Publications by authors named "Marek Grabiec"

68 Publications

Assessment of the SFlt-1 and sFlt-1/25(OH)D Ratio as a Diagnostic Tool in Gestational Hypertension (GH), Preeclampsia (PE), and Gestational Diabetes Mellitus (GDM).

Dis Markers 2019 6;2019:5870239. Epub 2019 Aug 6.

Department of Obstetrics and Gynecology, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, ul. Ujejskiego 75, Bydgoszcz 85-168, Poland.

Background: Placental soluble fms-like tyrosine kinase-1 (sFlt-1), an antagonist of vascular endothelial growth factor, is considered an etiological factor of endothelial damage in pregnancy pathologies. An increase in the sFlt-1 level is associated with alterations of endothelial integrity. In contrast, vitamin D exerts a protective effect and low concentrations of 25(OH)D may have an adverse effect on common complications of pregnancy, such as gestational hypertension (GH), preeclampsia (PE), and gestational diabetes mellitus (GDM). The aim of this study was to analyze the levels of sFlt-1 in Polish women with physiological pregnancies and pregnancies complicated by GH, PE, and GDM. Moreover, we analyzed relationships between the maternal serum sFlt-1 level and the sFlt-1 to 25(OH)D ratio and the risk of GH and PE.

Material And Methods: The study included 171 women with complicated pregnancies; among them are 45 with GH, 23 with PE, and 103 with GDM. The control group was comprised of 36 women with physiological pregnancies. Concentrations of sFl-1 and 25(OH)D were measured before delivery, with commercially available immunoassays.

Results: Women with GH differed significantly from the controls in terms of their serum sFlt-1 levels (5797 pg/ml vs. 3531 pg/ml, = 0.0014). Moreover, a significant difference in sFlt-1 concentrations was found between women with PE and those with physiological pregnancies (6074 pg/ml vs. 3531 pg/ml, < 0.0001). GDM did not exert a statistically significant effect on serum sFlt-1 levels. Both logistic regression and ROC analysis demonstrated that elevated concentration of sFlt-1 was associated with greater risk of GH (AUC = 0.70, = 0.0001) and PE (AUC = 0.82, < 0.0001). Also, the sFlt-1 to 25(OH)D ratio, with the cutoff values of 652 (AUC = 0.74, < 0.0001) and 653 (AUC = 0.88, < 0.0001), respectively, was identified as a significant predictor of GH and PE.

Conclusions: Determination of the sFlt-1/25(OH)D ratio might provide additional important information and, thus, be helpful in the identification of patients with PE and GH, facilitating their qualification for intensive treatment and improving the neonatal outcomes.
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http://dx.doi.org/10.1155/2019/5870239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701428PMC
February 2020

Expression of zinc finger transcription factors (ZNF143 and ZNF281) in serous borderline ovarian tumors and low-grade ovarian cancers.

J Ovarian Res 2019 Mar 18;12(1):23. Epub 2019 Mar 18.

Department of Obstetrics and Gynecology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, ul. Ujejskiego 75, 85-168, Bydgoszcz, Poland.

Low-grade ovarian cancers represent up to 8% of all epithelial ovarian carcinomas (EOCs). Recent studies demonstrated that epithelial-mesenchymal transition (EMT) is crucial for the progression of EOCs. EMT plays a key role in cancer invasion, metastasis formation and chemotherapy resistance. An array of novel EMT transcription factors from the zinc finger protein family have been described recently, among them zinc finger protein 143 (ZNF143) and zinc finger protein 281 (ZNF281). The study included tissue specimens from 42 patients. Based on histopathological examination of surgical specimens, eight lesions were classified as serous borderline ovarian tumors (sBOTs) and 34 as low-grade EOCs. The proportions of the ovarian tumors that tested positively for ZNF143 and ZNF281 were 90 and 57%, respectively. No statistically significant differences were found in the expressions of ZNF143 and ZNF281 transcription factors in SBOTs and low-grade EOCs. Considering the expression patterns for ZNF143 and ZNF281 identified in this study, both sBOTs and low-grade EOCs might undergo a dynamic epithelial-mesenchymal interconversion. The lack of statistically significant differences in the expressions of the zinc finger proteins in sBOTs and low-grade serous EOCs might constitute an evidence for common origin of these two tumor types.
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http://dx.doi.org/10.1186/s13048-019-0501-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423742PMC
March 2019

The analysis of human leukocyte antigen-G level in patients with endometrial cancer by Western blot technique.

Am J Reprod Immunol 2019 01 29;81(1):e13070. Epub 2018 Nov 29.

Jagiellonian University Medical College, Kraków, Poland.

Problem: Aberrant expression of human leukocyte antigen-G (HLA-G) in various malignancies has been shown to participate in tumour development by suppressing immune regulation within the tumour microenvironment. The detection of HLA-G has reportedly been correlated with certain clinicopathological parameters in several neoplasms. Both the soluble and membranous forms of HLA-G are biologically active, and therefore, we aimed to evaluate the HLA-G level by Western blot technique.

Method Of Study: The total amount of HLA-G protein was analyzed in the primary tumour in 113 tissue samples derived from patients with endometrial cancer. The HLA-G protein level was measured by Western Blot technique and was analyzed with respect to the clinicopathological parameters.

Results: Human leukocyte antigen-G protein levels were statistically significantly higher in the cancerous tissues derived from the women with advanced endometrial cancer than those from women with early stage disease. Moreover, we showed that endometrial cancer patients with lymph node metastases had statistically significantly higher HLA-G levels in the primary uterine tumour.

Conclusion: The aberrant expression of HLA-G antigens by malignant cells could be one of the strategies tumour cells use to escape immune surveillance. The presence of HLA-G within the cancer nest and its microenvironment would seem to be linked to disease progression.
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http://dx.doi.org/10.1111/aji.13070DOI Listing
January 2019

Expression of selected epithelial-mesenchymal transition transcription factors in serous borderline ovarian tumors and type I ovarian cancers.

Tumour Biol 2018 Jun;40(6):1010428318784807

1 Department of Obstetrics and Gynecology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.

Epithelial ovarian neoplasms are a heterogeneous group including tumor subsets with distinct clinicopathologic and molecular features. Recent evidence from molecular and genomic studies suggests that whereas low-grade serous carcinomas and high-grade serous carcinomas likely develop on two separate pathways, the low-grade serous carcinomas and serous borderline ovarian tumors may represent various stages of the same developmental continuum. The transformation of borderline ovarian tumors into an invasive neoplasm is associated with an array of molecular changes, inter alia controlled by p53 and PI3K/Akt pathway, as well as with a decrease in E-cadherin expression. The latter implies that epithelial-mesenchymal transition is a critical determinant of borderline ovarian tumor invasiveness. The aim of this study was to analyze the expression of transcription factors involved in epithelial-mesenchymal transition: SNAIL, SLUG, TWIST 1, TWIST 2, ZEB 1, and ZEB 2 in borderline tumors and type I ovarian cancers. The study included tissue specimens from 42 patients with histopathologically verified ovarian masses. The expressions for SLUG, TWIST 1, ZEB1, and ZEB 2 were scored based on the nuclear staining, and the expressions of SNAIL and TWIST 2 based on the cytoplasmic and/or nuclear staining. The proportions of ovarian tumors with the immunoexpression of the epithelial-mesenchymal transition transcription factors were 85.7% for SNAIL, 100% for SLUG, 9.5% for TWIST 1, 95.2% for TWIST 2, 23.8% for ZEB 1, and 0% for ZEB 2. The expression patterns of SNAIL, SLUG, TWIST, and ZEB identified in this study suggest that both serous borderline ovarian tumors and type I ovarian cancers undergo dynamic epithelial-mesenchymal interconversions. Our findings obtained in the two groups of tumors which shared some etiopathogenic pathways imply that the expression of the epithelial-mesenchymal transition transcription factors may be activated at early stages of the epithelial-mesenchymal transition, and thus these molecules may play a pivotal role in the development of both serous borderline ovarian tumors and type I ovarian cancer.
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http://dx.doi.org/10.1177/1010428318784807DOI Listing
June 2018

Why do patients decline amniocentesis? Analysis of factors influencing the decision to refuse invasive prenatal testing.

