Multiple tumor suppressor cyclin dependent kinase inhibitor p21. Medical search. Frequent questions

The expression of cyclin-dependent kinase inhibitors was profoundly affected with early activation and then repression of p21 cip1/waf1 and persistent activation of both p27 kip1 and p57 kip2 , whereas genes involved in cell survival and proliferation were suppressed. (aacrjournals.org)
Several hallmarks of cellular senescence, such as cell cycle arrest, expression of cyclin-dependent kinase inhibitors, DNA damages, and senescence-associated secretory profile were evaluated. (aging-us.com)
SnCs exhibit irreversible growth arrest accompanied by increased expression of cyclin-dependent kinase inhibitors (CDKi) such as p16 INK4a , and p21 Cip1 , accumulation of DNA damages, and secretion of diverse bioactive molecules known as the senescence-associated secretory phenotype (SASP). (aging-us.com)

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)
Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. (nih.gov)
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)
Progression through the cell cycle is driven by the oscillating activity of Cyclin Dependent Kinases (CDKs). (intechopen.com)
The progression of cells through the cell cycle is regulated by a family of protein kinases known as the cyclin-dependent kinases (CDKs). (biomedcentral.com)
In contrast to this activity, TGFβ can also function as a tumor promoter by promoting cancer cell proliferation, stimulating epithelial-to-mesenchymal transition (EMT) and migration of cancer cells, and indirectly by acting on the tumor microenvironment, promoting angiogenesis, and/or immune evasion in advanced stages of tumor progression [ 8 ] [ 9 ] . (encyclopedia.pub)
Although PDCD4 in general suppresses the development and progression of tumors, its specific biological functions differ by cell type [8] . (plos.org)
Low AKAP12 expression in a larger cohort of patients (75) characterized tumor invasiveness, recurrence, and progression, indicating its potential as a prognostic biomarker. (nature.com)
The availability of a sophisticated genetic tool box makes Drosophila an excellent genetic model well suited to studying the biology of Lunasin and its effect on tumor progression in an in vivo model organism. (weeksmd.com)
Both elite controllers expressed multiple HLA Class I and II haplotypes previously associated with slower disease progression (HLA-A*74:01, HLA-B*44:03, HLA-B*81:01, HLA-B*57:03, HLA-DRB1*13). (biomedcentral.com)
Matrix metalloproteinases (MMPs) have been considered to be associated with tumor progression or poor prognosis. (cancerindex.org)
New sequencing technologies have shown that a large number of aberrantly expressed lncRNAs are associated with multiple cancer types and indicated they have emerged as an important class of pervasive genes during the development and progression of cancer. (biomedcentral.com)
Aggressive tumors typically demonstrate a high glycolytic rate, which results in resistance to radiation therapy and cancer progression via several molecular and physiologic mechanisms. (springer.com)
As a result, it negatively regulates cyclin-D-dependent phosphorylation of the retinoblastoma (pRb) gene product, thus blocking cell-cycle progression from G 1 -to S-phase ( 2 - 4 ). (iiarjournals.org)
Tumor dormancy may contribute to tumor progression and relapse, either locally or metastatically at distant sites, years or decades after treatment. (biomedcentral.com)

In a genome-wide screen for putative tumor suppressor genes, the EBF3 locus on the human chromosome 10q26.3 was found to be deleted or methylated in 73% of the examined cases of brain tumors. (aacrjournals.org)
EBF3 is expressed in normal brain but is silenced in brain tumors. (aacrjournals.org)
The mortality rate for those diagnosed with head and neck cancer (which does not include brain tumors) is high. (lifeextension.com)

