Production of Nitric Oxide and Expression of  Inducible Nitric Oxide Synthase in Ovarian Cystic Tumors

Nomelini, Rosekeila Simões; Ribeiro, Letícia; Tavares‐Murta, Beatriz Martins; Adad, Sheila Jorge; Murta, Eddie Fernando Cândido

doi:10.1155/2008/186584

Cited by 21 publications

(20 citation statements)

References 31 publications

(39 reference statements)

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“…In the case of mucinous tumors, the highest level of iNOS immunoreactivity was observed in malignant lesions. Our findings are consistent with studies by Nomelini et al [78] and Ali-Fehmi et al [2] who showed that expression of iNOS was increased in malignant ovarian cancer samples compared to non-neoplastic or benign tumor samples. It was found that the epithelial ovarian cancer cell lines overexpressed iNOS and had high baseline NO levels what was associated with high levels www.fhc.viamedica.pl of vascular endothelial growth factor production and angiogenesis induction [79].…”

Section: Discussionsupporting

confidence: 93%

Immunohistochemical visualization of pro-inflammatory cytokines and enzymes in ovarian tumors

Plewka

Kowalczyk²,

Jakubiec-Bartnik³

et al. 2014

Folia Histochem Cytobiol.

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Epithelial ovarian cancer represents one of the most deadly gynaecological neoplasms in developed countries and is a highly heterogeneous disease. Epidemiological studies show that anti-inflammatory drugs reduce the incidence and mortality of several types of cancer, indicating the potential role of pro-inflammatory factors in carcinogenesis. The expression of pro-inflammatory factors in various cancer types, including ovarian cancer, was assessed in many studies, yielding inconsistent results, often due to the histological heterogeneity of various cancers. The aim of the study was to investigate the expression of IL-1, IL-6, TGF-b, TNF-a, COX-2, iNOS, and NF-kB in serous and mucinous ovarian cancers. Ninety cases of ovarian tumors classified into mucous and serous type (45 patients in each group) were selected. Each group was classified into subgroups according to the three stages of tumor differentiation, i.e. into (i) benign, (ii) borderline and (iii) malignant tumors. The presence of proteins of interest in paraffin sections was analysed by immunohistochemistry. The expression of most of the studied factors depended on the histological tumor subtype and the degree of malignancy. Expression of NF-kB appears to be related to the level of the neoplastic differentiation only in the group of serous tumors, while the presence of IL-6 in the mucinous tumor subtype was observed only in the case of benign lesions. Expression of IL-1, TNF-a and COX-2 increased with the stage of the disease in both serous and mucinous tumors. The highest level of TGF-b expression was observed in serous borderline tumors. The different levels of iNOS immunoreactivity between the groups of serous and mucinous tumors were observed only in borderline tumors. The results of our study may be helpful in designing therapeutic strategies depending on the type of ovarian cancer.

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Section: Discussionsupporting

confidence: 93%

Immunohistochemical visualization of pro-inflammatory cytokines and enzymes in ovarian tumors

Plewka

Kowalczyk²,

Jakubiec-Bartnik³

et al. 2014

Folia Histochem Cytobiol.

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“…19 It has also been reported to contribute to chemoresistance. 20 In vitro studies on cell lines indicated that NO signaling can stimulate survivin, which in turn gives resistance to traditional chemotherapy.…”

Section: Recently Kurman Et Al Proposed a New Classification Ofmentioning

confidence: 99%

“…Previous studies have demonstrated iNOS overexpression in well-differentiated tumors and showed a correlation between iNOS overexpression and increasing tumor stage. 19 Improved progression-free survival has been described in patients with iNOS-negative ovarian tumors. [21][22][23] In our study, we found high iNOS expression in both type I and II tumors, but with a significantly higher frequency in the latter group.…”

