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

To assess their usefulness in the prediction of tumor recurrence, we retrospectively examined the accuracy of preoperative diagnosis of ovarian cancer based on tumor markers on 279 patients with benign and malignant ovarian tumors treated at our department. Of the tumor markers examined, CA125 had the highest diagnostic accuracy, suggesting that it is the most useful marker in the diagnosis of ovarian cancer. TPA and IAP were found to be relatively useful, the tumor markers recently identified, CA72-4 had a high true positive rate. We examined the factors affecting the cut-off value for CA125 in healthy volunteers and determined the corrected cut-off value. Using this value, we assessed the usefulness of CA125 in distinguishing between benign and malignant tumors and in predicting tumor recurrence. Factors found to affect the serum CA125 level included pregnancy, menstrual cycle, dysmenorrhea, menopause, and blood type. Using our equation for women over 40 years of age, we obtained a specific cut-off level of 16 U/ml for postmenopausal women, which was found to more accurately distinguish between ovarian tumors in this age group than did the conventional cut-off level of 35 U/ml, which has been used for all age groups. Furthermore, the specific cut-off level predicted tumor recurrence about 2 months earlier than did the conventional cut-off value. In tumor recurrence, CA125 had risen gradually but was within the normal range. Tumor recurrence was observed in all patients who had shown continuous three-stage elevation of CA125 within the normal range.
 ...
PMID:[Relationship between tumor markers and clinical symptoms in ovarian cancer]. 159 60

Influences of indomethacin, which has been known as an inhibitor of the production of prostaglandins, on the suppression of footpad reaction (FPR) of BALB/c mice against sheep red blood cells by the painting of 12-O-tetradecanoylphorbol 13-acetate (TPA, a typical tumor promoter) were studied. The temporary suppressive effect by the painting of TPA (8 nmol) was abrogated by the painting of indomethacin (7-70 nmol) 60 min before TPA treatments. The lasting suppressive effect by TPA treatment (8 nmol/d) for 7 d following the painting of 7,12-dimethylbenz[a]anthracene (DMBA, 400 nmol), which is a typical tumor initiator, also disappeared when indomethacin (7 nmol) was painted 30-90 min before each TPA treatment. Influences of some inhibitors of tumor promotion on the lasting suppressive effect of FPR by DMBA and TPA were also tested. Painting of 0.6 mumol of 1-phenyl-2-pyrazolidone, 8.2 nmol of salcophytol A, 17 nmol of retinoic acid, 5.6 mumol of 3(2)-tert-butyl-4-hydroxyanisol, and 3 mumol of quercetin 45 min before each TPA treatment decreased the suppressive effect on the footpad reaction.
 ...
PMID:Abrogation of the suppressive effect of 12-O-tetradecanoylphorbol 13-acetate and 7,12-dimethylbenz[a]anthracene on footpad reaction of mice by indomethacin and some inhibitors of tumor promotion. 160 43

Stromelysin gene expression is transcriptionally activated by a number of growth factors (e.g., EGF and PDGF), tumor promoters (e.g., TPA), and oncogenes (e.g., ras, src) through an AP-1-dependent mechanism. TGF-beta repression of stromelysin induction is mediated at the level of transcription by an element located at position -709 in the rat stromelysin promoter referred to as the TGF-beta inhibitory element (TIE). A TIE-binding protein complex is induced by treatment of rat fibroblasts with TGF-beta. This protein complex contains the protooncogene c-fos, and induction of c-fos by TGF-beta is required for the repressive effects of TGF-beta on stromelysin gene expression. Interestingly, c-fos induction is also required for stimulation of stromelysin expression by EGF in rat fibroblasts. Preliminary studies suggest that differential regulation of members of the jun family of early-response genes may explain this apparent paradox and determine whether stromelysin is induced or repressed by growth factors. TGF-beta stimulation therefore initiates a cascade of events that results in a specific pattern of gene expression: the direct stimulation of early-response genes can lead to subsequent induction or repression of other genes. Growth factor regulation of matrix metalloproteinases appears to play a role in embryonic development in the morphogenesis of the murine lung. Treatment of embryonic lungs in organ culture with the growth factors EGF or TGF-alpha results in stimulation of growth and inhibition of branching morphogenesis. A similar inhibition of branching was observed when these lung rudiments were treated with the matrix metalloproteinase collagenase. Most interestingly, the effects of EGF and TGF-alpha can be completely reversed by the tissue inhibitor of metalloproteinases, TIMP. TGF-beta has the opposite effect on growth of murine lung rudiments--growth is inhibited in a dose-dependent manner. This example illustrates a potential role for growth factor regulation of matrix-degrading metalloproteinases in complex developmental processes.
 ...
PMID:Negative regulation of gene expression by TGF-beta. 163 49

