The effect of selenium on cell proliferation in liver and colon

Epidemiologic and experimental evidence support a chemoprotective role for selenium (Se) in malignancy. Many mechanisms have been proposed to explain this phenomenon. In this study, the effect of Se intake on proliferation of hepatocytes and normal colonic epithelial cells in rats was determined using autoradiographic analysis of thymidine incorporation into DNA. Hepatocyte proliferation was measured 24 h after partial hepatectomy. Selenium-dosed animals demonstrated a significant reduction in hepatocyte labeling compared to the control group (6.1±2.6 vs 29.2±15.6,p=0.003). However, Se dosing did not affect the thymidine-labeling indices or distribution of labeling in colonic epithelium. Selenium may inhibit cell proliferation when it is the result of an unusually intense stimulus. This finding could explain in part the inhibitory effect of Se in some experimental cancer models. Dr. Tempero is a recipient of a Junior Clinical Faculty Fellowship from the American Cancer Society.     

The effect of alloantisera on antigen-induced T cell proliferation.

In the guinea pig, alloantisera raised by cross-immunization of strain 2 and strain 13 animals are capable of specifically inhibiting the in vitro proliferative response of (2 X 13)F1 T lymphocytes to those antigens the response to which is controlled by Ir genes linked to the genes controlling the alloantigens against which the serum is directed. However, in similar studies performed in the two parental strains, the responses to antigens not known to be under unigenic control were also markedly inhibited by the appropriate alloantisera. We have extended our studies of this "nonspecific" inhibitory effect of alloantisera on T cell proliferation and have demonstrated that the proliferative response of strain 2 and strain 13 T cells to a large number of antigens is markedly inhibited by anti-2 and anti-13 sera, respectively. Antisera to the B alloantigen, the product of a linked but distinct histocompatibility locus, which is present in both strain 2 and strain 13 animals, also produced a marked inhibition of T-lymphocyte proliferation. A number of possible explanations for the generalized inhibitory effect of alloantisera on T cell proliferation are discussed.     

Fucan effect on CHO cell proliferation and migration

Fucan is a term used to denominate sulfated l-fucose rich polysaccharides. Here, a heterofucan, named fucan B, was extracted from the Spatoglossum schröederi seaweed. This 21.5 kDa galactofucan inhibited CHO-K1 proliferation and migration when fibronectin was the substrate. Fucan B derivatives revealed that such effects depend on their degree of sulfation. Fucan B did not induce cell death, but promoted G₁ cell cycle arrest. Western blotting and flow cytometry analysis suggest that fucan B binds to fibronectin and activates integrin, mainly integrin α5β1, which induces FAK/RAS/MEK/ERK activation. FAK activation inhibits CHO-K1 migration on fibronectin and ERK blocks cell cycle progression. This study indicates that fucan B could be applied in developing new antitumor drugs.     

紫花牡荆素对胃癌SGC-7901增殖的影响及分子机制

目的:探讨紫花牡荆素(casticin)对胃癌SGC-7901细胞增殖的影响,以及对Bcl-2表达的调节作用.方法:用紫花牡荆素预处理胃癌SGC-7901细胞,MTT法分别检测紫花牡荆素不同浓度(1 g/mL、2g/mL、4g/mL、8g/mL)和不同处理时间(6h、12h、24h、48h)细胞增殖情况;IC50浓度处理胃癌SGC-7901细胞之后,Western blot和RT-PCR检测Bel-2蛋白和mRNA表达水平.结果:5.6g/mL紫花牡荆素处理SG-C-7901细胞12小时后,对细胞增殖抑制作用显著,Westernblot和RT-PCR结果显示Bcl-2表达显著下调.结论:花牡荆素可显著抑制SGC-7901细胞增殖,而这一作用可能与Bel-2表达下调有关.     

Antizyme1基因转染对K562细胞增殖与凋亡的影响

研究鸟氨酸脱羧酶抗酶蛋白对人红白血病K562细胞增殖、三氧化二砷（ As2O3）诱导凋亡时的影响。方法: 定点突变技术构建缺失frameshift位点的pEGFP-N1-AZ1-mutation重组表达载体。脂质体法转染K562细胞,通过G418筛选获得稳定表达antizyme1的K562pAZ1m细胞系。采用不同浓度的As2O3处理细胞,通过MTT法检测细胞增殖,流式细胞术分析细胞周期及凋亡变化。并通过RT-PCR方法检测antiyme1转染对cyclin D1和survivin基因表达的影响。结果：获得稳定表达antizyme1的K562-AZ1m细胞株后,其增殖能力明显减慢。CyclinD1基因表达降低,细胞主要停滞于G0/G1期。在 As2O3的诱导作用下,细胞凋亡增多,survivin基因表达降低。结论：AZ1基因能够抑制K562细胞增殖,通过对cyclinD1的负调控使细胞周期停滞于G0/G1期。并可能通过下调survivin表达来加强 As2O3对其的诱导凋亡作用     