BMC Pregnancy Childbirth 2018 May 16;18(1):174. Epub 2018 May 16.

Department of Obstetrics and Gynecology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University of Torun, ul. Ujejskiego 75, 85-168, Bydgoszcz, Poland.

Background: In recent years, determination of personalized risk for fetal chromosomal anomalies emerged as an important component of prenatal genetic counseling. Women in whom fetal risk for chromosomal aberrations is elevated are offered further testing. The aim of this study was to identify factors that may influence the decision to refuse invasive prenatal testing aimed at determination of fetal karyotype in a group of patients at increased risk of trisomy 21.

Methods: The analysis included 177 patients with singleton pregnancy, whose personalized risk score for trisomy 21 calculated on the basis of the combined test exceeded 1:300. Diagnostic amniocentesis was performed in 125 patients from this subset, since the remaining 52 women declined invasive prenatal testing. The following factors were analyzed as potential determinants of the decision to refuse amniocentesis: maternal age (≥35 years), gravidity, number of miscarriages in previous pregnancies, educational status, marital status, indications to prenatal testing, gestational age at the time of prenatal testing, personalized risk score for fetal chromosomal aberrations and nuchal translucency (NT) value.

Results: A statistically significant relationship was found between the decision to refuse amniocentesis and the number of previous miscarriages, maternal educational level, NT values and personalized risk score for fetal chromosomal aberrations. Multivariate logistic regression analysis identified primary maternal education and history of more than two miscarriages as independent significant predictors of declining amniocentesis. Women with personalized risk scores for trisomy 21 greater than 1:100 opted out of invasive prenatal diagnosis significantly less often than the remaining participants.

Conclusion: In conclusion, the key role of high quality and accuracy of non-invasive diagnostic tests conducted in the first trimester should be emphasized as personalized risk score for fetal chromosomal aberrations determined based on their results is pivotal for further management of pregnancy. Equally important is to provide the patients with an accurate and comprehensible information about potential benefits and risks of invasive testing.
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http://dx.doi.org/10.1186/s12884-018-1812-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956945PMC
May 2018

Testing for Mutations in Serous Borderline Ovarian Tumors and Low-Grade Serous Ovarian Carcinomas.

Dis Markers 2018 25;2018:1497879. Epub 2018 Feb 25.

Department of Obstetrics and Gynecology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.

The , performed on the Biocartis Idylla system, is an diagnostic tool for the qualitative assessment of 18 mutations in codons 12, 13, 59, 61, 117, and 146. Low-grade serous ovarian cancer (LGSC) represents less than 10% of all serous ovarian carcinomas. LGSCs are believed to arise from preexisting cystadenomas or serous borderline tumors (SBOTs) that eventually progress to an invasive carcinoma. The molecular analysis of cancer-causing mutations and the development of targeted biological therapies constitute a milestone in the diagnosis and therapy of ovarian malignancies. According to some authors, may be an important oncogene for the progression of SBOT to a frankly invasive disease. The primary aim of this study was to verify if a fully integrated, real-time PCR-based Idylla system can be used for the rapid determination of the mutation status in patients with serous borderline ovarian tumors and low-grade serous ovarian carcinomas. The study included tissue specimens from 12 patients with histopathologically verified ovarian masses, operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz (Poland), between January 2009 and June 2012. The mean age of the study patients was 52.5 years (range 27-80 years). NRAS mutation in codon 13 (G13D, p.Gly13Asp; nucleotide: c.38G>A) was found in one patient, a woman with low-grade serous ovarian carcinoma. To the best of our knowledge, our experiment was the first published study using the novel Idylla NRAS Mutation Test for the evaluation of ovarian tumors in a clinical setting. The Idylla platform is an interesting ancillary first-line rapid and fully automated instrument to detect mutations in SBOTs and LGSCs. However, the clinical usefulness of this method still needs to be verified in larger groups of cancer patients.
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http://dx.doi.org/10.1155/2018/1497879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845515PMC
September 2018

Human Adipose-Derived and Amniotic Fluid-Derived Stem Cells: A Preliminary In Vitro Study Comparing Myogenic Differentiation Capability.

Med Sci Monit 2018 Mar 24;24:1733-1741. Epub 2018 Mar 24.

Department of Oncology, Radiotherapy and Oncological Gynecology, Nicolaus Copernicus University, Bydgoszcz, Poland.

BACKGROUND Around the world, disabilities due to musculoskeletal disorders have increased and are a major health problem worldwide. In recent years, stem cells have been considered to be powerful tools for musculoskeletal tissue engineering. Human adipose-derived stem cells (hADSCs) and amniotic fluid-derived stem cells (hAFSCs) undergo typical differentiation process into cells of mesodermal origin and can be used to treat muscular system diseases. The aim of the present study was to compare the biological characteristic of stem cells isolated from different human tissues (adipose tissue and amniotic fluid) with respect to myogenic capacity and skeletal and smooth muscle differentiation under the same conditions. MATERIAL AND METHODS hAFSCs and hADSCs were isolated during standard medical procedures and widely characterized by specific markers expression and differentiation potential. Both cell types were induced toward smooth and striated muscles differentiation, which was assessed with the use of molecular techniques. RESULTS For phenotypic characterization, both stem cell types were assessed for the expression of OCT-4, SOX2, CD34, CD44, CD45, and CD90. Muscle-specific markers appeared in both stem cell types, but the proportion of positive cells showed differences depending on the experimental conditions used and the source from which the stem cells were isolated. CONCLUSIONS In this study, we demonstrated that hADSCs and hAFSCs have different capability of differentiation toward both muscle types. However, hADSCs seem to be a better source for myogenic protocols and can promote skeletal and smooth muscle regeneration through either direct muscle differentiation or by paracrine mechanism.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882157PMC
http://dx.doi.org/10.12659/msm.905826DOI Listing
March 2018

Molecular diagnosis in type I epithelial ovarian cancer.

Ginekol Pol 2017 ;88(12):692-697

Katedra i Klinika Połoznictwa, Chorób Kobiecych i Ginekologii Onkologicznej Collegium Medicum UMK w Bydgoszczy, ul. Ujejskiego 75, 85-168 Bydgoszcz, Poland.

The term epithelial ovarian cancer (EOC) refers to a heterogeneous group of tumors, including serous, mucinous, endometrioid and clear cell carcinomas, each characterized by specific molecular background and clinical outcome. A growing body of evidence suggests that molecular pathogenesis of ovarian cancer involves two general pathways. The first pathway results in transformation of normal ovarian tissue to borderline tumors, which may further progress to low-grade serous, mucinous, endometrioid and clear cell carcinomas. Tumors from this group are characterized by slow proliferation, and approximately 55% 5-year survival rate. Type I tumors often harbor somatic mutations in protein kinase genes, as well as in genes for other signaling molecules. Both BRAF and KRAS mutations lead to a constitutive activation of their downstream target, mitogen-activated protein kinase. Identification of molecular profile may be crucial for the diagnosis of ovarian tumors, choice of adjuvant targeted therapy after primary cytoreductive treatment, or management of recurrence in patients with advanced type I epithelial ovarian neoplasms. Point mutations in cancer cells can be detected with many various methods. KRAS, NRAS and BRAF mutational status can be determined by Sanger sequencing (still considered a gold standard), as well as using numerous various techniques, such as allele-specific PCR, single nucleotide primer extension assays, pyrosequencing, real-time PCR, high-resolution melting curve analysis, amplification refractory mutation system, strip or chip assay combining PCR followed by hybridization to a KRAS or NRAS-specific probe, next-generation sequencing (NGS), and matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Application of direct sequencing as a routine method for cytological diagnosis used in a hospital setting requires expensive equipment and implementation of complicated procedures. Another factor limiting application of this method in everyday clinical practice are long analytical times. This stimulated search for a simple, rapid, specific and sensitive methodology to detect point mutations. Recently, some new molecular assays for the detection of BRAF, KRAS and NRAS mutations have become available. These are fully-automated molecular diagnostic systems for quantitative allele-specific RT-PCR-based analyses. Using this instrument, even pathologists from less experienced laboratories can easily integrate morphological findings with molecular data being crucial for further diagnostic and therapeutic decisions.
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http://dx.doi.org/10.5603/GP.a2017.0123DOI Listing
July 2018

Obstetric outcomes of pre-induction of labor with a 200 μg misoprostol vaginal insert.

