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Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a common chemotherapy side effect, but its prevention and treatment remains a challenge. Neurotoxicity may lead to dose limitation or even treatment discontinuation, and therefore potentially affect the efficacy of anticancer treatment and long term outcomes. The practice to administer gabapentin for neuropathy may be applicable, but is limited by insufficient studies. The aim of our study was to assess the presence of chemotherapy-induced peripheral neuropathy in ovarian cancer patients treated with first-line paclitaxel and carboplatin chemotherapy and evaluate the effectiveness of gabapentin in treatment of this condition. Material and methods: 61 ovarian cancer patients treated with first line chemotherapy were included in the study. The first phase of the study was to assess neurological condition of each patient by: neuropathy symptoms scale, McGill’s scale, neurological deficit and quality of life, during the chemotherapy. In the second phase of the study we evaluated the response to gabapentin treatment in a group of patients who developed neuropathy. Results: 78.7% of the patients developed chemotherapy related neuropathy. During the course of chemotherapy these patients experienced significant exacerbation of neuropathy symptoms (p < 0.0001), neuropathic pain (p < 0.0001), neurologic deficit (p < 0.0012) and worsening of quality of life (p < 0.0002). Patients who were qualified to undergo the gabapentin treatment observed improvement in symptoms (p < 0.027), pain (p < 0.027) and neurologic deficit (p < 0.019). Quality of life did not change significantly after gabapentin treatment (p < 0.128). Conclusions: Chemotherapy substantially deteriorates the neurologic condition of the patients and the quality of life. Paclitaxel and carboplatin treated patients may benefit from gabapentin therapy in chemotherapy-induced peripheral neuropathy.

BACKGROUND/AIM It has been shown in many studies that expression of pyruvate kinase (PK) enzyme plays a key role during cellular metabolism. There is evidence that cancer cells manifesting very dynamic proliferation may control their division in various mechanisms, i.a. by expression of PKM2 isoform. The exact role of PKM2 in ovarian cancer (OC) cells and cancer associated fibroblasts (CAFs) have not been elucidated. MATERIALS AND METHODS The present study was focused on analysis of PKM2 expression in cancer cells and CAFs in 97 OC cases, mostly of serous histological type. Moreover, relationships between expression of PKM2 and proliferation (Ki-67; MCM-2, -3, -7; cyclin D1), vascular (CD31, D2-40) and mesenchymal (Vim and αSMA) markers as well as receptors (ER, PR, HER2, EGFR) were examined. All observations were evaluated in regard to available clinicopathological data. RESULTS The expression of PKM2 was disclosed only in cytoplasm of OC cells. No statistically significant correlation between PKM2 and tested markers was found. In regard to available clinicopathological data only an increasing trend of PKM2 expression with increasing grade of histological malignancy G was found (p=0.07). CONCLUSION Due to achieved results concerning expression of PKM2 there is a lack of evidence for its diagnostic and prognostic usage in OC.

Objectives: Since metformin was reported to decrease overall cancer incidence and mortality and to have antiproliferative and antiinvasive properties, we investigated the impact of metformin intake on survival in endometrial cancer patients. Material and methods: Medical records and survival data of 126 patients with endometrial cancer were analyzed retrospectively. U Mann-Whitney and chi-square tests were applied to compare clinicopathological features. Kaplan Meier model with log-rank test was used to compare survival in the subgroups. Cox proportional hazard model was applied to analyze the relationships between particular factors and overall survival. Results: 107 patients met study criteria and were divided into three groups: 1) patients with type 2 diabetes and metformin users (n=30), 2) patients with type 2 diabetes and metformin non-users (n=38), 3) patients without diabetes mellitus (n=39). No difference in survival between metformin users versus metformin non-users (p=0,86) was observed. Metformin intake, diabetes mellitus co morbidity, plasma glucose level and BMI appeared without influence on survival. When the analysis was restricted to the subgroup of type I endometrial cancer or to endometroid histological type, still neither metformin intake nor diabetes influenced the prognosis. Conclusions: Metformin intake does not alter overall survival in endometrial cancer patients. Diabetes mellitus has no influence on survival in endometrial cancer patients.

Objectives: The aim of this study was to assess the sensitivity and specificity of HE4 in detecting and differentiating between types I and II epithelial ovarian cancer (EOC) in comparison with CA125. Material and methods: We measured HE4 and CA125 serum concentrations in 206 samples taken from patients operated in Gynecologic Oncology Department due to ovarian tumors. Ovarian cancer was confirmed in 89 cases divided into type I and type II. 52 healthy patients without any gynecological disease formed the control group. The sensitivity and specificity for type I and type II EOC detection and differentiating between both types was evaluated for HE4 and CA125. Results: The HE4 and CA125 serum concentrations were significantly higher in type II than in type I EOC (p=0.008696, p=0.000243 respectively).The HE4 and CA125 sensitivity for type I and benign tumors differentiation was 63.16% for both of them and specificity was 87.29% vs 67.89% respectively. For CA125 these differences did not reach statistical significance. The HE4 sensitivity and specificity for type II and benign tumors differentiation were 87.14% and 96.61%, respectively, and for CA125 these values were 82.86% and 94.07%, respectively. Conclusions: Pretreatment analysis of HE4 serum concentration is superior to CA125 in differential diagnosis of ovarian cancer subtypes (I and II). HE4 is superior to CA125 in detecting ovarian cancer type II. Neither HE4 nor CA125 is an effective diagnostic tool for type I ovarian cancer detection. A new highly specific and highly sensitive tumor marker for type I EOC is needed.

