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https://www.readbyqxmd.com/read/27909956/docking-and-three-dimensional-quantitative-structure-activity-relationship-analyses-of-imidazole-and-thiazolidine-derivatives-as-aurora-a-kinase-inhibitors
#1
Chaeuk Im
Aurora A kinase is involved in the inactivation of apoptosis leading to ovarian, breast, colon, and pancreatic cancers. Inhibitors of Aurora A kinase promote aberrant mitosis resulting in arrest at a pseudo G1 state to induce mitotic catastrophe, ultimately leading to apoptosis. In this study, ligand-based and docking-based three-dimensional quantitative structure-activity relationship (3D-QSAR) analyses of imidazole and thiazolidine derivatives as potential Aurora A kinase inhibitors were performed. The results provided highly reliable and predictive 3D-QSAR comparative molecular similarity index analysis (CoMSIA) models with a cross-validated q(2) value of 0...
December 1, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27902925/targeted-inhibition-of-wrn-helicase-replication-stress-and-cancer
#2
REVIEW
Natalie Orlovetskie, Raphael Serruya, Ghada Abboud-Jarrous, Nayef Jarrous
WRN helicase has several roles in genome maintenance, such as replication, base excision repair, recombination, DNA damage response and transcription. These processes are often found upregulated in human cancers, many of which display increased levels of WRN. Therefore, directed inhibition of this RecQ helicase could be beneficial to selective cancer therapy. Inhibition of WRN is feasible by the use of small-molecule inhibitors or application of RNA interference and EGS/RNase P targeting systems. Remarkably, helicase depletion leads to a severe reduction in cell viability due to mitotic catastrophe, which is triggered by replication stress induced by DNA repair failure and fork progression arrest...
November 27, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27895742/comparative-analysis-of-gene-expression-profiles-of-gastric-cardia-adenocarcinoma-and-gastric-non-cardia-adenocarcinoma
#3
Bin Song, Juan Du, Neng Deng, Ji-Chen Ren, Zhen-Bo Shu
In the present study, gene expression profiles were analyzed to identify the molecular mechanisms underlying gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA). A gene expression dataset (accession number GSE29272) was downloaded from Gene Expression Omnibus, and consisted of 62 GCA samples and 62 normal controls, as well as 72 GNCA samples and 72 normal controls. The two groups of differentially-expressed genes (DEGs) were compared to obtain common and unique DEGs. A differential analysis was performed using the Linear Models for Microarray Data package in R...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27889750/metformin-protects-neurons-against-oxygen-glucose-deprivation-reoxygenation-induced-injury-by-down-regulating-mad2b
#4
Xianfang Meng, Guangpin Chu, Zhihua Yang, Ping Qiu, Yue Hu, Xiaohe Chen, Wenpeng Peng, Chen Ye, Fang-Fang He, Chun Zhang
BACKGROUND/AIMS: Metformin, the common medication for type II diabetes, has protective effects on cerebral ischemia. However, the molecular mechanisms are far from clear. Mitotic arrest deficient 2-like protein 2 (MAD2B), an inhibitor of the anaphase-promoting complex (APC), is widely expressed in hippocampal and cortical neurons and plays an important role in mediating high glucose-induced neurotoxicity. The present study investigated whether metformin modifies the expression of MAD2B and to exert its neuroprotective effects in primary cultured cortical neurons during oxygen-glucose deprivation/reoxygenation (OGD/R), a widely used in vitro model of ischemia/reperfusion...
November 11, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27889646/mirvetuximab-soravtansine-imgn853-a-folate-receptor-alpha-targeting-antibody-drug-conjugate-potentiates-the-activity-of-standard-of-care-therapeutics-in-ovarian-cancer-models
#5
Jose F Ponte, Olga Ab, Leanne Lanieri, Jenny Lee, Jennifer Coccia, Laura M Bartle, Marian Themeles, Yinghui Zhou, Jan Pinkas, Rodrigo Ruiz-Soto
Elevated folate receptor alpha (FRα) expression is characteristic of epithelial ovarian cancer (EOC), thus establishing this receptor as a candidate target for the development of novel therapeutics to treat this disease. Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate (ADC) that targets FRα for tumor-directed delivery of the maytansinoid DM4, a potent agent that induces mitotic arrest by suppressing microtubule dynamics. Here, combinations of IMGN853 with approved therapeutics were evaluated in preclinical models of EOC...
