Differential microRNA Expression Analysis in Patients with HPV-Infected Ovarian Neoplasms.

This study aimed to identify microRNAs (miRNAs) whose expression levels are altered by high-risk human papillomavirus (HR-HPV) infection in women with epithelial ovarian neoplasms. MiRNA expression was quantified by real-time polymerase chain reaction, while HR-HPV DNA was quantified using digital-droplet PCR. Analysis of 11 miRNAs demonstrated significantly lower hsa-miR-25-5p expression in HPV-infected compared to uninfected ovarian tissues (p = 0.0405), while differences in miRNA expression in corresponding serum were statistically insignificant. The expression of hsa-miR-218-5p in ovarian tumors was significantly higher in high-grade serous ovarian carcinoma (HGSOC) cases than in other neoplasms (p = 0.0166). In addition, hsa-miR-218-5p was significantly upregulated, whereas hsa-miR-191-5p was significantly downregulated in tissues with stage III/IV FIGO (p = 0.0009 and p = 0.0305, respectively). Using unsupervised clustering, we identified three unique patient groups with significantly varied frequencies of HPV16/18-positive samples and varied miRNA expression profiles. In multivariate analysis, high expression of hsa-miR-16-5p was an independent prognostic factor for poor overall survival (p = 0.0068). This preliminary analysis showed the changes in miRNA expression in ovarian neoplasms during HPV infection and those collected from HGSOCs or patients with advanced disease. This prospective study can provide new insights into the pathogenesis of ovarian neoplasms and host-virus interactions.

Evaluation of serum levels of soluble (s)L- and (s)P-selectins in endometrial cancer.

OBJECTIVES: A number of reports on the role of selectin in the process of carcinogenesis, at the stage of proliferation and metastasis, have been available. The aim of the study was to analyze (s)P- and (s)L-selectin serum concentrations in women with EC and to compare these concentrations to clinical/pathological parameters and disease progression using surgical-pathological staging data. MATERIAL AND METHODS: A total of 46 patients with EC and 50 healthy controls were included in the study. Serum concentrations of sL- and sP-selectins were measured in all participants. The oncologic protocol was implemented in all women from the study group. RESULTS: Significantly higher serum concentrations were found in EC women as compared to controls. No statistically significant differences were found between the concentrations of the soluble forms of selectins and the following parameters: histologic type of EC, histologic tumor differentiation, depth of myometrial infiltration, cervical involvement, distant metastases, vascular space invasion, and disease advancement. Slightly higher (s)P-selectin concentrations were observed in serous carcinoma, in women with cervical involvement, in the sera of women with vascular space invasion and with advanced stages of the disease. Slightly higher mean (s)P-selectin concentrations correlated with lower differentiation of the tumor. Slightly higher mean (s)P-selectin concentration was detected in the sera of women with lymph node metastases and with the serosal and/or adnexal involvement. The results were statistically insignificant, but they almost reached statistical significance. CONCLUSIONS: L- and P-selectins play a role in the biology of EC. The absence of an unambiguous relationship between differences in (s)L- and (s)P-selectin levels and disease advancement suggests that they do not play a vital role in tumor progression in endometrial cancer.

The Toll-like Receptor 4 Polymorphism Asp299Gly Is Associated with an Increased Risk of Ovarian Cancer.

Ovarian cancer (OC) is one of the most common cancers threatening women's lives around the world. Epithelial ovarian tumors represent the most common ovarian neoplasms. Most OC patients are diagnosed at the advanced stage, and there is an urgent need to identify novel biomarkers of the disease. Single-nucleotide polymorphisms (SNPs) in TLR genes may serve as crucial markers of cancer susceptibility. We investigated the frequency of TLR polymorphisms in a group of 200 women, including 70 with OC. Four SNPs, two each in TLR4 (rs4986790 and rs4986791) and TLR9 (rs187084 and rs5743836), were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The digested fragments were separated and identified by multicapillary electrophoresis. The load quantification of human papillomavirus (HPV) types 16/18 was determined using a digital droplet PCR method. We found an increased frequency of heterozygous genotype and minor allele of the TLR4 rs4986790 SNP in women with OC compared with healthy controls, and this result remained highly significant after Bonferroni's correction for multiple testing (p < 0.0001). No evidence of linkage disequilibrium was found with any of the examined TLR SNPs. The findings suggest that the TLR4 Asp299Gly polymorphism could be a genetic risk factor for the development of OC.

