Cyclooxygenase-2 overexpression associated with a poor prognosis in chondrosarcomas

Matsumura, Tsuyoshi; Yamaguchi, Takehiko; Yamaguchi, Umio; Morimoto, Yuki; Nakatani, Fumihiko; Kawai, Akira; Chuman, Hirokazu; Beppu, Yasuo; Shimoda, Tadakazu; Hasegawa, Tadashi

doi:10.1016/j.humpath.2005.12.001

Cited by 26 publications

(28 citation statements)

References 30 publications

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“…Despite the cardiovascular side effects of one inhibitor (Vioxx), PTGS2 inhibitors (coxibs) are currently in clinical trials for various malignancies including colorectal, non-small cell lung, breast, prostate, and pancreatic cancers (26 -28). PTGS2 was shown previously to be overexpressed in chordoma and chondrosarcoma; however, the use of coxibs for sarcomas has yet to be explored (29,30). Our analysis identified several novel cancers in which PTGS2 appears to be overexpressed including the difficult-to-treat sarcomas, chondromyxoid fibroma, and malignant peripheral nerve sheath tumor.…”

Section: Discussionmentioning

confidence: 85%

Genomics screen in transformed stem cells reveals RNASEH2A, PPAP2C, and ADARB1 as putative anticancer drug targets

Flanagan

Funes

Henderson

et al. 2009

Molecular Cancer Therapeutics

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Since the sequencing of the human genome, recent efforts in cancer drug target discovery have focused more on the identification of novel functions of known genes and the development of more appropriate tumor models. In the present study, we investigated in vitro transformed human adult mesenchymal stem cells (MSC) to identify novel candidate cancer drug targets by analyzing the transcriptional profile of known enzymes compared with non-transformed MSC. The identified enzymes were compared with published cancer gene expression data sets. Surprisingly, the majority of up-regulated enzymes are already known cancer drug targets or act within known druggable pathways. Only three enzymes (RNASEH2A, ADARB1, and PPAP2C) are potentially novel targets that are up-regulated in transformed MSC and expressed in numerous carcinomas and sarcomas. We confirmed the overexpression of RNASEH2A, PPAP2C, and ADARB1 in transformed MSC, transformed fibroblasts, and cancer cell lines MCF7, SK-LMS1, MG63, and U2OS. In functional assays, we show that small interfering RNA knockdown of RNASEH2A inhibits anchorage-independent growth but does not alter in vitro proliferation of cancer cell lines, normal MSC, or normal fibroblasts. Knockdown of PPAP2C impaired anchorage-dependent in vitro growth of cancer cell lines and impaired the in vitro growth of primary MSC but not differentiated human fibroblasts. We show that the knockdown of PPAP2C decreases cell proliferation by delaying entry into S phase of the cell cycle and is transcriptionally regulated by p53. These in vitro data validate PPAP2C and RNASEH2A as putative cancer targets and endorse this in silico approach for identifying novel candidates.

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Section: Discussionmentioning

confidence: 85%

Genomics screen in transformed stem cells reveals RNASEH2A, PPAP2C, and ADARB1 as putative anticancer drug targets

Flanagan

Funes

Henderson

et al. 2009

Molecular Cancer Therapeutics

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“…Two isoforms of COX have been characterized: ubiquitously expressed COX-1 and inducible COX-2. Overexpression of COX-2 is often observed in the tissues of chronic inflammation and several cancers, which probably substantiate the existence of mechanisms common to both inflammation and tumorigenesis, such as proliferation, progression, induction of several growth factors, invasion, and tumor cell resistance to apoptosis in the various epithelial cell tumors and some mesenchymal lesions 1,2,3,4,5,6,7,8. The COX-2 gene is tightly regulated, and its 3' untranslated region (UTR) is the principal region determining the inherent instability of COX-2.…”

