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Cancer Science

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https://www.readbyqxmd.com/read/28211214/anti-cancer-stem-cell-activity-of-a-hedgehog-inhibitor-gant61-in-estrogen-receptor-positive-breast-cancer-cells
#1
Junichi Kurebayashi, Yoshikazu Koike, Yusuke Ohta, Wataru Saitoh, Tetsumasa Yamashita, Naoki Kanomata, Takuya Moriya
Estradiol (E2) increases not only the cell growth but also cancer stem cell (CSC) proportion in estrogen receptor (ER)-positive breast cancer cells. It was suggested that the non-canonical hedgehog (Hh) pathway activated by E2 plays an important role in the regulation of CSC proportion in ER-positive breast cancer cells. We studied anti-CSC activity of a non-canonical Hh inhibitor GANT61 in ER-positive breast cancer cells. Effects of GANT61 on the cell growth, cell cycle progression, apoptosis and CSC proportion were investigated in four ER-positive breast cancer cell lines...
February 17, 2017: Cancer Science
https://www.readbyqxmd.com/read/28211204/evaluation-of-the-enhanced-permeability-and-retention-effect-in-the-early-stages-of-lymph-node-metastasis
#2
Mamoru Mikada, Ariunbuyan Sukhbaatar, Yoshinobu Miura, Sachiko Horie, Maya Sakamoto, Shiro Mori, Tetsuya Kodama
Most solid cancers spread to new sites via the lymphatics before hematogenous dissemination. However, only a small fraction of an intravenously administered anti-cancer drug enters the lymphatic system to reach metastatic lymph nodes (LNs). Here, we show that the enhanced permeability and retention (EPR) effect is not induced during the early stages of LN metastasis. Luciferase-expressing tumor cells were injected into the subiliac LN of the MXH10/Mo-lpr/lpr mouse to induce metastasis to the proper axillary LN (PALN)...
February 17, 2017: Cancer Science
https://www.readbyqxmd.com/read/28208216/msc-derived-ccn2-promotes-the-proliferation-migration-and-invasion-of-human-tongue-squamous-cell-carcinoma-cells
#3
Yu-Ling Wu, Hong-Yu Li, Xiao-Peng Zhao, Jiu-Yang Jiao, Dong-Xiao Tang, Ling-Jian Yan, Quan Wan, Chao-Bin Pan
Recent studies have demonstrated that mesenchymal stem cells (MSCs) exhibit a tropism to tumors and form the tumor stroma. Additionally, we found that MSCs can secrete different types of factors. However, the involvement of MSC-derived factors in human tongue squamous cell carcinoma (TSCC) growth has not been clearly addressed. The CCN family includes multifunctional signaling molecules that affect the initiation and development events of various tumors. In our study, we report that CCN2/connective tissue growth factor (CTGF) was the most highly induced among the CCN family members in MSCs that were co-cultured with TSCC cells...
February 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28208209/the-emergence-of-tnik-inhibitors-in-cancer-therapeutics
#4
REVIEW
Tesshi Yamada, Mari Masuda
The outcome of patients with metastatic colorectal cancer remains unsatisfactory. To improve patient prognosis, it will be necessary to identify new drug targets based on molecules that are essential for colorectal carcinogenesis, and to develop therapeutics that target such molecules. The great majority of colorectal cancers (>90%) have mutations in at least one Wnt signaling pathway gene. Aberrant activation of Wnt signaling is a major force driving colorectal carcinogenesis. Several therapeutics targeting Wnt pathway molecules, including porcupine, frizzled receptors, and tankyrases, have been developed, but none of them have yet been incorporated into clinical practice...
