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)

Cellular immune competence and cell-mediated immunity to tumor antigens have been studied in patients with breast cancer. Some patients have been shown to have depressed lymphoproliferative responses to phytohemagglutinin and in mixed leukocyte culture. In some cases, this depression appeared attributable to suppressor cells. Many patients with breast cancer had a cellular immunity to extracts of autologous or allogenetic tumors, as detected by lymphoproliferation and leukocyte migration inhibition assays. In addition, some breast cancer patients reacted to antigens associated with murine mammary tumor virus. Some of the tests for cellular immunity have revealed correlations with clinical course and, therefore, may be of use in the management of patients with breast cancer.
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PMID:Assessment of cellular immune response to cancer of the breast. 22 63

Depression is often characterized by increased cortisol secretion caused by hyperactivity of the hypothalamic-pituitary-adrenal axis and by nonsuppression of cortisol secretion following dexamethasone administration. This hyperactivity of the hypothalamic-pituitary-adrenal axis could result from a reduced glucocorticoid receptor (GR) activity in neurons involved in its control. To investigate the effect of reduced neuronal GR levels, we have blocked cellular GR mRNA processing and/or translation by introduction of a complementary GR antisense RNA strand. Two cell lines were transfected with a reporter plasmid carrying the chloramphenicol acetyltransferase (CAT) gene under control of the mouse mammary tumor virus long terminal repeat (a glucocorticoid-inducible promoter). This gene construction permitted assay of the sensitivity of the cells to glucocorticoid hormones. Cells were also cotransfected with a plasmid containing 1,815 bp of GR cDNA inserted in the reverse orientation downstream from either a neurofilament gene promoter element or the Rous sarcoma virus promoter element. Northern (RNA) blot analysis demonstrated formation of GR antisense RNA strands. Measurement of the sensitivity of CAT activity to exogeneous dexamethasone showed that although dexamethasone increased CAT activity by as much as 13-fold in control incubations, expression of GR antisense RNA caused a 2- to 4-fold decrease in the CAT response to dexamethasone. Stable transfectants bearing the GR antisense gene fragment construction demonstrated a 50 to 70% decrease of functional GR levels compared with normal cells, as evidenced by a ligand-binding assay with the type II glucocorticoid receptor-specific ligand [3H]RU 28362. These results validate the use of antisense RNA to GR to decrease cellular response to glucocorticoids.
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PMID:Decreased glucocorticoid receptor activity following glucocorticoid receptor antisense RNA gene fragment transfection. 199 14

Four different canine mammary tumor (CMT) cell lines and a nonneoplastic primary culture of mammary cells were examined for their in vitro responsiveness to selenium supplementation. These cell lines were found to vary in their metabolic response to increasing concentrations of selenium. Sensitivity to selenium, as sodium selenite, increased with increasing concentrations of this trace element in all of the neoplastic lines. These data also suggest that increasing the plating density of tumor cells further increases the sensitivity to selenium. A relatively selenium-sensitive cell line (CMT-13) and relatively insensitive cell line (CMT-11) were characterized on the basis of reduced growth resulting from selenium supplementation. Increasing the concentration of selenium to 0.75 microgram/ml depressed the growth of CMT-13 and CMT-11 cells by 75% and 11%, respectively, while no inhibition was observed in nonneoplastic cells. These cell lines also varied in their sensitivity to different forms of selenium. Selenodiglutathione was the most effective form of selenium examined that inhibited tumor cell growth. The sensitivity of the neoplastic lines was selenodiglutathione much greater than sodium selenite much greater than selenocystine greater than selenomethionine. None of the forms of selenium examined inhibited the growth of the nonneoplastic mammary cells in culture. Supplementation with sodium selenite (1 microgram Se per ml) for 60 min resulted in a dramatic depression in RNA biosynthesis in CMT-13, but not CMT-11 or nonneoplastic cells.
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PMID:Differential effects of selenium on normal and neoplastic canine mammary cells. 242 32

