Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies reactive with human epidermal growth factor receptor (EGFr), such as 225 IgG1 (Masui et al., Cancer Res., 44: 1002-1007, 1984), are effective tumor-suppressive agents in xenograft models. In the present study an additional antibody reactive with EGFr was made and compared to 225 IgG1 for antitumor activity as an unmodified antibody or as a drug immunoconjugate. This IgG1 clone, designated EGFrL11, competed with EGF and immunoprecipitated a Mr 178,000 protein identical to that immunoprecipitated with 225 IgG1. Cross-competition and immunodepletion studies indicated that the two antibodies bound to distinct epitopes on the same molecule. Immunofluorescence studies confirmed that the EGFrL11 epitope was expressed on the surface of viable human squamous cell carcinoma lines including T222. Unmodified EGFrL11 and 225 IgG1 were tested for antitumor activity in T222 xenografts. At a dose of 81 mg/kg given twice weekly for 3 weeks, tumor suppression, but not regression, occurred with EGFrL11. A similar result was obtained with 225 IgG1. To gauge the potential of these antibodies as immunoconjugates, both were tested for antitumor activity in the T222 model after conjugation to the Vinca derivative 4-desacetylvinblastine-3-carboxhydrazide. Both immunoconjugates completely regressed established tumors. These data suggest that Vinca conjugates with EGFr-reactive monoclonal antibodies warrant further investigation as possible clinical candidates.
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PMID:Epidermal growth factor receptor-reactive monoclonal antibodies: xenograft antitumor activity alone and as drug immunoconjugates. 191 67

Epidemiological and experimental data strongly support a causal relationship between exposure to excessive levels of estrogens and the development of cancer in various tissues. In this paper, we have presented background information that shows a correlation between the prolonged use of oral contraceptives and the development of liver cancer. The clinical data supported the hypothesis that the estrogenic components of oral contraceptives were promoters of hepatocarcinogenesis, and the experimental evidence in support of this hypothesis and bearing on the mechanisms involved are also reviewed. The effects of estrogens on liver neoplasia and growth are: (i) synthetic steroidal estrogens are potent promoters of hepatocarcinogenesis in female rats; (ii) these estrogens stimulate liver growth at doses that are not hepatotoxic; (iii) the mechanisms by which the estrogens stimulate liver growth are indirect and include the enhancement of a serum/plasma growth factor, co-mitogenic effects which result in enhanced responsiveness of cultured hepatocytes to epidermal growth factor and decreased sensitivity of hepatocytes to growth inhibition by transforming growth factor-beta; (iv) the co-mitogenic effects of synthetic estrogens extend to endogenous estrogens and natural product estrogens; and (v) the co-mitogenic effects of estrogens for epidermal growth factor are associated with increased epidermal growth factor receptor protein levels caused by an increase in the half-life of the receptor protein. The synthetic estrogens also have weak "complete" carcinogenic activity in rat liver and strong complete carcinogenic activity in Syrian hamster kidney and Armenian hamster liver. Evidence from the literature is presented in support of a hypothesis that this process may involve indirect genotoxicity mediated through redox cycling and the formation of hydroxylated DNA bases. This process, together with the potent promoting activity of these estrogenic chemicals, may account for their complete carcinogenicity.
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PMID:Sex hormones and tumor promotion in liver. 192 3