February 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28207963/nardilysin-promotes-hepatocellular-carcinoma-through-activation-of-signal-transducer-and-activator-of-transcription-3
#5
Yosuke Kasai, Kan Toriguchi, Etsuro Hatano, Kiyoto Nishi, Mikiko Ohno, Tomoaki Yoh, Keita Fukuyama, Takahiro Nishio, Masayuki Okuno, Keiko Iwaisako, Satoru Seo, Kojiro Taura, Masato Kurokawa, Makoto Kunichika, Shinji Uemoto, Eiichiro Nishi
Nardilysin (NRDC) is a metalloendopeptidase of the M16 family. We previously showed that NRDC activates inflammatory cytokine signaling, including interleukin-6-signal transducer and activator of transcription 3 (STAT3) signaling. NRDC has been implicated in the promotion of breast, gastric, and esophageal cancer, as well as the development of liver fibrosis. In this study, we investigated the role of NRDC in the promotion of hepatocellular carcinoma (HCC), both clinically and experimentally. We found that NRDC expression was up-regulated 3-fold in HCC tissue compared to the adjacent non-tumor liver tissue, which was confirmed by immunohistochemistry and western blotting...
February 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28205334/long-non-coding-rna-tug1-promotes-migration-and-invasion-by-acting-as-a-cerna-of-mir-335-5p-in-osteosarcoma-cells
#6
Yong Wang, Tao Yang, Zhen Zhang, Ming Lu, Wei Zhao, Xiandong Zeng, Weiguo Zhang
Long non-coding RNAs (lncRNAs) have now become the new hotspots in an ocean of diseases including osteosarcoma. The function of taurine up-regulated gene 1 (TUG1) and its working mechanism in osteosarcoma remain unclear. In our research, we found that TUG1 was elevated and correlated with a poor prognosis in osteosarcoma patients. Also, the following functional experiment showed that decreased TUG1 could remarkably inhibit osteosarcoma cell migration and invasion, indicating that TUG1 functioned as an oncogene in osteosarcoma...
February 15, 2017: Cancer Science
https://www.readbyqxmd.com/read/28196303/the-long-noncoding-rna-schlah-suppresses-metastasis-of-hepatocellular-carcinoma-through-interacting-with-fus
#7
Zhouhong Ge, Zhuoan Cheng, Xinrong Yang, Xisong Huo, Ning Wang, Hui Wang, Cun Wang, Dishui Gu, Fangyu Zhao, Ming Yao, Jia Fan, Wenxin Qin
Emerging evidence has indicated that deregulation of long non-coding RNAs (lncRNAs) can contribute to the progression and metastasis of human cancer, including hepatocellular carcinoma (HCC). However, the roles of most lncRNAs in HCC remain largely unknown. Here we found a long noncoding RNA termed SchLAH (seven chromosome locus associated with HCC; also called BC035072) was generally downregulated in HCC. Low expression of SchLAH was significantly correlated with shorter overall survival of HCC patients. In vitro and in vivo assays indicated that overexpression of SchLAH inhibited the migration and lung metastasis of HCC cells...
February 14, 2017: Cancer Science
https://www.readbyqxmd.com/read/28192623/pd-l1-is-prognostic-factor-in-esophageal-squamous-cell-carcinoma-and-is-associated-with-egfr
#8
Wencheng Zhang, Qingsong Pang, Xiaodong Zhang, Cihui Yan, Qifeng Wang, Jinsong Yang, Shufei Yu, Xiao Liu, Yi Pan, Zhiyong Yuan, Ping Wang, Zefen Xiao
Programmed death-ligand 1 (PD-L1) expression either indicates immune inhibitory status or concurrent immune response. Although the relationship between PD-L1 and clinical outcomes has been studied widely in recent years, its role in prognosis of esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we assessed the significance of PD-L1 in ESCC and its association with epidermal growth factor receptor (EGFR) and radiation response. We found that PD-L1 was present both on the surface of tumor cells and tumor-infiltrating immune cells...
