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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of epidermal growth factor receptor (EGF-R) in normal gastric mucosa, gastric mucosal dysplasia, early and advanced gastric carcinoma was studied with the monoclonal antibody to EGF-R by using immunohistochemical ABC method. Normal gastric mucosa was negative for EGF-R, but a relatively high positive rate was found in dysplasia. When gastric carcinoma occurred, the positive rate decreased. The expression of EGF-R was related to the poor differentiation and strong infiltration of gastric carcinoma. The carcinoma with the expression of EGF-R was easy to metastasize to lymph nodes. The result suggests that EGF-R might play some role in the process of carcinogenesis of gastric mucosa, and be used as a useful marker for the assessment of the biological behavior of gastric carcinoma.
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PMID:[Expression of EGF-R in gastric carcinoma and precancerous lesion]. 826 63

EGFR is a member of the tyrosine kinase family of cell surface receptors with a wide range of expression throughout development and in a variety of different cell types. The receptor can transmit signals to cells: i) upon interaction with ligands such as EGF, TGF alpha, amphiregulin or heparin binding EGF, ii) upon truncation or mutation of extracellular and/or intracellular domains, iii) upon amplification of a basal receptor activity (in the absence of ligand) through cooperation with other cellular signaling pathways or nuclear events (e.g. expression of v-erbA). The activated EGFR can exert pleiotropic functions on cells, depending on their tissue origin and state of differentiation. Under certain conditions it can also contribute to neoplasia and development of metastases. Such conditions can exist upon aberrant receptor/ligand expression and activation (e.g. in the wrong cell; at the wrong time; in the wrong amounts). Aberrant signalling can also occur through constitutive EGFR activation. Oncogenic potential of EGFR has been demonstrated in a wide range of experimental animals. EGFR is also implicated in human cancer, where it may contribute both to the initiation (glioblastoma) and progression (epithelial tumors) of the disease. EGFR may influence key steps in the processes of tumor invasion and dissemination. Involvement of EGFR in tumor spread may indicate a potential use of this receptor as a target for antimetastatic therapy.
Cancer Metastasis Rev 1993 Sep
PMID:EGF receptor in neoplasia and metastasis. 828 12

In this study of papillary thyroid carcinomas, immunopositivity for EGF-receptor was present in a majority of the cases (96%), although different staining patterns were observed. A distinct membraneous reaction was found in 46%, whereas cytoplasmatic positivity of various degrees was present in 90% of the cases. Strong cytoplasmic EGF-receptor staining was significantly associated with extra-thyroidal growth of the primary tumour (P = 0.009), and it was furthermore related to decreased recurrence free survival (P = 0.006). Membraneous EGF-receptor staining was not associated with recurrence free survival or patient survival. Multivariate Cox analysis showed that lymph node metastases (P = 0.0009) and cytoplasmic EGF-receptor staining (P = 0.0048) was independent indicators of tumour recurrences in this group of surgically treated papillary thyroid carcinomas.
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PMID:Prognostic impact of EGF-receptor in papillary thyroid carcinoma. 839 12

In the highly metastatic rat mammary adenocarcinoma cell clone MTLn3, EGF induced increased adhesion to fibronectin while in the human epidermoid carcinoma cell line A431 EGF induced diminished adhesive properties. Flattening of cells with extensive formation of filopodia was observed in MTLn3 cells within 5 min of EGF addition, while in A431 cells EGF induced rounding up and only occasional formation of filopodia. Immunofluorescent analysis revealed extension of microtubules (MT) into the filopodia and Western blot analysis demonstrated an EGF-induced 2- to 3-fold increase in the amount of assembled tubulin in MTLn3 but not in A431 cells. In MTLn3, but only marginally in A431 cells, EGF treatment resulted in phosphorylation of a 280 kD cytoskeleton-associated protein, which was rapid and dose-dependent. These results suggest differential signal transduction pathway of cytoskeleton-associated EGFRs in highly metastatic MTLn3 as compared with A431 cells.
Clin Exp Metastasis 1993 Jan
PMID:Rapid effects of EGF on cytoskeletal structures and adhesive properties of highly metastatic rat mammary adenocarcinoma cells. 842 2