EBF3 bound directly to p21 cip1/waf1 promoter and regulated transcription from both p21 cip1/waf1 and p27 kip1 promoters in reporter assays. (aacrjournals.org)
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)
Subcellular localisation of cyclin B, Cdc2 and p21(WAF1/CIP1) in breast cancer. (ox.ac.uk)
The heterodimeric cyclin B/Cdc2 protein kinase governs entry into mitosis, and can be negatively regulated through p53-mediated transcriptional induction of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1). (ox.ac.uk)
Ectopic expression of p21(WAF1/CIP1) in cultured cells has been shown previously to influence the subcellular distribution of the cyclin-dependent kinases (CDKs) including Cdc2. (ox.ac.uk)
In this study, we have examined the subcellular localisation of Cdc2, cyclin B and p21(WAF1/CIP1) by immunohistochemistry in a well characterised series of primary breast cancers. (ox.ac.uk)
cytoplasmic p21(WAF1/CIP1) and high cyclin B levels were also significant predictors of poor prognosis. (ox.ac.uk)
Investigation of the subcellular distribution of cell cycle regulatory proteins, particularly p21(WAF1/CIP1), could provide valuable prognostic markers in breast cancer. (ox.ac.uk)
AKT prevents cell death by inactivating proapoptotic factors including BAD, procaspase-9 and Forkhead transcription factor family proteins (FOXOs), activates transcription factors that upregulate antiapoptotic genes, including NF-kB, inactivates p53 through Mdm2, and phosphorylates the cell cycle inhibitors p21 CIP1/WAF1 and p27 KIP1 , thus increasing cell proliferation (Hennessy et al. (ebrary.net)

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)
The activity of CDKs is controlled by their binding to coactivator subunits termed Cyclins, as well as by CDK inhibitory proteins termed CKIs. (intechopen.com)
The accumulation of both Cyclin and CKI proteins is tightly regulated at the level of transcription. (intechopen.com)
In addition, Cyclin and CKI proteins are controlled at the level of their destruction. (intechopen.com)
Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.com)
The presence of replication stress activates the DNA damage response and downstream checkpoint proteins including ataxia telangiectasia and Rad3 related kinase (ATR), checkpoint kinase 1 (CHK1), and WEE1-like protein kinase (WEE1), which trigger cell cycle arrest while protecting and restoring stalled replication forks. (bmj.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)

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)
TP53 activates the expression of genes involved in apoptosis, cell cycle regulation (p21), and MDM2. (medscape.com)
Diminution of p53 by RNA interference induced necrosis instead of apoptosis in A549 cells following terpinen-4-ol treatment, indicating that terpinen-4-ol-elicited apoptosis is p53-dependent. (hindawi.com)
Recent reports have indicated that terpinen-4-ol exerts its antitumor effects by triggering caspase-dependent apoptosis in human melanoma cells or by inducing necrotic cell death and cell-cycle arrest in mouse mesothelioma and melanoma cell lines without affecting normal cells [ 14 , 15 ]. (hindawi.com)
Our results indicated that terpinen-4-ol induced apoptosis through a mitochondria-mediated pathway in NSCLC cells and that the apoptosis elicited by terpinen-4-ol was p53 dependent. (hindawi.com)
Because of its ability to induce cell growth inhibition and apoptosis in normal and pre-malignant cells, TGFβ has been described as a potent tumor suppressor [ 8 ] [ 9 ] . (encyclopedia.pub)
Dormancy can be induced by more than one mechanism: cellular dormancy (quiescence), angiogenic dormancy (tumor mass size limit), and immunologic dormancy (immunosurveillance, balance between proliferation and apoptosis). (biomedcentral.com)

p21 and other tumor suppressor genes' inactivation are therefore most likely involved in the first steps of the cancer model, with later stages possibly involving protooncogene activation and inflammation. (medscape.com)
These events are dependent on the proper levels of transcription and translation of certain genes. (cancerquest.org)
This first category also includes genes that contribute to tumor growth by inhibiting cell death. (cancerquest.org)
The genes in the second group are called tumor suppressors. (cancerquest.org)
This is in contrast with tumor suppressor genes which must BOTH be defective to lead to abnormal cell division. (cancerquest.org)
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)
Inactivation of tumor suppressor genes, whose products normally provide negative control of cell proliferation, contributes to malignant transformation in various cell types. (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)
For some of the genomic regions that are deleted in some neuroblastomas, on 1p, 3p and 11q, candidate tumor suppressor genes have been identified. (biomedcentral.com)
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)
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)

Cyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs). (biomedcentral.com)
CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs). (biomedcentral.com)
Cyclins function as the positive regulators of CDKs. (biomedcentral.com)
D-type and E-type cyclins assemble with CDKs during the G1 phase and these holoenzymes act as rate-limiting controllers to regulate passage through the restriction point and the subsequent onset of DNA replication [ 2 , 3 ]. (biomedcentral.com)
Cyclins and CDKs assemble into complexes with one another as cells progress through G1 phase, cyclins being required to activate the serine-threonine kinase activity of their catalytic partners. (biomedcentral.com)
Furthermore, CDK-activating kinase (CAK) phosphorylates cyclin-bound CDKs on a single threonine residue, a modification that is essential for their activity [ 6 - 9 ]. (biomedcentral.com)
The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)

also known as CDK4I, Cyclin-dependent kinase 4 inhibitor A, Multiple tumor suppressor 1, MTS-1, p16-INK4, p16-INK4a, p16INK4A) is encoded by the CDKN2A (also known as CDKN2, MTS1) gene (Gene ID 1029) in human. (sigmaaldrich.com)
Tumors that developed in mice deficient in INK4A were enhanced by the topical application of carcinogens and ultraviolet light. (medscape.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)

Altered expression of this gene has been observed in multiple human cancers. (cancerindex.org)
BACKGROUND/AIM: Cancer of unknown primary (CUP), representing 3-5% of all newly diagnosed cancers in the United States, is a presumptive, non-definitive diagnosis rendered when a primary tumor site cannot be identified after exhaustive diagnostic evaluation, including cases of neuroendocrine neoplasms (NENs). (bvsalud.org)
CUPs are characterized by findings that are challenging to reconcile, including inconclusive immunohistochemical (IHC) stains, an undifferentiated morphologic phenotype, history of multiple cancers, a clinical presentation that is discordant from histologic findings, an atypical distribution of metastases, or lack of expected response to treatment. (bvsalud.org)
In addition, numerous monoterpenes have been proposed to exert potent antitumor action, and some have shown promising results in the prevention and treatment of a variety of cancers in tumor model systems [ 5 , 6 ]. (hindawi.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)
Elevated levels of replicative stress in gynecological cancers arising from uncontrolled oncogenic activation, loss of key tumor suppressors, and frequent defects in the DNA repair machinery are an intrinsic vulnerability for therapeutic exploitation. (bmj.com)
This gene exhibits elevated expression levels in multiple human cancers. (cancerindex.org)
Acute leukemias induced by MLL chimeric oncoproteins are among the subset of cancers distinguished by a paradoxical dependence on GSK-3 kinase activity for sustained proliferation. (stanford.edu)

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)

Inactivation of CDKN2A and CDKN2B are found in a wide variety of human malignancies and murine tumor models. (sigmaaldrich.com)
In particular, the p16/cyclin-dependent kinase inhibitor 2A (CDKN2A) gene located on chromosomal region 9p21 frequently is altered in several types of cancer. (iiarjournals.org)
The tumor suppressor gene p16/cyclin-dependent kinase inhibitor-2A (CDKN2A) is located within the chromosomal region 9p21 and encodes a cell-cycle protein that is an inhibitor of cyclin-dependent kinases (CDK)-4 and -6. (iiarjournals.org)

The protein encoded by this gene is a member of the CMGC family of serine/threonine protein kinases. (cancerindex.org)

This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. (cancerindex.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)
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)
CDK4 is a member of the Ser/Thr protein kinase family. (thermofisher.com)

The INK and CIP/KIP families of cyclin dependent kinase inhibitors (CDKis) protect cells from oncogenic signals-initiated cellular transformation. (sigmaaldrich.com)
In this study we tested the expression of CDKIs p15, p16, p21 and p27 by immunohistochemistry to determine the role of CDKIs in the initiation of primordial follicle growth. (biomedcentral.com)
p15, p16, p21 and p27 in mouse ovaries by immunohistochemistry to assess whether the initiation of primordial follicle growth was associated with the expression of CDKIs. (biomedcentral.com)

