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Current Cancer Drug Targets

Lei Lei, Yuan Wang, Yi-Wen Zheng, Liang-Ru Fei, Hao-Yue Shen, Zhi-Han Li, Wen-Jing Huang, Juan-Han Yu, Hong-Tao Xu
Nemo-like kinase (NLK) is an evolutionarily conserved MAP kinase-related kinase involved in the pathogenesis of several human cancers. We examined the expression of NLK in lung cancer tissues through western blot analysis. We enhanced or knocked down NLK expression by gene transfection or RNA interference, respectively, in lung cancer cells and examined expression alterations of key proteins in the Wnt signaling pathway and in epithelial-mesenchymal transition (EMT). We also examined the roles of NLK in the proliferation and invasiveness of lung cancer cells by cell proliferation, colony formation, and Matrigel invasion assays...
November 19, 2018: Current Cancer Drug Targets
Omel Baneen Qallandar, Faeza Ebrahimi, Farhadul Islam, Riajul Wahab, Bin Qiao, Peter Reher, Vinod Gopalan, Alfred King-Yin Lam
BACKGROUND: Co-culture of cancer cells with alveolar bone cells could modulate bone invasion and destructions. However, the mechanisms of interaction between oral squamous cell carcinoma (OSCC) and bone cells remain unclear. OBJECTIVE: The aim of this study is to analyse the direct and indirect effects of OSCC cells in the stimulation of osteolytic activity and bone invasion. METHOD: Direct co-culture was achieved by culturing OSCC (TCA8113) with a primary alveolar bone cell line...
November 2, 2018: Current Cancer Drug Targets
Yige Qi, Ting Yan, Lu Chen, Qiang Zhang, Weishu Wang, Xu Han, Dangdang Li, Jinming Shi, Guangchao Sui
The oncoprotein binding (OPB) domain of Yin Yang 1 (YY1) consists of 26 amino acids between G201 and S226, and is involved in YY1 interaction with multiple oncogene products, including MDM2, AKT, EZH2 and E1A. Through the OPB domain, YY1 promotes the oncogenic or proliferative regulation of these oncoproteins in cancer cells. We previously demonstrated that a peptide with the OPB sequence blocked YY1-AKT interaction and inhibited breast cancer cell proliferation. In the current study, we characterized the OPB domain and determined a minimal region for peptide design to suppress cancer cells...
October 31, 2018: Current Cancer Drug Targets
Caixia Liang, Ningning Zhang, Qiaoyun Tan, Shuxia Liu, Rongrong Luo, Yanrong Wang, Yaunkai Shi, Xiaohong Han
BACKGROUND: Crizotinib established the position of anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKI) in the treatment of non-small cell lung cancer(NSCLC) while the therapy-resistance hindered those patients from benefitting continuously from the treatment. CT-707 is an inhibitor of ALK/focal adhesion kinase (FAK) and IGFR-1. H2228CR (crizotinib resistance, CR) and H3122CR NSCLC cell lines were generated from the parental cell line H2228 (EML4-ALK, E6a/b:A20, variant 3) and H3122(EML4-ALK, E13:A20, variant 1), respectively...
October 31, 2018: Current Cancer Drug Targets
Mingxia Wu, Christy W S Tong, Wei Yan, Kenneth K W To, William C S Cho
The stability of mRNA is one of the key factors governing the regulation of eukaryotic gene expression and function. Human antigen R (HuR) is a RNA-binding protein that regulates the stability, translation, and nucleus-to-cytoplasm shuttling of its target mRNAs. While HuR is normally localized within the nucleus, it has been shown that HuR binds mRNAs in the nucleus and then escorts the mRNAs to the cytoplasm where HuR protects them from degradation. It contains several RNA recognition motifs, which specifically bind to adenylate and uridylate-rich regions within the 3'-untranslated region of the target mRNA to mediate its effect...
October 31, 2018: Current Cancer Drug Targets
María Jesús Ramírez-Expósito, María Dolores Mayas, María Pilar Carrera-González, José Manuel Martínez-Martos
BACKGROUND: Brain tumorigenesis is related to oxidative stress and a decreased response of antioxidant defense systems. Due to it is well known that gender differences exists in the incidence and survival rates of brain tumors, it is important to recognize and understand the ways in which their biology can differ. OBJECTIVE: To analyze gender differences in redox status in animals with chemically-induced brain tumors. METHODS: Oxidative stress parameters, non-enzyme and enzyme antioxidant defense systems are assayed in animals with brain tumors induced by transplacental N-ethyl-N-nitrosourea (ENU) administration...
October 18, 2018: Current Cancer Drug Targets
Richard L Carpenter, Yesim Gokmen-Polar
Heat shock factor 1 (HSF1) was discovered in 1984 as the master regulator of the heat shock response. In this classical role, HSF1 is activated following cellular stresses such as heat shock that ultimately lead to HSF1-mediated expression of heat shock proteins to protect the proteome and survive these acute stresses. However, it is now becoming clear that HSF1 also plays a significant role in several diseases, perhaps none more prominent than cancer. HSF1 appears to have a pleiotropic role in cancer by supporting multiple facets of malignancy including migration, invasion, proliferation, and cancer cell metabolism among others...
