China
Africa
Explore chapters and articles related to this topic
Urological Anti-cancer Agents
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Bernadett Szabados, Thomas Powles
Interphase = cell growth.G1 phase (Post mitotic gap phase). The cell growth begins after mitosis, with the production of cytoplasm and extra organelles.S phase = DNA replication.G2 phase = preparation for mitosis; production of microtubules.M Phase (Mitotic phase) = active cell division.
Assessment of Airway Smooth Muscle Growth and Division: In Vitro Studies
Published in Alastair G. Stewart, AIRWAY WALL REMODELLING in ASTHMA, 2020
These techniques rely on the cellular uptake and nuclear incorporation of radiolabelled DNA-precursor nucleotides such as tritiated (3H-)thymidine into newly synthesised DNA during S phase of the cell cycle, although the advent of bromodeoxyuridine (BrdU) labelling and its detection by monoclonal antibodies has also allowed the study of S phase by non-radiolabelling techniques. Typically, S phase lasts 6–12 h in mammalian cells, and mitosis is complete within 60 min. The short duration of mitosis as an index of proliferation is, therefore, intrinsically less sensitive than S phase, since the fraction of the cell population which can be detected in mitosis is much smaller than it is in S phase. For this reason, methods such as thymidine and BrdU labelling have continued to be erroneously employed as indices of cell division, when instead their more correct use is as S or G2 phase markers. These and other limitations are discussed below.
Alteration in Cell Cycle Control Factors and the Induction of Oxygen-Regulated Proteins by Hypoxic Stress
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
Harold C. Smith, Robert L. Howell, John W. Ludlow
If this speculation is true, then what constitutes a “memory” of where the cell was within the cell cycle before hypoxia? Upon reperfusion, do the S phase cells resume DNA synthesis from the 2n+ DNA content point, or do they commence from the Gl/S phase gate? In other words, does the loss of pRB and cyclin A control perturb the order of chromosomal replication? These questions may be most relevant in tissues that experience periodic acute hypoxia where repurfusion would intermittently reactivate DNA replication. Hypoxia has been shown to induce DNA amplification in experimental settings,6,9 and enzymes involved in the topological management of chromosomes are severely inhibited by hypoxia.54 In solid tumors, periodic or long-term vascular collapse is of concern due to the ability of ischemia to establish therapeutically resistant cell populations.5,29,30,55 DNA analyses of chromosome stability relative to solid tumor mass and neoplastic progression suggest a high degree of chromosomal amplification, loss, and/or mutation.56–58 Many of these alterations may be related to an ever-increasing population of cells in the hypoxic fraction of the tumor. Moreover, it is a common observation that an increasing number of cells acquire a DNA content typical of S phase cells or greater during tumor growth and progression. It is not clear whether all of these cells are actual carrying out active replicating DNA. Some may have stalled in S phase due to hypoxia or have an aneuploid G1 chromosome content.
Design, synthesis, docking, and anticancer evaluations of new thiazolo[3,2-a] pyrimidines as topoisomerase II inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Mona S. El-Zoghbi, Samiha A. El-Sebaey, Hanan A. AL-Ghulikah, Eman A. Sobh
The cell cycle is required for cell division and replication. The cell cycle was divided into four distinct phases: G1 phase (synthesis), S phase (synthesis), G2 phase (interphase), and M phase (mitosis). The G1 phase, also known as the post-mitotic pre-synthesis phase, is distinguished by direct cell division. DNA replication identifies the S phase. The G2 phase, premitotic, or post-synthetic phase, which can be considered the actual division, is when the cell prepares to split into two cells. Finally, the doubled DNA organised in chromosomes is separated during the M- or mitosis-phase division25. Many anticancer drugs cause apoptosis, cell cycle arrest, or a combination of both as part of their cytotoxic action52. As a result, it was worth investigating whether cell cycle arrest was involved in the cytotoxicity mechanism of the most active cytotoxic agent 4c on A549 cells using flow cytometry analysis, and the results were demonstrated in Table 4 and Figure 7. The results revealed a 69.07% increase in cell count at the G0-G1 phase, compared to 56.39% for control cells. While the percentage of cells in the S phase was reduced by 26.89% compared to the control (29.64%). On the other hand, a dramatic fall in the cell population in the G2/M phase was observed upon treatment with compound 4c from 13.97 to 4.04%. As a result, compound 4c was demonstrated to significantly disrupt the cell cycle profile and cause cell cycle arrest.
Expanding roles of cell cycle checkpoint inhibitors in radiation oncology
Published in International Journal of Radiation Biology, 2023
Sissel Hauge, Adrian Eek Mariampillai, Gro Elise Rødland, Lilli T. E. Bay, Helga B. Landsverk, Randi G. Syljuåsen
Upon irradiation, cells typically show a transient slowdown of DNA replication. This is termed the S phase checkpoint and is mainly due to a global suppression of DNA replication initiation. WEE1, ATR and CHK1 are all required for the radiation-induced S phase checkpoint (Sørensen et al. 2003; Beck et al. 2012). ATR and CHK1 are activated after irradiation as described above, and CHK1 then phosphorylates CDC25A, causing CDC25A degradation (Sørensen et al. 2003) and thus leading to reduced CDK1 and CDK2 activity. Since loading of the replication initiation factor CDC45 depends on CDK activity, the suppression of CDK activity results in less loading of CDC45 and thus inhibition of origin firing after irradiation. In addition, CHK1 may also restrain CDC45 loading by CDK-independent mechanisms (Hauge et al. 2017), e.g., via suppression of the replication factor Treslin (Guo et al. 2015). Notably, although ATR/CHK1 signaling restrains origin firing globally, dormant origins nearby stalled replication forks may be fired to ensure completion of replication between the stalled forks (Ge and Blow 2010; Yekezare et al. 2013). WEE1 is active in interphase and is most likely not further activated by radiation, as described above. Anyway, WEE1 inhibitors will lead to less Y15 phosphorylation on CDK1 and CDK2 in irradiated cells, and therefore cause abrogation of the S phase checkpoint.
An overview of potential novel mechanisms of action underlying Tumor Treating Fields-induced cancer cell death and their clinical implications
Published in International Journal of Radiation Biology, 2021
Narasimha Kumar Karanam, Michael D. Story
Genome instability due to defects in the DNA damage response (DDR) is another hallmark of cancer. Exogenous and endogenous factors cause constant stress to the mammalian genome, and the failure of protective mechanisms leads to genomic instability. Faults in the DNA replication process during S phase leads to mutations or DNA replication blockage that in turn leads to DNA damage. This effect slows DNA synthesis and/or causes replication fork stalling/collapse is called replication stress. Many commonly used cancer chemotherapeutic agents target replication stress, which is thought to be the primary cause of genome instability (Gaillard et al. 2015). Cancer cells maintain unrestrained proliferation by keeping low to mild levels of replication stress with defective DDR and loss of cell cycle checkpoints. Normal cells maintain genome stability through the coordinated actions of DDR and cell cycle checkpoints. Defects in DDR and mild to low levels of replication stress are unique to cancer cells (Zhang et al. 2016) and, therefore, can be therapeutically exploited.