Ovarian cancer (OC) is the leading cause of death among women with genital tract disorders. Melatonin exhibits oncostatic properties which it may effect through binding to its membrane receptor, MT1. The aim of this study was to determine the expression of MT1 in OC cells and to correlate this with clinical and pathological data. Immunohistochemistry was performed on 84 cases of OC. Normal ovarian epithelial (IOSE 364) and OC (SK-OV-3, OVCAR-3) cell lines were used to examine the MT1 expression at protein level using the western blot and immunofluorescence technique. The expression of MT1 was observed as cytoplasmic-membrane (MT1(CM)) and membrane (MT1(M)) reactions. A positive correlation between MT1(CM) and MT1(M) was found in all the studied cases. There were no significant differences between the expression of MT1(CM), MT1(M), and histological type, staging, grading, presence of residual disease, or overall survival time. Immunofluorescence showed both MT1(M) and MT1(CM) expression in all the tested cell lines. Western blot illustrated the highest protein level of MT1 in IOSE 364 and the lowest in the OVCAR-3. The results indicate the limited prognostic significance of MT1 in OC cells.

The HPV-16/18 AS04-adjuvanted vaccine (Cervarix®, GlaxoSmithKline Biologicals) has been shown to induce a robust immune response in women aged 15–55 years (103514/NCT00196937). This follow-up study is the first report of persistence of immune response and safety profile through 48 months after vaccination in women aged 15–55 years. In this open-label, age-stratified Phase III study in Germany and Poland (105882/NCT00196937), healthy women aged 15–55 years received 3 doses of HPV-16/18 AS04-adjuvanted vaccine at 0, 1 and 6 months. Anti-HPV-16/18 seropositivity rates and geometric mean antibody titers (GMTs) were assessed by enzyme-linked immunosorbent assay (ELISA) in women aged 15–25 (n = 168), 26–45 (n = 186) and 46–55 years (n = 177) from the time of first vaccination through 48 months. At Month 48, all subjects were seropositive for anti-HPV-16 antibodies and 99.4% were seropositive for anti-HPV-18. Antibody kinetics were as previously reported, with peak response at Month 7 followed by a gradual decline tending towards a plateau in all age groups. Anti-HPV-16/18 GMTs were sustained at Month 48 in all age groups, including women aged 46–55 years in whom GMTs were respectively 11-fold and 5-fold higher than natural infection levels. The vaccine exhibited a clinically acceptable safety profile in all age groups. In summary, the HPV-16/18 AS04-adjuvanted vaccine induces high and sustained immune responses in women aged 15–55 years, with antibody levels remaining several-fold higher than natural infection levels for at least 4 years after the first vaccine dose.

Estrogen as a potential factor of ovarian carcinogenesis, acts via two nuclear receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), but the cellular signal pathways involved are not completely clear so far. In this study we have described the expression of ERα, detected by immunocytochemistry in 11 ovarian carcinoma cell lines and by immunohistochemistry in 43 Federation Internationale des Gyneacologistes et Obstetristes stage III ovarian carcinoma specimens prepared before and after treatment with cisplatin-based schemes. For cisplatin resistance is a major obstacle in the treatment of ovarian carcinoma, analysis of cisplatin sensitivity in 11 ovarian carcinoma cell line was also performed. The strong nuclear ERα expression was only shown in the single A2780P cell line. Expression of ERα in tissue specimens did not reveal any correlations between histopathological parameters (histologic type and grading). We demonstrated a significant association with ERα expression in specimens from primary laparotomies (PL) and cause–specific survival. In the cases terminated by death of the patient, overall immunoreactivity score of ERα expression at PL was significantly lower than in surviving patients. In addition, Kaplan-Meier analysis revealed significantly shorter overall survival time and progression-free time in cases with lower immunoreactivity score of ERα expression at PL. Our findings support the hypothesis that aberrant hormone activity, by way of altered receptor expression, might be an important factor in the malignant transformation of ovarian cancer.

Resistance to cis- or carboplatin represents the principal cause of therapeutic failures in ovarian carcinoma. The phenomenon of resistance to platinum-based drugs is partly related to expression of metallothionein (MT) and of glutathione S-transferase pi (GST-pi), but opinion on the subject is discordant. Documentation of a negative predictive effect of MT and GST-pi expression for the therapy employing platinum-based drugs would permit to select resistant cases in which other therapeutic approaches could be employed. The present study aimed at examining the relation between intensities of MT and GST-pi expressions in ovarian carcinomas and dynamics of the clinical course in the neoplastic disease in a group of cisplatin-treated patients. The analyses were performed on samples of ovarian carcinoma originating from 43 first-look laparotomies (FLLs) and, in 30 cases, from second-look laparotomies (SLL) from the same patients. Immunohistochemical reactions were performed on paraffin sections of studied tumors, using monoclonal antibodies to MT and GST-pi. The calculations showed that in cases with augmented expression of MT, mortality was higher. On the other hand, augmented expression of GST-pi predisposed to more frequent relapses, deaths and progression of the tumor. Kaplan-Meier analysis showed that a significantly shorter survival time was linked to cases of higher expression of MT at FLL and of higher expression of GST-pi at FLL, whereas a shorter progression-free time was manifested by cases with higher expression of GST-pi at FLL. The performed investigations indicate that augmented expressions of MT at FLL and GST-pi at FLL in ovarian cancer represent an unfavourable predictive factor in cisplatin-treated patients.

