Tumor inhibit the cyclin cyclin dependent kinase inhibitor. Medical search. Frequent questions

The p53 protein is an important tumor suppressor that is essential for regulating cell division, senescence, and self-destruction (apoptosis). (medlineplus.gov)
Our simulations show that, if HMGB1 is overexpressed, then the oncoproteins CyclinD/E, which regulate cell proliferation, are overexpressed, while tumor suppressor proteins that regulate cell apoptosis (programmed cell death), such as p53, are repressed. (biomedcentral.com)
The protein p53 is one of the most important tumor suppressor proteins: its activation can lead to cell cycle arrest, DNA repair, or apoptosis. (biomedcentral.com)
Inhibition of these kinases may result in cell cycle arrest and apoptosis of tumor cells that express these kinases. (ncats.io)
Upon treatment with Plk1 inhibitors, p53 in tumor cells is activated and induces strong apoptosis, whereas tumor cells with inactive p53 arrest in mitosis with DNA damage. (oncotarget.com)
In addition, compared to the mono-treatment, combination of Polo-like kinase 1 inhibition with anti-mitotic or DNA damaging agents boosts more severe mitotic defects, effectually triggers apoptosis and strongly inhibits proliferation of cancer cells with functional p53. (oncotarget.com)
It affects cell proliferation, differentiation and inhibits apoptosis, and its role in tumor development has received attention ( 9 ). (spandidos-publications.com)
Overexpression of IGF-1 in serum and tissue alters the growth of normal cells and causes uncontrolled proliferation, inhibits differentiation and reduces apoptosis, resulting in the incidence and development of malignant tumors ( 10 ). (spandidos-publications.com)
LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seem to have to effect on cell-cycle regulation. (lsbio.com)
Isoform 7 inhibits isoform 1-mediated apoptosis. (lsbio.com)
inhibit apoptosis of cell lines apart from C2C12. (biotech-angels.com)
Vinca alkaloids are also thought to increase apoptosis by increasing concentrations of p53 (cellular tumor antigen p53) and p21 (cyclin-dependent kinase inhibitor 1) and by inhibiting Bcl-2 activity. (smpdb.ca)
Cyclin D3-CDK6 inhibits the glycolytic enzymes PFK1 and PKM2 to prevent T-ALL cell apoptosis. (aacrjournals.org)
However, in T-cell acute lymphoblastic leukemia (T-ALL), which predominately expresses CDK6 and the activating cyclin, cyclin D3, inhibition of CDK6 or cyclin D3 induces apoptosis. (aacrjournals.org)
Thus, the CDK4/6 inhibitor palbociclib reduced NADPH and GSH levels in T-ALL cells, thereby increasing ROS levels to induce apoptosis, which could be rescued by the antioxidant N -acetyl-cysteine. (aacrjournals.org)
Moreover, in breast cancer cells, which express CDK4 instead of CDK6, palbociclib induced cell-cycle arrest instead of apoptosis, further indicating that expression of cyclin D3 and CDK6 in T-ALL cells promotes apoptosis in response to palbociclib. (aacrjournals.org)
Additionally, 16 of 18 nonleukemic cancer cell lines exhibiting high expression of cyclin D3 and CDK6 underwent apoptosis in response to palbociclib, and, in melanoma patient-derived xenografts, high cyclin D3 and CDK6 expression was associated with tumor regression after CDK4/6 inhibition. (aacrjournals.org)

