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

Estrogen-binding proteins were observed in the cytosol of human pituitary adenomas. The Kd for estradiol was 0.44 nM at 0 C, and hormonal specificity was that expected for estrogen receptors. Sucrose gradient sedimentation experiments revealed that receptors from different tumors existed in either the 8S or the 4S form or both. Of the 23 tumors examined, 14 contained estrogen receptors. Receptors were more often present and their concentration was higher in PRL-secreting adenomas (mean +/- SEM, 20.6 +/- 13.4 fmol/mg proteins; 7 determinations) than in GH-secreting adenomas (1.4 +/- 0.8 fmol/mg protein; 9 determinations) and chromophobe tumors (4.1 +/- 1.6 fmol/mg protein; 7 determinations). There was also a correlation between the presence of estrogen receptors and histological signs of cell proliferation and tumor growth.
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PMID:Estrogen receptors in human pituitary adenomas. 741 71

Linomide, a quinoline-3-carboxamide, has the ability to inhibit the growth of prostatic cancer in vivo but not in vitro (T. Ichikawa et al., Cancer Res., 52: 3022-3028, 1992). The reason for this discrepancy is that linomide inhibits tumor growth not directly but indirectly in vivo via its ability to inhibit the angiogenic response induced within the growing prostatic cancer (J. Vukanovic, et al., Cancer Res., 53: 1833-1837, 1993). Tumor associated macrophages can stimulate angiogenesis via their ability to secrete various cytokines, particularly tumor necrosis factor alpha (TNF-alpha). Treatment of rats with linomide decreases significantly (P < 0.05), by more than 50%, the number of tumor associated macrophages within both locally invasive (i.e., from 20-40 to 10 macrophages/high power field) and highly metastatic primary prostatic cancers (i.e., from 60-70 to 15-37 macrophages/high power field). Monocytes/macrophages isolated from linomide treated rats had a decreased ability to secrete TNF-alpha when challenged in vitro with the bacterial endotoxin, lipopolysaccharide [i.e., 702 +/- 76 (SEM) ng of TNF-alpha/10(5) monocytes/macrophages from control versus 401 +/- 2 ng of TNF-alpha/10(5) monocytes/macrophages from linomide treated rats]. In addition, when rats were treated with linomide and than challenged with lipopolysaccharide in vivo, the resulting elevation in serum TNF-alpha was inhibited by approximately 50% (i.e., 4.56 +/- 1.8 ng/ml of TNF-alpha in control versus 2.9-2.2 ng/ml depending upon the dose of linomide). The ability of linomide to decrease monocyte/macrophage secretion of TNF-alpha is not immediate, however, since the secretion of TNF-alpha induced by lipopolysaccharide challenge of monocytes/macrophages isolated from untreated animals is not decreased by acute (i.e., < 4 h) linomide treatment in vitro. These results demonstrate that the ability of linomide to inhibit the secretion of TNF-alpha by monocytes/macrophages requires either additional time or host factors. To test if natural killer (NK) cells might be one of the additional host factors required for the in vivo abilities of linomide, prostatic cancer bearing rats were treated with appropriate antiserum to deplete NK cells and then tested for their response to linomide treatment. These studies demonstrated that the antitumor, antimetastatic, and antimacrophage effects of linomide were unaffected by NK cell depletion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Linomide inhibits angiogenesis, growth, metastasis, and macrophage infiltration within rat prostatic cancers. 753 63

The effect of the irreversible S-adenosyl-L-homocysteine hydrolase inhibitor, (Z)-5'-fluoro-4',5'-didehydro-5'-deoxyadenosine (MDL 28,842), on C-1300 murine neuroblastoma (MNB) cell proliferation in tissue culture and MNB tumor growth in vivo were investigated. MNB cells were incubated with MDL 28,842 at concentrations ranging from 8 x 10(-9) M to 1.6 x 10(-5) M for 3 days, and cell proliferation was determined by use of a CellTiter 96-well Proliferation Assay Kit. In tissue culture, MDL 28,842 inhibited MNB cell proliferation in a concentration-dependent manner, and the IC50 of MDL 28,842 against MNB in tissue culture was 1.8 x 10(-7) M. The response of in vivo tumor growth and host survival to MDL 28,842d was evaluated in a syngeneic mouse tumor model prepared by s.c. implantation of 1 x 10(6) MNB cells into A/J mice. Following palpation of a tumor mass, osmotic minipumps were implanted into each mouse. MDL 28,842 was infused at rates of 1.0 or 1.5 mg/kg/day over a 10-day period and 1.25 mg/kg/day over a 30-day period. The mean survival time of tumor-bearing mice significantly increased from 28.75 +/- 1.06 days (mean +/- 2 SEM) in the control group (diluent infusion) to 39.33 +/- 1.58 days, 44.11 +/- 1.74 days, and 41.0 +/- 1.30 days in the MDL 28,842-treated groups receiving 10-day infusions of 1.0 and 1.5 mg/kg/day or 30-day infusions of 1.25 mg/kg/day, respectively. No significant differences in survival rate were noted between groups receiving 10 vs 30 days of drug treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Suppression of C-1300 murine neuroblastoma cell proliferation in tissue culture and tumor growth in vivo by (Z)5'-fluoro-4',5'-didehydro-5'-deoxyadenosine (MDL 28,842), an irreversible inhibitor of S-adenosyl-L-homocysteine hydrolase. 805 4

