Braicu C.,University of Medicine and Pharmacy, Cluj-Napoca |
Braicu C.,The Oncological Institute Prof Dr Ion Chiricuta |
Cojocneanu-Petric R.,University of Medicine and Pharmacy, Cluj-Napoca |
Jurj A.,University of Medicine and Pharmacy, Cluj-Napoca |
And 7 more authors.
BMC Genomics | Year: 2016
Background: Zearalenone (ZEA) is a secondary metabolite produced by Fusarium species. ZEA was proved to exert a wide range of unwanted side effects, but its mechanism of action, particularly at duodenum levels, remains unclear. In our study based on the microarray technology we assessed the alteration of gene expression pattern Sus scrofa duodenum which has been previously exposed to ZEA. Gene expression data was validated by qRT-PCR and ELISA. The gene expression data were further extrapolated the results to their human orthologues and analyzed the data in the context of human health using IPA (Ingenuity Pathways Analysis). Results: Using Agilent microarray technology, we found that gene expression pattern was significantly affected by ZEA exposure, considering a 2-fold expression difference as a cut-off level and a p-value < 0.05. In total, we found 1576 upregulated and 2446 downregulated transcripts. About 1084 genes (764 downregulated and 751 overexpressed) were extrapolated to their human orthologues. IPA analysis showed various altered key cellular and molecular pathways. As expected, we observed a significant alteration of immune response related genes, MAPK (mitogen activate protein kinases) pathways or Toll-Like Receptors (TLRs). What captured our attention was the modulation of pathways related to the activation of early carcinogenesis. Conclusions: Our data demonstrate that ZEA has a complex effect at duodenum level. ZEA is able to activate not only the immune response related genes, but also those relate to colorectal carcinogenesis. The effects can be more dramatic when connected with the exposure to other environmental toxic agents or co-occurrence with different microorganisms. © 2016 The Author(s).
PubMed | University of Medicine and Pharmacy, Cluj-Napoca, The Oncology Institute Prof Dr Ion Chiricuta, National Institute for Research and Development for Biology and Animal Nutrition and The Oncological Institute Prof Dr Ion Chiricuta
Type: | Journal: BMC genomics | Year: 2016
The gastrointestinal tract is the primary site of toxin interaction, an interface between the organism and its surroundings. In this study, we assessed the alteration of intestinal mRNA profile in the case of co-occurrence of zearalenone (ZEA), a secondary Fusarium metabolite, and Escherichia coli (E. coli), on the intestinal porcine epithelial cells IPEC-1. We chose this model since the pig is a species which is susceptible to pathogen and mycotoxin co-exposure.After treating the cells with the two contaminants, either separately or in combination, the differential gene expression between groups was assessed, using the microarray technology. Data analysis identified 1691 upregulated and 797 downregulated genes as a response to E. coli exposure, while for ZEA treated cells, 303 genes were upregulated and 49 downregulated. The co-contamination led to 991 upregulated and 800 downregulated genes. The altered gene expression pattern was further classified into 8 functional groups. In the case of co-exposure to ZEA and E.coli, a clear increase of proinflammatory mechanisms.These results demonstrate the complex effect of single or multiple contaminants exposure at cellular and molecular level, with significant implications that might lead to the activation of pathological mechanisms. A better understanding of the effects of co-contamination is mandatory in developing novel exposure regulations and prevention measures.
Chiorean R.,Clinical University Hospital of Dermatovenereology |
Chiorean R.,Albert Ludwigs University of Freiburg |
Chiorean R.,The Oncological Institute Prof Dr Ion Chiricuta |
Braicu C.,Albert Ludwigs University of Freiburg |
And 5 more authors.
Breast | Year: 2013
Triple negative breast cancer is a heterogeneous group of tumors, lacking the expression of estrogen, progesterone and HER-2 receptors. As frequency, it accounts about 15-20% of all breast cancers. Although in the last years there was a "boom" in publishing over this issue, multiple molecular classifications being elaborated, "the triple negative breast cancer odyssey " is still far away from ending, as the complicated molecular pathways of pathogenesis and drug resistance mechanisms remain yet insufficiently explored. The aim of this review is presentation of molecular signatures that could predict outcome and drug resistance in triple negative breast cancer. © 2013 Elsevier Ltd.
Gherman C.,The Oncology Institute Prof Dr Ion Chiricuta |
Gherman C.,University of Medicine and Pharmacy, Cluj-Napoca |
Braicu O.L.,University of Medicine and Pharmacy, Cluj-Napoca |
Braicu O.L.,The Oncological Institute Prof Dr Ion Chiricuta |
And 11 more authors.
Molecular and Cellular Biochemistry | Year: 2016
Ovarian cancer is a highly aggressive pathology, displaying a poor prognosis and chemoresistance to classical therapy. The present study was conducted to evaluate the effect of caffeic acid phenethyl ester (CAPE) on survival of ovarian cancer cell lines, A2780 (sensitive to cisplatin) and A2780cis (resistant to cisplatin). MTT assay was used to evaluate cell viability, while the apoptotic processes were examined by flow cytometry and qRT-PCR. A reduction of cell proliferation and activation of the apoptosis was observed in both cell lines. qRT-PCR evaluation demonstrated the activation of the pro-apoptotic genes (BAD, CASP8, FAS, FADD, p53) in both cell lines. The limited therapeutic effect in A2780 cells is explained by the activation of epithelial–mesenchymal transition-related genes (ZEB1, ZEB2, or TGFBB1) as displayed by Ingenuity Network analysis. Overall data suggest that CAPE can be used as an alternative in sensitizing cells to chemotherapy. © 2016, Springer Science+Business Media New York.
Tomuleasa C.,University of Medicine and Pharmacy, Cluj-Napoca |
Braicu C.,University of Medicine and Pharmacy, Cluj-Napoca |
Irimie A.,University of Medicine and Pharmacy, Cluj-Napoca |
Craciun L.,University of Medicine and Pharmacy, Cluj-Napoca |
And 2 more authors.
International Journal of Nanomedicine | Year: 2014
Nanoparticles have displayed considerable promise for safely delivering therapeutic agents with miscellaneous therapeutic properties. Current progress in nanotechnology has put forward, in the last few years, several therapeutic strategies that could be integrated into clinical use by using constructs for molecular diagnosis, disease detection, cytostatic drug delivery, and nanoscale immunotherapy. In the hope of bringing the concept of nanopharmacology toward a viable and feasible clinical reality in a cancer center, the present report attempts to present the grounds for the use of cell-free nanoscale structures for molecular therapy in experimental hematology and oncology. © 2014 Tomuleasa et al.