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1.
Cancers (Basel) ; 15(19)2023 Sep 28.
Article in English | MEDLINE | ID: mdl-37835474

ABSTRACT

BACKGROUND: The inappropriate action of WNT4 and estrogens affects uterine homeostasis and function, and may lead to endometrial cancer (EC). OBJECTIVE: The aim was to evaluate the alterations of WNT4 gene expression and WNT4 protein immunoreactivity (Ir) in EC, considering tumor characteristics, the clinicopathological association and estrogen dependence. METHODS: WNT4 mRNA levels were compared between benign (control) endometrium (n = 8) and endometroid EC (EEC) and non-endometroid EC (non-EEC) samples (n = 28) using the real-time PCR technique. The WNT4-Ir and ERα-Ir were evaluated by immunohistochemistry (IHC). WNT4 mRNA gene and WNT4-Ir were correlated with clinicopathological and blood morphological parameters. Overall survival (OS) was assessed. The bioanalysis was utilized to study WNT4 expression in large patient cohort (n = 549). RESULTS: WNT4 gene expression was decreased in EC samples (specifically in EEC but not in non-EEC) compared to the control. The WNT4 gene expression was also decreased in EC samples categorized by the tumor characteristics. There was no statistical difference in WNT4-Ir or ERα-Ir between the control and EC. There was no correlation between OS and WNT4 gene expression and WNT4-Ir. Bioanalysis showed that WNT4 and ESR1 gene expression alterations tended to be mutually exclusive. An alteration in WNT4 expression was found in different histological tumor types in a large group of EC patients. CONCLUSIONS: There is a great need to evaluate the molecular background of EC. Our study suggests that the WNT4 gene has the potential to be a marker of functional estrogen signaling in EEC.

2.
Biomedicines ; 11(10)2023 Sep 27.
Article in English | MEDLINE | ID: mdl-37893027

ABSTRACT

Although the impact of age, gender, and obesity on the skin wound healing process has been extensively studied, the data related to gender differences in aspects of skin scarring are limited. The present study performed on abdominal human intact and scar skin focused on determining gender differences in extracellular matrix (ECM) composition, dermal white adipose tissue (dWAT) accumulation, and Foxn1 expression as a part of the skin response to injury. Scar skin of men showed highly increased levels of COLLAGEN 1A1, COLLAGEN 6A3, and ELASTIN mRNA expression, the accumulation of thick collagen I-positive fibers, and the accumulation of α-SMA-positive cells in comparison to the scar skin of women. However, post-injured skin of women displayed an increase (in comparison to post-injured men's skin) in collagen III accumulation in the scar area. On the contrary, women's skin samples showed a tendency towards higher levels of adipogenic-related genes (PPARγ, FABP4, LEPTIN) than men, regardless of intact or scar skin. Intact skin of women showed six times higher levels of LEPTIN mRNA expression in comparison to men intact (p < 0.05), men post-injured (p < 0.05), or women post-injured scar (p < 0.05) skin. Higher levels of FOXN1 mRNA and protein were also detected in women than in men's skin. In conclusion, the present data confirm and extend (dWAT layer) the data related to the presence of differences between men and women in the skin, particularly in scar tissues, which may contribute to the more effective and gender-tailored improvement of skin care interventions.

3.
Cancers (Basel) ; 15(4)2023 Feb 15.
Article in English | MEDLINE | ID: mdl-36831570

ABSTRACT

Kisspeptin (KISS) is a natural peptide-discovered in 1996 as a factor inhibiting the ability to metastasize in malignant melanoma. This protein plays also a regulatory role in the process of puberty, the menstrual cycle, spermatogenesis, implantation and development of the human placenta. The present study aimed to evaluate the expression of KISS and its receptor GPR54 in endometrial cancer (EC) tissue, depending on the histological type of cancer, its stage, various demographic characteristics, and clinical conditions in 214 hysterectomy patients. Expression of KISS and GPR54 was confirmed in 99.5% and 100% of the cases, respectively. Hormone replacement therapy and the coexistence of the anti-Müllerian type 2 receptor in cancer tissue enhanced KISS expression. Smoking, on the other hand, decreased KISS expression. GPR54 expression increased with the advancement of the disease (according to FIGO classification). Also, the presence of the anti-Müllerian type 2 receptor in EC increased the level of GPR54. Hypertension, age and miscarriage harmed the presence of GPR54. The histological type of cancer, diabetes type 2, body mass index, hormonal contraception, number of deliveries, birth weight of newborns, breastfeeding time, and the presence of AMH in EC tissue were not associated with the expression of either KISS nor GPR54. The KISS level was also significantly related to the GPR54 level. Considering that KISS is a non-toxic peptide with antimetastatic properties, further investigation is essential to determine the clinical significance of this peptide.