A novel antitumor antibiotic, 2a,3,4,5,6,6a,7,11b-octahydro-11-methoxy-12-methyl-3,6-imino-1H-2-oxa-11 c- azanaphth(1,2,3-cd)azulene-5-carboxylic acid monocitrate (quinocarmycin citrate; KW2152) was selected for investigation in a number of experimental tumor systems because of its efficacy against P388 leukemia. In the initial studies with P388 leukemia (i.p.-i.p.), KW2152 gave an increase in life span of greater than 80%. The activity was schedule dependent and daily administration was the most effective. KW2152 caused marginal activity against L1210 leukemia, B16 melanoma, and M5076 sarcoma. The effect on cultured cells suggested that KW2152 was not cross-resistant to Adriamycin (ADM) but was cross-resistant to mitomycin C (MMC); however, KW2152 caused prolongation of life span against mice bearing P388/ADM or P388/MMC. In tests against human tumors xenografted s.c. in nude mice, KW2152 significantly inhibited the growth of MX-1 mammary carcinoma with all tumors cured at i.v. doses of 4.4 mg/kg/day and p.o. doses of 26.2 mg/kg/day given daily for 7 days. KW2152 also inhibited distinct human gastric carcinomas, St-4 and St-15 tumors, and colon carcinoma Co-3 by daily administration for 7 days. Against St-4, KW2152 gave a treated versus control percentage of 27, compared to 52 for cis-diamminedichloroplatinum. Against Co-3, KW2152 was at least as effective as MMC, ADM, cis-diamminedichloroplatinum, and bleomycin, giving a treated versus control percentage of 18 at a dose of 8.6 mg/kg/day given daily for 7 days. KW2152 showed growth inhibitory activity against cultured murine tumors and human cells. The order of in vitro efficacy of KW2152 against murine tumors, P388 leukemia greater than L1210 leukemia, B16 melanoma, correlated with the order of the sensitivity on the i.p.-i.p. systems of these tumors. The 50% inhibitory concentrations against P388 leukemia cells were 5.3 X 10(-6) and 1.1 X 10(-7) M after 1 and 72 h exposure, respectively. KW2152 caused significant inhibition of RNA synthesis after a short time exposure. In P388 leukemia cells exposed for 1 h with KW2152, the 50% inhibitory concentration for RNA synthesis was 10(-5) M, 30-fold less than that for DNA synthesis. White blood cell depression or platelet depression was not significant after administration of the i.v. 10% lethal dose given daily for 7 days. Because of its good activity against human mammary tumor MX-1 and some effectiveness against other gastric and colon carcinomas and its water solubility, a novel antitumor antibiotic, KW2152, is being developed as a Phase I anticancer agent.
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PMID:Antitumor activity of a novel antitumor antibiotic, quinocarmycin citrate (KW2152). 243 18

On the theory that early pregnancy may protect women against breast cancer by a long-term depression of prolactin secretion, basal and perphenazine-stimulated release of prolactin, as well as basal and GnRH- stimulated release of LH and FSH were assayed in women before and after their 1st full term pregnancy, and in groups of parous and nulliparous women. The study groups were 15 women aged 18-23 and 9 women aged 29- 40. All hormone samples were taken at 0800 in the early follicular phase on women who had never taken oral contraceptives, or in the cross section survey, women who had not been exposed for at least 6 months. There were no significant differences in LH or FSH basal or stimulated levels for 100 minutes after GnRH. In contrast after term pregnancy both basal and stimulated prolactin levels were significantly lower than comparable levels in nulliparous controls. Parous women returned for their second prolactin assay from 5-11 months after delivery. The cross-section basal prolactin levels were done from 12-150 months after delivery, with no evidence of an effect of age, parity or elapsed time. These results are appropriate for a protective factor against breast cancer, and prolactin is known to stimulate breast neoplasm in rodents.
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PMID:Long-term effect of a first pregnancy on the secretion of prolactin. 309 98

