Bad and Bid - potential background players in preneoplastic to neoplastic shift in human endometrium.

The most common malignancies of the female genital tract are endometrial carcinomas, whose are generally proceeded by hyperplasia. The maintenance of tissue homeostasis is to great extent governed by apoptosis, whose defects can lead to the preneoplastic and/or cancerous changes. Endometrial apoptosis involves among others three groups of proteins of the Bcl-2 family. First group contains anti-apoptotic proteins (e. g. Bcl-2, Bcl-xL). The other two groups belong to the pro-apoptotic proteins with three (e. g. Bax, Bak) or one (e. g. Bad, Bid) so-called BH domains. Bad and Bid trigger the oligomerization of Bak and Bax protein, which permeabilize the outer mitochondrial wall. Unlike Bid, Bad cannot directly trigger apoptosis. Instead, Bad lowers the threshold at which apoptosis is induced, by binding anti-apoptotic Bcl-2 proteins. However, their mutual counterbalance or synergism in the human endometrium has not been reported yet.In this study, the levels of Bid and Bad were measured using SDS-PAGE and Western blotting with specific antibodies, with the aim to analyse expression of Bid and Bad proteins in normal (NE), hyperplastic (HE) and cancerous (CE) endometrium. We demonstrated that Bid expression in CE reached only 47% and 50% of this observed in NE and HE. Conversely, Bad expression in HE reached only 40% and 36% of this observed in NE and CE, respectively. We detected no significant changes of Bid expression between HE and NE, and levels of Bad protein were not different between CE and NE.Trend of Bid and Bad protein expression is clearly opposite in HE and CE. We hypothesise that disrupted apoptotic program in CE seems to be reduced further by lowering levels of direct apoptotic trigger protein Bid. We suggest that the adenocarcinoma tissue of human endometrium thus tries to strengthen its apoptotic effort by lowering the apoptotic threshold via higher Bad levels.

[Current classification of malignant tumours in gynecological oncology--part II]. / Soucasná klasifikace zhoubných nádoru v onkogynekologii--cást II.

OBJECTIVE: Review of new staging systems for gynaecological cancers and their impact on prognosis and planning treatment. DESIGN: Review article. SETTING: Department of Gynaecology and Obstetrics, First Faculty of Medicine and University Hospital Na Bulovce, Charles University, Prague; Department of Radiotherapeutic Oncology, First Faculty of Medicine and University Hospital Na Bulovce, Charles University, Prague; Department of Pathology, University Hospital Na Bulovce, Prague. RESULTS: Every staging system should have 3 basic characteristics: it must be valid, reliable, and practical. Over the years, these staging classifications--with the exception of cervical cancer and gestational trophoblastic neoplasia--have shifted from a clinical to a surgical-pathological basis. Changes based on new findings were proposed in 2008 by the FIGO Committee on Gynecologic Oncology, approved in September 2008 by the FIGO Executive Board, and published in 2009. The greatest changes were made in the new staging system for carcinoma of the vulva and others in the new staging systems for carcinoma of the cervix and carcinoma of the endometrium. A new stanging system was also created for uterina sarcomas, based on the criteria used in other soft tissue sarcomas. A clinical staging system for carcinoma of cervix continues because surgical staging cannot be employed worldwide (especially in third world countries). Stage 0 has been deleted from the staging of all tumours, since it is pre-invasive lesion and it is not an invasive tumour. In the revised staging system for carcinoma of the endometrium, four fundamental changes have occurred, which will be discussed. Carcinosarcoma is still staged identically to carcinoma of the endometrium. A completely new staging system was created for adenosarcomas, along with an almost identical staging system for leiomyosarcoma and endometrial stromal sarcoma. The staging system for carcinoma of ovary and Fallopian tube remains without changes. CONCLUSION: Since medical research and practice in the field of oncology have shown explosive growth, the staging of some of the gynaecological cancers did not give a good spread of prognostic groupings. Therefore, revised FIGO and TNM staging system has been structured to represent major prognostic factors in predicting patients' outcomes and lending order to the complex dynamic behavior of gynaecological cancers. The purpose of good staging system is to offer a classification of the extent of gynaecological cancer in order to provide a method of conveying one's clinical experience to others for the comparison of treatment methods.

