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Cancer Letters

Mariko Kikuchi, Hiroshi Katoh, Mina Waraya, Yoko Tanaka, Satoru Ishii, Toshimichi Tanaka, Nobuyuki Nishizawa, Keigo Yokoi, Naoko Minatani, Akira Ema, Yoshimasa Kosaka, Hirokazu Tanino, Keishi Yamashita, Masahiko Watanabe
Epigenetic silencing of HOPX has been shown frequent and specific in human cancers. HOPX is thought as a tumor suppressor gene and its promoter methylation is the main mechanism of down-regulation. In non-hereditary breast cancer, since roles of epigenetic modifications are more critical than in other cancers, the aim of this study is to seek into the roles and clinical relevance of epigenetic silencing of HOPX. Down-regulation of HOPX was observed in all human breast cancer cell lines tested. The promoter methylation was found in six of seven cell lines, and demethylating agents restored HOPX expression...
October 15, 2016: Cancer Letters
Jiefang Guo, Jun Hao, Hongxue Jiang, Jing Jin, Hongyu Wu, Zhendong Jin, Zhaoshen Li
Pancreatic cancer has the worst prognosis among all cancers and novel markers and therapeutic targets are desperately needed for this terribly deadly disease. Proteasome activator subunit 3 (PSME3) is highly involved in the initiation and progression of many human cancers. However, the potential effect of PSME3 on pancreatic cancer remains largely unknown. In the present study, we first found that PSME3 was significantly upregulated in pancreatic cancer cells and tissues at both mRNA and protein levels using qRT-PCR, western blot analysis, Oncomine data mining and immunohistochemical analysis...
October 15, 2016: Cancer Letters
Rei Mimoto, Naoe T Nihira, Shinichi Hirooka, Hiroshi Takeyama, Kiyotsugu Yoshida
Mammalian target of rapamycin (mTOR) inhibitor, everolimus, provides benefit for metastatic hormone receptor positive breast cancer after failure of the endocrine therapy. The present report highlights Dual Specificity Tyrosine Phosphorylation Regulated Kinase 2 (DYRK2) as a predictive marker for everolimus sensitivity. The key node and KEGG pathway analyses revealed that mTORC1 pathway is activated in DYRK2-depleted cells. Everolimus was more effective in DYRK2-depleted cells compared with control cells. In xenograft model, everolimus treatment significantly inhibited tumor growth compared with vehicle or eribulin treatment...
October 13, 2016: Cancer Letters
Yuan-Chin Tsai, Wei-Yu Chen, Man Kit Siu, Hong-Yuan Tsai, Juan Juan Yin, Jiaoti Huang, Yen-Nien Liu
It has been suggested that ETV6 serves as a tumor suppressor; however, its molecular regulation and cellular functions remain unclear. We used prostate cancer as a model system and demonstrated a molecular mechanism in which ETV6 can be regulated by epidermal growth factor receptor (EGFR) signaling through microRNA-96 (miR-96)-mediated downregulation. In addition, EGFR acts as a transcriptional coactivator that binds to the promoter of primary miR-96 and transcriptionally regulates miR-96 levels. We analyzed two sets of clinical prostate cancer samples, confirmed association patterns that were consistent with the EGFR-miR-96-ETV6 signaling model and demonstrated that the reduced ETV6 levels were associated with malignant prostate cancer...
October 13, 2016: Cancer Letters
Xiao Zou, Michael Blank
The p38 MAPK signaling pathway is a key signal transduction cascade that cancer cells employ to sense and adapt to a plethora of environmental stimuli, and has attracted much attention as a promising target for cancer therapy. Accumulating evidence suggests a dual role of p38 signaling in various types of cancers, wherein the p38 pathway can both suppress and promote tumor growth, metastasis and chemoresistance. This dual role of p38 signaling, along with its context dependence and versatility, poses a great challenge for developing efficient anticancer treatment...
