Proliferative effect

CpG stands for cytosine phosphate guanine dinucleotide in a particular sequence context. CpG motifs are responsible for proliferative effects of antisense oligonucleotides, particularly with respect to B-lymphocytes. Die optimal immune-stimulatory consensus sequence surrounding CpG is R1R2CGY1Y2, where R1 is a purine (mild preference for G), R2 is a purine or T (preference for A), and Y1 and Y2 are pyrimidines (preference for T). 

Contain potential benefits for men in protection against age-related bone loss and increases in cholesterol levels, without displaying estrogenic proliferative effects in the prostate... 

Many of these intracellular events are critical to the prohferative effects of CXCL12. For example, the CXCL12-induced effect on proliferation is dependent on calcium. Pre-treatment of pituitary adenoma cells with BAPTA-AM abohshes the CXCL12-induced increase in prohferation (Florio et al. 2006). The increase in proliferation also requires activation of Erk 1/2, as pre-treatment with PD98059, a MEK inhibitor, blocks the proliferative effect of CXCL12, and this is correlated with a decrease in Erk 1/2 phosphorylation. Similarly, the proliferative effects of... 

While multiple signaling pathways are implicated in mediating the proliferative effects of CXCL12, only Akt activation, p38 activation, and suppression of cAMP levels have been shown to influence the survival response. Vlahakis et al. (2002) demonstrated that CXCL12 regulates survival in CD4-t T lymphocytes via the balance of pro-survival Akt activation and pro-apoptotic p38 activation. Whether the cellular response to CXCL12 was survival or apoptosis depended on coincident activation of these pathways by other factors. 

Table 4.2 Summary of smdies comparing the anti-proliferative effects against tumour cell lines of glucosinolate metabolites in vitro. The comparisons do not distinguish between increased cell death and reduced rate of cell division...

For long-term exposure, questions have been raised on proliferative effects of breast duct epithelial cells in premenopausal women (Messina and Loprinzi, 2001, and refs therein). 

Interferons induce a wide range of biological effects. Generally, type I interferons induce similar effects, which are distinct from the effects induced by IFN-y. The most pronounced effect of type I interferons relates to their antiviral activity, as well as their anti-proliferative effect on various cell types, including certain tumour cell types. Anti-tumour effects are likely due not only to a direct anti-proliferative effect on the tumour cells themselves, but also due to the ability of type I interferons to increase NK and T-cytotoxic cell activity. These cells can recognize and destroy cancer cells. 

The ability of interferons (especially type I interferons) to induce an antiviral state is unlikely to be solely dependent upon the enzymatic mechanisms discussed above. Furthermore the 2 -5 A synthetase and eIF-2a kinase systems may play important roles in mediating additional interferon actions. The ability of such systems to stall protein synthesis in cells may play a role in interferon-induced alterations of cellular differentiation or cell cycle progression. They may also be involved in mediating interferon-induced anti-proliferative effects on various transformed cells. 

It is also important to note that, as happened with tamoxifen, this decrease in risk concentrated exclusively in ER(+) tumors. ER status was determined for 88 cases, and 75% of these were considered positive. The decrease in risk in-ducedby raloxifene administration during the total 8 years of MORE plus CORE reached 76% of the invasive ER(+) cases, compared with the placebo group (0.8 vs. 3.2 cases per 1000 woman-years HR=0.24 95% Cl = 0.15 to 0.40). There was no influence of the raloxifene treatment on the incidence of ER(-) invasive tumors (0.53 versus 0.51 cases per 1000 woman-years HR = 1.06 95% Cl = 0.43 to 2.59). This confirms the hypothesis that raloxifene exerts its protective effect through its binding to breast cell ERs, avoiding the proliferative effect of estrogens to take place. Consequently ER(-) tumors cannot be influenced by the presence of raloxifene in the blood, and no difference in its incidence should be expected between placebo and treated groups (Cauley et al. 2001) (Fig. 10.11). 

A possible explanation for these results may be twofold. First, the raloxifene doses were too low to reduce or reverse the proliferative effect of serum estradiol in normal ovulatory women. In fact, in postmenopausal women serum estradiol levels are about tenfold lower in comparison with normally cycled premenopausal women. Second, it is possible that in postmenopausal women ERs have a different intratumoral pattern in terms of concentration, expression, and affinity in comparison with premenopausal women. 

Surfactants were tested at concentrations ranging from 0.1 mM to 10 nM dissolved in the culture medium, with the concentration of solvent always maintained below 0.1%. Results are expressed as means SD. In the proliferation yield experiments, each point represents the mean of three counts from the four culture wells. Mean cell numbers were normalised to the control, equal to 1, to correct for differences in the initial plating density. The proliferative effect (PE) was expressed as the ratio between the highest cell yield obtained with each chemical tested and the hormone-free control. Proliferation experiments were repeated at least three times. 

The relative proliferative potency (RPP) is the ratio between the minimum concentration of estradiol needed for maximal cell yield and the minimum dose of the test compound needed to obtain a similar effect. The relative proliferative effect (RPE) describes the ratio between the highest cell yield obtained with the chemical and with... 

IL-1, which has no proliferative effect when acting alone but modulates the responses of haematopoietic cells to other CSFs (possibly by enhancing CSF-receptor expression), enhances the differentiation and survival of early progenitor cells observed in response to IL-3 and stimulates the production of G- and GM-CSF by T lymphocytes, endothelial cells, macrophages and fibroblasts ... 

IL-6, which has no proliferative effect when acting alone but accelerates the formation of multilineage granulocyte-macrophage colonies induced by IL-3. 

Sugaya, A., Yuzurihara, M., Tsuda, T., Yasuda, K., Kajiwara, K., and Sugay, A. E. (1988). Proliferative effect of ginseng saponin on neurite extension of primary cultured neurons of the rat cerebral cortex. /. Ethnopharmacol. 22,173-181. 

Proliferative effect at higher concentration, antiproliferative effect at lower concentration -/+ - Antiproliferative effect at higher concentration, proliferative effect at lower concentration... 

Many intracellular targets of sphingosine that may contribute to its apoptotic and anti-proliferative effects have been identified (Figure 2). These include proteins of the bcl-2 family, the retinoblastoma gene product, several enzymes and its ability to interact with DNA (reviewed by Alessenko, 2000). For example, sphingosine-induced apoptosis of HL60 cells correlated with reduced expression of the cell survival protein bcl-2... 

Sobering published two patent applications describing a series of ethylthia-zolidinones as PLK-1 inhibitors [278,279]. The most potent compounds were 116 (PLK-1 ICso = 0.023 xM) and 117 (PLK-1 IC50 = 0.034 xM). Compounds 116 (MaTu IC50 = 1.1 xM) and 117 (MaTu IC50 = 1-4 xM) also demonstrated anti-proliferative effects in MaTu cells. 

Goldberg Y, Nassif II, Pittas A, et al. The anti-proliferative effect of sulindac and sulindac sulfide on HT-29 colon cancer cells alterations in tumor suppressor and cell cycle-regulatory proteins. Oncogene 1996 12 893-901. 

Feldman. Cytotoxic and proliferative effect of tobacco products on Lewis lung adenocarcinoma cells and spleen lymphocytes. Allergol Immunopathol (Madr) 1989 17(5) 257-261. 

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