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)

Previous studies showed that the human monocytic leukemia cell line THP-1 can be induced to undergo monocytic differentiation by tumor promoting phorbol esters (TPA), suggesting that protein kinase C (PK-C), the primary binding site of TPA, may play a role in the control of monocytic differentiation: The effect of exogenous phospholipase C (PLC) on THP-1 cells was investigated. Within 24-48 hr, PLC induced over 40% of THP-1 cells to undergo monocytic differentiation as manifested by adherence, growth arrest, functional expression, morphological changes and expression of c-fms gene which encode for M-CSF receptors. Compared to TPA, however, the inducing activity of PLC was weaker, slower and not as effective. PLC treatment also induced a transient expression of c-fos proto-oncogene prior to c-fms expression. On the contrary, the level of c-myc RNA, which is constitutively expressed in THP-1 cells, was down-regulated 48 hr after PLC treatment. The PLC-induced monocytic differentiation in THP-1 cells was inhibited by staurosporine, a potent PK-C inhibitor, further suggesting that direct activation of the PK-C is one of the metabolic events essential for monocytic differentiation. It is postulated that in THP-1 cells the metabolic pathway transducing PK-C activation has been permanently blocked, thereby leading to uncontrolled proliferation without differentiation.
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PMID:Phospholipase C-induced monocytic differentiation in a human monocytic leukemia cell line THP-1. 149 32

In a total of 194 cases, consisting of 86 cases of colorectal cancer undergone operation later, 7 cases of non resectable cancer, 34 cases of recurrence, 43 cases of NED (no evidence of a recurrence after radical surgery for colorectal cancer) and 24 cases of benign colorectal disease, serum CEA, TPA, CA50 and CA72-4 levels were determined. The positivity rate was high for all four markers in stage V cases among 86 cases of colorectal cancer, and in cases of non resectable cancer and cases of recurrence. The highest positive rate was obtained with CEA. On the contrary, in cases of stage I to IV the positivity rates of these four tumor markers were as low as 0 to 34.8%. Out of 127 cases of colorectal cancer excluded of 43 NED cases, 52 cases were negative for all four tumor markers and 14 cases were positive only for CEA. In 49 cases, CEA and at least one of the other three tumor markers gave positive results. In 12 cases, CEA gave negative results and at least one of the other three tumor markers positive results. In conclusion, measurement of blood levels of these tumor markers is limited of its usefulness in early diagnosis of colorectal cancer. However, in the diagnosis of advanced stage and of recurrence during the postoperative follow-up period the measurement of tumor markers provides useful information. CEA is most sensitive among the four tumor markers tested and any combination of these four markers is not advantageous because of an increase in false positivity rate.
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PMID:[Clinical evaluation of four tumor markers (CEA, TPA, CA50 and CA72-4) in colorectal cancer]. 150 78

Using an antibody to BN 52719, an analogue of platelet activating factor (PAF), immunoaffinity mini-columns for the separation of PAF from biological samples were prepared. Rabbits were immunized with BN 52719 and immunoglobulin G (IgG) from the antiserum was coupled with Sepharose 4B. The resulting suspension of the IgG-coated Sepharose 4B in 25 mM phosphate buffer (pH 6.9) was poured into a plastic mini-column (bed volume 2.0 x 0.8 cm). Stepwise elution of the column with methanol revealed that lyso-PAF is eluted with 20-30% methanol in water whereas PAF is eluted with 50-80% methanol. For the determination of PAF in biological samples, it is recommended that lipids are extracted from the samples and the extract, reconstituted in 20% methanol, is loaded on the column. The column is then washed with 50% methanol followed by elution of PAF with 80% methanol. A small amount of [3H]PAF is added to the samples for measurement of the recoveries of PAF during the procedures of extraction and elution. The PAF is then quantified by radioimmunoassay or bioassay. Employing the immunoaffinity mini-column and radioimmunoassay, the contents of PAF in macrophages and conditioned medium after stimulation with calcium ionophore A23187, or tumor promoters such as TPA and thapsigargin, were measured.
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PMID:Preparation of immunoaffinity mini-columns for the analysis of platelet activating factor (PAF) in biological samples. 151 34

