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(A) COX-2-negative immunostaining and (B) COX-2-positive immunostaining in ovarian carcinoma (Bar 50 m). (C) Western blot analysis of COX-2 expression in two ovarian tumor samples. -actin is shown as a control for protein loading.
Source publication
Cyclooxygenase-2 (COX-2) seems to be involved in critical steps of cancer onset and progression. Abnormalities of epidermal growth factor receptor (EGFR) and Her-2/neu have been actively investigated in ovarian cancer and associated with unfavorable clinical outcome. The involvement of COX-2 in ErbB family pathways has been proposed. We investigate...
Contexts in source publication
Context 1
... immunostaining was observed both in cytoplasm and in nuclei of tumor cells in 36 (47.4%) primary advanced ovarian tumors while barely detectable COX-2 staining was observed in the stromal compartment (Fig. 1B). Western blot analysis showed an immunoreactive band with a molecular weight of approximately 70 kDa (Fig. 1C). Membrane staining for EGFR and Her-2/neu proteins was found in 43 (56.6%) and 16 (21.0%) tumors, respectively (Table 1). Table 1 shows the distribution of COX-2, EGFR, and Her-2/neu status according to clinico-pathological ...
Context 2
... immunostaining was observed both in cytoplasm and in nuclei of tumor cells in 36 (47.4%) primary advanced ovarian tumors while barely detectable COX-2 staining was observed in the stromal compartment (Fig. 1B). Western blot analysis showed an immunoreactive band with a molecular weight of approximately 70 kDa (Fig. 1C). Membrane staining for EGFR and Her-2/neu proteins was found in 43 (56.6%) and 16 (21.0%) tumors, respectively (Table 1). Table 1 shows the distribution of COX-2, EGFR, and Her-2/neu status according to clinico-pathological ...
Citations
... Cyclooxygenase 2 (COX-2) is a main synthase of the AA pathway. COX-2, a key regulator of the inflammatory response, is significantly overexpressed in many types of cancer, including breast, ovarian, colorectal, and lung cancers [9][10][11][12][13]. COX-2 converts AA into prostaglandin H2 (PGH 2 ). ...
Long noncoding RNAs (lncRNAs) are known to regulate gene expression; however, in many cases, the mechanism of this regulation is unknown. One novel lncRNA relevant to inflammation and arachidonic acid (AA) metabolism is the p50-associated COX-2 extragenic RNA (PACER). We focused our research on the regulation of PACER in lung cancer. While the function of PACER is not entirely understood, PACER is known to play a role in inflammation-associated conditions. Our data suggest that PACER is critically involved in COX-2 transcription and dysregulation in lung cancer cells.
Our analysis of The Cancer Genome Atlas (TCGA) expression data revealed that PACER expression is significantly higher in lung adenocarcinomas than normal lung tissues. Additionally, we discovered that elevated PACER expression strongly correlates with COX-2 expression in lung adenocarcinoma patients. Specific siRNA-mediated knockdown of PACER decreases COX-2 expression indicating a direct relationship. Additionally, we show that PACER expression is induced upon treatment with proinflammatory cytokines to mimic inflammation. Treatment with prostaglandin E2 (PGE2) induces both PACER and COX-2 expression, suggesting a PGE2-mediated feedback loop. Inhibition of COX-2 with celecoxib decreased PACER expression, confirming this self-regulatory process. Significant overlap between the COX-2 promotor and the PACER promotor led us to investigate their transcriptional regulatory mechanisms. Treatment with pharmacologic inhibitors of NF-κB or AP-1 showed a modest effect on both PACER and COX-2 expression but did not eliminate expression. These data suggest that the regulation of expression of both PACER and COX-2 is complex and intricately linked.
... 111,112 Different components stimulating inflammatory pathway such as cytokines, STAT3, NF-κB, iNOS, free radicals and VEGF have been observed to participate in the development of EOC. 113 Cytokines induce ovarian tumor development in vivo. 114 Circulating levels of IL-6, IL-7 and IL-10 have been detected to be enhanced in patients with ovarian cancer. ...