Without p16(INK4A) to regulate cell growth and division (proliferation), cells can continue to grow and divide without control, which can lead to tumor formation. (medlineplus.gov)
To the best of the authors' knowledge, no computational model has been proposed to investigate the importance of HMGB1 in tumor proliferation. (biomedcentral.com)
Cyclin-dependent kinases (Cdks) are principal drivers of cell division and are an important therapeutic target to inhibit aberrant proliferation. (escholarship.org)
P15 INK4 is a cyclin dependent kinase inhibitor that blocks the activity of Cyclind-CDK4,6, inhibiting it from hypophosphorylating Rb, thereby, rendering the cell cycle unresponsive to external proliferation signals. (shu.edu)
The pharmaceutical industry currently uses cyclin-dependent kinase (CDK) inhibitors to target cell proliferation for cancer chemotherapy. (foxchase.org)
Induction of p16 inhibits cell proliferation and thus can help to block the growth of tumors in a specific manner. (foxchase.org)
Single-cell RNA-sequencing (scRNA-seq) analysis of thousands of DIPG tumor cells containing H3K27M mutations showed that most of these tumor cells resemble oligodendrocyte precursor cells (OPC-like)-a cell type that exhibits obviously enhanced proliferation and tumor-propagating potential compared with other cell subsets in tumor samples 9 . (nature.com)
The p27 protein is a canonical negative regulator of cell proliferation and acts primarily by inhibiting cyclin-dependent kinases (CDKs). (rcsb.org)
Tumor suppressor genes encode proteins that normally provide negative control of cell proliferation. (medscape.com)
PTEN encodes a protein kinase of the same name and functions as a tumor suppressor through regulation of cell proliferation. (medscape.com)
BTICs talk about these features but are recognized by their regularity proliferation aberrant appearance of differentiation markers chromosomal abnormalities and tumor development. (biopaqc.com)
We further demonstrated that overexpression of miR-24 suppressed the NPC cell proliferation and migration in vitro, and inhibited the xenograft tumor growth and lung metastasis in vivo. (biomedcentral.com)
2017. Divergent roles of p120-catenin isoforms linked to altered cell viability, proliferation, and invasiveness in carcinogen-induced rat skin tumors. . (oregonstate.edu)
Inactivation of tumor suppressor genes, whose products normally provide negative control of cell proliferation, contributes to malignant transformation in various cell types. (medscape.com)

The crosstalk is regulated by tumor suppressor proteins, including ARF, P21 and FBXW7, which are also frequently mutated in many cancers. (biomedcentral.com)
Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. (prospecbio.com)
CDKIs are capable of suppressing growth, and several lines of evidence strongly suggest that at least some CDKIs may be tumor suppressor proteins. (prospecbio.com)
In addition, numerous important cellular proteins, such as B-cell lymphoma-2 homologous antagonist/killer, Myc proto-oncogene protein, cyclin-dependent kinase inhibitor 1B, DNA replication licensing factor MCM-7, retinoblastoma 1 and Annexin A1, are degenerated through the UBE3A-mediated ubiquitin proteasome pathway ( 7 ). (spandidos-publications.com)
In order to solve this problem in 2009 under the guidance of prof. Slamon scientists began to research cyclin-dependent kinases (CDK), a group of proteins that play a leading role in regulating the cell cycle. (x7cpr.com)
We will discuss three key proteins that function as tumor suppressors implicated in the development of pediatric (and some adult) cancers: pRB, p53, and PTEN. (medscape.com)
Cyclin-dependent kinase 5 (CDK5) phosphorylated DRP1 to improve its activity in BTICs whereas Ca2+-calmodulin-dependent proteins kinase 2 (CAMK2) inhibited DRP1 in non-BTICs recommending tumor cell differentiation induces a regulatory change in mitochondrial morphology. (biopaqc.com)
Ethyl 2-((2 3 bis(nitrooxy)propyl)disulfanyl)benzoate (GT-094) a novel nitro-NSAID induced ROS and decreased mitochondrial membrane potential (MMP) in SW480 and RKO colon cancer cells and treatment with antioxidants GSH and DTT inhibited ROS generation prevented the loss of MMP and reversed the effects on downregulation of Sp1 Sp3 and Sp4 proteins and Sp dependent genes [42]. (tam-receptor.com)
Ribociclib (Kisqali) 200 mg is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow cancer progression by inhibiting two proteins called cyclin-dependent kinases 4 and 6 (CDK4/6). (indiangenericprice.com)
Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. (thermofisher.com)
Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.com)

The p16 family (p15, p16, p18 and p19) binds to and inhibits the activities of CDK4 and CDK6. (prospecbio.com)
Palbociclib instead primarily targeted monomeric CDK4 and CDK6 (CDK4/6) in breast tumor cells. (rcsb.org)
Inhibitors of the cyclin-dependent kinases CDK4 and CDK6 induce cell-cycle arrest in RB1-proficient tumors and have had promising results in several tumor types. (aacrjournals.org)

Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. (nih.gov)
The cyclin D1-Cdk4 complex phosphorylates the pRB protein leading to sequential phosphorylation by cyclin E-Cdk2 and release of free E2F. (shu.edu)
Structural and biochemical data revealed that binding of phosphorylated p27 (phosp27) to CDK4 altered the kinase adenosine triphosphate site to promote phosphorylation of the retinoblastoma tumor suppressor protein (Rb) and other substrates. (rcsb.org)
Phosphorylation at CDK1, CDK4, and CDK9 sites on, respectively, protein phosphatase 1alpha, retinoblastoma protein, and RNA polymerase II is inhibited in neuroblastoma SH-SY5Y cells exposed to meriolins. (rcsb.org)
Phosphorylation of Bcl-2 subsequently inhibits the formation Bcl-2-BAX heterodimers. (smpdb.ca)
This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). (thermofisher.com)

The encoded protein binds to and inhibits the activity of cyclin-cyclin-dependent kinase2 or -cyclin-dependent kinase4 complexes, and thus functions as a regulator of cell cycle progression at G1. (nih.gov)
MDM2 binds to and inhibits TP53 activity. (medscape.com)

An orally bioavailable inhibitor of cyclin-dependent kinases (CDKs) and thropomyosin receptor kinase A (TRKA), with potential antineoplastic activity. (ncats.io)
CDK2/TRKA inhibitor PHA-848125 AC potently inhibits cyclin-dependent kinase 2 (CDK2) and exhibits activity against other CDKs including CDK1 and CDK4, in addition to TRKA. (ncats.io)
A selectivity study done on 32 kinases showed that, compared with variolin B, meriolins display enhanced specificity toward CDKs, with marked potency on CDK2 and CDK9. (rcsb.org)
The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)

Both function as tumor suppressors, which means they keep cells from growing and dividing too rapidly or in an uncontrolled way. (medlineplus.gov)

Tissue microarrays were utilized to investigate the expression of genes in a large number of tumor samples and to identify overexpressed genes which could be potentially causing tumorigenesis. (biomedcentral.com)
The CDKN2A/B locus contains genes encoding cell cycle inhibitors, including p16 Ink4a , which have not yet been implicated in the control of hepatic glucose homeostasis. (diabetesjournals.org)
One of the activated genes is an inhibitor of cyclin-dependent kinases. (lsbio.com)
Driver events in pediatric malignancies can occur through loss of function in tumor suppressor genes or gain of function in proto-oncogenes. (medscape.com)
It is postulated to bind as a tetramer to a p53-binding site and activate expression of downstream genes that inhibit growth and/or invasion, and thus function as a tumor suppressor. (affbiotech.cn)
In addition, these alterations affect 3 principal categories of genes, as follows: proto-oncogenes, tumor suppressor genes, and DNA repair genes. (medscape.com)
This article briefly discusses tumor suppressor genes and then focuses on the role of proto-oncogenes in childhood cancer. (medscape.com)
Another important class of tumor suppressor genes involved in cell cycle control and in the generation of human cancers is the cyclin-dependent kinase (CDK) inhibitors. (medscape.com)
Although carcinogenic roles for the INK4B, INK4C, INK4D, CIP1, KIP1, and KIP2 genes appear to be limited, INK4A is among the most commonly mutated genes in human tumors. (medscape.com)

Programmed cell death 4 (PDCD4) is an important tumor suppressor in the development of various human cancers [1] and inhibits translation rather than transcription. (plos.org)
p53, the guardian of the genome, is the most important tumor suppressor. (oncotarget.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)

Conclusion: TGF-β induces p53-independent and p16Ink4a-independent, but Nox4-dependent, p21Cip1-dependent, p15Ink4b-dependent, and ROS-dependent senescence arrest in well-differentiated HCC cells. (bilkent.edu.tr)

Meriolin 3 potently inhibits tumor growth in two mouse xenograft cancer models, namely, Ewing's sarcoma and LS174T colorectal carcinoma. (rcsb.org)

