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https://www.readbyqxmd.com/read/28098872/trim29-promotes-progression-of-thyroid-carcinoma-via-activating-p13k-akt-signaling-pathway
#1
Jinkai Xu, Zongyu Li, Qinghua Su, Jun Zhao, Jiancang Ma
Thyroid cancer (TC) is a common malignancy of the endocrine system. Abnormal expression of tripartite motif-containing 29 (TRIM29) has been reported to promote tumorigenesis and predict poor prognosis in several human malignancies. The aim of this study was to assess the involvement of TRIM29 in the significance and prognosis of TC. Fifty-six tumor samples and their clinicopathological para-meters were obtained from TC patients; the expression level of TRIM29 was detected by RT-qPCR and western blotting. TRIM29 expression was knocked down by small interfering RNA (siRNA) among TT, TPC-1, and K1 cells to investigate the biological role of TRIM29 in TC cells...
January 13, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28091581/icaritin-enhances-mesc-self-renewal-through-upregulating-core-pluripotency-transcription-factors-mediated-by-er%C3%AE
#2
Wing Pui Tsang, Fengjie Zhang, Qiling He, Waijiao Cai, Jianhua Huang, Wai Yee Chan, Ziyin Shen, Chao Wan
Utilization of small molecules in modulation of stem cell self-renewal is a promising approach to expand stem cells for regenerative therapy. Here, we identify Icaritin, a phytoestrogen molecule enhances self-renewal of mouse embryonic stem cells (mESCs). Icaritin increases mESCs proliferation while maintains their self-renewal capacity in vitro and pluripotency in vivo. This coincides with upregulation of key pluripotency transcription factors OCT4, NANOG, KLF4 and SOX2. The enhancement of mESCs self-renewal is characterized by increased population in S-phase of cell cycle, elevation of Cylin E and Cyclin-dependent kinase 2 (CDK2) and downregulation of p21, p27 and p57...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28079286/design-synthesis-biological-evaluation-and-3d-qsar-analysis-of-podophyllotoxin-dioxazole-combination-as-tubulin-targeting-anticancer-agents
#3
Zi-Zhen Wang, Wen-Xue Sun, Xue Wang, Ya-Han Zhang, Han-Yue Qiu, Jin-Liang Qi, Yan-Jun Pang, Gui-Hua Lu, Xiao-Ming Wang, Fu-Gen Yu, Yong-Hua Yang
The advancement of cancer fighting drugs has never been a simple linear process. Those drugs design professionals begin to find inspiration from the nature after failing to find the ideal products by creative drugs design and high-throughput screening. To obtain new molecules for inhibiting tubulin, podophyllotoxin was adopted as the leading compound and 1,3,4-oxadiazole was brought in to the C-4 site of podophyllotoxin in this research. A series of seventeen podophyllotoxin derived esters have been achieved and then evaluated their antitumor activities against four different cancer cell lines: A549, MCF-7, HepG2 and HeLa...
January 12, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28078560/knockdown-of-pycr1-inhibits-cell-proliferation-and-colony-formation-via-cell-cycle-arrest-and-apoptosis-in-prostate-cancer
#4
Tengyue Zeng, Libing Zhu, Min Liao, Wenli Zhuo, Shunliang Yang, Weizhen Wu, Dong Wang
Pyrroline-5-carboxylate reductase 1 (PYCR1) is an enzyme involved in cell metabolism, which has been shown to be up-regulated in cancers. However, the functions of PYCR1 in prostate cancers (PCa) are still largely unknown. In the present study, we found that PYCR1 was highly expressed in prostate cancer tissues and then knocked down PYCR1 in PCa cell lines (DU145, PC-3 and LNCap) via lentivirus-mediated gene delivery and analyzed its biological function. Both qRT-PCR and western blotting indicated that PYCR1 was suppressed efficiently after sh-PYCR1 infection...
