OBJECTIVE: The objective of our study was to quantify and compare the immunostaining of IL-2, IL-5, IL-6, IL-8, and TNF-α in endometriomal tissue, non-neoplastic tumors, benign neoplasms, and malignant ovarian neoplasms. MATERIALS AND METHODS: The study involved 90 patients: 15 non-neoplastic ovarian lesions, 28 ovarian benign neoplasms, 28 ovarian malignant neoplasms, and 19 ovarian endometriomas were diagnosed. Immunohistochemistry was performed for cytokines IL-2, IL-5, IL-6, IL-8, and TNF-α and their concentrations were compared in these groups. Fisher's exact test was used, requiring a P-value of < 0.05 for significance. RESULTS: IL-5 and IL-8 epithelial immunostaining is stronger in endometriomas than in ovarian cancer (P-values of 0.0046 and 0.0149, resp.). The stromal immunostaining of TNF-α, IL-5, IL-6, and IL8 is stronger in endometriomas than in ovarian cancer (P-values of 0.0008, < 0.0001, 0.0003, and 0.0006, resp.). CONCLUSIONS: Stronger immunostaining of some cytokines in endometriomas compared to ovarian cancer reflects an inflammatory and immune response that could be future targets for new discoveries about the infiltrative behavior of endometriosis.
- Klíčová slova
- Cytokines, Endometriosis, cytokines, immunology, ovarian neoplasms,
- MeSH
- cytokiny * analýza metabolismus MeSH
- endometrióza * metabolismus MeSH
- imunohistochemie * metody MeSH
- lidé MeSH
- nádory vaječníků * metabolismus patologie diagnóza MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cytokiny * MeSH
BACKGROUND: Endometriosis is a common gynecological disease characterized by the presence of endometrial tissue outside the uterus causing chronic inflammation, severe pain, and infertility. However, the innate immunity of gamma-delta (γδ) T lymphocytes in endometriosis has not been characterized. Women with endometriosis present numerous endocrine and immune dysfunctions and elevated risk for endometrial, ovarian, and breast cancers. The tyrosine kinase EphA2 is often overexpressed in cancer including endometrial carcinoma. METHODS: We analyzed Vδ1 and Vδ2 γδ T cells in peripheral blood and paired peritoneal fluid samples in endometriosis patients (n = 19) and compared the counts with that of age- and sex-matched healthy donors (n = 33) using flow cytometry. Vδ1 and Vδ2 T cells isolated from healthy donors were used against KLE, RL-95, and Ishikawa endometrial tumor cells in 4 h flow cytometric cytotoxicity assays. The EphA2 blocking studies were performed using antibody, small-molecule inhibitor ALW-II-41-27, and the CRISPR/Cas9. RESULTS: We determined Vδ1 T cells substantially reduced in patients' peripheral blood (p < 0.01) and peritoneal fluid (p < 0.001). No differences were found for circulating Vδ2 T cells compared with peritoneal fluid samples. We observed inherent cytotoxic reactivity of Vδ1 and Vδ2 γδ T lymphocytes against endometrial tumor cells. Importantly, we found reduced specific lysis of EphA2-positive cell lines KLE and RL-95 by Vδ1 T cells in the EphA2 antibody blocking studies and by the EphA2 inhibitor. Furthermore, Vδ1 T-cell-mediated killing was significantly decreased in RL-95 cell EPHA2 knockout. Finally, potent cytolytic activity exerted by Vδ1 T cells was significantly reduced in EPHA2 knockouts in renal A-498 and colon HT-29 carcinoma cell lines. CONCLUSIONS: We determined variable levels of Vδ1 and Vδ2 γδ T cells in endometriosis patients. We observed inherent cytotoxic reactivity of γδ T-cell subsets against endometrial cell lines. Specifically, we found that blocking of EphA2 expression resulted in significant inhibition of endometrial tumor killing mediated by Vδ1 γδ T cells. These results suggest that EphA2 is involved in tumor cell lysis and contributes to susceptibility to Vδ1 γδ T cells cytotoxic reactivity.
