Neoplastic cell growth

Quackenbush, E., et al. Molecular doning of complementary DNAs encoding the heavy chain of the human 4F2 cell-surface antigen a type II membrane glycoprotein involved in normal and neoplastic cell growth. Proc. Natl. Acad. Sci. U. S. A. 1987, 84, 6526-6530. 

Pugh-Humphreys RG. Macrophage-neoplastic cell interactions implications for neoplastic cell growth. FEMS Microbiology Immunology 1992, 5(5-6), 289-308. 

Harris CS, Mo F, Migahed L, Chepelev L, Haddad PS, Wright JS, Wilhnore WG, Amason JT, Bennett SAL (2007) Plant phenolics regulate neoplastic cell growth and survival a quantitative stmctme-activity and biochemical analysis. Can J Physiol Pharmacol 85 1124... 

Modem cancer therapy has been primarily dependent upon surgery, radiotherapy, chemotherapy, and hormonal therapy (72) (see Chemotherapeutics,anticancer Hormones Radiopharmaceuticals). Chemotherapeutic agents maybe able to retard the rate of growth, but are unable to eradicate the entire population of neoplastic cells without significant destmction of normal host tissue. This serious side effect limits general use. More recentiy, the immunotherapeutic approach to cancer has involved modification and exploitation of the cellular and molecular mechanisms in host defense, regulation of tissue proliferation, tissue differentiation, and tissue survival. The results have been more than encouraging. 

Vitamin A (retinol) and its naturally occurring and synthetic derivatives, collectively referred to as retinoids (chemical structure), exert a wide variety of profound effects in apoptosis, embryogenesis, reproduction, vision, and regulation of inflammation, growth, and differentiation of normal and neoplastic cells in vertebrates. 

It now appears that both mechanical factors and finding a suitable environment are responsible for the preferred organ location of secondary growths. The relative importance of these factors is unknown and may vary depending on the type of tumor. Proctor (P4) has suggested that the initial dissemination of neoplastic cells is controlled mostly by mechanical factors, whereas later metastasis is determined more by appropriate environment. 

Neoplasms are, as we noted in Chapter 3, new growths. But they are new in several highly destructive ways. Normal processes of cell replication within tissues occur in orderly, well-controlled ways. Neoplastic cells replicate wildly, without apparent controls. The relationships between the various types of cells within an organ are, if the organ is to function properly, also orderly neoplastic cells, because of their disorderly replication patterns, can disrupt normal architecture and organ dysfunction can ensue. 

L5. Leithauser, F., Dhein, J., Mechtersheimer, G., Koretz, K., Bruderlein, S., Henne, C., Schmidt, A., Debatin, K. M., Krammer, R H., and Moller, R, Constitutive and induced expression of APO-1, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily, in normal and neoplastic cells. Lab. Invest. 69, 415-429 (1993). 

As so many physiological compounds regulating cell growth and metabolism appear to interact with gangliosides as components of cellular receptors, it has been suggested that the loss of growth control in certain transformed cells may partially be based on the altered gaug-lioside composition observed in neoplastic cells.541... 

Several effects of forskolin on B-lymphocytes, the cells of the immune system responsible for the production of immunoglobulins, have further been reported. This diterpene was found to inhibit cellular proliferation of B cells stimulated either by antibodies to surface immunoglobulins (anti-mu), and an antibody to CD20 antigen or 12-O-tetradecanoyl phorbol 13-acetate [219]. There was also a clear inhibition of G1 entry and DNA synthesis, and forskolin maintained its inhibitory effect even when added later after anti-mu stimulation. Additionally, no differences were found in the inhibitory effect of forskolin on neoplastic B cells, as compared to the responses of normal cells. Growth inhibition associated with an accumulation of cells in G1 was later found when cells of the B-lymphoid precursor cell line Reh were incubated with forskolin [220]. In that study, a delay of cells in G2/M prior to G1 arrest was observed, suggesting that important restriction points located in the G1 and G2 phases of the cell cycle may be controlled by forskolin (due to cAMP levels elevation). In a subsequent study [221], it was found that the arrest of Reh cells was accompanied by rapid dephosphorylation of retinoblastoma protein, which was suggested to be a prerequisite for the forskolin mediated arrest of these cells in Gl. 

Administration of copper dimethylglyoxime143), copper 2-keto-3-ethoxybutyralde-hyde bis(thiosemicabazone)144) or copper pyruvaldehyde bis(thiosemicarbazone)145) to rodents has led to inhibition of tumour growth. The copper(II) complex of 2-keto-3-ethoxybutyraldehyde bis(thiosemicarbazone) transports copper into neoplastic cells where it is deposited and inhibits a number of enzymes responsible for the synthesis of DNA146-. ... 

Four major types of genetic alterations that affect growth-controlling genes have been identified in neoplastic cells and are the basis of human cancers. 

Because MIB-1 monoclonal antibody is used extensively to determine the cell proliferation index, its applications are discussed below. This antibody detects the nuclear antigen Ki-67 expressed in proliferating cells but not in resting cells. The antibody reacts with the nuclei of cells in mid-Gj (first gap), S (DNA synthesis), G2 (second gap), and M (mitosis) phases, but not in the G0 or quiescent phases. The use of MIB-1 antibody is one of the simplest and most reliable labeling techniques for assessing the rate of proliferation of a neoplastic cell population. Thus, the antibody can be used to assess the growth fraction (i.e., the number of cells in cell cycle) of normal, reactive, and neoplastic tissues. 

Butyrate appears to have its most profound effects on neoplastic cells such as HeLa in addition to morphological and biochemical differentiation, the fatty acid inhibits cell growth (2). Previous studies have established a correlation between decreased ganglioside synthesis and malignant transformation (43-46). Transformed baby hamster kidney and newborn rat kidney cells exhibited a loss of GM3 and sialyl transferase activity (43,44). 

The mechanisms of action of steroid hormones on lymphoid, mammary, and prostatic cancer have been partially clarified. Specific cell surface receptors have been identified for estrogen, progesterone, corticosteroids, and androgens in neoplastic cells in these tissues. As in normal cells, steroid hormones also form an intracellular steroid-receptor complex that ultimately binds directly to nuclear proteins associated with DNA to activate transcription of a broad range of cellular genes involved in cell growth and proliferation (see Chapter 39 Adrenocorticosteroids Adrenocortical Antagonists). 

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