4.
Cells ; 12(3)2023 02 02.
Article in English | MEDLINE | ID: mdl-36766833

ABSTRACT

Although clinical trials on human neural stem cells (hNSCs) have already been implemented in the treatment of neurological diseases and they have demonstrated their therapeutic effects, many questions remain in the field of preclinical research regarding the biology of these cells, their therapeutic properties, and their neurorestorative potential. Unfortunately, scientific reports are inconsistent and much of the NSCs research has been conducted on rodents rather than human cells for ethical reasons or due to insufficient cell material. Therefore, a question arises as to whether or which conclusions drawn on the isolation, cell survival, proliferation, or cell fate observed in vitro in rodent NSCs can be introduced into clinical applications. This paper presents the effects of different spatial, nutritional, and dissociation conditions on NSCs' functional properties, which are highly species-dependent. Our study confirmed that the discrepancies in the available literature on NSCs survival, proliferation, and fate did not only depend on intra-species factors and applied environmental conditions, but they were also affected by significant inter-species variability. Human and rodent NSCs share one feature, i.e., the necessity to be cultured immediately after isolation, which significantly maintains their survival. Additionally, in the absence of experiments on human cells, rat NSCs biology (neurosphere formation potential and neural differentiation stage) seems closer to that of humans rather than mice in response to environmental factors.


Subject(s)
Neural Stem Cells , Rats , Mice , Humans , Animals , Cells, Cultured , Cell Differentiation , Cryopreservation , Biology
5.
Vaccines (Basel) ; 10(2)2022 Jan 27.
Article in English | MEDLINE | ID: mdl-35214659

ABSTRACT

The tolerance and safety of vaccination in pregnancy should be assessed in local populations based on ethnic differences across countries. Therefore, this study aimed to determine the tolerability of the BNT162b2 mRNA vaccination in pregnancy in a Polish population. An online questionnaire enquiring about the safety and tolerability of the BNT162b2 mRNA vaccine was distributed to pregnant and non-pregnant female healthcare professionals who had voluntarily received one or two doses of the COVID-19 vaccine in Poland. The two groups were compared simultaneously considering the COVID-19 infection status before vaccination. Compared with that noted in the control group, pregnant women in the COVID-19-free group were less likely to have fever (p = 0.002) or gastrointestinal symptoms (p = 0.009) after the second dose. In the COVID-19-exposed group, pregnant women were less likely to experience local skin reactions (p = 0.009), and myalgia (p = 0.003) after the first dose. After the second dose, the only noticeable difference was a lower incidence of myalgia (p = 0.001) in pregnant women. The tolerability of the BNT162b2 mRNA COVID-19 vaccine was similar in both the groups. No severe local, generalised, or pregnancy complications related to mother or foetus were observed. Good tolerability of the BNT162b2 mRNA COVID-19 vaccine in pregnancy in the Polish population may facilitate the decision to vaccinate pregnant women against COVID-19.

6.
Materials (Basel) ; 14(19)2021 Sep 27.
Article in English | MEDLINE | ID: mdl-34640010

ABSTRACT

This research study aimed to investigate the effect of the lightweight aggregate concrete and steel reinforcement interaction on the behaviour of continuous beams compared to the normal concrete of the same strength. This paper presents six full-scale, double-span beams with a rectangular cross-section made of both lightweight and normal concrete. The study confirmed that beams made of lightweight aggregate concrete achieve comparable flexural capacities to those made of NWC but their deformability and ductility are lower. Although the redistribution of internal forces depends mainly on the longitudinal reinforcement ratio, the influence of ultimate compressive strains of concrete is also noticeable. The ultimate compressive strains in LWAC are generally lower than in NWC. The lower rotational capacity of LWAC results in smaller degrees of moment redistribution in beams made of this concrete compared to normal concrete beams.

