Differentiation of tumor cells

Yu SY, Lu XP and Liao SD (1990) The regulatory effect of selenium on the expression of oncogenes associated with the proliferation and differentiation of tumor cells. In Collery P, Poirier LA, Manfait M and Etienne JC, eds. Metal ions in Biology and... 

C12H8O4, Mr 216.19, cryst., mp. 115-117°C, [ajp -34° (CHCI3/CH3OH). A pyranone derivative from cultures of the basidiomycete Jmghuhnia nitida. N. exhibits antibiotic and cytotoxic activities and induces morphological and physiological differentiation of tumor cells at nanomolar concentrations. 

Although fermentation of fiber tends to reduce its effectiveness as a source of fecal bulk, it has other very important benefits. The absorption and metabolism of short-chain fatty acids derived from carbohydrate fermentation provides the route for the recovery of energy from undigested polysaccharides. Butyrate functions as the preferred source of energy for the colonic mucosal cells, whilst propionate and acetate are absorbed and metabolized systemically. There continues to be much debate about the importance of butyrate for the colon. In vitro, butyrate causes differentiation of tumor cells, suppresses cell division, and induces programed cell death (apoptosis). These effects are thought likely to suppress the development of cancer, but it is not yet entirely clear whether they also occur in the intact intestine. Research continues on the importance of butyrate and other short-chain fatty acids for human health. 

Unlike differentiation antigens, prognostic markers are usually evaluated semiquantitatively, both in terms of the proportion of tumor cells showing positivity and the strength of the reaction. 

Fewer antibodies are available to characterize these tumors than those from the other categories. Table 12 lists the most useful antigens that can be detected in routinely processed tissues. Antibodies to desmin, an intermediate filament, are very specific for muscle tumors. Because of its sensitivity to fixation and its absence in the early differentiation of muscle cells, desmin is often difficult to detect in muscle sarcomas. 

Radiolabeled amino acids have been introduced as SPECT and PET tracers that allow a precise delineation of brain tumor in cerebral gliomas and differentiation of tumor tissue and edema. Radiolabeled amino acids are taken up by specific amino acid transporters in glioma cells [198-201]. Recently 0-(2-[ F] fluorethyl)-L-tyrosin (p FjFET) has been introduced as PET brain tumor imaging tracer [202,203]. 

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity direcdy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-cells, B-cells, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modality for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disseminated intravascular coagulation in mice administered TNF-a and IFN-y. 

GLP-1 increases beta-cell mass in animals. Thus, exenatide has the potential to cause increased beta-cell mass through augmented differentiation of precursor cells and inhibition of apoptosis (9). No malignant islet cell tumors were found in 130 mice and rats who received the... 

Interleukin-2 (IL-2) is an endogenous cytokine that normally exerts a number of beneficial immunologic responses. In particular, IL-2 stimulates the growth and differentiation of T-cell lymphocytes that are selectively toxic for tumor cells.11,33 Hence, recombinant DNA techniques are now used to synthesize IL-2 so that this agent can be used to treat cancers such as renal cancer and malignant melanoma (see... 

TCDD inhibits the terminal differentiation of B cells via alteration of an early activation event, perhaps increased protein phosphorylation and tyrosine kinase activity (Clark et al. 1991a Kramer et al. 1987 Luster et al. 1988 Morris et al. 1991). Macrophage functions, examined ex vivo, generally have been found to be resistant to suppression by 2,3,7,8-TCDD (Mantovani et al. 1980 Vos et al. 1978). There is also evidence suggesting that inflammatory cells may be activated by 2,3,7,8-TCDD via enhanced production of inflammatory mediators such as interleukin 1 and tumor necrosis factor (Clark et al. 1991b Taylor etal. 1992). 

The results of simulations indicate that, when the circadian delivery of 5-FU peaks at 4 a.m., differential effects of the drug on a population of healthy cells and on a population of tumor cells may be observed depending on whether the two cell populations are entrained or not by the circadian clock [33]. Another source of differential effect pertains to the degree of variability, given that, as previously noted, synchronization of the cells minimizes cytotoxic damage when the circadian 5-FU modulated delivery pattern peaks at 4 a.m. The results are markedly different when the circadian pattern of 5-FU delivery peaks at 4 p.m. [33]. Then the cytotoxic effect of the drug on the two populations is the inverse as that predicted for the circadian pattern peaking at 4 a.m. The effect of variability therefore depends on the circadian pattern of 5-FU delivery and on the possibility of entrainment of the cell cycle by the circadian clock. 

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