The eicosanoid cascade: possible role in gliomas and meningiomas

Nathoo, Narendra

doi:10.1136/jcp.57.1.6

Cited by 88 publications

(58 citation statements)

References 98 publications

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“…Inhibition of each one of them raises intracellular ARA levels, although combined inhibition could provide the most profound results [10]. Corticosteroids prevent the release of ARA from cancer cells via inhibition of cytosolic phospholipase A2 (cPLA2), an action which results in less available proinflammatory mediators, but also in less intracellular ARA.…”

Section: Discussionmentioning

confidence: 99%

A Case Report of Combination Treatment for Brain Meningioma: A Different Approach

Stathochristopoulou¹,

Gkinos²

2011

Cureus

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Section: Discussionmentioning

confidence: 99%

A Case Report of Combination Treatment for Brain Meningioma: A Different Approach

Stathochristopoulou¹,

Gkinos²

2011

Cureus

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“…13 Recently, gliomas and meningiomas were also found to overexpress both COX and LO enzymes compared with normal brain tissue. 6,8,37 Matsuo and coworkers 32 reported that the staining intensity in glioblastomas was relatively weak, but that meningiomas and WHO Grade II/III astrocytomas were strongly positive for COX-2. Although much attention has been focused on the role of COX-derived metabolites in cancer development and progression, accumulating evidence suggests that 5-LO-derived eicosanoids may play an equally important role.…”

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confidence: 99%

Are there attacking points in the eicosanoid cascade for chemotherapeutic options in benign meningiomas?

Pfister¹,

Ritz²,

Pfrommer³

et al. 2007

Neurosurgical FOCUS

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ENINGIOMAS are usually benign tumors that arise from the leptomeningeal cells of the arachnoid membrane surrounding the brain and spinal cord. However, recurrence after seemingly complete surgical removal occurs in eight to 15% of cases, and tumor control rates achieved with radiotherapy are only 80%. 20,35,36,53 Moreover, a surgical cure is not always achievable in meningiomas involving the skull base or vital neurovascular structures. Results achieved with chemotherapeutic treatments in the past were not convincing, and even drugs such as temozolomide-which have shown high efficacy against malignant brain tumors-have failed to inhibit the growth of refractory meningiomas in Phase II studies. 7,26,39,45 The development of novel treatment strategies based on molecular information has not yet been successfully translated into common clinical practice.Arachidonic acid is a v6 polyunsaturated fatty acid that is converted into biologically active lipid compounds called eicosanoids. Eicosanoids constitute a large family of biologically active lipid mediators produced by two enzyme classes: the cyclooxygenases (COX-1 and COX-2) and the lipoxygenases (5-LO, 12-LO, and 15-LO). Both classes catalyze the same enzymatic reaction that occurs in the synthesis of PG 2 and PGH 2 , which are successively metabolized to PGE 2 , PGD 2 , PGF 2 , thromboxane A 2 , and prostacyclin PGI 2 (Fig. 1 Object. The current treatment for recurrent or malignant meningiomas with adjuvant therapies has not been satisfactory, and there is an intense interest in evaluating new molecular markers to act as therapeutic targets. Enzymes of the arachidonic acid (AA) cascade such as cyclooxygenase (COX)-2 or 5-lipoxygenase (5-LO) are upregulated in a number of epithelial tumors, but to date there are hardly any data about the expression of these markers in meningiomas. To find possible targets for chemotherapeutic intervention, the authors evaluated the expression of AA derivatives at different molecular levels in meningiomas.Methods. One hundred and twenty-four meningioma surgical specimens and normal human cortical tissue samples were immunohistochemically and cytochemically stained for COX-2, COX-1, 5-LO, and prostaglandin E receptor 4 (PTGER4). In addition, Western blot and polymerase chain reaction (PCR) analyses were performed to detect the presence of eicosanoids in vivo and in vitro.Results. Sixty (63%) of 95 benign meningiomas, 21 (88%) of 24 atypical meningiomas, all five malignant meningiomas, and all normal human cortex samples displayed high COX-2 immunoreactivity. All cultured specimens and IOMM-Lee cells stained positive for COX-2, COX-1, 5-LO, and PTGER4. The PCR analysis demonstrated no changes in eicosanoid expression among meningiomas of different World Health Organization grades and in normal human cortical and dura mater tissue.Conclusions. Eicosanoid derivatives COX-1, COX-2, 5-LO, and PTGER4 enzymes show a high universal expression in meningiomas but are not upregulated in normal human cortex and dura tissue. This finding of the ...

