• Which medications in the drug class Antineoplastic Agents, mTOR Kinase Inhibitors are used in the treatment of Non-Hodgkin Lymphoma (NHL)? (medscape.com)
  • Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. (nature.com)
  • Polo-like kinase (PLK) inhibitors targets the mitotic phase of the cell cycle. (pharmaceutical-technology.com)
  • Immunotherapy mainly includes immune checkpoint inhibitors (ICIs), such as inhibitors of PD-1 (programmed cell death 1)/programmed cell death ligand 1 (PD-L1). (nature.com)
  • [ 2 ] Options for second-line therapy in patients with relapsed/refractory disease include chemotherapy-free regimens with biologic targeted agents such as covalent Bruton tyrosine kinase (BTK) inhibitors, lenalidomide,venetoclax, and chimeric antigen receptor (CAR) T-cell therapy. (medscape.com)
  • The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. (cancerindex.org)
  • Mutations in cyclin-dependent kinase inhibitors controlling the G1 phase of the cell cycle are prevalent in various cancers. (koreamed.org)
  • Here, we generated knockout mouse models for each of these three cyclin-dependent kinase inhibitors using engineered nucleases. (koreamed.org)
  • Namely cytokinins and cytokinin-derived purine inhibitors of cyclin-dependent kinases belongs to the most intensively studied compounds. (cas.cz)
  • Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated. (kegg.jp)
  • It has been suggested that the protein is essential for initiation of DNA replication and that it plays a role in regulating cell cycle progression. (wikipedia.org)
  • Chk1 facilitates the arrest of cell cycle progression and the inhibition of replication origin firing. (caltech.edu)
  • Here we analyzed the involvement of aberrant cell cycle progression in 3-NP-induced cell death in these brain regions. (nih.gov)
  • 3-NP also induced phosphorylation of retinoblastoma protein, a marker of cell cycle progression at late G(1) phase, only in striatum. (nih.gov)
  • These results suggest that 3-NP induces aberrant cell cycle progression and neuronal cell death via p27 down-regulation by calpain in striatum but not in the cerebral cortex. (nih.gov)
  • During cell growth and proliferation, ubiquitin plays an outsized role in promoting progression through the cell cycle. (intechopen.com)
  • Progression through the cell cycle is driven by the oscillating activity of Cyclin Dependent Kinases (CDKs). (intechopen.com)
  • It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (thermofisher.com)
  • Polo-like kinases play critical roles during multiple stages of cell cycle progression. (pharmaceutical-technology.com)
  • CDK4 may be useful as a prognostic marker for hepatocellular carcinoma and its kinase activity has been reported to promote the progression of T cell acute lymphoblastic leukemia. (rndsystems.com)
  • We studied the effect of doxorubicin (Dox) on cell cycle progression and its correlation with DNA damage and cytotoxicity in p53-mutant P388 cells. (aspetjournals.org)
  • In untreated control P388 cells, p34cdc2 kinase localizes in the nucleus and cytoplasms, particularly in the centrosomes, and p34cdc2 kinase activity is dependent on cell cycle progression, with the enzyme activity increasing steadily from G1/S to G2/M and markedly declining thereafter. (aspetjournals.org)
  • Use of the triple-negative TMX2-28 breast cancer cell line to address the role of SKP2 in cell cycle progression confirmed that SKP2 contributes to a more rapid cell cycle progression and may regulates pSer10p27 levels. (umass.edu)
  • Mice lacking the tumor suppressors p16(Ink4a) (Cdkn2a, cyclin-dependent kinase inhibitor 2a), p19(Arf) (an alternative reading frame product of Cdkn2a,), and p27(Kip1) (Cdkn1b, cyclin-dependent kinase inhibitor 1b) result in malignant progression of epithelial cancers, sarcomas, and melanomas, respectively. (koreamed.org)
  • In a Phase 3 Paloma-III study of Pfizer's CDK4/6 inhibitor ( Ibrance - palbociclib) and an estrogen receptor antagonist ( Faslodex - fulvestrant), patients receiving the combination had significantly prolonged progression-free survival than women with breast cancer who received Faslodex, alone. (shu.edu)
  • In vitro, palbociclib reduced cellular proliferation of estrogen receptor (ER)-positive breast cancer cell lines by blocking progression of the cell from G1 into S phase of the cell cycle. (shu.edu)
  • Rb blocks cell cycle progression in G1 by binding E2F transcription factors. (shu.edu)
  • The expression of further E2F target genes, as cyclin A, facilitates progression through S phase. (shu.edu)
  • ARF and p53 can block cell cycle progression via p21Cip1. (shu.edu)
  • Cell cycle progression is largely controlled by the activity of cyclin dependent kinases (CDKs) and their cyclin binding partners. (lancs.ac.uk)
  • Mitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. (kegg.jp)
  • CDKs regulate the cell's progression through the phases of the cell cycle by modulating the activity of key substrates. (kegg.jp)
