Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Groups of 15 female Syrian golden hamsters with N-nitrosobis(2-oxopropyl)amine-induced pancreatic cancers were treated for 2 mo with microcapsules of the luteinizing hormone-releasing hormone (LH-RH) antagonist [Ac-D-Nal(2)1-D-Phe(4Cl)2-D-Pal(3)3,D-Cit6,D-Ala10] LH-RH (SB-75) releasing 8 micrograms/day or with the microcapsules of the LH-RH agonist D-tryptophan-6-luteinizing hormone-releasing hormone (D-Trp-6-LH-RH) releasing 8 micrograms/day or 25 micrograms/day. Chronic treatment with SB-75 resulted in 70% inhibition of pancreatic tumor weight; D-Trp-6-LH-RH in doses of 8 micrograms/day and 25 micrograms/day produced 66% and 62% inhibition, respectively. The number of animals with pancreatic tumors was reduced by about 50% in each treated group. Tumorous ascites were found in seven control hamsters and in one hamster in each group treated with D-Trp-6-LH-RH but not in the group given SB-75. Reduction in serum luteinizing hormone levels and ovarian as well as uterine weights indicated that an inhibition of the pituitary-gonadal axis occurred during chronic SB-75 and D-Trp-6-LH-RH treatment. Membrane receptor assays showed a significant decrease of the concentration of binding sites for LH-RH in tumor cells after SB-75 or D-Trp-6-LH-RH treatment. Insulin-like growth factor I receptors, but not epidermal growth factor receptors, were down-regulated by D-Trp-6-LH-RH. SB-75 did not influence the concentration or the binding capacity of insulin-like growth factor I and epidermal growth factor receptors in the tumor cells. The inhibitory effect of chronic treatment with SB-75 and D-Trp-6-LH-RH on tumor growth was mediated by enhanced apoptosis (programmed cell death) induced by the change in hormonal environment. Apoptosis was also produced in hamsters with N-nitrosobis(2-oxopropyl)amine-induced pancreatic cancers by acute treatment (3 to 6 days) with high doses of D-Trp-6-LH-RH or SB-75. In view of its potency and an immediate powerful inhibitory effect, the LH-RH antagonist SB-75 might be considered as a possible new hormonal agent for the treatment of exocrine pancreatic cancer.
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PMID:Regression of nitrosamine-induced pancreatic cancers in hamsters treated with luteinizing hormone-releasing hormone antagonists or agonists. 216 Mar 23

The interferon (IFN)-gamma-mediated induction of indoleamine 2,3-dioxygenase (IDO) enzyme, which converts tryptophan into N-formylkynurenine, has been implicated in the inhibition of intracellular pathogens, e.g. Toxoplasma gondii and Chlamydia psittaci, and in the antiproliferative effect of IFN-gamma on tumor cells. The IDO activity is induced strongly in many cell types by IFN-gamma but rather poorly by IFN-alpha or -beta. A genomic DNA clone containing part of the transcribed region of the IDO gene and approximately 13 kilobases (kb) of the 5'-upstream DNA sequence was isolated and analyzed. An approximately 1.4-kb fragment of this clone, containing 329 nucleotides of the transcribed sequence and approximately 1.1 kb of the 5'-upstream sequence, when ligated to chloramphenicol acetyltransferase (CAT) structural gene made its expression inducible by IFN-gamma, but this construct responded poorly, if at all, to IFN-alpha 2. Deletion constructs derived from this plasmid narrowed down the IFN-gamma-responsive region to a 151-nucleotide segment (-495/-344) which also contained a 14-nucleotide sequence (GGTTTCAGTTTTCC) highly homologous to the IFN(alpha)-stimulated response element (ISRE) that has been found so far in all cellular genes inducible with IFN-alpha or -beta. Expression of CAT activity was stimulated by IFN-gamma more effectively than by IFN-alpha 2 when a 155-nucleotide fragment (-495/-340) containing the 151-nucleotide segment required for IFN-gamma response was inserted before herpes simplex virus thymidine kinase promoter linked to CAT structural gene. The results indicate that despite the presence of an ISRE, the control region of the IDO gene can distinguish between IFN-gamma and IFN-alpha. This may account for the differential activation of IDO gene expression by IFN-gamma as against IFN-alpha or -beta in intact cells, and suggests that the response of ISRE to IFN-alpha or -beta may be governed by other features in the upstream control region of this gene.
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PMID:Regulation of indoleamine 2,3-dioxygenase gene expression in human fibroblasts by interferon-gamma. Upstream control region discriminates between interferon-gamma and interferon-alpha. 217 56

