UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protective function of the pineal hormone melatonin in the etiology of cancer and carcinogenic activation is increasingly well-established. Low melatonin levels seem to parallel cancer growth. The question arises as to which factors cause the depression of melatonin levels and what the direct effects are. Melatonin is known to be metabolized in the liver by hydroxylation and subsequent conjugation yielding 6-sulfatoxymelatonin as a main product. Nevertheless, the microsomal monoxygenases catalyzing the first step have been poorly investigated. To further characterize these enzymes, typical inducers of three different sub-classes, namely phenobarbital, 7,12-dimethylbenz[a]anthracene, and 17 beta-estradiol, were administered to female Fischer rats. Circadian urinary excretion patterns of melatonin and 6-sulfatoxymelatonin were determined over a 24-hour period on the third (second) day of induction. Liver homogenates were used to monitor the in vitro conversion of melatonin or 6-hydroxymelatonin to 6-sulfatoxymelatonin. Results of both approaches showed the microsomal monoxygenases catalyzing the 6-hydroxylation of melatonin to be strongly inducible by phenobarbital and to a lesser degree by the polyaromatic hydrocarbon 7,12-dimethylbenz[a]anthracene. The dramatic depletion of circulating melatonin as a result of these induction patterns and its possible implications for oncogenesis are discussed.
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PMID:Hepatic hydroxylation of melatonin in the rat is induced by phenobarbital and 7,12-dimethylbenz[a]anthracene--implications for cancer etiology. 772 2

Despite the problems of interpreting epidemiological studies and the difficulty in developing appropriate animal models, there is growing evidence that moderate habitual physical activity can protect against certain types of neoplasm, particularly tumors of the colon and the female reproductive tract. Exercise programs also appear to have a beneficial influence on clinical course, at least in the early stages of the disease. Recent demonstration of exercise-induced changes in the activity of macrophages, natural killer cells, lymphokine activated killer cells, neutrophils, and regulating cytokines suggest that immuno-modulation may contribute to the protective value of exercise. Depression of immune function, such as in HIV infection and in old age, is associated with an enhanced susceptibility to tumors; but the sites of tumorigenesis in HIV infection are not those that gain protection from physical activity. Further research is thus needed before it can be asserted that favorable exercise-induced changes in immune function have a material influence on the risks posed by various types of cancer.
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PMID:Cancer, immune function, and physical activity. 774 65

We have previously found that natural killer (NK) activity is profoundly decreased in BALB/c mice bearing large mammary tumors. Kinetic studies showed that after 14 days of tumor implantation a reduction of 25-40% of NK cytotoxicity can be observed and by 21 days only very low levels of NK reactivity can be detected in the spleens of tumor bearers. Phenotypic analyses of the splenic NK cells of tumor bearing mice revealed that they have similar density, granularity and comparable levels of NK 2.1 antigen on their surfaces as compared to NK cells from normal mice. However, in tumor bearers there was a shift from a high surface asialo GM1-bearing NK population to low-density surface asialo GM1-positive bearing cells. Phenotypically characterized NK cells were quantitated to test the possibility that splenic NK cells from tumor bearers migrated to other organs and were therefore at lower levels in the spleen. No significant differences were observed in the percentages of NK cells from spleens from normal and tumor bearing mice. Using single cell conjugate assays it was found that there was no impairment in the capacity of NK from tumor bearers to bind the NK-sensitive Yac-1 cells, however, this event did not result in lysis of the target cells. To elucidate whether the lytic machinery of the tumor bearers' NK cells was inactivated, their capacity to effect antibody dependent cellular cytotoxicity (ADCC) was evaluated. In contrast to the results observed when NK activity was evaluated, NK cells from tumor bearing mice exerted higher levels of ADCC than their normal counterparts and they had a higher expression of Fc receptors on their surfaces. These results suggest that the depression of NK activity observed in tumor bearing mice occurs at a triggering step that is not necessary for the activation of the NK effectors via the Fc receptor and that no major impairment of the lytic machinery occurs during mammary tumorigenesis.
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PMID:NK cells from mammary tumor bearing mice do not exert natural killer activity but function as antibody dependent cellular cytotoxicity effectors. 847 11