November 24, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27885657/cdc25b-is-involved-in-the-centrosomal-microtubule-nucleation-in-two-cell-stage-mouse-embryos
#6
Cheng Cui, Tianxia Zang, Yu Cao, Xin Qin, Xuewei Zhang
CDC25B has been demonstrated to activate the complex of CDK1/Cyclin B and trigger mitosis. We have recently demonstrated that p-CDC25B-Ser351 is located at the centrosomes of mouse oocytes and contributes to the release of mouse oocytes from prophase I arrest. But much less is known about CDC25B function at the centrosome in two-cell stage mouse embryos. Here we investigate the effect of CDC25B regulating the microtubules nucleation. Microinjection of anti-CDC25B antibody caused aberrant microtubule nucleation...
November 25, 2016: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/27882722/designed-inhibitor-for-nuclear-localization-signal-of-polo-like-kinase-1-induces-mitotic-arrest
#7
Fangjin Chen, Xiaolong Zhuo, Tan Qin, Xiao Guo, Chuanmao Zhang, Luhua Lai
Polo-like kinase 1 (Plk1), a member of polo-like kinase family, regulates multiple essential steps of the cell cycle progression. Plk1 is overexpressed in multiple cancer cell lines and considered to be a prime anticancer target. Plk1 accumulates in the nucleus during S and G2 phases by its bipartite nuclear localization signal (NLS) sequence, which is crucial for Plk1 regulation during normal cell cycle progression. Here, through combined computational and experimental studies, we identified compound D110, which inhibits Plk1 kinase activity with an IC50 of 85 nm and blocks the nuclear localization of Plk1 during S and G2 phases...
November 24, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27879648/the-role-of-deoxycytidine-kinase-dck-in-radiation-induced-cell-death
#8
Rui Zhong, Rui Xin, Zongyan Chen, Nan Liang, Yang Liu, Shumei Ma, Xiaodong Liu
Deoxycytidine kinase (dCK) is a key enzyme in deoxyribonucleoside salvage and the anti-tumor activity for many nucleoside analogs. dCK is activated in response to ionizing radiation (IR)-induced DNA damage and it is phosphorylated on Serine 74 by the Ataxia-Telangiectasia Mutated (ATM) kinase in order to activate the cell cycle G2/M checkpoint. However, whether dCK plays a role in radiation-induced cell death is less clear. In this study, we genetically modified dCK expression by knocking down or expressing a WT (wild-type), S74A (abrogates phosphorylation) and S74E (mimics phosphorylation) of dCK...
November 21, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27875993/a-transcriptome-based-model-of-central-memory-cd4-t-cell-death-in-hiv-infection
#9
Gustavo Olvera-García, Tania Aguilar-García, Fany Gutiérrez-Jasso, Iván Imaz-Rosshandler, Claudia Rangel-Escareño, Lorena Orozco, Irma Aguilar-Delfín, Joel A Vázquez-Pérez, Joaquín Zúñiga, Santiago Pérez-Patrigeon, Enrique Espinosa
BACKGROUND: Human central memory CD4 T cells are characterized by their capacity of proliferation and differentiation into effector memory CD4 T cells. Homeostasis of central memory CD4 T cells is considered a key factor sustaining the asymptomatic stage of Human Immunodeficiency Virus type 1 (HIV-1) infection, while progression to acquired immunodeficiency syndrome is imputed to central memory CD4 T cells homeostatic failure. We investigated if central memory CD4 T cells from patients with HIV-1 infection have a gene expression profile impeding proliferation and survival, despite their activated state...
November 22, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27871934/v-src-induced-nuclear-localization-of-yap-is-involved-in-multipolar-spindle-formation-in-tetraploid-cells
#10
Keiko Kakae, Masayoshi Ikeuchi, Takahisa Kuga, Youhei Saito, Naoto Yamaguchi, Yuji Nakayama
The protein-tyrosine kinase, c-Src, is involved in a variety of signaling events, including cell division. We have reported that v-Src, which is a mutant variant of the cellular proto-oncogene, c-Src, causes delocalization of Aurora B kinase, resulting in a furrow regression in cytokinesis and the generation of multinucleated cells. However, the effect of v-Src on mitotic spindle formation is unknown. Here we show that v-Src-expressing HCT116 and NIH3T3 cells undergo abnormal cell division, in which cells separate into more than two cells...