... Usually, the longer the existence of the inflammation, the greater the risk of cancer. In general, chronic exposure to inflammatory mediators, which include free radicals, cytokines, COX-1, COX-2, and 5-LOX, leads to a sharp rise in mutagenesis, cell proliferation, and oncogene activation eventually leading to the proliferation of cells which lost control over normal growth [26][27][28][29][30][31]. So, as metabolites and CCE showed good anti-inflammatory properties, we further investigated their anticancer abilities using the SRB assay. ...
Background
Traditionally, the whole plant of Cardiospermum canescens has wide applications in the management of oxidative stress and inflammation in Africa and Asia. The present study investigated the antioxidant, anti-inflammatory, xanthine oxidase (XO) inhibitory, and anticancer activities of metabolites present in the crude methanolic extract of whole plant C . canescens ( CCE ).
Results
Chemical examination of CCE revealed the presence of six known compounds ( 1 – 6 ). From the results of in vitro studies, it can confirm that CCE exhibited notably inhibition of DPPH and superoxide free radicals, along with COX-1, COX-2, 5-LOX, and XO enzymes. Compounds 2 and 3 showed significant inhibition of DPPH and superoxide free radicals. Also, compound 2 exhibited good inhibition of COX-1 and COX-2 enzyme with IC 50 of 87.0 and 88.0 μg/mL. Furthermore, CCE exhibited significant inhibition of 5-LOX and XO enzymes with IC 50 of 42.5 and 56.0 μg/mL, respectively, while standard with IC 50 of 42.5 and 56.0 μg/mL, respectively. Among the test series of cancer cell lines, compounds 2 , 3 , and CCE showed a significant percentage of cell growth lysis of DLD-1 with IC 50 values of 52.5, 72.5, and 32.5 μg/mL, respectively. Besides, all the metabolites and CCE showed a very weak degree of specificity against NHME, indicates less toxicity to normal cells.
Conclusion
To conclude, the results of the present study indicated that the methanolic extract from the whole plant of C . canescens displayed antioxidant activity by inhibiting DPPH and superoxide free radicals; anti-inflammatory effects by regulating enzymes COX-1, COX-2, 5-LOX, and XO; and anticancer activity by inhibiting the growth of MCF-7, DLD-1, HeLa, and A549. These activities can link to natural active compounds 2 and 3 . This study supports the traditional uses of the root of C . canescens . These data findings suggest that C . canescens can be a promising natural source of biological medicines for oxidative stress, inflammation, gout, and cancer.
... Ovarian cancer [95][96][97] No correlation between COX-2 expression and EGFR, and HER-2/neu status [96]. ...
... Ovarian cancer [95][96][97] No correlation between COX-2 expression and EGFR, and HER-2/neu status [96]. ...
Cancer is one of the highest prevalent diseases in humans. The chances of surviving cancer and its prognosis are very dependent on the affected tissue, body location, and stage at which the disease is diagnosed. Researchers and pharmaceutical companies worldwide are pursuing many attempts to look for compounds to treat this malignancy. Most of the current strategies to fight cancer implicate the use of compounds acting on DNA damage checkpoints, non-receptor tyrosine kinases activities, regulators of the hedgehog signaling pathways, and metabolic adaptations placed in cancer. In the last decade, the finding of a lipid peroxidation increase linked to 15-lipoxygenases isoform 1 (15-LOX-1) activity stimulation has been found in specific successful treatments against cancer. This discovery contrasts with the production of other lipid oxidation signatures generated by stimulation of other lipoxygenases such as 5-LOX and 12-LOX, and cyclooxygenase (COX-2) activities, which have been suggested as cancer biomarkers and which inhibitors present anti-tumoral and antiproliferative activities. These findings support the previously proposed role of lipid hydroperoxides and their metabolites as cancer cell mediators. Depletion or promotion of lipid peroxidation is generally related to a specific production source associated with a cancer stage or tissue in which cancer originates. This review highlights the potential therapeutical use of chemical derivatives to stimulate or block specific cellular routes to generate lipid hydroperoxides to treat this disease.
