Endometriosis appears to share certain cancer-related processes, such as cell attachment, invasion, proliferation and neovascularization, some of which can also be found in other healthy tissues. In order to better understand the altered milieu of the peritoneal cavity, while acknowledging the reported similarities between endometriosis and neoplastic processes, we applied a multiplex oncology panel to search for specific biomarker signatures in the peritoneal fluid of women with endometriosis, women with deep-infiltrating endometriosis (DIE), as well as controls. In total, 84 patients were included in our study, 53 women with endometriosis and 31 controls. Ninety-two proteins were measured in prospectively collected peritoneal fluid (PF) samples, using the “Proseek® Multiplex Oncology I Panel”. We first compared patients with endometriosis versus controls, and in a second step, DIE versus endometriosis patients without DIE. Out of the 92 analyzed proteins, few showed significant differences between the groups. In patients with endometriosis, ICOS ligand, Endothelial growth factor, E-selectin, Receptor tyrosine-protein kinase erbB-2, Interleukin-6 receptor alpha, Vascular endothelial growth factor receptor 2, Fms-related tyrosine kinase 3 ligand, C-X-C motif chemokine 10, Epididymal secretory protein E4 and Folate receptor-alpha were decreased, while Interleukin-6 and Interleukin-8 were increased compared to controls. Looking at patients with DIE, we found Chemokine ligand 19, Stem cell factor, Vascular endothelial growth factor D, Interleukin-6 receptor alpha and Melanoma inhibitory activity to be increased compared to endometriosis patients without DIE. We have shown a distinct regulation of the immune response, angiogenesis, cell proliferation, cell adhesion and inhibition of apoptosis in PF of patients with endometriosis compared to controls. The specific protein pattern in the PF of DIE patients provides new evidence that DIE represents a unique entity of extrauterine endometriosis with enhanced angiogenetic and pro-proliferative features.
Endometriotic lesions are able to infiltrate surrounding tissue. This is made possible partly by an altered local and systemic immune response that helps achieve neoangiogenesis, cell proliferation and immune escape. Deep-infiltrating endometriosis (DIE) differs from other subtypes through the invasion of its lesions over 5 mm into affected tissue. Despite the invasive nature of these lesions and the wider range of symptoms they can trigger, DIE is described as a stable disease. This elicits the need for a better understanding of the underlying pathogenesis. We used the “Proseek® Multiplex Inflammation I Panel” in order to simultaneously detect 92 inflammatory proteins in plasma and peritoneal fluid (PF) of controls and patients with endometriosis, as well as in particular patients with DIE, in order to gain a better insight into the systemically and locally involved immune response. Extracellular newly identified receptor for advanced gycation end-products binding protein (EN-RAGE), C-C motif Chemokine ligand 23 (CCL23), Eukaryotic translation initiation factor 4—binding protein 1 (4E-BP1) and human glial cell-line derived neurotrophic factor (hGDNF) were significantly increased in plasma of endometriosis patients compared to controls, whereas Hepatocyte Growth factor (HGF) and TNF-related apoptosis inducing ligand (TRAIL) were decreased. In PF of endometriosis patients, we found Interleukin 18 (IL-18) to be decreased, yet Interleukin 8 (IL-8) and Interleukin 6 (IL-6) to be increased. TNF-related activation-induced cytokine (TRANCE) and C-C motif Chemokine ligand 11 (CCL11) were significantly decreased in plasma, whereas C-C motif Chemokine ligand 23 (CCL23), Stem Cell Factor (SCF) and C-X-C motif chemokine 5 (CXCL5) were significantly increased in PF of patients with DIE compared to endometriosis patients without DIE. Although DIE lesions are characterized by increased angiogenetic and pro-inflammatory properties, our current study seems to support the theory that the systemic immune system does not play a major role in the pathogenesis of these lesions.
The topics of endometriosis and pain imply far-reaching problems for women’s health. Using a qualitative research approach, this paper addresses the subjective experience and effects of pain, the methods for dealing with these issues, and the needs of affected women in Austria. Data were collected by problem-focused interviews conducted with ten women suffering from endometriosis, which were later transcribed and subjected to qualitative content analysis. Findings are therefore described using content-related categories. Results show that negative thoughts and feelings like fear, despair, and anger are associated with endometriosis and pain. Moreover, predominantly negative impacts and changes are found in various areas of life, such as the well-being and psyche of those affected, their attitude towards life in general, partnerships, social life, leisure time and work-life balance. In dealing with endometriosis and pain, both Western biomedicine and complementary medicine treatments are used. Support from one’s inner circle of friends and exchange and interaction with others affected by the disease are seen to be invaluable. Attending physicians as well as patients themselves and their private, social, and working environment should encourage open communication about endometriosis and the related pain.
Backround Endometriosis is one of the most common gynecological illnesses causing extensive psychological, physical and social impact on patient’s life and exerts negative effects on health-related quality of Life (HRQoL). However, the effects of surgery on the postoperative HRQoL in the different endometriosis subgroups have not been fully evaluated. Methods We performed a comparative retrospective study between 2014 and 2018 at the Medical University of Vienna, including all patients with surgically confirmed endometriosis who had completed the standardized Endometriosis Health Profile-30 (EHP-30) questionnaire 1 day after surgery (the questions refer to the 4 weeks preoperatively) and 6–10 weeks postoperatively. Results Compared to preoperative values, we found significant benefits, regarding postoperative conditions, in our study group (n = 115) in all five categories, “pain” (HR 0.78, p < 0.001); “self-determination” (HR 0.92, p < 0.001); “emotional health” (HR 0.83, p < 0.001);” social environment” (HR 0.67, p < 0.001); and “self-image” (HR 0.47, p < 0.001). Patients with only peritoneal endometriosis had the lowest preoperative clinical symptoms and there were no significant changes in any of the categories. In the subgroups deep infiltrating endometriosis (DIE) and DIE + ovarian endometrioma, surgical intervention results in a significantly greater improvement in all categories of EHP 30 compared to ovarian endometrioma without DIE or peritoneal endometriosis. Conclusion Our study shows, that especially women with DIE—with or without ovarian endometrioma—demonstrate a more pronounced benefit from surgical therapy compared to patients with peritoneal endometriosis or endometrioma without DIE.
Estrogen receptor α (ERα), encoded by the ESR1 gene, is a key prognostic and predictive biomarker firmly established in routine diagnostics and as a therapeutic target of breast cancer, and it has a central function in breast cancer biology. Genetic variants at 6q25.1, containing the ESR1 gene, were found to be associated with breast cancer susceptibility. The rs2046210 and rs9383590 single nucleotide variants (SNVs) are located in the same putative enhancer region upstream of ESR1 and were separately identified as candidate causal variants responsible for these associations. Here, both SNVs were genotyped in a hospital-based case-control study of 409 female breast cancer patients and 422 female controls of a Central European (Austrian) study population. We analyzed the association of both SNVs with the risk, age at onset, clinically and molecularly relevant characteristics and prognosis of breast cancer. We also assessed the concordances between both SNVs and the associations of each SNV conditional on the other SNV. The minor alleles of both SNVs were found to be non-significantly associated with an increased breast cancer risk. Significant associations were found in specific subpopulations, particularly in patients with an age younger than 55 years. The minor homozygotes of rs2046210 and the minor hom ozygotes plus heterozygotes of rs9383590 exhibited a several-years-younger age at onset than the common homozygotes, which was more pronounced in ER-positive and luminal patients. Importantly, the observed associations of each SNV were not consistently nullified upon correction for the other SNV nor upon analyses in common homozygotes for the other SNV. We conclude that both SNVs remain independent candidate causal variants.
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