- Klíčová slova
- cytotoxicity, endometriosis, gamma-delta T cells, innate immunity, peritoneal fluid, tyrosine kinase EphA2,
- MeSH
- dospělí MeSH
- endometrióza imunologie metabolismus MeSH
- intraepiteliální lymfocyty imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory endometria imunologie metabolismus MeSH
- receptor EphA2 metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- EPHA2 protein, human MeSH Prohlížeč
- receptor EphA2 MeSH
This cross-sectional clinical study was designed to explore the impact of tryptophan-kynurenine and tryptophan-serotonin (5 HT) pathways on reproductive performance during in vitro fertilization (IVF). Paired serum and follicular fluid (FF) samples were obtained from 64 consecutive IVF patients. The analysis was done by using LC-MS/MS. Ovarian hyperstimulation resulted in decreased serum tryptophan (p<0.004), 5-HT (p<0.049) and kynurenine (p<0.001). FF levels of tryptophan (R=0.245, p<0.051), kynurenine (R=0.556, p<0.001) and 5-HT (R=0.523, p<0.001) were positively related to their respective serum levels. Clinical pregnancy was associated with higher serum 5-HT (p<0.045) and FF 5-HT (p<0.020) and lower kynurenine to 5-HT ratio (p<0.024). Chemical pregnancy was also positively related to FF 5-HT (R=0.362, p<0.024). Moreover, there was a direct relationship of the number of mature oocytes to the FF 5-HT (R=0.363, p<0.020) but it was inversely related to FF tryptophan to 5-HT and FF kynurenine to 5-HT ratios (R=-0.389, p<0.016 and R=-0.337, p<0.036, respectively). Multivariate logistic regression revealed that the number of mature oocytes was significantly influenced by FF 5-HT (?=0.473, p<0.001). In IVF patients ovarian hyperstimulation results in a reduction of the availability of tryptophan to catabolic pathways to kynurenine and 5-HT. Outcome measures improved significantly when 5-HT predominated over kynurenine.
- MeSH
- dospělí MeSH
- endometrióza metabolismus patologie MeSH
- fertilizace in vitro metody MeSH
- indukce ovulace metody MeSH
- kynurenin metabolismus MeSH
- lidé MeSH
- průřezové studie MeSH
- serotonin metabolismus MeSH
- těhotenství MeSH
- tryptofan metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kynurenin MeSH
- serotonin MeSH
- tryptofan MeSH
PURPOSE: Endometriosis is defined as the presence of endometrial-like endometrial cells, glands and stroma outside the uterus, causing a strong inflammatory-like microenvironment in the affected tissue. This may provoke a breakdown in the peritoneal cavity homeostasis, with the consequent processes of immune alteration, documented by peripheral mononuclear cells recruitment and secretion of inflammatory cytokines in early phases and of angiogenic and fibrogenic cytokines in the late stages of the disease. Considering the pivotal role of interaction between immune and endometriotic cells, in this paper, we aim to shed light about the role of apoptosis pathways in modulating the fine-regulated peritoneal microenvironment during endometriosis. METHODS: Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. RESULTS: In normal conditions, endometriotic cells, refluxed through the fallopian tubes into the peritoneal cavity, should be attacked and removed by phagocytes and NK cells. During endometriosis, the breakdown of peritoneal homeostasis causes the failure of scavenging mechanisms, allowing the survival of endometriotic cells. The consequent so-called "immunoescaping" of endometriotic cells could be due, at least in part, to the reduction of apoptotic-mediated pathways previously described. CONCLUSION: Considering the large amount of evidence retrieved from in vitro as well as in vivo models, the reduced apoptosis of endometriotic cells together with the increased apoptosis of peritoneal fluid mononuclear cells may address the peritoneal homeostasis to a permissive environment for the progression of the disease.
- Klíčová slova
- Apoptosis, Endometriosis, Immunity, Peritoneal fluid,
- MeSH
- apoptóza fyziologie MeSH
- ascitická tekutina metabolismus MeSH
- endometrióza genetika metabolismus patologie MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OBJECTIVE: To find the differences of polychlorinated biphenyls (PCBs) levels in follicular fluid in different indications to treatment with IVF + ET program. DESIGN: Pilot study. SETTING: Department of Obstetrics and Gynecology, 1st Faculty of Medicine, Charles University and General Faculty Hospital, Prague, AXYS Varilab, s.r.o., Vrané nad Vltavou, Prague, Euromise Centrum, Charles University and Academy of Art, Prague. METHODS: We examinated 100 infertile women undergoing IVF + ET program in our pilot study. After ovarian pick-up, frozen follicular fluid were transported to the laboratory. We detected the levels of polychlorinated biphenyls in follicular fluid of infertile women. The levels were compared according to the different indications of treatment. The control group consist of patients with male factor of sterility. RESULTS: We confirmed the higher levels of PCB 114, 153, 156, 157, 180 and 189 in indication endometriosis compared with the others and with control group. The levels of PCBs were in ng/gram of fat. CONCLUSION: It has become apparent that higher levels of PCB 114, 153, 156, 157, 180 and 189 in endometriosis patients may be one of many factors participating in the origin of the disease.