  • Notch signaling mediates G1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases. (umassmed.edu)
  • Cyclin-dependent kinase (CDK) 10, is reported to play an essential role in the progression from the G2 to M phase of the cell cycle. (jcancer.org)
  • Deregulation of cell cycle progression is considered to be critical for carcinogenesis ( 9 ). (jcancer.org)
  • By blocking cell cycle progression, p27 prevents cells from dividing too quickly or at the wrong time. (medlineplus.gov)
  • For example, when p27 is held (sequestered) in the fluid that surrounds the nucleus (the cytoplasm) instead of being transported into the nucleus, the protein is unavailable to block cell cycle progression. (medlineplus.gov)
  • In mouse embryonic stem cells (ESCs), Cdc7 is needed for proliferation. (wikipedia.org)
  • Methotrexate may inhibit rapid proliferation of epithelial cells in skin. (medscape.com)
  • In addition, their osteogenic differentiation potential was increased, and genes involved in cell adhesion, FGF-2 signalling, cell cycle, stemness, cell differentiation, and cell proliferation were upregulated, compared to that of the MSCs cultured on uncoated plates. (hindawi.com)
  • Many potential anticancer mechanisms of these compounds were proposed, including the inhibition of cell proliferation, changes in enzyme activity and immune regulation ( 21 , 22 ). (spandidos-publications.com)
  • Notably, the G1/S boundary represents a major barrier to cell proliferation and is universally dysfunctional in cancer cells, allowing for the unbridled proliferation observed in malignancy. (intechopen.com)
  • Numerous E3 ubiquitin ligases, which facilitate the ubiquitination of specific substrates, have been shown to control G1/S. In this chapter, we will discuss components in the ubiquitin proteasome system that are implicated in G1/S control, how these enzymes are interconnected, gaps in our current knowledge, and the potential role of these pathways in the cancer cycle and disease proliferation. (intechopen.com)
  • Malignant lymphoma can arise in any organ containing lymphoid tissue and is characterized by malignant proliferation of lymphoid cells. (slu.se)
  • Moreover, TK1 is converting thymidine to thymidine monophosphate, and is related to DNA replication and cell proliferation, which makes it possible to use as a proliferation marker in malignant tumors. (slu.se)
  • A mutation in this gene resulting in reduced cell proliferation, and impaired cell motility and polarity, and has been identified in patients with primary microcephaly. (cancerindex.org)
  • This phosphorylation event is associated with increased cell proliferation and poor prognosis in patients with glioma. (umass.edu)
  • JAM3 knockdown additionally inhibited trophoblast proliferation and increased the number of trophoblasts in the sub-G1 and G2/M phases, indicating cell-cycle disturbance and apoptosis. (bioone.org)
  • Research program of the laboratory is aimed primary at small molecules that regulate cell division cycle, proliferation and growth of both plant and animal cells. (cas.cz)
  • Present study was designed to determine the impact of cadmium on cell proliferation, cell cycle and apoptosis, and to investigate the possible involvement of p53 and MAPKs signaling pathways in J774A.1 murine macrophages. (cdc.gov)
  • Cd inhibited cell proliferation via cell cycle arrest and induced apoptosis in a dose-dependent manner. (cdc.gov)
  • Inhibition of ERK suppressed DNA synthesis and had an additive effect with Cd-inhibited proliferation suggesting that Cd-induced ERK activity is not responsible for the G2/M arrest and subsequent inhibition of cell proliferation. (cdc.gov)
  • Uncontrolled cell proliferation is the hallmark of cancer, and genes that directly regulate the cell cycle are typically damaged in tumor cells ( 10 ). (jcancer.org)
  • Three sequential phosphorylation events on specific residues of p27, regulate the activity of these complexes and ultimately control cell cycle proliferation or arrest. (lu.se)
  • Malignant transformation and uncontrolled proliferation of an abnormally differentiated, long-lived hematopoietic progenitor cell results in a high circulating number of blasts, replacement of normal marrow by malignant cells, and the potential for leukemic infiltration of the central nervous system (CNS) and testes. (msdmanuals.com)
  • Abnormal proliferation, clonal expansion, aberrant differentiation, and diminished apoptosis (programmed cell death) lead to replacement of normal blood elements with malignant cells. (msdmanuals.com)
  • Agents in this class halt the cell cycle at the G1 phase in tumor cells. (medscape.com)
  • The main goal of RT consists in delivering a precise dose of radiation in a target volume, such as tumor, promoting the tumor cells eradication with as minimal damage as possible in surrounding normal tissues ( 13 ). (frontiersin.org)
