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https://www.readbyqxmd.com/read/29786792/protocols-for-the-study-of-taxanes-chemosensitivity-in-prostate-cancer
#1
M Luz Flores, Carmen Sáez
Prostate cancer is major cause of cancer-related death among men in Western countries. Locally advanced prostate cancers are treated with castration therapy, which is initially effective, but after months the disease progresses to a hormone-refractory state whose treatment is chemotherapy based on taxanes. Although taxanes improve the survival of patients with castration-resistant prostate cancers, these patients often develop chemotherapy resistance, and new therapeutic strategies are necessary. Taxanes exert their action through interaction with β-tubulin which triggers cell cycle arrest in mitosis and the subsequent induction of the intrinsic apoptotic pathway...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29785588/sam68-promotes-invasion-migration-and-proliferation-of-fibroblast-like-synoviocytes-by-enhancing-the-nf-%C3%AE%C2%BAb-p65-pathway-in-rheumatoid-arthritis
#2
Weiwei Sun, Rongqin Qin, Rui Wang, Dazhi Ding, Zhaohui Yu, Yuxi Liu, Ruilong Hong, Zhen Cheng, Youhua Wang
Src-associated substrate during mitosis of 68 KDa (Sam68), also known as KH domain containing, RNA binding, signal transduction associated 1 (KHDRBS1), is the prototypic member of the signal transduction activator of RNA (STAR) family of RNA-binding proteins. Previous studies have indicated that Sam68 regulates nuclear transcription factor kappa B (NF-κB) to mediate inflammation. In this study, we analyzed the effect and possible mechanisms of Sam68 in rheumatoid arthritis (RA). By western blot analysis and immunohistochemistry, we found that the expression of Sam68 in synovial tissue of RA patients was increased compared with the control group...
May 21, 2018: Inflammation
https://www.readbyqxmd.com/read/29783721/azd1775-increases-sensitivity-to-olaparib-and-gemcitabine-in-cancer-cells-with-p53-mutations
#3
Xiangbing Meng, Jianling Bi, Yujun Li, Shujie Yang, Yuping Zhang, Mary Li, Haitao Liu, Yiyang Li, Megan E Mcdonald, Kristina W Thiel, Kuo-Kuang Wen, Xinhao Wang, Meng Wu, Kimberly K Leslie
Tumor suppressor p53 is responsible for enforcing cell cycle checkpoints at G1/S and G2/M in response to DNA damage, thereby allowing both normal and tumor cells to repair DNA before entering S and M. However, tumor cells with absent or mutated p53 are able to activate alternative signaling pathways that maintain the G2/M checkpoint, which becomes uniquely critical for the survival of such tumor cells. We hypothesized that abrogation of the G2 checkpoint might preferentially sensitize p53-defective tumor cells to DNA-damaging agents and spare normal cells with intact p53 function...
May 19, 2018: Cancers
https://www.readbyqxmd.com/read/29782540/monte-carlo-simulations-of-microtubule-arrays-the-critical-roles-of-rescue-transitions-the-cell-boundary-and-tubulin-concentration-in-shaping-microtubule-distributions
#4
Lynne Cassimeris, Jessica C Leung, David J Odde
Microtubules are dynamic polymers required for a number of processes, including chromosome movement in mitosis. While regulators of microtubule dynamics have been well characterized, we lack a convenient way to predict how the measured dynamic parameters shape the entire microtubule system within a cell, or how the system responds when specific parameters change in response to internal or external signals. Here we describe a Monte Carlo model to simulate an array of dynamic microtubules from parameters including the cell radius, total tubulin concentration, microtubule nucleation rate from the centrosome, and plus end dynamic instability...
2018: PloS One
https://www.readbyqxmd.com/read/29782304/role-of-in-vivo-reflectance-confocal-microscopy-in-the-analysis-of-melanocytic-lesions
#5
Elena-Daniela Serban, Francesca Farnetani, Giovanni Pellacani, Maria Magdalena Constantin
Worldwide melanoma incidence and mortality are increasing (1). Despite the ongoing research, advanced melanoma is still incurable; therefore, the most appropriate solution seems to be early detection combined with complete surgical excision (2). Since the diagnostic protocol of suspicious lesions includes a complete excision with safety margins (2), the problem of unnecessary scarring is significant. The real challenge in this case is to have a properly formulated diagnosis before acquiring a biopsy. Currently available non-invasive techniques are coherence tomography, digital dermoscopy, and reflectance confocal microscopy...
