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)

Indoleamine 2,3-dioxygenase (IDO) is a flavin-dependent enzyme which uses superoxide anion as a cosubstrate to catalyze the decyclization of the pyrrole ring of L-tryptophan to form formylkynurenine. This enzyme is induced in some tumor cells after treatment with IFN-gamma. The mechanism of induction of IDO in tumor cells by IFN-gamma was studied in THP-1 human monocytic leukemia cells. Before the addition of IFN-gamma, no IDO could be detected in these cells. Treatment of THP-1 cells with IFN-gamma produced an induction of IDO, with peak activity occurring 72 to 96 h after addition of IFN-gamma. Because phorbol esters are known to induce many enzymes in cells, most likely through the activation of protein kinase C, the effects of PMA on the induction of IDO were determined. PMA potentiated the IFN-gamma-induced elevation of IDO, but by itself, was unable to induce enzyme activity. Maximum induction of IDO in the presence of PMA and IFN-gamma was obtained by preexposure of the cells to PMA for 48 h before the addition of IFN-gamma. Maximum induction of IDO after the addition of IFN-gamma occurred 24 to 48 h after addition of the cytokine to the culture medium. However, the induction of IDO does not appear to be potentiated through the activation of protein kinase C, because the addition of the protein kinase C inhibitor H-7 had no effect on the induction of IDO when the cells were exposed to PMA and IFN-gamma. Moreover, diacylglycerol was unable to replace PMA in these studies. Studies with cAMP and cGMP analogs suggest a role for these compounds in the regulation of IDO expression.
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PMID:Synergistic effects of phorbol ester and INF-gamma on the induction of indoleamine 2,3-dioxygenase in THP-1 monocytic leukemia cells. 255 14

The effects of the differentiation-inducing agents N6, O2'-dibutyryl cyclic AMP, beta-all-trans retinoic acid, dimethylsulfoxide and butyrate on the levels of galactoside-binding proteins (lectins) in cultured human and murine tumor cells were examined by immunoblotting. Differentiation was associated with decreased levels of a 34-kDa lectin in the K-1735P and B16-F1 melanoma cells and decreased levels of a 14.5-kDa lectin in S20 neuroblastoma, MDA-MB 175 breast carcinoma, HL-60 and THP-1 leukemia cells. The level of a 14.5-kDa lectin increased during differentiation of F-9 embryonal and KM12P colon carcinoma cells. These results indicate that tumor cell differentiation along specific pathways is accompanied by distinct modulation of lectin expression. These changes may recapitulate the normal developmental regulation of lectin expression.
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PMID:Modulation of galactoside-binding lectins in tumor cells by differentiation-inducing agents. 255 43

In this study we describe the surface features of non-MHC (Major Histocompatibility Complex)-restricted cytotoxic cells isolated from human peripheral blood. Purified populations of CD3-, natural killer (NK) cells were allowed to interact with NK-sensitive (K562) and NK-resistant (THP-1-0) tumor cell targets. The type of effector to target cell binding was investigated by scanning electron microscope (SEM) analysis. A different interaction with the effectors is described for NK-resistant targets in comparison with NK-susceptible tumor cells. SEM was also used to investigate the relationship between interleukin 2 (IL2)-activated cytotoxic cells (lymphokine-activated killer, LAK, cells) and the tumor targets. We also describe the unique growth features of certain clones of cytotoxic T cells expressing gamma delta antigen receptors which support the contention that these cells may have a special ability of homing into tissues. We conclude that non-specific cytotoxic cells constitute a diverse population of effectors which differ not only for the expression of surface antigens, but also for their ability to interact with tumor cell targets and to home into the peripheral tissues where they may exert their lytic functions.
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PMID:A scanning electron microscopy analysis of human cytotoxic cell subsets and of their mode of conjugation with tumor cell targets. 261 72