[Current classification of malignant tumours in gynecological oncology--part I]. / Soucasná klasifikace zhoubných nádoru v onkogynekologii--cást I.

OBJECTIVE: Review of new staging systems for gynaecological cancers and their impact on prognosis and planning treatment. DESIGN: Review article. SETTING: Department of Gynaecology and Obstetrics, First Faculty of Medicine and University Hospital Na Bulovce, Charles University, Prague. Department of Radiotherapeutic Oncology, First Faculty of Medicine and University Hospital Na Bulovce, Charles University, Prague. Department of Pathology, University Hospital Na Bulovce, Prague. RESULTS: The main objectives of any good staging system--essential to an evidence-based approach to cancer--include planning treatment, providing an assessement of prognosis and the evaluation of the results of treatment. With this approach, the exchange of relevant information between oncological centers is facilitated, thus disseminating knowledge and stimulating research in other parts of the world. A good staging system must have three basic characteristics: validity, reliability, and practicality. The first staging system for gynaecological cancers appeared around the turn of the 20th century and was applied to carcinoma of the cervix uteri. Classifications for the other gynaecological malignancies were not created until the 1950s. Over the years, these staging classifications--with the exception of cervical cancer and gestational trophoblastic neoplasia--have shifted from a clinical to a surgical-pathological basis. Some changes, brought about through new findings, were approved by the FIGO in 2008 and published in 2009. The greatest changes were made in the new staging system for carcinoma of the vulva, while others were made in the new staging systems for carcinoma of the cervix and carcinoma of the endometrium. A new stanging system was also created for uterine sarcomas, based on the criteria used in other soft tissue sarcomas. CONCLUSION: As a result of the explosion of medical research in the field of oncology, the staging of some of the gynaecological cancers became outdated and did not give a good spread of prognostic groupings. Therefore, revised FIGO and TNM staging system has been structured to represent major prognostic factors in predicting patients' outcomes and lending order to the complex dynamic behavior of gynaecological cancers. The purpose of a good staging system is to offer a classification of the extent of gynaecological cancer, in order to provide a method of conveying one's clinical experience to others for the comparison of different treatment methods.

Changes in expression of some apoptotic markers in different types of human endometrium.

The maintenance of tissue homeostasis and highly balanced counteraction of cellular proliferation and apoptosis are essential for tissue integrity. In our study, we evaluated the expression of apoptosis- regulating proteins Bcl-2, Bax and PARP, and executive apoptotic enzyme caspase-3 in normal, atrophic, hyperplastic and cancerous endometrium. Endometrial samples were obtained from patients who underwent curettage, hysteroresection or hysterectomy. The protein levels were quantified by immunoblotting. We observed a higher level of important apoptotic enzyme pro-caspase-3 and its active form in hyperplastic and cancerous endometrium, when compared to normal endometrium. The value of Bcl-2/Bax ratio, which reflects cellular resistance to apoptosis, was determined as > 1 for cancerous, normal, and atrophic endometrium. Thus, the effort to eliminate pre-neoplastic and neoplastic cells by apoptosis indicated by high pro-caspase-3 and caspase-3 levels seems to be overcome by a greater proliferative adjustment suggested by higher Bcl-2/Bax ratios in the samples examined. The PARP levels did not vary significantly among the groups. The levels of all examined proteins were significantly lower in atrophic endometrium. Our results suggest that pre-neoplastic and neoplastic states of human endometrium are not influenced simply by changes in apoptosis, but may also be affected by cellular proliferation. A high Bcl-2/Bax ratio as observed in cancerous endometrium can point to deregulation of apoptotic programmes. Thus, the onset and progression of endometrial malignancy could be linked to increased cellular proliferation with defects in apoptotic control.

[Significance of hysteroscopic resection in diagnostics of endometrial cancer]. / Význam resektoskopie v diagnostice karcinomu endometria.

