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Cancer Science

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https://www.readbyqxmd.com/read/28083970/molecular-subtypes-of-colorectal-cancers-determined-by-pcr-based-analysis
#1
Tamotsu Sugai, Makoto Eizuka, Yayoi Takahashi, Tomoyuki Fukagawa, Wataru Habano, Eiichiro Yamamoto, Risaburo Akasaka, Kouki Otuska, Takayuki Matsumoto, Hiromu Suzuki
Tumor tissue consists of a heterogeneous cell population. The allelic imbalance (AI) ratio, determined in isolated tumor glands, is a good index of tumor heterogeneity. However, associations of the patterns of AI and microsatellite instability (MSI) development, observed in most cases of colorectal cancer (CRC), with tumor progression have not been reported previously. In this study, we examined whether CRC genetic profiles stratified by a combination of the AI ratio and MSI facilitate categorization of CRC, and whether these genetic profiles are associated with specific molecular alterations in CRC...
January 13, 2017: Cancer Science
https://www.readbyqxmd.com/read/28075526/cetuximab-strongly-enhances-immune-cell-infiltration-into-liver-metastatic-sites-in-colorectal-cancer
#2
Yuka Inoue, Shoichi Hazama, Nobuaki Suzuki, Yukio Tokumitsu, Shinsuke Kanekiyo, Shinobu Tomochika, Ryouichi Tsunedomi, Yoshihiro Tokuhisa, Michihisa Iida, Kazuhiko Sakamoto, Shigeru Takeda, Tomio Ueno, Shigefumi Yoshino, Hiroaki Nagano
Cetuximab has activity against colorectal cancers. Recent studies demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity via immune cells, and a new immune-related mechanism of inducing immunogenic cell death. This study aimed to evaluate the immune responses induced by cetuximab in tumor microenvironments at liver metastasis sites of metastatic colorectal cancer patients. We assessed immune cell infiltration in the liver metastatic sites of 53 colorectal cancer patients. These patients were divided into three groups according to the treatment before operation: chemotherapy with cetuximab, chemotherapy without cetuximab, and no chemotherapy...
January 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28075524/topk-t-lak-cell-originated-protein-kinase-inhibitor-exhibits-growth-suppressive-effect-on-small-cell-lung-cancer
#3
Jae-Hyun Park, Hiroyuki Inoue, Taigo Kato, Makda Zewde, Takashi Miyamoto, Yo Matsuo, Ravi Salgia, Yusuke Nakamura
T-lymphokine-activated killer cell-originated protein kinase (TOPK) plays critical roles in cancer cell proliferation as well as maintenance of cancer stem cells (CSC). Small cell lung cancer (SCLC) has highly aggressive phenotype, reveals early spread to distant sites, and results in dismal prognosis with little effective treatment. In this study, we demonstrate that TOPK expression was highly upregulated in both SCLC cell lines and primary tumors. Similar to siRNA-mediated TOPK knockdown effects, treatment with a potent TOPK inhibitor, OTS514, effectively suppressed growth of SCLC cell lines (IC50 ; 0...
January 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28075522/crucial-role-of-carbonic-anhydrase-ix-in-tumorigenicity-of-xenotransplanted-adult-t-cell-leukemia-derived-cells
#4
Kentaro Nasu, Kazunori Yamaguchi, Tomoka Takanashi, Keiichi Tamai, Ikuro Sato, Shoji Ine, Osamu Sasaki, Kennichi Satoh, Nobuyuki Tanaka, Yuetsu Tanaka, Takuya Fukushima, Hideo Harigae, Kazuo Sugamura
Carbonic anhydrase IX (CA9) is a membrane-associated carbonic anhydrase that regulates cellular pH, is upregulated in various solid tumors, and is considered to be a therapeutic target. Here, we describe the essential role of CA9 in the tumorigenicity of cells derived from human adult T-cell leukemia/lymphoma (ATL). We previously established the highly tumorigenic ST1-N6 subline from the ATL-derived ST1 cell line by serial xenotransplantation in NOG mice. In the present study, we first show that CA9 expression is strongly enhanced in ST1-N6 cells...