We present preliminary treatment results of a nation-wide cooperative clinical study for advanced neuroblastoma supported by a grant-in-aid for cancer research from the Japanese Ministry of Health and Welfare. This study involves 28 major pediatric oncology institutions in Japan and started in May, 1985. Until 1987 we treated 84 patients with stage III and IV neuroblastoma whose prognosis was considered to be extremely poor. Every patient who entered this study received 6 cycles of A1 protocol consisted of high dose cyclophosphamide, vincristine, cis-platinum and THP-adriamycin, a newly introduced low-cardiotoxic anthracycline derivative. Having received 6 cycles of A1 protocol, patients were divided into 3 groups, i.e., ACNU course, DTIC course and bone marrow transplantation course preconditioned by high dose melphalan. Of 77 patients who received more than 3 cycles of A1 protocol, tumor extirpation was performed in 69 patients. Total or subtotal resection of the original tumor and the regional lymph-nodes was possible in 57 cases. The high resectability of the tumor indicates marked effectiveness of this protocol. Of the 57 patients who followed this treatment protocol from the beginning (virgin case), 31 (54.4%) showed complete response and 26 still remains in complete remission. 93.0% of response rate (CR + PR) was obtained by the treatment protocols, which was considerably high as compared with the results of other treatment protocol reported. This protocol also worked well in the patients who had failed with other treatment protocol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A preliminary treatment report of the Study Group of Japan for Advanced Neuroblastoma]. 267 8

The interaction between lymphokine-activated killer (LAK) cells and two types of target cells with different susceptibility to natural killer (NK) activity was investigated by scanning electron microscopy (SEM). In NK-susceptible tumor cells (K562) a different mode of conjugation with the effector was observed as compared with NK-resistant targets (THP-1-0). In LAK-K562 pairs, the contact region was characterized by the presence of long microvilli, blebs and ruffled membranes forming an intertwined and interdigitated binding site. Conversely, when LAK cells were conjugated with THP-1-0 cells, the surface structures of the target cell did not undergo significant modification and the interacting cells did not appear to establish close contact. In addition, cell lysis of the sensitive target was often characterized by plasma membrane blebbing, leading to cell death. In contrast, in the low percentage of resistant targets which underwent lysis after conjugation, cell death always occurred without formation of bulb- or bleb-like structures.
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PMID:An SEM analysis of the interaction between lymphokine-activated killer cells and tumor targets. 280 40

The growth-inhibitory activity of recombinant human tumor necrosis factor (rH-TNF: PAC-4D) against 32 human cultured cell lines derived from leukemias and lymphomas (7 T cell, 11 B cell, 5 non-T,non-B cell and 9 myeloid cell lines) was measured quantitatively by in vitro regrowth assay. The growth of two non-T,non-B-cell lines (Reh, P30/OHK) and six myeloid cell lines (ML-1, U937, THP-1-0, P31/FUJ, P39/TSU, HEL) was found to be significantly inhibited by a 72 hr treatment with PAC-4D. Although the levels of sensitivity of these cell lines to PAC-4D were different, it was common to all these cell lines that increasing the dose of PAC-4D did not augment the growth-inhibitory action above a certain level. Neither dose-dependent nor time-dependent growth-inhibitory action was observed, namely, exposure to 100 U/ml of PAC-4D for 48 hr was sufficient to exhibit maximum growth-inhibitory action. Furthermore U937 cells were found to become completely resistant to PAC-4D during a continuous 12-day exposure to it. This resistance, however, was lost on culture of the cells with PAC-4D-free growth medium for 15 days. These results suggested that some non-T,non-B acute lymphoblastic leukemias and acute myelogenous leukemias might show an initial response to PAC-4D therapy, but prolonged administration might induce resistance to PAC-4D rather than increase the anti-tumor effect.
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PMID:Potential limitation of growth-inhibitory action of recombinant human tumor necrosis factor (PAC-4D) due to easy induction of resistance: evidence in vitro. 282 76