OBJECTIVES: Endometrial cancer is the second most common malignancy of the female genital tract. Its incidence in the Czech Republic is 32/100 000 women and year with a permanent increasing tendency. In comparison with incidence, its mortality remains relatively low, with mortality ratio of 6.7 per 100,000 women and year. The decrease in mortality might be explained predominantly by early diagnostics. The most controversial issue is the potential risk of microscopic extrauterine dissemination of cancerous cells within the peritoneal cavity and circulation during hysteroscopy, and the question if the relatively high pressure of distension medium used during hysteroscopies may or may not multiply the risk. DESIGN: Retrospective study. MATERIALS AND METHODS: Totally, 400 endometrial biopsies were collected during years 2007-2009 at our clinic. In 56 patients, endometrial cancer was diagnosed. Afterwards, 44 women underwent surgery, during which peritoneal washing (lavage) and cytological examination were done. RESULTS: Fifty-six patients with histologically verified endometrial carcinoma were studied. The samples examined in the study were classified by grading as follows: G1 n=34, G1-2 n=10, G2 n=10, G3-4 n=2. In 44 cases that underwent radical surgery, no cancerous cells in peritoneal washings were found. Only in 1 case, the cytology obtained from peritoneal washing was considered to be suspicious. In 9 cases, carcinoma on the base of the polyp was detected, and in 2 cases, no residuum of cancer was observed after hysterectomy. CONCLUSION: In accordance with contemporary literature and based on our study, we suggest that hystero-resectoscopy does not increase the risk of dissemination of malignant cells within the peritoneal cavity and does not worsen the prognosis of the disease. On the contrary, the samples taken under visual control provide more precise and earlier diagnostics of endometrial cancer.

Cholinesterase inhibitory activities of some flavonoid derivatives and chosen xanthone and their molecular docking studies.

Flavonoids are one of the largest classes of plant secondary metabolites and are known to possess a number of significant biological activities for human health. In this study, we examined in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of four flavonoid derivatives--quercetin, rutin, kaempferol 3-O-beta-D-galactoside and macluraxanthone. The in vitro results showed that quercetin and macluraxanthone displayed a concentration-dependant inhibition of AChE and BChE. Macluraxanthone showed to be the most potent and specific inhibitor of both the enzymes having the IC(50) values of 8.47 and 29.8 microM, respectively. The enzyme kinetic studies revealed that quercetin inhibited both the enzymes in competitive manner, whereas the mode of inhibition of macluraxanthone was non-competitive against AChE and competitive against BChE. The inhibitory profiles of the compounds have been compared with standard AChE inhibitor galanthamine. To get insight of the intermolecular interactions, the molecular docking studies of these two compounds were performed at the active site 3D space of both the enzymes, using ICM-Dock module. Docking studies exhibited that macluraxanthone binds much more tightly with both the enzymes than quercetin. The calculated docking and binding energies also supported the in vitro inhibitory profiles (IC(50) values). Both the compounds showed several strong hydrogen bonds to several important amino acid residues of both the enzymes. A number of hydrophobic interactions could also explain the potency of the compounds to inhibit AChE and BChE.

Cholinesterase inhibitory effects of the extracts and compounds of Maclura pomifera (Rafin.) Schneider.

We have investigated anticholinesterase potential of the methanol extracts from the leaf, wood, flower, twig, and stem bark of the female and male individuals and rhizodermis and fruit from the female tree of Maclura pomifera (Rafin.) Schneider (Moraceae) along with its major isoflavonoids; osajin and pomiferin as well as their semi-synthetic derivatives; iso-osajin and iso-pomiferin. Anticholinesterase activity was determined by Ellman method using ELISA microplate reader. Osajin and pomiferin had a noticeable inhibition of AChE with IC(50) values of 2.239 and 0.096 mM, respectively, while their iso-derivatives were found to display less inhibition towards AChE. The extracts and compounds did not inhibit BChE. The extracts were analyzed for osajin and pomiferin contents by LC-DAD-MS and only the fruits and female flowers contained osajin (fruit: 8.87%, female flowers: 0.19%, w/w) and pomiferin (fruit: 13.6%, female flowers: 0.36%, w/w).

[Intravenous treatment of postpartum anemia with trivalent ferrum preparation]. / Intravenózní aplikace lécebného prípravku trojmocného zeleza pri lécbe poporodní anémie.