7.
Vaccines (Basel) ; 9(6)2021 Jun 19.
Article in English | MEDLINE | ID: mdl-34205434

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has given rise to the need to develop a vaccine as quickly as possible. As pregnant women are at increased risk of contracting severe COVID-19, with higher mortality, it is essential to assess the safety of the vaccines administered during pregnancy. METHODS: The aim of this study was to determine the titer of specific maternal and cord antibodies against severe acute respiratory syndrome coronavirus 2 S protein after antenatal vaccination. The secondary objective was to evaluate the ratio of the umbilical cord to the maternal antibody titers. Patients included in the study were enrolled after undergoing voluntary vaccination against COVID-19 during pregnancy at different weeks of gestation. All patients analyzed in our initial study were vaccinated with the BNT162b2 mRNA COVID-19 vaccine. RESULTS: The results of the current study document high anti-S total IgG antibody titers in cord serum at birth in all mother-infant pairs analyzed. The mean umbilical cord blood sample IgG antibody titer anti-S protein was 1026.51 U/mL (±SD 769.25). The mean cord-to-maternal anti-S IgG antibody ratio was 1.28 (±SD 0.798). A significant positive correlation was observed between the week of gestation at which the first dose was administered and the week of gestation at which the second dose was administered, and the respective cord-to-maternal ratio (r = 0.48; p = 0.0029) for the first dose and (r = 0.39; p = 0.0102) for the second dose. CONCLUSIONS: To date, despite the prevalence of COVID-19 vaccination, there is a lack of conclusive evidence supporting the safety and efficacy of vaccination of pregnant women. Therefore, the results we present are complementary. Our study suggests that maternal immunization may provide neonatal protection through the transplacental transfer of antibodies. Of particular importance is the demonstration that antibody transfer is correlated with the time from vaccination to delivery, which may allow future determination of the optimal timing of COVID-19 vaccination in pregnant women.

8.
Cells ; 9(10)2020 10 17.
Article in English | MEDLINE | ID: mdl-33080800

ABSTRACT

Anti-Müllerian hormone (AMH) is responsible for the Müllerian ducts' regression in male fetuses. In cells of cancers with AMH receptors (AMHRII), AMH induces cell cycle arrest or apoptosis. As AMH occurs naturally and does not exhibit significant side effects while reducing neoplastic cell colonies, it can be considered as a potential therapeutic agent for cancer treatment. The purpose of this study was to assess the AMHRII expression in endometrial cancer (EC) in correlation to various demographic data and clinical conditions. Immunohistochemical analysis was used to assess AMHRII expression in EC tissue samples retrieved from 230 women with pre-cancerous state of endometrium (PCS) and EC. AMHRII was detected in 100% of samples. No statistical difference was observed for AMHRII expression depending on the histopathological type of EC, cancer staging, body mass index, and age, as well as the number of years of menstruation, births and miscarriages, and average and total breastfeeding time. Diabetes mellitus type 2 is the only factor that has an impact on AMHRII expression in EC tissue. Thus, this study supports the idea of theoretical use of AMH in EC treatment because all histopathological types of EC at all stages of advancement present receptors for AMH.


Subject(s)
Endometrial Neoplasms/metabolism , Receptors, Peptide/metabolism , Receptors, Transforming Growth Factor beta/metabolism , Abortion, Spontaneous/metabolism , Anti-Mullerian Hormone/metabolism , Breast Feeding , Endometrial Neoplasms/pathology , Female , Humans
9.
Folia Histochem Cytobiol ; 57(2): 84-93, 2019.
Article in English | MEDLINE | ID: mdl-31198984

