Abstract
The second mitochondria-derived activator of caspase (Smac/DIABLO), vascular endothelial growth factor (VEGF), and survivin are known to play a significant role in the growth and development of numerous tumors. Serum concentrations of VEGF, survivin, and Smac/DIABLO were analyzed in 92 patients with serous ovarian cancer and 94 healthy controls. Values were correlated with clinicopathological characteristics and outcomes. The median pretreatment serum VEGF and survivin levels in patients with serous ovarian carcinoma were significantly higher, while Smac/DIABLO levels were significantly lower than that in healthy controls. Receiver operating characteristic (ROC) curve analysis showed that the best cutoff point for VEGF was determined to be 345 pg/ml; with 83 % sensitivity and 65 % specificity. For survivin, the cutoff point was 110 pg/ml and for Smac/DIABLO was 75 pg/ml, with 82 and 62 % sensitivity and 43 and 87 % specificity, respectively. In the patients group, higher VEGF and survivin levels and lower Smac/DIABLO levels in sera were significantly associated with poorer overall survival (OS) and disease-free survival (DFS). Preoperative measurement of serum VEGF, survivin, and Smac/DIABLO may be of help in early detection of serous ovarian cancer and may provide important information about the patient’s outcome and prognosis.
Highlights
Ovarian cancer is the most lethal cancer among gynecologic malignancies
Not to mention other regulators of ovarian cancer apoptosis, preoccupation has recently been addressed to survivin, a multifunctional member of the inhibitors of apoptosis (IAP) gene family that both neutralizes cell death and regulates mitotic progression
Some articles showed that survivin is a novel growth factorinducible protective gene expressed by endothelial cells during angiogenesis and that survivin was initiated by vascular endothelial growth factor (VEGF) via a PI3 K/Akt pathway [17]
Summary
Ovarian cancer is the most lethal cancer among gynecologic malignancies. In 2012, it was estimated that 238,719 cases were diagnosed and 151,905 women died from this disease worldwide [1]. The extrinsic one is essential for immune selection and inflammation It commences by the activation of cell death receptors, among them tumor necrosis factor alpha (TNF-α) receptor, which is located at the cell membrane. While activating the intrinsic approach, mitochondrial permeability rises, which results in the release of second mitochondria-derived activator of caspase (Smac/DIABLO) (direct inhibitor of apoptosis-binding protein with LOw pI). This proapoptotic protein has a share in both apoptotic pathways, intrinsic and extrinsic. Mature Smac/DIABLO finds its place in mitochondria, and an apoptotic incentive is released into the cytosol There, it binds IAPs and neutralizes its inhibitory action on caspases [6]. Survivin is suppressed by Smac/DIABLO which causes the displacement of bound IAPs, which in turn is likely to bind to and subdue caspase function [8]
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