  • In studies using animals or cells grown in labs, cinnamon has shown promise for its ability to slow cancer growth and even kill tumor cells. (webmd.com)
  • In addition, tumor-associated antigens (TAAs) produced by irradiated tumor cells can be captured by antigen-presenting cells (APCs) in the TME and presented to T cells. (nature.com)
  • In vitro , overexpression of the mdr-1 gene product, P-glycoprotein (Pgp), in tumor cells can confer high-level resistance to natural product-derived cytotoxics-anthracyclines, vinca alkaloids, epipodophyllotoxins, and taxanes. (cancer.gov)
  • 5) increasing the intrinsic radioresistance of normal cells through ketone bodies but decreasing that of tumor cells by targeting glycolysis. (springer.com)
  • they are not inherited and are present only in tumor cells. (medlineplus.gov)
  • Although expression levels of the protein appear to be constant throughout the cell cycle, the protein kinase activity appears to increase during S phase. (wikipedia.org)
  • Although the effective concentration of K-252a did not cause significant inhibition of affinity-purified p34cdc2 protein kinase activity in vitro, in vivo the full activation of p34cdc2 kinase during the G2/M was blocked by K-252a. (rupress.org)
  • On the other hand, the cyclic fluctuation of partially activated p34cdc2 kinase activity peaking in S phase still continued. (rupress.org)
  • In a cell-free system, Dox did not inhibit p34cdc2 kinase activity, indicating that is has no direct effect on the enzyme function. (aspetjournals.org)
  • A good correlation was found between extent of DNA double-strand breaks and p34cdc2 kinase activity inhibition. (aspetjournals.org)
  • However, MSCs need to be expanded in vitro in order to obtain sufficient cells for clinical trials since they are extremely rare in various tissues. (hindawi.com)
  • Unlike embryonic stem cells, adult stem cells (MSCs) have a limited lifespan and stop proliferating during in vitro culture due to replicative senescence [ 8 ]. (hindawi.com)
  • The major phosphopeptides derived from biosynthetically labeled c-Fos correspond to phosphopeptides generated after phosphorylation of c-Fos in vitro with both RSK and MAP kinase. (nih.gov)
  • In vitro treatment of ER-positive breast cancer cell lines with the combination of palbociclib and antiestrogens leads to increased cell senescence, which was sustained for up to 6 days following drug removal. (shu.edu)
  • In addition, NK cells stimulated with lunasin plus cytokines displayed higher tumoricidal activity than those stimulated with cytokines alone using in vitro and in vivo tumor models. (weeksmd.com)
  • Additionally, the in vitro effects of PTE on osteoclastic activities were investigated using the RAW 264.7 cell line as an osteoclast differentiation model. (researchgate.net)
  • Moreover, in the in vitro studies, osteoclast differentiation using the differentiation cell model was significantly inhibited by PTE without cytotoxic effects. (researchgate.net)
  • Here using an in vitro cell-free DNA replication system we analyse the interplay between Ciz1 and cyclin A/CDK2 in regulation of the initiation phase of DNA replication. (lancs.ac.uk)
  • NV556 treatment in an in vitro 3D human liver Extracellular Matrix (ECM) cultured with a TGFβ1-activated human hepatic stellate cell line led to decreased collagen production. (lu.se)
  • An image depicting head and neck squamous cell carcinoma in vitro can be seen below. (medscape.com)
  • Head and neck squamous cell carcinoma in vitro (cell culture). (medscape.com)
  • Neuronal differentiation and cell-cycle programs mediate response to BET-bromodomain inhibition in MYC-driven medulloblastoma. (cancerindex.org)
  • In whole cells, Dox treatment prevented p34cdc2 kinase dephosphorylation without altering its synthesis, and this effect was due to neither down-regulation of cdc25C nor inhibition of protein-tyrosine phosphatase activity. (aspetjournals.org)
  • consequently, genes encoding some of these proteins are being used to design constructs for the inhibition of multiplying cancer cells. (weeksmd.com)
  • We could confirm the increased polyploidy upon Mps1 inhibition in neuroblastoma cell lines and PDX model, leading to mitotic catastrophe activating the caspase-dependent mitochondrial apoptotic pathway. (lu.se)
  • With the loss of function of Cdc7 in ESCs the S phase is stopped at the G2/M checkpoint. (wikipedia.org)
  • Genotoxic stress which specifically affects cells in S-phase is detected by the replication checkpoint. (caltech.edu)
  • G 2 /M arrest was associated with DNA damage as indicated by phosphorylation of H 2 A.X at Ser139 and activation of checkpoint kinase 2 (Chk2) in all the three cell lines. (aspetjournals.org)
  • Cell-cycle arrest was associated with the engagement of checkpoint kinase 2-cell division cycle 25C-cyclin-dependent kinase 1/cyclin B1 signaling. (bioone.org)
