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)

Somatostatin is a regulatory hormone or tissue factor which plays an inhibitory role in the normal regulation of several organ systems, including the central nervous system, hypothalamus and pituitary gland, the gastrointestinal tract and the exocrine and endocrine pancreas. Sandostatin is an analogue of somatostatin which has characteristics which makes it a better compound for clinical use than native somatostatin: it inhibits GH preferentially over insulin. It has a long half-life in the circulation, causing a prolonged inhibitory effect in somatostatin-responsive target organs. It is active after subcutaneous administration and rebound hypersecretion does not occur. Sandostatin is very well tolerated by most patients. Somatostatin receptors remain present on a variety of tumours which arise in tissues that contain these receptors normally. High numbers of somatostatin receptors have been found on GH-secreting pituitary tumours and on most metastatic endocrine pancreatic tumours and carcinoids. Sandostatin treatment ameliorates clinical symptoms in most acromegalic patients while GH hypersecretion and elevated concentrations of circulating IGF-I are well controlled. In most patients hormonal hypersecretion from endocrine pancreatic tumours and carcinoids is also suppressed during Sandostatin therapy. This results in an instant improvement in the quality of life. There is preliminary evidence of control of tumour growth. The presence of high numbers of somatostatin receptors on tumours enables in vivo receptor-imaging, with 123iodine coupled to a somatostatin analogue. This newly developed technique provides for the first time the possibility of localization of the primary tumours and their metastases and a prediction of which patients may respond to treatment with Sandostatin. Theoretically this somatostatin-receptor imaging technique represents a new approach which may be extended to other receptor-containing tumours. Therefore it may provide a new, powerful alternative to tumour localization performed with monoclonal antibody technology. Another potential development is the use of beta-emitting isotopes coupled to somatostatin analogues for therapeutic irradiation. Somatostatin analogues exert potent inhibitory effects on the growth of a variety of experimental tumour models in animals. Several mechanisms of action have been proposed including the direct antiproliferative effects of somatostatin and its analogues in a variety of tumour cell cultures. Most well-differentiated human brain tumours like meningiomas and low-grade astrocytomas contain somatostatin receptors, while undifferentiated brain tumours mainly contain EGF receptors. Fifteen percent of human breast carcinomas contain somatostatin receptors; those which do have a better prognosis. It can be concluded that somatostatin is an endogenous, naturally occurring inhibitory growth factor.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The clinical use of somatostatin analogues in the treatment of cancer. 197 66

To select human melanoma cells that are highly tumorigenic and metastatic in nude mice we have implanted fragments of a fresh human melanoma metastasis subcutaneously (s.c.) into a nude mouse. After 3 passages in nude mice, part of the xenograft was cultured and a new melanoma cell line, MV3, was established. After intravenous (i.v.) inoculation of 2 x 10(6) MV3 cells, 95% of the nude mice (n = 20) developed lung colonies within 6 weeks. S.c. inoculation of 2 x 10(6) MV3 cells resulted in 95% tumor take, while 90% of the mice (n = 20) showed spontaneous metastases in the lungs within 7 weeks. Histological and immunohistological features of the original tumor of the patient were largely retained in the tumors of the mice and in the cell line in vitro. As shown by Alcian blue staining, MV3 cells contain large quantities of glycosaminoglycans (GAGs) and/or proteoglycanes (PGs), both in vivo and in vitro. The cells showed a marked expression of transferrin receptor, ICAM-1, EGF-receptor, and VLA-2 integrin. As only few human melanoma cell lines are available that frequently show metastasis in nude mice, the highly metastatic MV3 cell line represents a useful tool for studying the expression and regulation of molecules on human melanoma cells involved in the process of metastasis.
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PMID:Establishment and characterization of a human melanoma cell line (MV3) which is highly metastatic in nude mice. 201 61

Renal cell carcinomas (RCCs) frequently metastasize to distant organs in their clinical course. However, the mechanism of the metastasis had not been fully elucidated. In vitro invasion assay has been reported to be a rapid method for the evaluation of the invasive potential of various malignant cells. In vitro invasive potential of RCC has not been investigated by this method. Thus, in the present study, we first attempted to characterize the in vitro invasive potential of four human RCC cell lines which had been established in our institute. Secondly, we investigated the influence of two growth factors (EGF, TGF-beta 1) on the invasive potential of these cell lines when the two factors were applied as chemoattractants. SMKT-R-3 and R-4 cell lines showed more cell penetration through Matrigel than SMKT-R-1 and R-2 cell lines, suggesting that the former cell lines have higher invasive potential. While invasive potential varied in each cell line, it was enhanced by EGF in all cell lines. However, TGF-beta 1 suppressed the invasive potential of all four cell lines. These results suggest that two factors have different actions on the invasion of RCCs.
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PMID:[Study on in vitro invasive potential of renal cell carcinoma cell lines and effect of growth factors (EGF and TGF-beta 1) on their in invasions]. 205 99

