• M2 is characterized by many 'uncapped' chromosome ends, end-fusions, chromosome breakage fusion-bridge cycles, mitotic catastrophe and a high fraction of apoptotic cells. (elsevierpure.com)
  • PIG3 knockdown led to an abnormal DNA damage response, including decreased IR-induced phosphorylation of H2AX, Chk1, Chk2 and Kap-1 as well as a prolonged G2-M arrest and aberrant mitotic progression. (ijbs.com)
  • Chromosome association of minichromosome maintenance proteins in Drosophila mitotic cycles. (colorado.edu)
  • The G 2 checkpoint bars entry into the mitotic phase if certain conditions are not met. (openstax.org)
  • Cell proliferation includes a series of events that is tightly regulated by several checkpoints and layers of control mechanisms. (frontiersin.org)
  • BRCA2 gene expression is tightly regulated during the cell cycle in human breast cells. (biomedcentral.com)
  • Specifically, the boundary between G1 and S-phase is tightly regulated by the ubiquitin proteasome system. (intechopen.com)
  • The accumulation of both Cyclin and CKI proteins is tightly regulated at the level of transcription. (intechopen.com)
  • While BRCA2 expression is involved in cell cycle checkpoints and DNA repair, the mechanisms of cell cycle-dependent regulation of BRCA2 gene expression remains elusive. (biomedcentral.com)
  • In our recent study we found that circadian clock genes play a role in regulation of the hair growth cycle during synchronized hair follicle cycling, uncovering an unexpected connection between these two timing systems within skin. (aging-us.com)
  • Western Blotting was used to determine the level of expression of CDC2 protein as measure to quantify down regulation of CDC2 expression along with use of flow cytometry to investigate effect of shRNAs on cell cycles and detection of apoptosis. (biomedcentral.com)
  • Abnormalities in cell cycle regulation are reported to be strongly associated with tumorigenesis and progression of tumors. (biomedcentral.com)
  • Furthermore, poorer prognosis in cancer patients who display a glycolytic phenotype characterized by metabolic alterations, such as obesity and diabetes, is now well established, providing another link between metabolic pathways and cancer progression. (springer.com)
  • In the absence of cell-cycle checkpoint pathways (e.g. p53 and or p16/Rb), cells bypass M1 senescence and telomeres continue to shorten eventually resulting in crisis (also called the M2 stage). (elsevierpure.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)
  • Here, we used quantitative real-time PCR, profiling the expression of 93 genes in single-cells from three different cell lines. (frontiersin.org)
  • We found that the total transcript level per cell and the expression of most individual genes correlated with progression through the cell cycle, but not with cell size. (frontiersin.org)
  • Detailed analysis of cell cycle predictive genes allowed us to define subpopulations with distinct gene expression profiles and to calculate a cell cycle index that illustrates the transition of cells between cell cycle phases. (frontiersin.org)
  • In conclusion, we provide useful experimental approaches and bioinformatics to identify informative and predictive genes at the single-cell level, which opens up new means to describe and understand cell proliferation and subpopulation dynamics. (frontiersin.org)
  • Here, we employed single-cell gene expression profiling to describe the dynamic transition between cell proliferative states in three different cell lines using a panel consisting of 93 marker genes. (frontiersin.org)
  • Geyfman M , Andersen B , . Clock genes, hair growth and aging. (aging-us.com)
  • Interestingly, a large fraction of the genome, more than six thousand genes, exhibits changes in expression that correlates with the progression of the hair growth cycle, thus underscoring the complexity of this process [ 4 , 5 ]. (aging-us.com)
  • One of the surprises that came from this study was the finding that genes regulated by the core circadian clock mechanism showed expression changes that correlated with the hair growth cycle, with highest expression during the telogen-anagen transition. (aging-us.com)
  • REV-ERBĪ± regulates transcription of Bmal1 and other target genes by binding to retinoic acid-related orphan receptor response elements (ROREs) [ 8 ]. (aging-us.com)
  • While these genes show a clear circadian pattern of expression in skin, as was previously demonstrated [ 9 - 11 ], their amplitude was higher during telogen and early anagen (Figure 1 ), indicating that in skin, the expression of clock controlled genes is dependent both on circadian mechanism and the hair growth cycle. (aging-us.com)
  • The cell cycle is a complex process with myriad genes involved and elaborate and complex signaling mechanisms to allow for this critical cellular process. (biomedcentral.com)
  • The former include hypoxia, high lactate levels or the abundance of growth factors within the cellular microenvironment. (springer.com)