The ruthenium-dimethylsulfoxide complex Na(trans-RuCl4(DMSO)Im] was given i.v. to mice bearing MCa mammary carcinoma and its effects on tumor growth and on healthy host tissues were studied by macroscopic examination of primary tumor growth, by survival time, and by histological analysis using light microscopy and SEM. Either by means of vivo-vivo bioassays or by microscopic examination it appeared that the growth of lung tumors was markedly reduced, whereas the growth of the i.m. primary tumor was much less affected. These effects account for the prolongation of survival time and for the cure rate observed. The favourable effect on survival time was also influenced by the lack of significant cytotoxicity for normal tissues such as lung and kidney epithelia, muscle and liver cells, splenocytes and bone marrow. It thus appears that the selective interaction with tumor cells in the lungs cannot simply be attributed to a selectively higher localization of the compound at this site, nor to a modification of the histological structure of primary tumor. These results highlight the pharmacologic properties of this compound for the control of solid tumor metastases, an effect that was shown to be similarly exerted on advanced tumor metastases.
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PMID:Antimetastatic action and toxicity on healthy tissues of Na[trans-RuCl4(DMSO)Im] in the mouse. 830 32

The growth of implanted mammary adenocarcinoma 13762 was measured in rats consuming a liquid diet (35% fat, 18% protein, 47% carbohydrate) supplemented with pyruvate (37.3 g/liter; n = 13) or maltose-dextrin (placebo; n = 13) for 21 days. Mean tumor diameter, measured on day 11, 14, 18, and 21 subsequent to tumor implantation, was 41, 32, 21, and 19% smaller in the pyruvate group (P < 0.05). When euthanized, tumor weight was also smaller in the pyruvate group: pyruvate = 15.0 +/- 2.3 (SEM) g; placebo = 24.9 +/- 3.2 g, P < 0.05. Visual inspection of organs suggested decreased lung metastases with pyruvate feeding (P < 0.05). Upon microscopic evaluation of organs, hepatic tumor was found only in the placebo group. We conclude that pyruvate inhibits implanted tumor growth in rats.
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PMID:Pyruvate inhibits growth of mammary adenocarcinoma 13762 in rats. 831 54

The antitumor effect of 22-oxa-calcitriol (OCT), a newly developed noncalcemic analogue of calcitriol, was examined in vivo in athymic mice implanted with human breast carcinoma with or without estrogen receptor (ER). In ER-positive MCF-7 tumor, the growth of which was dependent on exogenous estrogen, administration p.o. of OCT as well as the antiestrogen tamoxifen five times a week for 4 weeks suppressed tumor growth in a dose-related fashion. The antitumor effect of 1.0 microgram/kg body weight (BW) OCT (mean +/- SEM of tumor weight in 6 mice: 28 +/- 4% of vehicle-treated group) was comparable to that of 2.0 mg/kg BW tamoxifen (25 +/- 6% of control group). In addition, a synergistic antitumor effect of submaximal doses of OCT and tamoxifen was observed in MCF-7 tumor in vivo as well as in ER-positive breast carcinoma cell lines (MCF-7 and ZR-75-1) in vitro. Administration of OCT p.o. three times a week for 4 weeks also suppressed the growth of ER-negative MX-1 tumor in a dose-dependent manner without raising serum calcium concentrations. The antitumor effect of 1.0 microgram/kg BW OCT (mean +/- SEM of tumor weight in 10 mice: 44 +/- 6% of vehicle-treated group) was greater than that of 500 micrograms/kg BW Adriamycin (71 +/- 6% of control group). These results indicate that OCT suppresses the growth of ER-negative as well as ER-positive breast carcinoma in vivo without causing hypercalcemia and that the antitumor effect of OCT can be enhanced by tamoxifen in an ER-positive tumor. It is suggested that OCT may provide a new strategy, either alone or in combination with other anticancer drugs, for systemic adjuvant therapy of breast carcinoma regardless of ER status.
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PMID:Antitumor effect of 22-oxa-calcitriol, a noncalcemic analogue of calcitriol, in athymic mice implanted with human breast carcinoma and its synergism with tamoxifen. 849 16