  • In response to DNA damage, the checkpoint kinase ATM phosphorylates and activates Chk2, which in turn directly phosphorylates and activates p53 tumor suppressor protein. (kegg.jp)
  • ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation. (kegg.jp)
  • The mitotic kinase monopolar spindle 1 (Mps1) is a key regulator of the Spindle assembly checkpoint, which ensures the correct chromosome segregation. (lu.se)
  • Treatment of breast cancer cell lines with the combination of palbociclib and antiestrogens leads to decreased retinoblastoma protein (Rb) phosphorylation resulting in reduced E2F expression and signaling and increased growth arrest compared to treatment with each drug alone. (shu.edu)
  • The Clb5-specific targets include several proteins (Sld2, Cdc6, Orc6, Mcm3 and Cdh1) involved in early S-phase events. (nature.com)
  • Eukaryotic expression vectors containing genes encoding plant proteins for killing of cancer cells. (weeksmd.com)
  • He mentioned this to David Stillman , who was at Stanford to interview for a faculty position, and who studied cell cycle regulation of proteins as a postdoc in Kim Nasmyth 's lab at the MRC Laboratory of Molecular Biology in the U.K. Stillman pointed out that ribonucleotide reductase was cell cycle regulated-rather than remaining stable, the RNA and protein levels fluctuate throughout the cell cycle. (the-scientist.com)
  • A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. (umassmed.edu)
  • Regulation can occur through modification of the p27 protein's structure, its interaction with other proteins, or its localization within the cell. (medlineplus.gov)
  • The Cdc7/Dbf4 kinase complex, along with another serine-threonine kinase, cyclin-dependent kinase (Cdk), phosphorylates the pre-RC which activates it at the G1/S transition. (wikipedia.org)
  • p34 is a component of the kinase complex that phosphorylates the repetitive C-terminus of RNA polymerase II. (prosci-inc.com)
  • Stern, B. & Nurse, P. A quantitative model for the cdc2 control of S phase and mitosis in fission yeast. (nature.com)
  • Fisher, D. L. & Nurse, P. A single fission yeast mitotic cyclin B p34 cdc2 kinase promotes both S-phase and mitosis in the absence of G1 cyclins. (nature.com)
  • Uncoupled cell cycle without mitosis induced by a protein kinase inhibitor, K-252a. (rupress.org)
  • The staurosporine analogues, K-252a and RK-286C, were found to cause DNA re-replication in rat diploid fibroblasts (3Y1) without an intervening mitosis, producing tetraploid cells. (rupress.org)
  • In a src-transformed 3Y1 cell line, as well as other cell lines, giant cells containing polyploid nuclei with DNA contents of 16C to 32C were produced by continuous treatment with K-252a, indicating that the agent induced several rounds of the incomplete cell cycle without mitosis. (rupress.org)
  • They also suggest that a periodic activation of p34cdc2 is required for S phases in the cell cycle without mitosis. (rupress.org)
  • It is required in higher cells for entry into S-phase and mitosis. (prosci-inc.com)
  • Here we compare the specificity of two budding yeast cyclins, the S-phase cyclin Clb5 and the M-phase cyclin Clb2, in the phosphorylation of 150 Cdk1 (Cdc28) substrates. (nature.com)
  • Donaldson, A. D. The yeast mitotic cyclin Clb2 cannot substitute for S phase cyclins in replication origin firing. (nature.com)
  • The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). (thermofisher.com)
  • These kinases are expressed throughout the cell cycle, but are only activated upon complex formation with their corresponding cyclins. (shu.edu)
  • The product encoded by this gene is predominantly localized in the nucleus and is a cell division cycle protein with kinase activity. (wikipedia.org)
  • We now provide evidence that two growth-regulated, nucleus- and cytoplasm-localized protein kinases, 90-kDa ribosomal S6 kinase (RSK) and mitogen-activated protein kinase (MAP kinase), contribute to the serum-induced phosphorylation of c-Fos. (nih.gov)
  • CDK4 shuttles between the cytoplasm and nucleus as part of its role in cell cycle regulation. (rndsystems.com)
  • While most molecular biologists thought signaling pathways worked by sensing signals extrinsic to the cell and relaying the information to the nucleus, Elledge was proposing an internal signaling pathway that senses cell-intrinsic events. (the-scientist.com)
  • Within cells, p27 is located primarily in the nucleus, where it plays a critical role in controlling cell growth and division. (medlineplus.gov)
  • All of these mutations reduce the amount of functional p27 that is available in the nucleus to regulate the cell cycle. (medlineplus.gov)
  • This complex inhibits mammalian target of rapamycin (mTOR) kinase, a key protein in cells that regulate the gene translation responsible for cell-cycle regulation. (medscape.com)
  • Among them, the sirtuin, AMP-activated protein kinase, mammalian target of rapamycin, p53, and insulin/insulin-like growth factor-1 signaling pathways are most widely studied. (frontiersin.org)
