Cell cycle and growth

Ramirez OT Mutharasan R (1990) Cell cycle- and growth phase-dependent variations in size distribution, antibody productivity, and oxygen demanding hybridoma cultures. Biotechnology and Bioengineering 36 839-848. 

To determine the cellular consequences of FASN inhibition, numerous studies have focused on the in vitro anti-tumor effects of these inhibitors. Many studies have linked FASN inhibitors with cell cycle and growth arrest (Fig. 7.3). Cerulenin acts in vitro to inhibit fatty acid synthesis-mediated growth of breast carcinoma cells that can be rescued with palmitate (Kuhajda et al., 1994). Cerulenin induces a block at the G2/M cell cycle checkpoint in an androgen-independent... 

The last part of this account will be devoted to protein kinases and protein phosphatases and some recent results we have obtained for them. Protein kinases and phosphatases are signaling biomolecules that control the level of phosphorylation and dephosphorylation of tyrosine, serine or threonine residues in other proteins, and by this means regulate a variety of fundamental cellular processes including cell growth and proliferation, cell cycle and cytoskeletal integrity. 

McMahon Perhaps there is one natural example of that — the hypertrophic chondrocyte. The cells exit the cell cycle and then undergo growth, get bigger and bigger, and their eventual fate is apoptosis. One potential reason for this is that they have reached the limits of growth. 

TGF-Ps are pleiotrophic cytokines. They are capable of inhibiting the cell cycle and, hence, cell growth of several cell types, most notably epithelial and haematopoietic cells. These factors, however, stimulate the growth of other cell types, most notably cells that give rise to connective tissue, cartilage and bone. They induce the synthesis of extracellular matrix proteins and modulate the expression of matrix proteases. They also serve as a powerful chemoattractant for monocytes... 

Understanding cancer involves not only knowledge of the genetic changes that cause a normal cell to develop into a tumour cell but also the response of the whole body to a tumour, factors that increase or decrease the risk of development of a tumour and the current therapies that arrest growth of, or kill, tumour cells. These topics are discussed in this chapter, but some basic information is required first the cell cycle, the growth of a tissue, the fuels used by tumour cells and, finally, the role of genes. 

A short cell cycle and a high cell proliferation fraction cause the rapid tumor growth and early metastasis. These factors account, in part, for the high sensitivity of SCLC to chemotherapy and radiation therapy. The mean doubling time of SCLC cell lines is 50 d (15-250 d) (15-17). The response to chemotherapy alone is approx 80% but with alow complete response rate of 30 -0% (18). The complete response rate to combination chemotherapy and radiation therapy is up to 80% (19). 

Up to 30% of cancers Involve mutations ofRas, a small GTPase that regulates the cell cycle and cellular signaling pathways In response to growth factors (see Chapter 14). 

An example of an important cell cycle transition is the restriction point R, which occurs in late G1 phase. Crossing the restriction point is an important decision for further progression in the cell cycle and for entry into S phase. At this point, the cell switches from a growth-factor-dependent state to a growth-factor-independent state. 

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