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)

It has been assumed that the rate-limiting step in the ligand-induced synthesis of prostaglandins is the release of arachidonic acid from membrane phospholipid stores as a result of the activation of phospholipase. The assumption has been that the arachidonic acid is converted to PGH2 by the constitutive prostaglandin synthase/cyclooxygenase EC1.14.99.1 (PGS-1) enzyme present in cells. In this model, PGS-1 is proposed to be present in excess, and the production of arachidonic acid is thought to be rate limiting. However, a second prostaglandin synthase gene, PGS-2 has recently been described. The PGS-2 gene is induced by a variety of ligands, in cells as diverse as fibroblasts, monocytes, macrophages, smooth muscle cells, ovarian granulosa cells, epithelial cells, endothelial cells, and neurons. Moreover, PGS-2 induction is inhibited in nearly all contexts by glucocorticoids. It seems likely, therefore, that the regulation of PGS-2 expression plays a critical role in the production of prostanoids, both in normal physiological processes and in pathophysiological processes involving these paracrine mediators. In this review, we consider the regulation of the two genes, PGS-1 and PGS-2, that encode the isoforms of prostaglandin synthase.
Cancer Metastasis Rev 1994 Dec
PMID:Regulation of prostaglandin synthase-1 and prostaglandin synthase-2. 771 87

Lymphogenous metastasis is a common feature of human lung cancers, but very little is known about the underlying mechanism. In the present study, in vivo selection was carried out to obtain a highly lymphogenous metastatic subline of a human large cell carcinoma of the lung, NCI-H460. The resulting subline, termed NCI-H460-LNM35 (LNM35), was shown to metastasize to regional lymph nodes with a 100% incidence not only as a result of orthotopic intrabronchial (i.b.) implantation, but also as a result of conventional s.c. implantation. LNM35 has a short latency period, allowing for the collection of experimental data within 28 days after i.b. inoculation and 45 days after s.c. inoculation. It was noted that orthotopically i.b.-propagated LNM35 closely mimicked the clinical manifestations of human lung cancer patients by infiltrating into lymphatic vessels and metastasizing to the mediastinal lymph nodes. The LNM35 cell line is, to the best of our knowledge, the first human lung cancer cell line to be reported as having lymphogenous metastatic properties, and the observed 100% incidence by s.c. inoculation gives LNM35 a significant advantage even over previously reported human cancer cell lines of other origins. Comparisons between LNM35 and its parental NCI-H460 cell lines were also made with regard to expression levels and/or activities of various molecules that are thought to play a part in the metastatic process. We show here that the expression of cyclooxygenase 2 is increased in LNM35 and that a specific cyclooxygenase 2 inhibitor, nimesulide, can inhibit the invasion of LNM35 in vitro through Matrigel containing basement membrane components.
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PMID:Establishment and characterization of a human lung cancer cell line NCI-H460-LNM35 with consistent lymphogenous metastasis via both subcutaneous and orthotopic propagation. 1081 Nov 36

Pheochromocytomas are rare tumors of the adrenal medulla or the paraganglion system. There are no histological or chemical markers available that define the malignant behavior of these tumors; so far only the discovery of metastases reveals malignancy. Cyclooxygenase (Cox) is the key enzyme in conversion of arachidonic acid to PGs, and two isoforms, Cox-1 and Cox-2, have been identified. Cox-2 has been associated with carcinogenesis, and it is overexpressed in many human malignancies. We have now investigated the expression of Cox-2 in normal adrenal gland, in 92 primary pheochromocytomas and in six metastases using immunohistochemistry and Northern blot and Western blot analyses. Cox-2 protein was expressed in the adrenal cortex, whereas the medulla was negative as detected by immunohistochemistry. Interestingly, all malignant pheochromocytomas (n = 8), regardless of the primary location of the tumor, showed moderate or strong Cox-2 immunoreactivity, whereas 75% of the benign adrenal tumors (n = 36) showed no or only weak immunopositivity. The staining was negative or weak in 79% of the adrenal tumors that showed histologically suspicious features (n = 24), but had not metastasized. Most of the pheochromocytoma samples studied also expressed low levels of Cox-2 mRNA. Our data show that normal adrenal medulla does not express Cox-2 immunohistochemically. However, strong Cox-2 protein expression was found in malignant pheochromocytomas, whereas most benign tumors expressed Cox-2 only weakly. To our knowledge, this is the first report on Cox-2 expression in pheochromocytomas and enhanced expression in malignant pheochromocytomas. These findings suggest that negative or weak Cox-2 expression in pheochromocytomas favors benign diagnosis.
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PMID:Increased expression of cyclooxygenase-2 in malignant pheochromocytomas. 1170 43