ERAP/HLA-C and KIR Genetic Profile in Couples with Recurrent Implantation Failure.

Proper embryo implantation depends on the tolerance of the maternal immune system to the fetus and its foreign paternal antigens. During implantation and early pregnancy, the dominant leukocytes in the uterus are uterine NK cells, expressing killer immunoglobulin-like receptors (KIR). KIRs recognize human leukocyte antigens (HLA-C) on the human trophoblast inherited from the father and mother. The antigenic peptides presented by the HLA are formed via their cleavage by endoplasmic reticulum aminopeptidases ERAP1 and ERAP2. The aim of this study was to assess the association of combined KIR genes and their HLA-C ligands, as well as ERAP1 and ERAP2 polymorphisms with recurrent implantation failure after in vitro fertilization (RIF). We tested 491 couples who underwent in vitro fertilization (IVF) and 322 fertile couples. Genotype CC rs27044 ERAP1 in female with a male's HLA-C1C1 or HLA-C1C2 protected from RIF (p/pcorr. = 0.005/0.044, OR = 0.343; p/pcorr. = 0.003/0.027, OR = 0.442, respectively). Genotype TT rs30187 ERAP1 in female with a male's HLA-C1C2 genotype increased the risk of RIF. Summarizing, in the combination of female ERAP1 and an HLA-C partner, the rs30187 C>T and rs27044 C>G polymorphisms play an important role in implantation failure.

Analysis of lncRNA sequences: FAM3D-AS1, LINC01230, LINC01315 and LINC01468 in endometrial cancer.

BACKGROUND: The analysis of long non-coding RNA (lncRNA) in endometrial cancer is a novel field of science. Although numerous lncRNA sequences have been identified until today, their correlation with endometrial cancer is still undetermined. The aim of this study was to analyze the expression of four lncRNA sequences: FAM3D-AS1, LINC01230, LINC01315 and LINC01468 and to investigate their significance in endometrial cancer. METHODS: LncRNA sequences were investigated in paraffin blocks (tumor tissue and non-malignant endometrial tissue in archival postoperative specimens) in endometrial cancer patients (Cases, n = 120) and in cancer-free controls (n = 80) using real-time PCR assay. RESULTS: This study revealed a lower expression of LINC01468 in endometrial cancer patients than in controls. Both LINC01468 and FAM3D-AS1 were positively correlated with Body Mass Index (BMI) in cancer-free controls. CONCLUSIONS: LncRNA LINC01468 may be a protective factor in development of endometrial cancer.

Large-Scale Functional Genomics Screen to Identify Modulators of Human ß-Cell Insulin Secretion.

Type 2 diabetes (T2D) is a chronic metabolic disorder affecting almost half a billion people worldwide. Impaired function of pancreatic ß-cells is both a hallmark of T2D and an underlying factor in the pathophysiology of the disease. Understanding the cellular mechanisms regulating appropriate insulin secretion has been of long-standing interest in the scientific and clinical communities. To identify novel genes regulating insulin secretion we developed a robust arrayed siRNA screen measuring basal, glucose-stimulated, and augmented insulin secretion by EndoC-ßH1 cells, a human ß-cell line, in a 384-well plate format. We screened 521 candidate genes selected by text mining for relevance to T2D biology and identified 23 positive and 68 negative regulators of insulin secretion. Among these, we validated ghrelin receptor (GHSR), and two genes implicated in endoplasmic reticulum stress, ATF4 and HSPA5. Thus, we have demonstrated the feasibility of using EndoC-ßH1 cells for large-scale siRNA screening to identify candidate genes regulating ß-cell insulin secretion as potential novel drug targets. Furthermore, this screening format can be adapted to other disease-relevant functional endpoints to enable large-scale screening for targets regulating cellular mechanisms contributing to the progressive loss of functional ß-cell mass occurring in T2D.