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)
2005). AKT also phosphorylates and inhibits glycogen synthase kinase-3 (GSK3), thus enhancing p-catenin and cyclin D1 stabilization (Vivanco and Sawyers 2002). (ebrary.net)
2004), and that blockade of PDK1, which acts upstream of AKT, inhibits tumor cell growth (Amornphimoltham et al. (ebrary.net)

Hypoxia and genetic defects that chronically drive proliferation leave such tumors dependent on a steady supply of nutrients, especially glucose. (springer.com)
Three molecular mechanisms involved in tumor dormancy have been identified: cellular dormancy (quiescence or mitotic arrest), angiogenic dormancy (limited tumor size), and immunologic dormancy (immunosurveillance, balance between clearance and proliferation) (Figure 1 ). (biomedcentral.com)
While AKT phosphorylates multiple downstream targets (see above), the emerging picture is that the ability of AKT to coordinate mitogenic and nutrient-sensing pathways controlling protein synthesis is a key mechanism by which AKT regulates cell proliferation. (ebrary.net)
Studies in recent years have demonstrated that long non-coding RNAs (lncRNAs) have multiple biological functions in cell growth, differentiation and proliferation. (oncotarget.com)

Using a p21 immunohistochemistry (IHC) assay, we compared tumor p21 levels with conventional clinico-pathological criteria in primary pancreatic endocrine tumor subsets with and without liver metastases. (bvsalud.org)

However, it remains unknown whether inactivation of EBF3 locus also occurs in other types of tumors and what functions of EBF3 underlie EBF3-mediated tumor suppression. (aacrjournals.org)

PCNA is a co-factor of cyclin-D and it makes a complex with cyclin-D, a cyclin dependent kinase (CDK), and a cyclin dependent kinase inhibitor (CDKI). (biomedcentral.com)

Therefore, EBF3 regulates a transcriptional program underlying a putative tumor suppression pathway. (aacrjournals.org)
However, recent studies have suggested that BRAFi/MEKi and ERK1/2i resistance can arise through activation of a parallel signalling pathway leading to activation of ERK5, an unusual protein kinase that contains both a kinase domain and a transcriptional transactivation domain. (babraham.ac.uk)

Subsequently, mTOR phosphorylates key eukaryotic translation regulators, including p70-S6 kinase (p70S6K) and the eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) (Hay and Sonenberg 2004). (ebrary.net)

However, many patients who exhibit no clinical symptoms after frontline therapy subsequently suffer, often many years later, aggressive tumor recurrence. (biomedcentral.com)
Tumor cell dormancy may help to explain treatment resistance and recurrence or metastatic reactivation. (biomedcentral.com)
Tumor dormancy can lead to tumor recurrence locally or to metastasis at a distant site. (biomedcentral.com)
6-7 Many of these lethal side effects, plus recurrence of the original tumor, can happen after the "five-year survival" milestone has been achieved. (lifeextension.com)

This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). (thermofisher.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)

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)

The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (prospecbio.com)

DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)
The phosphatidyl inositol 3-kinase (PI3K)/Akt pathway was involved in this ubiquitin-proteasome-mediated degradation of PDCD4. (plos.org)
Defects of the retinoblastoma protein (pRb)/cyclin-D1/p16 pathway have been shown to play a critical role in the development of human malignancies. (iiarjournals.org)
This pathway involves the sequential activation of Phosphoinositide 3-kinase (PI3K), AKT, and mTOR. (ebrary.net)

Neuroblastoma is one of the most common solid tumors of childhood, arising from immature sympathetic nervous system cells. (biomedcentral.com)
The meeting was attended by ∼70 investigators and included formal presentations, panel group discussions, and two breakout sessions that addressed targeted therapies in hematologic and solid tumors. (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)
Active TGFβ induces the heteromeric complex formation of two single transmembrane serine/threonine kinase family receptors, i.e. (encyclopedia.pub)