February 2017: Medical Oncology
https://www.readbyqxmd.com/read/28059623/coordinating-cell-cycle-regulated-histone-gene-expression-through-assembly-and-function-of-the-histone-locus-body
#5
Robert J Duronio, William F Marzluff
Metazoan replication-dependent (RD) histone genes encode the only known cellular mRNAs that are not polyadenylated. These mRNAs end instead in a conserved stem-loop, which is formed by an endonucleolytic cleavage of the pre-mRNA. The genes for all 5 histone proteins are clustered in all metazoans and coordinately regulated with high levels of expression during S phase. Production of histone mRNAs occurs in a nuclear body called the Histone Locus Body (HLB), a subdomain of the nucleus defined by a concentration of factors necessary for histone gene transcription and pre-mRNA processing...
January 6, 2017: RNA Biology
https://www.readbyqxmd.com/read/28058630/il-33-acts-as-a-foe-to-mia-paca-2-pancreatic-cancer
#6
Yujiang Fang, Lei Zhao, Huaping Xiao, Kathryn M Cook, Qian Bai, Elizabeth J Herrick, Xuhui Chen, Chenglu Qin, Ziwen Zhu, Mark R Wakefield, Michael B Nicholl
IL-33 is a member of the IL-1 family of cytokines, and no study has been performed to address its direct anti-tumor effect. This study is designed to investigate whether IL-33 has any direct effect on pancreatic cancer. Clonogenic survival assay, immunohistochemistry, TUNEL staining, proliferation, caspase-3 activity kits and RT-PCR were used to evaluate the effects of IL-33 on cell survival, proliferation and apoptosis of a pancreatic cancer cell line, MIA PaCa-2. We found that the percentage of colonies of MIA PaCa-2 cells, PCNA+ cells and the OD value of cancer cells were all decreased in the presence of IL-33...
February 2017: Medical Oncology
https://www.readbyqxmd.com/read/28056778/structural-prediction-of-the-interaction-of-the-tumor-suppressor-p27-kip1-with-cyclin-a-cdk2-identifies-a-novel-catalytically-relevant-determinant
#7
Jinyu Li, Jörg Vervoorts, Paolo Carloni, Giulia Rossetti, Bernhard Lüscher
BACKGROUND: The cyclin-dependent kinase 2 (CDK2) together with its cyclin E and A partners is a central regulator of cell growth and division. Deregulation of CDK2 activity is associated with diseases such as cancer. The analysis of substrates identified S/T-P-X-R/K/H as the CDK2 consensus sequence. The crystal structure of cyclin A/CDK2 with a short model peptide supports this sequence and identifies key interactions. However, CDKs use additional determinants to recognize substrates, including the RXL motif that is read by the cyclin subunits...
January 5, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28039837/explicit-treatment-of-active-site-waters-enhances-quantum-mechanical-implicit-solvent-scoring-inhibition-of-cdk2-by-new-pyrazolo-1-5-a-pyrimidines
#8
Michaela Hylsová, Benoit Carbain, Jindřich Fanfrlík, Lenka Musilová, Susanta Haldar, Cemal Köprülüoğlu, Haresh Ajani, Pathik S Brahmkshatriya, Radek Jorda, Vladimír Kryštof, Pavel Hobza, Aude Echalier, Kamil Paruch, Martin Lepšík
We present comprehensive testing of solvent representation in quantum mechanics (QM)-based scoring of protein-ligand affinities. To this aim, we prepared 21 new inhibitors of cyclin-dependent kinase 2 (CDK2) with the pyrazolo[1,5-a]pyrimidine core, whose activities spanned three orders of magnitude. The crystal structure of a potent inhibitor bound to the active CDK2/cyclin A complex revealed that the biphenyl substituent at position 5 of the pyrazolo[1,5-a]pyrimidine scaffold was located in a previously unexplored pocket and that six water molecules resided in the active site...