Among many alterations within the TP53 gene the rs1042522 (C72G, p.Pro72Arg) has been associated with numerous cancers , however the results differ between populations for opposite Pro or Arg alleles. Similar thus inconclusive results are observed in ovarian cancer, which may suggest that the rs1042522 does not influence ovarian carcinogenesis directly, but might be linked to another pathogenic alteration. WRAP53 which overlaps the TP53 is required to maintain normal levels of p53 upon DNA damage, but also when altered may independently increase the risk of cancer. To evaluate the association between three SNPs located in WRAP53-TP53 region: rs1042522, rs2287497, rs2287498 and ovarian cancer risk in Polish population we genotyped 626 cases and 1,045 healthy controls. Our results provide the evidence for an association between studied SNPs and a risk of invasive ovarian cancer in Poland. We found that CC homozygotes in rs1042522 were more frequent in cancers when compared to controls (OR = 1.46, p = 0.03). Similarly in WRAP53 both TT homozygotes in rs2287497 (OR = 1.95, p = 0.03) and AA homozygotes in rs2287498 (OR = 2.65, p = 0,01) were more frequent among cases than healthy individuals. There is also a suggestive evidence that specific homozygosity of studied SNPs in TP53-WRAP53 region is significantly overrepresented in ovarian cancer patients. In conclusion SNPs in WRAP53 (rs2287497 and rs2287498) have stronger association with an ovarian cancer risk than rs1042522 in TP53.

The aim of the study was to assess the diagnostic value of pap smears and detection of the p16 and Ki67 proteins in women with cervical intraepithelial neoplasia (CIN).630 women, aged between 25 and 65, with abnormal pap smears were included into the study All patients had a control pap smear and in each case punch biopsy with endocervical curettage were performed under the control of a colposcope. The presence of p16 and Ki67 proteins was detected using the CINtecPlus test. The results of the research were statistically assessed.Abnormal pap smears were found in 82.5% (520/630) of the studied women. In 40% (252/630) of the cases the LSIL changes were found. The recognition of ASC-US concerned 35.2% (222/630) of the patients, and pap smears with the HSIL result were found in 7.3% (46/630) of the women. In 17.5% (110/630) of the patients the result of the cytological examination was normal. Abnormal results of the pap smears were found significantly statistically more frequently (p0,0001) in women with cervical intraepithelial neoplasia (CIN). The results of the CINtecPlus test were positive in 68,4% of women with CIN and in 33,3% of patients with normal cervix. In the group of women with precancerous lesions (HGSIL/CIN2+) the diagnostic accuracy of the pap smear was 41% for the cytological results ASC-US, 56% LSIL and 73% for detection of HSIL. Immunocytochemical detection of p16 and Ki67 proteins gained the highest accuracy (78%) in recognition of cervical precancerous lesions.1. ASC-US and LSIL cytological recognition has low accuracy in the diagnosis of CIN2+ cervical changes. 2. Cytological recognition of HSIL has the highest accuracy in the diagnosis of CIN2+ changes. 3. Immunocytochemical detection of p16 and Ki67 proteins is more accurate in recognizing precancerous states and cervical cancer than cytological examination. 4. Immunocytochemical detection of the p16 and Ki67 proteins can be used to triage patients with atypical squamous cells of undetermined significance and low grade squamous intraepithelial lesions.

Degradation of the extracellular matrix and basement membrane is a critical step in tumor progression. Matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP 2) act in a coordinated manner to form an integrated system involved in ovarian cancer (OC) progression. In this study, the authors describe the expression of TIMP-2 detected by immunohistochemistry in 6 OC cell lines and in 43 malignant epithelial ovarian tumors (in tumor and stromal compartments) in sections originating from primary laparotomies. No significant correlations between overall and progression-free survival and TIMP-2 expression in tumor compartment were observed. The analysis demonstrated a significant association between enhanced stromal expression of TIMP-2 and better clinical response to cisplatin- and paclitaxel-based chemotherapy. Increased expression of TIMP-2 in the stromal compartment and simultaneous overexpression in both stromal and tumor compartments strongly correlated with increased survival. No significant correlations were found in vitro between resistance to cisplatin, paclitaxel, or topotecan and the expression of TIMP-2 in the OC cell lines, suggesting stromal influences on tumor chemoresistance in the physiological environment. This study supports the concept of TIMP-2 expression in the stromal compartment of OC as a promising marker of prognosis and response to cisplatin- and paclitaxel-based chemotherapy in OC patients.

This pooled analysis of data from four Phase III clinical trials was undertaken to assess the correlation between levels of anti-human papillomavirus (HPV)-16/18 antibodies in serum and cervicovaginal secretions (CVS) in girls and women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine. Serum and CVS samples were collected from a subset of women aged 10-65 years (N=350) at pre-specified time-points from 7 to 36 months post-vaccination. Anti-HPV-16/18 antibody levels in serum and CVS were measured by enzyme-linked immunosorbent assay. Pearson correlation coefficients between serum and CVS antibody levels, standardized for total immunoglobulin G, were calculated at each time-point in women with detectable antibodies in both serum and CVS. All subjects had seroconverted at Month 7 and remained seropositive through Month 36 for both antigens. Geometric mean titers of anti-HPV-16/18 antibodies in serum were substantially higher at all time-points than those in a control group of women who had cleared a natural HPV infection in another trial. In women with detectable antibodies in both serum and CVS, good correlation was seen between HPV-16/18 antibody levels at all time-points (Pearson correlation coefficient: 0.84-0.92 for HPV-16 and 0.90-0.91 for HPV-18). The strong correlation between levels of HPV-16/18 antibodies in serum and CVS up to 36 months post-vaccination in girls and women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine supports transudation of serum antibodies as the mechanism by which antibodies are introduced into CVS. These CVS antibodies may play a role in the protective efficacy of this vaccine.

