AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation ScienceHealth Care
Cell CycleCell Cycle ProteinsDNA DamageMitosisCheckpoint Kinase 2Protein-Serine-Threonine KinasesCell Cycle CheckpointsG2 PhaseGenes, cdcDNA ReplicationAtaxia Telangiectasia Mutated ProteinsS PhaseG2 Phase Cell Cycle CheckpointsM Phase Cell Cycle CheckpointsProtein KinasesG1 PhaseDNA RepairSpindle ApparatusTumor Suppressor Protein p53DNA-Binding ProteinsTumor Suppressor ProteinsHydroxyureaNuclear Proteinscdc25 PhosphatasesGamma RaysPhosphorylationRadiation, IonizingAtaxia TelangiectasiaCDC2 Protein KinaseCyclin BS Phase Cell Cycle CheckpointsCyclin-Dependent Kinase Inhibitor p21CyclinsSaccharomyces cerevisiae ProteinsSchizosaccharomycesKinetochoresNocodazoleMutationGenomic InstabilitySchizosaccharomyces pombe ProteinsRadiation ToleranceCell DivisionApoptosisSaccharomyces cerevisiaeG1 Phase Cell Cycle CheckpointsCyclin B1Ultraviolet RaysHeLa CellsDNA Breaks, Double-StrandedSignal TransductionChromosomal InstabilityCell Line, TumorCell LineFungal ProteinsFibroblastsModels, BiologicalRetinoblastoma ProteinHistonesBRCA1 ProteinMethyl MethanesulfonateCdc20 ProteinsMolecular Sequence DataIntracellular Signaling Peptides and ProteinsFlow CytometryCyclin-Dependent Kinase 2Chromosome SegregationMetaphaseCell NucleusGenes, p53DNARNA, Small InterferingDNA Repair EnzymesTumor Cells, CulturedCell ProliferationCell SurvivalProtein BindingAphidicolinCaffeineAnaphaseCyclin-Dependent KinasesCyclin EAmino Acid SequenceNucleic Acid Synthesis InhibitorsDNA, FungalCentrosomePolyploidyCDC2-CDC28 KinasesChromosomal Proteins, Non-HistoneMimosineCells, CulturedCyclin ADose-Response Relationship, RadiationRepressor ProteinsHCT116 CellsUbiquitin-Protein Ligase ComplexesAnaphase-Promoting Complex-CyclosomeCarrier ProteinsChromatinRNA InterferenceExonucleases
RegulationProgressionMitosisKinaseTumour cellsResistanceMicroenvironmentCancerReplicationGenesGenotoxicEukaryoticMolecular biologyBiolControlInhibitorsAnalyzeDivisionContextPartiallyFunctionResponsesCuesOrganismsDamageProteinPhasesArrestInhibitionSystemsGeneContentReceptorsAccurateActivityTechniquesProcessComponentsDeath
Regulation3
  • The precise regulation of the levels of cyclin proteins is fundamental to coordinate cell division with checkpoints, avoiding genome instability. (ox.ac.uk)
  • however, the mechanisms underlying the regulation of cyclin F are poorly understood. (ox.ac.uk)
  • A collection of basic cutting-edge techniques for studying the mechanisms underlying cell cycle regulation and checkpoint control. (buynsellbooksonline.com)
Progression5
  • Here we show that cell cycle progression through mitosis following double-stranded DNA breaks leads to the formation of micronuclei, which precede activation of inflammatory signalling and are a repository for the pattern-recognition receptor cyclic GMP-AMP synthase (cGAS). (nature.com)
  • We found that the total transcript level per cell and the expression of most individual genes correlated with progression through the cell cycle, but not with cell size. (frontiersin.org)
  • The molecular processes behind cell cycle progression have been dissected by numerous morphological studies on live or fixed single cells using a plethora of techniques to visualize components and processes during cell division. (frontiersin.org)
  • Using mammalian, yeast, and frog systems, these readily reproducible methods can be used to induce cell cycle checkpoints, detect changes in cell cycle progression, identify and analyze genes and proteins that regulate the process, and characterize chromosomal status as a function of cell cycle phase and progression. (buynsellbooksonline.com)
  • We are establishing new techniques for global analyses of the adhesion nexus in three-dimensional (3D) pancreatic organoids and defining how variations in extracellular rigidity initiate signalling at this site to influence cell cycle progression. (manchester.ac.uk)
Mitosis2
  • That high stromal rigidity impedes the changes in cell architecture needed for accurate segregation of chromosomes and daughter cell separation during mitosis. (manchester.ac.uk)
