Ascorbic acid (vitamin C) has been gaining attention as a potential treatment for human malignancies. Various experimental studies have shown the ability of pharmacological doses of vitamin C alone or in combinations with clinically used drugs to exert beneficial effects in various models of human cancers. Cytotoxicity of high doses of vitamin C in cancer cells appears to be related to excessive reactive oxygen species generation and the resulting suppression of the energy production via glycolysis. A hallmark of cancer cells is a strongly upregulated aerobic glycolysis, which elevates its relative importance as a source of ATP (Adenosine 5′-triphosphate). Aerobic glycolysis is maintained by a highly increased uptake of glucose, which is made possible by the upregulated expression of its transporters, such as GLUT-1, GLUT-3, and GLUT-4. These proteins can also transport the oxidized form of vitamin C, dehydroascorbate, permitting its preferential uptake by cancer cells with the subsequent depletion of critical cellular reducers as a result of ascorbate formation. Ascorbate also has a potential to affect other aspects of cancer cell metabolism due to its ability to promote reduction of iron(III) to iron(II) in numerous cellular metalloenzymes. Among iron-dependent dioxygenases, important targets for stimulation by vitamin C in cancer include prolyl hydroxylases targeting the hypoxia-inducible factors HIF-1/HIF-2 and histone and DNA demethylases. Altered metabolism of cancer cells by vitamin C can be beneficial by itself and promote activity of specific drugs.

It is well known that a decreased expression or inhibited activity of telomerase in cancer cells is accompanied by an increased sensitivity to some drugs (e.g., doxorubicin, cisplatin, or 5-fluorouracil). However, the mechanism of the resistance resulting from telomerase alteration remains elusive. There are theories claiming that it might be associated with telomere shortening, genome instability, hTERT translocation, mitochondria functioning modulation, or even alterations in ABC family gene expression. However, association of those mechanisms, i.e., drug resistance and telomerase alterations, is not fully understood yet. We review the current theories on the aspect of the role of telomerase in cancer cells resistance to therapy. We believe that revealing/unravelling this correlation might significantly contribute to an increased efficiency of cancer cells elimination, especially the most difficult ones, i.e., drug resistant.

Telomerase is perceived as an immortality enzyme that might provide longevity to cells and whole organisms. Importantly, it is generally inactive in most somatic cells of healthy, adult men. Consequently, its substrates, i.e. telomeres, get shorter in most human cells with time. Noteworthy, cell life limitation due to telomere attrition during cell divisions, may not be as bad as it looks since longer cell life means longer exposition to harmful factors. Consequently, telomere length (attrition rate) becomes a factor that is responsible for inducing the signaling that leads to the elimination of cells that lived long enough to acquire severe damage. It seems that telomere length that depends on many different factors (including telomerase activity but also genetic factors, a hormonal profile that reflects sex, etc.) might become a useful marker of aging and exposition to stress. Thus in the current paper, we review the factors that affect telomere length in human cells focusing on sex that all together with different environmental and hormonal regulations as well as parental aspect affect telomere attrition rate. We also raise some limitations in the assessment of telomere length that hinders a trustworthy meta-analysis that might lead to acknowledgment of the real value of this parameter.

Currently, food allergy is considered to be one of the diseases of civilization, which occurs as a result of the changing conditions of life and environmental changes (e.g. increased popularity of cesarean delivery, excessive hygienic regime during the neonatal-infantile period). Based on medical statistics, it can be concluded that this problem will be intensified. Consumption of food is one of the main activities in human life. What and how one eats affects our health. Meals eaten regularly provide the components necessary for the energy metabolism. Multicultural society, travel, and new trends affect the diversity of food consumed. The mechanism of food allergy reaction covers all 4 types of the immune response of the classical division of Gell and Coombs. The percentage of the immune response was assessed by Chandra as follows: type I – 48%, type II – 6%, type III – 10%, and type IV – 18%. The article presents the risk factors for food allergy, most common symptoms, preventive measures and characteristics of food products that are potential allergens.

