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https://www.readbyqxmd.com/read/29223097/recent-advances-in-microtubule-stabilizing-agents
#1
REVIEW
Ya-Nan Cao, Ling-Li Zheng, Dan Wang, Xiao-Xia Liang, Feng Gao, Xian-Li Zhou
Highly dynamic mitotic spindle microtubules are superb therapeutic targets for a group of chemically diverse and clinically successful anticancer drugs. Microtubule-targeted drugs disrupt microtubule dynamics in distinct ways, and they are primarily classified into two groups: microtubule destabilizing agents (MDAs), such as vinblastine, colchicine, and combretastatin-A4, and microtubule stabilizing agents (MSAs), such as paclitaxel and epothilones. Systematic discovery and development of new MSAs have been aided by extensive research on paclitaxel, yielding a large number of promising anticancer compounds...
November 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29222416/functional-analysis-of-human-intrafusal-fiber-innervation-by-human-%C3%AE-motoneurons
#2
A Colón, X Guo, N Akanda, Y Cai, J J Hickman
Investigation of neuromuscular deficits and diseases such as SMA, as well as for next generation prosthetics, utilizing in vitro phenotypic models would benefit from the development of a functional neuromuscular reflex arc. The neuromuscular reflex arc is the system that integrates the proprioceptive information for muscle length and activity (sensory afferent), to modify motoneuron output to achieve graded muscle contraction (actuation efferent). The sensory portion of the arc is composed of proprioceptive sensory neurons and the muscle spindle, which is embedded in the muscle tissue and composed of intrafusal fibers...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29222185/p37-ubxn2b-regulates-spindle-orientation-by-limiting-cortical-numa-recruitment-via-pp1-repo-man
#3
Byung Ho Lee, Francoise Schwager, Patrick Meraldi, Monica Gotta
Spindle orientation determines the axis of division and is crucial for cell fate, tissue morphogenesis, and the development of an organism. In animal cells, spindle orientation is regulated by the conserved Gαi-LGN-NuMA complex, which targets the force generator dynein-dynactin to the cortex. In this study, we show that p37/UBXN2B, a cofactor of the p97 AAA ATPase, regulates spindle orientation in mammalian cells by limiting the levels of cortical NuMA. p37 controls cortical NuMA levels via the phosphatase PP1 and its regulatory subunit Repo-Man, but it acts independently of Gαi, the kinase Aurora A, and the phosphatase PP2A...
December 8, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29220790/2-alkoxycarbonyl-3-arylamino-5-substituted-thiophenes-as-a-novel-class-of-antimicrotubule-agents-design-synthesis-cell-growth-and-tubulin-polymerization-inhibition
#4
Romeo Romagnoli, Maria Kimatrai Salvador, Santiago Schiaffino Ortega, Pier Giovanni Baraldi, Paola Oliva, Stefania Baraldi, Luisa Carlota Lopez-Cara, Andrea Brancale, Salvatore Ferla, Ernest Hamel, Jan Balzarini, Sandra Liekens, Elena Mattiuzzo, Giuseppe Basso, Giampietro Viola
Microtubules are recognized as crucial components of the mitotic spindle during cell division, and, for this reason, the microtubule system is an attractive target for the development of anticancer agents. Continuing our search strategy for novel tubulin targeting-compounds, a new series of 2-alkoxycarbonyl-3-(3',4',5'-trimethoxyanilino)-5-aryl/heteroarylthiophene derivatives was designed, synthesized and demonstrated to act as tubulin polymerization inhibitors at the colchicine site. A structure-activity relationship study on the phenyl at the 5-position of the thiophene ring was performed by introducing a variety of substituents containing electron-releasing and electron-withdrawing groups, with the 2-alkoxycarbonyl-3-(3',4',5'-trimethoxyanilino)thiophene scaffold being the minimum structural requirement for activity...
