Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tamoxifen is the endocrine treatment of choice for breast cancer. In several laboratory models in vivo tamoxifen is a tumoristatic agent. When MCF-7 breast cancer cells are inoculated into athymic mice, palpable tumors do not grow unless the animals are treated with estrogen, and tamoxifen inhibits estrogen-stimulated growth. If tamoxifen is stopped, tumors regrow. These results suggest that adjuvant tamoxifen therapy should involve long treatment periods (even lifetime) to prevent tumor recurrence. Unfortunately resistance to therapy and patient relapse inevitably occur, and such disease recurrence involving tamoxifen resistance is difficult to treat successfully. A laboratory model of endocrine therapy failure has been developed. When athymic mice with MCF-7 tumors are treated for 6-8 months with tamoxifen, several tumors grew and continued to grow in tamoxifen-treated mice. These estrogen receptor-positive tumors grow with either tamoxifen or estradiol. Tamoxifen-stimulated tumor growth has been observed in human endometrial tumors implanted into athymic animals. Growth of these tamoxifen-stimulated tumors can be inhibited with the pure antiestrogen ICI 164,384 upon withdrawal of tamoxifen. These data are discussed in terms of treatment strategies for tamoxifen-failed patients.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Sensitivity and insensitivity of breast cancer to tamoxifen. 228 88

The influence of modulating circulating levels of epidermal growth factor (EGF) and transforming growth factor beta 1 (TGF-beta 1) on tumor growth was examined in a variety of mouse models. Removal of the EGF-rich submandibular gland from host mice failed to alter the growth of a variety of human tumor xenografts or a C3H mouse tumor. Infusion of EGF from Alzet minipumps raised circulating EGF levels. However, only the A549 human tumor xenograft showed any significant increase in growth in the presence of EGF infusion and this response was marginal. The growth of Wehi 3BD+ and A549 tumor lines in culture was inhibited by TGF-beta 1. The growth of these lines in vivo, however, was not significantly altered by the administration of TGF-beta 1 via a variety of routes.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:In vivo evaluation of epidermal growth factor and transforming growth factor beta 1 in mouse tumor models. 228 1

The effects of chemotherapy or local irradiation on lymphokine-activated killer (LAK) cell accumulation into tumor sites were investigated. Lymphokine-activated killer cells labeled with 111In-oxine were injected into the caudal vein of C57BL/6 mice that had been previously transplanted with 3LL cancer. An adoptive transfer of LAK cells was carried out 4 days after treatments. Twenty-four hours after the transfer, tumor tissues were excised, and the accumulation of labeled LAK cells in the tumor was measured. In two different experiments, LAK cell accumulation in tumor in the nontreated group was 2.15% and 1.58% of the administered dose per gram of tissue. The accumulation in the groups of mice treated with cyclophosphamide, nimustine hydrochloride, or Adriamycin increased fourfold (7.38% dose/g, 6.61% dose/g), threefold (6.47% dose/g) and twofold (4.46% dose/g), respectively, as compared with the nontreated group. These agents induced significant tumor regression. In the group treated with bleomycin, which showed no significant effect on tumor growth, LAK cell accumulation in tumor remained unaltered (1.57% dose/g). However, the group treated with local irradiation, which induced significant tumor reduction, showed no increase in LAK cell accumulation into tumors. These results suggest that some antitumor drugs enhance LAK cell accumulation into tumor sites and that this increase is due to tumor modification by antitumor drugs.
Mol Biother 1990 Dec
PMID:Modification of lymphokine-activated killer cell accumulation into tumor sites by chemotherapy, local irradiation, or splenectomy. 228 22

