Anthelmintic drugs are widespread environmental contaminants, but their impact is still poorly understood. Although contact of parasitic nematode Haemonchus contortus with traces of anthelmintic drug albendazole (ABZ) altered the expression and activity of several UDP-glycosyl transferases (UGTs) and P-glycoproteins (Pgps, belonging to ABC-transporters), key enzymes in endogenous and xenobiotic metabolism, it is not known whether these changes will last during the life cycle and pass to the next generations. In the present study simulating the environmental-like exposure, free-living stages of H. contortus were exposed or unexposed to a sub-lethal dose of ABZ and its transformation products (ABZs) during L3 development. The L3 served for lambs' infection and obtaining of H. contortus adults and eggs, which were again exposed or unexposed to ABZs during L3 development. The expression pattern of UGTs and Pgps was analysed and compared in the first generation of L3, in the adults, and in the second generation of L3. The results showed that ABZs exposition during larvae development altered the expression of several ugt and pgp genes in L3 and adults. The intrageneration stability of ABZs-evoked changes was observed in the case of three genes, four genes maintained the intergeneration stability. Interestingly, ABZs-induced changes in the expression of some genes became apparent only in the second generation of L3. Taking together, contact of free-living stages of H. contortus with traces of ABZs in the environment evokes changes in the expression of certain UGTs and Pgps, with some of these changes being intra- and inter-generation stable.
Colorectal cancer (CRC) is the fourth most commonly diagnosed malignant condition in the world. Micro RNAs (miRNAs) as well as epithelial to mesenchymal transition (EMT) play an important role in the pathogenesis of CRC. We performed a comparative analysis of the expression of selected miRNA genes and EMT markers in bioptic samples from patients (n = 45) with primary CRC or metastatic (m)CRC to the regional lymph node using reverse transcription-quantitative PCR and IHC staining. Results: Out of all miRNA analyzed, the miR-17 expression was most significantly different and associated with lower risk of CRC spread to the lymph node. In addition, significant relationships were found between the tumor side localization and several miRNAs expressions (miR-9, miR-29b, miR-19a, miR-19b, miR-21, miR-106a, miR-20a and miR-17). In addition, of the examined EMT markers, only VEGFA expression correlated with tumor progression (tumor grade G2). In the examined set of patient samples and their matched healthy tissue, several specific molecular markers (miRNAs associated with EMT and tumor progression) were identified with a promising prognostic potential. Their further examination in larger patient cohorts is planned to validate the present data.
(1) Background: N-cadherin expression, epithelial-to-mesenchymal transition (EMT) and aggressive biological phenotype of tumor cells are linked although the underlying mechanisms are not entirely clear. (2) Methods: In this study, we used two different in vitro cell models with varying N-cadherin expression (stabilized lines and primocultures) and investigated their select biological features including the degree of their chemoresistance both in vitro as well as in vivo. (3) Results: We report that although enforced N-cadherin expression changes select morphological and behavioral characteristics of exposed cells, it fails to successfully reprogram cells to the aggressive, chemoresistant phenotype both in vitro as well as in vivo as verified by implantation of those cells into athymic mice. Conversely, primocultures of patient-colonic cells with naturally high levels of N-cadherin expression show fully aggressive and chemoresistant phenotype pertinent to EMT (in vitro and in vivo), with a potential to develop new mutations and in the presence of dysregulated regulatory pathways as represented by investigated miRNA profiles. (4) Conclusions: The presented results bring new facts concerning the functional axis of N-cadherin expression and related biological features of colon cancer cells and highlight colon cancer primocultures as a useful model for such studies.
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