Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ependymomas are glial cell-derived tumors. They are, in contrast to other gliomas (astrocytomas, oligodendrogliomas, and oligoastrocytomas), ill-defined with respect to the genes and chromosomal segments important in their tumorigenesis. In this study, we extensively screened 17 ependymomas for genetic changes characteristic of other gliomas. Allelic loss was detected on chromosome arm 22q in three tumors; on chromosome 10 in two tumors; on chromosome arm 17p in two tumors; and on chromosome arms 6q, 9p, 13q, and 19q, each in one tumor. No allelic losses were found on chromosome arms 1p and 16q. None of the tumors had EGFR gene amplification. In each case, the chromosomal segment affected by the deletion included the region known to harbor a tumor suppressor gene important in glioma tumorigenesis. We conclude that ependymomas resemble the other glial neoplasms with respect to type and location of the chromosomal changes involved. Given the relatively infrequent occurrence of these genetic changes, ependymomas should be considered genetically as low-grade gliomas.
Genes Chromosomes Cancer 1995 Aug
PMID:Molecular analysis of genetic changes in ependymomas. 754 35

ErbB-2 and EGFR (epidermal growth factor receptor) are expressed in lung adenocarcinomas and associated with a poor prognosis. Immunocytochemical analysis revealed erbB-2 and EGFR coexperession as a characteristic feature of most lung adenocarcinomas, and at levels of receptor expression present in bronchial epithelial cells. In primary lung tumours and cell lines, erbB-2 detected using Western blot analysis demonstrated low-level phosphotyrosine staining of the 185 kDa band, as compared with breast cancer cell lines. A549 and A427 lung adenocarcinoma cells treated with neu differentiation factor (NDF) showed increased erbB-2 phosphotyrosine staining, but to a much lesser extent than breast cancer cells. The lung cells were examined for expression of the potential autocrine growth factors NDF and transforming growth factor alpha (TGF-alpha) by Northern blot analysis. Both NDF and TFG-alpha mRNA were abundantly expressed in the A549 cells. NDF mRNA was highest during active cell proliferation and decreased in confluent cells or after treatment with the growth-inhibitory steroid dexamethasone. Primary tumours and cell lines expressed EGFR, showing higher basal level phosphotyrosine staining than erbB-2. Treatment with NDF and EGF (epidermal growth factor) stimulated cell growth, and in A549 cells the presence of both factors provided an additive increase in cell growth. The growth stimulus that ligand-activated erbB-2 and EGFR provides to lung adenocarcinoma cells may establish a background of continued cell proliferation over which other critical transforming events may occur.
Br J Cancer 1995 Jul
PMID:Expression and activation of erbB-2 and epidermal growth factor receptor in lung adenocarcinomas. 759 67

With diagnostic stereotactic biopsies in astrocytoma sometimes false results will be encountered. A false positive result is defined as a histological diagnosis which is afterwards proved to be untrue. Although this happens very seldom (1-2%) in characterizing the tumor type (e.g. astrocytoma versus lymphoma), there is a probability of undergrading in malignant astrocytomas due to regional heterogeneity in malignancy grade. The issue of 'sampling error' has been addressed by many authors. It was shown that undergrading in astrocytomas is a likely event in fibrillar astrocytomas that often show geographically distinct areas of well and poorly differentiated elements. In a recent study on histological grading versus genetic characterization of heterogeneous astrocytomas we published that low-grade areas within high-grade malignant astrocytomas have already the genetic features of high-grade malignancy. Therefore, particularly in stereotactic biopsies which contain relatively small samples of tumor tissue, this fact is of paramount importance. Undergrading may lead to withholding radiotherapy from the patient and to falsification of long-term survival results in series of so-called low-grade astrocytomas. We like to stress the importance of taking biopsies from different parts of the tumor, especially from parts with different density enhancement to contrast with CT scanning, and will discuss the technical advancements made in the genetic grading of astrocytomas. Particularly loss of heterozygosity of chromosome 10 and eventually amplification of the EGFR indicate a high grade of malignancy.
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PMID:Genetic versus histological grading in stereotactic biopsies. 762 52