February 13, 2017: Cancer Science
https://www.readbyqxmd.com/read/28192620/ypc-21661-and-ypc-22026-novel-small-molecules-inhibit-znf143-activity-in-vitro-and-in-vivo
#9
Hirotaka Haibara, Ryuta Yamazaki, Yukiko Nishiyama, Masahiro Ono, Tsuneyuki Kobayashi, Atsuko Hokkyo-Itagaki, Fukiko Nishisaka, Hiroyuki Nishiyama, Akinobu Kurita, Takeshi Matsuzaki, Hiroto Izumi, Kimitoshi Kohno
Zinc-finger protein 143 (ZNF143) is a transcription factor that is involved in anticancer drug resistance and cancer cell survival. In the present study, we identified a novel small molecule N-(5-bromo-2-methoxyphenyl)-3-(pyridine-3-yl) propiolamide (YPC-21661) that inhibited ZNF143 promoter activity and down-regulated the expression of the ZNF143-regulated genes, RAD51, PLK1, and Survivin, by inhibiting the binding of ZNF143 to DNA. In addition, YPC-21661 was cytotoxic and induced apoptosis in the human colon cancer cell line, HCT116 and human prostate cancer cell line, PC-3...
February 13, 2017: Cancer Science
https://www.readbyqxmd.com/read/28192613/sniper-tacc3-induces-cytoplasmic-vacuolization-and-sensitizes-cancer-cells-to-bortezomib
#10
Nobumichi Ohoka, Katsunori Nagai, Norihito Shibata, Takayuki Hattori, Hiroshi Nara, Nobuo Cho, Mikihiko Naito
We previously developed a hybrid small molecule SNIPER (Specific and Nongenetic IAP-dependent Protein ERaser) against transforming acidic coiled-coil-3 (TACC3), SNIPER(TACC3), that induces proteasomal degradation of TACC3 protein. In this study, we found that SNIPER(TACC3) induces cytoplasmic vacuolization derived from endoplasmic reticulum (ER) and paraptosis-like cell death selectively in cancer cells. Mechanistic analysis suggests that accumulation of ubiquitylated protein aggregates that requires X-linked inhibitor of apoptosis protein (XIAP) induces ER stress, which results in ER-stress responses involving X-box binding protein-1 (XBP-1) and ER-derived vacuolization in cancer cells...
February 13, 2017: Cancer Science
https://www.readbyqxmd.com/read/28188685/sox2-dependent-inhibition-of-p21-is-associated-with-poor-prognosis-of-endometrial-cancer
#11
Kaoru Yamawaki, Tatsuya Ishiguro, Yutaro Mori, Kosuke Yoshihara, Kazuaki Suda, Ryo Tamura, Masayuki Yamaguchi, Masayuki Sekine, Katsunori Kashima, Masaya Higuchi, Masahiro Fujii, Koji Okamoto, Takayuki Enomoto
Sex-determining region Y-box 2 (SOX2) is an essential factor involved in the self-renewal and pluripotency of embryonic stem cells and has functions in cell survival and progression in many types of cancers. Here, we found that several endometrial cancer cell lines expressed SOX2, which was required for cell growth. Additionally, SOX2 overexpression regulated the expression of cyclin-dependent kinase inhibitor 1A (CDKN1A), and SOX2 specifically bound to p21 promoter DNA in endometrial cancer cell lines expressing SOX2...
February 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28188673/socs-potential-immune-checkpoint-molecules-for-cancer-immunotherapy
#12
REVIEW
Shunsuke Chikuma, Mitsuhiro Kanamori, Setsuko Mise-Omata, Akihiko Yoshimura
Inhibition of immune checkpoint molecules, PD-1 and CTLA4, has been shown to be a promising cancer treatment. PD-1 and CTLA4 inhibit TCR and co-stimulatory signals, respectively. The third T cell activation signal represents the signals from the cytokine receptors. The cytokine Interferon-γ (IFNγ) plays an important role in anti-tumor immunity by activating cytotoxic T cells (CTLs). Most cytokines use the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, and the suppressors of cytokine signaling (SOCS) family of proteins are major negative regulators of the JAK/STAT pathway...