Urogynecology Section of the Polish Society of Gynecologists and Obstetricians Guidelines on the management of recurrent pelvic organ prolapse.

OBJECTIVES: The aim of the publication was to present the Guideline of the Urogynecology Section of the Polish Society of Gynecologists and Obstetricians (PSGO) for the management of recurrent pelvic organ prolapse, based on the available literature, expert knowledge and opinion, as well as everyday practice. MATERIAL AND METHODS: In 2005, 2006 and 2010, the panel of PSGO experts published guidelines for the diagnosis and treatment of patients with lower urinary tract symptoms (LUTS). This publication presents an update of those recommendations and concerns recurrent POP treatment. MAIN CONCLUSION: The analysis of data revealed that sacrocolpopexy with the use of commercial sets or polypropylene hernia mesh is the method of choice for the surgical repair of recurrent vaginal vault prolapse. However, a significantly higher risk of surgical and postoperative complications after sacrocolpopexy, as compared to vaginal surgeries, should be considered when making treatment decisions. In other types of recurrent POP, the choice of surgery method should be tailored to the individual needs of each patient and may depend on the medical center.

A Clinical Study of the Impact of Soft Contact Lenses on the Progression of Myopia in Young Patients.

PURPOSE: To assess the impact of soft contact lenses on the progression of myopia in young patients. PATIENTS AND METHODS: The observational study included 102 patients divided into 3 groups: MFCL (multifocal contact lenses) group: 15 girls and 9 boys, aged 8-20 (= 14.12 ± 2.863) with soft multifocal contact lenses with myopia: = -3.12 D ± 1.776 D and mean myopia progression -0.23 ± 0.233D after 2 years; SVCL (single vision contact lenses) group: 30 girls and 5 boys, 11-20 years old (=15.5 ± 2.24) with myopia = -2.88 ± 2.122 D at admission and mean myopia progression -0.54 ± 0.464 D after 2 years; the spectacle (single vision glasses) group: 25 girls and 18 boys, aged 8-18 years ( = 13.65 ± 2.448) with single vision glasses with myopia: = -1.74 ± 1.412 D at admission and mean myopia progression -0.86 ± 0.489D after 2 years. Medical history and physical examination were performed every 6, 12, 18 and 24 months. Refractive error was examined using the autorefractometry after cycloplegia. RESULTS: The analysis of myopia correction after 2 years showed differences between MFCL and spectacle correction. The change in myopia progression after 2 years was statistically significant for MFCL vs SVCL and MFCL vs spectacle correction when the myopia occured before the period of intensive growth. When myopia occurred during the period of intensive growth, difference was noted for MFCL vs spectacle correction and SVCL vs spectacle correction. When myopia occurred after a period of intensive growth, no significant differences between the groups were observed. CONCLUSION: 1) Multifocal contact lenses and some single vision contact lenses (Biofinity) may be useful in the control of myopia in younger patients, slowing the progression of nearsightedness; therefore, they can be a therapeutic option in inhibiting the progression of myopia. 2) The best effects of using multifocal contact lenses occur if myopia is diagnosed before the period of intensive growth.

ERAP, KIR, and HLA-C Profile in Recurrent Implantation Failure.

