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https://www.readbyqxmd.com/read/28185071/sagittal-spinal-alignment-in-asymptomatic-patients-over-30%C3%A2-years-old-in-the-korean-population
#1
Seil Sohn, Chun Kee Chung, Yongjung Jay Kim, Inbo Han, Su Min Kang, Ji Won Yoon, Hyejin Kim
BACKGROUND: We aim to provide sagittal and pelvic parameters according to different age groups in an asymptomatic population all over 30 years old and to investigate the possible causes of changes in these parameters. METHODS: Whole-spine, standing lateral radiographs were taken in 128 asymptomatic Korean people over 30 years old. The spinal parameters (the total thoracic kyphosis (TTK), maximal lumbar lordosis (MLL), total lumbar lordosis (TLL), lower lumbar lordosis (LLL), thoracolumbar junctional angle (TLJA), and lumbar inclination (LI)), pelvic parameters (pelvic incidence (PI), sacral slope (SS), and pelvic tilt (PT)), and spinal balance parameters (spinal balance, sacropelvic balance, and spinopelvic balance) were measured...
February 9, 2017: Acta Neurochirurgica
https://www.readbyqxmd.com/read/28165886/parsimony-and-complexity-cell-fate-assignment-in-the-developing-drosophila-eye
#2
Yannis Emmanuel Mavromatakis, Andrew Tomlinson
The specification of the R7 photoreceptor in the Drosophila eye has become a classic model for understanding how cell fates are assigned in developing systems. R7 is derived from a group of cells that also gives rise to the R1/6 photoreceptor class and the non-photoreceptor cone cells. Our studies examine the signals and cellular information that direct each of these cell types. The cell fates are directed by the combined actions of the Receptor Tyrosine Kinase (RTK) and Notch (N) signaling pathways. The RTK pathway acts to remove the transcription factor Tramtrack (Ttk) which represses the photoreceptor fate...
February 6, 2017: Fly
https://www.readbyqxmd.com/read/28069132/molecular-regulation-of-the-spindle-assembly-checkpoint-by-kinases-and-phosphatases
#3
G Manic, F Corradi, A Sistigu, S Siteni, I Vitale
The spindle assembly checkpoint (SAC) is a surveillance mechanism contributing to the preservation of genomic stability by monitoring the microtubule attachment to, and/or the tension status of, each kinetochore during mitosis. The SAC halts metaphase to anaphase transition in the presence of unattached and/or untensed kinetochore(s) by releasing the mitotic checkpoint complex (MCC) from these improperly-oriented kinetochores to inhibit the anaphase-promoting complex/cyclosome (APC/C). The reversible phosphorylation of a variety of substrates at the kinetochore by antagonistic kinases and phosphatases is one major signaling mechanism for promptly turning on or turning off the SAC...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/27924015/tstmp-target-selection-for-structural-genomics-of-human-transmembrane-proteins
#4
Julia Varga, László Dobson, István Reményi, Gábor E Tusnády
The TSTMP database is designed to help the target selection of human transmembrane proteins for structural genomics projects and structure modeling studies. Currently, there are only 60 known 3D structures among the polytopic human transmembrane proteins and about a further 600 could be modeled using existing structures. Although there are a great number of human transmembrane protein structures left to be determined, surprisingly only a small fraction of these proteins have 'selected' (or above) status according to the current version the TargetDB/TargetTrack database...
January 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923621/transcriptomic-analysis-of-gene-expression-profiles-of-stomach-carcinoma-reveal-abnormal-expression-of-mitotic-components
#5
Hongfei Tong, Jisheng Wang, Hui Chen, Zhaohong Wang, Henwei Fan, Zhonglin Ni
AIMS: In order to explore the etiology of gastric cancer on global gene expression level, we developed advanced bioinformatic analysis to investigate the variations of global gene expression and the interactions among them. MAIN METHODS: We downloaded the dataset GSE63288 from Gene Expression Omnibus (GEO) database which included 22 human gastric cancer and 22 healthy control samples. We identified the differential expression genes, and explored the Gene ontology (GO) and pathways of the differentially expressed genes...
