The prognostic value of E-cadherin and Ki-67 compared to standard histopathologic examination in non-muscle invasive bladder cancer.

OBJECTIVES: The objectives of this study were to determine the prognostic value of expression levels of selected biomarkers and their statistical analysis in relation to survival and standard histopathologic examination and other clinicopathologic variables in non-muscle invasive bladder cancer (NMIBC). BACKGROUND: Worldwide, bladder cancer is a frequent malignant disease with rising incidence. Characteristic invasiveness and high recurrence rates call for more diagnostic methods to obtain more accurate information. Prognosis is affected by a significant interpersonal variability of the disease. For this reason, constant search for alternative and better diagnostic methods is essential. METHODS: We analysed cancer tissue from patients with Ta and T1 bladder cancer. E-cadherin and Ki-67 expression levels were analysed using immunohistochemical staining. The expression levels quantified to a percentual amount were statistically analysed in relation to survival and their frequency distribution in the study group. RESULTS: E-cadherin and Ki-67 expression levels show high association with tumor stage and grade         (p<0.001), in contrast, the association with recurrence has proven insignificant. Patients with non-aberrant biomarker expression levels have much higher survival rates than the cases with aberrant expression. CONCLUSION: Low expression levels of Ki-67 and high expression levels of E-cadherin positively affect survival of patients, whereas aberrant expressions pose poorer prognosis (Tab. 2, Fig. 2, Ref. 33).

Natural polyphenols improve erectile function and lipid profile in patients suffering from erectile dysfunction.

OBJECTIVES: Erectile dysfunction (ED) is characterised as the inability to achieve or maintain an erection to complete sexual intercourse. ED may be considered as an early complication of diabetes mellitus (DM). The aim of this study was to assess the effect of registered food supplement, natural polyphenolic extract from the French maritime pine bark, Pycnogenol (PYC) on erectile function and lipid profile in ED patients. METHODS: 53 patients with ED were divided into two groups (32 with DM, 21 non-DM) in randomised, blinded and placebo-controlled study. During 3-month intervention with PYC or placebo and one month after the end of the intervention patients were investigated for ED with validated questionnaire International Index of Erectile Function-5 (IIEF-5); lipid profile, glycaemia was analysed in each group. RESULTS: In a randomised, blinded and placebo-controlled study, we found that natural polyphenolic extract, Pycnogenol improved erectile function in DM group by 45 % compared to the NDM group, where the improvement was also significant, but only by 22 %. Total cholesterol, LDL-cholesterol and glucose level was lowered by PYC in patients with DM. Glucose level was not affected by PYC in non-DM. Placebo showed no effect on monitored parameters in both groups. CONCLUSION: Administration of Pycnogenol leads in improvement of erectile function in patients with ED and diabetes (DM group) by 45 %, in NDM group by 22 %, in lowering of total-, LDL-cholesterol by 20 % and 21 % and glycaemia by 22 % in DM (Tab. 2, Fig. 2, Ref. 19).

Biomarkers for determination prostate cancer: implication for diagnosis and prognosis.

Prostate cancer (PCa) belongs to most common cancers and it is the second leading cause of cancer death in men. A genetic predisposition or acquired genetic and epigenetic changes with effect of other factors, such as advanced age, race and environmental factors contribute to PCa development. PCa is a very heterogeneous disease that is characterized by different clinical behavior, from indolent, slow-growing tumors to aggressive, fast-growing tumors with lethal progression. Early diagnostics and identification of PCa type are crucial prerequisites for efficient treatment of patients. Recently, the diagnostics of early stages of PCa is based mostly on evaluation of prostate-specific antigen (PSA) in serum of patients. Men with high levels of PSA undergo biopsy in order to determine histopatological grading of PCa - Gleason scoring which classifies tumors from most to least differentiated as well as staging - determination of the status of their primary tumors, with or without lymph node involvement. The results from this screening diagnosis lead into conventional treatment, including radical prostatectomy and brachytherapy. In case of advanced PCa, conventional treatment continues with androgen deprivation therapy. However, in many cases the cancer recurs. Therefore, the clinicians and researchers are forced to find more precise and sensitive biomarker suitable for PCa diagnostics as well as prognostics and therapy. This paper provides review of current most promising molecular and immunohistochemical biomarkers in PCa diagnosis, prognosis and clinical behavior.

Molecular Biomarkers of Bladder Cancer: A Mini-Review.

Cancers are quite common, but mostly very serious diseases and therefore belong to the most important areas of scientific research activity. Bladder cancer is one of the most common malignancies, it is a heterogeneous disease with significant diagnostic, therapeutic, and prognostic problems. It represents a disease with a variable course and a different response to therapy. The "conventional" prognostic markers used so far cannot reliably predict the natural course of the disease or estimate the tumor response to the chosen type of treatment. Molecular markers can provide us with the opportunity to diagnose a bladder tumor early, identify patients who are at risk of recurrence, or predict how tumors will respond to therapeutic approaches. As a result, diagnostics are found to help clinicians find the best therapeutic options for patients with bladder cancer. In this study, we focused on a brief description of potential molecular markers in bladder tumors in the context of precise diagnostics. Last but not least, we also focused on a new approach to the treatment of cancer using nanomaterials.

The Diagnostic Significance of C3d Antigen in Kidney and Skin Histopathology - The Current State-Of-The-Art and Practical Examples.

The aim of this narrative review is to summarize recent knowledge about the diagnostic significance of immunobiological detection of C3d with a focus on renal and skin tissue biopsies. We completed the present narrative review with our own experiences with preparation and practical use of monoclonal C3d antibodies at a small national level.

