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)

A human prostate cancer model was established by inoculating a prostate specific antigen (PSA)-producing LNCaP cell line with either prostate or bone fibroblasts. Alternatively, this human prostate cancer model can also be established by inoculating LNCaP cells with growth factor(s) (GFs) and extracellular matrix (ECM) immobilized on Gelfoam. The resulting LNCaP tumors were used to evaluate PSA production and excretion in athymic hosts. This model was also employed to examine the biochemical nature of mesenchymal cell-derived growth-promoting protein(s) and to assess the efficacy of potential chemotherapeutic agents. Because of the propensity of human prostate cancer to metastasize to the bone, this study defined a 1.0 M NaCl-eluted fraction, MS1, from the conditioned medium of a bone stromal cell line (MS) by heparin-affinity column chromatography. The growth-promoting activity was assayed both in vivo (e.g., tumor formation) and in vitro (e.g., soft agar colony formation). We found that the growth-promoting activity was trypsin- and heat-sensitive, and partially degraded by acid and dithiothreitol. Immunochemical studies indicated that the polyclonal antibody raised against MS1 blocked the growth-promoting effect elicited by the bone-conditioned media. This growth-promoting factor was found to be immunochemically dissimilar to KGF, HGF, and bFGF. However, addition of bFGF, HGF and NGF, but not aFGF, TGF beta, IGF1, IGF2, PDGF, EGF, TGF alpha and KGF, stimulated anchorage-independent growth of prostate cells, a condition closely parallel to tumor formation in vivo. We found that the MS1 fraction also contained fibronectin and tenascin but not laminin or collagen IV.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human prostate cancer model: roles of growth factors and extracellular matrices. 128 80

Among the various factors reported as having significant prognostic value in primary breast cancers, the author discusses the value of well established "classical" prognostic factors used routinely and "new" prognostic factors developed over recent years as a result of progress in cell and molecular biology. The presence of axillary lymph node metastases remains the most important prognostic factor of recurrence, justifying post-surgical adjuvant therapy. However, in patients with negative axillary nodes (N-), the size of the tumour, Scarff-Bloom-Richardson (SBR and MSBR) histological grade, certain particular histological types (carcinoma in situ and tubular, colloid or pure papillary cancer) and hormone receptors (ER and PR) appear to be well established prognostic factors allowing the identification, within this group of N- patients who generally have a good prognosis, those patients with a low risk of recurrence and therefore not requiring adjuvant therapy. In contrast, the proliferative activity (ploidy and S phase, Thymidine Labeling Index, antibody Ki67), cathepsin D, thymidine kinase, EGF receptors, several genes including oncogene HER-2/neu, are recently developed prognostic factors whose significance needs to be confirmed by further studies.
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PMID:[Prognostic factors in breast cancer]. 134 Jan 64

The expression of the protooncogene encoded proteins (c-erbB1, c-erb B2, c-myc, c-fos) and the suppressor gene product p53 was analyzed in 81 human squamous cell carcinomas of the lung and correlated with clinical parameters of the patients (patient survival, presence of metastases and tumor stage) and with biological characteristics of the tumors (tumor growth in nude mice, DNA-ploidy, proliferative activity, drug-resistance and P-glycoprotein or gluathione S-transferase expression). By means of immunohistochemistry, expression of c-erbB1 oncoprotein (EGF-receptor) was detected in 79% of the tumors, c-erbB2 (c-neu) proteins in 35%, c-myc proteins in 48%, c-fos proteins in 41%, and p53 in 43% of the tumors. Patients with c-erbB1 positive tumors had a poor prognosis (p = 0.021). In addition, these tumors were more frequently drug resistant (p = 0.0067). A significant correlation between the growth of the squamous lung carcinomas in nude mice and c-fos oncoprotein expression was demonstrated (p = 0.017). Therefore, EGF-receptor and c-fos products may serve as prognostic factors for the aggressiveness of squamous cell carcinomas of the lung and for the response of these tumors to chemotherapy. No significant correlation was found between the expression of the c-erbB1 or c-fos gene products and stage, metastasis and DNA-ploidy. In contrast to these results, no relationship was found between c-neu or c-myc gene products expression and any of the clinical or biological parameters examined. Aneuploid squamous cell carcinomas of the lung expressed p53 more frequently than diploid tumors (p = 0.027). However, there was no significant difference between p53 expression and stage, survival of patients, metastasis, growth of the tumors in nude mice, proliferative activity and drug-resistance of the tumors.
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PMID:Oncoprotein (c-myc, c-erbB1, c-erbB2, c-fos) and suppressor gene product (p53) expression in squamous cell carcinomas of the lung. Clinical and biological correlations. 134 20