February 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/27918555/gene-expression-profiling-of-anti-ctla4-treated-metastatic-melanoma-in-patients-with-treatment-induced-autoimmunity
#6
Scott C Bresler, Le Min, Scott J Rodig, Andrew C Walls, Shuyun Xu, Songmei Geng, F Stephen Hodi, George F Murphy, Christine G Lian
Ipilimumab (IPI) is a monoclonal antibody that targets the inhibitory CTLA4 receptor of T cells, enhancing T-cell-driven antitumor responses. IPI therapy in metastatic melanoma results in significant improvement in disease-free and overall survival, although after initial responses disease progression generally ensues. Identification of specific responses in tissue where melanoma tumor cells are subjected to IPI-driven immune attack may reveal mechanisms of treatment efficacy or resistance, permitting refinement of targeted therapeutic approaches...
December 5, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27833085/ttk-is-a-favorable-prognostic-biomarker-for-triple-negative-breast-cancer-survival
#7
Qianqian Xu, Yali Xu, Bo Pan, Liangcai Wu, Xinyu Ren, Yidong Zhou, Feng Mao, Yan Lin, Jinghong Guan, Songjie Shen, Xiaohui Zhang, Changjun Wang, Ying Zhong, Liangrui Zhou, Zhiyong Liang, Haitao Zhao, Qiang Sun
PURPOSE: Previous studies demonstrate that threonine and tyrosine kinase (TTK) is overexpressed in triple-negative breast cancer (TNBC), but there are conflicting results regarding its effect on TNBC survival. The purpose of this study was to assess the prognostic significance of TTK expression in primary TNBC. RESULTS: Of 169 consecutive cases eligible for this study, 164 included follow-up information. Cytoplasm and membrane TTK staining was observed in 99.4% of cases, while 5...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27819146/mps1-ttk-a-novel-target-and-biomarker-for-cancer
#8
Yuan Xie, Anqiang Wang, Jianzhen Lin, Liangcai Wu, Haohai Zhang, Xiaobo Yang, Xueshuai Wan, Ruoyu Miao, Xinting Sang, Haitao Zhao
Monopolar spindle1 (Mps1, also known as TTK) is the core component of the spindle assembly checkpoint, which functions to ensure proper distribution of chromosomes to daughter cells. Mps1 is hardly detectable in normal organs except the testis and placenta. However, high levels of Mps1 are found in many types of human malignancies, including glioblastoma, thyroid carcinoma, breast cancer, and other cancers. Several Mps1 inhibitors can inhibit the proliferation of cancer cells and exhibit demonstrable survival benefits...
December 1, 2016: Journal of Drug Targeting
https://www.readbyqxmd.com/read/27699881/structural-basis-of-reversine-selectivity-in-inhibiting-mps1-more-potently-than-aurora-b-kinase
#9
Yoshitaka Hiruma, Andre Koch, Shreya Dharadhar, Robbie P Joosten, Anastassis Perrakis
Monopolar spindle 1 (Mps1, also known as TTK) is a protein kinase crucial for ensuring that cell division progresses to anaphase only after all chromosomes are connected to spindle microtubules. Incomplete chromosomal attachment leads to abnormal chromosome counts in the daughter cells (aneuploidy), a condition common in many solid cancers. Therefore Mps1 is an established target in cancer therapy. Mps1 kinase inhibitors include reversine (2-(4-morpholinoanilino)-6-cyclohexylaminopurine), a promiscuous compound first recognized as an inhibitor of the Aurora B mitotic kinase...
December 2016: Proteins
https://www.readbyqxmd.com/read/27679546/association-between-polymorphisms-in-segregation-genes-bub1b-and-ttk-and-gastric-cancer-risk
#10
Petra Hudler, Nina Kocevar Britovsek, Snjezana Frkovic Grazio, Radovan Komel
BACKGROUND: Malignant transformation of normal gastric cells is a complex and multistep process, resulting in development of heterogeneous tumours. Susceptible genetic background, accumulation of genetic changes, and environmental factors play an important role in gastric carcinogenesis. Single nucleotide polymorphisms (SNPs) in mitotic segregation genes could be responsible for inducing the slow process of accumulation of genetic changes, leading to genome instability. PATIENTS AND METHODS: We performed a case-control study of polymorphisms in mitotic kinases TTK rs151658 and BUB1B rs1031963 and rs1801376 to assess their effects on gastric cancer risk...
