Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidation of low density lipoprotein (LDL) leads to more rapid uptake by arterial wall macrophages and foam cell formation. Inhibiting LDL oxidation may impede these processes and offers a new mechanism to retard atherogenesis. The 21-aminosteroids, derived from methylprednisolone, are potent inhibitors of free radical production by stimulated monocytes and also are scavengers of lipid peroxyl radicals. The 21-aminosteroid, U74500A, was added to a mixture of low density lipoprotein cholesterol and human monocytes to which lipopolysaccharide was add to stimulate the monocytes. At a final concentration of 10 microM, U74500A reduced the production of lipid peroxidation from 6.10 +/- 1.11 to 0.84 +/- 0.16 nmol (mean +/- SEM) MDA equivalent/1 x 10(6) monocytes, as measured by a thiobarbituric acid reacting substance (TBARS) assay. Similarly 10 microns U74500A reduced Cu2+ induced LDL oxidation from 12.28 +/- 0.10 (in vehicle) to 0.49 +/- 0.12. These observations suggest that the 21-aminosteroids should be evaluated in animal models as a potential therapy to retard atherogenesis, especially considering their apparent lack of mineralocorticoid and glucocorticoid side-effects.
 ...
PMID:A 21-aminosteroid inhibits oxidation of human low density lipoprotein by human monocytes and copper. 175 90

Although 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has been shown to inhibit the growth of certain malignant cells, its hypercalcemic effect has prevented clinical application. We have recently developed a novel vitamin D3 analog, 22-oxa-1,25-(OH)2D3 (OCT), that is capable of promoting differentiation and inhibiting proliferation without inducing hypercalcemia. The present study was undertaken to determine whether OCT could be applied for the treatment of breast cancer with or without estrogen receptor (ER). OCT inhibited the proliferation of both ER-positive (MCF-7, T-47D, and ZR-75-1) and ER-negative breast cancer cells (MDA-MB-231 and BT-20) in vitro in a time- and dose-dependent manner, as determined by cell number and [3H]thymidine uptake. The antiproliferative effect was observed with a concentration as low as 10(-11) M OCT, and treatment of MCF-7 cells with 10(-8) M OCT for 8 days caused more than a 50% reduction in cell number compared with that of vehicle-treated cells. OCT was approximately 1 order of magnitude more potent than 1,25-(OH)2D3 in inhibiting the proliferation of MCF-7 cells. The in vivo effect of OCT was examined in athymic mice implanted with ER-negative MX-1 tumor, which was established as the xenograft derived from human breast carcinoma. Intratumor administration of OCT three times a week remarkably delayed the growth of MX-1 tumor in a time- and dose-dependent manner. The antitumor effect of 1 microgram/kg BW OCT was greater than that of 500 microgram/kg BW adriamycin, and the relative tumor weights in each group on day 26 were 29.7% and 50.5% of that in the vehicle-treated group, respectively. The effects of OCT and adriamycin were additive, and the relative tumor weight after 26 days of combined treatment was 21.7% of that in the vehicle-treated group. Oral administration of OCT was also effective, and the relative tumor weight in the OCT-treated group (1 microgram/kg BW) was 54.6 +/- 0.1% (mean +/- SEM) of that in the vehicle-treated group. Neither intratumor nor oral administration of OCT raised the serum calcium level in these animals. These results demonstrate that OCT is a potent inhibitor of the proliferation of breast cancer cells with or without ER and that OCT inhibits the growth of breast cancer in vivo without inducing hypercalcemia. We suggest that OCT may provide a new strategy for the treatment of breast carcinoma regardless of ER status.
 ...
PMID:A novel vitamin D3 analog, 22-oxa-1,25-dihydroxyvitamin D3, inhibits the growth of human breast cancer in vitro and in vivo without causing hypercalcemia. 185 78