December 11, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28036012/emerging-roles-for-ciz1-in-cell-cycle-regulation-and-as-a-driver-of-tumorigenesis
#9
REVIEW
Tekle Pauzaite, Urvi Thacker, James Tollitt, Nikki A Copeland
Precise duplication of the genome is a prerequisite for the health and longevity of multicellular organisms. The temporal regulation of origin specification, replication licensing, and firing at replication origins is mediated by the cyclin-dependent kinases. Here the role of Cip1 interacting Zinc finger protein 1 (Ciz1) in regulation of cell cycle progression is discussed. Ciz1 contributes to regulation of the G1/S transition in mammalian cells. Ciz1 contacts the pre-replication complex (pre-RC) through cell division cycle 6 (Cdc6) interactions and aids localization of cyclin A- cyclin-dependent kinase 2 (CDK2) activity to chromatin and the nuclear matrix during initiation of DNA replication...
December 27, 2016: Biomolecules
https://www.readbyqxmd.com/read/28031483/speedy-a-cdk2-binding-mediates-initial-telomere-nuclear-envelope-attachment-during-meiotic-prophase-i-independent-of-cdk2-activation
#10
Zhaowei Tu, Mustafa Bilal Bayazit, Hongbin Liu, Jingjing Zhang, Kiran Busayavalasa, Sanjiv Risal, Jingchen Shao, Ande Satyanarayana, Vincenzo Coppola, Lino Tessarollo, Meenakshi Singh, Chunwei Zheng, Chunsheng Han, Zijiang Chen, Philipp Kaldis, Jan-Åke Gustafsson, Kui Liu
Telomere attachment to the nuclear envelope (NE) is a prerequisite for chromosome movement during meiotic prophase I that is required for pairing of homologous chromosomes, synapsis, and homologous recombination. Here we show that Speedy A, a noncanonical activator of cyclin-dependent kinases (Cdks), is specifically localized to telomeres in prophase I male and female germ cells in mice, and plays an essential role in the telomere-NE attachment. Deletion of Spdya in mice disrupts telomere-NE attachment, and this impairs homologous pairing and synapsis and leads to zygotene arrest in male and female germ cells...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28024406/the-effect-of-conformational-flexibility-on-binding-free-energy-estimation-between-kinases-and-their-inhibitors
#11
Mitsugu Araki, Narutoshi Kamiya, Miwa Sato, Masahiko Nakatsui, Takatsugu Hirokawa, Yasushi Okuno
Accurate prediction of binding affinities of drug candidates to their targets remains challenging because of protein flexibility in solution. Conformational flexibility of the ATP-binding site in the CDK2 and ERK2 kinases was identified using molecular dynamics simulations. The binding free energy (ΔG) of twenty-four ATP-competitive inhibitors toward these kinases was assessed using an alchemical free energy perturbation method, MP-CAFEE. However, large calculation errors of 2-3 kcal/mol were observed using this method, where the free energy simulation starts from a single equilibrated conformation...
December 27, 2016: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28024230/in-silico-study-of-porphyrin-anthraquinone-hybrids-as-cdk2-inhibitor
#12
Muhammad Arba, Sunandar Ihsan, La Ode Ahmad Nur Ramadhan, Daryono Hadi Tjahjono
Cyclin-Dependent Kinases (CDKs) are known to play crucial roles in controlling cell cycle progression of eukaryotic cell and inhibition of their activity has long been considered as potential strategy in anti-cancer drug research. In the present work, a series of porphyrin-anthraquinone hybrids bearing meso-substituents, i.e. either pyridine or pyrazole rings were designed and computationally evaluated for their Cyclin Dependent Kinase-2 (CDK2) inhibitory activity using molecular docking, molecular dynamics simulation, and binding free energy calculation...