- MeSH
- dospělí MeSH
- endometrióza komplikace metabolismus MeSH
- fertilizace in vitro MeSH
- folikulární tekutina chemie MeSH
- látky znečišťující životní prostředí analýza MeSH
- lidé MeSH
- polychlorované bifenyly analýza MeSH
- přenos embrya MeSH
- těhotenství MeSH
- ženská infertilita etiologie metabolismus terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- látky znečišťující životní prostředí MeSH
- polychlorované bifenyly MeSH
OBJECTIVE: To find out any relationship between presence of P450 aromatase and estrogen (ER) and progesterone (PR) receptors in eutopic endometrium of women with and without endometriosis and in estrogen-dependent gynecologic lesions (endometrial hyperplasia and endometriosis). DESIGN: Retrospective study. SETTING: Sikl's Institute of Pathology, Department of Gynecology and Obstetrics, University Hospital and Medical Faculty in Pilsen, Charles University. METHODS: The examined samples were obtained from patients of Department of Gynecology and Obstetrics, University Hospital and Medical Faculty in Pilsen (2001-2002) and elaborated in Sikl's Institute of Pathology, University Hospital and Medical Faculty in Pilsen. There were four experimental groups: endometrial hyperplasia, endometriosis and eutopic endometrium of women with and without endometriosis. P450 arom, ER and PR were detected by using immunohistochemical methods with specific antibodies. RESULTS: P450 aromatase was detected in a higher amount in endometriosis, hyperplasia and some samples of metaplasia. Estrogen and progesterone receptors were detected in all examined tissues. Number and spreading of ER and PR depend on the phase of the cycle. Lower number of ER was found in atrophic and metaplastic endometrium and in atypic hyperplasia. There was not found any direct relationship between presence of P450 aromatase and both types of receptors. CONCLUSION: Steroid metabolism in examined pathologically changed tissues is due to molecular aberrations regulated on the local level. It is not possible to use detection of P450 aromatase as a diagnostic test for pelvic endometriosis.
- MeSH
- aromatasa analýza MeSH
- dospělí MeSH
- endometrióza metabolismus MeSH
- endometrium metabolismus MeSH
- hyperplazie endometria metabolismus MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- receptory pro estrogeny analýza MeSH
- receptory progesteronu analýza MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- aromatasa MeSH
- receptory pro estrogeny MeSH
- receptory progesteronu MeSH
We present a unique case of composite skin tumor of the vulva consisting of dermatofibrosarcoma protuberans (DFSP) and giant cell fibroblastoma (GCF) with an intratumoral focus of endometriosis. A 31-year-old female with a 10-year-history of a recurring subcutaneous tumor in the vulvar area underwent excision of the seventh recurrence of the tumor. Microscopic examination revealed a composite fibrohistiocytic tumor consisting of DFSP and GCF. Additionally, a focus of endometriosis within the tumor tissue was found. Malignant transformation of extragonadal endometriosis has already been described; we present, however, the occurrence of a focus of endometriosis within the tissue of a hormonally independent soft tissue tumor. There is a possible link to the occurrence of cutaneous endometriosis at previous surgery sites and in the scars. The presence of endometriosis within the soft tissue tumor represents, to the best of our knowledge, a previously undescribed collision phenomenon.
- MeSH
- antigeny nádorové analýza MeSH
- dermatofibrosarkom chemie patologie chirurgie MeSH
- dospělí MeSH
- endometrióza metabolismus patologie chirurgie MeSH
- fibrom chemie patologie chirurgie MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- mnohočetné primární nádory chemie patologie chirurgie MeSH
- nádorové biomarkery analýza MeSH
- nádory měkkých tkání chemie patologie chirurgie MeSH
- nádory obrovskobuněčné chemie patologie chirurgie MeSH
- vulva patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- antigeny nádorové MeSH
- nádorové biomarkery MeSH
The authors examined the glycosaminoglycan level in the peritoneal fluid of 54 infertile women with or without endometriosis. The peritoneal fluid was collected during a routine laparoscopic examination. Glycosaminoglycans were assayed in complexes with Alcian blue. There was a higher concentration of glycosaminoglycans in peritoneal fluid during the follicular phase of women with endometriosis. The authors did not prove a statistically significant difference between women with and without endometriosis.
- MeSH
- ascitická tekutina chemie MeSH
- dospělí MeSH
- endometrióza komplikace metabolismus MeSH
- glykosaminoglykany analýza MeSH
- lidé MeSH
- mladiství MeSH
- ženská infertilita etiologie metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- glykosaminoglykany MeSH