Peptide growth factors are proteins that stimulate cellular proliferation by binding to specific cell membrane receptors. Evidence is accumulating that abnormal regulation of growth factors may contribute to carcinogenesis. The epithelial growth factors, EGF and TGF-alpha, which share the same receptor, EGFR, may play a pivotal role in the development and maintenance of head and neck cancer; preliminary studies concerning TGF-beta and IL-2 are inconclusive. There is increased production of TGF-alpha and EGFR mRNA in the majority of fresh tissues and cell lines from patients with SCCHN. This increase results from transcriptional activation of the gene(s). Therapies directed at the regulation of gene transcription may be useful in chemoprevention or modulation of disease. Nuclear studies that target up-regulated growth factor receptors may improve the ability to detect microscopic regional metastatic disease.
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PMID:The role of peptide growth factors in head and neck carcinoma. 140 94

Biopsy specimens of human brain metastases were examined for amplification and expression of the proto-oncogene c-erbB1 (located on chromosome 7) encoding the epidermal growth factor receptor (EGFR). Moreover, the tumour DNA was also examined for amplification of other cancer-related genes on this chromosome: the proto-oncogene c-met, the gene for platelet-derived growth factor A-chain, and the gene for plasminogen activator inhibitory type 1. All 18 brain metastases demonstrated positive binding of biotinylated EGF on cryosections. Three out of 18 metastases had amplification of the EGFR gene; the other chromosome-7 genes tested were not amplified. Thus, an increased EGFR gene expression seems to be a general finding in a wide range of carcinomas metastatic to the brain, whereas we found only occasional selective EGFR gene amplifications in single cases.
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PMID:Expression of the epidermal growth factor receptor gene in human brain metastases. 152 Apr 84

Clonogenic cultures from 27 lung cancers were realised. For 68% of cases a clonogenic growth was observed, but no direct correlation could be done with the differentiation of the tumor or with the presence of ganglion metastases. EGF in medium increased the number of colonies obtained in 60% of cases.
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PMID:[Clonogenic culture of identified cells of lung tumors and correlation with certain histopathologic aspects of the tumor mass]. 165 Jul 68

Transforming growth factor-alpha (TGF-alpha) is frequently coexpressed with its receptor, epidermal growth factor receptor (EGF-R), in several types of carcinoma and sarcoma. It is believed that this results in an autocrine stimulation of tumor growth in these tumors. We have found that TGF-alpha and EGF-R/c-erbB RNAs were co-expressed at significantly higher levels in papillary thyroid carcinomas and their lymph-node metastases than in non-neoplastic thyroid tissues. We also observed a low level of expression of RNA specific for insulin-like growth factor I in these tumors, which was highest in a lymph-node metastasis. Autocrine stimulation by TGF-alpha may thus be a common feature of papillary carcinomas of the thyroid. Since EGF is known to induce proliferation and dedifferentiation of normal thyroid cells in culture, TGF-alpha and its receptor may play an important role in thyroid carcinogenesis.
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PMID:Co-expression of the genes encoding transforming growth factor-alpha and its receptor in papillary carcinomas of the thyroid. 169 67

