Tumour growth and response to radiation
Michael C. Joiner, Albert J. van der Kogel in Basic Clinical Radiobiology, 2018
The net growth rate, or the VDT, of tumours results from the balance of cell production and cell loss. Cell production is determined by the proportion of cells in the compartment of actively dividing cells (growth fraction [GF]) and the time required to complete the cell cycle (cell-cycle time, TC). Cells from the GF compartment move through the cell cycle and are distinguished from cells outside the cell cycle. Cells outside the cell cycle (in G0 phase) may enter the cell cycle (recruitment of temporarily resting cells) or remain permanently in the G0 phase (sterile or differentiated cells). Taking these parameters together, tumours grow fast if the GF is high, the cell-cycle time is short or the cell loss is low.
The Mechanisms Behind Tumour Repopulation
Loredana G. Marcu, Iuliana Toma-Dasu, Alexandru Dasu, Claes Mercke in Radiotherapy and Clinical Radiobiology of Head and Neck Cancer, 2018
It was shown that both stem and differentiated cells can reside in the G0 phase, thus being capable of re-entering the cell cycle when stimulated (Cheung & Rando 2013). However, as far as tumour repopulation is concerned, due to their limited proliferative ability, differentiated cells will not contribute to regrowth, whereas CSCs will. More research is needed to quantify the proportion of quiescent CSCs that can potentially interfere with tumour control in HNC patients.
Genetic and Biological Alterations in Cancer
Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George in The Scientific Basis of Urology, 2010
The normal cell cycle consists of mitosis (nuclear and cytoplasmic division), G1 (First growth phase), S (DNA synthesis and chromosome replication) and G2 (second growth phase). When the cell is quiescent it is said to enter the G0 phase (out of the cell cycle). This process is controlled by cyclins in complex with cyclin-dependent kinases (CDK) as well as other proteins, which regulates the progression through the cell cycle. The retinoblastoma protein (Rb) functions as an inhibitor of cell cycling by blocking progression into the S phase. Its normal function is to prevent replication of damaged DNA. Loss of Rb therefore results in increased progression through the cell cycle. In bladder cancer Rb deletions or mutations have been detected in up to 30% of muscle invasive tumors (8). In prostate cancer loss of Rb has been suggested as an independent predictor of disease specific survival (54). Other studies have suggested that levels of Cyclin D1 (which phosphorylates and reduces Rb activity) are also expressed at higher levels in prostate cancer (60). p53 is a well-characterized tumor suppressor and has many known functions including DNA repair, initiating apoptosis after DNA damage and cell cycle progression. Its function in regulating the cell cycle is achieved through transcriptional regulation of p21 (also known as CDK inhibitor 1A). p21 inhibits cell cycling by forming a complex with CDK 2 and preventing progression into the S phase of the cycle. Mutations in the p53 gene results in increased expression of a non-functional protein. As a result of this there is reduced p21 expression and increased progression through the cell cycle. In bladder cancer high levels of p53 have been positively correlated with a poorer disease specific outcome for muscle invasive disease (8). p21 loss has also been reported as a frequent finding in aggressive bladder cancers (61). Tumors with a coordinated dysregulation of different cell cycle regulators (such as combined loss of p53 and Rb) seem to exhibit even poorer survival outcomes (62, 63).
Clinical efficacy and mechanism for focused ultrasound (FUS) in the management of cervical intraepithelial neoplasia 1 (CIN1)
Published in International Journal of Hyperthermia, 2020
Zhenhua Fu, Yijin Fan, Can Wu, Ping Yan, Yibi Ye, Huan Yang, Chengzhi Li
Ki-67, also known as a cell proliferation index, is a nuclear antigen expressed in proliferating cells. It is synthesized in the G1, S, G2 and M phases of cell proliferation cycle. It was not expressed in G0 phase and its half-life is short, which could accurately reflect the activity of cell proliferation. Bean confirmed [22] that the positive rate of Ki-67 expression increased gradually in cervical inflammatory disease, CIN and cervical cancer; therefore, it could be used as a potential biomarker for cervical biopsy to identify the precancerous epithelial lesions. Researchers reported [23–25] that there was a positive correlation and high consistency between the expression of p16 and Ki-67 in cervical tissues. Their expressions are similar in benign cervical lesions, CIN, cancer and glandular epithelial lesions; however, the expressions of p16 and Ki-67 are significantly enhanced with the increase of the grade of CIN. By combined testing, the sensitivity and specificity of the diagnosis of CIN lesions are both improved. The results of our study showed the expression of p16 and Ki-67 both decreased in cervical tissues of LSIL patients in 3 months after focused ultrasound treatment, which is consistent with the results of previous reported studies [23,24].
MiR-33a-5p targets NOMO1 to modulate human cardiomyocyte progenitor cells proliferation and differentiation and apoptosis
Published in Journal of Receptors and Signal Transduction, 2021
Wang Xing, Tiangang Li, Yixuan Wang, Yi Qiang, Chencheng Ai, Hanbo Tang
To further unveil the correlation between miR-33a-5p and NOMO1, overexpressed NOMO1 plasmid and small interfering RNA for NOMO1 (siNOMO1) were successfully transfected into hCMPCs (Figure 3(A,B), p < 0.001). As shown in Figure 3(C), CCK-8 assay analysis proved that hCMPCs proliferation was up-regulated by overexpressed NOMO1 (p < 0.05). And the inhibitory effect of miR-33a-5p mimic on hCMPCs proliferation was partially rescued by overexpressed NOMO1 (Figure 3(C), p < 0.05). Besides, the promotive effect of miR-33a-5p inhibitor on cell proliferation was partially mitigated by knockdown of NOMO1. (Figure 3(D), p < 0.05). At the same time, the results of flow cytometry shown in Figure 3(E) demonstrated that cell percentage at G0 phase was inhibited but promoted at S and G2/M phases by overexpressed NOMO1(Figure 3(E), p < 0.01). And the positive effect of miR-33a-5p mimic on cell percentage at G0 phase as well as the inhibitory effect of mimic on cell percentage at S and G2/M phases were both partially rescued by overexpressed NOMO1. (Figure 3(E), p < 0.01). In addition, as exhibited in Figure 3(F), cell percentage was decreased at G0 phase but increased at S and G2/M phases by miR-335-5p inhibitor, while siNOMO1 posed the opposite function (Figure 3(F), p < 0.05). Furthermore, the inhibitory effect of miR-33a-5p inhibitor on cell percentage at G0 phase as well as the encouraging effect of inhibitor on cell percentage at S and G2/M phases were both partially rescued by knockdown of NOMO1 (Figure 3(F), p < 0.01).
The biological effects of electromagnetic exposure on immune cells and potential mechanisms
Published in Electromagnetic Biology and Medicine, 2022
Chuanfu Yao, Li Zhao, Ruiyun Peng
The cell cycle refers to the time elapsed from the end of cell division to the end of the next cell division, including the interphase and split phase (M phase). And the interval could be divided into three phases, the early stage of DNA synthesis (G1 phase), the DNA synthesis stage (S phase) and the late stage of DNA synthesis (G2 phase). Moreover, cells might temporarily leave the cell cycle and stop cell division to perform a certain biological function after a cycle of division, which named G0 phase. Apoptosis, an active cell death caused by various internal and external factors triggering cellular death program, plays pivotal roles in maintaining internal environmental homeostasis via removing excess, useless and harmful cells.
Related Knowledge Centers
- Cell Growth
- Cellular Senescence
- DNA Damage
- G1 Phase
- Rna
- Cellular Differentiation
- Apoptosis
- Cell Cycle
- Neuron
- Restriction Point