  • The notion could be that unique cellular mechanisms are triggered in the breast cancer cells to stimulate BRCA2 gene expression as a temporary measure to regulate the growth of the breast cancer cells. (biomedcentral.com)
  • There is accumulating evidence that when only a few telomeres are short, they form end-associations, leading to a DNA damage signal resulting in replicative senescence (a cellular growth arrest, also called the M1 stage). (elsevierpure.com)
  • In a rare M2 cell, telomerase (a cellular reverse transcriptase) can be reactivated or up-regulated, resulting in indefinite cell proliferation. (elsevierpure.com)
  • Aging kidney and CKD share many common characteristic features with increased cellular senescence, a conserved program characterized by an irreversible cell cycle arrest with altered transcriptome and secretome. (frontiersin.org)
  • Cellular senescence is characterized by an irreversible and permanent cell cycle arrest coupled with altered transcriptome and secretome. (frontiersin.org)
  • Work across many laboratories is geared toward elucidating the genetics behind cancer, discovering cellular mechanisms that lead to cancer, and elucidating intracellular and intercellular interactions that allow this progression. (medscape.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)
  • Retroviral vectors expressing short hairpin RNAs (shRNAs) against CDC2 caused efficient deletion of CDC2, cellular G2/M arrest concluding in apoptosis and inhibition of proliferation in human glioma cells U251 and SHG-44 cell lines ex vivo. (biomedcentral.com)
  • Proper chromosome duplication is assessed at the G 2 checkpoint. (openstax.org)
  • Unlike apoptosis, senescence is a state of which cells are still alive and metabolically active. (frontiersin.org)
  • Beginning after completion of hair morphogenesis (postnatal day 14 in the mouse), hair growth cycles commence with catagen, an involution process of the hair follicle during which the majority of its epithelial compartments undergo apoptosis [ 1 ]. (aging-us.com)
  • Knockdown of KDM1B inhibits cell proliferation and induces apoptosis of pancreatic cancer cells. (cancerindex.org)
  • In some p53 mutants, induction of cell cycle arrest, but not apoptosis was found to be associated with a lack of induction of PIG3 expression ( 2 ). (ijbs.com)
  • Silencing of the transcription factor hCAS/CSE1L, which regulated PIG3 expression, led to decreased PIG3 transcription and concurrently decreased apoptosis ( 3 ). (ijbs.com)
  • Additionally, PIG3 mediates cancer cell death through the GPx3 pathway, and knocking down PIG3 or blocking the interaction between PIG3 and GPx3 would abolish the increase in ROS and apoptosis ( 5 ). (ijbs.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)
  • Background Renal cell carcinomas (CCR) account for 90% of renal tumors. (irjs.info)
  • Background Renal cell carcinomas (CCR) account for 1%C3% of all malignant visceral neoplasms and 90% of renal tumors. (irjs.info)
  • PIG3 is highly homologous to NADPH oxidoreductase TED2 in plants and zeta-Crystalline in mammalian cells, and is considered as a proapoptosis marker. (ijbs.com)
  • When fast-dividing mammalian cells are grown in culture (outside the body under optimal growing conditions), the length of the cycle is about 24 hours. (openstax.org)
  • While studying the activity of BRCA2 gene promoter in breast cancer cells, we discovered that this promoter has bi-directional activity and the product of the reverse activity (a ZAR1-like protein, we named ZAR2) silences the forward promoter at the G0/G1 phase of the cell. (biomedcentral.com)
  • Standard techniques like cell synchronization by serum starvation, flow cytometry, N-terminal or C-terminal FLAG epitope-tagged protein expression, immunofluorescence confocal microscopy, dual luciferase assay for promoter evaluation, and chromatin immunoprecipitation assay were employed during this study. (biomedcentral.com)
  • Binding of this protein to CXCR3 results in pleiotropic effects, including stimulation of monocytes, natural killer and T-cell migration, and modulation of adhesion molecule expression. (cancerindex.org)
  • However, a compensatory feedback of increased mRNA expression of DNA-PKcs was formed in PIG3-depleted cells after a few passages or cell cycles of subculture, which led the recovery of the DNA-PKcs protein level and the consequent recovered efficiency of the DNA damage response. (ijbs.com)
  • As at the G 1 checkpoint, cell size and protein reserves are assessed. (openstax.org)
  • Both the initiation and inhibition of cell division are triggered by events external to the cell when it is about to begin the replication process. (openstax.org)
  • Tumor specimens were obtained with informed consent from a 37-year-old female patient who underwent initial surgical removal in January 1999 and subsequent recurrent resections of a right temporal tumor July 1999 and February 2001 at the 2nd Affiliated Hospital of Soochow University (Suzhou, China) and did not receive chemotherapy and radiation between these stages of progression. (biomedcentral.com)
