Ocena stężenia IL-10 i TGF-beta oraz mieloidalnych i limfoidalnych komórek dendrytycznych u pacjentek chorych na raka jajnika

Abstract Aim: The aim of the study was to evaluate IL-10 and TGF-beta levels in the peritoneal fluid (PF) and plasma of patients with ovarian cancer (n=104), serous cyst (n=32) or normal controls (n=20). IL-10 and TGF-beta levels were correlated to myeloid (M) and lymphoid (L) dendritic cells (DC). Material and Methods: IL-10 and TGF-beta concentrations were evaluated using the enzyme linked immunosorbent assay (ELISA). The percentage of DC in mononuclear cells was quantified by using flow cytometry. Results: The PF and plasma IL-10 concentrations were significantly higher in epithelial ovarian cancer (EOC) patients when compared to the women with serous cyst (the reference group). Plasma levels of IL-10 were elevated in EOC patients in comparison with the reference and control groups. There were significant differences in the PF and plasma IL-10 levels with respect to tumor stage, grade and histology. Significant negative correlations were found between the plasma IL-10 levels, MDC and LDC in the peripheral blood. TGF-beta levels were detected in PF of all EOC patients and were significantly lower when compared with plasma. Plasma levels of TGF-beta were elevated in EOC patients compared with the control group. No significant differences in the PF and plasma TGF-beta levels were noted between EOC patients and the reference group. The authors did not find a correlation between the plasma and PF TGF-beta levels and the percentage of MDC and LDC. Conclusions: IL-10 production in EOC patients depends on the tumor stage, grade and histological type of the tumor cells. IL-10 may have impact on the percentage of dendritic cells in EOC patients.Streszczenie Cel: Ocena stężenia interleukiny (IL)-10 i transformującego czynnika wzrostu beta (TGF-β) w osoczu i płynie otrzewnowym (PO) chorych na raka jajnika oraz ustalenie czy istnieje zależność pomiędzy ich stężeniem a odsetkiem mieloidalnych (M) i limfoidalnych (L) komórek dendrytycznych (DC). Materiał i metody: Stężenie IL-10 i TGF-β oceniono u chorych na raka jajnika (n=104), z torbielą surowiczą jajnika (grupa referencyjna , n=32) oraz w grupie kontrolnej (n=20) metodą immunoenzymatyczną ELISA. Odsetek MDC i LDC oceniano metodą cytometrii przepływowej. Wyniki: Stężenie IL-10 w PO chorych na raka jajnika było istotnie wyższe niż w grupie referencyjnej. Ponadto stężenie IL-10 w osoczu chorych na raka jajnika było wyższe niż w grupie referencyjnej i kontrolnej. Odnotowano istotne statystycznie różnice stężeń IL-10 w osoczu i PO chorych na raka jajnika w zależności od stopnia zaawansowania nowotworu wg FIGO, stopnia zróżnicowania histologicznego oraz typu histologicznego nowotworu. Stężenie IL-10 w osoczu chorych na raka jajnika istotnie ujemnie korelowało z odsetkiem MDC oraz LDC krwi obwodowej. Stężenie TGF-β w osoczu i PO chorych na raka jajnika nie różniło się istotnie od odnotowanego w grupie referencyjnej. Stężenie TGF-β w osoczu chorych na raka jajnika jak i grupie referencyjnej było wyższe niż w grupie kontrolnej. Nie wykazano istotnej korelacji pomiędzy stężeniem TGF-β w osoczu i PO a odsetkiem MDC i LDC u chorych na raka jajnika. Wnioski: Zaobserwowana w badaniach istotna ujemna korelacja pomiędzy stężeniem IL-10 w osoczu chorych na raka jajnika a MDC oraz LDC krwi obwodowej może sugerować wpływ IL-10 na odsetek Komorek dendrytycznych

Nonstandard treatment of endometrial cancer in patient in a procreative age wishing to keep fertility-case report

Introduction: Endometrial cancer is the most common malignant neoplasm of female reproductive organs that develops from the lining of the womb. The peak incidence falls on the 5th decade of life. Diagnosis of endometrial cancer in young women under 30 years of age is very rare. Detection of cancer at such a young age is an extremely difficult case, because the treatment must consider the reproductive plans of patients so that they can maintain important fertility for them. Case report: In 2018, a 25-year-old patient was admitted to the Clinic of Oncological Gynaecology and Gynaecology to treat endometrial cancer in FIGO IB. The operation involving the removal of the uterus with fallopian tubes was rejected due to the young age of the patient and her reproductive plans. Prior to hospitalization, the patient was offered the possibility of hormonal treatment that saves fertility. After presenting a 6-month regimen of hormone therapy with medroxyprogesterone acetate (MPA), using a levonorgestrel-releasing intrauterine device, the patient refused consent for its implementation for personal reasons. The patient was proposed to perform electroresection of the endometrial polyp, fractionated erosion of the cavity and cervical canal during hysteroscopy. However, it was marked that it’s possible to not completely remove the cancer during the procedure. The patient agreed to this therapeutic procedure. The procedure was performed without any complications. Quarterly cytological control tests and bi-annual endometrial biopsies are correct and for over a year, there is no recurrence of endometrial cancer and the patient is feeling well. Conculsion: Electroresection of endometrial changes during hysteroscopy in endometrial cancer can be a promising therapeutic option in the early stages of endometrial cancer (FIGO I) in women who want to maintain fertility. However, this requires further validation. It should be remembered that the occurrence of endometrial cancer at such a young age may be a component of genetic syndromes such as Lynch syndrome. Patient awareness of possible relapses and emphasis on quick response in case of disturbing symptoms is extremely important in order to detect a recurrence as quickly as its possible, and thus extend the patient's life, maintaining its good quality