The role of human growth hormone (hGH) as a nutritional adjunct for cancer patients is controversial because of its potential mitogenic effects on tumor growth. No studies to date have examined the effect of hGH on human tumor response in vivo. In Vitro: Athymic mice were injected (s.c.) daily with hGH (GH, n=14) or saline (CTL, n=14). On Day 10, serum was collected and added to human pancreatic carcinoma cells in culture. In Vivo: Athymic mice were inoculated (s.c.) with human pancreatic carcinoma cells. On Day 14, mice were randomized to receive daily either hGH (GH, n=14) or saline (CTL, n=12). On Day 29, animals received [3H]phenylalanine for tissue protein fractional synthetic rate (FSR) measurement. Tumors were excised and cell cycle kinetics analyzed. Data are expressed as mean +/- SEM. Statistical analysis was performed by unpaired t test and/or ANOVA where appropriate. In Vitro: Serum from GH-treated animals had elevated IGF-1 levels (287 +/- 34 ng/ml vs 157 +/- 53 ng/ml, P<0.001) and significantly stimulated cell growth (No. cells x 10(3)/well) compared with CTL serum (925 +/- 31 vs 747 +/- 38, P<0.001). In Vivo: Serum for GH-treated animals had elevated IGF-1 levels (287 +/- 34 ng/ml vs 157 +/- 53 ng/ml, P<0.001) and significantly stimulated cell growth (No. cells x 10(3)/well) compared with CTL serum (925 +/- 31 vs 747 +/- 38, P<0.001). In Vivo: Growth hormone had no significant effect on tumor growth rate (mm3/day) (1.45 +/- 0.47 CTL vs 1.57 +/- 0.66 GH), final tumor weight (mg) (0.19 +/- 0.15 CTL vs 0.17+/- 0.06 GH), DNA Index (1.5 +/- 0.1 CTL vs 1.5 +/- 0.1 GH), percent S phase (20.3 +/- 3.3 CTL vs 22.1 +/- 3.0 GH), or tumor FSR (%/day) (51.1 +/- 17.8 CTL vs 70.2 +/- 61.1 GH). Growth hormone significantly elevated serum IGF-1 levels (ng/ml) (176 +/- 48 CTL vs 222 +/- 53 GH, P<0.005) and liver FSR (%/day) (62.8 +/- 17.8 CTL vs 79.7 +/- 12.7 GH, P<0.005). Serum of GH-treated mice increased human pancreatic cell growth in vitro. In vivo, GH administration raised serum IGF-1 levels and increased liver protein FSR, without tumor growth, cell cycle kinetics, or protein FSR.
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PMID:Effect of human growth hormone on human pancreatic carcinoma growth, protein, and cell cycle kinetics. 865 2

The objective of this study was to provide the first quantitative measurements of the process of vascular growth in the rat peritoneal disseminated tumor model in both arteriolar and venular systems. Male Fischer 344 rats were injected intraperitoneally with 1 x 10(7) cells of colon carcinoma cell line (RCN-9). Three to eleven days after tumor cell inoculation, the rats were subjected to intravital microscopic observation of the mesenteric microcirculation. Accompanying tumor growth, mesenteric windows showed a marked neovascularization. The branching pattern of the vascular network was analyzed based on Horton's law of bifurcation. Arterioles and venules were given an order of branching separately according to the Strahler's nomenclature, and the number of vessel segments (N) having the same order number was counted. A vascular density index (VDI) and a bifurcation ratio (BR) were calculated from a semilogarithmic plot of the vessel density (dividing N by the vascularized area) against vessel order. Values of the VDI in venules (3.1 +/- 0.3 in the tumor-free rats, mean +/- SEM, n = 6) were found to be larger than those in arterioles (1.8 +/- 0.2). These values in both arterioles and venules showed a significant increase with time after the tumor cell inoculation (in venules, 12.3 +/- 1.1 at 9-11 days after the tumor cell inoculation; in arterioles, 5.7 +/- 0.7). Moreover, the rate of increase in the venular VDI was larger than that of the arteriolar VDI. The arteriolar BR remained almost constant (3.8 +/- 0.2 for the tumor-free rats and 4.1 +/- 0.1 for 9-11 days after tumor cell inoculation), whereas the venular BR showed an increase with time (3.0 +/- 0.1 and 3.8 +/- 0.2, respectively). In conclusion, a marked angiogenesis was observed in the mesentery of the rats bearing peritoneal tumors. Neovascularization was found to occur predominantly in the venular system.
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PMID:Angiogenic vascular growth in the rat peritoneal disseminated tumor model. 881 50