We have developed a rapid colorimetric in situ mRNA hybridization procedure to analyze epidermal growth factor receptor (EGF-R) transcripts in paraffin-embedded surgical specimens of human colon carcinomas. This technique is based on the use of 24-base oligonucleotide probes labeled with 6 biotin molecules at the 3' end. mRNA integrity was verified using a hyperbiotinylated 30-residue-long deoxythymidylate oligonucleotide probe, and the specificity of the reaction was confirmed by using labeled EGF-R-specific sense and antisense probes. Avidin alkaline phosphatase detection and the capillary technology used in the Microprobe System allowed for completion of the procedure in under 5 h. The human A431 epidermoid carcinoma cells growing in culture and fixed with formalin as well as paraffin-embedded sections of this tumor growing s.c. in nude mice served as positive controls. In situ hybridization with antisense EGF-R oligonucleotide probes directly correlated with EGF-R mRNA and protein levels observed by Northern blot and immunohistochemistry, respectively. In situ hybridization of paraffin-embedded sections of primary human colon carcinoma and metastases from liver and lymph node revealed cell-specific staining with EGF-R antisense oligonucleotide probes that correlated directly with Northern blot and immunohistochemistry analyses. Since this rapid and sensitive in situ mRNA hybridization technique can be used in properly preserved paraffin-embedded tissue, it allows for retrospective analyses of human tumor specimens using archival material.
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PMID:A rapid colorimetric in situ messenger RNA hybridization technique for analysis of epidermal growth factor receptor in paraffin-embedded surgical specimens of human colon carcinomas. 843 66

A large number of cell biological parameters are currently available to predict the prognosis of patients with breast cancer, but it is still difficulty accurately to predict the response to treatment. A valuable prognostic factor can be a poor predictive factor for response, and vice versa. High tumor levels of ER, PgR, AR and pS2 predict a relatively good response to endocrine therapy, while EGF-R positively, HER2/neu positivity, aneuploidy, high proliferation indices and possibly high uPA levels indicate a high chance of poor response to endocrine therapy in metastatic breast cancer. With respect to chemotherapy, a high proliferation rate and HER2/neu amplification predict a good response to therapy in metastatic disease, while MDR gene expression and possibly c-myc amplification are related to a worse response. In conclusion, the newer cell biological parameters can be used to select high and low-risk patients, type of systemic treatment, and as targets for new treatment modalities.
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PMID:Cell biological factors associated with the response of breast cancer to systemic treatment. 848 34

Changes in lamellipod extension and chemotaxis in response to EGF were analysed for MTLn3 cells (a metastatic cell line derived from the 13762NF rat mammary adenocarcinoma). Addition of EGF produced a cessation of ruffling followed by extension of hyaline lamellipods containing increased amounts of F-actin at the growing edge. A non-metastatic cell line (MTC) derived from the same tumor did not show such responses. Lamellipod extension was maximal within 5 min, followed by retraction and resumption of ruffling. Maximal area increases due to lamellipod extension occurred at about 5 nM EGF. Chemotactic and chemokinetic responses, measured using a microchemotaxis chamber, were also greatest at 5 nM. Cytochalasin D inhibited EGF-stimulated responses including lamellipod extension, increases in F-actin in lamellipods, and chemotaxis. Nocodazole affected chemotaxis at higher concentrations but not EGF-induced lamellipod extension. We conclude that polymerization of F-actin at the leading edges of lamellipods is necessary for extension of lamellipods and chemotaxis of MTLn3 cells in response to EGF. The motility and chemotaxis responses of this metastatic cell line have strong similarities to those seen in well-characterized chemotactic cells such as Dictyostelium and neutrophils.
Clin Exp Metastasis 1996 Jan
PMID:EGF stimulates lamellipod extension in metastatic mammary adenocarcinoma cells by an actin-dependent mechanism. 852 18

