tanaka, Wataru Yasui and Kazuaki Chayama

      Article first published online: 18 MAR 2016 | DOI: 10.1111/cas.12907

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      Regorafenib inhibited tumor growth and metastasis by inhibiting both tumor cells and stromal reaction by sole administration. The tumor inhibitory effect of regorafenib was more obvious in colon tumors with activated stroma generated by co-implantation of mesenchymal stem cells. Targeting tumor microenvironment by regorafenib influences the interaction between MSCs and tumor cells and, hence, inhibits growth and metastasis of colon cancer.

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