January 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28064471/vasohibin-2-is-required-for-epithelial-mesenchymal-transition-of-ovarian-cancer-cells-by-modulating-tgf-%C3%AE-signaling
#5
Rie Norita, Yasuhiro Suzuki, Yutaka Furutani, Kazuki Takahashi, Yasuhiro Yoshimatsu, Katarzyna A Podyma-Inoue, Tetsuro Watabe, Yasufumi Sato
Vasohibin-2 (VASH2) is a homologue of VASH1, an endothelium-derived angiogenesis inhibitor. VASH2 is mainly expressed in cancer cells, and has been implicated in the progression of cancer by inducing angiogenesis and tumor growth. While VASH2 has been recently reported to be involved in epithelial-mesenchymal transition (EMT), its precise roles are obscure. The aim of the present study was to clarify the role of VASH2 in the EMT of cancer cells in relation to TGF-β signaling, which is a major stimulator of the EMT...
January 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28064454/hgf-met-in-cancer-progression-and-biomarker-discovery
#6
REVIEW
Kunio Matsumoto, Masataka Umitsu, Dinuka M De Silva, Arpita Roy, Donald P Bottaro
Signaling driven by hepatocyte growth factor (HGF) and MET receptor facilitates conspicuous biological responses such as epithelial cell migration, 3-D morphogenesis, and survival. The dynamic migration and promotion of cell survival induced by MET activation are bases respectively for invasion-metastasis and resistance against targeted drugs in cancers. Recent studies indicated that MET in tumor-derived exosomes facilitates metastatic niche formation and metastasis in malignant melanoma. In lung cancer, gene amplification-induced MET activation and ligand-dependent MET activation in autocrine/paracrine manner are causes for resistance to EGF receptor tyrosine kinase inhibitors and ALK inhibitors...
January 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28064445/a-panel-of-autoantibodies-against-multiple-tumor-associated-antigens-for-detecting-gastric-cancer
#7
Isamu Hoshino, Matsuo Nagata, Nobuhiro Takiguchi, Yoshihiro Nabeya, Atsushi Ikeda, Sana Yokoi, Akiko Kuwajima, Masatoshi Tagawa, Kazuyuki Matsushita, Yajima Satoshi, Shimada Hideaki
Gastric cancer is the second leading cause of cancer deaths in the world, and effective diagnosis is extremely important for good outcome. We assessed the diagnostic potential of an autoantibody panel that may provide a novel tool for the early detection of gastric cancer. We analyzed data from patients with gastric cancer and normal controls in a test and validation cohorts. Autoantibody levels were measured against a panel of six tumor-associated antigens [TAAs; p53, heat shock protein 70 (HSP70), HCC-22-5, peroxiredoxin VI (Prx VI), KM-HN-1, and p90 TAA (CYP2A)] via ELISA...
January 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28064442/tumor-derived-spheroids-relevance-to-cancer-stem-cells-and-clinical-applications
#8
REVIEW
Tatsuya Ishiguro, Hirokazu Ohata, Ai Sato, Kaoru Yamawaki, Takayuki Enomoto, Koji Okamoto
Recently, many types of in vitro three-dimensional (3D) culture systems have been developed to recapitulate the in vivo growth conditions of cancer. The cancer 3D culture methods aim to preserve the biological characteristics of original tumors better than conventional two-dimensional (2D) monolayer cultures, and include tumor-derived organoids, tumor-derived spheroids, organotypic multicellular spheroids, and multicellular tumor spheroids. The 3D culture methods differ in terms of cancer cell sources, protocols for cell handling, and the required time intervals...