The effect of oxygen tension on haemopoietic and fibroblast cell proliferation in vitro

The effects of providing low oxygen tension in the gas phase of two different types of cell culture systems were investigated. The clonal growth of granulocyte-macrophage progenitor cells in an agar culture system was improved markedly by incubation within a low oxygen tension gas phase (48 mmHg – 6.8%) instead of the conventional air (135 mmHg – 19%), the effects being measured by increases in numbers of colony forming cells detected and in the colony sizes. The increased efficiency of colony formation was observed both with mouse and human marrow cells. A similar effect was observed in a liquid adherence culture system with primary cultures of foetal mouse fibroblasts both at clonal and higher cell densities.     

The effect of enrofloxacin on cell proliferation and proteoglycans in horse tendon cells

Fluoroquinolone antibiotics have been used widely in humans and domestic animals, including horses, because of their broad-spectrum bactericidal activity, and relative safety. The use of fluoroquinolones, however, is not without risk. Tendonitis and spontaneous tendon rupture have been reported in people during or following therapy with fluoroquinolones. We have studied the effects of enrofloxacin, a fluoroquinolone antibiotic used commonly in domestic animals, on tendon cell cultures established from equine superficial digital flexor tendons. Effects on cell proliferation and morphology were studied using cell counting and scanning electron microscopy. Monosaccharide content and composition was determined by gas chromatography-mass spectrometry analysis. Western and Northern blot analyses were utilized to evaluate the synthesis and expression of two proteoglycans, biglycan and decorin. Our data demonstrate that enrofloxacin inhibits cell proliferation, induces morphological changes, decreases total monosacharide content and alters small proteoglycan synthesis at the glycosylation level in equine tendon cell cultures. These effects are more pronounced in juvenile tendon cells than in adult equine tendon cells. We hypothesize that morphological changes and inhibition of cell proliferation are a result of impaired production of biglycan and decorin, proteoglycans involved in fibrillogenesis of collagen, the most important structural component of the tendon of enrofloxacin-treated tendon cells. Our findings suggest that fluoroquinolones should be used with caution in horses, especially in foals.     

The effect of hyaluronate and its oligosaccharides on endothelial cell proliferation and monolayer integrity

Hyaluronidase treatment of hyaluronic acid produced a series of oligosaccharides. Those between 3 and 16 disaccharides in length stimulated angiogenesis in vivo and the proliferation of tissue cultured endothelial cells in vitro. This effect appears to be cell type specific, as no stimulation of fibroblasts or smooth muscle cells was observed. Endothelial cells were found to endocytose both high- and low-molecular-mass hyaluronate, which might be receptor mediated. Fibroblasts and smooth muscle cells, cultured under the same conditions, showed negligible uptake of hyaluronate. Thus, the cell-specific effects may be due to the differences in internalization of hyaluronate. High-molecular-weight hyaluronate both inhibited endothelial cell proliferation and disrupted newly formed monolayers. These data are consistent with the ability of hyaluronate to inhibit new blood vessel formation in vivo and also suggest that hyaluronate metabolism plays a pivotal role in the regulation of angiogenesis.     

The effect of growth hormone on the proliferation of human Th cell clones

The effects of human growth hormone (hGH) on human Th cell clones were examined. Both 20K and 22K hGH stimulated the proliferation of Th2 and Th0 cells in the presence of mite antigen, whereas they did not stimulate the proliferation of Thl cells. Because the effect of 20K hGH was almost the same as that of 22KhGH, it was suggested that the action of hGH was not mediated through prolactin receptor but through hGH receptors. The application of growth hormone binding protein (GHBP) inhibited the cell growth of Th1 clones. In Th2 and Th0 cells GHBP inhibited the hGH-stimulated cell proliferation. However, GHBP alone did not affect the proliferation of Th2 and Th0 cells. hGH was detected in the supernatant of Th1 clones in the presence of mite antigen but it was not detected in Th2 clones. hGH was detected in one out of 4 batches of Th0 clones. These data indicated that hGH was secreted from Thl clones, and that Th0 clones possessed characteristics of both Th2 and Th0 clones.     

