Analysis of Expression of the ANG1, CaSR and FAK Proteins in Uterine Fibroids.

Understanding the molecular factors involved in the development of uterine myomas may result in the use of pharmacological drugs instead of aggressive surgical treatment. ANG1, CaSR, and FAK were examined in myoma and peripheral tissue samples taken from women after myoma surgery and in normal uterine muscle tissue samples taken from the control group. Tests were performed using tissue microarray immunohistochemistry. No statistically significant differences in ANG1 expression between the tissue of the myoma, the periphery, and the normal uterine muscle tissue of the control group were recorded. The CaSR value was reduced in the myoma and peripheral tissue and normal in the group of women without myomas. FAK expression was also lower in the myoma and periphery compared to the healthy uterine myometrium. Calcium supplementation could have an effect on stopping the growth of myomas.

PCR diagnostics of Chlamydia trachomatis in asymptomatic infection by women.

OBJECTIVES: Chlamydial infection is often asymptomatic. The lack of symptoms may result in the infection developing into a chronic. Chlamydial infections of the genitourinary system in women can lead to serious complications like PID, fallopian tubes infertility, ectopic pregnancy, and chronic pelvic pain. An infection of the genitourinary system does not cause any lasting immune resistance and does not protect against re-infection. The aim of this research was to conduct tests for Chlamydia trachomatis on healthy women without any genital system symptoms and to estimate the frequency of asymptomatic infections. MATERIAL AND METHODS: During preventive examinations a cervical smear was obtained from the patients n = 100. The aver-age age of the patients was 24.86 ± 3.15. The swabs were sampled by gynecologists. During the examinations Geneproof PathogenFree DNA isolation Kit and GeneProof Chlamydia trachomatis PCR kit which detects 16S rRNA conservative coding sequence, conservative region of cryptic plasmid DNA, including deletion mutation in cryptic plasmid (Swedish variant). RESULTS: Swabs were sampled from 100 women aged 18-32 who had no symptoms of chlamydial genitourinary system infection. Within the study group 4% of women received a positive result, i.e. 4/100. CONCLUSIONS: The study confirmed asymptotic infection in 4% of women. In own research it was not possible to confirm cor-relation between the presence of Chlamydia trachomatis and the number of partners or the number of sexual intercourses.

Immunohistochemical Expression of Vitamin D Receptor in Uterine Fibroids.

One of the many factors involved in the development of uterine fibroids is vitamin D deficiency. One aspect of this deficiency is decreased serum concentration of calcidiol-25(OH)D, a metabolite of D3 vitamin. The active form of vitamin D3, which arises after numerous enzymatic reactions, is calcitriol-1,25(OH)2D3; this compound is transported to various body tissues. Vitamin D possesses extra-genomic effects due to its influence on various signaling pathways, i.e., through activating tyrosine kinases and by genomic effects via binding to a specific nuclear receptor, vitamin D receptor (VDR). The vitamin D/VDR complex regulates the expression of genes and is involved in the pathogenesis of fibroids. Numerous studies have shown that vitamin D supplementation reduces fibroid size. It has also been shown that the expression of VDR in myoma tissue is significantly lower than in the uterine muscle tissue at the tumor periphery. However, the expression of VDR in non-myoma uterine muscle has not previously been investigated. Our VDR expression studies were performed immunohistochemically with tissue microarrays (TMA) in three tissue groups: 98 uterine myoma tissues, 98 uterine tissues (tumor margin), and 12 tissues of normal uterine muscle (i.e., without fibroids). A statistical analysis showed significantly lower VDR expression in uterine muscle at the periphery of the fibroid than in healthy uterine muscle. Lower expression of VDR at the periphery of the myoma compared to that in normal uterine muscle may indicate potential for new myomas. This observation and the described reduction in the size of fibroids after vitamin D supplementation supports the hypothesis of causal development of uterine fibroids and may be useful for the prevention of re-development in the event of their excision from the uterus.