December 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29220700/prognostic-importance-of-aurora-kinases-and-mitotic-spindle-genes-transcript-levels-in-myelodysplastic-syndrome
#5
Daniela de Paula Borges, Antônio Wesley Araújo Dos Santos, Carlos Roberto Koscky Paier, Howard Lopes Ribeiro, Marília Braga Costa, Izabelle Rocha Farias, Roberta Taiane Germano de Oliveira, Ivo Gabriel da Frota França, Gabrielle Melo Cavalcante, Sílvia Maria Meira Magalhães, Ronald Feitosa Pinheiro
Myelodysplastic syndrome (MDS) are a heterogeneous group of clonal disease characterized by insufficiency of bone marrow, increase of apoptosis and increased risk of acute leukemia progression. Proteins related to the mitotic spindle (AURKA, AURKB, TPX2), to the mitotic checkpoint (MAD2, CDC20) and the regulation of the cell cycle (p21) are directly related to chromosomal stability and tumor development. This study aimed to evaluate the mRNA expression levels of these genes in 101 MDS patients using a real-time PCR methodology...
November 28, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29218302/canine-soft-tissue-sarcomas-can-being-a-dog-s-best-friend-help-a-child
#6
Bernard Séguin
Soft tissue sarcomas (STSs) remain a therapeutic challenge for pediatric and adolescent and young adult (AYA) patients. Still today, surgery, radiation therapy, and chemotherapy remain the mainstay of treatment. Obstacles in developing new treatment approaches to improve the outcome are: few patients to enroll in clinical trials, and the diversity of tumor biology between histologic subtypes. Pet dogs may offer an additional strategy to discover and test new therapeutic avenues. The number of dogs diagnosed with a STS each year in the United States is estimated to be around 27,000 to 95,000...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29217690/re-positioning-of-somatic-golgi-apparatus-is-essential-for-the-dendritic-establishment-of-adult-born-hippocampal-neurons
#7
Sneha Rao, Gregory W Kirschen, Joanna Szczurkowska, Adrian Di Antonio, Jia Wang, Shaoyu Ge, Maya Shelly
New dentate granule cells are continuously generated, and integrate into the pre-existing hippocampal network in the adult brain. How an adult-born neuron with initially simple spindle-like morphology develops into a complex dentate granule cell (DGC), consisting of a single apical dendrite with further branches, remains largely unknown. Here, using retroviruses to birth-date and manipulate newborn neurons, we examined initial dendritic formation, and possible underlying mechanisms. We found that GFP-expressing newborn cells began to establish a DGC-like morphology at around 7 days after birth, with a primary dendrite pointing to the molecular layer, but at this stage, with several neurites in the neurogenic zone...
December 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29217404/high-density-eeg-characterization-of-brain-responses-to-auditory-rhythmic-stimuli-during-wakefulness-and-nrem-sleep
#8
Caroline Lustenberger, Yogi A Patel, Sankaraleengam Alagapan, Jessica M Page, Betsy Price, Michael R Boyle, Flavio Frohlich
Auditory rhythmic sensory stimulation modulates brain oscillations by increasing phase-locking to the temporal structure of the stimuli and by increasing the power of specific frequency bands, resulting in Auditory Steady State Responses (ASSR). The ASSR is altered in different diseases of the central nervous system such as schizophrenia. However, in order to use the ASSR as biological markers for disease states, it needs to be understood how different vigilance states and underlying brain activity affect the ASSR...
December 4, 2017: NeuroImage
https://www.readbyqxmd.com/read/29214215/genomic-and-transcriptomic-heterogeneity-in-metaplastic-carcinomas-of-the-breast
#9
Salvatore Piscuoglio, Charlotte K Y Ng, Felipe C Geyer, Kathleen A Burke, Catherine F Cowell, Luciano G Martelotto, Rachael Natrajan, Tatiana Popova, Christopher A Maher, Raymond S Lim, Ino de Bruijn, Odette Mariani, Larry Norton, Anne Vincent-Salomon, Britta Weigelt, Jorge S Reis-Filho
Metaplastic breast cancer (MBC) is a rare special histologic type of triple-negative breast cancer, characterized by the presence of neoplastic cells showing differentiation towards squamous epithelium and/or mesenchymal elements. Here we sought to define whether histologically distinct subgroups of MBCs would be underpinned by distinct genomic and/or transcriptomic alterations. Microarray-based copy number profiling identified limited but significant differences between the distinct MBC subtypes studied here, despite the limited sample size (n = 17)...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29213094/sodium-fluoride-exposure-exerts-toxic-effects-on-porcine-oocyte-maturation
#10
Shuang Liang, Zheng-Wen Nie, Minghui Zhao, Ying-Jie Niu, Kyung-Tae Shin, Xiang-Shun Cui
Excessive long-term fluoride intake is associated with several health problems, including infertility. However, limited information is available on the toxic effects of fluoride exposure on the female reproductive system, especially oocyte maturation. In this study, we investigated the toxic effect of sodium fluoride (NaF) exposure on porcine oocyte maturation and its possible underlying mechanisms. Our results showed that NaF exposure during porcine oocyte maturation inhibited cumulus cell expansion and impaired polar body extrusion...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29212914/distributed-force-feedback-in-the-spinal-cord-and-the-regulation-of-limb-mechanics
#11
T Richard Nichols
This review is an update on the role of force feedback from Golgi tendon organs in the regulation of limb mechanics during voluntary movement. Some current ideas about the role of force feedback are based on circuit motifs linking idealized systems of agonists, synergists and antagonistic muscles. Force feedback is widely distributed across the muscles of a limb and cannot be understood based on these circuit motifs. Muscle architecture similarly cannot be understood in terms of idealized systems. It is hypothesized that distributed force feedback better represents the complex mechanical interactions of muscles, including viscoelastic coupling and inertial coupling across joints and axes of rotation...
