Read by QxMD icon Read


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
Ashwini Raghavendra, Priyakshi Kalita-de Croft, Ana Cristina Vargas, Chanel E Smart, Peter T Simpson, Jodi M Saunus, Sunil R Lakhani
AIMS: A better understanding of the expression of cancer testis antigens (CTA) in breast cancer might identify new immunotherapy options, especially for triple-negative (TN) tumours, which lack expression of conventional therapeutic targets ER, PR and HER2 (receptors for Oestrogen, Progesterone and Human epidermal growth factor). 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 clinicopathologic parameters. METHODS AND RESULTS: We surveyed MAGE-A and NY-ESO-1 protein expression in an unselected cohort of 367 breast tumours (out of which 65 tumours were TN), with accompanying clinical follow-up data, using immunohistochemistry (IHC) analysis of tissue microarrays...
February 21, 2018: Histopathology
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
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
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...
January 29, 2018: Proceedings of the National Academy of Sciences of the United States of America
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...
January 22, 2018: Oncogene
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
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
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 (H2O2) 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 H2O2-treated zygotes...
2017: Oxidative Medicine and Cellular Longevity
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
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
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
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
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
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
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
Julien Tierny, Guillaume Favelier, Joshua A Levine, Charles Gueunet, Michael Michaux
This system paper presents the Topology ToolKit (TTK), a software platform designed for the topological analysis of scalar data in scientific visualization. While topological data analysis has gained in popularity over the last two decades, it has not yet been widely adopted as a standard data analysis tool for end users or developers. TTK aims at addressing this problem by providing a unified, generic, efficient, and robust implementation of key algorithms for the topological analysis of scalar data, including: critical points, integral lines, persistence diagrams, persistence curves, merge trees, contour trees, Morse-Smale complexes, fiber surfaces, continuous scatterplots, Jacobi sets, Reeb spaces, and more...
August 29, 2017: IEEE Transactions on Visualization and Computer Graphics
Fei Chen, Eva P Szymanski, Kenneth N Olivier, Xinyue Liu, Hervé Tettelin, Steven M Holland, Priya Duggal
RATIONALE: Pulmonary nontuberculous mycobacterial (PNTM) disease often affects white postmenopausal women, with a tall and lean body habitus and higher rates of scoliosis, pectus excavatum, mitral valve prolapse, and mutations in the CFTR gene. These clinical features and the familial clustering of the disease suggest an underlying genetic mechanism. OBJECTIVES: To map the genes associated with PNTM, whole-exome sequencing (WES) was conducted in 12 PNTM families and 57 sporadic cases recruited at the NIH Clinical Center during 2001-2013...
August 4, 2017: American Journal of Respiratory and Critical Care Medicine
A Szymiczek, M Carbone, S Pastorino, A Napolitano, M Tanji, M Minaai, I Pagano, J M Mason, H I Pass, M R Bray, T W Mak, H Yang
Malignant mesothelioma (MM) is an aggressive malignancy, highly resistant to current medical and surgical therapies, whose tumor cells characteristically show a high level of aneuploidy and genomic instability. We tested our hypothesis that targeting chromosomal instability in MM would improve response to therapy. Thr/Tyr kinase (TTK)/monopolar spindle 1 kinase (Mps-1) is a kinase of the spindle assembly checkpoint that controls cell division and cell fate. CFI-402257 is a novel, selective inhibitor of Mps-1 with antineoplastic activity...
November 16, 2017: Oncogene
Guido J R Zaman, Jeroen A D M de Roos, Marion A A Libouban, Martine B W Prinsen, Jos de Man, Rogier C Buijsman, Joost C M Uitdehaag
The spindle assembly checkpoint kinase TTK (Mps1) is a key regulator of chromosome segregation and is the subject of novel targeted therapy approaches by small-molecule inhibitors. Although the first TTK inhibitors have entered phase I dose escalating studies in combination with taxane chemotherapy, a patient stratification strategy is still missing. With the aim to identify a genomic biomarker to predict the response of tumor cells to TTK inhibitor therapy, we profiled a set of preclinical and clinical TTK inhibitors from different chemical series on a panel of 66 genetically characterized cell lines derived from different tumors (Oncolines)...
November 2017: Molecular Cancer Therapeutics
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"