ABSTRACT

INTRODUCTION: WNT5A (Wnt family member 5A) belongs to the WNT family of secreted signaling glycoproteins that play essential role in developmental, physiological and pathological processes. WNT5A was shown to take part in carcinogenesis process playing both oncogenic and suppressor functions in various types of human malignancies. This study aimed to assess the expression of the WNT5A gene at the mRNA and protein levels in the specimens derived from endometrial cancer (EC) or unchanged control endometrium. The associations between the WNT5A expression levels and clinicopathological characteristics and survival of EC patients were evaluated. MATERIALS AND METHODS: Total RNA was isolated in order to assess the relative amounts of WNT5A mRNA by quantitative polymerase chain reaction (QPCR) in samples of unchanged endometrial control (n = 8) and tumor samples of EC patients (n = 28). Immunohistochemistry (IHC) was used to determine the presence of WNT5A protein in the sections of formalin-fixed, paraffin-embedded tissue specimens derived from unchanged endome-trial controls (n = 6) and EC tumors (n = 19). Significance of differences in WNT5A expression levels between the studied groups of EC patients and correlations between the WNT5A and demographic data, pathological features, hematological parameters and overall survival of the patients were evaluated by statistical analysis. RESULTS: The level of WNT5A mRNA was decreased in EC in comparison to unchanged endometrium. WNT5A expression was associated with primary tumor invasion status exhibiting reduced level of transcripts in EC that involved organs beyond the uterus when compared to the uterus-confined cancers. WNT5A immunoreactivity was visualized in the cytoplasm and nuclei of EC cells as well as in the luminal and glandular epithelial cells of unchanged endometrium. WNT5A mRNA expression levels correlated negatively with cytoplasmic, and positively with nuclear immunoreactivity of the WNT5A protein in the EC cells. In addition, the relationships between blood leucocyte count (in particular granulocytes and lymphocytes) of patients with EC and their WNT5A mRNA and protein expression levels were established. A positive correlation between the nuclear immunoexpression of WNT5A protein in the cancer cells in cell nuclei and mean platelet volume in blood was also found. CONCLUSIONS: The results of the first study of WNT5A expression at the transcript and protein levels indicate that it could be considered as a potential marker of molecular changes that take place during EC development.


Subject(s)
Endometrial Neoplasms/genetics , Endometrial Neoplasms/metabolism , RNA, Messenger/metabolism , Wnt-5a Protein/genetics , Wnt-5a Protein/metabolism , Adult , Biomarkers, Tumor/genetics , Biomarkers, Tumor/immunology , Biomarkers, Tumor/metabolism , Cell Nucleus/metabolism , Cytoplasm/metabolism , Down-Regulation , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/mortality , Endometrium/pathology , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Middle Aged , Prognosis , Protein Isoforms/genetics , Protein Isoforms/immunology , Protein Isoforms/metabolism , Wnt-5a Protein/immunology
10.
Reprod Sci ; 26(1): 139-150, 2019 01.
Article in English | MEDLINE | ID: mdl-29621954

ABSTRACT

Endometriosis has been considered as an estrogen (E2)-dependent and progesterone (P4)-resistant disease. On the other hand, lysophosphatidic acid (LPA) has been suggested as a significant modulator of ovarian pathology, acting via both LPA levels and LPA receptor (LPAR) upregulation. Therefore, the objective of the present study was to evaluate LPA concentration as well as LPARs, autotaxin (ATX), and phospholipase A2 (PLA2) expression in ovarian endometriotic cysts and normal endometrium with correlation of the expression of E2 and P4 receptors in endometriotic cysts. The analyses were carried out using the tissues derived from 37 patients with ovarian endometriosis and 20 endometrial samples collected from women without endometriosis were used as a control. We found that ovarian endometriotic cysts are a site of LPA synthesis due to the presence of enzymes involved in LPA synthesis in the tissue. Additionally, when we compared endometriotic cysts versus normal endometrium, we were able to show overexpression of 3 from 6 examined LPARs and both enzymes responsible for LPA synthesis in endometriotic cysts. Finally, we found the correlations between LPARs, ATX, and PLA2 and the expression of E2 and P4 receptors in endometriotic cysts. Owing to the high LPAR2 and LPAR4 transcript and protein expression in endometriotic ovarian cysts and positive correlations of both these receptors with the PR-B and ERß, respectively, those receptors seem to be the most promising predictors of the endometriotic cysts as well as the main receptors responsible for LPA action in the ovarian endometriosis.