Malignant progression in breast cancer represents the processes through which localized, hormone-dependent tumor cells become resistant to endocrine manipulations and metastasize to sites distant from the primary tumor. By selection in ovariectomized athymic nude mice, we have isolated a variant (MIII) of the hormone-dependent, poorly invasive, human breast cancer cell line MCF-7. MIII cells have lost their absolute requirement for estrogen to form proliferating tumors in nude mice. Furthermore, these tumors are significantly more invasive than the parental MCF-7 cell line. MIII cells retain some responsivity to estrogens and antiestrogens, indicating that they have progressed to a hormone-independent but hormone-esponsive phenotype. In an attempt to determine the nature of this process, we have compared the phenotype of MIII cells with that of other MCF-7 variants. These comparisons strongly suggest that the factors contributing to perturbations in antiestrogen sensitivity, hormone-dependent growth, metastatic potential and tumorigenicity are essentially independent of each other and acquired in a random manner. Loss of estrogen receptor expression and overexpression of EGF receptors tend to occur later in the process of malignant progression.
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PMID:The process of malignant progression in human breast cancer. 208 84

Prognostic variables in breast cancer are urgently needed to individualize adjuvant cytotoxic therapy, especially in those patients where metastases in the lymph nodes have not been detected (node-negative disease). So far histomorphological criteria, the determination of receptors for steroid hormones or EGF (epidermal growth factor), the protease cathepsin D or DNA-ploidy are used to distinguish between low- and high-risk patients. High-risk patients have a higher incidence of recurrences and/or shorter overall survival after surgery of the primary tumour than low-risk patients. High-risk patients (node-positive; hormone-receptor-negative) would receive adjuvant hormone therapy or chemotherapy. In the node-negative patient, adjuvant therapy is only recommended if a high content of cathepsin D and aneuploidy of the tumour (or high S-phase in diploid tumours) has been diagnosed. Determination of cathepsin D in tumour extracts as a variable in breast cancer patients is based on the fact that invasion and metastasis is correlated with elevated levels of tumour-associated proteases such as cathepsins B and D, collagenase IV and plasminogen activators. The urokinase-type plasminogen activator (uPA) which is secreted by tumour cells as an enzymatically inactive proenzyme (pro-uPA) seems to play a key role in mediating tumour cell invasion in cancer tissues. Receptor-bound uPA converts enzymatically inactive plasminogen into the serine protease plasmin which then degrades the extracellular matrix surrounding the tumour cells (tumour stroma). We localized pro-uPA/uPA immunohistochemically in paraffin-embedded formalin-fixed breast cancer tissue sections. Pro-uPA/uPA was detected in the cytoplasm and on the plasma membrane of the tumour cells reflecting receptor-bound pro-uPA/uPA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumour-associated fibrinolysis: the prognostic relevance of plasminogen activators uPA and tPA in human breast cancer. 213 50

Somatostatin receptors (SS-R) were measured with in vitro receptor autoradiography using the SS analog 125I-[Tyr3]-SMS 201-995 as radioligand in 342 breast-tumor samples. In a group of 158 "small" tumor samples (mean section surface: 14 mm2 +/- 0.4; mean +/- SEM), 34 tumors (21%) were SS-R positive. In a group of 72 "large" tumor samples (mean size: 180 mm2 +/- 8; mean +/- SEM), 33 tumors (46%) were SS-R positive. In this second group, more than half of the tumors had a non-homogeneous distribution of SS-R, i.e., tumor regions within SS-R positive tumors were SS-R negative. In a group of 48 additional patients, we could show that primaries and their metastases, or double primaries from right and left breasts, or 2 primaries resected consecutively, could both occasionally be SS-R positive. Finally, in 71 SS-R-positive primary tumors, 18 tumor samples were found to have simultaneously Epidermal Growth Factor receptors (EGF-R); in 12 of these 18 cases, the 2 receptor types were not topographically overlapping. Whereas SS-R were located on tumor tissue, EGF-R were often seen on adjacent normal lobules and ducts. These results show that a subgroup of breast tumors contain SS-R, in several cases non-homogeneously distributed. Their location does not coincide with that of EGF-R. Metastasis of SS-R-positive primaries may be SS-R-positive, as are sometimes second primaries. For evaluation of SS-R incidence and distribution, autoradiography is of advantage, specially if it is performed on large tumor samples, since it allows precise identification of the tissue elements containing these receptors.
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PMID:Somatostatin receptor incidence and distribution in breast cancer using receptor autoradiography: relationship to EGF receptors. 216 44