  • In the present study, the potential mechanism of PIG3 participation in the DNA damage response induced by ionizing radiation (IR) was investigated in multiple cell lines with depleted expression of PIG3 transiently or stably by the small interference RNA and lentivirus-mediated shRNA expression strategies. (ijbs.com)
  • The DNA double-strand break (DSB) is considered to be the most severe type of DNA damage induced by ionizing radiation, and this form of DNA damage must be repaired immediately to prevent cell death. (ijbs.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)
  • [ 6 ] These events lead the cancer cell to escape normal cell growth and control mechanisms, to avoid system control mechanisms (ie, immunologic surveillance), and to establish a nutrient supply. (medscape.com)
  • The timing of events in the cell cycle is controlled by mechanisms that are both internal and external to the cell. (openstax.org)
  • If the checkpoint mechanisms detect problems with the DNA, the cell cycle is halted, and the cell attempts to either complete DNA replication or repair the damaged DNA. (openstax.org)
  • 5) increasing the intrinsic radioresistance of normal cells through ketone bodies but decreasing that of tumor cells by targeting glycolysis. (springer.com)
  • AZD6738 biological activity RCC, renal cell carcinomas strong class="kwd-title" Keywords: Gallblader tumor, Renal cell carcinomas, Latente metastasis, Case report 1. (irjs.info)
  • While developmental senescence and acute senescence may positively contribute to the fine-tuning of embryogenesis and injury repair, chronic senescence, when unresolved promptly, plays a crucial role in kidney fibrogenesis and CKD progression. (frontiersin.org)
  • Senescent cells elicit their fibrogenic actions primarily by secreting an assortment of inflammatory and profibrotic factors known as the senescence-associated secretory phenotype (SASP). (frontiersin.org)
  • 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)
  • One potential mechanism of BRCA2 involvement in breast cancer progression may be through deregulation of the BRCA2 gene expression. (biomedcentral.com)
  • In this perspective we will present our views on the evidence for telomere dysfunction in aging and in cancer progression. (elsevierpure.com)
  • In turn, as a result of research into the abnormal cancer cell, the basic understanding of the cell has greatly improved. (medscape.com)
  • Cancer is characterized by uncontrolled growth and division of a cell, with extension beyond the normally limiting basement membrane and through the boundaries of normal cells. (medscape.com)
  • In head and neck cancer, the histologic progression of severity from hyperplasia, dysplasia, and carcinoma in situ to invasion provides a framework to understand the genetic progression of cancer. (medscape.com)
  • Clear Cell (CC) RCC is the most common type of renal cancer, accounting for 75% of all primary kidney tumours [1]. (irjs.info)
  • In order to systematically discover transcriptional activity associated with the hair growth cycle, we profiled mRNA expression at a genome-wide level over multiple time points corresponding to morphogenesis and two synchronized hair growth cycles. (aging-us.com)
  • Subcellular location of ZAR2 and its expression from the reverse promoter of the BRCA2 gene are stringently regulated in a cell cycle dependent manner. (biomedcentral.com)
  • Progression through the cell cycle is driven by the oscillating activity of Cyclin Dependent Kinases (CDKs). (intechopen.com)
  • In the G0/G1 growth phase ZAR2 is predominantly located inside the nucleus of the breast cells, binds to the BRCA2 promoter and inhibits the expression of BRCA2. (biomedcentral.com)
  • PIG3 knockdown can suppress intra-S phase and G2/M checkpoints ( 8 ). (ijbs.com)
  • Individual unsynchronized cells from three different cell lines were collected in different cell cycle phases (G0/G1 - S - G2/M) with variable cell sizes. (frontiersin.org)
  • This, in turn, creates a clonal population of a single abnormal cell. (medscape.com)
  • Mistakes in the duplication or distribution of the chromosomes lead to mutations that may be passed forward to every new cell produced from an abnormal cell. (openstax.org)
  • Telomeres progressively shorten in almost all dividing cells and most human cells do not express or maintain sufficient telomerase activity to fully maintain telomeres. (elsevierpure.com)
  • But as the mouse ages, the hair growth cycles become progressively less synchronized [ 3 ]. (aging-us.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)
  • The integrity of the DNA is assessed at the G 1 checkpoint. (openstax.org)
  • ZAR2 binds to BRCA2/ZAR2 bi-directional promoter in vivo and is responsible, at least in part, for the silencing of BRCA2 gene expression in the G0/G1 phase in human breast cells. (biomedcentral.com)
  • Retroviral vectors expressing short hairpin RNAs (shRNAs) targeted against CDC2 were designed and transducted into human glioma cell line ex vivo in order to downregulate the expression of CDC2. (biomedcentral.com)
