Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution of transforming growth factor alpha (TGF-alpha) in human normal tissues from the uterus, Fallopian tube, ovary, small and large intestine, lung, spleen, kidney, and skin was studied by immunohistochemistry. TGF-alpha was found in epidermis, bronchial epithelium, intestinal mucosa, renal tubules, endo- as well as in exocervical and endometrial epithelium, and in the serous epithelium of the Fallopian tube. No TGF-alpha was detected in the stromal components of any of the tissues nor in any of the pre- and post-menopausal ovaries studied. Twenty-nine ovarian tumours including 23 ovarian carcinomas, one malignant mixed Mullerian tumour, two ovarian metastases of gastrointestinal carcinomas, one dysgerminoma, one sarcoma, and one fibroma were studied for TGF-alpha by the same immunohistochemical method. In 25 cases, specific cytoplasmic staining for TGF-alpha of epithelial tumour cells could be demonstrated. The pattern and intensity of the TGF-alpha immunostain varied among the TGF-alpha-positive tumours. No TGF-alpha was found by immunohistochemistry in the remaining four cases nor in the stromal tumour components of any of the lesions studied. Northern blot analysis for TGF-alpha mRNA was performed on 12 of the tumours. While the immunohistochemistry and blotting results correlated well in ten cases, discordant results were obtained in two lesions.
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PMID:In situ distribution of transforming growth factor alpha in normal human tissues and in malignant tumours of the ovary. 226 59

A binding competition assay was used to measure the content of transforming growth factor alpha in human mammary carcinomas and their metastases. Thirty one percent of the primary and 50 percent of the metastases expressed the transforming growth factor alpha with values ranging between 1.6 to 278 EGF equivalent ng/mg tumour extract protein. There was no correlation between the transforming growth factor alpha content and the estrogen receptor value.
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PMID:Transforming growth factor alpha in human mammary carcinomas and their metastases. 270 46

The emerging concept of autocrine/paracrine control of tumour cell proliferation coupled with the identification of several polypeptide mitogens has created new opportunities for the discovery of novel classes of antineoplastic drugs. Growth factors (for example, transforming growth factor alpha, fibroblast growth factor and platelet-derived growth factor) and, in certain cases, their receptors have been identified in a number of human tumours and their expression may contribute to unregulated cell proliferation. Selective antagonists that block the activity of these mediators may have important therapeutic utility in the management of cancer patients, particularly in metastatic disease where patterns of tumour cell dissemination may be strongly influenced by paracrine mediators. However, since many, if not all, of these growth factors are polypeptides with molecular weights over 5 kDa, the discovery of potent antagonists represents an important pharmacological challenge. Advances in understanding protein structure-function relationships will be essential in guiding rational attempts at generating growth factor antagonists through site-directed mutagenesis and peptide synthesis, while better insights into the mechanisms by which growth factors are synthesized, processed, released and exert their mitogenic effects may also reveal new sites for pharmacological assault. The availability of (low molecular weight) potent growth factor antagonists will allow the autocrine/paracrine hypothesis to be clinically tested and in the process will throw considerable light on the function of these growth regulatory molecules in vivo.
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PMID:Growth factors as novel therapeutic targets in neoplastic disease. 307 70

The purpose of this study was to determine the mRNA expression level of multiple cytokine and growth factor genes in human malignant melanoma. Melanoma cells were isolated from several surgical specimens, adapted to growth in culture, characterized for their ability to produce experimental metastases in nude mice, and assessed for cytokine and growth factor steady-state gene expression. Highly metastatic in vivo- and in vitro-derived variants isolated from a single melanoma, A375, were also analyzed. Northern blot analyses revealed that all melanomas analyzed constitutively expressed steady-state mRNA transcripts for the growth and angiogenic factors, basic fibroblast growth factor (bFGF), and transforming growth factor alpha (TGF-alpha), which correlated with metastatic propensity. Only one highly metastatic melanoma, TXM-1, originally isolated from a lymph node metastasis, expressed mRNA transcripts specific for monocyte chemotactic and activating factor (MCAF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Similarly, of the nine melanomas examined, only TXM-1 expressed interleukin (IL)-1 alpha, IL-1 beta, and IL-6, important immunomodulatory cytokines. These data demonstrate the differential and heterogeneous expression of cytokine and growth factor genes in human malignant melanoma.
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PMID:Heterogeneity of cytokine and growth factor gene expression in human melanoma cells with different metastatic potentials. 764 37