Additionally, the use of simvastatin plus classII histone deacetylase (HDAC) inhibitor (MC1568) induced further overexpression of p27(KIP1) by inhibiting HDAC5 induction originated from downregulated EZH2 in CRC cells and synergistically led to considerable antiproliferative effects. (nih.gov)
Increasingly numerous results have demonstrated overexpression of CDC2/Cyclin B1 in various tumors however there is still no report of CDC2/Cyclin B1 expression in clinical samples from patients with gliomas. (biomedcentral.com)
The overexpression of miRNA‑375 significantly increased caspase‑3 and caspase‑9 activities, induced B‑cell lymphoma 2 (Bcl‑2)/Bcl‑2‑associated X protein, tumor protein 53 and cyclin‑dependent kinase inhibitor 1 protein expression and suppressed cyclin D1 and survivin protein expression in HPV‑18(+) cervical cancer cells. (spandidos-publications.com)
2011. NADPH oxidase overexpression in human colon cancers and rat colon tumors induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). . (oregonstate.edu)

Without one of these tumor suppressors, cells can grow and divide unchecked, leading to the development of cancer. (medlineplus.gov)
In contrast to normal cells, many tumors are resistant to the anti-proliferative effect of TGF-b. (tmc.edu)
Polyvinyl pyrrolidone-coated silver nanoparticles in a human lung cancer cells: time- and dose-dependent influence over p53 and caspase-3 protein expression and epigenetic effects. (sciendo.com)
Anti-PD-1 antibodies (dark green) or anti-PD-L1 antibodies (light green) can prevent the tumor cell from binding PD-1 and thus allow T cells to remain active. (shu.edu)
En face co-immunostaining of the mouse aortic arch revealed a low level of PDCD4 in endothelial cells undergoing pulsatile shear stress. (plos.org)
p53 represses the promoter of Polo-like kinase 1, whereas Polo-like kinase 1 inhibits p53 and its family members p63 and p73 in cancer cells lacking functional p53. (oncotarget.com)
Plk1 inhibitors target all rapidly dividing cells irrespective of tumor cells or non-transformed normal but proliferating cells. (oncotarget.com)
Thus, inactive p53 is not associated with a susceptible cytotoxicity of Polo-like kinase 1 inhibition and could rather foster the induction of polyploidy/aneuploidy in surviving cells. (oncotarget.com)
In this regard, restoration of p53 in tumor cells with loss or mutation of p53 will reinforce the cytotoxicity of combined Polo-like kinase 1 therapy and provide a proficient strategy for combating relapse and metastasis of cancer. (oncotarget.com)
Downregulation of CDC2 could potentialy inhibit human gliomas cells growth ex vivo and in vivo. (biomedcentral.com)
Previous studies have identified that UBE3A exhibits abnormal expression in numerous tumor cells, including prostate, cervical and breast cancer ( 6 , 7 ). (spandidos-publications.com)
We discovered that activation of BMP signaling promotes the exit of DIPG tumor cells from 'prolonged stem-cell-like' state to differentiation by epigenetically regulating CXXC5, which acts as a tumor suppressor and positive regulator of BMP signaling. (nature.com)
Whereas similar ST treatments moderately inhibited the growth of A549 cells by up to 13% (p ≤ 0.05) in 48 h and 14% (p ≤ 0.05-0.0001) in 72 h. (biomedcentral.com)
In MDA-MB-231 cells, ST caused a significant dose-dependent cell growth inhibition by 31- 63% (p ≤ 0.0001) in 48 h and 40-50% (p ≤ 0.0001) in 72 h. (biomedcentral.com)
Here, we show that Mcl-1 down-regulation by the cyclin-dependent kinase (CDK) inhibitor roscovitine or Mcl-1-shRNA dramatically increases ABT-737 lethality in human leukemia cells. (aacrjournals.org)
Brivanib markedly enhances cGAS-mediated type I IFN response in tumor cells treated with platinum. (bvsalud.org)
VERZENIO (Abemaciclib) contain cyclin-dependent kinases (CDK) 4 and 6 inhibitors which inhibit the growth of cancer cells by disrupting their cell cycle, resulting in the arrest at the G1 phase. (advochealth.com)
Mind tumor initiating cells (BTICs) coopt the neuronal high affinity GLUT3 blood sugar transporter to withstand metabolic tension. (biopaqc.com)
While all tumor cells display dysregulation of metabolic pathways the differential growth patterns of BTICs suggest that these tumor subpopulations have metabolic features that distinguish them from your tumor bulk17-20. (biopaqc.com)
IL-29 upregulated cyclin-dependent kinase inhibitor p21Waf1/Cip1 in cells sensitive, but not insensitive, to antiproliferative activity, and knockdown of p21 with small interfering RNA largely attenuated the antiproliferative effect. (elsevierpure.com)
2017. Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism. . (oregonstate.edu)
Although some mechanism-based medicines show some promise their beneficial restorative efficacy has been limited due to the complex labyrinth-like signaling pathways and regulatory networks that allow tumor cells to grow and survive. (tam-receptor.com)
Hence there is a need for restorative focuses on that can simultaneously target multiple pathways in malignancy cells and tumors. (tam-receptor.com)
It inhibits the growth of tumor cells by arresting cells at the G1 checkpoint, preventing tumor cells from proliferating. (indiangenericprice.com)
These changes can be inherited and are, therefore, found in every cell, but more often, they are somatically acquired and restricted to tumor cells. (medscape.com)