January 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28064436/mir-181b-5p-ets1-and-c-met-pathway-exacerbates-the-prognosis-of-pancreatic-ductal-adenocarcinoma-after-radiation-therapy
#9
Hideo Tomihara, Daisaku Yamada, Hidetoshi Eguchi, Yoshifumi Iwagami, Takehiro Noda, Tadafumi Asaoka, Hiroshi Wada, Koichi Kawamoto, Kunihito Gotoh, Yutaka Takeda, Masahiro Tanemura, Masaki Mori, Yuichiro Doki
Preoperative chemoradiation therapy (CRT) for pancreatic ductal adenocarcinoma (PDAC) has emerged as a reasonable strategy that shows good prognostic impact. However, after preoperative CRT, resected specimens exhibited remnant tumor cells, which indicated that some tumor cells had acquired or were selected for resistance to CRT. Recently, two oncological mechanisms, the epithelial-mesenchymal transition (EMT) and the presence of cancer stem cells (CSCs) were reported to be associated with resistance in various cancers...
January 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28035720/wp1066-suppresses-macrophage-cell-death-induced-by-inflammasome-agonists-independently-of-its-inhibitory-effect-on-stat3
#10
Shino Honda, Daichi Sadatomi, Yasuo Yamamura, Kazutaka Nakashioya, Susumu Tanimura, Kohsuke Takeda
The compound WP1066 was originally synthesized by modifying the structure of AG490, which inhibits the activation of signal transducer and activator of transcription 3 (STAT3) by directly targeting Janus kinases (JAKs). WP1066 exhibits stronger anti-cancer activity than AG490 against malignant glioma and other cancer cells and is regarded as a promising therapeutic agent. By screening a small library of target-known compounds, we identified WP1066 as an inhibitor of macrophage cell death induced by agonists of the NLRP3 inflammasome, an intracellular protein complex required for the processing of the proinflammatory cytokine interleukin (IL)-1β...
December 30, 2016: Cancer Science
https://www.readbyqxmd.com/read/28032932/androgen-induced-lncrna-potef-as1-regulates-apoptosis-related-pathway-to-facilitate-cell-survival-in-prostate-cancer-cells
#11
Aya Misawa, Ken-Ichi Takayama, Tetsuya Fujimura, Yukio Homma, Yutaka Suzuki, Satoshi Inoue
Although long noncoding RNAs (lncRNA) have been associated with a variety of cancers, the interplay between lncRNAs and androgen receptor (AR) signaling in prostate cancer is still unclear. Here, we identified an androgen-dependent lncRNA, prostate, ovary, testis expressed protein family member-F antisense transcript-1 (POTEF-AS1), whose expression was regulated by AR in two androgen-dependent cells by using directional RNA-seq analysis. POTEF-AS1 promoted cell growth, repressed genes related to the toll-like receptor (TLR) signaling and apoptosis pathways and inhibited apoptosis in docetaxel-treated LNCaP cells...
December 29, 2016: Cancer Science
https://www.readbyqxmd.com/read/28032931/fkbp51-regulates-cell-motility-and-invasion-via-rhoa-signaling
#12
Miho Takaoka, Shun Ito, Yoshio Miki, Akira Nakanishi
FK506 binding protein 51 (FKBP51), a member of the immunophilin family, is involved in multiple signaling pathways, tumorigenesis, and chemoresistance. FKBP51 expression correlates with metastatic potential in melanoma and prostate cancer. However, the functions of FKBP51, particularly involving the regulation of cell motility and invasion, are not fully understood. We discovered two novel interacting partner proteins of FKBP51, i.e., deleted in liver cancer 1 (DLC1) and deleted in liver cancer 2 (DLC2), using immunoprecipitation and mass spectrometry...