Expression of selected molecular factors in two types of endometrial cancer.

BACKGROUND: Endometrial cancers (EC) are a heterogeneous group of malignant neoplasms differing in etiology, clinical-pathological features and prognosis. OBJECTIVES: To determine the differences between the expression of selected molecular factors and find connections between them in order to isolate possible biomarkers influencing treatment options. MATERIAL AND METHODS: The investigated data involved archival histological preparations obtained from uterine EC samples taken from 137 patients, treated surgically between 2007 and 2014. The immunohistochemical Dako EnVisionTM Flex+ method was applied. RESULTS: The expression of ERß, MLH1 and BRCA1 was lower in ECI than in ECII patients. The ERα expression was higher in early Fédération internationale de gynécologie et d'obstétrique (FIGO) (IA) stages than in advanced (IB-IV) stages, while ERß expression was significantly higher in advanced stages compared to stage IA and increased with grading. The BRCA1 expression also increased with grading. In both type I and type II EC patients, ERα expression correlated with MYH9 and BRCA1, while ERß expression correlated with BAP expression. High expression of BRCA1 correlated with several proteins: BAP, MYH9 and FAK. High BAP expression also correlated with high MYH9 expression. A correlation in the expression of these proteins was also demonstrated in the group consisting only of patients with ECI. A significant correlation was found between BAP expression and MYH9 among patients diagnosed with ECI. In the ECII group, no correlation was found between the tested proteins. CONCLUSIONS: The ECI and ECII patients differed in the studied molecular factors, mainly in terms of ER and BRCA1 expression. Changes in BRCA1 expression were linked to alterations in BAP expression, but were also associated with the proteins MYH9 and FAK.

Streptococcus agalactiae and Chlamydia trachomatis detection in women without symptoms of infection.

BACKGROUND: Chlamydia trachomatis (C. trachomatis) and Streptococcus agalactiae (GBS) may be present in the female cervical canal without any symptoms of infection. Chronic chlamydial infections lead to many serious complications and perinatal infections, while the presence of GBS is a reservoir for infections of newborns or invasive streptococcal infection in adults. OBJECTIVES: To examine healthy women for C. trachomatis without symptoms from the reproductive system, assess the frequency of asymptomatic infections, detect GBS in the cervical canal, demonstrate differences in drug susceptibility, and determine the serotype of S. agalactiae strains and correlations among the ones present in the cervical canal. MATERIAL AND METHODS: A total of 315 cervical swabs were collected for genetic and microbiological analysis for the presence of C. trachomatis and S. agalactiae. Latex and diffusion-disk methods were used to determine the serotype and susceptibility of streptococci. RESULTS: Ten out of 315 women (3.2%) were C. trachomatis-positive. Using traditional methods of microscopy, culture and serology, 42 strains (13.3% of the subjects) obtained from patients were identified as S. agalactiae and further analyzed. The most common serotypes identified were II (18/42, 42.9%), V (11/42, 26.2%) and III (10/42, 23.8%). The less common serotypes found were VII (2/10, 4.8%), and Ib (1/10, 2.4%); no Ia, IV or VII serotypes were found. All the strains were susceptible to penicillin, while 71.4% of them were susceptible to erythromycin and 81.0% were susceptible to clindamycin. Seven isolates (16.7%) were concomitantly resistant to erythromycin and clindamycin. CONCLUSIONS: Chlamydia trachomatis was confirmed in 3.2% of the respondents, and GBS was found in 13.3%, despite a lack of symptoms of infection. The incidence of C. trachomatis infections and GBS colonization in Poland is similar to those in other European countries.

Expression of p53 protein phosphorylated at serine 20 and serine 392 in malignant and benign ovarian neoplasms: correlation with clinicopathological parameters of tumors.

