Increased Expression of 5-Lipoxygenase in High-Grade Astrocytomas

Nathoo, Narendra; Prayson, Richard A.; Bondar, Judy; Vargo, Linda; Arrigain, Susana; Mascha, Edward J.; Suh, John H.; Barnett, Gene H.; Golubić, Mladen

doi:10.1227/01.neu.0000195096.43258.94

Cited by 34 publications

(26 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with previous studies on other cancer types demonstrating an association between 5-LO expression and poor survival in patients with high-grade astrocytoma, and breast cancer (4,20). Furthermore, a larger panel of data supported that the 5-LO signaling pathway exerts profound effects on human tumorigenesis and progression, and that targeting 5-LO may lead to cancer treatment or prevention (20)(21)(22)(23)(24)(25). However, the mechanism underlying how 5-LO promotes malignant transformation and malignant tumor behavior in vivo remains unclear.…”

Section: -Lo Expression Regulates Escc Cell Viability and Migration supporting

confidence: 90%

“…Additionally, the limited in vitro data indicated that 5-LO expression induced tumor cell proliferation, whereas the knockdown of 5-LO expression suppressed tumor cell proliferation and migration. The current data indicated that 5-LO expression may serve as was observed in glioblastoma cell lines and astrocytoma tissue specimens (21). The current study demonstrated that 5-LO expression was upregulated in ESCC tissues compared with pericarcinoma tissue, and that high 5-LO expression was associated with ESCC metastasis to the regional lymph nodes and advanced pTNM stage.…”

Section: -Lo Expression Regulates Escc Cell Viability and Migration supporting

confidence: 54%

See 1 more Smart Citation

Association between 5‑lipoxygenase expression, and malignant behaviors and poor prognosis in esophageal squamous cell carcinoma

et al. 2018

View full text Add to dashboard Cite

Abstract. 5-lipoxygenase (5-LO) catalyzes the first step of arachidonic acid metabolism to inflammatory mediator leukotrienes. The present study assessed 5-LO expression in esophageal squamous cell carcinoma (ESCC) tissue specimens for associations with clinicopathological and survival data from patients, then explored 5-LO activity in ESCC cells in vitro. 5-LO expression was detected in tissue microarrays containing 297 ESCC samples using immunohistochemistry. Kaplan-Meier curves were used to analyze the survival significance of 5-LO expression and relative risk was evaluated using the multivariate Cox proportional hazards model. Cultured tumor cells were subjected to gene transfection, western blotting, and cell migration and proliferation assays. 5-LO protein was primarily expressed in normal cell cytoplasm and/or membrane, and never in the whole cytoplasm, whereas 5-LO was expressed diffusely in ESCC tissues with nearly homogeneous whole-cytoplasm staining. 5-LO expression was significantly associated with tumor regional lymph node metastasis (P=0.013) and pTNM stage (P=0.004). 5-LO expression was associated with poor overall survival (P=0.029). Multivariate analysis demonstrated that 5-LO overexpression was an independent prognostic factor for ESCC patients (P=0.041). Furthermore, the inhibition of 5-LO expression reduced ESCC cell viability and migration in vitro. These data provide further evidence that the upregulation of 5-LO expression is associated with advanced stages of disease and poor ESCC prognosis, and that 5-LO expression may independently predict overall survival in patients with ESCC. The inhibition of 5-LO expression reduced ESCC malignant behavior in vitro.

show abstract

Section: -Lo Expression Regulates Escc Cell Viability and Migration supporting

confidence: 90%

Section: -Lo Expression Regulates Escc Cell Viability and Migration supporting

confidence: 54%

Association between 5‑lipoxygenase expression, and malignant behaviors and poor prognosis in esophageal squamous cell carcinoma

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Because 5-LO inhibitors are cytotoxic to cancer cell lines derived from several types of malignant tumors, further research into the potential use of 5-LO inhibitors for cancer prevention and treatment is warranted. 1,15,16,38 Staining for COX-1 had a significantly lower expression than for the other observed eicosanoids, in agreement with the results of the reverse-transcriptase PCR analysis. These observations correlate with the findings of Matsuo et al, 32 who reported a weak expression of COX-1 compared to COX-2 in normal human brain tissues, meningiomas, and other brain tumors.…”

Section: Neurosurg Focus / Volume 23 / October 2007supporting

confidence: 84%

“…Nathoo and associates 38 have demonstrated 5-LO expression solely in the cytoplasm of neurons in the healthy adult brain, whereas, in most astrocytoma surgical specimens, strong staining for 5-LO was seen in the nuclei of tumor cells. The authors argued that the activation of tumor cells may lead to the translocation of 5-LO to the nuclear membrane rather than the plasma membrane; furthermore, the nuclear import…”

Section: Discussionmentioning

confidence: 98%

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

Pfister¹,

Ritz²,

Pfrommer³

et al. 2007

Neurosurgical FOCUS

View full text Add to dashboard Cite

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 ...

show abstract

“…The COX1 isoform (chromosome 9) is constitutively expressed while the COX2 isoform (chromosome 1) is induced particularly in inflammatory processes. COX2 expression is up regulated in gliomas and is correlated with increasing histological grade and poor patient prognosis [27][28][29][30][31]. Clinical trials are currently under way to study the COX2 inhibitor effects on tumor progression in patients with glioblastoma multiforme GBM [32,33].…”

Section: Introductionmentioning

confidence: 99%

Análise da expressão de proteínas envolvidas no controle do ciclo celular, apoptose, angiogênese, invasão e migração de células C6 in vitro e in vivo, após o tratamento com o ácido g-linolênico (GLA) e com um novo complexo dirutênico contendo Ibuprofeno (Ru-Ibp).