February 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28188670/a-randomized-phase-ii-trial-of-personalized-peptide-vaccine-with-low-dose-cyclophosphamide-in-biliary-tract-cancer
#13
Takahisa Shirahama, Daisuke Muroya, Satoko Matsueda, Akira Yamada, Shigeki Shichijo, Masayasu Naito, Takuto Yamashita, Shinjiro Sakamoto, Koji Okuda, Kyogo Itoh, Tetsuro Sasada, Shigeru Yutani
Since the prognosis of advanced biliary tract cancer (aBTC) still remains very poor, new therapeutic approaches, including immunotherapies, need to be developed. In the current study, we conducted an open-label randomized phase II study to test whether low dose cyclophosphamide (CPA) could improve antigen-specific immune responses and clinical efficacy of personalized peptide vaccination (PPV) in 49 previously treated aBTC patients. Patients with aBTC refractory to at least one regimen of chemotherapies were randomly assigned to receive PPV with low dose CPA (100 mg/ day for 7 days before vaccination) (PPV/CPA, n=24) or PPV alone (n=25)...
February 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28182320/proton-beam-therapy-for-bone-sarcomas-of-the-skull-base-and-spine-a-retrospective-nationwide-multicenter-study-in-japan
#14
Yusuke Demizu, Masashi Mizumoto, Tsuyoshi Onoe, Naoki Nakamura, Yasuhiro Kikuchi, Tetsushi Shibata, Tomoaki Okimoto, Sakurai Hideyuki, Tetsuo Akimoto, Kota Ono, Takashi Daimon, Shigeyuki Murayama
We conducted a retrospective, nationwide multicenter study to evaluate the clinical outcomes of proton beam therapy for bone sarcomas of the skull base and spine in Japan. Eligibility criteria included: (1) histologically proven bone sarcomas of the skull base or spine, (2) no metastases, (3) ≥20 years of age, and (4) no prior treatment with radiotherapy. Of the 103 patients treated between January 2004 and January 2012, we retrospectively analyzed data from 96 patients who were followed-up for >6 months or had died within 6 months...
February 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/28182306/effect-of-a-hypoxic-microenvironment-after-radiofrequency-ablation-on-residual-hepatocellular-cell-migration-and-invasion
#15
Yuyang Tong, Haiyun Yang, Xiaolin Xu, Jingliang Ruan, Ming Liang, Jiayi Wu, Baoming Luo
Clinical observations have shown that the boundary of tumor ablation is often less than safe border and that the use of radiofrequency ablation (RFA) in the treatment of hepatocellular carcinoma (HCC) may probably accelerate its recurrence and metastasis. RFA can cause the formation of a transition zone between normal liver tissues and necrotic coagulation, where blood stagnation and thrombosis expose residual cancer cells to a hypoxic microenvironment. As the blocked vessels are slowly reperfused, the oxygen supply is gradually restored...
February 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/28182302/podoplanin-promotes-progression-of-malignant-pleural-mesothelioma-by-regulating-motility-and-focus-formation
#16
Shinji Takeuchi, Koji Fukuda, Tadaaki Yamada, Sachiko Arai, Satoshi Takagi, Gen-Ichiro Ishii, Atsushi Ochiai, Shotaro Iwakiri, Kazumi Itoi, Hisanori Uehara, Hiroshi Nishihara, Naoya Fujita, Seiji Yano
Malignant pleural mesothelioma (MPM) is characterized by dissemination and aggressive growth in the thoracic cavity. Podoplanin (PDPN) is an established diagnostic marker for MPM, but the function of PDPN in MPM is not fully understood. The purpose of this study was to determine the pathogenetic function of PDPN in MPM. Forty-seven of 52 tumors (90%) from Japanese patients with MPM and 3/6 (50%) MPM cell lines tested positive for PDPN. Knocking down PDPN in PDPN-high expressing MPM cells resulted in decreased cell motility...