October 18, 2018: Current Cancer Drug Targets
Yuanyuan Song, Peng Liu, Yu Huang, Yanfang Guan, Xiaohong Han, Yuankai Shi
BACKGROUND: Leptomeningeal metastases (LM) are much more frequent in patients of non-small lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) shows promising efficacy for LM. OBJECTIVE: The aim of this study was to analyze the concentration of osimertinib and gene variation of circulating tumor DNA (ctDNA) in human plasma and cerebrospinal fluid (CSF)...
October 17, 2018: Current Cancer Drug Targets
Jia Wei, Ling Ma, Chenglong Li, Christopher R Pierson, Jonathan L Finlay, Jiayuh Lin
BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. Despite improvement in overall survival rate, it still lacks an effective targeted treatment strategy. The Janus family of cytoplasmic tyrosine kinases (JAKs) and Src kinases, upstream protein kinases of signal transducer and activator of transcription 3 (STAT3), play important roles in medulloblastoma pathogenesis and therefore represent potential therapeutic targets. METHODS: In this report, we examined the inhibitory efficacy of the JAK1/2 inhibitor, ruxolitinib, the JAK3 inhibitor, tofacitinib and two Src inhibitors, KX2-391 and dasatinib...
October 16, 2018: Current Cancer Drug Targets
Shunbin Ning, Ling Wang
The multifunctional signaling hub p62 is well recognized as ubiquitin sensor and selective autophagy adaptor under myriad stress conditions including cancer. As a ubiquitin sensor, p62 promotes NFκB activation by facilitating TRAF6 ubiquitination and aggregation. As a selective autophagy receptor, p62 links ubiquitinated substrates including p62 itself for lysosome-mediated degradation. p62 plays crucial roles in myriad cellular processes including DNA damage response, aging/senescence, infection and immunity, chronic inflammation, and cancerogenesis, dependent on or independent of autophagy...
October 16, 2018: Current Cancer Drug Targets
Panpan Ma, Xiaoying Si, Qiubing Chen, Lijun Ma, Meili Hou, Zhigang Xu, Yuejun Kang, Jianglin Wang, Bo Xiao
BACKGROUND: Oral administrations of microparticles (MPs) and nanoparticles (NPs) have been widely explored as therapeutic approaches for treatment of ulcerative colitis (UC). However, no previous study has comparatively investigated the therapeutic efficacy of MPs and NPs. METHODS: In this study, curcumin (CUR)-loaded MPs (CUR-MPs) and CUR-loaded NPs (CUR-NPs) were fabricated using an emulsion-solvent evaporation method. Their therapeutic efficacies against UC were comparatively studied...
October 16, 2018: Current Cancer Drug Targets
Junjie Zou, Juanfang Lin, Chao Li, Ruirui Zhao, Lulu Fan, Jesse Yu, Jingwei Shao
BACKGROUND: Cancer metastasis has emerged as a major public health threat that cause majority of cancer fatalities. Traditional chemotherapeutics have been effective in the past but suffer from low therapeutic efficiency and harmful side-effects. Recently, it has been reported ursolic acid (UA), one of the naturally abundant pentacyclic triterpenes, possesses a wide range of biological activities including anti-inflammatory, anti-atherosclerotic, and anti-cancer properties. More importantly, UA has the features of low toxicity, liver protection and the potential of anti-cancer metastasis...
October 16, 2018: Current Cancer Drug Targets
Li-Juan Yan, Xin-Hong Guo, Wei-Ping Wang, Yu-Rong Hu, Shao-Feng Duan, Ying Liu, Zhi Sun, Sheng-Nan Huang, Hui-Li Li
MicroRNA (miRNA) therapy, which was widely considered to treat a series of cancer, has been confronted with numerous obstacles to being delivered into target cells because of its easy biodegradation and instability. In this research, we successfully constructed 11-mercaptoundecanoic acid modified gold nanocages (AuNCs)/polyethyleneimine (PEI)/miRNA/hyaluronic acid (HA) complexes (abbreviated as AuNCs/PEI/miRNA/HA) using a layer-by-layer method for target-specific intracellular delivery of miRNA by HA receptor mediated endocytosis...
October 16, 2018: Current Cancer Drug Targets
Gang Wang, Jun-Jie Wang, Rui Guan, Yan Sun, Feng Shi, Jing Gao, Xing-Li Fu
Colorectal cancer is a heterogeneous group of diseases that result from the accumulation of different sets of genomic alterations, together with epigenomic alterations, and it is influenced by tumor-host interactions, leading to tumor cell growth and glycolytic imbalances. This review summarizes recent findings that involve multiple signaling molecules and downstream genes in the dysregulated glycolytic pathway. This paper further discusses the role of the dysregulated glycolytic pathway in the tumor initiation, progression and the concomitant systemic immunosuppression commonly observed in colorectal cancer patients...