  • During the mitotic mammalian cell cycle cells faithfully replicate their DNA utilizing multiple DNA replication sites known as origins of replication. (lancs.ac.uk)
  • Treatment with the novel cyclophilin inhibitor NV651, presented a potent antiproliferative effect in HCC cell lines via cell cycle perturbations arresting cells in the mitotic phase. (lu.se)
  • Targeting the cell cycle has been proposed as a therapeutic strategy in cancer treatment with special interest in the mitotic phase. (lu.se)
  • The mechanisms of radioresistance are still poorly understood, despite it has been suggested that miRNAs play an important role in cell signaling pathways. (frontiersin.org)
  • Indeed, it has been shown that miRNAs play an important role in gene expression, mainly when associated with the monitoring of several cell and metabolic pathways, being also an essential component of the gene silencing machinery in most eukaryotic organisms ( 4 , 8 ). (frontiersin.org)
  • Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. (kegg.jp)
  • Several pathways involved in cell cycle and DNA repair were affected upon NV651 treatment. (lu.se)
  • Cellular senescence refers to active cells that eventually enter a state of irreversible growth arrest. (hindawi.com)
  • Growth-inhibitory effects of DIM were mediated by cell cycle arrest in G 2 /M phase in all the three cell lines. (aspetjournals.org)
  • To further establish the involvement of Chk2 in DIM-mediated G 2 /M arrest, cells were transfected with dominant-negative Chk2 (DN-Chk2). (aspetjournals.org)
  • Blocking Chk2 activation by DN-Chk2 completely protected cells from DIM-mediated G 2 /M arrest. (aspetjournals.org)
  • These results were further confirmed in Chk2 knockout DT40 lymphoma cells, in which DIM failed to cause cell cycle arrest. (aspetjournals.org)
  • These results clearly indicate the requirement of Chk2 activation to cause G 2 /M arrest by DIM in ovarian cancer cells. (aspetjournals.org)
  • Blocking ROS generation by N -acetyl cysteine protects the cells from DIM-mediated G 2 /M arrest and apoptosis. (aspetjournals.org)
  • Cell cycle-dependent cytotoxicity, G2/M phase arrest, and disruption of p34cdc2/cyclin B1 activity induced by doxorubicin in synchronized P388 cells. (aspetjournals.org)
  • Treatment of synchronized cells in early S phase with 1 microM Dox (2 x ID50) for 1 hr induced a marked cell arrest at G2/M phase at 6-12 hr after drug incubation. (aspetjournals.org)
  • Our results suggest that anthracycline-induced cytotoxicity is cell cycle dependent and is mediated, at least in part, by disturbance of the regulation of p34cdc2/cyclin B1 complex, thus leading to G2/M phase arrest. (aspetjournals.org)
  • Cd at 20 microM markedly increased cells in G2/M and hypodiploid sub-G1 phases of the cell cycle suggesting cycle arrest and cell death. (cdc.gov)
  • Results suggested that p53 is not involved in Cd-induced cell cycle arrest and apoptosis in J774A.1 cells. (cdc.gov)
  • CDK4 is a member of the Ser/Thr protein kinase family. (thermofisher.com)
  • This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. (cancerindex.org)
  • Cyclin-dependent Kinase 4 (CDK4) is a 303 amino acid (aa) member of the Ser/Thr kinase family with a predicted molecular weight of 33.7 kDa. (rndsystems.com)
  • Activation of CDK4 requires binding of a D-type Cyclin and phosphorylation of Thr172 by the CAK kinase complex. (rndsystems.com)
  • Loss of both CDK4 and CDK2 increases neural stem cell differentiation. (rndsystems.com)
  • Virtually all mitogenic signals to the cell are processed through CDK4/6 - it is truly the central molecule that governs pRb phosphorylation status up through the R-point transition. (shu.edu)
  • In order to enter S phase, cells must sequentially activate CDK4/6 and CDK2. (shu.edu)
  • During early G1 phase, mitogenic signals trigger activation of the CDK4/6-cyclin D complex, which partially deactivates Rb by phosphorylation. (shu.edu)
  • Mutations/deletions in separate genes, each of which alone causes a minimal phenotype, but when combined in the same cell results in a more severe fitness defect or lethality under a given condition. (thebiogrid.org)
  • Results: Data addressing the function of vectors harbouring genes specifically encoding ricin, saporin, lunasin , linamarase, and tomato thymidine kinase 1 under the control of different promoters are summarised here. (weeksmd.com)
  • Numerous vectors have been engineered for the sole purpose of killing cancer cells, and some have successfully suppressed malignant tumours. (weeksmd.com)
  • Загальні відомості про лейкоз Leukemia is a malignant condition involving the excess production of immature or abnormal leukocytes, which eventually suppresses the production of normal blood cells and results in symptoms. (msdmanuals.com)
  • Malignant transformation usually occurs at the pluripotent stem cell level, although it sometimes involves a committed stem cell with more limited capacity for self-renewal. (msdmanuals.com)