February 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/28178396/immunological-evaluation-of-peptide-vaccination-for-cancer-patients-with-the-hla-a11-or-a33-allele
#17
Shijoro Sakamoto, Satoko Matsueda, Shinzou Takamori, Uhi Toh, Masanori Noguchi, Shigeru Yutani, Akira Yamada, Shigeki Shichijo, Teppei Yamada, Shigetaka Suekane, Kouichirou Kawano, Masayasu Naitou, Tetsuro Sasada, Noboru Hattori, Nobuoki Kohno, Kyogo Itoh
The HLA-A11 or -A33 allele is found in approximately 18% or 10% of the Asian population, respectively, but each of which is a minor allele worldwide, and therefore no clinical trials were previously conducted. To develop a therapeutic peptide vaccine for each of them, we investigated immunological responses of advanced cancer patients with the HLA-A11(+) /A11(+) (n=18) or -A33(+) /A33(+) (n=13) allele to personalized peptide vaccine (PPV) regimens. The primary sites of HLA-A11+/A11+ or -A33+/A33+ patients were the colon (n=4 or 2), stomach (2 or 3), breast (3 or 2), lung and pancreas(2 or 2), and so on...
February 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28178391/amino-terminal-enhancer-of-split-gene-aes-encodes-a-tumor-and-metastasis-suppressor-of-prostate-cancer
#18
Yoshiyuki Okada, Masahiro Sonoshita, Fumihiko Kakizaki, Naoki Aoyama, Yoshiro Itatani, Masayuki Uegaki, Hiromasa Sakamoto, Takashi Kobayashi, Takahiro Inoue, Tomomi Kamba, Akira Suzuki, Osamu Ogawa, M Mark Taketo
Major cause of cancer death is its metastasis to the vital organs. Few effective therapies are available for metastatic castration-resistant prostate cancer (PCa), and progressive metastatic lesions such as lymph nodes and bones cause mortality. We recently identified AES as a metastasis suppressor for colon cancer. Here, we have studied the roles of AES in PCa progression. We analyzed the relationship between AES expression and PCa stages of progression by immunohistochemistry of human needle biopsy samples...
February 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28178388/molecular-targeting-therapies-against-quantitative-abnormalities-in-gene-expression-with-malignant-tumors
#19
REVIEW
Toshiyuki Sakai, Yoshihiro Sowa
Genetic mutations in exons of oncogenes and tumor-suppressor genes causing qualitative abnormalities result in activation of the oncogenes and inactivation of the tumor-suppressor genes, thereby causing cancer. In contrast, we have previously demonstrated that decreases in the RB promoter activity by genetic or epigenetic abnormalities can also cause carcinogenesis. In addition, activation and inactivation of a variety of oncogenes and tumor-suppressor genes finally cause quantitative abnormalities in gene expression...
February 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28165654/identification-of-proteasomal-catalytic-subunit-psma6-as-a-therapeutic-target-for-lung-cancer
#20
Tomohiko Kakumu, Mitsuo Sato, Daiki Goto, Toshio Kato, Naoyuki Yogo, Tetsunari Hase, Masahiro Morise, Takayuki Fukui, Kohei Yokoi, Yoshitaka Sekido, Luc Girard, John D Minna, Lauren A Byers, John V Heymach, Kevin R Coombes, Masashi Kondo, Yoshinori Hasegawa
To identify potential therapeutic targets for lung cancer, we performed semi-genome-wide shRNA screening combined with the utilisation of genome-wide expression and copy number data. shRNA screening targeting 5,043 genes in NCI-H460 identified 51 genes as candidates. Pathway analysis revealed that the 51 genes were enriched for the five pathways, including ribosome, proteasome, RNA polymerase, pyrimidine metabolism and spliceosome pathways. We focused on the proteasome pathway that involved six candidate genes because its activation has been demonstrated in diverse human malignancies, including lung cancer...
February 6, 2017: Cancer Science
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