... 111,112 Different components stimulating inflammatory pathway such as cytokines, STAT3, NF-κB, iNOS, free radicals and VEGF have been observed to participate in the development of EOC. 113 Cytokines induce ovarian tumor development in vivo. 114 Circulating levels of IL-6, IL-7 and IL-10 have been detected to be enhanced in patients with ovarian cancer. ...
Inflammatory cytokines are highly inducible small glycoproteins or regulatory proteins of low molecular weight secreted by different cell types. They regulate intercellular communication and mediate a number of physiological functions in the human
immune system. Numerous prospective studies report that inflammatory cytokines strongly predict coronary artery disease,
myocardial infarction, heart failure and other adverse cardiac events. Inflammatory cascade is believed to be a causative factor
in the development of atherosclerotic process. Several aspects of atherogenesis are accelerated by cytokines. This article
provides an overall overview of current understanding of cytokines in various cardiovascular events. Besides, inflammatory
cytokines trigger cellular events that can induce malignancy and carcinogenesis. Elevated expression of several cytokines
such as interleukin-1, interleukin-6, interleukin-10, tumor necrosis factor-α, macrophage migration inhibitory factor and
transforming growth factor-β are involved in tumor initiation and progression. Thus, they exert a pivotal role in cancer
pathogenesis. This review highlights the role of several cytokines in various events of tumorigenesis. Actually, this article
summarizes the contributions of cytokines in the pathogenesis of cardiovascular disease and cancer.
... 111,112 Different components stimulating inflammatory pathway such as cytokines, STAT3, NF-κB, iNOS, free radicals and VEGF have been observed to participate in the development of EOC. 113 Cytokines induce ovarian tumor development in vivo. 114 Circulating levels of IL-6, IL-7 and IL-10 have been detected to be enhanced in patients with ovarian cancer. ...
... The risk of developing ovarian cancer is 2.5 times higher among patients with PCOS compared to the healthy population [29]. Ovarian cancer is categorized among immunogenic tumors [30,31]. Despite the availability of different modern therapeutic protocols, the majority of the patients with ovarian cancer experience recurrence following the initial treatment. ...
... Similarly, components of pro-inflammatory pathway signaling including ILs/cytokines, free radicals, NF-κB, STAT-3, iNOS, COX-2/PGs and VEGF have been shown to promote EOC genesis, growth, and progression [56,57]. COX-2 was found to be up regulated in non-mucinous ovarian cancers, and its expression was correlated with poorer prognosis [58]. Continual exposure of the ovarian surface epithelium (OSE) adjacent to the site of ovulation to this inflammatory and oxidative milieu results in an increased risk of neoplastic transformation. ...
Inflammation is a multifaceted process that involves a host of resident and recruited immune cell types working together to promote the elimination of insult or injury and initiate tissue repair. In the female reproductive tract (FMRT), inflammation-mediated alteration in epithelial, vascular and immune functions are important components of complex physiological processes as well as many local and systemic pathologies. It is well established that intra-coital and post-coital function of seminal fluid (SF) goes beyond nutritive support for the
spermatozoa cells. There is emerging evidence to support a role for SF, in particular, the inflammatory bioactive lipids, and prostaglandins present in vast quantities in SF in localized immune modulation and regulation of pathways that can exacerbate inflammation in the FMRT. In sexually active women SF-mediated inflammation have been implicated in physiologic conditions such as ovulation, implantation and parturition while also enhancing tumorigenesis, and susceptibility to infection such as HIV. This review highlight the molecular mechanism by which SF regulates inflammatory pathways in the FMRT and how alterations in these pathways contribute to physiology and pathology of the female reproductive function. In addition, based on findings from TaqMan® 96-Well Plate Arrays, on neoplastic cervical epithelial cells treated with SF, we discuss some of our new findings on the role of SF as a potent driver of inflammatory and tumorigenic pathways in the cervix. SF was found to regulate components of eicosanoid signaling, kallikrien-kinin-bradykinin receptor signaling, toll-like
receptor-2 (TLR2) signaling and chemokine/cytokine signaling in neoplastic cervical epithelial cells. Although the detailed molecular mechanisms require additional studies, the available data suggests that SF can regulate a wide range of inflammatory pathways to augment pathologic conditions within the FMRT.