  • Thymidine kinase is a cellular enzyme involved in the salvage pathway of DNA-synthesis. (slu.se)
  • Thymidine kinase 1 (TK1) is regulated by the cell cycle and is located in the cytoplasm. (slu.se)
  • Thymidine kinase 1 activity is present in the early S-phase of cell division in normal cells. (slu.se)
  • Recent evidence suggests that unscheduled cell cycle activity leads to neuronal cell death. (nih.gov)
  • Pharmacological experiments revealed that cyclin-dependent kinase activity and N-methyl-d-aspartate (NMDA) receptor were cooperatively involved in cell death by 3-NP in striatal neurons, whereas only NMDA receptor was involved in 3-NP-induced neurotoxicity in cortical neurons. (nih.gov)
  • Both striatal p27 down-regulation and cell death provoked by 3-NP were dependent on calpain activity. (nih.gov)
  • Although we did not identify any highly Clb2-specific substrates, we found that Clb2-Cdk1 possessed higher intrinsic kinase activity than Clb5-Cdk1, enabling efficient phosphorylation of a broad range of mitotic Cdk1 targets. (nature.com)
  • However, in abnormal cells the activity of TK1 is often much higher. (slu.se)
  • Judith Balmaña, MD, PhD, of Vall d'Hebron University Hospital, discusses in Spanish the findings of a single-agent phase II trial on the antitumor activity of lurbinectedin in BRCA1/2-associated metas. (ascopost.com)
  • This demonstrates that Ciz1 modulates and enhances the activity of cyclin A-CDK2 in cell free DNA replication assays and that Ciz1 increases the permissive CDK range that can promote DNA replication. (lancs.ac.uk)
  • Because p27 plays such a key role in controlling cell division, its activity is tightly regulated. (medlineplus.gov)
  • We characterized Xenopus Claspin as a kinase substrate of DDK which forms a stable nuclear complex with Cdc7 and Drf1 under both arrested and unperturbed replication conditions. (caltech.edu)
  • Phosphorylation of Clb5-specific targets during S phase was reduced by replacing Clb5 with Clb2 or by mutating the substrate RXL motif, confirming the importance of Clb5 specificity in vivo . (nature.com)
  • Brown, N. R., Noble, M. E., Endicott, J. A. & Johnson, L. N. The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases. (nature.com)
  • Schulman, B. A., Lindstrom, D. L. & Harlow, E. Substrate recruitment to cyclin-dependent kinase 2 by a multipurpose docking site on cyclin A. (nature.com)
  • The extracellular matrix (ECM) provides structural and biochemical support to the surrounding cells, and it has been used as a coating substrate for cell culture. (hindawi.com)
  • At present, it remains poorly understood how DDK docks onto the helicase and how the kinase targets distal Mcm subunits for phosphorylation. (imperial.ac.uk)
  • Cell division cycle 7-related protein kinase is an enzyme that in humans is encoded by the CDC7 gene. (wikipedia.org)
  • The Cdc7 kinase is involved in regulation of the cell cycle at the point of chromosomal DNA replication. (wikipedia.org)
  • this means that most eukaryotic cells have the Cdc7 kinase protein. (wikipedia.org)
  • The gene, CDC7, is involved in the regulation of cell cycle because of the gene product Cdc7 kinase. (wikipedia.org)
  • The Dbf4-dependent Cdc7 kinase (DDK) initiates replisome assembly by phosphorylating the MCM2-7 replicative helicase at the N-terminal tails of Mcm2, Mcm4 and Mcm6. (imperial.ac.uk)
  • Targets of the cyclin-dependent kinase Cdk1. (nature.com)
  • 3-NP reduced the level of cyclin-dependent kinase inhibitor p27 in striatum but not in cerebral cortex. (nih.gov)
  • The company's seliciclib is an orally available, cyclin dependent kinase inhibitor. (pharmaceutical-technology.com)
  • DIM treatment inhibited the growth of SKOV-3, TOV-21G, and OVCAR-3 ovarian cancer cells in both a dose- and time-dependent manner with effective concentrations ranging from 40 to 100 μM. (aspetjournals.org)
  • Reinitiation of DNA synthesis was inhibited by cycloheximide, actinomycin D, and serum deprivation, but not by Colcemid, suggesting that a functional G1 phase dependent on de novo synthesis of protein and RNA is essential for entry into the next S phase. (rupress.org)
  • S-phase kinase-associated protein 2 (SKP2) is an important cell cycle regulator, targeting the cyclin-dependent kinase (CDK) inhibitor p27 for degradation, and is frequently overexpressed in breast cancer. (umass.edu)
  • Ibrance (palbociclib) is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6. (shu.edu)
  • Endogenous regulation of the cell cycle depends on phosphorylation and dephosphorylation of the cyclin- cyclin-dependent kinase (CDK)-cyclin-dependent kinase inhibitor (CDKI) pathway. (jcancer.org)
  • Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. (bvsalud.org)
  • studies suggest that certain endocrine cells may be particularly dependent on the p27 protein to control cell division. (medlineplus.gov)