[ 5 ] Targeted disruption of TP53 in the mouse leads to the development of various tumors. (medscape.com)
DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)
The p19ARF protein, which is encoded by the same locus as p16, also leads to cell cycle arrest by inhibiting the ability of MDM2 to inactivate TP53. (medscape.com)

This gene encodes a potent cyclin-dependent kinase inhibitor. (nih.gov)
Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor. (ncats.io)
The protein p16INK4a is a potent cell cycle inhibitor and is a relatively selective CDK inhibitor. (foxchase.org)
Here we show that BMP ligands exert potent tumor-suppressive effects against H3.3K27M and ACVR1 WT DIPG in a SMAD-dependent manner. (nature.com)
Recently, a novel inhibitor (ABT-737) of Bcl-2, Bcl-xL, and Bcl-w, which is significantly more potent than previous compounds of this type, has been developed. (aacrjournals.org)

Although the frequency of p16INK4a abnormalities is higher in tumor derived cell lines than in unselected primary tumors, significant subsets of clinical cases with aberrant p16INK4a gene have been reported among melanomas, gliomas, esophageal, pancreatic, lung, and urinary bladder carcinomas, and some types of leukemia. (neobiotechnologies.com)

It is a specific inhibitor of cdk4/cdk6, and a tumor suppressor involved in the pathogenesis of a variety of malignancies. (neobiotechnologies.com)
High levels of cyclin D3 and CDK6 may predict response to CDK4/6 inhibitors in multiple tumor types. (aacrjournals.org)
The mechanisms underlying the prosurvival function of cyclin D3-CDK6 have not been elucidated, prompting Wang and colleagues to search for substrates that may promote cancer cell survival. (aacrjournals.org)
6-phosphofructokinase (PFK1) and pyruvate kinase M2 (PKM2), enzymes that catalyze irreversible, rate-limiting steps in glycolysis, were directly phosphorylated and inhibited by cyclin D3-CDK6, suggesting that cyclin D3-CDK6 may have a unique role in glucose metabolism. (aacrjournals.org)
Together, these findings elucidate a prosurvival role for cyclin D3-CDK6 in metabolism, in addition to its role in cell-cycle progression, and suggest that high levels of cyclin D3 and CDK6 may predict response to CDK4/6 inhibitors. (aacrjournals.org)
The metabolic function of cyclin D3-CDK6 kinase in cancer cell survival. (aacrjournals.org)

HMGB1 can activate a series of signaling components, including mitogen-activated protein kinases (MAPKs) and AKT, which play an important role in tumor growth and inflammation, through binding to different surface receptors, such as RAGE and TLR2/4. (biomedcentral.com)
Protein kinases represent promising anticancer drug targets. (rcsb.org)
The protein encoded by this gene is a member of the CMGC family of serine/threonine protein kinases. (cancerindex.org)