September 1, 2016: Radiology and Oncology
https://www.readbyqxmd.com/read/27635108/expression-of-cancer-testis-antigens-in-colorectal-cancer-new-prognostic-and-therapeutic-implications
#11
Maciej Tarnowski, Michał Czerewaty, Anna Deskur, Krzysztof Safranow, Wojciech Marlicz, Elżbieta Urasińska, Mariusz Z Ratajczak, Teresa Starzyńska
Background. While cancer/testis antigens (CTAs) are restricted in postnatal tissues to testes and germ line-derived cells, their role in cancer development and the clinical significance of their expression still remain to be better defined. Objective. The aim of this study was to investigate the level of CTA expression in colon samples from patients with colorectal cancer (CRC) in relation to patient clinical status. Methods. Forty-five patients with newly diagnosed colorectal cancer were included in the study...
2016: Disease Markers
https://www.readbyqxmd.com/read/27622813/pits-a-protein-interacting-with-ttk69-and-sin3a-has-links-to-histone-deacetylation
#12
Gwo-Jen Liaw
Histone deacetylation plays an important role in transcriptional repression. Previous results showed that the genetic interaction between ttk and rpd3, which encodes a class I histone deacetylase, is required for tll repression. This study investigated the molecular mechanism by which Ttk69 recruits Rpd3. Using yeast two-hybrid screening and datamining, one novel protein was found that weakly interacts with Ttk69 and Sin3A, designated as Protein interacting with Ttk69 and Sin3A (Pits). Pits protein expressed in the early stages of embryos and bound to the region of the tor response element in vivo...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27618777/utility-of-the-dual-specificity-protein-kinase-ttk-as-a-therapeutic-target-for-intrahepatic-spread-of-liver-cancer
#13
Ruoyu Miao, Yan Wu, Haohai Zhang, Huandi Zhou, Xiaofeng Sun, Eva Csizmadia, Lian He, Yi Zhao, Chengyu Jiang, Rebecca A Miksad, Tahereh Ghaziani, Simon C Robson, Haitao Zhao
Therapies for primary liver cancer, the third leading cause of cancer-related death worldwide, remain limited. Following multi-omics analysis (including whole genome and transcriptome sequencing), we were able to identify the dual-specific protein kinase TTK as a putative new prognostic biomarker for liver cancer. Herein, we show that levels of TTK protein are significantly elevated in neoplastic tissues from a cohort of liver cancer patients, when compared with adjacent hepatic tissues. We also tested the utility of TTK targeted inhibition and have demonstrated therapeutic potential in an experimental model of liver cancer in vivo...
September 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27618721/identification-of-rsk-and-ttk-as-modulators-of-blood-vessel-morphogenesis-using-an-embryonic-stem-cell-based-vascular-differentiation-assay
#14
Lamis Hammoud, Jessica R Adams, Amanda J Loch, Richard C Marcellus, David E Uehling, Ahmed Aman, Christopher Fladd, Trevor D McKee, Christine E B Jo, Rima Al-Awar, Sean E Egan, Janet Rossant
Blood vessels are formed through vasculogenesis, followed by remodeling of the endothelial network through angiogenesis. Many events that occur during embryonic vascular development are recapitulated during adult neoangiogenesis, which is critical to tumor growth and metastasis. Current antiangiogenic tumor therapies, based largely on targeting the vascular endothelial growth factor pathway, show limited clinical benefits, thus necessitating the discovery of alternative targets. Here we report the development of a robust embryonic stem cell-based vascular differentiation assay amenable to small-molecule screens to identify novel modulators of angiogenesis...
October 11, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27587489/cell-panel-profiling-reveals-conserved-therapeutic-clusters-and-differentiates-the-mechanism-of-action-of-different-pi3k-mtor-aurora-kinase-and-ezh2-inhibitors
#15
Joost C M Uitdehaag, Jeroen A D M de Roos, Martine B W Prinsen, Nicole Willemsen-Seegers, Judith R F de Vetter, Jelle Dylus, Antoon M van Doornmalen, Jeffrey Kooijman, Masaaki Sawa, Suzanne J C van Gerwen, Jos de Man, Rogier C Buijsman, Guido J R Zaman
Cancer cell line panels are important tools to characterize the in vitro activity of new investigational drugs. Here, we present the inhibition profiles of 122 anticancer agents in proliferation assays with 44 or 66 genetically characterized cancer cell lines from diverse tumor tissues (Oncolines). The library includes 29 cytotoxics, 68 kinase inhibitors, and 11 epigenetic modulators. For 38 compounds this is the first comparative profiling in a cell line panel. By strictly maintaining optimized assay protocols, biological variation was kept to a minimum...