Current tumor, node, and metastasis (TNM) staging and grading systems are insufficient to accurately predict the evolution of most invasive bladder cancers irrespective of treatment. Predicting which invasive tumors will or will not recur or metastasize early is crucial in order to dictate initial therapy and to better counsel the patient. A need for tumor markers that could be incorporated into clinical practice to add prognostic information to the conventional TNM and grading systems in terms of treatment response and prognosis is crucial. This review provides an update on the most promising reported single markers and pathways, including the cell cycle markers p53, p21 and p27, and potential targets for novel therapies, such as cyclooxygenase 2 (COX 2) and factors of angiogenesis. The critical steps remain the availability of large and well-characterized data sets to validate the combination of markers, as well as high throughput methods to study tumor molecular fingerprints, such as DNA microarrays.
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PMID:Prognostic markers in muscle invasive bladder cancer. 1219 3

Previously, oncostatin M (OSM) has been shown to inhibit the proliferation of breast cancer cells in vitro. Circumstantial evidence, however, suggests that OSM could be involved in the development of a metastatic phenotype in vivo. We examined the effects of OSM on the proliferation and metastatic potential of the murine mammary carcinoma cell lines M6 (adenocarcinoma) and M6c (metastatic adenocarcinoma). OSM inhibits the proliferation of both cell lines by 43%, but also causes a loss of cell-cell and cell-substratum adhesion that culminates in cell detachment from monolayer culture. OSM treatment results in a 258% and 550% increase in the detachment of M6 and M6c, respectively, in 32 hours. This effect was abrogated by the selective Cox-2 inhibitor NS-398, and by the anti-inflammatory glucocorticoid dexamethasone. Exogenous prostaglandin E2 (PGE2) partially reverses NS-398's inhibition of OSM-induced cell detachment, indicating Cox-2 involvement. In addition, OSM induces the expression of Cox-2 mRNA, and of the 74 kDa form of Cox-2 protein. M6 and M6c cells detached by OSM are viable and will re-adhere and proliferate in the absence of OSM. OSM-detached cells (M6DET and M6cDET) were collected and maintained in culture and their invasiveness was assessed in vitro. Importantly, M6DET and M6cDET are both significantly more invasive that their respective parental cells. These data suggest that OSM could contribute to the development of a metastatic phenotype in vivo, which would render OSM unsuitable as a cancer therapy and suggest that OSM itself is a potential therapeutic target.
Clin Exp Metastasis 2004
PMID:Oncostatin M stimulates the detachment of a reservoir of invasive mammary carcinoma cells: role of cyclooxygenase-2. 1516 34

Cyclooxygenases (particularily Cox-2) are involved in carcinogenesis and metastatic cancer progression. The expression profiles of the cyclooxygenases and the roles they play in established tumours of similar stage remains unclear. We report that Cox-1 and Cox-2 expression is highly variable in Dukes' C tumours, and changes in Cox-1 expression may be of importance.
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PMID:RNA profiling of cyclooxygenases 1 and 2 in colorectal cancer. 1532 21

We examined the expression of Her2/neu and Cox-2 in bladder cancer and its relationship to clinicopathological factors, survival data and patient outcome. From 153 consecutive patients who had undergone radical cystectomy for bladder cancer, tumour tissue was analysed for Her2/neu amplification by fluorescent in situ hybridisation and for Her2/neu and Cox-2 protein expression by immunohistochemistry. Results were correlated with clinical data and survival times. Cox-2 and Her2/neu co-expression was present in 44 (33%) of 132 transitional cell carcinomas. Although this association was significant (p = 0.003), there was no significant association between Cox-2 and Her2/neu amplification status. Each marker was independent of primary tumour stage and lymph node status, as well as histological grading. However, the co-existence of Her2/neu amplification and Cox-2 expression correlated with distant metastases: of 5 Cox-2-positive samples, 2 (40%) showed Her2/neu amplification. This was only a trend, amounting to no more than borderline statistical significance (p = 0.046). Kaplan-Meier survival analysis did not demonstrate any relationship between Cox-2 or Her2/neu expression or amplification alone or in combination with respect to overall and disease-free survival. Analysing the co-expression of Cox-2 and Her2/neu status does not add any prognostic information in patients with bladder cancer. Nevertheless, combined treatment with Her2/neu and Cox-2 inhibitors may be beneficial for the subgroup of Her2/neu- and Cox-2-expressing tumours and will have to be assessed in further preclinical and clinical studies.
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PMID:Cox-2 and Her2/neu co-expression in invasive bladder cancer. 1587 Aug 65