The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (prospecbio.com)
Binding of DLX4 to Smad4 prevented Smad4 from forming transcriptional complexes with Smad2 and Smad3, whereas binding of DLX4 to Sp1 inhibited DNA-binding activity of Sp1. (tmc.edu)
The structures of pCDK2/cyclin A/variolin B and pCDK2/cyclin A/meriolin 3 complexes reveal that the two inhibitors bind within the ATP binding site of the kinase, but in different orientations. (rcsb.org)
The p16INK4A protein is a cell-cycle inhibitor that acts by inhibiting activated cyclin D:CDK4/6 complexes, which play a crucial role in the control of the cell cycle by phosphorylating Rb protein. (medscape.com)

Thus, PD-1 targets Ras and PI3K/Akt signaling to inhibit transcription of Skp2 and to activate Smad3 as an integral component of a pathway that regulates blockade of cell cycle progression in T lymphocytes. (shu.edu)
The phosphatidyl inositol 3-kinase (PI3K)/Akt pathway was involved in this ubiquitin-proteasome-mediated degradation of PDCD4. (plos.org)

However, these mutations are absent from many other types of tumors that are resistant to TGF-b-mediated growth inhibition. (tmc.edu)
Inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) may provide protection against oncogenic processes in specific tissue types. (indiangenericprice.com)

Although PDCD4 in general suppresses the development and progression of tumors, its specific biological functions differ by cell type [8] . (plos.org)
Abnormalities in cell cycle regulation are reported to be strongly associated with tumorigenesis and progression of tumors. (biomedcentral.com)

Spy1 lacks the cyclin-binding site that mediates p27 and substrate affinity, explaining why Cdk-Spy1 is poorly inhibited by p27 and lacks specificity for substrates with cyclin-docking sites. (escholarship.org)

The scientist also raised the issue of therapy for patients with HER 2-negative hormone-positive breast cancer, and mentioned that these tumors are up to 65% of all breast cancers. (x7cpr.com)
Mutants of p53 that frequently occur in a number of different human cancers fail to bind the consensus DNA binding site, and hence cause the loss of tumor suppressor activity. (affbiotech.cn)

CDKN2A gene mutations involved in cancer impair production of functional p16(INK4A) or, less commonly, p14(ARF), which can result in uncontrolled cell growth and tumor formation. (medlineplus.gov)
In contrast, the deletion of TGF-β receptor 2 abolished in vitro senescence response and greatly accelerated in vivo tumor growth. (bilkent.edu.tr)
TGF-b inhibits cell growth by controlling a cytostatic program that includes activation of the cyclin-dependent kinase inhibitors p15 Ink4B and p21 WAF1/Cip1 and repression of c-myc. (tmc.edu)
The cyclin-dependent kinase inhibitor PHA-848125 suppresses the in vitro growth of human melanomas sensitive or resistant to temozolomide, and shows synergistic effects in combination with this triazene compound. (ncats.io)
Already the first clinical trial involved 12 patients showed that the drug inhibited tumor growth until its complete disappearance. (x7cpr.com)
Here, by using a high-throughput small-molecule microarray-based screening of cGAS interacting compounds, we identify brivanib, known as a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor, as a cGAS modulator. (bvsalud.org)
Quantitative RT-PCR, MTT, colony formation, soft-agar, wound healing, Transwell migration and invasion assays, and xenograft tumor growth and lung metastasis models were performed to test the expression levels and functions of miR-24 in NPC. (biomedcentral.com)
IL-29 significantly inhibited the in vitro growth of a wide range of NSCLC lines in a dose-dependent fashion. (elsevierpure.com)
Intratumoral and systemic administration of IL-29 inhibited OBA-LK1 and LK-1, but not A549, tumor growth in severe combined immunodeficiency mice. (elsevierpure.com)
Evidence from studies carried out in this laboratory and others show that Sp transcription factors are overexpressed in several tumor cell lines including colon bladder pancreatic prostate breast thyroid and esophageal malignancy cell lines and play a crucial part in tumor growth development and metastasis Semagacestat [48-53]. (tam-receptor.com)
For example, CDK4 is not required for normal mammary tissue growth based on knockout mouse studies, but it is required for Ras-induced breast tumor growth, suggesting a therapeutic window potential for treatment with lower toxicity. (indiangenericprice.com)