The properties of fatty acyl coenzyme A: estradiol-17 beta acyl transferase in microsomes derived from pooled human mammary cancer tissue have been examined. A pH optimum of 5.5 was found and addition of long-chained fatty acyl CoAs increased estradiol-17 beta (E2) 17-monoacyl ester synthesis; the apparent Km for E2 being 8 microM when oleoyl CoA, linolenoyl CoA or palmitoyl CoA were employed. Testosterone, dehydroepiandrosterone, and 5-androsterone-3 beta, 17 beta-diol acted as competitive inhibitors with Ki values of 36, 36 and 46 microM, respectively. The composition of E2 fatty acyl esters (E2-L) formed by incubation of [3H]E2 with human mammary cancer tissue and human mammary cancer cell lines has been determined by HPLC. Although the composition of E2-L in estrogen receptor negative cell lines (MDA-MB-231 and MDA-MB-330) was generally similar to that found for MCF-7 cells (estrogen receptor positive) and pooled human mammary cancer tissue, the former cell lines contained a 3-fold higher relative concentration of E2-17 beta stearate. MCF-7 cells were exposed to 30 nM [3H]E2 and the composition of the isolated [3H]E2-L fraction studied at various time intervals. At 0.5 h, the intracellular concentration of E2-L was 1.8 +/- 0.4 (SEM) pmol/mg DNA which increased to values of 3.6 +/- 0.6 and 4.3 +/- 0.5 at 4 h and 16 h, respectively. In the subsequent 3 h following transfer to medium lacking [3H]E2, the concentration of E2-L declined to 3.7 +/- 0.3 pmol/mg DNA. The subfraction of E2-L composed of E2-17 beta arachidonate, linolenate and docosahexaenoate, was seen to decline in relative abundance after 0.5 h and to reach significantly lower relative levels at 16 h, and again in the 3 h period following estrogen withdrawal. The data suggests that these components, derived from essential fatty acids, are more metabolically active. This may then provide a new lead to link these novel estrogen derivatives with the established relationship between unsaturated fatty acids and an increased mammary cancer incidence.
 ...
PMID:Selective turnover of the essential fatty acid ester components of estradiol-17 beta lipoidal derivatives formed by human mammary cancer cells in culture. 366 59

The purpose of the study was to compare the effects of dietary linoleic acid (LA) intake on the growth and metastasis of MDA-MB-435 and MDA-MB-231 human breast cancer cells in nude mice, together with their invasive capacity and secretion of type IV collagenase (gelatinase) in vitro. Each tumor cell line (10(6) cells) was injected into a right-sided mammary fat pad in 60 mice with equal numbers (30 mice/group) assigned to isocaloric diets containing 23% (w/w) total fat and 2% or 12% (w/w) LA. The MDA-MB-435-cell mammary fat pad tumors became palpable earlier and initially they grew more rapidly, but by 6 weeks the MDA-MB-231-cell tumors exhibited an acceleration of growth which was enhanced by the high-LA diet. At necropsy, 12 weeks after the tumor cell injections, the mean weight [10.2 +/- 1.4 g(SEM)] of mammary fat pad MDA-MB-231 cell tumors in 12% LA-fed mice was significantly higher (6.7 +/- 1.4 g) than that of the mice fed 2% LA; also, it was higher than that of MDA-MB-435 cell tumors in the 12% LA-fed mice (3.6 +/- 0.1 g) or the 2% LA-fed mice (3.3 +/- 0.1 g) (each P < 0.001). Mice fed the 12% LA diet had a higher incidence of grossly visible MDA-MB-435 cell pulmonary metastatic nodules than those fed the 2% LA diet (67% versus 33%; P < 0.02), more metastatic lesions (5.7 +/- 1.6 versus 2.3 +/- 0.8; P < 0.05), and greater total volumes (62.0 +/- 25.9 versus 24.8 +/- 9.0 mm3; P < 0.02) per mouse. Of the MDA-MB-231 cell tumor-bearing mice, only 1 in the 12% LA dietary group and 2 in the 2% LA dietary group had macroscopic nodules but the incidence of microscopic metastases was 68 and 42%, respectively. The MDA-MB-231 cell line exhibited a relatively high capacity for invasion in vitro and constitutively high levels of both total type IV collagenolytic activity and M(r) 92,000 gelatinase production which were unaffected by LA. In contrast, MDA-MB-435 cells had approximately only one-sixth the invasive capacity and secreted a relatively low level of type IV collagenase and little of the M(r) 92,000 gelatinase; both invasion and enzyme production were stimulated by LA.
 ...
PMID:Effects of linoleic acid on the growth and metastasis of two human breast cancer cell lines in nude mice and the invasive capacity of these cell lines in vitro. 798 56

In order to assess the liver protective activity and the antioxidant properties of a new silybin complex (IdB1016), we carried out a short-term pilot study on 20 patients with chronic active hepatitis (CAH), randomly assigned to 240 mg of silybin b.i.d. (10 patients, 4 m/6 f, mean age: 50 years) or placebo (10 patients, 2 m/8 f, mean age: 55 years). Blood samples were collected before and after 7 days of treatment for liver function tests (LFTs), malonaldehyde (MDA) as an index of lipid peroxidation, and copper (Cu) and zinc (Zn), two trace elements involved in protecting cells against free radical-mediated lipid peroxidation. In the treated group, there was a statistically significant reduction of mean (+/- SEM) serum concentrations of aspartate aminotransferase (AST) from 88.0 (+/- 13.3) to 65.9 (+/- 7.5) u/l, (p < 0.01), of alanine aminotransferase (ALT) from 115.9 (+/- 12.9) to 82.5 (+/- 10.6) u/l (p < 0.01), of gamma-glutamyltranspeptidase (gamma-GT) from 51.4 (+/- 9.3) to 41.3 (+/- 4.2) u/l (p < 0.02) and of total bilirubin (TB) from 0.76 (+/- 0.08) to 0.53 (+/- 0.04) mg/dl (p < 0.05). Alkaline phosphatase (AP) fell slightly from 143.4 (+/- 6.4) to 137.5 (+/- 7.8) u/l. There were no significant changes in MDA, Cu or Zn serum concentrations. These results show that IdB1016 may improve LFTs related to hepatocellular necrosis and/or increases membrane permeability in patients affected by CAH.
 ...
PMID:A pilot study on the liver protective effect of silybin-phosphatidylcholine complex (IdB1016) in chronic active hepatitis. 822 95

