Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant catarrhal fever was diagnosed in 3 herds of American bison (Bison bison) in South Dakota from 1973 to 1976. Clinical signs included depression, nasal and ocular discharge, conjunctivitis and keratitis, and diarrhea. Herd morbidity ranged from 3 to 53.8%, and mortality was 100%. At necropsy, ulcerative lesions were found throughout the alimentary tract, trachea, and bronchi. Microscopically, necrotizing vasculitis without thrombosis was found in virtually every organ examined.
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PMID:Malignant catarrhal fever in bison. 56 70

Previous studies have demonstrated an inverse relationship between estrogen receptor (ER) and epidermal growth factor receptor (EGF-R) gene expression in human breast cancer cells. This relationship was further investigated in MCF 7 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). Exposure to 10 nM TPA resulted in a time-dependent increase in EGF-R mRNA, first apparent at 3 h and maximal between 9 and 24 h. There was a concomitant fall in ER mRNA with a maximum decline to 15-20% of control between 12 and 24 h. Although EGF-R mRNA levels declined between 24 and 72 h, both EGF-R mRNA and EGF-R binding remained above control levels and this was accompanied by a sustained depression of ER mRNA. These data support the view that ER and EGR-R gene expression is inversely regulated in human breast cancer and describe for the first time an inhibitory effect of a phorbol ester on steroid hormone receptor gene expression.
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PMID:Modulation of estrogen receptor and epidermal growth factor receptor mRNAs by phorbol ester in MCF 7 breast cancer cells. 275 60

The successful evaluation of tamoxifen as an antiestrogenic therapy for advanced breast cancer in the early 1970's, has resulted in its availability in more than 70 countries around the world. Currently the drug development process is focusing attention upon long-term adjuvant therapy and the future prospect of chemosuppression. Progress at this stage, however, must be cautious. Trials conducted using women with stage I disease have a high proportion of women who may never have a recurrence. At this point, the risk is justified because the toxicity of tamoxifen is low and disease recurrence is invariably very difficult or impossible to control. Future studies in the general population must be carefully weighed to ensure that the hazards do not exceed the benefits. The pharmacology of tamoxifen seems to be a balance of estrogenic and antiestrogenic effects. Longer treatments with the drug must be carefully monitored. Uterine tissue should be examined to ensure that excessive stimulation does not occur. This is particularly true in the light of the recent report that a human uterine carcinoma, transplanted into athymic mice, can grow more rapidly during tamoxifen therapy (Satyaswaroop et al., 1984; Clark and Satyaswaroop, 1985). In fact, we have recently confirmed this observation in a collaborative study with Dr. Satyaswaroop. We have demonstrated that when athymic mice are transplanted in one axilla with an MCF-7 breast tumor and the human endometrial tumor in the other, tamoxifen causes the endometrial tumor to grow, but not the breast tumor. This again illustrates the target site specific effects of tamoxifen. If, in the long run, the estrogenic side effects of tamoxifen are too severe then there is a case for the development of a non-estrogenic antiestrogen. Clearly this may provide benefit for short term (1-2 years) therapy and avoid any estrogen-like stimulation of tumor growth. Similarly, the concern about antithrombin III depression will be avoided. On the negative side, however, the concerns about atherosclerosis and osteoporosis will again have to be addressed with a new generation of agents.
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PMID:Long-term tamoxifen therapy to control or to prevent breast cancer: laboratory concept to clinical trials. 328 87

We tried to demonstrate that the cell kinetics-directed chemoendocrine therapy is more effective on hormone dependent breast cancer than empirical combination of the endocrine therapy and chemotherapy. Cell kinetics of each tumor was measured by flow cytometric analysis. Estrogen dependent human breast cancer cell line MCF-7 was used in vitro. In vivo, androgen dependent SC-115 carcinoma was transplanted to DDS mice. In vitro, tamoxifen was administered as the endocrine therapy. In vivo, we carried out testectomy on DDS mice. Effect of the endocrine therapy on the cell kinetics of the tumor was thought to be G1-S depression. High density 5FU was administered as the chemotherapeutic agents, whose content was 1 microgram/ml in vitro and 40 mg/kg in vivo. 5FU brought temporary decrease of cells in S phase. Only anteceding 5FU administration had synergistic effect in combination of 5FU and the endocrine therapy. 5FU was convinced to act more effectively on cells in S phase, so it was shown that cell kinetics-directed schedule was superior to the empirical treatment schedule in chemoendocrine therapy.
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PMID:[Synergistic effect of cell kinetics-directed chemo-endocrine therapy on experimental mammary tumors]. 343 37

