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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our previous studies demonstrated TRH stimulation of TSH beta gene expression in rat pituitary cell cultures and GH3 tumor cells in a transient expression assay. To begin to characterize the gene-proximal elements of the pathways involved in TRH stimulation of TSH beta gene transcription, we examined the effects of factors that increase intracellular calcium concentration, [Ca2+]i, or activate protein kinase C on TSH beta promoter activity in transfected GH3 cells. TPA, a tumor-promoting phorbol ester, stimulated a dose-dependent increase in TSH beta promoter activity at 8 h similar to TRH (2-3-fold). TPA did stimulate protein kinase C activation without [Ca2+] mobilization. The calcium ionophore ionomycin increased cytoplasmic free [Ca2+] by stimulating both calcium influx and release from internal stores without affecting protein kinase C. Ionomycin also stimulated a dose-dependent increase (2-fold) in TSH beta promoter activity at 8 h. However, the voltage-dependent Ca2+ channel agonist Bay K 8644, which increased influx of extracellular calcium, had little or no effect on TSH beta gene expression until 48 h (5-fold). Similar effects on prolactin/mRNA levels were observed in these cells. Effects of these factors were not additive, suggesting a common pathway(s) to stimulate gene expression. Inhibition of intracellular calcium mobilization by treatment with 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8) inhibited ionomycin effects on gene expression without affecting phorbol ester activity, and, conversely, inhibition of protein kinase C activity by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) or TPA desensitization blocked TPA effects without affecting ionomycin activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thyrotropin-releasing hormone regulation of thyrotropin beta-subunit gene expression involves intracellular calcium and protein kinase C. 170 68

A cell line designated RMG-II was established from the ascites of a patient with ovarian clear cell carcinoma. The chromosomal analysis revealed aneuploidy with a hypertetraploid modal number and 8 marker chromosomes. Radioimmunoassay and immunocytochemical staining showed that RMG-II cells produced some tumor markers such as CA125 and TPA. Two monoclonal antibodies, designated MA602-1 and MA602-6, were generated by immunization of mice with an extract prepared from the culture supernatant of RMG-II cells. The epitopes recognized by these two monoclonal antibodies were proved to differ from the CA125 epitope, but to exist on the molecule bearing CA125. We developed a double-determinant sandwich enzyme immunoassay using these two monoclonal antibodies, and the antigen defined by this assay was termed CA602. CA602 was frequently found in the sera of ovarian cancer patients; the positive rates were 92%, 38%, 60%, and 80% for serous, mucinous, clear cell, and endometrioid ovarian carcinomas, respectively, when the cut-off value was set at 60 U/ml (= mean + 3SD of healthy females). CA602 levels in serum were also high in endometriosis patients and in early pregnancy, as is the case for CA125, and the correlation coefficient between CA602 and CA125 was high (r = 0.88). Our preliminary evidence suggests that this CA602 assay system has higher sensitivity than the CA125 one.
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PMID:A new CA125-like antigen (CA602) recognized by two monoclonal antibodies against a newly established ovarian clear cell carcinoma cell line (RMG-II). 171 39

Levels of serum tumor markers including CEA, AFP, CA 15-3, CA 19-9, CA 125 and TPA were measured in 26 patients with bone metastases and in 9 patients with primary bone tumors. TPA was the most sensitive marker to detect skeletal metastasis being elevated in 15 of the 22 patients (68.2%). High sensitivity was observed in CEA (46.1%), CA 15-3 (40%), and CA 125 (35%), and AFP showed relatively low sensitivity (4.3%). When elevation of TPA only or elevation of more than two tumor markers including TPA was used as a screening test for skeletal metastasis, over-all sensitivity, specificity, and accuracy were 73.1%, 88.9%, and 81% respectively. No definite correlation between the markers could be seen in this study. A combination of serum tumor markers was useful in the differential diagnosis of bone metastases from primary bone lesions. However, organ specificity of the markers were relatively low.
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PMID:[Diagnosis of skeletal metastases by serum tumor markers]. 172 Jan 62

Twenty patients (42-80 years old of whom 9 women) affected by instrumentally ascertained pancreatic cancer (7 cases were operated on) were studied. In all of them the following coagulation indices (fibrinopeptide A, FpA; beta-thromboglobulin, BTG; platelet factor IV, PF4; fibrinogen degradation products, XDP) and tumor markers (gastrointestinal cancer associated antigen, GICA; tissue polypeptide antigen, TPA; carcinoembryonic antigen, CEA; alpha-fetoprotein, or AFP) were assessed at the time of diagnosis, and 10 and 30 days after diagnosis, to test whether and which of the above parameters are more sensitive for entertaining the underlying affection. In both operated and nonoperated patients FpA was shown to be the most sensitive index. Lesser sensitivity was shown by XDP, GICA, and BTG. AFP proved to be quite useless as its serum levels constantly fell within the normal range.
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PMID:Coagulation disorders and tumor markers in the diagnosis of pancreatic cancer. 172 Aug 84

The authors evaluate the positivity of the tumor markers CEA, AFP, TPA and ferritin among an homogeneous group of 500 patients suffering from a chronic hepatopathy and positive for HBsAg. The obtained results show a significant increase of TPA, AFP and Ferritin (70.4%, 20% and 24% respectively of the examined patients), while CEA is increased only in the 3.2%. The correlation between the positivity of these markers and possible evolution of the chronic hepatopathy is at present under investigation.
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PMID:[A retrospective study of the serum CEA, AFP, TPA and ferritin values in 500 patients with chronic liver diseases]. 172 99