October 15, 2018: Current Cancer Drug Targets
Zhiquan Liang, Ziwen Lu, Yafei Zhang, Dongsheng Shang, Ruyan Li, Lanlan Liu, Zhicong Zhao, Peishan Zhang, Qiong Lin, Chunlai Feng, Yibang Zhang, Peng Liu, Zhigang Tu, Hanqing Liu
Ovarian cancer is a leading cause of death worldwide from gynecological malignancies, mainly because there are few early symptoms and the disease is generally diagnosed at an advanced stage. In addition, despite the effectiveness of cytoreductive surgery for ovarian cancer and the high response rates to chemotherapy, survival has improved little over the last 20 years. The management of patients with ovarian cancer also remains similar despite studies showing striking differences and heterogeneity among different subtypes...
October 9, 2018: Current Cancer Drug Targets
Yiting Yin, Xin Qi, Yuan Qiao, Huaxiang Liu, Zihan Yan, Hao Li, Zhen Liu
The notion that proteasome inhibitor bortezomib (BTZ) induced intracellular oxidative stress resulting in peripheral neuropathy has been generally accepted. The association of mitochondrial dysfunction, cell apoptosis, and endoplasmic reticulum (ER) stress with intracellular oxidative stress is ambiguous and still needs to be investigated. Here we report a mechanism underlying the action of BTZ-induced intracellular oxidative stress, mitochondrial dysfunction, cell apoptosis, and ER stress via the activation of activating transcription factor 3 (ATF3) in primary cultured dorsal root ganglion (DRG) neurons and in DRG from painful peripheral neuropathic rats...
October 3, 2018: Current Cancer Drug Targets
Jie Liu, Xiao Tan, Wennan Zhao, Jing Liu, Xiaoxue Xing, Guanwei Fan, Ping Zhang, Zhe Zhang, Yuxu Zhong, Dexin Kong
BACKGROUND: Metastasis is the main cause of lethality of prostate cancer. Inhibition of metastasis is expected to be a promising approach for prostate cancer therapy. Phosphatidylinositol 3-kinase (PI3K)/Akt pathway is known to play key roles in cell growth, migration, etc. Objective: Investigate the antimetastatic activities of pan-PI3K inhibitor ZSTK474 on prostate cancer DU145 cells. METHODS: 1. In vitro effect of ZSTK474 on the migration, invasion and adhesion of DU145 cells was determined with Transwell migration assay and wound healing assay, Tranwell invasion assay, and adhesion assay, respectively...
September 10, 2018: Current Cancer Drug Targets
Mousumi Tania, Jakaria Shawon, Kazi Saif, Rudolf Kiefer, Mahdi Safaei Khorram, Mohammad A Halim, Md Asaduzzaman Khan
Cordycepin is a small molecule from medicinal mushroom Cordyceps, which has been reported for anticancer properties. In this study, we investigated cordycepin effect on cervical cancer cells in vitro. Results indicate that treatment of cordycepin controlled SiHa and Hela cervical cancer cell growth, increased the rate of their apoptosis, and interfered with cell cycle, specifically elongated S-phase. By using qPCR, we investigated the expression of anti-apoptotic and pro-apoptotic proteins as well as cell cycle protein's expression in mRNA levels, and found there was a downregulation of cell cycle proteins CDK-2, CYCLIN-A2 and CYCLIN-E1 by cordycepin treatment but no significant change in pro-apoptotic or anti-apoptotic proteins...
September 4, 2018: Current Cancer Drug Targets
Merve Aksoz, Esra Albayrak, Galip Servet Aslan, Raife Dilek Turan, Lamia Yazgi Alyazici, Pinar Siyah, Emre Can Tusuz, Serli Canikyan, Dogacan Yucel, Neslihan Meric, Zafer Gulbas, Fikrettin Sahin, Fatih Kocabas
c-Myc plays a major role in the maintenance of glycolytic metabolism and hematopoietic stem cell (HSC) quiescence. Targeting modulators of HSC quiescence and metabolism could lead to HSC cell cycle entry with concomitant expansion. Here we show that c-Myc inhibitor 10074-G5 treatment leads to 2-fold increase in murine LSKCD34low HSC compartment post 7 days. In addition, c-Myc inhibition increases CD34+ and CD133+ human HSC number. c-Myc inhibition leads to downregulation of glycolytic and cyclin-dependent kinase inhibitor (CDKI) gene expression ex vivo and in vivo...
September 4, 2018: Current Cancer Drug Targets
Md Zahidul I Pranjol, Nicholas J Gutowski, Michael Hannemann, Jacqueline L Whatmore
BACKGROUND: Metastasis still remains the major cause of therapeutic failure, poor prognosis and high mortality in epithelial ovarian cancer (EOC) patients. Previously, we showed that EOC cells secrete a range of factors with potential pro-angiogenic activity, in disease-relevant human microvascular omental endothelial cells (HOMECs), including the lysosomal protease cathepsin L (CathL). Thus, the aim of this study was to examine potential pro-proliferative and pro-migratory effects of CathL in HOMECs and the activated signalling pathways, and whether these proangiogenic responses are dependent on CathL-catalytic activity...
August 31, 2018: Current Cancer Drug Targets
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