He presence of immune and inflammatory responses caused the tumor. The

He presence of immune and inflammatory responses caused the tumor. The results were not unexpected since different inflammatory mediators, which play diverse roles such as inducing angiogenesis, invasion, autocrine growth loops and resistance to apoptosis, are elevated in ovarian carcinoma [16]. Many acute phase proteins such as haptoglobin and transthyretin have also been recently characterized as ovarian cancer biomarkers for early detection [17]. Moreover, in a previous gene 69056-38-8 site profiling study, Bachvarov and colleagues found that down-regulated genes in chemosensitive serous EOC tumors included numerous genes involved in lipid metabolism and transport, inflammation, as well as genes known to enhance tumor progression and invasion [18]. These findings implicated acute phase proteins as candidate biomarkers of interest for further investigation. Ceruloplasmin, a plasma glycoprotein that transports copper throughout the body, was the only protein confirmed by ELISA in the current study to be differentially expressed in the ascites between the chemoresistant and chemosensitive patients in this study. Interestingly, high serum levels of ceruloplasmin have been demonstrated in various cancers such as thyroid, prostate and colon cancer [19], and microarray analysis has linked this gene to tumor invasion and metastasis in breast cancer [20]. Altered serum ceruloplasmin levels after treatment (chemotherapy or radiation) have been observed in many patients with malignancies, such as laryngeal, cervical and breast cancers. Evidently, a more significant decrease of the serum ceruloplasmin level after treatment is linked with a better response to therapy, as these alterations may influence disease outcome [21,22]. These previous observations support our finding that the concentration of ceruloplasmin was significantly lower in the ascites fluids of chemosensitive ovarian cancer patients. Roles for ceruloplasmin have been suggested in cancer-related processes, including angiogenesis and neovascularization. The protein also serves as a surrogate marker for total body copper. Therefore, the lower serum ceruloplasmin level in our study may be secondary to the deficiency in total body copper associated with tumor suppression. In a study by Cox et al., tetrathiomolybdate (TM), a copper chelator was used to reduce body stores of copper in a murine model of head and neck squamous cell carcinoma(SCC) 194423-15-9 established using the highly aggressive SCC VII/SF cell line [23]. The authors found that as the total body copper was reduced by TM, the serum ceruloplasmin level was proportionately reduced, with the baseline level decreasing from by28 . As significantly suppressed levels of both the growth of SCC and tumor vascularity were identified, their results suggested a potential efficacy of TM in the treatment of cancers via its effects on angiogenesis and neovascularization. Similar results were seen in a phase II trial with advanced kidney cancer patients in which the anti-tumor effects of TM (decreased vascularity and tumor mass) were associated with lower serum copper and ceruloplasmin levels [24]. Thus, the change in serum concentration of ceruloplasmin may indicate that it is an acute phase protein secreted in response to the oxidative stress in inflammation associated with the tumor and/or that it is secondary to the deficiency of total body copper. Our analysis 23115181 was based on primary serous EOC tumors without mixed histotypes of ovarian tumors, or recurrent and.He presence of immune and inflammatory responses caused the tumor. The results were not unexpected since different inflammatory mediators, which play diverse roles such as inducing angiogenesis, invasion, autocrine growth loops and resistance to apoptosis, are elevated in ovarian carcinoma [16]. Many acute phase proteins such as haptoglobin and transthyretin have also been recently characterized as ovarian cancer biomarkers for early detection [17]. Moreover, in a previous gene profiling study, Bachvarov and colleagues found that down-regulated genes in chemosensitive serous EOC tumors included numerous genes involved in lipid metabolism and transport, inflammation, as well as genes known to enhance tumor progression and invasion [18]. These findings implicated acute phase proteins as candidate biomarkers of interest for further investigation. Ceruloplasmin, a plasma glycoprotein that transports copper throughout the body, was the only protein confirmed by ELISA in the current study to be differentially expressed in the ascites between the chemoresistant and chemosensitive patients in this study. Interestingly, high serum levels of ceruloplasmin have been demonstrated in various cancers such as thyroid, prostate and colon cancer [19], and microarray analysis has linked this gene to tumor invasion and metastasis in breast cancer [20]. Altered serum ceruloplasmin levels after treatment (chemotherapy or radiation) have been observed in many patients with malignancies, such as laryngeal, cervical and breast cancers. Evidently, a more significant decrease of the serum ceruloplasmin level after treatment is linked with a better response to therapy, as these alterations may influence disease outcome [21,22]. These previous observations support our finding that the concentration of ceruloplasmin was significantly lower in the ascites fluids of chemosensitive ovarian cancer patients. Roles for ceruloplasmin have been suggested in cancer-related processes, including angiogenesis and neovascularization. The protein also serves as a surrogate marker for total body copper. Therefore, the lower serum ceruloplasmin level in our study may be secondary to the deficiency in total body copper associated with tumor suppression. In a study by Cox et al., tetrathiomolybdate (TM), a copper chelator was used to reduce body stores of copper in a murine model of head and neck squamous cell carcinoma(SCC) established using the highly aggressive SCC VII/SF cell line [23]. The authors found that as the total body copper was reduced by TM, the serum ceruloplasmin level was proportionately reduced, with the baseline level decreasing from by28 . As significantly suppressed levels of both the growth of SCC and tumor vascularity were identified, their results suggested a potential efficacy of TM in the treatment of cancers via its effects on angiogenesis and neovascularization. Similar results were seen in a phase II trial with advanced kidney cancer patients in which the anti-tumor effects of TM (decreased vascularity and tumor mass) were associated with lower serum copper and ceruloplasmin levels [24]. Thus, the change in serum concentration of ceruloplasmin may indicate that it is an acute phase protein secreted in response to the oxidative stress in inflammation associated with the tumor and/or that it is secondary to the deficiency of total body copper. Our analysis 23115181 was based on primary serous EOC tumors without mixed histotypes of ovarian tumors, or recurrent and.