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https://www.readbyqxmd.com/read/29757997/tetragonia-tetragonioides-pall-kuntze-regulates-androgen-production-in-a-letrozole-induced-polycystic-ovary-syndrome-model
#1
Bo-Jeong Pyun, Hyun Yang, Eunjin Sohn, Song Yi Yu, Dongoh Lee, Dong Ho Jung, Byoung Seob Ko, Hye Won Lee
Tetragonia tetragonioides (Pall.) Kuntze (TTK) is a medicinal plant traditionally used to treat various diseases such as diabetic, inflammatory, and female-related disorders. Polycystic ovary syndrome (PCOS) is a common endocrinological disorder in women of reproductive age, and hyperandrogenism is a prominent feature of PCOS resulting in anovulation and infertility. In this study, we investigated the effects of a TTK extract on androgen generation and regulation of steroidogenic enzymes in vitro and in vivo...
May 14, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29736010/mps1-inhibitors-synergise-with-low-doses-of-taxanes-in-promoting-tumour-cell-death-by-enhancement-of-errors-in-cell-division
#2
Ana Rita R Maia, Simon Linder, Ji-Ying Song, Chantal Vaarting, Ute Boon, Colin E J Pritchard, Arno Velds, Ivo J Huijbers, Olaf van Tellingen, Jos Jonkers, René H Medema
BACKGROUND: Chromosomal instability (CIN) is a common trait of cancer characterised by the continuous gain and loss of chromosomes during mitosis. Excessive levels of CIN can suppress tumour growth, providing a possible therapeutic strategy. The Mps1/TTK kinase has been one of the prime targets to explore this concept, and indeed Mps1 inhibitors synergise with the spindle poison docetaxel in inhibiting the growth of tumours in mice. METHODS: To investigate how the combination of docetaxel and a Mps1 inhibitor (Cpd-5) promote tumour cell death, we treated mice transplanted with BRCA1-/- ;TP53-/- mammary tumours with docetaxel and/or Cpd-5...
May 8, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29721084/a-novel-usp9x-substrate-ttk-contributes-to-tumorigenesis-in-non-small-cell-lung-cancer
#3
Xiangling Chen, Chengli Yu, Jing Gao, Hongwen Zhu, Binghai Cui, Tao Zhang, Yanting Zhou, Qian Liu, Han He, Ruoxuan Xiao, Ruimin Huang, Hua Xie, Daming Gao, Hu Zhou
The X-linked deubiquitinase, USP9X, is implicated in multiple cancers by targeting various substrates. Increased expression of USP9X is observed in non-small-cell lung cancer (NSCLC) and is correlated with poor prognosis. However, the molecular mechanism for USP9X regulation of tumor cell survival and tumorigenesis in NSCLC is less defined. Methods: In this study, chemical labeling, quantitative proteomic screening was applied to analyze A549 cells with or without USP9X RNA interference. Functional in vitro and in vivo experiments were performed to confirm the oncogenic effects of USP9X in NSCLC and to investigate the underlying mechanisms...
2018: Theranostics
https://www.readbyqxmd.com/read/29718100/tmcrys-predict-propensity-of-success-for-transmembrane-protein-crystallization
#4
Julia K Varga, Gábor E Tusnády
Motivation: Transmembrane proteins are crucial in the life of the cells. As they have special properties, their structure is hard to determine - the PDB database consists of 2% transmembrane proteins, despite the fact that they are predicted to make up to 25% of the human proteome. Crystallization prediction methods were developed to aid the target selection for structure determination, however, there is a need for a transmembrane protein specific service. Results: Here, we present TMCrys, a crystallization prediction method, that surpasses existing prediction methods in performance thanks to its specialization for transmembrane proteins...
April 26, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29514617/could-pelvic-parameters-determine-optimal-postoperative-thoracic-kyphosis-in-lenke-type-1-ais-patients
#5
Shunan Liu, Yuancheng Zhang, Hongda Bao, Peng Yan, Zezhang Zhu, Zhen Liu, Bangping Qian, Yong Qiu
BACKGROUND: A proper restoration of sagittal alignment is essential in AIS patients, but few studies provided a formula to predict an optimal surgical thoracic kyphosis (TK) gain in adolescent idiopathic scoliosis (AIS) patients. A formula was recently proposed (LL = (PI+TK)/2 + 10) to predict the optimal lumbar lordosis (LL) in adult spinal deformity patients, which has not been validated in adolescents. The aim of this study is to establish a formula with TK and pelvic parameters in normal adolescents and predict an optimal TK with this formula pre- and post-operatively in Lenke 1 AIS patients...