Section: Recently Kurman Et Al Proposed a New Classification Ofmentioning

confidence: 99%

Molecular typing of epithelial ovarian carcinomas using inflammatory markers

Ali-Fehmi

Semaan

Sethi

et al. 2010

Cancer

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BACKGROUND: Ovarian epithelial carcinomas have recently been classified as slow growing type I tumors and rapidly growing highly aggressive type II tumors. The present study sought to molecularly characterize type I and II tumors using known molecular markers. METHODS: Specimens from 213 patients with ovarian carcinoma were categorized as type I or type II, and evaluated by immunohistochemistry for the inflammatory markers glucose transporter protein-1 (Glut-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and nuclear factor kappa B. Statistical analysis was performed to investigate whether these molecular markers could distinguish between type I and type II tumors. Kaplan-Meier survival curves and COX regression analysis were used to determine the prognostic effect of these markers on survival in the 2 types of tumors. RESULTS: Overexpression of COX-1, COX-2, iNOS, and Glut-1 was significantly higher in type II tumors (P < .05). Women with type II tumors had a poorer median survival (60 months) as compared with those with type I tumors (141 months) (P ¼.0001). Multivariate analysis revealed type II tumors, late stage, and age >60 years as significant predictors of poor survival. For type II tumors, median survival of patients with tumors overexpressing COX-2 was 44 compared with 85 months for those with tumors with low COX-2 expression (P ¼.029). Looking at both type I and II tumors, the number of markers simultaneously overexpressed in each tumor was a significant predictor of poor patient survival (P ¼.005). CONCLUSIONS: The present study demonstrates that the new proposed histologic classification of ovarian epithelial carcinomas correlates with a distinct expression of inflammatory pathway proteins. High expression of these markers may explain the different biologic behavior of these 2 tumor types and provide targets for therapy. Cancer 2011;117:301-9.

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“…During early tumour development, there is up-regulation of iNOS, suggesting its inhibition as a cancer chemopreventive strategy (Park & Pezzuto 2002;Nomelini et al 2008). In the LPS-induced NO inhibition assay, five isolates showed more than 50% inhibition with IC 50 values ranging from 0.32 to 12.9 lg/mL.…”

Section: Discussionmentioning

confidence: 99%

Endophytic fungi associated withTaxus fuana(West Himalayan Yew) of Pakistan: potential bio-resources for cancer chemopreventive agents

Fatima

Kondratyuk

Park

et al. 2016

Pharmaceutical Biology

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Context: Endophytic fungi, being a prolific source of bioactive secondary metabolites, are of great interest for natural product discovery. Objective: Isolation and partial characterization of endophytic fungi inhabiting the leaves and woody parts of Taxus fuana Nan Li & R.R. Mill. (Taxaceae) and evaluation of biological activity. Materials and methods: Endophytic fungal isolates were identified by molecular analysis of internal transcribed spacer (ITS) regions of 18S rDNA. Extracts of the endophytic fungi cultured on potato dextrose agar and modified medium were evaluated using cancer chemoprevention bioassays [inhibition of TNF-ainduced NFjB, aromatase and inducible nitric oxide synthase (iNOS); induction of quinone reductase 1 (QR1)] and growth inhibition with MCF-7 cells. Results: Nine of 15 fungal isolates were identified as belonging to Epicoccum, Mucor, Penicillium, Chaetomium, Paraconiothriym, Plectania or Trichoderma. Five of the 15 extracts inhibited NFjB activity (IC 50 values ranging between 0.18 and 17 lg/mL) and five inhibited iNOS (IC 50 values ranging between 0.32 and 12.9 lg/mL). In the aromatase assay, only two isolates mediated inhibition (IC 50 values 12.2 and 10.5 lg/ mL). With QR1 induction, three extracts exhibited significant activity (concentrations to double activity values ranging between 0.20 and 5.5 lg/mL), and five extracts inhibited the growth of MCF-7 cells (IC 50 values ranging from 0.56 to 17.5 lg/mL). Six active cultures were derived from woody parts of the plant material. Conclusion: The endophytic fungi studied are capable of producing pharmacologically active natural compounds. In particular, isolates derived from the wood of Taxus fuana should be prioritized for the isolation and characterization of bioactive constituents. ARTICLE HISTORY

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Production of Nitric Oxide and Expression of Inducible Nitric Oxide Synthase in Ovarian Cystic Tumors

Cited by 21 publications

References 31 publications

Immunohistochemical visualization of pro-inflammatory cytokines and enzymes in ovarian tumors

Immunohistochemical visualization of pro-inflammatory cytokines and enzymes in ovarian tumors

Molecular typing of epithelial ovarian carcinomas using inflammatory markers

Endophytic fungi associated withTaxus fuana(West Himalayan Yew) of Pakistan: potential bio-resources for cancer chemopreventive agents

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