The mother's uterine immune system is dominated by uterine natural killer (NK) cells during the first trimester of pregnancy. These cells express killer cell immunoglobulin-like receptors (KIRs) of inhibitory or activating function. Invading extravillous trophoblast cells express HLA-C molecules, and both maternal and paternal HLA-C allotypes are presented to KIRs. Endoplasmic reticulum aminopeptidase 1 (ERAP1) and 2 (ERAP2) shape the HLA class I immunopeptidome. The ERAPs remove N-terminal residues from antigenic precursor peptides and generate optimal-length peptides to fit into the HLA class I groove. The inability to form the correct HLA class I complexes with the appropriate peptides may result in a lack of immune response by NK cells. The aim of this study was to investigate the role of ERAP1 and ERAP2 polymorphisms in the context of KIR and HLA-C genes in recurrent implantation failure (RIF). In addition, for the first time, we showed the results of ERAP1 and ERAP2 secretion into the peripheral blood of patients and fertile women. We tested a total of 881 women. Four hundred ninety-six females were patients who, together with their partners, participated in in vitro fertilization (IVF). A group of 385 fertile women constituted the control group. Women positive for KIR genes in the Tel AA region and HLA-C2C2 were more prevalent in the RIF group than in fertile women (p/pcorr. = 0.004/0.012, OR = 2.321). Of the ERAP polymorphisms studied, two of them (rs26653 and rs26618) appear to affect RIF susceptibility in HLA-C2-positive patients. Moreover, fertile women who gave birth in the past secreted significantly more ERAP1 than IVF women and control pregnant women (p < 0.0001 and p = 0.0005, respectively). In the case of ERAP2, the opposite result was observed; i.e., fertile women secreted far less ERAP2 than IVF patients (p = 0.0098). Patients who became pregnant after in vitro fertilization embryo transfer (IVF-ET) released far less ERAP2 than patients who miscarried (p = 0.0032). Receiver operating characteristic (ROC) analyses indicate a value of about 2.9 ng/ml of ERAP2 as a point of differentiation between patients who miscarried and those who gave birth to a healthy child. Our study indicates that both ERAP1 and ERAP2 may be involved in processes related to reproduction.

Association of Single Nucleotide Polymorphism LEP-R c.668A>G (p.Gln223Arg, rs1137101) of leptin receptor gene with endometrial cancer.

BACKGROUND: The aim of this study was to analyze the frequencies of genotypes and alleles of Single Nucleotide Polymorphism (SNP) LEP-R c.668A>G (p.Gln223Arg, rs1137101) of leptin receptor gene and to assess the influence this DNA marker has on endometrial cancer (EC) with respect to total body fat content. METHODS: The study comprised 120 patients treated for endometrial cancer and 90 controls treated for uterine fibroids. In total, 210 patients were included in this research. DNA was isolated from archival post-operative specimens. Polymerase Chain Reaction - Restriction Fragment Length Polymorphism was employed to analyze the SNP. RESULTS: In this paper we have demonstrated that heterozygous genotype AG of SNP LEP-R c.668A>G (p.Gln223Arg, rs1137101) is statistically less frequent in women with endometrial cancer (EC) than in controls: 33 versus 57%, respectively. Similarly, this heterozygous genotype is statistically significantly less frequent in obese (BMI > 30) women with EC than in lean controls (BMI < 25): 30 versus 63%, respectively. CONCLUSIONS: AG polymorphic variant of SNP LEP-R c.668A>G (p.Gln223Arg, rs1137101) in LEP-R may be considered a protective factor in the development of endometrial cancer.

The analysis of vaginal hysterectomy results depending on the uterine size.

OBJECTIVES: Vaginal hysterectomy is one of the oldest but still rarely used minimally invasive techniques. Although new surgical methods making use of robots in laparoscopy have been introduced recently, when compared with vaginal hysterectomy, these approaches do not offer significant benefits for the patients and the doctors operating on them. The purpose of this study was a thorough analysis of vaginal removal of non-prolapsed uterus with benign pathology. MATERIAL AND METHODS: The analysis included data of 1148 women who underwent vaginal hysterectomy in the Clinic of Surgical, Endoscopic and Oncological Gynecology between 2002 and 2014. A group of patients operated on were assessed, and data from the surgeries were obtained paying attention to such aspects as the operating time, the evaluation of morphotic blood elements, the type of perioperative complications, and the length of postoperative hospital stay. Additionally, all vaginal hysterectomies were divided into groups and analyzed taking into consideration uterus weight. RESULTS: Vaginal hysterectomy was performed even in cases of earlier abdominal surgeries. The mean operating time was and 69.51 ± 28.32 minutes. The patients left hospital after 2.93 days on average. The mean uterus weight was 179.69 ± 113.54 g. What is important, the enlarged uterus was not a significant obstacle during the surgery. In case of heavy uteri of more than 580g, when the fundus of the uterus reached above the navel, the attention was drawn to the need for careful preparatory procedures, which reduced the number of perioperative complications and thus had a significant influence on the length of the operation (p = 0.0170). CONCLUSIONS: Vaginal hysterectomy is an operating technique which is relatively easy to perform and safe for the patients because it involves a slight decrease of morphotic blood elements and a small number of mid- and postoperative complications. Vaginal hysterectomy is not a contraindication in case of large uteri, even those of more than 1000 g; however, in such cases, a longer operating time and an increased number of perioperative complications must be taken into consideration.