Twenty-one invasive squamous-cell carcinomas (SCC) of the bladder from Schistosoma-hematobium-infected patients were examined immunohistochemically for the expression of p53, Rb, EGFR and c-erbB-2 proteins; and screened by single-strand conformation polymorphism and sequencing for mutations in the ras (H, N, K) codon hotspots (12, 13, 61) and p53 (exons 4-9) genes. Positive staining for p53, EGFR and c-erbB-2 was reported in 38, 67 and 28% of tumors respectively. Only one of the tumors, the only one that was poorly differentiated, displayed an absence of nuclear Rb staining. Ras alterations were detected in the H-ras gene in 3 tumors, 2 of which harbored a codon-13 (Gly-->Arg) and one a codon-12 (Gly-->Ser) point mutation. p53 mutations were recorded in 12 tumors (57%), 6 of which stained positively for p53. Four tumors had exon-7 mutations (codons 235, 241 and 249; one tumor had 2 exon-7 mutations). Eight tumors were mutated in exon 8 (codons 264, 271, 273, 285, 286, 288 and 294), 5 of which harbored multiple mutations. One tumor had an insertion/deletion event in exon 9. The frequency of detection of over-expression of EGFR and c-erbB-2 in bilharzial-bladder lesions is comparable to that reported in TCC, contrasting with the infrequent loss of Rb expression found in invasive lesions associated with schistosomiasis infection. However, the detection of multiple p53 mutations in these lesions is suggestive of the involvement of a carcinogenic agent with maintenance of preferential activation of the H-ras gene.
Int J Cancer 1995 Jul 28
PMID:Molecular events underlying schistosomiasis-related bladder cancer. 762 66

The nuclear transcription factor Fos is inducible by both steroid hormones and peptide growth factors. It thus forms a potential point of interaction between steroid hormone- and growth factor-directed pathways and may be critical in the subversion of steroid hormone control in breast cancer. In this light, the present study has used immunocytochemistry to demonstrate in clinical primary breast cancer that Fos expression is indeed significantly associated with a failure to respond to endocrine therapy, with preliminary analysis revealing a survival advantage for those patients whose tumours lacked Fos. Sustained elevated levels of Fos expression were significantly associated with further factors, notably peptide growth factors and their receptors (e.g., EGFR, TGF alpha), as well as with the proliferation marker Ki-67, which have been linked previously to endocrine insensitivity in breast cancer. In contrast, there appeared to be a trend for Fos to be absent in those tumours expressing markers of endocrine responsiveness (e.g., oestrogen receptor [ER], and also ER-mediated markers i.e., PR, pS2 or bcl-2). Interestingly, many of these trends were maintained in ER+ patients, suggesting that Fos may be of importance in directing loss of endocrine sensitivity in ER+ disease.
Int J Cancer 1995 Aug 22
PMID:Immunocytochemical localization of Fos protein in human breast cancers and its relationship to a series of prognostic markers and response to endocrine therapy. 765 91

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.
Br J Cancer 1993 Feb
PMID:Immunotherapy of human tumour xenografts overexpressing the EGF receptor with rat antibodies that block growth factor-receptor interaction. 767 81

Epidermal growth factor receptor (EGFr) levels were evaluated in paraffin-embedded tumour specimens of non-small cell lung cancer (NSCLC) from 176 patients who underwent surgical resection. The EGFr expression was evaluated by immunocytochemical assay using a monoclonal antibody which recognises the external domain of the receptor. EGFr immunoreactivity was significantly higher in squamous than in non-squamous cell carcinomas (P = 0.0009). Hilar and/or mediastinal nodal involvement was found in 29 of 105 (27.4%) squamous cancers, and in this group of patients, the mean of EGFr positive cells was significantly higher than that of patients without nodal involvement (P = 0.01). No significant correlations were found between the expression of EGFr and other clinicopathological or biological parameters such as T-status, grading, proliferative activity. EGFR is suggested to represent a useful indicator of nodal metastasis in NSCLC.
Eur J Cancer 1995
PMID:Epidermal growth factor receptor (EGFr) expression in non-small cell lung carcinomas correlates with metastatic involvement of hilar and mediastinal lymph nodes in the squamous subtype. 771 22