  • Thus, integrated extracellular rigidity may sit alongside DNA damage, cell size and metabolic status as a factor that feeds into decisions whether to replicate DNA, commit to mitosis or partition chromosomes. (manchester.ac.uk)
Kinase2
  • In response to DNA damage, a synthetic lethal relationship exists between the cell cycle checkpoint kinase MK2 and the tumor suppressor p53. (nature.com)
  • This has led to the development of a range of ERK1/2 inhibitors (ERKi) that either inhibit kinase catalytic activity (catERKi) or additionally prevent the activating pT-E-pY dual phosphorylation of ERK1/2 by MEK1/2 (dual-mechanism or dmERKi). (babraham.ac.uk)
Tumour cells2
  • Despite this, clinical responses are typically transient as tumour cells develop resistance. (babraham.ac.uk)
  • We hope then to perturb the function of candidate molecules in organoids using knockdown and pharmacological inhibition, and employ molecular cell biology approaches to pinpoint how the sensory mechanisms vary between wild type (WT) and tumour cells. (manchester.ac.uk)
Resistance6
  • Innate or acquired resistance to small molecule BRAF or MEK1/2 inhibitors (BRAFi or MEKi) typically arises through mechanisms that sustain or reinstate ERK1/2 activation. (babraham.ac.uk)
  • Mutations and gene amplifications that confer drug resistance emerge frequently during chemotherapy, but their mechanism and timing are poorly understood. (babraham.ac.uk)
  • Here, we investigate amplification events that underlie resistance to the MEK inhibitor selumetinib (AZD6244/ARRY-142886) in COLO205 cells, a well-characterized model for reproducible emergence of drug resistance, and show that amplifications acquired are the primary cause of resistance. (babraham.ac.uk)
  • Our findings demonstrate that acquisition of MEK inhibitor resistance often occurs through gene amplification and can be suppressed by impeding cell cycle entry in drug. (babraham.ac.uk)
  • These resistance mechanisms frequently involve reinstatement of ERK1/2 signalling and BRAFi are now deployed in combination with one of three approved MEK1/2 inhibitors (MEKi) to provide more durable, but still transient, clinical responses. (babraham.ac.uk)
  • An understanding of the causes of this desmoplastic response, and the consequent effects of an altered extracellular niche on tumour cell growth, invasion and resistance, would therefore be a pivotal step in the quest to improve patient outcomes. (manchester.ac.uk)
Microenvironment1
  • The outcomes of the programme will advance our understanding of cancer in two ways: by defining how the adhesive stromal microenvironment influences tumour cell proliferation, and by identifying potential clinical targets in a cancer of massive unmet need. (manchester.ac.uk)
Cancer5
  • These findings establish a mechanism for co-targeting DNA damage-induced cell cycle checkpoints in combination with repair of cisplatin-DNA lesions in vivo using RNAi nanocarriers, and motivate further exploration of ASL as a generalized strategy to improve cancer treatment. (nature.com)
  • Because BRCA mutations are observed in fewer than 10% of cancer patients (cBioPortal: 6.7%) 11 , 12 , 13 the identification of additional genes that share synthetic lethal sensitivity relationships with mutated oncogenes or tumor suppressors would greatly enhance the implementation of tumor cell-specific synthetic lethal sensitivity to improve an anticancer therapeutic response. (nature.com)
  • Cancer cells that are defective in p53 function are deficient in their ability to transcriptionally upregulate the CDK inhibitor p21 after genotoxic stress. (nature.com)
  • Knowing the components of cells and how cells work is fundamental to all biological sciences while also being essential for research in biomedical fields such as cancer, and other diseases. (wikipedia.org)
  • We hope therefore to answer fundamental questions about the proteins that control normal cell behaviour, how these proteins are altered in disease, and how these changes convert normal cells into cancer cells. (manchester.ac.uk)
Replication5
Genes5