April 2018: Acta Dermatovenerologica Croatica: ADC
https://www.readbyqxmd.com/read/29782140/fluorescent-labeling-of-the-nuclear-envelope-by-localizing-gfp-on-the-inner-nuclear-membrane
#6
Toshiyuki Taniyama, Natsumi Tsuda, Shinji Sueda
The nuclear envelope (NE) is a double membrane that segregates nuclear components from the cytoplasm in eukaryote cells. It is well-known that the NE undergoes a breakdown and reformation during mitosis in animal cells. However, the detailed mechanisms of the NE dynamics are not yet fully understood. Here, we propose a method for the fluorescent labeling of the NE in living cells, which enables the tracing of the NE dynamics during cell division under physiological conditions. In our method, labeling of the NE is accomplished by fixing green fluorescent protein carrying the nuclear localization signal on the inner nuclear membrane based on a unique biotinylation reaction from the archaeon Sulfolobus tokodaii...
May 21, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29780816/identification-of-phosphohistone-h3-cutoff-values-corresponding-to-original-who-grades-but-distinguishable-in-well-differentiated-gastrointestinal-neuroendocrine-tumors
#7
Min Jeong Kim, Mi Jung Kwon, Ho Suk Kang, Kyung Chan Choi, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Ji-Young Choe, Hyoung-Chul Park
Mitotic counts in the World Health Organization (WHO) grading system have narrow cutoff values. True mitotic figures, however, are not always distinguishable from apoptotic bodies and darkly stained nuclei, complicating the ability of the WHO grading system to diagnose well-differentiated neuroendocrine tumors (NETs). The mitosis-specific marker phosphohistone H3 (PHH3) can identify true mitoses and grade tumors reliably. The aim of this study was to investigate the correspondence of tumor grades, as determined by PHH3 mitotic index (MI) and mitotic counts according to WHO criteria, and to determine the clinically relevant cutoffs of PHH3 MI in rectal and nonrectal gastrointestinal NETs...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29776402/mitotic-and-apoptotic-activity-in-colorectal-neoplasia
#8
Darina Kohoutova, Jaroslav Pejchal, Jan Bures
BACKGROUND: Colorectal cancer (CRC) is third most commonly diagnosed cancer worldwide. The aim of the prospective study was to evaluate mitosis and apoptosis of epithelial cells at each stage of colorectal neoplasia. METHODS: A total of 61 persons were enrolled into the study: 18 patients with non-advanced colorectal adenoma (non-a-A), 13 patients with advanced colorectal adenoma (a-A), 13 patients with CRC and 17 controls: individuals with normal findings on colonoscopy...
May 18, 2018: BMC Gastroenterology
https://www.readbyqxmd.com/read/29775579/a-mad2-mediated-translational-regulatory-mechanism-promoting-s-phase-cyclin-synthesis-controls-origin-firing-and-survival-to-replication-stress
#9
Sophie Gay, Daniele Piccini, Christopher Bruhn, Sara Ricciardi, Paolo Soffientini, Walter Carotenuto, Stefano Biffo, Marco Foiani
Cell survival to replication stress depends on the activation of the Mec1ATR -Rad53 checkpoint response that protects the integrity of stalled forks and controls the origin firing program. Here we found that Mad2, a member of the spindle assembly checkpoint (SAC), contributes to efficient origin firing and to cell survival in response to replication stress. We show that Rad53 and Mad2 promote S-phase cyclin expression through different mechanisms: while Rad53 influences Clb5,6 degradation, Mad2 promotes their protein synthesis...
May 17, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29773558/genetic-analyses-of-elys-mutations-in-drosophila-show-maternal-effect-lethality-and-interactions-with-nucleoporin-genes
#10
Kazuyuki Hirai, Zhuo Wang, Kohei Miura, Takaaki Hayashi, Takeshi Awasaki, Moe Wada, Yoko Keira, Hiroyuki O Ishikawa, Kyoichi Sawamura
ELYS determines the subcellular localizations of Nucleoporins (Nups) during interphase and mitosis. We made loss-of-function mutations of Elys in Drosophila melanogaster and found that ELYS is dispensable for zygotic viability and male fertility but the maternal supply is necessary for embryonic development. Subsequent to fertilization, mitotic progression of the embryos produced by the mutant females is severely disrupted at the first cleavage division, accompanied by irregular behavior of mitotic centrosomes...