October 8, 2016: Cancer Letters
Diego De Miguel, Ana Gallego Lleyda, José María Ayuso, Dolores Pejenaute-Ochoa, Vidal Jarauta, Isabel Marzo, Luis J Fernández, Ignacio Ochoa, Blanca Conde, Alberto Anel, Luis Martinez-Lostao
During the last years, a great effort has been invested into developing new TRAIL formulations with increased bioactivity, trying to overcome the resistance to conventional soluble TRAIL (sTRAIL) exhibited by many primary tumours. In our group, we have generated artificial lipid nanoparticles decorated with sTRAIL (LUV-TRAIL), emulating the physiological TRAIL-containing exosomes by which T-cells release TRAIL upon activation. We already demonstrated that LUV-TRAIL has greater cytotoxicity against both chemoresistant haematologic tumour cells and epithelial carcinoma cells compared to a form of sTRAIL similar to that used in clinical trials...
October 8, 2016: Cancer Letters
Fei-Yi-Fan Wang, Chun-Sheng Kang, Si-Yi Wang-Gou, Chun-Hai Huang, Cheng-Yuan Feng, Xue-Jun Li
Epidermal Growth Factor like domain 7 (EGFL7), also known as Vascular Endothelial-statin (VE-statin), is a secreted angiogenic factor. Recent data have demonstrated the potential oncogenic role and prognostic significance of EGFL7 in several human cancers. However, the clinical signature and further mechanisms of EGFL7's function in gliomagenesis are poorly understood. In the present study, we found that increased EGFL7 expression was associated with tumor grade. High expression of EGFL7 in EGFRvIII-positive glioblastoma multiforme (GBM) was determined to be a strong and independent risk factor for reduced life expectancy...
October 7, 2016: Cancer Letters
Chih-Chieh Yu, Wanglong Qiu, Caroline S Juang, Mahesh M Mansukhani, Balazs Halmos, Gloria H Su
Mutant allele specific imbalance (MASI) was initially coined to describe copy number alterations associated with the mutant allele of an oncogene. The copy number gain (CNG) specific to the mutant allele can be readily observed in electropherograms. With the development of genome-wide analyses at base-pair resolution with copy number counts, we can now further differentiate MASI into those with CNG, with copy neutral alteration (also termed acquired uniparental disomy; UPD), or with loss of heterozygosity (LOH) due to the loss of the wild-type (WT) allele...
October 7, 2016: Cancer Letters
Tsang-Chih Kuo, Chi-Kuan Chen, Kuo-Ti Hua, Pei Yu, Wei-Jiunn Lee, Min-Wei Chen, Yung-Ming Jeng, Ming-Hsien Chien, Kuang-Tai Kuo, Michael Hsiao, Min-Liang Kuo
Glutaminolysis that catabolizes glutamine to glutamate plays a critical role in cancer progression. Glutaminase 2 (GLS2) has been reported as a tumor suppressor. Recent studies implied that GLS2 may display its multifunction besides classical metabolic feature by different localizations and potential protein binding domains. Here, we showed that GLS2 expression correlates inversely with stage, vascular invasion, tumor size and poor prognosis in human hepatocellular carcinoma (HCC) tissues. We found that GLS2 significantly represses cell migration, invasion and metastasis of HCC through downregulation of Snail in vitro and in vivo...
October 7, 2016: Cancer Letters
Yiwen Bu, Guoshuai Cai, Yi Shen, Chenfei Huang, Xi Zeng, Yu Cao, Chuan Cai, Yuhong Wang, Dan Huang, Duan-Fang Liao, Deliang Cao
Inactivation of p53 occurs frequently in various cancers. RITA is a promising anticancer small molecule that dissociates p53-MDM2 interaction, reactivates p53 and induces exclusive apoptosis in cancer cells, but acquired RITA resistance remains a major drawback. This study found that the site-differential phosphorylation of nuclear factor-κB (NF-κB) RelA/p65 creates a barcode for RITA chemosensitivity in cancer cells. In naïve MCF7 and HCT116 cells where RITA triggered vast apoptosis, phosphorylation of RelA/p65 increased at Ser536, but decreased at Ser276 and Ser468; oppositely, in RITA-resistant cells, RelA/p65 phosphorylation decreased at Ser536, but increased at Ser276 and Ser468...