Subject(s)
Endometriosis/metabolism , Lysophospholipids/metabolism , Ovarian Cysts/metabolism , Receptors, Lysophosphatidic Acid/metabolism , Receptors, Purinergic P2/metabolism , Adult , Female , Humans , Middle Aged , Phospholipases A2/metabolism , Phosphoric Diester Hydrolases/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism
11.
Ginekol Pol ; 89(2): 89-96, 2018.
Article in English | MEDLINE | ID: mdl-29512813

ABSTRACT

OBJECTIVES: Quadratus Lumborum Block in contrast to Transversus Abdominis Plane Block contains a unique component which not only stops somatic pain but also inhibits visceral pain by spreading the local anesthetic to the paravertebral space. This study was designed to determine whether performing the Quadratus Lumborum Block type I in patients un-dergoing cesarean section would be associated with both decreased morphine consumption and decreased pain levels in the postoperative 48-hour period. MATERIAL AND METHODS: Sixty patients undergoing caesarean section under spinal anesthesia were randomly and equally assigned to one or other of two groups: QLB I (who received Bilateral Quadratus Lumborum Block type I with the use of 24 mL 0.375% ropivacaine per side) or a Control group. In both groups, on-demand morphine analgesia was administered postoperatively within the first 48 hours. The following were measured: the morphine consumption; the time elapsed from the C-section until the first dose of morphine; and the levels of pain intensity among patients in rest (numeral pain rating scale). RESULTS: There were no statistically significant demographic data differences between the QLB I and Control groups. The following significant differences were observed in the 48-hour postoperative period: morphine consumption was higher in the Control group (p = 0.000); the time elapsed from the C-section until the first dose of morphine was longer in QLB I group (p < 0.05); and the median of the pain numeric rating scale was higher in the Control group (p < 0.05). CONCLUSIONS: Quadratus Lumborum Block type I significantly reduces morphine consumption and pain levels up to 48 hours postoperatively.


Subject(s)
Amides , Anesthetics, Local , Cesarean Section/adverse effects , Nerve Block/methods , Pain, Postoperative/drug therapy , Adult , Analgesics, Opioid/administration & dosage , Female , Humans , Morphine/administration & dosage , Pain Measurement , Pain, Postoperative/etiology , Ropivacaine , Time Factors , Young Adult
12.
Gynecol Endocrinol ; 34(5): 422-427, 2018 May.
Article in English | MEDLINE | ID: mdl-29182028

ABSTRACT

To establish association between two main lysophosphatidic acid (LPA) receptors (LPAR2 and LPAR1) with the synthesis of estrogens and androgens in type-1 endometrial carcinoma (EC), we evaluated correlation of LPARs expression with expression of steroid 5 alpha-reductase 2 - aromatase (SRD5A2), or cytochrome P450 family 19 subfamily A member 1-5α-reductase (CYP19A1) in EC. Moreover, we aimed to investigate SRD5A2 and CYP19A1 expression in type 1 endometrial cancer and normal endometrium with its correlation to selected clinicopathological features. The studied cancerous samples showed higher CYP19A1 and SRD5A2 expression comparing to normal endometria. We also documented positive correlations between LPAR1 and LPAR2 with responsible for proliferation SRD5A2 in EC tissue which suggests that intratumoral estrogen metabolism and synthesis are pivotal in endometrial carcinoma progression, with the involvement of LPA in this process. However, positive correlation between CYP19A1 and LPAR1 accounts for supporting role of LPA acting via LPAR1 in intratumoral DHT concentration and the ethiology of endometrial cancer progression. Also, owing to the highest expression of LPARs, CYP19A1 and SRD5A2 as well as their association with depth of myoinvasion and FIGO stage LPAR2 and LPAR1 seem to be the efficient candidate prognostic markers in the individual, targeted therapies for EC.