Hepatocytes isolated from male B6C3F1 mice and maintained in primary culture were exposed to epidermal growth factor (EGF), hepatocyte growth factor (HGF), acidic fibroblast growth factor (aFGF) alone or in combination with the mitoinhibitory transforming growth factor beta 1 (TGF-beta 1). Groups of mice were exposed to 3.5 g/l dichloroacetic acid (DCA), 0.1% phenobarbital (PB) or the drinking water vehicle for 0, 2, 5, 10, 20, 30, 60, or 90 days. Following a 2 h attachment period, the growth factors with or without TGF-beta 1 were added together with [3H]thymidine. The cells were harvested 48 h later and the incorporation of the labeled thymidine into cellular DNA was determined. Basal DNA synthesis was enhanced following 2 days of PB treatment after which it declined to levels significantly below that in the untreated mice. No early time enhancement of DNA synthesis was measured in the hepatocyte cultures for animals exposed to DCA, but the late time inhibition was also seen. Primary cultures of hepatocytes isolated from control and DCA treated mice exhibited similarly enhanced DNA synthesis in response to eGF, HGF, or aFGF alone or in combination with TGF-beta 1. In contrast, hepatocytes from PB treated animals were refractory to the effects of the growth factors at all time periods. These data suggest that the early depression of cell proliferation we have seen during DCA induced hepatocellular cancer is not due to an impaired ability of hepatocytes to respond to growth factors and that the mechanisms of liver tumorigenesis in the mouse induced by PB and DCA are dissimilar.
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PMID:Responsiveness of hepatocytes from dichloroacetic acid or phenobarbital treated mice to growth factors in primary culture. 861 22

Protein proteinase inhibitors are widely distributed in plant seeds, particularly in legumes. The specificity and potency of inhibition depend on defined inhibitory sites and on the animal species of the target proteinase. Feeding experiments on diets containing isolated soybean trypsin inhibitors (the Kunitz soybean trypsin inhibitor STI and the Bowman-Birk trypsinchymotrypsin inhibitor BBI) caused insignificant growth depression in rats and chicks, but induced enlargement of the pancreas in rats, chicks and mice but not in pigs, dogs, calves, monkeys and presumably humans. The trypsin-inhibitory site has been responsible for induction of the pancreatic enlargement. The trypsin-chymotrypsin inhibitors from soybeans and from chickpeas inhibit insect midgut proteinases, supporting the hypothesis that proteinase inhibitors comprise a built-in defense mechanism of the seed against insects. Findings on the involvement of proteinase inhibitors, such as BBI, in prevention of tumorigenesis suggest a possible positive contribution of the inhibitors to the nutritional value of legume seeds. BBI is also an effective inhibitor of nephrotoxicity induced by the antibiotic gentamicin. BBI does not cause side effects and does affect the antimicrobial activity. The in vitro effects of proteinase inhibitors on animals should be interpreted with caution when related to humans.
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PMID:Protein proteinase inhibitors in legume seeds--overview. 913 35

Insulin-like growth factors (IGF-I and -II) play an active role in cell proliferation. In biological fluids, they are non-covalently bound to high-affinity binding proteins (IGFBPs), at least 6 species of which have been identified to date, but with poorly defined functions. One of these IGFBPs, IGFBP-2, is secreted by most cell lines and appears to be involved in cell proliferation. A human epidermoid carcinoma cell line, KB 3.1, which produces IGFBP-1 and -3 and small amounts of IGFBP-4, but no IGFBP-2, was stably transfected with an expression vector comprising IGFBP-2 complementary DNA (cDNA), whose expression was placed under the control of the constitutive and ubiquitous cytomegalovirus promoter. After an s.c. injection of these IGFBP-2-expressing KB 3.1 cells into nude mice, tumours developed more quickly than in controls, they were 3 to 4 times larger and grew about 3 times as fast. Concomitant with IGFBP-2 expression in these tumours, were a decrease in IGFBP-1 expression and an increase in IGFBP-3 proteolysis, both of which increase the bioavailability of the IGF-II produced by the cells. The increased IGFBP-3 proteolysis most probably resulted from amplified expression of tissue-type plasminogen activator (t-PA) and depression of its inhibitor (PAI-I) observed in IGFBP-2-expressing xenografts. Our findings suggest that IGFBP-2 plays a role in this model of experimental tumorigenesis via a mechanism that remains unclear, but appears to involve increased protease activity and IGF-II bioavailability.
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PMID:IGFBP-2 expression in a human cell line is associated with increased IGFBP-3 proteolysis, decreased IGFBP-1 expression and increased tumorigenicity. 971 57