The Boyden chamber assay is widely used for in vitro measurement of the invasive capacity of cells. However, results can be affected significantly if certain precautions are not taken. Using the Boyden chamber assay we investigated in vitro the invasive potential of a variety of human gynecological tumor cell lines to degrade and migrate through the artificial basement membrane matrix Matrigel. However, in the absence of this Matrigel layer large differences were observed in the ability of cells to adhere to, migrate through and attach to the lower side of the filter membranes. These differences were influenced by cell density, degree of directional locomotion, and the size of the filter pores. To adjust for these influences (which are not directly correlated to the capacity of cells to traverse the Matrigel layer), invasion results were corrected for the ability of cells to migrate through the filter membrane. In addition, the invasion of MDA-MB-231 cells was used as an internal standard to compensate for variations in the Matrigel layer between different experiments. Overall, in our experimental set up, the five human breast cancer cell lines were the most invasive (mean invasion +/- SEM relative to MDA-MB-231 invasion: 104.7 +/- 6.1%), the five human ovarian cancer cell lines the least invasive (60.2 +/- 2.2%) and the six human endometrial cancer cell lines showed an intermediate capacity (79.1 +/- 3.5%). In conclusion, the Boyden chamber assay can be used reliably for studying the invasive potential of cells in vitro, if the ability of the cells to migrate through the filter is taken into account, and a reference cell line is included to enable comparison of the data obtained from independently performed experiments on different cell lines.
 ...
PMID:Assessment of the invasive potential of human gynecological tumor cell lines with the in vitro Boyden chamber assay: influences of the ability of cells to migrate through the filter membrane. 900 6

The present experiments were undertaken to determine the levels of MDA, SOD and catalase in the testis of adolescent rats with experimental left varicoceles. Male Wistar rats, 7 weeks old and weighing 160-170 g, were randomly allocated into three groups. The first group of rats underwent partial ligation of the left renal vein (n = 15). The second group of rats underwent a sham operation (n = 7) and the third group acted as controls (n = 7). Animals were sacrificed 6 weeks after surgery and dilatation of the internal spermatic veins was observed. Levels of MDA, SOD and catalase activity were measured in testis. The experimental left varicocele group showed severe testicular changes compared to other groups. The mean MDA (SEM) levels in right and left testicular tissues of varicocele bearing rats, sham-operated rats, and control rats were 0.48 +/- 0.24 and 0.31 +/- 0.11, 0.22 +/- 0.02 and 0.35 +/- 0.12, 0.62 +/- 0.29 and 0.13 +/- 0.05, respectively (P > 0.05). The mean SOD (SEM) levels in right and left testicular tissues of varicocele bearing rats, sham-operated rats, and control rats were 7,790 +/- 606 and 6,974 +/- 574, 7,475 +/- 1,517 and 7020 +/- 1,106, 8,727 +/- 1,188 and 9,019 +/- 1,129, respectively (P > 0.05). The mean catalase (SEM) levels in right and left testicular tissues of varicocele bearing rats,sham-operated rats, and control rats were 75.77 +/- 11.5 and 53.82 +/- 10.1, 91.94 +/- 14 and 94.90 +/- 32, 65.40 +/- 5.7 and 90.93 +/- 16.4, respectively (P > 0.05). Our results suggest that oxidative status, which reflects a relative balance between reactive oxygen species (ROS) generated and ROS scavenged, may not be responsible for the testicular dysfunction associated with experimentally induced varicocele during adolescence in rats.
 ...
PMID:Effect of experimental varicocele in rats on testicular oxidative stress status. 1222 Feb 32