The purpose of this study was to determine the effect of the first rat monoclonal antibody (MAb ICR62) to the epidermal growth factor receptor (EGFR) in a phase I clinical trial in patients with unresectable squamous cell carcinomas. This antibody effectively blocks the binding of EGF, transforming growth factor (TGF)-alpha and HB-EGF to the EGFR, inhibits the growth in vitro of tumour cell lines which overexpress the EGFR and eradicates such tumours when grown as xenografts in athymic mice. Eleven patients with squamous cell carcinoma of the head and neck and nine patients with squamous cell carcinoma of the lung, whose tumours expressed EGFR, were recruited. Groups of three patients were treated with 2.5 mg, 10 mg, 20 mg or 40 mg of ICR62 and a further eight patients received 100 mg. All patients were evaluated for toxicity using WHO criteria. Patients' sera were tested for the clearance of MAb ICR62 and the development of human anti-rat antibodies (HARA). No serious (WHO Grade III-IV) toxicity was observed in patients treated with up to 100 mg of antibody ICR62. Antibody ICR62 could be detected at 4 h and 24 h in the sera of patients treated with 40 mg or 100 mg of ICR62. Only 4/20 patients showed HARA responses (one at 20 mg, one at 40 mg and two at 100 mg doses) and of these only the former two were anti-idiotypic responses. In four patients receiving doses of ICR62 at 40 mg or greater, biopsies were obtained from metastatic lesions 24 h later and examined for the localisation of ICR62 using anti-rat antibody reagent. In these patients we showed the localisation of MAb ICR62 to the membranes of tumour cells; this appeared to be more prominent at the higher dose of 100 mg. On the basis of these data we conclude that MAb ICR62 can be administered safely to patients with squamous cell carcinomas and that it can localise efficiently to metastases even at relatively low doses.
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PMID:Phase I trial and tumour localisation of the anti-EGFR monoclonal antibody ICR62 in head and neck or lung cancer. 854 11

The murine IgG2a monoclonal antibody (mAb) EMD 55900 was produced against the human epidermoid carcinoma cell line A431, with binding occurring to the polypeptide chain of the external domain of human epidermal growth factor receptor (EGF-R). In the present clinical study, 12 patients with advanced squamous cell carcinoma of the larynx or hypopharynx received a single dose of either 20, 100 or 400 mg EMD 55900 3 days prior to laryngectomy and neck dissection. Clinical signs and laboratory parameters of toxicity, development of human anti-mouse antibodies, and mAb plasma concentrations were monitored. In tumor specimens studied from primary tumors and lymph node metastases, expression of EGF-R, distribution of EMD 55900, and occupation of EGF-R by EMD 55900 (double staining) were determined by immunohistochemistry. Single-dose administration of EMD 55900 was very well tolerated in all patients, and good (100 mg) to excellent (400 mg) homogeneous binding of mAb to EGF-R was obtained in the advanced laryngeal and hypopharyngeal carcinomas studied.
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PMID:Dose-dependent access of murine anti-epidermal growth factor receptor monoclonal antibody to tumor cells in patients with advanced laryngeal and hypopharyngeal carcinoma. 856 40

Sixty-three patients with primary laryngeal squamous-cell carcinoma were followed up for a median of 33 months after surgery. Cathepsin D (Cath D) concentration was assayed using a solid phase 2-site immunoradiometric assay in which the first monoclonal antibody (MAb) was coated on the ELISA solid phase and the second one, MIG8 radiolabeled with 1125-EGF, was used as the tracer. The median value of Cath D (13.8 pM/mg protein) was chosen as cut-off. Cath D > or = median value was closely related to neck lymph node involvement at presentation and to a short metastasis-free survival (MFS) and actual overall survival (OS). The 5-year MFS was 71% for patients with Cath D < median value tumors as compared with 0% for patients with Cath D > or = median value tumors. Lymph node status at presentation was not related to a short MFS and OS. Cox's univariate regression analysis using Cath D as a continuous variable showed that Cath D levels are correlated with neck lymph node metastasis. On multivariate analysis, Cath D status proved to be an independent factor for predicting a short MFS. Cath D assay may prove to be particularly useful in identifying laryngeal cancer patients who, with or without neck lymph node involvement at presentation, are at high risk of metastatic disease and poor outcome.
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PMID:Cathepsin D concentration in primary laryngeal cancer: correlation with clinico-pathological parameters, EGFR status and prognosis. 860 76


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