Transforming growth factor alpha is an autocrine mitogen for nonneoplastic keratinocytes, which exerts its function by binding to the receptor for epidermal growth factor. In order to determine whether this autocrine pathway is activated in squamous carcinoma cells, we analyzed the production of transforming growth factor alpha as well as the expression and regulation of epidermal growth factor receptors in a panel of human squamous carcinoma cell lines. Immunoreactive transforming growth factor alpha was detectable in squamous carcinoma cells as well as in quiescent nonneoplastic keratinocytes. However, in the absence of exogenous mitogens, only the squamous carcinoma cells secreted the growth factor into the medium, whereas untransformed keratinocytes did not. Each of the squamous carcinoma cell lines expressed significantly greater numbers of cell surface epidermal growth factor receptors than normal keratinocytes. The epidermal growth factor receptor gene was amplified and overexpressed in three of the squamous carcinoma cell lines (A431, CaSki, SqCC/Y1). Two of the squamous carcinoma cell lines (C4-1 and CE-48) displayed a relative inability to down-regulate epidermal growth factor receptors in response to epidermal growth factor. The mechanism of receptor overexpression in the remaining three cell lines (A253, CaLu-1, FaDu) is unexplained. Thus, human squamous carcinoma cell lines frequently exhibit a combination of the constitutive secretion of transforming growth factor alpha and the overexpression of epidermal growth factor receptors. Treatment of these tumor cells with an antibody directed against the ligand-binding domain of the epidermal growth factor receptor inhibited their growth by approximately 50%. These findings suggest that designing strategies to interrupt the transforming growth factor alpha autocrine pathway might lead to new modalities to treat this class of malignant tumors.
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PMID:Activation of the autocrine transforming growth factor alpha pathway in human squamous carcinoma cells. 193 86

Twelve male patients with operable breast cancer were evaluated for the expression of prognostic factors by immunohistochemical staining assay. Seven patients were stage I & II, and five patients were stage III. Axillary lymph node positivity was 42%. Nine patients were nuclear grade I, three were nuclear grade II, and none were nuclear grade III. The expression rate of EGFR (epidermal growth factor receptor), ER (estrogen receptor) were 8.3%, 70.0% respectively. This limited data suggest better tumor behavior in male than in female breast cancer. Adjuvant treatment should be considered in male breast cancer just as in females, based on axillary lymph node and ER states.
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PMID:Expression of prognostic factors (EGFR, ER) by immunohistochemical staining method in male breast cancer. 194 15

A new human gastric cancer cell line (OCUM-1), which was derived from Borrmann type IV tumor of the stomach, was established. The cell line grew sometimes singly and sometimes in clusters, and continued to grow for more than 3 years. It's doubling time was 33.2 hours, chromosomal mode was 50, and nuclear DNA ploidy pattern was diploid. The cells could grow in nude mice. It produced carcinoembryonic antigen, carbohydrate antigen 19-9, and cancer-associated antigen SPan-1 and expressed epidermal growth factor receptor. Supplementation of epidermal growth factor to culture medium increased the cell number statistically significantly. It was decreased by supplementation of chondroitin sulphate. So the cell line OCUM-1 might be useful for the study of gastric cancer, especially Borrmann type IV gastric cancer.
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PMID:[Establishment and characterization of a new gastric cancer cell line (OCUM-1), derived from Borrmann type IV tumor]. 196 Nov 83

The content of the epidermal growth factor receptor (EGFr) and its relation to tissue CEA and NSE were examined in 22 intracranial neoplasms (18 primary intracranial tumors and 4 metastasis from lung cancer). The EGFr was measured by a radioligand assay on crude plasma membrane preparations. The tissue tumor markers (CEA and NSE) were measured on the high speed supernatant of tissue homogenates. In the primary intracranial tumors the EGFr was positive in 68%, CEA in 43% and NSE in 47% of all cases examined. As it concerns the metastasis from lung cancer the positivity was 75% for EGFr while for CEA and NSE was 50% and 32% respectively. These results suggest that the routine measurement of EGFr, associated with the determinations of tissue CEA and NSE could provide useful information on the type of the intracranial neoplasms.
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PMID:Epidermal growth factor receptor and tissue tumor markers in human intracranial neoplasms. 196 99

