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)

Modified nucleosides are components of ribosomal RNA (rRNA), transfer RNA (tRNA) and messenger RNA (mRNA). 1-methyladenosine and pseudouridine are members of those modified nucleosides. The urinary concentration of 1-methyladenosine and pseudouridine of cancer patients are higher than that of healthy controls, and those compounds were reduced after effective chemotherapy. Thus those compounds might be expected to use as tumor markers. In this study cellular origin of 1-methyladenosine and pseudouridine were analysed about two tumor cell lines (HUT-102, THP-1), peripheral blood lymphocytes (PBL) from healthy adult and PBL under the phytohemagglutinin stimulation, by flow cytometric analysis and immunofluorescent staining of cellular RNA using monoclonal antibodies specific for 1-methyladenosine (AMA) and pseudouridine (APU). Both 1-methyladenosine and pseudouridine were detected in more than 90% of tumor cells above the thresholds of flow cytometric detection (Spectrum III, Ortho). The PBL under the PHA stimulation also tended to take the same way of the tumor cell lines, whereas few of the PBL contained 1-methyladenosine above the thresholds. According to the DNA analysis of those cell lines, high contents of the modified nucleosides in the cell might follow DNA synthesis, this leads to one reason for high levels of the urinary excretion of the modified nucleosides in cancer patient.
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PMID:[Molecular and immunological approach to hematological disease: detection and analysis of intracellular modified nucleosides by flow cytometry]. 240 80

The in vitro evaluation of anticancer drug efficacy was performed using the human tumor clonogenic assay developed by Hamburger and Salmon, and correlation between the in vitro and clinical efficacy was analyzed retrospectively. The in vitro colony assay method used in this study was a minor modification of the above method. Thirty-two out of forty-eight samples from patients with ovarian cancer formed more than five colonies per plate on in vitro colony assay. The median plating efficiency was 0.06% (range 0.02-1.3%) and the median colony count per plate was 279 (range: 8-4,000). With regard to colony formation of ovarian cancer according to the source of the specimen, the colony-forming rate of solid tumor was high (72%) as compared with 63% for ascites and 43% for pleural effusion. In vitro chemosensitivity was defined as more than a 50% decrease in colony formation and the rates for standard drugs on ovarian cancer were as follows: adriamycin (0.04 micrograms/ml) 29%, bleomycin (0.1 micrograms/ml) 24% cisplatin (0.2 micrograms/ml) 31%, 5-FU (1.0 micrograms/ml) 22%, hexamethylmelamine (1.0 micrograms/ml) 19%, L-PAM (0.4 micrograms/ml) 44%, mitomycin C (0.1 micrograms/ml) 38% and THP-adriamycin (0.5 micrograms/ml) 36%. A group of patients who had not been exposed to any anticancer drug showed higher sensitivity in vitro as compared with a group of patients who had received prior chemotherapy (35% vs 22%, p less than 0.05). Correlation between in vitro drug sensitivity and clinical responses in patients treated with the same drugs were analysed retrospectively. In all twenty cases, two were true positive cases (29%), while in ten cases, the results were true negative (77%), The overall predictive accuracy was 60%. In conclusion, ovarian cancer cells can form colonies well when the soft agar method is used and this assay method is suitable for the evaluation of various anticancer drugs in vitro.
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PMID:[Chemotherapy testing for human ovarian cancer using in vitro colony assay]. 241 Dec 25

Tumor target cells (TC) are lysed by natural killer (NK) cells provided that they (1) form conjugates with the effector cells, (2) activate effector cells to release cytotoxic factors, and (3) they are susceptible to the lytic effect of these factors. While this cascade of events that leads to TC killing has been defined, the signal molecules responsible for each of the steps remain largely undetermined. A variety of human leukemia-derived TC lines and clones were analyzed for their sensitivity to NK cell-mediated lysis and for their ability to bind and activate NK cells. These characteristics have been correlated with TC surface expression of differentiation antigens and carbohydrate residues. Of the cell lines and clones tested, K562, SPI-802, MOLT-4, MOLT-4/C8-1, ZS, KG-1/A-3, and HL-60S were sensitive to NK cell-mediated lysis, while KG-1, THP-1-0, HL-60R, and LFM were resistant. KG-1, THP-1-0, HL-60R, and LFM cells were further studied to determine mechanisms responsible for their resistance to NK cells. It was found that HL-60R and LFM cells were unable to bind NK cells. In contrast, KG-1 and THP-1-0 cells were able to bind to and activate NK cells. Therefore, it is likely that the NK-resistance of KG-1 and THP-1-0 cells may be related to their lack of sensitivity to cytotoxic factors released by bound NK cells. All of the TC cell lines and clones capable of binding NK cells expressed the 3-fucosyl-N-acetyl-lactosamine hapten (Lex or SSEA-1 antigen) recognized by the monoclonal antibody Leu M1. These TC consistently lacked surface L-fucose residues, as shown by lack of Ulex europaeus agglutinin binding. In contrast, HL-60R and LFM which did not form conjugates with NK cells, did not express surface Lex determinants and avidly bound the Ulex agglutinin. Distinct subpopulations of NK-resistant KG-1 cells expressed Lex antigens or bound Ulex. We compared KG-1/A-3, a NK-sensitive cell clone, with the parental NK-resistant KG-1 cell line. KG-1/A-3 lost the ability to bind the Ulex lectin displayed by the parental cell line and showed increased expression of Lex determinants. Results from these phenotypic analyses suggest that expression of Lex determinants and Ulex binding sites on the TC membrane are mutually exclusive and their expression or absence may correlate with mechanisms which regulate TC-NK cell interactions.
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PMID:Human leukemia-derived cell lines and clones as models for mechanistic analysis of natural killer cell-mediated cytotoxicity. 243 54

