The Role of the Mitochondrial Genome in Ageing and Carcinogenesis

Mitochondrial DNA mutations and polymorphisms have been the focus of intensive investigations for well over a decade in an attempt to understand how they affect fundamental processes such as cancer and aging. Initial interest in mutations occurring in mitochondrial DNA of cancer cells diminished when most were found to be the same mutations which occurred during the evolution of human mitochondrial haplogroups. However, increasingly correlations are being found between various mitochondrial haplogroups and susceptibility to cancer or diseases in some cases and successful aging in others

Mechanisms of melanoma resistance to treatment with BRAF and MEK inhibitors

Several mechanisms of resistance to inhibition of BRAF activity in melanoma cells have been described so far. Genetic studies have shown that mutations in MEK1 kinase (MAP kinase kinase), which result in constitutive activation of ERK kinase, result in resistance to treatment. Another mechanism of the acquired BRAF inhibition resistance is the accumulation of activating mutations in the NRAS oncogene, which drives the activation of CRAF. This in turn leads to a permanent activation of the signal transduction to MEK and ERK. Another important mechanism of resistance is the formation of variants of the BRAF V600E gene splicing, including variants that lack exons 4 to 8 containing the RAS-binding domain. The presence of the p61 BRAF V600E variant leads to the constitutive ERK signal, which is resistant to RAF inhibition. In addition, treatment resistance is affected by hyperactivation of tyrosine kinase receptors such as platelet-derived factor receptor β (PDFRβ), insulin-like growth factor 1 receptor (IGF-1R) and erythropoietin-producing hepatocellular receptors (EPH) – leading to the induction of the 3-phosphoinositol kinase pathway (PI3K) in patients treated with BRAF or MEK inhibitors. Another interesting path of BRAFi/MEKi resistance is over-expression of the epidermal growth factor receptor (EGFR) through ne­gative feedback in patients treated with BRAF inhibitors (BRAFi) – EGFR is not normally expressed in untreated melanomas

Autobusem i tramwajem w przeszłość. Berlińskie zaszłości w twórczości Annett Gröschner

This paper concentrates on the strategies of reconstructing the past as  inscribed into the urban space of Berlin and discussed within the literary field. Developed by the German writer Annett Gröschner, they have been used to reexamine the history of the city – only dimly reflected in the present urban landscape. Her perspective emphasizes the distinctive spatial and architectural organization of the city, particularly after the fall of the Berlin Wall. In order to harness her dialec-tical composition of the spacing of-the-past, Gröschner uses the map of various routes on the Berlin public transport network, some inner-city artefacts set along those lines, and also the city map with its constant modifications to create appropriate landmarks through which she [re]constructs Berlin's past-present

Clinicoprognostical features of endometrial cancer patients with somatic mtDNA mutations

Somatic mitochondrial DNA (mtDNA) mutations have been found in a subset of endometrial cancers (EC) from different populations. We have investigated the relationship between mtDNA changes and clinical and pathological variables of women affected by EC. mtDNA mutations were detected both in early (3/32; 9%) and in advanced (1/8; 12%) stages of uterine tumors. However, patients carrying the mtDNA mutations or the normal mtDNA sequence had indistinguishable clinicopathological data, including age, clinical stage, histological grade and type or depth of myometrial invasion. It is noteworthy that mtDNA mutations were not detected in hyperplastic endometrial tissues or in ECs coexisting with hyperplasia, nor in a single case of endometrial stromal sarcoma. LOH at the tumor suppressor genes RB1 and TP53 as well as p16INK4A alterations (LOH, gene deletion) were found in tumors carrying mtDNA mutations. These results suggest that somatic mtDNA mutations are detected in a subset of ECs, although they are unrelated to clinicopathological variables of cancer

Secondary cervical cancer prevention in routine prenatal care — coverage, results and lessons for the future

Objectives: Cervical cancer is the fourth most common type of cancer among women worldwide and one of the most common malignancies diagnosed in gravidas. Therefore, routine antenatal Pap smear is such an important examination. The aim of the study was to assess the prevalence of Pap smear performance during prenatal care and to determine possible factors affecting it. Material and methods: A self-composed questionnaire was distributed among 638 women managed in a tertiary obstetric referral center. 33 questions regarded cervical cancer prevention and risk factors. Results: 96.9% of respondents had undergone Pap smear and 80.6% had it performed during pregnancy. For 11.5% women Pap smear in pregnancy was the first one in their life. The most common reasons for lack of Pap smear performance were: no subjective need to perform it (40.9%), no doctor’s recommendation (28.6%) and lack of gynecological care (16.3%). Among professionally active women the percentage of those who had not undergone Pap smear during pregnancy was statistically higher (28.5%) than among those who were on sick leave (13.5%) (p = 0.0003). Also, younger women were at risk of less frequent participation in cervical cancer screening Conclusions: Although performance of Pap smear among surveyed patients was relatively high, there was a significant group of women who had undergone their first test during pregnancy, which makes secondary cervical cancer prevention in prenatal care a useful prophylactic strategy. Special attention should be given to younger and professionally active women