An autoradiographic technique has been developed to determine the percentage of MCF-7 human breast adenocarcinoma cells in double-layer agar (DLA) culture that exhibit nuclear incorporation of 3H-thymidine (3H-TdR) after in vitro drug exposure. Depression of this percentage, termed the labeling index, correlated closely with colony count inhibition--relative to the respective control values--for cultures exposed to each of several agents including varying concentrations of 5-fluorouracil and adriamycin. If a similar autoradiographic technique can be applied to cultures from human tumor biopsy specimens, this may then lead to a clinically useful chemosensitivity assay especially applicable when DLA-cultured cell quantities are small.
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PMID:Methods for determining chemosensitivity of MCF-7 cells in double-layer agar culture: labeling index depression and colony count inhibition. 715 82

Malignant catarrhal fever (MCF) was transmitted to a bison (Bison bison) by intravenous inoculation of whole blood obtained from a calf showing signs of experimental MCF. Clinical signs evident on the 25th day following inoculation included depression, weakness, epiphora, serous nasal discharge, watery diarrhea and multifocal ulcerations of oral mucosa. Gross and histopathological lesions observed in the bison were similar to those in cattle with a few qualitative differences. Compared to bovine cases, MCF in bison was characterized by more severe edema, congestion, and hemorrhage and accumulation of fewer lymphoid cells in lesions.
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PMID:Experimental transmission of bovine malignant catarrhal fever to a bison (Bison bison). 743 30

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exhibits remarkably potent antiestrogenic activity. To further elucidate the role of estrogen receptor (ER) regulation in this response, we examined the effects of exposure to TCDD in MCF-7 human breast cancer cells on ER mRNA levels by using an RNase protection assay, on ER accumulation by using an ER immunocytochemical essay (ER-ICA), and on ER function by competitive binding assays under conditions of saturating 17 beta-estradiol (E2). Comparative studies were conducted with E2 and 12-O-tetradecanoylphorbol-13-acetate (TPA), as both compounds are known to suppress ER expression. Our results indicate that 1 nM E2 and 100 nM TPA both suppress ER mRNA levels as early as 4 h after exposure and to 33.6% and 16.5% of control levels, respectively, after 72 h. In contrast, no significant effect on ER mRNA levels was attributed to exposure to 10 nM TCDD. A greater than 50% reduction in positive staining was observed by ER-ICA after 72 h exposure to 1 nM E2 and to 100 nM TPA, while only an 11% reduction in positive staining was observed with 10 nM TCDD. Specific binding of [3H]E2 under saturating conditions (10 nM E2) in whole cells was reduced by 50% in cultures exposed to 100 nM TPA, although no effect on binding was observed with exposure to 10 nM TCDD. In contrast, specific binding using subsaturating 1 nM [3H]E2 was depressed by 49% in MCF-7 cells exposed to 10 nM TCDD for 72 h. This depression was inhibited by a 1-h treatment with 5 microM alpha-naphthoflavone, which inhibits TCDD-induced, P450-mediated, E2 metabolism, and subsequent E2 depletion. In conclusion, while TPA and E2 effectively down-regulate ER expression, TCDD, under antiestrogenic conditions, has little if any effect on total ER levels in MCF-7 cells, and thus ER modulation is probably not necessary for the suppression of estrogenic activity in MCF-7 cells by TCDD.
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PMID:Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin, 12-O-tetradecanoylphorbol-13-acetate and 17 beta-estradiol on estrogen receptor regulation in MCF-7 human breast cancer cells. 865 28

