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https://www.readbyqxmd.com/read/29340013/the-small-molecule-si113-synergizes-with-mitotic-spindle-poisons-in-arresting-the-growth-of-human-glioblastoma-multiforme
#1
Claudia Abbruzzese, Giada Catalogna, Enzo Gallo, Simona di Martino, Anna M Mileo, Mariantonia Carosi, Vincenzo Dattilo, Silvia Schenone, Francesca Musumeci, Patrizia Lavia, Nicola Perrotti, Rosario Amato, Marco G Paggi
Glioblastoma multiforme (GBM) is the deadliest brain tumor. State-of-art GBM therapy often fails to ensure control of a disease characterized by high frequency of recurrences and progression. In search for novel therapeutic approaches, we assayed the effect of compounds from a cancer drug library on the ADF GBM cell line, establishing their elevated sensitivity to mitotic spindle poisons. Our previous work showed that the effectiveness of the spindle poison paclitaxel in inhibiting cancer cell growth was dependent on the expression of RANBP1, a regulatory target of the serine/threonine kinase SGK1...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339720/plumbagin-inhibits-the-proliferation-and-survival-of-esophageal-cancer-cells-by-blocking-stat3-plk1-akt-signaling
#2
Ying-Ya Cao, Jing Yu, Ting-Ting Liu, Kai-Xia Yang, Li-Yan Yang, Qun Chen, Feng Shi, Jia-Jie Hao, Yan Cai, Ming-Rong Wang, Wei-Hua Lu, Yu Zhang
Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers, and it requires novel treatment approaches and effective drugs. In the present study, we found that treatment with plumbagin, a natural compound, reduced proliferation and survival of the KYSE150 and KYSE450 ESCC cell lines in a dose-dependent manner in vitro. The drug also effectively inhibited the viability of primary ESCC cells from fresh biopsy specimens. Furthermore, plumbagin-induced mitotic arrest and massive apoptosis in ESCC cells...
January 16, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29321280/analysis-of-mitotic-checkpoint-function-in-xenopus-egg-extracts
#3
Yinghui Mao
Accurate sister chromatid segregation is pivotal in the faithful transmission of genetic information during each cell division. To ensure accurate segregation, eukaryotic organisms have evolved a "mitotic (or spindle assembly) checkpoint" to prevent premature advance to anaphase before successful attachment of every chromosome to the microtubules of the mitotic spindle. An unattached kinetochore generates a diffusible signal that inhibits ubiquitination of substrates such as cyclin B and securins. This protocol presents an in vitro assay for studying the mitotic checkpoint using Xenopus laevis egg extracts...
January 10, 2018: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/29317645/computational-modelling-of-meiotic-entry-and-commitment
#4
Tanvi Bhola, Orsolya Kapuy, P K Vinod
In response to developmental and environmental conditions, cells exit the mitotic cell cycle and enter the meiosis program to generate haploid gametes from diploid germ cells. Once cells decide to enter the meiosis program they become irreversibly committed to the completion of meiosis irrespective of the presence of cue signals. How meiotic entry and commitment occur due to the dynamics of the regulatory network is not well understood. Therefore, we constructed a mathematical model of the regulatory network that controls the transition from mitosis to meiosis in Schizosaccharomyces pombe...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29316019/cell-cycle-dynamics-of-cultured-coral-endosymbiotic-microalgae-symbiodinium-across-different-types-species-under-alternate-light-and-temperature-conditions
#5
Lisa Fujise, Matthew R Nitschke, Jörg C Frommlet, João Serôdio, Stephen Woodcock, Peter J Ralph, David J Suggett
Dinoflagellates of the genus Symbiodinium live in symbiosis with many invertebrates, including reef-building corals. Hosts maintain this symbiosis through continuous regulation of Symbiodinium cell density via expulsion and degradation (post-mitotic) and/or constraining cell growth and division through manipulation of the symbiont cell cycle (pre-mitotic). Importance of pre-mitotic regulation is unknown since little data exists on cell cycles for the immense genetic diversity of Symbiodinium. We therefore examined cell cycle progression for several distinct Symbiodinium ITS2-types (B1, C1, D1a)...
