Sclerostin, a glycoprotein encoded by the SOST gene, is mainly produced by mature osteocytes and is a critical regulator of bone formation through its inhibitory effect on Wnt signaling. Osteocytes are differentiated osteoblasts that form a vast and highly complex communication network and orchestrate osteogenesis in response to both mechanical and hormonal cues. The three most commonly described pathways of SOST gene regulation are mechanotransduction, Wnt/β-catenin, and steroid signaling. Downregulation of SOST and thereby upregulation of local Wnt signaling is required for the osteogenic response to mechanical loading. This review covers recent findings concerning the identification of SOST, in vitro regulation of SOST gene expression, structural and functional properties of sclerostin, pathophysiology, biological variability, and recent assay developments for measuring circulating sclerostin. The three-dimensional structure of human sclerostin was generated with the AlphaFold Protein Structure Database applying a novel deep learning algorithm based on the amino acid sequence. The functional properties of the 3-loop conformation within the tertiary structure of sclerostin and molecular interaction with low-density lipoprotein receptor-related protein 6 (LRP6) are also reviewed. Second-generation immunoassays for intact/biointact sclerostin have recently been developed, which might overcome some of the reported methodological obstacles. Sclerostin assay standardization would be a long-term objective to overcome some of the problems with assay discrepancies. Besides the use of age- and sex-specific reference intervals for sclerostin, it is also pivotal to use assay-specific reference intervals since available immunoassays vary widely in their methodological characteristics.
We could not confirm that ROMA had diagnostic superiority over RMI in categorizing women with a pelvic mass into low-risk or high-risk groups for malignancy in a Swedish population. We have defined cut-off values for HE4 and ROMA. The lack of correlation between serum and urine HE4 obviates the introduction of urine HE4 analysis in clinical diagnostics.
Introduction: Epithelial Ovarian Cancer, tubal- and peritoneal cancer (EOC) is still the major cause of death in gynecological cancer. The outcome of primary surgery is an important prognostic factor. The primary aim of this study was to study the utility of HE4 and CA125 in monitoring the response of chemotherapy during treatment and in predicting prognosis and recurrence during follow-up. We have also evaluated the role of HE4 as a predictor of the result of surgical intervention. Methods: Seventy-eight patients scheduled for chemotherapy were monitored with serum HE4 and CA125 during treatment and follow-up. In 39 patients samples for tumor markers were also obtained prior to surgical intervention. Results: Both HE4 and CA125 decreased in response to treatment. PFS and OS were strongly dependent on HE4 levels prior to start of chemotherapy with significantly prolonged PFS and OS when HE4 levels were under upper reference limit of 82 pmol/L (P=0.018 resp. P<0.001). The levels of HE4 correlated with primary surgical outcome with significantly lower postoperative HE4 in the radically operated group (P<0.001). An increase in HE4 and/or CA125, signals a recurrence 3-6 months before diagnosis. Median levels for both HE4 and CA125 before start, during and at the end of treatment were significantly higher for platinum resistant patients (P<0.005). Conclusion: Both tumor markers are valuable in monitoring the response of chemotherapy as well as in predicting recurrence during follow-up. Postoperative HE4 holds promise as an objective marker to evaluate the result of surgery and is highly predictive for future prognosis.
Introduction: Epithelial Ovarian Cancer, tubal- and peritoneal cancer (EOC) is still the major cause of death in gynecological cancer. The outcome of primary surgery is an important prognostic factor. The primary aim of this study was to study the utility of HE4 and CA125 in monitoring the response of chemotherapy during treatment and in predicting prognosis and recurrence during follow-up. We have also evaluated the role of HE4 as a predictor of the result of surgical intervention. Methods: Seventy-eight patients scheduled for chemotherapy were monitored with serum HE4 and CA125 during treatment and follow-up. In 39 patients samples for tumor markers were also obtained prior to surgical intervention. Results: Both HE4 and CA125 decreased in response to treatment. PFS and OS were strongly dependent on HE4 levels prior to start of chemotherapy with significantly prolonged PFS and OS when HE4 levels were under upper reference limit of 82pmol/L (P=0.018 resp. P<0.001). The levels of HE4 correlated with primary surgical outcome with significantly lower postoperative HE4 in the radically operated group (P<0.001). An increase in HE4 and/or CA125, signals a recurrence 3-6months before diagnosis. Median levels for both HE4 and AC125 before start, during and at the end of treatment were significantly higher for platinum resistant patients (P<0.005). Conclusion: Both tumor markers are valuable in monitoring the response of chemotherapy as well as in predicting recurrence during follow-up. Postoperative HE4 holds promise as an objective marker to evaluate the result of surgery and is highly predictive for future prognosis.
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