Cyclo-oxygenase (Cox-2) plays an important role in mammary carcinogenesis, nevertheless, its role in canine mammary tumors, and particularly in inflammatory mammary carcinoma (IMC), is unknown. Tumor Cox-2 levels were analyzed by enzyme immunoassay, in post-surgical tumor homogenates of 129 mammary tumors (62 dysplasias and benign tumors, 57 malignant non-IMC and 10 IMC) from 57 female dogs. The highest Cox-2 values were detected in the IMC group. In non-IMC malignant tumors, high values of Cox-2 were related to skin ulceration (p < 0.001) and tumor size (p < 0.001). The follow-up study revealed that high Cox-2 levels were related with recurrence (p = 0.002), metastases (p < 0.001), disease-free survival (p < 0.001) and overall survival (p < 0.001). This study demonstrates an association between intra-tumor Cox-2 levels and poor prognosis. The high levels found in IMC cases could indicate a special role of Cox-2 in the inflammatory phenotype and open the possibility of additional new therapeutic approaches in this special type of mammary cancer in humans and dogs.
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PMID:Cox-2 levels in canine mammary tumors, including inflammatory mammary carcinoma: clinicopathological features and prognostic significance. 1630 27

The aim of this study is to determine immunohistochemical markers with prognostic significance for disease-specific survival in patients with squamous cell cancer of the vulva. The study material consisted of slides and paraffin blocks of 50 vulvectomy specimens. A tissue microarray was constructed and stained with 16 antibodies. The impact of lymph node metastases, size of tumor, vascular space involvement, and the marker expression on disease-specific survival was calculated. In univariate analysis lymph node metastases, tumor size more than 4 cm, vascular space involvement, strong cyclooxygenase 2 expression, and absent Caspase 3 expression were significantly associated with disease-specific survival. In a multivariate analysis, poor disease-specific survival is independently associated with absent Caspase 3 expression (hazard ratio, 0.2; 95% confidence interval, 0.04-0.97; P = 0.045). Five-year survival was 86% in patients with tumors positive for Caspase 3 (n = 20) and drops to 64% in patients with Caspase 3-negative tumors (n = 30). In this test set, cyclooxygenase 2 and Caspase 3 seem to be immunohistochemical markers with prognostic significance for vulva cancer. The results have to be validated.
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PMID:Identification of potential prognostic markers for vulvar cancer using immunohistochemical staining of tissue microarrays. 1741 88

Several new drugs that are targeted towards various angiogenic factors have shown considerable potential for controlling tumor proliferation and metastases. Expression levels of the targeted genes in primary tumors and metastases should be understood to maximize the use of such drugs. The present study aimed to clarify associations between mRNA levels of cyclooxygenase 2 (COX-2) and angiogenic factors [vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8)] in primary colorectal cancer and in corresponding liver metastasis. We also compared these gene expressions of primary colorectal cancer between patients with and without liver metastasis. In 31 pairs of formalin-fixed and paraffin-embedded primary and metastatic liver tumors as well as 27 specimens of consecutive stage II patients without recurrence, mRNA was quantified by real-time reverse transcription-polymerase chain reaction following the laser capture microdissection. We found a significantly positive correlation in IL-8 between primary tumors and matched liver metastases (p=0.034, rs=0.39) and in VEGF (p=0.0083, rs=0.48), but not in COX-2, which was associated with both VEGF (p=0.044, rs=0.37) and IL-8 (p=0.0004, rs=0.64) in primary colorectal cancers. Multiple regression analysis revealed that COX-2 was independently associated with IL-8 (p<0.0001). There were no differences in mRNA levels between patients with and without liver metastasis. The mRNA levels of VEGF and IL-8 in liver metastasis can be predicted from those in primary colorectal cancer. COX-2 might exert angiogenic activity more through the IL-8, than the VEGF pathway. These angiogenic factors were sufficiently up-regulated before hematogenous metastasis. These preliminary data merit further validation studies.
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PMID:Messenger RNA expression of COX-2 and angiogenic factors in primary colorectal cancer and corresponding liver metastasis. 1928 74


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