Subject(s)
Androgens/metabolism , Carcinoma/metabolism , Endometrial Neoplasms/metabolism , Endometrium/metabolism , Estrogens/metabolism , Receptors, Lysophosphatidic Acid/metabolism , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism , Aged , Aged, 80 and over , Aromatase/genetics , Aromatase/metabolism , Carcinoma/genetics , Carcinoma/pathology , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Endometrium/pathology , Female , Humans , Middle Aged , Receptors, Lysophosphatidic Acid/genetics
13.
Adv Med Sci ; 62(2): 405-413, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28646744

ABSTRACT

Personalized and precision medicine is gaining recognition due to the limitations by standard diagnosis and treatment; many areas of medicine, from cancer to psychiatry, are moving towards tailored and individualized treatment for patients based on their clinical characteristics and genetic signatures as well as novel imaging techniques. Advances in whole genome sequencing have led to identification of genes involved in a variety of diseases. Moreover, biomarkers indicating severity of disease or susceptibility to treatment are increasingly being characterized. The continued identification of new genes and biomarkers specific to disease subtypes and individual patients is essential and inevitable for translation into personalized medicine, in estimating both, disease risk and response to therapy. Taking into consideration the mostly unsolved necessity of tailored therapy in oncology the innovative project MOBIT (molecular biomarkers for individualized therapy) was designed. The aims of the project are: (i) establishing integrative management of precise tumor diagnosis and therapy including systematic biobanking, novel imaging techniques, and advanced molecular analysis by collecting comprehensive tumor tissues, liquid biopsies (whole blood, serum, plasma), and urine specimens (supernatant; sediment) as well as (ii) developing personalized lung cancer diagnostics based on tumor heterogeneity and integrated genomics, transcriptomics, metabolomics, and radiomics PET/MRI analysis. It will consist of 5 work packages. In this paper the rationale of the Polish MOBIT project as well as its design is presented. (iii) The project is to draw interest in and to invite national and international, private and public, preclinical and clinical initiatives to establish individualized and precise procedures for integrating novel targeted therapies and advanced imaging techniques.


Subject(s)
Biological Specimen Banks , Biomarkers, Tumor/analysis , Molecular Imaging , Molecular Targeted Therapy , Neoplasms/diagnosis , Neoplasms/therapy , Precision Medicine , Humans , Metabolome , Predictive Value of Tests , Proteome
14.
Przegl Epidemiol ; 71(4): 547-554, 2017.
Article in English | MEDLINE | ID: mdl-29415533

ABSTRACT

INTRODUCTION: Trichomonas vaginalis is considered to be the most common non-viral sexually transmitted infection. Trichomoniasis is not a reportable disease and due to this fact only estimates can be made about its incidence AIM OF THE STUDY: The aim of the study was to determine the prevalence of T. vaginalis in the female population of north-eastern Poland as well as to conduct an epidemiological analysis on the basis of the data from the years of 2009 ­ 2015 derived from the registers of the National Health Fund MATERIALS AND METHODS: In this study 300 women aged 19 ­ 50 were examined. Two vaginal swabs were taken from each patient. The first swab was used to prepare microscope slides, and stained with Giemsa stain. The second swab was used for a diagnostic immunochromatographic rapid test (OSOM Trichomonasis test). Each woman was also asked to complete a questionnaire. Additionally, on the basis of the data from the National Health Fund, epidemiological analysis was conducted. Statistical analysis was performed with SPSS Statistics ver. 24 using Fisher test RESULTS: T. vaginalis infection was confirmed in two women. The diagnosis of trichomoniasis was confirmed as a result of T.vaginalis antigen detection with the use of immunochromatographic diagnostic test (OSOM Trichomonas test). The data from the National Health Fund show that 160 cases of trichomoniasis were reported, of which women accounted for 135 (84%), and men for 25 (16%). The highest infection rate was found in women aged 50 ­ 59 and those over 60 years old CONCLUSIONS: Our results show that the prevalence of T. vaginalis infection remains low, the infection occurs mainly in elderly women. However, one should pay attention to the differences in the detection of T. vaginalis connected with a particular method used. Conducting screen tests on a larger scale using more advanced tests would allow a more accurate assessment of the scale of the problem in our country


Subject(s)
Trichomonas Infections/epidemiology , Trichomonas Infections/parasitology , Trichomonas Vaginitis/parasitology , Trichomonas vaginalis/isolation & purification , Adult , Age Distribution , Animals , Cross-Sectional Studies , Female , Humans , Middle Aged , Vaginal Discharge/epidemiology , Vaginal Discharge/parasitology , Women's Health , Young Adult
15.
Biomed Res Int ; 2015: 854056, 2015.
Article in English | MEDLINE | ID: mdl-26366420

