Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We analyzed the alteration of int-2, c-erbB-2 and EGFR genes in 32 cases of transitional cell carcinoma of the urinary tract, 15 cases of renal cell carcinoma and 14 cases of prostatic carcinoma by Southern blot hybridization method. Three- to 12 fold amplification of int-2 gene was observed in 4 (12.5%) of 32 transitional cell carcinomas. Of these 4 cases 3 were G3 tumor with muscle invasion and the remaining was G1, pTa tumor with subsequent recurrence of multiple tumors. The other 2 cases (6.3%) with invasive transitional cell carcinoma showed amplification of c-erbB-2 gene. Neither amplification nor gross rearrangement of EGFR gene was detected in transitional cell carcinoma. On the other hand, renal cell carcinomas and prostatic carcinomas had neither amplification nor gross rearrangement of these 3 genes. These results suggest that the int-2 gene located in chromosome locus 11q13 and the c-erbB-2 gene have a specific role in carcinogenesis and in progression of transitional cell carcinoma through their gene amplifications.
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PMID:[int-2 and c-erbB-2 gene amplification in urological cancers]. 136 54

In this study, 3 human pancreatic adenocarcinoma cell lines (PC-1, PC-2 and PC-3) and 3 other human cancer cell lines (adenocarcinoma of lung, LETP; gastric carcinoma, SGL7901; and breast carcinoma, BCP37) were investigated by adding EGF, anti-EGF antiserum and anti-EGFR monoclonal antibody into culture medium. EGF was found to exert a mild stimulating effect on the growth of PC-1 and LETP cells, but had no effect on the other 4 cell lines. Anti-EGF and anti-EGFR antibodies inhibited the proliferation of PC-1, LETP and SGL7901 cells. No significant effect on the other 3 cell lines was seen. By using the Northern blot technique, expression of EGFR mRNA was identified in all 6 cell lines. There were 3 bands (10.5 kb, 5.8 kb and 2.8 kb) of EGFR mRNA in all cell lines except for LETP, in which the 10.5 kb band was absent. The results indicate that the effect of EGF on the growth of cancer cells is very complicated and may involve an unknown regulatory mechanism of cancer cell growth. EGF may exert stimulating or inhibiting effects on cancer cell proliferation, or it may have no effect at all, even though the EGFR gene was expressed in these cell lines.
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PMID:[Effects of EGF, anti-EGF and anti-EGFR antibodies on the growth of human cancer cells]. 147 18

Four human colon adenocarcinoma cell lines, SNU-C1, SNU-C4, SNU-C5, and NCI-H716, that are capable of proliferating autonomously in serum-free medium containing no added peptide growth factors were identified. All four cell lines show epidermal growth factor (EGF) receptors (EGFRs), express transforming growth factor alpha (TGF-alpha) messenger RNA, and release anti-TGF-alpha-immunoreactive molecules. The blocking anti-EGFR monoclonal antibody (mAb) 225 blocks autonomous proliferation of SNU-C1 and SNU-C4 cells. In both of these cell lines, the inhibitory effect of mAb 225 is reversible by the addition of EGF, TGF-alpha, or conditioned medium from any of the four cell lines. In contrast, autonomous proliferation of SNU-C5 and NCI-H716 cells is not inhibited by mAb 225 and is not affected by exogenous EGF, TGF-alpha, or conditioned medium. Together, these data confirm the previous finding that anti-EGFR antibodies can inhibit the proliferation of some carcinoma cell lines that coexpress TGF-alpha and EGFR. However, here it is shown that the mechanisms of autonomous proliferation of colon carcinoma cell lines are heterogeneous and not always sensitive to antibody disruption of TGF-alpha/EGFR autocrine interactions.
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PMID:Autonomous proliferation of colon cancer cells that coexpress transforming growth factor alpha and its receptor. Variable effects of receptor-blocking antibody. 173 18

The expression of EGFR was determined immunohistochemically in two groups of patients with glottic carcinoma, one that recurred after a full course of radiotherapy and one that did not. Using a 4-graded scale (-,+,++, ) 80% (12/15) of the recurrent carcinomas had a staining intensity and proportion of stained cells of ++ or more. The same figure for non-recurrent carcinomas was 39% (7/18). The difference is statistically significant (chi-squared with Yates' correction, P less than 0.05). The results indicate that an increased expression of EGFR may influence the rate of recurrence of glottic squamous cell carcinoma after radiotherapy.
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PMID:Expression of epidermal growth factor receptor in glottic carcinoma and its relation to recurrence after radiotherapy. 174 94

