Przemysław Kopczyński

Telomerase and drug resistance in cancer

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.

Telomere shortening in Down syndrome patients--when does it start?

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 Alzheimers 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.

High concentration of urokinase-type plasminogen activator receptor in the serum of women with primary breast cancer.

Aim of the study The 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 methods The concentration of uPAR was assessed using an enzyme-linked immunosorbent assay (R&D Systems). Results The 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. Conclusions Concentration 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.

Co‐occurrence of Jalili syndrome and muscular overgrowth

Jalili syndrome is a rare disorder inherited in an autosomal recessive pattern manifesting as a combination of cone‐rod dystrophy including progressive loss of visual acuity, color blindness, photophobia, and amelogenesis imperfecta with hypoplastic, immature, or hypocalcified dental enamel. It is caused by mutations in CNNM4, which encodes the ancient conserved domain protein 4. Here we report three brothers with Jalili syndrome and muscle overgrowth of the legs. Myopathic changes were found in needle electromyography. Mutational analysis showed in all three brothers a novel likely pathogenic homozygous missense substitution in exon 1 (c.1076T>C, p.(Leu359Pro)) of CNNM4. Both parents were carriers for the variant. In order to exclude other causative variants that could modify the patients’ phenotype we performed exome sequencing and MLPA analysis of the DMD gene in Patient 1. These analyses did not identify any additional variants. Our results expand the mutational spectrum associated with Jalili syndrome and suggest that mild myopathy with muscle overgrowth of the legs could be a newly identified manifestation of the disorder.

Analysis of skeletal maturity of children with cleft palate in terms of healthy children by the CVM method.

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 2nd, 3rd and 4th cervical vertebra in line with the Cervical Stage method (CS), developed by Baccetti et al. in 2005. RESULTS Patients with malocclusions without malformations achieved various stages of bone development at an earlier chronological age compared with patients with primary and secondary palate. An exception was the phase CS 3 (early growth spurt) development disorders, in which patients with different types of cleft had lower chronological age compared with patients with malocclusion. CONCLUSIONS The method that allows for an assessment of the development of skeletal maturity is the analysis of the shape of the cervical vertebrae in lateral head film.

Changes in the masticatory organ in patients with Recklinghausen's disease – a case report

In the report the authors present changes in the masticatory organ in the case of a 9-year-old girl affected with Recklinghausens disease. The characteristics included neurofibromatosis of the face, salivary gland and external ear in the form of an extensive tumour. The disease also resulted in acute right hemifacial hypertrophy. The computer-assisted tomography examination identified acute atrophy of the zygomatic bone, maxilla, mandible alveolar ridge and right base of the skull. The clinical intraoral examination of the patient revealed right buccal occlusion and lingual occlusion on the opposite side. The patient underwent functional orthodontic treatment of the co-existing malocclusion with an orthodontic appliance for the upper and lower jaw which was to prevent further mandible movement towards the right. According to researchers, neoplasia is an inherent characteristic of a phenotype seen in patients suffering from Recklinghausens disease. Therefore, it is the main factor influencing the selection of a therapy. Although there are certain single attempts of pharmacological treatment of ganglioneurofibromas at their early development stage, it is agreed that, in fact, no preventive actions are possible. Hence, in the case of neurofibromatosis type 1, reconstruction and aesthetic procedures are widely applied in treating the disease.