AIM OF THE STUDY: To assess the effectivity and safeness of intravenous treatment of pospartal anemia with trivalent ferrum preparation. TYPE OF THE STUDY: Prospective randomized study. SETTING: Department of Obstetric and Gynecology 2nd Medical Faculty Charles University and Teaching Hospital Motol, Prague, and Department of Obstetric and Gynecology 1st Medical Faculty and Teaching Hospital Bulovka, Prague. METHODS: 500 mg of sacharose ferric oxide (Venofer) was intravenously administered in two days regimen to 50 women with clinical and lab signs of postpartal anemia. The effect of administered drug was determined by comparsion of values of red blood count recovered before the treatment, 2nd or 3rd day post administration and two weeks later. The serum values of soluble transferrin receptors and ferritin were observed as markers of iron cell saturation and body iron reserves, too. Integral part of the study was the monitoring of adverse events during the treatment. RESULTS: Venofer came in sight as effective drug in the treatment of pospartal anemia and could become as the alternative to blood transfusion in mid-severe cases. It should be emphasized that we have not encountered any serious adverse event with intravenous trivalent saccharose ferric oxide treatment.

[Pregnancy after laparoscopic myomectomy--long-term follow up]. / Tehotenství po laparoskopické myomektomii--dlouhodobé sledování.

OBJECTIVE: Analysis of pregnancy related complications in infertile patient after laparoscopic myometomy (LM). DESIGN: Retrospective analytic study. SETTING: Institute for the Care of Mother and Child, Prague; Institute for Postgraduate Medical Education, Prague. METHODS: The study group were infertile patients referred to our department with the finding of uterine fibroid(s). In all patients LM was the method of choice. Thorough information and results from all infertile patient after LM were assessed and analysed with 18 months follow-up after surgery. RESULTS: The aim of our study was to evaluate pregnancy rate and the possible risks during pregnancy and delivery following LM. We analysed 69 patients after LM. Mean size of a fibroid was 3.3 cm and the number of removed fibroids in one patient was 1.8. The conception rate after LM was 56.5%. We didn't observe any increased incidence of fetomaternal morbidity or severe pregnancy and labour related complications. There was no uterine rupture after LM in our group. The cesarean section was rate 44.8%. CONCLUSIONS: The impact of fiborids on infertility is still controversial. LM in infertile patient is one of the most common surgical procedure. The appropriate surgical management of uterine scar is mandatory. This operation must be performed by skilled reproductive surgeon. Thorough information to the patient before and after LM is necessary. The pregnancy following LM is at high risk with increased caesarean section rate.

[A survey of surgical techniques used for the correction of statics disorders of pelvic floor]. / Prehled operacních technik uzívaných ke korekci poruch statiky pánevního dna.

OBJECTIVE: To present an overview of current procedures used in female pelvic floor reconstructive surgery. SUBJECT: Review article. SETTING: Teaching Hospital Bulovka, 1st Faculty of Medicine, Charles University, Prague. SUBJECT AND METHOD: Pelvic organ prolapse (POP) in women including associated disorders belong to the top problems in current urogynecology. During the last decade a substantial progress in elucidation of detail morphology and function of each pelvic floor compartments had been made. These new findings could be rapidly implemented into clinical medicine, mainly as application of new mesh implants. The results of reconstructive operations are variable, one of the reason is the existence of many operation techniques. This review article represents a short overview of those methods. CONCLUSION: Wide range of current operation procedures must be re-evaluated respecting the existence of new techniques based on recent anatomical studies.

[Methods of assisted reproduction in HIV positive patients]. / Metody asistované reprodukce u HIV pozitivních pacientu.

AIM OF THE STUDY: Analysis of treatment possibilities of infertility in HIV positive patients and solution of child desire in discordant pairs. Authors also present their own case. TYPE OF STUDY: Literature review and two case report. NAME AND SETTING OF DEPARTMENT: Department of Obstetrics and Gynaecology, The First Medical Faculty of Charles University in Prague. MATERIALS AND METHODS: Review of papers published on risk of HIV transmission during sexual intercourse, fertility of HIV positive patients and possible solution of their child desire. Summary of papers published on safety and effectivity of artificial insemination and IVF ET in HIV discordant pairp. Analysis of our own cases of artificial insemination in pairs of HIV negative female and HIV positive male. CONCLUSION: Artificial insemination seems to be safe, relatively cheap and effective solution of child desire in HIV discordant pair.