Search

Ovarian cancer (OC) is the most lethal female gynecological malignancy, mostly due to diagnosis in late stages when treatment options are limited. Hedgehog-GLI (HH-GLI) signaling is a major developmental pathway involved in organogenesis and stem cell maintenance, and is activated in OC. One of its targets is survivin (BIRC5), an inhibitor of apoptosis protein (IAP) that plays a role in multiple processes, including proliferation and cell survival. We wanted to investigate the role of different GLI proteins in the regulation of survivin isoform expression (WT, 2&alpha, 2B, 3B, and &Delta, ex3) in the SKOV-3 OC cell line. We demonstrated that survivin isoforms are downregulated in GLI1 and GLI2 knock-out cell lines, but not in the GLI3 knock-out. Treatment of GLI1 knock-out cells with GANT-61 shows an additional inhibitory effect on several isoforms. Additionally, we examined the expression of survivin isoforms in OC samples and the potential role of BIRC5 polymorphisms in isoform expression. Clinical samples showed the same pattern of survivin isoform expression as in the cell line, and several BIRC5 polymorphisms showed the correlation with isoform expression. Our results showed that survivin isoforms are regulated both by different GLI proteins and BIRC5 polymorphisms in OC.

Inkontinencija urina (IU) čest je simptom koji može biti prisutan u žena svih dobnih skupina s različitim rasponom težine simptoma zbog čega može znatno utjecati na fizičku, psihološku i socijalnu kvalitetu života svakog pojedinca. Kao što je poznato, IU dijelimo na statičku, miješanu i urgentnu inkontinenciju te prekomjerno aktivan mokraćni mjehur (PAMM) sa znatno većom incidencijom u starijoj dobi, posebice nakon 65. godine. Inkontinencija urina, praćena sramom i isključivanjem iz svakodnevnog života, znatno remeti socijalni život žene. Pri prvom posjetu liječniku svakako je nužna pravilna inicijalna procjena tipa IU-a (statički, urgentni ili miješani) koja nas usmjerava prema prikladnom liječenju predominantnog simptoma. Brojni upitnici (ICIQ, I-QOL, SUIQQ, OAB-Q) te dnevnici mokrenja mogu biti korisni u evaluaciji težine simptoma i utjecaja IU-a na kvalitetu života žene. Bazični fizikalni pregled trebao bi biti vođen dobrom anamnezom i prisutnosti simptoma prolapsa organa male zdjelice. Testiranje urin-vrpčicom preporučljivo je, svakako, kod svih pacijentica s IU-om da bi se isključila infekcija urotrakta (IUT). Savjetuje se antibiotsko liječenje svih simptomatskih infekcija donjeg urotrakta (IUT) unatoč nalazu urin-vrpčice. U obzir dolaze i ostala testiranja za IU kao što su mjerenja rezidualnog urina ili testnim ulošcima (kratkotrajni ili 24-satni), ali ona daju nedostatne podatke pa se stoga i ne preporučuju pri rutinskoj kliničkoj procjeni IU-a. Međutim, u većine bolesnica invazivna se testiranja ne provode prije započinjanja konzervativnog liječenja IU-a. Konzervativni pristup u liječenju inkontinencije urina obuhvaća način života (navike crijeva, prehrambeni proizvodi, kofein, unos tekućina, pušenje, tjelesna težina, sport), fizikalnu terapiju (vježbanje mišića dna zdjelice, biofeedback, vaginalni konusi, magnetska i električna stimulacija) i bihevioralnu terapiju (vježbanje mokraćnog mjehura) te neurostimulaciju (T-SNS, T-PTNS, P-PTNS). U alternativnu konzervativnu terapiju pripadaju svi proizvodi koji skupljaju urin (npr., ulošci, kateteri) te oni koji sprječavaju istjecanje urina (npr., instrumenti koji su potpora vratu mokraćnog mjehura, pesari, intrauretralni ili ekstrauretralni dodaci). ICS (International Continence Society) smatra da je konzervativna terapija učinkovita, jeftina i minimalno štetnog učinka, a nije u koliziji s ostalom mogućom terapijom., Urinary incontinence (UI) is a common symptom that may be present in women of all ages, with varying degrees of symptom severity, which can significantly affect the physical, psychological and social well-being of each individual. As is well known, there are several types of UI: stress (static) incontinence, mixed incontinence and urge incontinence, including an overactive bladder syndrome with a significantly higher incidence rate in older age groups, especially in people aged 65 and over. Urine incontinence considerably disrupts the life of women, affecting their social interactions and generating feelings of embarrassment. During the patient’s first visit to a physician, it is crucial to get an accurate initial UI type assessment (stress, urge or mixed incontinence) that can point to adequate treatment of the predominant symptom. Numerous questionnaires (ICIQ, I-QOL, SUIQQ, OAB-Q) and bladder diaries can help evaluate the severity of the symptoms and the impact of UI on the quality of life of women. Basic physical examination should focus on proper medical history and the presence of the symptom of pelvic organ prolapse. Tests using a urine test strip are definitely recommended in all patients suffering from UI in order to exclude a urinary tract infection (UTI). It is advised to treat all symptomatic lower urinary tract infections (UTI) with antibiotics despite the results provided by testing using urine test strips. Other testing for UI includes the postvoid residual urine measurement or pad tests (short-term or 24-hour), which provide insufficient data and are therefore not recommended in routine clinical assessment of UI. However, in most cases, invasive testing is not performed prior to the conservative treatment of UI. Conservative approach to the treatment of urinary incontinence includes the lifestyle (bowel habits, food products, caffeine, fluid intake, smoking, body weight, sports), physical therapy (pelvic floor exercises, biofeedback, vaginal cones, magnetic and electrical stimulation), behavioural therapy (bladder training) and neurostimulation (T-SNS, T-PTNS, P-PTNS). Alternative conservative therapy involves all products that collect urine (e.g. pads, catheters) and products that prevent urine leakage (e.g. bladder neck support device, pessaries, urethral inserts or extra-urethral devices). The International Continence Society (ICS) considers the conservative therapy to be effective and inexpensive and to have a minimally invasive effect, without colliding with other potential therapies.