Inbred RIII mice, known to be infected neonatally with murine mammary tumor virus so that females develop mammary adenocarcinoma by 12-15 months of age, were examined with regard to antisheep red blood cell antibody responses at the cellular level. Female mice, 3-11 months old, compared to male mice of the same ages had consistent and significant depression of the antibody response of their splenocytes. Furthermore, female mice with adenocarcinoma showed an even greater depression of the antibody response. Spleen sizes were consistently increased in females as compared to those of male mice throughout the first year of life. The blastogenic responsiveness of the splenocytes to the B-cell mitogen Escherichia coli lipopolysaccharide and the T-cell mitogen phytohemagglutinin-P was not significantly different between male and female mice during the same periods, although the responses of the older tumor-bearing female mice to phytohemagglutinin-P were lower than those of non-tumor-bearing female mice. A complex relationship between age, sex, and immune responsiveness was evident in these mammary tumor virus-infected mice, which made it difficult to attribute a specific immune event to emergence of the mammary adenocarcinomas in the female as compared to male mice.
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PMID:Age- and sex-related differences in antibody formation and blastogenic responsiveness of splenocytes from RIII mice developing virus-induced mammary adenocarcinoma. 627 37

High doses of estrogen (5-500 micrograms) induce regression of hormone-dependent DMBA mammary tumors in rats at the same rate and degree as treatment with the antiestrogen C1628 (Parke-Davis). In contrast, high dose estrogen stimulated growth of uteri in tumor-bearing rats, while C1628 was antiuterotrophic. Within 72 h following treatment with estrogen, diethylstilbestrol (DES), or C1628, changes in the levels of estrogen receptor (ER) and progesterone receptor (PgR) were evident in both uterine and mammary tumor tissue. Both estrogen and antiestrogen induced depression of the total cytosolic ER and altered the 8S/4S receptor ratio. The tumor cytosolic ER levels of DES- and C1628-treated rats were 4.67 +/- 1.7 fmol/mg protein and 15.89 +/- 3.1 fmol/mg protein, respectively, compared to 48.89 +/- 13.6 fmol/mg protein in tumors of untreated rats. In spite of reduced levels of cytosolic ER, there was an apparent increase in the 8S/4S ratio (62% increase in 8S/4S ER ratio compared to control 8S/4S ratio; p less than 0.05). Total uterine cytosolic ER was low after treatments with DES (5.69 +/- 2.08 fmol/mg protein) or C1628 (94.76 fmol/mg +/- 30.3 fmol/mg protein), as compared to untreated controls (188.2 +/- 7.6 fmol/mg protein). The cytosolic PgR was consistently high in tumors of control rats (42.99 +/- 11.9 fmol/mg protein) and in castrated rats treated with high doses of DES or C1628 (DES, 55.15 +/- 27.0; C1628, 65.07 +/- 9.8 protein).
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PMID:Effect of high-dose estrogen on growth and steroid receptor activity in DMBA-induced mammary tumors and uteri of rats. 634 12

The proportion of single intact viable mouse mammary tumor cells containing estrogen receptor (ER) as determined by 17-fluoresceinated estrone binding and the proportion labeled with [3H]thymidine (LI) have been assessed in the same cell population after either primary tumor removal, radiation, cyclophosphamide, or tamoxifen administration. Subsequent to tumor removal, the increase in LI occurring in a cell population from a residual tumor focus was associated with a concomitant decrease in the proportion of cells demonstrating 17-fluoresceinated estrone binding (fluorescence). As the level of LI in the tumor focus returned to that observed prior to tumor removal, the proportion of ER-containing cells simultaneously reverted to its original value. Following cyclophosphamide administration, there was a decrease in tumor LI and a concomitant elevation in the proportion of fluorescent cells which were dose related. The prolonged depression in LI following radiation was accompanied by a sustained increase in the proportion of ER-containing cells. Thus, the change in ER-containing cells was related to the alteration of the proliferating cell population by the various therapies. The findings support the thesis that fewer cells in the growth fraction of the tumor studied contain ER than in the nonproliferating cell pool. Following tamoxifen administration, a decrease occurred in the proportion of fluorescing cells due to competitive binding. There was no alteration in LI. This observation is not in conflict with the thesis that there is a correlation between ER and LI since the mechanism for reduction in detectable ER is different. These studies provide additional support to the credibility of the use of 17-fluoresceinated estrone binding for the determination of ER in individual tumor cells. They also indicate the usefulness of the method for obtaining biological information regarding tumor ER which cannot be obtained with the use of conventional biochemical analyses.
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PMID:Interrelation between tumor cell proliferation and 17-fluoresceinated estrone binding following primary tumor removal, radiation, cyclophosphamide, or tamoxifen. 661 61