The effects of epidermal growth factor (EGF) on membrane potential were investigated in suspensions of the following three cell types endowed with a large complement of specific receptors: EGFR-T17 (a clone of mouse NIH-3T3 fibroblasts overexpressing EGF receptors); A431 and KB (two human carcinoma lines). In all these lines EGF induced a rapid and marked hyperpolarization constituted by an initial peak (in all three cell lines) and a subsequent sustained plateau phase, concomitant with the well-known increase of [Ca2+]i. The time course and phorbol ester inhibitability of the membrane potential effects were the same as for the [Ca2+]i response. Experiments with Na+-free and chloride-free media excluded a major role of the latter ions in the EGF-induced hyperpolarization. In contrast, experiments with high K+ media, with the monovalent cation ionophore gramicidin and with Ca2+-free media together with either a Ca2+ ionophore (ionomycin, in A431 and EGFR-T17), or an agonist (bradykinin, in A431) addressed to a receptor coupled to phosphoinositide hydrolysis, were consistent with the involvement of Ca2+-activated K+ channels. The EGF-induced hyperpolarization was completely blocked by the K+ channel blocker, quinidine, and unaffected by a variety of other drugs. Patch clamping of individual EGFR-T17 cells confirmed the initial hyperpolarization (from approximately -30 mV, the resting potential, to -60, -80 mV) was due to activation of an outward current. This initial hyperpolarization was followed by fluctuations (period approximately 1 min) persisting as long as the cells could be analyzed. Thus, the changes of membrane potential appear to be not only novel members of the group of early events triggered by EGF in target cells but also long-lasting effects of the growth factor, which continue for unexpectedly long periods of time after EGF application.
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PMID:The effect of epidermal growth factor on membrane potential. Rapid hyperpolarization followed by persistent fluctuations. 278 95

The prostatic growth factors require a membrane specific receptor to which they must bind in order to carry out their biological activities correctly. The aim of this study was to isolate and quantify the epidermal growth factor receptor in prostatic tissue and indirectly determine the growth factors acting on it (EGF, TGF alpha, PDGF, NGF, IGF). From September, 1992 to June, 1993, we studied 55 patients. These were divided into two groups: the first group comprised 49 patients with benign prostatic hyperplasia (BPH) and 6 patients with prostatic carcinoma comprised the second group. Samples of the prostate were obtained following suprapubic (12 cases), TUR (38 cases), radical prostatectomy (1 case) and transrectal biopsy (4 cases). The EGFR was determined by radioimmunoassay (EGFR-RIA, Vienna Lab, Labordiagnostica GmbH). For the overall group of patients, we obtained mean EGFR values of 6.36 +/- 0.59 fmol/mg of protein and a positivity of 96.36% and 100% for BPH and malignant proliferative processes, respectively. The foregoing data show that EGFR was isolated from the tissue we analyzed and has an evident role in the regulation of prostate growth.
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PMID:[Involvement of epidermal growth factor receptor (EGFR) in the etiopathogenesis of prostatic proliferative processes]. 752 95

T-CAR1 is a human carcinoma cell line established from a brain metastasis. The tumour cells overexpress EGFR and contain an amplified EGFR gene. In vitro in the presence of 5% human serum the tumour cells grow as adherent cells in monolayer. Shortly after exposure to EGF a large number of tumour cells round up and detach, whereas some remain adherent. At the same time a redistribution of actin occurs. Cytochalazin B prevented this reaction, which indicates that actin is involved in the detachment of the tumour cells. The EGF-detached tumour cells however, did not differ from the tumour cells which remained adherent after EGF-exposure with regard to parameters such as growth in soft agar, growth response to EGF, tumour necrosis factor-alpha, interferon-gamma, and carmustin (BCNU), level of EGFR gene expression and EGFR gene amplification, S-phase fraction, and amount of DNA. It was speculated whether the EGF-induced cellular detachment in vitro could be correlated to metastatic potential in vivo or not. In order to address this issue, in vivo studies with subcutaneous T-CAR1 tumours in nude mice were performed. Administration of EGF resulted in growth stimulation in contrast to growth inhibition in vitro, whereas no effect of EGF on the metastatic potential was observed. Thus, the EGF-mediated tumour cell detachment seems to be restricted to in vitro conditions only.
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PMID:EGF-effects in vitro and in vivo on a carcinoma cell line rich in EGFR. 764 40