INTRODUCTION: The modification of p53 protein by phosphorylation plays an important role in its stabilization and the regulation of its biological properties. The study investigated the expression of p53 protein phosphorylated at serine 20 (Ser20) and Ser392 and the association between clinicopathological parameters of ovarian neoplasms with respect to p53 protein overexpression. METHODS: p53 protein expression was evaluated on tissues from malignant and benign ovarian tumors. Protein expression was measured in a subset of the specimens using immunohistochemistry. RESULTS: The correlation between p53 protein overexpression and p53-Ser392 phosphorylation was found in ovarian carcinomas (P = 0.001, r = +0.27). In the total group of ovarian carcinomas, significant differences were observed in p53 protein overexpression between well (G1) and poor (G3) tumor grades (P = 0.005) and between serous and endometrioid types of tumor (P = 0.04), whereas p53-Ser20 phosphorylation was associated with advanced International Federation of Gynecology and Obstetrics stage (P = 0.004) and high tumor grade (P = 0.02). In p53-positive ovarian carcinomas, p53-Ser392 phosphorylation was associated with advanced tumor stage (P = 0.02) and high tumor grade (P = 0.049). p53-Ser20 phosphorylation was associated with low tumor grade of p53-positive ovarian carcinomas (P = 0.02) and with high tumor grade of p53-negative ovarian carcinomas (P = 0.02). CONCLUSIONS: These results revealed that p53 phosphorylation at Ser20 and Ser392 is an early event in ovarian tumor development. The authors suggest that the expression of p53 protein phosphorylated at Ser20 and Ser392 in ovarian carcinomas determines their individual clinical features depending on p53 protein status and may be useful biological biomarkers characterizing their behavior.

[Antiphospholipid syndrome in pregnancy--contemporary opinions concerning pathogenesis and diagnostic criteria]. / Zespól antyfosfolipidowy w ciazy--wspólczesne poglady na etiopatogeneze i kryteria diagnostyczne.

Antiphospholipid syndrome is an autoimmunological disease, characterized by coexistence of antiphospholipid antibodies in serum and vascular thrombosis or characteristic obstetrical complications. In spite of numerous clinical trials concerning antiphospholipid syndrome in pregnancy, performed in Poland as well as abroad, there are still some unclear aspects connected with this disease. In the paper, authors pay particular attention to patomechanism and contemporary diagnostic trends of antiphospholipid syndrome in pregnancy.

The role of nesfatin and selected molecular factors in various types of endometrial cancer.

OBJECTIVES: Endometrial cancers (ECs) are the most common gynaecological cancers in well developed countries. Diabetes and metabolic syndrome are among the biggest risk factors. Nesfatin-1, the adipokine derivative of NUCB2 (nucleobindin derivative 2) is linked to the clinical course of EC. Molecular factors, including mutations in MLH1 and MHS2 genes, c-MET and ARID1A are also related to prognosis in endometrial cancer. MATERIAL AND METHODS: Using sections of paraffin-embedded preparations and immunohistochemistry, the expression of NESF1, MLH1, MSH2,c-MET and ARID1A were examined. RESULTS: In this study on protein expression, EC tissues manifested (although insignificantly) an elevated expression of NESF-1 in type II EC. In type I EC, NESF-1 expression was significantly higher in G1 in comparison to G2 and G3 together. A significantly lower expression of MLH1 was demonstrated in type I EC. CONCLUSIONS: The most pronounced expression involved c-MET in all EC I and EC II tissues (in over 80% of cases). A tendency was detected for a high expression of NESF-1 in patients with type II EC, who also exhibited a high expression of MSH2.

Significance of BRCA1 expression in breast and ovarian cancer patients with brain metastasis - A multicentre study.