Ginekol Pol 2017 ;88(11):606-612

Department of Obstetrics and Gynecology, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Bydgoszcz, Poland, Poland.

Objectives: Labor induction is indicated in 20% to 40% of pregnancies. Over half of pregnancies qualified for the induction of labor require stimulation of the cervix to ripen. The drug used increasingly more often in pre-induction is the PGE-1 pros-taglandin analog - misoprostol 200 μg.

Material And Methods: The study includes a total of 100 patients qualified for labor pre-induction with Misodel® (miso-prostol 200 μg vaginal insert). The study group comprises two subgroups: primigravidas and multiparas. Assessments included: indications for labor pre-induction, time from Misodel application to delivery, caesarean section rate and indica-tions, duration of first and second stage of labor, rate of vaginal deliveries, need for oxytocin or fenoterol administration side effects and newborn condition.

Results: The most common indication for labor induction was gestational diabetes and pregnancy past term. The average time to vaginal delivery was 14 h 45 min, time to the onset of active phase of labor - 11 h 45 min, time to membranes' rupture - 15 h, time to vaginal delivery - 14 h 18 min. The times of multiparas were significantly shorter. The rate of vaginal deliveries within 12 hours amounted to 42.42%, while within 24 hours it reached 83.33%. The overall caesarean section rate was 33%. The most common indication for caesarean section was the risk of intrauterine hypoxia. Tachysystole and hyperstimulation was observed in 4% of cases, while abnormalities in the cardiotocographic tracing in 43%.

Conclusions: Misodel is an effective method for labor pre-induction, without affecting the caesarean section rate and has no adverse effect on the newborn condition.
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http://dx.doi.org/10.5603/GP.a2017.0109DOI Listing
July 2018

KRAS mutation testing in borderline ovarian tumors and low-grade ovarian carcinomas with a rapid, fully integrated molecular diagnostic system.

Tumour Biol 2017 Oct;39(10):1010428317733984

1 Department of Obstetrics and Gynecology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.

Epithelial ovarian neoplasms are a heterogeneous group of tumors, including various malignancies with distinct clinicopathologic and molecular features. Mutations in BRAF and KRAS genes are the most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous and mucinous borderline tumors. Implementation of targeted therapeutic strategies requires access to highly specific and highly sensitive diagnostic tests for rapid determination of mutation status. One candidate for such test is fully integrated, real-time polymerase chain reaction-based Idylla™ system for quick and simple detection of KRAS mutations in formaldehyde fixed-paraffin embedded tumor samples. The primary aim of this study was to verify whether fully integrated real-time polymerase chain reaction-based Idylla system may be useful in determination of KRAS mutation status in patients with borderline ovarian tumors and low-grade ovarian carcinomas. The study included tissue specimens from 37 patients with histopathologically verified ovarian masses, operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz (Poland) between January 2009 and June 2012. Based on histopathological examination of surgical specimens, 30 lesions were classified as low-grade ovarian carcinomas and 7 as borderline ovarian tumors. Seven patients examined with Idylla KRAS Mutation Test tested positive for KRAS mutation. No statistically significant association was found between the incidence of KRAS mutations and histopathological type of ovarian tumors. Mean survival of the study subjects was 48.51 months (range 3-60 months). Presence of KRAS mutation did not exert a significant effect on the duration of survival in our series. Our findings suggest that Idylla KRAS Mutation Test may be a useful tool for rapid detection of KRAS mutations in ovarian tumor tissue.
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http://dx.doi.org/10.1177/1010428317733984DOI Listing
October 2017

Determination of BRAF V600E (VE1) protein expression and BRAF gene mutation status in codon 600 in borderline and low-grade ovarian cancers.

Tumour Biol 2017 May;39(5):1010428317706230

1 Department of Obstetrics and Gynecology, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Bydgoszcz, Poland.

Epithelial ovarian tumors are a group of morphologically and genetically heterogeneous neoplasms. Based on differences in clinical phenotype and genetic background, ovarian neoplasms are classified as low-grade and high-grade tumor. Borderline ovarian tumors represent approximately 10%-20% of all epithelial ovarian masses. Various histological subtypes of ovarian malignancies differ in terms of their risk factor profiles, precursor lesions, clinical course, patterns of spread, molecular genetics, response to conventional chemotherapy, and prognosis. The most frequent genetic aberrations found in low-grade serous ovarian carcinomas and serous borderline tumors, as well as in mucinous cancers, are mutations in BRAF and KRAS genes. The most commonly observed BRAF mutation is substitution of glutamic acid for valine in codon 600 (V600E) in exon 15. The primary aim of this study was to determine whether fully integrated, real-time polymerase chain reaction-based Idylla™ system may be useful in determination of BRAF gene mutation status in codon 600 in patients with borderline ovarian tumors and low-grade ovarian carcinomas. The study included tissue specimens from 42 patients with histopathologically verified ovarian masses, who were operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz (Poland). Based on histopathological examination of surgical specimens, 35 lesions were classified as low-grade ovarian carcinomas, and 7 as borderline ovarian tumors. Specimens with expression of BRAF V600E (VE1) protein were tested for mutations in codon 600 of the BRAF gene, using an automated molecular diagnostics platform Idylla™. Cytoplasmic immunoexpression of BRAF V600E (VE1) protein was found in three specimens: serous superficial papilloma, serous papillary cystadenoma of borderline malignancy, and partially proliferative serous cystadenoma. All specimens with the expression of BRAF V600E (VE1) protein were tested positively for BRAF V600E/E2/D mutation. No statistically significant relationship (p > 0.05) was found between the presence of BRAF V600E mutation and the probability of 5-year survival. BRAF mutation testing with a rapid, fully integrated molecular diagnostics system Idylla™ may be also a powerful prognostic tool in subjects with newly diagnosed serous borderline tumors, identifying a subset of patients who are unlikely to progress.
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http://dx.doi.org/10.1177/1010428317706230DOI Listing
May 2017

Serum 25(OH) Vitamin D Levels in Polish Women during Pregnancies Complicated by Hypertensive Disorders and Gestational Diabetes.

Int J Mol Sci 2016 Sep 27;17(10). Epub 2016 Sep 27.

Department of Obstetrics and Gynecology, L. Rydygier Collegium in Bydgoszcz, Nicolaus Copernicus University, ul. Ujejskiego 75, Bydgoszcz 85-168, Poland.

Background: An association between the level of vitamin D and the risk of pregnancy-related complications remains unclear. The aim of this study was to examine concentrations of 25(OH) vitamin D in Polish women with normal pregnancies and pregnancies complicated by gestational hypertension, preeclampsia or gestational diabetes mellitus (GDM). Moreover, we analyzed an association between maternal serum 25(OH)D and the risk of gestational hypertension, preeclampsia and GDM.

