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      Biomarkers for the Noninvasive Diagnosis of Endometriosis: State of the Art and Future Perspectives

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          Background: Early and accurate diagnosis of endometriosis is crucial for the management of this benign, yet debilitating pathology. Despite the advances of modern medicine, there is no common ground regarding the pathophysiology of this disease as it continues to affect the quality of life of millions of women of reproductive age. The lack of specific symptoms often determines a belated diagnosis. The gold standard remains invasive, surgery followed by a histopathological exam. A biomarker or a panel of biomarkers is easy to measure, usually noninvasive, and could benefit the clinician in both diagnosing and monitoring the treatment response. Several studies have advanced the idea of biomarkers for endometriosis, thereby circumventing unnecessary invasive techniques. Our paper aims at harmonizing the results of these studies in the search of promising perspectives on early diagnosis. Methods: We selected the papers from Google Academic, PubMed, and CrossRef and reviewed recent articles from the literature, aiming to evaluate the effectiveness of various putative serum and urinary biomarkers for endometriosis. Results: The majority of studies focused on a panel of biomarkers, rather than a single biomarker and were unable to identify a single biomolecule or a panel of biomarkers with sufficient specificity and sensitivity in endometriosis. Conclusion: Noninvasive biomarkers, proteomics, genomics, and miRNA microarray may aid the diagnosis, but further research on larger datasets along with a better understanding of the pathophysiologic mechanisms are needed.

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          Most cited references 127

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          The functional role of the ELR motif in CXC chemokine-mediated angiogenesis.

          In this study, we demonstrate that the CXC family of chemokines displays disparate angiogenic activity depending upon the presence or absence of the ELR motif. CXC chemokines containing the ELR motif (ELR-CXC chemokines) were found to be potent angiogenic factors, inducing both in vitro endothelial chemotaxis and in vivo corneal neovascularization. In contrast, the CXC chemokines lacking the ELR motif, platelet factor 4, interferon gamma-inducible protein 10, and monokine induced by gamma-interferon, not only failed to induce significant in vitro endothelial cell chemotaxis or in vivo corneal neovascularization but were found to be potent angiostatic factors in the presence of either ELR-CXC chemokines or the unrelated angiogenic factor, basic fibroblast growth factor. Additionally, mutant interleukin-8 proteins lacking the ELR motif demonstrated potent angiostatic effects in the presence of either ELR-CXC chemokines or basic fibroblast growth factor. In contrast, a mutant of monokine induced by gamma-interferon containing the ELR motif was found to induce in vivo angiogenic activity. These findings suggest a functional role of the ELR motif in determining the angiogenic or angiostatic potential of CXC chemokines, supporting the hypothesis that the net biological balance between angiogenic and angiostatic CXC chemokines may play an important role in regulating overall angiogenesis.
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            Endometriosis and infertility.

            Endometriosis is a debilitating condition characterized by high recurrence rates. The etiology and pathogenesis remain unclear. Typically, endometriosis causes pain and infertility, although 20-25% of patients are asymptomatic. The principal aims of therapy include relief of symptoms, resolution of existing endometriotic implants, and prevention of new foci of ectopic endometrial tissue. Current therapeutic approaches are far from being curative; they focus on managing the clinical symptoms of the disease rather than fighting the disease. Specific combinations of medical, surgical, and psychological treatments can ameliorate the quality of life of women with endometriosis. The benefits of these treatments have not been entirely demonstrated, particularly in terms of expectations that women hold for their own lives. Although theoretically advantageous, there is no evidence that a combination medical-surgical treatment significantly enhances fertility, and it may unnecessarily delay further fertility therapy. Randomized controlled trials are required to demonstrate the efficacy of different treatments.
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              Retrograde menstruation in healthy women and in patients with endometriosis.

              Blood was found in the peritoneal fluid in 90% of women with patent tubes at laparoscopy during perimenstrual time. If the fallopian tubes were occluded, then only 15% of patients had evidence of blood in the pelvis. Also, 90% of patients with endometriosis and eight of nine women on oral contraceptives had bloody fluid during the menstrual period. The present observations indicate that retrograde menstruation through the fallopian tubes into the peritoneal cavity is a very common physiologic event in all menstruating women with patent tubes.

                Author and article information

                Int J Mol Sci
                Int J Mol Sci
                International Journal of Molecular Sciences
                04 March 2020
                March 2020
                : 21
                : 5
                [1 ]Department of Medical and Surgical Specialties, Faculty of Medicine, Transilvania University of Brasov, 500019 Brasov, Romania; canastasiu@ 123456gmail.com (C.V.A.); moga.og@ 123456gmail.com (M.A.M.); urologie_scarneciu@ 123456yahoo.com (I.S.); roxana.gidinceanu@ 123456unitbv.ro (R.M.D.)
                [2 ]Department of Fundamental, Prophylactic and Clinical Sciences, Faculty of Medicine, University Transilvania Brasov, 500019 Brasov, Romania
                [3 ]Regina Maria Hospital, 500091 Brasov, Romania; dullana2005@ 123456yahoo.com
                [4 ]“Victor Papilian” Medical School, University “Lucian Blaga” of Sibiu, 550024 Sibiu, Romania; liana.chicea@ 123456gmail.com
                Author notes
                [* ]Correspondence: andrea.neculau@ 123456unitbv.ro (A.E.N.); dr.andreeabalan@ 123456gmail.com (A.B.); Tel.: +40-268-41-30-00 (A.E.N.); +40-268-412-185 (A.B.)
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).


                Molecular biology

                biomarker, angiogenesis, cytokines, urinary biomarkers, endometriosis


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