PURPOSE: Cerebral metastases develop in 10-30% of patients with breast cancer (BC) and in around 3.3 to 4% of patients with ovarian cancer (OC). The aim of the multicenter study is to investigate the correlation between the expression of estrogen alpha receptors (ERα), progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), stromal cell-derived factor 1 (SDF1) and its receptor C-X-C chemokine receptor type 4 (CXCR4), breast cancer metastasis suppressor 1 (BRMS1), astrocyte elevated gene 1 (AEG1), depending on the status of BRCA1 protein, in patients suffering from OC and BC with brain metastases. PATIENTS AND METHODS: The analysis included 51 patients: 29 with BC and 22 with OC, in whom brain metastases were disclosed. RESULTS: In most patients (65.5% of BC patients and 68.2% of patients with OC tumors) BRCA1 protein loss was found. No correlation was disclosed between the levels of ERα, PR receptors, HER2, SDF1, CXCR4, AEG1, BRMS1 and BRCA1 status, patient age, stage of disease advancement, grade of histological maturity of the cells, presence of metastases to lymph nodes. A statistically significant correlation was disclosed between the negative expression of PR receptors and a high expression of CXCR4 in patients with BC. High values of the AEG1 protein (linked to metastases) were detected alongside a high expression of BRMS1 (a suppressor of metastases). CONCLUSIONS: Patients with BC and OC and brain metastases have a frequent loss of BRCA1 expression. The role of ERα, PR, HER2, SDF1, CXCR4, AEG1, BRMS1 in metastatic process needs further studies.

[Antiphospholipid syndrome in pregnancy--actual therapeutic methods]. / Zespól antyfosfolipidowy w ciazy--aktualne metody terapeutyczne.

Considering multidirectional mechanism of antiphospholipid antibodies activity, resulting in fetal loss, various therapeutic methods of antiphospholipid syndrome (APS) in pregnant women have been used until now. The paper is a review of literature concerning therapeutic methods of APS in pregnancy currently used or being clinically and experimentally investigated. Their efficacy, in particular, forms of the disease as well as risk of side effects occurrence were presented.

[Chlamydia trachomatis as an etiological factor of marital infertility--is a routine diagnostics worth to perform?]. / Chlamydia trachomatis jako czynnik etiologiczny nieplodnosci malzenskiej--czy warto przeprowadzac rutynowa diagnostyke?

Chlamydia trachomatis is one of the most common sexually transmitted human pathogens. Chlamydial infection is a problem concerning about 12% of young, sexually active persons at reproductive age. Because of subtle or, particularly at women, asymptomatic course, the disease may be imperceptible by patients and untreated until complications occur. When the infection spreads outside cervix and urethra,W irreversible damages in the range of genital-urinary system are often. Fever and leucocytosis can confirm the complications, occurring in the form of pelvic inflammatory disease, causing infertility. Health education, screening programs for high risk patients and proper early treatment of both sexual partners could contribute to decreasing dangerous results of chlamydial infections, especially in aspect of marital infertility problem.

[Mycoplasmatic infections and their role in marital infertility]. / Zakazenia mykoplazmatyczne i ich rola w nieplodnosci malzenskiej.

Mycoplasmas belong to the large group of microbes and may cause pathologic symptoms in different human organs and systems. The most of them are commensals. They are mostly detected in sexually active persons. Only few of mycoplasmatic species are unquestionable etiological factors of different human infections. They cause illness of respiratory system and kidneys. They are frequently connected with nongonococcal urethritis, epididymitis, prostatitis as well as female pelvic inflammatory disease. Mycoplasmas as etiological factors of genital organ infections have been kept in background of other pathogens for a long time. Recently, the connection between mycoplasmatic infections and marital infertility has been noticed more often. Nowadays this problem is frequently described in Polish as well as foreign scientific literature. The article is an attempt to introduce the problem of mycoplasmatic infections of urogenital male and female system. Simultaneously, it tries to answer the question whether and how they can be an essential cause of marital infertility.

[A case of Edwards' syndrome in pregnancy complicated by serologic incompatibility and preeclampsia]. / Przypadek zespolu Edwardsa w ciazy powiklanej konfliktem serologicznym oraz stanem przedrzucawkowym.