December 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27578794/sequoia-controls-the-type-i-0-daughter-proliferation-switch-in-the-developing-drosophila-nervous-system
#16
Erika Gunnar, Caroline Bivik, Annika Starkenberg, Stefan Thor
Neural progenitors typically divide asymmetrically to renew themselves, while producing daughters with more limited potential. In the Drosophila embryonic ventral nerve cord, neuroblasts initially produce daughters that divide once to generate two neurons/glia (type I proliferation mode). Subsequently, many neuroblasts switch to generating daughters that differentiate directly (type 0). This programmed type I>0 switch is controlled by Notch signaling, triggered at a distinct point of lineage progression in each neuroblast...
August 30, 2016: Development
https://www.readbyqxmd.com/read/27522003/hlf-mir-132-ttk-axis-regulates-cell-proliferation-metastasis-and-radiosensitivity-of-glioma-cells
#17
Shu Chen, Yang Wang, Chunxia Ni, Ge Meng, Xiaofang Sheng
Glioma is a malignant cancer with high mortality. A key prognostic factor of glioma is radiosensitivity. It has also been known that microRNAs (miR) significantly contribute to the development of glioma. miR-132 has been previously reported to inhibit tumor growth in some cancers, but not well studied in glioma. It is necessary to understand the association between miR-132 and glioma, including miR-132 expression in glioma, effects of miR-132 on cancer metastasis and radiosensitivity, and the involved molecular mechanism...
October 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27465922/multiple-sirna-delivery-against-cell-cycle-and-anti-apoptosis-proteins-using-lipid-substituted-polyethylenimine-in-triple-negative-breast-cancer-and-non-malignant-cells
#18
Manoj B Parmar, Bárbara E Arteaga Ballesteros, Timothy Fu, Remant Bahadur Kc, Hamidreza Montazeri Aliabadi, Judith C Hugh, Raimar Löbenberg, Hasan Uludağ
Conventional breast cancer therapies have significant limitations that warrant a search for alternative therapies. Short-interfering RNA (siRNA), delivered by polymeric biomaterials and capable of silencing specific genes critical for growth of cancer cells, holds great promise as an effective and more specific therapy. Here, we employed amphiphilic polymers and silenced the expression of two cell cycle proteins, TTK and CDC20, and the anti-apoptosis protein survivin to determine the efficacy of polymer-mediated siRNA treatment in breast cancer cells as well as side effects in non-malignant cells in vitro...
July 28, 2016: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/27437075/discovery-of-pyrazolo-1-5-a-pyrimidine-ttk-inhibitors-cfi-402257-is-a-potent-selective-bioavailable-anticancer-agent
#19
Yong Liu, Radoslaw Laufer, Narendra Kumar Patel, Grace Ng, Peter B Sampson, Sze-Wan Li, Yunhui Lang, Miklos Feher, Richard Brokx, Irina Beletskaya, Richard Hodgson, Olga Plotnikova, Donald E Awrey, Wei Qiu, Nickolay Y Chirgadze, Jacqueline M Mason, Xin Wei, Dan Chi-Chia Lin, Yi Che, Reza Kiarash, Graham C Fletcher, Tak W Mak, Mark R Bray, Henry W Pauls
This work describes a scaffold hopping exercise that begins with known imidazo[1,2-a]pyrazines, briefly explores pyrazolo[1,5-a][1,3,5]triazines, and ultimately yields pyrazolo[1,5-a]pyrimidines as a novel class of potent TTK inhibitors. An X-ray structure of a representative compound is consistent with 1(1)/2 type inhibition and provides structural insight to aid subsequent optimization of in vitro activity and physicochemical and pharmacokinetic properties. Incorporation of polar moieties in the hydrophobic and solvent accessible regions modulates physicochemical properties while maintaining potency...
July 14, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27427987/r7-photoreceptor-specification-in-the-developing-drosophila-eye-the-role-of-the-transcription-factor-deadpan
#20
Yannis Emmanuel Mavromatakis, Andrew Tomlinson
As cells proceed along their developmental pathways they make a series of sequential cell fate decisions. Each of those decisions needs to be made in a robust manner so there is no ambiguity in the state of the cell as it proceeds to the next stage. Here we examine the decision made by the Drosophila R7 precursor cell to become a photoreceptor and ask how the robustness of that decision is achieved. The transcription factor Tramtrack (Ttk) inhibits photoreceptor assignment, and previous studies found that the RTK-induced degradation of Ttk was critically required for R7 specification...
July 2016: PLoS Genetics
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