Gliomas are the most common and aggressive primary brain tumors for which unfortunately no effective treatment modalities exist despite advances in molecular biology as the knowledge base to unravel the extremely complex molecular mechanisms of tumorigenesis is limited. (biomedcentral.com)

Polo-like kinase 1, a pivotal regulator of mitosis and cytokinesis, is highly expressed in a broad spectrum of tumors and its expression correlates often with poor prognosis, suggesting its potential as a therapeutic target. (oncotarget.com)

While BTICs stay controversial because of unresolved problems over cell-of-origin and purification BTICs possess generated substantial curiosity because of their resistance to typical therapies evasion of anti-tumor immune system responses advertising of tumor angiogenesis and invasion into regular tissue8-11. (biopaqc.com)

But, how does PD-1 blunt the anti-tumor immune response? (shu.edu)

[ 1 ] His prediction was subsequently supported by the cloning of the retinoblastoma tumor suppressor gene ( RB1 ) and by functional studies of the retinoblastoma protein, Rb. (medscape.com)

Receptor-regulated SMADs (R-SMADs), SMAD1, 2, 3, 5, and 8, are the only SMADs directly phosphorylated and activated by the kinase domain of type I receptors. (shu.edu)

Collectively, these findings suggest down-regulation of Mcl-1 by either CDK inhibitors or genetic approaches dramatically potentiate ABT-737 lethality through cooperative interactions at two distinct levels: unleashing of Bak from both Bcl-xL and Mcl-1 and simultaneous induction of Bak activation and Bax translocation. (aacrjournals.org)

Five members of the Plk family have been discovered in humans and these serine/threonine kinases have emerged as key players by performing crucial functions in the cell cycle, DNA damage response and neuron biology [ 2 - 6 ]. (oncotarget.com)

Moreover, we tested the reliability of the model for predicting tumor aggressiveness and therapeutic susceptibility of colon cancer. (biomedcentral.com)
Studies have therefore proposed that blocking ACVR1 kinase activity may represent a useful therapeutic strategy for the DIPG subgroup carrying ACVR1 mutations 14 , 17 . (nature.com)
Overall, miR-24 acts as a novel tumor suppressor in the development and progression of NPC through targeting FSCN1 , which providing new insight into the mechanisms of NPC carcinogenesis and suggesting the possibility of miR-24 as a therapeutic target. (biomedcentral.com)

Furthermore, statin plus classII HDAC inhibitor could be a novel anticancer therapy by their synergistic effects in CRC. (nih.gov)
This article reviews current anticancer small-molecule inhibitors targeting epigenetic modified enzymes and displays their performances in different stages of clinical trials. (frontiersin.org)

Furthermore, this study also provides insights into how aberrant activation of a developmental patterning gene promotes tumor pathogenesis. (tmc.edu)
An important development in cancer research over the past 2 decades has been the recognition that genetic changes drive the pathogenesis of tumors of both adulthood and childhood. (medscape.com)

We found that p27, when phosphorylated by tyrosine kinases, allosterically activated CDK4 in complex with cyclin D1 (CDK4-CycD1). (rcsb.org)

AZD6738 biological activity RCC, renal cell carcinomas strong class="kwd-title" Keywords: Gallblader tumor, Renal cell carcinomas, Latente metastasis, Case report 1. (irjs.info)

These events resulted in upregulation of the Cdk4/6 inhibitor p15 INK4B and repression of the Cdk-activating phosphatase Cdc25A. (shu.edu)

ST caused G0/G1 cell cycle arrest which was accompanied by a decrease in CDK4 and cyclin D1, and an increase in p21/Cip1and p27/Kip1 protein levels. (biomedcentral.com)