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“…Os fosfolipídios de membrana são clivados por duas vias enzimáticas distintas: a da cicloxigenase, gerando as prostaglandinas (PGD) e as tromboxanas (TBX), e a da lipoxigenase, gerando os leucotrienos (LCT) e as lipoxinas. Os eicosanoides participam na modulação da motilidade e adesão celular, aumentam a permeabilidade vascular e medeiam diversos processos na inflamação (NATHOO et al, 2004). Recentes estudos mostram que o tratamento de monócitos humanos com PGE 2 afeta a expressão de receptores para quimiocinas e modula a responsividade destas células à ação quimiotática, diminuindo a expressão do receptor para MIP-1α e MIP-1β (CCR5), porém não interferindo na expressão dos receptores CCR2 ou CXCR4, importantes na quimiotaxia de monócitos em resposta as quimiocinas MCP-1 e RANTES (PANZER et al, 2004).…”

Section: Discussionunclassified

Avaliação do papel da nattectina, toxina do veneno de Thalassophryne nattereri, na respota imune inata e específica.

Saraiva¹

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RESUMOO objetivo deste trabalho foi avaliar a resposta imune inata induzida pela Nattectina, uma lectina tipo C isolada do veneno de Thalassophryne nattereri, em um modelo de inflamação murina e subseqüentemente seu papel na ativação das células dendríticas e indução da resposta imune específica. Nossos resultados mostram que a Nattectina induziu uma reação inflamatória na cavidade peritoneal de camundongos BALB/c caracterizada pelo influxo predominante de neutrófilos em 1 e 6 horas, substituído por macrófagos em 24 horas. Análises do sobrenadante da suspensão celular da cavidade peritoneal mostraram que a Nattectina induziu a liberação de mediadores inflamatórios como LTB 4 e PGE 2 em 6 horas, IL-1β em 1 e 6 h, IL-6 em 1 h, MCP-1 em 1 e 24 h e KC em 1 h. Além disso, IL-12p70 foi observada no peritônio em 1 e 24 h e IL-10 em 6 e 24 h. Células dendríticas imaturas de origem mieloíde (CD11b high CD11c high B220 low ) foram amadurecidas pela Nattectina com aumento na expressão das moléculas MHC de classe II e das coestimulatórias CD40, CD80 e CD86 e expressão de metaloproteinases de matriz MMP-2 e MMP-9, com síntese de IL-10 e IL-12p70. As células dendríticas imaturas apresentaram grande capacidade de captura e apresentação da Nattectina. Como conseqüência da ativação das células dendríticas, a Nattectina foi capaz de desencadear uma reposta imune adaptativa caracterizada pela ativação preferencial de linfócitos Th1, com síntese de IFN-γe de IL-10, favorecendo a produção de IgG2a específica. A presença de IL-10 pode ser responsável pela limitação da inflamação patológica induzida pelo veneno de T. nattereri e pela manutenção da inflamação crônica não resolvida observada no envenenamento. Finalmente, a Nattectina é um potente candidato antigênico juntamente com as células dendríticas para uso em imunoterapias.PDF Creator: PDF4U Pro DEMO Version. If you want to remove this line, please purchase the full version ABSTRACTRecently, it was identified a C-type lectin in the venom of Thalassophryne nattereri fish named Nattectin. In this study, we investigated the innate and adquired immune responses induced by Nattectin and consequently its role in the dendritic cell activation. The toxin was i.p. injected in BALB/c mice for evaluation of cellular recruitment and inflammatory mediators, antibody and cytokine production. Dendritic cells obtained after bone marrow cell culture with GM-CSF for 7d were stimulated with Nattectin for 24h. The expression of surface molecules and MMPs were analyzed by FACS and immunohistochemistry, respectively. Nattectin induced a significant cellular recruitment into peritoneal cavity, mainly neutrophils at 1 and 6hfollowed by macrophages at 24h. One hour after the Nattectin injection the levels of IL-6, IL-1β, MCP-1 and KC were detected, however in 6 or 24h only IL-1β and IL-10 or MCP-1 and IL-12p70 were determined, respectively. Nattectin induced the PGE 2 and LTB 4 synthesis at 6h. After immunization, mice produced elevated levels of anti- immune response that might be related to its activit...

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The eicosanoid cascade: possible role in gliomas and meningiomas

Cited by 88 publications

References 98 publications

A Case Report of Combination Treatment for Brain Meningioma: A Different Approach

A Case Report of Combination Treatment for Brain Meningioma: A Different Approach

Are there attacking points in the eicosanoid cascade for chemotherapeutic options in benign meningiomas?

Avaliação do papel da nattectina, toxina do veneno de Thalassophryne nattereri, na respota imune inata e específica.

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