November 18, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27864857/protein-sumoylation-is-involved-in-cell-cycle-progression-and-cell-morphology-in-giardia-lamblia
#11
Bruno M Di Genova, Richard C da Silva, Júlia P C da Cunha, Pablo R Gargantini, Renato A Mortara, Renata R Tonelli
The unicellular protozoa Giardia lamblia is a food- and waterborne parasite that causes giardiasis. This illness is manifested as acute and self-limited diarrhea and can evolve to long-term complications. Successful establishment of infection by Giardia trophozoites requires adhesion to host cells and colonization of the small intestine, where parasites multiply by mitotic division. The tight binding of trophozoites to host cells occurs by means of the ventral adhesive disc, a spiral array of microtubules and associated proteins such as giardins...
November 19, 2016: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/27863409/integrating-mechanisms-of-response-and-resistance-against-the-tubulin-binding-agent-eribulin-in-preclinical-models-of-osteosarcoma
#12
Valerie B Sampson, Nancy S Vetter, Wendong Zhang, Pratima U Patil, Robert W Mason, Erika George, Richard Gorlick, E A Kolb
Osteosarcoma is the most frequently occurring bone cancer in children and adolescents. Unfortunately, treatment failures are common. Eribulin is a synthetic microtubule inhibitor that has demonstrated activity in preclinical osteosarcoma models. The effects of eribulin were evaluated in two human osteosarcoma cell lines as well as in eribulin-sensitive and -resistant osteosarcoma xenograft tumors of the Pediatric Preclinical Testing Program (PPTP) by characterizing cell viability, microtubule destabilization, mitotic arrest and mechanism of cell death...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27861885/sensitivity-of-tp53-mutated-cancer-cells-to-the-phytoestrogen-genistein-is-associated-with-direct-inhibition-of-plk1-activity
#13
Sol-Bi Shin, Sang-Uk Woo, Young Won Chin, Young-Joo Jang, Hyungshin Yim
Polo-like kinase 1 (Plk1), a conserved Ser/Thr mitotic kinase, has been identified as a promising target for anticancer drug development because its overexpression is correlated with malignancy. Here, we found that genistein, an isoflavone, inhibits Plk1 kinase activity directly. Previously the mitotic disturbance phenomenon induced by treatment with genistein was not fully explained by its inhibitory effect on EGFR. In kinase profiling assays, it showed selectivity relative to a panel of kinases, including EGFR...
November 9, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27848932/lack-of-diaph3-relaxes-the-spindle-checkpoint-causing-the-loss-of-neural-progenitors
#14
Devid Damiani, André M Goffinet, Arthur Alberts, Fadel Tissir
The diaphanous homologue Diaph3 (aka mDia2) is a major regulator of actin cytoskeleton. Loss of Diaph3 has been constantly associated with cytokinesis failure ascribed to impaired accumulation of actin in the cleavage furrow. Here we report that Diaph3 is required before cell fission, to ensure the accurate segregation of chromosomes. Inactivation of the Diaph3 gene causes a massive loss of cortical progenitor cells, with subsequent depletion of intermediate progenitors and neurons, and results in microcephaly...
November 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27837030/clinicopathological-and-functional-significance-of-recql1-helicase-in-sporadic-breast-cancers
#15
Arvind Arora, Swetha Parvathaneni, Mohammed A Aleskandarany, Devika Agarwal, Reem Ali, Tarek Ma Abdel-Fatah, Andrew R Green, Graham R Ball, Emad A Rakha, Ian O Ellis, Sudha Sharma, Srinivasan Madhusudan
RECQL1, a key member of the RecQ family of DNA helicases, is required for DNA replication and DNA repair. Two recent studies have shown that germ-line RECQL1 mutations are associated with increased breast cancer susceptibility. Whether altered RECQL1 expression has clinicopathological significance in sporadic breast cancers is unknown. We evaluated RECQL1 at the transcriptomic level [METABRIC cohort, n=1977] and at the protein level [cohort 1, n=897; cohort 2, n= 252; cohort 3 (BRCA-germline deficient), n=74]...
November 11, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27836666/aurora-b-kinase-is-required-for-cell-cycle-progression-in-silkworm
#16
Xiaoxu Gang, Wenliang Qian, Tianlei Zhang, Xinxin Yang, Qingyou Xia, Daojun Cheng
Aurora B kinase, a member of serine/threonine kinase family, is the catalytic subunit of the chromosomal passenger complex and is essential for chromosome alignment, chromosome segregation, and cytokinesis during mitosis. Here, we cloned the full-length cDNA sequence of silkworm Aurora B (BmAurB) gene and predicted that BmAurB protein contains a conserved S_TKc domain. Phylogenetic analysis between BmAurB and other Aurora kinases indicates that Aurora kinases may have evolved after separation between mammalian and insect, and prior to radiation of either mammalian or insects...