Screening programs may contribute to decreasing the mortality rate in a given population and their main target, in case of cervical cancer; is to find and to cure preclinical stages of this malignancy. Regularly repeated tests in defined time intervals can diagnose the illness at its early stages but the results come with a high cost. Population program of early detection of cervical cancer has been conducted since 2007 and is run by the Central Coordinating Center and 16 regional centers. Funds for promotional, educational, monitoring and medical activities are obtained from the National Health Service.The aim of this study was to present the cost-effectiveness of the Program between 2007 and 2009.The material for the analysis was obtained from the SIMP system, where all the data about women participating in the Program are implemented. The analysis of the cervical carcinoma treatment and procedure costs was made on the basis of the National Health Service estimates. The number of new cervical carcinoma cases was calculated with the help of the newly introduced system code--C53.Between 2007 and 2009 the cost of one cytological smear was similar in all regions (about 10 PLN). The highest costs were noted in Lubuski and Swietokrzyski regions. The costs of promotional and educational activities amounted up to 4.5 million PLN. A single cervical smear test cost for one woman has increased in the analyzed years from 3.95 up to 7.34 PLN. The total cost of one woman cytological examination--medical and non-medical elements--was more than 60 PLN. In 2009, 622 new cases of cervical cancer were found thanks to the Program. The cost of one case of cervical cancer diagnosis was 15 000 PLN. The total costs of all cases of cervical cancer in 2009 was 45.5 million PLN.The situation calls for creating new and effective tools for monitoring medical, epidemiological and financial parameters of the Program. Otherwise, the estimates of the health and social impact of the Program will fail to be plausible. Increased attendance at the Program will only marginally lower the costs of the tests. Not to mention, that different means and solutions regarding cervical cancer prevention need to be suggested due to the fact that Polish population does not yet seem to have developed the habit of taking preventive tests.

In Poland in 2007, according to the National Cancer Registry 3431 women were diagnosed with cervical cancer and 1907 died. To change the unfavorable epidemiologic situation, in 2005 the Ministry of Health (MH), the National Health Fund (NHF) and the Polish Gynecological Society following WHO/IARC guidelines developed a National Population-Based Cervical Cancer Screening Program. Its implementation and roll-out started in 2006. The target population are women aged 25 to 59 insured in the National Health Fund. A Pap test is done with a three-year interval, free of charge. The system is based on personal invitations sent by regular post. Invitation to screening is supported by a social educational campaign "Choose Life" run under one slogan and logo across the whole country The NHF data base enables identification of women to screen. Pap smears are collected by gynecologists and since 2008 also by midwives trained and certified by the Program National Coordinating Center Pap test results are reported in the Bethesda 2001 system. The Screening Program has its system of quality assurance and control and is supported by a specially designed computer data base called SIMP (System of Information Monitoring in Prophylaxis) with online access to all records. In addition to organized, population-based screening there is also opportunistic screening in Poland practiced either by private gynecological practices or by some units that cooperate with the National Health Fund, but do Pap tests as an element of comprehensive gynecological examination. Those smears are not registered in the SIMP.Our aim was analysis of attendance rate in the Cervical Cancer Screening Program in the years 2007-2009. We also investigated correlation between screening coverage and invitation sending schedule, as well as between coverage and screening accessibility determined by the number of gynaecological practices where Pap smears are collected.Attendance rate in the Screening Program was evaluated for the years 2007, 2008 and 2009. The analysis included screening coverage in all voivodeships in the 12 months of the year as well as the number of gynaecological practices participating in the Program. In addition, the place of residence of screening attenders (urban/rural area) was taken into account. For the analysis the SIMP (System of Information Monitoring in Prophylaxis) data were used. Statistical analysis was performed using Statistica 9.0 software. P-values0.05 were considered statistically significant.The target population in the years 2007-2009 was 9,727,842 women. Personal invitations were sent to 99.7% of them. Pap Smears were collected from 24.14% of the target women (in 2007--21.25%; in 2008--24.39%; in 2009--26.77%). We noted that the number of 1400 gynecological practices participating in the Program was the minimal value to observe a significant increase in the number of Pap smears collected (p = 0.000). Polish women do not attend screening in the winter months. However when a batch of invitations was sent in the spring or summer months, within two following months we could observe an increase in the number of Pap smears collected (p = 0.000). There are significant differences in the screening uptake in particular regions of Poland (a stable trend). Compared to urban women, rural women participate in the screening more often (p = 0.003).All Pap test results including opportunistic screening should be registered in the SIMP In the regions where particularly low attendance rates were observed, an intensive promotional campaign should be run to encourage participation in the screening. Also, sending a repeated invitation to non-compliers should be considered. The currently unfavorable schedule of invitation sending should be changed. According to the analysis performed, invitations should be more effective if sent on a regular basis (in small but regular batches), more intensively in the summer and spring months. In the winter season it would probably be better to focus on an extensive media campaign followed by sending a large number of personal invitations.