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confidence: 77%

“…In the normal condition, COX-2 expression is tightly controlled and the alteration of HuR expression accelerates the expression of COX-2. The overexpression of COX-2 in several carcinomas and some sarcomatous lesions suggests its roles in tumorigenesis 1,2,3,4,5,6,7,8. Lee et al6 suggest that COX-2 is directly associated with cell proliferation, migration and invasion in human osteosarcoma cells.…”

Section: Discussionmentioning

confidence: 99%

Expression of HuR and Cyclooxygenase-2 in Nodular Fasciitis and Low-Grade Sarcoma: An Immunohistochemical Study

et al. 2014

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BackgroundNodular fasciitis is the most common reactive mesenchymal lesion to be misidentified as a type of sarcoma. HuR is an mRNA-binding protein that can stabilize cyclooxygenase-2 (COX-2) mRNA leading to COX-2 overexpression. The aim of this study is a comparison of the expressions of COX-2 and HuR and the relationships between their expressions and the clinicopathological parameters in nodular fasciitis and low-grade sarcoma.MethodsWe measured the expression of HuR and COX-2 in 21 cases of nodular fasciitis and 37 cases of low-grade sarcoma using immunohistochemistry.ResultsThe frequency of cytoplasmic immunoreactivity for HuR was 5 of 21 cases of nodular fasciitis (23.8%) and 23 of 37 cases of low-grade sarcoma (62.1%) (p=.013). COX-2 expression was moderate or strong in nodular fasciitis (12/21, 57.1%) and in low-grade sarcoma (29/37, 78.4%) (p=.034). In addition, a significant difference existed between these two entities in terms of the relationship between moderate or strong COX-2 expression and HuR cytoplasmic immunoreactivity (p=.009). Moderate or strong COX-2 immunoreactivity correlated with nuclear (p=.016) or cytoplasmic HuR (p=.024) expression in low-grade sarcoma but not in nodular fasciitis.ConclusionsThis study suggests that HuR and COX-2 expression may be useful to differentiate nodular fasciitis from low-grade sarcoma.

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“…COX-2 overexpression has also been documented in adult and pediatric sarcomas [44,45] associated with a poor prognosis in chondrosarcomas [46] . COX-2 expression studies performed on a variety of human sarcomas showed a signifi cant association with epitheloid diff erentiation [47] .…”

Section: Discussionmentioning

confidence: 99%

COX-2 Expression in Highly Aggressive Thyroid Malignancies – Indication for a Possible Therapeutic Option?

Sheu

Grabellus²,

Schwertheim³

et al. 2008

Horm Metab Res

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Both anaplastic thyroid carcinoma (ATC) and angiosarcoma of the thyroid (AST) are highly aggressive malignancies with very limited therapeutic options. Since selective inhibition of COX-2, for example, by celecoxib has been shown to suppress both tumour formation and progression, we investigated COX-2 protein expression in a series of ATC and AST (26 cases each) using immunohistochemistry. COX-2 expression was demonstrated in 13 ATC (50%) and 11 AST (42%); a strong COX-2 expression in more than 50% of vital tumour cells was found in 5 ATC and 5 AST, respectively. Although a recently performed phase II trial applying celecoxib failed overall to halt tumour progression in differentiated thyroid carcinoma, the two cases with partial or complete remission noted in this study were related to tumours with immunohistochemically proven strong COX-2 expression. The strong COX-2 expression observed in approximately 20% of our ATC and AST samples may thus indicate selective patients with a possible therapeutic option for an otherwise fatal disease.

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Cyclooxygenase-2 overexpression associated with a poor prognosis in chondrosarcomas

Cited by 26 publications

References 30 publications

Genomics screen in transformed stem cells reveals RNASEH2A, PPAP2C, and ADARB1 as putative anticancer drug targets

Genomics screen in transformed stem cells reveals RNASEH2A, PPAP2C, and ADARB1 as putative anticancer drug targets

Expression of HuR and Cyclooxygenase-2 in Nodular Fasciitis and Low-Grade Sarcoma: An Immunohistochemical Study

COX-2 Expression in Highly Aggressive Thyroid Malignancies – Indication for a Possible Therapeutic Option?

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