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)

Between 1975-1996, 39 patients underwent resection of pulmonary metastases from renal cell carcinoma. Multivariate analysis (COX model) for survival of preoperative risk factors showed that time of diagnosis (syn-/metachronous) of the metastases (p = 0.05) and the number of metastases (p = 0.01) were of prognostic significance. It is concluded that metastasectomy in patients with not more than six metachronous metastases after renal cell carcinoma has significant benefit and in cases of synchronous metastases or more than 6 pulmonary metastases indication for resection should be restricted.
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PMID:[Prognostic factors and subsequent indications for surgery in pulmonary metastasis of renal cell carcinoma]. 993 2

Cyclooxygenase-2 (COX-2) is the enzyme that normally synthesizes prostaglandins during an inflammatory response. Many primary and metastatic cancers express COX-2, and its presence is correlated with tumor angiogenesis, more invasive tumor phenotype, resistance to apoptosis, and systemic immunosuppression. The expression of COX-2 is associated with a worse prognosis. Inhibition of prostaglandin synthesis may be beneficial in human malignancy. Regular consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of, and mortality rate resulting from, a number of types of gastrointestinal cancers. Premalignant colonic lesions regress following the administration of nonspecific COX inhibitors, such as sulindac (Clinoril). Advanced solid tumor patients treated with indomethacin (Indocin) survive twice as long as do such patients who receive supportive care alone. The U.S. Food and Drug Administration has approved specific COX-2 inhibitors for the treatment of arthritis, pain, and familial adenomatous polyposis. Preclinical studies show that these drugs block angiogenesis, suppress solid tumor metastases, and slow the growth of implanted gastrointestinal cancer cell lines. The COX-2 inhibitors have safely and effectively been combined with chemotherapeutic agents in experimental studies. Ongoing clinical trials are currently assessing the potential therapeutic role of COX-2 inhibitors in both prevention and treatment of a diverse range of human cancers.
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PMID:Celecoxib with chemotherapy in colorectal cancer. 1201 63

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

The PC-3 Low Invasive cells and the PC-3 High Invasive cells were used to investigate the correlation of the COX-2 expression and its arachidonic acid metabolites, prostaglandins, with their invasiveness through Matrigel using a Boyden chamber assay. The COX-2 expression in PC-3 High Invasive cells was approximately 3-fold higher than in PC-3 Low Invasive cells while the COX-1 expression was similar in both cell sublines. When incubated with arachidonic acid, PGE2 was the major prostaglandin produced by these cells. PC-3 High Invasive cells produced PGE2 approximately 2.5-fold higher than PC-3 Low Invasive cells. PGD2 was the second most abundant prostaglandin produced by these cells. Both indomethacin (a nonspecific COX inhibitor) and NS-398 (a specific COX-2 inhibitor) inhibited the production of prostaglandins and the cell invasion. PGE2 alone did not induce the cell invasion of PC-3 Low Invasive cells. However, PGE2 reversed the inhibition of cell invasion by NS-398 and enhanced the cell invasion of the PC-3 High Invasive cells. In contrast, PGD2 slightly inhibited the cell invasion. These results suggest that in the PC-3 Low Invasive cells, COX-2-derived PGE2 may not be sufficient to induce cell invasion while in the PC-3 High Invasive cells, PGE2 may be sufficient to act as an enhancer for the cell invasion. Further, PGD2 may represent a weak inhibitor and counteracts the effect of PGE2 in the cell invasion.
Clin Exp Metastasis 2002
PMID:Requirement of cyclooxygenase-2 expression and prostaglandins for human prostate cancer cell invasion. 1249 88

Cyclooxygenase-2 (COX-2) is an inducible enzyme that regulates prostaglandin synthesis and is overexpressed at sites of inflammation and in several epithelial cancers. Recently, a causal link for COX-2 in epithelial tumorigenesis was shown in genetically-manipulated animal models of colon and breast carcinoma. Data indicate that COX-2 is involved in the regulation of apoptosis, angiogenesis, and tumor cell invasiveness, which appear to contribute to its effects on tumorigenesis. Multiple studies have shown that nonselective COX and selective COX-2 inhibitors effectively prevent experimental colon cancer. Furthermore, sulindac and the selective COX-2 inhibitor celecoxib were shown to regress colorectal polyps in patients with familial adenomatous polyposis. Although the exact anti-tumor mechanisms of these agents await further study, data indicate that both COX-dependent and COX-independent mechanisms may be important. In this review, the association between COX-2 and colorectal tumorigenesis and potential mechanisms of this effect are discussed. Additionally, evidence supporting the role of NSAIDs and selective COX-2 inhibitors for the prevention and treatment of human colorectal cancer is reviewed.
Cancer Metastasis Rev
PMID:Role of cyclooxygenase-2 in colorectal cancer. 1500 Jan 50

