[Corrigendum] Antiproliferative effects of imatinib mesylate on ZR­75­1 and MDA­MB­231 cell lines via PDGFR­ß, PDGF­BB, c­Kit and SCF expression.

An interested reader drew to our attention that the above study appeared to contain a high level of overlap with an article by the same authors published in the journal Drug Design, Development and Therapy [Kadivar A, Kamalidehghan B, Akbari Javar H, Karimi B, Sedghi R and Noordin MI: Antiproliferation effect of imatinib mesylate on MCF7, T­47D tumorigenic and MCF 10A nontumorigenic breast cell lines via PDGFR­ß, PDGF­BB, c­Kit and SCF genes. Drug Des Devel Ther 11: 469­481, 2017]. Following an internal investigation and also in liaison with the authors, it was established that, although the studies were conducted along broadly similar lines, the papers contained entirely different data involving two different subsets of cell lines; the submission to Drug Des Devel Ther aimed to explore the effects of imatinib mesylate on three different groups, with each group being represented by a cell line, whereas the submission to Int J Mol Med explored the effectiveness of imatinib mesylate in breast cancer cell lines. In spite of this, considering the relatedness of the articles and the fact that the paper to Drug Des Devel Ther was submitted first and published while the Int J Mol Med paper was passing through the peer­review process, the authors concede that they should have properly referenced their paper submitted to Drug Des Devel Ther in the Int J Mol Med paper. Note that the publishers of Drug Des Devel Ther, with whom we were liaising, agreed with the decision to issue a Corrigendum for this paper that acknowledges the article published in Drug Des Devel Ther. The authors regret their failure to acknowledge the related paper in this instance, and apologize to the readership for this oversight. [the original article was published in International Journal of Molecular Medicine 14: 414­424, 2018; DOI: 10.3892/ijmm.2018.3590].

Antiproliferative effects of imatinib mesylate on ZR­75­1 and MDA­MB­231 cell lines via PDGFR­ß, PDGF­BB, c­Kit and SCF expression.

Imatinib mesylate is an anti­neoplastic targeted chemotherapeutic agent, which can inhibit tyrosine kinase receptors, including BCR­ABL, platelet­derived growth factor receptors (PDGFRs) and c­Kit. Cellular processes, including differentiation, proliferation and survival are regulated by these receptors. The present study aimed to evaluate the antiproliferative effects of imatinib mesylate, and its effects on apoptotic induction and cell cycle arrest in breast cancer cell lines. In addition, the study aimed to determine whether the effects of this drug were associated with the mRNA and protein expression levels of PDGFR­ß, c­Kit, and their corresponding ligands PDGF­BB and stem cell factor (SCF), which may potentially modulate cell survival and proliferation. To assess the antiproliferative effects of imatinib mesylate, an MTS assay was conducted following treatment of cells with 2­10 µM imatinib mesylate for 96, 120 and 144 h; accordingly the half maximal inhibitory concentration of imatinib mesylate was calculated for each cell line. In addition, the proapoptotic effects and cytostatic activity of imatinib mesylate were investigated. To evaluate the expression of imatinib­targeted genes, PDGFR­ß, c­Kit, PDGF­BB and SCF, under imatinib mesylate treatment, mRNA expression was detected using semi­quantitative polymerase chain reaction and protein expression was detected by western blot analysis in ZR­75­1 and MDA­MB­231 breast carcinoma cell lines. Treatment with imatinib mesylate suppressed cell proliferation, which was accompanied by apoptotic induction and cell cycle arrest in the investigated cell lines. In addition, PDGFR­ß, PDGF­BB, c­Kit and SCF were expressed in both breast carcinoma cell lines; PDGFR­ß and c­Kit, as imatinib targets, were downregulated in response to imatinib mesylate treatment. The present results revealed that at least two potential targets of imatinib mesylate were expressed in the two breast carcinoma cell lines studied. In conclusion, the antiproliferative, cytostatic and proapoptotic effects of imatinib mesylate may be the result of a reduction in the expression of c­Kit and PDGFR tyrosine kinase receptors, thus resulting in suppression of the corresponding ligand PDGF­BB. Therefore, imatinib mesylate may be considered a promising target therapy for the future treatment of breast cancer.