Hedgehog signaling pathway has been implicated in the pathology of ovarian cancer, and Survivin (BIRC5) has been suggested as a novel target of this pathway. Herein we investigated the role of Hedgehog signaling pathway and Survivin in ovarian carcinoma and borderline tumor samples. We aimed to determine possible ways of pathway modulation on primary ovarian cancer cells and an established cell line. RNA was extracted from fresh tumors and control tissues and gene expression was examined using qRT-PCR. Pathway activity in cell lines was examined after treatment with cyclopamine, SHH protein, GANT-61 or lithium chloride using qRT-PCR, western blot and confocal microscopy. The difference between control tissue, borderline tumors and carcinomas can be seen in GLI1 and SUFU gene expression, which is significantly higher in borderline tumors compared to carcinomas. SUFU also shows lower expression levels in higher FIGO stages relative to lower stages. BIRC5 is expressed in all tumors and in healthy ovarian tissues compared to our control tissue, healthy fallopian tube samples. Primary cells developed from ovarian carcinoma tissue respond to cyclopamine treatment with a short-term decrease in cell proliferation, downregulation of Hedgehog pathway genes, including BIRC5, and changes in protein dynamics. Stimulation with SHH protein results in increased cell migration, while GLI1 transfection or PTCH1 silencing demonstrate pathway upregulation. The pathway activity can be modulated by LiCl at the GSK3β-SUFU-GLI level, suggesting at least partial non-canonical activation. Downregulation of the pathway with GANT-61 has proved to be more effective than cyclopamine. GLI inhibitors may be a superior treatment option in ovarian cancer compared to SMO inhibitors.

At any time during pregnancy intrauterine infection is an important risk factor for neonatal sepsis and is a frequent cause of mortality and morbidity in newborn infants. The aim of this study was to consider the patterns of procalcitonin (PCT) response in normal pregnancy and in pregnancies complicated with a premature rupture of the membranes, to compare the results of PCT with those of C-reactive protein (CRP) and to assess their diagnostic accuracy both to mothers and neonates. 120 mothers with singleton pregnancies were enrolled in this study. 60 pregnancies were complicated with a premature rupture of membranes, and 60 were control pregnancies. We analyzed PCT and CRP values, clinical chorioamnionitis, neonatal infection and other neonatal outcomes in both groups. We found significantly higher maternal serum concentrations of PCT and CRP in the Study group. Regarding our results, both markers are predictive for chorioamnionitis and neonatal infections, with almost similar significance.