Estrogen receptor (ER) activity can be modulated by the action of other nuclear receptors. To study whether ER activity is altered by orphan nuclear receptors that mediate the cellular response to xenobiotics, cross-talk between ER and constitutive androstane receptor (CAR), steroid and xenobiotic receptor, or peroxisome proliferator-activated receptor gamma was examined in HepG2 cells. Of these receptors, CAR substantially inhibited ER-mediated transcriptional activity of the vitellogenin B1 promoter as well as a synthetic estrogen responsive element (ERE)-containing promoter. Treatment with an agonist of CAR, 1,4-bis-(2-(3,5-dichloropyridoxyl))benzene, potentiated CAR-mediated transcriptional repression. In contrast, an antagonist of CAR, androstenol, alleviated the repression effect. Although CAR interacted with the ER in solution, CAR did not interact with the ER bound to the ERE. CAR/retinoid X receptor bound to the ERE but with much lower affinity than ER. Incremental amounts of CAR elicited a progressive reduction of the ER activity induced by the p160 coactivator glucocorticoid receptor interacting protein 1 (GRIP-1). In turn, increasing amounts of GRIP-1 progressively reversed the depression of ER activity by CAR. An agonist or antagonist of CAR potentiated or alleviated, respectively, the CAR-mediated repression of the GRIP-1-enhanced ER activity, which is consistent with the ability of theses ligands to increase or decrease, respectively, the interaction of CAR with GRIP-1. A CAR mutant that did not interact with GRIP-1 did not inhibit ER-mediated transactivation. Our data demonstrate that xenobiotic nuclear receptor CAR antagonizes ER-mediated transcriptional activity by squelching limiting amounts of p160 coactivator and imply that xenobiotics may influence ER function of female reproductive physiology, cell differentiation, tumorigenesis, and lipid metabolism.
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PMID:Inhibitory cross-talk between estrogen receptor (ER) and constitutively activated androstane receptor (CAR). CAR inhibits ER-mediated signaling pathway by squelching p160 coactivators. 1211 25

To investigate the effects of apoptosis on colorectal tumorigenesis and its possible biological significance, the apoptotic frequency in primary cultural cell of 9 normal mucosa, 4 adenomas and 9 adenocarcinomas in time period of 2, 12, 24, 48 hour was measured by flow cytometry. The apoptotic cells index (AI) in situ for 15 colorectal normal mucosa, 7 hyperplastic epithelial, 25 adenomas and 77 adenocarcinomas was identified by the terminal deoxynucleotidyl transferasemediated dUTP-biotin nick end labeling technique (TUNEL). Ki-67 proliferate index (KI), wafl and p53 genes were immunostained with ABC method. The results showed that culture related apoptotic incidence was obviously decreased in cultural tumor cell when compared with mucosa cell after 24-48 hour in vitro. There was a directly positive relationship between the spontaneous apoptosis and Ki-67-index in vivo. The well differentiated or early stage lesions with intensive bcl-2 expression were significantly more likely to have low AI and KI. Both mp53 accumulation and wafl depression which mainly related to KI, had no apparent correlation with AI, bcl-2/bax expression and clinicopathological features statistically; elevatory bax/bcl-2 and pervasive wafl depression led to an increasing AI/KI both in adenoma with atypia and in advanced cancer with distant metastasis or embolus, comparatively. The data indicated that the reduction of susceptibility to inductive apoptosis may contribute to the early phase of tumorigenesis, that AI in vivo may reflect proliferative activity, and that bcl family was closely associated with spontaneous apoptosis and biological behavior of human colorectal cancer.
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PMID:[Significance of apoptosis status and apoptosis-associated antigen expression in human colorectal adenocarcinoma sequence]. 1221 55

