Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Therapies for metastatic pediatric sarcomas have reached maximum tolerated doses, but continue to provide suboptimal cure rates. Additionally, these treatments are associated with numerous short- and long-term side effects. Therefore, the search for newer, less toxic therapeutic agents is warranted. Overexpression of the inducible enzyme, cyclooxygenase-2 (COX-2), has been discovered in a variety of adult solid tumors and numerous studies have shown COX-2 inhibitors to have significant antiproliferative effects. Therefore, we sought to determine the expression of COX-2 in pediatric sarcomas. We evaluated rhabdomyosarcoma (RMS), osteosarcoma (OS), and Ewing sarcoma (EWS) samples for COX-2 expression by immunohistochemical analysis as well as by cDNA microarray analysis. COX-2 expression was detected in 48/58 (82.8%) tumors by immunohistochemistry and in an additional 52/59 (88.1%) tumors tested by microarray gene analysis. There was a trend toward increased COX-2 expression in metastatic rhabdomyosarcoma and osteosarcoma, though it did not reach clinical significance. The degree of COX-2 immunoreactivity did not vary significantly with other clinicopathologic features such as age, gender, or histologic classification. We conclude that the majority of these pediatric sarcoma samples express COX-2 to varying degrees. Therefore, studies testing the efficacy of COX-2 inhibitors in the treatment of pediatric sarcomas are warranted.
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PMID:Cyclooxygenase-2 expression in pediatric sarcomas. 1202 86

Although accumulating evidence suggests the importance of cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)) in the pathogenesis of many cancers, the mechanism by which this enzyme and its metabolite promote cancer progression is unknown. In this study, we investigated the role of COX-2 in fibronectin-induced up-regulation of rhabdomyosarcoma matrix metalloproteinase (MMP)-2 activity and cellular invasiveness. We tested three human rhabdomyosarcoma cell lines: RMS559, RD, and SJRH30. Cell attachment to fibronectin up-regulated both COX-2 expression and PGE(2) production and concomitantly enhanced MMP-2 activity. Exogenous PGE(2) stimulated MMP-2 promoter activity, increased MMP-2 expression, and increased cellular invasiveness. Aspirin and rofecoxib (non-selective and selective COX-2 inhibitor, respectively) each abolished fibronectin-associated induction of MMP-2 and induced dose-dependent reductions in cellular invasiveness. These data implicated a role for inducible COX-2 and PGE(2) in the regulation of rhabdomyosarcoma cellular invasiveness and MMP-2 activity.
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PMID:Fibronectin-induced COX-2 mediates MMP-2 expression and invasiveness of rhabdomyosarcoma. 1512 Jun 41

Many studies have focused on cyclooxygenase-2 (COX-2) alterations as a critical step in the onset and progression of cancer. Moreover, a strong correlation between COX-2 and chemoresistance has been demonstrated in several carcinomas. Recently, COX-2 expression has been observed in uterine carcinosarcoma, osteosarcoma, and rhabdomyosarcoma. We investigated COX-2 expression in chemoresistant uterine leiomyosarcoma in 30 patients who had undergone surgical treatment. COX-2 expression was observed in 13 cases (43.3%). Of the 13 patients with distinct COX-2 positive immunoreactivity uterine leiomyosarcomas, 7 had stage I or II disease and 6 had stage III or IV disease. The expression of COX-2 in uterine stromal malignancies may reveal a therapeutic hypothesis in the context of uterine leiomyosarcoma molecular chemotherapeutic approach.
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PMID:Cyclooxygenase-2 expression in uterine leiomyosarcomas. 1570 Aug 50

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the pediatric and adolescent population. Though treatments for localized disease have reasonable long-term success rates, if disease is diffuse at diagnosis, outcomes are far poorer. Additional and/or alternative therapies are critical for improved clinical outcomes. One potentially therapeutic target is the signal transducer and activator of transcription 3 (STAT3) pathway. STAT3 has been shown to have constitutive activation in human rhabdomyosarcoma cells; thus, inhibition of STAT3 signaling may be a mechanism to induce tumor cell death. Celecoxib has been shown, by computer modeling, to bind STAT3 at the SH2 domain and competitively inhibit native peptide binding necessary for phosphorylation and subsequent propagation of the STAT3 signaling cascade. We found that celecoxib inhibits IL-6-induced and persistent STAT3 phosphorylation and inhibits cell viability in human rhabdomyosarcoma cells. We found that genes downstream of STAT3 (BCL-2, survivin, cyclin D1) were downregulated with celecoxib. Celecoxib also inhibits colony formation and cell migration. Our results suggest that, though known more commonly as a cyclooxygenase-2 (COX-2) inhibitor, celecoxib could act through the STAT3 pathway as well. More importantly, its effect on cell migration and clonogenic colony forming ability make it a potentially useful therapeutic agent for rhabdomyosarcoma, especially in metastatic disease whose clinical outcome is marginal at best with current therapies.
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PMID:Celecoxib inhibits STAT3 phosphorylation and suppresses cell migration and colony forming ability in rhabdomyosarcoma cells. 2139 87

Several studies have identified cyclooxygenase-2 (COX-2) expression in a variety of sarcomas, including rhabdomyosarcoma, osteosarcoma and chondrosarcoma. Although overexpression of COX-2 has been associated with poor prognosis and decreased survival in chondrosarcoma and osteosarcoma, no relationship between COX-2 expression and patient outcome has been demonstrated in rhabdomyosarcoma or adult soft tissue sarcomas. Little is known concerning the expression of COX-2 in synovial sarcoma. Therefore, the aim of this study was to examine the expression of COX-2 in synovial sarcoma and if shown, to identify any association with tumor stage and oncologic outcome. Paraffin-embedded specimens from 27 patients with synovial sarcoma who were treated with surgical resection or biopsy were obtained. Specimens were evaluated for the degree of COX-2 expression after immunohistochemical staining. Specimens were assigned an immunoreactivity score (IS) based on the percent positivity of the specimen. A retrospective chart analysis was performed to determine the clinical stage at presentation, incidence of local recurrence, presence of metastatic disease and overall survival. Statistical analysis was then performed to determine whether there was a significant relationship between IS and stage at presentation or patient outcomes. COX-2 expression was detected in 18 of 27 (66.67%) of the pathological specimens. There was a statistically significant relationship between COX-2 expression and patient clinical stage at presentation; however, we were unable to identify a significant relationship between IS and patient survival. We also found no significant relationship between IS and development of metastases or local recurrence. COX-2 was expressed to some degree in 67% of the tumor specimens. There was a significant relationship between IS and patient stage at presentation, but no significant relationship between COX-2 expression and clinical outcome could be identified. The fact that these tumors do express COX-2, however, suggests the potential for an additional target for more effective therapy.
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PMID:Cyclooxygenase-2 expression is not associated with clinical outcome in synovial sarcoma. 2187 58