In this study we investigated the types and role of different genetic changes of PTCH1 gene in three different types of ovarian tumors: carcinomas, fibromas and dermoids. LOH of the PTCH1 region was detected in 27.3% ovarian carcinoma samples, 18.18% ovarian fibroma samples and 55.56% ovarian dermoid samples. No point mutations were detected in any of the three types of ovarian tumors. SNP c.3944C>T showed significant differences between ovarian carcinoma and control samples with the minor T allele being significantly higher in controls compared to ovarian carcinomas. Interestingly, a new polymorphism c.−1184G>A was found only in tumor samples and further analyses should be performed in order to elucidate its potential role in ovarian tumors.

OBJECTIVE: To report the efficacy and complications of anterior pelvic organ prolapse (POP) repair with mesh placed through the transobturator route (Perigee system; AMS, Minnetonka, MN, USA). ----- METHODS: In total, 198 women with anterior POP grade II or higher according to the POP Quantification (POP-Q) system were treated with the Perigee procedure. The primary outcome was defined as anterior POP grade I or lower at 12months' follow-up. The secondary outcomes included the incidences of perioperative, mesh-related, short-term, and long-term postoperative complications. ----- RESULTS: The cure rate was 92.9% overall and 90.6% among women who had previously undergone a hysterectomy or a traditional anterior colporrhaphy. The mean POP-Q Aa and Ba values were significantly improved after the procedure (Aa 2.2cm [0.0 to 3.0cm] versus -2.1cm [-3.0 to -1.2cm]; Ba -2.5cm [-1.0 to 4.2cm] versus -2.2cm [-5.5 to -1.0cm]; P

We report a case of a 53-year-old woman with Grade 1 serous cystadenocarcinoma on her left ovary and metastatic serous adenocarcinoma on her right ovary. Serous carcinoma is the most common type of ovarian cancer, representing approximately half of all cases. Because of positive family history, the patient was referred for BRCA1/2 screening. Germline BRCA1 mutation c.676delT (p.C226VfsX8) was found, and in tumor tissue the normal allele was lost. Tumor tissue also had loss of heterozygosity in the PTCH1 gene, one of the major members of the Hedgehog-Gli (Hh-Gli) pathway. Gene expression analysis showed upregulation of the Hh-Gli pathway in both ovaries compared with healthy ovarian tissue. Primary cell culture was developed from the patient’s tissue and showed downregulation of gene expression in response to cyclopamine, a Hh-Gli pathway inhibitor. The Hh-Gli signaling pathway may play a role in malignant transformation and metastasis of ovarian cancer.

Objective To determine the perinatal risk factors of long-term neurologic impairment for preterm infants. Methods A case-control study was conducted with 60 neurologically impaired and 60 healthy children, all born prematurely. Results There was no relation between neurologic impairment and maternal pregnancy complications or prenatal steroid administration, bacteriologic content of cervical smear, fetal presentation, fetal heart rate, or mode of delivery. Cerebral palsy was associated with early neurologic signs, perinatal asphyxia, neonatal septicemia, abnormal brain ultrasound findings, prolonged interval between rupture of membranes and delivery, and multiple placental lesions. Children with minimal cerebral dysfunction were more frequently first born. Multiple placental lesions, neonatal septicemia, abnormal brain ultrasound findings, and perinatal asphyxia were independently correlated with long-term neurologic impairment. Conclusion Perinatal infection, perinatal asphyxia, and abnormal brain ultrasound findings seem to be risk factors for cerebral palsy whereas primigravidity seems to be correlated with minimal cerebral dysfunction.

Response to the letter by Dr. Köbel on manuscript titled "Hedgehog-Gli signaling pathway in ovarian borderline tumors and ovarian carcinoma".