  • To reveal the roles of CDC2/Cyclin B1 in human malignant gliomas, CDC2 in glioma cell line, it was down-regulated by retrovirus vectors expressing short hairpin RNAs (shRNAs) ex vivo and in vivo. (biomedcentral.com)
  • In humans, the frequency of cell turnover ranges from a few hours in early embryonic development, to an average of two to five days for epithelial cells, and to an entire human lifetime spent in G 0 by specialized cells, such as cortical neurons or cardiac muscle cells. (openstax.org)
  • These remedies at best only slow, but not completely halt, CKD progression, and they are often ineffective and possess adverse side effects. (frontiersin.org)
  • The cell can halt the cycle and attempt to remedy the problematic condition, or the cell can advance into G 0 and await further signals when conditions improve. (openstax.org)
  • The molecular processes behind cell cycle progression have been dissected by numerous morphological studies on live or fixed single cells using a plethora of techniques to visualize components and processes during cell division. (frontiersin.org)
  • Specifically, the concepts of tumour heterogeneity, oncogene addiction, non-oncogene addiction, tumour initiating cells, tumour microenvironment, non-coding sequences and DNA damage response will be reviewed. (bmj.com)
  • 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)
  • Most studies have been performed on large cell populations, but detailed understanding of cell dynamics and heterogeneity requires single-cell analysis. (frontiersin.org)
  • 2.?Case demonstration Male individual, 74 years of age, 9 years correct videolaparoscopic radical nephrectomy for quality 2 clear-cell adenocarcinoma post, T3BN0M0 (not put through systemic chemotherapy), during annual starting point on personal practice setting, it had been found out a gallbladder polyp with 0.7? (irjs.info)
  • By applying the random forests algorithm, a supervised machine learning approach, we show how a multi-gene signature that classifies individual cells into their correct cell cycle phase and cell size can be generated. (frontiersin.org)
  • The expression of BRCA2 gene is silenced at the G0/G1 phase of cell growth and is de-silenced at the S/G2 phase. (biomedcentral.com)
  • this growth phase is referred to as anagen [ 2 ]. (aging-us.com)
  • In eukaryotes, the entry into mitosis is regulated by the activation of CDC2/Cyclin B1 complex (M-phase promoting factor, MPF). (biomedcentral.com)
  • There is also variation in the time that a cell spends in each phase of the cell cycle. (openstax.org)
  • In rapidly dividing human cells with a 24-hour cell cycle, the G 1 phase lasts approximately nine hours, the S phase lasts 10 hours, the G 2 phase lasts about four and one-half hours, and the M phase lasts approximately one-half hour. (openstax.org)
  • Moving forward from this initiation point, every parameter required during each cell cycle phase must be met or the cycle cannot progress. (openstax.org)
  • A cell that does not meet all the requirements will not be allowed to progress into the S phase. (openstax.org)
  • Because of its mutated aggressive genetics, this cell has a selective growth advantage over its neighbors. (medscape.com)
  • The anatomopathological study of CDX4 the gallbladder was appropriate for infiltrating metastasis from clear-cell carcinoma of principal renal site. (irjs.info)
  • This technologic and biologic revolution continued through the 1960s to today, and the explosion in technology has fueled the current expansion of knowledge into the working of the human cell. (medscape.com)
  • An event may be as simple as the death of a nearby cell or as sweeping as the release of growth-promoting hormones, such as human growth hormone (HGH). (openstax.org)
  • These checkpoints occur near the end of G 1 , at the G 2 /M transition, and during metaphase ( Figure 10.10 ). (openstax.org)
  • Whatever the source of the message, the cell receives the signal, and a series of events within the cell allows it to proceed into interphase. (openstax.org)
  • This promoter is 8-20 fold more active in the reverse orientation than in the forward orientation when the cells are in the non-dividing stage (G0/G1). (biomedcentral.com)
  • In mice, the two initial hair growth cycles are synchronized such that the majority of hair follicles are in a similar stage of the hair growth cycle at a given time. (aging-us.com)
  • The mutations of BRCA2 gene predispose the cells towards neoplastic development. (biomedcentral.com)
  • Such data are only indirectly related to quantitative changes in cells at different states of division and growth. (frontiersin.org)
  • The G 1 checkpoint determines whether all conditions are favorable for cell division to proceed. (openstax.org)
  • The G 1 checkpoint, also called the restriction point (in yeast), is a point at which the cell irreversibly commits to the cell division process. (openstax.org)
  • During cell growth and proliferation, ubiquitin plays an outsized role in promoting progression through the cell cycle. (intechopen.com)
  • External influences, such as growth factors, play a large role in carrying the cell past the G 1 checkpoint. (openstax.org)