Cytologic specimens (FNA) from 42 primary invasive ductal breast carcinomas and 22 matched specimens of cancer tissue were tested for EGFR status, PCNA index and vimentin expression by immunocytochemical staining, using an Extravidin-Biotin method, and their relationship with various prognostic factors was investigated. EGFR positivity, high PC10 score and vimentin positivity were significantly correlated with high histologic grade. The coordinate expression of EGFR, PCNA and vimentin was significantly associated with ER-negative breast carcinomas. A positive trend was observed between high proliferating tumours and EGFR expression. EGFR status and PCNA index were not correlated with axillary lymph node involvement, tumour size, age and menopausal status. Vimentin was preferentially expressed in tumours, with lymph node metastases. Co-expression of EGFR, PCNA and vimentin was determined in most cases. These data suggest that EGFR status, PCNA index and vimentin expression may be important for the prediction of biologically aggressive tumours.
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PMID:Relationship of epidermal growth factor receptor (EGFR), proliferating cell nuclear antigen (PCNA) and vimentin expression and various prognostic factors in breast cancer patients. 773 97

EGFR was determined, before treatment; in tumors biopsies obtained from 109 consecutive patients with head and neck cancer (100 men and nine women), using iodine labelled recombinant EGF. The median age of the study population was 60 years. EGFR levels varied from 2 to 2302 fmol/mg membrane protein (median 71). There was a significant difference of distribution for EGFR levels between stages I and II tumors and stages III and IV tumors (P = 0.03). The EGFR cut-off value for overall survival was 120 fmol/mg protein and the median follow-up was 18 months (3-35) EGFR overexpression was associated with shorter relapse-free (P = 0.0125) and overall survival (P = 0.028). By multivariate analysis the only significant variables were EGFR for relapse-free survival and tumor staging and EGFR for overall survival. Analyzed in 60 patients treated by first-line chemotherapy CDDP-5FU, the longest survival was achieved for patients who had a complete response to chemotherapy and the lowest EGFR levels (P = 0.018). EGFR expression in the primary tumor allows survival among first line chemotherapy responder categories to be discriminated.
Bull Cancer 1994 Jul
PMID:[EGF receptor, a prognostic factor in epidermoid cancers of the upper aerodigestive tracts]. 774 4

Transcripts coding for transcription factors (RB, P53, FOS, MYC, MYB, ERBA, REL), growth factors (FGF1, FGF2, INT2, TGFA, TGFB, PDGF, IGF1, IGF2), interleukins, (IL1, IL2, IL3, IL4, IL6, TNF), growth-factor receptors or cytosolic protein kinases (RAF, PIM, FES, MET, SRC, ROS, TRK, KIT, CSFR, IGFR, PDGFR, EGFR, NEU) were quantified in cultured human mammary fibroblasts from normal tissues, benign tumours, carcinomas and post-radiation fibrosis lesions by slot-blot autoradiography and image analysis. The effects of a differentiating agent (cholera toxin) and of a tumour promoter (12-O-tetradecanoyl-phorbol-13-acetate) were also examined. The drugs modulated the levels of the anti-oncogene transcripts (RB, P53) and of ERBA, REL, RAF, MET, ROS, TRK, CSFR, EGFR, NEU, FGF1, INT2, IGF1, IL1, IL2, IL4 and IL6. Apart from this variation, there were multiple differences in gene expression among normal and pathological cells (concerning all but P53, TGFB and interleukin transcripts) and between sub-types defined by the presence of alpha-sm-actin (myofibroblasts) or EDB-fibronectin (RAF, ROS, FES, KIT, IGFR, NEU, INT2, TGFB, PDGF, IGFs, ILs). It appears, therefore, that mammary stroma progress irreversibly along with the epithelium during tumoral development, and that breast cancer is not only a multi-gene but also a multi-tissue phenotype.
Int J Cancer 1995 May 29
PMID:Quantitative variation of proto-oncogene and cytokine gene expression in isolated breast fibroblasts. 776 44


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