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

The CaSki cell line derived from an epidermoid carcinoma of the uterine cervix produces and releases a tumor associated-antigen, TA-4. The authors have already reported that EGF stimulated the production and secretion of TA-4 by the CaSki cells. EGF receptor is known to be one of the proteins phosphorylated by C-kinase. In order to elucidate a possible role of signal transduction systems (cAMP-A-kinase, diacyglycerol-C-kinase and Ca(2+)-calmodulin) in the regulation of TA-4 production and secretion by human cervical epidermoid carcinoma cells, the effects of cholera toxin (CT), an activator of adenylate cyclase, phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, and Ca2+ ionophore A23187, an activator of Ca2+ modulation on TA-4 production and secretion by CaSki cells were evaluated. TA-4 in the cultured cells and media were measured with a SCC RIA-Kit. The addition of PMA or Ca2+ ionophore to the medium caused increases in the cellular levels of TA-4 and TA-4 levels in the medium in a dose-dependent manner shortly after the addition. Combined treatment with PMA and Ca2+ ionophore did not cause additive increases in TA-4 levels in the cells and medium compared to the treatment with PMA alone or Ca2+ ionophore alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The role of signal transduction systems in the regulation of production and secretion of TA-4 by cultured cervical epidermoid carcinoma cells (CaSki)]. 160 73

The degree of gene amplification for epidermal growth factor receptor (EGFR) and its expression levels were examined in 4 cases of tumor lesions and their cell lines of human squamous cell carcinoma (SCC) of the oral cavity. The amplification was detected in 1 case (ZA), but not significantly in 3 other cases (HOC605, HOC815, and HOC927) in which the amplification did not occur during the cell line establishment. In those 3 cases, levels of EGFR synthesis and human EGF (hEGF) binding capacity were varied: HOC605 and HOC815 had slightly increased levels of hEGF binding capacity and EGFR synthesis, respectively. While HOC927 had the lowest levels of both, the hEGF binding capacity was elevated in the tumor lesion when compared with the normal counterpart of the same patient. These results suggest that the increased capacity for EGF binding plays a more important role than does gene amplification on the tumorigenesis of SCC of the head and neck.
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PMID:Gene amplification and overexpression of epidermal growth factor receptor in squamous cell carcinoma of the head and neck. 162 95

Analysis of epidermal growth factor receptor (EGFr) and estrogen receptor (ER) was performed on tumor samples from 231 patients with operable breast cancer followed for up to 6 years after surgery. The median duration of follow-up in patients still alive at the time of analysis was 45 months. Thirty-five percent of patients (82) had tumors greater than 10 fmol/mg of 125I-EGF binding (EGFr+) and 47% (109) had cystolic ER concentration greater than 5 fmol/mg (ER+), with a marked inverse relationship between EGFr and ER (P less than .00001). EGFr was second only to axillary-node status as a prognostic marker for all patients in terms of both relapse-free and overall survival in univariate analysis (P less than .001, log-rank EGFr + v EGFr-). For patients with histologically negative axillary nodes, EGFr was superior to ER in predicting relapse and survival (P less than .01 and P less than .005, respectively, compared to P less than .1 and P less than .1, log-rank). In a multivariate (Cox model) analysis, only EGFr--out of EGFr, ER, size, and grade--was predictive for either relapse-free or overall survival for patients with node-negative disease (P = .052 and P = .026, respectively). One hundred eighty-seven case patients in the series were assessed for neu expression immunochemically, and 31 were positive. There was a highly significant increased risk of relapse and death in the positive group. In patients with otherwise good prognostic markers (ER+, node-negative, well-differentiated tumors), neu expression predicted for significantly worsened overall survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Epidermal growth factor receptor and other oncogenes as prognostic markers. 162 26

We demonstrate for the first time that the expression of tyrosine containing membrane phosphoproteins is elevated in estrogen-induced kidney tumors, which is evident from both the types of experiments, i.e., alkali-resistant phosphorylation of membrane proteins and immunoprecipitation of tyrosine containing phosphoproteins. Tyrosine phosphorylation of proteins or peptides was modulated by the growth factors (EGF, IGF-I) and by the inhibitors of tyrosine protein kinase(s). The kinetic analyses revealed that tumor membranes have high affinity and catalytically more efficient tyrosine phosphorylating kinase enzyme(s) compared to that of normal membranes which have low affinity and catalytically less efficient kinase enzyme(s). It is proposed that overexpression of tyrosine containing membranal phosphoproteins may be involved in the induction and growth of estrogen-induced renal neoplasm.
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PMID:Enhanced expression of membrane phosphoproteins tyrosine phosphorylation in estrogen-induced kidney tumors. 163 68