January 8, 2018: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/29287997/marinobufagin-a-molecule-from-poisonous-frogs-causes-biochemical-morphological-and-cell-cycle-changes-in-human-neoplasms-and-vegetal-cells
#6
Paulo Michel Pinheiro Ferreira, Kátia da Conceição Machado, Lívia Queiroz de Sousa, Daisy Jereissati Barbosa Lima, Bruno Marques Soares, Bruno Coêlho Cavalcanti, Sarah Sant' Anna Maranhão, Janaina da Costa de Noronha, Domingos de Jesus Rodrigues, Gardenia Carmen Gadelha Militão, Mariana Helena Chaves, Gerardo Magela Vieira-Júnior, Cláudia Pessoa, Manoel Odorico de Moraes, João Marcelo de Castro E Sousa, Ana Amélia de Carvalho Melo-Cavalcante
Skin toad secretion present physiologically active molecules to protect them against microorganisms, predators and infections. This work detailed the antiproliferative action of marinobufagin on tumor and normal lines, investigate its mechanism on HL-60 leukemia cells and its toxic effects on Allium cepa meristematic cells. Initially, cytotoxic action was assessed by colorimetric assays. Next, HL-60 cells were analyzed by morphological and flow cytometry techniques and growing A. cepa roots were examined after 72 h exposure...
December 26, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29259156/dual-blockade-of-the-lipid-kinase-pip4ks-and-mitotic-pathways-leads-to-cancer-selective-lethality
#7
Mayumi Kitagawa, Pei-Ju Liao, Kyung Hee Lee, Jasmine Wong, See Cheng Shang, Noriaki Minami, Oltea Sampetrean, Hideyuki Saya, Dai Lingyun, Nayana Prabhu, Go Ka Diam, Radoslaw Sobota, Andreas Larsson, Pär Nordlund, Frank McCormick, Sujoy Ghosh, David M Epstein, Brian W Dymock, Sang Hyun Lee
Achieving robust cancer-specific lethality is the ultimate clinical goal. Here, we identify a compound with dual-inhibitory properties, named a131, that selectively kills cancer cells, while protecting normal cells. Through an unbiased CETSA screen, we identify the PIP4K lipid kinases as the target of a131. Ablation of the PIP4Ks generates a phenocopy of the pharmacological effects of PIP4K inhibition by a131. Notably, PIP4Ks inhibition by a131 causes reversible growth arrest in normal cells by transcriptionally upregulating PIK3IP1, a suppressor of the PI3K/Akt/mTOR pathway...
December 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29250165/evaluating-the-associations-between-human-circadian-rhythms-and-dysregulated-genes-in-liver-cancer-cells
#8
Andrea Polo, Sakshi Singh, Anna Crispo, Marilina Russo, Aldo Giudice, Maurizio Montella, Giovanni Colonna, Susan Costantini
Network analysis is a useful approach in cancer biology as it provides information regarding the genes and proteins. In our previous study, a network analysis was performed on dysregulated genes in HepG2 cells, a hepatoblastoma cell line that lacks the viral infection, compared with normal hepatocytes, identifying the presence of 26 HUB genes. The present study aimed to identify whether these previously identified HUB genes participate in the network that controls the human circadian rhythms. The results of the present study demonstrated that 20/26 HUB genes were associated with the metabolic processes that control human circadian rhythms, which supports the hypothesis that a number of cancer types are dependent from circadian cycles...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29249657/cells-escape-an-operational-mitotic-checkpoint-through-a-stochastic-process
#9
Paolo Bonaiuti, Elena Chiroli, Fridolin Gross, Andrea Corno, Claudio Vernieri, Martin Štefl, Marco Cosentino Lagomarsino, Michael Knop, Andrea Ciliberto
Improperly attached chromosomes activate the mitotic checkpoint that arrests cell division before anaphase. Cells can maintain an arrest for several hours but eventually will resume proliferation, a process we refer to as adaptation. Whether adapting cells bypass an active block or whether the block has to be removed to resume proliferation is not clear. Likewise, it is not known whether all cells of a genetically homogeneous population are equally capable to adapt. Here, we show that the mitotic checkpoint is operational when yeast cells adapt and that each cell has the same propensity to adapt...
December 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29246495/elevated-peripheral-myelin-protein-22-reduced-mitotic-potential-and-proteasome-impairment-in-dermal-fibroblasts-from-charcot-marie-tooth-disease-type-1a-patients
#10
Sooyeon Lee, Hannah Bazick, Vinita Chittoor-Vinod, Mohammed Omar Al Salihi, Guangbin Xia, Lucia Notterpek
A common form of hereditary autosomal dominant demyelinating neuropathy known as Charcot-Marie-Tooth disease type 1A (CMT1A) is linked with duplication of the peripheral myelin protein 22 (PMP22) gene. Although studies from animal models have led to better understanding of the pathobiology of these neuropathies, there continues to be a gap in the translation of findings from rodents to humans. As PMP22 was originally identified in fibroblasts as growth arrest specific gene 3 (gas3) and is expressed broadly in the body, it was tested whether skin cells from neuropathic patients would display the cellular pathology observed in Schwann cells from rodent models...