epithelial ovarian cancer (EOC) has the highest mortality rate among patients with gynecologic malignancies. Lack of specific and early symptoms and of screening tests causes that most patients are diagnosed in advanced stage of disease. Radical surgery followed by chemotherapy does not bring satisfactory curative effects.the urgent need exists to define the optimum biomarker for ovarian cancer to predict patients' response to curative therapy. Our current study aimed at correlation between the expression of survivin, SDF-1, CXCR-4 on tumor tissue and clinical outcome of patients with ovarian cancer.We showed that survivin expression correlates with histological grading of the tumor. No correlation was found in terms of SDF-1/ CXCR-4 expression and clinicopathologic data.further studies covering larger number of patients are needed to determine whether SDF-1 and CXCR-4 might be considered as biomarkers for ovarian cancer.

Increasing evidence indicates that genetic factors are involved in the process of carcinogenesis. BRCA 1 mutation has been proven to be responsible for increased risk of ovarian cancer However the importance of other genetic disorders, such as MTHFR polymorphism for increased risk of carcinogenesis, is still to be determined. Abnormal methylation seems to play a significant role in ovarian cancer pathogenesis. MTHFR catalyses the conversion of 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate which is a co-substrate in homocysteine remethylation into methionine. Thermolabile MTHFR protein variants with lower enzymatic activity are the effects of the mutation.The evaluation of 677CT MTHFR polymorphism frequency in the group of ovarian cancer women with BRCA 1 mutation. The assessment of the MTHFR 677CT polymorphism influence on ovarian cancer risk.A group of 153 patients with ovarian cancer (Caucasian, Polish population in Wielkopolska region) were included into the study 3 mutations: 5382insC, C61G and 4153delA in BRCA1 gene, and genotype frequency within 677CT MTHFR polymorphism, were identified. The analysis of genotype frequency was performed by means of PCR/RFLP method.127 women without BRCA1 mutation and 26 with one of the mutations: 5382insC, C61G or 4153delA were qualified for the investigation. In the group with BRCA 1 mutation, 3 out of 26 patients were with TT genotype mutation of 677CT polymorphism (12%). Heterozygotic genotype CT appeared in 13 cases out of 26 (50%), homozygotic CC in 10 out of 26 (38%). In the group of 127 ovarian cancer patients without BRCA1 mutation, TT genotype in 677CT polymorphism was present in 5 women (4%). Heterozygotic genotype CT appeared in 61 cases (48%), similarly to homozygotic genotype CC-61 (48%). The highest value (OR = 3.18) was obtained when comparing the homozygotic TT genotype groups. None of the obtained values was statistically significant.Contrary to numerous suggestions in various publications, we did not confirm the correlation between MTHFR 677CT polymorphism and the influence on the risk of ovarian cancer in BRCA1 mutation carriers in the investigated group of Polish women.

Photodynamic diagnosis (PDD) is based on the phenomenon of selective accumulation of a photosensitizer in the tissues where carcinogenesis has started. The change may be identified by fluorescence which takes place when a photosensitizer is activated by the light of an appropriate wave length. The aim of this study was: 1. Evaluation of photodynamic diagnosis in detection and precise location of cervical neoplastic lesions. 2. Comparison of sensitivity and specificity of PDD, colposcopy and cytology in detection of cervical neoplastic lesions.The study was carried out between October 2006 and December 2007 and included 73 women, patients of Gynecologic Oncology Division of the Poznan University of Medical Sciences Hospital. The examined patients were divided into two groups: the first consisted of 43 women with neoplastic lesions and the second, consisting of 30 patients with no oncologic changes of uterine cervix, comprised the control group.Each patient had PDD, cytological smear and colposcopy performed. For PDD 3% 5-delta-aminolevulinic acid (5-ALA) gel was used as a photosensitizer, applied on cervical surface 4 hours before the examination. To activate fluorescence of the areas with highest accumulation of the photosensitizer the cervix was exposed to the light of 405 nm wave length.1. Photodynamic diagnosis with 3% 5-ALA enables the detection of cervical intraepithelial neoplasia with higher sensitivity than colposcopy and higher specificity than cytological diagnosis. 2. Fluorescence allows for precise location of a cervical neoplastic change as well as its extension, borders or multifocal character. 3. Location of the change indicated by fluorescence may facilitate the choice of the place for direct biopsy as well as the extension of the therapy.

Sexual dysfunctions in women is a topic that has only just started to appear in scientific publications. Relatively little is known about the extent of the problem, but some reports suggest that sexual dysfunctions are highly prevalent, affecting 20% to even over 40% of all women. Most authors agree that female sexual dysfunctions are age-related. Epidemiological data confirms that fact and shows that one third of women demonstrate lack of interest in sex and nearly one fourth do not achieve orgasm. Approximately 20% of women report difficulties with vaginal lubrication and for 20% sex is not enjoyable. For many of them such problems influence the relationships with their partner in a negative way and are the reason of personal failures and. It should be emphasized that Hypoactive Sexual Desire Disorder is the most prevalent sexual dysfunction in all female age groups. Until 50 years ago, sexual dysfunction was not regarded as a serious medical problem which is directly responsible for scarce or limited clinical data available on the topic nowadays. The mechanisms underlying Hypoactive Sexual Desire Disorder remain elusive and, as a consequence, in most cases there is still no effective treatment In recent months, reports have been published suggesting that the situation may change soon. The introduction of new diagnostic tools and data from completed clinical trial phases may prove a real breakthrough in the diagnostics and treatment of the hypoactive sexual desire disorder.