A human acute monocytic leukemia cell line, THP-1, releases a factor which activates human cytotoxic (killer) T lymphocytes (CTL) against autologous tumor in vitro. The factor, named cytotoxic (killer) T cell activating factor (KAF), is an acidic protein of 70,000 to 100,000 dalton molecular size. Peripheral blood leukocytes from two patients, bearing epithelioid sarcoma or malignant schwannoma, were cultured for 7 days with individual autologous tumor to induce CTL directed to the corresponding tumor. Monocyte-depleted peripheral leukocytes generated lesser CTL activity than the monocyte-containing leukocyte population. However, the KAF was able to replace the monocyte function. The KAF acted at the CTL generation phase as well as the effector phase. The KAF-activated killer cells possessed CD4-8+ surface phenotype. The CTL killed autologous tumor or other unrelated tumor cell lines only when they shared some of the HLA class I antigens. It was also demonstrated that the KAF does not activate killer cells without proper antigenic stimuli, because the KAF-augmented CTL possess specificity against autologous tumor or other HLA-A or -B matched tumor cell lines. The therapeutic applicability of human KAF for anti-tumor CTL therapy against autologous tumor is discussed.
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PMID:Augmentation of human cytotoxic T lymphocytes against autologous tumor by a factor released from human monocytic leukemia cell line. 250 75

Tumor necrosis factor (TNF) has been reported to have a high selective cytotoxicity to various kinds of tumor cells, but its effect on head and neck cancer is uncertain. To evaluate the effect of TNF on squamous cell carcinoma, we measured TNF sensitivity of six established cell lines derived from esophageal squamous cell carcinomas, TE-1, 2, 3, 4, 5 and 7 as well as L-M, FL, WISH, HEp-2 and THP-1 by means of 3H-thymidine incorporation method. HEp-2 derived from human laryngeal cancer, L-M, TE-3 and TE-4 were sensitive to TNF while THP-1, TE-1, 2, 5 and 7 were not. IFN gamma is known to be an inducer of TNF receptor of some kinds of tumor cells. TE-2 and TE-3 were sensitive to IFN gamma. Combined use of these two cytokines resulted in additive inhibitory effect on TE-2 and 3, but no remarkable synergistic effect on any of TE-1, 2, 3 or 4.
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PMID:[TNF sensitivity of the established cell lines derived from esophageal squamous cell carcinomas and combined effect of TNF and IFN gamma]. 251 Dec 89

Three distinct Fc receptors for IgG, Fc gamma RI, Fc gamma RII and Fc gamma RIII are known to be associated with human myeloid cells. Using mAb specific for these receptors, and the hydridoma cells lines that produce these mAb, we have examined the ability of each of these receptors on different myeloid cells and cell lines to mediate killing of tumor and red cell targets. Hybridoma cells (HC) expressing anti-Fc gamma RI, Fc gamma RII or Fc gamma RIII upon their surface were used as model self-directed tumor targets. Chicken erythrocytes (CE) were used as another type of target cell and in this case effector cell cytotoxicity was mediated by heteroantibodies (HA) composed of Fab fragments of anti-Fc gamma R mAb covalently linked to Fab fragments of rabbit anti-CE antibodies. Monocytes, lymphocytes, polymorphonuclear cells (PMNs) and the myeloid cell lines U937, HL-60 and THP-1 were used as effector cells either in their native state or after activation with rIFN-gamma. Direct comparison of cytotoxicity by the same effector cell population against both tumor and erythroid targets has permitted definitive evaluation of the ability of the different Fc gamma R to promote cytolysis under two different conditions. Monocytes were able to utilize Fc gamma RI, Fc gamma RII and Fc gamma RIII in killing both CE and HC targets, and incubation with rIFN-gamma augmented their ability to kill CE, particularly through Fc gamma RI. Fc gamma RII and Fc gamma RIII mediated killing of CE by untreated neutrophils. rIFN-gamma induced PMNs to express Fc gamma RI and to mediate killing of CE through this receptor. Moreover, HC targets were not lyzed by untreated neutrophils, but rIFN-gamma activated neutrophils killed HC bearing surface anti-Fc gamma RI and anti-Fc gamma RII, but not anti-Fc gamma RIII. Myeloid cell lines HL-60 and U937 were unable to perform cytotoxicity without prior culture with rIFN-gamma, following which they killed CE through Fc gamma RI and Fc gamma RII, but were still incapable of HC lysis. THP-1, another myeloid cell line, was cytotoxic to CE through Fc gamma RI and Fc gamma RII without activation. Following rIFN-gamma treatment, cytotoxicity through these two Fc gamma R increased and was also mediated by Fc gamma RIII but these cells were still unable to kill HC.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The functional properties of Fc gamma RI, II and III on myeloid cells: a comparative study of killing of erythrocytes and tumor cells mediated through the different Fc receptors. 253 42