Osteogenic tumours from c-fos (MT-c-fos-LTR)-transgenic mice and from mice infected with the v-fos-bearing FBR murine osteosarcoma virus (FBR MSV) showed close morphological and neoplastic similarities. Fos mRNA expression was elevated in both types of tumours, and expression of several genes characteristic of differentiated bone cells was either lower, enhanced, or not detectable in comparison to that in normal bone. Tumour-derived cell lines showed variable levels of exogenous fos expression; bone-cell-specific genes were similarly expressed in both primary tumours and tumour-derived cell lines. Upon transplantation the tumour cells formed fibrosarcomas, some of which contained areas of focal osseochondrous differentiation. Non-tumorigenic cell lines established from bone tissue of normal and MT-c-fos-LTR transgenic mice showed osteoblastic characteristics, whereas no parathyroid hormone (PTH) response was observed in transgenic tumour cell lines in spite of high alkaline phosphatase activity. These data indicate that deregulated fos expression interferes with terminal osteogenic differentiation in v-fos- and c-fos-induced bone tumours.
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PMID:Characterization of fos-induced osteogenic tumours and tumour-derived murine cell lines. 217 37

Functional gastrin-containing tumor cells were maintained for up to 8 wk without fibroblastoid cell overgrowth. Short-term cultures consisted mainly of colonies composed of small polygonal cells, 70%-90% of which stained positive for immunoreactive gastrin. Cultures exhibited limited growth but viability remained high for 2-3 wk. Culture medium contained component I, and gastrin 34, 17, and 14. With time the major C-terminal gastrin species in medium changed from gastrin 17 at 3 days to gastrin 34 at 5 wk. Extracts of cultured cells contained gastrin 34, 17, and 14; gastrin 17 was the major form detected at all times. Ultrastructurally, cultured tumor cells retained morphological integrity for several weeks; however, with time changes in the appearance of the secretory granules accompanied by evidence of cellular retrodifferentiation were gradually observed. Secretin, gastrin-releasing peptide, 8-bromoadenosine 3':5'-cyclic monophosphate, and phorbol, 12-myristate, 13-acetate stimulated the release of gastrin from cultured cells in a time-dependent fashion. Secretin, bombesin, gastrin-releasing peptide, L-tryptophan, and ethylamine stimulated gastrin release in a dose-dependent fashion. Somatostatin 14 inhibited secretin, bombesin, and gastrin-releasing peptide stimulated gastrin release but did not alter basal release. Cultured cells demonstrated de novo gastrin synthesis, evidenced by their ability to incorporate radiolabeled amino acids into immunoadsorbable gastrinlike material. Primary cultures of gastrin-containing tumor cells free from stromal contamination offer unique advantages for studies of factors that regulate the synthesis and secretion of gastrin and may prove of potential value for studies on cell differentiation and growth.
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PMID:Gastrinoma in vitro: morphological and physiological studies of primary cell cultures. 217 34

The prognostic significance of lymphocyte transformation rate, E-RFC%, 29 degrees C E-RFC%, serum IgG, IgA, IgM and C3 levels were studied in 286 patients with acute leukemia. In acute lymphoblastic leukemia (ALL), the pretreatment immunological parameters were not related to whether the patients could achieve complete remission (CR), but the patients with E-RFC% greater than 30% before treatment or E-RFC% restored to normal after treatment had a significantly longer survival time. In acute nonlymphocytic leukemia (ANLL), pretreatment LTR and E-RFC% were significantly higher in patients who could achieve CR subsequently, the patients with higher pretreatment levels of LTR, E-RFC% or 29 degrees C E-RFC% survived significantly longer than patients with lower levels of these parameters, and the patients whose LTR could return to normal after treatment had a significantly higher CR rate and longer survival times. Except that the pretreatment IgM level was related to the survival of ANLL patients, serum levels of immunoglobulins and C3 had no prognostic value for both ALL and ANLL. In both ALL and ANLL, the immunological parameters changed significantly when relapse occurred.
Med Oncol Tumor Pharmacother 1990
PMID:Prognostic significance of general immune competence in acute leukemia. 228 91