We examined the effect of a maximum tolerated, split-dose chemotherapy protocol of cyclophosphamide, cisplatin, and 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) on neutrophil and lymphocyte subpopulations in the peripheral blood leukocytes (PBLs), thymus, bone marrow, and spleen. It was found that this protocol of polychemotherapy, modeled after the induction protocol used with autologous bone marrow transplantation (AuBMT) for breast cancer, suppressed both B- and T-cell populations and T-cell function at times when the absolute neutrophil count had returned to normal or supernormal numbers. We observed an organ- and phenotype-specific T- and B-cell recovery to normal levels following chemotherapy. However, despite normalization of cellularity and phenotype frequency, splenic lymphocytes remained unable to respond to normally concanavalin A (ConA). This polychemotherapy protocol in mice with an extensive experimental metastasis mammary tumor burden, was a dose lethal to 20% of the test group, which could be overcome with treatment by BMT and rHu interleukin (IL)-7. Furthermore, therapy with the T-cell augmenting agent rHu IL-7 had additive therapeutic activity and significantly prolonged survival beyond that of chemotherapy and BMT although it did not cure any mice with a heavy tumor burden. In summary, these studies demonstrate an organ-specific and selective polymorphonuclear neutrophil and T- and B-cell reconstitution following multidrug, split-dose chemotherapy on tissue and PBL populations, and a chronic depression in T-cell function, which when modified can result in significant therapeutic activity.
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PMID:T-cell reconstitution by molecular, phenotypic, and functional analysis in the thymus, bone marrow, spleen, and blood following split-dose polychemotherapy and therapeutic activity for metastatic breast cancer in mice. 750 77

Nocturnal (23.00-07.00 h) urinary melatonin and total biopterin (tBI; after acidic oxidation of reduced biopterins) were analyzed during the growth of two passages of a mammary tumor line in female F344 Fischer rats. In addition, nocturnal (02.00-03.00 h) peak concentrations of pineal melatonin in plasma were analyzed when tumors had reached comparable average tumor volumes of 25-30 cm3. Since tetrahydrobiopterin (BH4) is produced by murine macrophages in response to interferon-gamma released by activated T lymphocytes, measurements of tBI can serve to estimate the state of cellular immunity. At passage 2, a slow-growing localized carcinosarcoma, tBI showed a progressing increase during tumor growth reaching more than 200% (p < 0.05-0.005) of controls by the end of the experiment. Urinary and plasma melatonin were elevated by 30-50% (p < 0.05) and 42% respectively. At passage 12, a fast-growing metastasizing sarcoma, a depression of about 20-30% was found for tBI (p < 0.05) and urinary melatonin (p < 0.025); plasma melatonin was depleted by 70% (p < 0.005). Parallel changes of both parameters at each tumor passage indicate a close link between the pineal hormone melatonin and cellular immunity. The opposite trends observed at the two passages indicate a clear stimulation of the immune system and the pineal gland at early but inhibition at advanced stages of cancer.
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PMID:Serial transplants of DMBA-induced mammary tumors in Fischer rats as model system for human breast cancer. IV. Parallel changes of biopterin and melatonin indicate interactions between the pineal gland and cellular immunity in malignancy. 777 39


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