  • SL originally described a relationship between two genes, where alteration of either gene alone results in viable cells, but alteration (mutation, loss, or inhibition) of both genes simultaneously was lethal. (nature.com)
  • Here, we used quantitative real-time PCR, profiling the expression of 93 genes in single-cells from three different cell lines. (frontiersin.org)
  • Detailed analysis of cell cycle predictive genes allowed us to define subpopulations with distinct gene expression profiles and to calculate a cell cycle index that illustrates the transition of cells between cell cycle phases. (frontiersin.org)
  • In conclusion, we provide useful experimental approaches and bioinformatics to identify informative and predictive genes at the single-cell level, which opens up new means to describe and understand cell proliferation and subpopulation dynamics. (frontiersin.org)
  • Here, we employed single-cell gene expression profiling to describe the dynamic transition between cell proliferative states in three different cell lines using a panel consisting of 93 marker genes. (frontiersin.org)
Genotoxic2
  • Because most tumors are deficient in one or more aspects of the function of the p53 tumor suppressor, either as a consequence of mutations within p53, or impairment of upstream and downstream modulators of p53 activity 19 , targeting MK2 has the potential to selectively enhance tumor cell killing without increasing the genotoxic effects of chemotherapy on normal p53-wild type tissues. (nature.com)
  • These findings implicate temporal modulation of the cell cycle as an important consideration in the context of therapeutic strategies that combine genotoxic agents with immune checkpoint blockade. (nature.com)
Eukaryotic4
  • Cell biology encompasses both prokaryotic and eukaryotic cells and has many subtopics which may include the study of cell metabolism, cell communication, cell cycle, biochemistry, and cell composition. (wikipedia.org)
  • There are two fundamental classifications of cells: prokaryotic and eukaryotic. (wikipedia.org)
  • Prokaryotic cells are distinguished from eukaryotic cells by the absence of a cell nucleus or other membrane-bound organelle. (wikipedia.org)
  • Prokaryotic cells are much smaller than eukaryotic cells, making them the smallest form of life. (wikipedia.org)
Molecular biology1
  • Cell culture is one of the major tools used in cellular and molecular biology, providing excellent model systems for studying the normal physiology and biochemistry of cells (e.g., metabolic studies, aging), the effects of drugs and toxic compounds on the cells, and mutagenesis and carcinogenesis. (wikipedia.org)
Biol1
Control3
  • Cell proliferation includes a series of events that is tightly regulated by several checkpoints and layers of control mechanisms. (frontiersin.org)
  • A universal feature is the generation of a dense and highly rigid stromal extracellular matrix (ECM) that, based on analyses of the adhesion-dependent control of cell phenotype in other systems, is likely to alter proliferation, migration and differentiation. (manchester.ac.uk)
  • That driver mutations in cancers lead to a rewiring of signalling networks, one outcome of which is evasion of these checkpoint control mechanisms. (manchester.ac.uk)
Inhibitors1
  • Therefore, compared to normal p53-proficient cells, p53-defective cells are more reliant on MK2 activity, which drives an alternative cell cycle checkpoint pathway that stabilizes the CKI inhibitors p27 Kip1 and Gadd45α in order to maintain G 1 /S and G 2 /M arrest after certain types of DNA damage 16 , 18 . (nature.com)
Analyze1
  • A few years later, in 1674, Anton Van Leeuwenhoek was the first to analyze live cells in his examination of algae. (wikipedia.org)
Division3
Context1
  • Moreover, STING loss prevented the regression of abscopal tumours in the context of ionizing radiation and immune checkpoint blockade in vivo . (nature.com)
Partially1
  • There is burgeoning evidence that this is the case, but the mechanisms are only partially elucidated. (manchester.ac.uk)
Function3
  • Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. (wikipedia.org)
