Bogdan Michalski

High-grade serous ovarian cancer: the clone wars

BackgroundThe last 5 years’ studies using next-generation sequencing provided evidences that many types of solid tumors present spatial and temporal genetic heterogeneity and are composed of multiple populations of genetically distinct subclones that evolve over time following a pattern of branched evolution. The evolutionary nature of cancer has been proposed as the major contributor to drug resistance and treatment failure. In this review, we present the current state of knowledge about the clonal evolution of high-grade serous ovarian cancer and discuss the challenge that clonal evolution poses for efforts to achieve an optimal cancer control.MethodsA systemic search of peer-reviewed articles published between August 2007 and October 2016 was performed using PUBMED and Google Scholar database.Results and conclusionsRecent studies using next-generation sequencing have allowed us to look inside the evolutionary nature of high-grade serous ovarian cancer, which in the light of current evidence can explain the relapsing course of the disease frequently observed in the clinical practice. Since only minimal improvement in the survival of patients treated with standard therapy has been observed in the last decade, novel molecular targeted therapies are of great interest in high-grade serous ovarian cancer. However, both spatial and temporal intratumoral genetic heterogeneity is a major challenge for personalized medicine, and greater knowledge of the molecular rules that drive tumor evolution through space and time is required to achieve a long-term clinical benefit from personalized therapy.

Cancer related fatigue syndrome in neoplastic diseases.

Fatigue is one of the most important factors which has a considerable influence on treatment and the life quality of oncological patients. The fatigue syndrome is often diagnosed during cancer treatment and this syndrome is not related to the physical effort. Cancer related fatigue is a patients subjective, psychologically, physically and emotionally based feeling. It is disproportionate to patients daily activity. The pathogenesis of this syndrome remains still unknown. However, on the basis of various questionnaires, it is possible to test the diseases complex nature. Cancer related fatigue causes deterioration of patients life along with lower motivation to struggle with the disease. It is thought that the factor which increases the incidence of cancer related fatigue is a long-term use of drugs such as opioids, benzodiazepine, and medicines containing codeine, tranquilizers, anxiolytics and antidepressants. On the basis of the results, one can choose an appropriate treatment method for cancer related fatigue such as rehabilitation, psychotherapy or public assistance. A great number of patients consider excessive fatigue a typical concomitant symptom in neoplastic disease; therefore, they do not report it. It is of a paramount importance to make patients aware of the fact that cancer related fatigue is a serious disease which can be treated.

Twelve-week exercise training and the quality of life in menopausal women - clinical trial.

Introduction The menopause transition is associated with decreased health functioning. About 80-90% of women experience mild to severe physical or physiological menopause-related complaints per year when approaching menopause. Physical activity may reduce some climacteric symptoms and improve the quality of life. Aim of the study Aim of the study was to investigate the influence of a 12-week training programme on the quality of life (QoL) in menopausal-aged women living in a rural area. Material and methods Participants were 80 women aged 40-65 years and divided into two randomly selected groups in training sessions (exercising group, n = 40 and control group, n = 40). SF36 was used to assess the quality of life in both groups before and after 12 weeks. Exercising women participated in training session 3 times a week. Each 60-minute exercise session included warming-up exercises, walking, stretching, strengthening exercises with an elastic band and cooling down exercises. Results A non-significant positive difference in all SF36 domains in the exercising group was observed. The results of the study showed a statistically significant higher QoL in the exercising group compared to the control group after 12-week training in two domains: vitality and mental health. The improvement in the quality of life in the study group was 0.19 points (role limits – physical domain, least change) and 4.96 (vitality domain, most change). Conclusions Controlled and regular exercise for 12 weeks was significantly correlated with a positive change in vitality and mental health. Sedentary women should consider modification of their lifestyle to include physical activity as it leads to improvement of their quality of life.

Post-transcriptional modifications of VEGF-A mRNA in non-ischemic dilated cardiomyopathy