Loss of DNA mismatch repair may result in resistance to platinum- based anticancer drugs. The hMLH1 and hMSH2 proteins play a critical role in the maintenance of genome integrity and are involved in resistance to platinum-based therapy in colorectal cancer, which is deficient in hMLH1 protein and endometrial cancer, as well as in hMSH2 protein. However, the predictive value of MLH1 and MSH2 expression in ovarian cancer cisplatin-resistance is still to be determined.The aim of this study was to investigate the expression of hMLH1 and hMSH2 proteins in ovarian carcinoma specimens and to evaluate their prognostic significance by means of overall survival (OS) and progression-free survival rates (PSF).Ovarian cancer tissues were obtained from 61 patients: 45 platinum-sensitive and 16 platinum-resistant. hMLH1 and hMSH2 proteins expression was evaluated by immunohistochemistry, with the use of mouse monoclonal antibodies clone 14 for hMLH1 and clone FE11 for hMSH2. The log-rank test and Kaplan-Meier statistics were used to analyze the relationship between proteins expression and progression free survival, as well as the overall survival.No significant correlation was found between hMLH1 and hMSH2 expression and overall survival and progression free survival in the group of patients sensitive and resistant to cisplatin. No significant difference was found in proteins expression intensity between the two compared groups of patients. Age of patients, type of cancer histology, FIGO staging, grading, clinical response and CA 125 did not reveal correlation with the expression of the analyzed proteins.The immunohistochemical expression of hMLH1 and hMSH2 proteins in ovarian cancer has no predictive value in resistance to cisplatin.

One of the most important risk factors for osteoporotic fractures in postmenopausal women is elevated bone turnover (EBT), occurring in 25-30% of this population. This study's aim was to find a correlation between bone resorption and bone formation markers to assess bone turnover rate and qualify an individual postmenopausal woman as a possible EBT subject.Three hundred twenty postmenopausal women (or = one year after the last menstruation,or = 70 years old) were enrolled at seven clinical sites in this cross-sectional observational study conducted within the EPOLOS. The group was a random sample of the population. The study was performed in a referral center involved in the diagnosis and treatment of osteoporosis. The exclusion criteria included pregnancy, cancer, fracture in the last year, and overweight (100 kg). Bone mineral density (BMD) measurements of the lumbar spine, total hip, trochanter, and femoral neck regions were performed. Bone resorption and formation rates were evaluated by serum levels of C-terminal telopeptide of type I collagen (CTX) and osteocalcin (OC), respectively.Using logistic regression to correlate the concentrations of CTX and OC it was possible not only to distinguish the EBT subgroup, but also to construct a simple nomogram for easy classification of individual patients as possible EBT subjects. EBT patients showed generally decreased BMD values and increased bone formation and resorption rates.Evaluation of both CTX and OC levels enables a more proper indication for EBT. The proposed nomogram may assist in evaluating outcome from the two markers of bone turnover.

Background This Phase 3, randomized, open-label, multicenter study conducted at 44 sites in Europe evaluated the safety and efficacy of a continuous, daily regimen of levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg compared with a 21-day, cyclic LNG 100 mcg/EE 20 mcg regimen. Study Design Three hundred twenty-three healthy women were randomized to continuous LNG 90 mcg/EE 20 mcg and 318 subjects to cyclic LNG 100 mcg/EE 20 mcg for 1 year (13 pill packs). Pearl index, adverse event (AE) incidence and bleeding profiles were assessed. Results No pregnancies occurred with the continuous oral contraceptive (OC) (Pearl index=0.00). As the study progressed, the percentage of women who achieved amenorrhea during each 28-day pill pack increased: 40% at pill pack 7, 53% at pill pack 13. The percentage of women with no bleeding [with or without spotting (defined as not requiring sanitary protection)] was 50%, 69% and 79% at pill packs 3, 7 and 13, respectively. The incidence of AEs was similar to that of the cyclic OC (except for metrorrhagia and vaginal bleeding in the first 6 months). Conclusions Continuous LNG 90 mcg/EE 20 mcg was shown to be a safe and effective OC in this direct comparison to a cyclic OC. Suppression of menses and the potential for no bleeding requiring sanitary protection may be provided by this continuous, low-dose OC.