Estrogen is thought to stimulate the proliferation of human breast tumors indirectly, through induced production of autocrine polypeptide growth factors. Constitutive production of such growth factors would lead to the loss of 17 beta-estradiol (E2)-dependence that is associated with progression of the disease. Our data, however, do not support this hypothesis and suggest that hormone-dependent breast tumor cell lines like MCF7 do not react to the growth factors which they produce. Moreover, we provide evidence that E2 directly stimulates proliferation by inducing, like many growth factors, the c-fos proto-oncogene. E2 by itself, however, is poorly mitogenic. This may be caused by the lack of induction of genes from the jun family, whose gene products are necessary for dimerization with the c-fos encoded protein, leading to an important step in growth factor signalling pathways; stimulation of TPA responsive element (TRE)-dependent transcriptional activity. In combination with insulin-like growth factors, efficient inducers of c-jun in these cells, E2 synergistically stimulates proliferation and TRE-activity. Constitutive TRE-activation may lead to loss of E2-dependence.
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PMID:Direct stimulation by estrogen of growth factor signal transduction pathways in human breast cancer cells. 152 51

The mechanism by which intravesical recombinant tissue plasminogen activator (rTPA) prevents tumor cell adherence to injured bladder surfaces, and the optimal parameters for the in vivo use of rTPA for adherence prevention, were evaluated. Intravesical rTPA decreased tumor cell adherence to sites of urothelial injury as a direct function of drug concentration in the intravesical fluid. Recombinant TPA concentrations of 1 mg/ml and 0.1 mg/ml significantly decreased tumor cell adherence relative to the control group. The efficacy of rTPA in removing adherent cells was time-dependent with maximal activity occurring at 15 min or later following intravesical administration. Intravesical rTPA effectively reduced the size of the tumor inoculum when administered either concomitant with, or subsequent to, tumor cell exposure. The relative efficacy of these two approaches was dependent upon the presence of serum in the intravesical fluid. Administration of rTPA concomitant with tumor cell exposure proved more effective in the absence of serum, while postadherence administration was more effective in the presence of 10% fetal calf serum. The addition of exogenous plasminogen to the rTPA solution did not increase anti-adherence activity relative to rTPA alone. However, blockade of endogenous plasminogen conversion with systemically administered epsilon-amino-caproic acid reversed the anti-adherence activity of exogenous rTPA. In vitro experiments evaluating cellular adherence to fibrin substrate confirmed that rTPA's anti-adherence activity was dependent on the presence of plasminogen. Exogenous rTPA administered immediately following tumor cell adherence decreased tumor cell implantation in animals receiving low to moderate tumor inoculums. These data suggest that rTPA prevents cellular adherence as a result of plasminogen activation and subsequent fibrinolysis. Intravesical rTPA administered in sufficient concentration for relatively short periods of time effectively reduces the adherent tumor inoculum and alters implantation as an inverse function of the tumor inoculum. This approach represents a novel strategy which may prove applicable for the prevention of implantation-mediated tumor recurrence at sites of surgical trauma.
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PMID:Intravesical recombinant tissue plasminogen activator for the prevention of implantation-mediated bladder tumor recurrence. 153 39

Four tumor promoters, i.e. PB, TPA, NAF, and DDT, added singly to a calcium-deprived synthetic medium, elicited early and late mitogenic effects and concurrent surges of nuclear poly(ADP-ribose) polymerase (pADPRP) activity in primary neonatal rat hepatocytes mutagenized with an intra-uterine dose of DMN. These actions were fully abated by the pADPRP inhibitor 3-MBA. Conversely, EGF only acted as a full mitogen when medium's calcium was at physiological levels, and its effects could not be blocked by 3-MBA. The same tumor promoters, but not EGF, also evoked a swift and lingering amplification of pADPRP transcripts in DMN-initiated hepatocytes kept in low-calcium medium. Hence, a coordinated modulation of both pADPRP transcripts and activity by xenobiotics is likely to be involved in the clonal expansion of early preneoplastic hepatocytes.
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PMID:The exposure of carcinogen-initiated primary neonatal rat hepatocytes to tumor promoters modulates both the transcripts and the enzymatic activity of nuclear poly(ADP-ribose) polymerase. 154 Jan 55