Material And Methods: The study included 207 pregnant women, among them 171 with pregnancy-related complications: gestational hypertension ( = 45), preeclampsia ( = 23) or GDM ( = 103). The control group consisted of 36 women with normal pregnancies. Concentrations of serum 25(OH)D were measured at admission to the hospital prior to delivery Results: Patients with hypertension did not differ significantly from the controls in terms of their serum 25(OH)D concentrations (18.20 vs. 22.10 ng/mL, = 0.15). Highly significant differences were found in 25(OH)D concentrations of women with preeclampsia and the controls (14.75 vs. 22.10 ng/mL, = 0.0021). GDM was not associated with significant differences in 25(OH)D concentration. A low level of 25(OH)D turned out to be associated with an increased risk of preeclampsia during pregnancy on both univariate and multivariate regression analysis, and was a significant predictor of this condition on ROC (receiver operating characteristic) analysis (AUC = 0.70, < 0.01).

Conclusions: 25(OH)D deficiency is common among pregnant Polish women. Low concentrations of 25(OH)D may play a role in the etiopathogenesis of preeclampsia. Routine assessment of the 25(OH)D level during pregnancy may be crucial for the identification of women at increased risk of preeclampsia.
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http://dx.doi.org/10.3390/ijms17101574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085625PMC
September 2016

Prenatal Clinical Assessment of NT-proBNP as a Diagnostic Tool for Preeclampsia, Gestational Hypertension and Gestational Diabetes Mellitus.

PLoS One 2016;11(9):e0162957. Epub 2016 Sep 29.

Department of Obstetrics and Gynecology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University of Torun, Torun, Poland.

Common complications of pregnancy include preeclampsia (PE), gestational hypertension (GH) and gestational diabetes mellitus (GDM). Hypertensive disorders (PE/GH) and GDM may result in greater maternal, fetal and neonatal morbidity and mortality. Women with PE/GH, one of the most common causes of heart burden in an obstetrical setting, present with elevated serum levels of BNP and NT-proBNP. The aim of this study was to shed more light on the role of NT-proBNP in pathophysiology of PE, GH and GDM. The study included 156 pregnant women with singleton pregnancies. A total of 26 women developed arterial hypertension during pregnancy, 14 were diagnosed with PE, and GDM was detected in 81 patients. The control group included 35 women with uncomplicated pregnancies, normal arterial blood pressure and normal glucose concentrations. Patients with GH presented with significantly higher serum concentrations of NT-proBNPthan normotensive women (65.5 vs. 37.4 pg/ml; p = 0.0136). Serum levels of NT-proBNP in patients with PE were the highest of all the analyzed subsets, being significantly higher than in women without this condition (89.00 vs. 37.4pg/ml,p = 0,0136). However, women with and without GDM did not differ significantly in terms of their serum NT-proBNPconcentrations. Serum NT-proBNP (pg/ml) (p = 0.0001) and BMI (p<0.0001) turned out to be independent predictors of GH on multivariate logistic regression analysis.Moreover, serum NT-proBNP (pg/ml) was identified as an independent indicator of PE (p = 0.0016). A significant inverse correlation was found between birth weight and maternal serum NT-proBNP concentrations. In our opinion, NT-proBNP can be a useful clinical marker of GH and PE. Determination of NT-proBNP levels may be helpful in identification of patients with PE and GH and in their qualification for intensive treatment; this in turn, may be reflected by better neonatal outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0162957PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042470PMC
September 2016

High Quality Independent From a Donor: Human Amniotic Fluid Derived Stem Cells-A Practical Analysis Based on 165 Clinical Cases.

J Cell Biochem 2017 01 28;118(1):116-126. Epub 2016 Jun 28.

Department of Tissue Engineering, Nicolaus Copernicus University, Bydgoszcz, 85-092, Poland.

The aim of the study was to extend the potential use of human stem cells isolated from amniotic fluid in medical applications by confirming their high homogeneity and quality. Amniotic fluid samples were collected during amniocentesis from 165 women during pregnancy. The proliferation rate, clonogenicity, karyotype, aging process, pluripotent cell markers, expression of surface markers, and the potential to differentiate into adipose, bone and cartilage cells of hAFSCs were analyzed. Obtained results revealed that mesenchymal stem cells could be derived successfully from amniotic fluid, which exhibit properties comparable with MSCs of other origins. It is the first study, in which such a large group of patients was involved. Comprehensive statistical and biological analysis were conducted some of which clearly being innovative in relation to human amniotic fluid-derived stem cells. J. Cell. Biochem. 118: 116-126, 2017. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jcb.25618DOI Listing
January 2017

[Evaluation of carbetocin and oxytocin efficacy in prevention of postpartum hemorrhage in women after cesarean section].

Ginekol Pol 2015 Sep;86(9):689-93

Introduction: Postpartum hemorrhage (PPH) constitutes the main cause of delivery-related maternal mortality worldwide. Identification of the risk factors, as well as knowledge about preventive measures and adequate management, allow to limit blood loss. Oxytocin, carbetocin, methylergometrine, dinoprostone, suiprostone, and misoprostol are commonly used drugs in prevention of PPH.

Objectives: The aim of the study was to evaluate the efficacy of carbetocin and oxytocin in prevention of PPH after cesarean section.

Material And Methods: The study included 130 female patients after C-section who received 1 00 pg of carbetocin i.v. as a preventive agent after the surgery The control group consisted of 60 women who received 10 units of oxytocin i.v. In the study the risk factors for PPH were determined, and hemoglobin and hematocrit values before and 12 hours after birth, as well as blood loss and the need to use other prevyentfive and operational methods were evaluated. Results were compared between the groups. Statistical analysis was performed with the use of Statistica for hemoglobin and hematocrit values. The p-value of < or = 0.05 was considered as statistically significant.

Results: Risk factors for PPH occurred in almost 100% of the women with carbetocin and in 90% of the women with oxytocin. The decrease in hemoglobin and hematocrit levels was not statistically significant, although a greater drop was detected in the group with oxytocin (hemoglobin - 1.24 vs. 1.17 g%, hematocrit - 3.26 vs. 2.93%). The decrease in hematological values was not statistically significant between both groups. In the group with'carbetocin, there was no need for additional pharmacological therapy or operative procedures. No adverse events in either of the groups were observed.

Conclusions: (1.) Carbetocin effectively prevents PPH after C-section. (2.) Carbetocin seems to have high efficiency in PPH prevention in pregnant women classified to the PPH risk group. (3.) Efficacy of Carbetocin in PPH prevention is higher than oxytocin.
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September 2015

Gestational diabetes mellitus worsens the profile of cardiometabolic risk markers and decrease indexes of beta-cell function independently of insulin resistance in nondiabetic women with a parental history of type 2 diabetes.

J Diabetes Res 2014 6;2014:743495. Epub 2014 Jul 6.

Department of Pathophysiology, Nicolaus Copernicus University, Dr. A. Jurasz University Hospital, Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland.

Background: Women with a history of both parental type 2 diabetes (pt2DM) and previous gestational diabetes (pGDM) represent a group at high risk of cardiovascular events. We hypothesized that pGDM changes cardiometabolic risk markers levels as well as theirs associations with glucose indices in nondiabetic pt2DM women.

Methods: Anthropometric parameters, glucose regulation (OGTT), insulin resistance (HOMA-IR), beta-cell function, lipid levels, parameters of endothelial dysfunction, and inflammation were evaluated in 55 women with pt2DM, 40 with both pt2DM and pGDM 2-24 months postpartum, and 35 controls.

Results: Prediabetes was diagnosed more frequently in women with both pt2DM and pGDM in comparison with women with only pt2DM (10 versus 8, P = 0.04). The pGDM group had higher LDL-cholesterol, sICAM-1, tPa Ag, fibrinogen, and lower beta-cell function after adjustment for HOMA-IR, in comparison with pt2DM group. In pt2DM group postchallenge glucose correlated independently with hsCRP and in pGDM group fasting glucose with HOMA-IR.