Benadiba¹

View full text Add to dashboard Cite

Tese apresentada ao Instituto de Ciências Biomédicas da Universidade de São Paulo, para obtenção do Título de Doutor em Ciências (Biologia Celular e Tecidual). São Paulo 2008MARCEL BENADIBA ANÁLISE DA EXPRESSÃO DE PROTEÍNAS ENVOLVIDAS NO CONTROLE DO CICLO CELULAR, APOPTOSE, ANGIOGÊNESE, INVASÃO E MIGRAÇÃO DE CÉLULAS C6 IN VITRO E IN VIVO, APÓS O TRATAMENTO COM O ÁCIDO γ-LINOLÊNICO (GLA) E COM UM NOVO COMPLEXO DIRUTÊNICO CONTENDO IBUPROFENO (Ru-Ibp)Tese apresentada ao Instituto de Ciências Biomédicas da Universidade de São Paulo, para obtenção do Título de Doutor em Ciências. Área de concentração: Biologia Celular e TecidualOrientador: Profa. Dra. Alison Colquhoun São Paulo 2008Aos irmãos da mesinha de caridade pelos conselhos e direcionamentos espirituais.Aos meus queridos pais Moses e Rosa pelo eterno amor, carinho e incentivo que nunca me faltaram.Aos meus queridos irmãos Felix e Vidal pelo carinho, apoio e compreensão.À minha querida esposa Alisan pela companhia, respeito, paciência e sincero amor.Aos meus futuros filhos. AGRADECIMENTOSÀ Karina Lawrence Ramos em especial os meus sinceros agradecimentos, pois sem ela eu não estaria aqui. Além do fato de me apresentar à Profa. Alison, sua paciência e atenção nos momentos mais difíceis do início das pesquisas ainda na iniciação científica foram cruciais para meu progresso no Doutorado.À minha orientadora e segunda mãe Alison Colquhoun, que com sua humildade e paciência admiráveis me ensinou a ser o cientista apaixonado que hoje sou. Que apesar das dificuldades no mundo da pesquisa, não desanima nunca! Muito Obrigado Chefe! Ao professor Dr. Jarbas Arruda Bauer pelo espaço em seu laboratório, respeito, risadas, conversas construtivas e pelas maravilhosas aulas que presenciei, das quais, com certeza, lembrarei sempre que estiver dando aula.Às professoras Dra. Marília Cerqueira Leite Seelaender e Dra. Marinilce Fagundes dos Santos pelo importante acolhimento e agradabilíssima convivência.À Profa. Dra. Denise de Oliveira Silva e à Dra. Geise Ribeiro do Instituto de Química da USP pela colaboração.Ao Prof. Dr. Rui Curi e à Dra. Thais Martins de Lima do Departamento de Fisiologia e Biofísica do ICB-USP pela colaboração.Aos meus colegas de laboratório: Fábio Luiz Tavares (que com muita paciência me ajudou nos meus primeiros PCRs), Fio (por todos os momentos que passamos no laboratório, incluindo nos finais de semana), Juliano Andreoli Myialke (pelos favores, paciência, palavras e pelas gargalhadas contagiantes e inconfundíveis), Camila Sommerauer Franchim (pelas incontáveis ajudas, gargalhadas, conversas e muito mais...), Luiz Carnevali Junior (pela amizade e companheirismo em diversos momentos), Emília Ribeiro (pela paciência e compreensão) e às recentes estagiárias Débora e Renata, que apesar do pouco tempo que estão no laboratório já considero grandes amigas.À Celiana, Bete e Heloísa pelo indispensável apoio administrativo.Ao pessoal da Biblioteca do Instituto de Ciências Biomédicas pela atenção e exemplo profissional.Ao pessoal do Xerox, pela eficiência, paciência e...

show abstract

Increased Expression of 5-Lipoxygenase in High-Grade Astrocytomas

Abstract: These data indicate that 5-LO is overexpressed in high-grade astrocytomas and supports the idea that eicosanoids may play a role in tumorigenesis of these brain tumors.

Cited by 34 publications

References 32 publications

Association between 5‑lipoxygenase expression, and malignant behaviors and poor prognosis in esophageal squamous cell carcinoma

Association between 5‑lipoxygenase expression, and malignant behaviors and poor prognosis in esophageal squamous cell carcinoma

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

Análise da expressão de proteínas envolvidas no controle do ciclo celular, apoptose, angiogênese, invasão e migração de células C6 in vitro e in vivo, após o tratamento com o ácido g-linolênico (GLA) e com um novo complexo dirutênico contendo Ibuprofeno (Ru-Ibp).

Contact Info

Product

Resources

About