ABSTRACT

WNT proteins are involved in embryonic development, sex determination, stem cell recruitment, angiogenesis, and cancer. They take part in morphological changes in the endometrium during development, regulate processes of endometrial proliferation and differentiation. This review presents current knowledge about implication of WNT proteins and ß-catenin in physiological endometrial functions as well as their involvement in uterine carcinogenesis. Influence of WNT proteins on the formation of blood vessel, taking place both under healthy and pathological conditions, is also considered. Participation of WNT proteins, ß-catenin, and inhibitors and inducers of WNT signaling in the process of endometrial angiogenesis is largely unknown. Thus, confirmation of their local and systemic participation in the process of endometrial angiogenesis may in the long term help to establish new diagnostic and therapeutic approaches in conditions associated with the pathology of the female reproductive system.


Subject(s)
Endometrium/metabolism , Endometrium/pathology , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Wnt Proteins/metabolism , beta Catenin/metabolism , Cell Differentiation/physiology , Female , Humans
16.
Oncol Rep ; 34(5): 2760-7, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26327335

ABSTRACT

In order to study lysophosphatidic acid (LPA) signaling associated with type 1 endometrial carcinoma (EC), we evaluated the LPA receptors (LPARs), autotaxin (ATX) and phospholipase A2 (PLA2) expression in EC and normal endometrium with correlation to clinicopathological features. We investigated LPAR1, LPAR2, LPAR3, LPAR4, ATX and PLA2 expression at mRNA and protein levels using quantitative real-time PCR and western blot analyses in 37 ECs and 10 normal endometria. All the examined LPARs (except for LPAR3 protein), ATX and PLA2 were overexpressed in cancerous compared to healthy endometrium. The studied ECs showed the highest LPAR2 and LPAR1 expression. Statistically positive correlations were found between depth of myoinvasion and levels of LPAR1, LPAR2 and PLA2 transcripts and proteins. We also found positive correlations between LPAR1, LPAR2, LPAR4 and PLA2 expression with the International Federation of Gynecology and Obstetrics (FIGO) stage. The expression of LPAR1, LPAR2 and PLA2 was positively associated with the age of patients. Positive correlations were found between the expression of LPAR1 mRNA, LPAR2 mRNA and protein and LPAR3 mRNA and body mass index (BMI) of the examined patients. We found no association between the expression levels of the studied factors and diabetes or hypertension among the examined patients. Owing to the highest LPAR2 and LPAR1 expression in EC and positive correlations of these two receptors with the depth of myoinvasion and the FIGO stage, we believe that LPAR2 and LPAR1 show promise as predictors of the EC progression as well as the main receptors responsible for LPA action in the EC tissue.


Subject(s)
Endometrial Neoplasms/pathology , Receptors, Lysophosphatidic Acid/genetics , Receptors, Lysophosphatidic Acid/metabolism , Age Factors , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Endometrial Neoplasms/genetics , Endometrial Neoplasms/metabolism , Female , Gene Expression Regulation, Neoplastic , Humans , Middle Aged , Phospholipases A2/genetics , Phospholipases A2/metabolism , Phosphoric Diester Hydrolases/genetics , Phosphoric Diester Hydrolases/metabolism , Prognosis , Real-Time Polymerase Chain Reaction
18.
Reprod Biol ; 14(3): 176-81, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25152514

ABSTRACT

In the present study, we evaluated the clinical value of the following parameters: basal anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), inhibin B and antral follicle count (AFC) in predicting live birth outcomes. The study involved 603 women undergoing in vitro fertilization (IVF) using the long protocol for controlled ovarian hyperstimulation (COH). Serum levels of AMH, FSH and inhibin B as well as AFC were measured on the first three days of the menstrual cycle prior to the beginning of stimulation. AMH was the only independent parameter that correlated with the chance of live birth. We found that live birth rates of 46.2% (patient age <35 years), 44.7% (35-37 years), 32.1% (38-39) and 15.3% (>39) were associated with concentrations of AMH>1.4 ng/ml. For the AMH range 0.6-1.4 ng/ml, the live birth rates were 29.3%, 12.5%, 5.6% and 2.7%, respectively, and for AMH concentrations below 0.6 ng/ml the rates were 7.1%, 8.3%, 0% and 5.8%, respectively. Independently of other parameters affecting the chance of live birth, the success rate was the highest when the AMH level was >2 ng/ml, significantly lower when the AMH concentration was about 1 ng/ml, and 0% when the AMH concentration was ∼0.1 ng/ml. In conclusion, this is the first report to demonstrate that AMH level correlated better than age, FSH or inhibin B concentrations or AFC with live birth outcome. Therefore, the basal serum concentration of AMH may become a new, substantial prognostic factor regarding live birth above and beyond other currently available predictors of IVF outcome.