Conclusions: pGDM exerts a combined effect on cardiometabolic risk markers in women with pt2DM. In these women higher LDL-cholesterol, fibrinogen, sICAM-1, tPa Ag levels and decreased beta cell function are associated with pGDM independently of HOMA-IR index value. Fasting glucose is an important cardiometabolic risk marker and is independently associated with HOMA-IR.
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http://dx.doi.org/10.1155/2014/743495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4109116PMC
April 2015

[Indications for genetic amniocentesis investigated at the Department of Gynecology, Obstetrics, and Oncologic Gynecology, Nicolaus Copernicus University, Collegium Medicum, Bydgoszcz].

Ginekol Pol 2014 Jun;85(6):420-3

Introduction: Genetic amniocentesis (GA) is the most common prenatal diagnostic test. One of the main indications for GA is maternal age of > or = 35 years. In many countries, the age indication has been replaced by an assessment of individual risk for chromosomal abnormalities, calculated on the basis of maternal age, pregnancy duration, as well as a combination of biochemical and ultrasound markers.

Objectives: The aim of the study was to investigate indications for and results of GA performed between 2010-2012 at the Department of Gynecology Obstetrics, and Oncologic Gynecology Nicolaus Copernicus University Collegium Medicum, Bydgoszcz.

Materials And Methods: A total of 632 GA tests were performed at the Department of Gynecology Obstetrics, and Oncologic Gynecology Nicolaus Copernicus University Collegium Medicum, Bydgoszcz. Average maternal age was 34 (between 17 and 47 years), with patients < 35 constituting 47.9% (N = 303), and patients > or = 35 constituting 52.1% (N = 329) of the investigated group. Indications for GA as well as test results were analyzed in relation to maternal age. The result of earlier non-invasive tests were also analyzed.

Results: Abnormal ultrasound findings, combined with abnormal first-trimester screening results, were the most common indication (46.53%) for GA in patients < 35 years, whereas abnormal first-trimester screening results, combined with a history of obstetric complications, were the reason for GA in patients > or = 35 years. Mean time of GA was 16 gestational weeks in both groups. Abnormal karyotype was detected in 74 (11.7%) cases. 13 or any other abnormal karyotypes occurrence were observed in both age groups. GA-related complications (miscarriage/intrauterine fetal death) occurred in 9 (1.42%) cases.

Conclusions: If performed properly GA between 15 and 20 weeks of pregnancy is a harmless procedure both, for the mother and the fetus, associated with an acceptable complication rate. Prenatal screening for the most common malformations and chromosomal aberrations should be offered to all pregnant women in Poland, regardless of their age.
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June 2014

[Clinical study of perinatal hysterectomy between 2000-2011 in the clinic of obstetrics, gynecological diseases and oncological gynecology in Bydgoszcz].

Ginekol Pol 2014 Mar;85(3):192-6

Introduction: Perinatal hysterectomy (PH) is usually a life-saving procedure, which is performed after all conservative treatment options fail. The PH frequency rate ranges from 0.04 to 0.23%. The most frequent indications for this procedure include: abnormal placental implantation, placenta previa, uterine rupture and uterine atony

Objective: Clinical study of perinatal hysterectomy cases taking into consideration the frequency indications, complications and risk factors related to this procedure.

Materials And Methods: The study included 16 women who underwent perinatal hysterectomy at the Department and Clinic of Obstetrics and Gynecological Diseases between 2000-2011. The following data were collected from medical records: course of pregnancy labor and puerperium. The profile of the study group was conducted in terms of: maternal age, parity gestation length, history of caesarean sections and gynecological operations. The following factors were studied: the termination of pregnancy, indications for caesarean section, hysterectomy-related complications and indications, neonatal birth weight and Apgar score. The statistical analysis was performed using Statistica 9.1 by StatSoft. Data are expressed as the arithmetic mean and standard deviation (SD).

Results: Sixteen perinatal hysterectomy procedures were performed, accounting for 0.066% of the overall number of labors. Average maternal age and pregnancy length were 31.6 years [SD+/-6.3] and 36.1 weeks of gestation [SD+/-3.4], respectively PH was more frequently performed among multiparous women (81.25%) and after caesarean sections (87.5%). Fetal asphyxia was the most frequent indication for caesarean section (35.7%). Fourteen percent of all indications accounted for the lack of consent from a pregnant woman to make an attempt at spontaneous vaginal delivery after previous c-section. Fifty percent of the women from the study group had a previous caesarean section, whereas 25% had more than one prior c-section. Between 2009-2011, as compared to previous years, the highest percentage of hysterectomies (80%) was reported in pregnant women after a previous caesarean section. The most frequent indication for hysterectomy included abnormal placental implantation (43.75%) diagnosed more often in patients with a history of caesarean section (57%). Among PH complications, a hemorrhagic shock was reported in 37.4% and bladder injury in 18.7% of the women. Every patient required a transfusion of erythrocyte concentrate, 4.7 units [SD+/-3.5] on average. Twenty-five percent of the neonates were born in poor condition with an Apgar score of 1-3. In case of all women, the therapy required cooperation of different specialists including obstetricians, anesthesiologists, urologists, surgeons and general practitioners.

Conclusions: 1. Current and previous caesarean section constitutes a risk factor for perinatal hysterectomy 2. Placental pathology is the most frequent indication for perinatal hysterectomy 3. The growing number of caesarean sections should encourage obstetricians to conduct a more careful analysis of indications.
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http://dx.doi.org/10.17772/gp/1712DOI Listing
March 2014

The role of Hypoxia-inducible factor-1 α , glucose transporter-1, (GLUT-1) and carbon anhydrase IX in endometrial cancer patients.

Biomed Res Int 2014 12;2014:616850. Epub 2014 Mar 12.

Department of Obstetrics and Gynecology, The Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University of Torun, Ulica Ujejskiego 75, 85-168 Bydgoszcz, Poland.

Hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1), and carbon anhydrase IX (CAIX) are important molecules that allow adaptation to hypoxic environments. The aim of our study was to investigate the correlation between HIF-1α, GLUT-1, and CAIX protein level with the clinicopathological features of endometrial cancer patients. Materials and Methods. 92 endometrial cancer patients, aged 37-84, were enrolled to our study. In all patients clinical stage, histologic grade, myometrial invasion, lymph node, and distant metastases were determined. Moreover, the survival time was assessed. Immunohistochemical analyses were performed on archive formalin fixed paraffin embedded tissue sections. Results. High significant differences (P = 0.0115) were reported between HIF-1α expression and the histologic subtype of cancer. Higher HIF-1α expression was associated with the higher risk of recurrence (P = 0.0434). The results of GLUT-1 and CAIX expression did not reveal any significant differences between the proteins expression in the primary tumor and the clinicopathological features. Conclusion. The important role of HIF-1α in the group of patients with the high risk of recurrence and the negative histologic subtype of the tumor suggest that the expression of this factor might be useful in the panel of accessory pathomorphological tests and could be helpful in establishing more accurate prognosis in endometrial cancer patients.
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http://dx.doi.org/10.1155/2014/616850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972900PMC
December 2014

The preoperative maximum standardized uptake value measured by 18F-FDG PET/CT as an independent prognostic factor of overall survival in endometrial cancer patients.

Biomed Res Int 2014 20;2014:234813. Epub 2014 Jan 20.

Department of Obstetrics and Gynecology, The Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University of Torun, Ujejskiego 75, 85-168 Bydgoszcz, Poland.

Purpose: The aim of this study was to determine if the preoperative maximum standardized uptake value (SUVmax) measured by 18F-FDG PET/CT in the primary tumor has prognostic value in the group of patients with endometrial cancer.

Patients, Materials, And Methods: A total of one hundred one consecutive endometrial cancer patients, age range 40-82 years (mean 62 years) and FIGO I-IV stage, who underwent 18-FDG-PET/CT within two weeks prior radical surgery, were enrolled to the study. The maximum SUV was measured and compared with the clinicopathologic features of surgical specimens. The relationship between SUVmax and overall survival was analyzed.