The Shc gene encodes three overlapping proteins which all contain a carboxy-terminal SH2 domain. Shc proteins are ubiquitously expressed and are downstream targets and effectors of activated tyrosine kinases (TK). We investigated tyrosine-phosphorylation of Shc proteins in normal and transformed cells. In tumor cells with known TK gene alterations Shc proteins were constitutively phosphorylated and complexed with the activated TK. No constitutive Shc phosphorylation was found in primary cell cultures and normal tissues. In 14 of 27 tumor cell lines with no reported TK alterations, Shc proteins were constitutively phosphorylated and formed stable complexes with novel tyrosine-phosphorylated polypeptides. Ten distinct Shc-associated phosphoproteins were identified with molecular weights ranging from 30 to 200 kDa. In a subset of carcinoma cell lines, phosphorylated Shc proteins complexed with a p175 phosphoprotein that was identified as the constitutively activated EGFR. In one glioblastoma cell line, a Shc-associated p190 was identified as the activated PDGFR. In 13 of 14 acute leukemia samples phosphorylated Shc proteins were constitutively complexed with a p140 phosphoprotein. Some of the Shc-associated phosphoproteins (EGFR, PDGFR, erbB-2, Met, bcr-abl, H4-ret) bound both the Shc- and Grb2-SH2 domains in vitro; others (p175; p70-p80) only the Shc-SH2 domain and yet others (p140) only the Grb2-SH3 domains. These results indicate that Shc proteins are common substrates of constitutively activated TKs and that the analysis of Shc phosphorylation allow the identification of tumors with constitutive TK activation.
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PMID:Constitutive phosphorylation of Shc proteins in human tumors. 767 49

Athymic mice bearing xenografts of human tumours that overexpress the receptor (EGFR) for EGF and TGF alpha have been used to evaluate the therapeutic potential of three new rat monoclonal antibodies (mAbs) directed against two distinct epitopes on the extracellular domain of the human EGFR. The antibodies, ICR16 (IgG2a), ICR62 (IgG2b) and ICR64 (IgG1), have been shown (Modjtahedi et al., 1993) to be potent inhibitors of the growth in vitro of a number of human squamous cell carcinomas because they block receptor-ligand interaction. When given i.p. at 200 micrograms dose, the three antibodies were found to induce complete regression of xenografts of the HN5 tumour if treatment with antibody commenced at the time of tumour implantation (total doses: ICR16, 3.0 mg; ICR62, 1.2 mg; ICR64, 2.2 mg). More importantly when treatment was delayed until the tumours were established (mean diam. 0.5 cm) both ICR16 and ICR62 induced complete or almost complete regression of the tumours. Furthermore, treatment with a total dose of only 0.44 mg of ICR62 was found to induce complete remission of xenografts of the breast carcinoma MDA-MB 468, but ICR16 was less effective at this dose of antibody and only 4/8 tumours regressed completely. ICR16 and ICR62 were poor inhibitors of the growth in vitro of the vulval carcinoma A431, but both induced a substantial delay in the growth of xenografts of this tumour and 4/8 tumours regressed completely in the mice treated with ICR62 (total dose 2.2 mg). Although ICR16 and ICR64 were more effective than ICR62 as growth inhibitors in vitro, ICR62 was found to be substantially better at inducing regression of the tumour xenografts due perhaps to additional activation of host immune effector functions by the IgG2b antibody. We conclude that these antibodies may be useful therapeutic agents that can be used alone without conjugation to other cytotoxic moieties.
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PMID:Immunotherapy of human tumour xenografts overexpressing the EGF receptor with rat antibodies that block growth factor-receptor interaction. 767 81

Increased protein tyrosyl phosphorylation in response to growth factors has been assumed to be solely due to activation of protein tyrosine kinases (PTKs). We report that total cellular protein tyrosine phosphatase (PTPase) activity declined in MDA-MB 468 breast carcinoma cells exposed to epidermal growth factor (EGF). The PTPase activity decreased with concentration as well as with time of EGF incubation. As EGF induces increases in intracellular Ca2+ concentrations and such changes may result in depression of PTPase activity, we treated cells with the calcium ionophore A 23187. Increases in calcium induced by the ionophore resulted in activation of cellular PTPases as indicated by increased dephosphorylation of tyrosine phosphorylated EGFR by cellular lysates. Thus, both the extracellular ligand EGF and the intracellular messenger Ca2+ were shown to modulate cellular PTPase activity in MDA-MB 468 breast carcinoma cells. However, EGF-induced decreases in PTPase activity cannot be attributed to EGF-induced increases in intracellular Ca2+ levels.
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PMID:Role of intracellular Ca2+ in the epidermal growth factor induced inhibition of protein tyrosine phosphatase activity in a breast cancer cell line. 768 60


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