Limfoangiogeneza w guzach nowotworowych

Summary The lymphatic vasculature is essential for the maintenance of fluid homeostasis, immune surveillance and fat absorption. A role of the lymphatic vessels in the development of human diseases, such as inflammation and tumorigenesis, has proven to be both essential and active. The molecular mechanisms of lymphangiogenesis are not clear, but vascular endothelial growth factors (VEGF-C and VEGF-D) within tumours may simulate endothelial cells within tumour tissues to grow and generate new lymphatics. Recently, several markers specific for lymphatic endothelium and models for lymphatic vascular research have been characterized and many critical regulators of lymphatic vessel growth have been identified. This review focuses on the mechanisms of lymphangiogenesis in general, and especially on the role of lymphatic vessels in ovarian cancerStreszczenie Układ limfatyczny jest niezbędny do utrzymania homeostazy płynu tkankowego oraz odgrywa ważną rolę w regulacji funkcji układu immunologicznego. Naczynia limfatyczne maja istotny i aktywny udział w patofizjologii stanów zapalnych oraz rozwoju nowotworów. Mechanizmy molekularne regulujące limfangiogenezę pozostają jak dotąd słabo poznane chociaż wiadomo, że śródbłonkowe czynniki wzrostu naczyń (VEGF-C i VEGF-D) stymulują wzrost endoteliocytów i powstawanie nowych naczyń chłonnych. W ostatnich latach zidentyfikowano szereg markerów specyficznych dla śródbłonka naczyń limfatycznych oraz opisano nowe modele badawcze wzrostu naczyń chłonnych. Artykuł przedstawia poglądy dotyczące regulacji limfangiogenezy w guzach nowotworowych

Peritoneal fluid iron levels in women with endometriosis

Summary Aim: Endometriosis is characterized by a cyclic hemorrhage within the peritoneal cavity. Accumulating data suggests that iron homeostasis in the peritoneal cavity may be disrupted by endometriosis. The aim of our study was to evaluate iron levels in peritoneal fluid (PF) of women with and without endometriosis. Material and Methods: Seventy-five women were studied: 50 women with endometriosis and, as a reference group, 25 patients with functional follicle ovarian cysts. Iron concentrations in the PF were measured using a commercially available colorimetric assay kit. Results: Iron concentrations were significantly higher in PF from women with endometriosis as compared to the reference group. Patients with stages III/IV endometriosis had significantly higher PF iron concentrations than women with stages I/II of the disease. Conclusions: Disrupted iron homeostasis in the peritoneal cavity of women with endometriosis plays a role in the pathogenesis of the disease

Subpopulations of peripheral blood dendritic cells during chemotherapy of ovarian cancer

Peripheral blood dendritic cells subpopulations in women with ovarian carcinoma during chemotherapy. Objectives: Ovarian carcinoma (OVC) is often diagnosed at an advanced stage and requires effective chemotherapy as a first-line treatment. However, chemotherapy may be associated with significant side-effects, like nausea, vomiting, hair loss, cognitive dysfunction, fatigue and changes in sexual functioning. Leucopenia is one of the most common and dangerous side effects of chemotherapy. Little is known about possible effects of chemotherapy on dendritic cells (DCs) counts and function, although it is well documented that primary and secondary cell-mediated immune response are suppressed during this treatment. Design: In this study we evaluated the myeloid and lymphoid DCs in the peripheral blood (PB) of 37 women with OVC before and after first-line based on platin and taxane chemotherapy, and in 24 healthy blood donors. Patients received 6 courses of treatment, administered at 21-day intervals. Material and Methods: The myeloid (M) and lymphoid (L) DCs were estimated by flow cytometry before and after 9th and 15th week of treatment. Results: The percentage of both MDCs and LDCs was significantly lower (0.09% and 0.04%) in PB of patients with ovarian cancer comparing to healthy women (0.25% and 0.33%). The percentage of both, myeloid and lymphoid DCs after 9th and 15th week (0.08% vs 0.08% and 0.06% vs 0.08%) of chemotherapy did not differ from that found before treatment (0.09% and 0.04%). The Myeloid to Lymphoid DCs ratio was significantly lower in patients receiving chemotherapy

Does the patients age at cancer diagnosis affect microvessels density in uterine sarcoma tissues?