This study describes ultrastructural alterations of the interstitial stroma in the rat bladder epithelium during N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder carcinogenesis using scanning (SEM) and transmission (TEM) electron microscopy with NaOH treatment. The results obtained with SEM demonstrated the occurrence and development of stroma protrusions which exhibited pipe-like structures in the rat bladder epithelium following administration of BBN. Number and size of blood vessel sections also gradually increased both in the stroma and within the layer of the proliferated epithelial cells as examined by light microscopy (LM) and TEM. In this study stroma alterations were not only observed in malignant lesions of rat bladder, but hyperplastic lesions were also accompanied by stroma alterations. It is suggested that: (1) the interstitial stroma of the rat bladder epithelium may exhibit pathological changes in structure and these changes may correlate with the progression of epithelial cell proliferation following administration of BBN and (2) one of the most important alterations in the stroma is the occurrence of neovascularization, which may induce structural modification of the stroma in the processes of bladder tumor growth and development.
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PMID:Interstitial stroma and carcinogenesis: ultrastructural observations in the rat bladder treated with N-butyl-N-(4-hydroxybutyl)nitrosamine. 883 86

Resistance to bromocriptine, defined as the absence of normalization of prolactin (PRL) levels despite a 15-30 mg daily dose of bromocriptine during at least 6 months, has been observed in 5-17% of the prolactinomas according to the literature. The recent availability of a new potent dopamine agonist, quinagolide, prompted us to analyze its long-term therapeutic effects in 28 patients with prolactinomas resistant to bromocriptine. Before bromocriptine, their PRL levels were 520 +/- 185 micrograms/l (mean +/- SEM) and decreased to 291 +/- 154 micrograms/l after a 6-21 month period of bromocriptine treatment. All the women (N = 20) remained amenorrheic and hypogonadism was not improved in men (N = 8). Subsequently, after 1 year of 150-300 micrograms/day quinagolide, 12/28 patients of the present series recovered normal gonadal function and their initial mean baseline PRL value (404 +/- 180 micrograms/l) was 16 +/- 2 micrograms/l after 1 year of treatment. A significant tumor shrinkage was observed in 5/8 macroadenomas (62%). During the 3-year follow-up period under quinagolide, a similar good control was achieved in these patients, with the exception of one man presenting with a secondary rise of PRL under quinagolide. In contrast, 15 other patients (one patient interrupted quinagolide at 6 months because of poor tolerance) were not normalized under 150-450 micrograms/day quinagolide. Their initial PRL levels (606 +/- 298 micrograms/l) were reduced to 343 +/- 187 micrograms/l (versus 463 +/- 265 micrograms/l under bromocriptine after the same duration of treatment). Despite such a partial inhibitory effect of quinagolide, 7/12 women resumed menstrual cycles and three pregnancies occurred. In no case was any tumor shrinkage noticed during the 3-4-year follow-up. Three patients even presented, after 2 years of quinagolide treatment, with a secondary rise of PRL values associated with a further tumor growth in two patients. During the 3-year follow-up period, nine pregnancies occurred in seven women. In five women, after quinagolide withdrawal, the plasma PRL baseline values ranged from 52 to 158 micrograms/l and from 65 to 192 micrograms/l, respectively, at the first trimester and at the end of uneventful pregnancies. In contrast, in two women a rapid increase of PRL (240-400 micrograms/l) correlated with tumor growth during the first trimester. Such a tumor progression was blocked by quinagolide treatment but not by bromocriptine. These data, although observed in a limited series, justify the careful follow-up of pregnancies in this subclass of patients at risk. Finally, in the whole population, long-term control of hyperprolactinemia by quinagolide was obtained in 11/28 patients (39%) previously resistant to bromocriptine, and 15/20 women (75%) resumed normal gonadal function with a quinagolide daily dose of 300 micrograms in most of them.
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PMID:Prolactinomas resistant to bromocriptine: long-term efficacy of quinagolide and outcome of pregnancy. 892 22


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