Expression of cyclooxygenase-2 and inducible nitric oxide synthase in ovarian surface epithelial carcinomas: is there any correlation with angiogenesis or clinicopathologic parameters?

Madej

Folia Histochem Cytobiol.

et al. 2013

Uterine myomas represent one of the most frequently manifested benign tumors in women. They originate from smooth muscle cells of myometrium or its blood vessels. Many studies suggest that inflammation and pro-inflammatory factors may play a role in the carcinogenesis with an involvement of the transcription factor NF-kB which activity can be controlled by various environmental factors, including many cytokines. The aim of the study was to investigate the expression of NF-B, interleukin-1b (IL-1b), tumor necrosis factor a (TNF-a), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) in myometrium and uterine myomas of women of various age. The expression of NF-kB, selected cytokines and enzymes was estimated in women of reproductive or perimenopausal age by semiquantitative immunohistochemistry. The expression of the examined proteins was higher in myomas than in control myometrium and was dependent on the size of myomas and the age of women. However, the expression of the cytoplasmic NF-kB observed in uterine myomas was independent on the size of myomas and no significant differences were observed in the number of stained nuclei between control and myoma groups. Thus, the expression of proinflammatory factors in myomas was not accompanied by the nuclear activation of NF-kB p65. The results of our study indicate that the examined factors may be involved in the pathogenesis of benign tumors and not only malignant diseases.

“…Nitric oxide, synthesized by iNOS, is a mediator involved in various cellular processes. Expression of iNOS was found also in tumors of female reproductive tract [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical localization of selected pro-inflammatory factors in uterine myomas and myometrium in women of various ages

Madej

Folia Histochem Cytobiol.

et al. 2013

“…It is difficult to explain reasons for these discrepancies, but some authors suggest that inconsistent results between studies may be due to differences in staining assessment, differences in staining techniques, source of antibody and population differences [17,51]. Although Özel et al [16] failed to detect a correlation between histological type of tumor and expression of COX-2, our results confirm suggestions of Seo et al [51] that expression of COX-2 in ovarian carcinoma is specific to histologic type of tumor and COX-2 may enhance the metastatic potential as well as tumorigenicity and may be involved in the progression of ovarian tumors [62].…”

Section: Discussionmentioning

confidence: 93%

“…Activation of COX-2 is associated with the function of inducible NOS [16]. iNOS synthesizes nitric oxide (NO), which is thought to play various roles in physiologic and pathologic conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Both promoting and deterring actions have been described, presumably depending upon the local concentration of iNOS within tumor microenvironment [15]. One of the role of iNOS in carcinogenesis is activation of cyclooxygenase 2 (COX-2) [16]. The cyclooxygenase enzyme isoforms 1 and 2 are involved in the conversion of arachidonic acid to prostaglandins and have distinct functions.…”

Section: Introductionmentioning

confidence: 99%

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

Folia Histochem Cytobiol.

Kowalczyk²,

Jakubiec-Bartnik³

et al. 2014

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.

“…These iNOS effects seem to be mediated by its angiogenic properties and intensified by Cycloxygenase 2 (COX2) upregulation [133] . However, no correlation of iNOS overexpression with prognosis has been reported for pancreatic and ovarian tumors [134,135] . F u r t h e r m o r e , i N o s a b l a t i o n d i d n o t p r e v e n t hepatocarcinogenesis induced by a choline-deficient, L-aminoacid-deficient diet in mice [136] , suggesting a relatively minor role of iNOS signaling.…”

Section: Inducible Nitric Oxide Synthase Signalingmentioning

confidence: 99%

Interaction of major genes predisposing to hepatocellular carcinoma with genes encoding signal transduction pathways influences tumor phenotype and prognosis

Feo¹,

Frau²,

Pascale³

2008

WJG

Studies on rodents and humans demonstrate an inherited predisposition to hepatocellular carcinoma (HCC). Analysis of the molecular alterations involved in the acquisition of a phenotype resistant or susceptible to hepatocarcinogenesis showed a deregulation of G1 and S phases in HCC of genetically susceptible F344 rats and a G1-S block in lesions of resistant Brown norway (BN) rats. Unrestrained extracellular signal-regulated kinase (ERK) activity linked to proteasomal degradation of dual-specificity phosphatase 1 (DUSP1), a specific ERK inhibitor, by the CKS1-SKP2 ubiquitin ligase complex occurs in more aggressive HCC of F344 rats and humans. This mechanism is less active in HCC of BN rats and human HCC with better prognosis. Upregulation of iNos cross-talk with IKK/NF-kB and RAS/ERK pathways occurs in rodent liver lesions at higher levels in the most aggressive models represented by HCC of F344 rats and c-Myc-TGF-α transgenic mice. iNOS, IKK/NF-kB, and RAS/ERK upregulation is highest in human HCC with a poorer prognosis and positively correlates with tumor proliferation, genomic instability and microvascularization, and negatively with apoptosis. Thus, cell cycle regulation and the activity of signal transduction pathways seem to be modulated by HCC modifier genes, and differences in their efficiency influence the susceptibility to hepatocarcinogenesis and probably the prognosis of human HCC.