New computational studies to support cyclin-dependent kinase 9 inhibitor screening and design

Aims: Cyclin-dependent kinase 9 (CDK9) plays a major role in the regulation of transcription. Its overexpression – which occurs in several types of cancer – increases the levels of certain antiapoptotic proteins that can lead to tumorigenesis, therefore the identification of new, more potent and more selective inhibitors is essential. Methods: In this study we present a computational approach, which can facilitate lead selection and optimization. Results: First, a pharmacophore hypothesis based on the active compounds has been developed to identify the key features for the ligand-target interaction. This was followed by the docking of the compounds into the active site of CDK9, the poses and interactions with the amino acids were compared with those of the co-crystallized ligand. The mode of their binding further explained the characteristics of these inhibitors while the docking scores can be a factor in the selection of active compounds in the future. Finally, a field-based QSAR model was also created, to predict the activity of inhibitor candidates. Conclusion: With our current work we deepened our knowledge about the interactions between CDK9 and its inhibitors, which can contribute to the discovery of novel CDK9 inhibitors

Primary alveolar rhabdomyosarcoma of the bone: two cases and review of the literature

BACKGROUND: Rhabdomyosarcoma (RMS) is a malignant tumor of mesenchymal origin and comprises the largest category of soft-tissue sarcomas both in children and adolescents. From a pediatric oncology point of view, RMS has traditionally been classified into alveolar (ARMS) and embryonal (ERMS) subtypes. The anatomical localization of the tumor may vary, but commonly involve the head/neck regions, male and female urogenital tract or the trunk and extremities. CASE PRESENTATION: Here, we report two challenging cases involving 17- and 9-years-olds males where diffuse and multiplex bone lesions suggested either a hematological disease or a primary bone tumor (mesenchymal chondrosarcoma). Biopsies, proved a massive infiltration of the bone marrow cavity with rhabdomyosarcoma. In both cases, the ARMS subtype was confirmed using FOXO1 break-apart probes (FISH). Radiological examination could not identify primary soft tissue component in any localization at the time of diagnosis in either cases. CONCLUSIONS: Primary alveolar rhabdomyosarcoma of the bone as a subtype of ARMS, seems to be a distinct clinico-pathological entity with challenging diagnostic difficulties and different, yet better, biological behavior in comparison to soft tissue ARMS. However, it is difficult to be characterized or predict its prognosis and long-term survival as only sporadic cases (four) were reported so far

Social and ethnic segregation amongst the smallest Hungarian villages

Social segregation is one of the most important social problems in Central-Eastern Europe not only in urban, but also rural areas. The social segregation usually coexists with ethnic segregation. In Western-Europe we can see segregation mainly in towns, but in Eastern-Europe also in villages, usually connecting with Roma people. In the last decades number of population of small villages dropped dramatically and in some regions the most disadvantaged social groups appeared in these villages. Nowadays some of these villages have geographical, social and ethnic disadvantages together. To stop marginalization of people living in poverty is one of the biggest challenges nowadays in Hungary. According to the definition of Hungarian Statistical Office the whole settlement is regarded segregated if it has less than 200 inhabitants, therefore we also determined this limit. These settlements with population below 200 were the subject of this study. A complex indicator system was established containing six indicators (educational level, unemployment, comfort level of homes, etc.) These indicators served as the base of cluster analysis using the K-means algorithm resulted in five clusters. The 58 segregated settlements can be found mainly in peripheral areas of Northeastern- and Southwestern-Hungary. The proportion of Roma population is high in most of the segregated settlements. The aim of the paper is to describe the most important social problems of the smallest Hungarian villages, to find the groups of villages with social segregation and marginalization and to find context between marginalization, social and ethnic segregation amongst the tiny Hungarian villages

EQUINE HERPESVIRUS TYPE 5 IN BRONCHOALVEOLAR LAVAGE FLUID OF HORSES WITH EQUINE MULTINODULAR PULMONARY FIBROSIS (EMPF) AND WITH OTHER CHRONIC RESPIRATORY DISORDERS.

The aim of the study was to estimate the prevalence and the potential role of equine herpesvirus type 5 (EHV-5) in the bronchoalveolar lavage fluid (BALF) samples of horses with chronic respiratory signs. Altogether 60 horses with chronic respiratory signs of minimum of 2 weeks duration were involved in the study. Horses were clinically examined, respiratory endoscopy, thoracic radiography, ultrasonography, tracheal culture and evaluation of BALF cytology was performed. EHV-5 PCR assay was carried out on BALF samples of 15 horses in a commercial laboratory (IDEXX-VetMedLab Germany), 54 BALF samples were tested in the research laboratory of Szent Istvan University, Faculty of Veterinary Science and samples of 9 horses were tested by both laboratories. PCR testing by the two different laboratories gave homogenous results. Altogether there were 7 horses (prevalence: 11,6%) with positive PCR results. Three of them were diagnosed with EMPF based on histologic results of lung biopsy specimens or post-mortem tissue samples. These three horses were genetically closely related warmbloods. Two other horses suffered of suspected EMPF based on thoracic radiograpy with nodular interstitial pattern, EHV-5 positivity and intranuclear inclusion bodies but pulmonary biopsy was not performed on any of them. One positive horse was diagnosed with inflammatory airway disease and one with systemic granulomatous disease. Presence of EHV- 5 in BALF significantly (Fisher test, p < 0,001) correlated with the diagnosis of EMPF. BALF testing for EHV-5 is an important examination when establishing the diagnosis of EMPF. Genetic predisposition might render the patient more susceptible to EMPF or viral infection