Short-term chronic exposures of rats to furan were recently found by us to preferentially induce a unique liver lobe pattern of development of small intestinal metaplasia and subsequent cholangiofibrosis, being essentially localized to the caudate and right liver lobes (L. W. Elmore, and A. E. Sirica, Cancer Res., 51: 5752-5759, 1991). We now demonstrate the preferential development of primary hepatic adenocarcinomas exhibiting small intestine mucosal cell differentiation, which have arisen at 70 to 90% incidences from the right/caudate liver lobes of Fischer 344 adult male rats by 16 months after their receiving furan by gavage at a daily dose of 30 mg/kg of body weight, five times a week, for 9, 12, and 13 weeks, respectively. In contrast, the incidences of primary hepatocellular carcinomas that developed in the furan-treated rats ranged from 0 to 20%, with the two hepatocellular carcinomas observed to be originating from the median/left liver lobes. Twenty-six of 27 hepatic adenocarcinomas analyzed exhibited glands containing on average 30.2% goblet cells, 2.1% Paneth cells, and 0.5% serotonin-positive neuroendocrine cells. Phenotypically, the glandular epithelial cells of the furan-induced intestinal-type adenocarcinomas were immunohistochemically positive for cytokeratin 19, but exhibited a heterogeneous pattern of immunohistochemical staining for gamma-glutamyl transpeptidase and showed no detectable immunostaining for transforming growth factor alpha. In addition, many of the glandular structures within these primary hepatic adenocarcinomas showed evidence of basement membrane disruption, as demonstrated by both electron microscopy and immunohistochemical staining for basement membrane laminin. While these intestinal-type adenocarcinomas appeared to have spread intrahepatically, none showed evidence of extrahepatic metastases. However, six of eight randomly selected adenocarcinomas grew progressively and retained their intestinal pattern of differentiation following serial transplantation into the fat pads of young adult Fischer 344 recipient rats. In this study, we also observed one primary hepatic cholangiocarcinoma that was characterized by a more native biliary rather than intestinal-type of differentiation. Interestingly, this was the only primary liver cancer observed by us to exhibit extrahepatic metastasis. In conclusion, our current findings clearly indicate that the small intestinal metaplasia and subsequent cholangiofibrosis developing early in the right/caudate liver lobes of furan-treated rats do not simply reflect reactive changes, but strongly correlate with the high incidences of intestinal-type of primary hepatic adenocarcinoma that occurs in the right/caudate liver lobes of rats after long-term exposures to furan.
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PMID:"Intestinal-type" of adenocarcinoma preferentially induced in right/caudate liver lobes of rats treated with furan. 767 71

The epidermal growth factor receptor and its ligands have been implicated as being involved in normal mammary development and breast cancer genesis. Northern blotting was used to assay the mRNA levels of the epidermal growth factor receptor and three of its ligands: the epidermal growth factor, the transforming growth factor alpha and the Amphiregulin in 16 primary carcinomas, 2 metastases and 5 fibroadenomas. In addition, the mRNA levels of the other members of the epidermal growth factor receptor family, erbB2 and erbB3 were also analysed. We found limited expression in the breast carcinomas while all the fibroadenomas showed expression at high levels. Therefore we suggest that the epidermal growth factor receptor plays an important role in the development of fibroadenomas. The erbB2 and erbB3 were more strongly expressed than the epidermal growth factor receptor in the primary carcinomas. This suggests that they could be of importance in breast carcinogenesis.
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PMID:High expression of the EGFR in fibroadenomas compared to breast carcinomas. 784 1

Prostate adenocarcinoma, the most common tumor occurring among North American men, preferentially metastasizes to bone, where it characteristically forms osteoblastic lesions. The following growth regulatory factors are expressed in some human prostate cancers and/or established cell lines: epidermal growth factor (EGF), transforming growth factor alpha, transforming growth factor beta, basic fibroblast growth factor (bFGF), and insulin-like growth factor. Some of these, especially EGF, bFGF, and TGF-beta, are also implicated in growth regulation in normal and benign hyperplastic prostates. Although evidence from in vitro study of the small number of prostate cell lines available demonstrates that these growth regulatory pathways are exploited by some of these cells, direct in vivo evidence is limited. The development of human prostate cancer cell lines which grow and metastasize in immune-deficient rodents is an advance which now permits experimental analysis of the role of these growth factors in prostatic metastasis, particularly to bone. The progression and metastasis of human prostate cancer results from the complex interactions of multiple growth factors, androgens, and cellular communication, which form a dynamic network. Continued progress in the study and treatment of this disease will require new conceptual frameworks as well as successful application of the techniques of molecular and cellular biology.
Cancer Metastasis Rev 1993 Sep
PMID:Growth factors and their receptors as determinants in the proliferation and metastasis of human prostate cancer. 828 14