A body shape index (ABSI) and endometrial pathology.

A body shape index (ABSI) is an anthropometric measure that allows evaluating abdominal adiposity. Obesity is considered a risk factor for endometrial cancer (EC). Due to the increase in EC's incidence, identifying risk factors for endometrial pathology is essential in women's health. The study aimed to identify an association between EC/endometrial pathology and ABSI. We identified well-known risk factors for endometrial cancer and calculated ABSI in 408 women who were admitted to the Polish Mother's Memorial Hospital Research Institute between January 2016 and December 2017. Patients were divided into four subgroups: no endometrial pathology, endometrial polyps, hyperplasia without atypia, and hyperplasia with atypia/cancer. Statistical analysis showed a correlation between ABSI and the presence of cancer/atypical hyperplasia (Kruskal-Wallis test, p = .042). Additional multivariate analysis revealed that both ABSI and body mass index (BMI) z scores might potentially be associated with EC presence (ABSI z score quintiles Q1, Q2, Q3 vs. Q4, Q5: p = .039; BMI z score quintiles Q1, Q2, Q3 vs. Q4, Q5: p = .038). We found an association between cancer/atypical hyperplasia and ABSI. Further studies on ABSI are needed to establish ABSI as a risk factor for EC fully.

Is Single Nucleotide Polymorphism ADIPOQ (NM_004797.4):c.214+62G>T (rs1501299) Associated With Uterine Leiomyomas? A Pilot Study.

Objective: Although polymorphisms of adiponectin gene (ADIPOQ) in obesity-related conditions have been the target of research efforts, little is known about this genetic marker in uterine leiomyomas. The aim of this pilot study was to analyze the frequencies of alleles and genotypes of Single Nucleotide Polymorphism ADIPOQ (NM_004797.4):c.214+62G>T (rs1501299) and to correlate it with the risk of uterine fibroids. Study Design: The Test Group comprised 90 women treated surgically for uterine leiomyomas in the Department of Operative Gynecology, Endoscopy and Gynecologic Oncology, Polish Mother's Memorial Hospital-Research Institute. 90 disease-free individuals were used as Controls. Patients within both groups were additionally stratified into lean, overweight and obese, according to Body Mass Index. Statistical analysis was performed between the two major groups and, furthermore, within the abovementioned subgroups. Results: The study revealed no statistically significant differences in the distribution of alleles and genotypes of SNP ADIPOQ (NM_004797.4):c.214+62G>T (rs1501299) between the two main groups. A weak correlation within distributions of alleles was observed between obese Test Patients and lean Controls. Conclusion: This pilot study has revealed no association between SNP ADIPOQ (NM_004797.4):c.214+62G>T (rs1501299) and uterine fibroids. Further studies on larger groups are warranted to elucidate whether this SNP may be correlated with uterine leiomyomas.

The Association of HLA-G Gene Polymorphism and Its Soluble Form With Male Infertility.