Epidermal growth factor receptor (EGF-R) expression was studied immunohistologically in 38 patients with esophageal squamous cell carcinoma. The EGF-R was faintly expressed in basal and parabasal layers of normal esophageal epithelia and in cancer nests of 20 patients; it was strongly expressed in all areas of dysplastic epithelia and in cancer nests of 18 patients. The patients with strongly expressed EGF-R had lymph node metastases more frequently, and their prognosis was poorer than those with faintly expressed EGF-R. The EGF-R expression showed a mosaic pattern in 17 patients and a diffuse pattern in 21 patients. The patients with a mosaic pattern had lymph node metastases more frequently and a worse prognosis than those with a diffuse pattern. Expression of EGF-R in metastatic lymph nodes was similar to that in strongly expressing areas of primary cancers with a mosaic pattern. Thus EGF-R expression may be an important indicator for malignancies of esophageal squamous cell carcinomas because primary cancer cells with strongly expressed EGF-R metastasize to lymph nodes more frequently.
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PMID:Immunohistologic detection of the epidermal growth factor receptor in human esophageal squamous cell carcinoma. 170 47

The growth of human prostate cancer and its relationship to the surrounding stroma are controlled by complex mechanisms that are incompletely understood. Clearly, peptide growth factors appear to have crucial roles in these processes. One of these factors, TGF-beta, and its family members are notable for their wide spectrum of biological effects. In terms of growth, TGF-beta inhibits the growth of prostate cancer cells in a cytostatic fashion while stimulating the growth of critical stromal cells, such as fibroblasts. Since the inhibitory effects of TGF-beta on prostate cancer cells appear to diminish as the process of transformation progresses towards less differentiated states, the net effect on prostate tumour growth may be positive. Recent evidence suggests that the inhibitory effects of TGF-beta on growth, at least, might be mediated through the RB tumour suppressor gene product and the proto-oncogene c-myc. Beyond its direct growth effects, TGF-beta also alters the response of prostate cancer cells to positive mitogenic factors, such as members of the EGF and FGF families, suggesting that growth control is a delicate balance between positive and negative influences. Non-mitogenic responses to TGF-beta by prostate cancer cells, the immune system, the stroma and the vascular system provide evidence that TGF-beta might also be important in the processes of carcinogenesis, tumour establishment and metastases. In addition, TGF-beta appears to influence metabolic pathways important to drug metabolism and steroidogenesis. In vivo, limited evidence suggests that TGF-beta can alter the growth and differentiation of some tumour types but appears to be very toxic when administered in high doses. A better understanding of the response of prostate cancer cells to members of the TGF-beta family may open new avenues of treating and controlling this disease.
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PMID:Response of prostate cancer cells to peptide growth factors: transforming growth factor-beta. 184 49

Melanomas are highly variable with respect to aberrant gene expression and chromosomal lesions but share a common characteristic of an acquired independence from environmental growth factors that are needed for proliferation of normal melanocytes. Receptors with tyrosine kinase activity play a critical role in normal melanocyte proliferation and in the uncontrolled growth of melanomas. Normal human melanocytes depend on exogenous peptide growth factors such as basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), or mast cell growth factor (MGF), all of which stimulate receptors with tyrosine kinase activity. In contrast, human melanoma cells from primary nodular and metastatic lesions grow autonomously partially because of inappropriate production of bFGF and continuous activation of the bFGF-receptor kinase. Animal models also provide evidence for the importance of receptor-tyrosine kinases in normal melanocyte proliferation and in malignant transformation. In the mouse, genes residing in three loci in which inactivation mutations lead to piebaldism, the dominant spotting (W), patch (Ph), and Sl encode, respectively, the receptor-kinases c-kit and platelet derived growth factor receptor, and the ligand for c-kit: MGF. In vivo transformation of mouse melanocytes to melanoma, due to constitutive expression of a transmembrane tyrosine kinase, the oncogene ret, was recently demonstrated in transgenic mice. Studies on a fish model, Xiphophorus, in which melanoma is inherited, showed that the dominant tumor inducing gene, Tu, encodes an EGF-receptor related tyrosine kinase which is expressed only in melanomas and not in normal tissues. Taken together, the results suggest that the uncontrolled growth of melanomas is due, in large part, to constitutive activation of receptors with tyrosine kinase activity.
Cancer Metastasis Rev 1991 Jun
PMID:Growth factors and tyrosine protein kinases in normal and malignant melanocytes. 187 53


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