We obtained a Ca(2+)-independent but 12-O-tetradecanoyl phorbol ester (TPA).phospholipid-activated protein kinase from rat embryo fibroblast 3Y1 cells by succeeding steps of DEAE-cellulose, H-9 affinity, and hydroxylapatite chromatography. This kinase was separated chromatography. This kinase was separated from a conventional PKC (Type III), by H-9 affinity column chromatography. The major peak from H-9 affinity column was eluted at 0.4 M of arginine and on the following step of hydroxylapatite column chromatography, at the KPO4 concentration of 0.1 M. The enzyme could be stimulated by phospholipids and by the tumor promoter TPA, but did not respond to calcium. The Ca(2+)-independent, phospholipid-activated protein kinase activity was susceptible to the protein kinase C inhibitors H-7 and K252a, but showed a phospholipid dependency and substrate specificity distinct from the conventional types of PKC. This protein kinase did not react with monoclonal antibodies against Types I, II, and III PKC. The activity of this enzyme was specifically reduced by immunoprecipitation, depending on the concentration of the polyclonal antibody, PC-delta, which was raised against a peptide synthesized according to a sequence of rat brain nPKC delta. The enzyme had a Mr of 76,000 as estimated by Western blotting. These results provide evidence for a unique type of Ca(2+)-independent, phospholipid-activated kinase, as expressed in 3Y1 cells.
 ...
PMID:Ca(2+)-independent, phospholipid-activated protein kinase in 3Y1 cells. 165 33

Previous studies from our laboratory have demonstrated that epidermal growth factor (EGF), induces intracellular alkalinization in chicken granulosa cells by activating a sodium-dependent and amiloride-sensitive Na+/H+ antiporter. In the present investigation we have examined the possible involvement of protein kinase C (PKC) in the regulation of intracellular pH (pHi) by EGF in chicken granulosa cells. Intracellular pH in granulosa cells obtained from the two largest preovulatory follicles was determined spectrofluorometrically using the dye 2',7'-bis-(carboxyethyl)-5(6)-carboxyfluorescein. The resting pHi was 6.81 +/- 0.01 (n = 30) when the extracellular pH and sodium concentration were 7.3 and 144 mM, respectively. 12-O-Tetradecanoyl-phorbol-13-acetate (TPA; 50-400 ng/ml) and 1-oleoyl-2-acetylglycerol (OAG; 1-75 micrograms/ml) mimicked the actions of EGF by inducing a concentration-dependent increase in pHi which reached a maximum of 0.25-0.30 pH units. 4 alpha-Phorbol 12,13-didecanoate, a phorbol ester with no tumor promoting activity had no effect on pHi. Cytosolic alkalinization was observed within 10 min of the addition of each agent and increased over the 60-min observation period. Like EGF-induced cytosolic alkalinization, the increases in pHi in response to TPA or OAG were dependent on the presence of sodium concentration and were inhibited by amiloride, an inhibitor of the Na+/H+ antiporter. The effects of EGF, TPA, and OAG were attenuated by the PKC inhibitors 5-isoquinolinylsulfonyl-2-methyl piperazine and trifluoperazine. Down-regulation of granulosa cell PKC by pretreatment with TPA (200 ng/ml) for 2.5 h inhibited EGF-, TPA-, and OAG-induced cytosolic alkalinization. The effects of maximally stimulatory concentrations of EGF and TPA on cytosolic alkalinization were not additive. The increases in pHi induced by TPA and OAG, but not by EGF, were dependent on the presence of extracellular Ca++. These studies suggest that the EGF-induced intracellular alkalinization in chicken granulosa cells involves a PKC-mediated activation of the Na+/H+ antiporter.
 ...
PMID:Epidermal growth factor elevates intracellular pH in chicken granulosa cells by activating protein kinase C. 165 20

An ELISA method for the determination of circulating specific HSV-TAA antibodies has recently become available (TAF test). The presence of TAF was tested in serum of 154 patients with primary esophageal carcinoma, collected in three institutions. The overall TAF-test positivity rate was 57.1%, being significantly lower in stage IV than in stage III patients. The concordance rate between TAF and CEA, ferritin, TPA, SCC and TATI was low, suggesting that TAF is probably independent of the other tumor markers evaluated. The clinical role of TAF-test determination in patients with esophageal carcinoma is currently under evaluation.
 ...
PMID:TAF test in primary esophageal carcinoma: comparison with other tumor markers. 166 64

Topical application of tumor-promoting agents to the dorsal skin of female SENCAR mice on a twice-weekly basis resulted in a reduction in density per unit area of bone marrow-derived Thy-1+ dendritic cells. Activity was observed for well-established tumor-promoting doses of promoting agents of several different chemical types, including 12-O-tetradecanoylphorbol-13-acetate (TPA, diterpene diester), anthralin (dihydroxyanthrone), and n-dodecane (n-alkane). A reduction in density of the same cells was also observed on the basis of the asialoGM1 lipid as a surface marker after TPA treatment. No parallel effect was observed for epidermal Langerhans (Ia+) cells, the second major epidermal immunofunctional cell type, except in the case of anthralin, a finding which is consistent with the reported toxicity of this agent. The stage 2 promoting agent mezerein was unique in inducing a consistent increase in Langerhans cell densities, but did not affect the density of Thy-1+ cells when applied for a prolonged period unless applied following four doses of TPA. In contrast to the SENCAR strain, the promotion-resistant Balb/c and C56BL/6 strains showed no response with respect to TPA-induced reduction of Thy-1+ cell density. In addition to effects on density, the above tumor-promoting agents induced morphological changes in both Thy-1+ and Langerhans cells. When these changes were placed on a quantitative basis by the calculation of shape and area fraction parameters, marked and significant effects were observed for the above agents, but not for the partial promoting agent mezerein nor the non-promoting phorbol diester 4-O-methyl-TPA. The effects of TPA were largely blocked by the potent anti-promoting agent fluocinolone acetonide, moreover. These findings further support an important role for quantitative and qualitative alterations in dendritic epidermal cells in tumor promotion.
 ...
PMID:Effect of tumor-promoting agents on density and morphometric parameters of mouse epidermal Langerhans and Thy-1+ cells. 167 59

