Tissue differentiation

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. 

The specific role of vitamin A in tissue differentiation has been an active area of research. The current thinking, developed in 1979, involves initial dehvery of retinol by holo-B >V (retinol-binding protein) to the cell cytosol (66). Retinol is then ultimately oxidized to retinoic acid and binds to a specific cellular retinoid-binding protein and is transported to the nucleus. Retinoic acid is then transferred to a nuclear retinoic acid receptor (RAR), which enhances the expression of a specific region of the genome. Transcription occurs and new proteins appear during the retinoic acid-induced differentiation of cells (56). 

Retinoic Acid Has a Role in the Regulation of Gene Expression Tissue Differentiation... 

A most important function of vitamin A is in the control of cell differentiation and mrnover. PsA-trans-retinoic acid and 9-cw-retinoic acid (Figure 45-1) regulate growth, development, and tissue differentiation they have different actions in different tissues. Like the steroid hormones and vitamin D, retinoic acid binds to nuclear receptors that bind to response elements of DNA and regulate the transcription of specific genes. There are two families of nuclear retinoid receptors the retinoic acid receptors (RARs) bind all-rrijw-retinoic acid or 9-c -retinoic acid, and the retinoid X receptors (RXRs) bind 9-cw-retinoic acid. 

Wiebel, F. J., Leutz, J. C., Diamond, L., and Gelboin, H. V. Aryl hydrocarbon (benzo[a]pyrene) hydroxylase in microsomes from rat tissues differential inhibition and stimulation by benzoflavones and orqanic solvents. Arch. Biochem. Biophys. (1971) 144 78-86. 

Martinez-Pomares, L., Platt, N., McKnight, A.J., da Silva, R.P., and Gordon, S., 1996, Macrophage membrane molecules markers of tissue differentiation and heterogeneity. Immunobiology 195 407-416. 

The activity of vitamin A is related to vision process, tissue differentiation, growth, reproduction, and the immune system. A deficiency of this micronutrient mainly leads to visual problems, impaired immune function, and growth retardation in children. Hypervitaminosis could lead to hepatotoxicity, affect bone metabolism, disrupt lipid metabolism, and teratogenicity [417]. The isomerization of P-carotene, due to technological processes in foods, leads to a reduction of the vitamin A activity it is therefore important to analyze it. 

As a hormone IAA has a broad range of effects on plants, altering tissue differentiation, root growth, cell elongation, and cell division.2413 The fastest observed response is an effect on cell elongation, which can be observed within 15-20 minutes.242 In A. thaliana IAA... 

Vitamin A is a necessary micronutrient in the diet for vision, growth, tissue differentiation, reproduction, and maintenance of the immune system. A deficiency of vitamin A affects reproduction in both male and female experimental animals. In the male, retinol is required for normal spermatogenesis in the female, the vitamin is necessary for both conception and normal development of the fetus. 

Mammalian MTs are known to accumulate after administration of various metal salts. This control is not exclusive, however, as a variety of other stimuli also trigger MT synthesis, including several hormones, tissue injury, bacterial endotoxin and interferon (see Karin, 1985 Hamer, 1986). Each of these factors relates directly or indirectly to various acute stresses. This could indicate that MT is a general stress protein. Such a definition is incomplete because MT levels also change during embryo-genesis and tissue differentiation. This has prompted the suggestion that the primary role of MT is as a modulator of cellular activity (Karin, 1985). 

Enzyme induction and/or isoenzyme variation have been used to characterise widely different phenomena. These enzymatic parameters were shown to be useful criteria for monitoring air pollution (Keller, 1974 Fliickiger et al., 1978 Rabe and Kreeb, 1979), for ecogenetic characterisation of plant populations (Verkleij et al, 1980 Triest, 1991), for the study of callus tissue differentiation (Coppens and Gillis, 1987) and plant development and differentiation (Scandalios, 1974). The evaluation of phytotoxicity of metal-polluted soils and other substrates can also be realised by enzymatic parameters. 

The study of differentiation in multicellular animals is beset by problems arising from the complex and poorly understood interactions of the various tissues. These interactions can be limited or eliminated in cell culture and a number of systems are described below which are leading to an understanding of the mechanisms of cell and tissue differentiation. This chapter supplements material presented earlier, especially in Chapter 6. 

As well as being the causative organisms of a number of major human and animal diseases (e.g. cysticercosis, hydatidosis), cestodes serve as elegant experimental models for the study of fundamental biological phenomena. These include not only problems of specific parasitological interest, such as host-specificity, but also more basic problems such as enzyme dynamics, membrane transport and cell and tissue differentiation (especially asexual/sexual differentiation), common to many other biological fields. 

In his book Symbionticism and the Origin of Species from 1927, Ivan Wallin (1883-1969) at the University of Colorado advanced the theory that the inheritance of acquired bacteria was the source of new genes and the primary mechanism for the origin of species. Wallin had come to symbiosis and mitochondria through studies of tissue differentiation and development in the lamprey Ammocetes. The continental research on mitochondria and their proposed roles in development and heredity were introduced to English-speaking researchers by Edmund Cowdry (1918). Wallin had also made a study of Portier s Les symbiotes, and he pressed the idea in the context of heredity, development, and evolution. 

Y. Guan, E. N. Lewis, and I. W. Levin, Biomedical applications of Raman spectroscopy Tissue differentiation and potential clinical usage, in Analytical Applications of Raman Spectroscopy (M. J. Pelletier, ed.), Chap. 7. Blackwell Science, Oxford, England, 1999. 

Alterations in the protein pattern are immanent for mammalian body fluids or tissues. Differential expression profiles for the comparison of distinct samples are to be expected due to the biological variability related to patient age, gender or lifestyle. In order to distinguish disease-related features from false-positive differences the critical validation and assessment of putative markers is of fundamental importance (Zolg and Langen, 2004). 

Retinoic acid modulates gene expression and tissue differentiation, acting by way of nuclear receptors. Historically, there was confusion between the effects of deficiency of vitamins A and D by the 1950s, it was believed that the confusion had been resolved. Elucidation of the nuclear actions of the two vitamins has shown that, in many systems, the two act in concert, forming retinoid-vitamin D heterodimeric receptors hypervitaminosis A can antagonize the actions of vitamin D. 

In vitro, and in experimental animals, vitamin A has anticancer action related to its role in modulating gene expression and tissue differentiation. It retards the initiation and growth of some experimental tumors. However, it only shows these effects at toxic levels, and a number of synthetic analogs. 

---