Forty oral squamous cell carcinomas have been investigated immunohistochemically for the presence of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF). The same cases were recently characterized for the expression of EGF-receptors. TGF-alpha was detected with a monoclonal mouse antibody and EGF with polyclonal rabbit antiserum. Thirty-five of the tumours were positive for TGF-alpha and 26 of the tumours for EGF. None of the poorly differentiated tumours was positive for EGF, but they all were for TGF-alpha. In sections including normal differentiated oral mucosa, the cells above the basal cell layer were positive for both TGF-alpha and EGF. The same staining pattern was observed in oral mucosa obtained from healthy persons. In moderately to well differentiated carcinomas, the immunoreactivity was mainly confined to the cytologically more differentiated cells, thus paralleling the situation observed in the normal differentiated oral mucosa. In four cases, material was available from both a primary tumour and a metastasis. Three of these were positive for TGF-alpha and EGF with the same staining pattern as that of the primary tumours. This investigation together with our previous results confirms the existence of TGF-alpha, EGF, and EGF-receptors in the majority of oral squamous cell carcinomas and their metastases.
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PMID:Immunoreactive transforming growth factor alpha and epidermal growth factor in oral squamous cell carcinomas. 849 25

To determine whether the expression of transforming growth factor alpha (TGF-alpha), its receptor (epidermal growth factor receptor [EGFr]), p53 nuclear protein, and proliferation influences prognosis of patients with liver metastases, a study was performed in 45 liver metastases and 33 corresponding primary colorectal carcinomas in patients referred for liver surgery. The expression of TGF-alpha, EGFr, p53 nuclear protein, and proliferation rate was correlated with clinicopathological characteristics and survival after partial liver resection. In liver metastases, TGF-alpha expression was low in 42%, intermediate in 35%, and high in 23%. TGF-alpha expression was higher in liver metastases derived from lymph node-positive primary carcinomas, in synchronous and in irresectable liver metastases compared with those derived from lymph node-negative primary carcinomas, metachronous, and resectable liver metastases. Nuclear p53 expression was found in 83% of primary tumors and 71% of liver metastases. p53 expression did not correlate with the various clinicopathological characteristics. Ki67 expression was not associated with clinicopathological characteristics in primary and metastatic tumors. In the 38 patients in whom a partial liver resection was performed, median survival was 25 months in patients with a higher TGF-alpha expression in the metastasis than in the primary tumor and 60 months in patients with comparable or lower TGF-alpha expression in the metastasis than in the primary tumor (P = .036). Median survival after liver resection was 21 months in patients with p53-negative liver metastases and 58 months in patients with p53-positive metastases (P = .043). By multivariate analysis, p53 and EGFr expression on liver metastases were the best predictors of disease-free survival after partial liver resection, with relative risks of 2.38 and 3.33, respectively. In patients with colorectal liver metastases, referred for liver surgery, a higher TGF-alpha expression is associated with unfavorable tumor characteristics, whereas p53 and absence of EGFr expression is associated with a better survival after partial liver resection.
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PMID:Clinical relevance of transforming growth factor alpha, epidermal growth factor receptor, p53, and Ki67 in colorectal liver metastases and corresponding primary tumors. 975 33

The autocrine/paracrine interaction of the epidermal growth factor receptor (EGFr) and transforming growth factor alpha (TGF-alpha) has been implicated in prostate cancer cell growth and proliferation. To evaluate the role of EGFr and TGF-alpha in prostate cancer progression, we studied the immunohistochemical staining pattern of EGFr and TGF-alpha in malignant primary and hormone-independent metastatic prostate lesions. The specimens evaluated included 37 primary carcinomas (34 hormone-naive and 3 hormone-refractory tumors) and 22 metastases. For each specimen, the pattern of expression was evaluated and staining reactivities graded from 0-3, with 0 representing no staining and 3 representing homogeneous and intense staining. Primary malignant prostate epithelial cells in areas with discrete gland formation showed strong EGFr immunostaining, while stromal cells were generally nonreactive. In untreated primary tumors, TGF-alpha expression was primarily in the stroma, while epithelial cells were weakly positive in several cases. Malignant epithelial cells adjacent to neural elements that stained positive for TGF-alpha was frequently observed. A homogeneous staining pattern for EGFr was noted in 17 (89%) of 19 evaluable androgen-independent-refractory metastases, while TGF-alpha expression was found in 14 (78%) of 18 evaluable cases. Overall, 14 of 18 androgen-independent metastases coexpressed the receptor and the ligand. These results suggest that, unlike primary prostate tumors where a paracrine relationship between EGFr and TGF-alpha appears to predominate, the potential for autocrine stimulation may exist in the majority of metastatic androgen-independent tumors. Furthermore, the changing pattern of expression as the disease evolves from the localized hormone-naive to metastatic androgen-independent condition suggests that strategies aimed at blocking this growth factor pathway may be of therapeutic importance for androgen-independent disease.
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PMID:Changing pattern of expression of the epidermal growth factor receptor and transforming growth factor alpha in the progression of prostatic neoplasms. 981 14


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