CEA, GICA, TPA, Fibrinopeptide-A (FpA) and Gamma-GT serum levels were evaluated in 312 patients affected by gastric cancer, to assess their effectiveness in diagnosis, evaluation of disease extension and follow-up of gastric cancer. In 204 patients neoplasia was limited to the stomach, in 108 liver metastases, ascertained by ultrasonography and/or TAC, were present. CEA was increased in 224 cases (71.8%); mean values were significantly higher in metastatic patients than in metastasis-free group (p less than 0.001), but overlap of values between the two groups was observed in about one third of cases. GICA was increased in 268 patients (86%) and TPA in 306 (98%), without significant differences between metastatic and metastasis-free group. FpA was increased in all patients; when metastases were present it was significantly higher than in metastasis-free patients (p less than 0.001), with negligible overlap of values between the two groups. Gamma-GT was normal in 202 metastasis-free patients (99%) and increased in 105 patients with liver metastases (97%). On the basis of these data CEA does not seem to have striking diagnostic sensibility nor reliability in differentiating presence from absence of liver metastases in patients with gastric cancer. Combined assay of TPA, FpA and Gamma-GT seems to be the most reliable serological approach in diagnosis, staging and follow-up of gastric cancer.
 ...
PMID:[CEA, GICA, TPA, fibrinopeptide-A, gamma-GT and gastric cancer. A contribution to the rationalization of a combined assay]. 168 76

The present study is based on the assay of four markers (AFP, CEA, TPA, Ca 19-9) using IRMA methods in 36 normal subjects, 44 cirrhosis and 66 HCC patients. Parametric and non parametric tests were used to test differences and correlations. ROC curves and discriminant functions were also elaborated. Normal 95% "cut-off" was determined by the "boostrap" method yielding: CEA 3.4 ng/ml; Ca 19-9 55 U/ml; TPA 58U/l and AFP 5.2 ng/ml. In HCC patients the values of the four markers were, on average, significantly different from those of normal subjects. However, only AFP and TPA exhibited high diagnostic accuracy (90%) for detection of the tumor. Higher than normal mean values for all markers were, also observed in cirrhotic patients. Only AFP yielded effective discrimination between HCC and cirrhosis. The positive prediction for the presence of the tumor on cirrhotic ground was 95% for AFP values higher than 18.5 ng/ml, with a 78% negative predictive value with a 6 ng/ml threshold. Association of AFP with TPA showed only a marginal diagnostic improvement. Results were not improved at all by combining CEA and Ca 19-9 with AFP and/or TPA. In conclusion, AFP is and remains the best marker for HCC and the only one effective in discriminating of HCC from cirrhosis. TPA may be considered a valid alternative if cirrhosis is not present. CEA and Ca19-9 are of no use.
 ...
PMID:AFP, CEA, CA 19-9 and TPA in hepatocellular carcinoma. 170 5

The aim of this study is to elucidate the change in serum levels of gynecological tumor markers throughout the period from the early gestational stage to puerperium. We measured eight tumor markers of--CA 125, TPA, SCC, AFP, haptoglobin, ferritin, CA19-9 and CEA--in 17 healthy women with a normal course of pregnancy, delivery and puerperium, and obtained the following results: 1) Profiles of change in serum levels of CA125, SCC, haptoglobin and ferritin were similar during pregnancy, with those levels being the highest at 4-15 weeks of gestation and declining gradually from 16 to 27 weeks. Serum levels of these four markers decreased significantly (p less than 0.01) at 16-27 and 28-40 weeks of gestation, respectively. 2) A significant (p less than 0.01) increase in CA125 and SCC was observed 2 hours after delivery compared with the levels in the first stage of delivery. However, these two markers decreased to the normal range after the fifth day postpartum. 3) Serum TPA decreased significantly (p less than 0.05) in 16-27 weeks of gestation, comparing with those of 4-15 weeks. Serum CA19-9 and CEA remained almost unchanged within the normal range throughout the period from pregnancy to puerperium. 4) Tumor markers of CA125, TPA, SCC, haptoglobin, ferritin and CEA of which serum levels decreased during the course of pregnancy and puerperium might be a clue to judge whether gynecological tumors in pregnant women are malignant or benign.
 ...
PMID:[Changes in serum levels of gynecological tumor markers throughout the period from early gestation to puerperium]. 170 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>