December 19, 2016: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28009971/dacomitinib-a-new-pan-egfr-inhibitor-is-effective-in-killing-ovarian-cancer-cells
#13
Lei Xu, Huini Wu, Chao Jiang, Hongcai Wang, Bei Gao, Shumei Yan, Yushu Qi, Shufeng Zhou
OBJECTIVE: Aberrant epidermal growth factor receptor (EGFR) is involved in a variety of cancers and its inhibitors have been studied for over a decade. We aim to investigate the effects of dacomitinib, a second generation pan-EGFR inhibitor, on ovarian cancer cells. METHODS: By immunohistochemistry, we studied the clinical significance of EGFR expression in epithelial ovarian cancer (EOC). The correlations between EGFR expression and the clinicopathological variables of patients with EOC were assessed using Pearson's X2 test...
November 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28005359/cyclin-dependent-kinase-cdk-inhibitors-structure-activity-relationships-and-insights-into-the-cdk-2-selectivity-of-6-substituted-2-arylaminopurines
#14
Christopher R Coxon, Elizabeth Anscombe, Suzannah Jane Harnor, Mathew P Martin, Benoit Jean-Pierre Carbain, Bernard Thomas Golding, Ian Robert Hardcastle, Lisa K Harlow, Svitlana Korolchuk, Christopher J Matheson, David R Newell, Martin E M Noble, Mangaleswaran Sivaprakasam, Susan J Tudhope, David M Turner, Lan-Zhen Wang, Stephen R Wedge, Christopher Wong, Roger John Griffin, Jane A Endicott, Celine Cano
Purines and related heterocycles substituted at C-2 with 4'-sulfamoylanilino and at C-6 with a variety of groups have been synthesized with the aim of achieving selectivity of binding to CDK2 over CDK1. 6-Substituents that favour competitive inhibition at the ATP binding site of CDK2 were identified and typically exhibited 10-80-fold greater inhibition of CDK2 compared to CDK1. Most impressive was 4-((6-([1,1'-biphenyl]-3-yl)-9H-purin-2-yl)amino) benzenesulfonamide (73) that exhibited high potency towards CDK2 (IC50 0...
December 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28003546/adenylyl-cyclase-activating-polypeptide-reduces-phosphorylation-and-toxicity-of-the-polyglutamine-expanded-androgen-receptor-in-spinobulbar-muscular-atrophy
#15
Maria Josè Polanco, Sara Parodi, Diana Piol, Conor Stack, Mathilde Chivet, Andrea Contestabile, Helen C Miranda, Patricia M-J Lievens, Stefano Espinoza, Tobias Jochum, Anna Rocchi, Christopher Grunseich, Raul R Gainetdinov, Andrew C B Cato, Andrew P Lieberman, Albert R La Spada, Fabio Sambataro, Kenneth H Fischbeck, Illana Gozes, Maria Pennuto
Spinobulbar muscular atrophy (SBMA) is an X-linked neuromuscular disease caused by polyglutamine (polyQ) expansion in the androgen receptor (AR) gene. SBMA belongs to the family of polyQ diseases, which are fatal neurodegenerative disorders mainly caused by protein-mediated toxic gain-of-function mechanisms and characterized by deposition of misfolded proteins in the form of aggregates. The neurotoxicity of the polyQ proteins can be modified by phosphorylation at specific sites, thereby providing the rationale for the development of disease-specific treatments...
December 21, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/28002795/sodium-fluoride-naf-causes-toxic-effects-on-splenic-development-in-mice
#16
Ping Kuang, Huidan Deng, Hengmin Cui, Lian Chen, Jing Fang, Zhicai Zuo, Junliang Deng, Xun Wang, Ling Zhao
At present, very limited studies focus on the toxic effect of sodium fluoride (NaF) on splenic development of human and animals in vivo. This study was firstly designed to evaluate the toxic effects of NaF on the splenic development of mice in vivo by observing histopathological lesions, changes of splenic growth index (GI), T and B cells, immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM) contents, cytokine protein expression levels, and cell cycle and cyclins/cdks protein expression levels using the methods of pathology, flow cytometry (FCM), western blot (WB), and enzyme-linked immunosorbent assay (ELISA)...