March 7, 2018: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/29465777/expression-of-mage-a-and-ny-eso-1-cancer-testis-antigens-is-enriched-in-triple-negative-invasive-breast-cancers
#6
Ashwini Raghavendra, Priyakshi Kalita-de Croft, Ana C Vargas, Chanel E Smart, Peter T Simpson, Jodi M Saunus, Sunil R Lakhani
AIMS: A better understanding of the expression of cancer/testis antigens (CTAs) in breast cancer might enable the identification of new immunotherapy options, especially for triple-negative (TN) tumours, which lack expression of the conventional therapeutic targets oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The aim of this study was to quantify the expression of MAGE-A and NY-ESO-1 CTAs in breast cancer, and relate this to known clinicopathological parameters...
February 21, 2018: Histopathology
https://www.readbyqxmd.com/read/29423030/targeting-dual-specificity-protein-kinase-ttk-attenuates-tumorigenesis-of-glioblastoma
#7
Jia Wang, Yuchen Xie, Xiaobin Bai, Ning Wang, Hai Yu, Zhong Deng, Minxue Lian, Shuo Yu, Hao Liu, Wanfu Xie, Maode Wang
Accumulating evidence has proved that glioma stem-like cells (GSCs) are responsible for tumorigenesis, treatment resistance, and subsequent tumor recurrence in glioblastoma (GBM). In this study, we identified dual specificity protein kinase TTK (TTK) as the most up-regulated and differentially expressed kinase encoding genes in GSCs. Functionally, TTK was essential for in vitro clonogenicity and in vivo tumor propagation in GSCs. Clinically, TTK expression was highly enriched in GBM, moreover, was inversely correlated with a poor prognosis in GBM patients...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29385418/dibs-a-repository-of-disordered-binding-sites-mediating-interactions-with-ordered-proteins
#8
Eva Schad, Erzsébet Fichó, Rita Pancsa, István Simon, Zsuzsanna Dosztányi, Bálint Mészáros
Motivation: Intrinsically Disordered Proteins (IDPs) mediate crucial protein-protein interactions, most notably in signaling and regulation. As their importance is increasingly recognized, the detailed analyses of specific IDP interactions opened up new opportunities for therapeutic targeting. Yet, large scale information about IDP-mediated interactions in structural and functional details are lacking, hindering the understanding of the mechanisms underlying this distinct binding mode...
February 1, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29378962/disruption-of-the-anaphase-promoting-complex-confers-resistance-to-ttk-inhibitors-in-triple-negative-breast-cancer
#9
K L Thu, J Silvester, M J Elliott, W Ba-Alawi, M H Duncan, A C Elia, A S Mer, P Smirnov, Z Safikhani, B Haibe-Kains, T W Mak, D W Cescon
TTK protein kinase (TTK), also known as Monopolar spindle 1 (MPS1), is a key regulator of the spindle assembly checkpoint (SAC), which functions to maintain genomic integrity. TTK has emerged as a promising therapeutic target in human cancers, including triple-negative breast cancer (TNBC). Several TTK inhibitors (TTKis) are being evaluated in clinical trials, and an understanding of the mechanisms mediating TTKi sensitivity and resistance could inform the successful development of this class of agents. We evaluated the cellular effects of the potent clinical TTKi CFI-402257 in TNBC models...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29353882/igf1r-signaling-drives-antiestrogen-resistance-through-pak2-pix-activation-in-luminal-breast-cancer
#10
Yinghui Zhang, Lynn Wester, Jichao He, Tamar Geiger, Marja Moerkens, Ram Siddappa, Jean A Helmijr, Mieke M Timmermans, Maxime P Look, Caroline H M van Deurzen, John W M Martens, Chantal Pont, Marjo de Graauw, Erik H J Danen, Els M J J Berns, John H N Meerman, Maurice P H M Jansen, Bob van de Water
Antiestrogen resistance in estrogen receptor positive (ER+ ) breast cancer is associated with increased expression and activity of insulin-like growth factor 1 receptor (IGF1R). Here, a kinome siRNA screen has identified 10 regulators of IGF1R-mediated antiestrogen with clinical significance. These include the tamoxifen resistance suppressors BMPR1B, CDK10, CDK5, EIF2AK1, and MAP2K5, and the tamoxifen resistance inducers CHEK1, PAK2, RPS6KC1, TTK, and TXK. The p21-activated kinase 2, PAK2, is the strongest resistance inducer...