December 29, 2016: Cancer Science
https://www.readbyqxmd.com/read/28032929/downregulation-of-mir-100-mir-125b-is-associated-with-lymph-node-metastasis-in-early-colorectal-cancer-with-submucosal-invasion
#13
Yasuteru Fujino, Shunsaku Takeishi, Kensei Nishida, Koichi Okamoto, Naoki Muguruma, Tetsuo Kimura, Shinji Kitamura, Hiroshi Miyamoto, Akiko Fujimoto, Jun Higashijima, Mitsuo Shimada, Kazuhito Rokutan, Tetsuji Takayama
A majority of early colorectal cancers (CRCs) with submucosal invasion undergo surgical operation despite very low incidence of lymph node metastasis. Our study aimed to identify microRNAs (miRNAs) specifically responsible for lymph node metastasis in submucosal CRCs. MicroRNA microarray analysis revealed that miR-100 and miR-125b expression levels were significantly lower in CRC tissues with lymph node metastases than in those without metastases. These results were validated by quantitative real-time PCR in a larger set of clinical samples...
December 29, 2016: Cancer Science
https://www.readbyqxmd.com/read/28032401/targeting-human-vasohibin-2-by-a-neutralizing-monoclonal-antibody-for-anti-cancer-treatment
#14
Takahiro Koyanagi, Yasuhiro Suzuki, Kazuki Komori, Yasushi Saga, Shigeki Matsubara, Hiroyuki Fujiwara, Yasufumi Sato
There are 2 members of the vasohibin (VASH) family, VASH1 and VASH2. VASH1 is expressed mainly in endothelial cells to inhibit angiogenesis, whereas VASH2 is expressed mainly in cancer cells to stimulate tumor growth. The aim of the present study was to establish neutralizing monoclonal antibody (mAb) against human VASH2 and apply it as an anti-cancer treatment. We previously raised mAbs against several synthetic peptides of hVASH1, and found that one of them exhibited neutralizing activity against hVASH1. Because of the similarity in the amino acid sequences between VASH1 and VASH2, we hypothesized that they shared the bioactive center...
December 29, 2016: Cancer Science
https://www.readbyqxmd.com/read/28032400/increasing-circulating-exosomes-carrying-trpc5-predicts-chemoresistance-in-metastatic-breast-cancer-patients
#15
Teng Wang, Kuan Ning, Ting-Xun Lu, Xu Sun, Linfang Jin, Xiaowei Qi, Jian Jin, Dong Hua
Chemoresistance, the major obstacle in breast cancer chemotherapy, results in unnecessary chemotherapy and wasting of medical resources. Up to now, no feasible method is available to predict chemoresistance before chemotherapy. In our previously study, elevated expression of transient receptor potential channel TRPC5 was found as an essential element for chemoresistance in breast cancer cells, and could be transferred to chemosensitive breast cancer cells through releasing extracellular vesicles (EVs)-containing TRPC5 from chemoresistant cells, resulting in acquired chemoresistance...
December 29, 2016: Cancer Science
https://www.readbyqxmd.com/read/28012234/hypoxia-promotes-the-phenotypic-change-of-aldehyde-dehydrogenase-activity-of-breast-cancer-stem-cells
#16
Akira Shiraishi, Kana Tachi, Nesrine Essid, Ikki Tsuboi, Masumi Nagano, Toshiki Kato, Toshiharu Yamashita, Hiroko Bando, Hisato Hara, Osamu Ohneda
Stable breast cancer cell (BCC) lines are valuable tools for the identification of breast cancer stem cell (BCSC) phenotypes that develop in response to several stimuli as well as for studying the basic mechanisms associated with the initiation and maintenance of BCSCs. However, the characteristics of individual, BCC-derived BCSCs varies and these cells show distinct phenotypes depending on the different BCSC markers used for their isolation. Aldehyde dehydrogenase (ALDH) activity is just such a recognized biomarker of BCSCs with a CD44(+) /CD24(-) phenotype...