Decellularization techniques of human foreskin for tissue engineering application.

The rapid development of tissue engineering (TE) and regenerative medicine brings an acute need for biocompatible and bioactive biological scaffolds to regenerate or restore damaged tissue. Great attention is focused on the decellularization of tissues or even whole organs, and the subsequent colonization of such decellularized extracellular matrices by recipient cells. The foreskin is an integral, normal part of the external genitalia that forms the anatomical covering of the glans penis and the urinary meatus of all human and non-human primates. It is mucocutaneous tissue that marks the boundary between mucosa and skin. In this work, we compared two innovative decellularization techniques for human foreskins obtained from donors. We compared the efficacy and feasibility of these protocols and the biosafety of prepared acellular dermal matrixes that can serve as a suitable scaffold for TE. The present study confirms the feasibility of foreskin decellularization based on enzymatic or detergent methods. Both techniques conserved the ultrastructure and composition of natural ECM while being DNA-free and non-toxic, making it an excellent scaffold for follow-up research and TE applications.

Our First Experience Implementing "Clinical Embryology and Reproductive Medicine" as a Curriculum Course of the Study Program General Medicine at the Faculty of Medicine in Bratislava, Slovakia.

There is no separate course in the medical curriculum summarizing all aspects of human reproduction in most medical school curricula. At the same time, such a course would logically connect knowledge from clinical embryology and assisted reproduction, encompassing the issue of female and male infertility, mechanisms of birth defect formation, their prenatal diagnosis and subsequent specialized neonatal care. The aim of a wide team of university teachers comprising embryologists, gynecologists, neonatologists, endocrinologists, geneticists and others was to create and implement a new course entitled "Clinical Embryology and Reproductive Medicine" into the fourth-year curriculum of the study program General Medicine at the Faculty of Medicine, Comenius University in Bratislava. There has been a great interest in the course, as evidenced by the number of medical students enrolled. The lecture syllabuses have been divided into several thematic areas: 1) Clinical embryology including a laboratory part of assisted reproduction, 2) Cause and treatment options of female and male infertility, 3) A comprehensive view of the issue of birth defects, 4) The issue of preconception education, prenatal and childbirth training, family planning, 5) Reproductive immunology and endocrinology. Despite the complexity of human reproduction being a mainstay of gynecology and obstetrics, it is underemphasized in the medical school curricula worldwide. It is often reflected in shorter hospital / practical trainings during undergraduate studies and lower requirements at the final exam. Therefore, as students almost unanimously valued, this new course is extremely helpful in preparing for the final state exam.

Evaluation of bone mass density on patients with prostate cancer prior to the start of androgen deprivation therapy.

BACKGROUND: Men with prostate cancer older than 60 years who are treated with androgen deprivation therapy (ADT) represent a specific subpopulation of patients being at high risk of bone loss and subsequent complications. In contrast to this fact, there is not much data (if any) about this specific subpopulation of men and their BMD prior to the start of ADT. The aim of this study is to evaluate BMD in such patients. PATIENTS AND METHODS: Femoral neck and lumbar spine (L1-L4) were determined by dual-x-ray absorbtiometry (DXA) in 80 men (mean age 75.3 yrs, mean PSA 27.5 ng/ml) at the beginning of ADT. RESULTS: 38 out of 80 patients (47.5%) had femoral and/or L1-L4 osteopenia, and 6 patients (7.5%) were diagnosed with femoral and/or L1-L4 osteoporosis before the start of ADT. Less than a half (45%) of examined patients had normal values of femoral and L1-L4 BMD. CONCLUSION: Osteopenia is very common in men with prostate cancer who receive ADT. It is advisable to examine BMD prior to the start of ADT, and periodically thereafter. BMD measurement prior to ADT via DXA should be a common practice that can help in early detection of osteoporosis (Tab. 3, Ref. 36).

Bone mineral density, pathological fractures and bisphosphonate therapy in prostate cancer patients on androgen deprivation therapy.

OBJECTIVES: The aim of the study is to evaluate the changes of bone mineral density (BMD), incidence of pathological fractures and to asses the effect of bisphosphonate therapy in prostate cancer patients (PCa) on androgen deprivation therapy (ADT) with the use of LHRH. METHODS: In this prospective study bone mass density (BMD) was assessed by dual x-ray absorptiometry (DXA) in 97 PCa patients and 89 patients of compared group. DXA was examined at baseline and patients in the study group were subjected to ADT. PCa patients with osteoporosis were treated by calcium, vitamin D, and bisphosphonate and the subsequent DXA was made after 10 months. All other PCa patients (non-osteoporotic) had DXA examined every 12-14 months. RESULTS: Patients of the study group had significantly lower baseline L1-L4 and total hip BMD (p=0.028, p=0.022). BMD was significantly lower in L1-L4 and total hip (p=0.004, p<0.001, resp.) after 10-14 months and in L1-L4, femoral neck, and total hip (p=0.001, p=0.037, p< 0.001, resp.) after 20-26 months of ADT. After the treatment for osteoporosis with bisphosphonate a significant increase of BMD (p=0.04) was found in a total of 23 patients. Overall, the incidence of fractures after 20-26 months of ADT was 8.5 %. CONCLUSIONS: Osteopenia is very common in hormone naive PCa patients. There was a significant loss of BMD after 12 months of ADT which was progressive while the patients were on ADT. Bisphosphonate therapy was effective after 20 months of treatment. The incidence of pathological fractures was 7-fold higher in the study group.