December 6, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29212393/-noninvasive-follicular-thyroid-neoplasm-with-papillary-like-nuclear-features-with-focal-spindle-cell-metaplasia
#12
Grégoire Arnoux, Marc Pusztaszeri
"Noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) is a recent reclassification of the encapsulated follicular variant of papillary thyroid carcinoma, which is supposed to reflect its indolent clinical behavior and to prevent overtreatment of patients with this neoplasm. The diagnosis of NIFTP can only be made histologically on the surgical specimen according to specific inclusion and exclusion criteria, which requires the examination of the whole nodule and its capsule. Spindle cell proliferations, especially of follicular cell origin, arising within thyroid follicular neoplasms are very rare and may cause diagnostic difficulties...
December 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29211342/functional-bkca-channel-in-human-resident-cardiac-stem-cells-expressing-w8b2
#13
Oualid Ayad, Christophe Magaud, Stéphane Sebille, Jocelyn Bescond, Chloé Mimbimi, Christian Cognard, Jean-Francois Faivre, Patrick Bois, Aurelien Chatelier
Recently, a new population of resident cardiac stem cells positive for W8B2 marker has been identified. These cardiac stem cells (CSCs) are considered as an ideal cellular source to repair myocardial damage after infarction. However, the electrophysiological profile of these cells has not been characterized yet. We first establish the conditions of isolation and expansion of W8B2+ CSCs from human heart biopsies using magnetic sorting system followed by flow cytometry cell sorting. These cells display a spindle-shaped morphology, are highly proliferative and possess self-renewal capacity demonstrated by their ability to form colonies...
December 6, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29210713/intradermal-proliferative-fasciitis-occurring-with-chondrodermatitis-nodularis-helicis
#14
Ashley Elsensohn, Sasha Getty, Jessica Shiu, Sébastien de Feraudy
Nodular fasciitis is a benign myofibroblastic tumor. Its uncommon variant, proliferative fasciitis (PF), can present in an even less common intradermal form. We report a case of intradermal PF of the ear in a 45-year-old man who presented with recurrent episodes of pain and swelling of the lesion. Histologic examination showed a dermal, nodular proliferation of ganglion-like basophilic fibroblasts with prominent nuclei and nucleoli, admixed with foamy histiocytes and areas of spindle cells arranged in intersecting fascicles in a fibromyxoid background...
November 21, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/29210499/supramolecular-step-polymerization-of-preassembled-micelles-a-study-of-polymerization-kinetics
#15
Chaoying Yang, Xiaodong Ma, Jiaping Lin, Liquan Wang, Yingqing Lu, Liangshun Zhang, Chunhua Cai, Liang Gao
In nature, sophisticated functional materials are created through hierarchical self-assembly of nanoscale motifs, which has inspired the fabrication of man-made materials with complex architectures for a variety of applications. Herein, a kinetic study on the self-assembly of spindle-like micelles preassembled from polypeptide graft copolymers is reported. The addition of dimethylformamide and, subsequently, a selective solvent (water) can generate a "reactive point" at both ends of the spindles as a result of the existence of structural defects, which induces the "polymerization" of the spindles into nanowires...
