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Mitotic cell death

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https://www.readbyqxmd.com/read/28337125/neuronal-mitophagy-in-neurodegenerative-diseases
#1
REVIEW
Marta Martinez-Vicente
Neuronal homeostasis depends on the proper functioning of different quality control systems. All intracellular components are subjected to continuous turnover through the coordinated synthesis, degradation and recycling of their constituent elements. Autophagy is the catabolic mechanism by which intracellular cytosolic components, including proteins, organelles, aggregates and any other intracellular materials, are delivered to lysosomes for degradation. Among the different types of selective autophagy described to date, the process of mitophagy involves the selective autophagic degradation of mitochondria...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28335397/emerging-anti-mitotic-activities-and-other-bioactivities-of-sesquiterpene-compounds-upon-human-cells
#2
REVIEW
Alessandra Bosco, Roy M Golsteyn
We review the bio-activities of natural product sesquiterpenes and present the first description of their effects upon mitosis. This type of biological effect upon cells is unexpected because sesquiterpenes are believed to inactivate proteins through Michael-type additions that cause non-specific cytotoxicity. Yet, certain types of sesquiterpenes can arrest cells in mitosis as measured by cell biology, biochemical and imaging techniques. We have listed the sesquiterpenes that arrest cells in mitosis and analyzed the biological data that support those observations...
March 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28334731/characterisation-of-cct271850-a-selective-oral-and-potent-mps1-inhibitor-used-to-directly-measure-in-vivo-mps1-inhibition-vs-therapeutic-efficacy
#3
Amir Faisal, Grace W Y Mak, Mark D Gurden, Cristina P R Xavier, Simon J Anderhub, Paolo Innocenti, Isaac M Westwood, Sébastien Naud, Angela Hayes, Gary Box, Melanie R Valenti, Alexis K De Haven Brandon, Lisa O'Fee, Jessica Schmitt, Hannah L Woodward, Rosemary Burke, Rob L M vanMontfort, Julian Blagg, Florence I Raynaud, Suzanne A Eccles, Swen Hoelder, Spiros Linardopoulos
BACKGROUND: The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterised checkpoint pathways is the spindle assembly checkpoint, which prevents anaphase onset until the appropriate attachment and tension across kinetochores is achieved. MPS1 kinase activity is essential for the activation of the spindle assembly checkpoint and has been shown to be deregulated in human tumours with chromosomal instability and aneuploidy...
March 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28323576/tat-rasgap317-326-enhances-radiosensitivity-of-human-carcinoma-cell-lines-in-vitro-and-in-vivo-through-promotion-of-delayed-mitotic-cell-death
#4
Pelagia Tsoutsou, Alessandro Annibaldi, David Viertl, Jonathan Ollivier, Franz Buchegger, Marie-Catherine Vozenin, Jean Bourhis, Christian Widmann, Oscar Matzinger
The synthetic peptide TAT-RasGAP317-326 has been shown to potentiate the efficacy of anti-cancer drugs. In this study, we explored the action of TAT-RasGAP317-326 when combined with radiation by investigating its radiosensitizing activity in vitro and in vivo. To investigate the modulation of intrinsic radiosensitivity induced by TAT-RasGAP317-326, clonogenic assays were performed using four human cancer cell lines, HCT116 p53(+/+) (ATCC: CCL-247), HCT116 p53(-/-), PANC-1 (ATCC: CRL-1469) and HeLa (ATCC: CCL-2), as well as one nontumor cell line, HaCaT (CLS: 300493)...
March 21, 2017: Radiation Research
https://www.readbyqxmd.com/read/28314740/dual-recognition-of-chromatin-and-microtubules-by-incenp-is-important-for-mitotic-progression
#5
Michael S Wheelock, David J Wynne, Boo Shan Tseng, Hironori Funabiki
The chromosomal passenger complex (CPC), composed of inner centromere protein (INCENP), Survivin, Borealin, and the kinase Aurora B, contributes to the activation of the mitotic checkpoint. The regulation of CPC function remains unclear. Here, we reveal that in addition to Survivin and Borealin, the single α-helix (SAH) domain of INCENP supports CPC localization to chromatin and the mitotic checkpoint. The INCENP SAH domain also mediates INCENP's microtubule binding, which is negatively regulated by Cyclin-dependent kinase-mediated phosphorylation of segments flanking the SAH domain...