  • Cellular senescence, which is morphologically characterized by an enlarged and flattened cell shape, was first described by Hayflick [ 9 ]. (hindawi.com)
  • This is the multihit theory of tumorigenesis, in which a series of multiple triggering events in the genetic and cellular makeup of a cell ultimately cause cancer. (medscape.com)
  • tRNAs are essential for cells and their synthesis is under stringent cellular control. (cdc.gov)
  • The differentiation of mesenchymal stem cells (MSCs) into multiple cell lineages can be exploited as an attractive strategy for cell-based therapy and regenerative medicine [ 1 ]. (hindawi.com)
  • The ECM provides structural and biochemical support to the cells and has various other functions including cell adhesion, cell to cell communication, and differentiation [ 17 , 18 ]. (hindawi.com)
  • Runx2, p53, and pRB status as diagnostic parameters for deregulation of osteoblast growth and differentiation in a new pre-chemotherapeutic osteosarcoma cell line (OS1). (umassmed.edu)
  • Studies suggest that p27 is also involved in controlling cell differentiation, which is the process by which cells mature to carry out specific functions. (medlineplus.gov)
  • He found that RNR2 RNA levels increased dramatically, even more than the protein levels, upon exposure of cells to DNA damage and that mutations in RNR2 resulted in hypersensitivity to DNA damage. (the-scientist.com)
  • Like the mutations that cause multiple endocrine neoplasia type 4, these genetic changes reduce the amount of functional p27 available to control cell division. (medlineplus.gov)
  • Replication blockages activate the ATR kinase which, in turn, activates the downstream effector kinase Chk1 through the mediator protein, Claspin. (caltech.edu)
  • This study suggests a role for nuclear RSK and MAP kinase in modulating newly synthesized c-Fos phosphorylation and downstream signaling. (nih.gov)
  • We summarized that four main organic sulfides in garlic, diallyl disulfide (DADS), diallyl trisulfide (DATS), S‑allylmercaptocysteine (SAMC) and allicin, may contribute to the regulation of tumor cell apoptosis, migration and the cell cycle. (spandidos-publications.com)
  • The active ingredients in garlic oil correspond mainly to a family of organosulfur molecules, which selectively increase redox stress in cancer cells, leading to apoptosis and death ( 23 ). (spandidos-publications.com)
  • RT can directly induce cancer cell death through various mechanisms, such as apoptosis, necrosis, and autophagy. (nature.com)
  • Effect of cadmium on P53 and mitogen-activated protein kinases in a murine macrophage cell line: relation to apoptosis. (cdc.gov)
  • It is immunotoxic in vivo and induces apoptosis in many cultured cells. (cdc.gov)
  • Junctional adhesion molecule 3 (JAM3) is involved in epithelial cell junction, cell polarity, and motility. (bioone.org)
  • Then I thought, there must be a sensory pathway that recognizes the DNA damage that's going on in the cell," says Elledge. (the-scientist.com)
  • We hypothesize that a dynamic equilibrium between the dominant buried state and an transiently open, kinase-accessible state is present in the p27-cyclin A-CDK2 complex, and aim to test this hypothesis through the use of unbiased molecular dynamics and metadynamics simulations. (lu.se)
  • Our results establish Chk2 as a potent molecular target of DIM in ovarian cancer cells and provide the rationale for further clinical investigation of DIM. (aspetjournals.org)
  • These results suggest that a putative protein kinase(s) sensitive to K-252a plays an important role in the mechanism for preventing over-replication after completion of previous DNA synthesis. (rupress.org)
  • Cycloheximide, an inhibitor of protein synthesis, did not alter Cd-induced cytotoxicity indicating that J774A.1 cell death by Cd is independent of de novo protein synthesis including p53. (cdc.gov)
  • Replication is catalysed by processive replication enzymes known as DNA polymerases and is limited to the synthesis phase (S phase) of the cell cycle. (lancs.ac.uk)
  • DNA replication is initiated by the S-CDK and DDK kinases which mediate the unwinding of the replication fork. (caltech.edu)
  • The S. cerevisiae ORC binds to specific DNA sequences throughout the cell cycle but becomes active only when it binds to the replication initiator Cdc6. (imperial.ac.uk)
  • Elledge's idea that eukaryotic cells sense the progress of DNA replication and transform that information into a DNA-damage response was new. (the-scientist.com)
  • Those results led him to study how cells monitor roadblocks to replication and DNA damage, such as nicks and double-stranded breaks, and how the cell handles that information. (the-scientist.com)
  • Next the inhibitory effect of Ap4A in cell free DNA replication assays is studied. (lancs.ac.uk)
  • Here we find that the replication fork progresses at 1.3kbp/min in mouse fibroblast cells, consistent with other studies, and quantify replication fork stalling by replication inhibitor aphidicolin. (lancs.ac.uk)