The urokinase-system--role of cell proliferation and apoptosis

The serine protease urokinase-type plasminogen activator (uPA) and its receptor (uPAR) are involved in the control of extracellular matrix turnover, cell migration, invasion and cell signalling leading to a variety of different responses, under both physiological and pathological conditions. The urokinase receptor, binding to the growth factor-like domain of uPA, directs membrane-associated extracellular proteolysis and signals through transmembrane proteins, thus regulating tissue regeneration, angiogenesis, cancer growth and metastasis. Since these physiological and patho-physiological processes of the uPA-system are known, less informations concerning uPA-induced cell proliferation and anti-apoptotic effects of the uPA-system are available. Recent studies show a close relationship of the uPA-system and cell proliferation/ apoptosis. uPA is responsible for the activation and release of different growth factors and modulates the cell proliferation/apoptosis ratio through the dynamic control of cell-matrix interactions. This article focuses on the important role of the uPA/uPAR-system for cell proliferation and apoptosis.     

The effect of continuous irradiation on cell proliferation and maturation in small intestinal epithelium.

Autoradiographic studies and scintillation counting of crypt material after pulse labelling with 3H-thymidine showed that during continuous irradiation with 290 rads/day a reduced proliferative activity is present in the crypts of rat small intestine after 1 day of irradiation and of normal activity during the remaining period (5 days) irradiation. After cessation of irradiation an increase in proliferative activity can be observed after 1 day of recovery. From the time (36-48 hr after starting of the irradiation) that the number of villus cells is reduced an expansion of the proliferation zone in the crypt was observed. Both effects last until 1 day of recovery after cessation of irradiation. The process of crypt cell maturation and of villus cell function has also been studied during and after continuous irradiation by micro-chemical enzyme analyses in isolated crypts and villi. It was found that the expansion of the proliferation zone in the crypt is accompanied by a decrease in activity of only those enzymes (i.e. non-specific esterases) which normally become active during crypt cell maturation. The activity of enzymes normally present mainly in the functional villus cells remained relatively unaffected by changes in crypt cell kinetics. A hypothesis of different regulation mechanisms of the proliferative activity in the intestinal crypt and a possible explanation of the different behaviour of various enzyme activities as a result of changes in crypt cell proliferation is discussed.     

The effect of mouse euthanasia technique on subsequent lymphocyte proliferation and cell mediated lympholysis assays

The purpose of this study was to determine the effects that specific euthanasia methods have on mitogen induced lymphocyte proliferation (LP) and the induction of alloantigen specific cytolytic T-lymphocytes (CTL). Mice were euthanatized by cervical dislocation (CD), or anesthesia with methoxyflurane or pentobarbital followed by CD (M-CD or P-CD respectively), CO2 overexposure (CO2-OD) or halothane overexposure (H-OD). Mitogenic lymphoproliferation was increased in cells derived from mice euthanatized by M-CD and P-CD. In contrast, the cytolytic profile of CTL derived from mice euthanatized by P-CD, CO2-OD and H-OD was decreased. The results of this study show that euthanasia techniques involving the use of methoxyflurane, pentobarbital, CO2 and halothane affect in vitro lymphoproliferation and CTL function. We conclude that the method of euthanasia influences certain immunologic parameters and selection of a particular technique should be given careful consideration.     

The effect of transforming growth factor-beta on cell proliferation and collagen formation by lung fibroblasts

We examined the effects of transforming growth factor-beta (TGF-beta) on the production of collagen by cultures of human embryonic lung fibroblasts. TGF-beta at 0.1 ng/ml appeared to activate selectively extracellular collagen accumulation as compared with total protein production. A maximal effect inducing a 2-3-fold increase in collagen and total protein production occurred at a dose of 1.0 ng/ml in fibroblast cultures. TGF-beta had no effect on fibroblast proliferation after a 24- and 48-h exposure, including cultures that received a second dose after 24 h. Collagenase digestion of radiolabeled collagen derived from TGF-beta-treated and -untreated cultures revealed no differences in the extent of hydroxylation (37.3 versus 33.4%). TGF-beta increased the production of types I and III collagen without affecting the proportion of collagen types. Fibroblast cultures maintained in medium containing TGF-beta sustained an activated rate of collagen production of 5 nmol/ml/24 h over at least 72 h. We found that epidermal growth factor slightly enhanced TGF-beta-induced collagen formation, whereas TGF-beta increased the proliferative effect of epidermal growth factor. Taken together, these data indicate that collagen production and cell proliferation can be independently regulated and that TGF-beta may have a role in the resolution of tissue injury by stimulating fibroblast-derived collagen synthesis.