Several studies have suggested that cyclooxygenase-2 (COX-2) expression is associated with parameters of aggressive breast cancer, including large tumor size, positive axillary lymph node metastases, and HER2-positive tumor status. Studies of mammary tumors in mice and rats have indicated that moderate to high COX-2 expression is related to the genesis of mammary tumors that are sensitive to treatment with nonspecific and specific COX-2 inhibitors. Moreover, these studies also suggest that mammary tumors are associated with high prostaglandin levels and induction of aromatase, a cytochrome P450 enzyme that catalyses estrogen production. Mechanistically, lack of apoptosis and increased angiogenesis and invasiveness have been implicated as mechanisms of tumor growth in COX-2-dependent mammary tumors. Based on these observations, clinical trials are evaluating adjunctive therapy with a selective COX-2 inhibitor, celecoxib, in combination with several regimens used in the metastatic and adjuvant or neoadjuvant settings of breast cancer. In addition, proof-of-principle trials are being conducted to ascertain the effects of celecoxib on known markers of proliferation, angiogenesis, and apoptosis. Finally, based on the apparent synergy between celecoxib and the aromatase inhibitor exemestane, the National Cancer Institute of Canada Clinical Trials Group is launching a phase III trial comparing exemestane with or without celecoxib against placebo in postmenopausal women with elevated risk of breast cancer. Results of these trials will help to define the role of celecoxib in the management and prevention of breast cancer. Epidemiologic evidence suggests the incidence of breast, colon, and lung cancers is inversely related to the use of aspirin and nonsteroidal anti-inflammatory drugs, which are nonspecific inhibitors of COX. COX-1 and COX-2 are enzymes that generate prostaglandins and thromboxanes from free arachidonic acid. Genetic approaches pursued in animal models and biochemical evidence obtained from human tumor cell lines have strongly implicated COX-2, an inducible enzyme, in many preinvasive and invasive human tumors. In this article we will first review data that point to COX-2 as an important indicator in the genesis of breast cancer and discuss planned and ongoing clinical trials evaluating specific COX-2 inhibitors in the treatment and prevention of breast cancer.
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PMID:The role of COX-2 inhibition in breast cancer treatment and prevention. 1517 21

Evidence continues to accumulate that cyclooxygenase-2 (COX-2), an inducible COX isoform, represents a potential pharmacological target for the prevention and treatment of cancer, including tumors affecting the entire upper aerodigestive tract. Studies in experimental models of these malignancies show that selective COX-1 inhibitors reduce tumor formation and growth. Clinical studies have been initiated to determine the chemoprotective effects of selective COX-2 inhibitors in patients with oral leukoplakia and Barrett's esophagus, and other studies are assessing the feasibility of incorporating these agents into existing treatment modalities for patients with locally advanced or metastatic cancer.
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PMID:COX-2 inhibition in upper aerodigestive tract tumors. 1525 27

The prognosis of pancreatic cancer with metastases or recurrence is quite poor. Chemotherapy has not resulted in a significant survival benefit; median survival is 3-6 months. Various chemotherapeutic agents have been evaluated and the standard chemotherapy of pancreatic cancer is gemcitabine. The response rate, however, is low at 13%. Thalidomide and celecoxib have different mechanisms of action and activity in various malignant tumors. Both have been evaluated and shown to demonstrate activity against solid tumors. Thalidomide decreased the stability of TNF-mRNA and COX-2 mRNA. COX-2 is a bifunctional enzyme possessing both cyclooxygenase and peroxidase activities. Although celecoxib inhibits PG biosynthesis, most do not affect the peroxidase activity of COX, which can generate proximate carcinogens. Because thalidomide does not completely inhibit COX-2 expression or PG biosynthesis, a therapeutic strategy combining celecoxib with thalidomide might be more effective than using either agent alone. Differences in the mechanism of action of gemcitabine and irinotecan suggest that a change of gemcitabine to irinotecan could provide clinically efficacious outcomes. In order to accomplish new treatment strategies, we have been using thalidomide, celecoxib and irinotecan in low-doses. We believe this combination represents a viable treatment for patients of pancreatic cancer with recurrence or metastases.
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PMID:[A case report of metastatic pancreatic cancer that responded remarkably to the combination of thalidomide, celecoxib and irinotecan]. 1544 66