Antitumor activity, mitogenicity, and lethal toxicity of chemically synthesized lipid A analogs, acylglucosamine-4- or -6-phosphate with the alpha, beta-hydroxyacyl, acyloxyacyl, or hydroxyacyloxacyl groups at the C-2 and C-3 positions, were examined. Meth A fibrosarcoma cells (5 X 10(5)) were inoculated subcutaneously into BALB/c mice on day 0, and six compounds (50 micrograms/mouse) were administered intravenously on days 7 and 9. Although the antitumor activity of these compounds was weaker than that of natural lipopolysaccharide (LPS) or the synthetic lipid A analog (506) of Escherichia sp type, all groups exhibited tumor inhibition rates of 40% to 50% and delayed tumor growth. Six compounds, with the exception of compound A-173 (with the hydroxytetranoyl group at the C-2 and C-3 positions), were capable of increasing the incorporation of [3H]thymidine into cultured splenocytes of C57BL/6 mice, and caused lethal toxicity in C57BL/6 mice sensitized with galactosamine. However, these compounds had lower toxicity than bacterial LPS (about 500- to 1,000-fold). Compounds A-172 and A-174, which have the same structure except for the C-4 or C-6 position of the phosphate group, exerted similar antitumor activity, mitogenicity, and lethality. The results discussed above indicate that the biologic activity of these compounds correlates with the carbon number of fatty acid but is not affected by the different location of the phosphate group. Furthermore, it seems that the difference between the alpha, beta-hydroxy position of fatty acid and the R or S configuration does not alter the biologic effects.
Mol Biother 1990 Jun
PMID:Antitumor activity against Meth A fibrosarcoma and biologic activities of synthetic monosaccharide analogs of lipid A in mice. 236 54

To investigate the role of transforming growth factor alpha (TGF alpha) in tumor development, we introduced the human TGF alpha (hTGF alpha) cDNA into cultured primary mouse epidermal cells or papilloma cells using a replication-defective retroviral vector and analyzed skin grafts constructed with such cells. Expression of the exogenous gene was confirmed by detection of hTGF alpha mRNA by northern RNA blot analysis, and the secreted hTGF alpha was measured by ELISA of culture supernatants. Tumor cells expressing hTGF alpha produced benign tumors (papillomas), which were 1.5- to 2-fold larger than tumors of parental cells when tested as skin grafts on nude mice. Grafts of normal cells that expressed hTGF alpha produced normal skin. When mixtures of parental tumor cells and normal mouse keratinocytes were grafted to nude mice, papilloma formation was suppressed and tumors that did form were small. Grafts of hTGF alpha-producing papilloma cells combined with either normal epidermal cells or hTGF alpha-producing epidermal cells yielded large tumors. Mixed grafts containing keratinocytes expressing hTGF alpha and parental papilloma cells also produced large tumors. While the tumor size was substantially increased by hTGF alpha expression, the tumors that developed in all groups were histologically benign and reached a stable size 4-5 wk after grafting. These results indicate that expression of hTGF alpha by either tumor cells (autocrine) or adjoining normal cells (paracrine) can stimulate tumor growth, particularly when tumor growth is suppressed by normal tissue. However, expression of this growth factor did not appear to influence tumor progression directly.
Mol Carcinog 1988
PMID:TGF alpha stimulates growth of skin papillomas by autocrine and paracrine mechanisms but does not cause neoplastic progression. 247 36

Complex polymers containing mannose (mannans) possess significant biological activity when administered to mammals. When given orally, they inhibit cholesterol absorption and induce hypocholesterolemia. If administered by other routes, they bind to mannose-binding proteins and induce macrophage activation and interleukin-1 release, inhibit viral replication, stimulate bone marrow activity, promote wound healing and inhibit tumor growth. This range of activities makes the mannans, potentially important biological-response modifiers and therapeutic agents.
Mol Biother 1989
PMID:The biological activities of mannans and related complex carbohydrates. 269 29

Tumor necrosis factor (TNF) dramatically alters the levels of various surface components of the blood vessel wall, such as blood coagulation enzyme receptors, leukocyte-adhesive receptors, and class 1 major histocompatibility complex antigens, which may have relevance to its effects in septic shock, angiogenesis, and tumor growth. However, the precise mechanism by which the cytokine is able to accomplish this remodeling of the endothelial cell surface has not been defined. We have demonstrated that exposure of bovine and human endothelial cells to TNF leads to suppression of the functional cell surface thrombin receptor, thrombomodulin (TM), and TM mRNA of virtually identical magnitude. The cytokine has no significant effect on the stability of TM mRNA or endothelial receptor turnover. Nuclear run-on studies reveal that the treatment of endothelial cells with TNF for short periods reduces TM gene transcription to as little as 3% of control values and that this inhibition does not require new protein synthesis.
Mol Cell Biol 1988 Dec
PMID:Tumor necrosis factor suppresses transcription of the thrombomodulin gene in endothelial cells. 285 3