Subject(s)
Anti-Mullerian Hormone/blood , Infertility, Female/therapy , Ovulation Induction , Sperm Injections, Intracytoplasmic , Up-Regulation , Adult , Age Factors , Biomarkers/blood , Birth Rate , Cell Count , Female , Humans , Infertility, Female/blood , Infertility, Female/diagnosis , Infertility, Male , Live Birth , Male , Menstruation/blood , Ovarian Reserve , Ovulation Induction/adverse effects , Poland/epidemiology , Prognosis , ROC Curve , Sperm Injections, Intracytoplasmic/adverse effects
19.
Mediators Inflamm ; 2014: 649702, 2014.
Article in English | MEDLINE | ID: mdl-24744506

ABSTRACT

Lysophosphatidic acid (LPA) through activating its G protein-coupled receptors (LPAR 1-6) exerts diverse cellular effects that in turn influence several physiological processes including reproductive function of the female. Studies in various species of animals and also in humans have identified important roles for the receptor-mediated LPA signaling in multiple aspects of human and animal reproductive tract function. These aspects range from ovarian and uterine function, estrous cycle regulation, early embryo development, embryo implantation, decidualization to pregnancy maintenance and parturition. LPA signaling can also have pathological consequences, influencing aspects of endometriosis and reproductive tissue associated tumors. The review describes recent progress in LPA signaling research relevant to human and ruminant reproduction, pointing at the cow as a relevant model to study LPA influence on the human reproductive performance.


Subject(s)
Genitalia, Female/metabolism , Lysophospholipids/chemistry , Signal Transduction , Animals , Cattle , Endometriosis/metabolism , Estrous Cycle/drug effects , Female , Follicle Stimulating Hormone/metabolism , Granulosa Cells/cytology , Granulosa Cells/drug effects , Humans , Ovarian Follicle/drug effects , Ovarian Follicle/metabolism , Pregnancy , Pregnancy, Animal , Receptors, G-Protein-Coupled/metabolism , Ruminants
20.
Biomed Res Int ; 2014: 165352, 2014.
Article in English | MEDLINE | ID: mdl-24738048

ABSTRACT

Anti-Müllerian hormone (AMH) measurements are widely used to optimize the stimulation protocols. First generation AMH kits correlated well with ovarian reserve and response to stimulation. In the present study we aimed to asses if the new generation kits share the same accurate correlations. Retrospective data were collected from 8323 blood samples. For comparison we used Immunotech I generation kit (ImI 4035 samples), Beckman Coulter II generation kit RUO (BCII RUO 3449, samples) and Beckman Coulter II generation kit with IVD certificate (BCII IVD 839 samples). We compared average AMH concentrations measured with different kits, as well as correlation between kits. We also compared average AMH concentrations in sera collected on different cycle days and samples of different quality of preservation. AMH serum concentrations differed for each kit, ranging 4.4 ± 4.12 (mean ± SD) for the ImI, 2.68 ± 3.15 for the BCII RUO, and 1.64 ± 2.85 for BCII IVD. The mean differences from an adjusted regression model were -48.7%, -40%, and -69.2%, respectively. In conclusion, the changes of the BC AMH kits are unpredictable; however, the improvement of them is still possible. It would be very dangerous to use elaborated stimulation protocol (based on the Ist generation AMH results) with the results from the IInd generation assays.


Subject(s)
Anti-Mullerian Hormone/chemistry , Biological Assay/methods , Adolescent , Adult , Child , Female , Humans , Middle Aged , Reagent Kits, Diagnostic , Retrospective Studies , Young Adult
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