In this short review, we summarize recent experimental and clinical evidence for these three mechanisms and other possible tumor microenvironment mechanisms that may influence tumor dormancy. (biomedcentral.com)
A tumor microenvironment that is altered (such as by frontline treatment) can mediate tumor cell entrance into, maintenance, and exit from dormancy through interaction with cells at niches, such as endothelial cells, stroma, or immune cells. (biomedcentral.com)

Prostate cancer is the most common malignant tumor in male adults in the Western world, which represents a major cause of cancer-related morbidity and mortality. (compassionateacupuncture.com)
Normal oral keratinocytes are transformed into precancerous lesions through various signaling pathways, which further deteriorate into malignant tumors. (biomedcentral.com)

Cyclin E forms complexes during this interval with CDK2. (biomedcentral.com)

A useful analogy to consider when thinking about tumor suppressors and oncogenes is an automobile. (cancerquest.org)
The first miRNA was discovered in 1993 by Lee, Freinbaum and Ambros ( 6 , 7 ), and since then an increasing load of literature data have pointed that they can act as both tumor suppressors and oncogenes ( 1 - 3 ). (frontiersin.org)

Activation of p21 or p16 therefore causes cell cycle arrest. (medscape.com)

Moreover, the identification of fork protection as a key mechanism of resistance to chemo- and poly (ADP-ribose) polymerase inhibitor therapy in ovarian cancer further increases the priority that should be accorded to the development of strategies targeting replicative stress. (bmj.com)
The aim of the present study was to determine the significance of this tumor suppressor gene for ovarian tumorigenesis, investigating both numerical aberrations of chromosome 9 and p16 gene alterations in 28 cases of ovarian tumors, by the fluorescence in situ hybridization (FISH) technique. (iiarjournals.org)

For a significant subset of NENs (10%), traditional diagnostic evaluation is unable to determine a primary tumor site using histomorphology and IHC stains. (bvsalud.org)
NB tumors are divided into different stages according to the localization and extension of the primary tumor and the absence or presence of distant metastases. (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)

2006). In turn AKT plays a key role in the transmission of pro-proliferative and transforming pathways initiated by EGFR and multiple growth factor receptors, as well as by oncogenic active PI3K mutants (Luo et al. (ebrary.net)

Silencing of the EBF3 locus was observed in brain, colorectal, breast, liver, and bone tumor cell lines and its reactivation was achieved on treatment with 5-aza-2′-deoxycytidine and trichostatin A in a significant portion of these tumor cells. (aacrjournals.org)
Previous studies have identified that UBE3A exhibits abnormal expression in numerous tumor cells, including prostate, cervical and breast cancer ( 6 , 7 ). (spandidos-publications.com)

[ 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)

This gene encodes a potent cyclin-dependent kinase inhibitor. (nih.gov)

Metastatic tumors (stage M) have a dismal prognosis, whereas patients with locoregional tumors (L1 and L2) usually have an excellent outcome. (biomedcentral.com)

The synthesis of another G1 phase cyclin, cyclin E, increases in late G1 and decreases once DNA replication is initiated. (biomedcentral.com)
Replication of DNA is initiated at multiple sites along the genome, known as replication origins, which form bidirectional replication forks. (bmj.com)
Fitness assays revealed that both women were infected with replication competent viruses, and both expressed higher mRNA levels of p21 , a host restriction factor associated with viral control. (biomedcentral.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)
Increasing evidence indicates that senescent cells could be a promising new target for therapeutic intervention known as senotherapy, which includes depleting senescent cells, modulating SASP and restoration of senescence inhibitors. (frontiersin.org)
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)
Expression of p15, p16, p21 and p27 did not vary in granulosa and theca cells by the follicle stage. (biomedcentral.com)
D-type cyclins are usually synthesized by mid-G1 phase and accumulate to a maximum as cells advance through the G1/S boundary. (biomedcentral.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)
Furthermore, treatment of s.c xenografts derived from A549 cells with intratumor injections of terpinen-4-ol significantly inhibited tumor growth compared with the control group. (hindawi.com)
En face co-immunostaining of the mouse aortic arch revealed a low level of PDCD4 in endothelial cells undergoing pulsatile shear stress. (plos.org)
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 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)
5) increasing the intrinsic radioresistance of normal cells through ketone bodies but decreasing that of tumor cells by targeting glycolysis. (springer.com)
Understanding the dormant stage of tumor cells may help in discovering ways to maintain the dormant state or permanently eliminate dormant residual disseminated tumor cells. (biomedcentral.com)
Tumor dormancy is a recognized clinical phenomenon in which disseminated tumor cells (DTCs) remain occult, asymptomatic, and undetectable over a prolonged period of time. (biomedcentral.com)
Dormancy can occur at the earliest stage of tumor development but also when remnant tumor cells escape treatment. (biomedcentral.com)
Quiescent normal adult stem cells serve as a source of self-renewal in the maintenance of multiple adult epithelial tissues. (biomedcentral.com)
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)
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)
Despite this, clinical responses are typically transient as tumour cells develop resistance. (babraham.ac.uk)