Successful reproduction depends on many factors. Male factors contribute to infertility in approximately 50% of couples who fail to conceive. Seminal plasma consists of secretions from different accessory glands containing a mixture of various cytokines, chemokines, and growth factors, which together can induce a local immune response that might impact on a male's as well as a female's fertility. Human leukocyte antigen (HLA)-G expression has been suggested as an immunomodulatory molecule that influences pregnancy outcome. The HLA-G gene encodes either membrane-bound or/and soluble proteins. The aim of this study was the evaluation of HLA-G polymorphisms and their impact on soluble HLA-G (sHLA-G) production. We tested the HLA-G polymorphism in three positions: rs1632947: c.-964G>A; rs1233334: c.-725G>C/T in the promoter region; rs371194629: c.∗65_∗66insATTTGTTCATGCCT in the 3' untranslated region. We tested two cohorts of men: 663 who participated in in vitro fertilization (test material was blood or sperm), and 320 fertile controls who possessed children born after natural conception (test material was blood). Since 50% of men visiting assisted reproductive clinics have abnormal semen parameters, we wondered if men with normal sperm parameters differ from those with abnormal parameters in terms of HLA-G polymorphism and secretion of sHLA-G into semen. We found that certain rs1632947-rs1233334-rs371194629 HLA-G haplotypes and diplotypes were associated with male infertility, while others were protective. Normozoospermic men with the A-C-del haplotype and A-C-del/A-C-del diplotype secreted the most sHLA-G into semen (574.1 IU/mL and 1047.0 IU/mL, respectively), while those with the G-C-ins haplotype and G-C-ins/G-C-ins diplotype - the least (80.8 IU/mL and 75.7 IU/mL, respectively). Men with the remaining haplotypes/diplotypes secreted sHLA-G at an intermediate level. However, only in one haplotype, namely G-C-ins, did we observe strong significant differences in the concentration of sHLA-G in the semen of men with teratozoospermia compared to men with normal sperm parameters (p = 0.009). In conclusion, fertile men differ in the profile of HLA-G polymorphism from men participating in IVF. Among all HLA-G haplotypes, the most unfavorable for male fertility is the G-C-ins haplotype, which determines the secretion of the lowest concentration of the soluble HLA-G molecule. This haplotype may reduce sperm parameters.

MiRNA-103/107 in Primary High-Grade Serous Ovarian Cancer and Its Clinical Significance.

High levels of miRNA-103/107 are associated with poor outcomes in the case of breast cancer patients. MiRNA-103/107-DICER axis may be one of the key regulators of cancer aggressiveness. MiRNA-103/107 expression levels have never been related to patients' clinicopathological data in epithelial ovarian cancer. We aimed to assess miRNA-103/107 expression levels in high grade serous ovarian cancer tissues. Expression levels of both miRNAs were related to the clinicopathological features and survival. We also evaluated expression levels of miRNA-103/107 and DICER in selected ovarian cancer cell lines (A2780, A2780cis, SK-OV-3, OVCAR3). We assessed the relative expression of miRNA-103/107 (quantitative reverse transcription-polymerase chain reaction) in fifty archival formalin-fixed paraffin-embedded tissue samples of primary high grade serous ovarian cancer. Then, miRNA-103/107 and DICER expression levels were evaluated in selected ovarian cancer cell lines. Additionally, DICER, N-/E-cadherin protein levels were assessed with the use of western blot. We identified miRNA-107 up-regulation in ovarian cancer in comparison to healthy tissues (p = 0.0005). In the case of miRNA-103, we did not observe statistically significant differences between cancerous and healthy tissues (p = 0.07). We did not find any correlations between miRNA-103/107 expression levels and clinicopathological features. Kaplan-Meier survival (disease-free and overall survival) analysis revealed that both miRNAs could not be considered as prognostic factors. SK-OV-3 cancer cell lines were characterized by high expression of miRNA-103/107, relatively low expression of DICER (western-blot), and relatively high N-cadherin levels in comparison to other ovarian cancer cell lines. Clinical and prognostic significance of miRNA-103/107 was not confirmed in our study.

The Polish Society of Gynecologists and Obstetricians statement on surgery in gynecology during the COVID-19 pandemic.

The publication presents recommendations on the performance of surgical procedures in gynecology during the COVID- 19 pandemic. The recommendations were prepared by the Polish Society of Gynecologists and Obstetricians, based on current knowledge of SARS CoV-2. These recommendations contain the latest guidelines of scientific societies related to the subject of operational procedures.

Recommendations of the Polish Society of Gynaecologists and Obstetricians for removal of the uterus by vaginal, laparoscopic and abdominal routes.

The recommendations represent the current procedure, which may be modified and changed where justified, after a thorough analysis of the given clinical situation, which may be the basis for their modification and updating in the future.