In 1986, a pilot Phase I/II project was initiated using Iodine-125 labeled anti-epidermal growth factor receptor-425 in the treatment of patients with recurrent glioblastoma multiforme of the brain. The monoclonal antibody was administered intra-arterially by the internal carotid arterial system or the vertebral arterial system depending upon the blood supply to the tumor. The treatment program was repeated at intervals for two or three times. Demonstrated was the intense localization of the monoclonal antibody in the brain tumor prior to therapy using Indium-111 labeled anti-epidermal growth factor receptor-425. This localization was demonstrated prior to any therapy as well as after failure from primary radiation therapy with or without concomitant chemotherapy. To date, 15 patients have been treated following recurrence of their glioma (1/15 metastatic adenocarcinoma) with the monoclonal antibody labeled with Iodine-125. Of the 15 patients, there has been one surgically documented complete response, two partial responders, and five patients with stable disease. The results indicate the potential activity of this radiolabeled monoclonal antibody and have prompted continued accession of patients into a Phase II study as a part of the primary treatment regimen (surgery, radiation therapy with or without chemotherapy) followed by administration of the Iodine-125 labeled anti-epidermal growth factor receptor-425.
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PMID:Iodine125 labeled anti-epidermal growth factor receptor-425 in the treatment of malignant astrocytomas. A pilot study. 196 3

Interference with autocrine or paracrine loops offers a potential means of treatment of tumors which currently lack effective therapies. Hormonally responsive breast cancers generally respond to treatment with antiestrogens but a frequent occurrence is an outgrowth of populations of tumor cells that are no longer dependent on estrogen for growth. If the acquisition of the ability to constitutively express growth factors or growth factor receptors is associated with this form of tumor progression, identification of the growth factors and their receptors having the capability of reducing the dependence on estrogen for growth is an important first step in the design of strategies aimed at interfering with their function. Experimental systems employing transfection with eukaryotic expression vectors are described that are designed to test the hypothesis that overexpression of epidermal growth factor receptor or the related protein C-ERB-B2 may confer an increased growth rate under conditions of estrogen deprivation. The transfected cells are also being used to explore the molecular mechanisms underlying the regulation of epidermal growth factor receptor expression by estrogen.
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PMID:Growth factor receptors and the progression of breast cancer. 196 91

The C-erbB-2 gene was first found in human genomic DNA as a sequence which had homology in nucleotide sequence to the V-erbB by molecular hybridization under relaxed conditions. The product of this gene is a receptor type protein-tyrosine kinase which has a structure highly related to that of epidermal growth factor receptor (EGF-r: C-erbB-1). The proto-neu gene is a rat counterpart of the C-erb B-2 gene. The C-erbB-2 gene is also called as the HER-2 gene. The C-erbB-2 gene acquires the ability to transform NIH 3 T 3 cells by, 1) mutation which alters valine 659 in transmembrane region to glutamic acid as was found in neu gene activation, 2) deletion of c-terminal regulatory domain or 3) gene-amplification or overexpression. C-erbB-2 expresses in human embryos on mucous membranes and glands, but only faintly in adult tissues. High expression or gene amplification in human tumor appeared to be an indication for high risk of metastasis or high degree of malignancy.
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PMID:[Proto-oncogene C-erbB-2 and human cancer]. 196 37

On the prognostic value of c-erbB2-encoded protein p185 in breast cancer there are controversal opinions. With the outlook of an evaluation of the prognostic value of p185 expression in breast cancer the relationships between p185 expression and known prognosis factors were investigated. Using polyclonal antibody against p185 33% out of 163 primary breast carcinomas are p185-positive. Within the various histological types of tumors the percentage of p185 expression differs. It is suggested that p185 indicates a certain type of biological behavior and plays a role in the pathogenesis of breast cancer. Thus the determination of p185 could allow definition of biological subclasses. A statistically significant correlation between expression of p185 and the presence of lymph node metastases or tumor size can not be proved. Nevertheless p185 expression is increased in cases with more than three positive lymph nodes. Expression of p185 correlates statistically significantly positively with histological grade and epidermal growth factor receptor, and negatively with steroid receptor status. Furthermore, high-proliferating tumors are more common in p185-positive cases than in p185-negative cases. It is concluded that p185 may be associated with an increased malignancy and proliferation activity of tumors.
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PMID:c-erbB2 expression in correlation to other biological parameters of breast cancer. 196 2


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