The adenocarcinoma produced by transplantation into nude mice of a neoplastic human salivary intercalated duct cell line was treated with 0.1 ml of minimal essential medium (MEM) containing dibutyryl cyclic AMP (dB-cAMP) at a final concentration of 1 mM daily for 28 days and examined morphologically and immunohistochemically. The dB-cAMP treatment resulted in a marked suppression of tumor growth. In addition, tumor nests with a myoepithelial cell phenotype characterized by the presence of microfilament systems reactive with antimyosin and anti-S-100 protein sera were often observed in the treated tumors, but not in untreated controls. These findings lead us to suggest that neoplastic intercalated duct cells can be induced to differentiate into myoepithelial cells and that levels of cAMP within the cells may regulate this cytodifferentiation.
Virchows Arch B Cell Pathol Incl Mol Pathol 1985
PMID:Induction of cells with a myoepithelial cell phenotype by treatment with dibutyryl cyclic AMP in human salivary adenocarcinoma cells grown in athymic nude mice. 286 38

A permanent rat rhabdomyosarcoma cell line (BA-HAN-1C) has been established, the phenotype of which is characterized by the coexistence of undifferentiated mononuclear cells and differentiated multinuclear myotube-like giant cells. The failure of attempts to separate these two cell types by repeated recloning procedures indicates their close histogenetic relationship and suggests that differentiation in this tumor proceeds in a similar manner to that in normal striated muscle where postmitotic myotubes arise from mononuclear myoblasts by fusion. The morphologically undifferentiated mononuclear tumor cells were shown to be actively proliferating and to incorporate thymidine methyl-3H(3H-TdR). The myotube-like giant cells neither incorporated 3H-TdR nor underwent mitosis or exhibited any clonogenic potential. After retransplantation into syngenic rats, tumor growth was markedly retarded when the tumor cell inoculum contained a high percentage of myotube-like giant cells. These data show that proliferative activity in this rhabdomyosarcoma cell line is confined to the mononuclear tumor cell compartment, the multinuclear myotube-like giant cells having withdrawn from the cell cycle and represent terminally differentiated postmitotic cells. This cell line should provide a valuable tool for further investigation of coherent aspects of proliferation and differentiation using various differentiation inducers.
Virchows Arch B Cell Pathol Incl Mol Pathol 1988
PMID:Terminally differentiated postmitotic tumor cells in a rat rhabdomyosarcoma cell line. 290 Nov 65

The cause of the state of anergy which often accompanies advanced tumor growth has been attributed to several factors, including nonspecific suppressor cells capable of suppressing humoral and cell-mediated responses. Induction of suppressor cells in tumor-bearing hosts has been attributed to the release of immunoregulatory factors by the tumor, as well as by the host's own lymphoid cells. Several such "suppressor cell-inducing factors" have been described. However, in only a few cases has the inducing material been characterized. We have recently reported the existence of a suppressor cell inducing factor (SIF) in the 18 hr culture supernatant of spleen cells from mice bearing an advanced M-1 fibrosarcoma. Our aim was to characterize SIF, both biochemically and mechanistically. In order to purify the inducing factor, as well as to dissect the cellular and molecular events that occur as a result of suppressor cell activation, we isolated the M1-A5 cell line from the spleen cells of a mouse bearing an advanced M-1 fibrosarcoma. Induction of suppressor cells by supernatants from M1-A5 cells closely resembled the situation seen with the whole spleen cells. In both cases: 1) an inducing factor with an estimated Mr less than 12 kDa was found, and 2) the release, but not the effector function, of the inducing factor was prostaglandin-dependent. The 18 hr culture supernatant of M1-A5 cells was used as the source of the inducing factor and suppressor cells were activated by exposure of normal spleen cells to the inducing factor for 4 hr. The nature of the inducing factor was investigated by subjecting the M1-A5 culture supernatant to molecular weight sieving on Sephadex G-100 medium. The results showed that M1-A5 supernatants contained a high- (Mr 70 kDa) and a low- (Mr 5.5 kDa) molecular weight factor, which were termed SIF alpha and SIF beta, respectively. SIF alpha and SIF beta were further purified by ion exchange chromatography. SIF beta bound to QAE-Sephadex A-25 and was eluted in a single peak. However, SIF alpha displayed heterogeneity with respect to binding to DEAE-Sephacel, as SIF activity was seen in the void volume as well as in fractions eluted from the anionic exchanger. Mechanistically, we demonstrate that the induction of suppressor cells by SIF alpha and SIF beta is genetically non-restricted. In addition, we show that SIF alpha and SIF beta suppress the in vivo antibody response to sheep red blood cells.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Cell Immunol 1987
PMID:Induction of suppression by a murine nonspecific suppressor-inducer cell line (M1-A5). III. Partial purification of the suppressor cell-inducing factors. 297 41


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