Results: The mean preoperative SUVmax was 14.34; range (3.90-33.80) and was significantly lower for FIGO I than for higher stages (P = 0.0012), as well as for grade 1 than for grade 2 and 3 (P = 0.018), deep myometrial invasion (P = 0.0016) and for high risk group (P = 0.0004). The analysis of survival ROC curve revealed SUVmax cut-off value of 17.7 to predict high risk of recurrence. Endometrial cancer patients with SUVmax higher than 17.7 characterized by lower overall survival.

Conclusion: The preoperative SUVmax measured by 18F-FDG PET/CT is considered as an important indicator reflecting tumor aggressiveness which may predict poor prognosis. High value of SUVmax would be useful for making noninvasive diagnoses and deciding the appropriate therapeutic strategy for patients with endometrial cancer.
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http://dx.doi.org/10.1155/2014/234813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956283PMC
December 2014

Human amniotic-fluid-derived stem cells: a unique source for regenerative medicine.

Expert Opin Biol Ther 2014 Jun 22;14(6):831-9. Epub 2014 Mar 22.

Nicolaus Copernicus University, Department of Tissue Engineering , Karlowicza 24, 85-092 Bydgoszcz , Poland +48 525853737 ; +48 525853742 ;

Introduction: The first application of tissue engineering was based on the use of differentiated cells from the adult organism, which was associated with an invasiveness and high risk of diseased cells' transplantation. Over the years, the range of available cell populations for tissue engineering has widened.

Areas Covered: We review the comprehensive information concerning the characteristic features of amniotic-fluid-derived stem cells (AFSCs). We also review the potential applications of these cells in clinical practice.

Expert Opinion: AFSCs hold promise for the future treatment of many incurable diseases. However, such cell-based therapies have some limitations, and there are questions relating to the use of stem cells, which should be carefully analyzed before translation of these cells into clinical practice.
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http://dx.doi.org/10.1517/14712598.2014.898749DOI Listing
June 2014

Serum inhibin A and inhibin B levels in epithelial ovarian cancer patients.

PLoS One 2014 5;9(3):e90575. Epub 2014 Mar 5.

Department of Obstetrics and Gynecology, L.Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Bydgoszcz, Poland.

The Aim: of our study was to examine serum inhibin A and inhibin B concentrations in ovarian cancer patients in relation to clinicopathological features and 5-year survival.

Material And Methods: We enrolled 90 epithelial ovarian cancer patients in our study, aged 45-81 years, who underwent optimal cytoreductive surgery. In all patients, serum inhibin A and inhibin B concentrations were measured using a two-step sandwich type enzyme immunoassay before surgery.

Results: In the group of patients with ovarian cancer median serum concentration of inhibin A was 3.87 pg/mL (0.96-10.09) and inhibin B was 13.9 pg/mL (5.1-45.0). Median concentrations of inhibin A and B in relation to FIGO stage and histological subtype did not differ significantly. Inhibin A levels were significantly higher in patients with lower grading (G1 and G2) in comparison to those with higher grade G3 (p=0.001). There were no differences in inhibin B concentrations in relation to grading. The Kaplan-Meier analyses demonstrated no differences in survival rate in relation to inhibin A levels, while there was a stepwise impairment of 5-years survival with increased inhibin B level. In the group of patients with inhibin B levels higher than 20 pg/ml the survival rate was lower (p=0,00625, log-rank test).

Conclusion: 1. Higher inhibin A serum levels were found in patients with highly differentiated ovarian carcinoma compared to the group of patients with a poorly differentiated cancer, which may confirm the influence of inhibin A on cell proliferation processes. 2. A significant importance of inhibin B was demonstrated in the prediction of death within less than a five year period. The probability of survival in patients featuring high inhibin B levels was lower with statistical significance. This may indicate the need for further studies on how to block the inhibin B activation pathway in the ovarian carcinoma therapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0090575PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944095PMC
January 2015

Stromal derived factor-1 (SDF-1) and its receptors CXCR4 and CXCR7 in endometrial cancer patients.

PLoS One 2014 9;9(1):e84629. Epub 2014 Jan 9.

Department of Obstetrics and Gynecology, The Ludwik Rydygier Collegium Medicum in Bydgoszcz, the Nicolaus Copernicus University of Torun, Bydgoszcz, Poland.

Purpose: One of the most important function of stromal derived factor-1 (SDF-1) and its receptors, is regulating the process of metastasis formation. The aim of our study was to investigate the correlation between SDF-1, CXCR4 and CXCR7 protein levels measured by immunohistochemistry with the clinicopathological features and the survival of endometrial cancer patients.

Materials And Methods: 92 patients aged 37-84 (mean 65.1±9.5) were enrolled to our study between January 2000 and December 2007. After the diagnosis of endometrial cancer, all women underwent total abdominal hysterectomy, with bilateral salpingoophorectomy and pelvic lymph node dissection. In all patients clinical stage (according to FIGO classification), histologic grade, myometrial invasion, lymph node and distant metastases were determined.Furthermore, the survival time was assessed. Immunohistochemical analyses of SDF-1, CXCR4 and CXCR7 were performed on archive formalin fixed paraffin embedded tissue sections.

Results: Statistically significant correlations (p<0.01) were reported between SDF-1 and the clinical stage of disease, lymph node metastases, distant metastases, deep myometrial invasion (≥50%), cervical involvement, involvement of adnexa. Statistically significant correlation (p<0.01) was found between SDF-1 expression and the risk of the recurrence. Higher SDF-1 expression was associated with a higher risk of recurrence (p = 0.0001). The results of CXCR4 and CXCR7 expression didn't reveal any significant differences(p>0.05) between the proteins expression in the primary tumor cells and the clinicopathological features. Moreover, the Kaplan-Meier analyses demonstrated a stepwise impairment of cancer overall survival (OS) with increasing SDF-1 expression.

Conclusion: The important role of SDF-1 as a predictor of negative clinicopathological characteristics of a tumor suggests that the expression of this stromal factor should be included in the panel of accessory pathomorphological tests and could be helpful in establishing a more accurate prognosis in endometrial cancer patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084629PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887002PMC
September 2014

Analysis of serum protein fractions from women with recurrent miscarriage.

Ginekol Pol 2013 Oct;84(10):851-6

Department of Laboratory Medicine, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Poland.

Unlabelled: Recurrent miscarriage occurs in 1-5% of women at reproductive age. The most common cause of recurrent miscarriage is chromosomal abnormalities of the embryo (41%), chromosomal aberrations parents (10%), anatomical abnormalities of the uterus (5%), infectious and hormonal factors. In about 25% of women, no cause of recurrent miscarriage is usually found. Therefore it seems important to study all factors possibly inducing pregnancy disorders.

Objective: The aim of this study was to find a difference in serum protein fractions between women with primary and secondary recurrent miscarriage.

Methods: The study group consisted of 52 women (aged 36.0 +/- 4.9) with recurrent miscarriage. Nine of them (17%) reported one earlier regular pregnancy ending with childbirth without complications. Control group comprised 30 non-pregnant women (aged 36.1 +/- 3.6), who had given vaginal birth to healthy children at least twice. Serum protein fractions were separated by electrophoresis in the SDS PAGE buffer system using a Mini PROTEAN 3 cell device. BioRad SDS PAGE Molecular Weight Standards covering mass range of 6.5-200 kDa were used as a reference. Gels were stained with Coomassie Blue R 250 solution. BioRad QuantityOne software was used for the assessment of molecular weight of each protein fraction.

Results: Electrophoretic separation revealed 39 protein fractions of 10,243 kDa. Particularly interesting was a 38 kDa fraction present exclusively in serum of women with recurrent pregnancy who had never given birth. Another fraction (74 kDa), not detected in the control group, was found in all women with recurrent pregnancy loss. Protein fractions of 76 and 151 kDa were present only in the control group.