There is an increasing evidence that genetic factors play a role in the etiology of malignant tumors. Mutations of BRCA1 and BRCA2 genes are responsible for an increased risk of ovarian cancer. The role of mutations in NOD2 gene in this type of neoplasm is still under investigation.The aim of this study was to determine: 1. incidence of NOD 2 3020insC constitutional mutation in a group of consecutive women with ovarian cancer, 2. risk of developing ovarian cancer in patients with NOD2 gene mutation, 3. clinical and pathological features of ovarian cancer in NOD2 gene mutation carriers.Clinical and pathological data were collected from 257 non-selected patients with primary epithelial ovarian cancer. The researches identified NOD2 3020insC gene mutation. On the basis of patient source documentation we obtained the data concerning the age of patients at diagnosis, histopathological recognition, FIGO stage and morphological grade G.19 out of 257 women were identified with germ-line 3020insC mutation of NOD2 gene (7.39%). An increased risk of ovarian cancer in NOD2 mutation carriers was not revealed (OR=1.01; p=0.928; 95% Cl=0.61-1.66). The mean age at diagnosis of patients with NOD2 mutation was 54.8 (SD=9.9), while for non-carriers it was 53.2 (SD=10.2). The difference between these frequencies was statistically irrelevant (p=0.550). Clinical and pathological profile of ovarian cancer was made. We assessed the following features: age at disease onset, histopathology, FIGO stage and morphological grade G. For NOD2 mutation carriers no statistically significant features of ovarian cancer were revealed.1. Despite high frequency of constitutional mutations occurrence in NOD2 gene in women with ovarian cancer, genetic testing seem not to be justified in all women diagnosed with this disease. 2. Due to a lack of increased risk of ovarian cancer in NOD2 gene mutation carriers, proceedings for them may not differ from recommendations for general population. 3. It is difficult to determine characteristic clinical and pathological features of ovarian cancer for NOD2 gene mutation carriers.

Biophysics is becoming an important factor in prevention of cervical cancer. One of the most promising concepts of biophysical program for the prevention of cervical cancer is the optoelectronic method--Truscreen.The objective of the work was to determine the usefulness of the real optoelectronic device in the detection of cervical intraepithelial neoplasiaFrom August 2006 till September 2007, 147 patients were examined in the Laboratory of Pathophysiology of Uterine Cervix in Gynecology and Obstetrics Clinical Hospital of Karol Marcinkowski University of Medical Sciences. The study reports prospective, blind trial. The following diagnostic examinations were carried out: examination with the use of optoelectronic method, DNA HPV HIGH RISK test, colposcopy examination and histopatologic biopsy.The specificity of the optoelectronic method for positive diagnoses amounted to 84%. The sensitivity for intraephitelial changes (CIN 1, CIN 2) was estimated at 53%, and for severe grades (CIN 3, Carcinoma planoepitheliale) at 80%.Optoelectronic diagnostics is useful in the detection of cervical neoplastic changes. The optoelectronic method may prove to be a significant diagnostic device at the basic and advanced level of cervical screening. The advantage of the optoelectronic method over prevention based on cytodiagnostics and colposcopy, includes the immediate result of the examination and its automation as well as standardization.

Purpose: Cisplatin resistance is a major obstacle in the treatment of ovarian carcinoma. ABCC2 is commonly localized in apical cell membranes and could confer cisplatin resistance. Here, we show that ABCC2 can be localized in the cytoplasmic membrane as well as in the nuclear membrane of various human tissues including ovarian carcinoma cells. Experimental Design: For the subcellular detection of ABCC2, immunohistochemistry was done using 41 Federation Internationale des Gynaecologistes et Obstetristes stage III ovarian carcinoma specimens prepared before treatment with cisplatin-based schemes and 35 specimens from the same group after chemotherapy. Furthermore, 11 ovarian carcinoma cell lines as well as tissue microarrays consisting of various human tissues were analyzed. Results: Nuclear membranous localization of ABCC2 was associated with response to first-line chemotherapy at primary (P = 0.0013) and secondary surgery (P = 0.0060). Cases with relapse showed higher nuclear membrane expression at primary (P = 0.0003) and secondary surgery (P = 0.0024). Kaplan-Meier analyses showed that weak nuclear membrane ABCC2 expression before treatment was associated with significantly longer overall (P = 0.04) and progression-free survival (P = 0.001); following chemotherapy, it correlated with significantly longer progression-free survival (P = 0.038). Tissue microarrays confirmed nuclear membranous localization of ABCC2, in particular, in poorly differentiated cells. In ovarian carcinoma cells, it correlated with resistance against cisplatin, whereas localization in the cytoplasmic membrane did not. Conclusions: ABCC2 confers resistance to cisplatin of ovarian carcinoma in cell culture systems and in clinics when expressed in the nuclear membrane. Thus, ABCC2 localization can predict platinum therapy outcome. Furthermore, expression of ABCC2 in nuclear membranes in human tissues is specific for poorly differentiated cells including stem cells.

An obstacle in chemotherapy of ovarian cancer is the development of drug resistance. Taxol (paclitaxel)-resistance-associated gene-3 (TRAG-3/CSAG2) was found to be overexpressed in a paclitaxel-resistant ovarian carcinoma cell line. However, clinical impact of TRAG-3 in ovarian carcinoma has not been demonstrated previously. For demonstration of potential clinical impact of TRAG-3, immunohistochemistry was applied to determine TRAG-3 protein expression in specimens obtained from ovarian carcinoma patients (n=37) who received a paclitaxel-based chemotherapy at two different time points, initial laparotomy before chemotherapy, and secondary cytoreduction after chemotherapy. The TRAG-3-specific immunohistochemical staining was correlated with clinical outcome. In ovarian carcinoma specimens obtained at the initial laparotomy, an advantage in overall (P < 0.001) and progression-free (P = 0.003) survival for patients with weak TRAG-3 expression could be demonstrated. Tumor specimens excised at secondary cytoreduction procedure were not predictive for clinical outcome. In summary, TRAG-3 was found to be a prognostic factor for the prediction of clinical outcome after the application of paclitaxel-based chemotherapy.