May 18, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29772403/theoretical-study-of-the-intermolecular-recognition-mechanism-between-survivin-and-substrate-based-on-conserved-binding-mode-analysis
#11
Chao Wu, Liguang Mao, Xie Huang, Weitao Fu, Xiong Cai, Yuepiao Cai, Liqun Shen, Xiaoxia Ye
Survivin is the smallest member of IAP (inhibitor of apoptosis protein) family, which plays important roles in both mitosis and apoptosis. It has become an attractive drug target due to its overexpression in many human cancers. Survivin has been proven to bind to Smac/DIABLO protein that indirectly inhibits apoptosis. Meanwhile, it is the key subunit of chromosome passenger complex (CPC) which bind to the N-terminal tail of phosphorylated histone H3T3ph during mitosis. Up to now, Survivin directly targeting inhibitor has yet to merge since the difficulty of disrupting the protein-protein interactions (PPIs) between Survivin and its substrate proteins...
May 8, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29771379/cdk-phosphorylation-licenses-kif4a-chromosome-localization-required-for-early-mitotic-progression
#12
Zhixiong Dong, Changjun Zhu, Qimin Zhan, Wei Jiang
The chromokinesin Kif4A controls proper chromosome condensation, congression/alignment, and cytokinesis to ensure faithful genetic inheritance. Here, we report that Cdk phosphorylation of human Kif4A at T1161 licenses Kif4A chromosomal localization, which, in turn, controls Kif4A early mitotic function. Phosphorylated Kif4A (Kif4AWT) or Cdk phospho-mimetic Kif4A mutant (Kif4ATE) associated with chromosomes and condensin I (non-SMC subunit CAP-G and core subunit SMC2) to regulate chromosome condensation, spindle morphology, and chromosome congression/alignment in early mitosis...
May 16, 2018: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29769606/malonylation-of-histone-h2a-at-lysine-119-inhibits-bub1-dependent-h2a-phosphorylation-and-chromosomal-localization-of-shugoshin-proteins
#13
Tadashi Ishiguro, Kana Tanabe, Yuki Kobayashi, Shinsuke Mizumoto, Motomu Kanai, Shigehiro A Kawashima
Post-translational modifications of histones, such as acetylation and phosphorylation, are highly conserved in eukaryotes and their combination enables precise regulation of many cellular functions. Recent studies using mass spectrometry have revealed various non-acetyl acylations in histones, including malonylation and succinylation, which change the positive charge of lysine into a negative one. However, the molecular function of histone malonylation or succinylation is poorly understood. Here, we discovered the functions of malonylation in histone H2A at lysine 119 (H2A-K119) in chromosome segregation during mitosis and meiosis...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769558/high-speed-fourier-ptychographic-microscopy-based-on-programmable-annular-illuminations
#14
Jiasong Sun, Chao Zuo, Jialin Zhang, Yao Fan, Qian Chen
High-throughput quantitative phase imaging (QPI) is essential to cellular phenotypes characterization as it allows high-content cell analysis and avoids adverse effects of staining reagents on cellular viability and cell signaling. Among different approaches, Fourier ptychographic microscopy (FPM) is probably the most promising technique to realize high-throughput QPI by synthesizing a wide-field, high-resolution complex image from multiple angle-variably illuminated, low-resolution images. However, the large dataset requirement in conventional FPM significantly limits its imaging speed, resulting in low temporal throughput...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769406/spindle-assembly-disruption-and-cancer-cell-apoptosis-with-a-cltc-binding-compound
#15
Michael J Bond, Marina Bleiler, Lauren E Harrison, Eric W Scocchera, Masako Nakanishi, Narendran G-Dayanandan, Santosh Keshipeddy, Daniel W Rosenberg, Dennis L Wright, Charles Giardina
AK3 compounds are mitotic-arrest agents that induce high levels of γH2AX during mitosis and apoptosis following release from arrest. We synthesized a potent AK3 derivative, AK306, that induced arrest and apoptosis of the HCT116 colon cancer cell line with an EC50 of ~50 nM. AK306 was active on a broad spectrum of cancer cell lines with total growth inhibition values ranging from ~25 nM to 25 µM. Using biotin and BODIPY-linked derivatives of AK306, binding to clathrin heavy chain (CLTC/CHC) was observed, a protein with roles in endocytosis and mitosis...