Vascular endothelial growth factor (VEGF-A) is one of the most important proangiogenic factors. It has many isoforms encoded by one gene. The occurrence of these isoforms is associated with the process of alternative splicing of mRNA. Some of the splice forms are perceived as tissue specific. The aim of this study was to determine the alternative splicing of VEGF-A mRNA in dilated cardiomyopathy, especially at the level of particular myocardial layers. The assessment of post-transcriptional modifications of VEGF-A mRNA was made on specimens taken from the explanted hearts of patients undergoing cardiac transplantation. Molecular and histopathological studies were perfomed on particular layers of the myocardial muscle (endocardium, myocardium, epicardium). A molecular analysis of cardiac samples was performed by quantitative analysis of the mRNA of the studied VEGF-A isoforms (VEGF121, -145, -165, -183, -189, and -206) using QRTPCR with an ABI-PRISM 7700-TaqMan sequence detector. 72 cardiac specimens taken from the explanted hearts were analyzed. Each of the studied VEGF-A splice forms was present in the evaluated hearts, but the types of alternative splicing of mRNA were different in particular layers. Quantitative analysis revealed different amounts of the studied isoforms. Generally, significantly increased expression of the VEGF-A isoforms was observed in samples taken from hearts with post-inflammatory etiology of cardiomyopathy. Our conclusions are: 1. All the studied VEGF-A isoforms were found in the human hearts, including those thusfar considered characteristic for other tissues. 2. Significant differences were observed in the expression of the VEGF-A splice forms with respect to the myocardial layers and the location of the cardiac biopsy. 3. Repetitive and comparable results for samples with post-inflammatory etiology were obtained, and they revealed considerably higher amounts of VEGF-A isoforms compared to specimens with idiopathic etiology.

Identification of a gene expression profile associated with the regulation of angiogenesis in endometrial cancer

The publication of the human genome sequence provided direction in the search for novel diagnostic and therapeutic methods for the treatment of human diseases. The aim of the present study was to investigate the hypothesis that the expression profile of genes involved in the regulation of angiogenesis may be a marker in endometrial cancer that facilitates the diagnosis and prognosis of patients, as well as the identification of novel therapeutic targets. The current study included 36 patients with grade (G) 1 to 3 endometrial cancer, and a control group of patients consisting of females that qualified for the removal of the uterus. Out of these, 28 samples (control, 3; G1, 7; G2, 12; and G3, 6) were selected for microarray analysis. Molecular analysis of the endometrial samples involved the extraction of total RNA, purification of the obtained extracts and subsequent analysis of the gene expression profiles using an oligonucleotide microarray technique (GeneChip® Human Genome U133A plates). The results indicated that the mRNA expression profile of genes involved in the regulation of angiogenesis varies depending on the degree of histological differentiation of endometrial adenocarcinoma. Similar results were obtained from descriptive statistics characterizing the expression profile of 691 mRNAs associated with the regulation of angiogenesis in the groups of patients with endometrial adenocarcinoma. In addition, the results of the present study indicated that neuropilin2 (NRP2) may serve an important role in the activity of endothelial cells, and may affect vascular endothelial growth factor, and potentially plexins and integrins via regulation of their functions. An understanding of how these proteins interact remains to be determined; however, elucidating these interactions may provide an explanation for the mechanisms underlying angiogenesis. In conclusion, the results of the present study suggest that NRP2 may be a valuable target for investigation in future pharmacological studies involving angiogenesis in endometrial cancer.

Lymphangiogenesis in cervical cancer evaluated by expression of the VEGF-C gene in clinical stage IB-IIIB

Introduction The aim of the present study was to evaluate the profile of VEGF-C gene expression in particular stages of cervical cancer (IB-IIIB) and to estimate the correlation between VEGF-C mRNA quantity profile and clinical stage. Material and methods Material for molecular analysis consisted of cervical cancer tissue specimens collected from 38 women (10, 15, 13 cases were classified as IB, IIB and IIIB, respectively). The control group was composed of normal cervical tissues collected from 10 women who underwent hysterectomy for non-oncological reasons. The number of VEGF-C mRNA copies in particular groups was estimated by the reverse transcription quantitative polymerase chain reaction (RT-qPCR) method. Results In the control group the average number of mRNA copies was 134 ± 36 (median: 106), in a group with stage IB it was 16 077 ± 7090 (median: 580), for stage IIB – 35 019 ± 8945 (median: 40 870). The highest number of mRNA VEGF-C copies was derived in a group of patients with cervical cancer of stage IIIB. The average quantity was 56 155 ± 12 470, whereas median 55 981. A statistically significantly higher level of VEGF-C gene expression was disclosed in cervical cancer specimens with stage IIB and IIIB than in the control group. In stage IIIB, the VEGF-C gene expression was significantly higher than in specimens derived from individuals in stage IB. Conclusions In squamous cell carcinoma of the uterine cervix of stage IB-IIIB genes involved in lymphangiogenesis, especially VEGF-C, are expressed, which expression increases as the clinical stage of cervical cancer is higher.