Palliative treatment of intestinal obstruction in patients with gynecologic malignancies — single center experience

Objectives: One of the common symptoms in patients with advanced gynecologic tumors is intestinal obstruction. Palliative management may include pharmacological treatment, stenting as well as surgical removal of obstruction cause. Selection of appropriate treatment should be based on careful and individual assessment of advantages, disadvantages and possible complications. The aim of the study was to analyze the effectiveness of non-invasive treatment in patients with gynecologic malignancies suffering from intestinal obstruction.  Material and methods: It was a retrospective analysis of factors associated with primary non-invasive intestinal obstruction treatment effectiveness. Data were collected from medical records of 17 patients managed and followed-up in a single gynecologic oncology center due to endometrial cancer, fallopian tube cancer, uterine leiomyosarcoma, and ovarian cancer admitted to the ward because of symptomatic intestinal obstruction. Mean observation time lasted 40.6 months. Non-invasive treatment included fluid therapy, dexamethasone, buscolysin, mebeverine, ranitidine, simethicone, omeprazole, magnesium sulphate, semi-liquid diet, and parenteral nutrition. Characteristics including age, BMI, comorbidities, oncological treatment, histology type, stage, grade, presence of ascites, location of primary tumor and metastases were analyzed.  Results: The number of obstruction episodes varied from 1 to 5. Mean time between multiple episodes lasted 3.2 months. 5 patients required surgical treatment. For the rest of the patients primary non-invasive treatment was sufficient.  Conclusions: Most cases of bowel obstruction in patients with advanced gynecologic malignancies can be successfully managed without invasive treatment. Moreover, non-invasive obstruction management can be applied multiple times in case of recurrence

Pregnant surgeon — assessment of potential harm to the woman and her unborn child

Although most countries developed regulations concerning pregnant women at work, they are not strictly adjusted for every profession. In the European countries directives prevent pregnant women from working during night shifts, but apart from a vague paragraph about avoiding hazardous agents, there are no guidelines specific for pregnant surgeons. The aim of the study was to analyse the risks and consequences of working in the operating theatre during pregnancy. An in-depth analysis of available literature, laws and regulations concerning health and safety of pregnant surgeons was performed. Not only they are surgeons exposed to radiation and infectious agents like any other physicians, but they also face the risk of strenuous physical activity affecting their pregnancy. The unpredictability of this occupation, prolonged hours and stress associated with work can all affect the future mother and her child. The available research on potential risks for pregnant women performing surgical activities named such consequences as premature birth, miscarriage, foetal growth retardation, hypertensive disorders and infertility. There are no unanimous guidelines for pregnant surgeons on how long and to which extent they should work. The key is to maintain a balance between limiting the likelihood of pregnancy complications and respecting women’s voluntary wish to continue professional development

Leber hereditary optic neuropathy -a disease with a known molecular basis but a mysterious mechanism of pathology

Abstract. Leber hereditary optic neuropathy is a maternally inherited type of blindness caused by degeneration of the optic nerve. It is caused by point mutations in mitochondrial DNA. Like in other mitochondrial diseases, its penetrance and inheritance is complicated by heteroplasmy, tissue distribution, and the bottleneck phenomenon in oocyte maturation. On the cellular level, the mechanism of the disease development is still mysterious. Currently three theories of pathomechanism of LHON are considered: biochemical, ROS (reactive oxygen species) and apoptotic

Physical activity during pregnancy — the state of Polish women’s knowledge

Objectives: Regular and moderate physical activity during uncomplicated pregnancy has been considered beneficial for both the expectant mother and her unborn child. It reduces the risk of gestational diabetes mellitus (GDM) and preeclampsia. The aim of the study was to assess women’s knowledge concerning specific aspects of physical activity during uncomplicated pregnancy. Material and methods: A cross-sectional survey study on a sample of Polish women in a tertiary referral centre was performed. A questionnaire that was validated in the Polish language was based on the Committee Opinion of American College of Obstetricians and Gynaecologists, which was published in December 2015. Sociodemographic parameters in relation to specific aspects of physical activity during pregnancy were analysed. Results: A total of 259 (92.5%) women were aware of the beneficial impact of physical activity on the course of pregnancy. Higher education was associated with greater awareness (p = 0.001). Regarding the optimal frequency and recommended duration of exercise, the overall rates of correct answers were only 106 (38.1%) and 167 (59.6%), respectively. The most common sources of information on physical activity during pregnancy were the Internet (81, 50.0%) and books (62, 38.3%). Doctors and midwives instructed the respondents only in 36 (22.4%) and 31 (18.9%) cases, respectively. Conclusions: Women’s knowledge about physical activity during pregnancy seems satisfactory. However, awareness concerning the optimal duration and frequency of exercise, as well as recommended voluntary activities during pregnancy, should be improved. Medical professionals may also reinforce their role as a provider of reliable information, resulting in the prevention of many pregnancy complications