March 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28300575/correlation-of-histological-grade-of-dedifferentiation-with-clinical-outcome-in-55-patients-with-dedifferentiated-liposarcomas
#6
Kossivi Dantey, Karen Schoedel, Oleksandr Yergiyev, David Bartlett, Uma N M Rao
In this study the histologic grade of dedifferentiated liposarcomas was correlated with outcome in surgically resected specimens in 55 patients over a 19-year period at the University of Pittsburgh Medical Center. The tumors were located in the retroperitoneum (N=34); the extremities and thigh (N=16), and the remainder involved the spermatic cord and head and neck. Most tumors were large (mean=21 cm.) Follow up was available in all 55 patients (median=36months). Forty-one tumors classified as high-grade dedifferentiated liposarcoma (HG-DDLPS) had mitotically active pleomorphic and spindle cells and foci of necrosis...
March 11, 2017: Human Pathology
https://www.readbyqxmd.com/read/28296564/azd1775-induces-toxicity-through-double-stranded-dna-breaks-independently-of-chemotherapeutic-agents-in-p53-mutated-colorectal-cancer-cells
#7
Peter John Webster, Anna Tiffany Littlejohns, Hannah Jane Gaunt, K Raj Prasad, David John Beech, Dermot Anthony Burke
AZD1775 is a small molecule WEE1 inhibitor used in combination with DNA-damaging agents to cause premature mitosis and cell death in p53-mutated cancer cells. Here we sought to determine the mechanism of action of AZD1775 in combination with chemotherapeutic agents in light of recent findings that AZD1775 can cause double-stranded DNA (DS-DNA) breaks. AZD1775 significantly improved the cytotoxicity of 5-FU in a p53-mutated colorectal cancer cell line (HT29 cells), decreasing the IC50 from 9.3 μM to 3.5 μM...
March 15, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28270075/comparative-effects-of-polo-like-kinase-1-inhibitors-as-monotherapy-and-in-combination-with-current-treatments-for-medulloblastoma
#8
Julia Alejandra Pezuk, Maria Sol Brassesco, Priscila Maria Manzini Ramos, Carlos Alberto Scrideli, Luiz Gonzaga Tone
BACKGROUND: Medulloblastoma (MB) is one of most frequent malignant tumors that affects children. Despite relative good survival rates, long time sequels are still significant and represent a challenge for treatment of MB patients. Therefore, in an attempt to reduce treatment aftereffects new therapeutic targets are constantly being explored. Polo like kinase 1 (PLK1) is a master cell cycle regulator that has been reported increased in proliferative cells, while its depletion has been repeatedly proposed as an oncological therapeutic strategy...
February 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28255247/prognostic-significance-of-tumor-budding-and-single-cell-invasion-in-gastric-adenocarcinoma
#9
Keying Che, Yang Zhao, Xiao Qu, Zhaofei Pang, Yang Ni, Tiehong Zhang, Jiajun Du, Hongchang Shen
PURPOSE: Gastric carcinoma (GC) is a highly aggressive cancer and one of the leading causes of cancer-related deaths worldwide. Histopathological evaluation pertaining to invasiveness is likely to provide additional information in relation to patient outcome. In this study, we aimed to evaluate the prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma. MATERIALS AND METHODS: Hematoxylin and eosin-stained slides generated from 296 gastric adenocarcinoma patients with full clinical and pathological and follow-up information were systematically reviewed...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28253265/structurally-simplified-biphenyl-combretastatin-a4-derivatives-retain-in-vitro-anti-cancer-activity-dependent-on-mitotic-arrest
#10
Daniel Tarade, Dennis Ma, Christopher Pignanelli, Fadi Mansour, Daniel Simard, Sean van den Berg, James Gauld, James McNulty, Siyaram Pandey
The cis-stilbene, combretastatin A4 (CA4), is a potent microtubule targeting and vascular damaging agent. Despite promising results at the pre-clinical level and extensive clinical evaluation, CA4 has yet to be approved for therapeutic use. One impediment to the development of CA4 is an inherent conformational instability about the ethylene linker, which joins two aromatic rings. We have previously published preliminary data regarding structurally simplified biphenyl derivatives of CA4, lacking an ethylene linker, which retain anti-proliferative and pro-apoptotic activity, albeit at higher doses...