The in vitro effect of short-term culture as well as the effect of retinol (ROH), retinoic acid (RA), muramyl dipeptide [( Abu']MDP), lipopolysaccharide (LPS), and gamma interferon (IFN-gamma) on the induction of the purine metabolic enzymes, adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'nucleotidase (5NT) in human peripheral blood monocytes (HPBM) was examined. HPBM isolated by centrifugal elutriation were cultured for up to 96 h. Following an initial time lag of 24 h, mean ADA activity from seven separate experiments as measured in nmoles/10(6) cells/h increased from a baseline of 31.3 +/- 9.3 to 57.8 +/- 16.4 (P less than 0.005) at 72 h and to 72 +/- 21.5 (P less than .025) by 96 h. 5NT activity increased from a baseline of 2.2 +/- 0.9 to a maximum of 44 +/- 10.1 by 72 h and then declined to 29 +/- 18 (P less than 0.005) by 96 h, while no significant change in PNP activity was observed. HPBM incubated for 3 d with optimal concentrations of LPS, RA, and IFN-gamma had increases in ADA and 5NT activity ranging from three- to 10-fold compared to HPBM cultured in media alone, whereas no effect was observed with ROH and [Abu']MDP. RA, but not ROH, significantly enhanced ADA activity in a monocytic leukemia cell (THP-1) line. Addition of RA or the tumor promoter, phorbol 12-myristic 13-acetate (PMA), to HPBM or THP-1 cells resulted in significant increases in 5NT activity with opposite effects on ADA activity. These findings suggest that the biological mechanisms associated with differentiation in normal and malignant monocytes seem to be related and that the sequence and degree to which the various differentiation agents induce the enzyme elevations are also related to the mechanisms of activation/differentiation.
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PMID:Induction of adenosine deaminase and 5' nucleotidase activity in cultured human blood monocytes and monocytic leukemia (THP-1) cells by differentiating agents. 284 22

Exposure of Chinese hamster ovary, mouse adrenal cortex tumor (Y-1), THP-1 and U-937 cells and human erythrocytes to adenylate-cyclase-containing urea extracts of Bordetella pertussis (strain 114) organisms promotes the formation of large concentrations of intracellular cAMP. Accumulation is dependent on dose and temperature, with significant accumulation occurring at 4 degrees C, and is virtually instantaneous, with a doubling at 1 min. There is an absolute Ca2+ requirement but external calmodulin (the activator of cyclase activity) has no effect except in erythrocytes and U-937 cells, where it reduces cAMP accumulation. However, calmodulin antagonists inhibit cAMP accumulation. In Y-1 adrenal cells the urea-extract adenylate cyclase stimulates steroidogenesis. Anti-(B. pertussis) antibodies inhibit cyclase activity and prevent further cAMP accumulation after 10 min in cells previously exposed to urea extract. The same effect is obtained by washing. This suggests that a portion of the cyclase is associated with cells in a form not accessible to antibody or washing but accessible to substrate, which we interpret as internalized enzyme with a short lifetime. Continuing cAMP accumulation thus appears to need a continuing source of external cyclase. Inhibitors of the effect of diphtheria toxin, such as NH4Cl, methylamine, chloroquine or monensin, have no inhibitory effect on the accumulation of intracellular cAMP promoted by the internalized adenylate cyclase of urea extracts of B. pertussis organisms. We conclude that entry of the cyclase into cells is not by receptor-mediated endocytosis.
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PMID:Bordetella pertussis adenylate cyclase. Penetration into host cells. 290 Jul 63

A novel basic heparin-binding monocyte chemotactic factor (MCF) was purified to homogeneity from the conditioned media of human myelomonocytic cell line THP-1 based on its in vitro monocyte chemotactic activity. The purified MCF was homogenous and estimated to be 15 kD on SDS-PAGE. Purified MCF stimulated normal human monocytes to be growth inhibitory in vitro at 2-3 d for several human tumor cell lines. This represents the first report of the identification and purification of a chemoattractant cytokine that also activates monocytes but is distinct from interferons and other known cytokines.
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PMID:Purification and characterization of a novel monocyte chemotactic and activating factor produced by a human myelomonocytic cell line. 292 31

Intraarterial injection of anti-tumor drugs (THP-ADR, CDDP, 5-FU) dispersed in lipid contrast medium (Lipiodol, Laboratorie Guerbert, France) was used in an infant with initially unresectable hepatoblastoma. Lipiodol complex selectively accumulated in the tumor tissue and may keep the chemotherapeutic agents in the tumor tissue for a longer period of time, and a significant reduction of the tumor with a four-day half-life of alpha-fetoprotein (AFP) was followed immediately after the institution of chemotherapy. Successful resection of decreased tumor by extended right hepatectomy under more favorable conditions was performed 2 months after diagnosis. Intraarterial chemotherapy with Lipiodol was particularly useful in potentiating the cytoreduction of anti-tumor drugs and was also useful in reducing the toxicities of anti-tumor drugs to the host.
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PMID:Intraarterial injection of anti-tumor drugs dispersed in lipid contrast medium: a choice for initially unresectable hepatoblastoma in infants. 303 59


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