... The risk of developing ovarian cancer is 2.5 times higher among patients with PCOS compared to the healthy population [29]. Ovarian cancer is categorized among immunogenic tumors [30,31]. Despite the availability of different modern therapeutic protocols, the majority of the patients with ovarian cancer experience recurrence following the initial treatment. ...
Introduction: Polycystic ovarian syndrome (PCOS) is a proinflammatory state that underpins the development of metabolic aberration and ovarian dysfunction in the disorder. Chronic inflammation and increased levels of androgens in these patients and their impact on the immune system, may be able to disrupt antitumor activity and thus increase the risk of developing malignancies including ovarian cancer. Materials and Methods: Peripheral blood mononuclear cells of 50 patients with PCOS and healthy controls were purified by Ficoll density gradient centrifugation. We then measured cell proliferation and concentrations of cytokines TNF-α at different time intervals (48 and 72 hours) after co-culture of ovarian (SKOV3, A2780) and breast (MCF-7, MDA-468) tumor cell lines with PBMC in indirect contact of transwell system. Results: Proliferative response of executive cells during stimulation with tumor cell lines after 48 hours was not statistically significant between patients and healthy controls. Between the 2 groups, proliferation rates at the end of 72h were significantly higher than after 48h (P<0.01). The production of TNF-α in co-culture of A2780 cell lines significantly increased in the patient group in time compared to the controls (P<0.05). Conclusion: Our findings confirmed that, compared to healthy individuals low levels of chronic inflammation in patients with PCOS exhibit increased proliferative response of immune cells and TNF-α levels. An increased risk of cancers in patients with PCOS however requires investigation of other aspects of anti-tumor responses in vitro, with larger sample sizes.
... Nineteen trials evaluated the relationships between the expression of HER family members and OS with multivariate analyses (10-12, 20, 21, 23, 31-43), 9 studies reported adjusted PFS (11,23,31,32,38,(42)(43)(44)48), 14 studies assessed chemotherapy responses (20, 24-26, 29, 32, 33, 38, 45-47, 49-51), 4 studies provided lymph node metastasis data (22,25,30,52), and 9 studies reported ascites (24,25,27,28,45,46,(51)(52)(53). ...
... III), and the heterogeneity between studies was low (I 2 = 14.1%, p = 0.324). Regarding EGFR (25,27,45,46), Her-3 (52), and Her-4 (28, 52), we found no associations between the statuses of these receptors and the risk of ascites (pooled RR EGFR = 1.07, 95% CI 0.95-1.21; RR Her-3 = 2.30, 95% CI 0.94-5.65; ...
Human epidermal receptor (HER) family receptors are commonly overexpressed in various human tumors, and their overexpression is thought to play a critical role in tumor progression. The aim of this meta-analysis was to evaluate the prognostic significance of HER family members in epithelial ovarian cancer (EOC).
Relevant studies published between January 1, 1980, and April 24, 2013, that evaluated the associations of HER family members with overall survival (OS), progression-free survival (PFS), response to platinum-based chemotherapy, lymph node metastasis, or ascites in EOC were identified via searches of PubMed and EMBASE.
We identified 37 eligible articles that met the inclusion criteria. The results of the meta-analysis revealed that significantly poorer OS of patients with EOC was predicted by high Her-2 expression levels (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.31-2.19). Furthermore, high Her-2 expression was significantly associated with poor PFS (HR 1.88, 95% CI 1.46-2.41) and an increased risk of ascites (risk ratio 1.21, 95% CI 1.02-1.42).
High levels of expression of Her-2 are significantly related to poor survival and an increased risk of ascites in patients with EOC. Future prospective cohorts with larger samples are needed to verify the prognostic value of Her-2 expression in EOC.