December 23, 2016: Cancer Science
https://www.readbyqxmd.com/read/28012230/targeting-muc1-and-jnk-by-rna-interference-and-inhibitor-inhibit-the-development-of-hepatocellular-carcinoma
#17
Juan Wang, Wei-Hua Ni, Ke-Bang Hu, Xiao-Yu Zhai, Fei Xie, Jing Jie, Nan-Nan Zhang, Li-Na Jiang, Hong-Yan Yuan, Gui-Xiang Tai
Mucin 1 (MUC1), as an oncogene, is overexpressed in hepatocellular carcinoma (HCC) cells and promotes the progression and tumorigenesis of HCC through JNK/TGF-β signaling pathway. In the present study, RNA interference (RNAi) and JNK inhibitor SP600125, which target MUC1 and/or JNK, were used to treat HCC cells in vitro, and the results showed that both silencing the expression of MUC1 and blocking the activity of JNK inhibited the proliferation of HCC cells. In addition, MUC1-stable-knockdown and SP600125 significantly inhibited the growth of tumors in the subcutaneous transplant tumor models that established in BALB/c nude mice rather than MUC1 or JNK siRNAs transiently transfection...
December 23, 2016: Cancer Science
https://www.readbyqxmd.com/read/28012229/mir-3941-a-novel-microrna-that-controls-igbp1-expression-and-is-associated-with-malignant-progression-of-lung-adenocarcinoma
#18
Taiki Sato, Aya Shiba-Ishii, Yunjung Kim, Tomoko Dai, Ryan Edbert Husni, JeongMin Hong, Junko Kano, Shingo Sakashita, Tatsuo Iijima, Masayuki Noguchi
Immunoglobulin (CD79a) binding protein 1 (IGBP1) is universally overexpressed in lung adenocarcinoma and exerts an anti-apoptotic effect by binding to PP2Ac. However, the molecular mechanism of IGBP1 overexpression is still unclear. In the present study, we used a microRNA (miRNA) array and TargetScan Human software to detect IGBP1-related miRNAs that regulate IGBP1 expression. The miRNA array analysis revealed more than 100 miRNAs that are dysregulated in early invasive adenocarcinoma. On the other hand, in silico analysis using TargetScan Human revealed 79 miRNAs that are associated with IGBP1 protein expression...
December 23, 2016: Cancer Science
https://www.readbyqxmd.com/read/28012218/met4-expression-predicts-poor-prognosis-of-gastric-cancers-with-helicobacter-pylori-infection
#19
Naoko Sakamoto, Hironori Tsujimoto, Risa Takahata, Cao Brian, Zhao Ping, Nozomi Ito, Hideyuki Shimazaki, Takashi Ichikura, Kazuo Hase, George F Vande Woude, Nariyoshi Shinomiya
Role of HGF/SF-MET signaling is important in cancer progression, but its relation with Helicobacter pylori-positive gastric cancers remains to be elucidated. In total, 201 patients with primary gastric carcinoma who underwent curative or debulking resection without preoperative chemotherapy were studied. MET4 and anti-HGF/SF mAbs were used for immunohistochemical analysis. Survival of gastric cancer patients was estimated by Kaplan-Meier method and compared with log-rank. Cox proportional hazards models were fit to determine the independent association of MET-staining status with outcome...
December 23, 2016: Cancer Science
https://www.readbyqxmd.com/read/28012214/long-term-outcomes-of-proton-beam-therapy-in-patients-with-previously-untreated-hepatocellular-carcinoma
#20
Kuniaki Fukuda, Toshiyuki Okumura, Masato Abei, Nobuyoshi Fukumitsu, Kazunori Ishige, Masashi Mizumoto, Naoyuki Hasegawa, Haruko Numajiri, Kayoko Ohnishi, Hitoshi Ishikawa, Koji Tsuboi, Hideyuki Sakurai, Ichinosuke Hyodo
Long-term efficacy of proton beam therapy (PBT) remains unclear for patients with previously untreated hepatocellular carcinoma (HCC). We aimed to study the long-term outcomes of PBT according to Barcelona Clinic Liver Cancer (BCLC) staging classifications in patients with previously untreated HCC. The major eligibility criteria of this observational study were an Eastern Cooperative Oncology Group performance status (PS) 0-2, Child-Pugh grade A or B, previously untreated HCC covered within an irradiation field, and no massive ascites...
December 23, 2016: Cancer Science
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