Objectives: The objective of the study was to retrospectively evaluate the density of vessels exhibiting positive glycoprotein CD34 expression in the uterine leiomyosarcoma tissues and their correlation with the age of patients at the time of tumor diagnosis. Material and methods: The archival paraffin blocks with the cancer tissues collected from 50 patients suffering from uterine leiomyosarcoma were used together with their clinical and demographic data. The immunohistochemical peroxidase-de­pendent methods were used to detect microvessels with positive CD34 expression. The glycoprotein CD34 expression was evaluated as a density of microvessel showing the positive immunohistochemical reaction (MVDCD34). Results: The negative, statistically significant correlation between the age of patients (at the moment diagnosis) and the MVDCD34+ (R = –0.289, p = 0.042) was found. Conclusions: The study’s findings may suggest that the tissues of younger people constitute a permissive environment for pro-angiogenic factors

Clinical Relevance and Immunosuppressive Pattern of Circulating and Infiltrating Subsets of Myeloid-Derived Suppressor Cells (MDSCs) in Epithelial Ovarian Cancer

Myeloid-derived suppressor cells (MDSCs) expansion is a hallmark of cancer. Three major MDSC subsets defined as monocytic (M)-MDSCs, polymorphonuclear (PMN)-MDSCs and early stage (e)MDSCs can be revealed in human diseases. However, the clinical relevance and immunosupressive pattern of these cells in epithelial ovarian cancer (EOC) are unknown. Therefore, we performed a comprehensive analysis of each MDSC subset and immunosupressive factors in the peripheral blood (PB), peritoneal fluid (PF), and the tumor tissue (TT) samples from EOC and integrated this data with the patients' clinicopathological characteristic. MDSCs were analyzed using multicolor flow cytometry. Immunosuppressive factors analysis was performed with ELISA and qRT-PCR. The level of M-MDSCs in the PB/PF/TT of EOC was significantly higher than in healthy donors (HD); frequency of PMN-MDSCs was significantly greater in the TT than in the PB/PF and HD; while the level of eMDSCs was greater in the PB compared with the PF and HD. Elevated abundance of tumor-infiltrating M-MDSCs was associated with advanced stage and high grade of EOC. An analysis of immunosuppressive pattern showed significantly increased blood-circulating ARG/IDO/IL-10-expressing M- and PMN-MDSCs in the EOC patients compared with HD and differences in the accumulation of these subsets in the three tumor immune microenvironments (TIME). This accumulation was positively correlated with levels of TGF-β and ARG1 in the plasma and PF. Low level of blood-circulating and tumor-infiltrating M-MDSCs, but neither PMN-MDSCs nor eMDSCs was strongly associated with prolonged survival in ovarian cancer patients. Our results highlight M-MDSCs as the subset with potential the highest clinical significance

The effect of hormonal contraception on symptoms associated with the menstrual cycle

Nowadays, there exist a large number of methods that allow to prevent unintended pregnancy. One of the most common technique in Poland is hormonal contraception in the form of contraceptive pills. This method is effective, easy to use, and more importantly it does not cause permanent sterility. Moreover, hormonal contraception comes with plenty of additional health benefits that are not related to contraception alone, such as: reduction of menstrual pain, regular cycles and lack of menorrhagia. Due to the beneficial effect on the body, hormonal contraception is used in the treatment of certain diseases, such as acne and endometriosis. Reduction of numerous existing symptoms leads to an improvement in the quality of women’s lives

The role of iron metabolism and oxidative stress in the pathogenesis of endometriosis

Despite many years of extensive investigations and increasing number of studies, the pathogenesis of endometriosis remains unclear. Accumulated data suggests that disrupted iron metabolism may induce oxidative stress in the peritoneal cavity of endometriosis patients

Expression of lymphangiogenesis marker neuropilin-1 in different types of ovarian cancer

Background: Neuropilin (NRP) may be used as a marker of lymphangiogenesis in malignant tumors. Significant correlations of the expression of NRP with tumor progression and overall survival prognosis were found in several cancer types. However, its potential role in epithelial ovarian cancer (EOC) has not been clarified. AIMS: The aim of the work was to study a possible correlation of neuropilin-1 (NRP-1) expression with selected clinical and histological features of EOC. Material and Methods: The study included 53 women (aged 23 to 81, mean 56.6+/-4.4yrs), 38 of which were postmenopausal (71.7%). Immunohistochemical staining with a specific anti-NRP-1 antibody was performed in representative tumor tissue samples of patients with EOC. Both, percentage of stained lymphatic cells and intensity of staining were assessed under 200x magnification. The results were correlated with the menopausal status, FIGO stage, histological type and histological grade of EOC. Results: Histological examination revealed that there were 27 cases of serous cancers (50%), 15 cases of mucinous cancer (28.3%) and 11 endometrioid cancers (20.7%). In 41.5% (n=22) cases of EOC no NRP-1 staining was found, a weak (+) or strong (++) staining were found in 13 (24.5%) and 18 tumors, respectively. There were no significant differences between neuropilin-1 expression and both menopausal status of women and histological type of EOC. Except for stage II, clinical EOC patients’ FIGO stage was not correlated with the lack of expression (38.8% for stage I, 71.4% for stage II and 35.7% for stage III). Conclusion: We believe that neuropilin-1 expression is probably not related to clinical and histological features of epithelial ovarian cancer