Benzo-[a]-pyrene (B[a]P), a carcinogenic component of cigarette smoke, has been shown to increase both COX-II expression and prostaglandin output in vascular smooth muscle and oral epithelial cells. In addition, invasive breast cancer cells have been reported to over express COX-II and PGE(2). Therefore, the objective of this study was to quantify the effect of increasing B[a]P concentrations on COX-II expression, PGE(2) output, and invasion using MDA-MB-231 cells, an invasive estrogen unresponsive breast cancer cell line. B[a]P significantly increased invasion in MDA-MB-231 cells at concentrations greater than 4 x 10(-8) M. Treatment of MDA-MB-231 cells with Vomitoxin (a selective COX-II inducer) enhanced invasion whereas co-treatment with NS398 (a selective COX-II inhibitor) attenuated B[a]P-induced invasion in MDA-MB-231 cells. Immunohistochemical staining and Western blots demonstrated a significant B[a]P treatment-induced increase in both the number of COX-II immunopositive MDA-MB-231 cells and COX-II protein levels. Moreover, B[a]P-treatment induced a profound (46 fold) increase in PGE(2) production by MDA-MB-231 cells. The aryl hydrocarbon receptor (AhR) antagonists resveratrol (RES) and alpha-naphthaflavone (alpha-NF) had no effect on their own, whereas B[a]P-induced invasion was significantly inhibited by co-treatment with RES and alpha-NF. Our data demonstrate that B[a]P-induced changes in invasion are mediated through augmented COX-II expression and PGE(2) production involving an AhR regulated pathway. Moreover, these results suggest a potential role for the AhR signalling pathway in breast cancer invasion.
Clin Exp Metastasis 2005
PMID:Benzo-[a]-pyrene increases invasion in MDA-MB-231 breast cancer cells via increased COX-II expression and prostaglandin E2 (PGE2) output. 1608 35

Cyclooxygenase-2 (COX-2) is overexpressed in various types of human malignancies, including squamous cell carcinomas of the esophagus, but its clinicopathologic role in esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study was to analyze expression of COX-2 in ESCC and to correlate this expression with clinicopathologic parameters and survival. From 1999 to 2003, endoscopic tissue samples from 110 patients with ESCC were collected for analysis. COX-2 expression was examined through immunohistochemical staining. Clinicopathologic data were analyzed to verify significance. COX-2 expression was detected in 50 of 110 ESCC specimens (45%). COX-2 expression was negative to weak in 73% (COX-2 low) and moderate to strong in 27% (COX-2 high) of tumors. Statistical differences between COX-2 high and COX-2 low were found according to status of the stage (stage IVM1a/IVM1b) (P=.001): cancer antigen (CA) 19-9 (normal/high) (P%.011), CA 12-5 (normal/high) (P=.011), and CA 15-3 (normal/high) (P=.035). Survival was significantly reduced among patients with high COX-2 expression (median overall survival, 3 mo) when compared with the COX-2 low group (median overall survival, 6 mo) (P=.0001). In the univariate analysis, age, body mass index, stage, COX-2, lactate dehydrogenase, CA 12-5, and CA 15-3 were significant factors for survival. With the use of COX regression analysis, only stage (P=.000), COX-2 (P=.000), lactate dehydrogenase (P=.023), and CA 15-3 (P=.002) were independent prognostic factors. Results showed that in patients with ESCC, COX-2 overexpression was significantly correlated with visceral metastases IVM1b). COX-2 overexpression is an unfavorable prognostic factor in ESCC.
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PMID:Prognostic factors and COX-2 expression in advanced stage esophageal squamous cell carcinoma. 1714 1


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