Witold Kędzia

Unfavourable prognostic significance of S100P expression in ovarian cancers

pylori-associated chronic gastritis and hepatocellular carcinoma due to hepatitis B virus and hepatitis C virus. Although the causal relationship between IBD and HAC is unknown, one of the three cases of large intestinal HAC reported in the literature arose in ulcerative colitis. One of our two cases is the second report of HAC arising in ulcerative colitis and the other case is the first report of HAC arising in Crohn’s disease. In a context of inflammation-associated cancer, only three cases of HAC have been reported in the oesophagus and all three cases occurred with a background of Barrett’s oesophagus.

Transcriptional analysis of CXCR4, DNMT3A, DNMT3B and DNMT1 gene expression in primary advanced uterine cervical carcinoma.

The development of cervical cancer requires genetic and epigenetic factors which result in the persistence of a malignant phenotype. Cervical cancer exhibits also some unique differences from other solid tumors. Normal cervical stratified epithelia have characteristics of hypoxic tissue with over-expression of HIF-1 (hypoxia-inducible factor-1) transcription factor, which targets the transcription of over 70 genes involved in many aspects of cancer biology. One of the genes, which could be induced by HIF-1 is chemokine (C-X-C motif) receptor 4 (CXCR4). CXCR4 could also be epigenetically regulated by methylation of CpG dinucleotides located in the promoter region. Here, we examined the CXCR4, DNMT3A, DNMT3B and DNMT1 transcript levels in cancer tissue (n=30) and non-cancer, normal uterine cervical tissue (n=30) from a Polish cohort. We also compared the methylation status of CXCR4 promoter region in cancer and normal tissue samples. Our result showed significantly higher levels of CXCR4, DNMT3A, DNMT3B and DNMT1 transcript (p=0.0058, 0.0163, 0.0003 and <0.0001, respectively) levels in cancer tissue as compared to normal samples. We did not observe DNA methylation in the CXCR4 promoter region in either control or cancer tissue samples. CXCR4 has a functional hypoxia response element (HRE) in the promoter region, located -1.3 kb from the transcription start site. Our work shows for the first time that HIF-1A could promote the induction of CXCR4 gene expression (Spearmans correlation coefficient = 0.515, p=0.003) in patients with primary advanced uterine cervical carcinoma.

Expression of the MT1 Melatonin Receptor in Ovarian Cancer Cells

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 (MT1CM) and membrane (MT1M) reactions. A positive correlation between MT1CM and MT1M was found in all the studied cases. There were no significant differences between the expression of MT1CM, MT1M, and histological type, staging, grading, presence of residual disease, or overall survival time. Immunofluorescence showed both MT1M and MT1CM 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.

Overweight, obesity and female sexuality in perimenopause: a preliminary report

Introduction The research was conducted among patients of the Department of Perinatology and Gynaecology of the Poznań University of Medical Sciences. Its aim was to investigate the influence of overweight and obesity on female sexuality during the perimenopausal period. Preliminary results of the research are presented in the thesis, which was as a matter of fact intended as a preliminary report. The examination of sexual functions of the patients was performed with the use of the Female Sexual Function Index (FSFI) form. Material and methods Sixty-one women during the perimenopausal period filled out the survey, with the average age of these women being 51 years. Forty-two of the examined women had an appropriate body mass index (BMI), i.e. between 18.5 and 25, while for 19 of the women, the BMI was above normal. For statistical analysis and in order to assess the differences between the two above-mentioned groups of patients, the nonparametric Mann-Whitney test was applied. A statistically significant value was assumed at p < 0.05. The results of the conducted research indicated no such difference between the women with differing BMI for the specific domains of the FSFI test. Results The results obtained show that research in the area needs to be continued. Conclusions All the hitherto existing scientific studies also seem to indicate that the influence of overweight and obesity on female sexuality during the perimenopause has not yet been unambiguously proven. Beyond any doubt, however, sexual disorders appear in women at this time of life and the factors which determine them can vary greatly. Given the character of the situation, women ought to be supported both by a team of specialists representing different branches of medicine as well as by their relatives. The whole situation also calls for more research of the important subject matter.

Functional hypothalamic amenorrhoea – diagnostic challenges, monitoring, and treatment

Functional hypothalamic amenorrhoea (FHA) is associated with functional inhibition of the hypothalamic-pituitary-ovarian axis. Causes of FHA can be classified into the three groups: 1) stress-related factors, 2) consequences of weight loss and/or underweight, and 3) consequences of physical exercise or practicing sports. Diagnosis of FHA should be based on a history of menstrual disorders. During physical examination, patients with FHA present with secondary and tertiary sex characteristics specific for the pubertal stage preceding development of the condition and with the signs of hypoestrogenism. Laboratory results determine further management of patients with amenorrhea, and thus their correct interpretation is vital for making appropriate therapeutic decisions. Treatment of chronic anovulation, menstrual disorders, and secondary amenorrhea resulting from hypothalamic disorders should be aimed at the elimination of the primary cause, i.e. a decrease in psycho-emotional strain, avoidance of chronic stressors, reduction of physical exercise level, or optimisation of BMI in patients who lose weight. If menses do not resume after a period of six months or primary causative treatment is not possible, neutralisation of hypoestrogenism consequences, especially unfavourable effects on bone metabolism, become the main issue. Previous studies have shown that oestroprogestagen therapy is useful in both the treatment of menstrual disorders and normalisation of bone mineral density. Hormonal preparations should be introduced into therapeutic protocol on an individualised basis.

Ten years of anti-HPV vaccinations: what do we know?