DNAs from 37 human gastric carcinomas and seven lymph node metastases were analyzed for alterations of the epidermal growth factor receptor (EGFR) gene and oncogenes by the Southern blot hybridization method. The probes used were EGFR gene, c-Ha-ras, v-Ki-ras, N-ras, c-myc, v-myb, v-fos, c-erbB-2, v-erbA, v-abl and v-fes. Amplification of the EGFR gene was detected in only one poorly differentiated adenocarcinoma. Amplifications of c-myc gene and c-erbB-2 gene were each observed in two well differentiated adenocarcinomas. One of these tumors had coamplification of c-erbB-2 and c-erbA genes but there were no amplifications nor rearrangements of other oncogenes. The poorly differentiated adenocarcinom with amplified EGFR gene also showed enhanced expression of EGFR gene by Northern blot analysis and additionally had strong synchronous immunoreactivity for EGFR and EGF.
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PMID:Amplification of epidermal growth factor receptor (EGFR) gene and oncogenes in human gastric carcinomas. 257 Apr 89

Breast cancer is a highly heterogeneous disorder with regard to biologic and clinical characteristics. Identification of patients with different biologic subtypes is important both prognostically and therapeutically. The recent introduction of estrogen and progesterone receptor measurement has considerably increased our ability to identify patients with hormone-dependent tumors who are likely to respond to endocrine therapy and enjoy a longer survival. Assessment of the tumor growth fraction by autoradiographic or flow cytometric methods and measurement of EGF receptors in tumor specimens are likely to produce additional independent information on the clinical outcome of patients with breast cancer. The endocrine therapy of breast cancer has been greatly facilitated with the introduction of newer forms of therapy such as antiestrogens and aromatase inhibitors. These forms of treatments are well established, not only in patients with metastatic disease but also in selected subgroups of women with operable breast cancer following surgery. In view of its low toxicity and ease of administration, modern endocrine therapy has obviated the need for major ablative procedures such as surgical adrenalectomy and hypophysectomy. Unfortunately, duration of response and survival have not been prolonged by these newer endocrine treatments when compared with traditional hormonal therapy. Thus, new treatment strategies need to be developed, since current therapy does not cure any patient with advanced disease and at best only a small fraction of women with early breast cancer. Hormonally induced manipulation of tumor cell kinetics may provide a tool to enhance the efficacy of cytotoxic chemotherapy, in both metastatic as well as locally advanced disease. This potential approach needs to be further evaluated in prospective randomized clinical trials. Prostate cancer is the male counterpart of hormone-dependent neoplasia. Conventional therapy of this malignancy consists of surgical or medical castration. However, despite a high initial response rate, disease progression invariably occurs with poor response to secondary forms of therapy. Potential new treatment strategies currently being tested in the attempt to improve clinical outcome include simultaneous early blockade of both adrenal and testicular androgens as well as hormonally induced tumor cell growth synchronization and recruitment prior to administration of cytotoxic chemotherapy.
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PMID:Endocrine therapy of breast and prostate cancer. 266 86

Recent studies have demonstrated that epidermal growth factor receptor (EGF-R) shows great homology with the v-erbB transforming protein and the amplified expression of EGF-R accompanies the malignant transformation of squamous epithelium of the uterine cervix. In this study, the tissue localization of EGF-R in the oncogenesis of uterine cervical cancer was examined by the avidin/biotin immunoperoxidase technique using anti-EGF-R monoclonal antibody. Normal squamous and columnar epithelium was almost negative for EGF-R. The positive rate of EGF-R increased in the precancerous lesions, whereas it decreased in invasive and metastatic cancer (mild dysplasia: 36%, moderate dysplasia: 57%, severe dysplasia: 77%, carcinoma in situ: 82%, microinvasive carcinoma: 80%, squamous cell carcinoma: 24%, glandular dysplasia: 67%, adenocarcinoma in situ: 75%, adenocarcinoma: 8%, adenosquamous carcinoma: 33%, metastatic carcinoma of the pelvic lymph node: 21%). The positive rate of dysplasia in follow up cases was high in the progressive group (regressive group: 0%, persistent group: 62%, progressive group: 80%). These results suggest that EGF-R may play an important role in the early stage of carcinogenesis of uterine cervical cancer, and it will be used as one of the markers in the prognosis of precancerous lesions of the uterine cervix.
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PMID:[Immunohistochemical studies on epidermal growth factor receptor in oncogenesis of uterine cervical cancer]. 268 40

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


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