In the "minimal change" nephrotic syndrome (MCNS), steroids induce remissions in most cases (93% in children and 81% in adults). Response occurs in an average time of 11 days in children but may take up to 16 weeks in adults. The dose of prednisone is 60 mg/m(2)/day (maximum 80 mg/day) given usually for 4 weeks and then reduced to 40 mg/m(2) on alternate days for a few weeks. The medication may be discontinued abruptly at the end of the course of treatment. Children who do not respond to prednisone should be biopsied. Those whose biopsy shows minimal changes may have a remission with more prolonged alternate day treatment, or may need cyclophosphamide or cyclosporine. Relapses of nephrotic syndrome are common and usually respond to steroids given daily until remission, then on alternate days for 4 weeks. In adults prednisone on alternate days for 1 year after the presenting attack decreases the risk of relapse. Toxicity is a problem only in steroid-dependent patients who may require other drugs. Cyclophosphamide (2-3 mg/kg/day) and chlorambucil (0.15 mg/kg/day) for 8-12 weeks induce long-term remissions in 25-70% of children and are also beneficial in adults. The effectiveness of cyclophosphamide in steroid-resistant MCNS is limited to bringing about a faster remission. In children with MCNS who are initially steroid-responsive and later become resistant, cyclophosphamide usually induces a remission and restores steroid responsiveness. The toxicity of cyclophosphamide and chlorambucil in MCNS has generally been mild and reversible. It includes bone marrow depression, hemorrhagic cystitis, some hair loss, infertility and, extremely rarely, oncogenesis. The risk of gonadal toxicity is minimized with total doses below 200 mg/kg for cyclophosphamide and 7-10 mg/kg for chlorambucil. Seizures have been reported in 8% of children treated with chlorambucil. Cyclosporine (6 mg/kg/day initially) produces complete remissions in 85% of children and 79% of adults with steroid dependence and in 67% of children and 61% of adults with steroid resistance. Levamisole may be helpful in steroid-dependent cases, but data about its efficacy are conflicting. Cyclosporine and levamisole usually do not induce permanent remissions.
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PMID:Pharmacological treatment of nephrotic syndrome. 1297 5

Disruption of the regulatory communication from the stroma to the epithelium mediated by the FGF7/10-FGFR2 signaling axis in the prostate and expression of ectopic FGFR1 in prostatic epithelial cells often correlate with prostate cancer progression both in human and in experimental animals. Ectopic expression of constitutively active FGFR1 mutant (caFGFR1) at low levels in prostate epithelial cells induces low- to intermediate-grade prostatic intraepithelial neoplasia (PIN) within 6-8 months and high-grade PIN in 20-25 months. Depression of the FGFR2 signaling in the prostate also disturbs homeostasis in the prostate and induces prostate hyperplasia. To study whether PIN lesions induced by the caFGFR1 were expression-level dependent, and whether expression of the caFGFR1 and depression of the FGFR2 signaling in the prostate synergistically disturbed prostate homeostasis, we generated two new strains of ARR2PBi-caFGFR1 transgenic mice, which highly expressed caFGFR1 in prostatic epithelial cells. The mice were crossed with KDNR mice to generate ARR2PBi-caFGFR1/KDNR bigenic mice. The ARR2PBi-caFGFR1 mice developed high-grade PIN within 8 months, which was significantly faster than the mice expressing caFGFR1 at low levels. In addition, depression of the FGFR2 signaling clearly promoted perturbation of cellular homeostasis induced by the caFGFR1. The results demonstrated that the PIN development in caFGFR1 transgenic mice was caFGFR1 dosage-dependent, and indicated that the ectopic FGFR1 and the resident FGFR2 in epithelial cells had opposite impacts on intercompartmental homeostasis in the prostate. The bigenic mice provide a model with cooperative aberrations in the fibroblast growth factor signaling axis for evaluation of tumor-initiating events in prostate tumorigenesis.
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PMID:Cooperation between ectopic FGFR1 and depression of FGFR2 in induction of prostatic intraepithelial neoplasia in the mouse prostate. 1469 95

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