November 9, 2016: Gene
https://www.readbyqxmd.com/read/27835911/prognostic-and-predictive-values-of-cdk1-and-mad2l1-in-lung-adenocarcinoma
#17
Yuan-Xiang Shi, Tao Zhu, Ting Zou, Wei Zhuo, Yi-Xin Chen, Ma-Sha Huang, Wei Zheng, Chen-Jing Wang, Xi Li, Xiao-Yuan Mao, Wei Zhang, Hong-Hao Zhou, Ji-Ye Yin, Zhao-Qian Liu
Lung cancer remains as the leading cause of cancer-related death worldwide, and lung adenocarcinoma (LUAD) is the most common histological subtype. This study aims to investigate biomarkers associated with cancer progression and prognosis of LUAD. We integrated expression profiles of 668 lung cancer patients in five datasets from the Gene Expression Omnibus (GEO) and identified a panel of differentially expressed genes (DEGs). Function enrichment analysis highlighted that these genes were closely associated with the carcinogenesis of LUAD, such as cell cycle, ECM-receptor interaction and p53 signaling pathway...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27835873/proteomic-identification-of-the-oncoprotein-stat3-as-a-target-of-a-novel-skp1-inhibitor
#18
Xin Cheng, Yong-Qiang Liu, Gui-Zhen Wang, Li-Na Yang, Yong-Zhi Lu, Xin-Chun Li, Bo Zhou, Li-Wei Qu, Xiao-Lu Wang, Yong-Xian Cheng, Jinsong Liu, Sheng-Ce Tao, Guang-Biao Zhou
The S phase kinase-associated protein 1 (Skp1), an adaptor protein of the Skp1-Cul1-F-box protein complex, binds the ubiquitin E3 ligase Skp2 and is critical to its biological functions. Targeting of Skp1 by a small compound 6-O-angeloylplenolin (6-OAP) results in dissociation and degradation of Skp2 and mitotic arrest of lung cancer cells. Here, by using a proteome microarray containing 16,368 proteins and a biotinylated 6-OAP, we identified 99 proteins that could bind 6-OAP, with Skp1 and STAT3 sitting at the central position of the 6-OAP interactome...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27832139/a-subpopulation-of-the-k562-cells-are-killed-by-curcumin-treatment-after-g2-m-arrest-and-mitotic-catastrophe
#19
Macario Martinez-Castillo, Raul Bonilla-Moreno, Leticia Aleman-Lazarini, Marco Antonio Meraz-Rios, Lorena Orozco, Leticia Cedillo-Barron, Emilio J Cordova, Nicolas Villegas-Sepulveda
Curcumin is extensively investigated as a good chemo-preventive agent in the development of many cancers and particularly in leukemia, including treatment of chronic myelogenous leukemia and it has been proposed as an adjuvant for leukemia therapies. Human chronic myeloid leukemia cells (K562), were treated with 20 μM of curcumin, and we found that a subpopulation of these cells were arrested and accumulate in the G2/M phase of the cell cycle. Characterization of this cell subpopulation showed that the arrested cells presented nuclear morphology changes resembling those described for mitotic catastrophe...
2016: PloS One
https://www.readbyqxmd.com/read/27831827/mitotic-entry-the-interplay-between-cdk1-plk1-and-bora
#20
Alfonso Parrilla, Luca Cirillo, Yann Thomas, Monica Gotta, Lionel Pintard, Anna Santamaria
Polo-like kinase 1 (Plk1) is an important mitotic kinase that is crucial for entry into mitosis after recovery from DNA damage-induced cell cycle arrest. Plk1 activation is promoted by the conserved protein Bora (SPAT-1 in C. elegans), which stimulates the phosphorylation of a conserved residue in the activation loop by the Aurora A kinase. In a recent article published in Cell Reports, we show that the master mitotic kinase Cdk1 contributes to Plk1 activation through SPAT-1/Bora phosphorylation. We identified 3 conserved Sp/Tp residues that are located in the N-terminal, most conserved part, of SPAT-1/Bora...
November 10, 2016: Cell Cycle
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