May 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29768533/investigation-of-the-effect-of-gestational-diabetes-on-fetal-cardiac-tissue-in-streptozotocin-%C3%A4-nduced-in-rats
#16
Ugur Turhan, Ercan Yilmaz, Mehmet Gul, Rauf Melekoglu, Yusuf Turkoz, Fatma Ozyalin, Hakan Parlakpinar, Yavuz Simsek
PURPOSE: To investigate the cause of congenital anomalies resulted from gestational diabetes on fetal cardiac tissue in experimental animal study model. METHODS: Totally 12 female Wistar albino rats were divided into two groups, each consisting of 6 rats. Streptozotocin (60 mg/kg) was administered intraperitoneally to the study group by dissolving in citrate solution. The rats with a blood glucose level of 200 mg/dL and above were considered to be diabetic rats...
April 2018: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/29768402/condensin-i-protects-meiotic-cohesin-from-wapl-1-mediated-removal
#17
Margarita R Hernandez, Michael B Davis, Jianhao Jiang, Elizabeth A Brouhard, Aaron F Severson, Györgyi Csankovszki
Condensin complexes are key determinants of higher-order chromatin structure and are required for mitotic and meiotic chromosome compaction and segregation. We identified a new role for condensin in the maintenance of sister chromatid cohesion during C. elegans meiosis. Using conventional and stimulated emission depletion (STED) microscopy we show that levels of chromosomally-bound cohesin were significantly reduced in dpy-28 mutants, which lack a subunit of condensin I. SYP-1, a component of the synaptonemal complex central region, was also diminished, but no decrease in the axial element protein HTP-3 was observed...
May 16, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29766411/gastrointestinal-stromal-tumors-risk-of-recurrence-stratification-by-tumor-volume-is-a-best-predictor-compared-with-risk-based-on-mitosis-and-tumor-size
#18
Leonardo S Lino-Silva, Patricia Segales-Rojas, Eduardo Aguilar-Cruz, Rosa A Salcedo-Hernández, César Zepeda-Najar
PURPOSE: Gastrointestinal stromal tumors (GIST) have the potential to recur and metastasize. Several prognostic schemes have been developed, mostly based on the mitotic count, diameter, and tumor site. However, these systems are not precise enough. The research question was whether the tumor size determined by volumetry allows a better risk stratification than the traditional system, and our aim was to determine the value of tumor volumetry, a feasible and simple parameter, in the recurrence of GIST...
May 16, 2018: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/29765534/bi2536-induces-mitotic-catastrophe-and-radiosensitization-in-human-oral-cancer-cells
#19
Chieh-Yuan Cheng, Chung-Ji Liu, Yu-Chuen Huang, Shu-Hua Wu, Hsu-Wei Fang, Yu-Jen Chen
BI2536 has been developed as a potential therapeutic agent for various cancers but not in oral cancer cells. Since BI2536 exhibits mitosis-regulating activity which are the most radiosensitive, we hypothesized that BI2536 might modulate the radiosensitivity of oral cancer cells. Human normal fibroblasts, oral cancer SAS, and OECM1 cells were treated with BI2536 (0-50 nM) and/or radiation (0-4 Gy). MTT assay, Liu's staining, flow cytometry, clonogenic assay, Annexin V/propidium iodide (PI) staining, western blot analysis, and small interfering RNA knockdown experiments were used to assess cell viability, morphology, cell cycle progression, radiation survival, and expression of regulatory proteins in vitro ...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764992/aurora-b-opposes-pp1-function-in-mitosis-by-phosphorylating-the-conserved-pp1-binding-rvxf-motif-in-pp1-regulatory-proteins
#20
Isha Nasa, Scott F Rusin, Arminja N Kettenbach, Greg B Moorhead
Protein phosphatase 1 (PP1) is a highly conserved protein phosphatase that performs most of the serine- and threonine-dephosphorylation reactions in eukaryotes and opposes the actions of a diverse set of serine and threonine (Ser-Thr) protein kinases. PP1 gains substrate specificity through binding to a large number (>200) of regulatory proteins that control PP1 localization, activity, and interactions with substrates. PP1 recognizes the well-characterized RVxF binding motif that is present in many of these regulatory proteins, thus generating a multitude of distinct PP1 holoenzymes...
May 15, 2018: Science Signaling
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