KIR and HLA-C genes in male infertility.

PURPOSE: Approximately 50% of men reporting to clinics for assisted reproduction have abnormal sperm parameters; we therefore considered whether they differ from fertile males in terms of the frequency of KIR and HLA-C genes, suggesting the involvement of NK cells and some T cells in the inflammatory reaction that can occur in the testes, vas deferens, or epididymis. METHOD: We tested a total of 1064 men: 445 of them were patients who, together with their female partners, participated in in vitro fertilization (IVF), 298 men whose female partners suffered from recurrent spontaneous abortion. Three hundred twenty-one fertile men constituted the control group. KIRs were genotyped using KIR Ready Gene kits and HLA-C by PCR-SSP methods. RESULTS: We found differences in KIR gene frequencies between men who became fathers via natural conception and men who participated in in vitro fertilization for KIR2DL2 (p/pcorr. = 0.0015/0.035, OR = 1.61), KIR2DL5 gr.2 (p/pcorr. = 0.0023/0.05, OR = 1.64), KIR2DS2 (p/pcorr. = 0.0019/0.044, OR = 1.59), and KIR2DS3 (p/pcorr. = 0.0016/0.037, OR = 1.67). KIRs in Cen AA region were significantly overrepresented in fertile males than in IVF males (p/pcorr. = 0.0076/0.03, OR = 0.67), whereas Cen AB + Cen BB frequency was higher in IVF males than in fertile males (p/pcorr. = 0.0076/0.03, OR = 1.50). We also observed a limited association in KIR-HLA-C combinations. CONCLUSION: Fertile men differ in profile of KIR genes and KIR-HLA-C combinations from men participating in IVF.

MiRNAs in endometrioid endometrial cancer metastatic loci derived from positive lymph nodes.

INTRODUCTION: MicroRNAs (miRNAs) take part in tumorigenesis and show aberrant expression levels in cancerous tissues. We aimed to perform miRNA profiling of endometrioid endometrial cancer (EEC) metastatic loci derived from lymph nodes. Identification of aberrant miRNAs in positive lymph nodes could contribute to establishing new diagnostic markers and therapeutic targets. MATERIAL AND METHODS: During the screening phase of the study, we performed profiling of 754 human miRNAs in endometrioid endometrial cancer tissues, microdissected metastatic loci from lymph nodes and healthy lymph nodes (Taqman Array). Selection of candidate miRNAs and subsequent validation using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 50 tissue samples were performed. RESULTS: After the screening phase of the study, five miRNAs were selected (hsa-miR-18b, hsa-miR-148a-5p, hsa-miR-204, hsa-miR-424, hsa-miR-129-1-3p). Validation revealed that miRNA-204 and miRNA-424 were highly downregulated in metastatic tissues compared with endometrial cancer samples (hsa-miR-204-P = .0008; hsa-miR-424-P = .0001). Receiver operating characteristic curves, which were constructed to compare endometrioid endometrial cancer and positive endometrioid endometrial cancer lymph nodes yielded the following area under the curves (AUCs): hsa-miR-204-.802 (96% confidence interval CI 0.676-0.927), hsa-miR-424-.84 (95% CI 0.711-0.969). CONCLUSIONS: Compared with primary endometrioid endometrial cancer tissue, metastatic loci derived from positive lymph nodes are characterized by profound downregulation of miRNA-204 and miRNA-424.

Generation of a human induced pluripotent stem cell line (HMGUi002-A) from a healthy male individual.

Induced pluripotent stem cells (iPSCs) can be used to generate different somatic cell types in vitro, including insulin-producing pancreatic ß-cells. Here, we have generated iPSCs from a healthy male individual using an episomal reprogramming method. The resulting iPSCs are integration-free, have a normal karyotype and are pluripotent in vitro and in vivo. Furthermore, we show that this iPSC line can be differentiated into pancreatic lineage cells. Taken together, this iPSC line will be useful to test differentiation protocols towards ß-cell as well as other cell types and will also serve as a control for drug development and disease modelling studies.