December 12, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29245942/r383c-mutation-of-human-cdc20-results-in-idiopathic-non-obstructive-azoospermia
#11
Lingwei Li, Liqing Fan, Nanni Peng, Lihua Yang, Lisha Mou, Weiren Huang
Idiopathic azoospermia (IA) is a severe form of male infertility due to unknown causes. To investigate relative gene expression in human idiopathic non-obstructive azoospermia, we sequenced all the exons of cell division cycle 20 (CDC20) in 766 patients diagnosed with IA, as well as in 521 normally fertile men. Three novel missense mutations (S72G, R322Q, R383C) of CDC20 were detected and further confirmed by Sanger sequencing. The mRNA levels of securin, cyclin B, cyclin dependent kinase 1 (CDK1), and cyclin dependent kinase 2 (CDK2), which are all targeted for destruction via the anaphase-promoting complex/cyclosomeCDC20 (APC/CCDC20) pathway, were detected at relatively high levels using real-time quantitative polymerase chain reaction analysis...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228593/proteasome-inhibitor-bortezomib-enhances-the-effect-of-standard-chemotherapy-in-small-cell-lung-cancer
#12
Sanaz Taromi, Florentine Lewens, Ruza Arsenic, Dagmar Sedding, Jörg Sänger, Almut Kunze, Markus Möbs, Joana Benecke, Helma Freitag, Friederike Christen, Daniel Kaemmerer, Amelie Lupp, Mareike Heilmann, Hedwig Lammert, Claus-Peter Schneider, Karen Richter, Michael Hummel, Britta Siegmund, Meike Burger, Franziska Briest, Patricia Grabowski
Small cell lung cancer (SCLC) is an aggressive cancer showing a very poor prognosis because of metastasis formation at an early stage and acquisition of chemoresistance. One key driver of chemoresistance is the transcription factor Forkhead box protein M1 (FOXM1) that regulates cell cycle proliferation, maintenance of genomic stability, DNA damage response, and cell differentiation in numerous tumor entities. In this study we investigated the role of FOXM1 in SCLC progression and analyzed the effect of FOXM1 inhibition using two proteasome inhibitors, bortezomib and siomycin A...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29225722/cellular-senescence-in-age-related-macular-degeneration-can-autophagy-and-dna-damage-response-play-a-role
#13
REVIEW
Janusz Blasiak, Malgorzata Piechota, Elzbieta Pawlowska, Magdalena Szatkowska, Ewa Sikora, Kai Kaarniranta
Age-related macular degeneration (AMD) is the main reason of blindness in developed countries. Aging is the main AMD risk factor. Oxidative stress, inflammation and some genetic factors play a role in AMD pathogenesis. AMD is associated with the degradation of retinal pigment epithelium (RPE) cells, photoreceptors, and choriocapillaris. Lost RPE cells in the central retina can be replaced by their peripheral counterparts. However, if they are senescent, degenerated regions in the macula cannot be regenerated...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29220798/aegeline-inspired-synthesis-of-novel-amino-alcohol-and-thiazolidinedione-hybrids-with-antiadipogenic-activity-in-3t3-l1-cells
#14
Sabbu Satish, Ankita Srivastava, Pragya Yadav, Salil Varshney, Rakhi Choudhary, Vishal M Balaramnavar, Tadigoppula Narender, Anil Nilkanth Gaikwad
Excess adiposity is a hallmark of obesity, which is caused due to an imbalance between energy intake and energy consumed. Obesity is often associated with several metabolic disorders like dyslipidemia, cardiovascular diseases and type 2 diabetes. Earlier, our group had reported natural product Aegeline (amino-alcohol) isolated from the plant Aegle marmelos as an anti-diabetic and anti-dyslipidemic compound. With this background, we synthesized a series of novel amino alcohol and thiazolidinedione hybrid molecules and studied their antiadipogenic activity...