Conclusions: The presence of the protein fractions of low- or mid-weight in serum from women with recurrent miscarriage may potentially play a role in the pathomechanism of this disorder
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http://dx.doi.org/10.17772/gp/1651DOI Listing
October 2013

[SUVmax measured by 18F FDG PET/CT in the primary tumor in relation to clinical and pathological features of endometrial cancer].

Ginekol Pol 2013 Sep;84(9):748-53

Katedra Połoznictwa, Chorób Kobiecych i Ginekologii Onkologicznej, Collegium Medicum w Bydgoszczy, Uniwersytet Mikołaja Kopernika w Toruni, Polska.

The Aim: The aim of the study was to determine the value of SUVmax by PET/CT measured before surgery with special focus on FIGO stage, myometrial invasion, grading and risk stratification.

Methods: A total of 90 women, aged 37-84 (mean 65.1 +/- 9.5) with endometrial cancer (FIGO I and II) underwent 18F FDG PET/CT imaging before surgery SUVmax of the primary tumor was assessed and compared with histological prognostic factors (FIGO stage, grading, myometrial invasion, risk group).

Results: The mean SUVmax in the study group was 13.95 +/- 5.49. SUVmax was significantly higher with high FIGO stage (p=0,0009), deep myometrial invasion (p=0.0005), high grade (p=0.0331) and high risk tumors (0.0007). Patients with the poor prognosis had significantly higher SUVmax values.

Conclusions: The preoperative SUVmax measurements of the primary tumor of endometrial cancer may give additional clinical and prognostic information about risk factors and poor prognosis. High value of SUVmax might be useful in making noninvasive diagnoses and deciding the appropriate therapeutic strategy for patients with endometrial cancer However there is not enough evidence that it could in fact replace surgical staging.
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http://dx.doi.org/10.17772/gp/1634DOI Listing
September 2013

Serum anti-müllerian hormone levels in patients with epithelial ovarian cancer.

Int J Endocrinol 2013 28;2013:517239. Epub 2013 Jul 28.

Department of Obstetrics and Gynecology, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Ulica Ujejskiego 75, 85-168 Bydgoszcz, Poland.

Objectives. The aim of our study was to examine serum anti-Müllerian hormone (AMH) concentration in ovarian cancer patients in relation to clinicopathological features, such as a pathological subtype of the tumor, (FIGO) stage, grading, and overall 5-year survival. Material and Methods. We enrolled 72 epithelial ovarian cancer patients in our study, aged 45-79 years, who underwent optimal cytoreductive surgery. In all patients, serum AMH concentration was measured using a two-step sandwich type enzyme immunoassay before surgery. As a reference value for women over 45 years we accepted anti-Müllerian hormone concentration below 1 ng/mL. Results. In the whole group of patients with ovarian cancer, median serum concentration of AMH was 0.07 (0.0-0.37) ng/mL, whereas in the group of those with positive AMH values (≥0.14 ng/mL) it was 0.31 (0.15-0.73) ng/mL. No significant correlation was found between serum AMH levels and FIGO stage, histological subtype, or grading (P > 0.05). The analysis of five-year survival rate related to AMH levels showed no statistically significant differences. There were no differences in survival rates between patients with positive or negative serum AMH levels. Conclusion. Measurement of serum anti-Müllerian hormone levels was not useful in predicting clinicopathological features and survival in patients with ovarian cancer.
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http://dx.doi.org/10.1155/2013/517239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3745840PMC
August 2013

Altered expression of ERs, aromatase, and COX2 connected to estrogen action in type 1 endometrial cancer biology.

Tumour Biol 2013 Dec 20;34(6):4007-16. Epub 2013 Jul 20.

Department of Biology and Pathology of Human Reproduction in Bialystok, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Sklodowskiej 24A, 15-276, Bialystok, Poland,

In order to study estrogen-driven microenvironment associated with type 1 endometrial carcinoma, we evaluated estrogen receptors (ERs), aromatase, and cyclooxygenase II (COX2) molecular and immunohistochemical profiles with correlation to clinicopathological features. We investigated aromatase, ERα, ERβ, and COX2 expression at the mRNA and protein levels using quantitative real-time PCR and immunohistochemical method in 51 endometrial carcinomas and 16 normal endometria. All the studied tumors, as well as normal endometria, expressed ERα, ERβ, and COX2 mRNAs. Five endometrial carcinoma tissues and one normal endometrium showed no aromatase mRNA expression. The majority of tumors expressed ERα (82%), aromatase (80%), and COX2 (88%) proteins. Forty-one percent of the studied tumors were ERβ-negative. ERα and ERβ showed significantly decreased mRNA and protein expression levels in endometrial carcinoma as compared to normal endometrium. An opposite trend was shown for COX2 and aromatase proteins. ERα expression correlated positively with COX2 expression at both mRNA and protein levels (P < 0.005, r = 0.398; P < 0.0005, r = 0.510, respectively). There was also a positive correlation between COX2 and aromatase expression in cancer tissue (P < 0.002, r = 0.433 for transcriptional level; P < 0.0005, r = 0.614 for protein level). We observed positive correlations between ERβ and ERα, as well as between ERβ and COX2 at the transcriptional level only (P < 0.0005, r = 0.644; P < 0.002, r = 0.444, respectively). Negative correlations were found between pT category of primary tumor and levels of ERα and ERβ transcripts (P < 0.02, r = -0.332; P < 0.02, r = -0.348, respectively). A negative association between ERβ and the International Federation of Gynecology and Obstetrics (FIGO) staging was also found. The growth of EC1 with the presence of ERα and overexpression of aromatase and COX2 is dependent on estrogens. We believe that ERβ may be considered as a potential marker in the progression of disease in endometrial cancer patients.
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http://dx.doi.org/10.1007/s13277-013-0991-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858613PMC
December 2013

[The role of vitamin D in the carcinogenesis of breast and ovarian cancer].

Ginekol Pol 2013 Apr;84(4):305-8

Katedra Połoznictwa, Chorób Kobiecych i Ginekologii Onkologicznej, Collegium Medicum w Bydgoszczy, Uniwersytet Mikołaja Kopernika w Toruniu, Polska.

The review evaluates the role of vitamin D in carcinogenesis. Based on ecological studies, the incidence of many cancers has been shown to be higher in northern countries, suggesting an association with latitude and solar radiation. Vitamin D produced in skin under the influence of sun exposure may play a protective role in the process leading to cancer. Vitamin D deficiency is now recognized as a pandemic, mainly due to lack of knowledge that sun exposure in moderation is the major source of vitamin D for most humans. After vitamin D was discovered to be the necessary element of nourishment to prevent rickets at the beginning of the twentieth century the theory concerning its role has evolved. It is now recognized that vitamin D, and particularly its active form 1.25 (OH)2D, is an important hormone playing a crucial role in human homeostasis. [1.25(OH)2D3 has been shown to inhibit cancer cell growth, induce cancer cell maturation, induce apoptosis, and decrease angiogenesis. Several studies suggested that living at higher geographical latitudes increased the risk of developing and dying of colon, prostate, breast and other cancers. People exposed to sunlight were noted to less likely develop cancer. Several studies evaluated circulating levels of 25(OH)D and its possible association with cancer. Case-control studies and laboratory tests have consistently demonstrated that vitamin D plays an important role in the prevention of breast cancer. Vitamin D supplementation is a much needed, low cost, effective, and safe intervention strategy for breast cancer prevention that should be implemented. It has been shown that vitamin D levels are lower in ovarian cancer patients. Low 25(OH) D concentration associated with lower overall survival rate might suggest for the important role of severe deficiency in more aggressive course of ovarian cancer. Testing for 25(OH)D in the standard procedure could help to find ovarian cancer patients with worse prognosis, who would benefit from special attention and supplementation. Vitamin D3 supplementation in moderate doses achieving 25(OH)D concentrations of 30-80 ng/ml, can be recommended as many benefits may be expected, including decreased risk of developing cancer.
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http://dx.doi.org/10.17772/gp/1581DOI Listing
April 2013

[Evaluation of the efficacy and safety of Foley catheter pre-induction of labor].