2017: PloS One
https://www.readbyqxmd.com/read/28252645/neuroblastoma-cells-depend-on-hdac11-for-mitotic-cell-cycle-progression-and-survival
#11
Theresa M Thole, Marco Lodrini, Johannes Fabian, Jasmin Wuenschel, Sebastian Pfeil, Thomas Hielscher, Annette Kopp-Schneider, Ulrike Heinicke, Simone Fulda, Olaf Witt, Angelika Eggert, Matthias Fischer, Hedwig E Deubzer
The number of long-term survivors of high-risk neuroblastoma remains discouraging, with 10-year survival as low as 20%, despite decades of considerable international efforts to improve outcome. Major obstacles remain and include managing resistance to induction therapy, which causes tumor progression and early death in high-risk patients, and managing chemotherapy-resistant relapses, which can occur years after the initial diagnosis. Identifying and validating novel therapeutic targets is essential to improve treatment...
March 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28249963/cell-death-response-to-anti-mitotic-drug-treatment-in-cell-culture-mouse-tumor-model-and-the-clinic
#12
Jue Shi, Timothy J Mitchison
Anti-mitotic cancer drugs include classic microtubule-targeting drugs, such as taxanes and vinca alkaloids, and the newer spindle-targeting drugs, such as inhibitors of the motor protein, Kinesin-5 (aka KSP, Eg5, KIF11), and Aurora-A, Aurora-B and Polo-like kinases. Microtubule-targeting drugs are among the first line of chemotherapies for a wide spectrum of cancers, but patient responses vary greatly. We still lack understanding of how these drugs achieve a favorable therapeutic index, and why individual patient responses vary...
March 1, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28249757/suppression-of-spindly-delays-mitotic-exit-and-exacerbates-cell-death-response-of-cancer-cells-treated-with-low-doses-of-paclitaxel
#13
Patrícia M A Silva, Nilza Ribeiro, Raquel T Lima, Cláudia Andrade, Vânia Diogo, Joana Teixeira, Cláudia Florindo, Álvaro Tavares, M Helena Vasconcelos, Hassan Bousbaa
Microtubule-targeting agents (MTAs) are used extensively for the treatment of diverse types of cancer. They block cancer cells in mitosis through the activation of the spindle assembly checkpoint (SAC), the surveillance mechanism that ensures accurate chromosome segregation at the onset of anaphase. However, the cytotoxic activity of MTAs is limited by premature mitotic exit (mitotic slippage) due to SAC silencing. Here we have explored the dual role of the protein Spindly in chromosome attachments and SAC silencing to analyze the consequences of its depletion on the viability of tumor cells treated with clinically relevant doses of paclitaxel...
February 27, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28243113/efficacy-of-eribulin-in-breast-cancer-a-short-report-on-the-emerging-new-data
#14
REVIEW
Gelareh Eslamian, Caroline Wilson, Robin J Young
Eribulin is a novel microtubule-targeting agent that is approved for the treatment of patients with locally advanced or metastatic breast cancer who have previously received treatment with an anthracycline and a taxane in either the adjuvant or metastatic setting. Eribulin induces mitotic catastrophe leading to cell death but has other important antitumor effects, including reversal of epithelial-mesenchymal transition and remodeling of the tumor vasculature. Eribulin was licensed for the treatment of advanced breast cancer based on results from two large randomized Phase III clinical trials...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28224044/mastl-is-essential-for-anaphase-entry-of-proliferating-primordial-germ-cells-and-establishment-of-female-germ-cells-in-mice
#15
Sanjiv Risal, Jingjing Zhang, Deepak Adhikari, Xiaoman Liu, Jingchen Shao, Mengwen Hu, Kiran Busayavalasa, Zhaowei Tu, Zijiang Chen, Philipp Kaldis, Kui Liu
In mammals, primordial germ cells (PGCs) are the embryonic cell population that serve as germ cell precursors in both females and males. During mouse embryonic development, the majority of PGCs are arrested at the G2 phase when they migrate into the hindgut at 7.75-8.75 dpc (days post coitum). It is after 9.5 dpc that the PGCs undergo proliferation with a doubling time of 12.6 h. The molecular mechanisms underlying PGC proliferation are however not well studied. In this work. Here we studied how MASTL (microtubule-associated serine/threonine kinase-like)/Greatwall kinase regulates the rapid proliferation of PGCs...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28215142/small-molecule-modulation-of-hdac6-activity-the-propitious-therapeutic-strategy-to-vanquish-neurodegenerative-disorders
#16
Shabir Ahmad Ganai
Histone deacetylases (HDACs) are epigenetic enzymes creating the transcriptionally inactive state of chromatin by erasing acetyl moiety from histone and non-histone substrates. HDAC6 modulates several biological pathways in dividing cells as well as in post-mitotic neurons, and has been implicated in the pathophysiology of neurodegeneration. The distinct cellular functions and survival in these cells are reliant on HDAC6-mediated processes including intracellular trafficking, chaperone-mediated stress responses, anti-oxidation and protein degradation...
