6 research outputs found
Protein-protein interaction network analysis of human fibroblast cells treated with ethanol
Introduction: Studies show that ethanol can induce changes in proteomic profile of human fibroblast cells. Some of these proteins are important in promoting cancer. Thus, analyzing function and interaction networks of these proteins are essential for better understanding the carcinogenesis mechanism of ethanol. Materials and Methods: In this study the protein-protein interaction network (PPI) of six significant down-regulated proteins in human fibroblast cells (HFFF2) treated with ethanol were analyzed by using Cytoscape software and its algorithms. Results: PPI network analysis showed that the constructed network consisted of 756 nodes and 1166 edges. Results indicated that Heterogeneous nuclear ribonucleoprotein A1 with degree = 528 and Betweenness Centrality = 0.74 is a hub protein that ethanol can alter its expression. In addition, module evaluation showed that the hub protein has a key role in different overlapped complexes. On the other hand, annotation studies by using DAVID program indicated that this protein is involved in different important biological processes in the cell. Conclusion: The six down-regulated proteins treated with ethanol may become carcinogenic and can impose vast alterations in other vital biological processes of the cell. Among them, Heterogeneous nuclear ribonucleoprotein A1 is the most important one. © 2016, Semnan University of Medical Sciences. All rights reserved
Comparison of behavioural responses of two neuropathic pain models in male rats
Background: Neuropathic pain syndromes are changes resulted from damage to neuronal pathways which is characterized by spontaneous burning pain with accompanying allodynia and hyperalgesia. The mechanisms underlying neuropathic pain are poorly understood. The present study explores behavioral characteristics of the neuropathic pain models chronic constriction injury (CCI) and spared nerve injury (SNI).
Materials and Methods: Experiments were performed on four groups (n= 8) of male Sprague-Dawley rats (230-280 g). Anesthesia was initially induced with sodium pentobarbital (i.p.) at a dose of 50 mg/kg. The CCI model was made by loose ligation of the sciatic nerve. Also a lesion of two of three terminal branches of the sciatic nerve leads to a SNI model. The animals were tested for behavioral responses cold-and mechano-allodynia and heat-and mechano-hyperalgesia. The cold and mechanical stimulations in the cold- and mechano-allodynia phenomena were applied through acetone and von Frey filament respectively. Pin-prick and radiant heat were applied as thermal and mechanical stimulations in the heat- and mechano-hyperalgesia respectively. Behavioral tests were conducted on the animals prior to surgery (the day 0), and 3, 7, 14, 21 and 28 days post-operation.
Results: Our results indicate that, in comparison to the controlled group, the rats in both SNI and CCI groups reveal an obvious difference in behavioral responses. Although the SNI, compared to the CCI group were more sensitive to mechano-allodynia shortly after surgery (p<0.5) however, both groups share a similar pattern of behavior. In the heat-hyperalgesia testing, again, the animals in the CCI and SNI groups behaved differently than those in the controlled group, but no variation was evident among the test groups, themselves.
Conclusion : These findings clearly show that the two neuropathic models produce abnormal pain-related disorders in the rats. A major feature of the SNI model was the very marked hypersensitivity to normally innocuous mechanical stimuli
Cost-effectiveness of osimertinib in the treatment of advanced EGFR-mutated non-small cell lung cancer: a systematic review.
BACKGROUND: The most common type of lung cancer is advanced and mutant non-small cell lung cancer (NSCLC). Although targeted tyrosine kinase inhibitors (TKIs) have reconstructed the care of these patients, the resistance of TKIs to the secondary EGFR-T790M mutation in advanced or metastatic NSCLC led to the introduction of the third generation of them, like osimertinib. Osimertinib has represented a remarkable increase in progression-free survival (PFS) and a decrease in death and hazard ratios in patients with required T790 mutation and sensitizing EGFR mutation without T790M. We aimed to evaluate the cost-effectiveness of osimertinib for the treatment of these patients compared to chemotherapy or immunotherapy with the last generations of EGFR-TKIs. AREAS COVERED: Electronic searches were conducted on PubMed, Embase, Science Direct, Scopus, , Web of Knowledge, NHSEED, NHS Health Technology assessment (CRD), and Cost-Effectiveness Analysis Registry databases. Related articles were reviewed from January 2015 to the end of August 2020. Out of 2708 initial studies, 10 articles had the inclusion criteria. EXPERT OPINION: Although osimertinib improves the quality of life and PFS for the mentioned patients based on its greater efficacy compared to standard EGFR-TKIs and chemotherapy, its high cost prevents considering it a cost-effective option. And, since most entered studies have been done in developed countries, it certainly does not true to extend these results to low-income and developing countries. Therefore, further studies in those countries are needed to evaluate the cost-effectiveness of osimertinib for sensitizing EGFR mutation without T790M and required T790M in advanced or metastatic NSCLC