April 2018: Oncogene
https://www.readbyqxmd.com/read/29212506/chromosome-9p-copy-number-gains-involving-pd-l1-are-associated-with-a-specific-proliferation-and-immune-modulating-gene-expression-program-active-across-major-cancer-types
#11
Jan Budczies, Carsten Denkert, Balázs Győrffy, Peter Schirmacher, Albrecht Stenzinger
BACKGROUND: Inhibition of the PD-L1/PD-1 immune checkpoint axis represents one of the most promising approaches of immunotherapy for various cancer types. However, immune checkpoint inhibition is successful only in subpopulations of patients emphasizing the need for powerful biomarkers that adequately reflect the complex interaction between the tumor and the immune system. Recently, recurrent copy number gains (CNG) in chromosome 9p involving PD-L1 were detected in many cancer types including lung cancer, melanoma, bladder cancer, head and neck cancer, cervical cancer, soft tissue sarcoma, prostate cancer, gastric cancer, ovarian cancer, and triple-negative breast cancer...
December 6, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/29149186/cell-cycle-time-series-gene-expression-data-encoded-as-cyclic-attractors-in-hopfield-systems
#12
Anthony Szedlak, Spencer Sims, Nicholas Smith, Giovanni Paternostro, Carlo Piermarocchi
Modern time series gene expression and other omics data sets have enabled unprecedented resolution of the dynamics of cellular processes such as cell cycle and response to pharmaceutical compounds. In anticipation of the proliferation of time series data sets in the near future, we use the Hopfield model, a recurrent neural network based on spin glasses, to model the dynamics of cell cycle in HeLa (human cervical cancer) and S. cerevisiae cells. We study some of the rich dynamical properties of these cyclic Hopfield systems, including the ability of populations of simulated cells to recreate experimental expression data and the effects of noise on the dynamics...
November 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29147457/oxidative-stress-delays-prometaphase-metaphase-of-the-first-cleavage-in-mouse-zygotes-via-the-mad2l1-mediated-spindle-assembly-checkpoint
#13
Que Wu, Zhiling Li, Yue Huang, Diting Qian, Man Chen, Wanfen Xiao, Bin Wang
In zygotes, DNA damage delays the first cleavage to enable repair. Our previous study found that 0.03 mM hydrogen peroxide (H2 O2 ) was the minimum concentration required for induction of oxidative DNA damage in mouse zygotes and that this represented the most similar situation to the clinical phenomenon. In this study, we quantified the cleavage rates of cells in blastocysts at different developmental stages, followed by immunofluorescence to detect activation of γ -H2A histone family member X (a marker of DNA damage) in zygotes to confirm that oxidative DNA damage was induced in H2 O2 -treated zygotes...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29100415/the-e2f-activators-control-multiple-mitotic-regulators-and-maintain-genomic-integrity-through-sgo1-and-bubr1
#14
Miyoung Lee, Yainyrette Rivera-Rivera, Carlos S Moreno, Harold I Saavedra
The E2F1, E2F2, and E2F3a transcriptional activators control proliferation. However, how the E2F activators regulate mitosis to maintain genomic integrity is unclear. Centrosome amplification (CA) and unregulated spindle assembly checkpoint (SAC) are major generators of aneuploidy and chromosome instability (CIN) in cancer. Previously, we showed that overexpression of single E2F activators induced CA and CIN in mammary epithelial cells, and here we show that combined overexpression of E2F activators did not enhance CA...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29036655/mfib-a-repository-of-protein-complexes-with-mutual-folding-induced-by-binding
#15
Erzsébet Fichó, István Reményi, István Simon, Bálint Mészáros
Motivation: It is commonplace that intrinsically disordered proteins (IDPs) are involved in crucial interactions in the living cell. However, the study of protein complexes formed exclusively by IDPs is hindered by the lack of data and such analyses remain sporadic. Systematic studies benefited other types of protein-protein interactions paving a way from basic science to therapeutics; yet these efforts require reliable datasets that are currently lacking for synergistically folding complexes of IDPs...