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.
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PMID:Negative regulation of gene expression by TGF-beta. 163 49

1246-3A is an insulin-independent tumorigenic cell line isolated from the C3H mouse teratoma-derived adipogenic cell line 1246. In the present paper, we have demonstrated that testosterone inhibits the in vivo tumorigenic properties of the 1246-3A cells. Castrated male mice receiving injections of 1246-3A cells developed larger tumors at a higher frequency than sham-operated animals. Administration of testosterone to castrated male mice resulted in a dramatic decrease in tumor development. In vitro studies indicated that testosterone inhibited by 50% the proliferation of the 1246-3A cells in culture. However, growth inhibition was observed only if the cells had been cultivated in the presence of testosterone for at least 4 days. In contrast, testosterone had little effect on the proliferation of the parent cell line 1246. Binding of several polypeptide growth factors was examined in cells cultivated in the absence and in the presence of testosterone. Testosterone increased 125I-EGF specific binding to 1246-3A cells. Scatchard analysis of EGF binding indicated that testosterone treatment induced a 2.4-fold increase in the number of cell surface EGF binding sites. This was accompanied by an increase in the intensity of cross-linked EGF receptors on the cells treated with testosterone. In addition, 1246-3A cells cultivated for 9 days in the presence of testosterone displayed a 10-fold increase in the level of EGF receptor mRNA when compared to 1246-3A cells maintained in its absence. Similar to its action on cell proliferation, the increase in EGF receptor number and mRNA expression was observed mainly if 1246-3A cells had been exposed to testosterone for 9 days. The data presented in this paper demonstrate that both in vivo and in vitro, testosterone induces in the teratoma-derived 1246-3A cell line phenotypic changes such as growth inhibition and modulation of EGF receptor expression.
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PMID:Effect of testosterone on the growth properties and on epidermal growth factor receptor expression in the teratoma-derived tumorigenic cell line 1246-3A. 163 38

Clonogenic cultures from 27 lung cancers were realised. For 68% of cases a clonogenic growth was observed, but no direct correlation could be done with the differentiation of the tumor or with the presence of ganglion metastases. EGF in medium increased the number of colonies obtained in 60% of cases.
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PMID:[Clonogenic culture of identified cells of lung tumors and correlation with certain histopathologic aspects of the tumor mass]. 165 Jul 68

We have shown in previous studies that metastatically-competent variant subpopulations (B5, C1) derived from a non-metastatic murine mammary adenocarcinoma (SP1) have a pronounced growth advantage over their non-metastatic tumor cell counterparts in primary tumors. As a result, primary tumors can be progressively overgrown by cells having the competence to spread elsewhere in the body. This occurs despite any evidence to indicate an intrinsic in vivo growth rate advantage of the metastatic cells when grown as isolated populations. This suggested that cell-cell interactions between metastatic and non-metastatic tumor populations may be involved in the metastatic cell growth dominance process. Evidence was therefore sought for growth factors released by SP1 cells which could preferentially stimulate the B5 or C1 variants and thereby mediate this cell-cell interaction process. We found that cocultures of SP1 and C1 or B5 cells with irradiated C1, B5, or SP1 "feeder" cells showed significant stimulation of C1 and B5 by SP1 "feeder" cells. Cell growth stimulation in response to EGF, TGF-alpha, TGF-beta 1, bFGF, PDGF, NGF, IGF-1, or IGF-2 demonstrated that only TGF-beta 1 could duplicate this effect. A repeat of the coculture experiment in the presence of specific neutralizing anti-TGF-beta antibodies was therefore undertaken and this was found to markedly reduce the stimulation of C1 or B5 cells by irradiated SP1 cells. Conditioned media from the SP1 and C1 cell lines was quantitated for TGF-beta activity and contained 4.5 ng/ml and 2.0 ng/ml, respectively. However, the majority of the TGF-beta released by SP1 cells was found to be spontaneously active, whereas 70% of the TGF-beta released by C1 cells was in its latent form. Scatchard analysis revealed approximately four times the number of TGF-beta receptors, of similar type and affinity, present on C1 as compared with SP1 cells. The in vitro results support the hypothesis that active TGF-beta released by SP1 cells may stimulate the proliferation of metastatic variant cells in a paracrine like fashion. In vivo evidence for this was obtained by showing that coinjection of irradiated SP1 cells could selectively stimulate tumor growth of viable C1 cells and this effect was markedly diminished by neutralizing polyclonal anti-TGF-beta antibodies. Taken together, the results suggest a novel role for TGF-beta in clonal evolution of malignant tumor growth and as a molecular mediator of tumor cell-tumor cell interactions involved in facilitating tumor progression.
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PMID:Reduction of TGF-beta activity abrogates growth promoting tumor cell-cell interactions in vivo. 165 15