Human papillomavirus (HPV) is one of the most important carcinogens in humans. Vaccines against HPV are now considered the first anti-cancer vaccinations. Since 2007, in many developed countries, there have been recommendations present for preventive vaccines against HPV. At present, the degree of implementation of these recommendations depends on a number of country-specific factors such as the health care system organization or the ways of funding. HPV vaccines are primarily to prevent the development of cervical cancer and other genital cancers. Therefore, only their long-term effectiveness can be measured, when a correspondingly large cohort of vaccinated teenagers reaches the age of the greatest incidence of these cancers. However, great care should be taken in assessing the results of vaccinations due to the possibility of misinterpretation and possible erroneous data. Undoubtedly, teenagers are the target population of HPV vaccines. However, vaccinating young sexually active women is also justified from an individual point of view. A 9-valent vaccine has been registered in the USA and in Europe – including Poland – as one of the three preventive vaccines. It is recommended to vaccinate women between 13 and 26 and men between 13 and 21, previously unvaccinated. It is also recommended to vaccinate men aged 26 years or less who have sexual relations with other men and people with reduced immunity, including HIV-positive people who have not been vaccinated previously.

The Role of Matrix Gla Protein (MGP) Expression in Paclitaxel and Topotecan Resistant Ovarian Cancer Cell Lines

The major cause of ovarian cancer treatment failure in cancer patients is inherent or acquired during treatment drug resistance of cancer. Matrix Gla protein (MGP) is a secreted, non-collagenous extracellular matrix protein involved in inhibition of tissue calcification. Recently, MGP expression was related to cellular differentiation and tumor progression. A detailed MGP expression analysis in sensitive (A2780) and resistant to paclitaxel (PAC) (A2780PR) and topotecan (TOP) (A2780TR) ovarian cancer cell lines and their corresponding media was performed. MGP mRNA level (real time PCR analysis) and protein expression in cell lysates and cell culture medium (Western blot analysis) and protein expression in cancer cells (immunofluorescence analysis) and cancer patient lesions (immunohistochemistry) were determined in this study. We observed increased expression of MGP in PAC and TOP resistant cell lines at both mRNA and protein level. MGP protein was also detected in the corresponding culture media. Finally, we detected expression of MGP protein in ovarian cancer lesions from different histological type of cancer. MGP is an important factor that might contribute to cancer resistance mechanism by augmenting the interaction of cells with ECM components leading to increased resistance of ovarian cancer cells to paclitaxel and topotecan. Expression found in ovarian cancer tissue suggests its possible role in ovarian cancer pathogenesis.

The incidence of cervical intraepithelial neoplasia in a population of pregnant women with an abnormal cytology

OBJECTIVES To assess the incidence of cervical intraepithelial neoplasia - SIL and cervical cancer in a population of pregnant women with an abnormal cytology. MATERIAL AND METHODS In pregnant women with abnormal cytology results according to The Bethesda System, a verifying diagnostics was carried out, including colposcopy and cervical biopsy. RESULTS The most common histological and oncologic diagnosis in the whole study group of pregnant women were HGSIL changes, covering cervical intraepithelial neoplasia of medium and high grade - CIN 2 and CIN 3. CONCLUSIONS HGSIL changes are the most common oncological pathology in a population of pregnant women with an abnormal cytology. Precise risk identification of HGSIL changes with the use of molecular tests can significantly reduce the number of surgical procedures in a population of pregnant patients with a cytological diagnosis of ASCUS and LSIL.

The application of positron emission tomography (PET/CT) in diagnosis of breast cancer. Part II. Diagnosis after treatment initiation, future perspectives

Similarly to the applications described in the first part of this publication, positron emission tomography with computed tomography (PET/CT) is also gaining importance in monitoring a tumours response to therapy and diagnosing breast cancer recurrences. This is additionally caused by the fact that many new techniques (dual-time point imaging, positron emission tomography with magnetic resonance PET/MR, PET/CT mammography) and radiotracers (16α-18F-fluoro-17β-estradiol, 18F-fluorothymidine) are under investigation. The highest sensitivity and specificity when monitoring response to treatment is achieved when the PET/CT scan is made after one or two chemotherapy courses. Response to anti-hormonal treatment can also be monitored, also when new radiotracers, such as FES, are used. When monitoring breast cancer recurrences during follow-up, PET/CT has higher sensitivity than conventional imaging modalities, making it possible to monitor the whole body simultaneously. New techniques and radiotracers enhance the sensitivity and specificity of PET and this is why, despite relatively high costs, it might become more widespread in monitoring response to treatment and breast cancer recurrences.

Application of positron emission tomography (PET/CT) in diagnosis of breast cancer. Part I. Diagnosis of breast cancer prior to treatment

Positron emission tomography with computed tomography (PET/CT) is gaining popularity as a method for overall staging assessment of breast cancer. Currently, it is not a part of the routine workup before the beginning of treatment, because of insufficient sensitivity for the detection of small tumors (due to its limited spatial resolution), the heterogeneity of radiotracer uptake by the primary tumor, and unsatisfactory sensitivity in detection of lymph node metastases (particularly when they are small). Nevertheless, it should be considered when there is a high risk of metastases, because then initial PET/CT examination allows for accurate staging and may change the treatment algorithm in up to almost 50% of stage III patients, due to detection of distant and lymph node metastases throughout the whole body. Despite the discussed limitations of PET/CT, there is ongoing research concerning the recommendations for the examination prior to treatment. For a particular group of patients with high risk of metastases, PET/CT may be expected to become a part of the routine workup as the most appropriate staging method.