Cost-Effectiveness Analysis of the Unfractionated Heparin versus Low-Molecular-Weight Heparin in Hospitalized Patients with Stroke Due to Atrial Fibrillation in Shiraz, South of Iran.

BACKGROUND: Patients with atrial fibrillation (AF) make a unique group of strokes. Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are among the medications used for preventing blood coagulation. This study was carried out aiming at analyzing the cost effectiveness of LMWH versus UFH in hospitalized patients with stroke due to AF with respect to the Iranian population. METHODS: This randomized study was an economic evaluation of cost effectiveness with the help of the cross-sectional data of 2013-2015. In this study, 74 patients had undergone treatment in two groups, before being evaluated. Half of the patients were treated by LMWH, while the other half was treated by UFH. Effectiveness criterion was prevention of new stroke recurrence. RESULTS: Average medical direct costs, non-medical direct costs, and indirect costs of UFH were 110375 ± 40411$, 15594 ± 11511$, and 21723 ± 19933$, respectively. Same average medical direct costs, non-medical direct costs, and indirect costs of LMWH were 99573 ± 59143$, 9016 ± 17156$, and 10385 ± 10598$, respectively. The number of prevention of new strokes due to AF in LMWH and UFH was 2 and 0, respectively. Expected effectiveness in LMWH and UFH groups was 0.56 and 0.51, respectively. Moreover, the expected costs were 26737.61$ and 30776.18$, respectively. The incremental cost-effectiveness ratio for stroke due to AF was -150, 201, 26$ per prevention of stroke recurrence (p-values ≤ 0/05). CONCLUSION: The results of the cost-effectiveness analysis of LMWH versus UFH showed that LMWH is a dominant strategy for patients with stroke due to AF in Iranian population.

Antiproliferation effect of imatinib mesylate on MCF7, T-47D tumorigenic and MCF 10A nontumorigenic breast cell lines via PDGFR-ß, PDGF-BB, c-Kit and SCF genes.

Recent cancer molecular therapies are targeting main functional molecules to control applicable process of cancer cells. Attractive targets are established by receptor tyrosine kinases, such as platelet-derived growth factor receptors (PDGFRs) and c-Kit as mostly irregular signaling, which is due to either over expression or mutation that is associated with tumorigenesis and cell proliferation. Imatinib mesylate is a selective inhibitor of receptor tyrosine kinase, including PDGFR-ß and c-Kit. In this research, we studied how imatinib mesylate would exert effect on MCF7 and T-47D breast cancer and MCF 10A epithelial cell lines, the gene and protein expression of PDGFR-ß, c-Kit and their relevant ligands platelet-derived growth factor (PDGF)-BB and stem cell factor (SCF). The MTS assay was conducted in therapeutic relevant concentration of 2-10 µM for 96, 120 and 144 h treatment. In addition, apoptosis induction and cytostatic activity of imatinib mesylate were investigated with the terminal deoxynucleotidyl transferase dUTP nick end labeling TUNEL and cell cycle assays, respectively, in a time-dependent manner. Comparative real-time PCR and Western blot analysis were conducted to evaluate the expression and regulation of imatinib target genes and proteins. Our finding revealed that imatinib mesylate antiproliferation effect, apoptosis induction and cytostatic activity were significantly higher in breast cancer cell lines compared to MCF 10A. This effect might be due to the expression of PDGFR-ß, PDGF-BB, c-Kit and SCF, which was expressed by all examined cell lines, except the T-47D cell line which was not expressed c-Kit. However, examined gene and proteins expressed more in cancer cell lines. Therefore, imatinib mesylate was more effective on them. It is concluded that imatinib has at least two potential targets in both examined breast cancer cell lines and can be a promising drug for targeted therapy to treat breast cancer.