N-heterocyclic aromatics are environmentally important carcinogenic pollutants produced by incomplete combustion of organic material. 7H-Dibenzo-(c,g)carbazole (DBC), is a potent skin and systemic carcinogen, whereas dibenz(a,j)acridine (DBA), is a carcinogen with local effects. Therefore, the overall objective of these studies was to determine the initiating ability of DBC and DBA in mouse skin using an initiation-promotion protocol. Acetone-, TPA- or BaP-treated animals were used as negative and positive controls, respectively. DBC, DBA or BaP (200 nmol) dissolved in acetone was applied once to the backs of thirty shaved Hsd:(ICR)Br female mice, followed 2 weeks later with 2 micrograms of TPA in 50 microliters of acetone applied twice a week for up to 24 weeks. Skin tumors developed in 26, 17 and 27 animals, respectively. DBC plus TPA produced a significant influx of dermal macrophages similar to that seen for BaP. Initiation with BaP, DBC or DBA moderated the effect of TPA on most other dermal parameters, particularly neutrophils. These data indicate that, DBC, with apparently different activation pathways than BaP shows similar tumor initiating ability and morphological changes as BaP.
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PMID:Comparative tumor-initiating ability of 7H-dibenzo(c,g)carbazole and dibenz(a,j)acridine in mouse skin. 173 15

To characterize basic fetoprotein (BFP) as a new tumor marker, we measured serum levels of BFP and 5 other tumor markers (CA19-9, CEA, NSE, SCC, and TPA) concomitantly in 65 patients with lung cancer, 57 patients with benign pulmonary disease, and 40 healthy volunteers. The sensitivity of BFP was 43%, the specificity 82% and the accuracy 61%. The positivity increased in relation to stage of the disease. There was no correlation between positivity of BFP and histologic type. On the whole, BFP appeared to be analogous to TPA in terms of broad spectrum and to have an auxiliary value in diagnosing lung cancer.
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PMID:Preliminary study on auxiliary value of serum basic fetoprotein in diagnosing lung cancer. 174 51

Cremophor EL, a polyloxyethylene castor oil derivative used clinically as a parenteral vehicle, inhibits protein kinase c activity in vitro. The tumor promoting agent TPA (12-0-tetradecanoylphorbol-13-acetate) activated protein kinase C and induced phosphorylation of cellular proteins of human myeloblastic leukemia ML-1 cells. Polypeptides of 56 KDa, 44 KDa, 37 KDa, 35 KDa and 31 KDa were particularly phosphorylated in response to TPA activation. However, the phosphorylations of these polypeptides, especially that of 37 KDa, were greatly reduced by treatment of the TPA-activated ML-1 cells with Cremophor EL. Cremophor EL also inhibited the growth of ML-1 cells. On the other hand, the TPA-induced cell differentiation in ML-1, which is considered a separate event from protein kinase C activation, was not affected by Cremophor EL. These studies suggest biological implications for the observed in vitro activity of Cremophor EL. The studies may also provide a mechanism for the Cremophor EL-associated cytotoxicities observed when it is used clinically as a parenteral vehicle.
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PMID:Cremophor EL inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced protein phosphorylation in human myeloblastic leukemia ML-1 cells. 174 8

To examine whether protein kinase C (PKC) plays a role in mediating growth inhibitory effects of hexamethylene bisacetamide (HMBA) we compared a control H29 colon cancer cell line to a derivative, HT29-PKC7, that overexpresses high levels of PKC beta 1. We found that although HMBA markedly inhibited the growth of the control cells, no inhibition was seen with the HT29-PKC7 cells. On the other hand the tumor promoter 12-0-tetradecanoyl-phorbol-13 acetate inhibited the growth of HT29-PKC7 cells, but no inhibition was seen with the control cells. Maximum inhibition of the growth of both cell lines was obtained by combined treatment with HMBA and TPA. These results may be relevant to the use of HMBA in combination with other agents in the therapy of specific cancers.
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PMID:The modulation of growth by HMBA in PKC overproducing HT29 colon cancer cells. 175 60

The 2-5 A synthetase is a system of several isozymes, whose expression is induced by interferons (IFNs) at the transcriptional level. These enzymes mediate part of the antiviral effects of IFNs and are thought to have an important role in cell growth or differentiation. The different isozymes -100, 69, 46 and 40 kDa expressed in human cells, or the 105, 71 and 43 kDa expressed in mouse cells--are induced by IFNs with cell type specificity, and exhibit individual differences in their biochemical and enzymatic properties. Here we studied the effects of the tumor promoter phorbol ester (TPA), or the calcium ionophore A23187, on the pattern of expression of 2-5 A synthetase isoforms, and found a role of protein kinase C (PKC) in the adjustments of this pattern. We show that in HeLa cells the 100 kDa 2-5 A synthetase can be specifically induced by short term treatments with TPA, or with the calcium ionophore A23187. Induction of the 100 kDa form is mainly post-transcriptional. By contrast long term treatments by TPA resulting in the down regulation of PKC, or employing H7, a specific PKC inhibitor, reduced drastically the induction by IFNs of the 100 kDa enzyme in HeLa or fibroblast cells, without reducing the expression of the other forms. Moreover, using a mouse Swiss 3T3 cell line in which the cDNA coding for PKC-alpha was introduced, leading to its overexpression, we could show that the mouse 105 kDa synthetase was constitutively expressed. Thus, a direct correlation was found between the expression of PKC-alpha and the specific induction of the 105 kDa form. Neutralization of autocrine IFNs by antibodies reduces the expression of the 105 kDa species. However the autocrine IFN in the medium of the cells overexpressing PKC is not able to induce 2-5 A synthetase in control transfected Swiss 3T3 cells. Thus, IFN is probably essential for the expression of the 105 kDa synthetase but may be not produced in sufficient amounts to induce the 105 kDa protein.
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PMID:Specific regulation of the 100 kDa 2-5 A synthetase by protein kinase C. 175 33


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