December 6, 2017: Macromolecular Rapid Communications
https://www.readbyqxmd.com/read/29209796/-spindle-cell-osteosclerotic-bone-lesion-with-mdm2-amplification
#16
C Mogler, M Boxberg, C Knebel, W Weichert, K Wörtler, K Specht
This case report presents an osteosclerotic bone lesion in a 49-year-old man with MDM2 amplification. The final diagnosis shows metastasis to the bones from stomach cancer. In primary bone tumours, the MDM2 amplifications observed have been described for many other tumour entities as well, and therefore do not exclude bone metastasis from a carcinoma.
December 5, 2017: Der Pathologe
https://www.readbyqxmd.com/read/29209640/some-assembly-required-redefining-the-mitotic-checkpoint
#17
John C Meadows, Jonathan B A Millar
The spindle assembly checkpoint (also known as the spindle or mitotic checkpoint) is a surveillance system that ensures fidelity of chromosome segregation. Here we suggest, in light of historical and more recent evidence, that this signaling system monitors kinetochore attachment and spindle assembly by two distinct, but functionally overlapping, pathways.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/29209533/vinorelbine-in-braf-v600e-mutated-metastatic-colorectal-cancer-a-prospective-multicentre-phase-ii-clinical-study
#18
Chiara Cremolini, Filippo Pietrantonio, Gianluca Tomasello, Vincenzo Dadduzio, Roberto Moretto, Federica Morano, Marta Schirripa, Carlotta Antoniotti, Giovanni Fucà, Francesca Bergamo, Daniele Rossini, Federico Nichetti, Stamatia Ziampiri, Michele Ghidini, Federica Marmorino, Michele Prisciandaro, Alfredo Falcone, Filippo De Braud, Fotios Loupakis, Sara Lonardi
Background: BRAF V600E mutation defines a specific colorectal cancer (CRC) subgroup with poor prognosis. Promising preclinical data showed synthetically lethal activity of mitotic spindle poisons on BRAF-mutated and BRAF-like CRC models. We designed a phase II trial to test the activity of vinorelbine in patients with BRAF V600E mutated metastatic CRC (mCRC). Patients and methods: Patients progressed to or not deemed eligible for standard treatments received oral (60 mg/sqm) or intravenous (25 mg/sqm) vinorelbine, on days 1 and 8 every 21 days...
2017: ESMO Open
https://www.readbyqxmd.com/read/29208896/mechanistic-insight-into-trip13-catalyzed-mad2-structural-transition-and-spindle-checkpoint-silencing
#19
Melissa L Brulotte, Byung-Cheon Jeong, Faxiang Li, Bing Li, Eric B Yu, Qiong Wu, Chad A Brautigam, Hongtao Yu, Xuelian Luo
The spindle checkpoint maintains genomic stability and prevents aneuploidy. Unattached kinetochores convert the latent open conformer of the checkpoint protein Mad2 (O-Mad2) to the active closed conformer (C-Mad2), bound to Cdc20. C-Mad2-Cdc20 is incorporated into the mitotic checkpoint complex (MCC), which inhibits the anaphase-promoting complex/cyclosome (APC/C). The C-Mad2-binding protein p31comet and the ATPase TRIP13 promote MCC disassembly and checkpoint silencing. Here, using nuclear magnetic resonance (NMR) spectroscopy, we show that TRIP13 and p31comet catalyze the conversion of C-Mad2 to O-Mad2, without disrupting its stably folded core...
December 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/29208529/vesicular-transport-protein-arf6-modulates-cytoskeleton-dynamics-for-polar-body-extrusion-in-mouse-oocyte-meiosis
#20
Xing Duan, Hao-Lin Zhang, Meng-Hao Pan, Yu Zhang, Shao-Chen Sun
Arf6 (ADP-ribosylation factor 6) is known to play important roles in membrane dynamics through the regulation of actin filament reorganization for multiple cellular processes such as cytokinesis, phagocytosis, cell migration and tumor cell invasion. However, the functions of Arf6 in mammalian oocyte meiosis have not been clarified. In present study we showed that Arf6 expressed in mouse oocytes and was mainly distributed around the spindle during meiosis. Depletion of Arf6 by morpholino microinjection caused oocytes failing to extrude first polar body...
December 2, 2017: Biochimica et Biophysica Acta
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