A case of Edwards' syndrome (trisomy 18) diagnosed in the third pregnancy trimester is described. The diagnosis was based on sonographic examination and cytogenetic amniocentesis. Lethal genetic fetal malformation determined the medical indication to preterm delivery. Additionally, serologic incompatibility during pregnancy was observed, as well as pregnancy induced hypertension turning into preeclampsia after the labour action was evoked. A caesarean section due to obstetric indications was done. Phenotype and lethal congenital malformations in the newborn have confirmed of the chromosome aberration prenatally diagnosed.

[The outcome of pregnancy and delivery in primigravid pregnancy with Kearn-Sayre's syndrome]. / Przebieg ciazy i porodu u pierwiastki z zespolem Kearnsa-Sayre'a.

The Kearn-Sayre's syndrome is an uncommon, non-hereditary disease which belongs to the group of mitochondrial myopathy. The characteristic symptoms of this syndrome often appear before the age of 20. In this report we describe the outcome of primigravid pregnancy of a 33 year old woman with early diagnosed Kearn-Sayre's syndrome.

[Mental disorders during pregnancy and postpartum period--epidemiology, etiology, classification and treatment]. / Zaburzenia psychiczne okoloporodowe--epidemiologia, etiologia, klasyfikacja, leczenie.

The paper presents current knowledge about the prevalence of mental disorders during pregnancy and postpartum period and its' classification. Possible pathomechanisms of its incidence, risk factors and therapeutic possibilities based on the newest research were described.

[Total and ionized magnesium concentration in the blood plasma and erythrocytic magnesium concentration of women in the third trimester of pregnancy with imminent preterm labor]. / Stezenie magnezu calkowitego i zjonizowanego w surowicy krwi oraz magnezu erytrocytarnego w krwinkach czerwonych u kobiet w III trymestrze cia,zy z zagrazajacym porodem przedwczesnym, ciazy prawidlowej oraz u kobiet zdrowych nie ciezarnych.

OBJECTIVES: There are some data concerning magnesium concentration influence on the risk of preterm labor. The estimation of magnesium concentration changes may be useful in prevention of preterm labor. DESIGN: Therefore the aim of our study was to find out the correlation between magnesium concentration and the risk of preterm labor. MATERIALS AND METHODS: Total magnesium concentration and ionized magnesium concentration in blood plasma and erythrocytic magnesium concentration ware examined in the three groups of: 23 women in the third trimester of pregnancy with imminent preterm labor under tocolytic therapy; 20 women in the third trimester of physiologic pregnancy and 19 non-pregnant healthy women in the reproductive age. RESULTS: We discovered statistically confirmed differences (p < 0,05 ) in ionized magnesium concentration as well between the group of women in physiologic pregnancy and non-pregnant women and between the group of pregnant women with imminent preterm labor and non-pregnant women. CONCLUSIONS: Although there were no statistically confirmed differences in total magnesium concentration and erythrocytic magnesium concentration between the three groups of examined women, there were statistically confirmed differences in ionized magnesium concentration between the pregnant and non-pregnant women. Our results suggest that ionized magnesium concentration is better indicator of magnesium balance in human's body than total magnesium concentration.

[Immunosuppressive drug therapy during pregnancy after kidney transplantation]. / Leczenie immunosupresyjne kobiet ciezarnych z przeszczepiona nerka.

The authors expounded present state of knowledge concerning immunosuppressive drugs therapy during pregnancy after kidney transplantation. Pregnancy is uncommon in women with end-stage renal disease treated with dialysis and in most cases it ends with pregnancy failure. Resuming the normal function of the ovaries after kidney transplantation substantially increases the chances of conception and successful pregnancy. The immunosuppression scheme and dosage of drugs used in pregnant women are vital to both the normal course of pregnancy and delivery of a healthy child. Considering the safety of the fetus it is acceptable to use prednisone, azathioprine, cyclosporine and tacrolimus. Due to the necessity to administer immunosuppressive drugs in relatively small doses, an important factor conditioning the normal course of pregnancy is maintaining a 1- or 2-year interval between the kidney transplantation and the conception.