Background. For many years, the analysis of bone age X-rays have been used for the hand and wrist, which were assessed on the basis of changes in the various centers of ossification. These images, however, do not constitute a diagnostic element of cleft defects, leading to additional exposure of the patient to X-rays. The problem was solved by using lateral head films, which enabled the interpretation of the morphological changes in the cervical spine to evaluate skeletal development stages. Objectives. The objective of this work is to define the differences between the skeletal age and chronological age of children with malocclusion and congenital craniofacial disorders -primary and secondary palate cleft. Material and Methods. The study material comprised 90 lateral cephalometric radiographs of patients at the age of 7 to 16 (45 lateral head radiographs of patients with various occlusion disorders and 45 lateral head radiographs of patients with various types of primary and secondary palate cleft). Then, all the lateral cephalometric radiographs were analysed in terms of the shape of the 2

Down syndrome (DS) is one of the most common aneuploidy. In general population, its prevalence is 1:600-1:800 live births. It is caused by a trisomy of chromosome 21. DS is phenotypically manifested by premature aging, upward slant to the eyes, epicanthus, flattened face, and poor muscle tone. In addition to physical changes, this syndrome is characterized by early onset of diseases specific to old age, such as Alzheimer's disease, vision and hearing problems, and precocious menopause. Since DS symptoms include premature aging, the shortening of telomeres might be one of the markers of cellular aging. Consequently, the aim of the study was to determine the length of the telomeres in leukocytes from the blood of juvenile patients with DS (n = 68) compared to an age-matched control group (n = 56) and also to determine the diagnostic or predictive value for this parameter. We show that, for the first time, in juveniles, the average relative telomere length in studied subjects is significantly longer than in the control group (50.46 vs. 40.56, respectively arbitrary units [AU]; p = 0.0026). The results provide interesting basis for further research to determine the causes and consequences of telomere maintaining and the dynamics of this process in patients with DS.

Telomerase is known to contribute to telomere maintenance and to provide cancer cell immortality. However, numerous reports are showing that the function of the enzyme goes far beyond chromosome ends. The study aimed to explore how telomerase downregulation in MCF7 and MDA-MB-231 breast cancer cells affects their ability to survive. Consequently, sensitivity to drug resistance, proliferation, and adhesion were assessed. The lentiviral-mediated human telomerase reverse transcriptase (hTERT) downregulation efficiency was performed at gene expression and protein level using qPCR and Western blot, respectively. Telomerase activity was evaluated using the Telomeric Repeat Amplification Protocol (TRAP) assay. The study revealed that hTERT downregulation led to an increased sensitivity of breast cancer cells to doxorubicin which was demonstrated in MTT and clonogenic assays. During a long-term doubling time assessment, a decreased population doubling level was observed. Interestingly, it did not dramatically affect cell cycle distribution. hTERT downregulation was accompanied by an alteration in β1-integrin- and by focal adhesion kinase (FAK)-driven pathways together with the reduction of target proteins phosphorylation, i.e., paxillin and c-Src. Additionally, autophagy activation was observed in MDA-MB-231 cells manifested by alternations in Atg5, Beclin 1, LC3II/I ratio, and p62. These results provide new evidence supporting the possible therapeutic potential of telomerase downregulation leading to induction of autophagy and cancer cells elimination.

Aim of the studyThe purpose of this study was to assess the concentration of urokinase-type plasminogen activator receptor (uPAR) in the serum of 103 women with breast cancer. Commonly recognized prognostic factors were taken into account, including age, histological grade of malignancy, stage of clinical advancement of the disease, status of local axillary lymph nodes and the size of the primary tumour.Material and methodsThe concentration of uPAR was assessed using an enzyme-linked immunosorbent assay (R&D Systems).ResultsThe concentration of uPAR in women with breast cancer was found to be higher than in a control group and the difference was statistically significant. The concentration of uPAR was found to increase in line with increasing disease stage and this too was of statistical significance. Raised levels of uPAR were found in women with breast cancer both with and without metastases to the lymph nodes of the axilla. A positive relationship was also found between the concentration of the tested receptor and the size of the primary tumour. No significant relationship, however, was found between the concentration of uPAR and the histological grade of malignancy of the tumour. No statistically significant results were obtained regarding the menopausal status of the women, that is, whether they were pre- or post-menopausal.ConclusionsConcentration of uPAR in serum of women with breast cancer is positively correlated with the stage of advancement of the disease. Thus, the assessment of this parameter can be useful in the clinical evaluation of women with breast cancer.