Since the discovery of Polo kinase in Drosophila in 1988 [ 1 ], the Polo-like kinase (Plk) family has been attracting enormous attention, both in academia and in pharmaceutical industry. (oncotarget.com)

However, curcumin, a highly pleiotropic molecule with an excellent safety profile targeting multiple diseases with strong evidence on the molecular level, could not achieve its optimum therapeutic outcome in past clinical trials, largely due to its low solubility and poor bioavailability. (blogspot.com)
Immunostimulatory cytokines can enhance anti-tumor immunity and are part of the therapeutic armamentarium for cancer treatment. (weeksmd.com)
We review the possible roles for calorie restriction (CR) and very low carbohydrate ketogenic diets (KDs) in modulating the five R's of radiotherapy to improve the therapeutic window between tumor control and normal tissue complication probability. (springer.com)
This may be relevant to the suggestion of kinase-independent effects of ERK1/2 and the therapeutic use of ERKi. (babraham.ac.uk)

Small molecule inhibitors designed to target the DNA damage sensors, such as inhibitors of ataxia telangiectasia-mutated (ATM), ATR, CHK1 and WEE1, impair smooth cell cycle modulation and disrupt efficient DNA repair, or a combination of the above, have demonstrated interesting monotherapy and combinatorial activity, including the potential to reverse drug resistance and have entered developmental pipelines. (bmj.com)
Phosphoproteomic techniques have been widely employed to identify kinase activity, which may lend itself to pharmaceutical blockade. (nature.com)
NK activation was evaluated, and its tumoricidal activity was assessed using in vitro and in vivo tumor models. (weeksmd.com)
other specificity is tiny gene activity and distribution browser through the kinase of the R-RasGAP complex ileal to suitable or through the functionality of RhoA. (evakoch.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)

and Fisher's exact test was used to compare the association among tumor p21 scores, conventional prognostic criteria, and liver metastases. (bvsalud.org)

Multiple E2F-induced microRNAs prevent replicative stress in response to mitogenic signaling. (virosin.org)

Anatomy11

Organisms5

Diseases16

Chemicals and Drugs98

Analytical, Diagnostic and Therapeutic Techniques and Equipment14

Phenomena and Processes49

Disciplines and Occupations1

Information Science3

Expression of cyclin-dependent kinase3

Progression15

Brain tumors3

Cip19

Proteins9

Apoptosis10

Genes12

CDKs7

INK4A3

Cancers8

Important tumor suppressor1

Including D-type cyclins1

CDKN2A3

Protein kinases1

CDK45

CDKIs3

Inhibits3

Proliferation4

Immunohistochemistry1

Types of tumors1

CDKI1

Transcriptional2

Phosphorylates1

Recurrence4

Phosphorylation2

Metastasis1

Inhibit1

Pathway4

Solid tumors2

Serine2

Microenvironment2

Malignant2

Complexes1

Oncogenes2

Arrest1

Ovarian2

Primary tumor2

Poor prognosis1

Oncogenic1

Breast2

Retinoblastoma protein1

Potent1

Prognosis1

Replication3

Cells19

Drosophila1

Therapeutic4

Activity4

Tumorigenesis1

Prognostic1

Replicative stress1