Gomisin A, isolated from the fruits of Schisandra chinensis, is one of the dibenzocyclooctadiene lignans. Application of 12-O-tetradecanoylphorbol-13-acetate (TPA, 1 microgram/ear), a tumor-promoting agent, to the ears of mice induces inflammation. Among seven dibenzocyclooctadiene lignans assayed, gomisin A, gomisin J, and wuweizisu C inhibited the inflammatory activity induced by TPA in mice. The ED50 of these compounds for TPA-induced inflammation was 1.4-4.4 mumol. Gomisin A, with an ED50 of 1.4 mumol, showed the strongest inhibitory effect. Furthermore, at 5 mumol/mouse, it markedly suppressed the promotion effect of TPA (2.5 micrograms/mouse) on skin tumor formation in mice following initiation with 7,12-dimethylbenz[a]anthracene (50 micrograms/mouse). It is assumed that the inhibition of tumor promotion by gomisin A is due to its anti-inflammatory activity.
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PMID:Gomisin A inhibits tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin. 154 98

Under normal culture conditions, the tumor cell lines MPC-11 and HL-60 exhibit high rates of proliferation and show a peculiar expression of intermediate filament proteins as they appear to synthesize only lamin B. A 48-h exposure of murine plasmacytomas MPC-11 to the phorbol ester TPA reduces their growth and induces vimentin synthesis without affecting the composition of their nuclear lamina. When applied to human leukemic promyelocytes HL-60, such treatment promotes their maturation into macrophage-like cells: their proliferative ability is suppressed, a differentiated phenotype is developed, and their content in intermediate filament proteins now includes vimentin and a full complement of lamins A, B, and C. In the present study, a kinetic analysis of vimentin and lamin A/C expression in relation to proliferation and differentiation has been performed in these two cellular systems. Proliferation rates of MPC-11 and HL-60 populations were evaluated by monitoring cell growth and measuring thymidine incorporation. Maturation of HL-60 cells was assessed by Giemsa staining and percentage of adherent cells. Expression of vimentin and lamins A/C was analyzed using immunofluorescence and immunoblotting techniques. Our data show that there is a relationship between the level of vimentin expression and the extent of growth inhibition in both systems. They also suggest that the expression of lamins A/C during the TPA-induced maturation of HL-60 promyelocytes might be part of the processes which lock these cells into the macrophage pathway.
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PMID:Expression of intermediate filament proteins in TPA-induced MPC-11 and HL-60 cells. 154 77

The role of protein kinase C in migration of tumor cells from spheroid cultures was investigated using parental rat glioma cells and their TPA resistant counterparts. These two lines differed in their PKC content as judged by the histone phosphorylation method. Also 4 days of treatment with IRA led to PKC down-regulation. Cells having a drastically decreased PKC level migrated better than those having a normal PKC content.
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PMID:The role of protein kinase C in migration of rat glioma cells from spheroid cultures. 156 92

Values of CA125, CA19-9, TPA, CA72-4, BFP and LDH in sera were detected in 148 malignant ovarian tumors, 41 borderline malignant ovarian tumors, 71 benign ovarian tumors and 64 benign uterine diseases. A new cut-off value was determined by ROC graph for distinguishing malignant and borderline ovarian tumors from benign ovarian tumors. CA125 (cut off: 30 U/ml) was a highly sensitive marker for malignant and borderline malignant ovarian tumors, the value being 88.1% (52/59) and 81.8% (9/11), respectively. On the other hand, in 37 benign ovarian tumors, the positive rate was 21.6% and in 21 benign uterine diseases it was 52.4%. CA19-9 (cut off: 150 U/ml) was inferior to CA125, but it was an effective marker for mucinous ovarian tumors. TPA (cut off: 40 U/ml) was also a sensitive (84.7%, 50/59) marker of malignant ovarian tumors. CA72-4 (cut off: 4 U/ml) was a highly specific (87.0%, 60/69) marker of malignant ovarian tumors. Combination assays of CA125/CA19-9, CA125/TPA and CA125/CA72-4 were not effective. Usefulness of BFP for early malignant ovarian tumors was suggested. Seven cases of dysgerminoma showed extremely elevated LDH levels (1,248 +/- 886 IU/1/37 degrees C). Malignancy and histological type of ovarian tumors could be decided by combination assay of these tumor markers, before surgical operation.
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PMID:[Diagnosis of ovarian tumor by measuring tumor markers]. 158 85


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