  • These data demonstrate the potential for cell free DNA replication assays to be combined with DNA combing to dissect replication parameters and characterise DNA replication stress in future studies. (lancs.ac.uk)
  • A phase II study showed that patients with resected local-regionally advanced head and neck squamous cell carcinoma (HNSCC) had improved survival when pembrolizumab was added to adjuvant RT (NCT02641093). (nature.com)
  • Mantle cell lymphoma (MCL) is a lymphoproliferative disorder derived from a subset of naive pregerminal center cells localized in primary follicles or in the mantle region of secondary follicles. (medscape.com)
  • IL-2 treatment acutely increased the CD4 cells, all within the CD4RO subset, and increased NK and LAK cells. (cancer.gov)
  • Interleukin (IL)-9-producing subset called Th9 cell, Th22 cells which primarily secrete IL-22, IL-13 and tumor necrosis factor- and Th25 cells via producing IL-25 are believed to be important for initiating allergic reactions and developing airway inflammation. (cdc.gov)
  • In this study, we reexamined pneumococci collected from sickle cell disease patients in Memphis, Tennessee, from 1994 to 1995, the time of the original description of the TN 23F -4 clone, to determine the prevalence of this clone and any other highly cephalosporin-resistant clones circulating in the sickle cell disease population. (cdc.gov)
  • Sixty-four nasopharyngeal isolates were collected from 42 patients between July 1994 and December 1995 at the Mid-South Sickle Cell Center ( 3 ). (cdc.gov)
  • The gene coding for the Dbf4 or ASK protein is regulated during the different phases of cell cycle. (wikipedia.org)
  • This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). (thermofisher.com)
  • The protein encoded by this gene is a member of the CMGC family of serine/threonine protein kinases. (cancerindex.org)
  • Unlike preexisting embryonic stem cell-based knockout mice, our mouse models are free from selectable markers or other external gene insertions, permitting more precise study of cell cycle-related diseases without confounding influences of foreign DNA. (koreamed.org)
  • 1. Artelt P, Grannemann R, Stocking C, Friel J, Bartsch J, Hauser H. The prokaryotic neomycin-resistance-encoding gene acts as a transcriptional silencer in eukaryotic cells. (koreamed.org)
  • The underlying mechanism responsible for the effects of lunasin on NK cells is likely due to epigenetic modulation on target gene loci. (weeksmd.com)
  • Gene therapy has attracted attention for its potential to specifically and efficiently target cancer cells with minimal toxicity to normal cells. (weeksmd.com)
  • In particular, ubiquitin-mediated degradation is critically important at transition points where it provides directionality and irreversibility to the cell cycle, which is essential for maintaining genome integrity. (intechopen.com)
  • DNA is replicated to provide each daughter cell a complete copy of the genome. (lancs.ac.uk)
  • Thus, Clb5 and Clb2 use distinct mechanisms to enhance the phosphorylation of S-phase and M-phase substrates. (nature.com)
  • Bhaduri S, Valk E, Winters MJ, Gruessner B, Loog M, Pryciak PM. A docking interface in the cyclin Cln2 promotes multi-site phosphorylation of substrates and timely cell-cycle entry. (umassmed.edu)
  • Cyclosporine is a calcineurin inhibitor that mainly works by suppressing T cell function. (medscape.com)
  • It helps regulate the cell cycle, which is the cell's way of replicating itself in an organized, step-by-step fashion. (medlineplus.gov)
  • Based on our results showing EPOCH to be effective and well tolerated, we began a phase II study of EPOCH in previously untreated patients with aggressive lymphomas. (cancer.gov)
  • We have recently developed and tested a "second generation" EPOCH regimen (EPOCH II) to replace stem cell transplant for lymphomas requiring high-dose intensity, including poor prognosis untreated aggressive lymphomas, potentially curable relapsed lymphomas, and low-grade lymphomas. (cancer.gov)
  • The concentration of Dbf4 at the G1/S transition of the cell cycle is higher than the concentration at the M/G1 transition. (wikipedia.org)
  • According to GlobalData, Phase II drugs for Diffuse Large B-Cell Lymphoma have a 40% phase transition success rate (PTSR) indication benchmark for progressing into Phase III. (pharmaceutical-technology.com)
  • GlobalData tracks drug-specific phase transition and likelihood of approval scores, in addition to indication benchmarks based off 18 years of historical drug development data. (pharmaceutical-technology.com)
  • It promotes the transition from G1 to S phase by phosphorylating and inactivating RB1. (rndsystems.com)
  • We then studied the effect of Dox on the p34cdc2/cyclin B1 complex because it plays a key role in regulating G2/M phase transition. (aspetjournals.org)