Catechol-O-methyltransferase (COMT, EC 2.1.1.6) is a ubiquitous enzyme that is crucial to the metabolism of carcinogenic catechols and catecholamines. Regulation of human COMT gene expression may be important in the pathophysiology of various human disorders including estrogen-induced cancers, Parkinson's disease, depression, and hypertension. The gender difference in human COMT activity and variations in rat COMT activity during the estrous cycle led us to explore whether estrogen can regulate human COMT gene transcription. Our Northern analyses showed that physiological concentrations of 17-beta-estradiol (10(-9)-10(-7) M) could decrease human 1. 3-kilobase COMT mRNA levels in MCF-7 cells in a time- and dose-dependent manner through an estrogen receptor-dependent mechanism. Two DNA fragments immediately 5' to the published human COMT gene proximal and distal promoters were cloned. Sequence analyses revealed several half-palindromic estrogen response elements and CCAAT/enhancer binding protein sites. By cotransfecting COMT promoter-chloramphenicol acetyltransferase reporter genes with human estrogen receptor cDNA and pSV-beta-galactosidase plasmids into COS-7 cells, we showed that 17-beta-estradiol could down-regulate chloramphenicol acetyltransferase activities, and COMT promoter activities dose-dependently. Functional deletion analyses of COMT promoters also showed that this estrogenic effect was mediated by a 280 base pair fragment with two putative half-palindromic estrogen response elements in the proximal promoter and a 323-base pair fragment with two putative CCAAT/enhancer binding protein sites in the distal promoter. Our findings provide the first evidence and molecular mechanism for estrogen to inhibit COMT gene transcription, which may shed new insight into the role of estrogen in the pathophysiology of different human disorders.
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PMID:Characterization and implications of estrogenic down-regulation of human catechol-O-methyltransferase gene transcription. 1038 81

Hypericin is the presumed active moiety within Saint John's wort. Extracts of Saint John's wort are widely used as an effective treatment for depression. Available as "over-the-counter" drugs, they are frequently part of the self-medication of patients undergoing radiation therapy for malignant diseases. In addition to antidepressive properties, hypericin has been shown to be able to induce apoptosis and radiosensitize tumor cells, and to have antiinflammatory and phototoxic skin effects. However, the underlying mechanisms are not clear. In this study, we investigated possible inhibitory effects of hypericin on proteasome function and related pathways. Extracts from U373 human glioma cells were incubated with different concentrations of hypericin. Three proteasome activities were monitored using a fluorogenic peptide assay. Activity of the transcription factor NF-kappaB and protein levels of p65, p50, IkappaBalpha and caspase-3 were investigated by EMSA and Western blotting, respectively. Hypericin caused a dose-dependent and photoactivation-independent inhibition of proteasome function. Hypericin treatment (6.25-50 microM) inhibited NF-kappaB, caused accumulation of phosphorylated IkappaBalpha, decreased p50 protein levels and induced cleavage of p65 protein in U373 cells. These effects were observed in MCF-7 cells only at higher concentrations of hypericin (12.5-50 microM). Additionally, inhibition of NF-kappaB activity in U373 cells by hypericin was prevented by caspase inhibition. Although hypericin clearly inhibits proteasome function, its effect NF-kappaB DNA-binding activity was not exclusively proteasome-dependent. The underlying mechanism might also involve caspase activation, a consequence of proteasome inhibition.
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PMID:Hypericin-an inhibitor of proteasome function. 1567 61

Malignant catarrhal fever was transmitted from affected to recipient red deer (Cervus elaphus) using blood or lymphoid suspension as inoculum. Incubation periods ranged from 11 to 26 days. The disease was also transmitted using lymphoid suspension stored overnight at 4 degrees C or at -70 degrees C for 8 months. The experimental disease was characterised by fever, depression, anorexia, diarrhoea and dysentry. The course of the disease was approximately 96 hours. Major lesions consisted of acute mesenteric lymphadenitis and acute haemorrhagic typhlitis and colitis. Lesions in the caecum and colon started as multifocal mucosal haemorrhages and progressed rapidly to massive mucosal haemorrhage.
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PMID:Experimental transmission of malignant catarrhal fever to red deer (Cervus elaphus). 1603 Sep 36


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