The expression of the oncogene products ras p21, c-myc and the growth factor EGF (epidermal growth factor) was studied immunohistochemically in the tissue of 119 benign and malignant human breasts. In most cases, histologically normal breast tissues and benign lesions were found to be negative or poorly-expressive for reactivity with each antibody. Similar findings were observed in carcinoma in situ. Invading breast carcinomas demonstrated a significantly higher percentage of stained cells than that observed in benign lesions or carcinoma in situ; forty-two of 66 invasive breast carcinomas (63.6%) were highly-expressive for ras p21, thirty-eight (57.6%) for c-myc and twenty (30.3%) for EGF, but overall correlations between each oncogene expression and the clinical stage, tumor size or degree of differentiation were not found. The overall 5-year survival rate was studied in 58 patients with Stage II and III in association with each oncogene or EGF expression. Their survival rate was significantly effected by the EGF expression (0.05 less than p less than 0.1) but not by ras p21 or c-myc expression. Analysis of 36 specimens available with ER (estrogen-receptor) level revealed a significant correlation between the ER status and c-myc or E2 (estradiol) and a significant inverse correlation between ER status and ras p21 or EGF expression (P less than 0.05). The expression of ras p21, EGF and c-myc was not associated with metastatic tumor progression.
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PMID:Immunohistochemical study of oncogene product ras p21, c-myc and growth factor EGF in breast carcinomas. 166 Jun 89

Alpha fetoprotein (AFP) is present at high concentrations in fetal fluids, certain neoplasias, and regenerating liver. Its physiological function remains largely unknown. Using a primary monolayer culture system, we investigated the proliferative activity of human (h) cord blood (CB) and highly purified AFP. hAFP, purified from hCB by Cibacron blue and immunoaffinity chromatography was homogeneous on SDS-PAGE and silver stain. Porcine granulosa cells from ovarian small follicles were cultured (25,000/cm2) for 2 days in medium (Ham's F-12:DMEM, 1:1) + 5% fetal calf serum (FCS) to facilitate attachment, followed by 6 days in medium containing: FCS, hCB or h amniotic fluid (1-20%)+/- EGF (10 ng/ml); or 0.25% plasma-derived serum (PDS) containing human low density lipoprotein (LDL, 25 ug/ml), +/- AFP (0.05-5 ug), and +/- EGF and IGF-I (10 ng/ml). In this system, single growth factors do not stimulate proliferation, a characteristic also exhibited by AFP. When combined with EGF, however, AFP dose-dependently increased proliferation to levels equal to that obtained with 10% FCS (2.3-fold increase vs PDS/LDL controls). When combined with EGF+IGF-I, AFP again dose-dependently increased proliferation to levels equal to that obtained with 10% FCS+EGF (6.7-fold increase vs controls). Purified human albumin used in place of AFP was not effective. TGF-a but not PDGF could replace the proliferative activity of EGF. These results suggest that AFP at physiological levels, although not itself mitogenic, can enhance the mitogenic activity of EGF and TGF-a and may function to modulate growth factor-mediated proliferation during development and neoplasia.
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PMID:Human alpha fetoprotein enhances epidermal growth factor proliferative activity upon porcine granulosa cells in monolayer culture. 168 14


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