November 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29025594/gene-expression-profiling-pathway-analysis-and-subtype-classification-reveal-molecular-heterogeneity-in-hepatocellular-carcinoma-and-suggest-subtype-specific-therapeutic-targets
#16
Rahul Agarwal, Jitendra Narayan, Amitava Bhattacharyya, Mayank Saraswat, Anil Kumar Tomar
A very low 5-year survival rate among hepatocellular carcinoma (HCC) patients is mainly due to lack of early stage diagnosis, distant metastasis and high risk of postoperative recurrence. Hence ascertaining novel biomarkers for early diagnosis and patient specific therapeutics is crucial and urgent. Here, we have performed a comprehensive analysis of the expression data of 423 HCC patients (373 tumors and 50 controls) downloaded from The Cancer Genome Atlas (TCGA) followed by pathway enrichment by gene ontology annotations, subtype classification and overall survival analysis...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/28991472/the-discovery-of-a-dual-ttk-protein-kinase-cdc2-like-kinase-clk2-inhibitor-for-the-treatment-of-triple-negative-breast-cancer-initiated-from-a-phenotypic-screen
#17
Jennifer R Riggs, Mark Nagy, Jan Elsner, Paul Erdman, Dan Cashion, Dale Robinson, Roy Harris, Dehua Huang, Lida Tehrani, Gordafaried Deyanat-Yazdi, Rama Krishna Narla, Xiaohui Peng, Tam Tran, Leo Barnes, Terra Miller, Jason Katz, Yang Tang, Ming Chen, Mehran F Moghaddam, Sogole Bahmanyar, Barbra Pagarigan, Silvia Delker, Laurie LeBrun, Philip P Chamberlain, Andrew Calabrese, Stacie S Canan, Katerina Leftheris, Dan Zhu, John F Boylan
Triple negative breast cancer (TNBC) remains a serious unmet medical need with discouragingly high relapse rates. We report here the synthesis and structure-activity relationship (SAR) of a novel series of 2,4,5-trisubstituted-7H-pyrrolo[2,3-d]pyrimidines with potent activity against TNBC tumor cell lines. These compounds were discovered from a TNBC phenotypic screen and possess a unique dual inhibition profile targeting TTK (mitotic exit) and CLK2 (mRNA splicing). Design and optimization, driven with a TNBC tumor cell assay, identified potent and selective compounds with favorable in vitro and in vivo activity profiles and good iv PK properties...
November 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28911857/new-mouse-model-for-inducing-and-evaluating-unilateral-vestibular-deafferentation-syndrome
#18
R Cassel, P Bordiga, D Pericat, C Hautefort, B Tighilet, C Chabbert
BACKGROUND: Unilateral vestibular deafferentation syndrome (uVDS) holds a particular place in the vestibular pathology domain. Due to its suddenness, the violence of its symptoms that often result in emergency hospitalization, and its associated original neurophysiological properties, this syndrome is a major source of questioning for the otoneurology community. Also, its putative pathogenic causes remain to be determined. There is currently a strong medical need for the development of targeted and effective countermeasures to improve the therapeutic management of uVDS...
January 1, 2018: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28892033/ultrasound-guided-intracardiac-injection-of-human-mesenchymal-stem-cells-to-increase-homing-to-the-intestine-for-use-in-murine-models-of-experimental-inflammatory-bowel-diseases
#19
Maneesh Dave, Paola Menghini, Keiki Sugi, Rodrigo A Somoza, Zhenghong Lee, Mukesh Jain, Arnold Caplan, Fabio Cominelli
Crohn's disease (CD) is a common chronic inflammatory disease of the small and large intestines. Murine and human mesenchymal stem cells (MSCs) have immunosuppressive potential and have been shown to suppress inflammation in mouse models of intestinal inflammation, even though the route of administration can limit their homing and effectiveness 1 , 3 , 4 , 5 . Local application of MSCs to colonic injury models has shown greater efficacy at ameliorating inflammation in the colon. However, there is paucity of data on techniques to enhance the localization of human bone marrow-derived MSCs (hMSCs) to the small intestine, the site of inflammation in the SAMP-1/YitFc (SAMP) model of experimental Crohn's disease...
September 1, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28883705/threonine-and-tyrosine-kinase-may-serve-as-a-prognostic-biomarker-for-gallbladder-cancer
#20
Yuan Xie, Jian-Zhen Lin, An-Qiang Wang, Wei-Yu Xu, Jun-Yu Long, Yu-Feng Luo, Jie Shi, Zhi-Yong Liang, Xin-Ting Sang, Hai-Tao Zhao
AIM: To detect the expression of threonine and tyrosine kinase (TTK) in gallbladder cancer (GBC) specimens and analyze the associations between TTK expression and clinicopathological parameters and clinical prognosis. METHODS: A total of 68 patients with GBC who underwent surgical resection were enrolled in this study. The expression of TTK in GBC tissues was detected by immunohistochemistry. The assessment of TTK expression was conducted using the H-scoring system...
August 21, 2017: World Journal of Gastroenterology: WJG
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