October 6, 2016: Cancer Letters
Pei Jing, Shousong Cao, Shuangli Xiao, Xiaoqin Zhang, Siyun Ke, Famin Ke, Xin Yu, Li Wang, Shurong Wang, Yuling Luo, Zhirong Zhong
The peptide aptamer DUP-1 targets prostate-specific membrane antigen (PSMA)-negative cells, while the RNA aptamer A10-3.2 targets PSMA-positive prostate cancer cells. Moreover, the tumor-suppressor gene phosphatase and tensin homolog (PTEN) and the chemotherapeutic agent doxorubicin (DOX) effectively inhibit prostate cancer, and a recombinant adenovirus (Ad5) mediates high gene transfer efficiency. Here, we design a dual-aptamer modified tumor targeting gene and DOX delivery system mediated by recombinant adenovirus (A10-3...
October 6, 2016: Cancer Letters
Jipei Du, Yufang Wang, Degao Chen, Guangyu Ji, Qizhao Ma, Shiping Liao, Yanjiang Zheng, Ji Zhang, Yiping Hou
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is well known for its ability to preferentially induce apoptosis in malignant cells without causing damage to most normal cells. However, inherent and acquired resistance of tumor to TRAIL-induced apoptosis limits its therapeutic applicability. Here we show that the orally available tyrosine kinase inhibitor, BAY61-3606, enhances the sensitivity of human colon cancer cells, especially those harboring active mutations in Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene, to TRAIL-induced apoptosis in vitro and in vivo...
October 6, 2016: Cancer Letters
Tian Fang, Hongwei Lv, Fuquan Wu, Changzheng Wang, Ting Li, Guishuai Lv, Liang Tang, Linna Guo, Shanhua Tang, Dan Cao, Mengchao Wu, Wen Yang, Hongyang Wang
Accumulating evidence suggests that cancer stem cells (CSCs), a small subset of cancer cells, are responsible for tumor initiation, progression, relapse and metastasis. Musashi 2 (MSI2), a RNA-binding protein, was proposed to be a potent oncogene playing key roles in myeloid leukemia and gastrointestinal malignancies. However, it remains elusive how MSI2 regulates stem cell features in HCC. Herein, we demonstrated that MSI2 was highly expressed in liver CSCs. Overexpression or knockdown of MSI2 altered CSC-related gene expression, self-renewal as well as resistance to chemotherapy in HCC cell lines...
October 6, 2016: Cancer Letters
Mingqi Li, Cheng Yang, Xin Liu, Liang Yuan, Fubin Zhang, Muhong Wang, Dazhuang Miao, Xinyue Gu, Shixiong Jiang, Binbin Cui, Jinxue Tong, Zhiwei Yu
Ephrin Type-A Receptor 3 (EphA3) belongs to the ephrin receptor subfamily of the protein tyrosine kinase family, and plays an important role in embryogenesis and neurogenesis. This study aimed to investigate the role of EphA3 in promoting malignant transformation of colorectal epithelial cells, and explore underlying molecular mechanisms. Colorectal cancer tissue specimens from 68 patients were analyzed for EphA3 expression. EphA3 expression levels were manipulated in rat colon epithelial cell lines. We found that EphA3 expression level in tumor tissues was associated with patient age (P = 0...
October 6, 2016: Cancer Letters
Pranav Gupta, Rishil J Kathawala, Liuya Wei, Fang Wang, XiaoKun Wang, Brian J Druker, Li-Wu Fu, Zhe-Sheng Chen
Chronic Myeloid Leukemia (CML) is largely caused by the Philadelphia (Ph) chromosome carrying the Break point Cluster Region-Abelson (BCR-ABL) oncogene. Imatinib is a BCR-ABL-targeted therapy and considered the standard of care in CML management. Resistance to imatinib therapy often develops because of mutations in the BCR-ABL kinase domain. In this study, we evaluated PBA2, a novel BCR-ABL inhibitor, for its anti-cancer activity against BCR-ABL expressing BaF3 cells. PBA2 shows potent activity against wild-type and T315I mutated BaF3 cells as compared with imatinib...