Ginekol Pol 2013 Mar;84(3):180-5

Katedra i Klinika Połoznictwa, Chorób Kobiecych i Ginekologi Onkologicznej Collegium Medicum w Bydgoszczy UMK w Toruniu, Polska.

Introduction: Labor induction is being increasingly used (15-30% of pregnancies). The most common indications include late pregnancy preeclampsia, intrauterine fetal growth retardation (IUGR), hypertension. Preinduction by speeding up the ripening of the cervix increases the chances of successful induction. There are mechanical and pharmacological methods of pre-induction: the Foley catheter hygroscopic dilators, prostaglandin gel, misoprostol. There are various schemes of labor pre-induction and the differences relate primarily to duration of catheter time, amniotomy or the start of the oxytocin. Numerous studies on pre-induction and induction of labor aimed to compare the efficacy of these different methods. The effectiveness of the Foley catheter is usually assessed by comparing cervical maturity (Bishop score) and ripening of the cervix, evaluated in centimeters, before and after removing the cathetec time to labor since pre-induction and the number of births. In order to select the appropriate method, its safety for the mother and the fetus/newborn needs to be assessed. According to most authors, the use of a Foley catheter does not cause over-stimulation of the uterus, does not increase the risk of rupture or intrauterine infection, and does not adversely affect the fetus and newborn.

Aim Of The Study: To assess the efficacy and safety of labor pre-induction using a Foley catheter

Material And Methods: The study included 109 women hospitalized between 03.01.2011 and 11.30.2011, who underwent labor pre-induction with a Foley catheter The inclusion criteria were: one fetal pregnancy longitudinal cephalic fetal position, completed 36 weeks of pregnancy fetal bladder preserved, Bishop score < 5 points. The exclusion criteria were: placenta previa, uterine infection, unexplained bleeding, abnormal fetal heart rate, and other reasons preventing vaginal delivery such as fetal weight above 4500 g. Vaginal swabs for the presence of Streptococcus agalactiae (GBS) were obtained from each patient. In case of a positive result perinatal antibiotic prophylaxis was administered before insertion of the catheter The study group was divided into two subgroups according to parity: primiparous and multiparous. Indications for induction, method of pregnancy termination, the pregnancy and its complications were evaluated. The condition of the newborns was evaluated using the Apgar score, cord blood pH and infant birth weight. We analyzed cervical ripeness (Bishop score) before the insertion and after the removal of the catheter and serum C-reactive protein (CRP) before and 20 hours after insertion. CRP was not studied in pregnant women diagnosed with GBS colonization. The results were compared between the subgroups. An increase in the Bishop score to> 5 and delivery within 12 hours since the planned removal of the catheter regardless of the method of pregnancy and the use of oxytocin, was considered as successful induction of labor

Results: Catheter pre-induction was performed in 109 pregnant women, what amounted to 7.87% all of deliveries in our department during the analyzed period. Mean patient age was 29.3 +/- 5.35 years, mean duration of pregnancy 40 weeks of gestation (+/- 1 week 5 days), and primiparas constituted 66.06% of all cases. The most common indication for labor induction was post-term pregnancy (55.05%), hypertension and preeclampsia (16.51%). The following complications were observed in the study group after insertion of the catheter: 8 (7.34%) cases of premature rupture of the membranes (PROM), but none of them occurred in the process of inserting the catheter 11 (10.09%) women had the catheter removed (patients request) due to pain and the feeling of discomfort before the scheduled time, 2 (1.84%) cases of bleeding (in the first case the cesarean section was performed and the baby was born in a good overall condition, in the second case the bleeding subsided spontaneously). There was a statistically significant increase in the Bishop score for the entire study group and in the two subgroups. Mean increase in the Bishop score was 2.68 +/- 1.39 points for the entire cohort (p < 0.005). The rate of successful pre-induction resulting in a delivery was 69.4%, with vaginal births accounting for 66.67% of all cases. Also, 30.66% of the pregnant women did not require the use of oxytocin. The most common indication for cesarean section was threatening intrauterine fetal asphyxia. Higher efficiency of pre-induction was found in the multiparous group. The observed increase in CRP (p < 0.005) was within the normal range for pregnant women (< 12 mg/I). None of the patients showed any clinical signs of infection. Mean birth weight of the infants was 3392 +/- 644.72 g, mean Apgar score was 9.5 +/- 0.80 and mean cord blood pH was 7.3 +/- 0.08.

Conclusions: The Foley catheter is an effective method of inducing cervical maturation. The Foley catheter is safe method of labor induction for the mother fetus and newborn.
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http://dx.doi.org/10.17772/gp/1560DOI Listing
March 2013

The analysis of metallothionein immunoreactivity in stromal fibroblasts and macrophages in cases of uterine cervical carcinoma with respect to both the local and distant spread of the disease.

Am J Reprod Immunol 2013 Sep 17;70(3):253-61. Epub 2013 Apr 17.

Department of Obstetrics and Gynecology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Bydgoszcz, Poland.

Problem: The tumor microenvironment is made up of tissue that is responsible for the growth and progression of the tumor as well as its ability to initiate metastases. The cancer cells on the front of the tumor together with the macrophages and fibroblasts help to constitute the aggressive phenotype of the tumor. The presence of this aggressive phenotype is indicated by the local infiltration of cancer cells and by the development of lymph node metastases. In cases of uterine cancer, the extent of the local and distant spread of the disease is crucial for determining the type of therapeutic strategy to be applied - surgery alone, surgery followed by radio-chemotherapy, or radio-chemotherapy alone. In the interest of trying to improve the patient's quality of life, different studies supporting the therapeutic model of surgery alone have been conducted. While the cancer cells on the tumor front together with the macrophages and the fibroblasts help to constitute the aggressive phenotype of the tumor, metallothionein (MT) has been shown to have both pro-proliferative and anti-apoptotic activities and to participate in microenvironment remodeling. The aim of the current study was to determine the levels of MT immunoreactivity in the uterine cervical cancer cells as well as in the stromal fibroblasts and macrophages of the tumor microenvironment with respect to the depth of the local invasion and the extent of the distant metastases, so that its potential predictive value as a therapeutic strategy for cervical cancer can be ascertained.

Methods: We determined the levels of immunoreactivity of MT in a total of 57 carcinoma tissue samples (in the tumor front, in its central part, and in the macrophages and fibroblasts present within the tumor microenvironment). The patients from whom the samples derived were divided into groups with respect to the presence of lymph node metastases (distant spread) and to the depth of invasion (local spread) in relation to the FIGO stage.

Results: Metallothionein immunoreactivity was observed in uterine cervical cancer cells; it was also identified in the fibroblasts and macrophages found within the microenvironments of the tumors of patients suffering from the disease. The MT immunoreactivity level significantly increased within the whole cancer nest in relation to the FIGO stage (intensity of the local spread of the disease). Similarly, the infiltration of MT-positive CAFs and TAMs statistically significantly increased in relation to the FIGO stage.

Conclusion: The level of MT immunoreactivity found in the fibroblasts and macrophages within the tumor microenvironment seems to be indicative of the intensity of the remodeled cervical tumor microenvironment, and this in turn may be related to the local advancement of the disease. Moreover, it appears that the intensity of the metallothionein immunoreactivity in the immunoreactivity profile of the cervical tumor may be linked to both the depth of the local invasion and the extent of the distant advancement of the disease.
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http://dx.doi.org/10.1111/aji.12120DOI Listing
September 2013