The present study evaluates the changes in sperm motility due to H202 induced membrane damage. Washed human sperm suspended in HAM's F-10 (20-30 x 10 6/ml) were incubated (37 degrees Celsius) with varying concentrations (0-0.05%) of H202 for up to 15 minutes. Sperm were analyzed for % motility, % viability, the ratio of cholesterol to phospholipids (C/PL), and the degree of lipid peroxidation (LPO). Motility was monitored manually and viability was evaluated by the Eosin Y staining method. Total lipids were extracted with chloroform:methanol (1:2) and used in colorimetric determination of cholesterol and phospholipid contents (mcmol/106 sperm). Lipid peroxidation was measured by the production of malondialdehyde (nmol MDA/108 sperm). The results (mean +or- SEM, n=8) indicate a dose a time-dependent effect on % motility during the 15 minute incubation period. In comparison to control (8 +or- 4%), samples incubated with 0.01% H202 exhibited a 25 +or- 3% decrease in % motility, while a complete loss of motility was observed with 0.05% H202. No significant differences in decrease in sperm viability were observed between control (211 +or- 4) and H202 (0.01%) treated samples (14 +or- 2%). An increase of (54 +or- 5%) in lipid peroxidation was observed with 0.01% H202, as compared with an 18 +or- 1% increase in control samples at 15 minutes. The C/PL ratio increased by 46 +or- 4% at 15 minutes in H202 treated samples while showing a 34.3% decrease in control samples. H202 inhibited sperm motility while increasing membrane LPO and C/PL, without altering sperm viability. It would appear that lipid peroxidation and alteration of sperm membrane composition lead to the loss of sperm motility.
 ...
PMID:Time course of hydrogen peroxide induced changes in the lipid peroxidation of human sperm membranes. 1228 60

The role and expression of ROCKI and ROCKII in human breast cancer was investigated and the effect on clinical outcome assessed. ROCK knockdown cells (MDA-MB-231DeltaROCKI and MDA-MB-231DeltaROCKII were tested for their in vitro invasiveness, motility and in vivo tumour growth. Samples of fresh frozen breast tumour tissue (n=113) and normal background tissue (n=30) were processed for immunohistochemical and quantitative RT-PCR analyses. MDA-MB-231DeltaROCKI and MDA-MB-231DeltaROCKII cells showed significantly decreased invasiveness compared with control cells (mean +/- SEM 4.33+/-0.84 MDA-MB-231DeltaROCKI vs. 18.4+/-1.4 control, p<0.001; 6.8+/-1.2 MDA-MB-231DeltaROCKII vs. 18.4+/-1.4 control, p<0.001). Similarly, both exhibited reduced motility compared with control cells (p<0.001) and lost their response to HGF. Importantly, no significant difference existed between knockdown and control cells in in vivo tumour growth. ROCKI was significantly higher in human mammary tumours than normal background tissue (2.9+/-1.1 vs. 0.29+/-0.13, p=0.023), although expression of ROCKII was fairly consistent in both (2050+/-646 vs. 2303+/-2079). ROCKI expression was greater in patients who died from breast cancer than in patients who remained disease free (11.6+/-7.1 vs. 1.95+/-0.95). Higher levels of ROCKI were associated with increased grade (0.95+/-0.73 grade-1; 2.11+/-1.72 grade-2; and 4.06+/-1.99 grade-3). Levels of ROCKI, but not ROCKII, were significantly correlated with overall survival of patients (p=0.004, Univariate analysis, median follow-up 120 month). These results show that ROCKI and possibly ROCKII are key factors in regulation of motility/invasion of breast cancer cells. This, together with significant correlation between ROCKI and poor outcome in clinical breast cancer, indicates that it is a potential target in human breast cancer.
 ...
PMID:The expression and prognostic value of ROCK I and ROCK II and their role in human breast cancer. 1869 90

We performed this research mainly to explore the effect of bone sialoprotein (BSP) silence by siRNA on the adhesion ability to bone matrix of bone-seeking breast cancer cells (MDA-MB-231BO). Also we aimed to provide experimental data for prevention and treatment of breast cancer bone metastasis by targeting BSP. We explored the effects of BSP gene silence on characteristics of bone-seeking breast cancer cells: proliferation by MTS[3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay, bone adhesion ability by a mouse bone adhesion model in vitro, morphology of the cells by SEM, and secretion of transforming growth factor-beta1 (TGF-beta1) and receptor activator of nuclear factor-kappa B ligand (RANKL) by ELISA kits. We performed intra-cardiac injection in nude mice to explore bone metastatic ability of different cell lines. The results showed that knockdown of BSP significantly inhibited the proliferation of MDA-MB-231BO cells and their adhesion to bone matrix. We also observed bone destruction caused by bone resorption around some adhering cells. The appearances of the cells changed in BSP gene silenced group, and the secretion of TGF-beta1 and RANKL decreased. The results showed BSP gene silence can partial inhibition bone metastasis of breast cancer cells in nude mice by X-ray assay and hematoxylin-eosin staining. Based on our research, siRNA-mediated BSP silencing can inhibit proliferation and adhesion to bone matrix of bone-seeking breast cancer cells and change their surface structure, thus inhibits their bone metastatic ability.
 ...
PMID:[Inhibitory effect of bone sialoprotein silencing on the adhesion ability of breast cancer cells to bone matrix]. 2165 48


1 2 3 4 5 6 Next >>