November 26, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29217775/chemotherapy-induced-differential-cell-cycle-arrest-in-b-cell-lymphomas-affects-their-sensitivity-to-wee1-inhibition
#15
Xiaoguang Wang, Zhangguo Chen, Ameet K Mishra, Alexa Silva, Wenhua Ren, Zenggang Pan, Jing H Wang
Chemotherapeutic agents, e.g., cytarabine or doxorubicin cause DNA damages. However, it remains unknown whether such agents differentially regulate cell cycle arrest in distinct types of B cell lymphomas, and whether this phenotype can be exploited for developing new therapies. Here, we treated various types of B cells including primary and B lymphoma cells, with cytarabine or doxorubicin, and determined DNA damage responses, cell cycle regulation and sensitivity to Wee1 inhibitor. We found that cyclin A2/B1 upregulation appear to be an intrinsic programmed response to DNA damage; however, different types of B cells arrest in distinct phases of cell cycle...
December 7, 2017: Haematologica
https://www.readbyqxmd.com/read/29214152/identification-of-candidate-casein-kinase-2-substrates-in-mitosis-by-quantitative-phosphoproteomics
#16
Scott F Rusin, Mark E Adamo, Arminja N Kettenbach
Protein phosphorylation is a crucial regulatory mechanism that controls many aspects of cellular signaling. Casein kinase 2 (CK2), a constitutively expressed and active kinase, plays key roles in an array of cellular events including transcription and translation, ribosome biogenesis, cell cycle progression, and apoptosis. CK2 is implicated in cancerous transformation and is a therapeutic target in anti-cancer therapy. The specific and selective CK2 ATP competitive inhibitor, CX-4945 (silmitaseratib), is currently in phase 2 clinical trials...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29209646/re-investigating-plk1-inhibitors-as-antimitotic-agents
#17
Quentin Delacour, Olivier Gavet
Polo-like kinase 1 (PLK1) plays key roles during mitosis, prompting the development of PLK1 inhibitors for anticancer therapy. We recently determined that PLK1 is crucially required for entry into mitosis. Hence, we discuss the potential and limitations of PLK1 inhibition strategies to promote mitotic arrest and death of cancer cells.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/29200877/microtubule-targeting-agents-can-sensitize-cancer-cells-to-ionizing-radiation-by-an-interphase-based-mechanism
#18
Daniel Markowitz, Grace Ha, Rosamaria Ruggieri, Marc Symons
Background: The cytotoxic effects of microtubule-targeting agents (MTAs) are often attributed to targeted effects on mitotic cells. In clinical practice, MTAs are combined with DNA-damaging agents such as ionizing radiation (IR) with the rationale that mitotic cells are highly sensitive to DNA damage. In contrast, recent studies suggest that MTAs synergize with IR by interfering with the trafficking of DNA damage response (DDR) proteins during interphase. These studies, however, have yet to demonstrate the functional consequences of interfering with interphase microtubules in the presence of IR...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29199006/lb-100-a-novel-protein-phosphatase-2a-pp2a-inhibitor-sensitizes-malignant-meningioma-cells-to-the-therapeutic-effects-of-radiation
#19
Winson S C Ho, Saman Sizdahkhani, Shuyu Hao, Hua Song, Ashlee Seldomridge, Anita Tandle, Dragan Maric, Tamalee Kramp, Rongze Lu, John D Heiss, Kevin Camphausen, Mark R Gilbert, Zhengping Zhuang, Deric M Park
Atypical and anaplastic meningiomas (AAM) represent 20% of all meningiomas. They are associated with poor outcomes due to their tendency to recur. While surgery and radiation (RT) are first line therapy, no effective systemic medical treatment has been identified. Protein phosphatase 2A (PP2A) is a ubiquitously expressed serine/threonine phosphatase involved in cell cycle regulation and DNA repair. Here, we examined radiosensitizing effects of LB-100, a novel inhibitor of PP2A against AAM as a novel treatment strategy...
November 30, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29196757/mitotic-slippage-and-the-subsequent-cell-fates-after-inhibition-of-aurora-b-during-tubulin-binding-agent-induced-mitotic-arrest
#20
Yasuo Tsuda, Makoto Iimori, Yuichiro Nakashima, Ryota Nakanishi, Koji Ando, Kippei Ohgaki, Hiroyuki Kitao, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara
Tubulin-binding agents (TBAs) are designed to target microtubule (MT) dynamics, resulting in compromised mitotic spindles and an unsatisfied spindle assembly checkpoint. The activity of Aurora B kinase is indispensable for TBA-induced mitotic arrest, and its inhibition causes mitotic slippage and postmitotic endoreduplication. However, the precise phenomenon underlying mitotic slippage, which is caused by treatment with both Aurora B inhibitors and TBAs, and the cell fate after postmitotic slippage are not completely understood...
December 1, 2017: Scientific Reports
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