  • These have allowed for and are currently being used for discoveries and research pertaining to how cells function, ultimately giving insight into understanding larger organisms. (wikipedia.org)
  • Due to advancements in microscopy, techniques and technology have allowed scientists to hold a better understanding of the structure and function of cells. (wikipedia.org)
Responses1
  • The inflammatory and fibrotic responses in PDA are the result of complex interplay between tumour and host cells. (manchester.ac.uk)
Cues1
  • We propose that cells have evolved mechanisms to monitor adhesive status, and that mechanical cues in the extracellular environment are converted into signals linking to one or more cell cycle checkpoints. (manchester.ac.uk)
Organisms3
  • All living organisms are made of cells. (wikipedia.org)
  • A cell is the basic unit of life that is responsible for the living and functioning of organisms. (wikipedia.org)
  • All of this preceded the cell theory which states that all living things are made up of cells and that cells are organisms' functional and structural units. (wikipedia.org)
Damage1
  • Research in the Andreassen Laboratory at Cincinnati Children's Hospital Medical Center focuses on DNA damage response mechanisms, including cell cycle checkpoint signaling and DNA repair by homologous recombination (HR), that maintain genome stability and thereby prevent tumorigenesis. (cincinnatichildrens.org)
Protein1
  • The precise regulations of pre-RC protein levels and assembly are effective ways to prevent reassembly of de novo MCM2-7 onto the replicated origins to re-license and re-replicate the genomic DNA in the subsequent phases of the same cell cycle ( Figure 1) . (intechopen.com)
Phases1
  • Individual unsynchronized cells from three different cell lines were collected in different cell cycle phases (G0/G1 - S - G2/M) with variable cell sizes. (frontiersin.org)
Arrest1
  • Combined treatment with selumetinib and a dose of palbociclib sufficient to reinforce G1 arrest in selumetinib-sensitive cells, but not to impair proliferation of resistant cells, delays the emergence of resistant colonies, meaning that escape from G1 arrest is critical in the formation of resistant clones. (babraham.ac.uk)
Inhibition1
  • ERKi treatment of cells drives the poly-ubiquitylation and proteasome-dependent turnover of ERK2 and pharmacological or genetic inhibition of Cullin-RING E3 ligases prevents this. (babraham.ac.uk)
Systems1
  • Checkpoint systems allow the accurate execution of each cell-cycle phase. (ox.ac.uk)
Gene1
  • By applying the random forests algorithm, a supervised machine learning approach, we show how a multi-gene signature that classifies individual cells into their correct cell cycle phase and cell size can be generated. (frontiersin.org)
Content1
  • Cytometry: The cells are placed in the machine which uses a beam to scatter the cells based on different aspects and can therefore separate them based on size and content. (wikipedia.org)
Receptors1
  • That the sensing of stromal rigidity originates at the adhesion nexus, the junctional structure that links cells to the ECM via integrin receptors. (manchester.ac.uk)
Accurate1
Activity1
  • Melanoma in particular exhibits a high incidence of activating BRAF and NRAS mutations and such cells are addicted to the activity of these mutant oncoproteins. (babraham.ac.uk)
Techniques2
  • Cell biology research looks at different ways to culture and manipulate cells outside of a living body to further research in human anatomy and physiology, and to derive medications.The techniques by which cells are studied have evolved. (wikipedia.org)
  • Many techniques commonly used to study cell biology are listed below: Cell culture: Utilizes rapidly growing cells on media which allows for a large amount of a specific cell type and an efficient way to study cells. (wikipedia.org)
Process1
  • Cell fractionation: This process requires breaking up the cell using high temperature or sonification followed by centrifugation to separate the parts of the cell allowing for them to be studied separately. (wikipedia.org)
Components1
  • They gave no indication to the actual overall components of a cell. (wikipedia.org)
Death1