In several types of tumors, particularly those of gastrointestinal origin, resistance to the anti-proliferative effect of TGF-b has been attributed to TGF-b receptor or Smad mutations. (tmc.edu)
This study provides a molecular explanation as to why tumors are resistant to the anti-proliferative effect of TGF-b in the absence of mutations in the TGF-b signaling pathway. (tmc.edu)
Metabolic adjustments aren't merely a consequence of oncogenesis as mutations in essential enzymes are principal tumor initiating lesions13. (biopaqc.com)

Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. (lsbio.com)
In vitro results showed naringin presented cytotoxic effects, reduced the number of colonies, inhibited cell migration, and changed the morphology and cell cycle progression of the two cell lines evaluated. (bvsalud.org)
This kinase is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression and G1/S transition. (cancerindex.org)
Tumor protein p53, a nuclear protein, plays an essential role in the regulation of cell cycle, specifically in the transition from G0 to G1. (affbiotech.cn)

Cdk enzymatic activity is tightly controlled through cyclin interactions, posttranslational modifications, and binding of inhibitors such as the p27 tumor suppressor protein. (escholarship.org)
Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. (nih.gov)
At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. (nih.gov)
p27 is a cyclin dependent kinase inhibitor that blocks the activity of Cyclin E-CDK2, which phosphorylates pRb, thereby ushering the cell from G1 into S phase through the Restriction point (Figure 2). (shu.edu)
Full holoenzyme activity of the cyclin D1-Cdk4 complex is induced by mitogen recruitment of CAK. (shu.edu)
Increasing concentrations of p53 and p21 lead to changes in protein kinase activity. (smpdb.ca)
This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. (cancerindex.org)
Ribociclib (Kisqali) is reported to be the most selective CDK4/6 inhibitor and has dose-dependent antitumor activity in several preclinical models. (indiangenericprice.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)

RB1 encodes the protein pRB and was the first tumor suppressor gene to be molecularly defined. (medscape.com)

Here, we summarize the different types of epigenetic enzymes which target corresponding protein domains, emphasize DNA methylation , histone modifications, and microRNA-mediated cooperation with epigenetic modification, and highlight recent achievements in developing targets for epigenetic inhibitor therapy. (frontiersin.org)

p16INK4a is a tumor suppressor protein. (neobiotechnologies.com)

Importantly, brivanib synergizes with cisplatin in tumor control by boosting CD8+ T cell response in a tumor-intrinsic cGAS-dependent manner, which is further validated by a patient-derived tumor-like cell clusters model. (bvsalud.org)

Increasing evidence indicates that the dysregulation of miRNAs expression is involved in the tumorigenesis by acting as tumor suppressors or oncogenes. (biomedcentral.com)

In this review, we summarize the basic principles manipulating the abovementioned epigenetic pathways and highlight the evidence of the promising clinical and preclinical results using small-molecule inhibitors against chromatin regulators for cancer treatment. (frontiersin.org)
These observations have prompted the development of small-molecule Bcl-2 inhibitors (refs. (aacrjournals.org)

The answer was the creation of a selective inhibitor of CDK 4/6 (cyclin-dependent kinases 4 and 6). (x7cpr.com)

Anatomy12

Organisms8

Diseases18

Chemicals and Drugs147

Analytical, Diagnostic and Therapeutic Techniques and Equipment18

Phenomena and Processes51

Disciplines and Occupations1

Information Science3

Apoptosis17

Proliferation14

Proteins11

CDK4 and CDK63

Phosphorylation6

Binds to and inhibits2

Cdks4

Function as tumor suppressors1

Genes9

Important tumor2

INK41

Induces1

Potently inhibits1

Overexpression4

Cells25

TP533

Potent5

Unselected primary1

CDK66

Protein kinases3

Complexes4

PI3K2

Inhibition2

Progression of tumors2

Substrates1

Cancers2

Growth11

Brain tumors1

Regulator1

Angiogenesis1

Anti-tumor immune1

Retinoblastoma tumor1

Directly phosphorylated1

Induction1

Serine1

Therapeutic3

Anticancer2

Pathogenesis2

Tyrosine1

Metastasis1

Ink4B1

Arrest1

Mutations3

Cell cycle4

Activity9

Encodes1

Targets1

P16INK4a1

Patient-derived1

Oncogenes1

Small-molecule2

Selective1