Granulocyte-macrophage colony stimulating factor (GM-CSF) is a glycoprotein which controls growth and differentiation of hemopoietic cells to form mature granulocytes and macrophages. The presence of specific high-affinity receptors for this factor on myeloid cell lines was investigated using radiolabelled recombinant human GM-CSF. Eight cell lines representing different stages of myeloid differentiation were examined. Equilibrium binding at 37 degrees C using different concentrations of 125I-GM-CSF and Scatchard Plot analysis was used to determine the equilibrium dissociation constant and the average number of receptors per cell. Low receptor numbers were found with an average of 74 on HL-60 cells and decreasing numbers on U-937, KG-1, X-376 and THP-1. Receptors were not detectable on RC-2A, CTV-2 and HEL cells. Other cell lines were also investigated including a Burkitt type ALL cell line, X-308 and a Hodgkin's tumor cell line, L 428 KSA. No receptors were detectable on these lines. Normal blood mononuclear cells were examined and indicated that more mature cells have a higher receptor density. Receptors were detectable on normal bone marrow cells but the nature and receptor density of the binding cells remains to be elucidated.
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PMID:Human myeloid cells possessing high-affinity receptors for granulocyte-macrophage colony stimulating factor. 253 82

The antitumor effects of ultrasonic (US) irradiation in combination with the administration of an anthracycline drug, such as adriamycin and THP-adriamycin, were investigated from a viewpoint of the generation of superoxide radicals (SOR). In the in vitro experiments, the generation of SOR by US irradiation was measured by the amount of cytochrome c reduced. The addition of the drug stimulated the generation of SOR by US irradiation. In the in vivo experiments, Donryu rats inoculated subcutaneously by Yoshida sarcoma were treated with US irradiation in combination with the drug. During US irradiation, the temperature of the rat tissue irradiated was kept below 37 degrees C to avoid thermal effects. To know the optimum timing of US irradiation after the administration of the drug, the drug concentrations in the tumor and blood were determined and the time course of drug concentrations was analyzed pharmacokinetically. The effects of drugs and/or US irradiation showed antitumor activity judged by the growth of the tumor size or the survival time of rats. The combination treatments of US irradiation with the drug marked additional or synergistic effects on Yoshida sarcoma. Considering the relationship between the antitumor effect in vivo and the generation of SOR in vitro, the increase of anti-tumor effect of US irradiation by the anthracycline drug may be caused by the stimulation of the generation of SOR.
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PMID:[Increase in the generation of superoxide radicals and in the inhibitory effect on Yoshida sarcoma of anthracycline antitumor agents by ultrasound]. 254 50

Since 1987, 14 patients (10 colorectal, 3 gastric and 1 lung cancer) with unresectable liver metastases received intra-arterial infusion chemo-embolization therapy using implantable infusion port. All patients had more than one lesion in bilateral lobe (H2 and H3). Infusion catheters were placed in the proper hepatic artery through the gastroduodenal artery on laparotomy. Infusion ports were implanted in the subcutaneous tissue of the abdominal wall. Various kinds of chemotherapeutic agents such as MMC, ADR, THP-ADR, CDDP and 5-FU were injected with embolization material (DSM or Lipiodol), every 1 to 4 weeks at the outpatient clinic. Among 10 cases of H2 grade metastases, 1 CR and 3 PR (40% clinical response) were obtained. However, all 4 cases of H3 grade were judged PD. All patients except one with H2 grade metastases are still alive, but 3 out of 4 with H3 grade died within 7 to 11 months. Catheter occlusion was observed in 4 cases for 3 to 7 months. Infection around the port occurred in 1 patient. A patient with metastatic liver cancer was treated by intermittent bolus injection with MMC and DSM. Partial response was confirmed by CT and tumor markers. Histological response was demonstrated in the specimen obtained at partial hepatectomy. It is concluded that this treatment is variable to prolong the survival of patients with H2 grade metastatic liver cancer, together with maintenance of the quality of life.
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PMID:[Chemo-embolization therapy of unresectable liver metastases using implantable infusion port]. 255 Dec 30

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


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