Expression of matrix metalloproteinases and endogenous inhibitors in abdominal aortic aneurysm and aortoiliac occlusive disease (syndrome leriche)

© 2017 Charles University. All rights reserved. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a complex role in the pathogenesis of atherosclerosis. We compared (1) the histopathological findings in patients with abdominal aortic aneurysms (AAA) and aortoiliac occlusive disease (AOD); (2) the expression of MMP-2/MMP-9 and TIMP-1/TIMP-2 in aortic layers, inflammatory cells and smooth muscle cells (SMCs), aiming to identify the common underlying pathogenic mechanisms of the disease development. Samples were obtained from 30 patients with AAA and 30 with AOD. Aortic histology and immunohistochemistry were performed to evaluate inflammatory changes and MMP and TIMP expression. Thrombosis and ulceration were more frequent in AOD than in AAA. The MMP-9 expression was elevated in all aortic layers of AAA patients and in media/adventitia of AOD patients, mainly followed by lower expression of its inhibitor TIMP-1. Higher MMP-9 expression was also found in SMCs and macrophages of both AAA and AOD specimens, while higher TIMP-1/TIMP-2 were predominantly observed in the lymphocytes and macrophages of the aneurysm. These results showed that both conditions exhibited increased MMP-9 expression; however, the MMP expression pattern differed to some degree between the aneurysms and occlusive disease. The variations in molecular mechanisms underlying dilatative/stenosing disease warrant further investigation

Affective temperament, social support and stressors at work as the predictors of life and job satisfaction among doctors and psychologists

Background/Aim. Affective temperament, social support and work-related stresors belong to the group of life and job satisfaction indicators. The aim of this research was to examine predictive roles of the basic affective temperament traits, social support and work-related stressors in the feeling of job and life satisfaction among doctors and psychologists. Methods. The sample consisted of 203 individuals out of whom there were 28% male and 72% female doctors (61%) and psychologists (39%), 25–65 years old (39.08 ± 9.29), from the two university towns in Serbia. The set of questionnaires included Serbian version of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego – autoquestionnaire version (TEMPS-A), Satisfaction with Life scale, Job Satisfaction Survey, short Interpersonal Support Evaluation List, and Source of Stress at Work Scale (IRSa) for estimating the frequency of stressors at work. Results. According to the existing norms our examinees are satisfied with their life, but considerably less satisfied with their work, specially with pay and benefits, while they are most satisfied with nature of work itself and social relations with co-workers and supervisors. Our results show that depressive and hyperthymic, and to some extent cyclothymic temperament traits of the affective temperament significantly predict 21% of life satisfaction variance. Situational factors, such as stressors at work and social support, are important in predicting job satisfaction (58% of variance) with no significant contribution of temperament traits. The analysis did not point out any significant relation of sex, occupation, and age with life and job satisfaction. Conclusions. Affective temperaments can be regarded as predictors of life satisfaction, but in order to better predict satisfaction the aspects of wider social surrounding and sources of stressors at work must be taken in consideration. Future studies should consider other indicators of life satisfaction such as family or health satisfaction, stressors outside of work situations, and negative aspects of caregiving, for example hyperactivation. [Projekat Ministarstva nauke Republike Srbije, br. III 47023: Kosovo and Metohija between national identity and European integration, br. 175014 i br. 175007

Gene Expression and DNA Methylation in Human Papillomavirus Positive and Negative Head and Neck Squamous Cell Carcinomas

High-risk human papillomaviruses (HPV) are important agents, responsible for a large percentage of the 745,000 cases of head and neck squamous cell carcinomas (HNSCC), which were identified worldwide in 2020. In addition to being virally induced, tobacco and heavy alcohol consumption are believed to cause DNA damage contributing to the high number of HNSCC cases. Gene expression and DNA methylation differ between HNSCC based on HPV status. We used publicly available gene expression and DNA methylation profiles from the Cancer Genome Atlas and compared HPV positive and HPV negative HNSCC groups. We used differential gene expression analysis, differential methylation analysis, and a combination of these two analyses to identify the differences. Differential expression analysis identified 1854 differentially expressed genes, including PCNA, TNFRSF14, TRAF1, TRAF2, BCL2, and BIRC3. SYCP2 was identified as one of the top deregulated genes in the differential methylation analysis and in the combined differential expression and methylation analyses. Additionally, pathway and ontology analyses identified the extracellular matrix and receptor interaction pathway as the most altered between HPV negative and HPV positive HNSCC groups. Combining gene expression and DNA methylation can help in elucidating the genes involved in HPV positive HNSCC tumorigenesis, such as SYCP2 and TAF7L

Immunohistochemical expression of cyclin-dependent kinase inhibitors p16 and p57 in rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is a highly malignant cancer and is the most common soft tissue sarcoma in children and adolescents, but it is rare in adults ( 50 yrs. (HR 2.447), tumors > 5 cm (HR 21.31), involvement of regional lymph nodes (HR 3.96), the presence of metastases (HR 2.53), and low p57 expression (HR 2.11) as predictors of lower OS. Tumor size, regional lymph nodes involvement, and metastases were the independent predictors after multivariate analysis, while p57 did not predict OS in an independent way. In summary, although p57 was not confirmed to be an independent predictor of OS, our results indicate that its low expression may be the marker of aggressive phenotype and poor prognosis in adult RMS patients. Also, our findings suggest that epigenetic inactivation of p16 is not important in the pathogenesis of rhabdomyosarcoma

The heterogeneous cancer phenotype of individuals with biallelic germline pathogenic variants in CHEK2

PURPOSE: Females with biallelic CHEK2 germline pathogenic variants (gPVs) more often develop multiple breast cancers than individuals with monoallelic CHEK2 gPVs. This study is aimed at expanding the knowledge on the occurrence of other malignancies.METHODS: Exome sequencing of individuals who developed multiple primary malignancies identified 3 individuals with the CHEK2 (NM_007194.4) c.1100del p.(Thr367MetfsTer15) loss-of-function gPV in a biallelic state. We collected the phenotypes of an additional cohort of individuals with CHEK2 biallelic gPVs (n = 291).RESULTS: In total, 157 individuals (53.4%; 157/294 individuals) developed ≥1 (pre)malignancy. The most common (pre)malignancies next to breast cancer were colorectal- (n = 19), thyroid- (n = 19), and prostate (pre)malignancies (n = 12). Females with biallelic CHEK2 loss-of-function gPVs more frequently developed ≥2 (pre)malignancies and at an earlier age compared with females biallelic for the CHEK2 c.470T&gt;C p.(Ile157Thr) missense variant. Furthermore, 26 males (31%; 26/84 males) with CHEK2 biallelic gPVs developed ≥1 (pre)malignancies of 15 origins.CONCLUSION: Our study suggests that CHEK2 biallelic gPVs likely increase the susceptibility to develop multiple malignancies in various tissues, both in females and males. However, it is possible that a substantial proportion of individuals with CHEK2 biallelic gPVs is missed as diagnostic testing for CHEK2 often is limited to individuals who developed breast cancer.</p