Regulation of cathepsin B and L expression in vitro in gastric cancer tissues by egg cystatin.

BACKGROUND: Degradation of the basement membrane and surrounding extracellular matrix is likely to represent a key step in cancer invasion and metastasis. The purpose of this study was to determine whether gastric cancer tissues demonstrate higher cysteine proteases activities: cathepsins B and L during cancer progression in compression with non-cancerous tissues. METHODS: We measured the expression of both cathepsins B and L in 30 patients with gastric cancer tissues and non-cancerous tissues activities by a fluorescence assay and immunohistochemical staining. We attempted to regulate cathepsin B and L expression using egg white cystatin. RESULTS: The activities of cathepsins B and L were significantly higher in cancerous than in non-cancerous tissues (P

Effects of combined in vivo treatment of transplantable solid mammary carcinoma in wistar rats using vitamin E and cysteine peptidase inhibitors from human placenta.

Cysteine cathepsin B and its endogenous inhibitor play an important role in tumor progression. Increase in cathepsin B expression and reduced levels of its inhibitors were associated with tumor malignancy in breast cancer. The objective of this study was to investigate the effects of a new therapy combining vitamin E and placental inhibitor on the level of endogenous protease inhibitor in sera and tumor tissues with mammary cancer. The inhibitor was used in doses of 100 and 200 micrograms per animal for 8 days. Vitamin E was added after the last treatment with inhibitor and was injected daily in doses of 10 and 20 mg per animal for one mouth. The size and survival time of treated animals as well as cathepsin B and the inhibitor activity in tumor and sera before and after treatment in comparison with the control groups were determined. The activity of cathepsin B significantly decreased both in tumor tissues and in sera (P < or = 0.0001). Cathepsin B activity in tumor tissue homogenates and in sera decreased two-fold and three-fold, respectively, after the animals were treated with vitamin E at a dose of 20 mg, and decreased five-fold and 15-fold, respectively, when treated with vitamin E plus inhibitor in comparison with untreated animals. Endogenous inhibitor activity increased six-fold and 12-fold in the sera and tissue homogenates, respectively, after the animals were treated with 200 micrograms of cysteine protease inhibitor plus 20 mg of vitamin E, in comparison with untreated animals. The total cure responses were higher in eight of 10 rats, as compared with untreated animals. The combination of placental inhibitor and vitamin E resulted in a significant reduction in breast metastasis and might provide a therapeutic basis for anti-metastasis therapy.

Inhibition of cathepsin B activity in human breast cancer tissue by cysteine peptidase inhibitor isolated from human placenta: immunohistochemical and biochemical studies.

Cysteine peptidases and their endogenous inhibitors (CPI) have been shown to be involved in tumor progression and metastasis. Since their activity has been found to be changed in tumor tissue and/or body fluids of cancer patients, the determination of the peptidase/inhibitor levels is considered as a procedure of diagnostic value. Determination of cathepsin B, its precursor and inhibitor activity in homogenates of tumors and control breast tissue samples of patients with invasive ductal and lobular breast carcinoma and with benign breast disease (BBD) was performed using fluorometric assay. Immunohistochemical staining of the breast tissue samples was carried out using polyclonal antibody against cysteine peptidase inhibitor isolated from human placenta. Procathepsin B and cathepsin B were found to be significantly increased and their endogenous inhibitors decreased in homogenates of tumors from patients with breast cancer. A correlation between procathepsin B or cathepsin B activities as well as cysteine peptidase inhibitor activity and the histopathological grading of the tumor was observed. All samples of the tumor tissue showed positive immunostaining with antibody raised against cysteine peptidase inhibitor, while in the control tissue samples the immunostaining was much weaker. Significant difference observed between the activities of cathepsin B and/or its precursor in malignant and benign tumors might serve as a useful clinical indicator in discrimination between benign and invasive tumors.