High cytoplasmic expression of maspin was described in ovarian cancers of shorter survival rates. Until now, no relationship has been described between expression of maspin and sensitivity to cisplatin in ovarian cancers. This study aimed at examining the relationship between expression of maspin, detected by immunohistochemistry and clinical response to cisplatin in ovarian cancer cases as well as the in vitro sensitivity to cisplatin of 11 ovarian cancer cell lines. The analyzes were performed on 73 samples of ovarian cancer and on A2780P, A2780RCIS, CAOV-3, EFO 21, EFO 27, ES-2, Mdah 2774, OAW 42, OVCAR-3, PA-1, and SKOV-3 ovarian cancer cells. Cytoplasmic maspin expression in studied cells significantly correlated with cisplatin sensitivity. A significantly shorter overall survival and progression-free survival was associated with lower cytoplasmic maspin expression at first-look laparotomies and nuclear maspin expression and secondary cytoreductions. Higher nuclear maspin at first-look laparotomies expression was specific for cases of complete response. In the study, the elevated expression of maspin was shown to be typical for cisplatin-sensitive ovarian cancers.

It was suggested that genetic factors play an important role in the regulation of bone mineral density and in the pathogenesis of bone fracture in osteoporosis. PvuII restriction polymorphism in the intron 1 of the gene coding estrogen receptor alpha (ER-alpha) is indicated to play a significant role in osteopenia and osteoporosis development. The goal of our study was to determine the frequency and the significance of PvuII polymorphism of the ER-alpha gene in the group of postmenopausal women with osteopenia and osteoporosis.93 postmenopausal women with osteopenia and osteoporosis (t-score lower than (-1), and 141 healthy postmenopausal women have been investigated for PvuII polymorphism of the ER-a gene using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays.We have observed higher frequency of homozygous genotype PP (25.8 vs. 19.8%) and P allele (50.6 vs. 46.1%) in the group of women with low level of t-score. In the osteopenic women (-2.5T-score-1.0) the significant difference in the distribution of t-score index and genotypes has been found. t-score index correlated with body mass index (BMI), mean body weight, BMD aged matched (AM) and BMD young adults (YA) index. The AM and YA index correlated with the number of pregnancies.The presence of PP genotype and P allele could be connected with higher bone loss and with the development of osteopenia and osteoporosis in postmenopausal women.

Estrogen receptor beta (ERβ) belongs to a large family of nuclear receptors. Recent studies have suggested that ERβ in contrast to ERα might act as a tumour suppressor in ovarian cancer (OVCA).Expression of ERβ was detected by immunocytochemistry in 11 OVCA cell lines and by immunohistochemistry in 43 (41 FIGO stage III) OVCA specimens prepared before chemotherapy and 30 specimens from the same group after chemotherapy. Cisplatin sensitivity in the 11 cell lines was also analysed.No significant correlations between cisplatin-sensitivity and expression of ERβ was found in the cell lines. In the cases which responded well to chemotherapy (complete response) ERβ expression at preliminary laparotomy (PL) was significantly higher (p = 0.0004) than in those with progressive disease. Kaplan-Meier analysis revealed that the patients with higher ERβ expression (30% of cells) at PL had an increased overall survival time and progression-free time (p = 0.00161 and p = 0.03255, respectively) than the patients with lower ERβ expression. Significantly shorter overall survival time characterized the cases with lower immunoreactivity score of ERβ expression at secondary cytoreduction (SCR) (p = 0.00346).The loss of ERβ expression in ovarian tumours may be a feature of malignant transformation.

Despite great progress in the understanding of ovarian cancer biology, clinicopathological data (i.e. grade, stage, histological type and residual disease after surgery) seem to be the most important prognostic factors.The present study aimed to investigate the relationship between expression of minichromosome maintenance proteins (MCM-3, MCM-7), metallothioneins (MT-I/II, MT-III), and Ki-67 in 103 ovarian cancer cases, mostly of the serous histological type.Statistical analysis revealed strong positive correlations in the expression of MCM-3 vs. Ki-67 (r=0.492), MCM-7 vs. Ki-67 (r=0.651), and MCM-3 vs. MCM-7 (r=0.515) (all p0.0001). The Kruskal-Wallis test showed an association of increased expression of MCM-3 and Ki-67 with increasing grade of histological malignancy (p=0.0011, p=0.029, respectively). Regarding clinical progression, cytoplasmic MT-I/II expression was significantly higher in more advanced disease stages (III+IV vs. I+II; p=0.0247).Due to the correlations shown here, the determination of MCM proteins as proliferation markers of ovarian cancer, should be strongly considered.

A major obstacle in treatment of ovarian cancer is intrinsic or acquired drug resistance causing failure of chemotherapy followed by a poor clinical outcome. Drug resistance of ovarian carcinoma can be caused by dysregulation of cellular factors involved in regulation of apoptosis and DNA repair pathways. In this study, 73 ovarian carcinoma specimens obtained before and after chemotherapy were analysed by immunohistochemistry for expression of seven proteins playing an important role in regulation of DNA mismatch repair and apoptosis. The prognostic significance of these proteins in the meaning of overall and progression-free survival was evaluated in univariate and multivariate analysis. Bcl-x L , hMSH2, caspase-3, p21 and p53 displayed prognostic importance in univariate analysis. Furthermore, it was demonstrated that caspase-3 and p21 were also independent prognostic markers for both, overall and progression-free survival. In conclusion, these data indicate that analysis of proteins involved in DNA mismatch repair and apoptosis can be useful for prediction of clinical outcome in ovarian carcinoma patients.