October 5, 2016: Cancer Letters
Chuangyu Wen, Junxiong Chen, Di Zhang, Huihui Wang, Jia Che, Qiyuan Qin, Lu He, Zerong Cai, Mengmeng Lin, Qiong Lou, Lanlan Huang, Daici Chen, Aikichi Iwamoto, Donglin Ren, Lei Wang, Ping Lan, Jianping Wang, Huanliang Liu, Xiangling Yang
5-fluorouracil (5-FU)-based chemotherapy is the main chemotherapeutic approach for colorectal cancer (CRC) treatment. Because chemoresistance occurs frequently and significantly limits CRC therapies, a novel agent is needed. Pseudolaric acid B (PAB), a small molecule derived from the Chinese medicinal herb ''Tujinpi'', exhibits strong cytotoxic effects on a variety of cancers. However, the detailed mechanisms by which PAB inhibits CRC cell growth and its potential role in overcoming 5-FU resistance have not been well studied...
October 3, 2016: Cancer Letters
Jia You, Jia Liu, Yantao Bao, Liqun Wang, Yang Yu, Lei Wang, Di Wu, Chang Liu, Nan Wang, Fei Wang, Falin Wang, Lu Xu, Xing Tian, Hongbin Liang, Yating Gao, Rongwei Guan, Jing Bai, Xiangning Meng, Wenjing Sun, Xin-Yuan Guan, Chunyu Zhang, Songbin Fu, Yan Jin
Previous studies have shown that the oncogene SEI1 is highly expressed in ovarian carcinomas, and promoting genomic instability. However, the molecular mechanism of SEI1 in promoting genomic instability remains unclear. We observed SEI1 overexpression in 30 of 46 cases of ovarian cancer compared to non-tumor tissues and the overexpression of SEI1 was positively associated with the tumor FIGO stage. Our functional studies revealed that overexpression of SEI1 could induce genomic instability and increased DNA strand breaks...
October 3, 2016: Cancer Letters
Lei Chang, Yufeng Yuan, Cuicui Li, Tao Guo, Haolong Qi, Yusha Xiao, Xu Dong, Zhisu Liu, Quanyan Liu
Emerging evidence suggests that small nucleolar RNAs (snoRNAs) and their host genes (SNHGs) have malfunctioning roles in the development of human cancers. We globally investigated the molecular mechanisms by which snoRNA host gene 6 (SNHG6) promotes hepatocellular carcinoma (HCC) progression using human tissues and cell lines. We found that SNHG6 is overexpressed in HCC tissues and in hepatoma cell lines and is closely associated with histologic grade, hepatitis B virus DNA, Barcelona Clinic Liver Cancer stage and portal vein tumor thrombus in patients with HCC...
October 1, 2016: Cancer Letters
Guoke Liu, Xiaoyu Fan, Min Tang, Rui Chen, Hao Wang, Rongjie Jia, Xuyu Zhou, Wei Jing, Huajing Wang, Yang Yang, Fan Yin, Huafeng Wei, Bohua Li, Jian Zhao
Hepatocellular carcinoma (HCC) is a major health burden worldwide for its high incidence and mortality. Osteopontin (OPN) is a chemokine-like, matricellular phosphoglycoprotein whose expression is elevated in various types of cancer including HCC. OPN has been shown to be involved in tumorigenesis, chemo-resistance, metastasis and sustaining stem-like properties of cancer cells. Autophagy is a cellular process by which cytoplasmic components are degraded and recycled for maintaining cellular homeostasis. There is increasing evidence supports that autophagy plays a critical role for stem-like properties and chemo-resistance of cancer cells...
October 1, 2016: Cancer Letters
Min Tu, Cheng Lu, Nan Lv, Jishu Wei, Zipeng Lu, Chunhua Xi, Jianmin Chen, Feng Guo, Kuirong Jiang, Qiang Li, Junli Wu, Guoxin Song, Shui Wang, Wentao Gao, Yi Miao
Vasohibin 2 (VASH2) is an angiogenic factor and cancer-related protein that acts via paracrine mechanisms. Here, we investigated the angiogenic function and mechanism of action of VASH2 in 200 human breast cancer tissues by performing immunohistochemical staining, western blot, indirect sandwich enzyme-linked immunosorbent assay (ELISA), and a semi-quantitative sandwich-based antibody array. Breast cancer cells stably overexpressing VASH2 or with knocked-down VASH2 were established and used for in vivo and in vitro models...
October 1, 2016: Cancer Letters
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