Rat alpha-fetoprotein (AFP) contains one binding site for estradiol with an association constant, Ka = 1 X 10(8) M-1. This site overlaps with a high affinity arachidonic acid binding site (Ka = 1 X 10(7) M-1) and with a tryptophan methyl ester binding site, AFP also possesses a second site able to bind retinoids with a Ka = 1 X 10(6) M-1, and a third site for the binding of bilirubin (Ka = 1 X 10(6) M-1). These two sites presented no interaction and do not overlap with the estrogen or fatty acid binding site. It is suggested that these three binding sites reflect the three-domain structure of the rat AFP molecule deduced from the studies on the nucleotide sequence of AFPmRNA and AFPcDNA segments.
Tumour Biol 1985
PMID:Presence of three different binding sites for retinoids, bilirubin and estrogen or arachidonic acid on rat alpha-fetoprotein. 241 17

Human Y79 retinoblastoma cells are capable of synthesizing the putative retinal neurotransmitters dopamine and serotonin. Separation of the catecholamines and indolamines by high performance liquid chromatography combined with electrochemical detection showed that the cells readily convert tyrosine to 3,4-dihydroxyphenylalanine (DOPA) and, to a lesser extent, dopamine. When DOPA was added, a large quantity of dopamine was produced, as well as norepinephrine, epinephrine, and 3,4-dihydroxyphenylacetic acid. Exogenous tryptophan added to the cells was partially converted to 5-hydroxytryptophan and serotonin. A larger quantity of serotonin was produced when 5-hydroxytryptophan was added. Y79 cells have a high- and low-affinity uptake system for dopamine and serotonin. The K'm and V'max for the high-affinity uptake of dopamine and serotonin are 2.34 +/- 0.64 and 3.63 +/- 1.15 microM and 4.77 +/- 1.12 and 3.20 +/- 1.20 pmol min-1 mg protein-1, respectively. These kinetic parameters are similar to those reported for other retinal preparations where dopamine and serotonin have been suggested to function as neurotransmitters. Tyrosine and tryptophan, the physiologic precursors of dopamine and serotonin, respectively, and phenylalanine are also taken up by high- and low-affinity transport systems. The kinetic parameters for their high-affinity uptake systems are all very similar, suggesting that they may be taken up by the same transporter. These studies show that a tumor cell line derived from the human retina synthesizes dopamine and serotonin and has high-affinity uptake systems for these compounds and their precursors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Synthesis and high affinity uptake of serotonin and dopamine by human Y79 retinoblastoma cells. 244 11

Effects of temperature and pH on the spatial structures of trophoblast-specific beta 1-glycoprotein (TSG) and its various derivatives and fragments have been studied by circular dichroic spectroscopy. The spatial organization of the protein portion of TSG derivatives, as revealed by the spectroscopic evidence, has been discussed with respect to the antigenic activity of the species studied. We concluded that the TSG protein portion consists mainly of a beta-structural type. The antigenic determinants were shown to be topographic, and are preferentially localized in the protein portion; only about 15% of the TSG antigenic activity failed to bear a direct relation to the spatial structure. The antigenic determinants seemed to include a tryptophan residue.
Tumour Biol 1988
PMID:Trophoblast-specific beta 1-glycoprotein: its spatial structure and localization of antigenic determinants. 246 78

Different types of altered proviruses of Rous sarcoma virus (RSV) have been detected in mammalian tumor cell lines. We cloned and sequenced one of these altered proviruses with the structure LTR, v-src, LTR. The presence of an intact viral splice junction, as well as duplications of the chromosomal sequence GCGGGG flanking the two 2-base-pair-deleted LTRs, demonstrated reverse transcription and normal retroviral integration of src mRNA in mammalian cells. In addition, a 1-nucleotide deletion 2 bases upstream from the AAUAAA polyadenylation signal is suspected to be responsible for the absence of a poly(A) track in the src mRNA present in virions of rescued viruses.
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PMID:The LTR, v-src, LTR provirus generated in the mammalian genome by src mRNA reverse transcription and integration. 246 74

Indoleamine 2,3-dioxygenase (IDO) is an interferon (IFN)-induced protein that initiates the metabolism of tryptophan along the kynurenine pathway. Although IDO can be induced by IFN-gamma in many cell types, only mononuclear phagocytes have been shown to be induced to decyclize tryptophan by all three IFN classes. Since tryptophan is an essential amino acid necessary for a variety of metabolic processes, depletion of available tryptophan may be an important mechanism for control of rapidly-dividing microbial pathogens and tumors. The purpose of this review is to present evidence that documents the effects of IFN-induced IDO on prokaryotic and eukaryotic pathogens, as well as on a variety of tumor cell lines.
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PMID:Interferons and indoleamine 2,3-dioxygenase: role in antimicrobial and antitumor effects. 247 88


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