February 8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28211871/expression-level-is-a-key-determinant-of-e2f1-mediated-cell-fate
#17
Igor Shats, Michael Deng, Adam Davidovich, Carolyn Zhang, Jungeun S Kwon, Dinesh Manandhar, Raluca Gordân, Guang Yao, Lingchong You
The Rb/E2F network has a critical role in regulating cell cycle progression and cell fate decisions. It is dysfunctional in virtually all human cancers, because of genetic lesions that cause overexpression of activators, inactivation of repressors, or both. Paradoxically, the downstream target of this network, E2F1, is rarely strongly overexpressed in cancer. E2F1 can induce both proliferation and apoptosis but the factors governing these critical cell fate decisions remain unclear. Previous studies have focused on qualitative mechanisms such as differential cofactors, posttranslational modification or state of other signaling pathways as modifiers of the cell fate decisions downstream of E2F1 activation...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28197640/sb-t-121205-a-next-generation-taxane-enhances-apoptosis-and-inhibits-migration-invasion-in-mcf-7-ptx-cells
#18
Xiaowei Zheng, Changwei Wang, Yuanming Xing, Siying Chen, Ti Meng, Haisheng You, Iwao Ojima, Yalin Dong
Breast cancer is the leading cause of cancer death among women. Paclitaxel, a mitotic inhibitor, is highly effective in the treatment of breast cancer. However, development of resistance to paclitaxel limits its clinical use. Identifying new compounds and new strategies that are effective against breast cancer, in particular drug-resistant cancer, is of great importance. the aim of the present study was to explore the potential of a next-generation taxoid, SB-T-121205, in modulating the proliferation, migration and invasion of paclitaxel-resistant human breast cancer cells (MCF-7/PTX) and further evaluate the underlying molecular mechanisms...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28181578/anti-leukemia-effects-of-the-novel-synthetic-1-benzylindole-derivative-21-900-in-vitro-and-in-vivo
#19
Wei-Chun HuangFu, Min-Wu Chao, Chun-Chun Cheng, Yu-Chieh Wei, Yi-Wen Wu, Jing-Ping Liou, George Hsiao, Yu-Ching Lee, Chia-Ron Yang
Cancers are the major cause of death worldwide. Chemotherapy using cytotoxic drugs and targeted therapy is required when surgery is difficult, ineffective, or impossible. We previously synthesized the novel synthetic 1-benzylindole derivative 21-900 and found that it inhibits histone deacetylase (HDAC) activities and tubulin assembly. Here we tested its effects on the human leukaemia cell lines HL-60 and MOLT-4 in vitro and in vivo. We found that its potent cytotoxic effects were mediated through cell cycle arrest at the G2/M phase, which increased the population of sub-G1 cells, leading to apoptosis...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28177753/histone-h3-3-regulates-mitotic-progression-in-mouse-embryonic-fibroblasts
#20
Aysegul Ors, Christophe Papin, Bertrand Favier, Yohan Roulland, Defne Dalkara, Mehmet Ozturk, ALi Hamiche, Stefan Dimitrov, Kiran Padmanabhan
H3.3 is a histone variant, which marks transcription start sites as well as telomeres and heterochromatic sites on the genome. H3.3 presence is thought to positively correlate with transcriptional status of its target genes. Using a conditional genetic strategy against H3.3B combined with short hairpin RNAs against H3.3A, we essentially depleted all H3.3 gene expression in mouse embryonic fibroblasts. Following nearly complete loss of H3.3 in cells, our transcriptomic analyses show very little impact on global gene expression as well as on histone variant H2A...
February 1, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
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