December 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27998760/nucleostemin-gnl3-promotes-nucleolar-polyubiquitylation-of-p27-kip1-to-drive-hepatocellular-carcinoma-progression
#17
Baoying Hu, Lu Hua, Wenkai Ni, Miaomiao Wu, Daliang Yan, Yuyan Chen, Cuihua Lu, Buyou Chen, Chunhua Wan
p27(kip), as a cyclin dependent kinase inhibitor (CDKI), plays a pivotal role in the regulation of cell cycle progression and hepatocarcinogenesis. Herein, we revealed that p27 exhibited apparent nucleolar distribution and interacted with nucleolar protein nucleostemin (NS) in Hepatocellular carcinoma (HCC) cells. Furthermore, subcellular fractionation experiments demonstrated that nucleolar p27 had significantly higher level of polyubiquitylation, compared with nucleoplasmic fraction. Depletion of NS inhibited nucleolar polyubiquitylation of p27, indicating an involvement of NS in triggering p27 ubiquitylation and inactivation during HCC development...
December 18, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27997894/zedoarondiol-inhibits-platelet-derived-growth-factor-induced-vascular-smooth-muscle-cells-proliferation-via-regulating-amp-activated-protein-kinase-signaling-pathway
#18
Huimin Mao, Tianqi Tao, Dandan Song, Mi Liu, Xiaoren Wang, Xiuhua Liu, Dazhuo Shi
BACKGROUND/AIMS: Vascular smooth muscle cells (VSMCs) proliferation contributes significantly to atherosclerosis and in-stent restenosis. Platelet-derived growth factor-BB (PDGF-BB) plays a vital role in VSMCs proliferation. Zedoarondiol, a sesquiterpene lactone compound, has an anti-inflammatory activity. However, the role of zedoarondiol in PDGF-BB-mediated VSMCs proliferation remains unclear. In this study, we investigated the effects of zedoarondiol on PDGF-BB-induced VSMCs proliferation and explored the possible mechanisms...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27996312/overexpression-of-tspan8-promotes-tumor-cell-viability-and-proliferation-in-nonsmall-cell-lung-cancer
#19
Zheng Dong, Lijiang Zhao, Shijun Lu, Jie Xiong, Zhiguang Geng
BACKGROUND: Overexpression of TSPAN8 has been involved in several epithelial cancers and TSPAN8 can form a complex with a variety of proteins to participate in several import cellular functions. However, the effects of TSPAN8 in nonsmall cell lung cancer (NSCLC) remain unclear. MATERIALS AND METHODS: In this study, the authors determined the expression of TSPAN in several NSCLC cell lines (95C, A549, H1299, and 95D) and human bronchial epithelial (HBE) cells. Furthermore, the authors investigated the biological function of TSPAN8 in NSCLC cell lines using gain-of-function and loss-of-function assays, as well as the underlying mechanisms...
December 2016: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/27991682/the-role-of-metastasis-associated-in-colon-cancer-1-macc1-in-endometrial-carcinoma-tumorigenesis-and-progression
#20
Shuo Chen, Zhi-Hong Zong, Dan-Dan Wu, Kai-Xuan Sun, Bo-Liang Liu, Yang Zhao
Metastasis-associated in colon cancer-1 (MACC1), has recently been identified as a key regulator in the progression of many cancers. However, its role in endometrial carcinoma (EC) remains unknown. MACC1 expression was determined in EC and normal endometrial tissues by immunohistochemistry. EC cell phenotypes and related molecules were examined after MACC1 downregulation by Small interfering RNA (siRNA) or microRNA (miRNA) transfection. We found that MACC1 was highly expressed in EC tissues than normal samples, and was significantly different in FIGO staging (I and II vs...
December 19, 2016: Molecular Carcinogenesis
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